Septic arthritis is the purulent invasion of a joint by an infectious agent which produces arthritis. The main organisms having great potential to infect human beings as well as other mammals are Staphylococcus aureus, Streptococcus pneumoniaeand Streptococcus pyrogens. In Silico comparative analysis ofall the pathways of host Homo sapiens and pathogens was performed by using KEGG and Protein BLAST. 25, 20 and 16 unique pathways were identified for Staphylococcus aureus, Streptococcus pyrogensand Streptococcus pneumonia respectively. Out of these we identified 3 enzymes for Staphylococcus aureus, 4 for Streptococcus pneumoniae and 1 for Streptococcus pyrogens, which are non-homologous to Homo sapiens proteins. The enzymes essential for survival of the pathogens were found out by DEG database. Further CELLO analysis results showed that 50% enzymes are found to be Extracellular, 25% to be cytoplasmic and 25% to be membranous for Staphylococcus aureus. For Streptococcus pneumoniae, 50% enzymes are found to be Extracellular, 12% cytoplasmic, 13% membranous and 25% as cell wall proteins. 100% enzymes were found to be membranous for Streptococcus pyrogens. Finally the enzymes from DEG were submitted in Drug Bank database to identify approve drug targets. This Data Mining approach found that mostly the enzymes which can act as targets belong to extracellular level in Staphylococcus aureus, Streptococcus pneumoniae and membranous in Streptococcus pyrogens. This findings gives an understanding of these enzymes interaction with human protein protein interaction at extracellular and membrane level.
Dr. Qing-Hua Wu is a lecturer at Yangtze University who received his Ph.D. in Veterinary Pharmacology and Toxicology from Huazhong Agricultural University in 2013. His research focuses on the metabolism, toxicity, and signal transduction pathways of mycotoxins such as trichothecenes. Specifically, he investigates the functional crosstalk of MAPK and JAK/STAT signaling pathways induced by trichothecenes and the regulation of cell apoptosis. He has also studied the biotransformation of T-2 toxin in various food-producing animals and the degradation of deoxynivalenol during extrusion cooking processes. Dr. Wu has published over 30
This study analyzed phenotypic virulence factors and antibiotic resistance patterns in 156 uropathogenic E. coli (UPEC) isolates from patients with urinary tract infections (UTIs). The researchers found that 85.3% of isolates produced biofilm and 34% produced hemolysin. 62.8% exhibited mannose-sensitive hemagglutination (MSHA) and 37.2% exhibited mannose-resistant hemagglutination (MRHA). Biofilm formation correlated with infection type. Resistance was highest for ampicillin, tetracycline, amoxicillin and cotrimoxazole. 26.9% of isolates were extended-spectrum beta-lactamase producers. The results indicate relationships
The Influence of Various Drags on Mortality of Mice and the Concentration of ...CrimsonPublishersAICS
ย
The Influence of Various Drags on Mortality of Mice and the Concentration of Proinflammatory Cytokines in Blood at Sepsis Caused by E. Coli by Zabrodskii PF* in Advancements in Case Studies
This document discusses proteomics research for biomarkers of endometriosis. It provides the following key points:
1) Proteomics studies the expressed proteins in cells/tissues and can detect protein changes that genomic methods may miss, with the goal of finding biomarkers for endometriosis diagnosis.
2) Despite many studies, no single biomarker or panel has proven accurate enough for clinical use due to the heterogeneous nature of endometrial tissue.
3) The document reviews various biological samples and mass spectrometry techniques used in proteomics research for endometriosis, including plasma, peritoneal fluid, endometrial fluid and tissue.
Data mining visualization to support biochemical markers for liver fibrosis i...Waqas Tariq
ย
The reference diagnostic test to detect fibrosis is liver biopsy (LB), a procedure subject to various limitations, including risk of patient injury and sampling error. FibroTest (FT) and ActiTest (AT) are biochemical markers (noninvasive tests) used in determining the level of fibrosis and the degree of necroinflammatory activity in the liver. The objective of this work is to discover the differences in the temporal patterns between noninvasive tests and liver biopsy by visualization tools, which made it easier to understand the relations of the complicated rules. This Study ware focused on the major serum fibrosis markers (FT/AT). The test uses a combination of serum biochemical markers with visualization technique to evaluate whether biochemical markers can be used to estimate the stage of liver fibrosis and necro-inflammatory activity in the liver.
Chemogenomic profiling involves using collections of gene deletion mutants to efficiently identify cellular targets and mechanisms of action of compounds. Homozygous profiling (HOP) and haploinsufficiency profiling (HIP) are two types of profiling that delete non-essential genes or exploit increased sensitivity, respectively. These methods have been used to identify targets of anti-fungal compounds like GGTase I and acetolactate synthase. The CRISPR-Cas9 system allows for quantification of individual mutants and was first used in a genome-wide study to identify targets of a broad-spectrum antiviral compound. Chemogenomic profiling continues to be applied across species to characterize substance interactions at the cellular level.
DOI: 10.21276/ijlssr.2016.2.3.7
ABSTRACT- The aim of the study was to determine the values of selected haematological indices in Gallus gallus
domesticus, which is naturally infected with cesode parasites. In spite of the fact that the haematological value of birds
(Gallus gallus domesticus) are of clinical significant rate than commercial importance. The total erythrocytes and
leukocyte count, haemoglobin and mean corpuscular volume were determined. There is a decrease in RBC count i.e
(Normal host- 3.98 x 106/ฮผl to infected host-2.96 x 106/ฮผl) and Hb concentration (Normal host- 10.1g/dl to infected
host-8.5g/dl). While the total WBC count was increase up to (Normal host- 86.9 x 103/ฮผl to infected host-98.2 x 103/ฮผl)
while PCV, MCH, MCV is a decrease in the infected as compare to the normal Gallus gallus domesticus. The study
deepens and organizes the knowledge within the possibilities of using and interpreting levels of haematological indicators
for monitoring health.
Key-words- Cestode parasite, Gallus gallus domesticus, Haematological parameters
Dr. Qing-Hua Wu is a lecturer at Yangtze University who received his Ph.D. in Veterinary Pharmacology and Toxicology from Huazhong Agricultural University in 2013. His research focuses on the metabolism, toxicity, and signal transduction pathways of mycotoxins such as trichothecenes. Specifically, he investigates the functional crosstalk of MAPK and JAK/STAT signaling pathways induced by trichothecenes and the regulation of cell apoptosis. He has also studied the biotransformation of T-2 toxin in various food-producing animals and the degradation of deoxynivalenol during extrusion cooking processes. Dr. Wu has published over 30
This study analyzed phenotypic virulence factors and antibiotic resistance patterns in 156 uropathogenic E. coli (UPEC) isolates from patients with urinary tract infections (UTIs). The researchers found that 85.3% of isolates produced biofilm and 34% produced hemolysin. 62.8% exhibited mannose-sensitive hemagglutination (MSHA) and 37.2% exhibited mannose-resistant hemagglutination (MRHA). Biofilm formation correlated with infection type. Resistance was highest for ampicillin, tetracycline, amoxicillin and cotrimoxazole. 26.9% of isolates were extended-spectrum beta-lactamase producers. The results indicate relationships
The Influence of Various Drags on Mortality of Mice and the Concentration of ...CrimsonPublishersAICS
ย
The Influence of Various Drags on Mortality of Mice and the Concentration of Proinflammatory Cytokines in Blood at Sepsis Caused by E. Coli by Zabrodskii PF* in Advancements in Case Studies
This document discusses proteomics research for biomarkers of endometriosis. It provides the following key points:
1) Proteomics studies the expressed proteins in cells/tissues and can detect protein changes that genomic methods may miss, with the goal of finding biomarkers for endometriosis diagnosis.
2) Despite many studies, no single biomarker or panel has proven accurate enough for clinical use due to the heterogeneous nature of endometrial tissue.
3) The document reviews various biological samples and mass spectrometry techniques used in proteomics research for endometriosis, including plasma, peritoneal fluid, endometrial fluid and tissue.
Data mining visualization to support biochemical markers for liver fibrosis i...Waqas Tariq
ย
The reference diagnostic test to detect fibrosis is liver biopsy (LB), a procedure subject to various limitations, including risk of patient injury and sampling error. FibroTest (FT) and ActiTest (AT) are biochemical markers (noninvasive tests) used in determining the level of fibrosis and the degree of necroinflammatory activity in the liver. The objective of this work is to discover the differences in the temporal patterns between noninvasive tests and liver biopsy by visualization tools, which made it easier to understand the relations of the complicated rules. This Study ware focused on the major serum fibrosis markers (FT/AT). The test uses a combination of serum biochemical markers with visualization technique to evaluate whether biochemical markers can be used to estimate the stage of liver fibrosis and necro-inflammatory activity in the liver.
Chemogenomic profiling involves using collections of gene deletion mutants to efficiently identify cellular targets and mechanisms of action of compounds. Homozygous profiling (HOP) and haploinsufficiency profiling (HIP) are two types of profiling that delete non-essential genes or exploit increased sensitivity, respectively. These methods have been used to identify targets of anti-fungal compounds like GGTase I and acetolactate synthase. The CRISPR-Cas9 system allows for quantification of individual mutants and was first used in a genome-wide study to identify targets of a broad-spectrum antiviral compound. Chemogenomic profiling continues to be applied across species to characterize substance interactions at the cellular level.
DOI: 10.21276/ijlssr.2016.2.3.7
ABSTRACT- The aim of the study was to determine the values of selected haematological indices in Gallus gallus
domesticus, which is naturally infected with cesode parasites. In spite of the fact that the haematological value of birds
(Gallus gallus domesticus) are of clinical significant rate than commercial importance. The total erythrocytes and
leukocyte count, haemoglobin and mean corpuscular volume were determined. There is a decrease in RBC count i.e
(Normal host- 3.98 x 106/ฮผl to infected host-2.96 x 106/ฮผl) and Hb concentration (Normal host- 10.1g/dl to infected
host-8.5g/dl). While the total WBC count was increase up to (Normal host- 86.9 x 103/ฮผl to infected host-98.2 x 103/ฮผl)
while PCV, MCH, MCV is a decrease in the infected as compare to the normal Gallus gallus domesticus. The study
deepens and organizes the knowledge within the possibilities of using and interpreting levels of haematological indicators
for monitoring health.
Key-words- Cestode parasite, Gallus gallus domesticus, Haematological parameters
Drug Repurposing Against Infectious Diseases Philip Bourne
ย
This document discusses challenges in drug repurposing against infectious diseases and proposes an integrated computational approach using chemical genomics and structural systems biology. It presents an algorithm called geneSAR that improves prediction of drug-target interactions. Case studies demonstrate how the approach identified selective estrogen receptor modulators as potential anti-virulence agents against Pseudomonas aeruginosa and how targets of compounds from an open access malaria box could enable drug repurposing and optimization. The integrated computational pipeline generates testable hypotheses for improving treatments of infectious diseases.
Proteomics Analysis of Three Different Strains of Mycobacterium tuberculosis...Santhi Devasundaram
ย
The study analyzed protein expression profiles of three Mycobacterium tuberculosis strains (H37Rv, S7, S10) under aerobic and hypoxic conditions using two-dimensional electrophoresis and mass spectrometry. 49 protein spots were found to be overexpressed or newly emergent under hypoxia. Two antigens (ESAT-6, Lpd) were selected and used to stimulate blood samples from healthy household contacts and active TB patients. Flow cytometry analysis showed higher levels of antigen specific memory T cells in household contacts, suggesting these antigens could be potential vaccine targets. In vitro hypoxia experiments with clinical strains help identify antigens involved in persistence.
This document reports on a case study where researchers found high mortality in mice given the pain medication ketorolac after embryo transfer surgery. Between October and December 2009, 14 out of 49 mice (29%) died 1-2 days after surgery when treated with ketorolac, compared to only 1 death out of 75 mice treated with the alternative pain medication ketoprofen in a previous period. Autopsies of the deceased ketorolac-treated mice found acute kidney damage and gastrointestinal bleeding, suggesting the postoperative toxicity of ketorolac caused the deaths. The researchers concluded ketorolac analgesia was associated with increased postoperative mortality in mice after embryo transfer surgery.
This study validated a rat pharmacokinetic/pharmacodynamic model to rapidly assess drug candidates intended to inhibit tumor necrosis factor-alpha (TNFฮฑ) synthesis or release for inflammatory diseases. Lipopolysaccharide was administered to rats to induce TNFฮฑ production, and a selective TNFฮฑ converting enzyme inhibitor was used as a model compound. The model demonstrated an ability to correlate plasma drug concentrations with inhibition of lipopolysaccharide-induced TNFฮฑ levels in vivo. Areas under the concentration-time curves were calculated for the drug and TNFฮฑ to determine the overall percentage reduction of TNFฮฑ release. This PK/PD model provides integrated information on pharmacokinetics and in vivo potency of test articles.
[Interdisciplinary Toxicology] Evaluation of miR-9 and miR-143 expression in ...mostafa khafaei
ย
The document discusses a study that evaluated the expression levels of miR-9 and miR-143 in urine samples from 32 sulfur mustard exposed patients and 32 healthy subjects. The study found that the expression levels of both miR-9 and miR-143 were significantly decreased in the sulfur mustard exposed patients compared to the healthy subjects, with p-values of 0.0480 and 0.0272, respectively. This suggests an imbalance in several pathways involved in the pathogenic effects of sulfur mustard exposure, such as NF-ฮบB signaling, TGF-ฮฒ signaling, WNT pathway, inflammation, DNA repair, and apoptosis. The decreases in miR-9 and miR-143 expression may play an important role in the pathogenicity of patients exposed to
The genomes of four tapeworm species reveal adaptations to parasitismJoรฃo Soares
ย
The genomes of four tapeworm species reveal adaptations to parasitism. The genomes range from 115 to 141 megabases and show maintenance of synteny with blood flukes but extreme losses of genes and pathways found in other animals, including 34 homeobox families and stem cell fate determinants. Tapeworms have specialized detoxification pathways, metabolism finely tuned to rely on host nutrients, and expansions of heat shock proteins and known antigen families. The genomes provide insights into tapeworm evolution and identify potential new drug targets, furthering development of urgently needed treatments.
QIVIVE extrapolation requires a precise correlation between exposure and the effective chemical concentration at the site where the MIE occurs.
This work demonstrates that intracellular distribution is not ruled only by physical-chemical parameters, rather it is mainly regulated by specific biological-mediated mechanisms. Substances with
apparent chemical similarity may show different distribution profile, as shown by the intra-nuclear distribution of polyphenols. While our results derive from a limited number of substances applied to
one cell line, it is plausible that using different substances and/or different cell lines would also have shown that intracellular distribution is not directly related to physical-chemical parameters.
Chemical uptake should be specifically measured and simple extrapolations based on physical-chemical properties may provide misleading decision
This study used mass spectrometry to validate genome annotations of nine diverse mycobacteriophages and identify their expressed proteins during infection of Mycobacterium smegmatis. Peptides matching both characterized and uncharacterized putative phage proteins were detected, validating the genome annotations. Over 100 peptides were identified for some phages, including proteins for virion structure, DNA replication, and host lysis. The study demonstrates mass spectrometry can rapidly validate phage genome annotations and identify expressed proteins, aiding characterization of phage-host interactions.
Conformation of the Human Immunoglobulin G2 Hinge Imparts Superagonistic Prop...World ADC
ย
Monoclonal antibody (mAb) drugs that stimulate antitumor immunity are transforming cancer treatment but require optimization for maximum clinical impact. Here, we show that, unlike other immunoglobulin isotypes, human IgG2 (h2) imparts FcgR-independent agonistic activity to immune-stimulatory mAbs such as anti-CD40, -4-1BB, and -CD28. Activity is provided by a subfraction of h2, h2B, that is structurally constrained due its unique arrangement of hinge region disulfide bonds. Agonistic activity can be transferred from h2 to h1 by swapping their hinge and CH1 domains, and substitution of key hinge and CH1 cysteines generates homogenous h2 variants with distinct agonistic properties. This provides the exciting opportunity to engineer clinical reagents with defined therapeutic activity regardless of FcgR expression levels in the local microenvironment.
The Joint FAO/WHO Meeting on Pesticide Residues (JMPR) re-evaluated the toxicity of glyphosate residues in food, particularly related to genotoxic and carcinogenic risks. They concluded that glyphosate is unlikely to pose a carcinogenic risk to humans through diet based on the absence of carcinogenicity in rodents at human-relevant doses and absence of genotoxicity by oral route in mammals. They found some evidence of positive association between glyphosate exposure and non-Hodgkin lymphoma in case-control studies but not in the large, high-quality Agricultural Health Study cohort. The JMPR determined glyphosate does not interact with hormone receptors and has no gen
Cytogenetic, Hematological and Enzymes Levels Parameters in the Biomonitoring...inventionjournals
ย
This study assessed the genotoxic effects of pesticide exposure on 61 agricultural workers in Piauรญ, Brazil. Workers exposed to pesticides had significantly higher numbers of micronuclei in buccal mucosa cells compared to unexposed controls, indicating cytogenetic damage. No significant increases were found for hematological or enzyme levels. Longer exposure time (10 years vs 1 year) correlated with higher micronuclei frequency, and smoking/alcohol consumption among long-term exposed workers was also associated with more micronuclei. The results suggest occupational pesticide exposure induces genetic damage detectable via the micronucleus test.
This publication list summarizes research publications from 2012 to 1999 by W.G.E.J. Schoonen and collaborators. The publications cover a range of topics including in vitro toxicity screening methods, mechanisms of toxicity, biomarker identification, and endocrine disrupting activities of compounds. Many publications involve the application of high-throughput and high-content screening assays using cell lines like HepG2, HeLa and CHO to study genotoxicity and cytotoxicity.
The document discusses alternatives to animal testing that are being used in preclinical research studies. It describes the strategy of the 3Rs - reduction, refinement, and replacement. Reduction involves using fewer animals through methods like in vitro cell cultures. Refinement means reducing pain and distress in animals, like through cage enrichment. Replacement substitutes animals with alternatives like computer models, cell/tissue cultures, and lower organisms. The goal is to minimize animal use through an integrated approach combining various alternative methods.
Molecular Detection and Therapeutic Management of Feline MycoplasmosisIOSRJAVS
ย
Mycoplasma haemofelis and Candidatus Mycoplasma haemominutum (formerly known as Haemobartonellafelis) are the causes of hemotropic mycoplasmosis in cats. The parasites attach to the surface of the red blood cell, and have the potential to cause severe alterations of the cellโs shape, resulting in anaemia. A three-year-old tom cat was presented in University Veterinary Hospital with symptoms of lethargy, reduced appetite and fever for past 3 days. Clinical examination revealed increased temperature(103ยบ โ 105ยบ F), blanched mucous membranes and lymphadenopathy. Upon peripheral blood smear examination small coccoid organisms could be noticed in the periphery of the RBCs. Hematobiochemical examination revealed anaemia, thrombocytopaenia and decreased haematocrit values. The blood samples were subjected to DNA extraction and followed by Polymerase Chain Reaction which confirmed mycoplasmosis due to Mycoplasma haemofelis. The animal was treated with intravenous administration of oxytetracycline@ 10mg/kg BW for five days along with prednisolone and vitamin supplements. Uneventful clinical recovery was noticed 7 days post therapy.
ANTICLOTTING PROPERTIES OF SRI LANKAN LOW GROWN ORTHODOX ORANGE PEKOE GRADE B...Jing Zang
ย
The document evaluates the anticlotting (blood thinning) properties of Sri Lankan low grown black tea of the Orange Pekoe grade. In vitro and in vivo experiments were conducted. The in vitro experiments found that higher concentrations of 7.5 and 10 mg/ml prevented clotting up to 24 hours. The in vivo acute experiments found a curvilinear dose response in rats, with the mid dose prolonging clotting time the most. The subchronic experiments found that all doses increased clotting time on days 8 and 16. The black tea did not alter prothrombin time. It was concluded that regular consumption of this tea may benefit cardiovascular health.
Evaluation of Analgesic Activity of Some Polyherbal Extracts against Acetic A...Jing Zang
ย
Aloe vera contains salicylic acid which is an aspirin like compound with anti-inflammatory, analgesic and anti bacterial properties. Cannabis sativa is an annual herbaceous plant in the cannabaceae family. The aim of present study was to evaluate analgesic activity of that combination extract against acetic acid induced writhing in mice. All animals were divided into four groups of six mice each. Group I was treated as toxicant control to observe writhing and group II was pretreated with diclofenac sodium (100 mg/kg, i.p.) Group III and IV were pretreated with polyherbal leaves extract of Aloe vera and Cannabis sativa at two doses 100mg/kg and 200mg/kg p.o. respectively. Polyherbal extract and Diclofenac sodium were given before 60 minute of acetic acid administration. The results showed that polyherbal extract significantly reduced number of writhing when compared with group I (Toxicant control) mice and the results were dose dependent. The toxicity study also revealed its safeness, thus the combination of plant extract can be hypothesized it is nontoxic. It is concluded that polyherbal extract can offer protection against acetic acid induced writhing in mice.
WOUND HEALING POTENTIAL OF LEAVES OF EUCALYPTUS CITRIODORALIN RATSJing Zang
ย
The aim of the study was to evaluate the effects of Eucalyptus citriodora(EAEEC)ethyl acetate and ethanol (EEEC)extracts on wound healing activity. Excision, incision and dead space wound healing activity was examined on wistar rats, dressed with 10% and 200 mg/kg p.o of the extracts respectively. Control groups were dressed with the simple ointment (negative control) and 5% povidone-iodine (standard) respectively. Healing was assessed based on contraction of wound size, mean epithelisation time, hydroxyproline content and histopathologicalexaminations. Excision wound healing study revealed significant reduction in wound size and mean epithelisation time and scar area. In incision model showed significant (p<0.01) variation in breaking strength and dead space model shows increase wet & dry weight of cotton pellet this indicate higher collagen synthesis in the 10% extract-treated group compared to the vehicle group. These findings were supported by histolopathological examinations of healed wound sections which showed greater tissue regeneration, more fibroblasts and angiogenesis in the 200 mg/kg extract-treated group. The extracts of Eucalyptus citriodorais a potential candidate for the treatment of dermal wounds by topical and oral administration. The extracts are deduced to have accelerated the wound repair at all the phases of the healing.
ANTIDIABETIC POTENTIAL OF MEMECYLON TERMINALE DALZ EXTRACTS IN ALLOXAN INDUCE...Jing Zang
ย
Memecylon terminale Dalz is an endemic plant that is exclusively present in the Western Ghat region of Southern India. The traditional healers in this region have been using this plant extract to cure disorders such as dysentery, diabetes, diarrhea, piles, haemoptysis, menorrhagia and shown to possess carminative stomachic astringent property. The present study was carried out to evaluate the hypoglycemic activity of different extracts of M. terminale Dalz in alloxan induced diabetic rats. Chloroform and methanolic extracts of M. terminale Dalz leaves were screened for hypoglycemic activity in alloxan induced diabetes in Swiss albino rats. The lipid profile was also examined in diabetic rats administered with these extracts. The efficacy of these extracts was also analyzed for their ability to inhibit ฮฑ-glucosidase and ฮฑ-amylase. Of the two extracts, chloroform extract (500 mg/kg body weight) showed dose dependent decrease in blood glucose level which was comparable to that of control after 24 h of extract administration. On the other hand, chloroform extract also showed good lipid profile that was comparable with standard drug. As compared to chloroform extract, the methanolic extract showed good inhibition of ฮฑ-amylase and ฮฑ-glucosidase enzyme activity. The results of our study indicate that M. terminale Dalz plant possesses significant protective effects against alloxan induced diabetes. However, detailed structure function analysis of active ingredients of the extract is needed to be validated.
EFFECT OF DIFFERENT CHROMATOGRAPHIC FRACTION AQUEOUS AND ALCOHOLIC EXTRACTS O...Jing Zang
ย
In recent studies Teucrium polium(T. polium ) was known as a hypoglycemic plants. But further research is needed to better understand the effect of Teucrium polium and biological active part of it. The purpose of this investigation is to examine the effect of different chromatographic fractions of aqueous and alcoholic extract of this plant on the level of insulin secretion and glucose content in hyperglycemic rat model. Also, our aim is determination of biological active fraction of aqueous and alcoholic extract of this plant. This study was carried out on the 36 rats. Hyperglycemia induced by administrating of 50 mg/kg alloxan intraperitoneally and glucose level was monitored for hyperglycemic status. Hyperglycemic was confirmed by blood glucose measurement. In each experiment 100 grams of Teucrium polium aerial parts powder were boiled with 2 Litter of distilled water for 36 h. The decoction preparation was then filtered through a gauz cloth followed by filtration through filter paper. The extract was evaporated to one-fifth of its original volume and kept at 4oC until its use. Determination of different fraction aqueous extract effect of Teucrium polium on glucose level and insulin secretion was carried out. Blood was collected from the tail of the rats. Then glucose and insulin level was evaluated. The hyperglycemic animals showed significant decrease in the blood glucose level in rats administered with fourth fraction compared with other factions. Administration of fourth fraction Teucrium polium aerial parts extract cause increase in insulin levels in alloxan-treated rats. Results suggest that treatment of fourth fraction Teucrium polium aerial parts extract may be useful in preventing the increase of glucose level in hyperglycemic rats. The interesting phenomenon of our results has shown that fourth fraction given parenterally possesses a hypoglycemic effect in alloxan hyperglycemic rats. Fourth fraction was found biological active and to be responsive to glucose challenge as evidenced by increase in insulin secretion.
Drug Repurposing Against Infectious Diseases Philip Bourne
ย
This document discusses challenges in drug repurposing against infectious diseases and proposes an integrated computational approach using chemical genomics and structural systems biology. It presents an algorithm called geneSAR that improves prediction of drug-target interactions. Case studies demonstrate how the approach identified selective estrogen receptor modulators as potential anti-virulence agents against Pseudomonas aeruginosa and how targets of compounds from an open access malaria box could enable drug repurposing and optimization. The integrated computational pipeline generates testable hypotheses for improving treatments of infectious diseases.
Proteomics Analysis of Three Different Strains of Mycobacterium tuberculosis...Santhi Devasundaram
ย
The study analyzed protein expression profiles of three Mycobacterium tuberculosis strains (H37Rv, S7, S10) under aerobic and hypoxic conditions using two-dimensional electrophoresis and mass spectrometry. 49 protein spots were found to be overexpressed or newly emergent under hypoxia. Two antigens (ESAT-6, Lpd) were selected and used to stimulate blood samples from healthy household contacts and active TB patients. Flow cytometry analysis showed higher levels of antigen specific memory T cells in household contacts, suggesting these antigens could be potential vaccine targets. In vitro hypoxia experiments with clinical strains help identify antigens involved in persistence.
This document reports on a case study where researchers found high mortality in mice given the pain medication ketorolac after embryo transfer surgery. Between October and December 2009, 14 out of 49 mice (29%) died 1-2 days after surgery when treated with ketorolac, compared to only 1 death out of 75 mice treated with the alternative pain medication ketoprofen in a previous period. Autopsies of the deceased ketorolac-treated mice found acute kidney damage and gastrointestinal bleeding, suggesting the postoperative toxicity of ketorolac caused the deaths. The researchers concluded ketorolac analgesia was associated with increased postoperative mortality in mice after embryo transfer surgery.
This study validated a rat pharmacokinetic/pharmacodynamic model to rapidly assess drug candidates intended to inhibit tumor necrosis factor-alpha (TNFฮฑ) synthesis or release for inflammatory diseases. Lipopolysaccharide was administered to rats to induce TNFฮฑ production, and a selective TNFฮฑ converting enzyme inhibitor was used as a model compound. The model demonstrated an ability to correlate plasma drug concentrations with inhibition of lipopolysaccharide-induced TNFฮฑ levels in vivo. Areas under the concentration-time curves were calculated for the drug and TNFฮฑ to determine the overall percentage reduction of TNFฮฑ release. This PK/PD model provides integrated information on pharmacokinetics and in vivo potency of test articles.
[Interdisciplinary Toxicology] Evaluation of miR-9 and miR-143 expression in ...mostafa khafaei
ย
The document discusses a study that evaluated the expression levels of miR-9 and miR-143 in urine samples from 32 sulfur mustard exposed patients and 32 healthy subjects. The study found that the expression levels of both miR-9 and miR-143 were significantly decreased in the sulfur mustard exposed patients compared to the healthy subjects, with p-values of 0.0480 and 0.0272, respectively. This suggests an imbalance in several pathways involved in the pathogenic effects of sulfur mustard exposure, such as NF-ฮบB signaling, TGF-ฮฒ signaling, WNT pathway, inflammation, DNA repair, and apoptosis. The decreases in miR-9 and miR-143 expression may play an important role in the pathogenicity of patients exposed to
The genomes of four tapeworm species reveal adaptations to parasitismJoรฃo Soares
ย
The genomes of four tapeworm species reveal adaptations to parasitism. The genomes range from 115 to 141 megabases and show maintenance of synteny with blood flukes but extreme losses of genes and pathways found in other animals, including 34 homeobox families and stem cell fate determinants. Tapeworms have specialized detoxification pathways, metabolism finely tuned to rely on host nutrients, and expansions of heat shock proteins and known antigen families. The genomes provide insights into tapeworm evolution and identify potential new drug targets, furthering development of urgently needed treatments.
QIVIVE extrapolation requires a precise correlation between exposure and the effective chemical concentration at the site where the MIE occurs.
This work demonstrates that intracellular distribution is not ruled only by physical-chemical parameters, rather it is mainly regulated by specific biological-mediated mechanisms. Substances with
apparent chemical similarity may show different distribution profile, as shown by the intra-nuclear distribution of polyphenols. While our results derive from a limited number of substances applied to
one cell line, it is plausible that using different substances and/or different cell lines would also have shown that intracellular distribution is not directly related to physical-chemical parameters.
Chemical uptake should be specifically measured and simple extrapolations based on physical-chemical properties may provide misleading decision
This study used mass spectrometry to validate genome annotations of nine diverse mycobacteriophages and identify their expressed proteins during infection of Mycobacterium smegmatis. Peptides matching both characterized and uncharacterized putative phage proteins were detected, validating the genome annotations. Over 100 peptides were identified for some phages, including proteins for virion structure, DNA replication, and host lysis. The study demonstrates mass spectrometry can rapidly validate phage genome annotations and identify expressed proteins, aiding characterization of phage-host interactions.
Conformation of the Human Immunoglobulin G2 Hinge Imparts Superagonistic Prop...World ADC
ย
Monoclonal antibody (mAb) drugs that stimulate antitumor immunity are transforming cancer treatment but require optimization for maximum clinical impact. Here, we show that, unlike other immunoglobulin isotypes, human IgG2 (h2) imparts FcgR-independent agonistic activity to immune-stimulatory mAbs such as anti-CD40, -4-1BB, and -CD28. Activity is provided by a subfraction of h2, h2B, that is structurally constrained due its unique arrangement of hinge region disulfide bonds. Agonistic activity can be transferred from h2 to h1 by swapping their hinge and CH1 domains, and substitution of key hinge and CH1 cysteines generates homogenous h2 variants with distinct agonistic properties. This provides the exciting opportunity to engineer clinical reagents with defined therapeutic activity regardless of FcgR expression levels in the local microenvironment.
The Joint FAO/WHO Meeting on Pesticide Residues (JMPR) re-evaluated the toxicity of glyphosate residues in food, particularly related to genotoxic and carcinogenic risks. They concluded that glyphosate is unlikely to pose a carcinogenic risk to humans through diet based on the absence of carcinogenicity in rodents at human-relevant doses and absence of genotoxicity by oral route in mammals. They found some evidence of positive association between glyphosate exposure and non-Hodgkin lymphoma in case-control studies but not in the large, high-quality Agricultural Health Study cohort. The JMPR determined glyphosate does not interact with hormone receptors and has no gen
Cytogenetic, Hematological and Enzymes Levels Parameters in the Biomonitoring...inventionjournals
ย
This study assessed the genotoxic effects of pesticide exposure on 61 agricultural workers in Piauรญ, Brazil. Workers exposed to pesticides had significantly higher numbers of micronuclei in buccal mucosa cells compared to unexposed controls, indicating cytogenetic damage. No significant increases were found for hematological or enzyme levels. Longer exposure time (10 years vs 1 year) correlated with higher micronuclei frequency, and smoking/alcohol consumption among long-term exposed workers was also associated with more micronuclei. The results suggest occupational pesticide exposure induces genetic damage detectable via the micronucleus test.
This publication list summarizes research publications from 2012 to 1999 by W.G.E.J. Schoonen and collaborators. The publications cover a range of topics including in vitro toxicity screening methods, mechanisms of toxicity, biomarker identification, and endocrine disrupting activities of compounds. Many publications involve the application of high-throughput and high-content screening assays using cell lines like HepG2, HeLa and CHO to study genotoxicity and cytotoxicity.
The document discusses alternatives to animal testing that are being used in preclinical research studies. It describes the strategy of the 3Rs - reduction, refinement, and replacement. Reduction involves using fewer animals through methods like in vitro cell cultures. Refinement means reducing pain and distress in animals, like through cage enrichment. Replacement substitutes animals with alternatives like computer models, cell/tissue cultures, and lower organisms. The goal is to minimize animal use through an integrated approach combining various alternative methods.
Molecular Detection and Therapeutic Management of Feline MycoplasmosisIOSRJAVS
ย
Mycoplasma haemofelis and Candidatus Mycoplasma haemominutum (formerly known as Haemobartonellafelis) are the causes of hemotropic mycoplasmosis in cats. The parasites attach to the surface of the red blood cell, and have the potential to cause severe alterations of the cellโs shape, resulting in anaemia. A three-year-old tom cat was presented in University Veterinary Hospital with symptoms of lethargy, reduced appetite and fever for past 3 days. Clinical examination revealed increased temperature(103ยบ โ 105ยบ F), blanched mucous membranes and lymphadenopathy. Upon peripheral blood smear examination small coccoid organisms could be noticed in the periphery of the RBCs. Hematobiochemical examination revealed anaemia, thrombocytopaenia and decreased haematocrit values. The blood samples were subjected to DNA extraction and followed by Polymerase Chain Reaction which confirmed mycoplasmosis due to Mycoplasma haemofelis. The animal was treated with intravenous administration of oxytetracycline@ 10mg/kg BW for five days along with prednisolone and vitamin supplements. Uneventful clinical recovery was noticed 7 days post therapy.
ANTICLOTTING PROPERTIES OF SRI LANKAN LOW GROWN ORTHODOX ORANGE PEKOE GRADE B...Jing Zang
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The document evaluates the anticlotting (blood thinning) properties of Sri Lankan low grown black tea of the Orange Pekoe grade. In vitro and in vivo experiments were conducted. The in vitro experiments found that higher concentrations of 7.5 and 10 mg/ml prevented clotting up to 24 hours. The in vivo acute experiments found a curvilinear dose response in rats, with the mid dose prolonging clotting time the most. The subchronic experiments found that all doses increased clotting time on days 8 and 16. The black tea did not alter prothrombin time. It was concluded that regular consumption of this tea may benefit cardiovascular health.
Evaluation of Analgesic Activity of Some Polyherbal Extracts against Acetic A...Jing Zang
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Aloe vera contains salicylic acid which is an aspirin like compound with anti-inflammatory, analgesic and anti bacterial properties. Cannabis sativa is an annual herbaceous plant in the cannabaceae family. The aim of present study was to evaluate analgesic activity of that combination extract against acetic acid induced writhing in mice. All animals were divided into four groups of six mice each. Group I was treated as toxicant control to observe writhing and group II was pretreated with diclofenac sodium (100 mg/kg, i.p.) Group III and IV were pretreated with polyherbal leaves extract of Aloe vera and Cannabis sativa at two doses 100mg/kg and 200mg/kg p.o. respectively. Polyherbal extract and Diclofenac sodium were given before 60 minute of acetic acid administration. The results showed that polyherbal extract significantly reduced number of writhing when compared with group I (Toxicant control) mice and the results were dose dependent. The toxicity study also revealed its safeness, thus the combination of plant extract can be hypothesized it is nontoxic. It is concluded that polyherbal extract can offer protection against acetic acid induced writhing in mice.
WOUND HEALING POTENTIAL OF LEAVES OF EUCALYPTUS CITRIODORALIN RATSJing Zang
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The aim of the study was to evaluate the effects of Eucalyptus citriodora(EAEEC)ethyl acetate and ethanol (EEEC)extracts on wound healing activity. Excision, incision and dead space wound healing activity was examined on wistar rats, dressed with 10% and 200 mg/kg p.o of the extracts respectively. Control groups were dressed with the simple ointment (negative control) and 5% povidone-iodine (standard) respectively. Healing was assessed based on contraction of wound size, mean epithelisation time, hydroxyproline content and histopathologicalexaminations. Excision wound healing study revealed significant reduction in wound size and mean epithelisation time and scar area. In incision model showed significant (p<0.01) variation in breaking strength and dead space model shows increase wet & dry weight of cotton pellet this indicate higher collagen synthesis in the 10% extract-treated group compared to the vehicle group. These findings were supported by histolopathological examinations of healed wound sections which showed greater tissue regeneration, more fibroblasts and angiogenesis in the 200 mg/kg extract-treated group. The extracts of Eucalyptus citriodorais a potential candidate for the treatment of dermal wounds by topical and oral administration. The extracts are deduced to have accelerated the wound repair at all the phases of the healing.
ANTIDIABETIC POTENTIAL OF MEMECYLON TERMINALE DALZ EXTRACTS IN ALLOXAN INDUCE...Jing Zang
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Memecylon terminale Dalz is an endemic plant that is exclusively present in the Western Ghat region of Southern India. The traditional healers in this region have been using this plant extract to cure disorders such as dysentery, diabetes, diarrhea, piles, haemoptysis, menorrhagia and shown to possess carminative stomachic astringent property. The present study was carried out to evaluate the hypoglycemic activity of different extracts of M. terminale Dalz in alloxan induced diabetic rats. Chloroform and methanolic extracts of M. terminale Dalz leaves were screened for hypoglycemic activity in alloxan induced diabetes in Swiss albino rats. The lipid profile was also examined in diabetic rats administered with these extracts. The efficacy of these extracts was also analyzed for their ability to inhibit ฮฑ-glucosidase and ฮฑ-amylase. Of the two extracts, chloroform extract (500 mg/kg body weight) showed dose dependent decrease in blood glucose level which was comparable to that of control after 24 h of extract administration. On the other hand, chloroform extract also showed good lipid profile that was comparable with standard drug. As compared to chloroform extract, the methanolic extract showed good inhibition of ฮฑ-amylase and ฮฑ-glucosidase enzyme activity. The results of our study indicate that M. terminale Dalz plant possesses significant protective effects against alloxan induced diabetes. However, detailed structure function analysis of active ingredients of the extract is needed to be validated.
EFFECT OF DIFFERENT CHROMATOGRAPHIC FRACTION AQUEOUS AND ALCOHOLIC EXTRACTS O...Jing Zang
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In recent studies Teucrium polium(T. polium ) was known as a hypoglycemic plants. But further research is needed to better understand the effect of Teucrium polium and biological active part of it. The purpose of this investigation is to examine the effect of different chromatographic fractions of aqueous and alcoholic extract of this plant on the level of insulin secretion and glucose content in hyperglycemic rat model. Also, our aim is determination of biological active fraction of aqueous and alcoholic extract of this plant. This study was carried out on the 36 rats. Hyperglycemia induced by administrating of 50 mg/kg alloxan intraperitoneally and glucose level was monitored for hyperglycemic status. Hyperglycemic was confirmed by blood glucose measurement. In each experiment 100 grams of Teucrium polium aerial parts powder were boiled with 2 Litter of distilled water for 36 h. The decoction preparation was then filtered through a gauz cloth followed by filtration through filter paper. The extract was evaporated to one-fifth of its original volume and kept at 4oC until its use. Determination of different fraction aqueous extract effect of Teucrium polium on glucose level and insulin secretion was carried out. Blood was collected from the tail of the rats. Then glucose and insulin level was evaluated. The hyperglycemic animals showed significant decrease in the blood glucose level in rats administered with fourth fraction compared with other factions. Administration of fourth fraction Teucrium polium aerial parts extract cause increase in insulin levels in alloxan-treated rats. Results suggest that treatment of fourth fraction Teucrium polium aerial parts extract may be useful in preventing the increase of glucose level in hyperglycemic rats. The interesting phenomenon of our results has shown that fourth fraction given parenterally possesses a hypoglycemic effect in alloxan hyperglycemic rats. Fourth fraction was found biological active and to be responsive to glucose challenge as evidenced by increase in insulin secretion.
INFLUENCE OF DEMOGRAPHIC FACTORS ON PAIN KILLER USAGE AND ADDICTION SYMPTOMSJing Zang
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Pain killers have been a necessity for humans since their skin has been laden with pain receptors to signal them against any invasion or unusual going on in the body.This pain when exceeds the limits of tolerance has to be alleviated to reduce suffering. Since ancient times numerous natural substances like herbs and oils have been used to relieve pain, but in modern era more refined ways to relieve pain have been discovered that exactly target the precise pain. This research identifies the factors that govern painkiller usage and addiction and the people who, in majority fall prey to pleasures of pain killers. The research was carried out through a questionnaire and results were statistically analyzed by fishers exact test. Males, employed people, non medics and graduates are most attracted to pain killers and are susceptible to long term addiction. The reasons for these people falling prey to pain killers are work load, mental stress and physiological responses to the drug. These factors can be managed through proper intervention by health professionals. The role of friends and family too here cannot be ignored.
DESIGNING OF POTENTIAL NEW AROMATASE INHIBITOR FOR ESTROGEN DEPENDENT DISEASE...Jing Zang
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Aromatase inhibitor provides the best suitable approach at present for the treatment of many estrogen dependent diseases. The estrogen dependent diseases like breast cancer and endometriosis can be treated more effectively with new third generation aromatase inhibitors. As in case of breast cancer after mastectomy (removal of breast) regression of advance breast cancer is observed and in case of endometriosis even after total hysterectomy (removal of uterus and ovary) the reoccurrence of endometriosis is observed. So estrogen deprivation remains a main key as a therapeutic approach to cure estrogen dependent diseases. The third generation aromatase inhibitors are available in the preparations like Letrozole, Anastrazole, Vorazole and some more preparations are available. Among these preparations of aromatase inhibitor Letrozole is consider to be a better therapeutic agent. As it is found that patient using Letrozole as an aromatase inhibitor are having lower plasma estrogen level as compared to another third generation aromatase inhibitor and more over calcium reabsorption in bone is also seen with Letrozole. In this study we have designed some new aromatase inhibitor and reported them as potentially new aromatase inhibitor by comparing their pharmagological properties with Letrozole and some synthesized derivatives of Letrozole (Downloaded from Zinc data base with 90% structural similarity) (http://zinc.docking.org/search/structure) by using molecular docking analysis and various free internet based Insilco tools.
Chemical composition, Antioxidant and Antibacterial activity of Thuja orientalisJing Zang
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The document summarizes a study on the chemical composition, antioxidant, and antibacterial activity of Thuja orientalis essential oil. Gas chromatography-mass spectrometry analysis identified 19 constituents making up 96.4% of the oil, with the major components being alpha-pinene (83%), sabinene (2.6%), and delta-3-carene (2.5%). The oil showed antibacterial effects against 6 bacterial strains, including both gram-positive and gram-negative, with minimum inhibitory concentration values between 12.8-25.6 mg/ml. It also exhibited antioxidant activity in DPPH free radical scavenging assays, with 49.8% scavenging at 100 ฮผg/ml concentration. Therefore
Molecular docking studies of abelmoschus esculentus for anti diabetics and a...Jing Zang
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Okra (Abelmoschus esculentus (L) Moench) or bhendi also known as ladies finger is an important vegetable crop in India, and African regions. Abelmoscus esculentus having the medicinal property of anti inflammatory , anti diabetics, anti oxidant activities . In this studies we are going to analysis the anti diabetics and anti inflammatory property of Abelmoscus esculentus by using molecular docking studies. Diabetics is a major cause of death and the number of new cases, as well as the number of individuals living with Diabetics, is expanding continuously. Now a days It is one of the most common diseases in the worldwide .Foot ulceration remains a major health problem for diabetic patients and has a major impact on the cost of diabetes treatment. One major complication of diabetes is foot ulceration, which occurs in as many as 15โ25% of type 1 and type 2 diabetic patients over their lifetimes. The phytochemicals of Abelmoscus esculentus are analysed and optimized with the Arguslab to investigate the interactions between the target compounds and the amino acid residues of the Mafa and Mmp9. All the compound have shown binding pose between from โ 3.25 to -7.95 and -7.95 into -11.40 out of ten compound . [E,E] Farenesal with Mafa protein and gossypol with Mmp9 protein show best ligand energy -10.55 and -8.88 Kcal/mol with 1 and 1 hydrogen bond of distance is 3.0 and 2.3 respectively .
Genomics and proteomics in drug discovery and developmentSuchittaU
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This document discusses the role of genomics and proteomics in drug discovery and development. It explains that genomics and proteomics technologies can help identify new drug targets by comparing gene and protein expression between healthy and diseased cells. Proteomics in particular analyzes changes in protein levels and can quantify individual proteins using techniques like 2D gel electrophoresis and mass spectrometry. The integration of genomics and proteomics provides a more comprehensive understanding of biological systems and is improving the drug discovery process.
Src jbbr-20-120 Dr. ihsan edan abdulkareem alsaimary PROFESSOR IN MEDICAL M...dr.Ihsan alsaimary
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Dr. ihsan edan abdulkareem alsaimary
PROFESSOR IN MEDICAL MICROBIOLOGY AND MOLECULAR IMMUNOLOGY
ihsanalsaimary@gmail.com
mobile : 009647801410838
university of basrah - college of medicine - basrah -IRAQ
Studies show that about 20% of all recognized clinical pregnancies end in spontaneous abortion, mainly in the first trimester. Risk factors associated with the occurrence of a sporadic miscarriage have been established, with genetic factors being the most prevalent. As a problem that affects many couples, it is important to increase the quality of prognosis and diagnosis.
Diversity of O Antigens within the Genus Cronobacter - MartinaPauline Ogrodzki
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This study analyzed the diversity of O antigens in the bacterial genus Cronobacter by testing 82 strains representing all Cronobacter species. Restriction fragment length polymorphism analysis of the O-antigen gene cluster identified 11 previously reported and 6 new serotypes. Whole genome sequencing of reference strains confirmed the new serotypes and showed some existing PCR probes did not correctly identify genomic variations. Analysis of lipopolysaccharide phenotypes also differentiated 24 total serotypes among Cronobacter strains. Certain serotypes including C. sakazakii O2, O1, and O4 and C. turicensis O1 were found to predominately cause clinical infections. This work provides an updated systematic classification of Cronobacter serotypes.
Omics technology: an important tool in mechanism studies of Chinese herbal fo...LucyPi1
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Identifying the active ingredients from natural herbal medicines and demonstrating their potential mechanisms are key points in the traditional Chinese medicine (TCM) field. In recent years, increasing studies have focused on the effects and mechanisms of Chinese herbal formulas. Basic studies on these formulas further coincide with the theory and practical use of TCM according to the clinical experiences for thousands of years. Single compounds have specific molecular structures; therefore, their methodologies in effect and mechanism studies are similar in both Western and Eastern medicines, making them more acceptable by researchers worldwide. On the contrary, the multicomponent, multitarget, and multipathway structures of Chinese formulas make it challenging to explore their mechanisms accurately where the routine method used in Western medicine studies would be inapplicable, which is the main reason for the unacceptance of Chinese herbal formulas by researchers worldwide and presents a huge obstacle to the modernization of TCM. With the rapid progress in basic TCM studies, scientific and technological innovations have achieved a breakthrough in TCM. Omic technology, a series of research methods based on high-throughput analysis and detection techniques in modern biological research system such as genomics, transcriptomics, proteomics, and metabolomics, evaluates thousands of targets and pathways rather than focusing on a single target or pathway and could screen the global changes in genes, proteins, metabolites, and other factors involved in the process of biological signaling transduction [1]. This is in agreement with the โholismโ theory in TCM, which explains the overall mechanisms of Chinese herbal formulas comprehensively. In this study, we introduced the conventionally used omic technologies and their applications in research of mechanism studies of Chinese herbal formulas.
PTPRC as a Predictive Marker Related to PD-L1 for Prognosis and Immunotherapy...semualkaira
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The expression of programmed cell death protein 1 (PD-L1) has been found to be closely related to the efficacy
of immunotherapy. The aim of our study is to explore biomarkers
associated with PD-L1 expression that might influence the efficacy
of immunotherapy.
PTPRC as a Predictive Marker Related to PD-L1 for Prognosis and Immunotherapy...semualkaira
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The expression of programmed cell death protein 1 (PD-L1) has been found to be closely related to the efficacy of immunotherapy. The aim of our study is to explore biomarkers associated with PD-L1 expression that might influence the efficacy of immunotherapy.
PTPRC as a Predictive Marker Related to PD-L1 for Prognosis and Immunotherapy...semualkaira
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The expression of programmed cell death protein 1 (PD-L1) has been found to be closely related to the efficacy of immunotherapy. The aim of our study is to explore biomarkers associated with PD-L1 expression that might influence the efficacy of immunotherapy.
Assessment of immunomolecular_expression_and_prognostic_role_of_tlr7_among_pa...dr.Ihsan alsaimary
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This document summarizes a research study that assessed the immunomolecular expression and prognostic role of Toll-like receptor 7 (TLR7) in patients with prostatitis. The study included 135 confirmed prostatitis patients and 50 control patients. DNA was extracted from blood samples and amplified using PCR to assess TLR7 expression. Results showed the PCR product for TLR7 was 149bp, indicating a high percentage of TLR7 presence. The study suggests TLR alleles may be associated with risk of prostatitis.
Conferencia de la Dra. Ana Marรญa Roa, Biรณloga Molecular, sobre Epigenรฉtica, impartida en la Universidad Popular Carmen de Michelena de Tres Cantos el 1 de marzo de 2013.
Mรกs informaciรณn en:
http://www.universidadpopularc3c.es/index.php/actividades/conferencias/event/448-conferencia-una-revision-de-los-conocimientos-fundamentales-de-la-biologia-de-la-celula-la-epigenetica
Infective endocarditis is a life-threatening disease caused by bacterial infection of the endothelium and cardiac valves, either native or prosthetic. In the present work the role of the new microbiological techniques (techniques of detection and amplification of the subunit 16 ribosomal sRNA by means of the chain reaction of the polymerase in blood or tissue, fluorescent in situ hybridization, and matrix-assisted laser is reviewed desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF MS) in the diagnosis of infective endocarditis.
Metabolomics is the study of metabolite profiles in biological samples using techniques like NMR spectroscopy and mass spectroscopy. It provides knowledge about the actual cellular state, unlike genes and proteins which only predict function. Metabolite profiling can be used for drug discovery, diagnostics, and monitoring disease states. The metabolome reflects cellular processes and responses to the environment, making it useful for understanding health and disease.
This document discusses proteomics and systems biology. It explains that systems biology analyzes relationships between elements in a biological system in response to genetic or environmental changes, with the goal of understanding the system. Proteomics aims to characterize proteins, including structure, function, interactions, and expression levels. Integrating omics data like genomics, proteomics and metabolomics can provide insights into biological processes and disease. Proteomics can also play roles in drug development by aiding biomarker discovery, target identification, and toxicity prediction.
Cytogenetic, Hematological and Enzymes Levels Parameters in the Biomonitoring...inventionjournals
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Studies have demonstrated genotoxic effects by the presence of micronucleus in exfoliated cells from the buccal mucosa of agricultural workers exposed to pesticides. This study has assessed the genotoxic effects of pesticides on 61 agricultural workers from the state of Piauรญ, Brazil. 31 individuals were exposed to pesticides and 30 are from the same area, but were not involved in pesticides application. Cytogenetic damage were evaluated through micronucleus test in cells from the buccal mucosa and some parameters such as hematological and levels of enzymes. Exposed individuals exhibited cytogenetic damage with increased number of micronuclei in cells from the buccal mucosa in comparison with subjects from the control group with significant statistical difference (P < 0.01). We perceive that there is a statistically no significant (P > 0.05) increase in levels of plasmatic and eritrocytaireacetylcholinesterase and no statistically significant increase of phosphatase alkaline were detected in exposed workers in relation to the control group. No association was found in relation to smoking habits, alcohol consumption, protection utensils and the biomarkers analyzed or the biochemical analysis. Analysis of variance revealed a correlation between occupational exposure to pesticides of workers in Piauรญ and the presence of micronuclei (P < 0.05).
Cytogenetic, Hematological and Enzymes Levels Parameters in the Biomonitoring...inventionjournals
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Studies have demonstrated genotoxic effects by the presence of micronucleus in exfoliated cells from the buccal mucosa of agricultural workers exposed to pesticides. This study has assessed the genotoxic effects of pesticides on 61 agricultural workers from the state of Piauรญ, Brazil. 31 individuals were exposed to pesticides and 30 are from the same area, but were not involved in pesticides application. Cytogenetic damage were evaluated through micronucleus test in cells from the buccal mucosa and some parameters such as hematological and levels of enzymes. Exposed individuals exhibited cytogenetic damage with increased number of micronuclei in cells from the buccal mucosa in comparison with subjects from the control group with significant statistical difference (P < 0.01). We perceive that there is a statistically no significant (P > 0.05) increase in levels of plasmatic and eritrocytaireacetylcholinesterase and no statistically significant increase of phosphatase alkaline were detected in exposed workers in relation to the control group. No association was found in relation to smoking habits, alcohol consumption, protection utensils and the biomarkers analyzed or the biochemical analysis. Analysis of variance revealed a correlation between occupational exposure to pesticides of workers in Piauรญ and the presence of micronuclei (P < 0.05).
Microbiological tests detect microorganisms or the host immune response to infection. They can identify infectious agents, provide information to guide antimicrobial therapy, and assess drug susceptibility. Test results must be interpreted carefully based on factors like specimen type, test characteristics, clinical findings, and communication between clinician and microbiologist. A variety of methods are used, including microscopy, culture, antigen and antibody detection, and nucleic acid amplification tests.
This document provides an overview of pathogenomics and discusses several key areas:
1. It defines pathogenomics and describes how it utilizes genomics data to study infectious diseases.
2. Functional genomics and comparative genomics are applied to reveal pathogenesis genes and develop drugs, diagnostics and vaccines.
3. Identification of virulence factors in fungi and bacteria is discussed through direct sequence annotation and genome analysis.
4. Challenges include antibiotic resistance and potential misuse of information, while future trends involve in vivo expression analysis and reducing drug resistance.
Advances in cell biology: contribution to drug modern designEsayas Ayele
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This document discusses how advances in cell biology have contributed to modern drug design. It outlines how understanding cell structures and functions through areas like proteomics, genomics, and studies of proteins, membranes, and nucleic acids has provided insights for identifying new drug targets. Characterizing proteins of interest like G protein-coupled receptors and enzymes has allowed designing drugs that interact with specific targets linked to various diseases.
Target validation of the inosine monophosphate dehydrogenase (IMPDH) gene in ...Therese Horn
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This document summarizes research using a yeast-two hybrid system and Phylomer peptide library to identify peptides that interact with and potentially inhibit the inosine monophosphate dehydrogenase (IMPDH) enzyme in Cryptosporidium. IMPDH is a potential drug target as Cryptosporidium relies solely on purine salvage and IMPDH is essential for DNA synthesis. A Phylomer peptide library was screened against IMPDH from C. parvum and C. hominis, identifying 38 unique interacting peptides. 12 peptides were synthesized and 2 showed significant growth inhibition of C. parvum in vitro. One peptide consistently interacted with C. parvum and C. hominis IMPDH but not human
Similar to PUTATIVE DRUG TARGET IDENTIFICATION FOR SEPTIC ARTHRITIS THROUGH DATA MINING APPROACH (20)
Molecular docking studies of gloriosa superba for anti cancer and anti tuberc...Jing Zang
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Gloriosa superba is a medicinal plant generally found in western parts of Tamilnadu and kerala in India. Gloriosa superba having the medicinal property of anticancer, antibacterial, antifungal, anti Tuberculosis and mutagenic activities. In this studies we are going to analysis the anti cancer and anti tuberculosis property of Gloriosa superba by using molecular docking studies. Cancer is a major cause of death and the number of new cases, as well as the number of individuals living with cancer, is expanding continuously. Cervical cancer is one of the most common cancers among women worldwide . Tuberculosis is a common and often deadly infectious disease caused by mycobacteria , usually Mycobacterium tuberculosis in humans. Tuberculosis usually attacks the lungs but can also affect other parts of the body. The phytochemicals of Gloriosa superba are analysed and optimized with the Arguslab to investigate the interactions between the target compounds and the amino acid residues of the E7 and DAHP. All the compound have shown binding pose between from โ 3.25 to -7.95 and -7.95 into -11.40 out of ten compound .Chrysophanic acid with E7 protein and Colchicine with DAHP protein show best ligand energy -9.52049 and -7.47679Kcal/mol with 1 and 3 hydrogen bond of distance is 2.3 and 2.2,2.9 and 3.2 respectively .
A systemic review on antibiotic use evaluation in paediatricsJing Zang
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Drug utilization is the marketing, distribution, prescription, and use of drug in a society, with special emphasis on the resulting medical, social and economic consequences. Antibiotics are valuable discoveries of modern medicine and their definitive and or appropriate use has led to a decline in the morbidity and mortality associated with various infectious diseaseswhile inappropriate use of antibiotics can increase morbidity, mortality, patient cost and bacterial antibiotic resistance.Antimicrobial agents are among the most commonly prescribed drug in Paediatrics. Because of an overall rise in health care costs, lack of uniformity in drug prescribing and the emergence of antibiotic resistance, monitoring and control of antibiotic use are of growing concern and strict antibiotic policies should be warranted. The caution use for antimicrobial agents is very important as their unavailability or resistance can be life threatening. Irrational drug use is a common practice in developing countries. In India, clinician often prescribe three or four drugs to treat the most trivial conditions for the sake of satisfying the patients need to receive drugs or the drug sellers need for profit. Thus drug use evaluation studies are required for all drugs in general and particularly for antibiotics.
A review on medicinal properties of Camel milkJing Zang
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Many research findings proved that Camel milk is closer to human milk than any other milk. It is often easily digested by lactose-intolerant individuals. It is rich in healthy vitamins and minerals, especially B vitamins, vitamin C and iron. The lactoferrin in camel milk has antibacterial, antiviral and anti-tumor properties. It contains disease-fighting immunoglobulins which are small in size, allowing penetration of antigens and boosting the effectiveness of the immune system. It is a rich source of insulin and also it containing approximately 52 units of insulin in each liter of camel milk, making it a great treatment option for Type 1 or Type 2 diabetics as well as Gestational Diabetes. This review focused on the medicinal properties of camel milk which will be more useful to generate value added products formation from camel milk.
Formulation and Evaluation of Solid dispersion for Dissolution Enhancement of...Jing Zang
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The document summarizes research on developing solid dispersions of the poorly water soluble drug nifedipine to enhance its dissolution rate. Solid dispersions of nifedipine were prepared using different polymers (sodium starch glycollate, croscarmellose sodium, eudragit E-100) at various weight ratios using solvent evaporation. The best formulation with croscarmellose sodium at a 1:7 ratio showed over 70% increased dissolution compared to nifedipine API. This formulation was further adsorbed onto neusilin US2 to form a ternary mixture, which showed over 30% higher dissolution than the marketed product. Tablets prepared from the ternary mixture were stable
Glucose lowering potential of hydromethanolic extract of RauwolfiaJing Zang
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The objective of the present study was to evaluate the phytochemistry, acute toxicity and glucose lowering potential of hydromethanolic roots extract (HMREt) of Rauwolfia serpentina. The qualitative analysis of HMREt showed the presence of many important phyto-constituents except anthraquinones, carbohydrates and saponins whereas quantitatively it found rich in total phenols. In acute toxicity study, orally administrated HMREt from 5-250 mg/ kg was observed safe and non-sedative while its doses from 500-2500 mg/kg were found sedative and induced mortalities (17-100%) within 4 hours of administration. The median lethal dose (LD50) of same extract was calculated as 1412.54 mg / kg (log LD50 = 3.15 mg/ kg) from log doses verses probit graph. The HMREt in doses of 50, 100 and 150 mg/kg induced significant percent decrease in blood glucose level at 30, 60 and 120 minutes in normo-hyperglycemic test mice as compared to control and negative control groups (p<0.05). The results concluded that HMREt has glucose lowering potential either by developing glucose tolerance or by pancreatic action in normo-hyperglycemic mice.
Nutritive and Anti-nutritive composition of Wild grown Canavalia gladiata seedsJing Zang
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The wild Canavalia gladiata seeds were widely distributed in Nupeland, North Central Nigeria. It was obtained and processed by decoating, sun drying and grinding into powder. Using petroleum ether (40-60oC), the fats was extracted, the protein content, ash content, crude fibre, moisture, carbohydrate with respective values of 3.60ยฑ0.14, 11.1ยฑ0.83, 4.25ยฑ0.11, 3.39ยฑ0.27, 5.85ยฑ0.47 and 72.3ยฑ0.08 % as well as the mineral contents were determined using standard methods. The mineral composition determined from the C. gladiata seeds shows higher values of potassium, zinc, iron and calcium 25.15ยฑ0.03, 25.89ยฑ0.27, 18.3ยฑ0.14 and 17.25ยฑ0.49 mg/100 g respectively. This seed analyzed contains low yield of anti-nutritional contents which suggested that, it could be safe for human consumption since it fell below the lethal dose limit. The sample contains reasonable amount of essential and non-essential amino acids with yield varying between 48 and 52%. The presence of unsaturated and saturated fatty acids in the C. gladiata was 96 and 4% respectively. The higher percentage of unsaturated fatty acid present makes this seed desirable for consumption by the person with heart diseases. In addition, from the data obtained this oil becomes attractive options for commercial purposes since it is suitable for the manufacture of soaps, lubricating oil, candles as well as pharmaceutical industries.
Pharmacovigilance in South Africa: Undocumented undergraduate training and pr...Jing Zang
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Pharmacovigilance is a clinical discipline that is gaining more and more attention worldwide and in Africa. The rolling out of large scale programs on HIV/AIDS, tuberculosis and malaria has heightened the need to step up efforts to have pharmacovigilance concepts to be operationalized in clinical practice. A quick search in PubMed and Google Scholar and a review of available literature was conducted in order to establish whether medical, nursing and pharmacy undergraduate students are taught pharmacovigilance concepts and skills for effective practice. It seems that there is a paucity of data on the undergraduate training in pharmacovigilance in South Africa. It may be that there might be inadequate training on pharmacovigilance during undergraduate training of medical, nursing and pharmacy students in South Africa. More studies are needed to document the views and experiences of South African students and healthcare professionals on training and practice of pharmacovigilance.
Black Seed (Nigella sativa) Possess Bioactive Compounds Act as Anti-Helicobac...Jing Zang
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This document reviews the anti-Helicobacter pylori properties of black seed (Nigella sativa). It summarizes research showing that N. sativa contains bioactive compounds that exhibit antimicrobial activity against H. pylori, the primary cause of gastric ulcers. Specifically, thymoquinone, the most abundant constituent of N. sativa essential oil, has demonstrated anti-H. pylori effects. Studies have found N. sativa extracts inhibit the growth of H. pylori in vitro and are effective in eradicating H. pylori infections in human patients. The review concludes that N. sativa possesses therapeutic properties that can help protect against gastric damage caused by H. py
This document describes the development and validation of a new spectrofluorimetric method for the estimation of desvenlafaxine succinate in bulk and pharmaceutical formulations. Key points:
1) The method utilizes the native fluorescence of desvenlafaxine succinate with an excitation wavelength of 274 nm and emission wavelength of 305 nm in pH 6 phosphate buffer.
2) The method was found to be linear over a concentration range of 100-900 ng/ml. Validation studies established the method's accuracy, precision, selectivity, robustness and ruggedness according to ICH guidelines.
3) The developed method was successfully applied to the analysis of desvenlafaxine succinate in commercial extended-
This study evaluated the anti-osteoporotic effects of Bonton Active Granules in an ovariectomized rat model of postmenopausal osteoporosis. Rats were divided into four groups: a normal control group, an ovariectomized disease control group, and two ovariectomized groups treated with different doses of Bonton Active Granules. Treatment with Bonton Active Granules significantly decreased serum alkaline phosphatase levels and increased serum calcium levels compared to the disease control group, indicating reduced bone resorption. It also improved femoral bone parameters, bone breaking strength, and bone histopathology in a dose-dependent manner. The results suggest that Bonton Active Granules has anti
This document describes the development and validation of a spectrophotometric method for the determination of the antiepileptic drug rufinamide in bulk and pharmaceutical formulations. Rufinamide forms a colored complex with the dye bromocresol green under acidic conditions that can be extracted with chloroform and measured spectrophotometrically. The method was optimized and validated according to ICH guidelines, demonstrating good linearity, precision, accuracy, and sensitivity for quantifying rufinamide concentrations between 10-50 ฮผg/mL. The method was successfully applied to analyze rufinamide levels in commercial tablet formulations, indicating it is suitable for the routine analysis of this drug in quality control testing.
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In vitro enzyme inhibition studies on new sulfonamide derivatives of 4-tosyl ...Jing Zang
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Sulfonamides are considered to be pharmaceutically important class of compounds. In the present work, N-(2,4-dimethylphenyl)-4-toluenesulfonamide (3) was synthesized by the reaction of 2,4-dimethylaniline (1) and 4-tosyl chloride (2; 4-methylbenzenesulfonyl chloride) using 10% aqueous Na2CO3 solution as reaction medium. At the second step, the synthesized molecule 3 was made to react with different alkyl/aralkyl halides (4a-o) to yield the target compounds, 5a-o, using N,N-dimethylformamide (DMF) as reaction medium and lithium hydride as an activator. The synthesis of all the compounds was verified by spectral techniques using IR, 1H-NMR and EIMS; and further examined for their anti-enzymatic activities. The synthesized compound 5f represented a suitable inhibitory potential against ฮฑ-glucosidase and lipoxygenase enzymes.
This document describes the development and validation of a quantitative method for determining penbutolol and its metabolite 4-hydroxy penbutolol in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method involves solid phase extraction of the analytes from plasma followed by separation using liquid chromatography with mass spectrometric detection in multiple reaction monitoring mode. The method was validated according to FDA guidelines and showed good linearity, accuracy, precision, recovery, selectivity and stability. The developed and validated LC-MS/MS method was found to be suitable for pharmacokinetic studies of penbutolol in human volunteers.
In vitro sun screening activity of Sri Lankan orthodox black tea (Camellia Si...Jing Zang
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Currently, there is demand for the development of herbal sunscreen formulations to suppress harmful effects of UV rays. In this regard, this study, was conducted to investigate the sun screen potential of Sri Lankan Orthodox black tea (made from buds and top most leaves of Camellia sinensis L plant) using three grades (Dust No:1, Broken Orange Pekoe and Orange Pekoe) using UV spectroscopic technique and Mansur equation. Sun Protection Factor (SPF) value was determined using 20% aqueous extracts (Black tea brews). The results revealed that all three tea samples had markedly high absorbance values (1.4 to 4.2) at 290-320 nm range and SPF values above 15 which are considered as the threshold value for good sunscreen. The SPF value of Dust No:1, B.O.P.F and O.P were respectively 36, 23 and 22. This is a novel finding for Sri Lankan black tea. It is concluded that Sri Lankan black tea, especially, Dust No: 1 can function as an efficient sunscreen agent and has great promise to be developed as cheap, safe and effective topical botanical sunscreen acting via multiple mechanisms (considering its other reported bioactivities).
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Influence of host plants on the carotenoid profile of Loranthus longiflorus leaf and bark samples collected from Casuarina equisetifolia and Ficus religiosa host trees were determined by HPTLC method. The methanol extract of L. longiflorus leaf samples obtained from C. equisetifolia host trees showed 9 compounds while it was 8 compounds in the leaf samples collected from F. religiosa host tree. Among the compounds, 5 and 3 compound in each sample, respectively, was identified as carotinoids while the others were unknown. Four compounds from each leaf samples collected from C. equisetifolia (peak no. 4- 6 & 8) and F. religiosa (peak no. 1-3 & 6) host trees showed similar Rf values (0.15, 0.19, 0.23 & 0.53, respectively). Similarly, the methanol extract of L. longiflorus bark sample collected from C. equisetifolia and F. religiosa host trees contained 8 compounds each. Of these compounds only 3 from each sample was identified as carotenoids whereas others were unknown and none of these compounds showed any similar Rf values. One compound from leaf and park samples of L. longiflorus collected from C. equisetifolia (peak no. 6 & 4) and F. religiosa (peak no. 4 & 3) showed similar Rf values (0.23 & 0.26), respectively.
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Migraine is the most common problem affecting large population, with prevalence frequency 10-12 %. This study was conducted to evaluate the prevalence of migraine in a low income community in Karachi from June-Oct, 2013. Three hundred and seven participants were involved in this study. For this purpose cross-sectional community based questionnaire was designed in accordance with the diagnostic criteria given by International Headache Society. Data collection was carried out by personal visit to patients and through clinics. It was observed that females (65.5%) are more affected from migraine then male. 32.9% housewives reported that they are suffering from migraine. This medical problem is common among youngsters (38.1%) than old citizens. Employees working in different organizations (39.7%), were found to be mostly affected from migraine then self employed persons. Majority of the migraine patients (41%) reported that they are suffering from common symptoms including: photophobia, phonophobia, nausea, vomiting etc. Dietary habits of individuals were found to be closely associated with migraine such as use of caffeine, chocolate are prominent; and their use is common among 75% patients cumulatively. It was evaluated that certain disease conditions i.e. stress (33.6%), depression (22.1%) and anxiety (18.9%) are more common among sufferers of migraine.
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1. The document evaluates the roots of Hedychium coronarium J. Koening for antiurolithiatic (anti-kidney stone forming) activity.
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(๐๐๐ ๐๐๐) (๐๐๐ฌ๐ฌ๐จ๐ง ๐)-๐๐ซ๐๐ฅ๐ข๐ฆ๐ฌ
๐๐ข๐ฌ๐๐ฎ๐ฌ๐ฌ ๐ญ๐ก๐ ๐๐๐ ๐๐ฎ๐ซ๐ซ๐ข๐๐ฎ๐ฅ๐ฎ๐ฆ ๐ข๐ง ๐ญ๐ก๐ ๐๐ก๐ข๐ฅ๐ข๐ฉ๐ฉ๐ข๐ง๐๐ฌ:
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๐๐ฑ๐ฉ๐ฅ๐๐ข๐ง ๐ญ๐ก๐ ๐๐๐ญ๐ฎ๐ซ๐ ๐๐ง๐ ๐๐๐จ๐ฉ๐ ๐จ๐ ๐๐ง ๐๐ง๐ญ๐ซ๐๐ฉ๐ซ๐๐ง๐๐ฎ๐ซ:
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PUTATIVE DRUG TARGET IDENTIFICATION FOR SEPTIC ARTHRITIS THROUGH DATA MINING APPROACH
1. World Journal of Pharmaceutical Sciences
ISSN (Print): 2321-3310; ISSN (Online): 2321-3086
Published by Atom and Cell Publishers ยฉ All Rights Reserved
Available online at: http://www.wjpsonline.com/
Research Article
PUTATIVE DRUG TARGET IDENTIFICATION FOR SEPTIC ARTHRITIS
THROUGH DATA MINING APPROACH
Anup Tripathi, Sachidanand Singh, Atul Kumar*
Department of Bioinformatics, School of Biotechnology and Health Sciences, Karunya
University, Karunya Nagar, Coimbatore, Tamil Nadu, India
Received: 10-10-2013 / Revised: 15-11-2013 / Accepted: 30-11-2013
ABSTRACT
Septic arthritis is the purulent invasion of a joint by an infectious agent which produces arthritis. The main
organisms having great potential to infect human beings as well as other mammals are Staphylococcus aureus,
Streptococcus pneumoniaeand Streptococcus pyrogens. In Silico comparative analysis ofall the pathways of host
Homo sapiens and pathogens was performed by using KEGG and Protein BLAST. 25, 20 and 16 unique
pathways were identified for Staphylococcus aureus, Streptococcus pyrogensand Streptococcus pneumonia
respectively. Out of these we identified 3 enzymes for Staphylococcus aureus, 4 for Streptococcus pneumoniae
and 1 for Streptococcus pyrogens, which are non-homologous to Homo sapiens proteins. The enzymes essential
for survival of the pathogens were found out by DEG database. Further CELLO analysis results showed that
50% enzymes are found to be Extracellular, 25% to be cytoplasmic and 25% to be membranous for
Staphylococcus aureus. For Streptococcus pneumoniae, 50% enzymes are found to be Extracellular, 12%
cytoplasmic, 13% membranous and 25% as cell wall proteins. 100% enzymes were found to be membranous for
Streptococcus pyrogens. Finally the enzymes from DEG were submitted in Drug Bank database to identify
approve drug targets. This Data Mining approach found that mostly the enzymes which can act as targets belong
to extracellular level in Staphylococcus aureus, Streptococcus pneumoniae and membranous in Streptococcus
pyrogens. This findings gives an understanding of these enzymes interaction with human protein protein
interaction at extracellular and membrane level.
Keywords: Septic arthritis, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyrogens,
essential enzymes, KEGG, DEG, PLSPred, CELLO and Drug Bank
INTRODUCTION
Septic arthritis is a serious disease in which an
inflammatory reaction in a joint is caused by an
infection. This disease requires emergency surgical
intervention because it can cause irreversible and
irreparable joint lesions and life threatening
conditions in children and adults [1]. Most septic
joints develop as a result of hematogenous seeding
of the vascular synovial membrane due to a
bacteremic episode [2, 3]. The most common
infectious agents are Staphylococcus aureus [4],
Niesseriagonorrhea [5], Streptococcus pneumonia
[3], Streptococcus pyrogens [6] and haemophilus
influenza [7]. Microorganisms may invade the joint
via direct inoculation, contiguous spread from
infected
periarticular
tissues,
or
the
bloodstream.The major consequence of bacterial
invasion is hyperaemia and oedema of the synovial
membranes; the overproduced synovial fluid
contains polymorphonuclear leukocytes, which can
damage articular cartilage by releasing proteolytic
enzymes [8]. The direct introduction of bacteria
during joint surgery has increasingly been a source
of bacterial arthritis, particularly in association with
knee and hip arthroplasties.
In silico subtractive genomics approaches, based on
the strategy that an essential survival gene nonhomologous to any human host gene is a candidate
drug target for a given pathogen, [9, 10] have been
used to identify putative drug targets in
Staphylococcus aureus, Streptococcus pneumoniae
and Streptococcus pyrogens. In the present study, a
similar data mining approach has been carried out
to screen these organismโs genome and proteome in
*Corresponding Author Address: Mr. Atul Kumar, Department of Bioinformatics, School of Biotechnology and Health Sciences, Karunya
University, Karunya Nagar, Coimbatore, Tamil Nadu, India, E-mail ID: atul.0298@gmail.com
2. Atul et al., World J Pharm Sci 2014; 2(1): 25-31
order to identify its essential genes and subsequent
drug and vaccine targets from various metabolic
pathways.
CELLO [14] and PSLpred [15]. Surface membrane
proteins were selected for putative candidate
vaccine targets.
MATERIALS AND METHODS
RESULTS AND DISCUSSION
Identification of potential drug targets: For
metabolic pathway identification KEGG [11]
(Kyoto Encyclopedia of Genes and Genome)
(http://www.genome.jp/kegg/) was used. The
metabolic pathway identification numbers of the
host
Homosapiens
and
the
pathogens
Staphylococcus
aureus,
Streptococcus
pneumoniaeand Streptococcus pyrogens were
extracted from the KEGG database (Table 1).
According to KEGG database annotation, the
pathways which do not appear in host
Homosapiens but are present in above pathogens
have been identified as pathways unique to
pathogens in comparison to the host. Enzymes
present in these unique pathways as well as the
enzymes involved in several metabolic pathways
like
Carbohydrate
Metabolism,
Energy
Metabolism, Lipid Metabolism, Nucleotide
Metabolism, Amino Acid Metabolism, Glycan
Biosynthesis and Metabolism and Metabolism of
Cofactors and Vitamins were also identified from
KEGG database. The protein sequences
corresponding to the unique pathways were
retrieved from the KEGG database and a BLASTp
[12] search against the non-redundant database of
these protein sequences were performed. In this
search the e-value inclusion threshold was set to
0.005 and the search was restricted to proteins from
Homo sapiens by excluding Homo sapiens in
BLASTp. This helps in finding only those targets
which do not have detectable human homologues.
Thus potential drug targets are obtained by
selecting those enzymes which do not have hits
below e-value threshold of 0.005 in BLASTp
result.
From KEGG server all the pathways associated
with S.aureus,Streptococcus pneumoniae and
Streptococcus pyrogens were analyzed and each
enzyme of these pathways were compared with the
proteins of the host Homo sapiens with the help of
BLASTp search against the non-redundant
database restricted to Homosapiens. To remove the
homologous sequences from the BLASTp search
the e-value inclusion threshold was set as 0.005.
From KEGG, 15 strains and 25 unique pathways
were identified for Staphylococcus aureus.
Similarly for Streptococcus pyrogens 12 strains and
20 unique pathways and for Streptococcus
pneumonia 14 strains and 16 unique pathways were
identified. Finally by performing BLASTp search a
total of 3 enzymes for Staphylococcus aureus, 4 for
Streptococcus pneumoniae and 1 for Streptococcus
pyrogens, which are non-homologous to Homo
sapiens protein sequences were identified (Table
2). Inhibitors can be designed against these
sequences in order to find better drugs.
Dispensable or non-essential enzymes or pathways
are not considered to be a good drug target. Thus a
DEG server analysis of all the 8 enzymes identified
from KEGG server is necessary. To enhance the
specificity of these enzymes in various pathogens
the cutoff score was set to be > 100.From DEG, a
total of 37 essential enzymes were found out and
no essential enzymes were detected for SecE (SPY
2058), Sfb1 (SPT 1057) and Sfb1 (SNC 0837)
(Table 3).
These enzymes are finally considered as potential
drug targets. The subcellular localization analysis
of all these enzymes was also performed by two
tools: CELLO (http://cello.life.nctu.edu.tw/) and
PLSpred(http://www.imtech.res.in/raghava/pslpred/
). From the CELLO analysis (Figure 1), 50%
enzymes are found to be Extracellular, 25% to be
cytoplasmic and 25% to be membranous for
Staphylococcus
aureus.
For
Streptococcus
pneumoniae 50% enzymes are found to be
Extracellular, 12% cytoplasmic, 13% membranous
and 25% as cell wall proteins. 100% enzymes were
found to be membranous for Streptococcus
pyrogens. And the PLSPred analysis (Figure 2)
showed that for Staphylococcus aureus 33%
enzymes are cytoplasmic, 33% enzymes are Periplasmic and 34% enzymes are Extracellular. For
Streptococcus pneumonia, both the Extracellular
and Peri-plasmic enzymes were found to be 50%
Finding the essential targets: Essential genes are
the genes which are indispensable for the survival
of an organism and their functions are the
foundation of life. The non-homologous enzymes
obtained from the pBLAST result were subjected to
DEG database [13] (http://tubic.tju.edu.cn/deg/) for
analyzing the essentiality of these enzymes to
pathogens.
Finding the biological significance of the targets:
The non-homologous essential genes which do not
show any similarity with any human sequence were
considered as putative drug targets. The function
and the cellular localization of each protein of
identified targets were analyzed with Swiss-Prot
protein database (http://us.expasy.org/sprot) and by
using sub-cellular localization prediction tools:
26
3. Atul et al., World J Pharm Sci 2014; 2(1): 25-31
each. 100% enzymes were found to be Innermembranous for Streptococcus pyrogens.
The analysis of the essential enzymes of DEG
database result against the drug bank database [16]
was done and about 7 approved drug targets were
identified. The results are shown in Table 4.
aureus infection, Bacterial secretion system and
Bacterial invasion of epithelial cells respectively.
From these pathways non-detectable human
homologous enzymes were identified as TSST-1
(SA 1819), SCIN (SA 0221), SCIN (SA 1004) for
Staphylococcus aureus; SecE (SPY 2058) for
Stretococcuspyrogens and Sfb1 (SPJ 0350), Sfb1
(SPCG 0360), Sfb1 (SPT 1057), Sfb1 (SNC 0837)
for Streptococcus pneumonia. These nonhomologous enzymes showed 37 essential genes
through DEG database, which confirmed that these
enzymes wonโt perform their activity without the
presence of essential genes. The subcellular
localization of these enzymes was also found out
with the help of CELLO and PLSPred. These
enzymes were submitted in Drug Bank database
against approve drug targets, which showed their
relevance in septic arthritis. This approach gives us
an insight to find putative target enzymes which
play an important role in causing septic arthritis.
CONCLUSION
Septic arthritis is a serious problem worldwide and
and can be life threatening with lethal development
of sepsis, meningitis and other diseases, especially
caused by Staphylococcus aureus, Stretococcus
pneumonia and Streptococcus pyrogens. For the
identification and analysis of the essential genes of
these pathogens responsible for Septic arthritis,
data mining approach was used. The unique
pathways
for
Staphylococcus
aureus,
Stretococcuspyrogensand
Streptococcus
pneumoniawere identified as Staphylococcus
Table 1: DIFFERENT STRAINS AND UNIQUE PATHWAYS OF PATHOGENS IDENTIFIED FROM
KEGG
Organisms
Staphylococcus
aureus
Strains
Staphylococcus aureus N315
Staphylococcus aureus Mu50
Staphylococcus aureus Mu3
Staphylococcus aureus JH1
Staphylococcus aureus JH9
Staphylococcus aureus MW2
Staphylococcus aureus MSSA476
Staphylococcus aureus MRSA252
Staphylococcus aureus COL
Staphylococcus aureus
USA300_TCH1516
Staphylococcus aureus
USA300_FPR3757
Staphylococcus aureus NCTC8325
Staphylococcus aureus Newman
Staphylococcus aureus ED98
Staphylococcus aureus RF122
Streptococcus
pyrogens
Streptococcus pyogenes SF370
Streptococcus pyogenes MGAS5005
27
Unique Pathways
00660 C5-Branched dibasic acid metabolism
00680 Methane metabolism
00473 D-Alanine metabolism
00550 Peptidoglycan biosynthesis
00906 Carotenoid biosynthesis
00903 Limonene and pinene degradation
00281 Geraniol degradation
00312 beta-Lactam resistance
00521 Streptomycin biosynthesis
00401 Novobiocin biosynthesis
00362 Benzoate degradation
00627 Aminobenzoate degradation
00625 Chloroalkane and chloroalkene
degradation
00642 Ethylbenzene degradation
00621 Dioxin degradation
00626 Naphthalene degradation
00624 Polycyclic aromatic hydrocarbon
degradation
05150 Staphylococcus aureus infection
05100 Bacterial invasion of epithelial cells
00440 Phosphonate and phosphinate
metabolism
00363 Bisphenol degradation
00623 Toluene degradation
00361 Chlorocyclohexane and chlorobenzene
degradation
00791 Atrazine degradation
00121 Secondary bile acid biosynthesis
00680 Methane metabolism
00473 D-Alanine metabolism
5. Atul et al., World J Pharm Sci 2014; 2(1): 25-31
Table 3: ESSENTIAL ENZYMES OF PATHOGENS IDENTIFIED FROM DEG
Non homologous enzymes
from KEGG
Gene name
Function Class
Description
toxic shock syndrome toxin-1
Essential
enzymes from
DEG
DEG10020122
Smc
DNA packaging and segregation
Chromosome segregation
SMC protein
toxic shock syndrome toxin-1
DEG10020178
Alas
Protein synthesis
Alanyl-tRNAsynthetase
toxic shock syndrome toxin-1
DEG10020173
dnaK
Molecular chaperone
toxic shock syndrome toxin-1
toxic shock syndrome toxin-1
DEG10020268
DEG10020103
rplN
mutS2
toxic shock syndrome toxin-1
DEG10020024
guaA
toxic shock syndrome toxin-1
DEG10170336
toxic shock syndrome toxin-1
DEG10170214
SAOUHSC_0
2571
dnaK
Post-translational modification,
protein turnover, chaperones
Protein synthesis
DNA replication/modification and
repair
Nucleotide transport and
metabolism
Function unknown
toxic shock syndrome toxin-1
DEG10170324
rplN
Ribosomal proteins
Secretary antigen
precursor
Molecular chaperone
DnaK
50S ribosomal protein L14
toxic shock syndrome toxin-1
DEG10170020
guaA
Purine biosynthesis
GMP synthase
toxic shock syndrome toxin-1
DEG10170223
alaS
tRNAsynthetase
Alanyl-tRNAsynthetase
staphylococcal complement
inhibitor SA0221
staphylococcal complement
inhibitor SA0221
staphylococcal complement
inhibitor SA0221
staphylococcal complement
inhibitor SA0221
staphylococcal complement
inhibitor SA0221
staphylococcal complement
inhibitor SA0221
staphylococcal complement
inhibitor SA0221
DEG10020145
SA1147
Function unknown
Hypothetical protein
DEG10020122
Smc
DNA packaging and segregation
DEG10020195
polA
DEG10020297
SA2442
DNA replication, recombination,
and repair
Protein secretion
Chromosome segregation
SMC protein
DNA polymerase I
DEG10020039
lysS
Protein synthesis
PreproteintranslocaseSec
A homolog
Lysyl-tRNAsynthetase
DEG10020025
SA0422
Function unknown
Hypothetical protein
DEG10170190
SAOUHSC_0
1473
Lipids
BirAbifunctional
protein
staphylococcal complement
inhibitor SA0221
DEG10170159
SAOUHSC_0
1237
Peptidoglycan biosynthesis
Undecaprenyl
pyrophosphate synthase
staphylococcal complement
inhibitor SA0221
staphylococcal complement
inhibitor SA0221
DEG10170035
lysS
tRNAsynthetase
Lysyl-tRNAsynthetase
DEG10170278
SAOUHSC_0
2123
DNA replication
ATP-dependent DNA
helicase PcrA
staphylococcal complement
inhibitor SA1004
staphylococcal complement
inhibitor SA1004
staphylococcal complement
inhibitor SA1004
DEG10020038
ftsH
Cell division
Cell-division protein
DEG10020195
polA
DNA polymerase I
DEG10020207
ccpA
staphylococcal complement
inhibitor SA1004
staphylococcal complement
inhibitor SA1004
staphylococcal complement
inhibitor SA1004
staphylococcal complement
inhibitor SA1004
staphylococcal complement
inhibitor SA1004
staphylococcal complement
inhibitor SA1004
staphylococcal complement
inhibitor SA1004
DEG10020066
uvrB
DEG10020174
lepA
DEG10020151
glcT
DNA replication, recombination,
and repair (L)
Inorganic ion transport and
metabolism (P)/Signal
transduction (T)
DNA replication, recombination,
and repair (L)
General function prediction only
(R)
transcription antiterminator
DEG10020030
SA0447
Similar to unknown proteins
DEG10020197
pfk/pfkA
DEG10020132
tsf
Metabolism of carbohydrates and
related molecules
Protein synthesis
DEG10170129
SAOUHSC_0
1148
29
Protein folding
Cell division
50S ribosomal protein L14
MutS-like protein
GMP synthase
Catabolite control protein
A
Exonuclease ABC subunit
B
GTP-binding protein
Transcription
antiterminator
Conserved hypothetical
protein
6-phosphofructokinase
Homolog elongation
factor TS
Cell division
protein
6. Atul et al., World J Pharm Sci 2014; 2(1): 25-31
DEG10170157
pyrH
Pyrimidine biosynthesis
Uridylate kinase
DEG10170229
SAOUHSC_0
1739
Peptidoglycan biosynthesis
Hypothetical
staphylococcal complement
inhibitor SA1004
DEG10170253
SAOUHSC_0
1807
Glycolysis
6-phosphofructokinase
fibronectin-binding protein 1
SPJ 0350
DEG10070096
SP_1737
-
fibronectin-binding protein 1
SPCG 0360
DEG10070096
SP_1737
-
fibronectin-binding protein 1
SPCG 0360
DEG10070127
sulC/folE
Coenzyme metabolism
staphylococcal complement
inhibitor SA1004
staphylococcal complement
inhibitor SA1004
protein
DNA-directed RNA
polymerase, omega
subunit, putative
DNA-directed RNA
polymerase, omega
subunit, putative
GTP cyclohydrolase
Table 4: APPROVED DRUG TARGET IDENTIFICATION BY THE DRUG BANK SERVER
Target Enzyme
Target Drug
Drug Bank ID Target
toxic shock syndrome toxin-1
Phenobarbital
DB01174
GABA receptor subunit
alpha 1
staphylococcal complement inhibitor
Lincomycin
DB01627
50 S ribosomal protein L 10
preproteintranslocase subunit SecE
Lincomycin
DB01627
50 S ribosomal protein L 10
(Secretory System)
preproteintranslocase subunit SecE
Vancomycin
DB00512
DNA
(Secretory System)
preproteintranslocase subunit SecE
Clarithromycin
DB01211
GlycosyltransferaseGtfA
(Secretory System)
fibronectin-binding protein 1
Cefditoren
DB01066
Penecillin binding proteins
fibronectin-binding protein 1
Lincomycin
DB01627
50 S ribosomal protein L 10
(A)
(B)
(C)
Figure 1: Pie diagram showing subcellular localization of enzymes of Staphylococcus aureus(A),
Streptococcus pneumoniae(B), Streptococcus pyrogens(C)by CELLO
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7. Atul et al., World J Pharm Sci 2014; 2(1): 25-31
(A)
(B)
(C)
Figure 2: Pie diagram showing subcellular localization of enzymes of Staphylococcus aureus(A),
Streptococcus pneumoniae(B), Streptococcus pyrogens(C)by PLSPred
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