Recent advances in antitumour berberine
This document summarizes recent research on berberine and its derivatives for their antitumour properties. Berberine is an alkaloid extracted from plants that has been used in traditional Chinese and Ayurvedic medicine. Recent studies show berberine has anti-microbial, anti-inflammatory, and anticancer effects. Chemical modifications of berberine's structure have led to derivatives with improved DNA interaction and antitumour activity against various cancer cell lines, including mesothelioma and HER2-positive breast cancer. Several derivatives demonstrated antitumour effects in mouse models of cancer through oral or intraperitoneal administration. Ongoing research continues to elucidate the mechanisms
This document summarizes recent advances in the anticancer properties of berberine. Berberine is an alkaloid extracted from plants that has been used in traditional Chinese and Ayurvedic medicines. It has diverse pharmacological activities including antimicrobial, anti-inflammatory, and anticancer effects. Berberine shows anticancer activity against various cancer types in vitro and in vivo. Ongoing clinical trials are investigating berberine's effects on cancer as well as other diseases. Chemical modifications of berberine have produced derivatives with improved binding to DNA and anticancer activity. In particular, NAX035 has shown efficacy against mesothelioma in vitro and in vivo models at well-tolerated doses.
This document summarizes research on berberine derivatives with antiproliferative activity. Berberine is an alkaloid extracted from plants that has been used in traditional Chinese and Ayurvedic medicine. The researchers synthesized novel berberine derivatives with aromatic groups in the 13 position of the alkaloid skeleton. These derivatives showed improved binding to DNA and greater antiproliferative effects against cancer cell lines compared to berberine. Certain derivatives displayed promising activity against mesothelioma and liver cancer cell lines that warrants further preclinical development studies. The results support berberine's role in inhibiting cancer cell proliferation and its potential as a lead compound for anticancer drug discovery when modified with aromatic groups.
Synthesis, antiviral and cytotoxicity activities of N-Sulphonamidomethyl benz...SriramNagarajan15
A series of novel N-sulphonamido methyl benztriazole derivatives had been synthesized by combining benztriazole, formaldehyde and sulphonamides. Structure of synthesized compounds was elucidated by spectral analysis. Synthesized compounds were evaluated for in-vitro antiviral activity against HIV, HSV and Vaccinia viruses in cell culture. N-Sulphonamido methyl benzotriazole (BT-SN) inhibits Herpes Simplex Virus (HSV) -2 and Vaccinia virus at 34 µg/ml, respectively. HSV-1 at the concentration of 45 µg/ml. The minimum cytotoxic concentration was found to be more than 100µg/ml. So these compounds are suitable for designing newer derivatives and molecular modifications in them may help in optimizing antiviral activity.
Synthesis, antiviral and cytotoxicity activities of N-Sulphonamidomethyl benz...pharmaindexing
This document summarizes research on the synthesis and testing of novel N-sulphonamido methyl benztriazole derivatives for antiviral activity. A series of these derivatives were synthesized by combining benztriazole, formaldehyde, and sulphonamides. One compound, N-sulphonamido methyl benzotriazole (BT-SN), was found to inhibit Herpes Simplex Virus (HSV)-2 and Vaccinia virus at 34 μg/ml and HSV-1 at 45 μg/ml. All compounds had minimum cytotoxic concentrations over 100μg/ml. While devoid of anti-HIV activity, BT-SN showed the most toxicity. These compounds demonstrate potential as antiviral agents if
Synthesis, Anti-HIV activity and Cytotoxicity of N-Substituted Phthalimide de...pharmaindexing
A series of novel N-substituted phthalimide derivatives were synthesized by reacting phthalic anhydride with primary aromatic amines. The chemical structures of the synthesized compounds were characterized using spectral analysis. The compounds were screened for antiviral activity against HIV-1 and HIV-2 in MT-4 cells and were found to exhibit cytotoxicity with CC50 values ranging from 84-125 μg/ml. None of the compounds showed significant anti-HIV activity.
1) Berberine is a natural compound extracted from plants that has shown anti-microbial, anti-inflammatory, and anti-cancer properties. Recent research has focused on developing berberine derivatives with antitumor activity.
2) A chemical program was developed to synthesize berberine derivatives through alkylation, esterification, and condensation reactions. These derivatives were studied for their DNA binding abilities and antiproliferative effects on cancer cell lines.
3) Certain berberine derivatives showed stronger binding to DNA and greater antiproliferative activity than berberine itself. Specifically, compounds NAX035 and NAX038 reduced levels of thymidylate synthase and HER2 proteins
Exploring the Mycobactericidal potential of vitamin C rich fruits TARUNSAROCH
Mycobacterium tuberculosis, the infective agent of tuberculosis(TB) Causes one of the world’s most devastating global health crisis
The treatment of drug-susceptible TB lasts more than six-months and require the use of drugs to achieve a cure, whereas for XDR treatment lasts for more than1 year
The two most effective first- line TB drugs for drug susceptible TB are isoniazid (INH) and rifampicin(RIF), which has to be taken for six months.
The long treatment period is of major concern as it leads to the development of the drug resistant TB.
The study found that anti-tuberculosis drugs killed more bacteria in laboratory when the mice received vitamin C.
Assimilation Of Phosphite By A. Stolonifera L. And Its In Vitro Effect On Mic...JJDempsey
Abstract on the research into the assimilation and accumulation of phosphite in A. stolonifera and the in vitro effect phosphite has on the mycelial growth of M. nivale
This document summarizes recent advances in the anticancer properties of berberine. Berberine is an alkaloid extracted from plants that has been used in traditional Chinese and Ayurvedic medicines. It has diverse pharmacological activities including antimicrobial, anti-inflammatory, and anticancer effects. Berberine shows anticancer activity against various cancer types in vitro and in vivo. Ongoing clinical trials are investigating berberine's effects on cancer as well as other diseases. Chemical modifications of berberine have produced derivatives with improved binding to DNA and anticancer activity. In particular, NAX035 has shown efficacy against mesothelioma in vitro and in vivo models at well-tolerated doses.
This document summarizes research on berberine derivatives with antiproliferative activity. Berberine is an alkaloid extracted from plants that has been used in traditional Chinese and Ayurvedic medicine. The researchers synthesized novel berberine derivatives with aromatic groups in the 13 position of the alkaloid skeleton. These derivatives showed improved binding to DNA and greater antiproliferative effects against cancer cell lines compared to berberine. Certain derivatives displayed promising activity against mesothelioma and liver cancer cell lines that warrants further preclinical development studies. The results support berberine's role in inhibiting cancer cell proliferation and its potential as a lead compound for anticancer drug discovery when modified with aromatic groups.
Synthesis, antiviral and cytotoxicity activities of N-Sulphonamidomethyl benz...SriramNagarajan15
A series of novel N-sulphonamido methyl benztriazole derivatives had been synthesized by combining benztriazole, formaldehyde and sulphonamides. Structure of synthesized compounds was elucidated by spectral analysis. Synthesized compounds were evaluated for in-vitro antiviral activity against HIV, HSV and Vaccinia viruses in cell culture. N-Sulphonamido methyl benzotriazole (BT-SN) inhibits Herpes Simplex Virus (HSV) -2 and Vaccinia virus at 34 µg/ml, respectively. HSV-1 at the concentration of 45 µg/ml. The minimum cytotoxic concentration was found to be more than 100µg/ml. So these compounds are suitable for designing newer derivatives and molecular modifications in them may help in optimizing antiviral activity.
Synthesis, antiviral and cytotoxicity activities of N-Sulphonamidomethyl benz...pharmaindexing
This document summarizes research on the synthesis and testing of novel N-sulphonamido methyl benztriazole derivatives for antiviral activity. A series of these derivatives were synthesized by combining benztriazole, formaldehyde, and sulphonamides. One compound, N-sulphonamido methyl benzotriazole (BT-SN), was found to inhibit Herpes Simplex Virus (HSV)-2 and Vaccinia virus at 34 μg/ml and HSV-1 at 45 μg/ml. All compounds had minimum cytotoxic concentrations over 100μg/ml. While devoid of anti-HIV activity, BT-SN showed the most toxicity. These compounds demonstrate potential as antiviral agents if
Synthesis, Anti-HIV activity and Cytotoxicity of N-Substituted Phthalimide de...pharmaindexing
A series of novel N-substituted phthalimide derivatives were synthesized by reacting phthalic anhydride with primary aromatic amines. The chemical structures of the synthesized compounds were characterized using spectral analysis. The compounds were screened for antiviral activity against HIV-1 and HIV-2 in MT-4 cells and were found to exhibit cytotoxicity with CC50 values ranging from 84-125 μg/ml. None of the compounds showed significant anti-HIV activity.
1) Berberine is a natural compound extracted from plants that has shown anti-microbial, anti-inflammatory, and anti-cancer properties. Recent research has focused on developing berberine derivatives with antitumor activity.
2) A chemical program was developed to synthesize berberine derivatives through alkylation, esterification, and condensation reactions. These derivatives were studied for their DNA binding abilities and antiproliferative effects on cancer cell lines.
3) Certain berberine derivatives showed stronger binding to DNA and greater antiproliferative activity than berberine itself. Specifically, compounds NAX035 and NAX038 reduced levels of thymidylate synthase and HER2 proteins
Exploring the Mycobactericidal potential of vitamin C rich fruits TARUNSAROCH
Mycobacterium tuberculosis, the infective agent of tuberculosis(TB) Causes one of the world’s most devastating global health crisis
The treatment of drug-susceptible TB lasts more than six-months and require the use of drugs to achieve a cure, whereas for XDR treatment lasts for more than1 year
The two most effective first- line TB drugs for drug susceptible TB are isoniazid (INH) and rifampicin(RIF), which has to be taken for six months.
The long treatment period is of major concern as it leads to the development of the drug resistant TB.
The study found that anti-tuberculosis drugs killed more bacteria in laboratory when the mice received vitamin C.
Assimilation Of Phosphite By A. Stolonifera L. And Its In Vitro Effect On Mic...JJDempsey
Abstract on the research into the assimilation and accumulation of phosphite in A. stolonifera and the in vitro effect phosphite has on the mycelial growth of M. nivale
Susceptibility profiles of Enterobacteriaceae to temocillin, piperacillin-taz...Erin Vaughan
This study aimed to verify the use of temocillin, faropenem, and piperacillin/tazobactam disc testing to detect carbapenemase-producing Enterobacteriaceae (CPE) using 208 bacterial isolates with known or unknown resistance mechanisms. The study confirmed that high resistance to these agents correlated with CPE isolates. Combining cut-offs for the three agents achieved 92.2% sensitivity and 98.3% specificity for CPE detection. This supports using these antimicrobial agents as surrogate markers in routine diagnostic laboratories to help identify and treat CPE infections.
The document discusses research into identifying potential ganglioside-binding proteins in Borrelia burgdorferi that causes Lyme disease. Bioinformatics analysis identified VlsE1 as a top hit that is known to be involved in late-stage Lyme disease. VlsE1 was cloned and expressed, and expression studies showed that 0.1 mM IPTG produced the best yield of soluble VlsE1. While some VlsE1 remained insoluble, work is ongoing to optimize expression and purification conditions to study the potential function of VlsE1 in binding gangliosides.
Emergence of ndm1 resistance assessment of colistin sparing antibiotic combin...Meher Rizvi
This presentation details the emergence of pan drug resistance, the pipeline of antimicrobials is running dry and which colistin sparing protocols to use.
Abstract— To understand the responses of various soybean (Glycine max) cultivars to ultraviolet-B, Dongnong 42, Zhonghuang 57 and Jin 36 were cultured either under UV-B radiation (10.08 kJ / m-2 UV-B) or without UV-B for 25 days. Under UV-B irradiation, significant difference were observed in plant height, nodes length, contents of soluble sugar, proline, protein, flavionoids, GSH, ASA, relative content of anthocyanins, also the emzymes activities of APX ,SOD and GR. The lowest plant height was presented in Jin 36, followed Zhonghuang 57 and Dongnong 42. The node length of plant decreased from the first node to the fourth one, and the maximal reduction was observed in Jin 36. Contents of protein, flavionoids, GSH, ASA and anthocyanins as well as emzyme activities of APX, SOD and GR significantly increased under UV-B irradiation where content of protein and activities of emzyme APX, SOD and GR were higher in Zhonghuang 57 than those in Dongnong 42 and Jin 36; higher GSH, ASA, flavonoids, as well as the anthocyanins were showed in Donghong 42. Increased proline content was observed in the three cultivars upon UV-B (p<0.05)>Dongnong 42 > Jin36; for the soluble sugar content, the order was Zhongnong 57>Jin 36>Dongnong 42 (p<0.05). Various soybean cultivars showed varied physiological responses upon UV-B.
Strain development techniques of industrially important microorganismsMicrobiology
Strain improvement and development involves manipulating microbial strains to enhance their metabolic capacities for biotechnology applications. Targets of improvement include rapid growth, genetic stability, non-toxicity, large cell size, ability to use cheaper substrates, increased productivity, and reduced cultivation costs. Methods for optimization include modifying environmental conditions, nutrition, mutagenesis, transduction, conjugation, transformation, and genetic engineering. Common industrial microorganisms are bacteria such as Bacillus subtilis and yeasts such as Saccharomyces cerevisiae.
Combination antibiotic therapy can provide benefits over monotherapy in some situations. Combining antibiotics may result in synergistic effects against certain pathogens like MDROs or additive effects. It may help prevent resistance. However, combinations can also lead to antagonism or increased side effects. Appropriate combinations depend on the infection and organism. De-escalation of antibiotics is important for improving outcomes and reducing resistance. It involves narrowing therapy based on culture results and clinical response. Regular review and stopping antibiotics when no longer needed are key aspects of de-escalation.
Mutagenesis; A conventional tool for strain improvement in industry Zohaib HUSSAIN
The strain improvement is the process of improvement and manipulation of microbial strains for the icreasment of metabolic level for industrial applications. The yield of microbial enzymes can be increased by using microbe specific medium for fermentation, improving the fermentation process and strain improvement for higher yield of product.
All these things lead to decrease in cost production. Microbe produce product according to its need therefore there is great need for overproduction. There is tremendous contribution of conventional Mutagenesis for strain improvement. Mutagenesis is important tool for the production of mutants which are capable to produce large product i.e. hyperactive.
Recent advances in antisense drugs like morpholino oligonucleotides have broadened their therapeutic potential. Morpholinos can specifically block gene expression through steric blocking of translation or splicing. They are currently under clinical investigation for genetic disorders, viral infections, and cancers. Key challenges include improving delivery into tissues and reducing potential toxicity at high doses for clinical use.
Antibiotic strategy in nosocomial pneumoniaGamal Agmy
This document discusses antibiotic strategy in nosocomial pneumonia. It begins by outlining the main mechanisms of action for antimicrobial drugs, including inhibition of cell wall synthesis, protein synthesis, nucleic acid synthesis, metabolic pathways, and interference with cell membrane integrity. It then discusses the effects of drug combinations, noting that synergism can occur when two drugs together have greater effects than individually. The document also provides definitions and classifications for nosocomial pneumonias like HAP, VAP, and HCAP. It discusses diagnostic criteria and challenges, as well as risk factors for different pathogen types. Finally, it addresses considerations for empiric therapy, favoring initial monotherapy for early HAP but recommending combination therapy for late-onset and
Science and technology of manipulating and improving microbial strains, in order to enhance their metabolic capacities for biotechnological applications, are referred to as strain improvement.
PREDICTION OF ANTIMICROBIAL PEPTIDES USING MACHINE LEARNING METHODSBilal Nizami
Increasing resistance toward the conventional antibiotics has become a global concern. Antimicrobial peptides (AMPs) are potential alternatives for conventional antibiotics. Due to cost related reasons in designing and synthesis of AMPs. Machine learning based prediction tools are indispensable.
This document describes various tests used to evaluate analgesic agents and their mechanisms of action, including the hot plate test, tail clip method, and writhing test using mice. It also discusses the carrageenan-induced rat paw edema test and use of the Ehrlich ascites carcinoma model to study cancer cells. Parameters observed in developmental toxicity, fertility, and teratogenicity tests are outlined. Finally, the mechanisms and methods of genetic toxicology tests like the Ames test and mechanisms of mutation are summarized.
Ppt.strain improvement by ghalia nawalGhalia Nawal
Microbial strain improvement involves enhancing the biosynthetic capabilities of microbes to produce desired products in higher quantities. It can be achieved through various approaches like mutagenesis, genetic recombination, and cloning/genetic engineering. Mutagenesis uses chemical or physical agents to induce mutations in microbes. Genetic recombination combines DNA from two strains to generate superior hybrids. Cloning and genetic engineering allow assembling new DNA combinations to create novel microbes. Precision engineering evaluates relationships between growth, substrate use, and production to optimize industrial microbe performance. Strain improvement has various biotechnological applications such as producing medicines and improving microbe productivity and characteristics.
This document describes the development of an assay to detect anti-PEG antibodies using BioScale's Acoustic Membrane MicroParticle (AMMP) technology. The assay uses paramagnetic beads coated with biotinylated PEG to capture anti-PEG antibodies from serum samples. The bead-antibody complexes are then captured on an acoustic membrane coated with Protein A. Changes in mass on the membrane produce a signal proportional to the amount of anti-PEG antibodies present. Preliminary results suggest the assay can detect IgG anti-PEG antibodies at concentrations below 1000 ng/mL, which is more sensitive than other published methods. The AMMP technology provides a generic platform to detect antibodies against a variety of PEG molecules by modifying
Phytochemicals are considered as natural bio-active compounds with extraordinary bio-activities like free radical scavenging, enhancing mitochondrial integrity. preventing severe inflammation, regulating apoptosis and inhibiting toxic protein aggregations. This presentation deals with how phytochemicals are promoting brain health against various molecular assaults and wide range of diseases and disorders.
This document discusses antimicrobial chemotherapy and provides details about various chemotherapeutic agents. It begins by defining chemotherapeutic agents as chemical substances used to treat or prevent infectious diseases. There are three main types of agents - antibiotics, which are natural products; semi-synthetic antibiotics that are modified natural products; and synthetic drugs. The document then provides examples and details of mechanisms and clinical uses of several antibacterial, antiviral, antifungal and other antimicrobial agents. It also discusses ideal characteristics of chemotherapeutic agents and methods for determining antimicrobial susceptibility, including minimum inhibitory concentration.
This document discusses bioassay development for drug discovery. It covers in vitro and cell-based bioassays, as well as the molecular biology techniques used to develop these assays such as cloning DNA into plasmids, propagating plasmids in bacteria, purifying plasmid DNA, sequencing DNA, and expressing proteins in bacteria and mammalian cells through techniques like transfection. Recombinant protein expression and purification using affinity tags is also summarized.
Voss et al. - 2006 - Identification of potent anticancer activity in XiCristina Voss
An aqueous extract from Ximenia americana, a plant used in African traditional medicine, showed potent anticancer activity against various human and rat cancer cell lines. The extract was cytotoxic with IC50 values ranging from 1.7 to 170 mg/ml. In vivo, the extract significantly reduced tumor burden in a rat model of colorectal cancer when administered either orally or intraperitoneally. Phytochemical analysis identified the active compounds as proteins that bind galactose, with one protein containing an amino acid sequence identical to a peptide from the toxic ribosome-inactivating protein ricin. This suggests the extract's anticancer mechanism differs from common chemotherapeutics.
This document discusses various genetic recombination techniques, including protoplast fusion, transformation, transduction, conjugation, and genetic engineering methods. It provides details on how each technique is performed, such as using polyethylene glycol or electric shocks to fuse protoplasts, adding calcium chloride to allow DNA uptake during bacterial transformation, and using restriction enzymes and ligases in genetic engineering to cut and join DNA fragments. The overall document serves to explain the key methods for combining genetic material from different organisms or cells.
1) The document discusses recent advances in using berberine derivatives as antitumor agents. Berberine is an alkaloid extracted from plants that has been used in traditional medicines for centuries.
2) It describes how berberine and novel derivatives it were synthesized can target thymidylate synthase, a key enzyme for cancer treatment, by modulating its protein expression and interrupting abnormal production in cancer cells. This represents an innovative mechanism of action over current drugs.
3) In vitro studies showed several berberine derivatives significantly reduced thymidylate synthase protein levels and activity in human ovarian cancer cell lines, demonstrating their potential as antitumor compounds.
Susceptibility profiles of Enterobacteriaceae to temocillin, piperacillin-taz...Erin Vaughan
This study aimed to verify the use of temocillin, faropenem, and piperacillin/tazobactam disc testing to detect carbapenemase-producing Enterobacteriaceae (CPE) using 208 bacterial isolates with known or unknown resistance mechanisms. The study confirmed that high resistance to these agents correlated with CPE isolates. Combining cut-offs for the three agents achieved 92.2% sensitivity and 98.3% specificity for CPE detection. This supports using these antimicrobial agents as surrogate markers in routine diagnostic laboratories to help identify and treat CPE infections.
The document discusses research into identifying potential ganglioside-binding proteins in Borrelia burgdorferi that causes Lyme disease. Bioinformatics analysis identified VlsE1 as a top hit that is known to be involved in late-stage Lyme disease. VlsE1 was cloned and expressed, and expression studies showed that 0.1 mM IPTG produced the best yield of soluble VlsE1. While some VlsE1 remained insoluble, work is ongoing to optimize expression and purification conditions to study the potential function of VlsE1 in binding gangliosides.
Emergence of ndm1 resistance assessment of colistin sparing antibiotic combin...Meher Rizvi
This presentation details the emergence of pan drug resistance, the pipeline of antimicrobials is running dry and which colistin sparing protocols to use.
Abstract— To understand the responses of various soybean (Glycine max) cultivars to ultraviolet-B, Dongnong 42, Zhonghuang 57 and Jin 36 were cultured either under UV-B radiation (10.08 kJ / m-2 UV-B) or without UV-B for 25 days. Under UV-B irradiation, significant difference were observed in plant height, nodes length, contents of soluble sugar, proline, protein, flavionoids, GSH, ASA, relative content of anthocyanins, also the emzymes activities of APX ,SOD and GR. The lowest plant height was presented in Jin 36, followed Zhonghuang 57 and Dongnong 42. The node length of plant decreased from the first node to the fourth one, and the maximal reduction was observed in Jin 36. Contents of protein, flavionoids, GSH, ASA and anthocyanins as well as emzyme activities of APX, SOD and GR significantly increased under UV-B irradiation where content of protein and activities of emzyme APX, SOD and GR were higher in Zhonghuang 57 than those in Dongnong 42 and Jin 36; higher GSH, ASA, flavonoids, as well as the anthocyanins were showed in Donghong 42. Increased proline content was observed in the three cultivars upon UV-B (p<0.05)>Dongnong 42 > Jin36; for the soluble sugar content, the order was Zhongnong 57>Jin 36>Dongnong 42 (p<0.05). Various soybean cultivars showed varied physiological responses upon UV-B.
Strain development techniques of industrially important microorganismsMicrobiology
Strain improvement and development involves manipulating microbial strains to enhance their metabolic capacities for biotechnology applications. Targets of improvement include rapid growth, genetic stability, non-toxicity, large cell size, ability to use cheaper substrates, increased productivity, and reduced cultivation costs. Methods for optimization include modifying environmental conditions, nutrition, mutagenesis, transduction, conjugation, transformation, and genetic engineering. Common industrial microorganisms are bacteria such as Bacillus subtilis and yeasts such as Saccharomyces cerevisiae.
Combination antibiotic therapy can provide benefits over monotherapy in some situations. Combining antibiotics may result in synergistic effects against certain pathogens like MDROs or additive effects. It may help prevent resistance. However, combinations can also lead to antagonism or increased side effects. Appropriate combinations depend on the infection and organism. De-escalation of antibiotics is important for improving outcomes and reducing resistance. It involves narrowing therapy based on culture results and clinical response. Regular review and stopping antibiotics when no longer needed are key aspects of de-escalation.
Mutagenesis; A conventional tool for strain improvement in industry Zohaib HUSSAIN
The strain improvement is the process of improvement and manipulation of microbial strains for the icreasment of metabolic level for industrial applications. The yield of microbial enzymes can be increased by using microbe specific medium for fermentation, improving the fermentation process and strain improvement for higher yield of product.
All these things lead to decrease in cost production. Microbe produce product according to its need therefore there is great need for overproduction. There is tremendous contribution of conventional Mutagenesis for strain improvement. Mutagenesis is important tool for the production of mutants which are capable to produce large product i.e. hyperactive.
Recent advances in antisense drugs like morpholino oligonucleotides have broadened their therapeutic potential. Morpholinos can specifically block gene expression through steric blocking of translation or splicing. They are currently under clinical investigation for genetic disorders, viral infections, and cancers. Key challenges include improving delivery into tissues and reducing potential toxicity at high doses for clinical use.
Antibiotic strategy in nosocomial pneumoniaGamal Agmy
This document discusses antibiotic strategy in nosocomial pneumonia. It begins by outlining the main mechanisms of action for antimicrobial drugs, including inhibition of cell wall synthesis, protein synthesis, nucleic acid synthesis, metabolic pathways, and interference with cell membrane integrity. It then discusses the effects of drug combinations, noting that synergism can occur when two drugs together have greater effects than individually. The document also provides definitions and classifications for nosocomial pneumonias like HAP, VAP, and HCAP. It discusses diagnostic criteria and challenges, as well as risk factors for different pathogen types. Finally, it addresses considerations for empiric therapy, favoring initial monotherapy for early HAP but recommending combination therapy for late-onset and
Science and technology of manipulating and improving microbial strains, in order to enhance their metabolic capacities for biotechnological applications, are referred to as strain improvement.
PREDICTION OF ANTIMICROBIAL PEPTIDES USING MACHINE LEARNING METHODSBilal Nizami
Increasing resistance toward the conventional antibiotics has become a global concern. Antimicrobial peptides (AMPs) are potential alternatives for conventional antibiotics. Due to cost related reasons in designing and synthesis of AMPs. Machine learning based prediction tools are indispensable.
This document describes various tests used to evaluate analgesic agents and their mechanisms of action, including the hot plate test, tail clip method, and writhing test using mice. It also discusses the carrageenan-induced rat paw edema test and use of the Ehrlich ascites carcinoma model to study cancer cells. Parameters observed in developmental toxicity, fertility, and teratogenicity tests are outlined. Finally, the mechanisms and methods of genetic toxicology tests like the Ames test and mechanisms of mutation are summarized.
Ppt.strain improvement by ghalia nawalGhalia Nawal
Microbial strain improvement involves enhancing the biosynthetic capabilities of microbes to produce desired products in higher quantities. It can be achieved through various approaches like mutagenesis, genetic recombination, and cloning/genetic engineering. Mutagenesis uses chemical or physical agents to induce mutations in microbes. Genetic recombination combines DNA from two strains to generate superior hybrids. Cloning and genetic engineering allow assembling new DNA combinations to create novel microbes. Precision engineering evaluates relationships between growth, substrate use, and production to optimize industrial microbe performance. Strain improvement has various biotechnological applications such as producing medicines and improving microbe productivity and characteristics.
This document describes the development of an assay to detect anti-PEG antibodies using BioScale's Acoustic Membrane MicroParticle (AMMP) technology. The assay uses paramagnetic beads coated with biotinylated PEG to capture anti-PEG antibodies from serum samples. The bead-antibody complexes are then captured on an acoustic membrane coated with Protein A. Changes in mass on the membrane produce a signal proportional to the amount of anti-PEG antibodies present. Preliminary results suggest the assay can detect IgG anti-PEG antibodies at concentrations below 1000 ng/mL, which is more sensitive than other published methods. The AMMP technology provides a generic platform to detect antibodies against a variety of PEG molecules by modifying
Phytochemicals are considered as natural bio-active compounds with extraordinary bio-activities like free radical scavenging, enhancing mitochondrial integrity. preventing severe inflammation, regulating apoptosis and inhibiting toxic protein aggregations. This presentation deals with how phytochemicals are promoting brain health against various molecular assaults and wide range of diseases and disorders.
This document discusses antimicrobial chemotherapy and provides details about various chemotherapeutic agents. It begins by defining chemotherapeutic agents as chemical substances used to treat or prevent infectious diseases. There are three main types of agents - antibiotics, which are natural products; semi-synthetic antibiotics that are modified natural products; and synthetic drugs. The document then provides examples and details of mechanisms and clinical uses of several antibacterial, antiviral, antifungal and other antimicrobial agents. It also discusses ideal characteristics of chemotherapeutic agents and methods for determining antimicrobial susceptibility, including minimum inhibitory concentration.
This document discusses bioassay development for drug discovery. It covers in vitro and cell-based bioassays, as well as the molecular biology techniques used to develop these assays such as cloning DNA into plasmids, propagating plasmids in bacteria, purifying plasmid DNA, sequencing DNA, and expressing proteins in bacteria and mammalian cells through techniques like transfection. Recombinant protein expression and purification using affinity tags is also summarized.
Voss et al. - 2006 - Identification of potent anticancer activity in XiCristina Voss
An aqueous extract from Ximenia americana, a plant used in African traditional medicine, showed potent anticancer activity against various human and rat cancer cell lines. The extract was cytotoxic with IC50 values ranging from 1.7 to 170 mg/ml. In vivo, the extract significantly reduced tumor burden in a rat model of colorectal cancer when administered either orally or intraperitoneally. Phytochemical analysis identified the active compounds as proteins that bind galactose, with one protein containing an amino acid sequence identical to a peptide from the toxic ribosome-inactivating protein ricin. This suggests the extract's anticancer mechanism differs from common chemotherapeutics.
This document discusses various genetic recombination techniques, including protoplast fusion, transformation, transduction, conjugation, and genetic engineering methods. It provides details on how each technique is performed, such as using polyethylene glycol or electric shocks to fuse protoplasts, adding calcium chloride to allow DNA uptake during bacterial transformation, and using restriction enzymes and ligases in genetic engineering to cut and join DNA fragments. The overall document serves to explain the key methods for combining genetic material from different organisms or cells.
1) The document discusses recent advances in using berberine derivatives as antitumor agents. Berberine is an alkaloid extracted from plants that has been used in traditional medicines for centuries.
2) It describes how berberine and novel derivatives it were synthesized can target thymidylate synthase, a key enzyme for cancer treatment, by modulating its protein expression and interrupting abnormal production in cancer cells. This represents an innovative mechanism of action over current drugs.
3) In vitro studies showed several berberine derivatives significantly reduced thymidylate synthase protein levels and activity in human ovarian cancer cell lines, demonstrating their potential as antitumor compounds.
1) The document describes the synthesis and antiproliferative effects of novel berberine derivatives in HER2+ breast cancer cells. Berberine shows anticancer activity but the authors developed derivatives to improve properties.
2) Compounds NAX012, NAX013, NAX014, and NAX035 showed stronger antiproliferative effects than berberine against HER2+ breast cancer cells. NAX014 in particular had the most potent effects.
3) In a mouse model of HER2+ breast cancer, oral and injected administration of NAX014 delayed tumor onset and progression at well-tolerated doses, and also reduced lung metastases. NAX014 shows promise as an anticancer agent
XXII National Meeting in Medicinal Chemistry - Fisciano Campus- University of Salerno- September 6-9: Naxospharma's G. Fiorillo will read a paper at the Satellite 9th Young Medicinal Chemists Symposium
This document summarizes a keynote address about biosimilars and biotechnological medicines. It begins with statements that the speaker has received funding from various pharmaceutical companies but does not work for them. It then discusses that biotechnological medicines like proteins are much larger than conventional drugs. Biosimilars are similar but not generic versions of innovative biologics. The document outlines differences between biosimilars and intended copies, and concludes that biosimilars require their own clinical data to demonstrate similar efficacy and safety, while intended copies were approved without such regulations.
Drug response biomcare webinar - jan 2022Regin Jensen
WEBINAR: The role of the Gut Microbiome for Drug Response
Varying drug response is a key factor in both drug development and clinical practice and result in sub-optimal treatment and failed clinical trials.
Resent years research has detailed how the gut microbiome plays an essential role for drug response, and how the inter-individual variation in the composition of the gut microbiome is an important factor, both in drug trials and treatment.
Elements in the webinar
In this seminar, we will dive into this interesting topic, and take you through
-Key research into how the microbiome can affect drug response
-How microbiome profiling of patients can be used to gain insight and control in clinical trials at all stages,
-How microbiome profiling can be used to detect a novel type of biomarkers.
Biomcare is providing sampling support, sequencing, and data analysis for the microbiome aspects of the large NORDIC-SUN clinical trial of Immune Checkpoint Inhibitors, and we will finish the seminar by introducing this project and our solution for microbiome analysis in clinical studies and trials.
Antimicrobial Activity of Bauhinia Purpurea (L) by Minimum Inhibitory Concent...IOSRJPBS
MIC methods are widely used in the comparative testing of new agents, or when a more accurate result is required for clinical management. As there are no CLSI (formerly NCCLS) recommendations for the determination of MICs of varies bio-compounds against gram positive and gram negative organisms. The minimum inhibitory concentration is the lowest concentration (in μg/ml) of an antibiotic that inhibits the growth of a given strain of bacteria. In Diagnostic laboratories these MIC’S are used to confirm resistance and also most often used to determine antimicrobial invitro activity. In the present MIC method, one can get the information about Antibiotic agent, preparation of stock solutions, media and inoculation, conditions of incubation, ultimately reading and interpretation of results. The present study is focused to evaluate antibacterial activities of ethanolic extract and purified fractions of Bauhinia purpurea using a gram-positive and a gram-negative organisms Staphylococcus aureus , Klebsiella, E.coli and enterococcus
Synthesis of silver nanoparticles and its synergistic effects in combination ...Nanomedicine Journal (NMJ)
Abstract
Objectives:
Biofilms are communities of bacteria attached to surfaces through an external polymeric substances matrix. In the meantime, Acinetobacterbaumannii is the predominant species related to nosocomial infections. In the present study, the effect of silver nanoparticles alone and in combination with biocides and imipenem against planktonic and biofilms of A. baumannii was assessed.
Materials and Methods:
Minimum inhibitory concentrations (MICs) of 75 planktonic isolates of A. baumannii were determined by using the microdilution method as described via clinical and laboratory standards institute (CLSI). Among all strains, 10 isolates which formed strong biofilms were selected and exposed to silver nanoparticles alone and in combination with imipenem, bismuth ethandithiol (BisEDT) and bismuth propanedithiol (BisPDT) to determine minimum biofilm inhibitory concentrations (MBIC). Subsequently, minimum biofilm eradication concentrations (MBECs) of silver nanoparticles alone and in combination with imipenem against mature biofilm of the isolates were evaluated.
Results:
Results showed that 29.3% of isolates were susceptible to silver nanoparticles and could inhibit the growth and eradicate biofilms produced by the isolates. For this reason, ∑FIC, ∑FBIC and ∑FBEC ≤ 0.05 were reported which shows synergism between silver nanoparticles and imipenem against not only planktonic cells but also inhibition and eradication of biofilms. The results of ∑FBIC >2 indicated to antagonistic impacts between silver nanoparticles and BisEDT/BisPDT against biofilms.
Conclusion:
It can be concluded that silver nanoparticles alone can inhibit biofilm formation but in combination with imipenem are more effective against A. baumannii in planktonic and biofilm forms.
This study investigated the effectiveness of pulsed UV (PUV) light irradiation in damaging Bacillus cereus and Bacillus megaterium, two bacteria relevant to food safety issues. PUV treatment was found to inflict four types of cellular damage that prevented DNA replication. Total reduction of both bacteria was seen at 120P and 160P of PUV treatment. Bacillus megaterium was more sensitive, experiencing total reduction at 80P as well. Increased concentrations of leaked intracellular proteins also demonstrated the damaging effects of PUV. However, protein leakage did not correlate to reductions in viable bacterial counts. Further research is needed to determine the relationship between protein damage and DNA damage from PUV and its effects on pathogenic toxins produced by these bacteria
1) Cancer is caused by uncontrolled cell growth that can spread to other parts of the body. Herbal drugs provide an alternative to chemotherapy to treat cancer while avoiding harmful side effects.
2) Many herbal compounds have been shown to be effective against cancer through mechanisms like antioxidant effects, immune boosting, inducing apoptosis, and inhibiting angiogenesis.
3) Specific herbal compounds and plants discussed that have anti-cancer properties include polyphenols, citrus flavonoids, tannins, curcumin, gallacatechins, saponins, brassinosteroids, alkaloids, bromelain, cardiac glycosides, and dietary fiber. Combinations of herbal compounds may enhance their anti
This document describes the synthesis and in vitro anticancer screening of novel 2-amino benzothiazole derivatives. Several 2-amino benzothiazole compounds were synthesized and tested against nine cancer cell lines. Compound 4i showed promising antitumor activity, with a GI50 value of 7.18 × 10−8 M against non-small cell lung cancer cells. Computational docking was performed to explore if these compounds bind similarly to EGFR inhibitors in the ATP binding site. The synthesized compounds were characterized using techniques such as IR, NMR and HRMS.
Cytotoxicity of Blended Versus Single Medicinal Mushroom Extracts on Human Ca...Jolene1981
ABSTRACT: The use of mushrooms contributes to human nutrition by providing low lipid content of lipids and high dietary fiber content, as well as significant content of other biologically active compounds such as polysaccharides, minerals, vitamins, and polyphenolic antioxidants. This study aimed to determine the content of polyphenols and polysaccharides, as well as the cytotoxic and antioxidative properties of several medicinal mushroom preparations. The content of total phenols and flavonoids of preparations of blended mushroom extracts (Lentifom, Super Polyporin, Agarikon, Agarikon Plus, Agarikon.1, and Mykoprotect.1) was evaluated quantitatively by using ultraviolet–visible spectroscopy spectrophotometric methods. The antioxidant capacity of the preparations was evaluated using the ABTS (2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and ferric reducing/antioxidant power assays. The content of water-soluble polysaccharides was determined using a specific gravimetric method, based on ethanol precipitation. To determine cytotoxic effects of single and blended mushroom extracts, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and neutral red assays were conducted using human small cell lung cancer, lung adenocarcinoma, colon cancer, and brain astrocytoma cancer cells. The obtained results suggest that due to the significant content of beneficial polyphenolic antioxidants and soluble polysaccharides, use of these mushroom preparations is beneficial in maintaining good health, as well as in the prevention and adjuvant biotherapy of various human pathological aberrations. These results reveal that these extracts exhibit different cytotoxic effects on tumor cells originating from different tissues. In addition, the comparison of investigated blended mushroom extracts with three well-known commercial mushroom products derived from single mushroom species or single mushroom compounds shows that blended mushroom extracts exhibit significantly stronger cytotoxic effects on human tumor cell lines.
Oncodesign aacr 2018 morab-202 a folate receptor alpha-targeted antibody-dr...Florence Fombertasse
Folate receptor alpha (FRA) is a membrane protein with high affinity for binding and transporting folate into cells. Overexpression of FRA may confer a growth advantage to tumors by increasing folate uptake and affecting cell proliferation via alternative cell signaling pathways (1). FRA levels have been found to be elevated in tumors of epithelial origin compared to normal tissue as cancers of the breast (including TNBC (2)), colon, lungs and ovary (3).
In this study, we report the development of MORAb-202, an anti-FRA antibody-drug conjugate (ADC), consisting of a FRA-binding antibody (MORAb-003, farletuzumab) with a cathepsin-cleavable form of eribulin (eribulin mesylate, marketed as Halaven®), a highly potent anti-mitotic agent that induces cell-cycle arrest and cell death by targeting microtubules.*
We first study expression of FRA on a large panel of tumors patient-derived xenograft (PDX) and Cancer Cell Line-derived Xenograft (CDX). Then, we performed in vitro and in vivo anti-proliferation assays and compare antitumor activity of MORAb-202 with free eribulin accordingly to the FRA expression level. FRA expression was found to be determinant in the sensitivity of tumor cells to the cytotoxic effect of the ADC. Moreover, in case of high expression of FRA, MORAb-202 showed a higher antitumor activity compared with free eribulin.
These results suggest that FRA expression could be used as a response-predictive biomarker for this targeted therapy. The ability to identify and treat patients with an effective therapy based on the known expression of the tumor marker is a key point in predictive medicine progress. These findings support the clinical development of MORAb-202 ADC as a novel targeted therapy for patients with FRA-expressing tumors.
The ADC described in this abstract is investigational, as efficacy and safety have not been established. There is no guarantee that this ADC will be available commercially.
EFFICACY IN REDUCING BACTERIAL CONTENT IN ORAL CAVITY BY CANNABINIODS IN ORAL...DrHeena tiwari
The document discusses a study that compared the efficacy of cannabinoids and popular oral care products (Oral-B and Colgate) in reducing bacterial content in dental plaque. Plaque samples were collected from 30 participants and exposed to cannabinoid toothpaste, Oral-B, and Colgate. Cannabinoids were found to significantly reduce bacterial colony counts compared to the other products. The results suggest cannabinoids may be more effective at controlling oral bacteria and could provide a personalized alternative to traditional oral care products.
This study investigated the antimicrobial activity of Cinnamomum iners leaves extract and isolated compounds. The ethyl acetate fraction showed the highest activity against methicillin-resistant Staphylococcus aureus and Escherichia coli. Through bioautography and spectroscopic analysis, the active compound was isolated and identified as xanthorrhizol. Xanthorrhizol exhibited antimicrobial activity against both Gram-positive and Gram-negative pathogens such as MRSA and E. coli. This provides evidence that C. iners leaves and xanthorrhizol could be potential sources of antimicrobial agents.
Secondary metabolites are biologically active compounds found in plants that are not involved in their primary metabolism. They play important roles in plant defense against herbivores and pathogens. Many secondary metabolites have anti-cancer properties, including phenols, terpenoids, alkaloids, and organosulfur compounds. They can act as cancer inhibitors by blocking carcinogen formation, as blocking agents during cancer initiation, or as suppressing agents during promotion and progression. Examples that are used clinically or show promise include taxol, camptothecin, curcumin, garlic compounds, and resveratrol. These natural compounds offer promise as low-cost, accessible alternatives or adjuvants to conventional cancer therapies due to their ability to target multiple stages
The document discusses a biotechnology company focused on developing products that regenerate or strengthen the human immune system. It summarizes results showing that the company's drug candidate Homspera stimulates hematopoietic stem cells, increasing white blood cell and platelet production. Studies also suggest Homspera may help resolve neutropenia caused by radiation exposure and chemotherapy by boosting white blood cell counts in irradiated animals.
Protein was extracted from muscles of Channa striatus and attempts were
made to evaluate in vitro antibacterial activity against clinical bacterial isolates. The
higher concentration of protein (100μg/ml) extracts exhibited a pronounced activity
against Pseudomonas aeruginosa (21 mm), Proteus vulgaris (19 mm), Citrobacter sp
(19 mm), Klebsiella pneumoniae (18 mm), Micrococcus sp (17 mm), Bacillus subtilis (16
mm), Staphylococcus aureus (15 mm), E. coli (14 mm) and Serratia marcescens (5
mm). The minimum inhibitory concentration and minimum bactericidal concentration
were found to be 20-40 μg/ml and 80-100 μg/ml respectively for the extracts of
Channa striatus protein against test organisms. This study confirms that C. striatus fish
protein extracts possess antibacterial activity against a wide range of microbes and
justified that it could be used in the traditional medicine as a remedy for the
treatment of bacterial diseases.
This study investigated the prevalence of extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacilli at a tertiary care hospital over one year. A total of 6,672 clinical samples were tested, yielding 2,366 gram-negative bacteria isolates. Phenotypic confirmation testing found 141 isolates (5.95%) to be ESBL producers. The most common ESBL-producing organisms were Escherichia coli (6.43% of E. coli isolates) and Klebsiella pneumoniae (10.97% of K. pneumoniae isolates). The results suggest a high prevalence of ESBL producers in this hospital setting. Improved antibiotic stewardship and infection control practices are needed to
The debris of the ‘last major merger’ is dynamically youngSérgio Sacani
The Milky Way’s (MW) inner stellar halo contains an [Fe/H]-rich component with highly eccentric orbits, often referred to as the
‘last major merger.’ Hypotheses for the origin of this component include Gaia-Sausage/Enceladus (GSE), where the progenitor
collided with the MW proto-disc 8–11 Gyr ago, and the Virgo Radial Merger (VRM), where the progenitor collided with the
MW disc within the last 3 Gyr. These two scenarios make different predictions about observable structure in local phase space,
because the morphology of debris depends on how long it has had to phase mix. The recently identified phase-space folds in Gaia
DR3 have positive caustic velocities, making them fundamentally different than the phase-mixed chevrons found in simulations
at late times. Roughly 20 per cent of the stars in the prograde local stellar halo are associated with the observed caustics. Based
on a simple phase-mixing model, the observed number of caustics are consistent with a merger that occurred 1–2 Gyr ago.
We also compare the observed phase-space distribution to FIRE-2 Latte simulations of GSE-like mergers, using a quantitative
measurement of phase mixing (2D causticality). The observed local phase-space distribution best matches the simulated data
1–2 Gyr after collision, and certainly not later than 3 Gyr. This is further evidence that the progenitor of the ‘last major merger’
did not collide with the MW proto-disc at early times, as is thought for the GSE, but instead collided with the MW disc within
the last few Gyr, consistent with the body of work surrounding the VRM.
Unlocking the mysteries of reproduction: Exploring fecundity and gonadosomati...AbdullaAlAsif1
The pygmy halfbeak Dermogenys colletei, is known for its viviparous nature, this presents an intriguing case of relatively low fecundity, raising questions about potential compensatory reproductive strategies employed by this species. Our study delves into the examination of fecundity and the Gonadosomatic Index (GSI) in the Pygmy Halfbeak, D. colletei (Meisner, 2001), an intriguing viviparous fish indigenous to Sarawak, Borneo. We hypothesize that the Pygmy halfbeak, D. colletei, may exhibit unique reproductive adaptations to offset its low fecundity, thus enhancing its survival and fitness. To address this, we conducted a comprehensive study utilizing 28 mature female specimens of D. colletei, carefully measuring fecundity and GSI to shed light on the reproductive adaptations of this species. Our findings reveal that D. colletei indeed exhibits low fecundity, with a mean of 16.76 ± 2.01, and a mean GSI of 12.83 ± 1.27, providing crucial insights into the reproductive mechanisms at play in this species. These results underscore the existence of unique reproductive strategies in D. colletei, enabling its adaptation and persistence in Borneo's diverse aquatic ecosystems, and call for further ecological research to elucidate these mechanisms. This study lends to a better understanding of viviparous fish in Borneo and contributes to the broader field of aquatic ecology, enhancing our knowledge of species adaptations to unique ecological challenges.
Travis Hills' Endeavors in Minnesota: Fostering Environmental and Economic Pr...Travis Hills MN
Travis Hills of Minnesota developed a method to convert waste into high-value dry fertilizer, significantly enriching soil quality. By providing farmers with a valuable resource derived from waste, Travis Hills helps enhance farm profitability while promoting environmental stewardship. Travis Hills' sustainable practices lead to cost savings and increased revenue for farmers by improving resource efficiency and reducing waste.
Phenomics assisted breeding in crop improvementIshaGoswami9
As the population is increasing and will reach about 9 billion upto 2050. Also due to climate change, it is difficult to meet the food requirement of such a large population. Facing the challenges presented by resource shortages, climate
change, and increasing global population, crop yield and quality need to be improved in a sustainable way over the coming decades. Genetic improvement by breeding is the best way to increase crop productivity. With the rapid progression of functional
genomics, an increasing number of crop genomes have been sequenced and dozens of genes influencing key agronomic traits have been identified. However, current genome sequence information has not been adequately exploited for understanding
the complex characteristics of multiple gene, owing to a lack of crop phenotypic data. Efficient, automatic, and accurate technologies and platforms that can capture phenotypic data that can
be linked to genomics information for crop improvement at all growth stages have become as important as genotyping. Thus,
high-throughput phenotyping has become the major bottleneck restricting crop breeding. Plant phenomics has been defined as the high-throughput, accurate acquisition and analysis of multi-dimensional phenotypes
during crop growing stages at the organism level, including the cell, tissue, organ, individual plant, plot, and field levels. With the rapid development of novel sensors, imaging technology,
and analysis methods, numerous infrastructure platforms have been developed for phenotyping.
The use of Nauplii and metanauplii artemia in aquaculture (brine shrimp).pptxMAGOTI ERNEST
Although Artemia has been known to man for centuries, its use as a food for the culture of larval organisms apparently began only in the 1930s, when several investigators found that it made an excellent food for newly hatched fish larvae (Litvinenko et al., 2023). As aquaculture developed in the 1960s and ‘70s, the use of Artemia also became more widespread, due both to its convenience and to its nutritional value for larval organisms (Arenas-Pardo et al., 2024). The fact that Artemia dormant cysts can be stored for long periods in cans, and then used as an off-the-shelf food requiring only 24 h of incubation makes them the most convenient, least labor-intensive, live food available for aquaculture (Sorgeloos & Roubach, 2021). The nutritional value of Artemia, especially for marine organisms, is not constant, but varies both geographically and temporally. During the last decade, however, both the causes of Artemia nutritional variability and methods to improve poorquality Artemia have been identified (Loufi et al., 2024).
Brine shrimp (Artemia spp.) are used in marine aquaculture worldwide. Annually, more than 2,000 metric tons of dry cysts are used for cultivation of fish, crustacean, and shellfish larva. Brine shrimp are important to aquaculture because newly hatched brine shrimp nauplii (larvae) provide a food source for many fish fry (Mozanzadeh et al., 2021). Culture and harvesting of brine shrimp eggs represents another aspect of the aquaculture industry. Nauplii and metanauplii of Artemia, commonly known as brine shrimp, play a crucial role in aquaculture due to their nutritional value and suitability as live feed for many aquatic species, particularly in larval stages (Sorgeloos & Roubach, 2021).
hematic appreciation test is a psychological assessment tool used to measure an individual's appreciation and understanding of specific themes or topics. This test helps to evaluate an individual's ability to connect different ideas and concepts within a given theme, as well as their overall comprehension and interpretation skills. The results of the test can provide valuable insights into an individual's cognitive abilities, creativity, and critical thinking skills
Current Ms word generated power point presentation covers major details about the micronuclei test. It's significance and assays to conduct it. It is used to detect the micronuclei formation inside the cells of nearly every multicellular organism. It's formation takes place during chromosomal sepration at metaphase.
Describing and Interpreting an Immersive Learning Case with the Immersion Cub...Leonel Morgado
Current descriptions of immersive learning cases are often difficult or impossible to compare. This is due to a myriad of different options on what details to include, which aspects are relevant, and on the descriptive approaches employed. Also, these aspects often combine very specific details with more general guidelines or indicate intents and rationales without clarifying their implementation. In this paper we provide a method to describe immersive learning cases that is structured to enable comparisons, yet flexible enough to allow researchers and practitioners to decide which aspects to include. This method leverages a taxonomy that classifies educational aspects at three levels (uses, practices, and strategies) and then utilizes two frameworks, the Immersive Learning Brain and the Immersion Cube, to enable a structured description and interpretation of immersive learning cases. The method is then demonstrated on a published immersive learning case on training for wind turbine maintenance using virtual reality. Applying the method results in a structured artifact, the Immersive Learning Case Sheet, that tags the case with its proximal uses, practices, and strategies, and refines the free text case description to ensure that matching details are included. This contribution is thus a case description method in support of future comparative research of immersive learning cases. We then discuss how the resulting description and interpretation can be leveraged to change immersion learning cases, by enriching them (considering low-effort changes or additions) or innovating (exploring more challenging avenues of transformation). The method holds significant promise to support better-grounded research in immersive learning.
When I was asked to give a companion lecture in support of ‘The Philosophy of Science’ (https://shorturl.at/4pUXz) I decided not to walk through the detail of the many methodologies in order of use. Instead, I chose to employ a long standing, and ongoing, scientific development as an exemplar. And so, I chose the ever evolving story of Thermodynamics as a scientific investigation at its best.
Conducted over a period of >200 years, Thermodynamics R&D, and application, benefitted from the highest levels of professionalism, collaboration, and technical thoroughness. New layers of application, methodology, and practice were made possible by the progressive advance of technology. In turn, this has seen measurement and modelling accuracy continually improved at a micro and macro level.
Perhaps most importantly, Thermodynamics rapidly became a primary tool in the advance of applied science/engineering/technology, spanning micro-tech, to aerospace and cosmology. I can think of no better a story to illustrate the breadth of scientific methodologies and applications at their best.
The ability to recreate computational results with minimal effort and actionable metrics provides a solid foundation for scientific research and software development. When people can replicate an analysis at the touch of a button using open-source software, open data, and methods to assess and compare proposals, it significantly eases verification of results, engagement with a diverse range of contributors, and progress. However, we have yet to fully achieve this; there are still many sociotechnical frictions.
Inspired by David Donoho's vision, this talk aims to revisit the three crucial pillars of frictionless reproducibility (data sharing, code sharing, and competitive challenges) with the perspective of deep software variability.
Our observation is that multiple layers — hardware, operating systems, third-party libraries, software versions, input data, compile-time options, and parameters — are subject to variability that exacerbates frictions but is also essential for achieving robust, generalizable results and fostering innovation. I will first review the literature, providing evidence of how the complex variability interactions across these layers affect qualitative and quantitative software properties, thereby complicating the reproduction and replication of scientific studies in various fields.
I will then present some software engineering and AI techniques that can support the strategic exploration of variability spaces. These include the use of abstractions and models (e.g., feature models), sampling strategies (e.g., uniform, random), cost-effective measurements (e.g., incremental build of software configurations), and dimensionality reduction methods (e.g., transfer learning, feature selection, software debloating).
I will finally argue that deep variability is both the problem and solution of frictionless reproducibility, calling the software science community to develop new methods and tools to manage variability and foster reproducibility in software systems.
Exposé invité Journées Nationales du GDR GPL 2024
EWOCS-I: The catalog of X-ray sources in Westerlund 1 from the Extended Weste...Sérgio Sacani
Context. With a mass exceeding several 104 M⊙ and a rich and dense population of massive stars, supermassive young star clusters
represent the most massive star-forming environment that is dominated by the feedback from massive stars and gravitational interactions
among stars.
Aims. In this paper we present the Extended Westerlund 1 and 2 Open Clusters Survey (EWOCS) project, which aims to investigate
the influence of the starburst environment on the formation of stars and planets, and on the evolution of both low and high mass stars.
The primary targets of this project are Westerlund 1 and 2, the closest supermassive star clusters to the Sun.
Methods. The project is based primarily on recent observations conducted with the Chandra and JWST observatories. Specifically,
the Chandra survey of Westerlund 1 consists of 36 new ACIS-I observations, nearly co-pointed, for a total exposure time of 1 Msec.
Additionally, we included 8 archival Chandra/ACIS-S observations. This paper presents the resulting catalog of X-ray sources within
and around Westerlund 1. Sources were detected by combining various existing methods, and photon extraction and source validation
were carried out using the ACIS-Extract software.
Results. The EWOCS X-ray catalog comprises 5963 validated sources out of the 9420 initially provided to ACIS-Extract, reaching a
photon flux threshold of approximately 2 × 10−8 photons cm−2
s
−1
. The X-ray sources exhibit a highly concentrated spatial distribution,
with 1075 sources located within the central 1 arcmin. We have successfully detected X-ray emissions from 126 out of the 166 known
massive stars of the cluster, and we have collected over 71 000 photons from the magnetar CXO J164710.20-455217.
EWOCS-I: The catalog of X-ray sources in Westerlund 1 from the Extended Weste...
Fiorillo vi ewd_sy_siena_2016
1. Recent advances in antitumour berberine
Gaetano Fiorillo, Tanjia Monir Syeda , Paolo Lombardi
via G. Di Vittorio 70, 20026 Novate Milanese, Milano, Italy
Email: staff@naxospharma.eu
Siena, 15-19 May 2016
2. Berberine
Extracted from plants of the genus Berberis,
Coptis and others.
In use in the Ayurvedic and Chinese medicines.
Anti-microbial/parasitic,
Anti-diarrheal, anti-inflammatory,
Anti-arryhthmic,
Cholesterol-lowering
Anticancer1,2
Berberine Chloride
1L. M. Guamán Ortiz, P.Lombardi, M. Tillhon, A. I. Scovassi, Molecules ,2014, 19, 12349-12367
2 L. M. Guamán Ortiz, P.Lombardi, M. Tillhon, A. I. Scovassi, Biochemical Pharmacology, 2012, 84, 1260–1267
2011: 7 clinical trials
2016: 25 clinical trials
3. Mondello, R. et al.,Bioorg Med Chem, 2003,
505–514 (NMR Studies)
Gratteri, P et al.Chem. Commun. 2011, 4917-
4919 (RX studies)
minor groove binding
Berberine
DNA Interaction Mechanism
“ Interaction between nucleic acids and berberine sulfate “
Journal of Cellular Biology, 15, 1962, 589
…has been reported since decades…
Minor groove binding or Intercalation ????
4. Berberine represents an interesting and
attractive natural lead compound
Chemical modifications might select more
specific medical indications resulting in
derivatives with better (or different)
biological effects compared to the parent
berberine
Performing rational chemical modifications of
berberine structure led to a new class of
derivatives with antitumour properties
Chemical
Programme
Berberine
5. Aromatic interactions are ubiquitous in nature,
their geometry is relevant for the molecular recognition
in biological systems 1
Chemical
Programme
L = Linker with different functionalities
1 Waters ML, Curr Opin Chem Biol. 2002, 6, 736
6. from very low to low yields - better with activated halides or
iodides - berberine back from loss of acetone major by-product
Alkylation of enamine (7,8-dihydroberberine)
Berberine derivatives
Synthetic Methods_1
1)
from low to moderate yields -
berberine and tetrahydroberberine
from disproportionation of enamine
as major by-products
2)
7. generally from good to very good yields
Uncommon aldehyde-enamine condensation1,2
1 Cook, AG, Enamines Synthesis, Structure and reaction, 1988, 200
2 Iwasa, K, et al., Planta Medica, 1997, 196
Berberine derivatives
Synthetic Methods_2
8. 1) Commercially available aldehyde
2) Commercially available alcohol followed by oxidation
(e.g. : PCC or TEMPO)
3) Homologation starting from the above
Berberine Derivatives
Aldehyde Intermediates_1
Commercially
available
10. Improved DNA intereaction
of berberine derivatives_1
1.77
0.35
2.11
11.01
7.6 7.58
6.8
0
2
4
6
8
10
12
Kix10-5(M-1)
Interaction costants of NAXs 1
1.77
0.48 0.51
7.07
10.04
8.90
7.48
0
2
4
6
8
10
12
Kix10-5(M-1)
Interaction costants of NAXs2
1D. Bhowmik, M. Hossain, F. Buzzetti, R. D’Auria, P. Lombardi, G.S.Kumar, J. Phys. Chem. B, 2012, 116, 2314−24.
2D. Bhowmik, F. Buzzetti, G. Fiorillo, F. Orzi, T. Syeda Monir, P. Lombardi, G.S. Kumar, Med. Chem. Comm., 2014, 5, 226-31.
n = 3
n = 4
Monophenyl Derivatives
Diphenyl Derivatives
11. S. Chatterjee, S. Mallick, F. Buzzetti, G. Fiorillo, T. M. Syeda, Paolo Lombardi, K. Das Saha, G. S. Kumar,
RCS Adv., 2015, 5, 90632
n = 5
0
2
4
6
8
10
12
Kix10-5(M-1)
Interaction costants of NAXs
Pyridylalkyl Derivatives
Improved DNA intereaction
of berberine derivatives_2
12. Binding to human telomeric
G quadruplex
P. Gratteri, M. Ferraroni, C. Bazzicalupi, F. Papi, G. Fiorillo, L. M. Guamán Ortiz, A. Nocentini, A. I. Scovassi, P. Lombardi
Chemistry An Asian Journal, 2016, 11(7),1107-15
NAX 053 – d[TAG3(T2AG3)T]
adduct crystal structure
13. Our1 and others’ studies identified
berberine as a novel, non specific
inhibitor of the nascent synthesis
of some proteins, supposedly
acting as a RNA silencing agent
Berberine
effect on TS expression
1G. Marverti, A. Ligabue, P. Lombardi, S. Ferrari, M. G. Monti, C. Frassinetti, M.P. Costi,
Int. Journal of Oncology, 2013, 43, 129
2008 cells = cisplatin sensitive
C13 cells = cisplatin resistant
16. Antitumour activity of i.p. and oral
NAX035, on the peritoneal STO human
mesothelioma s.c. xenografted in nude
mice
Route Dose
mg/kg
TVI% (+32)
(PvsControls)
Max
BWL%
TOX
i.p. 1 52 (0.1181) 8 0/9
p.o. 10 72 (0.0434) 10 0/9
p.o. 15 74 (0.0373) 5 0/8
Correlation between TS protein levels in vitro and in vivo in tumour tissue
samples examined at the end of the p.o. treatment period
17. NAX 012 NAX 013 NAX 014 NAX 035 Berberine
24 h 94.2±1.2 >100 52.3±3.2 >100 91.8±2.8
48 h 46.6±2.5 >100 30.7±2.1 >100 58.4±1.9
72 h 31.9±2.9 >100 26.5±6.7 48.6±6.7 36.0±1.8
Antiproliferative effect (IC50 mM)
Method - Alamar Blue assay. The number of viable cells after treatment
is expressed as a % of the vehicle treated control
M. Provinciali, P. Lombardi, et al, Biofactors, 39, 2013, 672-679
Berberine derivatives
Antiproliferactive effects on HER2+
human Breast Cancer cells (SK-BR-3)
(SK-BR-3)
18. Tumour Number Tumour Growth Inhibition High % Tumour Free Mice
NAX014: antitumour efficacy in
HER-2/neu spontaneous tumours transgenic
female mice
Both i.p. [2.5mg/kg-(2xweek)x12]
and oral [20mg/kg-(2xweek)x8]
administrations of NAX014
reduced tumour volume and
number, delayed the onset
and progression of HER2+ BC
compared to control group
Tumour Growth Inhibition Tumour Number
i.p.
p. o.
Provinciali, M., Lombardi, P. et al., Carcinogenesis, 2015, 1–11
20. Innovative proprietary compound, structurally related
to the plant isoquinoline alkaloid berberine.
Novel mechanism of action, targeting the
expression of TS protein, differently from
previous TS inhibitors
Efficacy on chemoresistant tumour cells
Antitumour efficacy and tolerability at the
effective doses by oral and i.p. administration
in a human mesothelioma xenografted nude
mice
Conclusions:
NAX 035
21. Conclusions:
NAX 014
anticancer and anti-metastatic efficacy on HER2+ tumours
in vitro activity at µM concentrations
in vivo tolerability by i.p.and oral administration
at the effective dose
Innovative proprietary compound, structurally related
to the plant isoquinoline alkaloid berberine
Unique ability to reduce cellular HER2 expression via
a postulated novel mechanism
22. Financial supports were provided by
Ministero dello Sviluppo Economico (Grant 01705) to Naxospharma srl (Project
coordinator) and to Istituto Tumori Milano
and by
Agència per a la competitivitat de l'empresa ACC1O (Grant RDNET11-1-0001) to
Aromics SL, Barcelona
under the 6th call of the EuroTransBio initiative, Transnational joint project BERTA
(BERberine as antiTumour Agents).
Aknowledgeme
nts
Regione Lombardia (Grant 13810040) to Naxospharma srl and to Istituto di
Genetica Molecolare – CNR Pavia, Project PLANT CELL
Ente Cassa di Risparmio di Firenze (Grant 2014.0309) to Department
NEUROFARBA, University of Firenze
Editor's Notes
I’d like to thank the scientific committee for the opportunity to present our research work
Berberine is an isoquinoline quaternary alkaloid extracted of from plants of the genus Berberis and Coptis.
It shows diverse pharmacological activities: Anti-microbial/parasitic, Anti-diarrheal, anti-inflammatory, Anti-arryhthmic, Cholesterol-lowering, and anticancer
We have written two reviews in collaboration with CNR of Pavia, one of which specifically addresses anticancer properties of berberine
In two thousand eleven there were 7 ongoing clinical trials, which increased to 25 today
Now, how berberine explicates its anticancer effects? Evita di dire ciò, non si può dimostralo con certezza
Interaction between nucleic acids and berberine has been reported since nineteen sixty two.
The question whether the alkaoild is a minor groove binder or an intercalator was matter of debate
In any case… read…
Our chemistry programme was directed to the synthesis of novel Berberine derivatives characterized by the presence of (hetero)aromatic groups bonded to the 13-position of the parent alkaloid skeleton through a linker of variable length and functionality.
That would possibly creates a geometric propensity for additional stacking-type, non-covalent aromatic interactions with respect to the parent Berberine.
Aromatic interactions are ubiquitous in nature, their geometry is relevant for the molecular recognition in biological systems
That could result in better (or different) biological effects, possibly ameliorated antitumour properties.
Here on the right are some examplary derivatives
Synthetic methods of the prior art for C-13 functionalization imply:
preparation of a reactive acetonylberberine intermediate, followed by enamine alkyl halide alkylation and concomitant expulsion of acetone to restore the isoquinoline quaternary salt of the desired derivative
reduction of berberine to dihiydro berberine, followed by enamine alkyl alide alkylation to obtain an instable iminium ion, reduction with sodium borohydride, oxidation with appropriate reagents to obtain the isoquinoline quaternary salt of the desired derivative
In our hands, the most viable and direct preparative method was based on this uncommon enamine-aldehyde condensation.
The postulated mechanism implies an unstable alcoholic intermediate wich looses water and H+ to obtain the desired isoquinoline quaternary salt derivative
Good, we use aldehyde intermediates when commercially available, or commercially available alcohol followed by oxidation or we use homologation procedure. For example starting from diphenyl propanol we obtain diphenyl propanal with tempo or pcc oxidation. Than, aldehyde elongation by wittig reaction followed methanolysis or hydrolysis.
Moremore, wittig reaction without solvent, hydrogenation, reduction and tempo oxidation to obtain pyridyl alkyl derivative.
Alternatively, we use Darzen’s reaction as a homologation procedure.
This slide shows the partnership with Indian institute of chemical biology to estabilish the interaction costants of some of our berberine derivatives with calf thymus DNA
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With respect to parent berberine, the interaction depends on the length of the linker
For the monophenylalkyl derivatives the maximum interaction is obtained when the linker has three carbon atoms whereas for the diphenylalkyl the maximum interaction is obtained with four carbon atoms
Similarly for pyridyl alkyl derivatives, where the best constant interaction is with five carbon atoms linker. We did not investigate longer linkers.
Crystal structure of the adduct formed by NAX053 and the human telomeric sequence. The interaction is a Pi stacking.
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This compound affects the viability of HeLa cancer cell lines in a dose-dependent manner.
Our1 and others’ studies identified berberine as a novel, non specific inhibitor of the nascent synthesis of some proteins, supposedly acting as a RNA silencing agent.
We found that berberine inhibits the synthesis of thymidylate synthase (an imporant protein overexpressed in many cancers).
Noteworthy, berberine was more effective in cisplatin resistant cancer cells than in the sensitive ones.
Some of our berberine derivatives show a more pronounced effect on TS expression of, for example, pleural mesothelioma MSTO cell lines with respect to berberine
This slide shows the antiproliferative activity against one pleural and two peritoneal mesotelhelioma cell lines, for the monophenyl and diphenyl classes, resepctively.
Non ti perdere qui a fare commenti tra attività e struttura.
This in vivo study refers to the efficacy of NAX035 (administered either intraperitoneally or orally) in a peritoneal STO human mesothelioma s.c. xenografted in nude mice.
TVI = tumour volume inhibition BWL% = percent body wight loss TOX = 0 dead animals in the treated group ( 9 or 8)
Note correlation between downregulation of TS protein in vitro correlates with downregulation of TS protein in tumour tissue of treated animal = in vivo target modulation
We investigated also the antiproliferative activity of some of our novel berberine derivatives on a HER2+ human Breast Cancer cell line, in collaboration with IRCCS-INRCA in Ancona
Also on that basis of other pharmacological investigations (not reported here) NAX014 was chosen for in vivo studies
This in vivo study refers to a model of spontaneous development of HER2 positive breast cancer in transgenic mice, very similar to what happens in women.
Note that time course scale is in WEEKS
Quindi leggi Both ip and...
The antitumour efficacy of NAX014 is due to the inhibition of the expression of HER2 protein, whereas current anti breast cancer drugs transtuzumab (antibody) and lapatinib (kinase inhibitor) exert different mechanims BUT DO NOT AFFECT THE LEVEL OF THE PROTEIN, WHICH REMAINS OVEREXPRESSED
Noteworthy, NAX compounds which down regulate TS (e.g. NAX012 and NAX035) do not affect HER2 expression, and NAX014 which downregulates HER2, does not affect TS expression.
In conlusion we have selected two lead compound, The first is nax thirty five (e poi leggo)
And nax 014 that have unique ability to reduce ccellular HER2 expression via a postulated novel mechanism
Finally i want to thank the the funding agencies which supported our and our partners’ research