Statins Talk 2009
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This document outlines a study investigating the effects of statin drugs like Simvastatin on the gut microbiome in relation to clinical obesity. The hypothesis is that certain statins will selectively inhibit bacteria in the Fimicutes phylum, which are more prevalent in obese individuals. The methods test the susceptibility of various bacterial species to different statins in vitro. Results show the statins had varying effects, with some inhibiting Clostridium species. Future experiments will examine changes in fecal microbiome DNA from patients taking Simvastatin.
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The discharge of human pharmaceuticals via wastewater treatment plants represents a major threat to non-target aquatic organisms since they are continually exposed throughout their lifespan. The individual effects of the anaesthetic, lidocaine; the cytostatics, ifosfamide and cyclophosphamide; and the antimicrobials, sulfamethoxazole, amoxicillin and erythromycin on 24 hpf (hours post fertilization) zebrafish (Danio rerio) following a 96-h exposure was investigated by evaluating embryonic development, catalase (CAT) enzyme activity, and the gene expressions of CAT, cytosolic superoxide dismutase (SOD1), and mitochondrial superoxide dismutase (SOD2). Lidocaine, cyclophosphamide and sulfamethoxazole induced neurotoxicity (scoliosis, tail malformation) and cardiotoxicity (pericardial edema, bradycardia) in the zebrafish which correlate with their adverse effects in mammals. These observations were linked to oxidative stress as indicated by the significant alteration of CAT activity and amounts of transcripts of SOD1, SOD2, and CAT. The CAT activity and gene expressions of the antioxidants were significantly upregulated at sublethal and levels of ifosfamide, lidocaine, cyclophosphamide, and erythromycin non-toxic to embryonic development in this study which suggest that these antioxidants may play a role in the prevention of teratogenicity in the larvae. The multi-level effect approach adopted in this study provides a better understanding of the mechanisms of toxicity employed by lidocaine, cyclophosphamide and sulfamethoxazole towards zebrafish. This study shows the importance of evaluating stress biomarkers and emphasizes the need for chronic studies in assessing pharmaceutical effects on aquatic organisms.
The flavonoid quercetin transientyly inhibits the activity of taxol and nocod...
This study examined the effects of the flavonoid quercetin on cancer cell viability and cell cycle progression when administered alone or in combination with the microtubule-targeting drugs taxol and nocodazole. The researchers found that while quercetin induced cancer cell death in a dose-dependent manner, lower doses of quercetin protected cancer cells from the G2/M cell cycle arrest induced by taxol and nocodazole. Specifically, quercetin delayed cell cycle progression, inhibited the accumulation of cyclin B1 at the microtubule organizing center, and partially restored viability of drug-treated cells for up to 72 hours. However, long-term exposure to quercetin still suppressed cancer cell proliferation and
Anti cancer drugs
Malignant disease accounts for many deaths in industrialized countries. Cancer occurs when normal cells are transformed into abnormal cells through genetic alterations. Chemotherapy aims to palliate symptoms, induce remission, or cure cancer by destroying cancer cells. The document discusses the classification, mechanisms of action, indications, and side effects of various classes of anticancer drugs including alkylating agents, antimetabolites, and antibiotics. It also outlines the multi-phase process of clinical trials required to approve new anticancer drugs.
OBC
This document summarizes the development and in vitro evaluation of novel sulphonamide compounds as potential antimalarial drugs. Specifically:
1) Novel sulphonamide compounds were designed and synthesized based on the structures of bepotastine and sulphonamides.
2) In vitro screening showed several compounds inhibited the asexual development of Plasmodium falciparum parasites at low micromolar concentrations, particularly during late-stage parasite development.
3) The most potent compounds were further evaluated, with three inhibiting parasite growth below 4 μM, while demonstrating low toxicity to mammalian cells.
pone.0143384
This research article investigates the effects of the natural flavonoid luteolin on colon cancer cells. The researchers found that physiological concentrations of luteolin induce apoptosis in colon cancer cells by increasing levels of the sphingolipid ceramide. Luteolin inhibits the conversion of ceramide to more complex sphingolipids and disrupts the transport of ceramide between organelles. These effects are mediated by luteolin's ability to inhibit the enzymes sphingosine kinase 2 and Akt, thereby reducing levels of the molecule sphingosine-1-phosphate which normally promotes cell survival. Overall, the study reveals that luteolin exerts anticancer effects by targeting the balance between ceramide and sphingosine-1-
Maxton et al[1]
This document summarizes a study that isolated three strains of Lactobacillus (L. plantarum, L. acidophilus, L. casei) from human intestinal samples. It evaluated the antibacterial activity of these strains against five strains of Staphylococcus aureus, including three methicillin-resistant S. aureus strains. L. casei showed the highest inhibitory activity. The study aimed to explore the potential of isolated intestinal Lactobacillus strains to control methicillin-resistant S. aureus infections.
microbiata in medicine.pdf
the role of the gut microbiota in health and disease.diseases associated with different microbiome.Therapeutic-Microbiota/ Microbiome-modulation
microbiata in medicine.pdf
Microbiome: The genes and genomes of the microbiota, as well as the products of the microbiota and the host environment” [the collective genomes of the micro-organisms in a particular environment. Although the composition of the gut microbiota varies between individuals, the community in each individual is relatively stable over time.
Immunomodulatory Potential of Probiotic Lactobacillus casei
The current study investigated the immunomodulatory
potential of ethyl acetate soluble supernatant of
Lactobacillus casei (LC-EAS) in vitro. The effect of
LC-EAS on nitric oxide release was analyzed in RAW
264.7 cells, wherein, an inhibition in nitric oxide production
through suppression of inducible nitric oxide synthase
mRNA expression was observed. Evaluation of LC-EAS
on LPS-induced peripheral blood mononuclear cells
showed a down-regulation in TNF-a and IL-6 genes and an
upregulation of IL-10. An inhibition in the protein
expression of NF-kB, ERK1/2 and STAT3 phosphorylation
confirms the immunomodulatory potential of LC-EAS. The
effect of LC-EAS on in vitro intestinal epithelial cells was
investigated using HT-29 human colon adenocarcinoma
cancer cells. LC-EAS exhibited an inhibition of NF-jB and
ERK1/2 phosphorylation, whereas STAT3 phosphorylation
was unregulated. To evaluate the downstream target of
STAT3 upregulation, expression of the intestinal trefoil
factor TFF3 which is a NF-jB regulator and STAT3
downstream target was studied. LC-EAS was observed to
elevate TFF3 mRNA expression. Overall the study shows
that the anti-inflammatory potential of LC-EAS is through
inhibition of NF-kB in different cell types.
Plos one
Quercetin was found to inhibit quorum sensing in foodborne bacteria both in vitro and in silico. In laboratory experiments, quercetin reduced quorum sensing-dependent phenotypes like biofilm formation, exopolysaccharide production, and motility in a concentration-dependent manner in pathogens like Pseudomonas aeruginosa, Yersinia enterocolitica, and Klebsiella pneumoniae. Molecular docking analysis revealed that quercetin binds strongly to the LasR receptor protein involved in quorum sensing. Molecular dynamics simulations further suggested that quercetin inhibits quorum sensing by inducing conformational changes in the receptor-quercetin complex. The study provides evidence that quercetin can act as a competitive inhibitor of qu
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- 8. R s R S S Fimicute Clostridium sordellii See Fig. 3 and comments. R: Resistant, little or no zone of inhibition; S: susceptible, clear zone of inhibition; s: slightly susceptible, hazy zone of inhibtion S S S S S Fungi Candida albicans R R R R R Enterobacteria E. aerogenes R R R R R Enterobacteria S. marcescens R R s R R Enterobacteria K. pneumoniae R R s s s Fimicute S. epidemidis R R S S S Enterobacteria E. coli R R S S S Fimicute S. aureus (MRSA&MSSA) s S S S S Enterobacteria P. mirabilis R S S S S Fimicute B. subtilis Crestor Lovastatin Lipitor Fluvastatin Zocor Taxonomic group Species Table 1. Variable susceptibilities of bacterial species to individual statins by agar-based assay
- 9. Bacillus subtilis Zocor Lovastatin Lovastatin (1:10) Zocor (1:10) Fluvastatin Fluvastatin (1:10)
- 10. Clostridium sordellii Zocor Lovastatin Lovastatin (1:10) Zocor (1:10) Fluvastatin Fluvastatin (1:10)
- 11. Clostridium sordellii Crestor DMSO Act.Buffer Crestor (1:10) Lipitor Lipitor (1:10)