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Biofilm is complex and consists of bacterial colonies that reside in an exopolysaccharide matrix that attaches to foreign surfaces in a living organism. Biofilm frequently leads to nosocomial, chronic infections in clinical settings. Since the bacteria in the biofilm have developed antibiotic resistance, using antibiotics alone to treat infections brought on by biofilm is ineffective. This review provides a succinct summary of the theories behind the composition of, formation of, and drug-resistant infections attributed to biofilm and cutting-edge curative approaches to counteract and treat biofilm. The high frequency of medical device-induced infections due to biofilm warrants the application of innovative technologies to manage the complexities presented by biofilm.
Influenza virus is a globally important respiratory pathogen that causes a high degree of annual morbidity and mortality. Significant antigenic drift results in emergence of new, potentially pandemic, virus variants. The best prophylactic option for controlling emerging virus strains is to manufacture and administer pandemic vaccines in sufficient quantities and to do so in a timely manner without impacting the regular seasonal influenza vaccine capacity. Current, egg-based, influenza vaccine production is well established and provides an effective product, but has limited capacity and speed.
Coenzyme Q10 (CoQ10) is a lipid soluble, endogenous antioxidant present at highest levels in the heart followed by the kidney and liver. The reduced CoQ10 ubiquinol is well known for its chemical instability and low bioavailability. The present study was designed to synthesize ubiquinol acetate, which is more stable and biologically active, and further evaluate its safety and genotoxic potential. Synthesized ubiquinol acetate showed better stability than that of ubiquinol at the end of 3 months. In vitro genotoxicity studies (AMES test, in vitro micronucleus and chromosomal aberration) showed ubiquinol acetate as nongenotoxic with no clastogenic or aneugenic effects at high dose of 5000 and 62.5 μg/mL, respectively. In subchronic toxicity study, ubiquinol acetate was administered orally to Sprague Dawley rats at 150, 300, and 600 mg/kg/day for 90 days. No treatment related adverse effects were observed in males at 600 mg/kg/day; however, females showed treatment related increase in AST and ALT with small focal irregular white-yellow spots in liver on gross necropsy examination. Histopathological evaluation revealed hepatocellular necrosis in high dose females which was considered as adverse. Based on the results, the No-Observed-Adverse-Effect Level (NOAEL) of ubiquinol acetate in males and females was determined as 600 and 300 mg/kg/day, respectively.
Galectins and prostate specific membrane antigen (PSMA) are glycoproteins that are functionally implicated in prostate cancer (CaP). We undertook this study to analyze the "PSMA-galectin pattern" of the human CaP microenvironment with the overarching goal of selecting novel-molecular targets for prognostic and therapeutic purposes. We examined CaP cells and biopsy samples representing different stages of the disease and found that PSMA, Gal-1, Gal-3, and Gal-8 are the most abundantly expressed glycoproteins. In contrast, other galectins such as Gal-2, 4-7, 9-13, were uniformly expressed at lower levels across all cell lines. However, biopsy samples showed markedly higher expression of PSMA, Gal-1 and Gal-3. Independently PSA and Gleason score at diagnosis correlated with the expression of PSMA, Gal-3. Additionally, the combined index of PSMA and Gal-3 expression positively correlated with Gleason score and was a better predictor of tumor aggressiveness. Together, our results recognize a tightly regulated "PSMA-galectin- pattern" that accompanies disease in CaP and highlight a major role for the combined PSMA and Gal-3 inhibitors along with standard chemotherapy for prostate cancer treatment. Inhibitor combination studies show enzalutamide (ENZ), 2-phosphonomethyl pentanedioic acid (2-PMPA), and GB1107 as highly cytotoxic for LNCaP and LNCaP-KD cells, while Docetaxel (DOC) + GB1107 show greater efficacy in PC-3 cells. Overall, 2-PMPA and GB1107 demonstrate synergistic cytotoxic effects with ENZ and DOC in various CaP cell lines.
The standard of care chemotherapy drug presently used to treat castration-resistant prostate cancer (CRPC), docetaxel (Doc), also develops chemoresistance, thereby reducing its clinical utility. Since resistance to chemotherapy drugs can be overcome by co-treatment with plant-based bio-active compounds we undertook the present study to evaluate if quercetin (Que), a flavonoid present in plants such as onions, apples, olives, and grapes can enhance the efficacy of Doc. We studied the separate and combined effects of Que and Doc at different doses and different combination approaches in two different prostate cancer cell lines, DU-145 (moderately aggressive) and PC-3 (very aggressive), and assessed the effects of these combinations on viability, proliferation, and apoptosis. Monotherapy with these drugs showed dose-dependent cytotoxicity; however, only Doc monotherapy showed a statistically significant difference in IC50 levels (IC50 = 4.05 ± 0.52 nM for PC-3 and IC50 = 2.26 ± 0.22 nM for DU-145). In combination treatment, we used three different treatment approaches (TAP). The concentrations and range analyzed were chosen based on the approximate cytotoxicity of 30-50% when the drugs were used individually. Our observations indicate that the most beneficial effect of the Que and Doc combination was obtained with the TAP-2 approach, which is pre-treatment with all doses of Que for 24 h followed by low doses of Doc for another 24 h. Using this approach, we observed synergism at low concentrations of Doc (0.5 and 1.0 nM) and all concentrations of Que. An additive effect was observed at moderate and high concentrations of Doc (1.5, 2.0, and 2.5 nM) and all concentrations of Que in both cell lines. The TAP-2 strategy was also helpful in overcoming Doc resistance in resistant CaP cells. In summary, Que improved the therapeutic effect of Doc in CRPC, and it is proposed that this improvement is mediated through multiple mechanisms. This study provides a novel therapeutic modality for an effective combination using Doc and Que to enhance the efficacy of Doc in an innocuous manner for Doc resistance and CRPC treatment.
In dry deciduous tropical forests, both seasons (winter and summer) offer habitats that are essential ecologically. How these seasonal changes affect soil properties and microbial communities is not yet fully understood. This study aimed to investigate the influence of seasonal fluctuations on soil characteristics and microbial populations. The soil moisture content dramatically increases in the summer. However, the soil pH only gradually shifts from acidic to slightly neutral. During the summer, electrical conductivity (EC) values range from 0.62 to 1.03 ds m-1, in contrast to their decline in the winter. The levels of soil macronutrients and micronutrients increase during the summer, as does the quantity of soil organic carbon (SOC). A two-way ANOVA analysis reveals limited impacts of seasonal fluctuations and specific geographic locations on the amounts of accessible nitrogen (N) and phosphorus (P). Moreover, dehydrogenase, nitrate reductase, and urease activities rise in the summer, while chitinase, protease, and acid phosphatase activities are more pronounced in the winter. The soil microbes were identified in both seasons through 16S rRNA and ITS (Internal Transcribed Spacer) gene sequencing. Results revealed Proteobacteria and Ascomycota as predominant bacterial and fungal phyla. However, Bacillus, Pseudomonas, and Burkholderia are dominant bacterial genera, and Aspergillus, Alternaria, and Trichoderma are dominant fungal genera in the forest soil samples. Dominant bacterial and fungal genera may play a role in essential ecosystem services such as soil health management and nutrient cycling. In both seasons, clear relationships exist between soil properties, including pH, moisture, iron (Fe), zinc (Zn), and microbial diversity. Enzymatic activities and microbial shift relate positively with soil parameters. This study highlights robust soil-microbial interactions that persist mainly in the top layers of tropical dry deciduous forests in the summer and winter seasons. It provides insights into the responses of soil-microbial communities to seasonal changes, advancing our understanding of ecosystem dynamics and biodiversity preservation.
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