Protective effect of Vitex altissima L.f. bark extract on cisplatin-induced renal injury in Wistar rats

Cisplatin (CP) is a commonly used chemotherapeutic drug. The major limiting factor in the use of CP is the side effects in normal tissues, including the kidney. Since ancient times, medicinal plants are rich sources of various bioactive constituents used to treat multiple ailments, including drug toxicities. The present work is a preliminary study to explore the renoprotective actions of methanolic extract of Vitex altissima L.f. bark (Va) against CP-induced renal damage in Wistar rats. Va was found to have potent radical scavenging activity than metal ion reducing power properties, compared with ascorbic acid. Further, Va was evaluated for nephroprotective activity in rats induced by CP (8 mg/kg; intraperitoneal) on the 7th day. The animals were grouped (n = 6) and treated with Va (100 and 200 mg/kg) orally for 14 days. The outcomes of the study found that CP significantly (P < 0.001) altered the oxidative stress markers (MDA, SOD and CAT), serum urea and creatinine levels. The administration of Va significantly halted the toxic condition and maintained it towards normal levels. The higher dose of Va significantly (P < 0.001) raised the SOD and CAT levels and halted the MDA levels than the low dose. Also, a higher dose of Va maintained the normal integrity of the histopathological studies of kidneys than a low dose. The present study demonstrates that V. altissima can attenuate the oxidative stress induced by CP by enhancing the endogenous antioxidant levels and depleting the lipid peroxidation levels

Gamma-phage lysin PlyG sequence-based synthetic peptides coupled with Qdot-nanocrystals are useful for developing detection methods for Bacillus anthracis by using its surrogates, B. anthracis-Sterne and B. cereus-4342

<p>Abstract</p> <p>Background</p> <p>Previous reports of site-directed deletion analysis on gamma (γ)-phage lysin protein (PlyG) have demonstrated that removal of a short amino acid sequence in the C-terminal region encompassing a 10-amino acid motif (190LKMTADFILQ199) abrogates its binding activity specific to the cell wall of <it>Bacillus anthracis</it>. Whether short synthetic peptides representing the10-amino acid PlyG putative binding motif flanked by surrounding N- and C-terminal residues also selectively bind to the bacterial cell wall has not been evaluated. If such peptides do demonstrate selective binding to the cell wall, they could serve as bio-probes towards developing detection technologies for <it>B. anthracis</it>. Furthermore, by using <it>B. anthracis </it>(Sterne, 34F2), an animal vaccine and <it>B. cereus</it>-<it>4342</it>, a γ-phage susceptible rare strain as surrogates of <it>B. anthracis</it>, development of proof-of-concepts for <it>B. anthracis </it>are feasible.</p> <p>Results</p> <p>Using four different methods, we evaluated six synthetic peptides representing the putative binding motif including flanking sequences (PlyG-P1 through P6) for the bacterial cell wall binding capacity. Our analysis identified PlyG-P1, PlyG-P3 and PlyG-P5 to have binding capability to both <it>B. anthracis </it>(Sterne, 34F2) and <it>B. cereus-</it>4342. The peptides however did not bind to <it>B. cereus</it>-11778, <it>B. thuringiensis</it>, and <it>B. cereus</it>-10876 suggesting their specificity for <it>B. anthracis</it>-Sterne and <it>B. cereus</it>-<it>4342</it>. PlyG-P3 in combination with fluorescent light microscopy detected even a single bacterium in plasma spiked with the bacteria.</p> <p>Conclusion</p> <p>Overall, these studies illustrate that the short 10-amino acid sequence 'LKMTADFILQ' in fact is a stand-alone bacterial cell wall-binding motif of PlyG. In principle, synthetic peptides PlyG-P1, PlyG-P3 and PlyG-P5, especially PlyG-P3 coupled with Qdot-nanocrystals are useful as high-sensitivity bio-probes in developing detection technologies for <it>B. anthracis</it>.</p

The Effectiveness of the Biopatch Disc in Decreasing MRSA in Peripherally Inserted Intravenous Catheters

Methicillin-resistant Staphylococcus aureus (MRSA), drug-resistant bacterial infection, is a pressing global health care issue that decreases patientsâ quality of life and places a high burden on health care delivery systems. The purpose of this quality improvement evaluation project was to evaluate an infection prevention management program derived from evidence-based research to decrease the incidence of MRSA in peripherally inserted intravenous catheters (PIVs) in acute care settings through the utilization of the Biopatch disc. The practice-focused question addressed whether the use the Biopatch disc over a 6-month period in acute care would coincide with a reduction of the incidence of MRSA infection in PIVs. The number of MRSA infections at the hospital project site during a 30-day pre-implementation period was compared to those during 2 post-implementation phases of Biopatch disc usage. Demingâs model for continuous quality improvement served as the conceptual framework. Data were analyzed using the Fisherâs exact test. The plan, do, study, and act phases of Demingâs model were used in a rapid-cycle format during the evaluation, which allowed for changes in protocol as feedback was gathered. Results suggest that the Biopatch disc could possibly decrease the incidence of MRSA in PIVs when utilized according to organizational protocols. Infection prevention, quality improvement, and risk management teams should be able to collaborate and develop local and regional surveillance programs based on use of the Biopatch. This project had the potential to effect positive social change by improving the quality of life and safety of patients in acute care setting, and by reducing costs of healthcare overall so as to promote broader access to quality healthcare across populations

Osteoarthritis: insights into pathogenesis and futuristic treatment strategies

Osteoarthritis is the most common musculoskeletal condition world over that causes significant health, economic, and societal burdens. Till date, no therapeutic approaches have been able to stop or delay the progression of osteoarthritis satisfactorily. Structural and clinical features of the disease are characterized by a high inter-patient variability. This heterogeneity is believed to be a major factor associated with the complexity of osteoarthritis and the on-going difficulty to identify a single therapy for all sub-groups. The objective of this review is to highlight recent advances in the understanding of the pathophysiology of osteoarthritis and latest biological treatments available, their limitations and to bring to notice the latest state-of-the-art on-going research on novel therapies. For this study we searched different online databases such as PubMed and Cochrane Library from inception to January 2022. We identified eligible studies on the pathophysiologic findings, prevalence, or incidence of knee osteoarthritis, available treatments, and current research for future therapies. Besides the availability of vast literature on cartilage extracellular matrix and its changes in osteoarthritis, the complicated mechanism of the disease still has missing links in the chain. Presently, biological treatments such as platelet rich plasma, bone marrow mesenchymal stem cells and autologous fragmented adipose tissue containing structural vascular fraction are commonly used. In future, gene therapy could become a potential option for treating the disease. More extensive insights into the pathophysiology of osteoarthritis will be helpful in designing therapies that can curb structural progression and promote cartilage regeneration thus providing more potent relief from painful and disabling condition associated with osteoarthritis

Isolation, characterization, and biological evaluation of flavonols and 1,2-diphenylethanes from Bauhinia vahlii

In this study, three known flavonols, namely kaempferol (1), ombuin (2), and quercetin (3), and three known 1,2-diphenylethanes, namely 5-(2-hydroxyphenethyl)-3-methoxy-2-methylphenol (4), 2-(3,5-dimethoxyphenethyl) phenol (5) and 2-(2-hydroxyphenethyl)-4,6-dimethoxyphenol (6) from the methanolic extract (ME) of Bauhinia vahlii were identified and sucessfully isolated. They were also evaluated for in vitro antioxidant, anti-inflammatory, anti-gout and anticancer effects. Compound 3 (26.00±2.17 µg/mL) showed an almost equivalent IC50 value of standard drug (25.55±2.80 µg/mL) against superoxide free radicals. Moreover, compound 3 showed significant inhibition of COXs and 5-LOX enzymes, while compounds 1, 2, 4 and 5 exhibited good inhibition of XO enzymes. Except for compound 5, all compounds showed a significant reduction of cell growth lysis of MCF-7, DLD-1, HeLa, and A549. Besides, all the metabolites and ME showed a very weak degree of specificity against NHME, indicates less toxicity to normal cells. The results suggest that B. vahlii can be a favourable natural source for the treatment of oxidative stress, inflammation, gout and cancer, and these actions are linked to the natural active compounds 1, 3, 4 and 6

EXOSOME NANOCARRIERS: BASIC BIOLOGY, DIAGNOSIS, NOVEL AND PERSPECTIVE APPROACH IN DRUG DELIVERY SYSTEMS: A REVIEW

Exosomes are the extracellular vesicles surrounded by a phospholipid bilayer shed from all cell varieties and plays a significant role in the communication and Transportation of materials between the cells due to their ability to transfer the proteins and nucleic acids from One cell to the another cell. Analogous in size and performance to synthetic nanoparticles, exosomes provide several Advantages, rendering them the foremost promising candidates for targeted drug or gene delivery vehicles. This review highlights the isolation techniques and delivery potential of exosomes, and equally presents research or analysis gaps for enhancing the use of natural vesicles for delivery functions. Exosome-based drug formulations can be applied to an extensive variety of diseases such as various infectious, cardiovascular, cancer and neurodegenerative disorders. Mostly, exosomes combine the benefits of both synthetic nanocarriers and cell-mediated drug delivery systems however avoiding their limitations

Isolation, characterization, and biological evaluation of flavonols and 1,2-diphenylethanes from Bauhinia vahlii

312-319In this study, three known flavonols, namely kaempferol (1), ombuin (2), and quercetin (3), and three known 1,2-diphenylethanes, namely 5-(2-hydroxyphenethyl)-3-methoxy-2-methylphenol (4), 2-(3,5-dimethoxyphenethyl) phenol (5) and 2-(2-hydroxyphenethyl)-4,6-dimethoxyphenol (6) from the methanolic extract (ME) of Bauhinia vahlii were identified and sucessfully isolated. They were also evaluated for in vitro antioxidant, anti-inflammatory, anti-gout and anticancer effects. Compound 3 (26.00±2.17 µg/mL) showed an almost equivalent IC50 value of standard drug (25.55±2.80 µg/mL) against superoxide free radicals. Moreover, compound 3 showed significant inhibition of COXs and 5-LOX enzymes, while compounds 1, 2, 4 and 5 exhibited good inhibition of XO enzymes. Except for compound 5, all compounds showed a significant reduction of cell growth lysis of MCF-7, DLD-1, HeLa, and A549. Besides, all the metabolites and ME showed a very weak degree of specificity against NHME, indicates less toxicity to normal cells. The results suggest that B. vahlii can be a favourable natural source for the treatment of oxidative stress, inflammation, gout and cancer, and these actions are linked to the natural active compounds 1, 3, 4 and 6

Manglicolous lichen Parmotrema tinctorum (Despr. ex Nyl.) Hale: Isolation, characterization and biological evaluation

856-861The chemical examination of the ethanolic extract of manglicolous lichen Parmotrema tinctorum (Pt-Et) has resulted in isolation of six known metabolites, i.e., methyl-β-orcinolcarboxylate (1), isolecanoric acid (2), methyl-2,6-dihydroxy-4-methylbenzoate (3), haematommic acid (4), ethyl haematommate (5), and atranorin (6). All the isolates 1-6 and Pt-Et have been screened against DPPH and superoxide free radicals, six different cancer cell lines (MDA-MB-231, SW620, HeLa, FADU, A549, SKOV3) and one normal human cell line (NHME). Compound 3 exhibits prominent inhibition of superoxide free radical, which appears to be better than that of the standard (ascorbic acid) with an IC50 value of 26.0 µg/mL. From the SRB assay results, it is observed that the better IC50 values have been obtained from 4 and 5 on HeLa, FADU, and A549, respectively. In addition, all the tested samples show low cell lysis on NHME, which indicates low toxicity. Consequently, the outcomes revealed that P. tinctorum could be a new source to treat oxidative stress and cancer. This work is the first report of antioxidant and cytotoxicity studies on the isolated metabolites 1-6

Identification of XMRV Infection-Associated microRNAs in Four Cell Types in Culture

INTRODUCTION: XMRV is a gammaretrovirus that was thought to be associated with prostate cancer (PC) and chronic fatigue syndrome (CFS) in humans until recently. The virus is culturable in various cells of human origin like the lymphocytes, NK cells, neuronal cells, and prostate cell lines. MicroRNAs (miRNA), which regulate gene expression, were so far not identified in cells infected with XMRV in culture. METHODS: Two prostate cell lines (LNCaP and DU145) and two primary cells, Peripheral Blood Lymphocytes [PBL] and Monocyte-derived Macrophages [MDM] were infected with XMRV. Total mRNA was extracted from mock- and virus-infected cells at 6, 24 and 48 hours post infection and evaluated for microRNA profile in a microarray. RESULTS: MicroRNA expression profiles of XMRV-infected continuous prostate cancer cell lines differ from that of virus-infected primary cells (PBL and MDMs). miR-193a-3p and miRPlus-E1245 observed to be specific to XMRV infection in all 4 cell types. While miR-193a-3p levels were down regulated miRPlus-E1245 on the other hand exhibited varied expression profile between the 4 cell types. DISCUSSION: The present study clearly demonstrates that cellular microRNAs are expressed during XMRV infection of human cells and this is the first report demonstrating the regulation of miR193a-3p and miRPlus-E1245 during XMRV infection in four different human cell types

Perspective: Vitamin D supplementation prevents rickets and acute respiratory infections when given as daily maintenance but not as intermittent bolus: implications for COVID-19.

The value of vitamin D supplementation in the treatment or prevention of various conditions is often viewed with scepticism as a result of contradictory results of randomised trials. It is now becoming apparent that there is a pattern to these inconsistencies. A recent large trial has shown that high-dose intermittent bolus vitamin D therapy is ineffective at preventing rickets - the condition that is most unequivocally caused by vitamin D deficiency. There is a plausible biological explanation since high-dose bolus replacement induces long-term expression of the catabolic enzyme 24-hydroxylase and fibroblast growth factor 23, both of which have vitamin D inactivating effects. Meta-analyses of vitamin D supplementation in prevention of acute respiratory infection and trials in tuberculosis and other conditions also support efficacy of low dose daily maintenance rather than intermittent bolus dosing. This is particularly relevant during the current COVID-19 pandemic given the well-documented associations between COVID-19 risk and vitamin D deficiency. We would urge that clinicians take note of these findings and give strong support to widespread use of daily vitamin D supplementation