Cardioprotective effects of arjunolic acid in LPS-stimulated H9C2 and C2C12 myotubes via the My88-dependent TLR4 signaling pathway.

CONTEXT: Arjunolic acid (AA) is a triterpenoid saponin found in Terminalia arjuna (Roxb.) Wight & Arn. (Combretaceae). It exerts cardiovascular protective effects as a phytomedicine. However, it is unclear how AA exerts the effects at the molecular level. OBJECTIVE: This study investigates the cardioprotective effects of arjunolic acid (AA) via MyD88-dependant TLR4 downstream signaling marker expression. MATERIALS AND METHODS: The MTT viability assay was used to assess the cytotoxicity of AA. LPS induced in vitro cardiovascular disease model was developed in H9C2 and C2C12 myotubes. The treatment groups were designed such as control (untreated), LPS control, positive control (LPS + pyrrolidine dithiocarbamate (PDTC)-25 µM), and treatment groups were co-treated with LPS and three concentrations of AA (50, 75, and 100 µM) for 24 h. The changes in the expression of TLR4 downstream signaling markers were evaluated through High Content Screening (HCS) and Western Blot (WB) analysis. RESULTS: After 24 h of co-treatment, the expression of TLR4, MyD88, MAPK, JNK, and NF-κB markers were upregulated significantly (2-6 times) in the LPS-treated groups compared to the untreated control in both HCS and WB experiments. Evidently, the HCS analysis revealed that MyD88, NF-κB, p38, and JNK were significantly downregulated in the H9C2 myotube in the AA treated groups. In HCS, the expression of NF-κB was downregulated in C2C12. Additionally, TLR4 expression was downregulated in both H9C2 and C2C12 myotubes in the WB experiment. DISCUSSION AND CONCLUSIONS: TLR4 marker expression in H9C2 and C2C12 myotubes was subsequently decreased by AA treatment, suggesting possible cardioprotective effects of AA.

A Systematic Review of Molecular Hydrogen Therapy in Cancer Management.

BACKGROUND: Cancer remains a challenging target to cure, with present therapeutic methods unable to exhibit restorative outcomes without causing severe negative effects. Molecular hydrogen (H2) has been reported to be a promising adjunctive therapy for cancer treatment, having the capability to induce anti-proliferative, anti-oxidative, pro-apoptotic and anti-tumoural effects. This review summarises the findings from various articles on the mechanism, treatment outcomes, and overall effectiveness of H2 therapy on cancer management. METHODS: Using Cochrane, PubMed, and Google Scholar as the search engines, full-text articles in the scope of the study, written in English and within 10 years of publication were selected. RESULTS: Out of the 677 articles, 27 articles fulfilled the eligibility criteria, where data was compiled into a table, outlining the general characteristics and findings. Throughout the different forms of H2 administration, study design and types of cancers reported, outcomes were found to be consistent. CONCLUSION: From our analysis, H2 plays a promising therapeutic role as an independent therapy as well as an adjuvant in combination therapy, resulting in an overall improvement in survivability, quality of life, blood parameters, and tumour reduction. Although more comprehensive research is needed, given the promising outcomes, H2 is worth considering for use as a complement to current cancer therapy.

Review: antimicrobial properties of allicin used alone or in combination with other medications.

Garlic (Allium sativum L.) is a well-known spice widely utilised for its medicinal properties. There is an extensive record of the many beneficial health effects of garlic which can be traced back to as early as the ancient Egyptian era. One of the most studied properties of garlic is its ability to cure certain ailments caused by infections. In the 1940s, the antimicrobial activities exhibited by garlic were first reported to be due to allicin, a volatile compound extracted from raw garlic. Since then, allicin has been widely investigated for its putative inhibitory activities against a wide range of microorganisms. Allicin has demonstrated a preference for targeting the thiol-containing proteins and/or enzymes in microorganisms. It has also demonstrated the ability to regulate several genes essential for the virulence of microorganisms. Recently, it was reported that allicin may function better in combination with other antimicrobials compared to when used alone. When used in combination with antibiotics or antifungals, allicin enhanced the antimicrobial activities of these substances and improved the antimicrobial efficacy. Hence, it is likely that combination therapy of allicin with additional antimicrobial drug(s) could serve as a viable alternative for combating rising antimicrobial resistance. This review focuses on the antimicrobial activities exhibited by allicin alone as well as in combination with other substances. The mechanisms of action of allicin elucidated by some of the studies are also highlighted in the present review in order to provide a comprehensive overview of this versatile bioactive compound and the mechanistic evidence supporting its potential use in antimicrobial therapy.

Value Frameworks in Oncology: Comparative Analysis and Implications to the Pharmaceutical Industry.

BACKGROUND: As the cost of oncology care continues to rise, composite value models that variably capture the diverse concerns of patients, physicians, payers, policymakers, and the pharmaceutical industry have begun to take shape. OBJECTIVES: To review the capabilities and limitations of 5 of the most notable value frameworks in oncology that have emerged in recent years and to compare their relative value and application among the intended stakeholders. METHODS: We compared the methodology of the American Society of Clinical Oncology (ASCO) Value Framework (version 2.0), the National Comprehensive Cancer Network Evidence Blocks, Memorial Sloan Kettering Cancer Center DrugAbacus, the Institute for Clinical and Economic Review Value Assessment Framework, and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale, using a side-by-side comparative approach in terms of the input, scoring methodology, and output of each framework. In addition, we gleaned stakeholder insights about these frameworks and their potential real-world applications through dialogues with physicians and payers, as well as through secondary research and an aggregate analysis of previously published survey results. RESULTS: The analysis identified several framework-specific themes in their respective focus on clinical trial elements, breadth of evidence, evidence weighting, scoring methodology, and value to stakeholders. Our dialogues with physicians and our aggregate analysis of previous surveys revealed a varying level of awareness of, and use of, each of the value frameworks in clinical practice. For example, although the ASCO Value Framework appears nascent in clinical practice, physicians believe that the frameworks will be more useful in practice in the future as they become more established and as their outputs are more widely accepted. CONCLUSIONS: Along with patients and payers, who bear the burden of treatment costs, physicians and policymakers have waded into the discussion of defining value in oncology care, as well as pharmaceutical companies that seek to understand the impact of these value frameworks on each stakeholder, as they model the value and financial threshold of innovative, high-cost drugs.