Impact of the gastrointestinal tract microbiota on cardiovascular health and pathophysiology

The microbiota of the gastrointestinal tract (GIT) is an extremely diverse community of microorganisms, and their collective genomes (microbiome) provide a vast arsenal of biological activities, in particular enzymatic ones, which are far from being fully elucidated. The study of the microbiota (and the microbiome) is receiving great interest from the biomedical community as it carries the potential to improve risk-prediction models, refine primary and secondary prevention efforts, and also design more appropriate and personalized therapies, including pharmacological ones. A growing body of evidence, though sometimes impaired by the limited number of subjects involved in the studies, suggests that GIT dysbiosis, i.e. the altered microbial composition, has an important role in causing and/or worsening cardiovascular disease (CVD). Bacterial translocation as well as the alteration of levels of microbe-derived metabolites can thus be important to monitor and modulate, because they may lead to initiation and progression of CVD, as well as to its establishment as chronic state. We hereby aim to provide readers with details on available resources and experimental approaches that are used in this fascinating field of biomedical research, and on some novelties on the impact of GIT microbiota on CVD

In vitro investigation of genoprotective and antioxidant effects of santalol in CCD-1079Sk human skin fibroblast cells

Santalum album (S. album) is a plant in the family of Santalacea that has been used in Indian traditional medicine for many years due to its pharmacological properties such as antiseptic, antipyretic, antidiabetic, diuretic, expectorant, stimulant, antibacterial and antifungal. In recent studies, apoptotic, cytotoxic, antiviral, anti-Helicobacter pylori, hepatoprotective activity of S. album has been found. The main molecule in S. album is santalol. Considering its wide variety of use in the traditional medicine and cosmetic industry, it has been considered important to clarify its genoprotective and antioxidant properties. Starting from this point of view, the aim of our study is to examine the antioxidant and genoprotective effects of santalol against H2O2 induced damage in healthy human skin fibroblast cell line CCD-1079Sk. The cytotoxicity of santalol was investigated with the measuerement of intracellular ATP content and MTT cytotoxicity test. According to the results of the cytotoxicity tests, the dose of santalol that caused an increasement in cell viability was chosen. The antioxidant effect of santalol was investigated by measuring protein carbonyl levels. Comet Assay was performed to determine the genoprotective properties of santalol. The results showed that 50 µM santalol treatment after 50 µM H2O2 exposure reduced the protein carbonyl level and DNA damage. This revealed the potential antioxidant and genoprotective properties of santalol. Considering the results obtained from these in vitro studies, it has been seen that santalol is worth continuing to study further in terms of protection from oxidative stress and genotoxicity

Mitochondrial dynamics imbalance and mitochondrial dysfunction contribute to the molecular cardiotoxic effects of lenvatinib

Lenvatinib is a tyrosine kinase inhibitor (TKI) approved for the treatment of resistant differentiated thyroid cancer, advanced renal cell carcinoma, unresectable hepatocellular carcinoma, and endometrial carcinoma. Although it is successful in cancer treatment, it can cause life-threatening side effects such as cardiotoxicity. The molecular mechanism of cardiotoxicity caused by lenvatinib is not fully known. In this study, the molecular mechanism of lenvatinib's cardiotoxicity was investigated focusing on mitochondrial toxicity in the H9c2 cardiomyoblastic cell line. Lenvatinib inhibited cell viability at 48 and 72 h exposure with three selected concentrations (1.25 mu M, 5 mu M and 10 mu M); and inhibited intracellular ATP after 72 h exposure compared to the control group. Mitochondrial membrane potential was decreased after 48 h and did not show significant changes after 72 h exposure. Evaluated with real-time PCR, mitochondrial dynamics (Mfn1, Mfn2, OPA1, DRP1, Fis1) expression levels after lenvatinib treatment significantly changed. Lenvatinib triggered the tendency from fusion to fission in mitochondria after 48 h exposure, and increased both fusion and fission after 72 h. The mtDNA ratio increased after 48 h and decreased after 72 h. ASK1, JNK and AMPKa2 increased. UCP2 showed downregulation, SOD2 level showed upregulation and Cat levels decreased after drug treatment. Nrf1 and Nrf2 also changed concentration-dependently. Protein carbonyl levels increased significantly after lenvatinib treatments indicating oxidative stress. The protein levels of the electron transport chain complexes, LONP1, UCP2, and P21 showed significant differences after lenvatinib treatment. The outcome of our study is expected to be a contribution to the understanding of the molecular mechanisms of TKI-induced cardiotoxicity

A comprehensive health effects assessment of the use of sanitizers and disinfectants during COVID-19 pandemic: a global survey

COVID-19 has affected all aspects of human life so far. From the outset of the pandemic, preventing the spread of COVID-19 through the observance of health protocols, especially the use of sanitizers and disinfectants was given more attention. Despite the effectiveness of disinfection chemicals in controlling and preventing COVID-19, there are critical concerns about their adverse effects on human health. This study aims to assess the health effects of sanitizers and disinfectants on a global scale. A total of 91,056 participants from 154 countries participated in this cross-sectional study. Information on the use of sanitizers and disinfectants and health was collected using an electronic questionnaire, which was translated into 26 languages via web-based platforms. The findings of this study suggest that detergents, alcohol-based substances, and chlorinated compounds emerged as the most prevalent chemical agents compared to other sanitizers and disinfectants examined. Most frequently reported health issues include skin effects and respiratory effects. The Chi-square test showed a significant association between chlorinated compounds (sodium hypochlorite and per-chlorine) with all possible health effects under investigation (p-value <0.001). Examination of risk factors based on multivariate logistic regression analysis showed that alcohols and alcohols-based materials were associated with skin effects (OR, 1.98; 95%CI, 1.87-2.09), per-chlorine was associated with eye effects (OR, 1.83; 95%CI, 1.74-1.93), and highly likely with itching and throat irritation (OR, 2.00; 95%CI, 1.90-2.11). Furthermore, formaldehyde was associated with a higher prevalence of neurological effects (OR, 2.17; 95%CI, 1.92-2.44). Furthermore, formaldehyde was associated with a higher prevalence of neurological effects (OR, 2.17; 95%CI, 1.92-2.44). The use of sodium hypochlorite and per-chlorine also had a high chance of having respiratory effects. The findings of the current study suggest that health authorities need to implement more awareness programs about the side effects of using sanitizers and disinfectants during viral epidemics especially when they are used or overused