Gauthierrode8480

Doxorubicin (DOX) is an anticancer chemotherapy drug that is widely used in clinical practice. It is well documented that DOX impairs baroreflex responsiveness and left ventricular function and enhances sympathetic activity, cardiac sympathetic afferent reflexes and oxidative stress, which contribute to hemodynamic deterioration. Because resistance training (RT)-induced cardioprotection has been observed in other animal models, the objective of this study was to assess the effects of RT during DOX treatment on hemodynamics, arterial baroreflex, cardiac autonomic tone, left ventricular function and oxidative stress in rats with DOX-induced cardiotoxicity. Male Wistar rats were submitted to a RT protocol (3 sets of 10 repetitions, 40% of one-repetition maximum (1RM) of intensity, 3 times per week, for 8 weeks). The rats were separated into 3 groups sedentary control, DOX sedentary (2.5 mg/kg of DOX intraperitoneal injection, once a week, for 6 weeks) and DOX + RT. After training or time control, the animals were anesthetized and 2 catheters were implanted for hemodynamic, arterial baroreflex and cardiac autonomic tone. Another group of animals was used to evaluate left ventricular function. We found that RT in DOX-treated rats decreased diastolic arterial pressure, heart rate, sympathetic tone and oxidative stress. In addition, RT increased arterial baroreflex sensitivity, vagal tone and left ventricular developed pressure in rats with DOX-induced cardiotoxicity. In summary, RT is a useful non-pharmacological strategy to attenuate DOX-induced cardiotoxicity.Chloroquine is used in the treatment of patients with COVID-19 infection, although there is no substantial evidence for a beneficial effect. Chloroquine is known to prolong the QRS and QTc interval on the ECG. To assess the effect of chloroquine on QRS and QTc intervals in COVID-19 patients, we included all inpatients treated with chloroquine for COVID-19 in the Spaarne Gasthuis (Haarlem/Hoofddorp, the Netherlands) and had an ECG performed both in the 72 h before and during or at least 48 h after treatment. We analyzed the (change in) QRS and QTc interval using the one-sample t-test. Of the 106 patients treated with chloroquine, 70 met the inclusion criteria. The average change in QRS interval was 6.0 ms (95% CI 3.3-8.7) and the average change in QTc interval was 32.6 ms (95% CI 24.9-40.2) corrected with the Bazett's formula and 38.1 ms (95% CI 30.4-45.9) corrected with the Fridericia's formula. In 19 of the 70 patients (27%), the QTc interval was above 500 ms after start of chloroquine treatment or the change in QTc interval was more than 60 ms. A heart rate above 90 bpm, renal dysfunction, and a QTc interval below 450 ms were risk factors for QTc interval prolongation. Chloroquine prolongs the QTc interval in a substantial number of patients, potentially causing rhythm disturbances. Since there is no substantial evidence for a beneficial effect of chloroquine, these results discourage its use in COVID-19 patients.Patients with triple-negative breast cancer (TNBC) have a relatively poor prognosis and cannot benefit from endocrine and/or targeted therapy. Considerable effort has been devoted toward the elucidation of the molecular mechanisms and potential diagnostic/therapeutic targets. However, it is inefficient and often ineffective to study the biological nuances of TNBC in large-scale clinical trials. In contrast, the investigation of the association between molecular alterations induced through controlled variables and relevant physiochemical characteristics of TNBC cells in laboratory settings is simple, definite, and efficient in exploring the molecular mechanisms. In this study, microgravity was selected as the sole variable of study as it can inhibit cancer cell viability, proliferation, metastasis, and chemoresistance. Identifying the key molecules that shift cancer cells toward a less aggressive phenotype may facilitate future TNBC studies. We focused on extracellular vesicles (EV) derived from TNBC MDA-MB-231 cells in microgravity, which mediate intercellular communication by transporting signaling molecules between cells. Our results show that in comparison with cells in full gravity, EV release rate decreased in microgravity while average EV size increased. In addition, we found EVs may be superior to cells in analyzing differentially expressed proteins, especially those that are down-regulated ones and usually unidentified or neglected in analysis of intact cellular contents. Proteomic analysis of both EVs and cells further revealed a significant correlation with GTPases and proliferation of MDA-MB-231 cells in microgravity. Altogether, our findings would further inspire in-depth correlative cancer biological studies and subsequent clinical research.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently emanating human infectious coronavirus that causes COVID-19 disease. On 11th March 2020, it has been announced as a pandemic by the World Health Organization (WHO). Recently, several repositioned drugs have been subjected to clinical investigations as anti-COVID-19 drugs. Here, in silico drug discovery tools were utilized to evaluate the binding affinities and features of eighteen anti-COVID-19 drug candidates against SARS-CoV-2 main protease (Mpro). Molecular docking calculations using Autodock Vina showed considerable binding affinities of the investigated drugs with docking scores ranging from - 5.3 to - 8.3 kcal/mol, with higher binding affinities for HIV drugs compared to the other antiviral drugs. Molecular dynamics (MD) simulations were performed for the predicted drug-Mpro complexes for 50 ns, followed by binding energy calculations utilizing molecular mechanics-generalized Born surface area (MM-GBSA) approach. MM-GBSA calculations demonstrated promising binding affinities of TMC-310911 and ritonavir towards SARS-CoV-2 Mpro, with binding energy values of - 52.8 and - 49.4 kcal/mol, respectively. Surpass potentialities of TMC-310911 and ritonavir are returned to their capabilities of forming multiple hydrogen bonds with the proximal amino acids inside Mpro's binding site. https://www.selleckchem.com/products/uamc-3203.html Structural and energetic analyses involving root-mean-square deviation, binding energy per-frame, center-of-mass distance, and hydrogen bond length demonstrated the stability of TMC-310911 and ritonavir inside the Mpro's active site over the 50 ns MD simulation. This study sheds light on HIV protease drugs as prospective SARS-CoV-2 Mpro inhibitors.