Bovine milk-derived extracellular vesicles enhance doxorubicin sensitivity in triple negative breast cancer cells by targeting metabolism and STAT signalling

Metastatic triple-negative breast cancer (TNBC) has a low 5-year survival rate of below 30% with systemic chemotherapy being the most widely used treatment. Bovine milk-derived extracellular vesicles (MEVs) have been previously demonstrated to have anti-cancer attributes. In this study, we isolated bovine MEVs from commercial milk and characterised them according to MISEV guidelines. Bovine MEVs sensitised TNBC cells to doxorubicin, resulting in reduced metabolic potential and cell-viability. Label-free quantitative proteomics of cells treated with MEVs and/or doxorubicin suggested that combinatorial treatment depleted various pro-tumorigenic interferon-inducible gene products and proteins with metabolic function, previously identified as therapeutic targets in TNBC. Combinatorial treatment also led to reduced abundance of various STAT proteins and their downstream oncogenic targets with roles in cell-cycle and apoptosis. Taken together, this study highlights the ability of bovine MEVs to sensitise TNBC cells to standard-of-care therapeutic drug doxorubicin, paving the way for novel treatment regimens.     

List of medicinal plants from Epigraphia Indica

It is of interest to list plants and its usage in olden days. The history of plants is closely related with the history of medicine since time immemorial. Various literature data shows the usage of medicinal plants. It is linked to various system of medicine like Siddha, Ayurveda and Unani. This is in practice for more than 5000 years. People in olden age had a detailed knowledge on these plants. Hence, we collected such data from the first five volumes of Epigraphia Indica, which was published, by the Archeological survey of India from 1882 to 1977. These data provides a framework on various plants and its usage in various ways, in different time period in human history. This helps us to drive valuable bio-medical information for application in modern scientific biomedical methods. We further plan to sort and glean such data so as to help in evaluating the total biomedical data in Epigraphia Indica to extract useful biological knowledge for application in evidence-based biomedicine.     

Pharmacokinetics of Bevidox in functionally different muscles of albino rat during prolonged intense activity

Intramuscular Bevidox treatment for five days influenced the metabolic status and functional efficiency of the different types of muscles in rat during exhaustion. Glycogen and protein depletion observed during exhaustion was alleviated by Bevidox treatment to a greater extent in cardiac and soleus over the other muscles. The improved metabolic function of the muscles during contractile stress has been related to stepped up energy cycle operations through increased transamination reactions and consequent feeding of glycogenic and ketogenic amino acids into oxidative pathway besides, rapid supply of glucose moieties by stimulated phosphorylase action on vitamin treatment.     

Weight History in Clinical Practice: The State of the Science and Future Directions

Eliciting a weight history can provide clinically important information to aid in treatment decision‐making. This view is consistent with the life course perspective of obesity and the aim of patient‐centered care, one of six domains of health care quality. However, thus far, the value and practicality of including a weight history in the clinical assessment and treatment of patients with obesity have not been systematically explored. For these reasons, the Clinical Committee of The Obesity Society established a task force to review and assess the available evidence to address five key questions. It is concluded that weight history is an essential component of the medical history for patients presenting with overweight or obesity, and there are strong and emerging data that demonstrate the importance of life stage, duration of exposure to obesity, maximum BMI, and group‐based trajectory modeling in predicting risk for increased morbidity and mortality. Consideration of these and other patient‐specific factors may improve risk stratification and clinical decision‐making for screening, counseling, and management. Recommendations are provided for the key elements that should be included in a weight history, and several needs for future clinical research are outlined.     

Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies

The recently reported “UK variant” (B.1.1.7) of SARS-CoV-2 is thought to be more infectious than previously circulating strains as a result of several changes, including the N501Y mutation. We present a 2.9-Å resolution cryo-electron microscopy (cryo-EM) structure of the complex between the ACE2 receptor and N501Y spike protein ectodomains that shows Y501 inserted into a cavity at the binding interface near Y41 of ACE2. This additional interaction provides a structural explanation for the increased ACE2 affinity of the N501Y mutant, and likely contributes to its increased infectivity. However, this mutation does not result in large structural changes, enabling important neutralization epitopes to be retained in the spike receptor binding domain. We confirmed this through biophysical assays and by determining cryo-EM structures of spike protein ectodomains bound to 2 representative potent neutralizing antibody fragments.     

Administration of myelin basic protein-coupled spleen cells prevents experimental allergic encephalitis

Intravenous administration of mouse myelin basic protein covalently coupled with chromic chloride to syngeneic spleen cells (MBP-SC) prevents the subsequent induction of experimental allergic encephalitis (EAE). Whereas 1 in 28 mice receiving MBP-SC developed EAE after immunization with mouse spinal cord homogenate (MSCH) and adjuvants, 16 out of 25 mice receiving ovalbumin-coupled spleen cells (OA-SC) had EAE following encephalitogenic challenge. The effect of administration of antigen-coupled spleen cells on in vitro proliferation responses is shown.