A comprehensive review on the risks assessment and treatment options for Sarcopenia in people with diabetes.

Objectives: This comprehensive review aims to examine the reciprocal interplay between Type 2 diabetes mellitus (T2DM) and sarcopenia, identify prevailing research gaps, and discuss therapeutic approaches and measures to enhance healthcare practices within hospital settings. Methods: A thorough literature review was conducted to gather relevant studies and articles on the relationship between T2DM and sarcopenia. Various databases were searched, including Google Scholar, PubMed, Scopus, and Science Direct databases. The search terms included T2DM, sarcopenia, inflammation, insulin resistance, advanced glycation end products, oxidative stress, muscle dimensions, muscle strength, muscle performance, aging, nutrition, hormone levels, and physical activity. The collected articles were critically analysed to extract key findings and identify gaps in current research. Results: The prevalence and incidence of metabolic and musculoskeletal disorders, notably T2DM and sarcopenia, have surged in recent years. T2DM is marked by inflammation, insulin resistance, accumulation of advanced glycation end products, and oxidative stress, while sarcopenia involves a progressive decline in skeletal muscle mass and function. The review underscores the age-related correlation between sarcopenia and adverse outcomes like fractures, falls, and mortality. Research gaps regarding optimal nutritional interventions for individuals with T2DM and sarcopenia are identified, emphasizing the necessity for further investigation in this area. Conclusions: The reciprocal interplay between T2DM and sarcopenia holds significant importance. Further research is warranted to address knowledge gaps, particularly in utilizing precise measurement tools during clinical trials. Lifestyle modifications appear beneficial for individuals with T2DM and sarcopenia. Additionally, practical nutritional interventions require investigation to optimize healthcare practices in hospital settings. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01262-w.

Unraveling the Molecular Mechanisms of Activated Protein C (APC) in Mitigating Reperfusion Injury and Cardiac Ischemia: a Promising Avenue for Novel Therapeutic Interventions.

Ischemic heart disease, which results from plaque formation in the coronary arteries, hinders the flow of oxygenated blood to the heart, leading to ischemia. Reperfusion injury remains a significant challenge for researchers, and the mechanisms underlying myocardial ischemia-reperfusion injury (MIRI) are not entirely understood. The review directs future research into potential targets in clinical treatment based on our present understanding of the pathophysiological mechanisms of MIRI. The study provides insights into the mechanisms underlying MIRI and offers direction for future research in this area. The use of targeted therapies may hold promise in improving cardiac function in the elderly and minimizing the adverse effects of revascularization therapies. The purpose of this review is to analyze the role of activated protein C (APC) in the pathogenesis of ischemic heart disease, heart failure, and myocardial ischemia-reperfusion injury, and discuss the potential of APC-based therapeutics.

The selfish yeast plasmid exploits a SWI/SNF-type chromatin remodeling complex for hitchhiking on chromosomes and ensuring high-fidelity propagation.

Extra-chromosomal selfish DNA elements can evade the risk of being lost at every generation by behaving as chromosome appendages, thereby ensuring high fidelity segregation and stable persistence in host cell populations. The yeast 2-micron plasmid and episomes of the mammalian gammaherpes and papilloma viruses that tether to chromosomes and segregate by hitchhiking on them exemplify this strategy. We document for the first time the utilization of a SWI/SNF-type chromatin remodeling complex as a conduit for chromosome association by a selfish element. One principal mechanism for chromosome tethering by the 2-micron plasmid is the bridging interaction of the plasmid partitioning proteins (Rep1 and Rep2) with the yeast RSC2 complex and the plasmid partitioning locus STB. We substantiate this model by multiple lines of evidence derived from genomics, cell biology and interaction analyses. We describe a Rep-STB bypass system in which a plasmid engineered to non-covalently associate with the RSC complex mimics segregation by chromosome hitchhiking. Given the ubiquitous prevalence of SWI/SNF family chromatin remodeling complexes among eukaryotes, it is likely that the 2-micron plasmid paradigm or analogous ones will be encountered among other eukaryotic selfish elements.

Evidence of kinesin motors involved in stable kinetochore assembly during early meiosis.

During mitosis, the budding yeast, kinetochores remain attached to microtubules, except for a brief period during S phase. Sister-kinetochores separate into two clusters (bilobed organization) upon stable end-on attachment to microtubules emanating from opposite spindle poles. However, in meiosis, the outer kinetochore protein (Ndc80) reassembles at the centromeres much later after prophase I, establishing new kinetochore-microtubule attachments. Perhaps due to this, despite homolog bi-orientation, we observed that the Ndc80 are linearly dispersed between spindle poles during metaphase I of meiosis. The presence of end-on attachment marker Dam1 as a cluster near each pole suggests one of the other possibilities that the pole-proximal and pole-distal kinetochores are attached end-on and laterally to the microtubules, respectively. Colocalization studies of kinetochores and kinesin motors suggest that budding yeast kinesin 5, Cin8, and Kip1 perhaps localize to the end-on attached kinetochores while kinesin 8 and Kip3 resides at all the kinetochores. Our findings, including kinesin 5 and Ndc80 coappearance after prophase I and reduced Ndc80 levels in cin8 null mutant, suggest that kinesin motors are crucial for kinetochore reassembly and stability during early meiosis. Thus, this work reports yet another meiosis specific function of kinesin motors.

Clinical manifestations of human monkeypox infection and implications for outbreak strategy.

Monkeypox is an orthopoxvirus-based zoonotic illness that causes symptoms similar to smallpox in humans. Health care workers around the world are making it a priority to educate themselves on the many clinical manifestations and treatment options for this virus as public health agencies strive to stop the current outbreak. The infected do not have access to any treatment at this time. However, information obtained from the smallpox pandemic has led researchers to examine vaccinia immune globulin (IVG), tecovirimat, and cidofovir as viable treatments for monkeypox. Moreover, medication like tecovirimat may be given in extreme circumstances, and supportive therapy can help with symptom relief. The European Medicines Agency (EMA) certified tecovirimat as safe and effective against monkeypox in 2022, per the World Health Organization (WHO). As there are now no established guidelines for alleviating these symptoms, the efficacy of these treatments is highly questionable. Some high-profile cases in recent years have cast doubt on the long-held belief that this illness is rare and always resolves itself without treatment. We aimed to conduct this review to get a deeper comprehension of the evolving epidemiology of monkeypox by analysing such factors as the number of confirmed, probable, and potential cases, the median age at presentation, the mortality rate, and the geographic distribution of the disease. This study offers an updated review of monkeypox and the clinical treatments that are currently available as a result of the worldwide epidemics.

The selfish yeast plasmid utilizes the condensin complex and condensed chromatin for faithful partitioning.

Equipartitioning by chromosome association and copy number correction by DNA amplification are at the heart of the evolutionary success of the selfish yeast 2-micron plasmid. The present analysis reveals frequent plasmid presence near telomeres (TELs) and centromeres (CENs) in mitotic cells, with a preference towards the former. Inactivation of Cdc14 causes plasmid missegregation, which is correlated to the non-disjunction of TELs (and of rDNA) under this condition. Induced missegregation of chromosome XII, one of the largest yeast chromosomes which harbors the rDNA array and is highly dependent on the condensin complex for proper disjunction, increases 2-micron plasmid missegregation. This is not the case when chromosome III, one of the smallest chromosomes, is forced to missegregate. Plasmid stability decreases when the condensin subunit Brn1 is inactivated. Brn1 is recruited to the plasmid partitioning locus (STB) with the assistance of the plasmid-coded partitioning proteins Rep1 and Rep2. Furthermore, in a dihybrid assay, Brn1 interacts with Rep1-Rep2. Taken together, these findings support a role for condensin and/or condensed chromatin in 2-micron plasmid propagation. They suggest that condensed chromosome loci are among favored sites utilized by the plasmid for its chromosome-associated segregation. By homing to condensed/quiescent chromosome locales, and not over-perturbing genome homeostasis, the plasmid may minimize fitness conflicts with its host. Analogous persistence strategies may be utilized by other extrachromosomal selfish genomes, for example, episomes of mammalian viruses that hitchhike on host chromosomes for their stable maintenance.

Spectroscopic and molecular modelling study of binding mechanism of bovine serum albumin with phosmet.

Phosmet exerts its neurotoxicity by inhibiting acetylcholinesterase that catalyzes the degradation of acetylcholine (a neurotransmitter). Serum proteins are known to influence the biodistribution of various endogenous and exogenous compounds. In the present study, the binding interactions of phosmet with bovine serum albumin (BSA) was investigated to determine the free concentration of phosmet for its neurotoxicity. The binding mechanism was studied using fluorescence, UV-Vis absorption spectroscopy, circular dichroism (CD), and molecular docking techniques. UV-Vis absorption data showed an increase in absorbance of BSA upon binding with phosmet with a slight red-shift in the peak around 280 nm. Intrinsic fluorescence of BSA was quenched in the presence of phosmet. The quenching was observed to be inversely correlated to the temperature that indicated the formation of ground state non-fluorescent complex (static quenching). Binding constant values and n values for the binding of phosmet with BSA at three different temperatures confirmed non-covalent binding interactions with a single set of equivalent binding sites. Thermodynamic parameters ∆G (-137.40 ± 3.58 kJ mol-1); ΔH (-16.33 ± 5.28 kJ mol-1) and ΔS(-469 ± 12.45 kJ mol-1) confirmed that the binding was spontaneous and non-covalent interactions like electrostatic, hydrogen bonding and van der Waals forces played an important role in the binding. The CD data indicated the conformational change in BSA upon binding with phosmet which resulted in a change in the melting temperature. Molecular docking presented the binding model for BSA-phosmet complex and displayed that non-covalent interactions played a significant role in the binding mechanism.