Eisosome protein Pil1 regulates mitochondrial morphology, mitophagy, and cell death in Saccharomyces cerevisiae.

Mitochondrial morphology and dynamics maintain mitochondrial integrity by regulating its size, shape, distribution, and connectivity, thereby modulating various cellular processes. Several studies have established a functional link between mitochondrial dynamics, mitophagy, and cell death, but further investigation is needed to identify specific proteins involved in mitochondrial dynamics. Any alteration in the integrity of mitochondria has severe ramifications that include disorders like cancer and neurodegeneration. In this study, we used budding yeast as a model organism and found that Pil1, the major component of the eisosome complex, also localizes to the periphery of mitochondria. Interestingly, the absence of Pil1 causes the branched tubular morphology of mitochondria to be abnormally fused or aggregated, whereas its overexpression leads to mitochondrial fragmentation. Most importantly, pil1Δ cells are defective in mitophagy and bulk autophagy, resulting in elevated levels of reactive oxygen species and protein aggregates. In addition, we show that pil1Δ cells are more prone to cell death. Yeast two-hybrid analysis and co-immunoprecipitations show the interaction of Pil1 with two major proteins in mitochondrial fission, Fis1 and Dnm1. Additionally, our data suggest that the role of Pil1 in maintaining mitochondrial shape is dependent on Fis1 and Dnm1, but it functions independently in mitophagy and cell death pathways. Together, our data suggest that Pil1, an eisosome protein, is a novel regulator of mitochondrial morphology, mitophagy, and cell death.

Metallic ion-based graphene oxide functionalized silk fibroin-based dressing promotes wound healing via improved bactericidal outcomes and faster re-epithelization.

An ideal wound dressing material should enhance the wound healing process and must avoid bacterial contamination. In this study, the synergistic effect of graphene oxide (GO), silver (Ag) and magnesium (Mg) based silk electrospun nanofibrous film on wound healing was evaluated. It reports the influence of essential elements Mg and Ag during the skin regeneration process. Silver and magnesium nanoparticles were doped in graphene oxide. The goal of the present study was to fabricate an electrospun nanofibrous patch with nanoscale fillers to improve the wound recuperation manner and decrease the recuperation time to forestall microorganism infections and improve cellular behavior. Doping was done to insert Ag+and Mg2+ions in the crystal lattice of GO to overcome the disadvantage of aggregation of Ag and Mg nanoparticles. In this study, Mg2+and Ag+ions doped GO functionalized silk fibroin/PVA dressing material was prepared using the electrospinning technique. It was found that, Mg-GO@NSF/PVA and Ag/Mg-GO@NSF/PVA film possess good cytocompatibility, low hemolytic effect and effective antibacterial and anti-biofilm activities. Furthermore, their improved hydrophilicity and mid-range water vapor transmission rate allow them to be a suitable wound dressing material. Tensile strength of the composite silk film were enhanced relatively to silk/PVA film. The effect of prepared film on wound repair were investigated in excision rat model. It indicates, the wound covered with Ag/Mg-GO@NSF/PVA film showed the highest wound contraction rate and re-epithelization, allowing faster repair of wound sites. In conclusion, the development of metallic ions doped GO based silk fibroin/PVA is a promising approach towards development of antibiotic free wound dressing material. It prevents anti-biofilm formation and also provides adequate therapeutic effects for accelerating wound healing.

Adverse drug reactions monitoring: prospects and impending challenges for pharmacovigilance.

Pharmacovigilance plays a consequential role in the surveillance of adverse drug reactions, which is provoked by the drugs used to cure diseases. Adverse drug reactions (ADRs) produce detrimental or undesirable effects to the body after administration of drugs. It has been reported that the number of patients dying because of contrary effects of drugs per year increased upto 2.6-fold. Moreover, rates of hospitalization of patients are increasing owing to adverse effects of drugs. Thus, it becomes challengeable for physician, health care providers, WHO and pharmaceutical industries to resolve the associated problem of ADRs. During the clinical trial of a novel drug, it is prominent to explore the dependability of drug. In this review, we documented the details required to identify the ADRs in patients along with reported banned drugs.