Mccollumnelson7844

Hepatocellular carcinoma (HCC) poses a severe threat to human health. The NET-1 protein has been proved to be strongly associated with HCC proliferation and metastasis in our previous study. Here, we established and validated the NET-1 siRNA nanoparticles system to conduct targeted gene therapy of HCC xenograft in vivo with the aid of sonodynamic therapy. Then, we conducted a label-free proteome mass spectrometry workflow to analyze formalin-fixed and paraffin-embedded HCC xenograft samples collected in this study. The result showed that 78 proteins were differentially expressed after NET-1 protein inhibited. Among them, the expression of 17 proteins upregulated and the expression of 61 proteins were significantly downregulated. Of the protein abundance, the vast majority of Gene Ontology enrichment terms belong to the biological process. The KEGG pathway enrichment analysis showed that the 78 differentially expressed proteins significantly enriched in 45 pathways. We concluded that the function of the NET-1 gene is not only to regulate HCC but also to participate in a variety of biochemical metabolic pathways in the human body. Furthermore, the protein-protein interaction analysis indicated that the interactions of differentially expressed proteins are incredibly sophisticated. All the protein-protein interactions happened after the NET-1 gene has been silenced. Finally, our study also provides a useful proposal for targeted therapy based on tetraspanin proteins to treat HCC, and further mechanism investigations are needed to reveal a more detailed mechanism of action for NET-1 protein regulation of HCC.Hereditary spastic paraplegias (HSPs) are genetically heterogeneous conditions caused by the progressive dying back of the longest axons in the central nervous system, the corticospinal axons. A wealth of data in the last decade has unraveled disturbances of lipid droplet (LD) biogenesis, maturation, turnover and contact sites in cellular and animal models with perturbed expression and function of HSP proteins. As ubiquitous organelles that segregate neutral lipid into a phospholipid monolayer, LDs are at the cross-road of several processes including lipid metabolism and trafficking, energy homeostasis, and stress signaling cascades. However, their role in brain cells, especially in neurons remains enigmatic. Here, we review experimental findings linking LD abnormalities to defective function of proteins encoded by HSP genes, and discuss arising questions in the context of the pathogenesis of HSP.Ever since the "great oxidation event," Earth's cellular life forms had to cope with the danger of reactive oxygen species (ROS) affecting the integrity of biomolecules and hampering cellular metabolism circuits. Consequently, increasing ROS levels in the biosphere represented growing stress levels and thus shaped the evolution of species. Whether the ROS were produced endogenously or exogenously, different systems evolved to remove the ROS and repair the damage they inflicted. If ROS outweigh the cell's capacity to remove the threat, we speak of oxidative stress. The injuries through oxidative stress in cells are diverse. This article reviews the damage oxidative stress imposes on the different steps of the central dogma of molecular biology in bacteria, focusing in particular on the RNA machines involved in transcription and translation.This article is dedicated to the memory of Cyrus Chothia, who was a leading light in the world of protein structure evolution. His elegant analyses of protein families and their mechanisms of structural and functional evolution provided important evolutionary and biological insights and firmly established the value of structural perspectives. He was a mentor and supervisor to many other leading scientists who continued his quest to characterise structure and function space. He was also a generous and supportive colleague to those applying different approaches. In this article we review some of his accomplishments and the history of protein structure classifications, particularly SCOP and CATH. We also highlight some of the evolutionary insights these two classifications have brought. Finally, we discuss how the expansion and integration of protein sequence data into these structural families helps reveal the dark matter of function space and can inform the emergence of novel functions in Metazoa. Since we cover 25 years of structural classification, it has not been feasible to review all structure based evolutionary studies and hence we focus mainly on those undertaken by the SCOP and CATH groups and their collaborators.Ligand-protein association is the first and critical step for many biological and chemical processes. This study investigated the molecular association processes under different environments. In biology, cells have different compartments where ligand-protein binding may occur on a membrane. In experiments involving ligand-protein binding, such as the surface plasmon resonance and continuous flow biosynthesis, a substrate flow and surface are required in experimental settings. As compared with a simple binding condition, which includes only the ligand, protein, and solvent, the association rate and processes may be affected by additional ligand transporting forces and other intermolecular interactions between the ligand and environmental objects. We evaluated these environmental factors by using a ligand xk263 binding to HIV protease (HIVp) with atomistic details. Using Brownian dynamics simulations, we modeled xk263 and HIVp association time and probability when a system has xk263 diffusion flux and a non-polar self-assembled monolayer surface. We also examined different protein orientations and accessible surfaces for xk263. To allow xk263 to access to the dimer interface of immobilized HIVp, we simulated the system by placing the protein 20Å above the surface because immobilizing HIVp on a surface prevented xk263 from contacting with the interface. The non-specific interactions increased the binding probability while the association time remained unchanged. When the xk263 diffusion flux increased, the effective xk263 concentration around HIVp, xk263-HIVp association time and binding probability decreased non-linearly regardless of interacting with the self-assembled monolayer surface or not. The work sheds light on the effects of the solvent flow and surface environment on ligand-protein associations and provides a perspective on experimental design.The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium's collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com, we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form.The recently emerged coronavirus (SARS-CoV-2) has created a crisis in world health, and economic sectors as an effective treatment or vaccine candidates are still developing. Besides, negative results in clinical trials and effective cheap solution against this deadly virus have brought new challenges. The viral protein, the main protease from SARS-CoV-2, can be effectively targeted due to its viral replication and pathogenesis role. In this study, we have enlisted 88 peptides from the AVPdb database. The peptide molecules were modeled to carry out the docking interactions. The four peptides molecules, P14, P39, P41, and P74, had more binding energy than the rest of the peptides in multiple docking programs. Interestingly, the active points of the main protease from SARS-CoV-2, Cys145, Leu141, Ser139, Phe140, Leu167, and Gln189, showed nonbonded interaction with the peptide molecules. The molecular dynamics simulation study was carried out for 200 ns to find out the docked complex's stability where their stability index was proved to be positive compared to the apo and control complex. Our computational works based on peptide molecules may aid the future development of therapeutic options against SARS-CoV-2.Surgical management of renal cell carcinoma (RCC) with tumor thrombus (TT) extending into the inferior vena cava (IVC) and up to the hepatic veins and right atrium (RA) continues to be problematic and a challenging surgical operation. It becomes even more complicated when performing a re-sternotomy and cardiopulmonary bypass (CPB) in patients with previous coronary artery bypass grafting (CABG). Here, we report on two patients with previous CABG who presented with RCC and TT extending into the hepatic vein and above the diaphragm. These two patients underwent successful surgical resection and TT thrombectomy without the need of CBP. Recommendations are made for successfully accomplishing such surgical resections, including adequate prior preparation for the possible need to perform re-sternotomy and CPB with a coordinated team effort.The essential micronutrient selenium (Se) provides antioxidant defense and supports numerous biological functions. Obtained through dietary intake, Se is incorporated into selenoproteins via the amino acid, selenocysteine (Sec). Mice with genetic deletion of the Se carrier, selenoprotein P (SELENOP), and the Se recycling enzyme selenocysteine lyase (SCLY), suffer from sexually dimorphic neurological deficits and require Se supplementation for viability. These impairments are more pronounced in males and are exacerbated by dietary Se restriction. find more We report here that, by 10 weeks of age, female Selenop/Scly double knockout (DKO) mice supplemented with 1 mg/ml sodium selenite in drinking water develop signs of hyper-adiposity not seen in male DKO mice. Unexpectedly, this metabolic phenotype can be reversed by removing Se from the drinking water at post-natal day 22, just prior to puberty. Restricting access to Se at this age prevents excess body weight gain and restriction from either post-natal day 22 or 37 reduces gonadal fat deposits. These results provide new insight into the sex-dependent relationship between Se and metabolic homeostasis.Amaranthus spinosus is a common vegetable of Bangladesh and well-known for its ethnomedicinal uses. In this study, we have evaluated the ability of powdered supplementation, methanol extract, and aqueous extract of A. spinosus in attenuating in high-carbohydrate-high-fat (HCHF) diet-induced obesity and associated metabolic disorders in female obese rates. Several parameters have been analyzed in this study including body weight, organ weight, fat deposition, glycemic status, lipid levels, hepatic and renal biomarkers, hepatic antioxidant status, and hepatosteatosis. All three samples of A. spinosus significantly reduced weight gain, organ weight, and abdominal fat deposition. Improved glucose tolerance and lipid parameters were seen in obese rats administered with A. spinosus powder, methanol extract, and aqueous extract. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and creatine kinase levels were normalized by the test samples. A. spinosus boosted hepatic antioxidant levels including reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx).