Binding of therapeutic Fc-fused factor VIII to the neonatal Fc receptor at neutral pH associates with poor half-life extension.

Fusion of therapeutic proteins to the Fc fragment of human IgG1 promotes their FcRn-mediated recycling and subsequent extension in circulating half-life. However, different Fc-fused proteins, as well as antibodies with different variable domains but identical Fc, may differ in terms of extension in half-life. Here we compared the binding behaviour to FcRn of Fc-fused FVIII, Fc-fused FIX and two human monoclonal HIV-1 broadly-neutralizing IgG1, m66.

Deciphering the ameliorative effect of Aloe vera (L.) burm. F. extract on histopathological alterations in Streptozotocin-induced WNIN/GR-ob rats.

Ethnopharmacological Relevance: Natural products have emerged as a novel source in the management of non-communicable diseases, more so in diabetes mellitus and its comorbidities. Aloe vera is widely recognized for its anti-hyperglycemic and anti-hyperlipidemic properties and numerous researchers have identified component (s) from Aloe vera attributing to these therapeutic effects.

Aim Of The Study: The current work was undertaken to gain insight into the protective effect of Aloe vera (L.

Binding Promiscuity of Therapeutic Factor VIII.

The binding promiscuity of proteins defines their ability to indiscriminately bind multiple unrelated molecules. Binding promiscuity is implicated, at least in part, in the off-target reactivity, nonspecific biodistribution, immunogenicity, and/or short half-life of potentially efficacious protein drugs, thus affecting their clinical use. In this review, we discuss the current evidence for the binding promiscuity of factor VIII (FVIII), a protein used for the treatment of hemophilia A, which displays poor pharmacokinetics, and elevated immunogenicity.

The use of Bacillus subtilis as a cost-effective expression system for production of Cholera Toxin B fused factor VIII epitope regions applicable for inducing oral immune tolerance.

Coagulation factor replacement therapy for the X-linked bleeding disorder Haemophilia, characterized by a deficiency of coagulation protein factor VIII (FVIII), is severely complicated by antibody (inhibitors) formation. The development of FVIII inhibitors drastically alters the quality of life of the patients and is associated with a tremendous increase in morbidity as well as treatment costs. The ultimate goal of inhibitor control is antibody elimination.

Cholesterol transport and beyond: Illuminating the versatile functions of HDL apolipoproteins through structural insights and functional implications.

High-density lipoproteins (HDLs) play a vital role in lipid metabolism and cardiovascular health, as they are intricately involved in cholesterol transport and inflammation modulation. The proteome of HDL particles is indeed complex and distinct from other components in the bloodstream. Proteomics studies have identified nearly 285 different proteins associated with HDL; however, this review focuses more on the 15 or so traditionally named "apo" lipoproteins.

High factor VIII concentrations interfere with glycoprotein VI-mediated platelet activation in vitro.

Background: The recruitment of activated factor VIII (FVIII) at the surface of activated platelets is a key step toward the burst of thrombin and fibrin generation during thrombus formation at the site of vascular injury. It involves binding to phosphatidylserine and, possibly, to fibrin-bound αβ. Seminal work had shown the binding of FVIII to resting platelets, yet without a clear understanding of a putative physiological relevance.

Molecular Mechanisms Associated with Antifungal Resistance in Pathogenic Species.

Candidiasis is a highly pervasive infection posing major health risks, especially for immunocompromised populations. Pathogenic species have evolved intrinsic and acquired resistance to a variety of antifungal medications. The primary goal of this literature review is to summarize the molecular mechanisms associated with antifungal resistance in species.

GPR56 signaling pathway network and its dynamics in the mesenchymal transition of glioblastoma.

G protein-coupled receptor 56 (GPR56/ADGRG1) is a multifunctional adhesion GPCR involved in diverse biological processes ranging from development to cancer. In our earlier study, we reported that GPR56 is expressed heterogeneously in glioblastoma (GBM) and is involved in the mesenchymal transition, making it a promising therapeutic target (Ganesh et al., 2022).

The Effects of Oral Probiotics on Type 2 Diabetes Mellitus (T2DM): A Clinical Trial Systematic Literature Review.

Type 2 diabetes mellitus (T2DM) remains a global health concern. Emerging clinical trial (CT) evidence suggests that probiotic intervention may promote a healthy gut microbiome in individuals with T2DM, thereby improving management of the disease. This systematic literature review summarizes thirty-three CTs investigating the use of oral probiotics for the management of T2DM.

A Systematic Review of the Potential of Pichia pastoris (Komagataella phaffii) as an Alternative Host for Biologics Production.

The methylotrophic yeast Pichia pastoris is garnering interest as a chassis cell factory for the manufacture of recombinant proteins because it effectively satisfies the requirements of both laboratory and industrial set up. The optimisation of P. pastoris cultivation is still necessary due to strain- and product-specific problems such as promoter strength, methanol utilisation type, and culturing conditions to realize the high yields of heterologous protein(s) of interest.

A commentary on the paper, 'Development and validation of a novel automatable assay for cholesterol efflux capacity'.

The determination of functionality or quality of high-density lipoproteins (HDL) is assuming a central stage in the prediction of cardiovascular diseases (CVD). To assess HDL quality, several attempts have been made to develop an automated, cost-effective cholesterol efflux capacity (CEC) system with few operational steps that might be used in clinical settings for large throughput testing. The work of Dr.

Delineating the impact of pathogenic mutations on the conformational dynamics of HDL's vital protein ApoA1: a combined computational and molecular dynamic simulation approach.

Apolipoprotein A1 (ApoA1), is the important component of high-density lipoproteins (HDL), that has key role in HDL biogenesis, cholesterol trafficking, and reverse cholesterol transport (RCT). Non-synonymous Single Nucleotide Polymorphisms (nsSNPs) in ApoA1 have been linked to cardiovascular diseases and amyloidosis as they alter the protein's native structure and function. Therefore in this study, we attempted to understand the molecular pathogenicity profile of nsSNPs of ApoA1 using various computational approaches.

Leveraging knowledge of HDLs major protein ApoA1: Structure, function, mutations, and potential therapeutics.

Apolipoprotein A1 (ApoA1) is a member of the Apolipoprotein family of proteins. It's a vital protein that helps in the production of high-density lipoprotein (HDL) particles, which are crucial for reverse cholesterol transport (RCT). It also has anti-inflammatory, anti-atherogenic, anti-apoptotic, and anti-thrombotic properties.

Expression of a Tagless Single-Chain Variable Fragment (scFv) of Anti-TNF-α by a Salt Inducible System and its Purification and Characterization.

Background: Anti-TNF-α scFv is gaining acceptance as an effective drug for various diseases, such as rheumatoid arthritis and Crohn's disease that involve elevated levels of TNF-α. The single-chain variable fragment (scFv) consists of variable regions of heavy and light chains of monoclonal antibodies (mAb). Due to its smaller size, it curbs the mAb's auto-antibody effects and their limitation of penetration into the tissues during the neutralization of TNF-α.

Alleviation of diabetes mellitus through the restoration of β-cell function and lipid metabolism by Aloe vera (L.) Burm. f. extract in obesogenic WNIN/GR-Ob rats.

Ethnopharmacological Relevance: Aloe vera (L.) Burm. f.

GPR56: An adhesion GPCR involved in brain development, neurological disorders and cancer.

GPR56/ADGRG1 is a member of the adhesion G-protein coupled receptor (aGPCR) family and one of the important players in the normal development of the brain. It plays a pivotal role in the diverse neurobiological processes, including cortical formation, oligodendrocyte development, and myelination. Mutations in GPR56 are known to cause brain malformation, myelination defects and are also implied in many cancers, including brain tumors.

A dipyrrole derivative from inhibits an anti-diabetic drug target Dipeptidyl Peptidase (DPP)-IV .

, a succulent herb, has a long history of use in traditional medicine, including diabetes. Earlier studies from our laboratory demonstrated that the extract has the ability to inhibit the diabetic drug target dipeptidyl peptidase (DPP) IV . This current study focuses on the isolation of small water soluble active molecule(s) involved in DPP-IV inhibition from extract, and further to characterize its structure and to elucidate the mode of inhibition of the DPP-IV enzyme.

Recombinant irisin induces weight loss in high fat DIO mice through increase in energy consumption and thermogenesis.

Objective: Irisin is known to be an important metabolic regulator of glucose and lipid metabolism. The aims of the present study are to assess the role of mouse Irisin in obesity and energy metabolism and its glucose and lipid-lowering effects in a high-fat diet-induced obesity (DIO) mice model.

Methods: DIO mice were treated with recombinant murine Irisin or vehicle, and parameters such as body weight, feed intake, glucose, and lipid levels, obesity, energy consumption, and insulin sensitivity were assessed.

Development of anti-chloro tyrosine HDL apoA-I antibodies for the immunodiagnosis of cardiovascular diseases.

High density lipoproteins (HDL) are considered cardio protective. Apolipoprotein A-I (apoA-I), a major component of HDL helps in reverse cholesterol transport, whose function is greatly affected during atherosclerosis due to oxidation by myeloperoxidase. Amino acid tyrosine residue of apoA-I at position 192 and 166 are sensitive to oxidation by myeloperoxidase resulting in the generation of chlorinated and nitrated apoA-I and they are believed to be present in atherosclerotic plaques and in circulation.

Development and Characterization of Monoclonal Antibodies Against Nitro-Tyrosine of High-Density Lipoprotein: Apolipoprotein A1.

Apolipoprotein A1 (ApoA1) of the high-density lipoprotein (HDL) plays a cardinal role in alleviating atherosclerosis in various ways. Its role in reverse cholesterol transport is preeminent. However, the ApoA1 undergoes oxidation under chronic inflammatory conditions and these oxidations are mediated by myeloperoxidase.

Phenylethanolamine N-methyltransferase gene expression in PC12 cells exposed to intermittent hypoxia.

Epidemiological studies show a strong correlation between Obstructive Sleep Apnea (OSA) and cardiovascular disorders. OSA patients experience intermittent hypoxia (IH), characterized by brief, but recurring episodes of cessation in breathing. These patients have higher levels of circulating catecholamines and an increased incidence of hypertension; however the mechanisms defining this association are not clearly established.

Serovar prevalence of Leptospira in semirural India and the development of an IgM-based indirect ELISA.

Introduction: Leptospirosis is a major public health problem in India. However, it has been underreported and under-diagnosed due to a lack of awareness of the disease, a functional surveillance system, and appropriate laboratory diagnostic facilities.

Methodology: This multicenter study aimed to understand the Leptospira serovars causing leptospirosis in seven secondary-level hospitals in six states in India.

Development of Monoclonal Antibody Against Chlorinated 192tyrosine Containing ApoAI Peptide to Screen Quality of Human High Density Lipoprotein (HDL).

ApoAI, a major protein component of HDL is considered to be a key factor which contributes for HDL's cardio- protective functions. ApoAI is sensitive to myeloperoxidase mediated oxidative modifications under chronic inflammatory conditions such as atherosclerosis. The amino acid tyrosine at position 192 of ApoAI is considered to be one of the vulnerable sites for oxidation which impairs HDL functions and its quality.