Hotspots for Disease-Causing Mutations in the Mitochondrial TIM23 Import Complex.

The human mitochondrial proteome comprises approximately 1500 proteins, with only 13 being encoded by mitochondrial DNA. The remainder are encoded by the nuclear genome, translated by cytosolic ribosomes, and subsequently imported into and sorted within mitochondria. The process of mitochondria-destined protein import is mediated by several intricate protein complexes distributed among the four mitochondrial compartments.

An Update of Phenotypic-Genotypic IMNEPD Cases and a Bioinformatics Analysis of the New Gene Variants.

Background/objectives: Biallelic mutations in the gene are associated with a rare genetic disease known as infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD). In this study, we describe a new case carrying a previously identified mutation, provide an updated analysis of the relative frequencies of the clinical features across all published cases (including the three latest studies), and perform a bioinformatics analysis of the newly identified PTRH2 protein variants from a structural perspective.

Methods: Clinical examination of the patients was carried out, and genetic testing was performed using a genome sequencing strategy.

Discordance of 3rd and 4th generation QuantiFERON-TB Gold assays by pregnancy stages in India.

Background: Pregnancy and HIV affect CD4+ T lymphocytes and impact performance of QuantiFERON-TB Gold (QFT). We compared the results of QFT with QuantiFERON-TB Gold Plus (QFT-Plus), which also measures CD8+ responses to TB antigens, during pregnancy and postpartum.

Methods: We screened 516 pregnant women for TB infection (TBI) with IGRA.

Role of the transmembrane polar residues on CD151 in cholesterol binding.

Tetraspanins superfamily proteins have been shown to play an important role in several physiological processes and diseases such as cancer. Transmembrane polar residues of tetraspanins have an implication in regulating the process of cancer metastasis. Tetraspanin CD82 has been demonstrated to exert an anti-metastatic role while mutating polar residues in its transmembrane domains (TMDs) abrogates its metastasis inhibitory role.

From lab to life: advances inbioprinting and bioink technology.

Bioprinting has the potential to revolutionize tissue engineering and regenerative medicine, offering innovative solutions for complex medical challenges and addressing unmet clinical needs. However, traditionalbioprinting techniques face significant limitations, including difficulties in fabricating and implanting scaffolds with irregular shapes, as well as limited accessibility for rapid clinical application. To overcome these challenges,bioprinting has emerged as a groundbreaking approach that enables the direct deposition of cells, biomaterials, and bioactive factors onto damaged organs or tissues, eliminating the need for pre-fabricated 3D constructs.

Isolation and characterization of rabies monoclonal antibody charge variants.

Current postexposure prophylaxis of rabies includes vaccines, human rabies immunoglobulin (RIG), equine RIG, and recombinant monoclonal antibodies (mAb). In the manufacturing of rabies recombinant mAb, charge variants are the most common source of heterogeneity. Charge variants of rabies mAb were isolated by salt gradient cation exchange chromatography (CEX) to separate acidic and basic and main charge variants.

Preparation of glycopeptide-modified pH-sensitive liposomes for promoting antigen cross-presentation and induction of antigen-specific cellular immunity.

Cross-presentation, exogenous antigen presentation onto major histocompatibility complex class I molecules on antigen presenting cells, is crucially important for inducing antigen-specific cellular immune responses for cancer immunotherapy and for the treatment of infectious diseases. One strategy to induce cross-presentation is cytosolic delivery of an exogenous antigen using fusogenic or endosomolytic molecule-introduced nanocarriers. Earlier, we reported liposomes modified with pH-responsive polymers to achieve cytosolic delivery of an antigen.

HDAC inhibition by L. sprouts extract in hepatocellular carcinoma: an approach to study anti-cancer potential.

A wide variety of natural products have been widely used in chemoprevention therapy because they have antioxidant, anti-inflammatory, and anticancer activity. In the present study, we shed light on the 5th day germinated sprouts of seeds and evaluated them against HDAC inhibition and antioxidant activity. The extract from the seed and sprout was extracted and characterised by LC-MS/MS, FTIR, and NMR to reveal its chemical composition, especially thymol (THY) and thymoquinone (TQ).

Comparative docking analysis of tyrosine kinase inhibitors with HER2 and HER4 receptors.

Tyrosine kinase receptors promote the growth and differentiation of normal breast and malignant human breast cancer cells, known as ERBB receptors. Various ERBB receptors are EGFR/ErbB1 and ErbB2/neu, which get over expressed in different solid tumors that activate upon binding of ligand to the extra cellular domain of these receptors. Of note, the epidermal growth factor receptor (EGFR) is a prime contributor to cancer through the involvement of four receptor tyrosine kinases (RTKs), namely, HER1, HER2, HER3, and HER4.

Partial Activation of PPAR-γ by Synthesized Quercetin Derivatives Modulates TGF-β1-Induced EMT in Lung Cancer Cells.

Non-small cell lung cancer (NSCLC) has a very low survival rate due to poor response to chemotherapy and late detection. Epithelial to mesenchymal transition (EMT) is regarded as a major contributor to drive metastasis during NSCLC progression. Towards this, transforming growth factor-beta 1 (TGF-β1) is the key driver that endows cancer cells with increased aggressiveness.

Design, Synthesis, and Biological Evaluation of Novel Quercetin Derivatives as PPAR-γ Partial Agonists by Modulating Epithelial-Mesenchymal Transition in Lung Cancer Metastasis.

Epithelial-to-mesenchymal transition (EMT) is responsible for driving metastasis of multiple cancer types including lung cancer. Peroxisome proliferator-activated receptor (PPAR)-γ, a ligand-activated transcription factor, controls expression of variety of genes involved in EMT. Although several synthetic compounds act as potent full agonists for PPAR-γ, their long term application is restricted due to serious adverse effects.

Docking and simulation studies on cyclin D/CDK4 complex for targeting cell cycle arrest in cancer using flavanone and its congener.

Flavanone compounds are naturally occurring phytochemicals present in most of citrus fruits reported to be a potential anticancer moiety as it majorly participates in the inhibition of the cell cycle, apoptosis, and angiogenesis. Because of poor bioavailability, natural flavanones were not used as therapeutic targets so flavanone congeners were prepared by modifying at B-functional group using compound libraries such as PubChem Database. Cyclin-dependent kinase is primarily activating the cell cycle and potentiating the M phase, in order to control the cell cycle in cancer cyclin-dependent pathway was targeted and potential cyclin D/CDK4 receptor protein was retrieved from Protein Data Bank (PDBID:2W9Z).

Epitope imprinted polymeric materials: application in electrochemical detection of disease biomarkers.

Epitope imprinting is a promising method for creating specialized recognition sites that resemble natural biorecognition elements. Epitope-imprinted materials have gained a lot of attention recently in a variety of fields, including bioanalysis, drug delivery, and clinical therapy. The vast applications of epitope imprinted polymers are due to the flexibility in choosing monomers, the simplicity in obtaining templates, specificity toward targets, and resistance to harsh environments along with being cost effective in nature.

Computational approach to attenuate virulence of through bioinspired silver nanoparticles.

Unlabelled: In this study we aim to investigate the computational docking approach of biofabricated silver nanoparticles against virulent exoenzymes, such as ExoS and ExoY. Therefore, the synthesis and characterization of biofabricated silver nanoparticles using leaves (Pb-AgNPs) were carried out. The surface topology and functional group attachment on the surface of Pb-AgNPs were analyzed using UV-visible spectroscopy, Scanning Electron Microscopy, Fourier Transformed Infrared Spectroscopy (FTIR), and X-Ray Diffraction.

Molecular Docking and Simulation Studies of Flavanone and its Derived Compounds on PI3K-AKT Pathway Targeting against Cancer.

Background: Flavanone compounds and their related derivatives are reported in controlling cell cycle, angiogenesis, and metastasis. Phosphoinositide 3-kinases is a major drug target.

Methods: Crystalize structure of Phosphoinositide 3-kinases-Akt complex obtained from Protein Data Bank (PDBID: 3CQW) was selected as receptor protein and the binding site has been identified with PDBSum Database.

Probing intermolecular interactions and binding stability of kaempferol, quercetin and resveratrol derivatives with PPAR-γ: docking, molecular dynamics and MM/GBSA approach to reveal potent PPAR- γ agonist against cancer.

Peroxisome Proliferator-Activated Receptors-γ (PPAR-γ), a ligand-activated transcription factor, suggested having anti-inflammatory effects by activating the target genes when bound to the ligand. Herein, we examined a conformational analysis of 8708 derivatives of Kaempferol, Quercetin, and Resveratrol, the prime activators of PPAR-γ molecular target by employing molecular docking and dynamic simulation pipeline to screen out potential agonists. The structure-based docking procedure performed by FlexX tool shortlisted high binding affinities of these derivatives of Kaempferol, Quercetin and Resveratrol with the protein receptor with a score of -38.

Exploring conformational changes of PPAR-Ɣ complexed with novel kaempferol, quercetin, and resveratrol derivatives to understand binding mode assessment: a small-molecule checkmate to cancer therapy.

Peroxisome proliferator-activated receptors-γ (PPAR-γ), a ligand-activated transcription factor, activated by several ligands like fatty acids (linoleic acid being the most common) or their metabolites, can function as potential therapeutic target for various cancers. Although various synthetic ligands, thiazolidinediones (TZDs), serves as full agonist for PPAR-γ, application of these molecules has been discontinued due to adverse toxicity profile. Hence, with a dire need to identify novel PPAR-γ-agonists, the present in silico study aimed to determine the effectiveness of potent flavonoids, kaempferol (CID: 5280863), quercetin (CID: 5280343), and stilbenoid resveratrol (CID: 445154) and their 806 derivatives towards PPAR-γ that could combat the deleterious effect of TZDs.