Chaperone-assisted E3 ligase CHIP: A double agent in cancer.

The carboxy-terminus of Hsp70-interacting protein (CHIP) is a ubiquitin ligase and co-chaperone belonging to Ubox family that plays a crucial role in the maintenance of cellular homeostasis by switching the equilibrium of the folding-refolding mechanism towards the proteasomal or lysosomal degradation pathway. It links molecular chaperones . HSC70, HSP70 and HSP90 with ubiquitin proteasome system (UPS), acting as a quality control system.

Novel Imidazole Phenoxyacetic Acids as Inhibitors of USP30 for Neuroprotection Implication via the Ubiquitin-Rho-110 Fluorometric Assay: Design, Synthesis, and In Silico and Biochemical Assays.

USP30, a deubiquitinating enzyme family, forfeits the ubiquitination of E3 ligase and Parkin on the surface of mitochondria. Inhibition of USP30 results in mitophagy and cellular clearance. Herein, by understanding structural requirements, we discovered potential USP30 inhibitors from an imidazole series of ligands via a validated ubiquitin-rhodamine-110 fluorometric assay.

Ubiquitination and deubiquitination in the regulation of epithelial-mesenchymal transition in cancer: Shifting gears at the molecular level.

The process of conversion of non-motile epithelial cells to their motile mesenchymal counterparts is known as epithelial-mesenchymal transition (EMT), which is a fundamental event during embryonic development, tissue repair, and for the maintenance of stemness. However, this crucial process is hijacked in cancer and becomes the means by which cancer cells acquire further malignant properties such as increased invasiveness, acquisition of stem cell-like properties, increased chemoresistance, and immune evasion ability. The switch from epithelial to mesenchymal phenotype is mediated by a wide variety of effector molecules such as transcription factors, epigenetic modifiers, post-transcriptional and post-translational modifiers.

DEAD-box RNA helicases with special reference to p68: Unwinding their biology, versatility, and therapeutic opportunity in cancer.

In the era of advancement, the entire world continues to remain baffled by the increased rate of progression of cancer. There has been an unending search for novel therapeutic targets and prognostic markers to curb the oncogenic scenario. The DEAD-box RNA helicases are a large family of proteins characterized by their evolutionary conserved D-E-A-D (Asp-Glu-Ala-Asp) domain and merit consideration in the oncogenic platform.

S-Benzyl cysteine based cyclic dipeptide super hydrogelator: Enhancing efficacy of an anticancer drug via sustainable release.

Peptide-based low molecular weight supramolecular hydrogels hold promising aspects in various fields of application especially in biomaterial and biomedical sciences such as drug delivery, wound healing, tissue engineering, cell proliferation, and so on due to their extreme biocompatibility. Unlike linear peptides, cyclic peptides have more structural rigidity and tolerance to enzymatic degradation and high environmental stability which make them even better candidates for the above-said applications. Herein, a new small cyclic dipeptide (CDP) cyclo-(Leu-S-Bzl-Cys) (P1) consisting of L-leucine and S-benzyl protected L-cysteine was reported which formed a hydrogel at physiological conditions (at 37°C and pH = 7.

MicroRNA-129-5p-regulated microglial expression of the surface receptor CD200R1 controls neuroinflammation.

CD200R1 is an inhibitory surface receptor expressed in microglia and blood macrophages. Microglial CD200R1 is known to control neuroinflammation by keeping the microglia in resting state, and therefore, tight regulation of its expression is important. CCAAT/enhancer-binding protein β (CEBPβ) is the known regulator of CD200R1 transcription.

Wnt/β-catenin signaling and p68 conjointly regulate CHIP in colorectal carcinoma.

Emerging evidences suggest abundant expression of Carboxy terminus of Hsc70 Interacting Protein or CHIP (alias STIP1 Homology and U-box Containing Protein 1 or STUB1) in colorectal carcinoma, but the mechanistic detail of this augmented expression pattern is unclear. The signature driver of canonical Wnt pathway, β-catenin, and its co-activator RNA helicase p68, are also overexpressed in colorectal carcinoma. In this study, we describe a novel mechanism of Wnt/β-catenin and p68 mediated transcriptional activation of CHIP gene leading to enhanced proliferation of colorectal carcinoma cells.

Crystallographic and biophysical analyses of Pseudomonas aeruginosa ketopantoate reductase: Implications of ligand induced conformational changes in cofactor recognition.

Ketopantoate reductases (KPRs) catalyse NADPH-dependent reduction of ketopantoate to pantoate, the rate-limiting step of pantothenate biosynthetic pathway. In our recent study, we showed KPRs are under dynamic evolutionary selection and highlighted the possible role of ordered substrate binding kinetics for cofactor selection. To further delineate this at molecular level, here, we perform X-ray crystallographic and biophysical analyses of KPR in presence of non-canonical cofactor NAD.

Archived dengue serum samples produced false-positive results in SARS-CoV-2 lateral flow-based rapid antibody tests.

Co-endemicity of SARS-CoV-2 and dengue virus (DV) infection is becoming a matter of serious concern as it has been already reported that antibodies (Ab) elicited by SARS-CoV-2 infection can produce false-positive results in dengue IgG and IgM rapid tests and . Here we communicate that five of thirteen DV antibody-positive serum samples from Kolkata, archived in 2017 (predating the COVID-19 outbreak), produced false-positive results in SARS-CoV-2 IgG/IgM lateral flow-based rapid tests. Our results emphasize the importance of implementing tests with higher specificity to conduct sero-surveillance for accurate estimation of SARS-CoV-2/DV prevalence in regions where both viruses now co-exist.

Long noncoding RNAs in intestinal homeostasis, regeneration, and cancer.

Signaling pathways that regulate homeostasis and regeneration are found to be deregulated in various human malignancies. Accordingly, attempts have been made to target them at the protein level with little success. However, studies using high-throughput sequencing technologies suggest that only about 2% of the genome translates into proteins, whereas about 75% of the genome is transcribed into noncoding RNAs.

Tumor Suppressors Having Oncogenic Functions: The Double Agents.

Cancer progression involves multiple genetic and epigenetic events, which involve gain-of-functions of oncogenes and loss-of-functions of tumor suppressor genes. Classical tumor suppressor genes are recessive in nature, anti-proliferative, and frequently found inactivated or mutated in cancers. However, extensive research over the last few years have elucidated that certain tumor suppressor genes do not conform to these standard definitions and might act as "double agents", playing contrasting roles in vivo in cells, where either due to haploinsufficiency, epigenetic hypermethylation, or due to involvement with multiple genetic and oncogenic events, they play an enhanced proliferative role and facilitate the pathogenesis of cancer.

Computational modelling supports that dengue virus envelope antibodies can bind to SARS-CoV-2 receptor binding sites: Is pre-exposure to dengue virus protective against COVID-19 severity?

The world is going through the scourge of the COVID-19 pandemic since January 2020. However, the pandemic appears to be less severe in highly dengue endemic countries. In this connection, several studies reported that sero-diagnostic tests for dengue virus (DV) yielded considerable false-positive results for SARS-CoV-2 and in dengue endemic regions, thereby indicating towards potential cross-reactivity between these two viruses.

Dual Functionalized Injectable Hybrid Extracellular Matrix Hydrogel for Burn Wounds.

Low strength and rapid biodegradability of acellular dermal matrix (ADM) restrict its wider clinical application as a rapid cell delivery platform for management of burn wounds. Herein, the extracted ADM was modified by a dual cross-linking approach with ionic crosslinking using chitosan and covalent cross-linking using an iodine-modified 2,5-dihydro-2,5-dimethoxy-furan cross-linker, termed as CsADM-Cl. In addition, inherent growth factors and cytokines were found to be preserved in CsADM-Cl, irrespective of ionic/covalent crosslinking.

(p)ppGpp Metabolism and Antimicrobial Resistance in Bacterial Pathogens.

Single cell microorganisms including pathogens relentlessly face myriads of physicochemical stresses in their living environment. In order to survive and multiply under such unfavorable conditions, microbes have evolved with complex genetic networks, which allow them to sense and respond against these stresses. Stringent response is one such adaptive mechanism where bacteria can survive under nutrient starvation and other related stresses.

Neuroinvasion of SARS-CoV-2 may play a role in the breakdown of the respiratory center of the brain.

The recent outbreak of the novel coronavirus, SARS-CoV-2, has emerged to be highly pathogenic in nature. Although lungs are considered as the primary infected organs by SARS-CoV-2, some of the other organs, including the brain, have also been found to be affected. Here, we have discussed how SARS-CoV-2 might infect the brain.

Chrysin-loaded PLGA attenuates OVA-induced allergic asthma by modulating TLR/NF-κB/NLRP3 axis.

Asthma, one of the significant public health problems, is triggered by certain inflammatory processes in the airways that are not addressed propitiously by current therapies. Though pieces of evidence on allergic asthma mitigation by the anti-inflammatory bioflavonoid chrysin (CHR) are accumulating, poor bioavailability, and low solubility curtail drug development. To overcome these shortcomings, CHR loaded nanoparticle (CHR-NP) was formulated, and its salutary effect in preclinical murine allergic asthma model via the peroral route was evaluated.

Polysubstituted Imidazoles as LysoTracker Molecules: Their Synthesis via Iodine/HO and Cell-Imaging Studies.

An iodine-catalyzed, environmentally benign one-pot methodology has been developed for the synthesis of diverse substituted imidazoles. This transition-metal-free, aerobic, water-mediated cyclization reaction is operationally simple and works well with different amines or aldehydes by multiple C-N bond formations with satisfactory yield. The methodology is regioselective as well as scalable.

Deciphering the structural intricacy in virulence effectors for proton-motive force mediated unfolding in type-III protein secretion.

Given that the protein unfolding requisite for type-III secretion system (T3SS)-mediated secretion is an energetically unfavorable process, the question of how do pathogenic bacteria unfold and secrete hundreds of toxic proteins in seconds remain largely unknown. In this study, a systematic effort combining experimental and computational approaches has been employed to get some mechanistic insights on the unfolding of effectors in T3SS secretion. The in-depth analysis of pH-dependent folding and stability of a T3SS effector ExoY revealed that proton-concentration gradient (~pH 5.

A Novel Tool to Investigate the Early and Late Stages of α-Synuclein Aggregation.

The accumulation of an inherently disordered protein α-synuclein (α-syn) aggregates in brain tissue play a pivotal role in the pathology and etiology of Parkinson's disease. Aggregation of α-syn has been found to be complex and heterogeneous, occurring through multitudes of early- and late-stage intermediates. Because of the inherent complexity and large dynamic range (between a few microseconds to several days under in vitro measurement conditions), it is difficult for the conventional biophysical and biochemical techniques to sample the entire time window of α-syn aggregation.

Is the Collapse of the Respiratory Center in the Brain Responsible for Respiratory Breakdown in COVID-19 Patients?

Following the identification of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, we are now again facing a global highly pathogenic novel coronavirus (SARS-CoV-2) epidemic. Although the lungs are one of the most critically affected organs, several other organs, including the brain may also get infected. Here, we have highlighted that SARS-CoV-2 might infect the central nervous system (CNS) through the olfactory bulb.

Healthy Gut, Healthy Brain: The Gut Microbiome in Neurodegenerative Disorders.

Background: The central nervous system (CNS) known to regulate the physiological conditions of human body, also itself gets dynamically regulated by both the physiological as well as pathological conditions of the body. These conditions get changed quite often, and often involve changes introduced into the gut microbiota which, as studies are revealing, directly modulate the CNS via a crosstalk. This cross-talk between the gut microbiota and CNS, i.

Corrigendum: EBI-3 Chain of IL-35 Along With TGF-β Synergistically Regulate Anti-leishmanial Immunity.

[This corrects the article DOI: 10.3389/fimmu.2019.