Discovery of small molecules against porcine reproductive and respiratory syndrome virus replication by targeting NendoU activity.

Unlabelled: Porcine reproductive and respiratory syndrome (PRRS) remains a major threat to animal health and causes substantial economic losses worldwide. The nonstructural protein 11 (NSP11) of the causative agent, PRRS virus (PRRSV), contains a highly conserved nidoviral uridylate-specific endoribonuclease (NendoU) domain essential for viral replication and immune evasion. Targeting NSP11 offers a novel approach to antiviral intervention.

Genetic Characterization of HIV-1 Gene from Virologically Controlled Aging Individuals with HIV on Long-Term Antiretroviral Therapy.

Despite advancements in antiretroviral therapy (ART) that reduces the viral load to undetectable levels and improve CD4 T cell counts, viral eradication has not been achieved due to HIV-1 persistence in resting CD4 T-cells. We, therefore, characterized the gene, which is essential for HIV-1 replication and pathogenesis, from 20 virologically controlled aging individuals with HIV (HIV) on long-term ART and improved CD4 T-cell counts, with a particular focus on older individuals. Peripheral blood mononuclear cell genomic DNA from HIV were used to amplify gene by polymerase chain reaction followed by nucleotide sequencing and analysis.

Investigating antibacterial activity of biosynthesized silver oxide nanoparticles using Phragmanthera Macrosolen L. leaf extract.

The crude leaf extract of Phragmanthera macrosolen L. has been utilized for the first time as an effective reducing, capping and stabilizing agent to synthesize silver oxide nanoparticles (AgO NPs) through a green approach. The prepared AgO NPs were analyzed by scanning electron-microscopy (SEM), High Resolution Transmission electron microscope (HR-TEM), X-ray diffractions (XRD), Fourier transforms infrared (FTIR) spectroscopy, energy dispersive spectroscopy (EDS), and Ultra-violet visible spectrometry (UV-Vis).

Dynamic changes in extracellular vesicle-associated miRNAs elicited by ultrasound in inflammatory bowel disease patients.

Blood-based biomarkers that reliably indicate disease activity in the intestinal tract are an important unmet need in the management of patients with IBD. Extracellular vesicles (EVs) are cell-derived membranous microparticles, which reflect the cellular and functional state of their site of site of origin. As ultrasound waves may lead to molecular shifts of EV contents, we hypothesized that application of ultrasound waves on inflamed intestinal tissue in IBD may amplify the inflammation-specific molecular shifts in EVs like altered EV-miRNA expression, which in turn can be detected in the peripheral blood.

Effect of nonsteroidal anti-inflammatory drugs (aspirin and naproxen) on inflammation-associated proteomic profiles in mouse plasma and prostate during TMPRSS2-ERG (fusion)-driven prostate carcinogenesis.

Recent preclinical studies have shown that the intake of nonsteroidal anti-inflammatory drugs (NSAIDs) aspirin and naproxen could be an effective intervention strategy against TMPRSS2-ERG fusion-driven prostate tumorigenesis. Herein, as a follow-up mechanistic study, employing TMPRSS2-ERG (fusion) positive tumors and plasma from TMPRSS2-ERG. Pten mice, we profiled the stage specific proteomic changes (focused on inflammatory circulating and prostate tissue/tumor-specific cytokines, chemokines, and growth factors/growth signaling-associated molecules) that contribute to prostate cancer (PCa) growth and progression in the TMPRSS2-ERG fusion-driven mouse model of tumorigenesis.

Computation-aided Design of Rod-Shaped Janus Base Nanopieces for Improved Tissue Penetration and Therapeutics Delivery.

Despite the development of various drug delivery technologies, there remains a significant need for vehicles that can improve targeting and biodistribution in "hard-to-penetrate" tissues. Some solid tumors, for example, are particularly challenging to penetrate due to their dense extracellular matrix (ECM). In this study, we have formulated a new family of rod-shaped delivery vehicles named Janus base nanopieces (Rod JBNps), which are more slender than conventional spherical nanoparticles, such as lipid nanoparticles (LNPs).

Dexamethasone targets actin cytoskeleton signaling and inflammatory mediators to reverse sulfur mustard-induced toxicity in rabbit corneas.

Sulfur mustard (SM), a bi-functional alkylating agent, was used during World War I and the Iran-Iraq war. SM toxicity is ten times higher in eyes than in other tissues. Cornea is exceptionally susceptible to SM-injuries due to its anterior positioning and mucous-aqueous interphase.

Variant of uncertain significance Arg866Cys enhances disorderedness of h-BRCA1 (759-1064) region.

High structural flexibility has been reported in the central region of BRCA1, which hinders the structural and functional evaluations of mutations identified in the domain. Additionally, the need to categorize variants of unknown significance (VUS) has increased due to the growth in the number of variants reported in clinical settings. Therefore, unraveling the disease-causing mechanism of VUS identified in different functional domains of BRCA1 is still challenging.

Synoptic Operative Reporting in Cervical Cancer Surgeries: Experience From a Single Oncology Center.

Objective In today's era of highly methodological oncological practices in place, we have a huge database to regulate, and it is foreseeable that a humongous load of information is ahead of us that we need to organize and comprehend. With the advancement in surgical equipment and evolving procedures, we need to store the information in a transferrable, understandable, and systematic way to prevent any ebb in the future. The systematic recording of operative data is even more important for patient management, training, and research.

Phytochemicals as Immunomodulatory Molecules in Cancer Therapeutics.

Phytochemicals are natural plant-derived products that provide significant nutrition, essential biomolecules, and flavor as part of our diet. They have long been known to confer protection against several diseases via their anti-inflammatory, immune-regulatory, anti-microbial, and several other properties. Deciphering the role of phytochemicals in the prevention, inhibition, and treatment of cancer-unrestrained cell proliferation due to the loss of tight regulation on cell growth and replication-has been the focus of recent research.

Mutations at proximal cysteine residues in PML impair ATO binding by destabilizing the RBCC domain.

Acute promyelocytic leukemia (APL) is characterized by the fusion gene promyelocytic leukemia-retinoic acid receptor-alpha (PML-RARA) and is conventionally treated with arsenic trioxide (ATO). ATO binds directly to the RING finger, B-box, coiled-coil (RBCC) domain of PML and initiates degradation of the fusion oncoprotein PML-RARA. However, the mutational hotspot at C212-S220 disrupts ATO binding, leading to drug resistance in APL.

Phenylarsine oxide induced corneal injury involves oxidative stress mediated unfolded protein response and ferroptotic cell death: Amelioration by NAC.

Phenylarsine oxide (PAO), an analog of lewisite, is a highly toxic trivalent arsenical and a potential chemical warfare agent. PAO-induced toxicity has been studied in lung, liver, and skin tissues. Nevertheless, very few studies have been published to comprehend the impact of PAO-induced toxicity on ocular tissues, even though eyes are uniquely vulnerable to injury by vesicants.

Structural implications of amyloidogenic rare variants Ser282Leu and Gln356Arg identified in h-BRCA1.

Preliminary studies have shown BRCA1 (170-1600) residues to be intrinsically disordered with unknown structural details. However, thousands of clinically reported variants have been identified in this central region of BRCA1. Therefore, we aimed to characterize h-BRCA1(260-553) to assess the structural basis for pathogenicity of two rare missense variants Ser282Leu, Gln356Arg identified from the Indian and Russian populations respectively.

The SYSCID map: a graphical and computational resource of molecular mechanisms across rheumatoid arthritis, systemic lupus erythematosus and inflammatory bowel disease.

Chronic inflammatory diseases (CIDs), including inflammatory bowel disease (IBD), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are thought to emerge from an impaired complex network of inter- and intracellular biochemical interactions among several proteins and small chemical compounds under strong influence of genetic and environmental factors. CIDs are characterised by shared and disease-specific processes, which is reflected by partially overlapping genetic risk maps and pathogenic cells (e.g.

Differential Effect of Non-Steroidal Anti-Inflammatory Drugs Aspirin and Naproxen against (Fusion)-Driven and Non-Fusion-Driven Prostate Cancer.

The consumption of the non-steroidal anti-inflammatory drug (NSAID) aspirin is associated with a significant reduction in the risk of developing (fusion)-positive prostate cancer (PCa) compared to fusion-negative PCa in population-based case-control studies; however, no extensive preclinical studies have been conducted to investigate and confirm these protective benefits. Thus, the focus of this study was to determine the potential usefulness of aspirin and another NSAID, naproxen, in PCa prevention, employing preclinical models of both (fusion)-driven (with conditional deletion of ) and non--driven (Hi-Myc mice) PCa. Male mice ( = 25 mice/group) were fed aspirin- (700 and 1400 ppm) and naproxen- (200 and 400 ppm) supplemented diets from (a) 6 weeks until 32 weeks of Hi-Myc mice age; and (b) 1 week until 20 weeks post-Cre induction in the fusion model.

Proteasome inhibition potentiates Kv1.3 potassium channel expression as therapeutic target in drug-sensitive and -resistant human melanoma cells.

Primary and acquired therapy resistance is a major problem in patients with BRAF-mutant melanomas being treated with BRAF and MEK inhibitors (BRAFI, MEKi). Therefore, development of alternative therapy regimes is still required. In this regard, new drug combinations targeting different pathways to induce apoptosis could offer promising alternative approaches.

In-silico and structure-based assessment to evaluate pathogenicity of missense mutations associated with non-small cell lung cancer identified in the Eph-ephrin class of proteins.

Ephs belong to the largest family of receptor tyrosine kinase and are highly conserved both sequentially and structurally. The structural organization of Eph is similar to other receptor tyrosine kinases; constituting the extracellular ligand binding domain, a fibronectin domain followed by intracellular juxtamembrane kinase, and SAM domain. Eph binds to respective ephrin ligand, through the ligand binding domain and forms a tetrameric complex to activate the kinase domain.

Metabolomics for identifying pathways involved in vesicating agent lewisite-induced corneal injury.

Lewisite (LEW) is an arsenical vesicant that can be a potentially dangerous chemical warfare agent (CWA). Eyes are particularly susceptible to vesicant induced injuries and ocular LEW exposure can act swiftly, causing burning of eyes, edema, inflammation, cell death and even blindness. In our previous studies, we developed a LEW exposure-induced corneal injury model in rabbit and showed increased inflammation, neovascularization, cell death, and structural damage to rabbit corneas upon LEW exposure.

Insight on Plant for its Pharmacological Properties: A Review.

is a woody shrub of the family . Over 1500 species are distributed in tropical and subtropical regions of Africa and Asia. There are more than 54 species known to possess similar morphological features with the characteristic bitter taste.

Efficacy of a Novel Electroconductive Matrix To Treat Muscle Atrophy and Fat Accumulation in Chronic Massive Rotator Cuff Tears of the Shoulder.

The high retear rate after a successful repair of the rotator cuff (RC) is a major clinical challenge. Muscle atrophy and fat accumulation of RC muscles over time adversely affect the rate of retear. Since current surgical techniques do not improve muscle degenerative conditions, new treatments are being developed to reduce muscle atrophy and fat accumulation.