Overlapping Neuroimmune Mechanisms and Therapeutic Targets in Neurodegenerative Disorders.

Many potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases, such as Alzheimer's (AD) disease, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), as well as in a seemingly distinct Niemann-Pick type C disease with primarily juvenile onset. This strongly argues for an overlap in pathogenic mechanisms. The commonly researched immune targets include various immune cell subsets, such as microglia, peripheral macrophages, and regulatory T cells (Tregs); the complement system; and other soluble factors.

Mutant p53 sustains serine-glycine synthesis and essential amino acids intake promoting breast cancer growth.

Reprogramming of amino acid metabolism, sustained by oncogenic signaling, is crucial for cancer cell survival under nutrient limitation. Here we discovered that missense mutant p53 oncoproteins stimulate de novo serine/glycine synthesis and essential amino acids intake, promoting breast cancer growth. Mechanistically, mutant p53, unlike the wild-type counterpart, induces the expression of serine-synthesis-pathway enzymes and L-type amino acid transporter 1 (LAT1)/CD98 heavy chain heterodimer.

VirulentPred 2.0: An improved method for prediction of virulent proteins in bacterial pathogens.

Virulence proteins in pathogens are essential for causing disease in a host. They enable the pathogen to invade, survive and multiply within the host, thus enhancing its potential to cause disease while also causing evasion of host defense mechanisms. Identifying these factors, especially potential vaccine candidates or drug targets, is critical for vaccine or drug development research.

Identification of Novel, Potent, and Selective Compounds against Malaria Using Glideosomal-Associated Protein 50 as a Drug Target.

Phylum apicomplexan consists of parasites, such as and . These obligate intracellular parasites enter host cells an energy-dependent process using specialized machinery, called the glideosome. In the present study, we used GAP50, a glideosome-associated protein, as a target to screen 951 different compounds from diverse chemical libraries.

Adjunct Therapy With All-trans-Retinoic Acid Improves Therapeutic Efficacy Through Immunomodulation While Treating Tuberculosis With Antibiotics in Mice.

Tuberculosis is the second leading infectious killer after coronavirus disease 2019 (COVID-19). Standard antitubercular drugs exhibit various limitations like toxicity, long treatment regimens, and lack of effect against dormant and drug-resistant organisms. Here, we report that all-trans-retinoic acid (ATRA) improves Mycobacterium tuberculosis clearance in mice during treatment with the antitubercular drug isoniazid.

Functional and transcriptional heterogeneity within the massively expanding HLADRCD38 CD8 T cell population in acute febrile dengue patients.

CD8 T cells play a crucial role in protecting against intracellular pathogens such as viruses by eliminating infected cells and releasing anti-viral cytokines such as interferon gamma (IFNγ). Consequently, there is significant interest in comprehensively characterizing CD8 T cell responses in acute dengue febrile patients. Previous studies, including our own, have demonstrated that a discrete population of CD8 T cells with HLADR CD38 phenotype undergoes massive expansion during the acute febrile phase of natural dengue virus infection.

Elucidating the structure-function attributes of a trypanosomal arginyl-tRNA synthetase.

Aminoacyl-tRNA synthetases (aaRSs) are fundamental components of the protein translation machinery. In light of their pivotal role in protein synthesis and structural divergence among species, they have always been considered potential targets for the development of antimicrobial compounds. Arginyl-tRNA synthetase from Trypanosoma cruzi (TcArgRS), the parasite responsible for causing Chagas Disease, contains a 100-amino acid insertion that was found to be completely absent in the human counterpart of similar length, as ascertained from multiple sequence alignment results.

An emerging role of heterotrimeric G-proteins in nodulation and nitrogen sensing.

A comprehensive understanding of nitrogen signaling cascades involving heterotrimeric G-proteins and their putative receptors can assist in the production of nitrogen-efficient plants. Plants are immobile in nature, so they must endure abiotic stresses including nutrient stress. Plant development and agricultural productivity are frequently constrained by the restricted availability of nitrogen in the soil.

Engineered heart tissue maturation inhibits cardiomyocyte proliferative response to cryoinjury.

The cellular and molecular mechanisms that are responsible for the poor regenerative capacity of the adult heart after myocardial infarction (MI) are still unclear and their understanding is crucial to develop novel regenerative therapies. Considering the lack of reliable in vitro tissue-like models to evaluate the molecular mechanisms of cardiac regeneration, we used cryoinjury on rat Engineered Heart Tissues (rEHTs) as a new model which recapitulates in part the in vivo response after myocardial injury of neonatal and adult heart. When we subjected to cryoinjury immature and mature rEHTs, we observed a significant increase in cardiomyocyte (CM) DNA synthesis when compared to the controls.

Proteomics Profiling of Bladder Cancer Tissues from Early to Advanced Stages Reveals NNMT and GALK1 as Biomarkers for Early Detection and Prognosis of BCa.

The high recurrence rate and invasive diagnostic and monitoring methods in bladder cancer (BCa) clinical management require the development of new non-invasive molecular tools for early detection, particularly for low-grade and low-stage BCa as well as for risk stratification. By using an in-solution digestion method and label-free data-independent LC-MS/MS coupled with ion mobility, we profiled the BCa tissues from initiation to advanced stages and confidently identified and quantified 1619 proteins (≥2 peptides). A statistically significant difference in abundance (Anova ≤ 0.

Quorum sensing going wild.

The first discovered and well-characterized bacterial quorum sensing (QS) system belongs to , which uses -acyl homo-serine lactones (AHLs) for cell-cell signaling. AHL QS cell-cell communication is often regarded as a cell density-dependent regulatory switch. Since the discovery of QS, it has been known that AHL concentration (which correlates imperfectly with cell density) is not necessarily the only QS trigger.

Plasmodium falciparum OPA3-like protein (PfOPA3) is essential for maintenance of mitochondrial homeostasis and parasite proliferation.

Metabolic pathways and proteins responsible for maintaining mitochondrial dynamics and homeostasis in the Plasmodium parasite, the causative agent of malaria, remain to be elucidated. Here, we identified and functionally characterized a novel OPA3-like domain-containing protein in P. falciparum (PfOPA3).

Broad Genome Sequencing of Environmental and Clinical Strains and Genotyping.

The Next-Generation Sequencing revolution had a great impact on the genomics of Pseudomonas aeruginosa. Since the first release of the P. aeruginosa PAO1 genome, there are more than 5700 genomes published.

Atosiban and Rutin exhibit anti-mycobacterial activity - An integrated computational and biophysical insight toward drug repurposing strategy against Mycobacterium tuberculosis targeting its essential enzyme HemD.

With the advancements of high throughput computational screening procedures, drug repurposing became the privileged framework for drug discovery. The structure-based drug discovery is the widely used method of drug repurposing, consisting of computational screening of compounds and testing them in-vitro. This current method of repurposing leaves room for mechanistic insights into how these screened hits interact with and influence their targets.

Annickia affinis (Exell) Versteegh & Sosef methanol stem bark extract, potent fractions and isolated Berberine alkaloid target both blood and liver stages of malaria parasites.

Ethnopharmacological Relevance: Having identified Annickia affinis as the most potent antiplasmodial plant constituent in a hepta-herbal Agbo-iba (HHA) formula commonly used to manage malaria in Benin city, Nigeria, we have in this study attempted to identify the specialized metabolites responsible for antiplasmodial activity of A. affinis through anti-blood stage malaria parasite activity guided isolation of potent molecules from its stem bark methanol extract. After that, phenotypic effects, including stage-specific kill kinetics, were investigated.

Advancing microbiome research with machine learning: key findings from the ML4Microbiome COST action.

The rapid development of machine learning (ML) techniques has opened up the data-dense field of microbiome research for novel therapeutic, diagnostic, and prognostic applications targeting a wide range of disorders, which could substantially improve healthcare practices in the era of precision medicine. However, several challenges must be addressed to exploit the benefits of ML in this field fully. In particular, there is a need to establish "gold standard" protocols for conducting ML analysis experiments and improve interactions between microbiome researchers and ML experts.

Anti-tumor activity of selinexor in combination with antineoplastic agents in chronic lymphocytic leukemia.

Despite recent relevant therapeutic progresses, chronic lymphocytic leukemia (CLL) remains an incurable disease. Selinexor, an oral inhibitor of the nuclear export protein XPO1, is active as single agent in different hematologic malignancies, including CLL. The purpose of this study was to evaluate the anti-tumor effects of selinexor, used in combination with chemotherapy drugs (i.

The management and outcomes of hepatocellular carcinoma in sub-Saharan Africa: a systematic review.

Background: Hepatocellular carcinoma (HCC) is a leading cause of mortality in sub-Saharan Africa (SSA). This systematic review aimed to appraise all population-based studies describing the management and outcomes of HCC in SSA.

Methods: A systematic review based on a search in PubMed, PubMed Central, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), AfricaWide and Cochrane up to June 2023 was performed.

Development of engineered Candida tropicalis strain for efficient corncob-based xylitol-ethanol biorefinery.

Background: Xylitol has a wide range of applications in the pharmaceuticals, cosmetic, food and beverage industry. Microbial xylitol production reduces the risk of contamination and is considered as environment friendly and sustainable compared to the chemical method. In this study, random mutagenesis and genetic engineering approaches were employed to develop Candida tropicalis strains with reduced xylitol dehydrogenase (XDH) activity to eliminate co-substrate requirement for corn cob-based xylitol-ethanol biorefinery.

Systematic identification of CAZymes and transcription factors in the hypercellulolytic fungus Penicillium funiculosum NCIM1228 involved in lignocellulosic biomass degradation.

Background: Penicillium funiculosum NCIM1228 is a filamentous fungus that was identified in our laboratory to have high cellulolytic activity. Analysis of its secretome suggested that it responds to different carbon substrates by secreting specific enzymes capable of digesting those substrates. This phenomenon indicated the presence of a regulatory system guiding the expression of these hydrolyzing enzymes.

Phosphorylation of CFP10 modulates virulence.

Secreted virulence factors play a critical role in bacterial pathogenesis. Virulence effectors not only help bacteria to overcome the host immune system but also aid in establishing infection. , which causes tuberculosis in humans, encodes various virulence effectors.

Exploiting the molecular subtypes and genetic landscape in pancreatic cancer: the quest to find effective drugs.

Pancreatic Ductal Adenocarcinoma (PDAC) is a very lethal disease that typically presents at an advanced stage and is non-compliant with most treatments. Recent technologies have helped delineate associated molecular subtypes and genetic variations yielding important insights into the pathophysiology of this disease and having implications for the identification of new therapeutic targets. Drug repurposing has been evaluated as a new paradigm in oncology to accelerate the application of approved or failed target-specific molecules for the treatment of cancer patients.

In-silico and in-vitro study reveals ziprasidone as a potential aromatase inhibitor against breast carcinoma.

Aromatase enzyme plays a fundamental role in the development of estrogen receptors, and due to this functionality, the enzyme has gained significant attention as a therapeutic for reproductive disorders and cancer diseases. The currently employed aromatase inhibitors have severe side effects whereas our novel aromatase inhibitor is more selective and less toxic, therefore has greater potential to be developed as a drug. The research framework of this study is to identify a potent inhibitor for the aromatase target by profiling molecular descriptors of the ligand and to find a functional pocket in the target by docking and MD simulations.

Expression Analysis Reveals Differentially Expressed Genes in BPH and WBPH Associated with Resistance in Rice RILs Derived from a Cross between RP2068 and TN1.

BPH (brown planthopper) and WBPH (white backed planthopper) are significant rice pests that often co-occur as sympatric species and cause substantial yield loss. Despite their genetic similarities, different host-resistance genes confer resistance against these two hoppers. The defense mechanisms in rice against these pests are complex, and the molecular processes regulating their responses remain largely unknown.