Comparative genome analysis reveals putative and novel antimicrobial resistance genes common to the nosocomial infection pathogens.

The 21st century has witnessed several clinical outcomes regarding AMR. One health concept has been foreseen as a standard global public health initiative in ensuring human, animal and environmental health. The present study explores critical Gram-negative ESKAPE pathogens encompassing Acinetobacter baumannii (ACB), Klebsiella pneumoniae (KPX) and Pseudomonas aeruginosa (PAE).

In Vitro and In Vivo Biological Evaluation of Novel 1,4-Naphthoquinone Derivatives as Potential Anticancer Agents.

A novel library of naphthoquinone derivatives (3-5 aa) was synthesized and evaluated for their anticancer properties. Specifically, compounds 5 i, 5 l, 5 o, 5 q, 5 r, 5 s, 5 t, and 5 v demonstrated superior cytotoxic activity against the cancer cell lines that were studied. All the studied compounds exhibited a higher selectivity index (SI) and a favourable safety profile than the standard drug doxorubicin.

Mammalian maltase-glucoamylase and sucrase-isomaltase inhibitory effects of Artocarpus heterophyllus: An in vitro and in silico approach.

Alpha-glucosidase (maltase, sucrase, isomaltase and glucoamylase) activities which are involved in carbohydrate metabolism are present in human intestinal maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI). Hence, these proteins are important targets to identify drugs against postprandial hyperglycemia thereby for diabetes. To find natural-based drugs against MGAM and SI, Artocarpus heterophyllus leaf was explored for MGAM and SI inhibition in in vitro and in silico.

Elucidation of escitalopram oxalate and related antidepressants as putative inhibitors of PTP4A3/PRL-3 protein in hepatocellular carcinoma: A multi-computational investigation.

Hepatocellular carcinoma (HCC) persists to be one of the most devastating and deadliest malignancies globally. Recent research into the molecular signaling networks entailed in many malignancies has given some prominent insights that can be leveraged to create molecular therapeutics for combating HCC. Therefore, in the current communication, an in-silico drug repurposing approach has been employed to target the function of PTP4A3/PRL-3 protein in HCC using antidepressants: Fluoxetine hydrochloride, Citalopram, Amitriptyline, Imipramine, and Escitalopram oxalate as the desired ligands.

Bacoside-A repressed the differentiation and lipid accumulation of 3T3-L1 preadipocytes by modulating the expression of adipogenic genes.

Obesity is one of the more complicated diseases, it can induce numerous life-threatening diseases mainly diabetes mellitus, cardiovascular disease, hypertension, and certain cancers. In this study, we assessed the efficacy of bacoside-A (a dammarane-type triterpenoid saponin derived from the plant Bacopa monniera Linn.) on the adipogenesis of 3T3-L1 preadipocytes.

A dual fluorescence protein expression system detects cell cycle dependent protein noise.

Inherently identical cells exhibit significant phenotypic variation. It can be essential for many biological processes and is known to arise from stochastic, 'noisy', gene expression that is determined by intrinsic and extrinsic components. It is now obvious that the noise varies as a function of inducer concentration.

Ameliorative inhibition of sirtuin 6 by imidazole derivative triggers oxidative stress-mediated apoptosis associated with Nrf2/Keap1 signaling in non-small cell lung cancer cell lines.

Redox homeostasis is the vital regulatory system with respect to antioxidative response and detoxification. The imbalance of redox homeostasis causes oxidative stress. Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2, also called Nfe2l2)/Kelchlike ECH-associated protein 1 (Keap1) signaling is the major regulator of redox homeostasis.

and functional validation of imidazole derivatives as potential sirtuin inhibitor.

Introduction: Epigenetic enzymes can interact with a wide range of genes that actively participate in the progression or repression of a diseased condition, as they are involved in maintaining cellular homeostasis. Sirtuins are a family of Class III epigenetic modifying enzymes that regulate cellular processes by removing acetyl groups from proteins. They rely on NAD as a coenzyme in contrast to classical histone deacetylases (HDACs) (Class I, II, and IV) that depend on Zn for their activation, linking their function to cellular energy levels.

Design, synthesis and anticancer evaluation of novel arylhydrazones of active methylene compounds.

Nerve growth factor (NGF) and its receptor, tropomyosin kinase receptor kinase type A (TrkA) is emerging as an important target for Glioblastoma (GBM) treatment. TrkA is the cancer biomarker majorly involved in tumor invasion and migration into nearby normal tissue. However, currently, available Trk inhibitors exhibit many adverse effects in cancer patients, thus demanding a novel class of ligands to regulate Trk signaling.

Recent Development and Application of "Nanozyme" Artificial Enzymes-A Review.

Nanozymes represent a category of nano-biomaterial artificial enzymes distinguished by their remarkable catalytic potency, stability, cost-effectiveness, biocompatibility, and degradability. These attributes position them as premier biomaterials with extensive applicability across medical, industrial, technological, and biological domains. Following the discovery of ferromagnetic nanoparticles with peroxidase-mimicking capabilities, extensive research endeavors have been dedicated to advancing nanozyme utilization.

Vitamin C fortification: need and recent trends in encapsulation technologies.

The multifaceted role of vitamin C in human health intrudes several biochemical functions that are but not limited to antioxidant activity, homoeostasis, amino acid synthesis, collagen synthesis, osteogenesis, neurotransmitter production and several yet to be explored functions. In absence of an innate biosynthetic pathway, humans are obligated to attain vitamin C from dietary sources to maintain its optimal serum level (28 μmol/L). However, a significant amount of naturally occurring vitamin C may deteriorate due to food processing, storage and distribution before reaching to the human gastrointestinal tract, thus limiting or mitigating its disease combating activity.

Benzenesulfonamide Analogs: Synthesis, Anti-GBM Activity and Pharmacoprofiling.

The tropomyosin receptor kinase A (TrkA) family of receptor tyrosine kinases (RTKs) emerge as a potential target for glioblastoma (GBM) treatment. Benzenesulfonamide analogs were identified as kinase inhibitors possessing promising anticancer properties. In the present work, four known and two novel benzenesulfonamide derivatives were synthesized, and their inhibitory activities in TrkA overexpressing cells, U87 and MEF cells were investigated.

Structural diversity, functional versatility and applications in industrial, environmental and biomedical sciences of polysaccharides and its derivatives - A review.

Recent efforts on the expansion of sustainable and commercial primal matters are essential to enhance the knowledge of their hazards and noxiousness to humans and their environments. For example, polysaccharide materials are widely utilized in food, wound dressing, tissue engineering, industry, targeted drug delivery, environmental, and bioremediation due to their attractive degradability, nontoxicity and biocompatibility. There are numerous easy, quick, and efficient ways to manufacture these materials that include cellulose, starch, chitosan, chitin, dextran, pectin, gums, and pullulan.

Onco-Pathogen Mediated Cancer Progression and Associated Signaling Pathways in Cancer Development.

Infection with viruses, bacteria, and parasites are thought to be the underlying cause of about 8-17% of the world's cancer burden, i.e., approximately one in every five malignancies globally is caused by an infectious pathogen.

Elucidation of 7,8-dihydroxy flavone in complexing with the oxidative stress-inducing enzymes, its impact on radical quenching and DNA damage: an and approach.

Oxidative stress (OS) has been attributed to the progression of various disorders, including cancer, diabetes, and cardiovascular diseases. Several antioxidant compounds and free radical quenchers have been shown to mitigate oxidative stress. However, large-scale randomized controlled trials of such compounds on chronic disease aversion have yielded paradoxical and disappointing results due to the constrained cognizance of their oxidative mechanisms and therapeutic targets.

A novel EGFR inhibitor, HNPMI, regulates apoptosis and oncogenesis by modulating BCL-2/BAX and p53 in colon cancer.

Background And Purpose: Colorectal cancer (CRC) is the second most lethal disease, with high mortality due to its heterogeneity and chemo-resistance. Here, we have focused on the epidermal growth factor receptor (EGFR) as an effective therapeutic target in CRC and studied the effects of polyphenols known to modulate several key signalling mechanisms including EGFR signalling, associated with anti-proliferative and anti-metastatic properties.

Experimental Approach: Using ligand- and structure-based cheminformatics, we developed three potent, selective alkylaminophenols, 2-[(3,4-dihydroquinolin-1(2H)-yl)(p-tolyl)methyl]phenol (THTMP), 2-[(1,2,3,4-tetrahydroquinolin-1-yl)(4-methoxyphenyl)methyl]phenol (THMPP) and N-[2-hydroxy-5-nitrophenyl(4'-methylphenyl)methyl]indoline (HNPMI).

Innate Immune Response Assessment in L. upon Experimental Administration with Bio-Encapsulated Bacterin.

The present study aimed to analyze the enhancement of innate immune responses in juvenile-stage common carp ( L.), upon the administration of heat-killed at a dosage of 1 × 10 CFU ml through bio-encapsulation in the aquatic crustacean, . This work emphasizes the modulation of innate immune response when administered with the bio-encapsulated heat-killed antigen that acts as an inactivated vaccine against Motile Aeromonas Septicemia disease.

Mitochondrial complex III bypass complex I to induce ROS in GPR17 signaling activation in GBM.

Guanine nucleotide binding protein (G protein) coupled receptor 17 (GPR17) plays crucial role in Glioblastoma multiforme (GBM) cell signaling and is primarily associated with reactive oxidative species (ROS) production and cell death. However, the underlying mechanisms by which GPR17 regulates ROS level and mitochondrial electron transport chain (ETC) complexes are still unknown. Here, we investigate the novel link between the GPR17 receptor and ETC complex I and III in regulating level of intracellular ROS (ROSi) in GBM using pharmacological inhibitors and gene expression profiling.

Methanodibenzo[,][1,5]dioxocins as Novel Glutaminase Inhibitor with Anti-Glioblastoma Potential.

Glutamine metabolism is an important hallmark of several cancers with demonstrated antitumor activity in glioblastoma cancer cells (GBM). GBM cells regulate glutamine and use it as a major energy source for their proliferation through the glutaminolysis process. Enzymes, such as glutaminase in glutaminolysis, can be targeted by small-molecule inhibitors, thus exhibiting promising anticancer properties.

Structural analysis of human G-protein-coupled receptor 17 ligand binding sites.

The human G protein coupled membrane receptor (GPR17), the sensor of brain damage, is identified as a biomarker for many neurological diseases. In human brain tissue, GPR17 exist in two isoforms, long and short. While cryo-electron microscopy technology has provided the structure of the long isoform of GPR17 with Gi complex, the structure of the short isoform and its activation mechanism remains unclear.

Bias-force guided simulations combined with experimental validations towards GPR17 modulators identification.

Glioblastoma Multiforme (GBM) is known to be by far the most aggressive brain tumor to affect adults. The median survival rate of GBM patient's is < 15 months, while the GBM cells aggressively develop resistance to chemo- and radiotherapy with their self-renewal capacity which suggests the pressing need to develop novel preventative measures. We have recently proved that GPR17 -an orphan G protein-coupled receptor- is highly expressed on the GBM cell surface and it has a vital role to play in the disease progression.

Marine halophyte derived polyphenols inhibit glioma cell growth through mitogen-activated protein kinase signaling pathway.

Plants that are pharmacologically significant require intensive phytochemical characterization for bioactive profiling of the compounds, which has enabled their safe use in ayurvedic medicine. The present study is focused on the phytochemical analyses, quantitative estimation and profiling of secondary metabolites of leaf extract, as well as the antioxidant and cytotoxic activity of the potent halophytes such as Avicennia marina, Ceriops tagal, Ipomoea pes-caprae, and Sonneratia apetala. The in vitro antioxidant property was investigated using DPPH, ferric reducing antioxidant capacity (FRAP) assay.

Signaling landscape of mitochondrial non-coding RNAs.

Human mitochondria are the vital cell organelle acting as a storehouse of energy generation and diverse regulatory functions. Mitochondrial DNA comprises 93% coding region and 7% non-coding regions, in which the non-coding region hypothesized as responsible for signaling is our specific interest. Here, we explored the unknown functions of mitochondrial non-coding RNAs by studying their respective signaling pathways.

Advances in the Lung Cancer Immunotherapy Approaches.

Despite the progress in the comprehension of LC progression, risk, immunologic control, and treatment choices, it is still the primary cause of cancer-related death. LC cells possess a very low and heterogeneous antigenicity, which allows them to passively evade the anticancer defense of the immune system by educating cytotoxic lymphocytes (CTLs), tumor-infiltrating lymphocytes (TILs), regulatory T cells (Treg), immune checkpoint inhibitors (ICIs), and myeloid-derived suppressor cells (MDSCs). Though ICIs are an important candidate in first-line therapy, consolidation therapy, adjuvant therapy, and other combination therapies involving traditional therapies, the need for new predictive immunotherapy biomarkers remains.

Immunomodulatory Role of Thioredoxin Interacting Protein in Cancer's Impediments: Current Understanding and Therapeutic Implications.

Cancer, which killed ten million people in 2020, is expected to become the world's leading health problem and financial burden. Despite the development of effective therapeutic approaches, cancer-related deaths have increased by 25.4% in the last ten years.