Suzuki-Miyaura/Mizoroki-Heck coupling cascade to access 2,2'-bifunctionalized biaryls.

Biaryl motifs are essential structural features in several drugs and functional molecules. Cyclic diaryliodonium has been scarcely explored as a bifunctional agent compared to ring opening and annulation reactions. Herein, a three-component cascade approach is developed to synthesize bifunctionalized biaryls employing cyclic diaryliodoniums as a biarylating agent.

Pancreastatin inhibitor PSTi8 improves ovarian health in Letrozole-HFD induced PCOS rats by ameliorating metabolic and reproductive parameters.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder associated with insulin resistance (IR) and hyperandrogenism. IR plays a crucial role in the etiology of PCOS. An insulin-sensitizing agent like metformin is most commonly used as an off-label drug for the treatment of PCOS.

Design, synthesis and biological evaluation of ethyl 5-(1-benzyl-1H-indol-5-yl)isoxazole-3-carboxylates as antimycobacterial agents.

The continued prevalence of drug-resistant Mycobacterium tuberculosis (Mtb) strains, particularly against first-line antitubercular (anti-TB) drugs, presents an impending public health threat that necessitates the exploration and development of New Chemical Entities (NCEs). In search of new anti-TB leads, a library of ethyl 5-(1-benzyl-1H-indol-5-yl)isoxazole-3-carboxylates were generated through a strategy of scaffold hopping from the proven isoxazole-3-carboxylate-based anti-TB pharmacophore. We evaluated their antibacterial potential against a panel of pathogenic bacteria and MtbH37Rv strains.

Emerging role of EZH2 in solid tumor metastasis.

Cancer cells experience multiple reversible changes during their metastatic spread. Epigenetic reprogramming, being reversible, has emerged as a critical driver of cancer metastasis. Epigenetic modulator Enhancer of Zeste homolog 2 (EZH2) is an important candidate for such reprogramming events.

FDA-approved polypeptide PTH 1-34 impedes palmitic acid-mediated osteoblasts dysfunction by promoting its differentiation and thereby improving skeletal health.

Excessive consumption of saturated fatty acids creates a debilitating cellular environment that hinders the normal function and survival of osteoblasts, contributing to bone metabolic disorders such as osteoporosis. The FDA-approved polypeptide PTH 1-34 is a well-established therapy for post-menopausal osteoporosis, yet its protective effects in a palmitic acid (PA)-rich hyperlipidemic environment are not well understood. This study investigates the impact of PTH 1-34 on PA-induced cellular responses in osteoblasts.

Generating a Peptide Library Using the Repeats of Amino Acid Scaffolds Created by Sliding the Framework of a 7-mer Human Chemerin Segment and Discovery of Potent Antibacterial and Antimycobacterial Peptides.

The quest for new approaches for generating novel bioactive designer proteins/peptides has continued with their success in various biomedical applications. Previously, we designed a 14-mer α-helical peptide with antimicrobial and antimycobacterial activities by employing a tandem repeat of the 7-mer, "KVLGRLV" human chemerin segment. Herein, we devised a new method of "sliding framework" with this segment to create amino acid scaffolds of varying sizes and sequences and explored the design of a peptide library with antibacterial and antimycobacterial activities.

Design, Synthesis, and Antibacterial Activities of Multi-functional C2-Functionalized 1,4-Naphthoquinonyl Organoseleniums.

A practical and efficient reaction for C2-selenylation of 1,4-naphthoquinones has been explored. This coupling reaction of two redox structural motifs, such as 2-bromo-1,4-naphthoquinone with diaryldiselenide / ebselen has been achieved by using sodium borohydride reducing agent at room temperature. Using this approach, several 2-selenylated-1,4-naphthoquinones were obtained in moderate to good yields and thoroughly characterized by multinuclear (1H, 13C, and 77Se) NMR, cyclic voltammetry, and mass spectrometry.

Assessment of azithromycin-induced toxicity in : Effects on morphology, behavior, and lipid metabolism.

Antibiotics are indispensable in modern healthcare, playing a critical role in mitigating bacterial infections. Azithromycin is used to fight upper respiratory tract infections, however has potential toxic effects that remain inadequately understood. In our present study, azithromycin exposure to led to significant physiological and behavioral change, with pronounced effects observed at the studied concentration.

Autophagy protein Atg7 is essential for maintaining malaria parasite cellular homeostasis and organelle biogenesis.

parasites have a complex life cycle that transitions between mosquito and mammalian hosts, and undergo continuous cellular remodeling to adapt to various drastic environments. Following hepatocyte invasion, the parasite discards superfluous organelles for intracellular replication, and the remnant organelles undergo extensive branching and mature into hepatic merozoites. Autophagy is a ubiquitous eukaryotic process that permits the recycling of intracellular components.

MicroRNAs as Biomarker in Rheumatoid Arthritis: Pathogenesis to Clinical Relevance.

MicroRNAs (miRNAs) have emerged as intricate players in rheumatoid arthritis (RA), holding promise as discerning biomarkers for diagnostic and prognostic purposes. The lack of sensitivity and specificity in current diagnostic techniques, such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), causes diagnosis delays in RA. The miR-146a and miR-155 act in inflammatory cascades and reduce joint deterioration, and miR-223 is paradoxical, acting differently in different illness scenarios.

BF-Mediated C2-Amidation of Quinoline Oxides Employing Trifluorodiazoethane and Acetonitrile: Access to 2-(Trifluoroethyl)amidoquinolines.

A Lewis acid-mediated C2-trifluoroethylamidation of quinolines, employing quinoline oxides, trifluorodiazoethane, and acetonitrile to forge a new class of (quinolin2-yl)-(trifluoroethyl)acetamide is presented in this Letter. The reaction proceeds through a carbene generation/nitrile ylide formation/(3 + 2) cycloaddition/rearrangement cascade to furnish quinoline-2-(trifluoroethyl)acetamide derivatives in high yields.

A survey of physicians, biomedical researchers and college-educated adults in urban north India about inhaled therapies.

We surveyed 15 persons with a medical qualification, 133 graduate students doing biomedical research and 56 students or working people with a college education in any discipline. Questions were designed to gauge awareness about inhaled therapies for tuberculosis (TB), non-tubercular mycobacterial lung disease (NTM-LD) and idiopathic pulmonary fibrosis (IPF). Respondents from six cities in North India, aged between 21 and 57 years answered 20 questions.

The Root-Tuber Trypsin Inhibitor of Winged Bean and Its Anti-cancerous Activity Against Osteosarcoma Cell-Line.

Trypsin inhibitor from the root-tuber of underutilized legume Winged bean (Psophocarpus tetragonolobus (L.) DC.) (WbT-TI) was purified using ion exchange chromatography followed by size-exclusion chromatography.

Salmonella Typhimurium effector SseI regulates host peroxisomal dynamics to acquire lysosomal cholesterol.

Salmonella enterica serotype Typhimurium (Salmonella) resides and multiplies intracellularly in cholesterol-rich compartments called Salmonella-containing vacuoles (SCVs) with actin-rich tubular extensions known as Salmonella-induced filaments (SIFs). SCV maturation depends on host-derived cholesterol, but the transport mechanism of low-density lipoprotein (LDL)-derived cholesterol to SCVs remains unclear. Here we find that peroxisomes are recruited to SCVs and function as pro-bacterial organelle.

induced SIRT1 and SIRT3 are crucial for maintaining the metabolic switch in bacteria and host for successful pathogenesis.

Sirtuins are the major players in host immunometabolic regulation. However, the role of sirtuins in the modulation of the immune metabolism pertaining to salmonellosis is largely unknown. Here, our investigation focussed on the role of two important sirtuins, SIRT1 and SIRT3, shedding light on their impact on intracellular 's metabolic switch and pathogenesis establishment.

MD simulations for rational design of high-affinity HDAC4 inhibitors - Analysis of non-bonding interaction energies for building new compounds.

This study investigates the contributions of non-bonding energy (NBE) to the efficacy of four HDAC4 co-crystallized inhibitors (HA3, 9F4, EBE, and TFG) through 100ns Molecular Dynamics (MD) simulations. These inhibitors contain hydroxamic acid (HA3, 9F4, EBE) or diol (TFG) as zinc-binding groups. In PDBs 2VQJ and 2VQM, the HDAC4 catalytic domain is in the 'open' conformation, while in PDBs 4CBT and 6FYZ, the same is in the 'closed' conformation.

The role of glucagon-like peptides in osteosarcopenia.

Various metabolic abnormalities including obesity, insulin resistance, hypertension, dyslipidemia, hyperthyroidism, and low vitamin D levels have been linked to both osteopenia and sarcopenia. Osteo-sarcopenia is also commonly observed due to aging that notably include postmenopausal women. GLP-1, a labile incretin secreted from the intestinal L-cells stimulates insulin secretion and sensitivity, making it an effective anti-diabetic medication.

iDCNNPred: an interpretable deep learning model for virtual screening and identification of PI3Ka inhibitors against triple-negative breast cancer.

Triple-negative breast cancer (TNBC) lacks estrogen, progesterone, and HER2 expression, accounting for 15-20% of breast cancer cases. It is challenging due to low therapeutic response, heterogeneity, and aggressiveness. The PI3Ka isoform is a promising therapeutic target, often hyperactivated in TNBC, contributing to uncontrolled growth and cancer cell formation.

Glutathione S-transferase: A keystone in Parkinson's disease pathogenesis and therapy.

Parkinson's disease is a progressive neurodegenerative disorder that predominantly affects motor function due to the loss of dopaminergic neurons in the substantia nigra. It presents significant challenges, impacting millions worldwide with symptoms such as tremors, rigidity, bradykinesia, and postural instability, leading to decreased quality of life and increased morbidity. The pathogenesis of Parkinson's disease is multifaceted, involving complex interactions between genetic susceptibility, environmental factors, and aging, with oxidative stress playing a central role in neuronal degeneration.

Fission yeast Bsd1 is required for ER stress response in Ire1 independent manner.

Background: Endoplasmic reticulum plays a central role in protein folding and cellular detoxification. NEDD4, a HECT E3 ubiquitin ligase, has been implicated in endoplasmic reticulum stress in humans. In this study, we have explored the role of S.

Bacterial Rps3 counters oxidative and UV stress by recognizing and processing AP-sites on mRNA via a novel mechanism.

Lesions and stable secondary structures in mRNA severely impact the translation efficiency, causing ribosome stalling and collisions. Prokaryotic ribosomal proteins Rps3, Rps4 and Rps5, located in the mRNA entry tunnel, form the mRNA helicase center and unwind stable mRNA secondary structures during translation. However, the mechanism underlying the detection of lesions on translating mRNA is unclear.

Differential Immune Responses of Th1 Stimulatory Chimeric Antigens of in BALB/c Mice.

Visceral leishmaniasis (VL) is the third most severe infectious parasitic disease and is caused by the protozoan parasite . To control the spread of the disease in endemic areas where the asymptomatic patients act as reservoirs as well as in nonendemic areas, an effective vaccine is indispensable. In this direction, we have developed three chimeric proteins by the combination of three already known Th1 stimulatory leishmanial antigens, i.

USP10 deubiquitinates and stabilizes CD44 leading to enhanced breast cancer cell proliferation, stemness and metastasis.

Despite extensive research, strategies to effectively combat breast cancer stemness and achieve a definitive cure remains elusive. CD44, a well-defined cancer stem cell (CSC) marker is reported to promote breast cancer tumorigenesis, metastasis, and chemoresistance. However, mechanisms leading to its enhanced expression and function is poorly understood.

Three Strikingly Different Crystal Habits of Tadalafil: Design, Characterization, Pharmaceutical Performance, and Computational Studies.

The present study aims at improving the physicochemical properties of a widely used drug Tadalafil through crystal habit modification, without changing the polymorphic form. Three distinct types of crystal habits, namely, needle, plate, and block, were obtained under controlled crystallization protocols with optimized solvent compositions. Complete characterization of these three crystal habits was carried out using powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and Fourier transform infrared spectroscopy.