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.

Addressing overlooked design considerations for nanoemulsions.

Despite progress in genetic and molecular research, which has opened up a myriad of targeted therapeutic possibilities, the compromised solubility and absorption profile of therapeutic entities restrict their passage across lipid barriers compromising efficacy. Consequently, nanoemulsions accrued significance as futuristic, safe, and effective lipid-based drug delivery systems due to their inherent array of physicochemical properties and provide exquisite bioavailability, reduced toxicity, and improved solubility of hydrophobic entities based on size and surface area. However, a pronounced gap exists in understanding and addressing challenges that arise during design and development of nanoemulsions.

Multifaceted evaluation of pyrazole derivative (T4)-chitosan (CS) nanoparticles: Morphology, drug release, and anti-tumor efficacy in a rat model.

The development of targeted nanotherapeutics has emerged as a pivotal advancement in cancer treatment, aiming to enhance the efficacy and specificity of drug delivery while minimizing systemic toxicity. Due to their biocompatibility and modifiable surface properties, Chitosan-based nanoparticles have shown considerable promise in encapsulating and delivering therapeutic agents directly to tumor sites. This study investigates the potential of 1,5-diary pyrazole derivative (T4)-loaded chitosan (CS) nanoparticles as a novel anticancer agent, evaluating their physical characteristics, in vivo biodistribution, and therapeutic efficacy against cancerous cells.

Case report: exome sequencing identified mutations in the and genes in a case of osteoporosis with recurrent fractures and extraskeletal manifestations.

Background: Genetic mutations have been reported in a number of bone disorders with or without extra-skeletal manifestations. The purpose of the present study was to investigate the genetic cause in a middle-aged woman with osteoporosis, recurrent fractures and extraskeletal manifestations.

Methods: A 56-year-old Indian woman presented to the clinic with complaints of difficulty in walking, recurrent fractures, limb bending, progressive skeletal deformities, and poor overall health.

Improved metabolic stability in iNOS knockout mice with Lactobacillus supplementation.

Oxidative and nitrosative stress play pivotal roles in normal physiological processes and the pathogenesis of metabolic disorders. Previous studies from our lab demonstrated insulin resistance (IR), and dyslipidemia in iNOS mice, emphasizing the importance of maintaining optimal redox balance. These mice exhibited altered gut microbiota with decreased Lactobacillus.

Bioavailability enhancement of formononetin by incorporation of natural bioenhancer in phospholipid complex.

Formononetin (FNT) has limited application due to poor water solubility and substantial phase II metabolism. In the present study, we used phospholipid complex (PC) containing FNT and UDP-glucuronosyltransferase (UGT1A1) inhibitor piperine (PIP) to overcome FNT limitations. We characterized and compared both FNT-PC and FNT-PIP-PC complexes.

The Neoteric Paradigm of Biomolecule-Functionalized Albumin-Based Targeted Cancer Therapeutics.

Albumin is a nature-derived, versatile protein carrier, that has been explored extensively by researchers for anticancer drug delivery due to its role in enhancing drug stability, solubility, circulation time, targeting capabilities, and overall therapeutic efficacy. Albumin nanoparticles possess inherent biocompatibility, biodegradability, and passive tumor-targeting ability due to the enhanced permeability and retention effect. However, non-specific accumulation of cytotoxic agents in healthy tissues remains a challenge.

Enantioselective Synthesis of Azatricycles via Post-Ugi Cyclizations.

We report a new method to create enantioenriched azatricycles using chiral α-amino acids in a two-step process after an Ugi reaction. Amino acids are great building blocks for making pure chiral molecules. Using chiral natural molecules in multicomponent reactions (MCRs) helps increase their variety by adding new chiral centers.

Synergistic defense: Quercetin and chondroitin sulfate combat bacterial trigger of rheumatoid arthritis, Proteus mirabilis through in-vitro and in-vivo mechanisms.

Rheumatoid arthritis, a chronic autoimmune disorder characterized by joint inflammation, is thought to be exacerbated by bacterial infections, notably Proteus mirabilis. This study explores the combined effects of quercetin, a potent antioxidant and anti-inflammatory flavonoid, and chondroitin sulfate, known for its cartilage-protective properties, as a potential therapeutic approach. Molecular docking analyses revealed favourable interactions between these compounds and key pro-inflammatory cytokines IL-6 and TNF-α, suggesting their potential to disrupt inflammation-related signaling pathways.

A peptide derived from the amino terminus of leptin improves glucose metabolism and energy homeostasis in myotubes and db/db mice.

Leptin is an adipokine, which plays key roles in regulation of glucose metabolism and energy homeostasis. Therefore, identification of a short peptide from leptin which improves glucose-metabolism and energy-homeostasis could be of significant therapeutic importance. Mutational studies demonstrated that N-terminal of human leptin hormone is crucial for activation of leptin-receptor while its C-terminal seems to have lesser effects in it.

Design, Synthesis, and Biological Studies of C-5-Substituted Diazenyl Derivatives of Uracil as Potent and Selective Antileishmanial Agents Targeting Uridine Biosynthesis Pathway Enzymes.

Herein, we describe the design and synthesis of a series of C-5-substituted diazenyl derivatives of uracil, exhibiting selective and potent antileishmanial but not antibacterial or antifungal activity. The formation of the substituted derivatives was confirmed by using FTIR, H, C NMR, and HRMS analysis. Among all of the sets of tested compounds, only three [, and ] showed the highest activity against (LD) promastigote and amastigote models of LD infections.

A Systematic Review and Meta-Analysis of the Effects of Dietary Isoflavones on Female Hormone-Dependent Cancers for Benefit-Risk Evaluation.

Female hormone-dependent cancers depend on estrogen for their growth. Numerous studies have explored the antitumor effect of dietary isoflavones on female hormone-dependent cancers. Still, few clinical evidence supports the use of isoflavones in female hormone-dependent cancer patients.

Pharmacophore-based 3D-QSAR modeling, virtual screening, docking, molecular dynamics and biological evaluation studies for identification of potential inhibitors of alpha-glucosidase.

Context: Alpha-glucosidase enzyme is considered an important therapeutic target for controlling hyperglycemia associated with type 2 diabetes. Novel scaffolds identified as potential alpha-glucosidase inhibitors from the Maybridge library utilizing pharmacophore modeling, molecular docking and biological evaluation are reported in this manuscript.

Method: A total of 51 xanthone series scaffolds previously reported as alpha-glucosidase inhibitors were collected and used as training and test sets.

Rationally Designed G-Quadruplex Selective "Turn-On" NIR Fluorescent Probe with Large Stokes Shift for Nucleic Acid Research-Based Applications.

Guanine-rich DNA/RNA sequences can form Hoogsteen bonds to adopt noncanonical secondary structures called G-quadruplexes, and these have been associated with diverse cellular processes. There has been considerable research interest in the design of G4-interacting ligands for cellular probing of the G4 structure and understanding its associated biological function. Most of the fluorescent G4 ligands either do not have significant selectivity over other nucleic acid structures, have high Stokes shift, or are not in the near-infrared (NIR) region, which limits its cellular visualization.

Therapeutic targeting of Wnt antagonists by small molecules for treatment of osteoporosis.

Wnt signaling is one of the key regulators of bone development and homeostasis. Wnt signaling regulates key biological events, including stem cell fate and osteoblast and osteoclast activity, leading to the maintenance of bone mass and strength. Wnt ligands are secreted glycoproteins that bind to Frizzled (FZD) receptors and their coreceptors, lipoprotein receptor-related proteins-5/6 (LRP5/6).

Silver-Catalyzed Synthesis of 5-Amino-4-sulfonyl Pyrazoles from 1,2-Diaza-1,3-dienes.

A facile and dependable synthetic route for 5-amino-4-sulfonyl pyrazoles, which are substantially important in pharmaceuticals, is highly desirable. This work presents a novel cascade reaction for their efficient synthesis. The approach utilizes silver as a catalyst for C(sp)-H sulfonylation of readily available starting materials 1,2-diaza-1,3-dienes with sulfinate salts, followed by intramolecular cascade cyclization annulation to afford the desired 5-amino-4-sulfonyl pyrazoles in good to excellent yields under mild conditions.

Novel techniques for early diagnosis and monitoring of Alzheimer's disease.

Introduction: Alzheimer's disease (AD) is the most common neurodegenerative disorder, which is characterized by a progressive loss of cognitive functions. The high prevalence, chronicity, and multimorbidity are very common in AD, which significantly impair the quality of life and functioning of patients. Early detection and accurate diagnosis of Alzheimer's disease (AD) can stop the illness from progressing thereby postponing its symptoms.

A Plasmodium late liver stage arresting GAP provides superior protection in mice.

Liver-stage genetically attenuated malaria parasites (GAPs) are powerful immunogens that provide protection against sporozoite challenge. We previously generated two late liver-stage-arresting GAPs by deleting the stearoyl-CoA desaturase (Scd) or sporozoite conserved orthologous transcript 1 (Scot1) genes in Plasmodium berghei. Immunization with Scd or Scot1 GAP conferred complete protection against a sporozoite challenge.

Unravelling biochemical and molecular mechanism of a carboxylesterase from Dietzia kunjamensis IITR165 reveal novel activities against polyethylene terephthalate.

Plastics and plasticizers accumulate in the ecological niches affecting biodiversity, and human and environmental health. Bacteria degrading polyethylene terephthalate (PET) were screened and PETases involved in PET degradation were characterized. Here, we identified a carboxylesterase Dkca1 of 48.

ER stress aggravates NOD1-mediated inflammatory response leading to impaired nutrient metabolism in hepatoma cells.

Nucleotide-binding Oligomerization Domain 1 (NOD1) is a cytosolic pattern recognition receptor that senses specific bacterial peptidoglycan moieties, leading to the induction of inflammatory response. Besides, sensing peptidoglycan, NOD1 has been reported to sense metabolic disturbances including the ER stress-induced unfolded protein response (UPR). However, the underpinning crosstalk between the NOD1 activating microbial ligands and the metabolic cues to alter metabolic response is not yet comprehensively defined.

A novel copper(II) complex with a salicylidene carbohydrazide ligand that promotes oxidative stress and apoptosis in triple negative breast cancer cells.

We report the synthesis, characterization, anti-cancer activity and mechanism of action of a novel water-soluble Cu(II) complex with salicylidene carbohydrazide as the ligand and -phenanthroline as the co-ligand. The synthesized complex (1) was characterized by FT-IR, EPR, and electronic spectroscopy, as well as single crystal X-ray diffraction. This compound was found to be paramagnetic from EPR spectra and X-ray crystallography revealed that the molecule crystallized in an orthorhombic crystal system.