Hydrogen-Bond-Mediated Glycosylation Reactions with Glycosyl Picolinates.

Herein, we report a generally applicable hydrogen-bond-mediated glycosylation protocol of glycosyl picolinate donors with a charged (thio)urea hydrogen-bond-donor catalyst. A variety of nucleophiles, including complex natural products, glycosides, amino acids, and less nucleophilic phenolic acceptors were also glycosylated successfully. Hydrogen-bond-mediated glycosylation systems combined with different strategies were also explored to achieve stereoselective glycosylation.

Expression, Purification, and Preliminary Characterization of Putative Protein Tyrosine Phosphatase Oca1.

Introduction/objective: Protein phosphatases act as counterparts to protein kinases and are considered crucial for the homeostatic balance of cell signalling. In contrast to kinases, which can be categorized according to their substrate specificity, phosphatases are versatile and can detect substrates with much less distinction; hence, it is challenging to identify the physiological phosphatase-substrate pair. The Oca1 of Saccharomyces cerevisiae is a putative protein tyrosine phosphatase (PTP) and is required for cell cycle arrest in response to oxidative stress.

Engineering Bacopa monnieri for improved bacoside content and its neurological evaluation.

Bacosides are triterpenoidal saponins with numerous pharmacological benefits. One of the significant drawbacks is the low availability of these bacosides. The bacoside pathway is not well elucidated, and there is no prior report of a metabolic engineering approach in this plant.

Mitochondrial calcium uniporter regulates human fibroblast-like synoviocytes invasion via altering mitochondrial dynamics and dictates rheumatoid arthritis pathogenesis.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that currently has no cure. Fibroblast-like synoviocytes (FLS), present in the RA synovium, play a pivotal role in RA pathogenesis. Notably, FLS in the RA patients (RA-FLS) exhibit characteristics similar to cancer cells, like enhanced migration, invasiveness, uncontrolled proliferation, resistance to apoptosis, and metabolic reprogramming.

Machine learning-guided Orbitrap-HRAMS-based metabolomic fingerprinting for geographical origin, variety and tissue specific authentication, and adulteration detection of turmeric and ashwagandha.

The increasing global demand for herbs and spices in food and nutraceutical industries highlights their key functional benefits, including antioxidant and anti-inflammatory properties. Ensuring authenticity and traceability is essential to counteract challenges such as geographical origin (GO) mislabelling and tissue- or variety-specific adulteration, which can undermine product quality and safety. This study employs LC-Orbitrap-MS-based untargeted metabolomics coupled with machine learning to authenticate the GO, variety, and tissue specificity of turmeric (Curcuma longa) and ashwagandha (Withania somnifera), two widely used food ingredients.

Oxidative and nitrosative stress in bipolar affective disorder and its familial aggregation.

Introduction: Bipolar disorder (BD) is one of the most encountered disorders in psychiatric clinics. Despite extensive research and advancements in BD treatment, little is known about the disease's primary etiopathogenesis and relationship with different pathophysiological traits. The present study is aimed to evaluate the pathophysiological role of oxidative and nitrosative stress in BD patients and identify their familial aggregation.

Organocatalyzed O-glycosylation of glycosyl trichloroacetimidates donors: l-prolinethioamide as brønsted acid catalyst.

In this study, we present the utilization of l-proline-derived thioamide small organic molecules as an effective organocatalyst for the O-glycosylation of various glycosyl trichloroacetimidate donors, eliminating the need for any cocatalysts or additives. The catalytic process achieves high yields with a wide array of alcohol and sugar nucleophiles, demonstrating a broad substrate scope and operational simplicity under mild reaction conditions. Preliminary mechanistic investigations indicate that l-prolinethioamide facilitates the glycosylation reaction via Brønsted acid/base catalysis, involving the formation of a catalyst-acceptor adduct.

Base-Assisted and Silica Gel-Promoted Indole-Substituted Indene Synthesis.

Herein, we report for the first time a transition-metal-free and mild protocol that requires inexpensive KCO and silica gel for direct access to polysubstituted indenes from readily obtainable starting precursors. Notably, sequential Michael addition, intramolecular cyclization, and silica gel-promoted nucleophilic substitution reactions afford the desired products. A broad range of indoles and other aromatic nucleophiles are well-tolerated, affording indenes in moderate to good yields.

Ormeloxifene induces mitochondrial fission-mediated pro-death autophagy in colon cancer cells.

Ormeloxifene (ORM) is a nonsteroidal selective estrogen receptor modulator (SERM), developed by the CSIR-Central Drug Research Institute that is approved as an oral contraceptive. However, it has also shown promising anti-cancer activity, especially in breast cancer. Here, we have investigated the anti-cancer effect of ORM on colon cancer cells and show that its antiproliferative activity is mediated through mitochondrial fission and autophagy-associated cell death.

Comparative assessment of flavonoid content in banana pulp and peel and their role in mitigating bone loss conditions and promoting osteoblast differentiation.

Banana fruit is widely grown and serves as a source of income across the tropics. It is known for its nutritional qualities and well-recognized medicinal applications. Given that banana pulp and peel are rich in flavonoids, such as naringenin, kaempferol, and quercetin, which are already known for their role in bone health, we hypothesize that banana pulp and peel can accelerate fracture healing, mitigate bone loss in post-menopausal conditions, and promote osteoblast differentiation.

Ruthenium(II)-catalyzed synthesis of poly-substituted furans intermolecular oxidative annulation of 3-(phenylethynyl) oxazolidin-2-ones.

This study presents a new method for the synthesis of poly-substituted furans by an oxidative annulation reaction of ynamides in the presence of Ru(II) as a catalyst, copper(II) triflate Cu(OTf) as an oxidant, and cesium carbonate (CsCO) as a base. The reaction shows broad substrate scope and compatibility with readily available starting materials, with yields ranging from good to excellent.

Microglial NOX2 as a therapeutic target in traumatic brain injury: Mechanisms, consequences, and potential for neuroprotection.

Traumatic brain injury (TBI) is a leading cause of long-term disability worldwide, with secondary injury mechanisms, including neuroinflammation and oxidative stress, driving much of its chronic pathology. While NADPH oxidase 2 (NOX2)-mediated reactive oxygen species (ROS) production is a recognized factor in TBI, the specific role of microglial NOX2 in perpetuating oxidative and inflammatory damage remains underexplored. Addressing this gap is critical, as current therapeutic approaches primarily target acute symptoms and fail to interrupt the persistent neuroinflammation that contributes to progressive neurodegeneration.

Design, synthesis and evaluation of novel carboline-triazole hybrids as promising antimalarial agents.

A series of twenty-four carboline-triazole derivatives were synthesized using a molecular hybridization approach and evaluated for their antimalarial activity against Plasmodium parasites. Ten compounds exhibited strong in vitro antimalarial activity against both chloroquine-sensitive Pf3D7 and chloroquine-resistant PfK1 strains, with IC values ranging from 0.21 to 0.

Unravelling the transcriptomic characteristics of bronchoalveolar lavage in post-covid pulmonary fibrosis.

Background: Post-Covid Pulmonary Fibrosis (PCPF) has emerged as a significant global issue associated with a poor quality of life and significant morbidity. Currently, our understanding of the molecular pathways of PCPF is limited. Hence, in this study, we performed whole transcriptome sequencing of the RNA isolated from the bronchoalveolar lavage (BAL) samples of PCPF and compared it with idiopathic pulmonary fibrosis (IPF) and non-ILD (Interstitial Lung Disease) control to understand the gene expression profile and associated pathways.

Self-responsive biomimetic short lipopeptide-based delivery systems for enhanced antibiotic efficacy against drug-resistant infections.

Biocompatible short peptide amphiphile nanostructures were developed as an innovative platform for the efficient delivery of meropenem. These nanostructures exhibit self-responsive behavior, specifically targeting infection sites and releasing the antibiotic in a controlled manner. Testing against clinically relevant bacteria, including methicillin-resistant (MRSA) and vancomycin-resistant (VRSA), demonstrated their ability to enhance antibiotic concentration at the site of infection, significantly improving therapeutic efficacy.

Catalytic stereoselective synthesis of all-carbon tetra-substituted alkenes -selective alkyne difunctionalization.

We report a Ni-catalyzed cascade reaction leading to the arylation of an alkyne-induced acyl migration and the formation of all-carbon tetra-substituted alkenes in good yields with exclusive -selectivity. This transformation involves the generation of a nucleophilic vinyl-Ni species through regioselective -aryl nickelation of the alkynes, followed by an intramolecular acyl migration. The steric and electronic properties of the phosphine ligands are crucial for achieving high regio- and stereocontrol in this migratory carbo-acylation process.

Dry powder Inhalation of lytic mycobacteriophages for adjunct therapy in a mouse model of infection with Mycobacteriumtuberculosis.

Inhaled therapy of tuberculosis (TB) by a Dry Powder Inhalation (DPI) comprising mycobacteriophage D29 and TM4 was non-inferior to oral anti-tuberculosis therapy (ATT) with isoniazid and rifampicin in a mouse model of infection with Mycobacterium tuberculosis (Mtb). No pharmaceutical phage product of mycobacteriophages is approved for large-scale production. We scaled up preparation and downstream processing of phages, developed DPI formulations, and established methods for determining identity, purity, assay, stability, and critical quality attributes (CQA).

A new sesquiterpene lactone isolated from and cytotoxic activity against the A549 cancer cell line.

A new sesquiterpene lactone ainslialide and eighteen known compounds were isolated from aq. methanolic extract of Mattf (Compositae). All the isolates were structurally elucidated by the analysis of spectroscopic data 1D, 2D-NMR, HR-ESI-MS and previously reported literature for the known compounds.

Exploring the potential anti-senescence effects of soybean-derived peptide Soymetide in mice hippocampal neurons via the Wnt/β-catenin pathway.

Soybean-based foods enhance cognitive functions by influencing hippocampal mechanisms. These salutary effects have so far been attributed to isoflavones present in soybeans. Considering cellular senescence contributes to cognitive decline and that no specific soy-derived peptides are known for their potential to mitigate senescence, we examined the efficacy of a thirteen amino acid soy-derived peptide, Soymetide, on a doxorubicin-induced senescence mice model.

Designing pegylated dextran sheathed doxorubicin loaded iron nanoparticles against premenopausal breast cancer.

Premenopausal women, often iron-deficient, face a heightened risk of breast cancer. Magnetic nanoparticles (MNPs) show promise for cancer therapy but are limited by challenges in pharmacokinetics, biocompatibility, and magnetic property stability, leading to reduced efficacy and resistance. To overcome these hurdles, a double-shelled magnetic nanoparticle (DOX-RA-MNP) system was developed for pH-sensitive delivery of Retinoic acid and Doxorubicin using an immunomodulatory polymeric approach.

The composition of human sperm sncRNAome: a cross-country small RNA profiling.

Background: Over the last decade, numerous studies have implicated sperm-borne small non-coding RNAs (sncRNAs) in fertility and transgenerational inheritance. Spermatozoa contain a variety of small RNAs; however, inter-individual and inter-population variations in the human sperm sncRNA content (sncRNAome) have not yet been ascertained.

Methods: We performed sncRNA sequencing in 54 normozoospermic proven fertile Indian donors.

MCP-1 promotes ILK phosphorylation at Ser246 during endometriosis development and affects the pregnancy outcome.

In women with endometriosis, monocyte chemoattractant protein 1 (MCP-1) or chemokine (C-C motif) ligand 2 (CCL2) is elevated in serum, peritoneal fluid, and endometriotic lesions, though its exact role in endometriosis is still unknown. The MCP-1 downstream molecule integrin-linked kinase (ILK) is involved in several cellular events. Our recent findings suggest that MCP-1 promotes an inflammatory response via ILK in a mouse endometriosis model.

PARP-2 acts on ILK signaling and pharmacological targeting of PARP-2 ameliorate endometriosis in a mouse model.

Endometriosis, an endocrine disorder in reproductive-aged women with an occurrence of ∼10 %, gives rise to inflammation, pelvic pain, menstrual irregularity, infertility, etc. One study demonstrated the elevated plasma level of PARP during endometriosis. Thus, we studied the role of PARP-2 during endometriosis using human endometriotic tissue and cells along with an endometriosis mouse model.

Understanding the Role of RING-Between-RING E3 Ligase of the Human Malaria Parasite.

E3 ligases constitute an important component of proteostasis machinery, which plays a critical role in the survival of malaria parasites through post-translational modifications of their protein substrates. In contrast to humans, parasite E3 ligases have not been extensively studied. Here, we characterize a unique Plasmodium E3 ligase that has both RING and HECT-like features with zinc-coordinating domains.