Unlocking the antimalarial potential of novel steroid-tetraoxane hybrids through consensus molecular docking and molecular dynamics investigation.

Unlabelled: The emergence of resistance to artemisinin-based combination therapies necessitates the development of novel antimalarial agents. This study presents the first computational investigation of steroid-tetraoxane hybrids targeting cyclophilin, a key protein implicated in artemisinin resistance mechanisms. We designed a library of 127 steroid-1,2,4,5-tetraoxane hybrid compounds combining steroidal sapogenin (∆-diosgenin-3-one) and gem-dihydroperoxides, and employed consensus molecular docking across eight platforms to minimize algorithm-specific biases.

Antihypertensive potential of diosgenin: A comparative pharmacoinformatics study.

The angiotensin II type 1 receptor (ATR) is an important target protein involved in the regulation of hypertension, a major public health concern affecting 1.28 billion individuals globally. The existing drugs have serious side-effects on medium to long term use, and therefore, search for safer and more effective drug molecules is highly needed.

Geochemical characterization of heavy metal bearing phases in the sediments of Ganges, India: analyzing the toxicity status of sedimentary environment.

The present study characterizes the heavy metal contamination in the bottom sediments of the Ganga River and the toxicity status of the associated aquatic environment. Cd was identified as a heavy metal of substantial concern, with levels surpassing baseline values, showing the effect of anthropogenic factors such as untreated urban-industrial wastewater and runoff from agricultural regions, among other local causes. The grain size distribution reveals that sediments contain dominant sand fractions (up to 60%), followed by silt and a small percentage of clay fractions.

Unveiling Targeted Approaches to Combat Drug Resistance in Cancer Chemotherapy.

Despite significant advancements in medical science, cancer continues to be a major cause of morbidity and mortality worldwide. A key factor contributing to this persistent burden is the emergence of resistance to conventional therapeutic modalities, including chemotherapy, radiation therapy, and surgery. This phenomenon of drug resistance significantly hampers the efficacy of these treatments, leading to therapeutic failure and poor clinical outcomes.

Challenges and Progress of Orphan Drug Development for Rare Diseases.

Rare diseases, defined as conditions affecting fewer than 200,000 people in the United States or less than 1 in 2,000 people in Europe, pose significant challenges for healthcare systems and pharmaceutical research. This comprehensive review examines the evolving landscape of orphan drug development, analyzing scientific, economic, and regulatory challenges while highlighting recent technological breakthroughs and innovative approaches. We explore how artificial intelligence, next-generation sequencing, and personalized medicine are revolutionizing rare disease research and treatment development.

Identification, Detection, and Management of Soft Rot Disease of Ginger in the Eastern Himalayan Region of India.

Ginger is an important spice crop in the north-eastern region of India. Rhizome rot, also called soft rot, is one of the most devastating diseases found in ginger that causes yield losses of up to 100% under favourable conditions. Initially, the disease symptoms appear as a light yellowing of the leaf tips that gradually spreads down to the leaf blade of lower leaves and the leaf sheath along the margin.

Design, synthesis, docking, DFT, and MD simulation studies of new piperazine, 1,3,4-oxadiazole, and quinoline conjugates: A search for potent antiepileptic agents.

In this study, novel substituted 2-(5-(2-phenylquinolin-4-lyl)-1,3,4-oxadiazol-2-ylthio)-1-(4-phenylpiperazine-1-yl) ethanones (11a-i) were synthesized and assessed for their anticonvulsant potential. The structures of the synthesized compounds were confirmed through FT-IR, H NMR, C NMR, and mass spectrometry. In vivo, anticonvulsant investigations were performed using the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazol (scPTZ) induced epilepsy animal models.

Targeting Agrobacterium tumefaciens: A Computational Study on Quorum Sensing Inhibition.

Crown gall disease, caused by Agrobacterium tumefaciens, results in significant loss in agricultural productivity losses due to induced tumor-like growths on various crops. The virulence of A. tumefaciens is controlled by its quorum sensing (QS) system, specifically through the TraR protein, which regulates the expression of genes essential for pathogenicity and plasmid transfer.

Discovery of novel HBV core protein inhibitors by high throughput virtual screening.

Hepatitis B Virus (HBV) constitutes a chronic viral infection with limited therapeutic options and a significant global health challenge. The virus lifecycle intricacy significantly relies on the core protein crucial for virus structure stability and interaction with host cells thus contributing to the infection's persistence and severity. This study employs advanced techniques for the identification of novel core protein inhibitors through the screening of two chemical databases ZINC and BIMP utilizing computational methods such as structure-based virtual screening, drug-likeness, ADME, toxicity, consensus molecular docking, density functional theory, and 100 ns molecular dynamics simulation.

Evaluating the Phytohormone Proficiencies of Multifarious Bacillus rugosus for Growth Promotion in Arachis hypogaea (L.).

The application of Plant Growth-Promoting Rhizobacteria (PGPR) in agriculture is increasingly emphasized as a sustainable alternative to hazardous agrochemicals. This study aimed to isolate and characterize PGPR strains from the rhizospheric soil of Arachis hypogaea L., hypothesizing that the rhizosphere of a healthy plant harbors beneficial microbes with significant plant growth-promoting (PGP) attributes.

Targeting Undruggable Proteins: The siRNA Revolution Beyond Small Molecules - Advances, Challenges, and Future Prospects in Therapeutic Innovation.

The field of drug discovery has long been challenged by the existence of "undruggable" proteins - targets that have resisted traditional small molecule approaches due to their structural or functional characteristics. This review explores the revolutionary potential of small interfering RNA (siRNA) technology in addressing these elusive targets, marking a paradigm shift in therapeutic development. We discuss the historical development of siRNA technology and its unique mechanism of action, which allows for the silencing of virtually any gene, including those coding for proteins previously deemed undruggable.

Identification of novel cyclin-dependent kinase 4/6 inhibitors from marine natural products.

Cyclin-dependent kinases 4 and 6 (CDK4/6) are crucial regulators of cell cycle progression and represent important therapeutic targets in breast cancer. This study employs a comprehensive computational approach to identify novel CDK4/6 inhibitors from marine natural products. We utilized structure-based virtual screening of the CMNPD database and MNP library, followed by rigorous filtering based on drug-likeness criteria, PAINS filter, ADME properties, and toxicity profiles.

Targeting PD-1 in Squamous Cell Carcinoma: Flavonoid-based Therapeutics Unveiled through in silico and in vitro Approaches.

Introduction: Squamous cell carcinoma is a major public health concern, with traditional treatments such as surgery, chemotherapy, and radiation therapy frequently resulting in significant side effects. Immunotherapy targeting checkpoints such as PD-1, CTLA-4, and B7- H3 provides a more specific approach but incurs high costs due to monoclonal antibodies.

Aim And Objective: This study aims to investigate the potential of natural flavonoids as lowtoxicity, small molecule-based alternatives targeting the PD-1 immunological checkpoint for SCC treatment.

Quest for discovering novel CDK12 inhibitor.

CDK12 is essential for cellular processes like RNA processing, transcription, and cell cycle regulation, inhibiting cancer cell growth and facilitating macrophage invasion. CDK12 is a significant oncogenic factor in various cancers, including HER2-positive breast cancer, Anaplastic thyroid carcinoma, Hepatocellular carcinoma, prostate cancer, and Ewing sarcoma. It is also regarded as a potential biomarker, emphasizing its broader significance in oncology.

Pollution status of microplastics in the sediments of warm monomictic Dal lake, India: Abundance, composition, and risk assessment.

This report presents the first investigation of microplastic (MP) contamination in the shoreline sediments of Dal Lake, Jammu and Kashmir, India. The MP concentrations ranged from 503 to 3154 MP/kg, with a notable seasonal variation. The highest concentrations of microplastics occurred in the Spring, ranging from 467 to 3445 MP/kg.

Development of Luminescent and Photosensitive Cellulose Microfibers From Palm Sprout Fibers: Antibacterial Efficacy and Dye Adsorption Potential.

A key contemporary challenge is enhancing the value of agro-industrial byproducts. Cellulose, the most abundant renewable resource, offers significant industrial potential due to its versatile properties. Produced in its pure form by various bacteria, cellulose is increasingly utilized in microscale and nanoscale fibers for composite reinforcement.

Discovery of Novel PTP1B Inhibitors by High-throughput Virtual Screening.

Aim: To Discover novel PTP1B inhibitors by high-throughput virtual screening Background: Type 2 Diabetes is a significant global health concern. According to projections, the estimated number of individuals affected by the condition will reach 578 million by the year 2030 and is expected to further increase to 700 million deaths by 2045. Protein Tyrosine Phosphatase 1B is an enzymatic protein that has a negative regulatory effect on the pathways involved in insulin signaling.

Role of PD-1 in Skin Cancer: Molecular Mechanism, Clinical Applications, and Resistance.

Skin cancer is a widespread worldwide health concern, manifesting in many subtypes such as squamous cell carcinoma, basal cell carcinoma, and melanoma. Although all these types occur frequently, they generally lack the possibility of being cured, emphasizing the importance of early discovery and treatment. This comprehensive study explores the role of programmed cell death protein 1 (PD-1) in skin cancer, focusing on its molecular mechanisms in immune regulation and its critical role in tumor immune evasion, while also clarifying the complexities of immune checkpoints in cancer pathogenesis.

Physicochemical and photocatalytic properties of AgCrO/FeO/CeO ternary nanocomposite.

The study presents AgCrO/FeO/CeO ternary nanocomposite, based on FeO/CeO binary composites, which demonstrated excellent photocatalytic performance in the photodegradation of methylene blue under solar irradiation. The AgCrO/FeO/CeO nanocomposites was orthorhombic, ilmenite, and cubic-fluorite phases of AgCrO, FeO, and CeO, respectively, according to the XRD examination. A strong bond between AgCrO, FeO, and CeO within the nanocomposite was demonstrated by the SEM and TEM investigations.

miRNA-Targeted Vaccines: A Promising Approach for Viral Attenuation and Immunogenicity Enhancement.

MicroRNAs (miRNAs) have emerged as a significant tool in the realm of vaccinology, offering novel approaches to vaccine development. This study investigates the potential of miRNAs in the development of advanced vaccines, with an emphasis on how they regulate immune response and control viral replication. We go over the molecular features of miRNAs, such as their capacity to direct post-transcriptional regulation toward mRNAs, hence regulating the expression of genes in diverse tissues and cells.

Advancements of Glucose Monitoring Biosensor: Current State, Generations of Technological Progress, and Innovation Dynamics.

Glucose monitoring is essential for managing diabetes, and continuous glucose monitoring biosensors can offer real-time monitoring with little invasiveness. However, challenges remain in improving sensor accuracy, selectivity, and overall performance. This article aims to review current trends and recent advancements in glucose-monitoring biosensors while evaluating their benefits and limitations for diabetes monitoring.

One-pot synthesis of g-CN/N-doped CeO nanocomposites and their potential visible light-driven photocatalytic degradation of methylene blue dye.

In the pursuit of efficient photocatalytic materials for environmental applications, a new series of g-CN/N-doped CeO nanocomposites (g-CN/N-CeO NCs) was synthesized using a straightforward dispersion method. These nanocomposites were systematically characterized to understand their structural, optical, and chemical properties. The photocatalytic performance of g-CN/N-CeO NCs was evaluated by investigating their ability to degrade methylene blue (MB) dye, a model organic pollutant.