Triazole-Pyrimidine Hybrids as EGFR Inhibitors via Synthesis, In Silico, In Vitro, and In Vivo Evaluation as Anticancer Agents.

The epidermal growth factor receptor (EGFR) is a common diver gene for lung cancer (NSCLC), which leads to an increasing death rate worldwide. This study reports the design, synthesis, and biological evaluation of triazole-clubbed pyrimidine derivatives (RDa-RDm) as potential anticancer agents. Thirteen compounds were synthesized and screened against the A549 lung cancer cell line.

Harnessing PHGDH Inhibition for Cancer Therapy: Mechanisms, SAR, Computational Aspects, and Clinical Potential.

3-Phosphoglycerate dehydrogenase (PHGDH) is a key enzyme in the serine biosynthesis pathway, supporting cancer cell growth, survival, and proliferation. Its overexpression is frequently observed in aggressive cancers such as breast cancer, melanoma, and glioma, where it drives tumor growth, metastasis, and resistance to oxidative stress. Targeting PHGDH with small-molecule inhibitors has emerged as a promising therapeutic strategy.

Recent Developments in Vesicular Nanocarriers for Targeted Drug Delivery in Breast Cancer.

Breast cancer remains one of the most challenging malignancies worldwide due to its heterogeneity, which affects tumor behavior, progression, and treatment response. The complexity of breast cancer necessitates innovative therapeutic strategies to improve treatment outcomes. This review explores the potential of vesicular nanocarriers, including liposomes, niosomes, ethosomes, polymerosomes, phytosomes, and transferosomes, in enhancing breast cancer treatment efficacy through targeted drug delivery.

Insights to phytochemistry, analytical methods, pharmacological activities, stability, and specifications of alantolactone.

Alantolactone, a sesquiterpene lactone derived from plants of the Asteraceae family, has been extensively studied for its diverse pharmacological potential. Research suggests that various biochemical pathways are involved in the bioactivity of alantolactone, such as STAT3 (Single transducer and activator of transcription 3), MAPK/NF-κB (Mitogen-activated protein kinases/ Nuclear factor kappa-light chain enchancerof B cells), and YAP1/TAZ (Yes-associated protein 1/Transcriptional co-activator with PDZ-binding motif pathway) pathways for anticancer, proinflammatory cytokines NF-ΚB and STAT3 signaling for anti-inflammatory, Nrf2 (Nuclear factor erythroid 2-related factor 2) pathway for antioxidant, L-type voltage-gated calcium channels for antihypertensive, enhanced reactive oxygen species (ROS) production for antifungal properties, and potential to alter lipid metabolism via suppression of IL-6 (Interleukin-6) stimulated TLR-4 (Toll-like receptor) expression. Additionally, alantolactone has been explored for its insecticidal, antibacterial, and antiviral properties.

Recent Progression and Treatment Approaches of Kidney Fibrosis: Evidence to Clinic Approach.

Background: Fibrosis is a pathological complication that arises from an abnormal tissue healing response to chronic inflammation or repeated injury. It is characterized by Excessive Extracellular Matrix (ECM) deposition, leading to progressive organ dysfunction. Chronic Kidney Disease of unknown etiology (CKDu) is a newly recognized public health crisis characterized by slow, irreversible progression and late-stage asymptomatic onset.

Updated insights on ASK1 signaling: mechanisms, regulation, and therapeutic potential in diseases.

Apoptosis signal-regulating kinase 1 (ASK1) is a serine-threonine kinase, that is a member of the mitogen-activated protein kinase kinase (MAP3K) family, which is expressed or incorporated in nucleated cells which leads to the activation of multiple mitogen-activated protein kinases (MAPK) to regulate cell stress, tumour necrosis factor-α (TNF-α) ligand, lipopolysaccharides and apoptosis. ASK1 gets activated by the ROS, oxidative stress, endoplasmic stress (ER) and various inflammatory cytokines. Dysregulation of ASK1 can lead to various diseases like neurodegenerative disease, cardiovascular disease, cancer, and various other metabolic diseases such as diabetes.

Unveiling the medicinal diversity of benzoic acid containing molecules: Insights on druggable targets for type 2 diabetes mellitus.

Benzoic acid, a versatile aromatic carboxylic acid, has gained attention as a promising scaffold for developing therapeutic agents targeting diabetes mellitus, a chronic metabolic disorder characterized by persistent hyperglycemia and associated complications. Structural analysis elucidated how modifications to the benzoic acid structure enhance pharmacological efficacy by influencing glucose metabolism, insulin sensitivity, and oxidative stress pathways. Notably, benzoic acid derivatives exhibit inhibitory effects on key enzymes such as protein tyrosine phosphatase 1B (PTP1B), dipeptidyl peptidase-4 (DPP-4), α-glucosidase, peroxisome proliferator-activated receptor gamma (PPAR-γ), and aldose reductase, which are implicated in diabetes pathophysiology.

Advancing Drug Stability Using Non-Aqueous Gels: Properties, Applications, and Emerging Challenges.

This study explores the emerging potential of non-aqueous gels for topical therapy, examining their unique properties, diverse applications, and the challenges involved in their formulation and clinical use. By highlighting these aspects, the article aims to shed light on the future of localized drug delivery and inspire further research and innovation in this promising field. Additionally, the article addresses the critical need for regulatory considerations, stability testing, and patient acceptability.

Advances in pancreatic cancer diagnosis: from DNA methylation to AI-assisted imaging.

Introduction: Pancreatic Cancer (PC) is a highly aggressive tumor that is mainly diagnosed at later stages. Various imaging technologies, such as CT, MRI, and EUS, possess limitations in early PC diagnosis. Therefore, this review article explores the various innovative biomarkers for PC detection, such as DNA methylation, Noncoding RNAs, and proteomic biomarkers, and the role of AI in PC detection at early stages.

Recent Progression and Treatment Approaches for the Kidney Stone Management.

Background: Kidney stones have always been a significant matter in the healthcare sector worldwide, with a high prevalence rate, especially in women. Urolithiasis is the solid mineral deposits in the renal calyces and kidney pelvis. Expounding upon the pathophysiology, various mechanisms such as supersaturation, crystallization, and aggregation are explored.

Unveiling the research directions for pyrrolidine-based small molecules as versatile antidiabetic and anticancer agents.

The pyrrolidine moiety, a five-membered saturated nitrogen-containing heterocycle, emerged as a crucial pharmacophore in medicinal chemistry due to its distinctive physicochemical properties, including hydrophilicity, basicity, and structural rigidity. Extensive modifications of pyrrolidine derivatives yielded novel compounds with pronounced antidiabetic and anticancer activities. The structural investigation of pyrrolidine-based molecules demonstrated that substitutions at the N1, 3, and 5 positions offer significant opportunities for optimizing biological activity and enhancing target-specific interactions.

Progression and expansion of ALK inhibitors against NSCLC: A dual target approach.

ALK gene is a member of the tyrosine kinase receptor family found on chromosome 2 (2p23) that plays an important role in the progression of the non-small cell lung cancer (NSCLC). Since the ALK inhibitors such as Crizotinib, Ceritinib, Brigatinib, Alectinib and Lorlatinib, was endorsed for the treatment of advanced NSCLC linked to ALK gene rearrangement. But eventually, patients become resistant to the medication, which will result in treatment failure.

A comprehensive update on phytochemistry and medicinal developments of apocynin.

The natural phenolic compound apocynin, referred to as acetovanillone, generated significant attention due to its diverse pharmacological properties, especially as an NADPH oxidase inhibitor, and it was applicable orally and effectively even at small doses. During chronic inflammation, various pro-inflammatory-related factors such as nuclear factor kappa β (NF-kβ), nitrotyrosine, poly adenosine diphosphate ribose polymerase (PARP), inducible nitric oxide synthase (iNOS), cluster of differentiation 31 (CD), intercellular adhesion molecule-1 (ICAM-1), glycoproteins granule membrane protein 140 (GMP140), tumor necrosis factor-alpha (TNFα), p38 mitogen-activated protein kinases (p38 MAPK), membrane cofactor protein (MCP), interleukin-6 (IL-6), all of which could be targeted by apocynin. Research suggests that apocynin significantly benefits conditions like diabetes, cardiovascular diseases, and neurological disorders due to its ability to mitigate inflammation and enhance endothelial function.

Ball-mill-assisted mechanochemical approaches for heterocyclic compound synthesis (2015-2024).

Ball milling has emerged as a powerful and sustainable technique for the synthesis of heterocyclic compounds, offering significant advantages over conventional methods. This review explores recent advancements in the application of ball milling for environmentally friendly synthesis, highlighting its role in accelerating reaction times, enhancing yields, and minimizing solvent usage. Various studies have demonstrated its efficacy in synthesizing diverse nitrogen, oxygen, and sulfur-containing heterocyclic frameworks, including benzoxazines, quinoxalines, pyrazolothienopyrimidines, chalcones, spiro(indole-pyrrolidine) derivatives, quinolines, pyridazines, triazolochromenes, arylsulfonyl 4H-pyrans, aminothiophenes, methylcoumarins, and benzothiazoles.

Integrating Gut-Brain Axis: Exploring the Neurogastrointestinal Interactions and Therapeutic Potentials in Autism Spectrum Disorder.

This comprehensive review critically examines the gut-brain axis (GBA) and its implications in autism spectrum disorder (ASD). The GBA is a complex, bidirectional communication network that integrates the gastrointestinal tract, the central nervous system, and the gut microbiota. This axis is mediated through various physiological pathways, including the enteric nervous system (ENS), the vagus nerve, immune responses, and metabolic activities of gut microorganisms.

Recent doxorubicin-conjugates in cancer drug delivery: Exploring conjugation strategies for enhanced efficacy and reduced toxicity.

Doxorubicin is a first-line treatment of cancer that works on the mechanism of DNA intercalation and topoisomerase II poisoning. Since the 20th century, Doxorubicin has been used as a promising drug to treat several types of cancer, both solid or metastatic, including breast, thyroid, bladder, ovarian, or gastric cancer, etc. Even though it shows promising effects on cancer cells, it also shows its effects on healthy cells with cancerous cells, which leads to several severe side effects, such as cardiomyopathy, phlebitis, congestive heart failure (CHF), etc.

Therapeutic potential of Baicalin against experimental obsessive compulsive disorder: Evidence from CSF, blood plasma, and brain analysis.

Obsessive-Compulsive Disorder (OCD) is a complex neuropsychiatric condition characterized by recurrent obsessions and compulsions, significantly impacting an individual's functionality and quality of life. This study aimed to explore the neuroprotective and therapeutic potential of baicalin, a flavonoid with known antioxidant, anti-inflammatory, and neurotropic properties, in an animal model of OCD induced by 8-OH-DPAT (8HPAT). The research utilized in silico docking studies and in vivo experiments to assess baicalin's interactions with key intracellular targets: SIRT-1, Nrf2, HO-1, and PPAR-gamma, and its effects on neurochemical, neurobehavioral, and histopathological parameters.

A Mini-Review on the Symptoms and Pathogenesis of Psoriasis and Recent Nanotechnological Developments in its Treatment Strategies.

Psoriasis is a chronic illness that is common and incurable. In psoriasis, skin cells proliferate more quickly than normal cells, suggesting a possible immune system connection. The topical treatment of psoriasis is best when applied in combination with anti-inflammatory medications; however, the lack of an appropriate delivery method limits the drugs' ability to be delivered.

CRISPR-Cas9: Transforming Functional Genomics, Precision Medicine, and Drug Development - Opportunities, Challenges, and Future Directions.

CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats) is a groundbreaking gene-editing technology that enables scientists to make precise changes to the DNA of living organisms. It was first discovered in Escherichia coli and emerged as a breakthrough tool in molecular biology. This technique is essential because of its adaptability, affordability, and ease of use.

Green Synthesis of Curcumin Loaded Carbon Dots as a Sustained Drug Delivery for Anticancer Therapy.

Aims: To enhance curcumin's bioavailability with the help of carbon dot and piperine, due to its promising anticancer activity.

Background: Cancer is a disease condition, where some cells grow uncontrollably, and if not controlled, they spread to other parts of the body. Concerning anticancer agents, curcumin has anticancer properties along with anti-inflammatory, antimicrobial, and antioxidant.

Molecular mechanisms of GDNF/GFRA1/RET and PI3K/AKT/ERK signaling interplay in neuroprotection: Therapeutic strategies for treating neurological disorders.

Neurological disorders, marked by progressive neuronal degeneration, impair essential cognitive functions like memory and motor coordination… This manuscript explores the significant roles of glial cell line-derived neurotrophic factor (GDNF), its co-receptors (GFRA1), and the receptor tyrosine kinase (RET) in mediating neuronal survival and function in various neurodegenerative conditions. The interplay between pivotal signaling pathways-PI3K/AKT and ERK1/2-facilitated by GDNF/GFRA1/RET, is emphasized for its neuroprotective effects. Dysregulation of these pathways is implicated in neurodegenerative and neuropsychiatric processes, with overactivation of GSK3β contributing to neuronal damage and apoptosis.

Navigating the complexities of neuronal signaling and targets in neurological disorders: From pathology to therapeutics.

Neurological disorders arising from structural and functional disruptions in the nervous system present major global health challenges. This review examines the intricacies of various cellular signaling pathways, including Nrf2/Keap1/HO-1, SIRT-1, JAK/STAT3/mTOR, and BACE-1/gamma-secretase/MAPT, which play pivotal roles in neuronal health and pathology. The Nrf2-Keap1 pathway, a key antioxidant response mechanism, mitigates oxidative stress, while SIRT-1 contributes to mitochondrial integrity and inflammation control.

Therapeutic potential of chalcone-1,2,3-triazole hybrids as anti-tumour agents: a systematic review and SAR studies.

The study of chalcone-1,2,3-triazole hybrids for anticancer activity is quite a recent area of focus, primarily because of the increasing demand for developing new drugs to treat cancer. The chalcones and 1,2,3-triazole rings in hybrid compounds has recently emerged as a promising strategy for developing novel anticancer agents. The 1,2,3-triazole ring, known for its stability and hydrogen bonding capabilities, enhances the target binding affinity of these hybrids.

The Polygenic Nature of Multiple Sclerosis: Genetic Variants, Immunological Modulation, and Environmental Connections.

Multiple Sclerosis (MS), a debilitating inflammatory disorder of the central nervous system characterized by demyelination, is significantly influenced by polygenic variations. Although the precise cause of MS remains unclear, it is believed to arise from a complex interplay of genetic and environmental factors. Recent investigations have focused on the polygenic nature of genetic alterations linked to MS risk.