Novel dihydrobenzofuran derivatives: design, synthesis, cytotoxic activity, apoptosis, molecular modelling and DNA binding studies.

Pyrazoline derivatives () and () were designed and synthesized through chalcones () cyclization with NHNH/HCOOH and NHCSNHNH/CHCOOH, respectively. The molecular structures were elucidated by using various techniques such as UV-visible, FT-IR, H, C NMR spectroscopy and mass spectrometry. The purity of all synthesized compounds was checked by the liquid chromatography-mass spectrometry (LC-MS).

Necrolytic migratory erythema: a fortuitous diagnosis.

A woman in her late 60s presented with widespread, itchy, dark lesions over her trunk and legs for 1 month. Initially, she was managed as nutritional dermatitis and experienced partial improvement. However, her condition worsened over 2 months, characterised by aggravated skin lesions, new-onset diabetes and a 12 kg weight loss.

Synthesis and evaluation of novel ethyl ferulate derivatives as potent Keap1 inhibitors to activate the Nrf2/ARE pathway in Parkinson's disease.

The Kelch-like ECH-associated protein 1/Nuclear factor erythroid 2 related factor 2/Antioxidant Response Elements (Keap1/Nrf2/ARE) pathway is essential for neuronal resilience against the complex pathogenesis of Parkinson's disease (PD). Activating this pathway by covalently modifying Keap1 cysteine residues is a promising strategy for regulating neuroprotective gene expression. Our study aimed to identify phytochemicals that could irreversibly inhibit Keap1.

In silico inspired design of urea noscapine congeners as anticancer agents: Chemical synthesis and experimental evaluation using breast cancer cells and a xenograft mouse model.

A series of semisynthetic noscapine-urea congeners (7a-7h) as potential tubulin-binding agents are being developed by integrating a urea pharmacophore at the C-9 position of the noscapine scaffold. Their binding affinity to tubulin was predicted through molecular docking, molecular dynamics (MD) simulations, and the MM-PBSA approach. These molecules were subsequently chemically synthesized and assessed using breast cancer cell lines (MCF-7 and MDA-MB-231) and normal human embryonic kidney cells (HEK).

Doxophylline, a Non-Selective Phosphodiesterase Inhibitor, Protects Against Chronic Fatigue-Induced Neurobehavioral, Biochemical, and Mitochondrial Alterations.

Chronic fatigue stress (CFS) is a multisystem disorder which exhibits multiple signs of neurological complications like brain fog, cognitive deficits and oxidative stress with no specific treatment. Doxophylline, a non-selective phosphodiesterase inhibitor (PDEI), has anti-inflammatory properties with enhanced blood-brain barrier penetration and tissue specificity. We have evaluated the neuroprotective potential of doxophylline in a murine model of forced swim test (FST) induced CFS and in HO (hydrogen peroxide) induced oxidative stress in PC12 cells.

Exploring the impact of 2-hydroxyestradiol on heme oxygenase-1 to combat oxidative stress in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation driven by complex signaling pathways. Recent therapeutic approaches focus on small molecules targeting intracellular signaling to address specific physiological aspects of the disease. Previously we identified a small molecule, 2-hydroxyestradiol (2-OHE2), an inhibitor of TNF-α by an in-silico study.

Understanding the Directed Evolution of a Natural-like Efficient Artificial Metalloenzyme.

The artificial metalloenzyme containing iridium in place of iron along with four directed evolution mutations C317G, T213G, L69V, and V254L in a natural cytochrome P450 presents an important milestone in merging the extraordinary efficiency of biocatalysts with the versatility of small molecule chemical catalysts in catalyzing a new-to-nature carbene insertion reaction. This is a show-stopper enzyme, as it exhibits a catalytic efficiency similar to that of natural enzymes. Despite this remarkable discovery, there is no mechanistic and structural understanding as to why it displays extraordinary efficiency after the incorporation of the four active site mutations by directed evolution methods, which so far has been intractable to any experimental methods.

Fluorescence Turn-Off-On Sensing Strategy for the Detection of Pb and Metalaxyl Fungicide Using Yellow Fluorescent Carbon Dots From Cordia dichotoma Fruits.

In this work, a facile and rapid fluorescence turn-off-on sensing method was developed for the detection of Pb and metalaxyl fungicide in environmental samples using yellow carbon dots (CDs) from Cordia dichotoma fruits. The prepared C. dichotoma-CDs showed the emission band (𝜆) at 535 nm under 448 nm of excitation wavelength.

Higher isoform of hnRNPA1 confer Temozolomide resistance in U87MG & LN229 glioma cells.

Background: Gliblastoma is a malignant brain tumor; despite available treatment modalities, the tumor reoccurrence rate persist in the currently prescribed Temozolomide chemotherapy. Study aimed to study the inquisitive role of RNA binding splice factor protein hnRNPA1 in promoting glioma resistance against Temozolomide drug and therapeutic insights.

Methods: In this study two non-expressing O-methylguanine-DNA methyltransferase (MGMT) glioma cell lines U87MG & LN229.

Epigallocatechin-3-gallate inhibit the protein arginine methyltransferase 5 and enhancer of Zeste homolog 2 in breast cancer both in vitro and in vivo.

Purpose: Histone methyltransferases are enzymes that selectively methylate lysine or arginine residues on both histone and non-histone proteins, categorized into lysine methyltransferases and arginine methyltransferases. Notably, EZH2 and PRMT5 are known for catalyzing trimethylation of H3 at K27 and symmetric dimethylation of H4 at R3, respectively. These methylation events are recognized as characteristic histone-repressive marks in cancer.

Assessing the Impact of TLR4 rs4986790 Polymorphism on Bacterial Meningitis Risk: A Systematic Review and Meta-Analysis.

Background And Objectives: Toll-like receptor ( TLR2 ) gene plays an important role in the pathogenesis of bacterial meningitis (such as meningococcal meningitis and pneumococcal meningitis). The association between TLR4 rs4986790 polymorphism and the susceptibility to bacterial meningitis has been extensively studied. However, the results of these studies remain inconsistent.

A Review of The Opportunities and Challenges with Large Language Models in Radiology: The Road Ahead.

In recent years, generative artificial intelligence (AI), particularly large language models (LLMs) and their multimodal counterparts, Multi-Modal Large Language Models (MM-LLMs), including Vision Language Models (VLMs), have generated considerable interest in the global AI discourse. LLMs, or pre-trained language models (such as ChatGPT, Med-PaLM, LLaMA, etc.), are neural network architectures trained on extensive text data, excelling in language comprehension and generation.

Effect of Staphylococcal Decolonization Regime on Post-Craniotomy Meningitis.

Post craniotomy meningitis (PCM), an uncommon complication following craniotomy can be categorized as either bacterial meningitis (BM) or aseptic meningitis (AM) based on the results of CSF culture. Staph. aureus is a common causative organism.

Non-RBD peptides of SARS-CoV-2 spike protein exhibit immunodominance as they elicit both innate and adaptive immune responses.

Severe acute respiratory coronavirus-2 (SARS-CoV-2) emerged in 2019 as a new virus and caused worldwide outbreaks, quickly turning into a pandemic disease called coronavirus disease-19 (COVID-19). All the existing methodologies were used for developing vaccines for this virus. But sporadic infections of this virus and the emergence of new strains to date suggest the incomplete protection offered by the developed vaccines and the need for new research.

Modulation of Proinflammatory Cytokines by Parmotrema reticulatum Derived Dioxepine Derivative and Benzoic Methyl Ester in Adjuvant-Induced Arthritis.

The present investigation aims to study the therapeutic effect and to identify the lead molecules from lichen Parmotrema reticulatum (Pr) that can solve the complications associated with arthritis. Purification of Pr extract led to isolation of two lead molecules i.e.

Tissue adhesive hyaluronan-quercetin (Ag)@halloysite-fungal carboxymethyl chitosan nanocomposite hydrogels for wound dressing applications.

This study investigates nanocomposite hydrogels reinforced with hyaluronan-quercetin‑silver nanoparticles intercalated halloysite clay (HAQ-Hal-Ag) for potential application as wound dressings. HAQ-Hal-Ag (at 1, 3, and 5 wt%) was incorporated into a fungal carboxymethyl chitosan (FC)/polyacrylamide (PAM) network (FC-PAM) using methylene bisacrylamide (MBA) as the crosslinker and ammonium persulfate (APS) as the initiator. Various physicochemical analyses were performed to characterize the resulting hydrogels.