Current Topics in Medicinal Chemistry - Online First

Thiazole-based compounds have attracted considerable interest due to their potent antioxidant abilities, which are crucial for combating diseases associated with oxidative stress. Over the last decade, significant progress has been made in the development and evaluation of thiazole derivatives exhibiting improved antioxidant properties.

This review aims to provide a comprehensive overview of the antioxidant properties of thiazole-derived compounds established over the past decade, emphasizing their SAR (Structure-activity relationships), mechanistic understanding, and potential therapeutic applications.

A comprehensive evaluation of peer-reviewed research from 2016 to 2025 was conducted, with an emphasis on studies investigating the antioxidant properties of thiazole-based compounds. SARs were evaluated to assess the effects of various substituents on antioxidant activity. Investigations into the mechanism were done further to understand the contribution of thiazole moieties in antioxidant activity.

Various thiazole derivatives exhibited remarkable radical scavenging ability, frequently outperforming standard antioxidants. Structural characteristics including electron-donating substituents, catechol-containing scaffolds, and Schiff-base frameworks significantly improved activity. Metal complexes and hybrid structures enhanced the efficiency of electron transfer and the stability of radical intermediates.

The findings indicate that thiazole derivatives exhibit antioxidant properties via synergistic structural and electronic characteristics that promote hydrogen-atom transfer along with single-electron transfer mechanisms. The integration of heterocyclic hybrids and metal coordination represents a promising strategy for the development of next-generation antioxidant agents characterized by enhanced stability and biological significance.

Over the last ten years, there have been significant advances in the development of thiazole-based antioxidants, including various derivatives exhibiting potent free radical scavenging capabilities. The results highlight the therapeutic efficacy of thiazole scaffolds in addressing diseases associated with oxidative stress. Future studies should focus on improving bioavailability and in vivo efficacy to facilitate the translation of these results into clinical applications.

The genus Allamanda (Apocynaceae), comprising approximately 16 species distributed in tropical and subtropical regions, is widely used in Southeast Asian and South American traditional medicine. Rich in terpenoids, flavonoids, and phenolics, it exhibits broad pharmacological potential. This review provides a comprehensive summary of the ethnobotany, phytochemistry, and therapeutic relevance of Allamanda to guide future research and drug development.

An extensive literature survey was conducted up to May 2025 using databases including SciFinder, PubMed, Scopus, and Google Scholar by using keywords such as Allamanda, Phytochemistry, Pharmacological activity, and Ethnobotany.

Across the genus, a total of 209 compounds have been reported, predominantly terpenoids, followed by phenolics and volatiles. Preclinical studies have highlighted the antioxidant, antimicrobial, anti-inflammatory, antiviral, antifertility, wound-healing, and cytotoxic activities of Allamanda, supporting it as a promising source of new therapeutics.

The rich phytochemical profile and broad pharmacology position Allamanda as a valuable ethnomedicinal resource with potential for modern drug discovery. However, the majority of studies are limited to preclinical studies, with minimal clinical validation and restricted species diversity. Future research should focus on chemical profiling, clinical trials, and safety assessment.

Allamanda offers a diverse array of bioactive compounds with significant pharmacological relevance. By integrating traditional uses with scientific evidence, this review highlights the potential of ethnomedicine in bridging the gap between traditional and modern pharmacology, while underscoring the need for future research on unexplored species.

Novel potassium-competitive acid blockers (P-CABs) are recognized to have more potent acid-suppressive efficacy than proton pump inhibitors (PPIs). This study comprehensively summarizes the clinical evidence regarding P-CABs in patients with gastro-oesophageal reflux disease (GERD), with a particular focus on erosive oesophagitis (EO).

A network meta-analysis was carried out by retrieving randomized controlled trials of P-CABs and PPIs for the management of EO patients from PubMed, Embase, and CENTRAL between January 1^st, 1990, and November 19^th, 2022. The selected participants received oral treatment with 20 mg keveprazan (KPZ), 10-40 mg vonoprazan (VPZ), or 30 mg lansoprazole (LPZ), once daily for 2-8 weeks. We compared the efficacy and safety of KPZ, VPZ, and LPZ at different doses and follow-up time points in EO patients.

From 183 initially identified citations, six eligible studies were included, encompassing 2,864 participants. Robust evidence indicated that 20 mg VPZ was superior to 30 mg LPZ in achieving EO healing at the 2-week follow-up. Furthermore, 40 mg VPZ demonstrated greater efficacy than 5 mg VPZ. Both 20 mg VPZ and 30 mg LPZ were less effective in patients with severe reflux disease (LA classification C/D) than in those with mild disease (A/B). Additionally, 20 mg VPZ was more effective than 30 mg LPZ in reducing serum gastrin and pepsinogen I levels after 4 weeks of intervention. Notably, 20 mg KPZ was associated with a higher incidence of treatment-emergent adverse events (TEAEs) compared to 40 mg VPZ.

In patients with EO, both 20 mg VPZ and 30 mg LPZ demonstrated relatively lower efficacy in subtypes C/D compared to subtypes A/B. Furthermore, 8-week interventions with either 20 mg VPZ or 30 mg LPZ provided significantly greater clinical benefit compared to 2-week regimens. Notably, 40 mg VPZ was associated with the lowest incidence of TEAEs, as well as TEAEs occurring in at least 2% of patients (TEAEs ≥2%).

Feline infectious peritonitis (FIP), a fatal disease caused by feline coronavirus (FCoV), poses a serious threat to feline health. Natural product-based virtual screening offers a promising avenue for identifying antiviral agents targeting FCoV. In this study, a structure-based computational approach was employed to discover potential inhibitors of the 3C-like protease (3CLpro) of FCoV.

A library of 96,677 natural compounds from the ZINC database was screened using molecular docking to assess their binding affinities to the protease. The initial hits were refined by evaluating ADMET properties and visually inspecting the binding poses, yielding 68 candidate molecules. These were further assessed through 100-nanosecond molecular dynamics simulations and binding free energy calculations.

Through computational filtering, 14 compounds were identified that exhibited strong interaction stability and minimal conformational fluctuation. An analysis of the binding modes revealed that key residues, such as His162, Glu165, and Cys144, formed crucial hydrogen bonds and hydrophobic contacts, contributing to the stability of the protein-ligand complexes.

The identified interactions highlighted the importance of specific residues in stabilizing the protein-ligand complex. Among the 14 compounds, eight maintained stable binding profiles throughout extended 500-nanosecond molecular dynamics simulations and also exhibited elevated binding free energy values, suggesting a stronger potential for antiviral development.

The findings indicated the compounds’ strong potential for further development as antiviral leads. The results also revealed several core molecular frameworks that may serve as an initial reference for designing FCoV 3CLpro inhibitors, laying the groundwork for structure-guided drug discovery efforts.

Considering the shared physiological mechanisms between type 2 diabetes (T2D) and colorectal cancer (CRC), it is plausible that certain compounds may exert therapeutic effects on both diseases. Opuntia ficus-indica (nopal) has been traditionally used to manage these conditions. This study aims to elucidate the molecular mechanisms through which nopal exerts its effects on T2D and CRC.

Bioactive compounds of nopal, their molecular targets, and genes associated with T2D and CRC were identified from public databases. Gene Ontology (GO) analysis, metabolic pathway analysis, protein-protein interaction (PPI) network construction, and molecular docking were conducted to investigate the shared molecular targets.

Nopal contains bioactive compounds that interact with molecular targets common to both T2D and CRC. These shared targets are implicated in lipid metabolism, apoptosis, kinase activity, interleukin-related pathways (IL-2 and IL-3), inflammation, gastrin signaling, and other critical processes. Key molecular targets identified include HSP90AA1 and MAPK8, while the principal bioactive compounds of nopal are eriodictyol and aromadendrin.

The identification of eriodictyol and aromadendrin as modulators of HSP90AA1 and MAPK8 elucidates a pleiotropic mechanism underlying the link between type 2 diabetes and colorectal cancer. By modulating apoptotic and inflammatory pathways, these bioactive compounds offer a promising foundation for developing dual-action therapies targeting both metabolic and oncogenic pathways in patients with comorbid conditions.

The bioactive compounds of nopal engage multiple biological pathways relevant to T2D and CRC, suggesting that this plant may serve as a promising pharmacological candidate for the management of these diseases.

In recent years, oxazoles' usefulness as an intermediate in the synthesis of novel chemical entities has grown in medicinal chemistry. Oxazole is a significant heterocyclic nucleus with a diverse range of biological activities, attracting the interest of researchers worldwide to synthesize numerous oxazole derivatives because of their notable biological potential. Owing to their distinctive physicochemical characteristics, these nuclei frequently have enhanced pharmacokinetic profiles and therapeutic effects relative to those of analogous heterocycles.

This evaluation presents an overview of the advancement in biological activities of oxazole derivatives (2009–2025). The review elucidates the mechanisms of action of these chemicals across numerous disorders, identifies the most effective ones along with their associated IC50/MIC values, and examines the models employed for assessing their activity.

According to the review, oxazole and its derivatives have powerful anti-inflammatory, anticancer, antibacterial, and antitubercular effects, and SAR evidence shows that substituting phenyl, methoxy, halogen, or electron-withdrawing increases effectiveness. The scaffold's adaptability and translational ability are demonstrated by its broad activity spectrum, which includes repression of COX/LOX and tubulin polymerisation blockage. As a whole, oxazoles are great leads for potential new drugs because of their structural adaptations at C-2, C-4, and C-5.

The literature analysis indicates that the anticancer and anti-inflammatory efficacy of oxazole derivatives is especially significant among their many actions. The inclusion of phenyl, methoxyphenyl, or halogen-substituted phenyl groups markedly improves therapeutic efficacy relative to reference medications. The substitution versatility at three positions of oxazole derivatives enhances their range of pharmacological actions.

Primary Sclerosing Cholangitis (PSC) remains a significant challenge in hepatology with an unclear pathogenesis and limited treatment options. This study employed Mendelian Randomization (MR) to explore novel pathogenic mechanisms of PSC.

We analyzed publicly available datasets, including cis-eQTL, cis-pQTL, 731 immune cell profiles, DNA methylation data, and PSC GWAS summary statistics. Using Inverse Variance Weighted (IVW) as our primary method, we identified genes causally associated with PSC. Subsequent mediation analyses elucidated how DNA methylation regulates gene expression and how these genes influence PSC through specific immune cell subpopulations.

Our analysis revealed a significant protective effect of BTN3A2 expression against PSC risk (IVW OR 0.838, 95% CI 0.792–0.887, P = 1.12E-09). Mediation analysis indicated that methylation at cg23465465 had a largely mediated effect on PSC risk through BTN3A2 regulation (89.3% mediated effect). Additionally, BTN3A2 exerted partial protection via CD14+CD16+ monocytes (4.7% mediation).

This study suggests a protective role for BTN3A2 in PSC pathogenesis, supported by reliable DNA methylation regulation. Although CD14+CD16+ monocytes had a minor impact, they provide new insights into the immune mechanisms of PSC. However, these findings require cautious interpretation pending experimental validation.

These findings identify BTN3A2 as a causal protective factor in PSC, mediated by DNA methylation and CD14+CD16+ monocyte-driven immunity, highlighting its therapeutic potential for precision medicine.

Skin wounds represent a worldwide problem. Biopolymers have been attracting interest in healthcare products for wound dressing. Among these, bacterial nanocellulose membranes (BNC) are attractive for their unique structure, but they lack antimicrobial activity. Thus, the incorporation of the monoterpenes Carvacrol (Car) and Thymol (Thy) - which present antimicrobial and healing properties - toward the improvement of skin wound healing, consists of an appealing approach. This research aimed to produce and characterize nanocellulose membranes containing carvacrol and/or thymol, and investigate their release behavior, cytotoxicity, and antimicrobial properties.

BNC/Car, BNC/Thy, and BNC/Car-Thy membranes were produced at doses of 0.1 and 1.0 mg/cm².

The natural components incorporation into the nanocellulose did not interfere with the ultra-structure or its physical characteristics. Pilot studies showed that membranes with 1.0 mg/cm² of monoterpenes were toxic to fibroblasts. Therefore, all further studies used the lower dose of 0.1 mg/cm². Release experiments showed a burst release between 2-4 h with sustained release till 24 h, reaching around 80% of the initial amount of the incorporated monoterpenes. Studies with fibroblast and keratinocytes indicated no cytotoxicity and that cells could proliferate over the BNC/Car-Thy membranes. Microbiological studies suggested some antimicrobial potential of the BNC doped with Car and Thy.

BNC membranes incorporated with Car and Thy were successfully produced and the monoterpenes incorporation into the BNC did not interfere with either ultra-structure or with its physico-chemical characteristics. Natural products incorporation induced cell proliferation and presented antimicrobial properties, besides increasing the solubility and stability of these natural compounds.

This innovative biomaterial has the potential for healthcare products.

The ethyl acetate extract of Wenxia Formula (WFEA) is the most effective antitumor component of the Wenxia formula. Its key active components, emodin and quercetin, exhibit unique advantages in targeting TGF-β1 and regulating the function of Tregs. This study explored the mechanism of WFEA in enhancing the immune environment in lung cancer by influencing immune cell balance and the level of cytokines.

Lewis lung cancer xenograft mouse models were established. WFEA was administered at low (100 mg/kg), medium (200 mg/kg), and high (400 mg/kg) doses, while a cisplatin (DDP) group served as the positive control. Tumor weight, spleen index, and serum cytokine levels (IL-10, TGF-β1) were measured. Flow cytometry, qPCR, and immunohistochemistry were employed to analyze the proportion of CD4⁺CD25⁺Foxp3⁺ Treg cells and Foxp3 expression in tumor and spleen tissues. The regulatory mechanism of WFEA on the TGF-β/Smads signaling pathway was investigated via combined intervention with the TGF-β1 inhibitor halofuginone (HF), cell differentiation assays, and molecular docking analyses.

WFEA inhibited tumor growth in a dose-dependent manner, with the 400 mg/kg group exhibiting a 60% tumor inhibition rate comparable to that of DDP. The agent significantly increased the spleen index by 106.42% and reduced serum levels of IL-10 and TGF-β1. Mechanistically, WFEA downregulated Foxp3 mRNA and protein expression in both tumor and spleen tissues, leading to a decrease in the proportion of Treg cells. It blocked the TGF-β/Smads pathway by downregulating TGF-β1, upregulating Smad4/Smad7, and inhibiting Smad2/3 phosphorylation. Cell-based experiments confirmed that WFEA-containing serum inhibited the differentiation of CD4⁺ T cells into Tregs, an effect enhanced by TGF-β1 interference. Molecular docking analyses revealed that the active components emodin and quercetin directly bound to TGF-β1 with binding energies of -5.4 kcal/mol and -5.1 kcal/mol, respectively.

WFEA could serve as a new adjunct treatment for lung cancer; however, further clinical trials are required to evaluate its long-term safety and effectiveness across various treatment stages.

WFEA may regulate the growth of Tregs to modulate the immune microenvironment of the LLC model mice, indicating its potential as an anti-LLC agent.

Schizophrenia is a heterogeneous chronic brain disorder driven by multiple pathophysiological processes. While dopaminergic theories dominate current therapies, emerging evidence highlights glutamatergic dysregulation, particularly N-methyl-D-aspartate receptor (NMDAR) hypofunction, as a key mechanism alongside dopaminergic, serotonergic, and neurodevelopmental pathways. This article synthesizes mechanistic insights, focusing on neurotransmitter disruptions, oxidative stress, neuroinflammation, and Wnt signaling, to elucidate the clinical diversity of schizophrenia and identify biomarkers for precise diagnostics and therapeutics.

A comprehensive literature search was conducted using Web of Science, Scopus, Google Scholar, and PubMed, with keywords including “schizophrenia,” “psychosis,” “pathophysiology,” “mechanism,” and “biomarker.” Studies were selected to explore NMDAR hypofunction, glutamatergic dysregulation, and associated signaling pathways, integrating preclinical and human data to map circuit-based interactions and biomarker profiles.

We present a novel circuit-based model of schizophrenia pathophysiology, centered on NMDAR hypofunction and glutamatergic dysregulation, integrating dopaminergic, GABAergic, and inflammatory pathways. Key biomarkers, including inflammatory (e.g., high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6]), neurochemical (e.g., brain-derived neurotrophic factor [BDNF]), and functional (e.g., mismatch negativity [MMN]), are categorized by symptomatic domains and clinical stages, providing diagnostic and prognostic insights.

The findings underscore NMDAR hypofunction’s role in driving schizophrenia’s symptomatic spectrum, though its interplay with other pathways highlights the disorder’s complexity. Neuronal loss, although not universal, is context-specific (e.g., hippocampal interneurons), complementing functional biomarkers such as MMN. Limitations include the need for robust human validation of biomarkers and broader exploration of non-glutamatergic mechanisms.

Considering the multifaceted nature of the disorder, our emphasis on the NMDAR hypofunction model can help explain many of the synergies involved among the seemingly independent dysregulated events.

The present study is based on the most recent and extensive research on the Thiazolidine structure in the fields of organic synthesis and biological activities from 2015 to 2024, as well as the most widely used methodologies in recent years.

The three methods described in this review for the synthesis of thioazolidine derivatives are the most commonly used in recent decades and have given rise to interesting biological activities and the promotion of compounds with chemical and biological significance.

The synthesis of compounds with a thiazolidine skeleton plays a vital and interesting role in organic chemistry, with methods that are becoming increasingly sophisticated and easy to use, making it possible to obtain derivatives of biological and pharmacological importance, and a basis for future research.

The thiazolidine scaffold provides an efficient synthetic route for constructing complex molecular structures with significant biological activities. Their versatile reactivity makes them particularly interesting in organic chemistry, as well as biochemistry and pharmacology.

Oroidins are marine-derived alkaloids known for their structural complexity and a broad range of pharmacological activities. This review aims to explore their emerging role as promising scaffolds in medicinal chemistry, particularly focusing on their unique chemical structure, diverse biological effects, and recent synthetic advancements.

An extensive literature review was conducted to analyze peer-reviewed articles on the isolation, synthesis, structural characterization, and pharmacological evaluation of oroidins and their derivatives. The review highlights significant developments in synthetic strategies, including the incorporation of pyrrole carboxamide units, isotopic labeling approaches, and palladium-catalyzed reactions.

Oroidins exhibit a wide spectrum of biological activities, including antibacterial, antiviral, antimalarial, antiprotozoal, anticancer, anti-inflammatory, neurotropic, and antimuscarinic properties. Their characteristic pyrrole-imidazole core, containing a glycocyamidine moiety and azepinone ring, has been instrumental in targeting key biological pathways such as kinases, NF-κB, and the Raf/MEK-1/MAPK cascade. Structural modifications have led to enhanced potency and specificity of oroidin-based compounds.

The findings emphasize the potential of oroidins as lead compounds in drug development. Their structural diversity, bioactivity profile, and ability to inhibit critical cellular targets position them as attractive templates for therapeutic design. However, further research is needed to optimize their pharmacokinetic properties and evaluate their clinical relevance.

Oroidins represent a valuable class of marine alkaloids with significant therapeutic promise. Advances in synthetic methodologies have expanded their applicability in drug discovery, supporting continued exploration of these compounds for the development of novel therapeutic agents.

This study aims to establish a novel, straightforward, and reliable UPLC-MS method for determining the stability and impurity profile of Nirogacestat under various stress conditions, in accordance with ICH guidelines. The stability of Nirogacestat was investigated under various stress conditions, including acid/base hydrolysis, oxidation (H2O2​), photolysis, reduction, and thermal degradation. This research addresses the need for a validated, stability-indicating method that performs reliably across key analytical parameters, thereby contributing to pharmaceutical quality assurance.

Stress testing was performed by exposing Nirogacestat to various degradation conditions, including acid (0.1 and 1N HCl), base (NaOH), oxidative (30% H2O2), thermal (105°C), photolytic, and reductive environments. The mobile phase consisted of acetonitrile and 0.1% triethylamine/formic acid, adjusted to pH 2.5 in a 30:70 (v/v) ratio. Chromatographic separation was achieved using an Acquity UPLC BEH Shield RP-18 column (50 × 1.0 mm, 1.7 µm), with a flow rate of 0.5 mL/min and detection at 251 nm. Linearity was evaluated over a concentration range of 0.25 to 1.5 µg/mL. Validation studies assessed parameters such as selectivity, linearity, accuracy, precision, robustness, and solution stability.

The method demonstrated excellent linearity (r² = 0.999), with peak area directly proportional to concentration within the studied range. All validation parameters were within acceptable limits. Forced degradation studies revealed distinct degradation products under each stress condition. Notably, alkaline degradation resulted in the least degradation, while acid, peroxide, photolytic, thermal, and reductive conditions produced a variety of degradation products. These were effectively separated from Nirogacestat using the developed method. The relative retention times for Nirogacestat and its impurities remained consistent, and mass spectrometry confirmed the identities of the degradation products.

The validated UPLC-MS method exhibited high sensitivity, selectivity, and robustness in detecting Nirogacestat and its impurities. It effectively distinguishes degradation products even within complex matrices and fully complies with ICH guidelines for analytical method validation. The degradation profile of Nirogacestat under various stress conditions provides critical insights into its stability behavior, which is essential for formulation development and regulatory compliance. The successful separation and identification of degradation products further underscore the method’s applicability as a stability-indicating assay.

The developed UPLC-MS method is the first validated stability-indicating technique for Nirogacestat, offering comprehensive impurity profiling. It is precise, accurate, linear, and robust, making it highly suitable for routine quality control and regulatory submission. This method enables the reliable detection of degradation products, thereby enhancing the safety and efficacy profile of Nirogacestat in pharmaceutical preparations.

To explore the molecular mechanism of α7 nicotinic acetylcholine receptor (α7nAChR) mediated by Formononetin (FMN) in inhibiting macrophage inflammatory polarization and stabilizing atherosclerotic plaque.

SiRNA α7nAChR was transfected into THP-1-induced M0 cells and treated with FMN. Oil Red O staining was used to evaluate macrophage lipid deposition. RT-qPCR was used to detect α7nAChR, COX-2, IL-1β, IL-6, HO-1, and SHIP1 expression in M1 and M2 macrophages. Western blot was used to detect α7nAChR, iNOS, CD206, CD68, p-JAK2, and p-STAT3 protein expression in M1 and M2 macrophages.

Compared with the control group, FMN-mediated α7nAChR reduced lipid deposition in M1 and M2 macrophages. RT-qPCR results showed that FMN intervention significantly downregulated COX-2 and IL-1β expression in M1 (P < 0.05). α7nAChR expression significantly reduced COX-2, IL-6, and IL-1β expression in M2 (P < 0.05) and significantly increased HO-1 and SHIP1 expression (P < 0.05). FMN-mediated α7nAChR significantly decreased the expression of iNOS, CD68, p-JAK2, and p-STAT3 in M1 and M2 macrophages and significantly increased the expression of CD206 protein by Western blot (P < 0.05).

This study, for the first time, elucidated the mechanism of FMN regulating macrophage polarization through the α7nAChR/JAK2/STAT3 axis, providing new experimental evidence for the role of the cholinergic anti-inflammatory pathway in cardiovascular diseases. However, there are some limitations, such as the limited applicability of the THP-1 cell line, the need to strengthen the dose correlation study, the bioavailability and solubility limiting clinical translation, and the lack of human toxicological data.

FMN effectively modulates macrophage polarization through inhibition of the JAK/STAT signaling pathway while promoting α7nAChR expression.

Crohn's disease (CD) is a complex inflammatory bowel disorder with incompletely understood mechanisms. This study aimed to identify novel biomarkers and elucidate macrophage-related pathogenesis in CD.

Using gene expression data (GSE17928522) from the Gene Expression Omnibus (GEO) database, we compared 1135 CD patients with 180 healthy controls to identify altered gene expression profiles. Immune infiltration analysis was conducted to evaluate changes in immune cell subpopulations. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to construct gene co-expression networks and identify macrophage-associated modules. Mendelian randomization was used to validate the causal role of macrophages. For ex vivo validation, immunohistochemical staining of GBP4 protein expression was performed in colonic tissue samples from 6 CD patients (with ileal or colonic lesions). Non-lesional tissues from the same patients served as intra-individual controls to minimize inter-patient variability.

Our analysis revealed significant changes in immune cell subpopulations, particularly macrophages, within the CD microenvironment. A macrophage-associated module was identified, with GBP4 emerging as a critical gene. Immunohistochemical staining confirmed differential expression of GBP4 in CD tissue samples compared to controls.

This multi-modal study establishes GBP4 as a novel macrophage-associated biomarker for CD, supported by causal Mendelian randomization and immunohistochemical validation. The integration of WGCNA and genetic evidence strengthens the role of macrophage dysregulation in CD pathogenesis. Limitations include population bias in genomic data and small validation cohorts, but the consistency across methodologies underscores GBP4's potential as a therapeutic target.

Our findings highlight GBP4 as a novel potential biomarker and therapeutic target in CD, providing insights into the immune-mediated mechanisms underlying the disease. These results contribute to a better understanding of CD pathogenesis and may lead to new therapeutic strategies.

At present, malignant tumors are still under development with an increasing trend, and their prevention, treatment, and prognosis are also difficult. The INHBA gene, also known as inhibin β, has a wide range of roles to play in this context. Through studies, several researchers have confirmed that an abnormal expression of the INHBA gene affects the development and prognosis of several malignant tumors (cervical, colorectal, breast, gastric, etc.). This study aims to investigate the relationship between INHBA and the occurrence, development, treatment, and prognosis of malignant tumors.

This review, which involved scanning of pertinent literature, describes and evaluates recent research on the biological functions and mechanisms of INHBA in malignancies.

An aberrant expression of INHBA can lead to a variety of tumors, including cervical, esophageal, breast, colorectal, squamous cell, bladder, nasopharyngeal, gastric, and ovarian cancers.

INHBA, as a protein-coding gene, can affect the development of various tumors and the prognosis of tumor patients, suggesting that INHBA can be a target for tumor therapy. However, the research on targeted therapy is still immature and has certain safety risks.

Research findings indicate that the INHBA gene plays a role in both carcinogenesis and prognosis. As such, it may have the potential utility as a biomarker or therapeutic target in the treatment of malignant tumors.

During cerebral ischemia, brain tissue is damaged in two successive stages: ischemia and reperfusion (I/R). In the ischemic phase, brain tissue undergoes energy failure due to an impaired circulatory system (cerebrovascular), resulting in oxygen and glucose deprivation and consequent brain damage.

The study aimed to determine the effect of a two-week administration of naringin on caspase-3, IL-17, and NF-κB levels in cerebellar tissue in experimental focal brain ischemia-reperfusion in rats.

The research was conducted on 10- to 12-week-old Wistar-type rats obtained from the Selcuk University Experimental Animals Research and Application Center. Experimental brain ischemia-reperfusion in rats was performed under general anesthesia (carotid arteries were exposed to ischemia for 30 minutes). Experimental groups were formed as follows. 1) Control group, 2) Sham, 3) Sham + vehicle, 4) Ischemia-reperfusion, 5) Ischemia-reperfusion + Naringin supplemented group for two weeks (100mg/kg). At the end of the experiments, the levels of IL-17, caspase-3, and NF-κB were determined in the cerebellum tissue of the animals under general anesthesia. First of all, blood was drawn from the heart, and the animals were killed by cervical dislocation.

Experimental brain ischemia-reperfusion significantly increased caspase-3, IL-17, and NF-κB levels in the brain tissue of rats. In contrast, naringin supplementation for 2 weeks significantly suppressed the ischemia-reperfusion-induced inflammatory process.

The findings obtained from our research generally showed that, as a result of focal brain ischemia-reperfusion in rats, the levels of NF-κB, a key molecule involved in inflammatory pathways, as well as the pro-inflammatory cytokine IL-17 and caspase-3, an indicator of apoptosis, increased significantly in cerebellar tissue. However, intragastric naringin supplementation for two weeks following ischemia-reperfusion led to significant improvements in the adverse effects caused by the ischemic injury.

The study's results demonstrate that naringin treatment effectively mitigates inflammatory activation in the cerebellum following brain ischemia-reperfusion in rats.

This study explores the unbinding dynamics of alpha-ketoglutarate (AKG) from wild-type and mutant IDH1/IDH2 enzymes through steered molecular dynamics (SMD) simulations, examining how mutations influence binding, stability and enzymatic behaviour.

Isocitrate dehydrogenase (IDH) enzymes are essential for cellular metabolism, catalyzing the conversion of isocitrate to AKG in the tricarboxylic acid cycle. Mutations in IDH1 and IDH2 lead to the aberrant accumulation of the oncometabolite 2-hydroxyglutarate (2-HG), disrupting normal metabolic processes and contributing to tumorigenesis.

SMD simulations were employed to investigate AKG unbinding from both wild-type and mutant IDH1/IDH2. External forces were applied to quantify rupture forces and assess differences in stability among enzyme variants.

Wild-type IDH1 exhibited strong and stable AKG interactions, reflected by higher rupture forces and a greater number of hydrogen bonds, consistent with its normal catalytic function. In contrast, the R132H mutation in IDH1 weakened AKG binding, facilitating dissociation and potentially promoting 2-HG formation. Among IDH2 variants, the R140Q mutant demonstrated lower binding stability compared to R172K, while the wild-type enzyme maintained stronger interactions.

Mutations in IDH1 and IDH2 disrupt AKG binding and alter the stability, which may contribute to the pathological accumulation of 2-HG. These findings provide molecular insights into the oncogenic effects of IDH mutations and may aid in the development of targeted therapeutic strategies to inhibit mutant enzyme activity in cancer.

Diabetic nephropathy is a common microvascular complication that affects 20-40% of individuals with diabetes worldwide. This study aimed to evaluate the therapeutic potential of amla fruit against streptozotocin-induced diabetic nephropathy using animal models.

The male Wistar rats procured for the study were divided into four groups randomly, G1 (negative control group), G2 (positive control group), G3 (rats receiving amla powder at 5% of their diet), and G4 (rats receiving amla powder at 7% of their diet). Diabetic nephropathy (DN) was induced using streptozotocin at a dose of 65 mg/kg. High-performance liquid chromatography (HPLC) was used to quantify the bioactive constituents of amla. Physical, glycemic, oxidative, inflammatory, and renal biomarkers were assessed periodically.

HPLC analysis confirmed the presence of high levels of vitamin C, gallic acid, and quercetin in amla. Amla supplementation significantly improved body weight, controlled kidney hypertrophy, reduced blood glucose levels, enhanced antioxidant enzyme activity such as superoxide dismutase (SOD) and catalase (CAT), and suppressed inflammatory cytokines. Renal function markers, including serum creatinine, blood urea nitrogen (BUN), and urine albumin, were significantly improved in the amla-treated groups. The 5% amla diet showed slightly superior effects compared to the 7% amla diet, although the differences were not statistically significant.

The findings suggested that amla mitigates DN progression by targeting key pathological pathways, particularly oxidative stress and inflammation. Its bioactive compounds appear to modulate glucose homeostasis, restore antioxidant defence, and reduce inflammatory responses. The findings also suggested a potential non-linear dose-response relationship, indicating 5% as a more effective dietary inclusion.

Conclusively, amla fruit effectively alleviated streptozotocin-induced diabetic nephropathy in rats by controlling oxidative stress, inflammation, and hyperglycemia.

The development of secondary brain injury following intracerebral hemorrhage (ICH) involves multiple pathophysiological processes. Da-cheng-qi decoction (DCQD) has a long history of effectiveness in treating ICH and exhibits a variety of pharmacological effects. However, the phytochemicals and targets of DCQD targeting the pathophysiological processes of ICH still require further elucidation. This study aims to investigate the mechanism and key phytochemicals of DCQD in treating ICH based on the pathophysiological processes.

We used the UHPLC-MS/MS method to identify the main phytochemicals of DCQD and evaluate their pharmacological and toxicological parameters. We obtained and systematically analyzed the action targets of the main phytochemicals of DCQD and screened the targets related to ICH key pathophysiological processes and the corresponding phytochemicals. The results of molecular docking, molecular dynamic simulations, the GEO database and in vitro validation experiments confirmed the results of network pharmacology.

The 20 main phytochemicals of DCQD interact with a total of 186 targets, with 75 targets specifically associated with the treatment of ICH identified through pathophysiological processes. Among them, chrysophanol 1-glucoside, aloe emodin, emodin, hesperidin, tangeritin, rhein and physcion were recognized as the potential phytochemicals of DCQD for the treatment of ICH. Neuroinflammation is a crucial factor in the development of secondary brain injury following ICH. Further analysis results suggest that targeting ferroptosis is one of the mechanisms by which DCQD regulates the pathophysiology processes of ICH to improve ICH. In vitro cell experiment results have demonstrated the regulatory effect of naringin on TNF-α and Cox2. In addition, the phytochemicals in DCQD also contribute to enhancement of cognitive function impaired by ICH.

This study contributes to a better understanding of the underlying mechanisms behind DCQD's medicinal effects in treating ICH, offering insights into potential lead compounds for the development of anti-ICH drugs.

Long noncoding RNAs are essential regulators in numerous biological processes and have been linked to various diseases including cancer. Despite their initial classification as transcriptional byproducts lncRNAs have been shown to modulate chromatin structure transcription RNA processing protein translation and intranuclear transport. LINC-PINT a lncRNA induced by P53 is particularly noteworthy for its role in tumor suppression across multiple cancers

By utilizing the PubMed database and applying inclusion criteria based on relevance literature quality and data availability we conducted a comprehensive analysis of 128 studies to provide an overview of the functions of LINC-PINT and its mechanisms of action in cancers

LINC-PINT was confirmed to function as a tumor suppressor factor in many cancers such as triple-negative breast cancer non-small cell lung cancer gastric cancer glioma melanoma osteosarcoma laryngeal squamous cell carcinoma esophageal cancer colorectal cancer nasopharyngeal carcinoma retinoblastoma ovarian cancer thyroid cancer hepatocellular carcinoma and pancreatic cancer by promoting apoptosis and senescence inhibiting proliferation migration invasion drug resistance cell stemness EMT radioresistance and DNA damage repair

LINC-PINT serves as a tumor suppressor with its ability to sponge miRNAs regulate epigenetic modulation DNA damage repair etc. Despite the promising findings the complex and tissue-specific functions of LINC-PINT along with the need for further clinical validation underscore the importance of continued research to fully understand its mechanisms and potential as a therapeutic target

LINC-PINT is a potential target in cancer progression and treatment

Diabetes affects over 537 million people, with 20% developing chronic wounds. These wounds are made worse by inflammation, stress, immune problems, and poor blood vessel growth. Plants like Aloe barbadensis, Nigella sativa, and Moringa oleifera contain compounds that help heal wounds by reducing inflammation, stress, and boosting tissue growth.

This review explains why diabetic wounds heal slowly, focusing on factors like ROS, NO, and immune problems. It also looks at natural compounds that help healing and how traditional medicines can work with modern treatments for better wound care.

A systematic literature review was conducted using Scopus, Elsevier, PubMed, ScienceDirect, and Web of Science for studies published between 2000 and 2024. Inclusion criteria comprised clinical trials, preclinical studies, and ethnopharmacological research related to diabetic wound healing, pathophysiology, herbal medicine, active constituents, and mechanisms of action. Studies lacking diabetic wound specificity or methodological clarity were excluded. PRISMA guidelines were followed for study selection and synthesis.

Numerous studies demonstrated that traditional medicines enhance diabetic wound healing by regulating cytokine levels, promoting macrophage polarization, reducing oxidative damage, and remodelling the extracellular matrix. Flavonoids and polyphenols notably improved angiogenesis and tissue repair, while alkaloids and saponins exhibited antimicrobial and anti-inflammatory effects.

Traditional medicinal plants, through their diverse bioactive constituents, offer significant therapeutic potential for diabetic wound care. By targeting key molecular pathways involved in immune regulation and tissue repair, they present a viable adjunct to conventional therapies, potentially improving clinical outcomes in diabetic wound management.

The link between telomere length and Colorectal Cancer (CRC) risk and survival has been established. This study aims to investigate Telomere Maintenance-related Genes (TMGs) for predicting immunotherapy response and prognosis in CRC patients.

In this study, gene expression data and clinical information of CRC patients were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and TMG-related scores were calculated for the samples. Subsequently, Weighted Gene Co-Expression Network Analysis (WGCNA) was used to identify gene modules that were highly correlated with the TMG score and intersected with differentially expressed genes to screen for potential functionally relevant candidate genes. The key genes significantly associated with prognosis were further analyzed using Cox regression analysis, from which the key genes were identified, and a risk score model was constructed. Finally, the survival prediction ability of the model was evaluated across multiple cohorts, and differences in immune cell infiltration characteristics and drug sensitivity were analyzed within different risk groups.

A higher TMG score was noticed in CRC, and the TMG score was negatively correlated with the StromalScore, ImmuneScore, and ESTIMATEScore. Gene modules significantly associated with the TMG score were identified using WGCNA. Two key genes, CDC25C and USP39, which were closely associated with prognosis, were screened through differential expression analysis, and a risk score model was constructed. The model showed good survival prediction in both TCGA and GSE17537 independent cohorts. The scores of activated CD4 T cells, Type 17 T helper cells, Type 2 T helper cells, and neutrophils in high-risk patients were lower, while that of macrophages was higher in high-risk patients. Additionally, a negative correlation was observed between the risk score and the IC50 values of most drugs, as well as the enriched pathways of patients at high risk, which included epithelial-mesenchymal transition, angiogenesis, and myogenesis.

This study unveiled a TMG-related signature that predicts prognosis and immunotherapy in CRC. Based on the 2 prognostically relevant genes CDC25C and USP39, a reliable risk score model was established for the prognostic prediction, and the correlation between the drug sensitivity and the risk score was also explored.

This study reveals the significant value of TMGs in CRC prognostic assessment and immunotherapy response prediction, providing a new molecular basis for the development of individualized treatment strategies.

Exosomes, which are vesicles that are naturally derived and contain a biomolecular payload, are promising vehicles for melanoma therapy because of their biocompatibility, targeting capabilities, and stability. This review emphasizes their capacity to circumvent the constraints of conventional treatments.

We carried out a comprehensive search of PubMed, ScienceDirect, and Google Scholar for peer-reviewed articles published between 2015 and 2024 utilizing terms such as “exosomes,” “melanoma,” and “chemotherapy.” Studies on exosome characterization or non-melanoma malignancies were excluded from the inclusion criteria, which centered on exosome-based therapeutics.

Drugs delivered via exosomes, such as small interfering RNA (siRNA) and chemotherapeutics, demonstrated enhanced tumor accumulation, achieving 2.5 times greater bioavailability and resulting in a tumor reduction of 60 to 90% when compared to their free counterparts. Surface modifications, such as cRGD peptides, have been shown to enhance targeting capabilities, whereas exosome-mediated photodynamic therapy has been effective in augmenting reactive oxygen species generation and promoting apoptosis.

Exosomes tackle significant challenges such as drug resistance and systemic toxicity; however, they encounter obstacles related to scalability and immunogenicity. Their dual function in tumor advancement and treatment highlights the necessity for standardized protocols.

Exosome-based therapies signify a groundbreaking advancement in the treatment of melanoma. Future endeavors should refine engineering methodologies, enhance production capabilities, and substantiate effectiveness through rigorous clinical trials.

This study aims to discover and design β-5 tubulin-specific covalent inhibitors for non-small cell lung cancer (NSCLC) that can minimize hematotoxicity, a major side effect of current microtubule-targeting agents (MTAs).

Current microtubule-targeting drugs cause toxicities such as hematotoxicity and multidrug resistance (MDR). The colchicine binding site in β-5 has Cys-239, whereas β-1 has Ser-239, allowing selective inhibition based on the reactivity differences for covalent reactions.

β-5 and β-1 tubulin models were developed, and covalent docking and virtual screening were conducted to identify selective inhibitors targeting the β-5 tubulin colchicine binding site. Twenty hits were selected, and a comparative study was carried out between β-5 and β-1 to evaluate the selectivity and binding potential of the inhibitors.

Among the 20 identified hits, four compounds demonstrated selective inhibition of β-5 tubulin, exhibiting stronger binding affinity for β-5 over β-1 tubulin. Molecular dynamics studies further confirmed their stability and enhanced binding, highlighting their potential as promising candidates for further drug development.

The study identified four novel β-5 tubulin-specific covalent inhibitors that may act as potential therapeutic agents for NSCLC, with the possibility of reduced hematotoxicity. These findings suggest that selective inhibition could help minimize side effects, addressing a critical need in cancer treatment.

Clear cell renal cell carcinoma (ccRCC) is the most prevalent of renal cancers, with a 5-year survival rate of less than 10% for metastatic cases. The most efficient current strategies to treat ccRCC in advanced settings slightly increase progression-free survival. Chimeric antigen receptor T cells (CAR T cells) targeting carbonic anhydrase IX (CAIX) have reemerged as a promising alternative to ccRCC treatment based on recent preclinical data. CAIX and cyclooxygenase-2 (COX-2) are key players in tumor progression across various malignancies, overexpressed in 95% and 50% of ccRCC cases, respectively.

This study employed in silico analysis to examine the expression of CAIX and COX-2 in ccRCC cell lines. The effects of celecoxib, anti-CAIX monoclonal antibodies, and anti-CAIX CAR T cells were evaluated using immunofluorescence microscopy and flow cytometry techniques.

Herein, we show a positive correlation between CAIX and COX-2 expression in ccRCC cell lines in vitro and in silico. Notably, COX-2 blockade with celecoxib led to a significant downregulation of CAIX expression in ccRCC cell lines. This effect is retroactive since treatment of these ccRCC cells with two different anti-CAIX monoclonal antibodies (mAbs) resulted in the downregulation of COX-2 expression. The association of celecoxib with anti-CAIX CAR T cell therapy impaired their cytotoxic potential over ccRCC in vitro, depending on CAIX cellular density.

These findings suggest a regulatory interaction between CAIX and COX-2 levels, indicating that COX-2 inhibitors may diminish the efficacy of CAIX-targeted therapies and should be avoided in combination treatments.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by the impaired utilization of glucose, insulin resistance, or reduced insulin production. Although conventional pharmacologic agents like metformin, sulfonylureas, and thiazolidinediones are effective in regulating elevated blood glucose levels, they are often associated with some adverse effects, such as weight gain and liver problems.

The present review summarizes the possibility of using phytochemicals as safer alternatives for the management of DM by modulation of molecular receptors.

Several studies have reported that certain antioxidant phytochemicals exhibit inhibitory effects on key signaling pathways involved in glucose metabolism and insulin sensitivity under in vitro conditions. Therefore, this review will focus on the therapeutic potential of phytochemicals in modulating molecular targets, such as PPARs, GPR119, free fatty acid (FFA) receptors, glucocorticoid receptors, and others. For this purpose, a systematic and extensive literature search was carried out to obtain relevant data, focusing on the prospect of phytochemicals in modulating molecular receptors for diabetes mellitus (DM) management. Electronic databases, including PubMed, Scopus, ScienceDirect, and Google Scholar, were accessed for articles up to March 2025.

Curcumin, resveratrol, and quercetin are bioactive molecules that increase the sensitivity of the body to insulin and protect the pancreatic β-cells from oxidative stress. Natural agents, such as garlic, green tea, and blackcurrants, possess an antidiabetic action by inhibiting enzymes, such as α-glucosidase, and increasing the uptake of glucose. The co-administration of synthetic drugs along with natural agents has a synergistic effect in improving glycemic control with fewer side effects. Examples include resveratrol with metformin or curcumin with thiazolidinediones.

The findings of this review should be validated at the clinical level in future research studies, including toxicity profiling and formulation optimization, to maximize the therapeutic potential of phytochemicals in the management of DM.