Functional study of chitosan oligosaccharide in ameliorating colitis in rats

Glial activation and increased blood brain barrier permeability in the medial preoptic area of male mice lacking neural androgen receptor.

Nitric oxide and α-glucosidase inhibitors from Ludwigia adscendens: An integrated in vitro and in silico study.

Tiaojing Cuyun Recipe (TJCYR), a known Chinese herbal compound, has been shown to improve endometrial receptivity and embryo implantation in patients with embryo implantation dysfunction (EID). This study investigated the mechanism by which TJCYR improves endometrial receptivity. High-performance liquid chromatography (HPLC) was used to detect the compounds of TJCYR. A mouse EID model was established by subcutaneous injection of mifepristone into the neck. The rats were randomized into control, EID, Prog, TJCYR-L, and TJCYR-H groups. Hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM) were performed to assess pathological changes in the endometrium. The aggregation of Fe3+ was assessed using Prussian blue staining. Western blotting, immunofluorescence, and assay kits were used to determine the endometrial receptivity, ferroptosis indicators, and SLC7A11/GSH/GPX4 axis-related biomarkers. TJCYR-H group significantly increased the implanted sites (P<0.05), improved endometrial pathological changes and enhanced the expression of progestogen receptor (PR), estrogen receptor α (ERα), leukocyte inhibitory factor (LIF), osteopontin (OPN), integrin αV, SLC7A11, GPX4 (glutathione peroxidase 4), and ferritin, as well as the serum estradiol (E2), progesterone (Pg), reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and T-GSH levels in EID. TJCYR inhibited the reduction in mitochondrial volume and membrane shrinkage, increased density, and decreased cristae in endometrial glandular epithelial cells of EID. Furthermore, TJCYR reduced the aggregation of Fe3+, downregulated serum MDA and GSSG levels, and reduced the expression of cyclooxygenase-2 (COX2), 4-hydroxy-2-nonenal (4-HNE), acyl-CoA synthetase long-chain family member 4 (ACSL4), and transferrin receptor (TFR) in EID mice. TJCYR can improve endometrial receptivity of EID mice by inhibiting ferroptosis, which may be related to the SLC7A11/GSH/GPX4 axis.

Novel thiadiazole derivatives: synthesis, in silico, in vitro and in vivo evaluation of analgesic and anti-inflammatory activities.

Topical delivery of Vismodegib using fourth-generation PAMAM dendrimers: a potential treatment for Kaposi's sarcoma.

Thromboxane A2 (TXA2), a metabolite of arachidonic acid, is well known for its role in vasoconstriction and platelet aggregation via activation of thromboxane prostanoid receptors (TPR). Although other prostanoid receptors have established roles in pain modulation, the contribution of TXA2-TPR signaling to nociceptive processing remains unclear. This study evaluated the analgesic effects of a TPR agonist in mouse models of pain. Four-week-old male ddY mice, an outbred mouse strain, received intrathecal (i.t.) administration of (Z)-7-((1S,2R,3R,4R)-3-((R,E)-3-hydroxy-4-(4-iodophenoxy)but-1-en-1-yl)-7-oxabicyclo[2.2.1]heptan-2-yl)hept-5-enoic acid (I-BOP), a TPR agonist, in four pain models (n = 6-10 per group): hot plate test, formalin test, prostaglandin E2 (PGE2)-induced allodynia, and L5 spinal nerve transection (L5-SNT). Behavioral tests evaluated pain responses as the primary outcome. The mRNA expression levels of cyclooxygenase (COX)-1, COX-2, TXA2 synthase (TXAS), and TPR were analyzed by reverse transcription-polymerase chain reaction and compared between ipsilateral and contralateral L4-L6 spinal dorsal horns. TPR localization in the spinal dorsal horn was determined by immunohistochemistry. Data were analyzed using appropriate parametric or nonparametric tests based on the results of normality assessment. Comparisons between groups were performed using Student t test, the Mann-Whitney U test, 1-way analysis of variance (ANOVA) with Dunnett post hoc test, 2-way ANOVA with Bonferroni post hoc test, or Friedman test followed by Wilcoxon signed-rank tests with Bonferroni correction as appropriate. All behavioral assessments were conducted in a blinded manner. In the PGE2-induced allodynia model, coadministration of I-BOP dose dependently reduced the allodynia score compared with PGE2 alone. When the response to PGE2 alone was defined as 100%, the allodynia scores were reduced to 20% (95% confidence interval [CI], -7 to 47; P = .0012) at 1 ng and 10% (95% CI, -11 to 31; P < .001) at 10 ng I-BOP. In the L5-SNT neuropathic pain model, i.t. I-BOP produced a dose-dependent elevation of mechanical withdrawal thresholds, with significant main effects of dose (P < .001) and time (P < .001) and a significant dose × time interaction (P = .0012). In the formalin test, I-BOP selectively reduced nociceptive behavior during the second phase (I-BOP 140 ± 6.2 seconds; saline 623 ± 18.1 seconds, expressed as mean ± standard error of the mean [SEM]; P = .008), without affecting the first phase. The ipsilateral spinal dorsal horn of L5-SNT mice showed increased TPR mRNA expression. Immunohistochemistry revealed TPR localization in both the substantia gelatinosa and deep laminae of the spinal dorsal horn. These findings suggest that a TPR agonist exerts analgesic effects by acting on TPR expressed in the spinal cord, highlighting the potential role of TPR signaling in pain modulation.

Puerarin and DHEA combination therapy alleviates primary dysmenorrhea via inhibition of the Hsp90ab1/p38/JNK pathway.

Pharmacological modulation of NF-κB-dependent COX-2/PGE₂ signaling influences inflammatory lesion development during Leishmania mexicana infection.

Cross-reactivity among nonsteroidal anti-inflammatory drugs (NSAIDs) creates a significant clinical difficulty, especially in patients with NSAID hypersensitivity. These reactions are based on cyclooxygenase-1 (COX-1) inhibition and non-immunoglobulin E (IgE)-mediated reactions. COX-1 inhibition leads to dysregulation of arachidonic acid metabolism, with decreased prostaglandin synthesis and increased leukotriene production. Clinically, cross-intolerant reactions manifest in different phenotypes, including NSAID-exacerbated respiratory disease (NERD), NSAID-induced urticaria/angioedema (NIUA), and NSAID-exacerbated cutaneous disease (NECD). In contrast, true allergic reactions—such as single-NSAID-induced urticaria/angioedema and anaphylaxis (SNIUAA) and single-NSAID-induced delayed hypersensitivity reactions (SNIDHR)—are immunologically mediated and drug-specific. These phenotypes differ in underlying conditions, clinical manifestations, and patterns of NSAID tolerance. Paracetamol is generally considered a safer alternative due to its weak COX-1 inhibition; however, reactions may still occur, particularly at higher doses. Selective COX-2 inhibitors are usually better tolerated, however their safety should be confirmed, preferably through controlled drug provocation testing due to sporadic reactions in cross-intolerant patients. Understanding the distinction between pharmacologically mediated cross-intolerance and true allergic reactions is essential for accurate diagnosis, risk stratification, and therapeutic decision-making. This review summarizes current evidence on the mechanisms underlying NSAID hypersensitivity, analyzes the tolerability of paracetamol and alternative analgesics, and discusses practical management strategies to reduce the risk of adverse reactions.

In this work, Eucalyptus salubris seeds extract (ESS) was characterized using liquid chromatography (LC) coupled to mass spectrometry (MS), and its in vitro and in vivo anti-inflammatory properties were evaluated. Through LC-MS and MS2 analysis, flavanonols and monounsaturated fatty acids were found to be the most abundant components, while unreported galloylated flavanonols were profiled. ESS attenuated the denaturation of Bovine Serum Albumin (BSA), significantly stabilized rats Red Blood Cells (RBC) membranes, and inhibited both Cyclooxygenase-1 (COX-1) and Cyclooxygenase-2 (COX-2) enzymes, indicating its ability to reduce inflammation. The in vivo study showed that ESS significantly reduced the carrageenan-induced paw edema in rats and normalized the inflammatory cytokines Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-6 (IL-6) levels. In addition, ESS alleviated formaldehyde-induced arthritis symptoms through a remarkable reduction in oxidative stress biomarkers (evidenced by decreased Malondialdehyde (MDA), Glutathione (GSH), and Nitric Oxide (NO) levels, along with increased Superoxide Dismutase (SOD) and Catalase (CAT) activities), as well as the restoration of the hematological profile (reduction in white blood cell (WBC) count and erythrocyte sedimentation rate (ESR), accompanied by an increase in red blood cell (RBC) count and hemoglobin (Hb) levels). These effects are largely attributable to the richness of ESS in phenolic compounds, flavonoids, and other bioactive secondary metabolites. Collectively, these findings supported the therapeutic potential of E. salubris extract as a natural source of anti-inflammatory and antioxidant agents, warranting further investigation for potential pharmaceutical or nutraceutical applications.

Cyclooxygenase-2 (COX-2) is reported to be upregulated in many cancers that promote cancer growth and angiogenesis. Therefore, inhibiting COX-2 can inhibit cancer growth and advances its treatment. In the present work, Zingerone, a reported anticancer agent, has been hybridized with 1,2,3-triazole scaffold to develop effective anticancer compounds targeting COX-2 enzyme. Eleven zingerone-1,2,3-triazole hybrids (3-13) have been synthesized and assessed for antiproliferative activity against HepG2, MCF-7, and HCT-116 cell lines and COX-2 inhibition. Cell cycle and apoptosis studies have also been carried out for the best candidate by flow cytometry. Molecular docking and ADMET profiles were performed to inquire about drug likeness parameters. Among all the zingerone hybrids, compound 11 was found to be the most promising cytotoxic agent with IC50 1.86 against HepG2 and displayed COX-2 inhibitory effect with IC50 0.21 µM. The same compound also arrests cell cycle at G2/M phase and triggers late apoptosis with 95.33% in HepG2 cells. The docking study revealed strong hydrophobic interactions with key residues of the COX-2 protein. Furthermore, zingerone hybrids possess drug-likeness properties with no mutagenicity/cardiotoxicity. Zingerone hybrid (11) displayed potent anticancer and COX-2 inhibitory activity, with favorable pharmacokinetics and low toxicity.

The objective of this study is to investigate the therapeutic potential and underlying mechanisms of Chimonanthus praecox-derived coumarins in Alzheimer's disease (AD)-related neuroinflammatory and cognitive impairments. Network pharmacology was employed to identify active components and targets of Chimonanthus praecox-derived coumarins, followed by intersection analysis with AD-related genes. A protein-protein interaction (PPI) network was constructed and subjected to functional enrichment analysis. Molecular docking was performed to validate the binding affinity between key compounds and core targets. An AD-like rat model characterized by aging-related cognitive impairment and neuroinflammation was established using D-galactose and aluminum chloride, and therapeutic effects of coumarin treatment were evaluated via behavioral testing, HE staining, immunohistochemistry, Western blotting, and electroencephalography (EEG). Four active compounds, 58 drug targets, and 19 AD-related intersecting targets were identified, primarily enriched in neuroinflammation-related pathways including NF-κB p65, NLRP3, and Alzheimer's disease-related pathways. Molecular docking showed strong binding of key coumarin derivatives to amyloid precursor protein (APP), apolipoprotein E4 (APOE4), NF-κB p65, and prostaglandin-endoperoxide synthase 2 (PTGS2). In vivo, Chimonanthus praecox-derived coumarin treatment improved aging-associated cognitive deficits, alleviated hippocampal neuronal injury, inhibited APP and APOE4 expression, and significantly downregulated NF-κB p65, PTGS2, IL-6, and NLRP3 levels. EEG analysis further confirmed attenuation of abnormal neural activity. Chimonanthus praecox-derived coumarins exert neuroprotective and anti-inflammatory effects through multi-target modulation, supporting their potential as candidate agents for AD-related neuroinflammatory and cognitive dysfunction.

Background Paclitaxel (PTX) is a first-line chemotherapeutic agent extensively employed in the management of breast cancer (BC); however, the emergence of drug resistance frequently results in unsatisfactory clinical outcomes and poor prognosis. This study aimed to investigate the pathogenic mechanisms that drive PTX resistance in BC. Methods Tumor and matched adjacent normal tissues were collected from 30 BC patients treated with PTX. Untargeted metabolomics was performed to analyze the metabolic differences. The expression of lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF), protein L-isoaspartyl (D-aspartyl) methyltransferase (PCMT1), and cyclooxygenase-2 (COX-2) was assessed using RT-qPCR, immunoblotting, and immunohistochemistry (IHC). Cell proliferation was determined via CCK-8 and colony formation assays, cell apoptosis was analyzed by flow cytometry, and enzyme-linked immunosorbent assay (ELISA) was used to measure arachidonic acid (AA) and prostaglandin E2 levels. The interaction between LITAF and PCMT1, as well as the ubiquitination level of PCMT1, was investigated using co-immunoprecipitation (Co-IP). In vivo , nude mice were used to explore the effect of LITAF on tumor response to PTX treatment. Results PCMT1 and COX-2 were upregulated in BC tissues, particularly in PTX-resistant patients, whereas LITAF expression was downregulated. In BC tissues, LITAF expression was negatively correlated with PCMT1 levels, while PCMT1 expression showed a positive correlation with COX-2 levels. PCMT1 knockdown attenuated COX-2-mediated AA metabolism, suppressed BC cell proliferation, and increased the sensitivity of BC cells to PTX. LITAF interacted with PCMT1 and promoted ubiquitination-mediated degradation of PCMT1, thereby inhibiting COX-2-mediated AA metabolism, reducing the proliferation of PTX-resistant BC cells, and enhancing the sensitivity of BC cells to PTX in vivo . Conclusion LITAF regulates the ubiquitination-mediated degradation of PCMT1 to inhibit COX-2-dependent AA metabolism, thereby enhancing the sensitivity of BC cells to PTX and providing a potential therapeutic strategy to overcome PTX resistance in BC.

Numerous inflammation-mediated molecular pathways, including the cyclooxygenase (COX)-2, epidermal growth factor receptor (EGFR), p38a MAP kinase, TNF, NF-kB, STAT, RhoC, and PPARy pathways, have been investigated and evaluated as significant players in OSCC carcinogenesis, Such gene mutations can further cause cancer development near the pharynx and oral cavity and more than 90% of such cancer cases are OSCCs (Oral Squamous Cell Carcinoma). Till date, there is minimal study that has analyzed allele, genotype, or haplotype frequencies of CCL-2 polymorphisms in patients with OSCC. Objective We hypothesized that CCL-2 polymorphisms might modify the relative risk for the development of OSCC. On the basis of these findings, we evaluated SNP in CCL-2 gene in groups of non-OSCC controls and OSCC participants. Materials and Methods This study employed a cross‐sectional design involving individuals from Chennai, Tamil Nadu, India. A total of 50 individuals who reported to Saveetha Dental College, Chennai, were included in this study. The subjects were divided into a control group A (N = 25) and OSCC group B (N = 25) based on clinical examination. Sample collection and DNA extraction, A volume of 5 mL of venous blood was collected and DNA isolation was performed according to the modified Miller et al 1998 protocol. CCL2 gene (OSCC) polymorphisms were assessed by PCR amplification and restriction digestion.statistical analysis was performed using the Statistical Package for the Social Sciences version 23.0 for Windows (SPSS Inc., Chicago, IL). The distribution of genotypes and allele frequencies in the CP and control groups was compared using the Chi- square test. Results Genotype frequencies of CCL2 gene polymorphism (rs1024611) among the cases and controls, The genotype frequency of cases and controls do not differ significantly χ2df (P = 0.8353). Agarose gel electrophoretogram showed partial amplification of CCL2 gene spanning polymorphic site (rs1024611) run along with standard DNA ladder. Agarose gel electrophoretogram showed PvuII digested amplicon of CCL2 spanning rs1024611 site (Homozygous TT - 333 bp; Heterozygous CT - 333 + 250 + 73 bp; Homozygous CC - 250 + 73 bp). Conclusion: It has been concluded that there is no significant association between CCL2 gene polymorphism with susceptibility to OSCC among South Indian Populations.

Diabetic retinopathy (DR) is a leading cause of preventable vision loss, yet current therapies primarily address late, VEGF-driven vascular complications rather than early upstream drivers. Emerging evidence indicates that early DR originates from metabolic stress within the retinal neurovascular unit, where dysregulated lipid metabolism, oxidative stress, and inflammation precede visible microvascular damage. Disturbances in polyunsaturated fatty acid (PUFA) metabolism, together with related metabolic stressors such as elevated homocysteine (Hcy), drive lipid dysregulation, oxidative stress, and inflammation preceding visible microvascular damage, promoting endothelial dysfunction and blood–retinal barrier (BRB) breakdown. Hyperglycemia shifts retinal lipid composition toward oxidation-prone omega-6 PUFAs and activates lipoxygenase (LOX), cyclooxygenase (COX), and cytochrome P450 (CYP450) eicosanoid pathways. LOX-derived metabolites such as 12- and 15-HETE stimulate NADPH oxidase, disrupt tight junctions, and promote inflammatory signaling in endothelial and Müller cells. COX-2–driven prostaglandin E2 signaling increases vascular permeability, while CYP450 metabolites and their soluble epoxide hydrolase (sEH) derived products exert context-dependent effects on vascular integrity. Elevated Hcy further enhances oxidative stress and NF-κB activation, amplifying PUFA-mediated inflammatory signaling. These mechanisms identify modifiable upstream targets that complement glycemic control. Higher dietary omega-3 intake and lower omega-6:omega-3 ratios are associated with reduced DR risk, particularly in well-controlled diabetes. Omega-3–rich diets, exercise, and correction of folate and B-vitamin deficiencies may help improve systemic inflammation and retinal barrier integrity. Integrating lipid pathway modulation, nutritional support, and metabolic control with careful ocular monitoring may help slow the progression of DR before irreversible blindness occurs.

This study aimed to evaluate whether polydatin (Poly) could eliminate the harmful effects of vancomycin (VCM) on the lungs of rats. Rats were administered VCM (200 mg/kg) and Poly (50 mg/kg), both separately and in combination, for a duration of 7 days. Following this, various methods were utilized to analyze proteins and pathological changes in lung tissue related to oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, and ferroptosis. It was found that Poly application significantly enhanced antioxidant enzyme activities and nonenzymatic antioxidants while decreasing VCM-induced lipid peroxidation. The study showed that VCM elevated the expression of inflammatory cytokines as well as Janus kinase 2 (JAK-2) and signal transducer and activator of transcription 3 (STAT-3), whereas Poly treatment inhibited these genes. Furthermore, VCM was found to induce apoptotic markers, but Poly offered protection to lung tissue against the harmful effects of VCM by demonstrating an antiapoptotic effect. Additionally, the increased expression of prostaglandin endoperoxide synthase 2 (PTGS2) and transferrin receptor 1 (TFR1), along with the decreased expression of glutathione peroxidase 4 (GPX4) in lung tissue induced by VCM, showed improvement following Poly administration. VCM was observed to increase, while Poly decreased the expression of endoplasmic reticulum stress markers. Overall, the findings of this study suggest that Poly has therapeutic potential in combating VCM-induced lung toxicity.

Aggressive brain tumors such as glioblastoma (GBM) remain among the most lethal human cancers, with a median survival of only 15months despite multimodal treatment. Their resistance arises from a triad of barriers-the blood-brain barrier (BBB), marked intratumoral heterogeneity, and a profoundly immunosuppressive tumor microenvironment (TME). Immunotherapeutic strategies based on natural killer (NK) and T cells, leveraging antigen-independent cytotoxicity and antigen-specific precision, respectively, offer potential breakthroughs but are often limited by chronic neuroinflammation. A key driver of TME suppression is prostaglandin E2 (PGE2), produced via the cyclooxygenase-2 (COX-2) pathway. PGE2 exerts a dual role: Intracellularly, it can promote apoptosis, whereas extracellularly, it fosters tumor progression, immune evasion, and therapeutic resistance. Through activation of EP2 and EP4 receptors, PGE2 signals via Gαs proteins to elevate cyclic adenosine monophosphate (cAMP), leading to impaired cytotoxic immunity. This signaling downregulates NK cell activating receptors (e.g., NKG2D, NKp30), induces CD8⁺ T cell exhaustion, and promotes regulatory T cell expansion. The COX-2/PGE₂ axis further mediates resistance to checkpoint inhibitors, CAR-T therapy, and chemotherapy by enhancing neuronal excitation through EP1 receptor activation in GBM. Targeting this pathway has therefore emerged as a compelling therapeutic strategy, which can restore NK and T cell function and sensitize tumors to immunotherapy. Combining PGE₂ modulation with next-generation NK/T cell approaches-including CAR-NK and CAR-T platforms-holds promise to overcome immune resistance and redefine therapeutic paradigms for GBM and other central nervous system malignancies.

ABSTRACT Plants exhibit significant biological activity and are widely used in the pharmaceutical and food industries due to their bioactive compounds. Medicago lupulina is a plant species belonging to the Fabaceae family. In this study, dried flowers of M. lupulina were extracted with methanol. The total phenolic content and DPPH˙ radical scavenging activity of the obtained extract were determined using a potentiometric biosensor method. In addition, the phenolic content of the extract was determined by LC‐ESI‐MS/MS. The inhibitory properties of the main components against cyclooxygenase‐2 (COX2) were theoretically investigated using molecular docking. Moreover, the pharmacokinetic properties of the main molecules were determined by SwissADME. The methanol extract exhibited a DPPH radical scavenging activity of 39.43% and contained 117.2 mg GAE g −1 extract of total phenolics at 500 ppm. In the LC‐ESI‐MS/MS analysis, coumarin (23.93), kaempferol (15.79), syringic acid (9.44), isoquercitrin (8.31), salicylic acid (7.49), kaempferol‐3‐glucoside (6.03), quercetin (4.88) and hesperidin (4.15) were the major constituents (mg g −1 extract). Molecular docking results showed that isoquercitrin (−10.40 kcal/mol), kaempferol‐3‐glucoside (−10.10 kcal/mol) and hesperidin (−9.90 kcal/mol) exhibited the strongest binding affinities toward the COX‐2 enzyme. The BOILED‐Egg model indicated that coumarin and salicylic acid possess high gastrointestinal absorption and favorable brain permeability. Therefore, M. lupulina is rich in biologically active secondary metabolites, highlighting its promising potential for applications in the food, pharmaceutical and cosmetic industries.

Cancer is a multifactorial disease involving multiple interrelated molecular targets and signaling pathways. Some epidemiological studies have suggested that nonsteroidal anti-inflammatory drugs could reduce the incidence of certain types of cancer, indicating the interplay between inflammation and cancer. Designing compounds that inhibit an enzyme of the arachidonic acid inflammatory cascade while exhibiting anticancer effects has emerged as a promising strategy. A descriptive review and analysis of recently published studies on the synthesis of compounds that target two enzymes of the arachidonic acid cascade and simultaneously exhibit anticancer activity was performed. Numerous cyclooxygenase-2 (COX-2) inhibitors with anticancer activity are known. Fewer examples exist for 5-lipoxygenase (5-LOX) inhibitors, while many dual COX-2/5-LOX inhibitors also display anticancer effects. Some examples of dual inhibitors with anticancer potential include 5-LOX/microsomal prostaglandin E2 synthase (mPGES), and COX-2/soluble epoxide hydrolase inhibitors. There are also compounds designed to inhibit three targets: COX-2, 15-LOX, and carbonic anhydrase. Given the complex interplay between inflammation and cancer, the term "anticancer effects" encompasses various therapeutic opportunities, ranging from adjuvant therapy and chemoprevention to angiogenic and cytotoxic activity. This multitarget approach highlights the broad therapeutic possibilities of targeting inflammatory pathways, establishing a direction for the development of innovative anticancer therapies with improved safety profiles.