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Photodynamic therapy (PDT) often faces challenges such as oxygen dependence and limited tumour specificity. We report a tumour-targeting photosensitizer (PS), RUCXB, which enhances uptake by cancer cells by targeting overexpressed cyclooxygenase-2 enzyme in tumours. RUCXB also reduces oxygen dependence via a type I PDT mechanism and achieves a strong therapeutic effect through the synergistic induction of ferroptosis and apoptosis. This work presents a reliable strategy for developing potent PSs with enhanced PDT efficacy, tumour selectivity, and diminished oxygen dependence. [ABSTRACT FROM AUTHOR]

Unmeasured confounding is often raised as a source of potential bias during the design of nonrandomized studies, but quantifying such concerns is challenging. We developed a simulation-based approach to assess the potential impact of unmeasured confounding during the study design stage. The approach involved generation of hypothetical individual-level cohorts using realistic parameters, including a binary treatment (prevalence 25%), a time-to-event outcome (incidence 5%), 13 measured covariates, a binary unmeasured confounder (u 1; 10%), and a binary measured "proxy" variable (p 1) correlated with u 1. Strengths of unmeasured confounding and correlations between u 1 and p 1 were varied in simulation scenarios. Treatment effects were estimated with (1) no adjustment, (2) adjustment for measured confounders (level 1), and (3) adjustment for measured confounders and their proxy (level 2). We computed absolute standardized mean differences in u 1 and p 1 and relative bias with each level of adjustment. Across all scenarios, level 2 adjustment led to improvement in the balance of u 1, but this improvement was highly dependent on the correlation between u 1 and p 1. Level 2 adjustments also had lower relative bias than level 1 adjustments (in strong u 1 scenarios: relative bias of 9.2%, 12.2%, and 13.5% at correlations of 0.7, 0.5, and 0.3, respectively, vs 16.4%, 15.8%, and 15.0% for level 1). An approach using simulated individual-level data is useful to explicitly convey the potential for bias due to unmeasured confounding while designing nonrandomized studies, and can be helpful in informing design choices. This article is part of a Special Collection on Pharmacoepidemiology. [ABSTRACT FROM AUTHOR]

Gastric and duodenal ulcers are increasingly becoming global health burdens. The side effects of conventional treatments such as non-steroid anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), antibiotics, and cytoprotective agents have necessitated the search for new medications. Plants are a rich source of active metabolites and herbal medicines have been used in the treatment of ulcers and cancers. In this study, we used in silico methods like molecular docking and MM-GBSA calculations to evaluate the effects of some anti-ulcer and anti-inflammatory phytochemicals on some key enzymes, cyclooxygenase (COX), and lipoxygenase (LOX), which are implicated in the protection and destruction of the gastric mucosa. The phytochemicals were retrieved from the literature and docked toward the binding sites of the three enzymes (COX-1, COX-2, and 5-LOX). Five compounds, rhamnetin, kaempferol, rutin, rosmarinic acid, and chlorogenic acid were observed to putatively bind to cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LOX) but not to cyclooxygenase 1 (COX-1). The interaction mechanisms between these phytochemicals and the target proteins are discussed. The compounds' drug metabolism, pharmacokinetics, and toxicity have been evaluated to assess their suitability as potential next-generation anti-ulcer and anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

Hypertrophic scar (HTS) formation is a pathological fibrotic skin disease, with no satisfactory treatments available currently. Inducing apoptosis of HTS-derived fibroblasts (HSFs) are becoming promising approaches. In this research, we aim to improve the technology with co-delivery COX-2 and TGF-β1 siRNAs and further investigate the underlying mechanism. Firstly, the HSFs were transfected with 1 µg/ml COX-2 and/or TGF-β1 siRNAs, and proved that the apoptosis of HSFs was greater induced by COX-2/TGF-β1 siRNAs than either COX-2 or TGF-β1 siRNA alone by flow cytometry. To investigate the impact of co-silencing TGF-β1 and COX-2 mRNA expression in vivo, we established HTSs model in rat tails. Our results confirmed that co-silencing of TGF-β1 and COX-2 mRNA expression could significantly alleviate the HTS formation in vivo. Furthermore, we explored the potential molecular mechanism and revealed that the protein levels of TP53, Bcl-2 and Caspase-3 were downregulated while Bax and Cleaved Caspase-3 were upregulated in the COX-2/TGF-β1 siRNA groups compared with HKP group. Taken together, our results demonstrated that simultaneous silencing of COX-2 and TGF-β1 expression by siRNAs induced HSF apoptosis through a TP53 mediated caspase pathway. Therefore, COX-2/TGF-β1 siRNAs might serve as a novel and effective therapeutic alternative for HTSs treatments. [ABSTRACT FROM AUTHOR]

AbstractIn order to make more rational use of Flemingia Philippinensis, a systematic separation from the roots of F. philippinensis was performed in the current study. The investigation of chemical constituents resulted in the isolation of a rare prenylated isoflavone-quinone, fleminquinone A (1), together with four known analogues (2–5). Their structures were established by extensive physical and spectroscopic data analysis. Anti-inflammatory activities of the isolated compounds were evaluated in lipopolysaccharide induced mouse mononuclear macrophage leukemia cells RAW 264.7 model. Compound 1 exhibited significant inhibitory effects on LPS-induced NO production and COX-2. Compound 1 also significantly affected the levels of inflammatory cytokines. [ABSTRACT FROM AUTHOR]

In search of new active molecules, a small focused library of novel 1,2,3-triazoles based chalcone derivatives has been efficiently prepared via the click chemistry approach. All the synthesized compounds were characterized with the help of IR, 1H NMR, 13C NMR and mass spectroscopic techniques. The synthesized novel 1,2,3-triazoles based chalcone derivatives evaluated for their anti-inflammatory and antioxidant activity. Furthermore, molecular modeling study could support these outcomes by demonstrating very good binding affinities at the active site of the cyclooxygenase 2 (COX-2) iterating the potential of this scaffold for further optimization. [ABSTRACT FROM AUTHOR]

• LPS-induced somnogenic and febrile effects are mediated by COX-2-dependent mechanism. • Sleep induced by tumor necrosis factor α is independent of COX-2-related signaling. • Spontaneous sleep is reduced in COX-2 KO mice at thermoneutral ambient temperatures. • COX-2-derived prostaglandins facilitate increased sleep in warm environment. • Homeostatic sleep responses to sleep loss are COX-2 independent. Prostaglandins (PGs) play a crucial role in sleep regulation, yet the broader physiological context that leads to the activation of the prostaglandin-mediated sleep-promoting system remains elusive. In this study, we explored sleep-inducing mechanisms potentially involving PGs, including microbial, immune and thermal stimuli as well as homeostatic sleep responses induced by short-term sleep deprivation using cyclooxygenase-2 knockout (COX-2 KO) mice and their wild-type littermates (WT). Systemic administration of 0.4 µg lipopolysaccharide (LPS) induced increased non-rapid-eye movement sleep (NREMS) and fever in WT animals, these effects were completely absent in COX-2 KO mice. This finding underscores the essential role of COX-2-dependent prostaglandins in mediating sleep and febrile responses to LPS. In contrast, the sleep and fever responses induced by tumor necrosis factor α, a proinflammatory cytokine which activates COX-2, were preserved in COX-2 KO animals, indicating that these effects are independent of COX-2-related signaling. Additionally, we examined the impact of ambient temperature on sleep. The sleep-promoting effects of moderate warm ambient temperature were suppressed in COX-2 KO animals, resulting in significantly reduced NREMS at ambient temperatures of 30 °C and 35 °C compared to WT mice. However, rapid-eye-movement sleep responses to moderately cold or warm temperatures did not differ between the two genotypes. Furthermore, 6 h of sleep deprivation induced rebound increases in sleep with no significant differences observed between COX-2 KO and WT mice. This suggests that while COX-2-derived prostaglandins are crucial for the somnogenic effects of increased ambient temperature, the homeostatic responses to sleep loss are COX-2-independent. Overall, the results highlight the critical role of COX-2-derived prostaglandins as mediators of the sleep-wake and thermoregulatory responses to various physiological challenges, including microbial, immune, and thermal stimuli. These findings emphasize the interconnected regulation of body temperature and sleep, with peripheral mechanisms emerging as key players in these integrative processes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Semen cuscutae has the effect of tonifying the liver and kidney system and benefiting the essence. The main pathogenesis of osteoarthritis is deficiency of the liver and kidneys. Therefore, it is hypothesized that there is a link between semen cuscutae and osteoarthritis. OBJECTIVE: To explore the potential relationship between osteoarthritis and semen cuscutae and validate the mechanism of semen cuscutae based on the network pharmacology and molecular docking analysis. METHODS: First, the active ingredients and targets of semen cuscutae were screened in TCMSP, and the genes related to osteoarthritis were collected in the disease databases GeneCard’s, OMIM and TTD. The intersected genes were taken and then subjected to a series of analyses and screened for hub genes. Through the enrichment analysis of hub genes, the pathway of semen cuscutae acting on osteoarthritis was selected. The role of hub genes was verified by molecular docking. Therefore, the appropriate active ingredients of semen cuscutae were selected for experimental verification. RESULTS AND CONCLUSION: There were 11 active ingredients of semen cuscutae, 66 intersection target genes of semen cuscutae and osteoarthritis, and 12 hub genes, including tumor necrosis factor, interleukin 1B, TP53, RAC-alpha serine/threonine protein kinase (AKT1), vascular endothelial growth factor A, matrix metalloproteinase 9, prostaglandin peroxidase 2, cystatinase 3, epidermal growth factor, peroxisome proliferator-activated receptor gamma, interleukin 10, vascular cell adhesion factor 1. After the enrichment analysis of the hub genes, the classical inflammatory pathway, nuclear factor-κB signaling pathway, was selected for subsequent validation of semen cuscutae to alleviate osteoarthritic inflammation. Through the results obtained after molecular docking of each active ingredient and the hub gene of the pathway prostaglandin peroxidase 2, sesamin with the highest affinity was selected for subsequent cell experiments, and the experimental results confirmed that sesamin, the active ingredient of semen cuscutae, could reduce the expression of cyclooxygenase 2 by inhibiting the nuclear factor-κB signaling pathway induced by interleukin-1β. To conclude, sesamin, the active ingredient of semen cuscutae, reduces the expression of cyclooxygenase 2 by inhibiting the nuclear factor-κB signaling pathway induced by interleukin-1β, thereby improving inflammation in osteoarthritis and expanding the therapeutic effect of semen cuscutae in osteoarthritis. [ABSTRACT FROM AUTHOR]

Categorised as a nonsteroidal anti-inflammatory drug targeting the COX-2 enzyme over COX-1, celecoxib (CXB) demonstrates high membrane permeability and low aqueous solubility, placing it in class II of the biopharmaceutical classification system. Therefore, comprehension of its solubility behaviour under different configurations is desirable. The current study explores CXB solubility in propylene glycol and ethanol binary mixtures by varying temperature and cosolvent concentration, using the shake-flask method followed by spectroscopy analysis. The results show increased solubility of CXB in this mixture as ethanol mass fraction and temperature increase. Several cosolvency models were used to correlate data, including van't Hoff, Jouyban-Acree, Jouyban-Acree-van't Hoff, and mixture response surface/modified Wilson models. The mathematical models' accuracy was investigated through mean relative deviation. The Gibbs and van't Hoff equations were employed to establish the thermodynamic features of CXB dissolution. [ABSTRACT FROM AUTHOR]

Novel benzophenone–thiazole hybrids with different substituents were synthesized and evaluated for anti‐inflammatory activity using an ex vivo human whole‐blood assay. All hybrids (3c and 5a–h) showed significant anti‐inflammatory activity via prostaglandin E2 (PGE2) release inhibition. Moreover, 5c (82.8% of PGE2 inhibition), 5e (83.1% of PGE2 inhibition), and 5h (82.1% of PGE2 inhibition) were comparable to the reference drugs. Molecular docking revealed potential preferable binding to the active sites of cyclooxygenase 2 (COX‐2) and microsomal prostaglandin E synthase‐1 (mPGES‐1) enzymes. This study provides the first evidence that benzophenone–thiazole hybrids may also dock in mPGES‐1, a new attractive anti‐inflammatory drug target, besides providing promising ex vivo anti‐inflammatory activity. Thus, the novel hybrids are promising anti‐inflammatory lead compounds and highlight the significance of optimal substituent selection in the design of potent PGE2 inhibitors. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of ultrasound-guided acupotomy (UgA) for the treatment of thoracodorsal myofascial pain syndrome (TDMPS) and monitor its mid-term efficacy at 3 months after treatment. Methods: A 3-week, evaluator-blinded randomized clinical trial was conducted among 100 patients with TDMPS (visual analogue scale [VAS] score > 3) in the outpatient clinic of the Department of Orthopaedics of the Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, with a 3-month follow-up starting after completion of treatment. These patients were randomly assigned to receive UgA (n = 50) or oral celecoxib (n = 50). Recruitment was conducted between January 2021 and July 2022. The primary outcome was the VAS score, and the secondary outcomes included the Oswestry Disability Index (ODI), Pain Anxiety Symptoms Scale (PASS), and TNF-α and IL-1β levels. Outcome data were collected at baseline, week 3 (post-treatment) and week 15 (follow-up). Results: Compared with that in the celecoxib group, the pain in the UgA group was alleviated more strongly, with an adjusted mean group difference of -0.69 (95% CI,-1.07 to -0.31 after multiple imputation) at week 3 and -1.96 (95% CI,-2.33 to -1.59 after multiple imputation) at week 15 (p < 0.001 for overall group x time interaction). Both groups exhibited improvements in the ODI and PASS scores at weeks 3 and 15, but these improvements were significantly greater in the UgA group (p < 0.05). At week 3, the TNF-α and IL-1 levels were significantly lower in both groups, but celecoxib was more effective (p < 0.05). Results from analyses with multilevel multiple imputation for missingness were similar. Conclusion: UgA led to greater and safer alleviation of pain, dysfunction, and pain anxiety in patients treated with TDMPS than did celecoxib and had a durable 3-month efficacy but was inferior to celecoxib in reducing the level of inflammatory factors. These findings may prompt clinicians to recommend UgA as an alternative and supplementary therapy for pain management in patients with TDMPS. [ABSTRACT FROM AUTHOR]

Background/Objectives: The beneficial effects of the flavonoid chrysin can be reduced by its poor oral bioavailability. It has been shown that chrysin-8-C-glucoside (1) has a better absorption capability. The aim of this study was to evaluate the antioxidant and anti-inflammatory activity of this glucoside, as well as the respective hexa-acetate derivative 1a and the hexa-ethyl carbonate derivative 1b since the inclusion of moieties in bioactive molecules may increase or modify their biological effects. Methods: THP-1 macrophages were used to determine the viability in the presence of chrysin derivatives, and non-cytotoxic concentrations were selected. Subsequently, lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) production and inflammatory mediators were examined. The involvement of chrysin derivatives with the Keap1 and Nrf2 antioxidant system was determined by docking and Western blotting studies. Results: Our data demonstrated, for the first time, that pretreatment with the three compounds caused a significant reduction in LPS-induced reactive oxygen species (ROS) production and pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin 1β (IL-1β) levels, as well as in cyclooxygenase 2 (COX-2) expression. The mechanisms underlying these protective effects were related, at least in part, to the competitive molecular interactions of these phenolic compounds with Kelch-like ECH-associated protein 1 (Keap1)–nuclear factor erythroid 2-related factor 2 (Nrf2), which would allow the dissociation of Nrf2 and its translocation into the nucleus and the subsequent up-regulation of hemo-oxygenase 1 (HO-1) expression. Conclusions: Compared to the 8-C-glucoside parent chrysin, compound 1a exhibited the strongest antioxidant and anti-inflammatory activity. We hypothesized that the incorporation of an acetate group (1a) may reduce its polarity and, thus, increase membrane permeability, leading to better pharmacological activity. These findings support the potential use of these phenolic compounds as Nrf2 activators against oxidative-stress-related inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background: Our previous study indicated that Hcy exacerbated DSS-induced colitis by facilitating the differentiation of intestinal T helper cell 17 (Th17), but the precise mechanism remains unidentified. Therefore, our current research aims to elucidate the signaling pathway through which Hcy promotes the differentiation of Th17 cells. Methods: BALb/c mice were randomly assigned into six groups. The model of mice colitis was induced using 3% DSS, while the model of Hyperhomocysteinemia was induced using 1.7% methionine. The concentrations of Hcy and prostaglandin E2 (PGE2) were measured using enzyme-linked immunosorbent assay (ELISA). The protein expressions of cytosolic phospholipase A2 (cPLA2), phosphorylated-cPLA2 (p-cPLA2), cyclooxygenase 2 (COX2), cyclic adenosine monophosphate (cAMP), signal transducer and activator of transcription 3 (STAT3), phosphorylated-STAT3 (p-STAT3), interleukin-17A (IL-17A), and retinoid-related orphan nuclear receptor-γt (RORγt) were assessed using western blot analysis. Results: Compared to the DSS + HHcy group, the addition of the COX inhibitor did not significantly alter the protein expression of p-PLA2/PLA2, but led to significant decreases in serum PGE2 concentration, cAMP, and p-STAT3/STAT3 protein expression. The protein expressions of p-PLA2/PLA2, COX2, and cAMP upstream of STAT3 inhibitor addition did not exhibit significant changes. However, PGE2 concentration and p-STAT3/STAT3 protein expression were notably reduced. After the COX inhibitor and STAT3 inhibitor added, the protein expression of IL-17A and RORγt and the levels of IL-17A and IL-23R in CD4+ T cells were significantly reduced. Conclusion: HHcy aggravated DSS-induced colitis by promoting the differentiation and proliferation of Th17 cells through the PGE2 / STAT3 signaling pathway. [ABSTRACT FROM AUTHOR]

Aim: To assess the effectiveness of intraoperative lidocaine in reducing the incidence of post‐laparoscopic shoulder pain (PLSP) after gynecologic laparoscopy. Methods: Patients undergoing total laparoscopic hysterectomy were randomly divided into two groups: the lidocaine group, receiving an initial intravenous dose of lidocaine (1.5 mg/kg) before anesthesia induction, followed by a continuous infusion at 2 mg/kg/h, and the placebo group, receiving saline. The primary endpoint was the determination of PLSP incidence over a 72‐h period post‐surgery. Secondary endpoints included a comprehensive evaluation of pain intensity, as measured by the Numeric Rating Scale (NRS), for shoulder, abdominal, and incisional pain within a 72‐hour period postoperatively. Additionally, the endpoints involved the assessment of Lofencodeine or Parexib Sodium usage frequency, incidence of nausea and vomiting, duration of anesthesia and surgical procedure, as well as the duration of hospital stay. Results: Our study did not demonstrate any significant benefit in the incidence of PLSP during the postoperative period. PLSP occurred in 14 out of 41 patients (34.1%) in the lidocaine group, compared with 15 out of 41 patients (36.6%) in the placebo group (p = 0.817). Intravenous lidocaine reduced abdominal pain scores and decreased the need for postoperative analgesics within 72 h after surgery. No significant differences were found in incisional and shoulder pain intensity, nausea and vomiting rates, or hospitalization duration between groups. Conclusions: The infusion of lidocaine did not yield a reduction in the incidence or severity of PLSP in patients undergoing laparoscopic total hysterectomy. [ABSTRACT FROM AUTHOR]

Chronic recurrent multifocal osteomyelitis (CRMO) or chronic nonbacterial osteitis is a sterile autoinflammatory disease of bone in children that can mimic infectious osteomyelitis and osteosarcoma. Early diagnosis, treatment, and long-term follow-up of CRMO are essential. We describe a 10-year-old boy who presented with 15 days of left ankle bone more than joint pain, swelling, and limp. Plain radiographs and magnetic resonance imaging scans were nondiagnostic of osteomyelitis and tibial irrigation and biopsy were negative for infection and malignancy. Four years later, he again presented with similar pain in his right ankle. Repeat bone biopsy noted reactive bone changes and bone culture was sterile. Whole-body magnetic resonance imaging revealed multiple enhancing lesions in the long bones of bilateral lower extremities, spine, and sternum. He was diagnosed with CRMO, and treatment with celecoxib and subsequently pamidronate, infliximab, and methotrexate were initiated. After 6 months of treatment, the patient's gait and pain improved, and 2 years later, his CRMO was in clinical and radiologic remission. Of note, he developed palmoplantar pustular psoriasis, commonly seen in CRMO, that was not determined to be from tumor necrosis factor inhibition. [ABSTRACT FROM AUTHOR]

Trained immunity results in long-term immunological memory, provoking a faster and greater immune response when innate immune cells encounter a secondary, often heterologous, stimulus. We have previously shown that house dust mite (HDM)-induced innate training is amplified in mice expressing the human macrophage migration inhibitory factor (MIF) CATT 7 functional polymorphism. This study investigated the ability of mesenchymal stromal cells (MSCs) to modulate MIF-driven trained immunity both in vitro and in vivo. Compared with wild-type mice, in vivo HDM-primed bone marrow-derived macrophages (BMDMs) from CATT 7 mice expressed significantly higher levels of M1-associated genes following lipopolysaccharide stimulation ex vivo. Co-cultures of CATT 7 BMDMs with MSCs suppressed this HDM-primed effect, with tumor necrosis factor alpha (TNF-α) being significantly decreased in a cyclooxygenase 2 (COX-2)-dependent manner. Interestingly, interleukin 6 (IL-6) was suppressed by MSCs independently of COX-2. In an in vitro training assay, MSCs significantly abrogated the enhanced production of pro-inflammatory cytokines by HDM-trained CATT 7 BMDMs when co-cultured at the time of HDM stimulus on day 0, displaying their therapeutic efficacy in modulating an overzealous human MIF-dependent immune response. Utilizing an in vivo model of HDM-induced trained immunity, MSCs administered systemically on day 10 and day 11 suppressed this trained phenomenon by significantly reducing TNF-α and reducing IL-6 and C-C motif chemokine ligand 17 (CCL17) production. This novel study elucidates how MSCs can attenuate an MIF-driven, HDM-trained response in CATT 7 mice in a model of allergic airway inflammation. [ABSTRACT FROM AUTHOR]

Ectoparasites Dactylogyrus spp. mainly infest fish gills and severely damage the host's gill tissues. Correspondingly, the explanation of the interaction of fish with Dactylogyrus spp. infection is still insufficient. The present study describes the changes in hemato-biochemical, immune, antioxidant, genotoxic, and pathological indices response of Nile tilapia (Oreochromis niloticus) severely (n > 50), mildly infected (n = 1–50), and uninfected with Dactylogyrus spp. Data showed the adverse effect of hemato-biochemical indices in infected fish compared to uninfected, notably in severely infected O. niloticus. Compared to uninfected fish, there is a significantly decreased serum lysozyme and complement C3 and increased IgM and phagocytic activity along with significant upregulation of (COX-2), (IL-1β), (TNF-α), and (IL-10) genes in infected fish partially, in severely infected fish. Concisely, indices of antioxidants in the liver and gills marked an increased level of MDA in the infected fish compared to the uninfected fish. Conversely, levels of SOD, CAT, and GSH were decreased significantly with damaged DNA in the gills and liver of infected groups, particularly in severely infected (P < 0.05). Histopathologically investigating livers and gills in infected Nile tilapia indicated damaging and degenerative alterations, particularly with severe infection. Findings showed that Dactylogyrus spp.–infected Nile tilapia were effective in improving our knowledge of fish-pathogen interactions, which may be essential for fish defense against parasite infection. [ABSTRACT FROM AUTHOR]

The pericellular matrix (PCM), with its hallmark proteins collagen type VI (COLVI) and fibronectin (FN), surrounds chondrocytes and is critical in transducing the biomechanical cues. To identify genetic variants that change protein function, exome sequencing is performed in a patient with symptomatic OA at multiple joint sites. A predicted damaging variant in COL6A3 is identified and introduced by CRISPR‐Cas9 genome engineering in two established human induced pluripotent stem cell‐derived in‐vitro neocartilage organoid models. The downstream effects of the COL6A3 variant on the chondrocyte phenotypic state are studied by a multi‐omics (mRNA and lncRNA) approach in interaction with hyper‐physiological mechanical loading conditions. The damaging variant in COL6A3 results in significantly lower binding between the PCM proteins COLVI and FN and provokes an osteoarthritic chondrocyte state. By subsequently exposing the neocartilage organoids to hyperphysiological mechanical stress, it is demonstrated that the COL6A3 variant in chondrocytes abolishes the characteristic inflammatory signaling response after mechanical loading with PTGS2, PECAM1, and ADAMTS5, as central genes. Finally, by integrating epigenetic regulation, the lncRNA MIR31HG is identified as key regulator of the characteristic inflammatory signaling response to mechanical loading. [ABSTRACT FROM AUTHOR]

Renovascular hypertension (RH), a secondary hypertension, can significantly impact heart health, resulting in heart damage and dysfunction, thereby elevating the risk of cardiovascular diseases. Coniferol (CA), which has vascular relaxation properties, is expected to be able to treat hypertension-related diseases. However, its potential effects on cardiac function after RH remain unclear. In this study, in combination with network pharmacology, the antihypertensive and cardioprotective effects of CA in a two-kidney, one-clip (2K1C) mice model and its ability to mitigate angiotensin II (Ang II)-induced hypertrophy in H9C2 cells were investigated. The findings revealed that CA effectively reduced blood pressure, myocardial tissue damage, and inflammation after RH. The possible targets of CA for RH treatment were screened by network pharmacology. The interleukin-17 (IL-17) and tumor necrosis factor (TNF) signaling pathways were identified using a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The inflammatory response was identified using a Gene Ontology (GO) enrichment analysis. Western blot analysis confirmed that CA reduced the expression of IL-17, matrix metallopeptidase 9 (MMP9), cyclooxygenase 2 (COX2), and TNF α in heart tissues and the H9C2 cells. In summary, CA inhibited cardiac inflammation and fibrohypertrophy following RH. This effect was closely linked to the expression of MMP9/COX2/TNF α/IL-17. This study sheds light on the therapeutic potential of CA for treating RH-induced myocardial hypertrophy and provides insights into its underlying mechanisms, positioning CA as a promising candidate for future drug development. [ABSTRACT FROM AUTHOR]

A series of {1-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]-1H-pyrazol-4-yl}(2-hydroxyphenyl)metha-nones 5 were synthesized from 1-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]hydrazine 3 and substituted 3-formyl-chromones 4. Compounds 5 were converted into 2-[(E)-{1-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]-1H-pyrazol-4-yl}(hydroxyimino)methyl]phenols 6. The synthesized compounds were characterized by spectral techniques screened for their anti-inflammatory activity. Compounds 6c and 6e showed good percent inhibition of haemolysis when compared with the standard drug celecoxib. The molecular docking study explored the essential binding mode and possible thermodynamic interactions within the binding site of COX-2 enzyme. [ABSTRACT FROM AUTHOR]

In search of novel anti-inflammatory and antioxidant agents with improved potency, a small focused library of 1,2,3-triazole-based chalcone derivatives has been efficiently prepared via the click chemistry approach. All synthesized compounds' Structures were characterized with the help of IR, 1H NMR, 13C NMR, and mass spectroscopic techniques. All the synthesized novel derivatives were evaluated for their anti-inflammatory activity. Molecular docking studies against COX-2 gave valuable insights into the mechanistic basis of the demonstrated anti-inflammatory activity. Further, the synthesized compounds were found to have potential antioxidant activity. [ABSTRACT FROM AUTHOR]

The objective of the study was to develop a novel topical gel by mixing Potentilla tormentilla ethanolic extract, thermosensitive poloxamer 407, and carbomer 940 and evaluating its stability and rheological behavior. The irritation potential of the gel was evaluated in accordance with the Organization for Economic Cooperation and Development Guidelines 404. The potential anti-inflammatory effects of the developed gel were evaluated in vivo in rats using the carrageenan-induced paw edema test. Moreover, the in silico binding affinity for chlorogenic and ellagic acid, as dominant components in the extract, against cyclooxygenase (COX) 1 and 2 was also determined. Our findings suggest that the gel containing Potentilla tormentilla extract remained stable throughout the observation period, exhibited pseudoplastic behavior, and caused no irritation in rats, thus being considered safe for topical treatment. Additionally, the developed gel showed the capability to reduce rat paw edema, which highlights significant anti-inflammatory potential. In silico analysis revealed that chlorogenic and ellagic acid exhibited a reduced binding affinity against COX-1 but had a similar inhibitory effect on COX-2 as flurbiprofen, which was confirmed by molecular dynamics results. The study proposes the possible application of Potentilla tormentilla ethanolic extract gel for the alleviation of localized inflammatory diseases; however, future clinical evaluation is required. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the combined effects of chlorpyrifos and cypermethrin combined on dopaminergic neurotoxicity, motor behaviours and level of selected inflammatory proteins in rats compared to either alone for delineating an interaction between these two pesticides. The rotarod and grip strength tests were employed to assess neurobehavioural changes. The striatal dopamine content and expression of tyrosine hydroxylase (TH), α-synuclein, cyclooxygenase-2 (COX-2), and tumour necrosis factor-α (TNF-α) proteins in the nigrostriatal tissue were measured. Chlorpyrifos impaired the neurobehavioural indexes, reduced the striatal dopamine level, augmented the level of α-synuclein, COX-2, and TNF-α and attenuated the expression of TH similar to but a little less than cypermethrin. Half the dose of both pesticides together produced additional neurotoxicity compared with the usual (highest employed) dose of either alone. The results showed that chlorpyrifos induced moderately less dopaminergic neurotoxicity than cypermethrin. In the combination, they produced a little higher toxicity than either pesticide alone. [ABSTRACT FROM AUTHOR]

Chemotherapy-associated side effects significantly contribute to the challenges of cancer treatment, impacting the well-being of patients and complicating existing conditions. Chemotherapy-induced oedema, characterized by abnormal fluid accumulation and swelling, worsens cancer-related issues, such as impaired wound healing. This oedema may result from drug-induced vascular changes and electrolyte imbalances. Addressing such side effects is crucial for improving prognostic outcomes of cancer patients. The rat paw oedema model is a valuable tool for studying inflammatory oedema, testing novel therapies, and understanding their mechanisms. Conventional treatments for cancer chemotherapy-induced oedema have limitations, highlighting the need for alternative or complementary approaches, such as exploring natural products like Syzygium aromaticum (clove), known for its anti-inflammatory properties and potential to alleviate edema. This study examined the effects of Syzygium aromaticum ethanol extract on inflammatory oedema in rats, identified the responsible active compound (s), and explored the possible mechanism involved through computational modeling. Ethanol extract of Syzygium aromaticum (SAEE) was prepared. In vivo anti-inflammatory activities of the extract were evaluated at a specific controlled timeframe in formalin-induced paw oedema in Wistar rats. The binding affinities and interactions of the initially identified chemical constituents of the extract were modeled, through Glide standard precision and quantum polarized ligand docking, against cyclooxygenase-2 for their potential for their possible inhibitory mechanism. SAEE displayed significant time- and dose-dependent amelioration of inflammatory oedema and dose-dependent inhibition of key proinflammatory cytokines in the rat models. In silico modeling of identified SAEE compounds revealed delphinidin, rhamnetin, and quercetin as responsible for the observed in vivo protective effects of SAEE in rat paw oedema models. This study found that Syzygium aromaticum ethanol extract effectively reduced inflammation-induced paw swelling and modulated key inflammatory markers in the rats, with the inhibitory activities of constituting delphinidin, quercetin, and rhamnetin against cyclooxygenase 2 being possibly responsible for the observed in vivo effects. Further experimental validation and dynamic simulations are needed to confirm their potential potency in more advanced preclinical and clinical models, as well as explore the mechanistic pathways involved. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: An elevated endogenous cortisol level due to the peripartum stress is one of the risk factors of postpartum bovine uterine infections. Selenium is a trace element that elicits anti-inflammation and antioxidation properties. This study aimed to reveal the modulatory effect of selenium on the inflammatory response of primary bovine endometrial stromal cells in the presence of high-level cortisol. The cells were subjected to lipopolysaccharide to establish cellular inflammation. The mRNA expression of toll-like receptor 4 (TLR4), proinflammatory factors, and selenoproteins was measured with qPCR. The activation of NF-κB and MAPK signalling pathways was detected with Western blot and immunofluorescence. Results: The pretreatment with sodium selenite (2 and 4 µΜ) resulted in a down-regulation of TLR4 and genes encoding proinflammatory factors, including interleukin (IL)-1β, IL-6, IL-8, tumour necrosis factor α, cyclooxygenase 2, and inducible nitric oxide synthase. Selenium inhibited the activation of NF-κB and the phosphorylation of mitogen-activated protein kinase kinase, extracellular signal-regulated kinase, p38MAPK and c-Jun N-terminal kinase/stress-activated protein kinase. The suppression of those genes and pathways by selenium was more significant in the presence of high cortisol level (30 ng/mL). Meanwhile the gene expression of glutathione peroxidase 1 and 4 was promoted by selenium, and was even higher in the presence of cortisol and selenium. Conclusions: The anti-inflammatory action of selenium is probably mediated through NF-κB and MAPK, and is augmented by cortisol in primary bovine endometrial stromal cells. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To predict the potential molecular mechanism of Angelicae sinensis radix-Chuanxiong rhizoma in the treatment of psoriasis based on network pharmacology and molecular docking techniques. METHODS: Active components and specific functional targets of Angelicae sinensis radix-Chuanxiong rhizoma were screened out by using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, psoriasis-related targets were obtained by retrieving GeneCard, OMIM, DrugBank and DisGeNET databases. The drug-disease common targets were acquired by using Venn web tools, which were imported into Cytoscape 3. 9. 1 software to map Angelicae sinensis radix-Chuanxiong rhizoma-common targets-psoriasis network diagram. The protein-protein interaction network was constructed by STRING database and Cytoscape 3. 9. 1 software, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed by DAVID database, the bubble diagram of enrichment analysis was made through bioinformatics. Molecular docking was verified by AutoDock software, and PyMOL software was using to conduct visualization on molecular docking. RESULTS: A total of 9 active ingredients and 28 potential targets were obtained from Angelicae sinensis radix-Chuanxiong rhizoma for the treatment of psoriasis, the key targets were Cystatinase 3, cyclooxygenase 2, estrogen receptor 1, transcription factor AP-1 and mitogenactivated protein kinase 14. Which mainly involved the drug-responsive signaling pathway, intracellular steroid hormone receptor signaling pathway, phosphatidylinositol 3-kinase-protein kinase B signaling pathway and interleukin 17 signaling pathway. CONCLUSIONS: Angelicae sinensis radix-Chuanxiong rhizoma realizes the treatment of psoriasis through multiple pathways, multiple active components and multiple effective targets. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Emerging data indicate that acetaminophen may adversely affect lung health.We examined whether acetaminophen compared with cyclooxygenase (COX) inhibitor alone for patent ductus arteriosus (PDA) is associated with mortality or respiratory morbidity in extremely preterm infants. METHODS: This is a retrospective cohort study using data from the National Institute of Child Health and Human Development Neonatal Research Network. Infants were born at 22 to 28 weeks' gestation or weighing 401 to 1000 g between 2016 and 2020 and received acetaminophen, ibuprofen, and/or indomethacin for PDA closure. The primary outcome was death or grade 2 to 3 bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age. Secondary outcomes included predischarge mortality and respiratory morbidities. Risk ratios were adjusted for baseline and early postnatal factors. Additional exploratory analyses were adjusted for later postnatal covariates. RESULTS: Of 1921 infants, 627 (32.6%) received acetaminophen and 1294 (67.3%) received COX inhibitor only. Multidrug therapy (42.9% vs 4.7%) and surgical or catheter PDA closure (26.5% vs 19.9%) were more common among acetaminophen-exposed infants. Death or grade 2 to 3 BPD at 36 weeks' postmenstrual age was similar between infants treated with acetaminophen versus COX inhibitor only (57.1% vs 58.3%; adjusted relative risk [aRR] 0.96, 95% confidence interval [CI] 0.87-1.06). Acetaminophen was associated with increased risk of predischarge mortality (13.3% vs 10.0%) when adjusting for perinatal and early postnatal factors (aRR 1.42, 95% CI 1.02-1.93), but not in exploratory analyses that included later postnatal factors (aRR 1.28, 95% CI 0.91-1.82). CONCLUSIONS: Treatment with acetaminophen versus COX inhibitor alone for PDA was not associated with the composite outcome of death or BPD in extremely preterm infants. Our results support further evaluation of whether acetaminophen for PDA increases mortality. [ABSTRACT FROM AUTHOR]

Hypericum beanii N. Robson, a perennial upright herb, predominantly inhabits temperate regions. This species has been utilized for the treatment of various inflammation-related diseases. One new xanthone 3,7-dihydroxy-1,6-dimethoxyxanthone (1) and twenty-three known xanthones (2–24) were isolated from the aerial parts of H. beanii. The structure of the new compound was determined based on high-resolution electrospray ionization mass spectroscopy (HR-ESIMS), nuclear magnetic resonance (NMR), Infrared Spectroscopy (IR), ultraviolet spectrophotometry (UV) spectroscopic data. The anti-inflammatory effects of all the isolates were assessed by measuring the inhibitory effect on nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages. Compounds 3,4-dihydroxy-2-methoxyxanthone (15), 1,3,5,6-tetrahydroxyxanthone (19), and 1,3,6,7-tetrahydroxyxanthone (22) exhibited significant anti-inflammatory effects at a concentration of 10 μM with higher potency compared to the positive control quercetin. Furthermore, compounds 15, 19, and 22 reduced inducible NO synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, and cyclooxygenase 2 (COX-2) mRNA expression in the LPS-stimulated RAW 264.7 macrophages, suggesting that these compounds may mitigate the synthesis of the aforementioned molecules at the transcriptional level, provisionally confirming their anti-inflammatory efficacy. [ABSTRACT FROM AUTHOR]

Microglia in the central nervous system regulate neuroinflammation that leads to a wide range of neuropathological alterations. The present study investigated the anti-neuroinflammatory properties of nobiletin (Nob) derivative, 5-acetoxy-6,7,8,3′,4′-pentamethoxyflavone (5-Ac-Nob), in lipopolysaccharide (LPS)-activated BV2 microglia. By using the MTT assay, Griess method, flow cytometry, and enzyme-linked immunosorbent assay (ELISA), we determined the cell viability, the levels of nitric oxide (NO), reactive oxygen species (ROS), and pro-inflammatory factors (interleukin 1 beta; IL-1β, interleukin 6; IL-6, tumor necrosis factor alpha; TNF-α and prostaglandin E2; PGE2) in LPS-stimulated BV2 microglia. Toll-like receptor 4 (TLR4)-mediated myeloid differentiation primary response gene 88 (MyD88)/nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK) signaling pathway and signal transducer and activator of transcription 3 (STAT3) were measured by western blotting. Analysis of NO generation and mRNA of pro-inflammatory cytokines was confirmed in the zebrafish model. 5-Ac-Nob reduced cell death, the levels of NO, ROS, inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and pro-inflammatory factors in LPS-activated BV-2 microglial cells. TLR4-mediated MyD88/NF-κB and MAPK pathway (p38, ERK and JNK) after exposure to 5-Ac-Nob was also suppressed. Moreover, 5-Ac-Nob inhibited phosphorylated STAT3 proteins expression in LPS-induced BV-2 microglial cells. Furthermore, we confirmed that 5-Ac-Nob decreased LPS-induced NO generation and mRNA of pro-inflammatory cytokines in the zebrafish model. Our findings suggest that 5-Ac-Nob represses neuroinflammatory responses by inhibiting TLR4-mediated signaling pathway and STAT3. As a result of these findings, 5-Ac-Nob has potential as an anti-inflammatory agent against microglia-mediated neuroinflammatory disorders. [ABSTRACT FROM AUTHOR]

BACKGROUND: Mitochondrial reactive oxygen bursts have been shown to play a key role in skeletal muscle ischemia-reperfusion injury. 3-Nitro-Nmethylsalicylamide (3-NNMS) can effectively reduce the electron transport rate and has a potential protective effect on limb ischemia-reperfusion injury, but there is no clear research and clinical application. OBJECTIVE: To investigate the protective effect of 3-NNMS on the skeletal muscle after limb ischemia-reperfusion injury in rats and its mechanism. METHODS: Forty healthy 8-week-old Sprague-Dawley rats were randomly divided into control group, 0, 25 and 125 μg/mL 3-NNMS groups, with 10 rats in each group. Animal models of limb ischemia-reperfusion injury were prepared in the latter three groups. 3-NNMS was injected into the injury site 30 minutes before reperfusion. The animals were sacrificed 2 hours after reperfusion. Blood from the apical part of the heart, and the tissue of the rectus femoris muscle of the right lower limb were taken for testing. The pathological morphology of the rectus femoris muscle was detected by hematoxylin-eosin staining. Serum levels of creatine kinase found in the skeletal muscle (CK-MM), lactate dehydrogenase, and myeloperoxidase were detected using ELISA; the levels of nuclear factor κB, tumor necrosis factor α, interleukin 1β, cyclooxygenase 2, malondialdehyde, reactive oxygen species, superoxide dismutase, catalase and glutathione peroxidase in the rectus femoris muscle were measured; and adenosine triphosphate (ATP) level, ATPase activity, and mitochondrial respiratory control rate were tested. RESULTS AND CONCLUSION: Compared with the control group, the model rats with ischemia-reperfusion injury had increased serum levels of CK-MM, lactate dehydrogenase, and myeloperoxidase, increased levels of nuclear factor κB, tumor necrosis factor α, interleukin 1β, cyclooxygenase 2, malondialdehyde and reactive oxygen species in the rectus femoris muscle, decreased levels of catalase and glutathione peroxidase in the rectus femoris muscle, and reduced ATPase activity and mitochondrial respiratory control rate. Moreover, cell morphology was irregular, inflammatory cell infiltration was obvious, and the cells were swollen in rats after ischemia-reperfusion injury. Compared with the 0 μg/mL group, the serum CK-MM and lactate dehydrogenase levels decreased, the levels of nuclear factor κB and cyclooxygenase 2 in the rectus femoris muscle decreased, reactive oxygen species level decreased, and superoxide dismutase activity increased in the 25 μg/mL group; cell morphology was more regular, inflammatory cell infiltration was lighter, and cell swelling was alleviated. Compared with the 0 μg/mL group, the 125 μg/mL group had a reduction in the serum levels of CK-MM, lactate dehydrogenase, and myeloperoxidase and the levels of nuclear factor κB, tumor necrosis factor α, cyclooxygenase 2, malondialdehyde and reactive oxygen species in the rectus femoris muscle, as well as an increase in the levels of superoxide dismutase and glutathione peroxidase in the rectus femoris muscle, and mitochondrial respiratory control rate. Moreover, the cells were arranged neatly, the outline was clear and complete, and the inflammatory cell infiltration was light. To conclude, 3-NNMS can alleviate the functional impairment of the skeletal muscle caused by limb ischemia-reperfusion, and its mechanism of action may be through improving mitochondrial function, reducing reactive oxygen species production, decreasing oxidative stress and inflammatory response, and thus reducing tissue damage and repairing skeletal muscle function. [ABSTRACT FROM AUTHOR]

Simple Summary: Simple Summary: The aim of our research was to assess the expression of the selected proteins involved with inflammation and carcinogenesis, in order to expand knowledge of FISS and non-FISS. Matrix metalloproteinase-2, matrix metalloproteinase-9, cyclooxygenase-2, and P-glycoprotein were evaluated with the immunohistochemistry method. Our results showed that the expressions of COX-2, MMP-9, and PGP were significantly higher in FISS than in non-FISS Feline injection-site sarcomas (FISSs) are aggressive neoplasms that have been associated mostly with vaccination. Feline noninjection-site sarcomas (non-FISSs) are less frequently observed in cats and may arise in any anatomic site. This study aimed to determine the differences in the expression of the selected proteins (matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2), and P-glycoprotein (PGP)) and their correlation with the mitotic count in FISS and non-FISS, in order to characterize their immunohistochemical features. A preliminary study of eleven samples of FISS and eight samples of non-FISS was performed using immunohistochemistry. Among all the tested sarcomas, 80.4% of the tumors were positive for COX-2, 90.2% were positive for MMP-9, and 100% were positive for PGP. The results showed that the expressions of COX-2, MMP-9, and PGP were significantly higher in FISS than in non-FISS (COX-2—p ≤ 0.001; MMP-9—p ≤ 0.05; and PGP—p ≤ 0.05). A Spearman rank correlation analysis showed a moderate negative correlation between the expression of COX-2 and MMP-9 in FISS (r = −0.52). A strong negative correlation between COX-2 and PGP (r = −0.81), a moderate positive correlation between MMP-2 and MMP-9 (r = +0.69), and a moderate negative correlation between MMP-2 and PGP (r = −0.44) were observed in non-FISS. In summary, our study presents the immunohistochemical profile of the proteins involved with inflammation and carcinogenesis in FISS and non-FISS, which can contribute to expanding the knowledge of tumor biology. [ABSTRACT FROM AUTHOR]

Introduction: Fu's subcutaneous needling (FSN) is a new type of acupuncture that uses subcutaneous tissue to oscillate from side to side to improve muscle pathology status and can be effective in treating Knee osteoarthritis. Nonetheless, whether the clinical effect is similar to that of most commonly used drugs is unclear. Thus, this study aims to determine the pain-relieving effect and improvement in the joint function of the FSN therapy by comparing it with that of a positive control drug (celecoxib). Furthermore, this clinical trial also aims to evaluate the effect of FSN on gait and lower limb muscle flexibility, which can further explore the scientific mechanisms of the FSN therapy. Methods and analysis: This study is a randomized, parallel-controlled, single-center prospective clinical study that includes 60 participants, with an FSN group (n = 30) and a drug group (n = 30). The Fu's subcutaneous needling (FSN) group undergo the FSN therapy 3 times a week for 2 weeks, while the drug group receives 0.2 g/day oral celecoxib for 2 weeks, with a follow-up period of 4 weeks after the completion of treatment. The primary outcome is the difference in the visual analog scale score after 2 weeks of treatment compared with baseline. The Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index, joint active range of motion test, three-dimensional gait analysis, and shear wave elastic imaging technology analysis in lower limb muscles are also performed to demonstrate clinical efficacy. Ethics and dissemination: The trial is performed following the Declaration of Helsinki. The study protocol and consent form have been approved by the Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine. All patients will give informed consent before participation and the trial is initiated after approval. The results of this trial will be disseminated through publication in peer-reviewed journals. Trial registration number: NCT06328153. [ABSTRACT FROM AUTHOR]

Background. Recent experimental and clinical studies have confirmed the effectiveness and safety of serratiopeptidase (SRP) as a powerful anti-inflammatory agent, highlighting its potential benefits across various fields of medicine. The purpose was to analyze current literature on the mechanisms of action of SRP as a means of systemic enzyme therapy for low-intensity chronic inflammation and pain syndromes, its clinical applications, and prospects for implementation in general medical practice. Materials and methods. To identify relevant literature sources, a comprehensive search was conducted in electronic databases, including PubMed, Scopus, Web of Science, and the Cochrane Library. Results. According to modern literature data, SRP demonstrates quite powerful anti-inflammatory, analgesic, reparative, fibrinolytic, and mucolytic properties, and exhibits a certain antimicrobial activity, especially against biofilm-forming bacteria. The combination of this enzyme with traditional antibiotics provides a more effective treatment of infectious processes. SRP has significant potential in the treatment of conditions and diseases associated with the development of low-intensity chronic inflammation and pain syndromes (especially in comorbid ones) due to its anti-inflammatory, anti-edematous, antithrombotic, and analgesic properties associated with the inhibition of cyclooxygenase 1 and 2, 5-lipoxygenase activity, myeloperoxidase and elastase, suppression of the formation and/or release of bradykinin, biogenic amines, pro-inflammatory cytokines, cell adhesion molecules, cleavage of bradykinin- related peptides, limitation of oxidative-nitrosative stress. The effectiveness of the enzyme notably increases when it is combined with some prebiotics and/or probiotics. Conclusions. The development of new dosage forms of SRP, along with further preclinical and clinical trials, could lead to new strategies for the prevention and treatment of inflamatory diseases. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide-1 (GLP-1)-based drugs have been approved by the United States Food and Drug Administration (FDA) and are widely used to treat type 2 diabetes mellitus (T2DM) and obesity. More recent developments of unimolecular peptides targeting multiple incretin-related receptors ("multi-agonists"), including the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) and the glucagon (Gcg) receptor (GcgR), have emerged with the aim of enhancing drug benefits. In this study, we utilized human and mouse microglial cell lines, HMC3 and IMG, respectively, together with the human neuroblastoma SH-SY5Y cell line as cellular models of neurodegeneration. Using these cell lines, we studied the neuroprotective and anti-inflammatory capacity of several multi-agonists in comparison with a single GLP-1 receptor (GLP-1R) agonist, exendin-4. Our data demonstrate that the two selected GLP-1R/GIPR dual agonists and a GLP-1R/GIPR/GcgR triple agonist not only have neurotrophic and neuroprotective effects but also have anti-neuroinflammatory properties, as indicated by the decreased microglial cyclooxygenase 2 (COX2) expression, nitrite production, and pro-inflammatory cytokine release. In addition, our results indicate that these multi-agonists have the potential to outperform commercially available single GLP-1R agonists in neurodegenerative disease treatment. [ABSTRACT FROM AUTHOR]

Aibika (Abelmoschus manihot (L.) Medic) is a garden vegetable whose flower has been shown to have various bioactivities. This study investigated the protective effect of aibika flower flavonoid extract (AFF) on ethanol-induced gastric injury in mice. The experimental results showed that pre-feeding 125 and 250 mg AFF/kg BW for 1 week significantly reduced the gastric injury area in the negative control group from 19.2% to 6.7% and 0.6%, respectively. The results of the pathological sections staining also showed that AFF had a protective ability against alcohol-induced injury of gastric tissue and liver tissue. When the mice were exposed to high concentrations of ethanol, AFF pretreatment significantly upregulated the expression of antioxidant enzymes. The pretreatment also promoted the production of the intracellular antioxidant, reduced glutathione, in both gastric tissue and serum. On the contrary, AFF delayed the lipid peroxidation process, which, in turn, reduced the damage to the gastric mucosa. When acute inflammation was induced by ethanol stimulation, AFF significantly downregulated the proinflammatory cytokines and mediators such as TNF-α, IL-1β, IL-6, NF-κB, COX-2, and iNOS. Furthermore, AFF pretreatment greatly promoted the production of healing factors, such as matrix metalloproteinase (MMP)-2, MMP-7, and MMP-9, in the gastric tissue. In addition, AFF significantly reduced gastric cell apoptosis induced by ethanol stimulation. These results demonstrate that AFF has a good protective effect on alcohol-induced gastric ulcer and has the potential to be used in gastrointestinal health care. [ABSTRACT FROM AUTHOR]

• High-fat diet during early life reshapes the gut microbiome later in life. • Early-life gut dysbiosis associates with disrupted mammary microenvironment later. • Shift of gut microbiome during early life may influence breast health later on. The influence of gut microbiota on gut health is well-documented, but it remains obscure for extraintestinal diseases such as breast cancer. Moreover, it is entirely unknown how gut dysbiosis during early life contributes to breast tumorigenesis later in life. In this study, we hypothesized that a high-fat diet during early life leads to alterations in the gut microbiome and is associated with disruptions in the mammary microenvironment. Female C57BL/6 mice were fed a low-fat diet (10% kcal fat) or a high-fat diet (HF, 60% kcal fat) for 8 weeks from the age of 4 to 12 weeks, which is equivalent to human childhood and adolescence. Twelve mice were sacrificed immediately after the 8-week feeding, the remainder were euthanized after switching to a normal lifecycle-supporting diet for an additional 12 weeks; the gut microbiome was then sequenced. The 8-week HF diet feeding altered the beta-diversity (Bray & Jaccard P <.01), and the difference remained significant after switching the diet (Bray & Jaccard P <.05). Immediately after HF feeding, a greater number of microbial taxa (>50) were altered, and about half of the taxa (25) remained significantly changed after switching the diet. The abundance of Alistipes, Bilophila , and Rikenellaceae stood out as significantly associated with multiple metabolic and inflammatory biomarkers in mammary tissue, including aromatase, Ccl2 , and Cox2. In conclusion, an 8-week early-life HF feeding reshaped the gut microbiome, which connected with disrupted mammary microenvironments. A high-fat diet during early life (4–12 weeks of age in mice), corresponding to childhood and adolescence in humans, significantly influences the gut microbiome and consequently affects the mammary microenvironment, which may ultimately lead to increase the risk of young-onset breast cancer later in life (24 weeks of age in mice), equivalent to the young to middle ages of adulthood in humans. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: The implications of SARS‐CoV‐2 infection on male fertility remain largely unknown. Besides their well‐known pro‐ and anti‐inflammatory actions, prostaglandins and polyamines are present in semen, where they play key roles in sperm quality. Objectives: To analyze semen parameters, oxidative profile and the seminal fluid prostaglandin and polyamine systems in samples collected from individuals without coronavirus disease 2019 diagnosis and men who recovered from coronavirus disease 2019. Materials and methods: This study compared semen collected from men without positive coronavirus disease 2019 diagnosis with samples obtained from individuals 1–6 months and 7–30 months post SARS‐CoV‐2 infection. Semen parameters, thiobarbituric acid reactive substances, cyclooxygenase 2 expression by fluorescence immunocytochemistry and immunoblotting, prostaglandin levels by enzyme immunoassay, ornithine decarboxylase activity by a radioactive assay, and polyamine and acetylated polyamine levels by thin‐layer chromatography were assessed. Results: In both groups of semen samples from coronavirus disease 2019 recovered men, sperm vitality, total and progressive sperm motility, and putrescine levels were significantly decreased when compared with samples from the uninfected group. In contrast, lipid peroxidation, leukocyte‐associated cyclooxygenase 2 expression, and prostaglandin D2 levels were higher in semen from coronavirus disease 2019 recovered men than in samples from uninfected individuals. While sperm concentration and morphology, ornithine decarboxylase activity, and N‐acetylputrescine levels were statistically diminished in semen obtained up to 6 months after coronavirus disease 2019 recovery, these parameters remained unchanged when samples were collected 7–30 months after coronavirus disease 2019 recovery. Coronavirus disease 2019 vaccination did not show negative effects on any of the parameters evaluated. Discussion and conclusion: Our work provides insights into the detrimental impact of coronavirus disease 2019 on several sperm parameters, in some cases, even more than a year after SARS‐CoV‐2 infection, which would be accompanied by alterations in the seminal fluid prostaglandin and polyamine profiles. Therefore, future treatments targeting the prostaglandin and polyamine pathways in coronavirus disease 2019 recovered men could lead to a successful reinstatement of semen parameters. [ABSTRACT FROM AUTHOR]

In this study, we investigated the anti-microbial and anti-inflammatory activities of the cosmopolite macrolichens Usnea articulata (L.) Hoffm., Umbilicaria crustulosa (Ach.) Lamy and Bryoria fuscescens (Gyeln.) Brodo & D.Hawksw hydroalcoholic extracts to contribute the potential pharmacological uses of lichens. In vitro antimicrobial activities of ethanol extracts against Gram-negative bacteria Escherichia coli, Gram-positive bacteria Staphylococcus aureus, and the yeast Candida albicans were presented using the Broth microdilution method. The most effective lichen extract against gram-positive bacteria S. aureus was U. articulata ethanol extract with a MIC value of 0.125 mg/ml. U. articulata and B. fuscences extracts have similar anti-fungal activities despite having MIC values of 0.5 mg/ml. The anti-inflammatory effects of the extracts on Lipopolysaccharide/Interferon-gamma (LPS/IF-γ) induced macrophage-like cellular systems (BV-2 microglia and RAW 264,7 macrophages) were evaluated by measuring P38 mitogen-activated protein kinase phosphorylation (P38MAPK), cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase 2 (NOS2) mRNA and protein expression. Especially, Usnea and Umbilicaria extracts also attenuated the LPS/IF-γ induced increase in P38MAPK phosphorylation, COX-2, and NOS2 expression in both macrophage-like cells without any cytotoxicity. According to the results of our study, we suggest that the anti-inflammatory mechanism of lichen extracts might result from the inhibition of P38MAPK phosphorylation through a reduction in COX-2 and NOS2 expressions. [ABSTRACT FROM AUTHOR]

Adverse drug reactions, multiple drug allergy syndrome, and multiple drug intolerance syndrome, are common terms used in clinical practice worldwide. Here we present a 61-year-old Caucasian female, who is diabetic and hypertensive, and started receiving doxycycline for an upper respiratory tract infection. Simultaneously, she selfprescribed Advil.®. The patient has had a previous episode of drug intolerance. In this episode, she presented with a skin rash included bullae on her arms, legs and in part of her abdomen along with some systemic symptoms such fever, cough, and upset stomach. Biopsies for hematoxylin and eosin (H&E), direct immunofluorescence (DIF), and immunohistochemistry (IHC) stain analysis were performed. The diagnosis was made based upon interpretation of the histology in the context of drug reaction with alterations on the dermal lymphatics. DIF showed significant deposits of fibrinogen, complement/C3c and IgA around the dermal vessels, and at the endothelial-mesenchymal dermal cell junctions. IHC staining showed lymphangiectases with strong staining of the lymphatic junctions to the adjacent upper dermis using D2-40 marker. In this case, it is possible that the drug reaction could be causing previously unreported damage in lymphatics, including fragmentation and dilatation. These channels are stimulated inhibited, contracted, and relaxed by interactions with multiple receptors and the inflammation could cause dysregulation in those including their shape. [ABSTRACT FROM AUTHOR]

A series of new phenanthroline‐based metal complexes, coordination polymers are synthesized using 1,10‐phenanthroline 2,9‐dicarboxylate (PDA) and different metal salts including tin (R‐1 to R‐3), manganese (R‐4), ruthenium (R‐5), and zinc (R‐6) respectively. The inhibitory activities of synthesized coordination compounds are evaluated towards COX‐2 (cyclooxygenase‐2) and 5‐LOX (5‐lipoxygenase) enzymes. Among all the metal‐organic coordination complexes, Zn‐PDA (R‐6) shows most prominent inhibitory activity than other systems with the IC50 value of 0.0524 μg/mL and 0.834 μg/mL for both COX‐2 and 5‐LOX enzymes, respectively. The synthesized systems were also evaluated for their activity against COX‐1 and standard COX‐2 inhibitors viz. Rofecoxib and Aspirin. The rationale for R‐6 being the most potent metal complex for dual COX‐2 and 5‐LOX inhibition is demonstrated using docking studies. [ABSTRACT FROM AUTHOR]

Inflammation is an essential body immune system response against various infections and tissue injuries and maintains normal homeostasis. Alterations in inflammatory responses lead to multiple disorders like heart diseases, obesity, diabetes, cancer, stroke, and neurodegenerative disorders. Cyclooxygenases (COXs), the enzymes, exist in two isoforms (COX‐1 and COX‐2) that catalyze the rate‐determining step of prostaglandin biogenesis and play a significant role in inflammation. COX‐2 inhibitors, although effective anti‐inflammatory agents are considered to be highly unsafe for long‐term usage due to their possible side and adversative effects. Recently, fused‐thienopyrimidines have emerged as a privileged scaffold with excellent anti‐inflammatory potential. In the present review, we have emphasized the recent developments in the design and synthetic strategies of fused‐thienopyrimidine derivatives and their detailed structure‐activity‐relationship (SAR) studies. The primary goal of this review is to provide restructuring knowledge about this template, which could prove beneficial and valuable for chemists working in the anti‐inflammatory area. [ABSTRACT FROM AUTHOR]

Cancer stem cells are pivotal players in tumors initiation, growth, and metastasis. While several markers have been identified, there remain challenges particularly in heterogeneous malignancies like adult soft tissue sarcomas, where conventional markers are inherently overexpressed. Here, we designed BODIPY scaffold fluorescence probes (BD‐IMC‐1, BD‐IMC‐2) that activate via disaggregation targeting for cyclooxygenase (COX), a potential marker for CSCs in sarcoma in clinical pathology. Based on their structures, BD‐IMC‐1 showcased higher susceptibility to disaggregation compared to BD‐IMC‐2, consistent with their selective interaction with COX. Notably, the BD‐IMC‐1 revealed positive cooperativity binding to COX‐2 at sub‐micromolar ranges. Both probes showed significant fluorescence turn‐on upon LPS or PMA triggered COX‐2 upregulation in live RAW264.7, HeLa, and human sarcoma cell line (Saos‐LM2) up to 2‐fold increase with negligible toxicity. More importantly, the BD‐IMC‐1 demonstrated their practical imaging for COX‐2 positive cells in paraffin‐fixed human sarcoma tissue. Considering the fixed tissues are most practiced pathological sample, our finding suggests a potential of disaggregation activated chemosensor for clinical applications. [ABSTRACT FROM AUTHOR]

Cancer stem cells are pivotal players in tumors initiation, growth, and metastasis. While several markers have been identified, there remain challenges particularly in heterogeneous malignancies like adult soft tissue sarcomas, where conventional markers are inherently overexpressed. Here, we designed BODIPY scaffold fluorescence probes (BD‐IMC‐1, BD‐IMC‐2) that activate via disaggregation targeting for cyclooxygenase (COX), a potential marker for CSCs in sarcoma in clinical pathology. Based on their structures, BD‐IMC‐1 showcased higher susceptibility to disaggregation compared to BD‐IMC‐2, consistent with their selective interaction with COX. Notably, the BD‐IMC‐1 revealed positive cooperativity binding to COX‐2 at sub‐micromolar ranges. Both probes showed significant fluorescence turn‐on upon LPS or PMA triggered COX‐2 upregulation in live RAW264.7, HeLa, and human sarcoma cell line (Saos‐LM2) up to 2‐fold increase with negligible toxicity. More importantly, the BD‐IMC‐1 demonstrated their practical imaging for COX‐2 positive cells in paraffin‐fixed human sarcoma tissue. Considering the fixed tissues are most practiced pathological sample, our finding suggests a potential of disaggregation activated chemosensor for clinical applications. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury (TBI) can cause rapid brain inflammation. There is debate over the safety and efficacy of anti-inflammatory agents in its treatment. With a particular focus on cyclooxygenase 2 (COX2) selective inhibition, we sought to determine the impact of celecoxib versus no celecoxib treatment on outcomes in patients with TBI and compare these with outcomes associated with nonselective COX inhibition (ibuprofen) and corticosteroid (dexamethasone) treatment. Methods: This retrospective cohort study used TriNetX, a large publicly available global health research network, to gather clinical data extracted from the electronic medical records. Using International Classification of Diseases, Tenth Revision and pharmacy codes, we identified patients with TBI who were and were not treated with celecoxib, ibuprofen, and dexamethasone. Analysis was performed on propensity-matched and unmatched cohorts, which were matched on demographics, comorbidities, and neurological injuries. Our primary end point was 1-year survival. Secondary end points were ventilator and tracheostomy dependence, gastrostomy tube placement, seizures, and craniotomy. Results: After propensity score matching, a total of 1443 patients were identified in both the celecoxib and no celecoxib cohorts. Ninety-two (6.4%) patients in the celecoxib cohort died within 1 year following TBI versus 145 (10.0%) in the no celecoxib cohort (odds ratio 0.61; 95% confidence interval 0.46–0.80; p = 0.0003). The 1-year survival rate was 96.1% in the celecoxib cohort versus 93.1% in the no celecoxib cohort (p < 0.0001). At the end of the 1-year period, celecoxib was associated with significantly lower gastrostomy tube dependence (p = 0.017), seizure activity (p = 0.027), and myocardial infarction (p = 0.021) compared with the control cohort. Ibuprofen was also associated with higher 1-year survival probability and lower rates of post-TBI complications. Dexamethasone was broadly associated with higher morbidity but was associated with higher 1-year survival probability compared with the no dexamethasone cohort. Conclusions: Early celecoxib and ibuprofen use within 5 days post TBI was associated with higher 1-year survival probabilities and fewer complications. With emerging yet controversial preclinical evidence to suggest that COX inhibition improves TBI outcomes, this population-level study offers suggestive support for these drugs' clinical benefit, which should be pursued in prospective clinical studies. [ABSTRACT FROM AUTHOR]

Comparative cancer studies help us determine if discoveries in one species apply to another. Feline and human oral squamous cell carcinoma (FOSCC and HOSCC) are invasive tumours in which inflammation and abnormal p16 expression are reported. Immunohistochemistry was used to determine the expression of p16 and microsomal prostaglandin E2 synthase 1 (mPGES1) in 42 HOSCC and 45 FOSCC samples with known expression of cyclooxygenase 2 (COX2) and cluster of differentiation 147 (CD147). High p16 expression was more common in HOSCC tumour cells compared to adjacent stroma and oral epithelium (p <.05), with a similar but statistically nonsignificant pattern in FOSCC. Interestingly, high mPGES1 expression in FOSCC was more common in the adjacent epithelium compared to the other compartments (p <.05). In HOSCC, mPGES1 was more similar between compartments but was numerically more common in the tumour compartment (p >.05). There were nominal (p > 0.05) differences in marker expression between high and low mPGES1 expressing tumours in both species, including high p16 observed more commonly in high mPGES1 tumours, and COX‐2 positive tumours being more common in low mPGES1 tumours. High CD147 HOSCC tumours were more common in the high mPGES1 HOSCC group (p <.05). In the FOSCC cohort, where there was no statistical difference in CD147 expression between high and low mPGES1 tumours, there were numerically higher CD147 cases in the high mPGES1group. Different expression patterns in FOSCC and HOSCC could be related to different risk factors. For example, p16 is a marker of papillomavirus‐driven HOSCC, but a causal relationship between papillomaviruses and FOSCC has yet to be definitively demonstrated. The significance of high P16 expression in the absence of papillomavirus infection deserves further study, and the relative contributions of COX2 and mPGES1 to tumour inflammation and progression should be explored. The findings reveal potential similarities in FOSCC and HOSCC biology, while also demonstrating differences that may relate to risk factors and pathogenesis that are unique to each species. [ABSTRACT FROM AUTHOR]

The monoterpene oxide, Eucalyptol (1,8-Cineole), a primary component of eucalyptus oil, has been evaluated pharmacologically for anti-inflammatory and analgesic activity. Current research aimed to evaluate Eucalyptol's anti-arthritic potential in a Complete Freund's adjuvant induced arthritis that resembles human rheumatoid arthritis. Polyarthritis developed after 0.1 mL CFA injection into the left hind footpad in rats. Oral administration of Eucalyptol at various doses (100, 200 and 400 mg/kg) significantly reduced paw edema, body weight loss, 5-LOX, PGE2 and Anti-CCP levels. Real‐time PCR investigation showed significant downregulation of COX-2, TNF-α, NF-κB, IL-17, IL-6, IL-1β and upregulation of IL-4 and IL-10 in Eucalyptol treated groups. Hemoglobin and RBCs counts significantly increased post-treatment with Eucalyptol while ESR, CRP, WBCs and platelets count significantly decreased. Eucalyptol significantly increased Superoxide Dismutase, Catalase and Glutathione levels compared to CFA-induced arthritic control however, MDA significantly decreased post-treatment. Further, radiographic and histopathological examination of the ankle joints of rodents administered Eucalyptol revealed an improvement in the structure of the joints. Piroxicam was taken as standard. Furthermore, molecular docking findings supported the anti-arthritic efficacy of Eucalyptol exhibited high binding interaction against IL-17, TNF-α, IL-4, IL-10, iNOS NF-κB, 5-LOX, and COX-2. Eucalyptol has reduced the severity of CFA induced arthritis by promoting anti-inflammatory cytokines for example IL-4, IL-10 and by inhibiting pro-inflammatory cytokines such as 5-LOX, COX-2, IL-17, NF-κB, TNF-α, IL-6 and IL-1β. Therefore, Eucalyptol might be as a potential therapeutic agent because of its pronounced anti-oxidant and anti-arthritic activity. [ABSTRACT FROM AUTHOR]

Based on their high antioxidant capacity and noteworthy phytochemistry, Terminalia ferdinandiana fruit and leaves have attracted considerable recent interest for their therapeutic potential. Whilst those studies have reported a variety of therapeutic properties for the fruit, the anti-inflammatory potential of T. ferdinandiana has been largely neglected and the leaves have been almost completely ignored. This study investigated the immune-modulatory and anti-inflammatory properties of T. ferdinandiana fruit and leaf extracts by evaluating their inhibition of multiple pro- and anti-inflammatory cytokines and chemokines secretion in lipopolysaccharide (LPS)-stimulated and unstimulated RAW 264.7 macrophages using multiplex bead immunoassays and ELISA assays. The methanolic extracts were particularly good immune-modulators, significantly inhibiting the secretion of all the cytokines and chemokines tested. Indeed, the methanolic extracts completely inhibited IL-10, IFN-γ, IL-1β, IL-6, MCP-1, and MIP-2a secretion, and almost completely inhibited the secretion of TNF-α. In addition, the methanolic T. ferdinandiana extracts also significantly inhibited cytosolic COX-2 levels (by 87–95%) and the synthesis of the PGE2 (by ~ 98%). In contrast, the methanolic extracts stimulated LTB4 secretion by ~ 60–90%, whilst the aqueous extracts significantly inhibited LTB4 secretion (by ~ 27% each). Exposure of RAW 264.7 cells to the methanolic T. ferdinandiana extracts also significantly down-regulated the cytosolic levels of NF-κB by 33–44%, indicating that the immune-modulatory and anti-inflammatory properties of the extracts may be regulated via a decrease in NF-κB transcription pathways. Taken together, these results demonstrate potent anti-inflammatory properties for the extracts and provide insights into their anti-inflammatory mechanisms. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) and reactive nitrogen species (RNS) exert profound biological impacts dictated by their chemistry. Understanding their spatial distribution is essential for deciphering their roles in diverse biological processes. This review establishes a framework for the chemical biology of NO and RNS, exploring their dynamic reactions within the context of cancer. Concentration-dependent signaling reveals distinctive processes in cancer, with three levels of NO influencing oncogenic properties. In this context, NO plays a crucial role in cancer cell proliferation, metastasis, chemotherapy resistance, and immune suppression. Increased NOS2 expression correlates with poor survival across different tumors, including breast cancer. Additionally, NOS2 can crosstalk with the proinflammatory enzyme cyclooxygenase-2 (COX-2) to promote cancer progression. NOS2 and COX-2 co-expression establishes a positive feed-forward loop, driving immunosuppression and metastasis in estrogen receptor-negative (ER-) breast cancer. Spatial evaluation of NOS2 and COX-2 reveals orthogonal expression, suggesting the unique roles of these niches in the tumor microenvironment (TME). NOS2 and COX2 niche formation requires IFN-γ and cytokine-releasing cells. These niches contribute to poor clinical outcomes, emphasizing their role in cancer progression. Strategies to target these markers include direct inhibition, involving pan-inhibitors and selective inhibitors, as well as indirect approaches targeting their induction or downstream effectors. Compounds from cruciferous vegetables are potential candidates for NOS2 and COX-2 inhibition offering therapeutic applications. Thus, understanding the chemical biology of NO and RNS, their spatial distribution, and their implications in cancer progression provides valuable insights for developing targeted therapies and preventive strategies. [ABSTRACT FROM AUTHOR]

Objective: to find a link between a single nucleotide polymorphism (SNP) caled rs20417 in the cyclooxygenase-2 gene and Aspirin resistance in Pakistani patients with heart disease. Study Design: Cross-sectional study. Place and Duration of Study: Pharmacology Department, National University of Medical Sciences, in colaboration with the National Institute of Heart Diseases and the Institute of Biomedical and Genetic Engineering in Islamabad Pakistan, from Oct 2018 to Dec 2021. Methodology: The study was carried out on 384 patients (272 males and 112 females) with ischemic heart disease. Patients who had been on Aspirin for at least seven days were selected using non-probability convenience sampling. Platelet aggregation was performed using a Transmission Aggregometer, with arachidonic acid as an agonist. DNA extraction was done using the kit method (Invitrogen, Thermofisher). Then, Polymerase chain Reaction, Restriction Fragment Length Polymorphism, and gel electrophoresis were used to identify SNP rs20417. Results: In this study, 14.0% (n=54) of ischemic heart disease patients were found to be Aspirin resistant, while 86.0% (n=330) were Aspirin responders. The genotyping of COX2 SNP rs20417 showed that 55.46% (n=213) of patients were homozygous with the GG genotype, 34.11%(n=131) had CG (heterozygous), and 10.41% (n=40) of patients were carriers of homogeneous (CC). Statistical analysis did not demonstrate a significant association of any of the aleles of the evaluated SNP with Aspirin resistance (p>0.05). Conclusion: In the Pakistani population, Aspirin resistance is not associated with any specific polymorphic form of Cyclooxygenase-2 at SNP rs20417. [ABSTRACT FROM AUTHOR]

The correction notice in the International Journal of Molecular Sciences addresses an error in Figure 4 of a study on licoricidin's effects on lung metastasis in murine mammary carcinoma cells. The images for F4/80 staining were mistakenly duplicated in place of CD45 staining across different dosages, but have since been corrected. The authors assure that this correction does not impact the scientific conclusions of the study. [Extracted from the article]