Search

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]

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]

Background: Hemophilia type A and B is associated with spontaneous bleeding in muscle tissues and joints. Acute hemarthrosis, representing 70–80% of all bleedings in severe hemophilia patients, is extremely painful. When surgical procedures are needed in hemophiliac patients, perioperative management should be planned with a multidisciplinary team. Our narrative review, through a rigorous analysis of the current literature, focuses on pain management in hemophiliac patients. Methods: The report synthesizes a literature review on hemophilia, adapting PRISMA guidelines. It identifies a research question on surgical procedures and perioperative pain management. Various sources, including electronic databases, are utilized. Study inclusion criteria are defined based on the research question. Forty studies are included. A detailed study selection is illustrated. Results: Guidelines for managing acute postoperative pain in the general population advocate for a multimodal analgesic administration to enhance synergistic benefits, reduce opioid requirements, and minimize side effects. Recent recommendations from the World Federation of Hemophilia (WFH) for postoperative pain management in hemophilia patients suggest tailoring treatment based on pain levels, in coordination with anesthesiologists. Conclusions: Pain management in hemophiliac patients undergoing orthopedic interventions requires a multidisciplinary approach, with further research needed to define a reliable global standard of treatment. [ABSTRACT FROM AUTHOR]

Background: Neonatal rats that receive sucrose during a critical postnatal period (CP, days 12 to 28) develop hypertension by the time they reach adulthood. Inflammation might contribute to changes during this period and could be associated with variations in the vascular smooth muscle (VSMC) phenotype. Objective: We studied changes in inflammatory pathways that could underlie the expression of the secretory phenotype in the VSMC in the thoracic aorta of rats that received sucrose during CP. Methods: We analyzed histological changes in the aorta and the expression of the COX-2, TLR4, iNOS, eNOS, MMP-2 and -9, and β- and α-actin, the quantities of TNF-α, IL-6, and IL-1β using ELISA, and the levels of fatty acids using gas chromatography. Results: The aortic wall presented disorganization, decellularization, and wavy elastic fibers and an increase in the lumen area. The α- and β-actin expressions were decreased, while COX-2, TLR4, TNF-α, and the activity of IL-6 were increased. Oleic acid was increased in CP in comparison to the control group. Conclusions: There is transient hypertension at the end of the CP that is accompanied by inflammation and a change in the phenotype of VSMC to the secretory phenotype. The inflammatory changes could act as epigenetic signals to determine the development of hypertension when animals reach adulthood. [ABSTRACT FROM AUTHOR]

Objectives: Houttuynia cordata Thunb., a member of the Saururaceae family, has been demonstrated to have potential in the treatment of different diseases. For the first time, aristolactam BII was isolated from the aerial part of Houttuynia cordata Thunb. and the anti-inflammatory effect of the extract and aristolactam BII was evaluated. Methods: After using chromatography to separate and obtain the compound, Nuclear Magnetic Resonance was used to identify the compound. An in vivo model of carrageenan-induced paw edema on mice was performed to test the anti-inflammation of the extract and compound. Furthermore, a ligand docking experiment was performed to determine the binding free energy of aristolactam to inflammatory proteins including COX-1, COX-2. Results: The findings showed that aristolactam BII effectively reduced the severity of the edema, similar to diclofenac, whereas the methanol extract showed low effectiveness. Particularly, the swelling rate of 50 mg/kg aristolactam BII treated mice was only 26.2 ± 7.1% (p < 0.01) after 5 h treatment. The in silico results described that aristolactam BII might inhibit COX-1 and COX-2 via creating h-bonds at the sites of Ser 530 residues. Conclusion: Our results demonstrate the potential anti-inflammatory activity of aristolactam BII. This study would provide more fundamental knowledge about the bioactivities of aristolactam BII isolated from Houttuynia cordata. [ABSTRACT FROM AUTHOR]

Background and Objectives: Head and neck squamous cell carcinomas (HNSCCs) vary significantly in terms of invasiveness, growth rate, and metastatic potential. This study aimed to investigate the expression of several prognostic biomarkers (Ki67, p53, EGFR, COX-2, Cx43, and p16) in HNSCC from various anatomical regions and to correlate these expressions with clinicopathological parameters. Materials and Methods: We performed immunohistochemistry on 91 histologically verified HNSCC cases from the County Emergency Hospital, Targu Mures. Biomarker expression for Ki67, COX-2, and Cx43 was assessed using a standard immunoexpression scoring system: S1: 0–10%, S2: 11–25%, S3: 26–50%, S4 > 50%; EGFR was scored based on membrane staining intensity: 0, 1+, 2+, 3+; we classified p16 as positive or negative; p53 was grouped into mutant and wild-type; and we compared these across histopathological types, tumor grades, anatomical locations, gender, and different age groups. We performed a comparative analysis of Cx43 expression levels in relation to the expression of the rest of the markers. Statistical analysis was conducted using GraphPad InStat 3 software, version 3.06 (GraphPad Software Inc., San Diego, USA). Results: The majority of tumors were in males (95.6%) aged 51–60 years. Mutant p53 expression was prevalent in most cases. Elevated Ki67 and EGFR expression were associated with more aggressive tumors. COX-2 levels varied, with a higher proportion of moderate and high immunoexpression (S3 + S4) observed in patients under 70 years old. Cx43 expression was generally low, especially in extralaryngeal tumors. Conclusions: HNSCC primarily affects older males, with the larynx being the most common site. High levels of Ki-67 and EGFR suggest more aggressive tumors, while low COX-2 levels reflect varying prognoses. Women may develop more aggressive tumors, and extralaryngeal tumors often present with more challenging prognoses. Low Cx43 expression may be more likely to coincide with higher Ki67 and COX-2 levels, possibly indicating a link with more aggressive tumor behavior. [ABSTRACT FROM AUTHOR]

This experiment mainly explored the protective role of sulforaphane (SFN) against physiological toxicity of triphenyltin (TPT) in Cyprinus carpio haematopterus. In total, 320 Fish (56.90 ± 0.40 g) were randomly divided into four groups with four replicates each. The control group was fed the basal diet, the TPT group (TPT) was exposed to 10 ng L−1 TPT on the basis of the control group, the SFN + TPT group (TPT + SFN) was fed a diet supplemented with 10 mg kg−1 SFN on the TPT group, and the SFN group (SFN) was fed a diet supplemented with 10 mg kg−1 SFN. After 56 days of breeding trials, the results showed that TPT exposure resulted in a remarkable decrease (p < 0.05) in final weight, weight gain rate (WGR), specific growth rate (SGR), and condition factor (CF), but an increase (p < 0.05) in feed conversion ratio (FCR) and hepatosomatic index (HSI) of fish. TPT treatment decreased (p < 0.05) the amounts of hematocrit (Hct) and hemoglobin (Hb), plasma complement component 3 (C3) and C4 contents, alternative complement pathway (ACH50), acid phosphatase (ACP) and lysozyme (LZM) activities, liver glutathione (GSH) content, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX) activities, interleukin 10 (IL-10), and SOD mRNA expressions, but increased (p < 0.05) plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, liver malonaldehyde (MDA) content, tumor Cyclooxygenase 2 (COX2), and necrosis factor α (TNFα), IL-1β, and MDA mRNA expressions. A histological analysis of the liver showed that a higher occurrence rates of the hepatocyte hypertrophy, nuclear disappearance and hepatocyte vacuolization was observed in the hepatocytes of fish exposed to TPT, and it was accompanied by the dilation of hepatic sinusoids. In addition, the toxicity induced by TPT was significantly improved in the groups that were treated with SFN, and SFN was able to improve growth performance and immunity, alleviate TPT-induced changes in inflammatory factors, ameliorate oxidative stress, and increase the activity of antioxidant enzymes (p < 0.05). The addition of SFN also alleviated liver damage caused by TPT and protected the structural integrity of the liver. Overall, these findings suggest that TPT inhibited the growth, immunity, and antioxidant capacity of Cyprinus carpio haematopteru. Dietary SFN could be beneficial for growth promotion, immunity, antioxidant capacity, and protection of liver structural integrity. Therefore, SFN is a prospective feed supplement for ameliorating the damage caused to fish by TPT contamination. [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]

Introduction: Fetal membrane inflammation is an integral event of parturition. However, excessive pro-inflammatory cytokines can impose threats to the fetus. Coincidentally, the fetal membranes express abundant 11b-hydroxysteroid dehydrogenase 1 (11b-HSD1), which generates biologically active cortisol to promote labor through induction of prostaglandin synthesis. Given the wellrecognized anti-inflammatory actions of glucocorticoids, we hypothesized that cortisol regenerated in the fetal membranes might be engaged in restraining fetus-hazardous pro-inflammatory cytokine production for the safety of the fetus, while reserving pro-labor effect on prostaglandin synthesis to ensure safe delivery of the fetus. Methods: The hypothesis was examined in human amnion tissue and cultured primary human amnion fibroblasts as well as a mouse model. Results: 11b-HSD1 was significantly increased in the human amnion in infectioninduced preterm birth. Studies in human amnion fibroblasts showed that lipopolysaccharide (LPS) induced 11b-HSD1 expression synergistically with cortisol. Cortisol completely blocked NF-kB-mediated pro-inflammatory cytokine expression by LPS, but STAT3-mediated cyclooxygenase 2 expression, a crucial prostaglandin synthetic enzyme, remained. Further studies in pregnant mice showed that corticosterone did not delay LPS-induced preterm birth, but alleviated LPS-induced fetal organ damages, along with increased 11b-HSD1, cyclooxygenase 2, and decreased pro-inflammatory cytokine in the fetal membranes. Discussion: There is a feed-forward cortisol regeneration in the fetal membranes in infection, and cortisol regenerated restrains pro-inflammatory cytokine expression, while reserves pro-labor effect on prostaglandin synthesis. This dual role of cortisol regeneration can prevent excessive pro-inflammatory cytokine production, while ensure in-time delivery for the safety of the fetus. [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 and aims: This study investigated the biochemical components present in the leaves of Cissus assamica. The primary aim was to analyze these components using advanced techniques and assess their potential therapeutic applications. Methodology: Fourier Transform Infrared (FT‐IR) spectroscopy, Gas Chromatography‐Mass Spectrometry (GC‐MS), and Mass Spectral analysis were employed to identify and characterize the compounds in Cissus assamica leaves. The mass spectra of each compound were compared with data from the Wiley and NIST libraries to determine their names, molecular masses, and chemical structures. FT‐IR analysis identified characteristic functional groups by their specific frequencies. Results and discussion: FT‐IR spectroscopic analysis revealed significant molecular vibrations at frequencies of 3265.63, 2853.81, 1638.60, 1469.21, and 1384.95 cm⁻¹, indicating the presence of specific functional groups. The GC‐MS analysis identified distinct compounds, such as "aR‐Turmerone," "Curlone," "7,8‐Epoxylanostan‐11‐ol, 3‐acetoxy‐," "13‐Docosenamide, (Z)‐," "Phenol, 3,5‐bis(1,1‐dimethylethyl)‐," "9,19‐Cyclolanostan‐3‐ol, 24,24‐epoxymethano‐, acetate," and "Quinoline‐5,8‐dione‐6‐ol, 7‐[[(4‐cyclohexylbutyl)amino]methyl]‐." These compounds exhibited potential therapeutic applications. Their cytotoxic, antimicrobial, antidiarrheal, anti‐hyperglycemic, and pain‐relieving properties were evaluated by comparing them with reference ligands targeting specific receptors, including dihydrofolate reductase (DHFR), epidermal growth factor receptor (EGFR), kappa opioid receptor (KOR), glucose transporter 3 (GLUT 3), and cyclooxygenase 2 (COX‐2). Conclusion: The results of this study suggest that Cissus assamica leaves contain bioactive compounds with potential therapeutic benefits for treating infections, diarrhea, hyperglycemia, and pain. However, further research is needed to conduct comprehensive phytochemical screening and establish the precise mechanisms of action for the crude extract or the plant‐derived compounds. Highlights: Compound isolation and characterization of the plant Cissus assamica was done by GC‐MS/MS and FTIR analyses.A total of 15 Phytochemicals were identified.In silico analysis of the identified phytochemicals were carried out for the evaluation of antidiarrheal, analgesic, hypoglycemic, anticancer and antimicrobial potentiality of the compounds.ADME/T were shown to observe potential drug likeliness. [ABSTRACT FROM AUTHOR]

This study investigates the composition characteristics and anti-inflammatory activity mechanisms of the essential oil from the leaves of Crossostephium chinense. C. chinense is a perennial herb commonly found in East Asia, traditionally used to treat various ailments. The essential oil extracted through water distillation, primarily contains 1,8-cineole (13.73%), santolina triene (13.53%), and germacrene D (10.67%). Three compounds were identified from the essential oil, namely 1-acetoxy-2-(2-hydroxypropyl)-5-methylhex-3,5-diene, 1-acetoxy-isopyliden-hex-5-en-4-one, and chrysanthemyl acetate, with the first two being newly discovered compounds. Then, the essential oil of C. chinense exhibits significant anti-inflammatory effects on RAW264.7 macrophages, effectively inhibiting the production of NO and ROS, with the IC50 value of 10.3 μg/mL. Furthermore, the essential oil reduces the expression of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β. Mechanistic studies indicate that the essential oil affects the inflammatory response by inhibiting the expression of iNOS but has no significant impact on COX-2. Further analysis suggests that the essential oil may regulate the inflammatory response through the ERK protein in the MAPK pathway and IκBα in the NF-κB pathway, while also promoting the activity of the NRF2/HO-1 antioxidant pathway, enhancing the cell's antioxidant capacity, thereby achieving an effect of inhibiting the inflammatory response. These results highlight the potential application value of C. chinense leaf essential oil in the medical and healthcare fields. [ABSTRACT FROM AUTHOR]

Neurodegeneration in conditions like Alzheimer's and Parkinson's disease is influenced by genetic and environmental factors. This study explores the potential neurodegenerative effects of lead (Pb) toxicity and amyloid beta peptides (Aβp 1–40 and Aβp 25–35) by promoting M1 polarization in microglial cells. To this end, we investigated and observed that IC50 concentrations of Pb (22.8 μM) and Aβp 25–35(29.6 μM). Our results demonstrated significant Pb uptake (31.13% at 25 μM Pb) and increased intracellular ROS levels (77.1%) upon treatment with Pb in combination of both Aβp 1–40 and Aβp 25–35. Protein carbonylation significantly increased (73.12 nmol/mL) upon treatment with Pb in combination of both Aβp 1–40 and Aβp 25–35, indicating oxidative damage and compromised cellular defenses against oxidative stress along with elevated DNA oxidative damage (164.9 pg/mL of 8‐OH‐dG) upon treatment with Pb in combination with both Aβp 1–40 and Aβp 25–35. Microglial polarization showed elevated M1 markers (inducible nitric oxide synthase and cyclooxygenase 2) and reduced M2 markers (arginase‐1 and cluster of differentiation 206), suggesting Pb's role in inducing neurodegenerative microglial polarization. These findings provide insights into the complex molecular events contributing to Pb‐induced neurotoxicity and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Objective: There is growing evidence that adding non-steroidal anti-inflammatory drugs to some psychopharmacological treatments may help to improve symptoms in patients suffering from major depressive disorder. The present study examined the therapeutic efficacy of adding celecoxib to escitalopram and the safety of doing so. Method: In this double-blind randomized controlled trial, 60 patients with major depressive disorder were randomly assigned to either treatment with escitalopram plus celecoxib (intervention group) or escitalopram and placebo. All patients were evaluated blind to treatment group with the Hamilton Depression Rating Scale (HDRS) before the intervention as well at 4 and 8 weeks after initiating treatment. Chi-square and paired t-test were used to examine between-group differences at those assessment times. Results: There was no significant difference in depressive symptoms between intervention and placebo groups at baseline. However, at 4 and 8 weeks after the beginning of treatment, there were significant between-group differences in HDRS scores, favoring the intervention group. No between-group differences were found in treatment-related side effects. Conclusions: Adding celecoxib to escitalopram may improve symptoms of depression in patients with major depressive disorder without increasing the risk of drug-related side effects. [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]

The galloyl group in catechins was confirmed to be crucial for their health benefits. However, whether the catechins' galloyl group had a contribution to their anti-inflammation remains unclear. This study investigated the anti-inflammation properties and mechanisms of catechins in RAW264.7 cells by using ELISA, fluorometry, flow cytometer, Western blot, and molecular docking. Results showed that the galloyl group enhanced the inhibitory abilities of catechins on inflammatory cytokines (NO, PGE2, IL-1β, and TNF-α) and ROS release in LPS-induced cells. This suppression was likely mediated by delaying cells from the G0/G1 to the S phase, blocking COX-2 and iNOS via the TLR4/MAPK/NF-κB pathway with PU.1 as an upstream target. The research proved that the existence of galloyl groups in catechins was indispensable for their anti-inflammatory capacities and offered a theoretical basis for the anti-inflammatory mechanism of galloylated catechins. Future research is needed to verify the anti-inflammatory effects of catechins in various sources of macrophages or the Caco-2/RAW264.7 cell co-culture system. [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]

Glycosylation is an important post-modification reaction in plant secondary metabolism, and contributes to structural diversity of bioactive natural products. In plants, glycosylation is usually catalyzed by UDP-glycosyltransferases. Flavonoid 2′- O -glycosides are rare glycosides. However, no UGTs have been reported, thus far, to specifically catalyze 2′- O -glycosylation of flavonoids. In this work, UGT71AP2 was identified from the medicinal plant Scutellaria baicalensis as the first flavonoid 2′- O -glycosyltransferase. It could preferentially transfer a glycosyl moiety to 2′-hydroxy of at least nine flavonoids to yield six new compounds. Some of the 2′- O -glycosides showed noticeable inhibitory activities against cyclooxygenase 2. The crystal structure of UGT71AP2 (2.15 Å) was solved, and mechanisms of its regio-selectivity was interpreted by p K a calculations, molecular docking, MD simulation, MM/GBSA binding free energy, QM/MM, and hydrogen‒deuterium exchange mass spectrometry analysis. Through structure-guided rational design, we obtained the L138T/V179D/M180T mutant with remarkably enhanced regio-selectivity (the ratio of 7- O -glycosylation byproducts decreased from 48% to 4%) and catalytic efficiency of 2′- O -glycosylation (k cat / K m , 0.23 L/(s·μmol), 12-fold higher than the native). Moreover, UGT71AP2 also possesses moderate UDP-dependent de-glycosylation activity, and is a dual function glycosyltransferase. This work provides an efficient biocatalyst and sets a good example for protein engineering to optimize enzyme catalytic features through rational design. This work reports a novel 2′- O -glycosyltransferase, unravels its regio-selectivity mechanism, and improves its catalytic function through protein engineering. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Coronary artery calcification (CAC) is in almost all patients with coronary artery disease and requires more effective therapies. We aim to explore the effects of phosphoglycerate dehydrogenase (PHGDH) on CAC. Methods: We identified the differentially expressed genes through bioinformatic analysis and selected PHGDH for further verification. Human coronary artery smooth muscle cells (HCASMCs) cultured with calcifying medium were used as models of CAC in vitro. Erastin was administered to induce ferroptosis. We determined the cell viability by the cell count kit-8 assay. The alkaline phosphatase activity, calcium content, and the expression of glutathione were evaluated by the corresponding detection kits. The calcification level was detected by alizarin red staining. Then we performed Western blot to examine the expression of runt-related transcription factor 2, bone morphogenetic protein 2, cyclooxygenase 2, glutathione peroxidase 4, P53, and solute carrier family 7a member 11 (SLC7A11). Results: We acquired 201 differentially expressed genes and selected PHGDH to verify. In calcifying medium-induced HCASMCs, PHGDH overexpression increased the cell viability and decreased the alkaline phosphatase activity, calcium content, calcification level, and the expression of bone morphogenetic protein 2 and runt-related transcription factor 2. Additionally, we found higher levels of glutathione, glutathione peroxidase 4, and SLC7A11 and lower levels of cyclooxygenase 2 and P53 after up-regulating PHGDH. Erastin reversed the effects of PHGDH on calcification of HCASMCs. Conclusion: PHGDH overexpression suppresses the calcification level of HCASMCs by inhibiting ferroptosis through the P53/SLC7A11 signaling pathway, suggesting PHGDH as a promising therapeutic target of CAC. [ABSTRACT FROM AUTHOR]

Background: Moringa oleifera is a highly nutritious plant widely used in traditional medicine. Results: The aroma constituents present in the fresh flowers of M. oleifera versus the hydrodistilled oil and hexane extract were studied using GC-MS. Aldehydes were the major class detected in the fresh flowers (64.75%) with E-2-hexenal being the predominant component constituting > 50%. Alkane hydrocarbons, monoterpenes, and aldehydes constituted > 50% of the hydrodistilled oil, while alkane hydrocarbons exclusively constitute up to 65.48% of the hexane extract with heptacosane being the major component (46.2%). The cytotoxicity of the hexane extract was assessed on RAW 264.7 macrophages using the MTT assay which revealed no significant cytotoxicity at concentrations of 1 µg/mL and displayed IC50 value at 398.53 µg/mL as compared to celecoxib (anti-inflammatory drug) with IC50 value at 274.55 µg/ml. The hexane extract of Moringa flowers displayed good anti-inflammatory activity through suppression of NO, IL-6, and TNF-α in lipopolysaccharide-induced RAW 264.7 macrophages. The total phenolic and flavonoid content in the hexane extract was found to be 12.51 ± 0.28 mg GAE/g extract and 0.16 ± 0.01 mg RuE/g extract, respectively. It displayed moderate antioxidant activity as indicated by the in vitro DPPH, ABTS, CUPRAC, FRAP, and phosphomolybdenum (PBA) assays. No metal chelating properties were observed for the extract. The enzyme inhibitory potential of the hexane extract was evaluated on acetyl- and butyrylcholinesterases (for neuroprotective assessment), α-amylase and α-glucosidase (for antihyperglycemic assessment), and tyrosinase (for dermoprotective assessment) revealing promising results on cholinesterases, tyrosinase, and α-glucosidase. Conclusion: Our findings suggested that M. oleifera leaves can be considered as a multidirectional ingredient for preparing functional applications. [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]

Background: In 2019, the International Olympic Committee published the first Olympic and Paralympic Model Formulary (OPF), which defined the standardised set of medications required at every Olympic and Paralympic Games for the treatment of athletes. This study aimed to test the OPF to determine whether it meets the clinical needs of the athlete population with respect to medications used for pain and/or inflammation (PI), and to present a revised set of essential PI medications for the OPF based on prevalence of athlete use. Medication-use data of athletes at the Tokyo 2020 and Beijing 2022 Olympic Games (n = 6155) from three sources were used to establish prevalence of PI medicine use and to revise the OPF: (i) doping control forms, (ii) pharmacy dispensing reports, and (iii) injection declaration forms. This revised list was further validated through (iv) medication importation declarations by teams (n = 156), and (v) survey of team physicians (n = 382). Results: Overall prevalence of PI medication use was 36.7%, with higher use by female athletes (female: 44.1%; male: 30.0%; p < 0.001), with non-steroidal anti-inflammatory drugs being the most used class (27%). Use of medications with safety risks were identified, including nimesulide, piroxicam and metamizole. A revised list of 48 PI medications was recommended for the OPF. Conclusion: The research led to a revised set of essential medications for the treatment of pain and inflammation to be available for athletes at the Olympic Games, which would lead to a 7% improvement in the numbers of athletes who could have their exact PI medication requirements met by the OPF. Key Points: Medicines are provided at the Olympic Games for prescribing to athletes by international team physicians, with those most commonly prescribed being for treatment of pain and inflammation due to musculoskeletal sports injury. This study presents an optimal list of 48 essential medicines for the treatment of pain and inflammation to be available at every summer and winter Olympic Games, selected based on prevalence of athlete use, avoidance of harms, and reflecting the preferred treatment options of international team physicians. The results of this study will inform the selection of medicines to be available through the medical services within the athlete villages and competition venues at future Olympic Games. The implementation of this formulary is expected to result in 7% more athletes having access to their preferred choice of treatment for pain and inflammation due to sports injury. [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: The Pro-inflammatory mediators such as prostaglandin E2, nitric oxide and TNF-α are the key players in the stimulation of the inflammatory responses. Thus, the pro-inflammatory mediators are considered to be potential targets for screening nutraceutical with anti-inflammatory activity. Methods: In this context, we explored the anti-inflammatory potency of seagrass extract with western blot (Bio-Rad) analysis by using LPS induced RAW macrophages as in-vitro models, western blot analysis, In-silico methods using Mastero 13.0 software. Results: The anti-inflammatory activity of Seagrass was demonstrated through down regulation of Pro-inflammatory markers such as Cyclooxygenase-2, induced Nitric oxide synthase and prostaglandin E synthase-1. The results were validated by docking the phytochemical constituents of seagrass namely Isocoumarin, Hexadecanoic acid, and Cis-9 Octadecenoic acid, 1,2 Benzene dicarboxylic acid and beta-sitosterol with TNF-alpha, COX-2, iNOS and PGES-1. Conclusion: The methanolic extract of seagrass Halophila beccarii is a potential nutraceutical agent for combating against inflammation with a significant anti-inflammatory activity. [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]