Inflammopharmacology最新文献

Objective: The aim of this study was to comprehensively investigate the clinical efficacy of intraoperative local joint injection and intramuscular injection of betamethasone in patients with severe traumatic knee osteoarthritis (KOA).

Methods: 80 patients with severe traumatic KOA undergoing total knee arthroplasty were retrospectively recruited and rolled into S1 group (intra-articular injection of ropivacaine + betamethasone and isotonic saline mixture at joint incision), S2 group (muscle local injection of betamethasone before incision closure, simultaneously intra-articular injection of ropivacaine + isotonic saline mixture at joint incision), and D group (intra-articular injection of ropivacaine + isotonic saline mixture at the joint incision). Visual analog scale (VAS) score, serum inflammatory factors (IFs), hospital for special surgery (HSS)score, Pittsburgh sleep quality index (PSQI), and adverse reaction events (AREs) were analyzed.

Results: Pain scores of patients in all three groups decreased drastically over time on postoperative days (PDs) 1, 2, and 3, with the scores in S1 and S2 groups markedly inferior to D group (P < 0.05). HSS scores of patients in S1 and S2 groups at postoperative months 1, 3, and 6 were considerably superior to those in D group (P < 0.05). PSQI scores of patients in S1 and S2 groups at postoperative months 1, 3, and 6 were notably inferior to those in D group (P < 0.05).

Conclusion: Both intraoperative local joint injection and muscle injection of betamethasone are effective in patients with severe traumatic KOA.

The aim of this study was to investigate the effectiveness of Zataria multiflora and carvacrol supplementation on inflammatory markers (IL-2, IL-4, IL-5, IL-6, TNF-α, IL-8, IL-10, interferon gamma (IFN-γ), C-reactive protein (CRP), monocyte chemotactic protein 1 (MCP-1), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF)) by conducting a systematic review and meta-analysis of randomized controlled trials (RCTs).The exploration of literature was conducted until August 2024 on databases like PubMed/Medline, Web of Science, Scopus, Cochrane CENTRAL, and Google Scholar. The current study incorporated trial studies examining how oral supplements of Zataria multiflora and carvacrol impact concentrations of inflammatory markers. By utilizing a random effects model, the mean differences (SMD) and 95% confidence intervals (CI) were pooled for analysis of the results. The Cochrane Q and I² values were used to evaluate heterogeneity. The meta-analysis included ten cases, with 562 participants in the Zataria multiflora group and 700 in the control group. A significant decrease in the levels of various cytokines including IL-2, IL-4, IL-5, IL-6, IL-8, CRP, EGF, VEGF, and MCP-1 was observed with the consumption of Zataria multiflora along with a noteworthy increase in both IFN-γ and IL-10. However, TNF-α levels remained unaffected by the intervention involving Zataria multiflora and carvacrol. It should be noted that limitations of this study include the fact that it draws from research in Iran, encompasses a range of different diseases, and overlooks potential confounders like smoking, physical activity, and diet. In summary, the results suggested that Zataria multiflora and carvacrol can be beneficial for reducing inflammation.

Ulcerative colitis is one of the inflammatory bowel diseases that manifest itself by uncontrolled inflammation of colon. The objective of this work was to evaluate the effects of aqueous extract of Waltheria indica on acetic acid-induced ulcerative colitis in rats. Six (6) groups of five (5) rats each, were anesthetized with a ketamine (50 mg/kg)/valium (10 mg/kg) mixture after eighteen (18) fasting hours. Colitis was induced by intrarectal administration of 1 mL of acetic acid (5%) in animals. Five (5) hours later, the normal control (NC) and the colitis control (CC) received distilled water (10 mL/kg bw), the positive control (Pre5) received prednisolone (5 mg/kg) and the other three test groups received the W. indica extract at 50 (Wi50), 100 (Wi100) and 200 (Wi200) mg/kg bw, orally for 7 days. At the end of the treatment, the animals were sacrificed and the blood was collected from the carotid artery, part in the ethylenediaminetetraacetate (EDTA) tube for hematological analyzes and part in dry tubes for biochemical assays. The abdomen was then opened, the colon, liver, spleen, lungs and heart were removed, drained, weighed and the indexes of each organ were determined. The extract at 200 mg/kg reduced myeloperoxidase (MPO) and inhibited the production of interleukin-1 beta (IL-1β) and interleukin-6(IL-6) in the colon and serum. The extract significantly increased the blood platelet level of the colitis rats. Thus, these results suggest that Walthera indica extract may have therapeutic potential for the treatment of inflammatory bowel diseases.

Following the acute COVID-19 disease, many countries see long-time sequences of this infectious disease, commonly known as Long COVID. This seems to be a multi-organ inflammatory chronic condition of variable intensity and incidence, partly due to the retention of the virus or viral particles in several organs. Based on our 6-country (4 in Europe, 2 from North America) collaborative investigations, we found that the incidence of Long COVID varied from 46 (Mexico) to 17% (Ukraine), the average being 25%. In a summary evaluation of all 6 countries, we characterized as "general" the most frequent presenting signs and symptoms: fatigue (47%), hair loss (39.2%), and myalgia (35%), but no two countries demonstrated the same top 3 clinical signs/symptoms. Hence, we promote the following 3 key points: 1. to expand international collaborations to better understand not only the prevalence and incidence of Long COVID but also to gain insights into the pathogenesis, and identify predisposing factors and diagnostic biomarkers of Long COVID; 2. find or develop new drugs for the treatments of Long COVID and identify appropriate rehabilitation, potentially organ-specific strategies; 3. most importantly, to start long-term observational studies (e.g., for 5-10-15 years) to identify potential increased cancer incidence in any organ, especially, since we know that certain viruses are carcinogens.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects the joints and causes pain, swelling, and deformity. Current treatments, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying antirheumatic drugs, often have limited efficacy and adverse side effects. Nanostructured lipid carriers (NLCs) are promising drug delivery agents for treating RA. NLCs are comprised of solid and liquid lipids, forming a nanostructured matrix that enhances drug solubility, stability, and controlled release. They offer advantages over traditional carriers such as improved skin penetration, increased bioavailability, and reduced systemic side effects. Topical NLC formulations show improved stability and skin absorption, targeting drugs specifically to the affected joints, thus reducing the required dose and systemic exposure. Studies on NLCs for delivering anti-inflammatory and antirheumatic drugs, such as methotrexate, indomethacin, and curcumin, in RA animal models indicate the potential for improved therapeutic efficacy and safety. NLCs represent a promising approach for targeted RA drug delivery, offering better efficacy, fewer side effects, and higher patient compliance. However, further research is needed to optimize NLC formulations and evaluate their clinical efficacy and safety in RA patients. The development of NLC-based drug delivery systems for RA treatment may lead to more effective and well-tolerated therapies, thereby improving the quality of life of patients with this debilitating disease.

Rheumatoid arthritis (RA) is defined as a chronic autoimmune disease that severely influences a patient's quality of life. Extracellular vesicles (EVs) have gained much attention in recent years as one of the most potent therapeutic agents for the treatment of RA. A systematic review was performed with the purpose of assessing the current evidence relating to the therapeutic applications of EVs in RA. The systematic search was performed in the databases of PubMed, Scopus, and Web of Science, from inception times to September 2024. All studies investigating the use of EVs for the treatment of RA were included. The quality appraisal of selected articles and data extraction regarding EV characteristics, therapeutic applications, and associated outcomes were performed. Of the 1418 initially identified articles, 59 studies met inclusion criteria. Regarding their cellular origins, most EVs were derived from mesenchymal stem cells, followed by immune cells. The main therapeutic mechanisms included modulation of the immune response, reduction of inflammation, and repair of tissues. Recent trends are toward increasing interest in engineered EVs and combination therapies. Indeed, most studies reported positive outcomes with regard to lowered inflammation and improved joint function. On the other hand, standardization of the metrics of evaluation considerably varied between different studies. EVs are promising therapeutic agents in the treatment of RA by modulating immune responses. Standardization, delivery systems, and clinical translation are challenges yet to be overcome. Future studies will be directed to optimize EV engineering, targeted delivery systems, and large-scale clinical trials.

Opioids/non-steroidal anti-inflammatory drugs are used to alleviate pain; however, they are expensive and can have adverse effects, especially when used over extended periods. Therefore, there is immense demand for innovative, non-addictive analgesics. Here, we report a novel plant-derived central anti-nociceptive agent, Liparis nervosa (Thunb.) Lindl. (LN), validated in animal pain models. Ethyl acetate fractions of L. nervosa (EALN) exhibited central anti-nociceptive activity in hot plate, tail immersion, formalin-induced paw oedema, and acetic acid-induced abdominal writhing tests. The chemical composition of the EALN was determined using ultra-high-performance liquid chromatography-mass spectrometry. Reserpine (monoamine transmitter-depleting agent) and naltrexone (opioid antagonist) partially suppressed the anti-nociceptive effect of EALN in both phases of the formalin test. Oral administration of EALN activated the endogenous opioid and central descending inhibitory systems by increasing β-endorphin, 5-hydroxytryptamine, and norepinephrine expression. EALN treatment increased the expression of γ-aminobutyric acid B; inhibited the expression of prostaglandin E2, substance P, calcitonin gene-related peptide, and c-Fos; and blocked the transmission of pain signals in the spinal cord. EALN treatment reduced the activity of nitric oxide and nitric oxide synthase in the central region and inhibited the nitric oxide-cyclic guanosine monophosphate signal transduction pathway, thereby attenuating the transmission of nociceptive information in the descending inhibitory pathways. The central anti-nociceptive effect of EALN was achieved by integrating these pathways. This study provides new insights into the pharmacologic action of LN and provide a therapeutic approach as a promising candidate for central anti-nociceptive agents.

Chronic painful autoimmune disorders such as multiple sclerosis (MS), inflammatory bowel disease (IBD), and rheumatoid arthritis (RA) induce significant discomfort. They are defined by persistent inflammation and immune-mediated tissue injury. The activation and sensitisation of nociceptors, mutated in various disorders, are fundamental components contributing to the pain experienced in these conditions. Recent discoveries indicate that immunological mediators and nociceptive receptors interact functionally within peripheral and central sensitisation pathways, amplifying chronic pain. This research examines the involvement of nociceptors in rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. It explores how immune cells and pro-inflammatory cytokines induce, sensitise and regulate various nociceptive receptors (P2X, TRPA1 and TRPV1). Finally, we address possible future directions with respect to the treatment of long-lasting effects on immunity, and what new drug targets could be pursued as well, in order to counteract such either neuro-immune interactions in conditions involving the immunological system. By studying nociceptive mechanisms across autoimmune illnesses, we want to identify shared pathways and activation of nociceptors specific to individual diseases. This will shed insight on potential therapies for managing pain associated with autoimmune diseases.

Janus kinase inhibitors (JAKi) have been associated with an increased risk of venous thromboembolism (VTE) limiting the use of JAKi-based therapy. To improve risk stratification and drug development, it is crucial to understand the implication of dysregulated JAK-Signal Transducers and Activators of Transcription (STAT) signaling in the pathogenesis of VTE. The objective of this study is to clarify the putative genomic vulnerability to dysregulated JAK-STAT signaling in VTE through systematic mining of large-scale datasets generated from studies comparing VTE patients with healthy controls. Particularly, we assess the representation of entities of the JAK-STAT signaling pathway including STAT target genes among sets of miRNA, mRNA, and proteins differentially abundant in VTE patients, and we explore the putative cumulative genetic association of JAK-STAT signaling gene sets to VTE. Genes related to the JAK-STAT pathway were found significantly altered in VTE patients compared to healthy controls, indicating that genes under transcriptional control of STAT may be dysregulated in VTE. In support of this notion, we find a significant overrepresentation of predicted STAT target genes among genes downregulated in VTE patients, and promoter sequences of differentially regulated genes were significantly enriched with STAT transcription factor binding site motifs. Further linking STAT signaling to the molecular signature of VTE, genes targeted by miRNAs differentially regulated in patients are significantly enriched with STAT target genes and genes acting in the JAK-STAT signaling pathway. Together, our findings indicate that disruptions in the JAK-STAT pathway contribute to the molecular profile of VTE. This offers hope for identifying ways to interact with the JAK-STAT pathway that do not carry the risk of VTE.

Background: Rheumatoid arthritis (RA) manifests through persistent synovitis and systemic inflammation, which ultimately result in the degradation of cartilage and bone. The current study was to scrutinize the anti-arthritic effect of Reynoutria japonica Houtt ameliorating complete Freund's adjuvant (CFA)-induced RA in rats and explore the underlying mechanism.

Material and methods: CFA was used for the induction of RA in the rats (rats were received the oral administration of Reynoutria japonica Houtt) and estimation of body weight and organ weight. The paw volume, arthritic score, paw withdrawn threshold, and paw withdrawn latency were estimated at regular time. The RF, hematological, hepatic, non-hepatic, ATG, oxidative stress, cytokines, and inflammatory parameters were estimated. The mRNA expression of different genes was scrutinized.

Results: Reynoutria japonica Houtt treatment improved the body weight and reduced the spleen and thymus index. Reynoutria japonica Houtt also suppressed the paw edema, arthritic score, paw withdrawn threshold, and paw withdrawn latency at regular time interval. Reynoutria japonica Houtt suppressed the RF and altered the hematological, hepatic, non-hepatic, cytokines and inflammatory parameters. Reynoutria japonica Houtt treatment significantly (P < 0.001) altered the expression of MMP-2, MMP-9, MMP-12, TNF-α, IL-1β, Il-6, IL-10, IL-17, COX-1, COX-2, NF-κB, iNOS, mTOR, LC3-II, AMPK, and Beclin 1.

Conclusion: The result clearly stated the promising effect of Reynoutria japonica Houtt against CFA-induced RA in rats via the suppression of NF-κB signaling pathway.