Inflammopharmacology最新文献

{"title":"Unlocking the therapeutic potential of Geraniol: an alternative perspective for metabolic disease management.","authors":"Shiva Singh, Anuradha Mishra, Alka","doi":"10.1007/s10787-024-01582-0","DOIUrl":"10.1007/s10787-024-01582-0","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Natural substance geraniol has anti-inflammatory and antioxidant qualities. It may be used to treat metabolic diseases such as diabetes, obesity, and cardiovascular illnesses. Innovations in nanoformulations enhance geraniol's absorption, stability, and targeted distribution, augmenting its therapeutic effectiveness and mitigating side effects, despite the limits of traditional treatment.</p><p><strong>Aim of the review: </strong>The therapeutic potential of geraniol in the management of metabolic disorders such as diabetes, obesity, neuroinflammation, and cardiovascular disease is examined in this review. It highlights the anti-inflammatory, antioxidant, and lipid-lowering qualities of geraniol as well as the potential for nanoformulations to increase bioavailability and therapeutic efficacy.</p><p><strong>Materials and methods: </strong>A collection of pertinent research articles about the potential of geraniol in metabolic illnesses, including obesity, type 2 diabetes, as well as cardiovascular diseases, was compiled from PubMed, Scopus, and Google Scholar. Terms such as \"metabolic syndrome,\" \"antioxidant,\" \"anti-inflammatory,\" \"geraniol,\" and \"nanoformulations\" were employed. Google Patents were also examined in order to offer insights into current and upcoming research.</p><p><strong>Results: </strong>The potential of geraniol to treat metabolic disorders, including obesity, diabetes, hyperlipidemia, and cardiovascular illnesses, is thoroughly reviewed in this article. Recent research has demonstrated the lipid-lowering, antioxidant, and anti-inflammatory properties of geraniol as well as its ability to improve endothelial function and reduce oxidative stress in preclinical animals. The paper delves into the various nanoformulations, including liposomes, nanoparticles, and nanoemulsions, which enhance geraniol's therapeutic efficacy and bioavailability, making it a viable option for managing metabolic syndrome.</p><p><strong>Conclusion: </strong>The antioxidant, anti-inflammatory, and lipid-lowering qualities of geraniol make it a promising treatment for metabolic diseases. Its bioavailability along with therapeutic efficacy are increased by nanoformulations, which makes it a compelling option for the treatment of conditions such as neuroinflammation, diabetes, and obesity.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":"3653-3668"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical composition and studying the possible neuroprotective effect of iridoids-rich fraction from Pentas lanceolata leaves using rotenone model of Parkinson's disease in mice.","authors":"Ahmed H Afifi, Heba-Tollah M Sweelam, Marwa E El-Shamarka, Hisham A Orban, Wessam H Elesawy, Maki Nagata, Kuniyoshi Shimizu, Howaida I Abd-Alla","doi":"10.1007/s10787-024-01509-9","DOIUrl":"10.1007/s10787-024-01509-9","url":null,"abstract":"<p><p>Parkinsonism is an age-related neurodegenerative illness that affects motor coordination leading to loss of dopaminergic neurons. Many medications are used for the treatment of Parkinson's disease but are only symptomatic and have a limited effect on the progression of this ailment. Therefore, bioactive compounds which derived from plants have been examined for their ability to improve the neuronal damage and cell death happened in parkinsonian patients. In this study the iridoids-rich fraction isolated from Pentas lanceolata (PIRF) leaves was investigated for its phytoconstituents. Seven iridoids (1-7) and one flavonol diglycoside (8) were isolated, and their chemical structures were achieved by ¹H and ¹³C nuclear magnetic resonance and ESI-MS spectral data. Compound 1 (6β,7β-epoxy-8-epi-splendoside) and 5 (gaertneroside) were isolated for the first time from Pentas genus as well as compound 8 (kaempferol-3-O-robinobioside). The current study aims to investigate the possible anti-parkinsonian effect of PIRF using a rotenone model of Parkinsonism in mice. Behavioural tests (wirehanging, stair and wooden-walking tests) were done to examine the motor coordination in mice after treatment. Biochemical and histopathological examinations for brain striatum in different groups were also evaluated. Results revealed that rotenone-treated mice had poor motor functions described by depletion of dopamine and Ach levels, a significant increase in proinflammatory cytokines, IL-1B, TNF-α and Mcp-1 and oxidative biomarkers with subsequent reduction in antioxidant mediators. Disorganization of striatum, degenerated neurocytes, slight vacuolation, shrunken neurons with pyknotic nuclei and apoptotic cells are displayed by histopathological examinations. Treatment with PIRF ameliorates the neurodegeneration-induced by rotenone in the brain of mice. The anti-parkinsonian effect of PIRF could be attributed to their bioactive constituents of iridoids.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":"3953-3971"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Essential oils: a potential alternative with promising active ingredients for pharmaceutical formulations in chronic wound management.","authors":"Pulukkunadu Thekkeveedu Roshni, Punchappady Devasya Rekha","doi":"10.1007/s10787-024-01571-3","DOIUrl":"10.1007/s10787-024-01571-3","url":null,"abstract":"<p><p>Chronic wound is a major clinical challenge that complicates wound healing, mainly associated with bacterial biofilms. Bacterial burden damages tissue and persists inflammation, failing to granulate, leading to morbidity and mortality. Various therapeutic strategies and approaches have been developed for chronic wound healing in clinical practice. As treating biofilm infection is crucial in chronic wounds, a potent antibiofilm agent, essential oils have been explored extensively for their therapeutic properties and as a replacement for antibiotic therapy. Currently, several studies on essential oils and their active compounds in therapeutics, such as adjunctive therapies, nanotechnology-based treatment and their drug delivery systems, help heal chronic wounds. The antimicrobial, anti-inflammatory and antioxidant properties of essential oils make them distinct and are renowned as natural remedies to improve the healing of infected chronic wounds. Consequently, it accelerates wound closure by reducing inflammation, increasing angiogenesis and tissue regeneration. This review focuses on different essential oils and their active compounds that are exploited for the treatment of biofilm infection, chronic inflammation and wound healing. Thus, an effective novel treatment can be developed to improve the current treatment strategy to overcome multidrug resistance bacteria or antibiotic resistance in various chronic wound infections that support wound healing.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":"3611-3630"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combinatorial intervention with dental pulp stem cells and sulfasalazine in a rat model of ulcerative colitis.","authors":"Riham M Aly, Rehab S Abohashem, Hanaa H Ahmed, Alyaa S Abdel Halim","doi":"10.1007/s10787-024-01532-w","DOIUrl":"10.1007/s10787-024-01532-w","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis is an inflammatory bowel disease (IBD) that involves inflammation of the colon lining and rectum. Although a definitive cure for IBD has not been identified, various therapeutic approaches have been proposed to mitigate the symptomatic presentation of this disease, primarily focusing on reducing inflammation. The aim of the present study was to evaluate the therapeutic potential of combining dental pulp stem cells (DPSCs) with sulfasalazine in an acetic acid-induced ulcerative colitis rat model and to assess the impact of this combination on the suppression of inflammatory cytokines and the regulation of oxidative stress in vivo.</p><p><strong>Methods: </strong>Ulcerative colitis was induced in rats through transrectal administration of 3% acetic acid. The therapeutic effect of combining DPSCs and sulfasalazine on UC was evaluated by measuring the colonic weight/length ratio and edema markers; performing histopathological investigations of colon tissue; performing immunohistochemical staining for NF-κB-P65 and IL-1β; and evaluating oxidative stress and antioxidant indices via ELISA. Moreover, the proinflammatory markers NF-κB-P65, TNF-α and TLR-4 were assessed in colon tissue via ELISA. Furthermore, qRT‒PCR was used to estimate the expression levels of the TLR-4, NF-κB-P65, and MYD88 genes in colon tissue.</p><p><strong>Results: </strong>The investigated macroscopic and microscopic signs of inflammation were markedly improved after the combined administration of sulfasalazine and DPSCs, where a noticeable improvement in histological structure, with an intact mucosal epithelium and mild inflammatory infiltration in the mucosa and submucosa, with slight hemorrhage. The administration of either DPSCs or sulfasalazine, either individually or in combination, significantly reduced ROS levels and significantly increased XOD activity. The immunohistochemical results demonstrated that the combined administration of DPSCs and sulfasalazine attenuated NFκB-p65 and IL-1β expression. Finally, the combined administration of DPSCs and sulfasalazine significantly downregulated MyD88, NF-κB and TLR4 gene expression.</p><p><strong>Conclusions: </strong>Cotreatment with DPSCs and sulfasalazine had synergistic effects on ulcerative colitis, and these effects were relieved.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":"3863-3879"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preoperative versus postoperative nonsteroidal anti-inflammatory drugs in femoroacetabular impingement patients undergoing hip arthroscopy surgery: analgesic effect, joint function, patients' satisfaction, and quality of life.","authors":"Zhiyuan Guo, Guangfei Liu, Weibin Li, Shouliang Lu, Ye Zhao, Lu Wang, Cai Cheng","doi":"10.1007/s10787-024-01540-w","DOIUrl":"10.1007/s10787-024-01540-w","url":null,"abstract":"<p><strong>Background: </strong>Nonsteroidal anti-inflammatory drugs (NSAIDs) have analgesic effects on femoroacetabular impingement (FAI) patients undergoing hip arthroscopy surgery (HAS). However, the influence of medication time on the analgesic effect of NSAIDs is uncertain. This study aimed to compare the analgesic effect, joint function, quality of life (QoL), and patients' satisfaction between preoperative and postoperative NSAIDs in these patients.</p><p><strong>Methods: </strong>In this prospective, observational study, 165 FAI patients undergoing HAS with NSAIDs (celecoxib, meloxicam, and nimesulide) for analgesia were divided into preoperative (PRE-A) and postoperative analgesia (POST-A) groups according to their actual medication.</p><p><strong>Results: </strong>The visual analog scale (VAS) pain scores on the 1st (P < 0.001) and 3rd (D3) (P = 0.015) days after the operation were lower in the PRE-A group versus the POST-A group but not preoperatively (P = 0.262) or on the 7th day after the operation (D7) (P = 0.302). The proportion of patients receiving rescue analgesia decreased in the PRE-A group versus POST-A group (P = 0.041). However, the modified Harris hip score (mHHS), proportion of patients with an mHHS ≥ 70, and EuroQol-5-dimensional score at preoperative, 1st month (M1), and 3rd month (M3) after the operation were similar between the groups (all P > 0.050). The VAS score on D7 was greater in the PRE-A group compared to the POST-A group (P = 0.014), but the scores at M1 and M3 and the satisfaction and very satisfaction rates at D7, M1, and M3 did not differ between the groups (all P > 0.050). Subgroup analysis revealed that the type of NSAID did not affect most outcomes.</p><p><strong>Conclusion: </strong>Preoperative NSAIDs elevate analgesic effect and patients' satisfaction, but not joint function or QoL compared to postoperative NSAIDs in FAI patients undergoing HAS.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":"3679-3686"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D: A key player in COVID-19 immunity and lessons from the pandemic to combat immune-evasive variants.","authors":"Hussein Sabit, Shaimaa Abdel-Ghany, Mahmoud S Abdallah, Osama Abul-Maaty, Ahmed I Khoder, Nabil A Shoman, Mohamed Sameh Farrag, Pavel Martasek, Ayman M Noreddin, Mahmoud Nazih","doi":"10.1007/s10787-024-01578-w","DOIUrl":"10.1007/s10787-024-01578-w","url":null,"abstract":"<p><p>As of the 7^th of July 2024, 775,754,322 confirmed cases of COVID-19, including 7,053,902 deaths worldwide, had been reported to the WHO (World Health Organization). Nevertheless, untill the 15^th of July 2024, a total of 13,578,710,228 vaccine doses had been administered, with almost no country spared from COVID-19 attacks. The pathophysiology of this virus is complicated, and several symptoms require a deep understanding of the actual mechanisms. It is unclear why some patients develop severe symptoms while others do not, although literature suggests a role for vitamin D. Vitamin D plays a crucial role in the infection or in ameliorating the severity of symptoms. The mechanism of action of vitamin D and vitamin D deficiency (VDD) is well understood. VDD is associated with increased hospitalization of severely ill patients and increased levels of COVID-19-caused mortality. Recent studies suggest that vitamin D levels and genetic variations in the vitamin D receptor (VDR) gene significantly impact the severity and outcomes of COVID-19, especially in the infections caused by Delta and Omicron variants. Furthermore, VDD causes immune system dysregulation upon infection with SARS-CoV-2, indicating that vitamin D sufficiency is crucial in fighting against COVID-19 infection. The therapeutic effect of vitamin D raises interest in its potential role as a prophylactic and treatment adjunct. We evaluate the immunomodulatory effects of vitamin D and its ability to enhance the efficacy of new antiviral drugs like molnupiravir and paxlovid against SARS-CoV-2. This review discusses the role of vitamin D sufficiency and VDD in COVID-19 initiation and progression, emphasizing the molecular mechanisms by which vitamin D exerts its actions as a proactive step for the next pandemic. However, there is still no clear evidence of vitamin D's impact on prevention and treatment, leading to contradictory findings. Therefore, large-scale randomized trials are required to reach a definitive conclusion. A bibliometric analysis of publications related to vitamin D, immunity, and COVID-19 revealed a significant increase in research activity in this area, particularly in 2020-2024, underscoring the growing recognition of vitamin D's potential role in the context of the pandemic.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":"3631-3652"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1, 2-benzothiazin-3-carboxamide 1,1-dioxide, a rapid-acting meloxicam formulation, for analgesia after orthopaedic surgery under general anaesthesia: a randomized controlled trial.","authors":"Yingyong Zhou, Yan Jiang, Kaiming Duan, Qiongcan Li, Mengchang Yang, Qing Lei, Mingsheng Bao, Guijie Xie, Jie Sun, Liang Chen, Hongmei Zhou, Yanzhuo Zhang, Yidan Huang, Yuanli Gao, Liu Han, Han Lin, Yafeng Zhang, Yongquan Chen, Ling Zhao, Shuangtao Chen, Chun Chen, Haitao Jiang, Jinghua Ren, Wen Ouyang, Shaowen Tang, Saiying Wang","doi":"10.1007/s10787-024-01575-z","DOIUrl":"10.1007/s10787-024-01575-z","url":null,"abstract":"<p><strong>Background: </strong>Postoperative pain management is one of the most challenging treatments after orthopaedic surgery, and improved medical treatment options are urgently needed. This study aimed to evaluate the efficacy and safety of 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1, 2-benzothiazin-3-carboxamide 1,1-dioxide (QP001) for moderate to severe pain following orthopaedic surgery.</p><p><strong>Methods: </strong>This randomized clinical trial enlisted patients experiencing moderate to severe pain following orthopaedic surgery in 20 hospitals in China. We allocated randomly 132 participants to receive 30 mg QP001 and 66 participants to receive 0.9% saline pre-surgery. The primary efficacy outcome was the total morphine consumption within 24 h.</p><p><strong>Results: </strong>The total morphine consumption in the QP001 group, versus placebo group, was significantly lower over the following 24 h [12.53 (10.51) vs. 26.13 (13.98), P < 0.001]. The total morphine consumption in the QP001 group, versus placebo group, was also significantly decreased over the following 48 h (P < 0.001). The QP001 group, versus placebo, showed a significant decrease in the effective pressing times of the analgesic pump, morphine relief analgesia ratio over the 24 h and 48 h periods and the area under the curve for pain intensity-time as well as a significant prolonged in the time of first pressing the analgesic pump and the time of first morphine rescue analgesia (P < 0.001). The QP001 groups, versus placebo, show no significant difference in adverse events, but the incidence of adverse drug reactions decreased (59.4% vs. 75.8%, P = 0.023).</p><p><strong>Conclusion: </strong>QP001 provides analgesia and reduces opioid consumption in patients with moderate to severe pain after orthopaedic surgery, with a favorable safety profile.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":"3799-3808"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methotrexate for osteoarthritis: a systematic review meta-analysis of randomized controlled trials.","authors":"Ivo Queiroz, Túlio Pimentel, Mariano Gallo Ruelas, Arthur Henrique Tavares, Lucas M Barbosa, Maria L R Defante, Giovanna N Leandro, Arthur Ribeiro Monteiro, Fernando Nunes Pimentel","doi":"10.1007/s10787-024-01604-x","DOIUrl":"10.1007/s10787-024-01604-x","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA) is a common joint disorder causing pain and stiffness, with limited effective treatment options. Methotrexate, known for its anti-inflammatory properties in rheumatoid arthritis, is being explored as a treatment for OA. This study evaluates Methotrexate's efficacy compared to placebo in reducing OA symptoms, such as stiffness in the knee and hand, and its impact on pain, physical function.</p><p><strong>Methods: </strong>We systematically searched PubMed, Google Scholar, Embase, Web of Science, and Cochrane databases for randomized controlled trials (RCTs), analyzing the efficacy of Methotrexate compared to placebo in patients with OA. We pooled risk ratios (RR) for binary outcomes. For continuous outcomes, we used standard mean difference (SMD) and mean difference (MD) with 95% confidence intervals (CI). Outcomes included were related to knee and hand pain, knee stiffness, and similar outcomes. We used R version 4.4.1 for statistical analyses. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach evaluated the quality of evidence.</p><p><strong>Results: </strong>This analysis included 5 RCTs comprising 465 patients, of whom 229 were randomized to Methotrexate. The age ranged from 52.4 to 67.5 years among studies. Compared with placebo, Methotrexate significantly reduced knee and hand stiffness at the end of follow-up (SMD - 0.36; 95% CI - 0.57 to - 0.15; p< 0.01), knee and hand stiffness at 6 months of follow-up (SMD - 0.48; 95% CI - 0.70 to - 0.27; p< 0.01).</p><p><strong>Conclusion: </strong>Methotrexate significantly reduced knee stiffness in both knee and hand OA. However, current literature might be underpowered, more robust RCTs are necessary to validate these findings.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shedding light on microglial dysregulation in Alzheimer's disease: exploring molecular mechanisms and therapeutic avenues.","authors":"Vanshu Bhardwaj, Sneha Kumari, Rishika Dhapola, Prajjwal Sharma, Samir Kumar Beura, Sunil Kumar Singh, Balachandar Vellingiri, Dibbanti HariKrishnaReddy","doi":"10.1007/s10787-024-01598-6","DOIUrl":"https://doi.org/10.1007/s10787-024-01598-6","url":null,"abstract":"<p><p>Alzheimer's disease (AD) stands out as the foremost prevalent neurodegenerative disorder, characterized by a complex etiology. Various mechanisms have been proposed to elucidate its onset, encompassing amyloid-beta (Aβ) toxicity, tau hyperphosphorylation, oxidative stress and reactive gliosis. The hallmark of AD comprises Aβ and tau aggregation. These misfolded protein aggregates trigger the activation of glial cells, primarily microglia. Microglial cells serve as a major source of inflammatory mediators and their cytotoxic activation has been implicated in various aspects of AD pathology. Activated microglia can adopt M1 or M2 phenotypes, where M1 promotes inflammation by increasing pro-inflammatory cytokines and M2 suppresses inflammation by boosting anti-inflammatory factors. Overexpressed pro-inflammatory cytokines include interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in adjacent brain regions. Furthermore, microglial signaling pathways dysregulated in AD are myeloid differentiation primary-response protein 88 (Myd 88), colony-stimulating factor-1 receptor (CSF1R) and dedicator of cytokinesis 2 (DOCK2), which alter the physiology. Despite numerous findings, the causative role of microglia-mediated neuroinflammation in AD remains elusive. This review concisely explores cellular and molecular mechanisms of activated microglia and their correlation with AD pathogenesis. Additionally, it highlights promising therapeutics targeting microglia modulation, currently undergoing preclinical and clinical studies, for developing effective treatment for AD.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating diclofenac's risks in COVID-19: strategies for mitigating adverse outcomes.","authors":"Chia Siang Kow, Dinesh Sangarran Ramachandram, Syed Shahzad Hasan, Kaeshaelya Thiruchelvam","doi":"10.1007/s10787-024-01601-0","DOIUrl":"https://doi.org/10.1007/s10787-024-01601-0","url":null,"abstract":"<p><p>The use of nonsteroidal anti-inflammatory drugs (NSAIDs), particularly diclofenac, during the COVID-19 pandemic has raised concerns due to its potential to worsen disease progression. This commentary evaluates key risks associated with diclofenac and highlights the critical role of pharmacists in mitigating adverse outcomes through careful medication management and patient education. Diclofenac poses unique risks due to its ability to generate reactive oxygen species (ROS), leading to oxidative stress and mitochondrial dysfunction. In COVID-19, a disease characterized by hyperinflammation, these effects may exacerbate systemic inflammation, contributing to severe outcomes. Moreover, diclofenac's known association with increased cardiovascular risks, such as myocardial infarction and stroke, is especially concerning in patients with COVID-19, who are predisposed to thrombotic complications. The drug's hepatotoxic potential adds another layer of concern, particularly in patients with pre-existing liver dysfunction or those at higher risk due to COVID-19-related liver involvement. Pharmacists play a pivotal role in addressing these risks by conducting thorough medication reviews and assessing patient-specific risk factors. They can guide clinicians and patients toward safer alternatives, such as ibuprofen or naproxen, which demonstrate a lower oxidative and cardiovascular burden. Patient education is equally critical; pharmacists should counsel individuals on potential adverse effects of diclofenac, such as cardiovascular symptoms, renal dysfunction, and liver complications, while advising on lifestyle modifications and adjunctive therapies to reduce NSAID dependence. Additionally, pharmacists contribute to pharmacovigilance by monitoring patients for adverse drug reactions and reporting safety concerns to improve NSAID usage guidelines during the pandemic. By adopting a personalized approach to NSAID therapy, pharmacists can minimize risks and enhance patient safety, ultimately improving outcomes in the management of COVID-19 and other inflammatory conditions. This underscores their indispensable role in optimizing care during complex clinical scenarios.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}