Annals of medicine最新文献

{"title":"A systematic review of the clinical characteristics and course of atrioventricular blocks in hyperthyroidism.","authors":"Fateen Ata, Haseeb Ahmad Khan, Hassan Choudry, Adeel Ahmad Khan, Shuja Tahir, Tiago Lemos Cerqueira, Ben Illigens","doi":"10.1080/07853890.2024.2365405","DOIUrl":"10.1080/07853890.2024.2365405","url":null,"abstract":"<p><strong>Background: </strong>Atrioventricular block (AVB) is rare in hyperthyroidism (HTH). Little is known about the true prevalence, clinical course, optimal management, and outcomes of different types of AVBs in patients with HTH. To address these uncertainties, we aimed to conduct a systematic review by combining the available literature to provide more meaningful data regarding AVBs in HTH.</p><p><strong>Methods: </strong>We systematically searched PubMed, Scopus, Embase, and Google Scholar for articles reporting patients who developed AVB in the context of HTH. Data were analysed in STATA 16. The main outcomes included types of AVB, frequency of pacemaker insertion, and resolution of AVB. The systematic review is registered with the International Prospective Register of Systematic Reviews (PROSPERO) with the identification number CRD42022335598.</p><p><strong>Results: </strong>A total of 56 studies (39 case reports, 12 case series, 3 conference abstracts, 1 retrospective study, and 1 prospective observational study) with 87 patients were included in the analysis, with a mean age of 39.1 ± 17.6 years. Females constituted 65.7% (<i>n</i> = 48) of the cohort. Complete heart block (CHB) was the most commonly reported AVB (<i>N</i> = 45, 51.7%), followed by first-degree AVB (16.1%) and second-degree AVB (14.9%). Overall, 21 patients underwent pacing. A permanent pacemaker was inserted in one patient with second-degree AVB and six patients with CHB. Mortality was reported in one patient with CHB. The clinical course and management of HTH and AVBs did not differ in patients with CHB or lower-degree blocks. Apart from lower rates of goitre and more use of carbimazole in those who underwent pacing, no differences were found when compared to the patients managed without pacing.</p><p><strong>Conclusion: </strong>Current data suggest that CHB is the most common type of AVB in patients with HTH. Most patients can be managed with anti-thyroid management alone. Additionally, whether pacemaker insertion alters the clinical outcomes needs further exploration.</p>","PeriodicalId":93874,"journal":{"name":"Annals of medicine","volume":"56 1","pages":"2365405"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11195459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141433576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of interleukin-6 with sarcopenia and its components in older adults: a systematic review and meta-analysis of cross-sectional studies.","authors":"Jie Ding, Guangyue Yang, Wen Sun, Yifei Li, Ning Wang, Jiening Wang, Yongfang Zhao","doi":"10.1080/07853890.2024.2384664","DOIUrl":"10.1080/07853890.2024.2384664","url":null,"abstract":"<p><strong>Background: </strong>Observational studies have documented increased serum IL-6 levels in elderly individuals afflicted with sarcopenia. Nevertheless, the relationship between serum IL-6 concentrations and sarcopenia prevalence in the aging population is yet to be defined.</p><p><strong>Methods: </strong>We executed a systematic review and meta-analysis of cross-sectional studies that scrutinized serum IL-6 levels in older adults with and without sarcopenia. Relevant studies were sourced from PubMed, Scopus, Embase, Cochrane Library, and Web of Science from inception until 10 September 2023. The standard mean differences (SMDs) in serum IL-6 levels between studies were synthesized using a random-effects model. To examine the influence of demographic and clinical factors on these outcomes, we performed subgroup analyses and meta-regression, focusing on variables such as sex, age, and body mass index (BMI). We also assessed the relationship between serum IL-6 levels and the defining components of sarcopenia: muscle mass, muscle strength, and physical performance. We used Fisher's Z transformation to standardize the interpretation of effect sizes from these relationships. The transformed values were then converted to summary correlation coefficients (r) for a clear and unified summary of the results.</p><p><strong>Results: </strong>We included twenty-one cross-sectional studies involving 3,902 participants. Meta-analysis revealed significantly elevated serum IL-6 levels in older adults with sarcopenia compared with those without sarcopenia (SMD = 0.31; 95% CI 0.18, 0.44). The difference was highly pronounced in the subgroups of male and those with female percentage below 50% or a mean BMI below 24 kg/m². Serum IL-6 levels were inversely correlated with muscle mass (summary r = -0.18; 95% CI -0.30, -0.06), but not with handgrip strength (summary r = -0.10; 95%CI: -0.25, 0.05) or gait speed (summary r = -0.09; 95%CI: -0.24, 0.07).</p><p><strong>Conclusions: </strong>This meta-analysis establishes a link between increased serum IL-6 levels and sarcopenia in the elderly, particularly in relation to decreased muscle mass.</p>","PeriodicalId":93874,"journal":{"name":"Annals of medicine","volume":"56 1","pages":"2384664"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring intimacy and family planning in Inflammatory Bowel Diseases: a qualitative study.","authors":"Kristyna Gabova, Hana Bednarikova, Zdenek Meier, Peter Tavel","doi":"10.1080/07853890.2024.2401610","DOIUrl":"10.1080/07853890.2024.2401610","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory bowel diseases (IBD), comprising ulcerative colitis and Crohn's disease, have a profound impact on people's lives. This study aims to investigate the perceived impact of IBD on sexual life and family planning to enhance understanding of the interplay between IBD, sexuality, intimacy and family planning to foster a better quality of life for those living with the condition.</p><p><strong>Materials and methods: </strong>The study used the qualitative DIPEx method (Database of Personal Experiences of Health and Illness) developed by the Health Experiences Research Group at the University of Oxford, standardized for the Czech Republic. Semi-structured interviews with 36 participants (19 with Crohn's disease, 17 with ulcerative colitis) were conducted, employing open coding and thematic analysis. The maximum variation sampling was utilized, considering various factors, such as disease stage, medications, treatments, age, age at diagnosis and sociodemographic characteristics.</p><p><strong>Results: </strong>Five main topics emerged: sexual activity, body image and discomfort, partner relationships, family planning, and the role of gastroenterologists in family planning decisions. Participants' perceptions of sexuality varied, with some experiencing reduced sexual activity during acute phases of the disease. IBD had contrasting effects on partner relationships, and family planning was an important concern, with women valuing support and collaboration with their gastroenterologists in making pregnancy decisions. Information dissemination and open communication from professionals are highly needed.</p><p><strong>Conclusions: </strong>This is the first study concerning the sexuality and family planning of people with IBD in the Czech Republic. It highlights the need for information and open communication from professionals.</p>","PeriodicalId":93874,"journal":{"name":"Annals of medicine","volume":"56 1","pages":"2401610"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astilbin exerts anti-hypersensitivity by regulating metabolic demand and neuronal activity in rodent model of neuropathic pain.","authors":"Qiru Wang, Dongxia Duan, Chao Luo, Jinlu Huang, Jinbao Wei, Yang Zhang, Ke Zhang, Tong Zhou, Wei Wang, Shaoxin Yang, Le Ma","doi":"10.1080/07853890.2024.2396561","DOIUrl":"10.1080/07853890.2024.2396561","url":null,"abstract":"<p><strong>Objective: </strong><i>Astilbe chinensis</i>, is a traditional Chinese medicine commonly employed for pain management. However, its primary active ingredient remains a subject of debate.</p><p><strong>Methods: </strong>Spinal nerve ligation (SNL) and formalin-induced pain models were employed. Network pharmacology and bioinformatics were utilized to identify targets. Verification was performed through spinal cord double immunofluorescence staining, quantitative PCR and whole-cell recording techniques.</p><p><strong>Results: </strong>In experiments conducted on neuropathic rats, both systemic and intrathecal administration of astilbin, an essential constituent, exhibited a noteworthy and dose-dependently decrease in chronic and acute pain behaviours. The ED₅₀ value, which represents the dose at which 50% effectiveness is achieved, was measure at 7.59 μg, while the <i>E</i>_max value, indicating the maximum attainable effect, was found to be 60% of the maximal possible effect (% MPE). Forty-two shared targets were identified, enriching the metabolic and synaptic pathways in the network pharmacology analysis, as confirmed by transcriptomic analysis. Weighted gene co-expression network analysis (WGCNA) revealed a strong correlation between the anti-nociceptive effects of astilbin and neuronal metabolic processes. Spinal functional ultrasound (FUS) analysis indicated increased spinal blood flow intensity and changes in metabolism-related enzyme activity, including stearoyl-CoA desaturase (<i>Scd</i>), 17beta-hydroxysteroid dehydrogenase (<i>Hsd17b7</i>) and sterol 14alpha-demethylase (<i>Cyp51</i>) in neuropathic rats, pretreatment with astilbin decreased formalin-induced blood flow in acute pain. Bath application of astilbin dose-dependently inhibited neuronal activity by reducing the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) without affecting miniature inhibitory postsynaptic currents (mIPSCs).</p><p><strong>Conclusions: </strong>In summary, this study provides evidence that astilbin alleviates pain by modulating neuronal metabolic processes and synaptic homeostasis.</p>","PeriodicalId":93874,"journal":{"name":"Annals of medicine","volume":"56 1","pages":"2396561"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11616750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating fatigue and excessive daytime sleepiness: a comparative analysis of prevalence and correlating factors in interstitial lung disease patients and healthy controls.","authors":"Xiaoli Ouyang, Qinxue Shen, Shiting Zhou, Pei Zhou, Min Song, Ting Guo, Wei Guo, Yi Zhang, Hong Peng","doi":"10.1080/07853890.2024.2398729","DOIUrl":"10.1080/07853890.2024.2398729","url":null,"abstract":"<p><strong>Introduction: </strong>Fatigue and excessive daytime sleepiness (EDS) frequently affect interstitial lung disease (ILD) patients, while studies are limited. The study aims to determine the prevalence and contributing factors of fatigue and EDS in ILD patients.</p><p><strong>Methods: </strong>This was a cross-sectional study. Consecutive patients diagnosed with ILD at the Second Xiangya Hospital of Central South University were recruited, and healthy volunteers were recruited as controls. Fatigue Assessment Scale and Epworth Sleepiness Scale scores were the basis for judging fatigue and EDS. The prevalence of fatigue and EDS between ILD patients and healthy volunteers were compared, and the differences in clinical characteristics between ILD patients with and without fatigue/EDS were analyzed. Binary logistic regression was used to analyze the correlation factors of fatigue and EDS.</p><p><strong>Results: </strong>In this study, 92 healthy volunteers and 108 ILD patients were recruited. The prevalence of fatigue and EDS was higher in ILD patients than in healthy volunteers (40.7% vs 9.8%, 35.2% vs 14.1%). ILD patients with fatigue showed significantly worse pulmonary diffusion function and exercise tolerance, alongside reduced quality of life, and increased instances of EDS, anxiety, and depression. Patients with EDS were older than non-EDS patients (68.5 vs 61.5 years; <i>p</i> = 0.038) and had a higher prevalence of fatigue and depression, along with decreased quality of life. Multivariable logistic regression identified chest pain/oppression and diminished exercise capacity as factors linked to fatigue, and age over 60 years and diminished exercise capacity as factors associated with EDS.</p><p><strong>Conclusion: </strong>ILD patients experience a higher prevalence and more severe impact of fatigue and EDS than healthy individuals, with associated factors including chest pain, diminished exercise capacity, and age. Pulmonary rehabilitation and evaluation and intervention of factors associated with fatigue and EDS such as pain, and diminished exercise capacity in ILD patients may help to improve the quality of life.</p>","PeriodicalId":93874,"journal":{"name":"Annals of medicine","volume":"56 1","pages":"2398729"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11616753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics profiling highlights karyopherin subunit alpha 2 as a promising biomarker for prognosis and immunotherapy respond in pediatric and adult adrenocortical carcinoma.","authors":"Yihao Chen, Shumin Fang, Chuanfan Zhong, Shanshan Mo, Yongcheng Shi, Xiaohui Ling, Fengping Liu, Weide Zhong, Junhong Deng, Zhong Dong, Jiahong Chen, Jianming Lu","doi":"10.1080/07853890.2024.2397092","DOIUrl":"10.1080/07853890.2024.2397092","url":null,"abstract":"<p><strong>Purpose: </strong>Adrenocortical carcinoma (ACC) afflicts both pediatric and adult populations and is characterized by dismal prognosis and elevated mortality. Given the inconsistent therapeutic benefits and significant side effects associated with the conventional chemotherapy agent, mitotane, and the nascent stage of immunotherapy and targeted treatments, there is an urgent need to identify novel prognostic biomarkers and therapeutic targets in ACC.</p><p><strong>Methods: </strong>Utilizing multi-omic datasets from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), we employed Weighted Gene Co-expression Network Analysis (WGCNA), Cox regression, Receiver Operating Characteristic (ROC) curves, and survival analyses to sift for potential prognostic biomarkers. We subsequently validated these findings through immunohistochemistry and cell assays, and delved into the biological role of KPNA2 in ACC through functional enrichment analysis, mutational landscape, and immune cell infiltration.</p><p><strong>Results: </strong>A total of 77 progression-associated genes with aberrant chromosomal accessibility were discerned within the TCGA-ACC dataset. By integrating ROC and Cox regression from GEO datasets, KPNA2 emerged as an independent risk factor portending poor outcomes in ACC. ATAC-seq analysis revealed attenuated chromatin accessibility of KPNA2 in cases with unfavorable prognosis. Immunohistochemistry corroborated elevated KPNA2 expression, which was linked to enhanced proliferation and invasion. Elevated KPNA2 levels were found to activate oncogenic pathways while simultaneously suppressing immunological responses. Immune infiltration analysis further revealed a decrement in CD8+ T-cell infiltration in KPNA2-high cohorts.</p><p><strong>Conclusion: </strong>This study demonstrates the clinical and biological significance of KPNA2 in ACC and suggests that KPNA2 could serve as a promising biomarker for predicting prognosis and immunotherapeutic responses in pediatric and adult ACC patients.</p>","PeriodicalId":93874,"journal":{"name":"Annals of medicine","volume":"56 1","pages":"2397092"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11616749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eosinophilic inflammation: a key player in COPD pathogenesis and progression.","authors":"Yueh-Lun Lee, Didik Setyo Heriyanto, Fara Silvia Yuliani, Vincent Laiman, Lina Choridah, Kang-Yun Lee, Jer-Hwa Chang, Kian Fan Chung, Li-Te Chang, Ta-Yuan Chang, Xiao-Yue Chen, Syue-Wei Peng, Kai-Jen Chuang, Hsiao-Chi Chuang","doi":"10.1080/07853890.2024.2408466","DOIUrl":"https://doi.org/10.1080/07853890.2024.2408466","url":null,"abstract":"<p><strong>Background: </strong>Chronic Obstructive Pulmonary Disease (COPD) remains a significant public health challenge due to its high morbidity and mortality rates. Emerging research has identified eosinophilic inflammation as a crucial factor in the pathogenesis and exacerbation of COPD, warranting a detailed exploration of its underlying mechanisms and therapeutic implications.</p><p><strong>Objective: </strong>This review aims to elucidate the role of eosinophils in COPD, focusing on their contribution to airway remodeling, exacerbation frequency, and the inflammatory cascade.</p><p><strong>Methods: </strong>We conducted a comprehensive literature review of recent studies that discuss the pathophysiological role of eosinophils in COPD and the clinical outcomes associated with modulating eosinophilic activity.</p><p><strong>Results: </strong>Eosinophils contribute to COPD progression by releasing cytotoxic proteins and cytokines that intensify the inflammatory response and airway alterations. Targeting specific eosinophil-related cytokines with monoclonal antibodies or receptor antagonists may potentially reduce eosinophil counts, mitigate exacerbations, and improve patient outcomes.</p><p><strong>Conclusion: </strong>Understanding eosinophilic involvement in COPD can facilitate the development of precision medicine approaches, offering more tailored and effective treatment options. Future research should continue to focus on the integration of eosinophil biomarkers in clinical practice to enhance therapeutic decisions and management strategies for COPD patients.</p>","PeriodicalId":93874,"journal":{"name":"Annals of medicine","volume":"56 1","pages":"2408466"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The curious physician: exploring the role of curiosity in professionalism, patient care, and well-being.","authors":"Till Johannes Bugaj, Tim Alexander Schwarz, Hans-Christoph Friederich, Christoph Nikendei","doi":"10.1080/07853890.2024.2392887","DOIUrl":"10.1080/07853890.2024.2392887","url":null,"abstract":"<p><strong>Introduction: </strong>Curiosity is a fundamental human trait that drives learning and exploration. However, research on curiosity has received little attention in the medical field, despite its potential to enhance knowledge acquisition, work performance, and psychosocial well-being. This study aimed to address part of this gap by investigating physicians' perspectives on their personal experiences with curiosity and its role in their professional practice and medical training.</p><p><strong>Materials and methods: </strong>This qualitative study was conducted with 12 physicians from the University of Heidelberg Medical Hospital. Participants were contacted randomly <i>via</i> email and invited to participate in the study. Data were collected through semi-structured interviews between September 2019 and February 2020. The authors employed Mayring's approach, which denotes a qualitative content analysis method characterized by its systematic and rule-guided approach to analyzing textual data, aiming to extract meaningful insights and patterns or themes. The identified themes were linked to overall categories to draw conclusions from the data.</p><p><strong>Results: </strong>The interviewees highlighted three main areas regarding curiosity's importance [1]: as a driving force for (lifelong) education [2], in building empathetic physician-patient relationships, and [3] as a core quality of a good researcher. They primarily linked curiosity with positive emotions, while the non-expression of curiosity was associated with dissatisfaction, boredom, and exhaustion. Factors such as heavy workloads, time constraints, stress, and lack of autonomy inhibit their curiosity, while varied activities, professional exchange with colleagues, and exposure to new challenges foster it. Physicians' perspectives on the link between burnout and curiosity were not consistent. Interestingly, some viewed curiosity as protective against burnout, while others saw excessive curiosity as a potential source of frustration and burnout.</p><p><strong>Conclusion: </strong>This study represents the first attempt to explore physicians' perspectives on curiosity in medicine. The findings highlight the potential importance of curiosity in shaping medical professionalism and improving patient care. However, its pursuit is hampered by the challenging working conditions faced by doctors, suggesting a need for enhanced support and cultivation.</p>","PeriodicalId":93874,"journal":{"name":"Annals of medicine","volume":"56 1","pages":"2392887"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regarding: \"Psychotherapeutic and pharmacological agents for post-traumatic stress disorder with sleep disorder: network meta-analysis\".","authors":"Kun Xu, Yuan Liu, Hua Zhao, Yuejun Zhou","doi":"10.1080/07853890.2024.2408459","DOIUrl":"10.1080/07853890.2024.2408459","url":null,"abstract":"","PeriodicalId":93874,"journal":{"name":"Annals of medicine","volume":"56 1","pages":"2408459"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic analysis based on bioinformatics and experimental validation identifies <i>Alox5</i> as a novel therapeutic target of quercetin for sepsis.","authors":"Chu-Yun Liu, Yu-Shen Yang, Meng-Qin Pei, Yan Zhang, Wei-Can Chen, Jin-Wei Liang, He-Fan He","doi":"10.1080/07853890.2024.2411015","DOIUrl":"https://doi.org/10.1080/07853890.2024.2411015","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigated the molecular mechanism of quercetin in the treatment of sepsis using network pharmacological prediction and experimentation.</p><p><strong>Methods: </strong>Hub genes were identified by intersecting the differentially expressed genes (DEGs) of the GSE131761 and GSE9960 databases with genes from the hub modules of Weighted Gene Co-Expression Network Analysis (WGCNA), targets of quercetin, and ferroptosis. Subsequently, in order to determine the functional characteristics and molecular link of hub gene obtained above, we redetermined the hub-DEGs in GSE131761 according to high or low hub gene expression. Afterward, the main pathways of enrichment analysis were validated using these hub-DEGs. Finally, an experiment was conducted to validate the findings.</p><p><strong>Results: </strong>By intersecting 1415 DEGs in GSE131761, 543 DEGs in GSE9960, 5784 key modular genes, 470 ferroptosis-related genes, and 154 quercetin-related genes, we obtained one quercetin-related gene, <i>Alox5</i>. Subsequently, 340 hub-DEGs were further validated according to high or low <i>Alox5</i> expression. The results of the enrichment analysis revealed that hub-DEGs were mainly associated with inflammation and the immune response. Immune infiltration analysis showed that higher expression of <i>Alox5</i> was related to macrophage infiltration and could be a predictor of diagnosis in patients with sepsis. The expression pattern of <i>Alox5</i> was then depicted and the upregulation of <i>Alox5</i> in the vital organs of septic mice was further demonstrated. <i>In vitro</i> and <i>in vivo</i> experiments showed that upregulation of <i>Alox5</i> and inflammation-related cytokines induced by sepsis could be inhibited by quercetin (<i>p</i> < 0.05).</p><p><strong>Conclusions: </strong><i>Alox5</i> may be involved in the occurrence and development of multi-organ functional disturbances in sepsis and is a reliable target of quercetin against sepsis.</p>","PeriodicalId":93874,"journal":{"name":"Annals of medicine","volume":"56 1","pages":"2411015"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11469444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}