Experimental and molecular pathology最新文献

Gut-lung Axis mediates asthma pathogenesis: Roles of dietary patterns and their impact on the gut microbiota

IF 2.8 4区医学

Experimental and molecular pathology Pub Date : 2025-04-06 DOI: 10.1016/j.yexmp.2025.104964

Yanbo Liu, Ying Zhou, Haoyue Zhang, Kaixuan Zhao, Dong Yang

{"title":"Gut-lung Axis mediates asthma pathogenesis: Roles of dietary patterns and their impact on the gut microbiota","authors":"Yanbo Liu, Ying Zhou, Haoyue Zhang, Kaixuan Zhao, Dong Yang","doi":"10.1016/j.yexmp.2025.104964","DOIUrl":"10.1016/j.yexmp.2025.104964","url":null,"abstract":"<div><div>The gut-lung axis, a vital signaling network linking the gastrointestinal and pulmonary systems, regulates immune responses and the progression of respiratory diseases. Nutritional components can modulate the gut microbiome and regulate the synthesis of critical intestinal microbial metabolites, which are essential for maintaining immune homeostasis and supporting respiratory health. Conversely, poor dietary habits exacerbate asthma and other respiratory conditions through the modulation of systemic inflammation and immune responses. Dietary interventions, such as the Mediterranean diet, are reported to restore microbial balance and improve respiratory health by increasing the production of anti-inflammatory metabolites, potentiating immune responses, and preserving epithelial barrier integrity. In contrast, Western dietary patterns, which are characterized by high fat and low fiber intake, disrupt microbial diversity, resulting in increased levels of pro-inflammatory metabolites that aggravate airway inflammation and asthma severity. This review aimed to elucidate the mechanisms underlying the regulatory effects of gut microbes and their metabolites on asthma. Additionally, previous findings related to the gut-lung axis have been summarized, providing insights into potential therapeutic strategies for asthma management.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"142 ","pages":"Article 104964"},"PeriodicalIF":2.8,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advances in sepsis research: Insights into signaling pathways, organ failure, and emerging intervention strategies 败血症研究进展：洞察信号通路、器官衰竭和新兴干预策略

IF 2.8 4区医学

Experimental and molecular pathology Pub Date : 2025-03-25 DOI: 10.1016/j.yexmp.2025.104963

Yehua Li , Siying Ren , Shen’ao Zhou

{"title":"Advances in sepsis research: Insights into signaling pathways, organ failure, and emerging intervention strategies","authors":"Yehua Li , Siying Ren , Shen’ao Zhou","doi":"10.1016/j.yexmp.2025.104963","DOIUrl":"10.1016/j.yexmp.2025.104963","url":null,"abstract":"<div><div>Sepsis is a complex syndrome resulting from an aberrant host response to infection. A hallmark of sepsis is the failure of the immune system to restore balance, characterized by hyperinflammation or immunosuppression. However, the net effect of immune system imbalance and the clinical manifestations are highly heterogeneous among patients. In recent years, research interest has shifted from focusing on the pathogenicity of microorganisms to the molecular mechanisms of host responses which is also associated with biomarkers that can help early diagnose sepsis and guide treatment decisions. Despite significant advancements in medical science, sepsis remains a major challenge in healthcare, contributing to substantial morbidity and mortality worldwide. Further research is needed to improve our understanding of this condition and develop novel therapies to improve outcomes for patients with sepsis. This review explores the related signal pathways of sepsis and underscores recent advancements in understanding its mechanisms. Exploration of diverse biomarkers and the emerging concept of sepsis endotypes offer promising avenues for precision therapy in the future.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"142 ","pages":"Article 104963"},"PeriodicalIF":2.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of lactate and lactylation in ischemic cardiomyopathy: Mechanisms and gene expression

IF 2.8 4区医学

Experimental and molecular pathology Pub Date : 2025-03-01 DOI: 10.1016/j.yexmp.2025.104957

Mei Zhang , Xue Kong , Chenlu Wu , Jiuhong Li , Hui Yang , Lingzhi Huang

引用次数: 0

Dynamic full-field optical coherence tomography for extemporaneous high-resolution imaging of adrenal glands

IF 2.8 4区医学

Experimental and molecular pathology Pub Date : 2025-02-19 DOI: 10.1016/j.yexmp.2025.104958

Irene A. Spiridon , Michel Vix , Didier Mutter , Barbara Seeliger

{"title":"Dynamic full-field optical coherence tomography for extemporaneous high-resolution imaging of adrenal glands","authors":"Irene A. Spiridon , Michel Vix , Didier Mutter , Barbara Seeliger","doi":"10.1016/j.yexmp.2025.104958","DOIUrl":"10.1016/j.yexmp.2025.104958","url":null,"abstract":"<div><h3>Background</h3><div>There is an interindividual variance in postoperative adrenocortical capacity, and the minimal functional remnant size is unknown. New imaging technologies may allow for improved intraoperative assessment of adrenal tissue morphology, cell activity, and surgery-related changes<em>.</em> The aim of this experimental study was to provide a pilot assessment of adrenal gland architecture with dynamic full-field optical coherence tomography (D-FF-OCT) in comparison to standard hematoxylin-eosin (HE) examination.</div></div><div><h3>Methods</h3><div>D-FF-OCT was performed on freshly resected porcine adrenal glands to simultaneously assess both morphology and metabolic activity in real time, and for comparison with standard histopathology. Left and right adrenal glands were assessed from 8 pigs (1 M, 7 F, mean weight 43.9 ± 8.3 kg).</div></div><div><h3>Results</h3><div>The evaluation with D-FF-OCT proved fast in terms of acquisition time, averaging 32 min/specimen. The technique required a relatively short learning curve and provided morphological details similar to standard microscopy. In the comparative analysis of both methods, D-FF-OCT scans allowed easy identification of normal adrenal morphology and facilitated differentiation of the structural components of the cortical and medullary areas based on architectural and vascular patterns. Furthermore, it was possible to distinguish more accurately between cell subpopulations based on their metabolic activity.</div></div><div><h3>Conclusion</h3><div>While HE examination remains the gold standard for morphological evaluation, time weighs heavy on this ancillary technique. In our study, we prove that D-FF-OCT is effective in achieving a comparable level of morphological details, with added metabolic activity of the cells, a combination which can prove useful in the real-time assessment of various diseases requiring adrenal surgery.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"141 ","pages":"Article 104958"},"PeriodicalIF":2.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Diagnostic next-generation sequencing to detect MYD88 L265P in Lymphoplasmacytic lymphoma compared to ddPCR

IF 2.8 4区医学

Experimental and molecular pathology Pub Date : 2025-02-15 DOI: 10.1016/j.yexmp.2025.104956

Lauren M. Wainman, Guohong Huang, Donald C. Green, Gregory J. Tsongalis, Laura J. Tafe, Wahab A. Khan, Prabhjot Kaur, Parth S. Shah , Jeremiah X. Karrs

{"title":"Diagnostic next-generation sequencing to detect MYD88 L265P in Lymphoplasmacytic lymphoma compared to ddPCR","authors":"Lauren M. Wainman, Guohong Huang, Donald C. Green, Gregory J. Tsongalis, Laura J. Tafe, Wahab A. Khan, Prabhjot Kaur, Parth S. Shah , Jeremiah X. Karrs","doi":"10.1016/j.yexmp.2025.104956","DOIUrl":"10.1016/j.yexmp.2025.104956","url":null,"abstract":"<div><div>Lymphoplasmacytic lymphoma (LPL) is a B-cell lymphoproliferative disorder typically involving the bone marrow with infiltration by small lymphocytes and plasma cells. Studies have identified MYD88 L265P mutation as a diagnostic marker to distinguish LPL from other small B-cell lymphomas. Detection rates for this mutation have varied depending on the analytic methodology, with previous data suggesting that routine next-generation sequencing (NGS) does not demonstrate the required sensitivity to reliably detect MYD88 L265P. NGS has become part of routine clinical testing because it allows detection of variants across multiple genes. To study the utility of NGS in the detection of MYD88 L265P, we performed droplet digital PCR (ddPCR) and routine NGS on a cohort of 34 cases of lymphoid neoplasms (22 LPL, 4 CLL, 1 MCL, 1 MGUS, 2 plasma cell myeloma, and 4 negative bone marrow cases). We utilized manual review and BAMtools to assess MYD88 L265P in NGS cases. Limit of detection for ddPCR was determined to be 0.4 % variant allele frequency (VAF) with 10 ng DNA input. MYD88 L265P VAF detection by NGS and ddPCR was comparable down to 0.5 % VAF (R<sup>2</sup> = 0.968). Setting an appropriate threshold for detection based on ddPCR results resulted in zero NGS false positives. We found that low tumor content did not impact the detection of MYD88 L265P by NGS. This study demonstrates that NGS can be a sensitive and reliable method for detection of MYD88 L265P with adequate coverage and specific assessment parameters.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"141 ","pages":"Article 104956"},"PeriodicalIF":2.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Matrix metalloproteinase-3 is a potent prognostic factor associated with cell proliferation and migration in prostate cancer

IF 2.8 4区医学

Experimental and molecular pathology Pub Date : 2025-02-11 DOI: 10.1016/j.yexmp.2025.104954

Ai Sato , Kiyoshi Takagi , Mio Yamaguchi-Tanaka , Jotaro Okushima , Yuto Yamazaki , Akihiro Ito , Takashi Suzuki

{"title":"Matrix metalloproteinase-3 is a potent prognostic factor associated with cell proliferation and migration in prostate cancer","authors":"Ai Sato , Kiyoshi Takagi , Mio Yamaguchi-Tanaka , Jotaro Okushima , Yuto Yamazaki , Akihiro Ito , Takashi Suzuki","doi":"10.1016/j.yexmp.2025.104954","DOIUrl":"10.1016/j.yexmp.2025.104954","url":null,"abstract":"<div><div>Prostate cancer is a common malignancy in men around the world, and it is crucial to explore novel biomarkers to improve its treatment. Prostate cancer cells typically invade the surrounding stroma, and remodeling of the extracellular matrix (ECM) is a crucial step in the progress of prostate cancer. Matrix metalloproteinase-3 (MMP3) is an enzyme that degrades several ECM components and is implicated in human malignancies. However, the clinical and biological significance of MMP3 has not been well elucidated.</div><div>We therefore immunolocalized MMP3 in prostate cancer tissues (<em>n</em> = 117) and demonstrated that MMP3 immunoreactivity was correlated with aggressive phenotype of prostate cancer, including higher proliferation/invasion ability, and shorter disease-free survival. In addition, subsequent in vitro analysis revealed that overexpression of MMP3 significantly increased the proliferative and migratory abilities of PC-3 and DU-145 prostate cancer cell lines, depending on conditioned media from WMPY-1 prostate stromal cells.</div><div>It was concluded that MMP3 might contribute to prostate cancer progression by modifying the ECM surrounding prostate cancer cells and could serve as a potent prognostic factor in prostate cancer.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"141 ","pages":"Article 104954"},"PeriodicalIF":2.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143377986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hyperinsulinemic male LEW.1WR1 rats show early signs of impaired liver metabolism

IF 2.8 4区医学

Experimental and molecular pathology Pub Date : 2025-02-11 DOI: 10.1016/j.yexmp.2025.104955

Madushika Wimalarathne , Bailey L. Bowser , Albert B. Arul , Quiana C. Wilkerson-Vidal , Moses A. David , Emily C. Hunt , Helen Gibson , Renã A.S. Robinson , Sharifa T. Love-Rutledge

{"title":"Hyperinsulinemic male LEW.1WR1 rats show early signs of impaired liver metabolism","authors":"Madushika Wimalarathne , Bailey L. Bowser , Albert B. Arul , Quiana C. Wilkerson-Vidal , Moses A. David , Emily C. Hunt , Helen Gibson , Renã A.S. Robinson , Sharifa T. Love-Rutledge","doi":"10.1016/j.yexmp.2025.104955","DOIUrl":"10.1016/j.yexmp.2025.104955","url":null,"abstract":"<div><div>Weanling LEW.1WR1 (1WR1) rats are susceptible to type 1 diabetes (T1D) and hyperinsulinemic. Similar to human patients with T1D, these animals are susceptible to developing fatty liver infiltrates. Insulin resistance-related steatosis can lead to the development of severe forms of nonalcoholic fatty liver disease (NAFLD). Previous work in 1WR1 rats suggests that in the absence of T1D, they have increased body mass that is not reconciled by measuring their abdominal fat pads; this suggests 1WR1 rats have an underlying predisposition to store fat in the liver unrelated to diabetes status. We hypothesized that 1WR1 rats show early signs of NAFLD development. We assessed proteomics changes in the livers of glucose intolerant and hyperinsulinemic young adult 1WR1 rats to identify early detectable characteristics of NAFLD development.</div><div>Our results show young adult 1WR1 rats have UBD/<em>FAT10</em> gene over expression in the liver. Additionally, they have decreased mitochondrial protein levels, which may lead to lipid accumulation in the liver. A quantitative proteomic analysis showed protein expression related to branch chain fatty acid metabolism, fatty acid beta-oxidation, and oxidative phosphorylation in the liver is significantly different in 1WR1 rats compared to control LEW/SsNHsd (SsNHsd) rats. In summary, our study shows that 1WR1 rats developed early characteristics of mitochondrial dysfunction and insulin resistance in the liver independent of T1D, which are commonly observed with NAFLD development.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"141 ","pages":"Article 104955"},"PeriodicalIF":2.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mediterranean diet improves liver health but does not protect against azoxymethane-induced colon tumorigenesis compared to Western diet in A/J mice

IF 2.8 4区医学

Experimental and molecular pathology Pub Date : 2025-02-06 DOI: 10.1016/j.yexmp.2025.104953

Weimin Guo , Nicholas Crossland , Jimmy W. Crott

{"title":"Mediterranean diet improves liver health but does not protect against azoxymethane-induced colon tumorigenesis compared to Western diet in A/J mice","authors":"Weimin Guo , Nicholas Crossland , Jimmy W. Crott","doi":"10.1016/j.yexmp.2025.104953","DOIUrl":"10.1016/j.yexmp.2025.104953","url":null,"abstract":"<div><h3>Introduction</h3><div>Abundant evidence indicates that the Mediterranean (MED) diet pattern is beneficial for health, especially cardiovascular health. Epidemiological evidence indicates that the MED diet also affords protection against colorectal cancer (CRC). To date, preclinical models have only evaluated specific MED diet components and therefore, although supportive, fall short of confirming the chemoprotective capacity of this complex dietary pattern. We sought to address this gap.</div></div><div><h3>Method</h3><div>A/J mice were randomized to receive Western (WRN) or MED diets differing in their fat, protein, and carbohydrate sources. Azoxymethane (AOM) was used to initiate colon tumorigenesis and mice were maintained for 19 weeks after the final dose.</div></div><div><h3>Result</h3><div>Unexpectedly high mortality was observed amongst male mice following the second AOM dose. At the end of the study hepatic Cyp2E1, an enzyme that metabolize AOM, was lower in males than females. Livers from MED diet mice were significantly lighter, had lower histologic Non-Alcoholic Fatty Liver Disease (NAFLD) scores, and contained less triglycerides than WRN mice. Amongst females, serum alanine transaminase (ALT) was also lower in MED than WRN mice. Amongst male mice, those fed MED diet presented with significantly more colonic tumors than those on the WRN diet.</div></div><div><h3>Conclusion</h3><div>In this study male mice displayed elevated sensitivity to AOM-induced hepatotoxicity and mortality than females. In agreement with human and preclinical data, livers of MED-diet-fed mice were healthier than those fed WRN diets. We could not confirm the chemoprotective capacity of the MED diet. Additional studies are required to evaluate the purported anticancer effect of the MED diet.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"141 ","pages":"Article 104953"},"PeriodicalIF":2.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143347669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of A1 adenosine receptor in cardiovascular diseases: Bridging molecular mechanisms with therapeutic opportunities

IF 2.8 4区医学

Experimental and molecular pathology Pub Date : 2025-01-28 DOI: 10.1016/j.yexmp.2025.104952

Warisara Parichatikanond , Ratchanee Duangrat , Narawat Nuamnaichati , Supachoke Mangmool

{"title":"Role of A1 adenosine receptor in cardiovascular diseases: Bridging molecular mechanisms with therapeutic opportunities","authors":"Warisara Parichatikanond , Ratchanee Duangrat , Narawat Nuamnaichati , Supachoke Mangmool","doi":"10.1016/j.yexmp.2025.104952","DOIUrl":"10.1016/j.yexmp.2025.104952","url":null,"abstract":"<div><div>Adenosine serves as a critical homeostatic regulator, exerting influence over physiological and pathological conditions in the cardiovascular system. During cellular stress, increased extracellular adenosine levels have been implicated in conferring cardioprotective effects through the activation of adenosine receptors with the A<sub>1</sub> adenosine receptor subtype showing the highest expression in the heart. A<sub>1</sub> adenosine receptor stimulation inhibits adenylyl cyclase activity via heterotrimeric G<sub>i</sub> proteins, leading to the activation of distinct downstream effectors involved in cardiovascular homeostasis. While the comprehensive characterization of the pharmacological functions and intracellular signaling pathways associated with the A<sub>1</sub> adenosine receptor subtype is still ongoing, this receptor is widely recognized as a crucial pharmacological target for the treatment of various states of cardiovascular diseases (CVDs). In this review, we focus on elucidating signal transduction of A<sub>1</sub> adenosine receptor, particularly G<sub>i</sub> protein-dependent and -independent pathways, and their relevance to cardiovascular protective effects as well as pathological consequences during cellular and tissue stresses in the cardiovascular system. Additionally, we provide comprehensive updates and detailed insights into a range of A<sub>1</sub> adenosine receptor agonists and antagonists, detailing their development and evaluation through preclinical and clinical studies with a specific focus on their potential for the management of CVDs, especially heart diseases.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"141 ","pages":"Article 104952"},"PeriodicalIF":2.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modulation of IL-6 receptor/STAT3 downstream signaling in rheumatoid arthritis patients 类风湿关节炎患者IL-6受体/STAT3下游信号的调节

IF 2.8 4区医学

Experimental and molecular pathology Pub Date : 2024-12-25 DOI: 10.1016/j.yexmp.2024.104951

Fabio Cacciapaglia , Simone Perniola , Stefano Stano , Vincenzo Venerito , Dorotea Natuzzi , Rita Bizzoca , Florenzo Iannone

{"title":"Modulation of IL-6 receptor/STAT3 downstream signaling in rheumatoid arthritis patients","authors":"Fabio Cacciapaglia , Simone Perniola , Stefano Stano , Vincenzo Venerito , Dorotea Natuzzi , Rita Bizzoca , Florenzo Iannone","doi":"10.1016/j.yexmp.2024.104951","DOIUrl":"10.1016/j.yexmp.2024.104951","url":null,"abstract":"<div><div>Interleukin-6 (IL-6) is a relevant cytokine in rheumatoid arthritis (RA) pathogenesis, potentially activating Janus kinases (JAK)-1, −2, and tyrosine kinase 2 (TYK2), and thus, three signal transducer and activator of transcription (STAT)-1, −3 or − 5 pathways. This pilot study aims to explore differences in phosphorylated (p)STAT3 levels among patients with RA, those not classified as RA (nRA), and healthy donors (HD), providing some clues on the relative contribution of each JAK protein to the downstream of the IL-6-induced STAT3 pathway. Clinical data and blood samples from 80 subjects (41 RA, 14 nRA, and 25 HD) were collected. The activity of the JAK-STAT3 pathway was assessed by Western Blot and Real Time-PCR analysis for the quantification of STAT3 in peripheral blood mononuclear cells (PBMC). Furthermore, the impact of JAK-1, −2, and TYK2 inhibitors on pSTAT3 was assessed in vitro by FACS, with and without IL-6 stimulation in RA patients naïve to treatment with DMARD and steroids. The pSTAT3 (%) was significantly higher in PBMC from RA compared to nRA patients and HD. Furthermore, pSTAT3 (%) was significantly associated with inflammation and disease activity (ESR, CRP, and DAS28). The JAK-1 inhibitor was more effective in reducing pSTAT3 expression in CD14<sup>pos</sup> cells of RA patients, while the JAK-2 selective compound was more effective in CD4<sup>pos</sup> cells of RA patients. On the contrary, the TYK2 selective agent showed no significant effects. This study highlights the importance of the JAK/STAT3 pathway in RA. Some differences among various JAK proteins have been pointed out, with JAK1 and JAK2 standing as the most relevant mediators of the STAT3 pathway in this in-vitro model after IL-6R activation.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"141 ","pages":"Article 104951"},"PeriodicalIF":2.8,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0