Experimental and molecular pathology最新文献

{"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 ,&nbsp;Nicholas Crossland ,&nbsp;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}

{"title":"Role of A1 adenosine receptor in cardiovascular diseases: Bridging molecular mechanisms with therapeutic opportunities","authors":"Warisara Parichatikanond ,&nbsp;Ratchanee Duangrat ,&nbsp;Narawat Nuamnaichati ,&nbsp;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 A₁ adenosine receptor subtype showing the highest expression in the heart. A₁ adenosine receptor stimulation inhibits adenylyl cyclase activity via heterotrimeric G_i 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 A₁ 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 A₁ adenosine receptor, particularly G_i 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 A₁ 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}

{"title":"Expression of concern: “Upregulation of immunomodulatory molecules by matrine treatment in experimental autoimmune encephalomyelitis” [Experimental and Molecular Pathology 97 (2014) 470–476]","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"142 ","pages":"Article 104961"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of concern: “Matrine ameliorates experimental autoimmune encephalomyelitis by modulating chemokines and their receptors” [Experimental and Molecular Pathology 99 (2015) 212–219]","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"142 ","pages":"Article 104962"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of IL-6 receptor/STAT3 downstream signaling in rheumatoid arthritis patients","authors":"Fabio Cacciapaglia ,&nbsp;Simone Perniola ,&nbsp;Stefano Stano ,&nbsp;Vincenzo Venerito ,&nbsp;Dorotea Natuzzi ,&nbsp;Rita Bizzoca ,&nbsp;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^pos cells of RA patients, while the JAK-2 selective compound was more effective in CD4^pos 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}

{"title":"Transcriptomic analysis of the HPT axis in a model of oligoasthenozoospermia induced by Adenine in rats","authors":"Nan Yang ,&nbsp;Xiao-ge Wei ,&nbsp;Kaiying Li ,&nbsp;Fei Wang ,&nbsp;Fei Song ,&nbsp;Wenjing Sun ,&nbsp;Yan Wang ,&nbsp;Zhenning Zhao ,&nbsp;Jing Mu ,&nbsp;Huisheng Ma","doi":"10.1016/j.yexmp.2024.104948","DOIUrl":"10.1016/j.yexmp.2024.104948","url":null,"abstract":"<div><div>Male infertility is most commonly caused by oligozoospermia, and its pathogenesis is still poorly understood at the molecular level. This study used RNA sequencing (RNA-Seq) technology to identify candidate genes and regulatory pathways that regulate semen quality in the hypothalamic, pituitary, and testicular tissues of healthy rats and Adenine-induced oligozoospermia model rats. Semen quality testing and histological analysis of testicular tissues were performed on both groups of rats. We identified 627, 692, and 437 differentially expressed genes in the hypothalamus, pituitary gland, and testes, respectively. Functional analysis indicates that “neuronal projections,” “positive regulation of hormone biosynthetic process,” and “neuroactive ligand-receptor interaction pathways” are closely related to the hypothalamic-pituitary-testicular (HPT) axis hormone regulation and sperm production. Seven genes (<em>Pomc, Rxfp1, Tac1, Npy, Insl3, Hsd3b3, Lhcgr</em>) have been identified as key candidate genes responsible for regulating sperm quality within the HPT axis, potentially affecting rat reproductive function by influencing testicular development and testosterone secretion. These data provide a theoretical basis for further understanding the molecular mechanisms of reproductive performance in a rat model of oligoasthenozoospermia.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"141 ","pages":"Article 104948"},"PeriodicalIF":2.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863861","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}

{"title":"In Silico analysis unveils rs2109069 of DPP9 as a potential catalyst for COVID-19 severity and risk of inflammatory symptoms","authors":"Chi-Ying Lee ,&nbsp;Zih-Yin Lai ,&nbsp;Yung-Jen Chuang","doi":"10.1016/j.yexmp.2024.104946","DOIUrl":"10.1016/j.yexmp.2024.104946","url":null,"abstract":"<div><h3>Background</h3><div>During the COVID-19 pandemic, the viral illness caused by SARS-CoV-2 spread through respiratory droplets, resulting in a global pandemic with a range of symptoms from mild to severe. Pathological inflammation posed a critical issue, yet the genetic mechanisms behind the excessive activation of inflammatory responses remained unclear. To uncover the genetic and regulatory basis of the pathogenesis, we first explored possible genetic mechanisms from phenome-wide association studies (PWAS) with different severity levels of COVID-19. PWAS is a genetic research approach that identifies pleiotropic risk variants that contribute to elucidating potential physiological mechanisms from different traits.</div></div><div><h3>Methods</h3><div>We used the PWAS approach to link the multiple clinical symptoms to the variants. We discovered a common variant, rs2109069, in dipeptidyl peptidase 9 (<em>DPP9</em>), which relates to the elevated odds ratio of developing severe illness from COVID-19. Interestingly, the proxy of rs2109069 has been identified as the susceptible locus of interstitial lung disease (ILD) and idiopathic pulmonary fibrosis (IPF). We thus examined the <em>DPP9</em> expression patterns in selected organs, including the lungs, blood vessels, and skin.</div></div><div><h3>Results</h3><div><em>In silico</em> analysis revealed conserved driver activation between COVID-19-induced inflammation and the association with ILD and IPF. Multi-omics analysis further verified the association of DPP9 with abnormal inflammatory responses in COVID-19. Lastly, gene homology analysis inferred a potential regulatory role of DPP9 in inhibiting inflammasome activation, which suggests that DPP9 deficiency may exacerbate inflammation observed in some COVID-19 patients.</div></div><div><h3>Conclusions</h3><div>Our <em>in silico</em> findings reveal that severe COVID-19 inflammatory responses and inflammatory lung diseases share the same genetic risk loci, helping to elucidate the underlying physiological mechanisms of severe COVID-19 inflammation. Additionally, the individual differences in immune sensitivity may contribute to the varying multi-organ inflammatory effects among patients. The rs2109069 of DPP9 could be a genetic marker to predict the risk of specific COVID-19 symptoms and severity.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"140 ","pages":"Article 104946"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142744210","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}

{"title":"Corrigendum to “Irisin and neuroinflammation: Challenges and opportunities” [Experimental and Molecular Pathology 140 (2024) 104941]","authors":"Erika Yolanda Hernández Sandoval,&nbsp;Zulma Dueñas","doi":"10.1016/j.yexmp.2024.104943","DOIUrl":"10.1016/j.yexmp.2024.104943","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"140 ","pages":"Article 104943"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617746","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}

{"title":"Influence of diet and exercise on leukocyte telomere length, markers of oxidative stress and inflammation in rats","authors":"Mehmet Mustafa Tilekli ,&nbsp;Ali Kerim Yılmaz ,&nbsp;Yavuz Yasul ,&nbsp;Nurhan Çon ,&nbsp;Sevcan Mercan ,&nbsp;Nilüfer Tek","doi":"10.1016/j.yexmp.2024.104947","DOIUrl":"10.1016/j.yexmp.2024.104947","url":null,"abstract":"<div><div>Telomere length is an important biomarker of biological aging and is affected by nutrition and physical activity. This study investigated the effects of diets with different fat content<del>s</del> and increased physical activity on certain pro/anti-inflammatory and oxidative stress markers and aging. The study is performed in a randomized, experimental, and controlled design with 48 rats, 8 weeks old, divided into 6 different groups (Control (C), exercise (E), unsaturated fat diet (USF), saturated fat diet (SF), unsaturated fat diet + exercise (USF + E), and saturated fat diet + exercise (SF + E)). The rats performed aerobic swimming exercise for 50 days and were fed a diet with different fat content. TAS, TOS, and MDA levels were determined by colorimetric analysis while 8-OHdG, IL-10, and TNF-α were determined by ELISA. Additionally, leukocyte telomere length is determined by the PCR method. Weight changes were also recorded. Plasma TOS, OSI, and TNF-α were lowest in the USF group and highest in the SF and SF + E groups. MDA, 8-OHdG and TG levels were highest in the SF group. The lowest IL-10 level was detected in group C. TL level was the highest in the USF group. There was also a moderate, negative, and significant correlation between telomeres and TOS, OSI, and TNF-α. The groups with the highest body weight gain were C, SF, and SF + E. Diets low in saturated fat or high in unsaturated fat, and physical activity were associated with leukocyte telomere length and alteration of oxidative and pro/anti-inflammatory markers.</div></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"140 ","pages":"Article 104947"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142744093","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}

{"title":"Corrigendum to “Anti-tumor effect of antibody-drug conjugate targeting cell adhesion molecule 1 on GIST cells representing small intestinal GIST” [Experimental and Molecular Pathology 139 (2024) 104922]","authors":"Makoto Yoshida ,&nbsp;Jiayin Yuan ,&nbsp;Takako Kihara ,&nbsp;Neinei Kimura ,&nbsp;Takashi Yamasaki ,&nbsp;Mizuka Ohkouchi ,&nbsp;Yuka Hashikura ,&nbsp;Koji Isozaki ,&nbsp;Man Hagiyama ,&nbsp;Akihiko Ito ,&nbsp;Seiichi Hirota","doi":"10.1016/j.yexmp.2024.104934","DOIUrl":"10.1016/j.yexmp.2024.104934","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"140 ","pages":"Article 104934"},"PeriodicalIF":2.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344367","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}