Pub Date : 2025-02-11DOI: 10.1016/j.yexmp.2025.104954
Ai Sato , Kiyoshi Takagi , Mio Yamaguchi-Tanaka , Jotaro Okushima , Yuto Yamazaki , Akihiro Ito , Takashi Suzuki
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.
We therefore immunolocalized MMP3 in prostate cancer tissues (n = 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.
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.
{"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}
Pub Date : 2025-02-11DOI: 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
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.
Our results show young adult 1WR1 rats have UBD/FAT10 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.
{"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}
Pub Date : 2025-02-06DOI: 10.1016/j.yexmp.2025.104953
Weimin Guo , Nicholas Crossland , Jimmy W. Crott
Introduction
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.
Method
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.
Result
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.
Conclusion
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.
{"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}
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 Gi 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 Gi 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.
{"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}
{"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}
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