{"title":"PPAR-<i>γ</i> Activation Alleviates Osteoarthritis through Both the Nrf2/NLRP3 and PGC-1<i>α</i>/<i>Δψ</i> <sub>m</sub> Pathways by Inhibiting Pyroptosis.","authors":"Zhencheng Feng, Qiuxiang Huang, Xingliang Zhang, Pengfei Xu, Siming Li, Dongli Ma, Qingqi Meng","doi":"10.1155/2023/2523536","DOIUrl":"https://doi.org/10.1155/2023/2523536","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a common degenerative joint disease with a gradually increasing morbidity in the aging and obese population. Emerging evidence has implicated pyroptosis in the etiology of OA and it may be recognized as a therapeutic target in OA. We have previously reported regarding another disease that peroxisome proliferator-activated receptor gamma (PPAR-<i>γ</i>) activation exerts an anti-inflammatory effect by suppressing the nucleotide-binding and oligomerization domain-like receptor containing protein (NLRP) 3 inflammasome. However, the relationship between PPAR-<i>γ</i> and NLRP3-mediated pyroptosis in OA cartilage and its underlying mechanisms is fully unclear. In this study, we found that the level of NLRP3-mediated pyroptosis in severe lateral femoral condyle cartilage wear in the knee of an OA patient was significantly higher than that in the mild lateral femoral condyle cartilage wear areas. Moreover, in lipopolysaccharide (LPS)/adenosine triphosphate (ATP)-induced primary chondrocytes and knee OA rat models, we demonstrated that activation of PPAR-<i>γ</i> by pioglitazone (Piog) attenuated LPS/ATP-induced chondrocyte pyroptosis and arthritis. These effects were partially counteracted by either blocking the nuclear factor erythroid-2-related factor (Nrf2)/NLRP3 or PGC1-<i>α</i>/<i>Δψ</i> <sub>m</sub> signaling pathway. Simultaneous depression of these two signaling pathways can completely abrogate the protective effects of Piog on OA and chondrocytes. Taken together, Piog protects OA cartilage against pyroptosis-induced damage by simultaneously activating both the Nrf2/NLRP3 and PGC-1<i>α</i>/<i>Δψ</i> <sub>m</sub> pathways, which enhances antioxidative and anti-inflammatory responses as well as mitochondrial biogenesis. Therefore, Piog may be a promising agent for human OA cartilage damage in future clinical treatments.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2023 ","pages":"2523536"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10070030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9612116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Peptide Helix-Y<sup>12</sup> as Potential Effector for Peroxisome Proliferator-Activated Receptors.","authors":"Mauricio Carrillo-Tripp, Yair Reyes, Blanca Delgado-Coello, Jaime Mas-Oliva, Roxana Gutiérrez-Vidal","doi":"10.1155/2023/8047378","DOIUrl":"https://doi.org/10.1155/2023/8047378","url":null,"abstract":"<p><p>Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors involved in the regulation of lipids and glucose metabolism, and immune response. Therefore, they have been considered pharmacological targets for treating metabolic diseases, such as dyslipidemia, atherosclerosis, and non-alcoholic fatty liver disease. However, the available synthetic ligands of PPARs have mild to significant side effects, generating the necessity to identify new molecules that are selective PPAR ligands with specific biological responses. This study aimed to evaluate some components of the atheroprotective and hepatoprotective HB-ATV-8 nanoparticles [the amphipathic peptide Helix-Y<sup>12</sup>, thermozeaxanthin, thermozeaxanthin-13, thermozeaxanthin-15, and a set of glycolipids], as possible ligands of PPARs through blind molecular docking. According to the change in free energy upon protein-ligand binding, ∆<i>G</i> <sub>b</sub>, thermozeaxanthins show a more favorable interaction with PPARs, followed by Helix-Y<sup>12</sup>. Moreover, Helix-Y<sup>12</sup> interacts with most parts of the Y-shaped ligand-binding domain (LBD), surrounding helix 3 of PPARs, and reaching helix 12 of PPAR<i>α</i> and PPAR<i>γ</i>. As previously reported for other ligands, Tyr314 and Tyr464 of PPAR<i>α</i> interact with Helix-Y<sup>12</sup> through hydrogen bonds. Several PPAR<i>α</i>'s amino acids are involved in the ligand binding by hydrophobic interactions. Furthermore, we identified additional PPARs' amino acids interacting with Helix-Y<sup>12</sup> through hydrogen bonds still not reported for known ligands. Our results show that, from the studied ligand set, the Helix-Y<sup>12</sup> peptide and Tzeaxs have the most significant probability of binding to the PPARs' LBD, suggesting novel ligands for PPARs.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2023 ","pages":"8047378"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10122583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9395758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PPAR ResearchPub Date : 2023-01-01DOI: 10.1155/2023/7550164
Yong-Jik Lee, Hyun-Min Kim, Yoo-Na Jang, Yoon-Mi Han, Hong Seog Seo, Tae Woo Jung, Ji Hoon Jeong, Hyun Jung Lee, Kyung Oh Jung
{"title":"Buspirone Induces Weight Loss and Normalization of Blood Pressure via the Stimulation of PPAR<i>δ</i> Dependent Energy Producing Pathway in Spontaneously Hypertensive Rats.","authors":"Yong-Jik Lee, Hyun-Min Kim, Yoo-Na Jang, Yoon-Mi Han, Hong Seog Seo, Tae Woo Jung, Ji Hoon Jeong, Hyun Jung Lee, Kyung Oh Jung","doi":"10.1155/2023/7550164","DOIUrl":"https://doi.org/10.1155/2023/7550164","url":null,"abstract":"<p><strong>Introduction: </strong>Buspirone, as a partial agonist for a 5-hydroxytryptamine (serotonin) receptor 1A (5-HT1A), has been prescribed as an anxiolytic drug for patients. In addition, the lowering effect of serotonin on blood pressure was reported in hypertensive animal model. We investigated the therapeutic mechanism of buspirone against lipid metabolism disturbed by hypertension of early stage via hypertensive and obese animal model.</p><p><strong>Methods: </strong>The levels of various biomarkers related to lipid metabolism and hypertension were estimated through the measurement of body weight and fat weight, blood analysis, western blotting, immunohistochemistry, and staining methods.</p><p><strong>Results: </strong>The lipid accumulation was lowered in differentiated 3T3-L1 cells by buspirone treatments of 50 and 100 <i>μ</i>M compared with untreated differentiated control. Body weight and abdominal fat weight were lowered in spontaneously hypertensive rats (SHRs) administered with buspirone of 10 mg/kg/day for 4 weeks than 8-week untreated group. Triglyceride (TG) level was decreased in SHRs administered with buspirone of 5 and 10 mg/kg/day compared to 8-week untreated group. High-density lipoprotein (HDL)-cholesterol concentration was elevated by buspirone 10 mg/kg/day treatment compared to 8-week untreated group. Blood pressures in SHRs were lowered by buspirone treatments of 5 and 10 mg/kg/day compared with 8-week untreated group. Protein levels for peroxisome proliferator-activated receptor <i>δ</i> (PPAR<i>δ</i>), 5' adenosine monophosphate-activated protein kinase (AMPK), and PPAR<i>γ</i> coactivator-1 alpha (PGC-1<i>α</i>) were increased both in C<sub>2</sub>C<sub>12</sub> cells treated by buspirone of 100 <i>μ</i>M and in SHRs administered by buspirone of 1, 5, and 10 mg/kg/day compared to untreated control cells and 8-week untreated group. Fat cell numbers decreased in 8-week untreated group were increased in SHRs administered by buspirone treats of 1, 5, and 10 mg/kg/day. Protein expression levels for angiotensin II type 1 receptor (AT1R) and vascular cell adhesion molecule 1 (VCAM1) were increased in 8-week untreated group compared to 4-week group, however, they were decreased by buspirone treatments of 1, 5, and 10 mg/kg/day.</p><p><strong>Conclusion: </strong>Buspirone may induce the losses of body weight and abdominal fat weight through the activation of PPAR<i>δ</i> dependent catabolic metabolism producing energy, and eventually, the ameliorated lipid metabolism could normalize high blood pressure.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2023 ","pages":"7550164"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10164918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9452810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PPAR ResearchPub Date : 2023-01-01DOI: 10.1155/2023/1743289
J Hernández-Valdez, A Velázquez-Zepeda, J C Sánchez-Meza
{"title":"Effect of Pesticides on Peroxisome Proliferator-Activated Receptors (PPARs) and Their Association with Obesity and Diabetes.","authors":"J Hernández-Valdez, A Velázquez-Zepeda, J C Sánchez-Meza","doi":"10.1155/2023/1743289","DOIUrl":"https://doi.org/10.1155/2023/1743289","url":null,"abstract":"<p><p>Obesity and diabetes mellitus are considered the most important diseases of the XXI century. Recently, many epidemiological studies have linked exposure to pesticides to the development of obesity and type 2 diabetes mellitus. The role of pesticides and their possible influence on the development of these diseases was investigated by examining the relationship between these compounds and one of the major nuclear receptor families controlling lipid and carbohydrate metabolism: the peroxisome proliferator-activated receptors (PPARs), PPAR<i>α</i>, PPAR<i>β</i>/<i>δ</i>, and PPAR<i>γ</i>; this was possible through <i>in silico</i>, <i>in vitro</i>, and <i>in vivo</i> assays. The present review aims to show the effect of pesticides on PPARs and their contribution to the changes in energy metabolism that enable the development of obesity and type 2 diabetes mellitus.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2023 ","pages":"1743289"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9984265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10854740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"PPARG: A Promising Therapeutic Target in Breast Cancer and Regulation by Natural Drugs.","authors":"De-Hui Li, Xu-Kuo Liu, Xiao-Tong Tian, Fei Liu, Xu-Jiong Yao, Jing-Fei Dong","doi":"10.1155/2023/4481354","DOIUrl":"https://doi.org/10.1155/2023/4481354","url":null,"abstract":"<p><p>Breast cancer (BC) is the most common type of cancer among females. Peroxisome proliferator-activated receptor gamma (PPARG) can regulate the production of adipocyte-related genes and has anti-inflammatory and anti-tumor effects. Our aim was to investigate PPARG expression, its possible prognostic value, and its effect on immune cell infiltration in BC, and explore the regulatory effects of natural drugs on PPARG to find new ways to treat BC. Using different bioinformatics tools, we extracted and comprehensively analyzed the data from the Cancer Genome Atlas, Genotype-Tissue Expression, and BenCaoZuJian databases to study the potential anti-BC mechanism of PPARG and potential natural drugs targeting it. First, we found that PPARG was downregulated in BC and its expression level correlates with pathological tumor stage (pT-stage) and pathological tumor-node-metastasis stage (pTNM-stage) in BC. PPARG expression was higher in estrogen receptor-positive (ER+) BC than in estrogen receptor-negative (ER-) BC, which tends to indicate a better prognosis. Meanwhile, PPARG exhibited a significant positive correlation with the infiltration of immune cells and correlated with better cumulative survival in BC patients. In addition, PPARG levels were shown to be positively associated with the expression of immune-related genes and immune checkpoints, and ER+ patients had better responses to immune checkpoint blocking. Correlation pathway research revealed that PPARG is strongly associated with pathways, such as angiogenesis, apoptosis, fatty acid biosynthesis, and degradation in ER+ BC. We also found that quercetin is the most promising natural anti-BC drug among natural medicines that upregulate PPARG. Our research showed that PPARG may reduce BC development by regulating the immune microenvironment. Quercetin as PPARG ligands/agonists is a potential natural drug for BC treatment.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2023 ","pages":"4481354"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10270765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10037006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PPAR ResearchPub Date : 2023-01-01DOI: 10.1155/2023/4672827
Haizhou Wang, Wen Xu
{"title":"A Promotion Role of MIR31 in the Process of Vocal Fold Wound Healing.","authors":"Haizhou Wang, Wen Xu","doi":"10.1155/2023/4672827","DOIUrl":"https://doi.org/10.1155/2023/4672827","url":null,"abstract":"<p><p>The role of MIR31 in the wound healing process, specifically in vocal fold wound healing (VFWH), remains uncertain despite its potential to facilitate the process. In this study, we first constructed a literature-based pathway to examine both the positive and negative effects of MIR31 on wound healing. We then conducted animal experiments on 20 rats to investigate MIR31 expression at different time points (1, 4, and 8 weeks) after vocal fold injury. Co-expression analysis and pathway analysis were performed to explore the potential function of MIR31 in VFWH. The literature-based pathway suggested that MIR31 could both impede and promote the wound healing process by regulating 14 and 47 wound healing upstream regulators, respectively. However, the rat experiment indicated that MIR31 expression significantly increased after vocal fold injury (<i>p</i> < 5.65 × 10<sup>-5</sup>) but decreased in the late stage of VFWH compared with the early and middle stages (<i>p</i> < 5.40 × 10<sup>-3</sup>. Strong co-expression was observed between MIR31 and 17 VFWH-significant genes (Pearson correlation coefficient ∈ (0.63, 0.83)), primarily involved in collagen production. Overall, our findings suggest that MIR31 plays a critical role in VFWH, particularly in collagen synthesis and other biological processes, which warrant further investigation.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2023 ","pages":"4672827"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10427237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10017654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PPAR ResearchPub Date : 2023-01-01DOI: 10.1155/2023/4962460
Yan Zhang, Xing Li, Jun Zhang, Lin Mao, Zou Wen, Mingliang Cao, Xuefeng Mu
{"title":"Development and Validation of the Promising PPAR Signaling Pathway-Based Prognostic Prediction Model in Uterine Cervical Cancer.","authors":"Yan Zhang, Xing Li, Jun Zhang, Lin Mao, Zou Wen, Mingliang Cao, Xuefeng Mu","doi":"10.1155/2023/4962460","DOIUrl":"https://doi.org/10.1155/2023/4962460","url":null,"abstract":"<p><p>A ligand-activated transcription factor, peroxisome proliferator-activated receptor (PPAR) regulates fatty acid uptake and transport. In several studies, upregulation of PPAR expression/activity by cancer cells has been associated with cancer progression. Worldwide, cancer of the cervix ranks fourth among women's cancers. Angiogenesis inhibitors have improved treatment for recurrent and advanced cervical cancer since their introduction 5 years ago. In spite of that, the median overall survival rate for advanced cervical cancer is 16.8 months, indicating that treatment effectiveness is still lacking. Thus, it is imperative that new therapeutic methods be developed. In this work, we first downloaded the PPAR signaling pathway-related genes from the previous study. In addition, the single-sample gene set enrichment analysis (ssGSEA) algorithm was applied to calculate the PPAR score of patients with cervical cancer. Furthermore, cervical cancer patients with different PPAR scores show different sensitivity to immune checkpoint therapy. In order to screen the genes to serve as the best biomarker for cervical cancer patients, we then construct the PPAR-based prognostic prediction model. The results revealed that PCK1, MT1A, AL096855.1, AC096711.2, FAR2P2, and AC099568.2 not only play a key role in the PPAR signaling pathway but also show good predictive value in cervical cancer patients. The gene set variation analysis (GSVA) enrichment analysis also proved that the PPAR signaling pathway is one of the most enriched pathways in the prognostic prediction model. Finally, further analysis revealed that AC099568.2 may be the most promising biomarker for the diagnosis, treatment, and prognosis in cervical cancer patients. Both the survival analysis and Receiver Operating Characteristic curve demonstrated that AC099568.2 plays a key role in cervical cancer patients. However, to our knowledge, this is the first time a study focused on the role of AC099568.2 in cervical cancer patients. Our work successfully revealed a new biomarker for cervical cancer patients, which also provides a new direction for future research.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2023 ","pages":"4962460"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10247326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9608643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PPAR ResearchPub Date : 2023-01-01DOI: 10.1155/2023/4779199
Caroline N Rivera, Jason S Hinkle, Rachel M Watne, Trent C Macgowan, Andrew J Wommack, Roger A Vaughan
{"title":"PPAR<i>β</i>/<i>δ</i> Agonism with GW501516 Increases Myotube PGC-1<i>α</i> Content and Reduces BCAA Media Content Independent of Changes in BCAA Catabolic Enzyme Expression.","authors":"Caroline N Rivera, Jason S Hinkle, Rachel M Watne, Trent C Macgowan, Andrew J Wommack, Roger A Vaughan","doi":"10.1155/2023/4779199","DOIUrl":"https://doi.org/10.1155/2023/4779199","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes is characterized by reduced insulin sensitivity, elevated blood metabolites, and reduced mitochondrial metabolism with reduced expression of genes governing metabolism such as peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1<i>α</i>). PGC-1<i>α</i> regulates the expression of branched-chain amino acid (BCAA) metabolism, and thus, increased circulating BCAA in diabetics may be partially explained by reduced PGC-1<i>α</i> expression. PGC-1<i>α</i> functions in-part through interactions with peroxisome proliferator-activated receptor <i>β</i>/<i>δ</i> (PPAR<i>β</i>/<i>δ</i>). The present report examined the effects of the PPAR<i>β</i>/<i>δ</i> agonism on cell metabolism and related gene/protein expression of cultured myotubes, with a primary emphasis on determining the effects of GW on BCAA disposal and catabolic enzyme expression.</p><p><strong>Methods: </strong>C2C12 myotubes were treated with GW501516 (GW) for up to 24 hours. Mitochondrial and glycolytic metabolism were measured via oxygen consumption and extracellular acidification rate, respectively. Metabolic gene and protein expression were assessed via quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, respectively. Media BCAA content was assessed via liquid chromatography-mass spectrometry (LC/MS).</p><p><strong>Results: </strong>GW significantly increased PGC-1<i>α</i> protein expression, mitochondrial content, and mitochondrial function. GW also significantly reduced BCAA content within culture media following 24-hour treatment; however, expression of BCAA catabolic enzymes/transporter was unchanged.</p><p><strong>Conclusion: </strong>These data confirm the ability of GW to increase muscle PGC-1<i>α</i> content and decrease BCAA media content without affecting BCAA catabolic enzymes/transporter. These findings suggest heightened BCAA uptake (and possibly metabolism) may occur without substantial changes in the protein levels of related cell machinery.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2023 ","pages":"4779199"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10264138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9654508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PPAR ResearchPub Date : 2023-01-01DOI: 10.1155/2023/6797694
Chao Lu, Shenglin Gao, Li Zhang, Xiaokai Shi, Yin Chen, Shuzhang Wei, Li Zuo, Lifeng Zhang
{"title":"<i>Nuclear Protein 1</i> Expression Is Associated with PPARG in Bladder Transitional Cell Carcinoma.","authors":"Chao Lu, Shenglin Gao, Li Zhang, Xiaokai Shi, Yin Chen, Shuzhang Wei, Li Zuo, Lifeng Zhang","doi":"10.1155/2023/6797694","DOIUrl":"https://doi.org/10.1155/2023/6797694","url":null,"abstract":"<p><strong>Background: </strong>The <i>Nuclear protein 1</i> gene was first discovered in acute pancreatitis and functions as an oncogene in cancer progression and drug resistance. However, the role of <i>Nuclear protein 1</i> in bladder transitional cell carcinoma (BTCC) is still unclear.</p><p><strong>Methods: </strong>The Cancer Genome Atlas database and immunohistochemical analysis were adopted to evaluate <i>Nuclear protein 1</i> expression in BTCC. We applied lentivirus-mediated small-interfering RNA to down-regulate the expression of <i>Nuclear protein 1</i> in BTCC cell lines. We further performed an Affymetrix microarray and Gene Set Enrichment Analysis (GSEA) to assess the genes and signaling pathways related to <i>Nuclear protein 1</i>.</p><p><strong>Results: </strong>We found that <i>Nuclear protein 1</i> expression was up-regulated in BTCC and positively related to the degree of BTCC malignancy. Compared with Caucasian patients with BTCC, <i>Nuclear protein 1</i> expression was attenuated in Asian patients. The Affymetrix microarray showed that lipopolysaccharide was the upstream regulatory factor of <i>Nuclear protein 1</i> in BTCC. The GSEA indicated that <i>Nuclear protein 1</i> expression was associated with signaling pathways in cancer, peroxisome proliferator-activated receptor (PPAR) pathways, and RNA degradation. The expression of <i>Nuclear protein 1</i> was negatively correlated with PPARG (<i>R</i> = -0.290, <i>P</i> < 0.001), but not with PPARA (<i>R</i> = 0.047, <i>P</i> = 0.344) and PPARD (<i>R</i> = -0.055, <i>P</i> = 0.260).</p><p><strong>Conclusions: </strong>The study findings indicate that <i>Nuclear protein 1</i> is positively associated with the malignancy degree of BTCC and that <i>Nuclear protein 1</i> expression is negatively correlated with PPARG.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2023 ","pages":"6797694"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10185424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9487460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PPAR ResearchPub Date : 2023-01-01DOI: 10.1155/2023/7405954
Manal A Malibary
{"title":"Vitamin A: A Key Inhibitor of Adipocyte Differentiation.","authors":"Manal A Malibary","doi":"10.1155/2023/7405954","DOIUrl":"https://doi.org/10.1155/2023/7405954","url":null,"abstract":"<p><p>Inhibiting adipocyte differentiation, the conversion of preadipocytes to mature functional adipocytes, might represent a new approach to treating obesity and related metabolic disorders. Peroxisome proliferator-activated receptor <i>γ</i> and CCAAT-enhancer-binding protein <i>α</i> are two master coregulators controlling adipogenesis both in culture and in vivo. Many recent studies have confirmed the relationship between retinoic acid (RA) and the conversion of embryonic stem cells into adipocytes; however, these studies have shown that RA potently blocks the differentiation of preadipocytes into mature adipocytes. Nevertheless, the functional role of RA in early tissue development and stem cell differentiation, including in adipose tissue, remains unclear. This study highlights transcription factors that block adipocyte differentiation and maintain preadipocyte status, focusing on those controlled by RA. However, some of these novel adipogenesis inhibitors have not been validated in vivo, and their mechanisms of action require further clarification.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2023 ","pages":"7405954"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9908342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10707322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}