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Buspirone Induces Weight Loss and Normalization of Blood Pressure via the Stimulation of PPARδ Dependent Energy Producing Pathway in Spontaneously Hypertensive Rats. 丁螺环酮通过刺激自发性高血压大鼠PPARδ依赖的能量产生途径诱导体重减轻和血压正常化。
IF 2.9 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 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

Introduction: 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.

Methods: 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.

Results: The lipid accumulation was lowered in differentiated 3T3-L1 cells by buspirone treatments of 50 and 100 μM 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 δ (PPARδ), 5' adenosine monophosphate-activated protein kinase (AMPK), and PPARγ coactivator-1 alpha (PGC-1α) were increased both in C2C12 cells treated by buspirone of 100 μM 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.

Conclusion: Buspirone may induce the losses of body weight and abdominal fat weight through the activation of PPARδ dependent catabolic metabolism producing energy, and eventually, the ameliorated lipid metabolism could normalize high blood pressure.

丁螺环酮作为5-羟色胺(5-羟色胺)受体1A (5-HT1A)的部分激动剂,已被作为一种抗焦虑药物开给患者。此外,在高血压动物模型中报道了血清素对血压的降低作用。通过高血压和肥胖动物模型,探讨丁螺环酮对早期高血压引起的脂质代谢紊乱的治疗机制。方法:通过测量体重和脂肪量、血液分析、免疫印迹、免疫组织化学和染色等方法,评估与脂质代谢和高血压相关的各种生物标志物水平。结果:丁螺环酮浓度为50 μM和100 μM的3T3-L1细胞与未处理的分化对照组相比,脂质积累明显减少。丁螺环酮10 mg/kg/d给药4周后自发性高血压大鼠体重和腹部脂肪重量较未给药8周组明显降低。与8周未治疗组相比,给予丁螺环酮5和10 mg/kg/天的SHRs甘油三酯(TG)水平降低。与未治疗8周组相比,丁螺环酮10 mg/kg/d组高密度脂蛋白(HDL)-胆固醇浓度升高。与8周未治疗组相比,丁螺环酮治疗5和10 mg/kg/天可降低SHRs患者的血压。100 μM丁螺环酮处理的C2C12细胞和1、5、10 mg/kg/d丁螺环酮处理的SHRs细胞中,过氧化物酶体增殖体活化受体δ (PPARδ)、5′腺苷单磷酸活化蛋白激酶(AMPK)和PPARγ共激活因子-1α (PGC-1α)的蛋白水平均高于未处理的对照组和未处理8周的组。给予丁螺环酮1、5和10 mg/kg/天治疗的SHRs, 8周未治疗组脂肪细胞数量减少,脂肪细胞数量增加。与4周组相比,8周治疗组血管紧张素II型1受体(AT1R)和血管细胞粘附分子1 (VCAM1)的蛋白表达水平升高,而1、5和10 mg/kg/d丁螺环酮治疗组的蛋白表达水平降低。结论:丁螺环酮可能通过激活PPARδ依赖的分解代谢产生能量,导致体重和腹部脂肪重量的减少,最终改善脂质代谢,使高血压正常。
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引用次数: 0
Effect of Pesticides on Peroxisome Proliferator-Activated Receptors (PPARs) and Their Association with Obesity and Diabetes. 农药对过氧化物酶体增殖物激活受体的影响及其与肥胖和糖尿病的关系
IF 2.9 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.1155/2023/1743289
J Hernández-Valdez, A Velázquez-Zepeda, J C Sánchez-Meza

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), PPARα, PPARβ/δ, and PPARγ; this was possible through in silico, in vitro, and in vivo 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.

肥胖和糖尿病被认为是21世纪最重要的疾病。最近,许多流行病学研究已经将农药暴露与肥胖和2型糖尿病的发展联系起来。通过研究农药与控制脂质和碳水化合物代谢的主要核受体家族之一:过氧化物酶体增殖体激活受体(PPARs)、PPARα、PPARβ/δ和PPARγ之间的关系,探讨农药在这些疾病发生中的作用及其可能的影响;这是可能通过在硅,体外和体内的分析。本文旨在揭示农药对ppar的影响及其在能量代谢变化中的作用,这些变化导致肥胖和2型糖尿病的发生。
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引用次数: 1
PPARG: A Promising Therapeutic Target in Breast Cancer and Regulation by Natural Drugs. PPARG:一个有前景的乳腺癌治疗靶点及天然药物的调控作用。
IF 2.9 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.1155/2023/4481354
De-Hui Li, Xu-Kuo Liu, Xiao-Tong Tian, Fei Liu, Xu-Jiong Yao, Jing-Fei Dong

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.

乳腺癌(BC)是女性中最常见的癌症。过氧化物酶体增殖物激活受体γ (PPARG)可以调节脂肪细胞相关基因的产生,具有抗炎和抗肿瘤作用。我们的目的是研究PPARG在BC中的表达、可能的预后价值及其对免疫细胞浸润的影响,并探讨天然药物对PPARG的调节作用,以寻找治疗BC的新方法。我们利用不同的生物信息学工具,提取并综合分析来自Cancer Genome Atlas、Genotype-Tissue Expression和bencozujian数据库的数据,研究PPARG潜在的抗bc机制和潜在的靶向天然药物。首先,我们发现PPARG在BC中下调,其表达水平与BC的病理肿瘤分期(pt期)和病理肿瘤-淋巴结-转移分期(ptnm期)相关。PPARG在雌激素受体阳性(ER+) BC中的表达高于雌激素受体阴性(ER-) BC,这往往预示着更好的预后。同时,PPARG与BC患者免疫细胞浸润呈显著正相关,与较好的累积生存率相关。此外,PPARG水平与免疫相关基因和免疫检查点的表达呈正相关,ER+患者对免疫检查点阻断的反应更好。相关通路研究表明,PPARG与ER+ BC血管生成、细胞凋亡、脂肪酸生物合成和降解等通路密切相关。我们还发现槲皮素是上调PPARG的天然药物中最有希望的天然抗bc药物。我们的研究表明,PPARG可能通过调节免疫微环境来减少BC的发展。槲皮素作为PPARG配体/激动剂是治疗BC的潜在天然药物。
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引用次数: 1
A Promotion Role of MIR31 in the Process of Vocal Fold Wound Healing. MIR31在声带伤口愈合过程中的促进作用。
IF 2.9 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.1155/2023/4672827
Haizhou Wang, Wen Xu

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 (p < 5.65 × 10-5) but decreased in the late stage of VFWH compared with the early and middle stages (p < 5.40 × 10-3. 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.

MIR31在伤口愈合过程中的作用,特别是在声带伤口愈合(VFWH)中的作用,尽管它可能促进这一过程,但仍不确定。在这项研究中,我们首先构建了一个基于文献的途径来研究MIR31对伤口愈合的积极和消极影响。然后,我们对20只大鼠进行动物实验,研究声带损伤后不同时间点(1、4和8周)MIR31的表达情况。通过共表达分析和通路分析,探讨MIR31在VFWH中的潜在功能。基于文献的途径表明,MIR31可以通过分别调节14和47个伤口愈合上游调控因子来阻碍和促进伤口愈合过程。然而,大鼠实验表明,MIR31表达在声带损伤后显著升高(p < 5.65 × 10-5),但在VFWH晚期较早中期降低(p < 5.40 × 10-3)。MIR31与17个vfwh显著基因(Pearson相关系数∈(0.63,0.83))之间存在强共表达,主要参与胶原蛋白的生成。总的来说,我们的研究结果表明MIR31在VFWH中起着关键作用,特别是在胶原合成和其他生物过程中,值得进一步研究。
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引用次数: 0
Development and Validation of the Promising PPAR Signaling Pathway-Based Prognostic Prediction Model in Uterine Cervical Cancer. 基于PPAR信号通路的子宫颈癌预后预测模型的建立与验证
IF 2.9 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.1155/2023/4962460
Yan Zhang, Xing Li, Jun Zhang, Lin Mao, Zou Wen, Mingliang Cao, Xuefeng Mu

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.

过氧化物酶体增殖物激活受体(PPAR)是一种配体激活的转录因子,可调节脂肪酸的摄取和转运。在一些研究中,癌细胞PPAR表达/活性的上调与癌症进展有关。在全球范围内,子宫颈癌在女性癌症中排名第四。血管生成抑制剂自5年前引入以来,改善了复发和晚期宫颈癌的治疗。尽管如此,晚期子宫颈癌的中位总生存率为16.8个月,表明治疗效果仍然不足。因此,开发新的治疗方法势在必行。在这项工作中,我们首先从之前的研究中下载了PPAR信号通路相关基因。此外,采用单样本基因集富集分析(ssGSEA)算法计算宫颈癌患者PPAR评分。此外,不同PPAR评分的宫颈癌患者对免疫检查点治疗的敏感性也不同。为了筛选这些基因作为宫颈癌患者的最佳生物标志物,我们构建了基于ppar的预后预测模型。结果显示,PCK1、MT1A、AL096855.1、AC096711.2、FAR2P2、AC099568.2不仅在PPAR信号通路中发挥关键作用,而且在宫颈癌患者中具有良好的预测价值。基因集变异分析(GSVA)富集分析也证明了PPAR信号通路是预后预测模型中富集程度最高的通路之一。最后,进一步分析表明AC099568.2可能是宫颈癌患者诊断、治疗和预后最有前景的生物标志物。生存分析和受试者工作特征曲线均显示AC099568.2在宫颈癌患者中起关键作用。然而,据我们所知,这是第一次有研究关注AC099568.2在宫颈癌患者中的作用。我们的工作成功揭示了一种新的宫颈癌患者生物标志物,也为今后的研究提供了新的方向。
{"title":"Development and Validation of the Promising PPAR Signaling Pathway-Based Prognostic Prediction Model in Uterine Cervical Cancer.","authors":"Yan Zhang,&nbsp;Xing Li,&nbsp;Jun Zhang,&nbsp;Lin Mao,&nbsp;Zou Wen,&nbsp;Mingliang Cao,&nbsp;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}
引用次数: 0
PPARβ/δ Agonism with GW501516 Increases Myotube PGC-1α Content and Reduces BCAA Media Content Independent of Changes in BCAA Catabolic Enzyme Expression. GW501516对PPARβ/δ的激动作用增加肌管PGC-1α含量,降低BCAA培养基含量,而不依赖于BCAA分解代谢酶表达的变化。
IF 2.9 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.1155/2023/4779199
Caroline N Rivera, Jason S Hinkle, Rachel M Watne, Trent C Macgowan, Andrew J Wommack, Roger A Vaughan

Background: 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-1α). PGC-1α regulates the expression of branched-chain amino acid (BCAA) metabolism, and thus, increased circulating BCAA in diabetics may be partially explained by reduced PGC-1α expression. PGC-1α functions in-part through interactions with peroxisome proliferator-activated receptor β/δ (PPARβ/δ). The present report examined the effects of the PPARβ/δ 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.

Methods: 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).

Results: GW significantly increased PGC-1α 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.

Conclusion: These data confirm the ability of GW to increase muscle PGC-1α 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.

背景:2型糖尿病的特点是胰岛素敏感性降低,血液代谢产物升高,线粒体代谢减少,代谢调控基因表达减少,如过氧化物酶体增殖物激活受体γ辅助激活因子1- α (PGC-1α)。PGC-1α调节支链氨基酸(BCAA)代谢的表达,因此PGC-1α表达降低可能是糖尿病患者循环BCAA增加的部分原因。PGC-1α通过与过氧化物酶体增殖物激活受体β/δ (PPARβ/δ)相互作用发挥部分功能。本报告研究了PPARβ/δ激动作用对培养肌管细胞代谢和相关基因/蛋白表达的影响,重点研究了GW对BCAA处理和分解代谢酶表达的影响。方法:用GW501516 (GW)处理C2C12肌管达24小时。分别通过耗氧量和细胞外酸化率测定线粒体和糖酵解代谢。分别采用实时荧光定量聚合酶链反应(qRT-PCR)和western blot检测代谢基因和蛋白的表达。采用液相色谱-质谱法(LC/MS)测定培养基BCAA含量。结果:GW显著提高PGC-1α蛋白表达、线粒体含量和线粒体功能。24小时处理后,GW也显著降低了培养基中BCAA的含量;然而,BCAA分解代谢酶/转运蛋白的表达没有变化。结论:这些数据证实了GW能够增加肌肉PGC-1α含量,降低BCAA培养基含量,而不影响BCAA分解代谢酶/转运蛋白。这些发现表明,在相关细胞机制的蛋白质水平没有实质性变化的情况下,BCAA摄取(可能还有代谢)可能会增加。
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引用次数: 0
Nuclear Protein 1 Expression Is Associated with PPARG in Bladder Transitional Cell Carcinoma. 核蛋白1在膀胱移行细胞癌中的表达与PPARG相关
IF 2.9 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.1155/2023/6797694
Chao Lu, Shenglin Gao, Li Zhang, Xiaokai Shi, Yin Chen, Shuzhang Wei, Li Zuo, Lifeng Zhang

Background: The Nuclear protein 1 gene was first discovered in acute pancreatitis and functions as an oncogene in cancer progression and drug resistance. However, the role of Nuclear protein 1 in bladder transitional cell carcinoma (BTCC) is still unclear.

Methods: The Cancer Genome Atlas database and immunohistochemical analysis were adopted to evaluate Nuclear protein 1 expression in BTCC. We applied lentivirus-mediated small-interfering RNA to down-regulate the expression of Nuclear protein 1 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 Nuclear protein 1.

Results: We found that Nuclear protein 1 expression was up-regulated in BTCC and positively related to the degree of BTCC malignancy. Compared with Caucasian patients with BTCC, Nuclear protein 1 expression was attenuated in Asian patients. The Affymetrix microarray showed that lipopolysaccharide was the upstream regulatory factor of Nuclear protein 1 in BTCC. The GSEA indicated that Nuclear protein 1 expression was associated with signaling pathways in cancer, peroxisome proliferator-activated receptor (PPAR) pathways, and RNA degradation. The expression of Nuclear protein 1 was negatively correlated with PPARG (R = -0.290, P < 0.001), but not with PPARA (R = 0.047, P = 0.344) and PPARD (R = -0.055, P = 0.260).

Conclusions: The study findings indicate that Nuclear protein 1 is positively associated with the malignancy degree of BTCC and that Nuclear protein 1 expression is negatively correlated with PPARG.

背景:核蛋白1基因首次在急性胰腺炎中被发现,并在肿瘤进展和耐药过程中作为致癌基因发挥作用。然而,核蛋白1在膀胱移行细胞癌(BTCC)中的作用尚不清楚。方法:采用肿瘤基因组图谱数据库和免疫组化分析方法检测BTCC中核蛋白1的表达。应用慢病毒介导的小干扰RNA下调BTCC细胞株核蛋白1的表达。我们进一步使用Affymetrix微阵列和基因集富集分析(GSEA)来评估与核蛋白1相关的基因和信号通路。结果:我们发现核蛋白1在BTCC中表达上调,且与BTCC恶性程度呈正相关。与白种人BTCC患者相比,亚洲患者的核蛋白1表达减弱。Affymetrix微阵列检测结果显示,脂多糖是BTCC中核蛋白1的上游调控因子。GSEA表明,核蛋白1的表达与肿瘤信号通路、过氧化物酶体增殖物激活受体(PPAR)通路和RNA降解有关。核蛋白1的表达与PPARG呈负相关(R = -0.290, P < 0.001),与PPARA (R = 0.047, P = 0.344)、PPARD (R = -0.055, P = 0.260)无显著相关性。结论:研究结果表明,核蛋白1与BTCC恶性程度呈正相关,而核蛋白1的表达与PPARG呈负相关。
{"title":"<i>Nuclear Protein 1</i> Expression Is Associated with PPARG in Bladder Transitional Cell Carcinoma.","authors":"Chao Lu,&nbsp;Shenglin Gao,&nbsp;Li Zhang,&nbsp;Xiaokai Shi,&nbsp;Yin Chen,&nbsp;Shuzhang Wei,&nbsp;Li Zuo,&nbsp;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}
引用次数: 0
Vitamin A: A Key Inhibitor of Adipocyte Differentiation. 维生素A:脂肪细胞分化的关键抑制剂。
IF 2.9 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.1155/2023/7405954
Manal A Malibary

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 γ and CCAAT-enhancer-binding protein α 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.

抑制脂肪细胞分化,将前脂肪细胞转化为成熟的功能性脂肪细胞,可能是治疗肥胖和相关代谢紊乱的新途径。过氧化物酶体增殖激活受体γ和ccaat增强结合蛋白α是两种主要的共调节因子,在培养和体内控制脂肪形成。最近的许多研究证实了维甲酸(RA)与胚胎干细胞转化为脂肪细胞之间的关系;然而,这些研究表明RA有效地阻断了前脂肪细胞向成熟脂肪细胞的分化。然而,RA在包括脂肪组织在内的早期组织发育和干细胞分化中的功能作用仍不清楚。本研究重点研究了阻断脂肪细胞分化和维持前脂肪细胞状态的转录因子,重点研究了由RA控制的转录因子。然而,这些新的脂肪生成抑制剂中的一些尚未在体内得到验证,其作用机制需要进一步阐明。
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引用次数: 2
Appraisal of the Possible Role of PPARγ Upregulation by CLA of Probiotic Pediococcus pentosaceus GS4 in Colon Cancer Mitigation. 益生菌戊糖Pediococcus GS4 CLA上调PPARγ在结肠癌缓解中的可能作用
IF 2.9 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-01-01 DOI: 10.1155/2023/9458308
Vinay Dubey, Alok Kumar Mishra, Asit Ranjan Ghosh

The prevalence of colon cancer (CC) is increasing at the endemic scale, which is accompanied by subsequent morbidity and mortality. Although there have been noteworthy achievements in the therapeutic strategies in recent years, the treatment of patients with CC remains a formidable task. The current study focused on to study role of biohydrogenation-derived conjugated linoleic acid (CLA) of probiotic Pediococcus pentosaceus GS4 (CLAGS4) against CC, which induced peroxisome proliferator-activated receptor gamma (PPARγ) expression in human CC HCT-116 cells. Pre-treatment with PPARγ antagonist bisphenol A diglycidyl ether has significantly reduced the inhibitory efficacy of enhanced cell viability of HCT-116 cells, suggesting the PPARγ-dependent cell death. The cancer cells treated with CLA/CLAGS4 demonstrated the reduced level of Prostaglandin E2 PGE2 in association with reduced COX-2 and 5-LOX expressions. Moreover, these consequences were found to be associated with PPARγ-dependent. Furthermore, delineation of mitochondrial dependent apoptosis with the help of molecular docking LigPlot analysis showed that CLA can bind with hexokinase-II (hHK-II) (highly expressed in cancer cells) and that this association underlies voltage dependent anionic channel to open, thereby causing mitochondrial membrane depolarization, a condition that initiates intrinsic apoptotic events. Apoptosis was further confirmed by annexin V staining and elevation of caspase 1p10 expression. Taken all together, it is deduced that, mechanistically, the upregulation of PPARγ by CLAGS4 of P. pentosaceus GS4 can alter cancer cell metabolism in association with triggering apoptosis in CC.

结肠癌(CC)的流行率在地方性规模上呈上升趋势,并伴随着随后的发病率和死亡率。尽管近年来在治疗策略方面取得了显著的成就,但CC患者的治疗仍然是一项艰巨的任务。本研究主要研究益生菌戊糖Pediococcus pentosaceus GS4 (CLAGS4)生物氢化衍生共轭亚油酸(CLA)在人CC HCT-116细胞中诱导过氧化物酶体增殖物激活受体γ (PPARγ)表达的作用。PPARγ拮抗剂双酚A二缩水甘油醚预处理显著降低了HCT-116细胞增强细胞活力的抑制效果,提示PPARγ依赖性细胞死亡。CLA/CLAGS4处理的癌细胞显示前列腺素E2 PGE2水平降低,COX-2和5-LOX表达降低。此外,这些结果被发现与ppar γ依赖性有关。此外,在分子对接LigPlot分析的帮助下,对线粒体依赖性凋亡的描述表明,CLA可以与己糖激酶- ii (hHK-II)结合(在癌细胞中高表达),这种结合是电压依赖性阴离子通道打开的基础,从而导致线粒体膜去极化,这是引发内在凋亡事件的条件。annexin V染色和caspase 1p10表达升高进一步证实细胞凋亡。综上所述,我们推断,在机制上,P. pentosaceus GS4的CLAGS4上调PPARγ可以改变癌细胞代谢并引发细胞凋亡。
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引用次数: 0
Activation of PPARγ Protects Obese Mice from Acute Lung Injury by Inhibiting Endoplasmic Reticulum Stress and Promoting Mitochondrial Biogenesis. 激活PPARγ通过抑制内质网应激和促进线粒体生物发生保护肥胖小鼠急性肺损伤。
IF 2.9 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2022-09-28 eCollection Date: 2022-01-01 DOI: 10.1155/2022/7888937
Yin Tang, Ke Wei, Ling Liu, Jingyue Ma, Siqi Wu, Wenjing Tang

Objective: Obesity-induced endoplasmic reticulum (ER) stress plays a role in increased susceptibility to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The activation of peroxisome proliferator-activated receptor-γ (PPARγ) is associated with lung protection and is effective in ameliorating ER stress and mitochondrial dysfunction. The aim of this study was to investigate the expression of PPARγ in the lung tissues of obese mice and explore whether the PPARγ-dependent pathway could mediate decreased ALI/ARDS by regulating ER stress and mitochondrial biogenesis.

Methods: We determined PPARγ expression in the lung tissues of normal and obese mice. ALI models of alveolar epithelial cells and of obese mice were used and treated with either PPARγ activator rosiglitazone (RSG) or PPARγ inhibitor GW9662. Lung tissue and cell samples were collected to assess lung inflammation and apoptosis, and ER stress and mitochondrial biogenesis were detected.

Results: PPARγ expression was significantly decreased in the lung tissue of obese mice compared with that in normal mice. Both in vivo and in vitro studies have shown that activation of PPARγ leads to reduced expression of the ER stress marker proteins 78-kDa glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP), and Caspase12. Conversely, expression of the mitochondrial biogenesis-related proteins peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1α), nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (TFAM) increased. Furthermore, activation of PPARγ is associated with decreased levels of lung inflammation and epithelial apoptosis and increased expression of adiponectin (APN) and mitofusin2 (MFN2). GW9662 bound to PPARγ and blocked its transcriptional activity and then diminished the protective effect of PPARγ on lung tissues.

Conclusions: PPARγ activation exerts anti-inflammation effects in alveolar epithelia by alleviating ER stress and promoting mitochondrial biogenesis. Therefore, lower levels of PPARγ in the lung tissues of obese mice may lead to an increased susceptibility to ALI.

目的:肥胖引起的内质网应激与急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)易感性增加有关。过氧化物酶体增殖物激活受体-γ (PPARγ)的激活与肺保护有关,并可有效改善内质网应激和线粒体功能障碍。本研究旨在研究肥胖小鼠肺组织中PPARγ的表达,探讨PPARγ依赖通路是否通过调节内质网应激和线粒体生物发生介导ALI/ARDS的减少。方法:测定正常和肥胖小鼠肺组织中PPARγ的表达。使用肺泡上皮细胞和肥胖小鼠的ALI模型,并使用PPARγ激活剂罗格列酮(RSG)或PPARγ抑制剂GW9662治疗。收集肺组织和细胞样本,评估肺部炎症和凋亡,检测内质网应激和线粒体生物发生。结果:肥胖小鼠肺组织中PPARγ的表达明显低于正常小鼠。体内和体外研究均表明,激活PPARγ可导致内质网应激标记蛋白78-kDa葡萄糖调节蛋白(GRP78)、C/EBP同源蛋白(CHOP)和Caspase12的表达降低。相反,线粒体生物发生相关蛋白过氧化物酶体增殖物激活受体γ共激活因子1 (PGC-1α)、核呼吸因子-1 (NRF-1)和线粒体转录因子A (TFAM)的表达增加。此外,PPARγ的激活与肺炎症和上皮细胞凋亡水平的降低以及脂联素(APN)和丝裂酶2 (MFN2)表达的增加有关。GW9662与PPARγ结合,阻断其转录活性,降低PPARγ对肺组织的保护作用。结论:PPARγ激活通过减轻内质网应激和促进线粒体生物发生,在肺泡上皮中发挥抗炎作用。因此,肥胖小鼠肺组织中PPARγ水平降低可能导致ALI易感性增加。
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引用次数: 0
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