Pub Date : 2024-05-20eCollection Date: 2024-01-01DOI: 10.1590/1414-431X2024e13468
T C M de Nóbrega, M A R C P da Silva, E M Rampani, R Curi, R B Bazotte
In this double-blind placebo-controlled randomized investigation, we assessed the tolerability of glutamine in older adults recruited from three daycare centers. The relevance of studying glutamine supplementation in elderly patients lies in its potential to provide a well-tolerated intervention. Glutamine, a crucial amino acid, plays a vital role in various physiological processes, including immune function and protein synthesis. Understanding its impact on older adults is essential, given the potential implications for their health and well-being. Participants received a daily dose of 12.4 g of oral effervescent glutamine (EGln group) or maltodextrin (placebo group) for 60 days. Fifteen patients from each group completed the study. The mean ages were 77.0±9.1 and 79.0±6.9 years for the EGln and placebo groups, respectively. We evaluated body mass index, aminogram, hemogram, plasma levels of glucose, prealbumin, albumin, urea, creatinine, uric acid, C-reactive protein, vitamin D, calcium, sodium, potassium, and the plasma activities of aspartate aminotransferase and alanine aminotransferase. Notably, we quantified a broad array of inflammatory markers and growth factors providing a holistic understanding of the potential effects of glutamine supplementation. The results demonstrated that oral glutamine did not induce significant changes in any evaluated parameters, and no adverse effects were reported. This finding suggested that the dosage of glutamine used in this study was well-tolerated and safe. This information contributes to the broader understanding of glutamine supplementation, emphasizing its safety and supporting its potential as a viable intervention for maintaining health in aging individuals.
{"title":"Tolerability of glutamine supplementation in older adults: a double-blind placebo-controlled randomized clinical trial.","authors":"T C M de Nóbrega, M A R C P da Silva, E M Rampani, R Curi, R B Bazotte","doi":"10.1590/1414-431X2024e13468","DOIUrl":"10.1590/1414-431X2024e13468","url":null,"abstract":"<p><p>In this double-blind placebo-controlled randomized investigation, we assessed the tolerability of glutamine in older adults recruited from three daycare centers. The relevance of studying glutamine supplementation in elderly patients lies in its potential to provide a well-tolerated intervention. Glutamine, a crucial amino acid, plays a vital role in various physiological processes, including immune function and protein synthesis. Understanding its impact on older adults is essential, given the potential implications for their health and well-being. Participants received a daily dose of 12.4 g of oral effervescent glutamine (EGln group) or maltodextrin (placebo group) for 60 days. Fifteen patients from each group completed the study. The mean ages were 77.0±9.1 and 79.0±6.9 years for the EGln and placebo groups, respectively. We evaluated body mass index, aminogram, hemogram, plasma levels of glucose, prealbumin, albumin, urea, creatinine, uric acid, C-reactive protein, vitamin D, calcium, sodium, potassium, and the plasma activities of aspartate aminotransferase and alanine aminotransferase. Notably, we quantified a broad array of inflammatory markers and growth factors providing a holistic understanding of the potential effects of glutamine supplementation. The results demonstrated that oral glutamine did not induce significant changes in any evaluated parameters, and no adverse effects were reported. This finding suggested that the dosage of glutamine used in this study was well-tolerated and safe. This information contributes to the broader understanding of glutamine supplementation, emphasizing its safety and supporting its potential as a viable intervention for maintaining health in aging individuals.</p>","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11136481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160090","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}
Adenine nucleotide translocator 4 (Ant4), an ATP/ADP transporter expressed in the early phases of spermatogenesis, plays a crucial role in male fertility. While Ant4 loss causes early arrest of meiosis and increased apoptosis of spermatogenic cells in male mice, its other potential functions in male fertility remain unexplored. Here, we utilized Ant4 knockout mice to delineate the effects of Ant4-deficiency on male reproduction. Our observations demonstrated that Ant4-deficiency led to infertility and impaired testicular development, which was further investigated by evaluating testicular oxidative stress, autophagy, and inflammation. Specifically, the loss of Ant4 led to an imbalance of oxidation and antioxidants. Significant ultrastructural alterations were identified in the testicular tissues of Ant4-deficient mice, including swelling of mitochondria, loss of cristae, and accumulation of autophagosomes. Our results also showed that autophagic flux and AKT-AMPK-mTOR signaling pathway were affected in Ant4-deficient mice. Moreover, Ant4 loss increased the expression of pro-inflammatory factors. Overall, our findings underscored the importance of Ant4 in regulating oxidative stress, autophagy, and inflammation in testicular tissues. Taken together, these insights provided a nuanced understanding of the significance of Ant4 in testicular development.
{"title":"The essential role of adenine nucleotide translocase 4 on male reproductive function in mice.","authors":"Fengyuan Yang, Xiali Yang, Hui Zhu, Xinbo Wang, Xin Liao, Yinxu Fu, Ting Fu, Xiandan Chen, Aliaksei Sysa, Jianxin Lyu, Huaibin Zhou","doi":"10.1590/1414-431X2024e13590","DOIUrl":"10.1590/1414-431X2024e13590","url":null,"abstract":"<p><p>Adenine nucleotide translocator 4 (Ant4), an ATP/ADP transporter expressed in the early phases of spermatogenesis, plays a crucial role in male fertility. While Ant4 loss causes early arrest of meiosis and increased apoptosis of spermatogenic cells in male mice, its other potential functions in male fertility remain unexplored. Here, we utilized Ant4 knockout mice to delineate the effects of Ant4-deficiency on male reproduction. Our observations demonstrated that Ant4-deficiency led to infertility and impaired testicular development, which was further investigated by evaluating testicular oxidative stress, autophagy, and inflammation. Specifically, the loss of Ant4 led to an imbalance of oxidation and antioxidants. Significant ultrastructural alterations were identified in the testicular tissues of Ant4-deficient mice, including swelling of mitochondria, loss of cristae, and accumulation of autophagosomes. Our results also showed that autophagic flux and AKT-AMPK-mTOR signaling pathway were affected in Ant4-deficient mice. Moreover, Ant4 loss increased the expression of pro-inflammatory factors. Overall, our findings underscored the importance of Ant4 in regulating oxidative stress, autophagy, and inflammation in testicular tissues. Taken together, these insights provided a nuanced understanding of the significance of Ant4 in testicular development.</p>","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11136480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160073","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 : 2024-05-20eCollection Date: 2024-01-01DOI: 10.1590/1414-431X2024e13238
Jia He, Jia Zuo, Xiaochen Fan, Zhe Li
Osteoarthritis (OA) is a highly prevalent joint disorder characterized by progressive degeneration of articular cartilage, subchondral bone remodeling, osteophyte formation, synovial inflammation, and meniscal damage. Although the etiology of OA is multifactorial, pro-inflammatory processes appear to play a key role in disease pathogenesis. Previous studies indicate that electroacupuncture (EA) exerts chondroprotective, anti-inflammatory, and analgesic effects in preclinical models of OA, but the mechanisms underlying these potential therapeutic benefits remain incompletely defined. This study aimed to investigate the effects of EA on OA development in a rat model, as well as to explore associated molecular mechanisms modulated by EA treatment. Forty rats were divided into OA, EA, antagomiR-214, and control groups. Following intra-articular injection of monosodium iodoacetate to induce OA, EA and antagomiR-214 groups received daily EA stimulation at acupoints around the knee joint for 21 days. Functional pain behaviors and chondrocyte apoptosis were assessed as outcome measures. The expression of microRNA-214 (miR-214) and its downstream targets involved in apoptosis and nociception, BAX and TRPV4, were examined. Results demonstrated that EA treatment upregulated miR-214 expression in OA knee cartilage. By suppressing pro-apoptotic BAX and pro-nociceptive TRPV4, this EA-induced miR-214 upregulation ameliorated articular pain and prevented chondrocyte apoptosis. These findings suggested that miR-214 plays a key role mediating EA's therapeutic effects in OA pathophysiology, and represents a promising OA treatment target for modulation by acupuncture.
骨关节炎(OA)是一种高发的关节疾病,其特点是关节软骨逐渐退化、软骨下骨重塑、骨质增生形成、滑膜炎症和半月板损伤。虽然 OA 的病因是多因素的,但促炎过程似乎在疾病发病机制中起着关键作用。先前的研究表明,电针(EA)可在 OA 临床前模型中发挥软骨保护、抗炎和镇痛作用,但这些潜在疗效的机制仍未完全明确。本研究旨在研究 EA 对大鼠模型 OA 发育的影响,并探索 EA 治疗调节的相关分子机制。40 只大鼠被分为 OA 组、EA 组、antagomiR-214 组和对照组。在关节内注射碘乙酸钠诱导 OA 后,EA 组和 antagomiR-214 组每天对膝关节周围的穴位进行 EA 刺激,持续 21 天。评估结果包括功能性疼痛行为和软骨细胞凋亡。研究还检测了microRNA-214(miR-214)及其参与细胞凋亡和痛觉的下游靶标BAX和TRPV4的表达。结果表明,EA 治疗可上调 OA 膝关节软骨中 miR-214 的表达。通过抑制促凋亡的 BAX 和促痛觉的 TRPV4,EA 诱导的 miR-214 上调可改善关节疼痛并防止软骨细胞凋亡。这些研究结果表明,miR-214在介导EA对OA病理生理学的治疗作用中起着关键作用,是针灸治疗OA的一个很有前景的靶点。
{"title":"Electro-acupuncture modulated miR-214 expression to prevent chondrocyte apoptosis and reduce pain by targeting BAX and TRPV4 in osteoarthritis rats.","authors":"Jia He, Jia Zuo, Xiaochen Fan, Zhe Li","doi":"10.1590/1414-431X2024e13238","DOIUrl":"10.1590/1414-431X2024e13238","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a highly prevalent joint disorder characterized by progressive degeneration of articular cartilage, subchondral bone remodeling, osteophyte formation, synovial inflammation, and meniscal damage. Although the etiology of OA is multifactorial, pro-inflammatory processes appear to play a key role in disease pathogenesis. Previous studies indicate that electroacupuncture (EA) exerts chondroprotective, anti-inflammatory, and analgesic effects in preclinical models of OA, but the mechanisms underlying these potential therapeutic benefits remain incompletely defined. This study aimed to investigate the effects of EA on OA development in a rat model, as well as to explore associated molecular mechanisms modulated by EA treatment. Forty rats were divided into OA, EA, antagomiR-214, and control groups. Following intra-articular injection of monosodium iodoacetate to induce OA, EA and antagomiR-214 groups received daily EA stimulation at acupoints around the knee joint for 21 days. Functional pain behaviors and chondrocyte apoptosis were assessed as outcome measures. The expression of microRNA-214 (miR-214) and its downstream targets involved in apoptosis and nociception, BAX and TRPV4, were examined. Results demonstrated that EA treatment upregulated miR-214 expression in OA knee cartilage. By suppressing pro-apoptotic BAX and pro-nociceptive TRPV4, this EA-induced miR-214 upregulation ameliorated articular pain and prevented chondrocyte apoptosis. These findings suggested that miR-214 plays a key role mediating EA's therapeutic effects in OA pathophysiology, and represents a promising OA treatment target for modulation by acupuncture.</p>","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11136484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159972","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 : 2024-05-20eCollection Date: 2024-01-01DOI: 10.1590/1414-431X2024e13645
Qinqin Song, Hongxue Xu, Hongjiao Wu, Jing Dong, Shanshan Ji, Xuemei Zhang, Zhi Zhang, Wanning Hu
Colorectal cancer is one of the most common malignant cancers. Pseudogenes have been identified as oncogenes or tumor suppressor genes in the development of various cancers. However, the function of pseudogene CSPG4P12 in colorectal cancer remains unclear. Therefore, the aim of this study was to investigate the potential role of CSPG4P12 in colorectal cancer and explore the possible underlying mechanism. The difference of CSPG4P12 expression between colorectal cancer tissues and adjacent normal tissues was analyzed using the online Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. Cell viability and colony formation assays were conducted to evaluate cell viability. Transwell and wound healing assays were performed to assess cell migration and invasion capacities. Western blot was used to measure the expression levels of epithelial-mesenchymal transition-related proteins. Colorectal cancer tissues had lower CSPG4P12 expression than adjacent normal tissues. The overexpression of CSPG4P12 inhibited cell proliferation, invasion, and migration in colorectal cancer cells. Overexpressed CSPG4P12 promoted the expression of E-cadherin, whereas it inhibited the expression of vimentin, N-cadherin, and MMP9. These findings suggested that CSPG4P12 inhibits colorectal cancer development and may serve as a new potential target for colorectal cancer.
{"title":"Pseudogene CSPG4P12 inhibits colorectal cancer progression by attenuating epithelial-mesenchymal transition.","authors":"Qinqin Song, Hongxue Xu, Hongjiao Wu, Jing Dong, Shanshan Ji, Xuemei Zhang, Zhi Zhang, Wanning Hu","doi":"10.1590/1414-431X2024e13645","DOIUrl":"10.1590/1414-431X2024e13645","url":null,"abstract":"<p><p>Colorectal cancer is one of the most common malignant cancers. Pseudogenes have been identified as oncogenes or tumor suppressor genes in the development of various cancers. However, the function of pseudogene CSPG4P12 in colorectal cancer remains unclear. Therefore, the aim of this study was to investigate the potential role of CSPG4P12 in colorectal cancer and explore the possible underlying mechanism. The difference of CSPG4P12 expression between colorectal cancer tissues and adjacent normal tissues was analyzed using the online Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. Cell viability and colony formation assays were conducted to evaluate cell viability. Transwell and wound healing assays were performed to assess cell migration and invasion capacities. Western blot was used to measure the expression levels of epithelial-mesenchymal transition-related proteins. Colorectal cancer tissues had lower CSPG4P12 expression than adjacent normal tissues. The overexpression of CSPG4P12 inhibited cell proliferation, invasion, and migration in colorectal cancer cells. Overexpressed CSPG4P12 promoted the expression of E-cadherin, whereas it inhibited the expression of vimentin, N-cadherin, and MMP9. These findings suggested that CSPG4P12 inhibits colorectal cancer development and may serve as a new potential target for colorectal cancer.</p>","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11136487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159977","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}
More attention has been paid to immunotherapy for ovarian cancer and the development of tumor vaccines. We developed a trichostatin A (TSA)-modified tumor vaccine with potent immunomodulating activities that can inhibit the growth of ovarian cancer in rats and stimulate immune cell response in vivo. TSA-treated Nutu-19 cells inactivated by X-ray radiation were used as a tumor vaccine in rat ovarian cancer models. Prophylactic and therapeutic experiments were performed with TSA-modified tumor vaccine in rats. Flow cytometry and ELISpot assays were conducted to assess immune response. Immune cell expression in the spleen and thymus were detected by immunohistochemical staining. GM-CSF, IL-7, IL-17, LIF, LIX, KC, MCP-1, MIP-2, M-CSF, IP-10/CXCL10, MIG/CXCL9, RANTES, IL-4, IFN-γ, and VEGF expressions were detected with Milliplex Map Magnetic Bead Panel immunoassay. TSA vaccination in therapeutic and prophylactic models could effectively stimulate innate immunity and boost the adaptive humoral and cell-mediated immune responses to inhibit the growth and tumorigenesis of ovarian cancer. This vaccine stimulated the thymus into reactivating status and enhanced infiltrating lymphocytes in tumor-bearing rats. The expression of key immunoregulatory factors were upregulated in the vaccine group. The intensities of infiltrating CD4+ and CD8+ T cells and NK cells were significantly increased in the vaccine group compared to the control group (P<0.05). This protection was mainly dependent on the IFN-γ pathway and, to a much lesser extent, by the IL-4 pathway. The tumor cells only irradiated by X-ray as the control group still showed a slight immune effect, indicating that irradiated cells may also cause certain immune antigen exposure, but the efficacy was not as significant as that of the TSA-modified tumor vaccine. Our study revealed the potential application of the TSA-modified tumor vaccine as a novel tumor vaccine against tumor refractoriness and growth. These findings offer a better understanding of the immunomodulatory effects of the vaccine against latent tumorigenesis and progression. This tumor vaccine therapy may increase antigen exposure, synergistically activate the immune system, and ultimately improve remission rates. A vaccine strategy designed to induce effective tumor immune response is being considered for cancer immunotherapy.
卵巢癌的免疫疗法和肿瘤疫苗的开发受到越来越多的关注。我们开发了一种具有强效免疫调节活性的三司他丁 A(TSA)修饰肿瘤疫苗,它能抑制大鼠卵巢癌的生长,并刺激体内免疫细胞的反应。经 X 射线辐射灭活的 TSA 处理的 Nutu-19 细胞被用作大鼠卵巢癌模型的肿瘤疫苗。用 TSA 改性肿瘤疫苗对大鼠进行了预防和治疗实验。流式细胞术和 ELISpot 试验评估了免疫反应。通过免疫组化染色检测脾脏和胸腺中免疫细胞的表达。用 Milliplex Map 磁珠板免疫测定法检测 GM-CSF、IL-7、IL-17、LIF、LIX、KC、MCP-1、MIP-2、M-CSF、IP-10/CXCL10、MIG/CXCL9、RANTES、IL-4、IFN-γ 和 VEGF 的表达。在治疗和预防模型中接种TSA疫苗能有效刺激先天性免疫,增强适应性体液免疫和细胞介导免疫反应,从而抑制卵巢癌的生长和肿瘤发生。这种疫苗能刺激胸腺进入再激活状态,并增强肿瘤大鼠的浸润淋巴细胞。疫苗组中关键免疫调节因子的表达得到了上调。与对照组相比,疫苗组浸润的 CD4+ 和 CD8+ T 细胞以及 NK 细胞的强度显著增加(P<0.05)。这种保护主要依赖于 IFN-γ 通路,其次是 IL-4 通路。仅用X射线照射的肿瘤细胞作为对照组,仍表现出轻微的免疫效应,说明照射细胞也可能引起某些免疫抗原的暴露,但疗效不如TSA修饰的肿瘤疫苗显著。我们的研究揭示了TSA修饰的肿瘤疫苗作为一种新型肿瘤疫苗在对抗肿瘤耐药性和生长方面的潜在应用。这些发现让我们更好地了解了疫苗对潜伏肿瘤发生和发展的免疫调节作用。这种肿瘤疫苗疗法可增加抗原暴露,协同激活免疫系统,并最终提高缓解率。目前正在考虑将旨在诱导有效肿瘤免疫反应的疫苗策略用于癌症免疫疗法。
{"title":"Trichostatin A-modified vaccine provides superior protection against ovarian cancer formation and development","authors":"Yingwei Liu, T. Yi, Shenglan Meng, Xia Zhao, Xiancheng Chen, Yanna Zhang","doi":"10.1590/1414-431X2024e12874","DOIUrl":"https://doi.org/10.1590/1414-431X2024e12874","url":null,"abstract":"More attention has been paid to immunotherapy for ovarian cancer and the development of tumor vaccines. We developed a trichostatin A (TSA)-modified tumor vaccine with potent immunomodulating activities that can inhibit the growth of ovarian cancer in rats and stimulate immune cell response in vivo. TSA-treated Nutu-19 cells inactivated by X-ray radiation were used as a tumor vaccine in rat ovarian cancer models. Prophylactic and therapeutic experiments were performed with TSA-modified tumor vaccine in rats. Flow cytometry and ELISpot assays were conducted to assess immune response. Immune cell expression in the spleen and thymus were detected by immunohistochemical staining. GM-CSF, IL-7, IL-17, LIF, LIX, KC, MCP-1, MIP-2, M-CSF, IP-10/CXCL10, MIG/CXCL9, RANTES, IL-4, IFN-γ, and VEGF expressions were detected with Milliplex Map Magnetic Bead Panel immunoassay. TSA vaccination in therapeutic and prophylactic models could effectively stimulate innate immunity and boost the adaptive humoral and cell-mediated immune responses to inhibit the growth and tumorigenesis of ovarian cancer. This vaccine stimulated the thymus into reactivating status and enhanced infiltrating lymphocytes in tumor-bearing rats. The expression of key immunoregulatory factors were upregulated in the vaccine group. The intensities of infiltrating CD4+ and CD8+ T cells and NK cells were significantly increased in the vaccine group compared to the control group (P<0.05). This protection was mainly dependent on the IFN-γ pathway and, to a much lesser extent, by the IL-4 pathway. The tumor cells only irradiated by X-ray as the control group still showed a slight immune effect, indicating that irradiated cells may also cause certain immune antigen exposure, but the efficacy was not as significant as that of the TSA-modified tumor vaccine. Our study revealed the potential application of the TSA-modified tumor vaccine as a novel tumor vaccine against tumor refractoriness and growth. These findings offer a better understanding of the immunomodulatory effects of the vaccine against latent tumorigenesis and progression. This tumor vaccine therapy may increase antigen exposure, synergistically activate the immune system, and ultimately improve remission rates. A vaccine strategy designed to induce effective tumor immune response is being considered for cancer immunotherapy.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140963162","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}
Pub Date : 2024-05-17DOI: 10.1590/1414-431X2024e13304
T.S. Araujo, M. A. Spadella, C.P. Carlos, C. R. Tirapelli, E.F.B. Chagas, J.C.D. Pinheiro, A.B. Chies
Arthritis has important cardiovascular repercussions. Phenylephrine-induced vasoconstriction is impaired in rat aortas in the early phase of the adjuvant-induced arthritis (AIA), around the 15th day post-induction. Therefore, the present study aimed to verify the effects of AIA on hyporesponsiveness to phenylephrine in rat aortas. AIA was induced by intradermal injection of Mycobacterium tuberculosis (3.8 mg/dL) in the right hind paw of male Wistar rats (n=27). Functional experiments in isolated aortas were carried out 15 days after AIA induction. Morphometric and stereological analyses of the aortas were also performed 36 days after the induction of AIA. AIA did not promote structural modifications in the aortas at any of the time points studied. AIA reduced phenylephrine-induced contraction in endothelium-intact aortas, but not in endothelium-denuded aortas. However, AIA did not change KCl-induced contraction in either endothelium-intact or denuded aortas. L-NAME (non-selective NOS inhibitor), 1400W (selective iNOS inhibitor), and ODQ (guanylyl cyclase inhibitor) reversed AIA-induced hyporesponsiveness to phenylephrine in intact aortas. 7-NI (selective nNOS inhibitor) increased the contraction induced by phenylephrine in aortas from AIA rats. In summary, the hyporesponsiveness to phenylephrine induced by AIA was endothelium-dependent and mediated by iNOS-derived NO through activation of the NO-guanylyl cyclase pathway.
{"title":"Adjuvant-induced arthritis promotes vascular hyporesponsiveness to phenylephrine through a nitric oxide-related mechanism","authors":"T.S. Araujo, M. A. Spadella, C.P. Carlos, C. R. Tirapelli, E.F.B. Chagas, J.C.D. Pinheiro, A.B. Chies","doi":"10.1590/1414-431X2024e13304","DOIUrl":"https://doi.org/10.1590/1414-431X2024e13304","url":null,"abstract":"Arthritis has important cardiovascular repercussions. Phenylephrine-induced vasoconstriction is impaired in rat aortas in the early phase of the adjuvant-induced arthritis (AIA), around the 15th day post-induction. Therefore, the present study aimed to verify the effects of AIA on hyporesponsiveness to phenylephrine in rat aortas. AIA was induced by intradermal injection of Mycobacterium tuberculosis (3.8 mg/dL) in the right hind paw of male Wistar rats (n=27). Functional experiments in isolated aortas were carried out 15 days after AIA induction. Morphometric and stereological analyses of the aortas were also performed 36 days after the induction of AIA. AIA did not promote structural modifications in the aortas at any of the time points studied. AIA reduced phenylephrine-induced contraction in endothelium-intact aortas, but not in endothelium-denuded aortas. However, AIA did not change KCl-induced contraction in either endothelium-intact or denuded aortas. L-NAME (non-selective NOS inhibitor), 1400W (selective iNOS inhibitor), and ODQ (guanylyl cyclase inhibitor) reversed AIA-induced hyporesponsiveness to phenylephrine in intact aortas. 7-NI (selective nNOS inhibitor) increased the contraction induced by phenylephrine in aortas from AIA rats. In summary, the hyporesponsiveness to phenylephrine induced by AIA was endothelium-dependent and mediated by iNOS-derived NO through activation of the NO-guanylyl cyclase pathway.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140962872","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}
Older adults have a high prevalence of falls due to a decline in physiological functions and various chronic diseases. This study aimed to investigate the prevalence of and risk factors for falls among older individuals in the Chinese Longitudinal Healthy Longevity Survey (CLHLS). We collected information from 9737 older individuals (average age=84.26 years) from the CLHLS and used binary logistic regression analysis to explore the independent risk factors and protective factors for falls. The logistic regression analysis results are reported as adjusted odds ratios (aORs) and 95% confidence intervals (95%CIs). The prevalence of falls among older adults in China was 21.6%, with women (24.6%) having a higher prevalence than men (18.1%). Logistic regression analysis revealed that never (or rarely) eating fresh fruit, difficulty with hearing, cataracts, and arthritis were the common independent risk factors for falls in older Chinese men and women. Among men, age ≥80 years (aOR=1.86), never doing housework (aOR=1.36), and dyslipidemia (aOR=1.47) were risk factors, while eating milk products once a week was a protective factor. Alcohol consumption (aOR=1.40), physical labor (aOR=1.28), and heart disease (aOR=1.21) were risk factors for falls in women, while a daily sleep duration of 6-12 h and garlic consumption once a week were protective factors. The prevalence of falls among older adults in China is 21.6% and is greater in women than in men. These risk and protective factors can be used to formulate reasonable recommendations for living habits, diet, and chronic disease control strategies.
{"title":"Prevalence and risk factors for falls among older Chinese adults in the community: findings from the CLHLS study","authors":"Haodong Liang, Zijie Zhang, Haitian Lai, Tianzhao Tian","doi":"10.1590/1414-431X2024e13469","DOIUrl":"https://doi.org/10.1590/1414-431X2024e13469","url":null,"abstract":"Older adults have a high prevalence of falls due to a decline in physiological functions and various chronic diseases. This study aimed to investigate the prevalence of and risk factors for falls among older individuals in the Chinese Longitudinal Healthy Longevity Survey (CLHLS). We collected information from 9737 older individuals (average age=84.26 years) from the CLHLS and used binary logistic regression analysis to explore the independent risk factors and protective factors for falls. The logistic regression analysis results are reported as adjusted odds ratios (aORs) and 95% confidence intervals (95%CIs). The prevalence of falls among older adults in China was 21.6%, with women (24.6%) having a higher prevalence than men (18.1%). Logistic regression analysis revealed that never (or rarely) eating fresh fruit, difficulty with hearing, cataracts, and arthritis were the common independent risk factors for falls in older Chinese men and women. Among men, age ≥80 years (aOR=1.86), never doing housework (aOR=1.36), and dyslipidemia (aOR=1.47) were risk factors, while eating milk products once a week was a protective factor. Alcohol consumption (aOR=1.40), physical labor (aOR=1.28), and heart disease (aOR=1.21) were risk factors for falls in women, while a daily sleep duration of 6-12 h and garlic consumption once a week were protective factors. The prevalence of falls among older adults in China is 21.6% and is greater in women than in men. These risk and protective factors can be used to formulate reasonable recommendations for living habits, diet, and chronic disease control strategies.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140963289","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}
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, with approximately 600,000 new cases each year. A small number of HNSCCs are caused by human papillomavirus (HPV) infection. Frizzled related protein (FRZB) has been reported in many inflammatory diseases and cancers, but it is yet unclear how FRZB affects HNSCC, as well as its role and underlying mechanism. TIMER2 database was utilized to evaluate FRZB expression in cancer tissues, and FRZB expression in HNSCC tissues was confirmed by samples obtained from Gene Expression Omnibus. To identify whether FRZB could be used as a prognostic predictor, we performed univariate and multivariate Cox regression analyses. FRZB co-expression profile was explored using the LinkedOmics database, then Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses were performed for these FRZB-related genes in HNSCC samples. Lasso regression analysis was subsequently used to screen for prognostic variables, and we determined the infiltration of immune cells in HNSCC patients to clarify the influence of FRZB on tumor immune microenvironment. At last, we assessed the association between FRZB expression and immune checkpoint gene, and compared the sensitivity of common chemotherapeutic agents. In this study, we found that FRZB was dysregulated in HNSCC tumor tissues and had a relationship with clinical parameters. The reliability and independence of FRZB as a factor in determining a patient's prognosis for HNSCC was also established. Additional investigation revealed that FRZB was linked to common immune checkpoint genes and may be implicated in immune infiltration.
{"title":"FRZB: a potential prognostic marker for head and neck squamous cell carcinoma","authors":"Yunshan Li, Feihan Gu, Xu Huang, Wenkai Huang, Junwei Xiang, Jiayuan Yue, Yuanyin Wang, Ran Chen","doi":"10.1590/1414-431X2024e13368","DOIUrl":"https://doi.org/10.1590/1414-431X2024e13368","url":null,"abstract":"Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, with approximately 600,000 new cases each year. A small number of HNSCCs are caused by human papillomavirus (HPV) infection. Frizzled related protein (FRZB) has been reported in many inflammatory diseases and cancers, but it is yet unclear how FRZB affects HNSCC, as well as its role and underlying mechanism. TIMER2 database was utilized to evaluate FRZB expression in cancer tissues, and FRZB expression in HNSCC tissues was confirmed by samples obtained from Gene Expression Omnibus. To identify whether FRZB could be used as a prognostic predictor, we performed univariate and multivariate Cox regression analyses. FRZB co-expression profile was explored using the LinkedOmics database, then Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses were performed for these FRZB-related genes in HNSCC samples. Lasso regression analysis was subsequently used to screen for prognostic variables, and we determined the infiltration of immune cells in HNSCC patients to clarify the influence of FRZB on tumor immune microenvironment. At last, we assessed the association between FRZB expression and immune checkpoint gene, and compared the sensitivity of common chemotherapeutic agents. In this study, we found that FRZB was dysregulated in HNSCC tumor tissues and had a relationship with clinical parameters. The reliability and independence of FRZB as a factor in determining a patient's prognosis for HNSCC was also established. Additional investigation revealed that FRZB was linked to common immune checkpoint genes and may be implicated in immune infiltration.","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140963749","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}
Pub Date : 2024-05-03eCollection Date: 2024-01-01DOI: 10.1590/1414-431X2024e13474
Delu Zheng, Chenli Cui, Chengsong Ye, Chen Shao, Xiujing Zha, Ying Xu, Xu Liu, Can Wang
Coenzyme Q10 (CoQ10) is a potent antioxidant that is implicated in the inhibition of osteoclastogenesis, but the underlying mechanism has not been determined. We explored the underlying molecular mechanisms involved in this process. RAW264.7 cells received receptor activator of NF-κB ligand (RANKL) and CoQ10, after which the differentiation and viability of osteoclasts were assessed. After the cells were treated with CoQ10 and/or H2O2 and RANKL, the levels of reactive oxygen species (ROS) and proteins involved in the PI3K/AKT/mTOR and MAPK pathways and autophagy were tested. Moreover, after the cells were pretreated with or without inhibitors of the two pathways or with the mitophagy agonist, the levels of autophagy-related proteins and osteoclast markers were measured. CoQ10 significantly decreased the number of TRAP-positive cells and the level of ROS but had no significant impact on cell viability. The relative phosphorylation levels of PI3K, AKT, mTOR, ERK, and p38 were significantly reduced, but the levels of FOXO3/LC3/Beclin1 were significantly augmented. Moreover, the levels of FOXO3/LC3/Beclin1 were significantly increased by the inhibitors and mitophagy agonist, while the levels of osteoclast markers showed the opposite results. Our data showed that CoQ10 prevented RANKL-induced osteoclastogenesis by promoting autophagy via inactivation of the PI3K/AKT/mTOR and MAPK pathways in RAW264.7 cells.
{"title":"Coenzyme Q10 prevents RANKL-induced osteoclastogenesis by promoting autophagy via inactivation of the PI3K/AKT/mTOR and MAPK pathways.","authors":"Delu Zheng, Chenli Cui, Chengsong Ye, Chen Shao, Xiujing Zha, Ying Xu, Xu Liu, Can Wang","doi":"10.1590/1414-431X2024e13474","DOIUrl":"10.1590/1414-431X2024e13474","url":null,"abstract":"<p><p>Coenzyme Q10 (CoQ10) is a potent antioxidant that is implicated in the inhibition of osteoclastogenesis, but the underlying mechanism has not been determined. We explored the underlying molecular mechanisms involved in this process. RAW264.7 cells received receptor activator of NF-κB ligand (RANKL) and CoQ10, after which the differentiation and viability of osteoclasts were assessed. After the cells were treated with CoQ10 and/or H2O2 and RANKL, the levels of reactive oxygen species (ROS) and proteins involved in the PI3K/AKT/mTOR and MAPK pathways and autophagy were tested. Moreover, after the cells were pretreated with or without inhibitors of the two pathways or with the mitophagy agonist, the levels of autophagy-related proteins and osteoclast markers were measured. CoQ10 significantly decreased the number of TRAP-positive cells and the level of ROS but had no significant impact on cell viability. The relative phosphorylation levels of PI3K, AKT, mTOR, ERK, and p38 were significantly reduced, but the levels of FOXO3/LC3/Beclin1 were significantly augmented. Moreover, the levels of FOXO3/LC3/Beclin1 were significantly increased by the inhibitors and mitophagy agonist, while the levels of osteoclast markers showed the opposite results. Our data showed that CoQ10 prevented RANKL-induced osteoclastogenesis by promoting autophagy via inactivation of the PI3K/AKT/mTOR and MAPK pathways in RAW264.7 cells.</p>","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11085036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875835","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 : 2024-05-03eCollection Date: 2024-01-01DOI: 10.1590/1414-431X2024e13549
E A Hase, L L Iervolino, H A Antico, N Bozzini, R P V Francisco
Expanding uterine masses can be the cause of pregnancy loss and add technical difficulties to uterus evacuation due to the intense anatomical distortion of the endocervical canal and uterine cavity. The literature is scarce in the peculiarities of the management of missed abortions in uterus with important distorted anatomies. We report a case of a primigravida patient who presented a rapid and expressive increase of abdominal volume due to a giant uterine mass, evolving to miscarriage. Ultrasound can be a useful tool, allowing visualization of the endocervical path and uterine cavity, helping to perform uterine evacuation in the presence of anatomical distortion without compromising the reproductive future. To the best of our knowledge, no such case has been previously reported.
{"title":"Giant uterine tumor and miscarriage: how to proceed?","authors":"E A Hase, L L Iervolino, H A Antico, N Bozzini, R P V Francisco","doi":"10.1590/1414-431X2024e13549","DOIUrl":"10.1590/1414-431X2024e13549","url":null,"abstract":"<p><p>Expanding uterine masses can be the cause of pregnancy loss and add technical difficulties to uterus evacuation due to the intense anatomical distortion of the endocervical canal and uterine cavity. The literature is scarce in the peculiarities of the management of missed abortions in uterus with important distorted anatomies. We report a case of a primigravida patient who presented a rapid and expressive increase of abdominal volume due to a giant uterine mass, evolving to miscarriage. Ultrasound can be a useful tool, allowing visualization of the endocervical path and uterine cavity, helping to perform uterine evacuation in the presence of anatomical distortion without compromising the reproductive future. To the best of our knowledge, no such case has been previously reported.</p>","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11085029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875837","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}