Pub Date : 2024-11-17DOI: 10.3390/biomedicines12112625
Paola Parrella, Raffaela Barbano, Katharina Jonas, Andrea Fontana, Serena Barile, Michelina Rendina, Antonio Lo Mele, Giuseppina Prencipe, Luigi Ciuffreda, Maria Grazia Morritti, Vanna Maria Valori, Paolo Graziano, Evaristo Maiello, Massimiliano Copetti, Martin Pichler, Barbara Pasculli
Background: MicroRNAs are well established as master regulators of carcinogenesis and potential biomarkers in breast cancer (BC). In a preliminary effort, we found miR-27a-5p to be significantly downregulated in experimentally derived mammospheres and BC patients from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) dataset. Objectives. Herein, we sought to investigate the putative involvement of miR-27a-5p in promoting a migratory phenotype of breast cancer cells, and establish whether miR-27a-5p is associated with patient clinicopathological characteristics. Methods: miR-27a-5p capability of inducing a metastasis-prone cell phenotype was analyzed in SUM159 and MDA-MB-231, both representing the triple negative BC subtype. miR-27a-5p expression profile was carried out in a cohort of 232 BC patients and normal breast tissues (NBTs) by RT-qPCR. Results: Transient miR-27a-5p inhibition did not affect cell proliferation but led to a significant increase of cell migration in knocked-down compared to control cells. Following quantification in the patient cohort, miR-27a-5p was found higher in NBTs (Median 2.28, IQR 1.50-5.40) and pre-invasive breast lesions (Median 3.32, IQR 1.68-4.32) compared to tumors. In particular, miR-27a-5p was less expressed in patients with synchronous (Median 1.03, IQR 0.83-1.58) or metachronous (Median 1.83, IQR 1.29-3.17) metastases than in patients free from metastases after a 5-year follow-up (Median 2.17, IQR 1.19-3.64), suggesting that miR-27a-5p expression is negatively correlated with breast pathology evolution (R = -0.13, p = 0.038). However, time-to-event analysis did not highlight significant associations with patient outcome in either our internal cohort or TCGA-BRCA dataset. Conclusions: Our study suggests a potential role of miR-27a-5p as tumor suppressor miRNA in breast cancer. Further investigations may help define its biomarker potential in each breast cancer subtype, and identify other molecular partners as targets for new interventions.
{"title":"Tumor Suppressor miR-27a-5p and Its Significance for Breast Cancer.","authors":"Paola Parrella, Raffaela Barbano, Katharina Jonas, Andrea Fontana, Serena Barile, Michelina Rendina, Antonio Lo Mele, Giuseppina Prencipe, Luigi Ciuffreda, Maria Grazia Morritti, Vanna Maria Valori, Paolo Graziano, Evaristo Maiello, Massimiliano Copetti, Martin Pichler, Barbara Pasculli","doi":"10.3390/biomedicines12112625","DOIUrl":"10.3390/biomedicines12112625","url":null,"abstract":"<p><p><b>Background:</b> MicroRNAs are well established as master regulators of carcinogenesis and potential biomarkers in breast cancer (BC). In a preliminary effort, we found miR-27a-5p to be significantly downregulated in experimentally derived mammospheres and BC patients from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) dataset. <b>Objectives.</b> Herein, we sought to investigate the putative involvement of miR-27a-5p in promoting a migratory phenotype of breast cancer cells, and establish whether miR-27a-5p is associated with patient clinicopathological characteristics. <b>Methods:</b> miR-27a-5p capability of inducing a metastasis-prone cell phenotype was analyzed in SUM159 and MDA-MB-231, both representing the triple negative BC subtype. miR-27a-5p expression profile was carried out in a cohort of 232 BC patients and normal breast tissues (NBTs) by RT-qPCR. <b>Results:</b> Transient miR-27a-5p inhibition did not affect cell proliferation but led to a significant increase of cell migration in knocked-down compared to control cells. Following quantification in the patient cohort, miR-27a-5p was found higher in NBTs (Median 2.28, IQR 1.50-5.40) and pre-invasive breast lesions (Median 3.32, IQR 1.68-4.32) compared to tumors. In particular, miR-27a-5p was less expressed in patients with synchronous (Median 1.03, IQR 0.83-1.58) or metachronous (Median 1.83, IQR 1.29-3.17) metastases than in patients free from metastases after a 5-year follow-up (Median 2.17, IQR 1.19-3.64), suggesting that miR-27a-5p expression is negatively correlated with breast pathology evolution (R = -0.13, p = 0.038). However, time-to-event analysis did not highlight significant associations with patient outcome in either our internal cohort or TCGA-BRCA dataset. <b>Conclusions:</b> Our study suggests a potential role of miR-27a-5p as tumor suppressor miRNA in breast cancer. Further investigations may help define its biomarker potential in each breast cancer subtype, and identify other molecular partners as targets for new interventions.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 11","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-17DOI: 10.3390/biomedicines12112628
Kamila Tańska, Piotr Glinicki, Beata Rebizant, Piotr Dudek, Wojciech Zgliczyński, Małgorzata Gietka-Czernel
Background/Objectives: Thyroid autoimmunity (TAI) affects about 15% of women of reproductive age and can negatively affect pregnancy outcomes. One possible mechanism for pregnancy complications can be attributed to a disturbed process of placentation caused by thyroid antibodies. To test this hypothesis, placental hormones and angiogenic factors in pregnant women with TAI were evaluated. Methods: Fifty-eight hypothyroid women positive for TPOAb/TgAb, thirty-three hypothyroid women negative for TPOAb/TgAb, and thirty-nine healthy controls were enrolled in this study. Maternal thyroid function tests were established every month throughout pregnancy, and angiogenic placental factors, pro-angiogenic placental growth factor (PlGF); two anti-angiogenic factors, soluble vascular endothelial growth factor receptor 1 (sFlt-1) and soluble endoglin (sEng); and placental hormones, estradiol, progesterone, and hCG, were determined during each trimester. Results: Obstetrical and neonatal outcomes did not differ between the groups. However, several detrimental effects of thyroid antibodies were observed. These included a positive correlation between TgAb and the sEng/PlGF ratio in the first trimester and positive correlations between TPOAb and sFlt-1 and between TgAb and the sFlt-1/PlGF ratio in the third trimester. TgAbs in the first trimester was a risk factor for gestational hypertension and preeclampsia. Conclusions: Our study indicates that TPOAbs and TgAbs can exert a direct harmful effect on placentation, leading to disturbances in the production of placental angiogenic factors and, consequently, to an increased risk of gestational hypertension and preeclampsia.
{"title":"Antithyroglobulin and Antiperoxidase Antibodies Can Negatively Influence Pregnancy Outcomes by Disturbing the Placentation Process and Triggering an Imbalance in Placental Angiogenic Factors.","authors":"Kamila Tańska, Piotr Glinicki, Beata Rebizant, Piotr Dudek, Wojciech Zgliczyński, Małgorzata Gietka-Czernel","doi":"10.3390/biomedicines12112628","DOIUrl":"10.3390/biomedicines12112628","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Thyroid autoimmunity (TAI) affects about 15% of women of reproductive age and can negatively affect pregnancy outcomes. One possible mechanism for pregnancy complications can be attributed to a disturbed process of placentation caused by thyroid antibodies. To test this hypothesis, placental hormones and angiogenic factors in pregnant women with TAI were evaluated. <b>Methods</b>: Fifty-eight hypothyroid women positive for TPOAb/TgAb, thirty-three hypothyroid women negative for TPOAb/TgAb, and thirty-nine healthy controls were enrolled in this study. Maternal thyroid function tests were established every month throughout pregnancy, and angiogenic placental factors, pro-angiogenic placental growth factor (PlGF); two anti-angiogenic factors, soluble vascular endothelial growth factor receptor 1 (sFlt-1) and soluble endoglin (sEng); and placental hormones, estradiol, progesterone, and hCG, were determined during each trimester. <b>Results</b>: Obstetrical and neonatal outcomes did not differ between the groups. However, several detrimental effects of thyroid antibodies were observed. These included a positive correlation between TgAb and the sEng/PlGF ratio in the first trimester and positive correlations between TPOAb and sFlt-1 and between TgAb and the sFlt-1/PlGF ratio in the third trimester. TgAbs in the first trimester was a risk factor for gestational hypertension and preeclampsia. <b>Conclusions</b>: Our study indicates that TPOAbs and TgAbs can exert a direct harmful effect on placentation, leading to disturbances in the production of placental angiogenic factors and, consequently, to an increased risk of gestational hypertension and preeclampsia.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 11","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-17DOI: 10.3390/biomedicines12112629
Jiahui Sun, Huiyi Wang, Junhong Xiao, Qiudong Yang, Heyu Liu, Zhengkun Yang, Yuqi Liu, Xin Huang, Liu Yang, Li Ma, Zhengguo Cao
Background/Objectives: Periodontitis is a common oral disease marked by gingival inflammation and alveolar bone loss. This study evaluated the efficacy of chamomile tincture and lidocaine hydrochloride (CLH) gel in mitigating periodontal inflammation and bone loss and uncovered the molecular mechanisms involved, both in vitro and in vivo. Methods: A periodontitis model was induced in Sprague Dawley rats by ligating the mandibular first molars. Sixty rats were divided into four groups: control (C), periodontitis (PD), periodontitis + CLH gel once daily (G1), and periodontitis + CLH gel thrice daily (G3). Clinical, micro-computed tomography (micro-CT), biological, and histological evaluations were performed, focusing on osteoclastogenesis, osteogenesis, and inflammatory cytokine production. The effect of CLH gel on inflammatory responses in RAW264.7 cells was also assessed through co-culture assays under Porphyromonas gingivalis (P. gingivalis) infection, with RNA-sequencing, qPCR, and Western blot analyses to explore underlying mechanisms. Results: CLH gel significantly reduced gingival and systemic inflammation and mitigated bone loss by enhancing the bone volume to tissue volume ratio and trabecular thickness via the RANKL/OPG axis in rats. The G3 group showed marked reductions in osteoclasts and increases in osterix-positive cells compared to other groups. In vitro, CLH gel reduced the inflammatory phenotype of macrophages in the periodontitis microenvironment by modulating Type II interferon (IFN-γ) networks. Conclusions: CLH gel reduced inflammation and bone loss in rat periodontitis, promoting osteogenesis and inhibiting osteoclastogenesis. It also suppressed macrophage inflammation via Type II interferon networks under P. gingivalis stimulation. These findings suggest that CLH gel has potential as an adjunctive therapy for periodontitis.
背景/目的:牙周炎是一种常见的口腔疾病,以牙龈发炎和牙槽骨流失为特征。本研究评估了洋甘菊酊和盐酸利多卡因(CLH)凝胶在减轻牙周炎症和骨质流失方面的疗效,并揭示了其中的体外和体内分子机制。研究方法通过结扎下颌第一磨牙诱导 Sprague Dawley 大鼠牙周炎模型。60 只大鼠被分为四组:对照组(C)、牙周炎组(PD)、牙周炎 + CLH 凝胶每日一次组(G1)和牙周炎 + CLH 凝胶每日三次组(G3)。对患者进行了临床、微型计算机断层扫描(micro-CT)、生物学和组织学评估,重点关注破骨细胞生成、骨生成和炎性细胞因子的产生。此外,还在牙龈卟啉单胞菌(P. gingivalis)感染的情况下,通过共培养试验评估了 CLH 凝胶对 RAW264.7 细胞炎症反应的影响,并通过 RNA 序列、qPCR 和 Western 印迹分析来探索其潜在机制。结果CLH凝胶通过RANKL/OPG轴提高大鼠的骨量与组织体积比和骨小梁厚度,从而明显减轻牙龈和全身炎症,缓解骨质流失。与其他组相比,G3 组的破骨细胞明显减少,而 osterix 阳性细胞则有所增加。在体外,CLH 凝胶通过调节 II 型干扰素(IFN-γ)网络,减少了牙周炎微环境中巨噬细胞的炎症表型。结论CLH凝胶可减少大鼠牙周炎的炎症和骨质流失,促进骨生成并抑制破骨细胞生成。它还能在牙龈脓疱刺激下通过 II 型干扰素网络抑制巨噬细胞炎症。这些研究结果表明,CLH凝胶具有辅助治疗牙周炎的潜力。
{"title":"Chamomile Tincture and Lidocaine Hydrochloride Gel Ameliorates Periodontitis: A Preclinical Study.","authors":"Jiahui Sun, Huiyi Wang, Junhong Xiao, Qiudong Yang, Heyu Liu, Zhengkun Yang, Yuqi Liu, Xin Huang, Liu Yang, Li Ma, Zhengguo Cao","doi":"10.3390/biomedicines12112629","DOIUrl":"10.3390/biomedicines12112629","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Periodontitis is a common oral disease marked by gingival inflammation and alveolar bone loss. This study evaluated the efficacy of chamomile tincture and lidocaine hydrochloride (CLH) gel in mitigating periodontal inflammation and bone loss and uncovered the molecular mechanisms involved, both in vitro and in vivo. <b>Methods</b>: A periodontitis model was induced in Sprague Dawley rats by ligating the mandibular first molars. Sixty rats were divided into four groups: control (C), periodontitis (PD), periodontitis + CLH gel once daily (G1), and periodontitis + CLH gel thrice daily (G3). Clinical, micro-computed tomography (micro-CT), biological, and histological evaluations were performed, focusing on osteoclastogenesis, osteogenesis, and inflammatory cytokine production. The effect of CLH gel on inflammatory responses in RAW264.7 cells was also assessed through co-culture assays under <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>) infection, with RNA-sequencing, qPCR, and Western blot analyses to explore underlying mechanisms. <b>Results</b>: CLH gel significantly reduced gingival and systemic inflammation and mitigated bone loss by enhancing the bone volume to tissue volume ratio and trabecular thickness via the RANKL/OPG axis in rats. The G3 group showed marked reductions in osteoclasts and increases in osterix-positive cells compared to other groups. In vitro, CLH gel reduced the inflammatory phenotype of macrophages in the periodontitis microenvironment by modulating Type II interferon (IFN-γ) networks. <b>Conclusions</b>: CLH gel reduced inflammation and bone loss in rat periodontitis, promoting osteogenesis and inhibiting osteoclastogenesis. It also suppressed macrophage inflammation via Type II interferon networks under <i>P. gingivalis</i> stimulation. These findings suggest that CLH gel has potential as an adjunctive therapy for periodontitis.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 11","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-17DOI: 10.3390/biomedicines12112627
Tudorel Mihoc, Silviu Constantin Latcu, Cosmin-Ciprian Secasan, Vlad Dema, Alin Adrian Cumpanas, Mircea Selaru, Catalin Alexandru Pirvu, Andrei Paul Valceanu, Flavia Zara, Cristina-Stefania Dumitru, Dorin Novacescu, Stelian Pantea
Acute pancreatitis is a complex inflammatory disorder with significant morbidity and mortality. This review aims to integrate the current knowledge of pancreatic morphology and immunology with the pathogenesis of acute pancreatitis, providing a comprehensive understanding of this critical condition. We conducted an extensive literature review, synthesizing data from recent studies and authoritative sources on pancreatic anatomy, histology, immunology, and the pathophysiology of acute pancreatitis. We also incorporated epidemiological data, clinical features, diagnostic criteria, and prognostic factors. The pancreas exhibits a complex morphology with intricate interactions between its exocrine and endocrine components. Its unique immunological landscape plays a crucial role in maintaining homeostasis and orchestrating responses to pathological conditions. In acute pancreatitis, the disruption of intracellular calcium signaling leads to premature enzyme activation, triggering a cascade of events including mitochondrial dysfunction, ATP depletion, and the release of proinflammatory mediators. This process can escalate from localized inflammation to systemic complications. The interplay between pancreatic morphology, immune responses, and pathophysiological mechanisms contributes to the varied clinical presentations and outcomes observed in acute pancreatitis. Understanding the intricate relationships between pancreatic morphology, immunology, and the pathogenesis of acute pancreatitis is crucial for developing more effective diagnostic and therapeutic strategies. This integrated approach provides new insights into the complex nature of acute pancreatitis and may guide future research directions in pancreatic disorders.
{"title":"Pancreatic Morphology, Immunology, and the Pathogenesis of Acute Pancreatitis.","authors":"Tudorel Mihoc, Silviu Constantin Latcu, Cosmin-Ciprian Secasan, Vlad Dema, Alin Adrian Cumpanas, Mircea Selaru, Catalin Alexandru Pirvu, Andrei Paul Valceanu, Flavia Zara, Cristina-Stefania Dumitru, Dorin Novacescu, Stelian Pantea","doi":"10.3390/biomedicines12112627","DOIUrl":"10.3390/biomedicines12112627","url":null,"abstract":"<p><p>Acute pancreatitis is a complex inflammatory disorder with significant morbidity and mortality. This review aims to integrate the current knowledge of pancreatic morphology and immunology with the pathogenesis of acute pancreatitis, providing a comprehensive understanding of this critical condition. We conducted an extensive literature review, synthesizing data from recent studies and authoritative sources on pancreatic anatomy, histology, immunology, and the pathophysiology of acute pancreatitis. We also incorporated epidemiological data, clinical features, diagnostic criteria, and prognostic factors. The pancreas exhibits a complex morphology with intricate interactions between its exocrine and endocrine components. Its unique immunological landscape plays a crucial role in maintaining homeostasis and orchestrating responses to pathological conditions. In acute pancreatitis, the disruption of intracellular calcium signaling leads to premature enzyme activation, triggering a cascade of events including mitochondrial dysfunction, ATP depletion, and the release of proinflammatory mediators. This process can escalate from localized inflammation to systemic complications. The interplay between pancreatic morphology, immune responses, and pathophysiological mechanisms contributes to the varied clinical presentations and outcomes observed in acute pancreatitis. Understanding the intricate relationships between pancreatic morphology, immunology, and the pathogenesis of acute pancreatitis is crucial for developing more effective diagnostic and therapeutic strategies. This integrated approach provides new insights into the complex nature of acute pancreatitis and may guide future research directions in pancreatic disorders.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 11","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hypertensive nephropathy (HN) is a leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD), contributing to significant morbidity, mortality, and rising healthcare costs. In this review article, we explore the role of epigenetic mechanisms in HN progression and their potential therapeutic implications. We begin by examining key epigenetic modifications-DNA methylation, histone modifications, and non-coding RNAs-observed in kidney disease. Next, we discuss the underlying pathophysiology of HN and highlight current in vitro and in vivo models used to study the condition. Finally, we compare various types of HN-induced renal injury and their associated epigenetic mechanisms with those observed in other kidney injury models, drawing inferences on potential epigenetic therapies for HN. The information gathered in this work indicate that epigenetic mechanisms can drive the progression of HN by regulating key molecular signaling pathways involved in renal damage and fibrosis. The limitations of Renin-Angiotensin-Aldosterone System (RAAS) inhibitors underscore the need for alternative treatments targeting epigenetic pathways. This review emphasizes the importance of further research into the epigenetic regulation of HN to develop more effective therapies and preventive strategies. Identifying novel epigenetic markers could provide new therapeutic opportunities for managing CKD and reducing the burden of ESRD.
{"title":"Epigenetics of Hypertensive Nephropathy.","authors":"Yize Zhang, Hamidreza Arzaghi, Zhehan Ma, Yasmin Roye, Samira Musah","doi":"10.3390/biomedicines12112622","DOIUrl":"10.3390/biomedicines12112622","url":null,"abstract":"<p><p>Hypertensive nephropathy (HN) is a leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD), contributing to significant morbidity, mortality, and rising healthcare costs. In this review article, we explore the role of epigenetic mechanisms in HN progression and their potential therapeutic implications. We begin by examining key epigenetic modifications-DNA methylation, histone modifications, and non-coding RNAs-observed in kidney disease. Next, we discuss the underlying pathophysiology of HN and highlight current in vitro and in vivo models used to study the condition. Finally, we compare various types of HN-induced renal injury and their associated epigenetic mechanisms with those observed in other kidney injury models, drawing inferences on potential epigenetic therapies for HN. The information gathered in this work indicate that epigenetic mechanisms can drive the progression of HN by regulating key molecular signaling pathways involved in renal damage and fibrosis. The limitations of Renin-Angiotensin-Aldosterone System (RAAS) inhibitors underscore the need for alternative treatments targeting epigenetic pathways. This review emphasizes the importance of further research into the epigenetic regulation of HN to develop more effective therapies and preventive strategies. Identifying novel epigenetic markers could provide new therapeutic opportunities for managing CKD and reducing the burden of ESRD.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 11","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-16DOI: 10.3390/biomedicines12112626
Zdenka Sunjic Lovric, Jasminka Resic Karara, Bianka Mimica, Marko Kumric, Daniela Supe-Domic, Roko Santic, Josko Bozic
Background: During pregnancy, significant cardiovascular changes occur to accommodate fetal growth, and catestatin may play a role in these changes. Evidence suggests that catestatin, a pleiotropic sympathoinhibitory peptide, is involved in multiple cardiovascular pathologies, including hypertensive disorders. The objective of this study was to compare serum catestatin levels between first-trimester pregnant women and non-pregnant women, aiming to investigate catestatin's role in blood pressure regulation during early pregnancy. Methods: This cross-sectional study included 72 first-trimester pregnant women and 57 age-matched non-pregnant controls, all without known cardiovascular or metabolic disorders. Results: Serum catestatin concentrations were significantly higher in pregnant women compared to controls (12.4 (9.9-21.2) ng/mL vs. 7.1 (4.5-10.9) ng/mL, p < 0.001). However, there was no significant difference in serum catestatin levels between those with a normal and abnormal uterine artery pulsatility index (17.8 (8.3-22.3) ng/mL vs. 12.5 (9.9-22.4) ng/mL, p = 0.962). Similarly, catestatin concentrations did not significantly differ between primiparous and multiparous women (14.0 (11.5-22.4) ng/mL vs. 10.7 (8.8-19.0) ng/mL). A positive correlation was observed between systolic blood pressure and serum catestatin levels in the control group (r = 0.335, p = 0.011) but not in pregnant women. Conclusions: Research on catestatin in pregnancy is still in its early stages, necessitating further studies to fully elucidate its roles and potential therapeutic applications.
{"title":"Analysis of Circulating Catestatin in Early Pregnancy: A Preliminary Investigation.","authors":"Zdenka Sunjic Lovric, Jasminka Resic Karara, Bianka Mimica, Marko Kumric, Daniela Supe-Domic, Roko Santic, Josko Bozic","doi":"10.3390/biomedicines12112626","DOIUrl":"10.3390/biomedicines12112626","url":null,"abstract":"<p><p><b>Background:</b> During pregnancy, significant cardiovascular changes occur to accommodate fetal growth, and catestatin may play a role in these changes. Evidence suggests that catestatin, a pleiotropic sympathoinhibitory peptide, is involved in multiple cardiovascular pathologies, including hypertensive disorders. The objective of this study was to compare serum catestatin levels between first-trimester pregnant women and non-pregnant women, aiming to investigate catestatin's role in blood pressure regulation during early pregnancy. <b>Methods:</b> This cross-sectional study included 72 first-trimester pregnant women and 57 age-matched non-pregnant controls, all without known cardiovascular or metabolic disorders. <b>Results:</b> Serum catestatin concentrations were significantly higher in pregnant women compared to controls (12.4 (9.9-21.2) ng/mL vs. 7.1 (4.5-10.9) ng/mL, <i>p</i> < 0.001). However, there was no significant difference in serum catestatin levels between those with a normal and abnormal uterine artery pulsatility index (17.8 (8.3-22.3) ng/mL vs. 12.5 (9.9-22.4) ng/mL, <i>p</i> = 0.962). Similarly, catestatin concentrations did not significantly differ between primiparous and multiparous women (14.0 (11.5-22.4) ng/mL vs. 10.7 (8.8-19.0) ng/mL). A positive correlation was observed between systolic blood pressure and serum catestatin levels in the control group (r = 0.335, <i>p</i> = 0.011) but not in pregnant women. <b>Conclusions:</b> Research on catestatin in pregnancy is still in its early stages, necessitating further studies to fully elucidate its roles and potential therapeutic applications.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 11","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-16DOI: 10.3390/biomedicines12112624
Michela Varone, Giuseppe Scavo, Mayra Colardo, Noemi Martella, Daniele Pensabene, Emanuele Bisesto, Andrea Del Busso, Marco Segatto
Background: Rett syndrome (RTT) is an early-onset neurological disorder primarily affecting females, leading to severe cognitive and physical disabilities. Recent studies indicate that an imbalance of redox homeostasis and exacerbated inflammatory responses are key players in the clinical manifestations of the disease. Emerging evidence highlights that the p75 neurotrophin receptor (p75NTR) is implicated in the regulation of oxidative stress (OS) and inflammation. Thus, this study is aimed at investigating the effects of p75NTR modulation by LM11A-31 on fibroblasts derived from RTT donors. Methods: RTT cells were treated with 0.1 µM of LM11A-31 for 24 h, and results were obtained using qPCR, immunofluorescence, ELISA, and Western blot techniques. Results: Our findings demonstrate that LM11A-31 reduces OS markers in RTT fibroblasts. Specifically, p75NTR modulation by LM11A-31 restores protein glutathionylation and reduces the expression of the pro-oxidant enzyme NOX4. Additionally, LM11A-31 significantly decreases the expression of the pro-inflammatory mediators interleukin-6 and interleukin-8. Additionally, LM11A-31 normalizes the expression levels of transcription factors involved in the regulation of the antioxidant response and inflammation. Conclusions: Collectively, these data suggest that p75NTR modulation may represent an effective therapeutic target to improve redox balance and reduce inflammation in RTT.
{"title":"p75NTR Modulation Reduces Oxidative Stress and the Expression of Pro-Inflammatory Mediators in a Cell Model of Rett Syndrome.","authors":"Michela Varone, Giuseppe Scavo, Mayra Colardo, Noemi Martella, Daniele Pensabene, Emanuele Bisesto, Andrea Del Busso, Marco Segatto","doi":"10.3390/biomedicines12112624","DOIUrl":"10.3390/biomedicines12112624","url":null,"abstract":"<p><p><b>Background:</b> Rett syndrome (RTT) is an early-onset neurological disorder primarily affecting females, leading to severe cognitive and physical disabilities. Recent studies indicate that an imbalance of redox homeostasis and exacerbated inflammatory responses are key players in the clinical manifestations of the disease. Emerging evidence highlights that the p75 neurotrophin receptor (p75NTR) is implicated in the regulation of oxidative stress (OS) and inflammation. Thus, this study is aimed at investigating the effects of p75NTR modulation by LM11A-31 on fibroblasts derived from RTT donors. <b>Methods:</b> RTT cells were treated with 0.1 µM of LM11A-31 for 24 h, and results were obtained using qPCR, immunofluorescence, ELISA, and Western blot techniques. <b>Results:</b> Our findings demonstrate that LM11A-31 reduces OS markers in RTT fibroblasts. Specifically, p75NTR modulation by LM11A-31 restores protein glutathionylation and reduces the expression of the pro-oxidant enzyme NOX4. Additionally, LM11A-31 significantly decreases the expression of the pro-inflammatory mediators interleukin-6 and interleukin-8. Additionally, LM11A-31 normalizes the expression levels of transcription factors involved in the regulation of the antioxidant response and inflammation. <b>Conclusions:</b> Collectively, these data suggest that p75NTR modulation may represent an effective therapeutic target to improve redox balance and reduce inflammation in RTT.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 11","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-16DOI: 10.3390/biomedicines12112621
Ala Alzubi, Jennifer M Monk
Background: Microbial fermentation of non-digestible carbohydrates and/or protein produces short-chain fatty acids (SCFA), whereas branched-chain fatty acids (BCFA) are produced from protein fermentation. The effects of individual SCFA and BCFA of comparable carbon chain length on adipocyte inflammation have not been investigated. Objective: To compare the effects of SCFA and BCFA on inflammatory mediator secretion in an adipocyte cell culture model designed to recapitulate obesity-associated adipocyte inflammation under normoxic and hypoxic conditions. Methods: The 3T3-L1 adipocytes were cultured (24 h) without (Control, Con) and with 1 mmol/L of SCFA (butyric acid (But) or valeric acid (Val)) or 1 mmol/L of BCFA (isobutyric acid (IsoBut) or isovaleric acid (IsoVal)) and were unstimulated (cells alone, n = 6/treatment), or stimulated with 10 ng/mL lipopolysaccharide (LPS, inflammatory stimulus, n = 8/treatment) or 10 ng/mL LPS + 100 µmol/L of the hypoxia memetic cobalt chloride (LPS/CC, inflammatory/hypoxic stimulus, n = 8/treatment). Results: Compared to Con + LPS, But + LPS reduced secreted protein levels of interleukin (IL)-1β, IL-6, macrophage chemoattractant protein (MCP)-1/chemokine ligand (CCL)2, MCP3/CCL7, macrophage inflammatory protein (MIP)-1α/CCL3 and regulated upon activation, normal T cell expressed, and secreted (RANTES)/CCL5 and decreased intracellular protein expression of the ratio of phosphorylated to total signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NFκB) p65 (p < 0.05). Val + LPS reduced IL-6 secretion and increased MCP-1/CCL2 secretion compared to Con + LPS and exhibited a different inflammatory mediator secretory profile from But + LPS (p < 0.05), indicating that individual SCFA exert individual effects. There were no differences in the secretory profile of the BCFA IsoBut + LPS and IsoVal + LPS (p > 0.05). Alternatively, under inflammatory hypoxic conditions (LPS/CC) Val, IsoVal, and IsoBut all increased secretion of IL-6, MCP-1/CCL2 and MIP-1α/CCL3 compared to Con (p < 0.05), whereas mediator secretion did not differ between But and Con (p > 0.05), indicating that the proinflammatory effects of SCFA and BCFA was attenuated by But. Interestingly, But + LPS/CC decreased STAT3 activation versus Con + LPS/CC (p < 0.05). Conclusions: The decreased secretion of inflammatory mediators that is attributable to But highlights the fact that individual SCFA and BCFA exert differential effects on adipocyte inflammation under normoxic and hypoxic conditions.
{"title":"Effect of Comparable Carbon Chain Length Short- and Branched-Chain Fatty Acids on Adipokine Secretion from Normoxic and Hypoxic Lipopolysaccharide-Stimulated 3T3-L1 Adipocytes.","authors":"Ala Alzubi, Jennifer M Monk","doi":"10.3390/biomedicines12112621","DOIUrl":"10.3390/biomedicines12112621","url":null,"abstract":"<p><p><b>Background:</b> Microbial fermentation of non-digestible carbohydrates and/or protein produces short-chain fatty acids (SCFA), whereas branched-chain fatty acids (BCFA) are produced from protein fermentation. The effects of individual SCFA and BCFA of comparable carbon chain length on adipocyte inflammation have not been investigated. <b>Objective</b>: To compare the effects of SCFA and BCFA on inflammatory mediator secretion in an adipocyte cell culture model designed to recapitulate obesity-associated adipocyte inflammation under normoxic and hypoxic conditions. <b>Methods:</b> The 3T3-L1 adipocytes were cultured (24 h) without (Control, Con) and with 1 mmol/L of SCFA (butyric acid (But) or valeric acid (Val)) or 1 mmol/L of BCFA (isobutyric acid (IsoBut) or isovaleric acid (IsoVal)) and were unstimulated (cells alone, <i>n</i> = 6/treatment), or stimulated with 10 ng/mL lipopolysaccharide (LPS, inflammatory stimulus, <i>n</i> = 8/treatment) or 10 ng/mL LPS + 100 µmol/L of the hypoxia memetic cobalt chloride (LPS/CC, inflammatory/hypoxic stimulus, <i>n</i> = 8/treatment). <b>Results</b>: Compared to Con + LPS, But + LPS reduced secreted protein levels of interleukin (IL)-1β, IL-6, macrophage chemoattractant protein (MCP)-1/chemokine ligand (CCL)2, MCP3/CCL7, macrophage inflammatory protein (MIP)-1α/CCL3 and regulated upon activation, normal T cell expressed, and secreted (RANTES)/CCL5 and decreased intracellular protein expression of the ratio of phosphorylated to total signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NFκB) p65 (<i>p</i> < 0.05). Val + LPS reduced IL-6 secretion and increased MCP-1/CCL2 secretion compared to Con + LPS and exhibited a different inflammatory mediator secretory profile from But + LPS (<i>p</i> < 0.05), indicating that individual SCFA exert individual effects. There were no differences in the secretory profile of the BCFA IsoBut + LPS and IsoVal + LPS (<i>p</i> > 0.05). Alternatively, under inflammatory hypoxic conditions (LPS/CC) Val, IsoVal, and IsoBut all increased secretion of IL-6, MCP-1/CCL2 and MIP-1α/CCL3 compared to Con (<i>p</i> < 0.05), whereas mediator secretion did not differ between But and Con (<i>p</i> > 0.05), indicating that the proinflammatory effects of SCFA and BCFA was attenuated by But. Interestingly, But + LPS/CC decreased STAT3 activation versus Con + LPS/CC (<i>p</i> < 0.05). <b>Conclusions</b>: The decreased secretion of inflammatory mediators that is attributable to But highlights the fact that individual SCFA and BCFA exert differential effects on adipocyte inflammation under normoxic and hypoxic conditions.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 11","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-16DOI: 10.3390/biomedicines12112623
Stephen P Chelko
Arrhythmogenic cardiomyopathy (ACM) is a nonischemic, familial heart disease with a high risk of sudden cardiac death (SCD) in the pediatric population and accounts for >20% of SCDs worldwide [...].
{"title":"Prognostic Value of Circulating Biomarkers of Fibrotic Remodeling in Arrhythmogenic Cardiomyopathy.","authors":"Stephen P Chelko","doi":"10.3390/biomedicines12112623","DOIUrl":"10.3390/biomedicines12112623","url":null,"abstract":"<p><p>Arrhythmogenic cardiomyopathy (ACM) is a nonischemic, familial heart disease with a high risk of sudden cardiac death (SCD) in the pediatric population and accounts for >20% of SCDs worldwide [...].</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 11","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-15DOI: 10.3390/biomedicines12112619
Tomas Jasenovec, Dominika Radosinska, Ivan Belica, Barbara Raskova, Angelika Puzserova, Norbert Vrbjar, Jana Radosinska
Background: Multiple research teams have documented various abnormalities in erythrocyte properties in children with autism spectrum disorder (ASD) compared with neurotypical individuals. Reduced erythrocyte deformability, a crucial factor for microcirculation and oxygen delivery, may affect brain function. Other key factors like nitric oxide (NO) and Na,K-ATPase-regulated cation transport also play roles in both erythrocyte deformability and ASD, suggesting a possible relationship between erythrocyte parameters and autism severity. Thus, this study aims to describe these associations, exploring erythrocyte properties as potential biomarkers in ASD.
Methods: A total of 179 ASD children were enrolled in this study. Diagnosis was confirmed by the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) and Autism Diagnostic Interview-Revised. The Vineland Adaptive Behavior Scales, Third Edition (VABS-3), was used to assess adaptive behavior. RBC deformability was measured using a filtration technique, while NO production by RBCs was assessed via DAF-2DA fluorescence. Na,K-ATPase kinetics and RBC osmotic resistance were evaluated spectrophotometrically.
Results: Children with more severe ASD symptoms had more impaired deformability and osmotic resistance than children with mild symptoms. Higher RBC NO production was linked to better scores in some VABS-3 subdomains, and in the social affect domain of ADOS-2. Higher affinity of Na,K-ATPase for sodium negatively correlated with the occurrence of repetitive and restricted behavior-one of the core ASD symptoms.
Conclusions: This study identified potential links between ASD severity and RBC properties. While erythrocyte quality can influence ASD symptomatology, the observed relationships-such as those involving RBC deformability, NO production, Na,K-ATPase kinetics, and osmotic resistance-were not strong or consistent enough to be considered reliable diagnostic or prognostic biomarkers.
{"title":"Examining Erythrocytes as Potential Blood Biomarkers for Autism Spectrum Disorder: Their Relationship to Symptom Severity and Adaptive Behavior.","authors":"Tomas Jasenovec, Dominika Radosinska, Ivan Belica, Barbara Raskova, Angelika Puzserova, Norbert Vrbjar, Jana Radosinska","doi":"10.3390/biomedicines12112619","DOIUrl":"10.3390/biomedicines12112619","url":null,"abstract":"<p><strong>Background: </strong>Multiple research teams have documented various abnormalities in erythrocyte properties in children with autism spectrum disorder (ASD) compared with neurotypical individuals. Reduced erythrocyte deformability, a crucial factor for microcirculation and oxygen delivery, may affect brain function. Other key factors like nitric oxide (NO) and Na,K-ATPase-regulated cation transport also play roles in both erythrocyte deformability and ASD, suggesting a possible relationship between erythrocyte parameters and autism severity. Thus, this study aims to describe these associations, exploring erythrocyte properties as potential biomarkers in ASD.</p><p><strong>Methods: </strong>A total of 179 ASD children were enrolled in this study. Diagnosis was confirmed by the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) and Autism Diagnostic Interview-Revised. The Vineland Adaptive Behavior Scales, Third Edition (VABS-3), was used to assess adaptive behavior. RBC deformability was measured using a filtration technique, while NO production by RBCs was assessed via DAF-2DA fluorescence. Na,K-ATPase kinetics and RBC osmotic resistance were evaluated spectrophotometrically.</p><p><strong>Results: </strong>Children with more severe ASD symptoms had more impaired deformability and osmotic resistance than children with mild symptoms. Higher RBC NO production was linked to better scores in some VABS-3 subdomains, and in the social affect domain of ADOS-2. Higher affinity of Na,K-ATPase for sodium negatively correlated with the occurrence of repetitive and restricted behavior-one of the core ASD symptoms.</p><p><strong>Conclusions: </strong>This study identified potential links between ASD severity and RBC properties. While erythrocyte quality can influence ASD symptomatology, the observed relationships-such as those involving RBC deformability, NO production, Na,K-ATPase kinetics, and osmotic resistance-were not strong or consistent enough to be considered reliable diagnostic or prognostic biomarkers.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 11","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11591841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}