RESUMO
There is increasing evidence that gender impacts the onset and progression of cardiovascular pathology. However, it is vastly unclear how this variable determines the ultimate outcomes, particularly in the setting of pressure overload-induced left ventricular hypertrophy (LVH). This study was carried out to fill this gap, at least in part, by assessing myocardial expression of G protein-coupled estrogen receptor (GPER) in female and male rats afflicted with LVH. Both female and male rats underwent abdominal aorta banding to induce LVH or were kept intact as control groups. At the end of the experiment, carotid artery catheterization was performed to measure systolic (SBP) and diastolic (DBP) blood pressure. Fibrosis and cardiomyocyte cross-sectional area were assessed by conventional histological analyses. Protein and mRNA expression were evaluated by Western blot/immunofluorescence staining and real-time RT-PCR technique, respectively. In LVH groups, male rats exhibited higher SBP and DBP, heart weight to body weight ratio, and fibrosis compared with female rats. However, both sexes showed a similar increase in cardiomyocyte size after LVH induction. In female, but not in male rats, LVH instigated the GPER mRNA and protein expression in the heart. These results, confirm a significant interaction between gender and myocardial remodeling in terms of GPER expression. Thus, it can be argued that sex differences in the cardiac GPER expression may be responsible for sex differences in the pressure overload-induced LVH. In other words, the female heart seems to unleash stronger protection against pressure overload than that of males in light of a higher GPER expression.
Assuntos
Hipertrofia Ventricular Esquerda , Receptores de Estrogênio , Receptores Acoplados a Proteínas G , Animais , Masculino , Feminino , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Ratos , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/genética , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Esquerda/etiologia , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/genética , Pressão Sanguínea , Miocárdio/metabolismo , Miocárdio/patologia , Caracteres Sexuais , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fibrose , Ratos Sprague-Dawley , Fatores SexuaisRESUMO
BACKGROUND AND OBJECTIVES: Some clinical trials have indicated the beneficial effects of statins in patients with kidney disease, while others have reported no positive effect of statins in these patients. We conducted this meta-analysis to identify the effects of statins on serum levels of interleukin-6 (IL-6) and Tumor Necrosis Factor Alpha (TNF-α) in patients with kidney disease. DESIGNS AND METHODS: A systematic literature search was performed using PubMed, Scopus, and Web of Science databases to identify all studies published from inception to August, 2022. The major outcome variable was the Weighted Mean Difference (WMD). Eligible studies were stratified based on target population, intervention duration, dosage and type of statins, and solubility of statins. RESULTS: Meta-analysis performed on seven publications (8 studies), including 213 patients with kidney disease and 188 control individuals, indicated that the concentration of IL-6 was marginally decreased in patients with kidney disease following statin therapy disease (WMD = -1.15 pg/mL; 95% CI = -2.33 to 0.04, P = 0.05, I2 = 68.5%). The findings of subgroup analysis based on the dosage of statins showed that neither highintensity nor moderate/low-intensity statin treatment could significantly influence the serum level of IL-6. Lipophilic statins were more effective than hydrophilic statins, and they marginally decreased the levels of IL-6 (WMD = -1.21 pg/mL; 95% CI = -2.43 to 0, P = 0.05, I2 = 55.7%). Meta-analysis of four publications (five studies) with 157 patients with kidney disease and 132 control subjects showed that statins reduced the serum levels of TNF-α in patients with kidney disease when compared with control individuals (WMD= -2.66 pg/mL; 95% CI = -4.26 to -1.06, P < 0.001, I2 = 63%). CONCLUSION: Statins only marginally decreased the concentration of IL-6 in patients with kidney disease, but neither high-intensity nor moderate/low-intensity statin treatment could significantly influence the level of IL-6. However, statins reduced serum levels of TNF-α in patients with kidney disease.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Interleucina-6 , Ensaios Clínicos Controlados Aleatórios como Assunto , Fator de Necrose Tumoral alfa , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Interleucina-6/sangue , Fator de Necrose Tumoral alfa/sangue , Nefropatias/tratamento farmacológico , Nefropatias/sangueRESUMO
Hydrogen sulfide (H2S) is known as a chemical gas in nature with both enzymatic and non-enzymatic biosynthesis in different human organs. A couple of studies have demonstrated the function of H2S in regulating the homeostasis of the human body. Additionally, they have shown its synthesis, measurement, chemistry, protective effects, and interaction in various aspects of scientific evidence. Furthermore, many researches have demonstrated the beneficial impacts of H2S on genital organs and systems. According to various studies, it is recognized that H2S-producing enzymes and the endogenous production of H2S are expressed in male and female reproductive systems in different mammalian species. The main goal of this comprehensive review is to assess the potential therapeutic impacts of this gasotransmitter in the male and female urogenital system and find underlying mechanisms of this agent. This narrative review investigated the articles that were published from the 1970s to 2022. The review's primary focus is the impacts of H2S on the male and female urogenital system. Medline, CINAHL, PubMed, and Google scholar databases were searched. Keywords used in this review were "Hydrogen sulfide," "H2S," "urogenital system," and "urogenital tract". Numerous studies have demonstrated the therapeutic and protective effects of sodium hydrosulfide (Na-HS) as an H2S donor on male and female infertility disorders. Furthermore, it has been observed that H2S plays a significant role in improving different diseases such as ameliorating sperm parameters. The specific localization of H2S enzymes in the urogenital system provides an excellent opportunity to comprehend its function and role in various disorders related to this system. It is noteworthy that H2S has been demonstrated to be produced in endocrine organs and exhibit diverse activities. Moreover, it is important to recognize that alterations in H2S biosynthesis are closely linked to endocrine disorders. Therefore, hormones can be pivotal in regulating H2S production, and H2S synthesis pathways may aid in establishing novel therapeutic strategies. H2S possesses pharmacological effects on essential disorders, such as anti-inflammation, anti-apoptosis, and anti-oxidant activities, which render it a valuable therapeutic agent for human urogenital disease. Furthermore, this agent shows promise in ameliorating the detrimental effects of various male and female diseases. Despite the limited clinical research, studies have demonstrated that applying H2S as an anti-oxidant source could ameliorate adverse effects of different conditions in the urogenital system. More clinical studies are required to confirm the role of this component in clinical settings.
RESUMO
The tripartite motif (TRIM) family proteins are a group of proteins involved in different signaling pathways. The changes in the expression regulation, function, and signaling of this protein family are associated with the occurrence and progression of a wide range of disorders. Given the importance of these proteins in pathogenesis, they can be considered as potential therapeutic targets for many diseases. TRIM25, as an E3-ubiquitin ligase, is involved in the development of various diseases and cellular mechanisms, including antiviral innate immunity and cell proliferation. The clinical studies conducted on restricting the function of this protein have reached promising results that can be further evaluated in the future. Here, we review the regulation of TRIM25 and its function in different diseases and signaling pathways, especially the retinoic acid-inducible gene-I (RIG-I) signaling which prompts many kinds of cancers and inflammatory disorders.
Assuntos
Imunidade Inata , Neoplasias , Humanos , Proteína DEAD-box 58/metabolismo , Transdução de Sinais , Proteínas com Motivo Tripartido , Fatores de Transcrição , Ubiquitina-Proteína Ligases/metabolismoRESUMO
BACKGROUND: Silibinin is a polyphenolic compound that could modulate estrogen receptor activation. Vascular dysfunction is considered a key initiator in atherosclerosis and may occur in the postmenopausal period. This manuscript compares estrogen and silibinin's impacts on factors that change endothelial function in ovariectomized (OVX) rats. METHODS: 32 female Wistar rats were subdivided into control; OVX; OVX + estrogen (1 mg/kg/day); and OVX + silibinin (50 mg/kg/day) groups. After the experimental period, lipid profile, atherogenic indices, and histopathology of endothelium were monitored. The vascular oxidative stress, adhesion molecules, inflammatory cytokine levels, nitric oxide (NO), angiotensin-II (Ang-II), and endothelin-1 (ET-1) were also analyzed. RESULTS: Silibinin treatment, similar to estrogen, significantly normalized the adverse changes of OVX on vascular function, including improved lipid profile and oxidative stress, increased endothelial nitric oxide synthase (eNOS) expression, diminished inflammatory status, and reduced adhesion molecule levels, ET-1 and Ang-II substances. Our findings also revealed that the administration with estrogen or silibinin resulted in a normal endothelium layer in the aorta tissues of OVX rats. CONCLUSION: Estrogen and silibinin have similar effects in improving vascular function. These treatments' protective impacts on vasculature indicate their potential benefits on the cardiovascular system in the postmenopausal period.