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1.
Rev. Ciênc. Plur ; 8(3): 27644, out. 2022. ilus, tab
Article in Portuguese | LILACS, BBO | ID: biblio-1399339

ABSTRACT

Introdução:uma vez conhecidos os mecanismos de patogênese do SARS-CoV-2, vários métodos de tratamento para a COVID-19 foram desenvolvidos, dentre eles destaca-se o uso dos anticorpos monoclonais para o contexto de pacientes em estágios graves da doença. Objetivo: compreender se o uso dos anticorpos monoclonais para tratamento da COVID-19 grave interfere nos níveis séricos da angiotensina II. Metodologia:Para a realização dessa pesquisa foram selecionados através do DeCS e MeSH os descritores "COVID-19", "Angiotensin II" e "Antibodies, Monoclonal" e seus respectivos "entry terms" sugeridos pela base MeSH. Posteriormente,utilizando-se os operadores booleanos OR e AND, foi montada uma estratégia de busca, a qual foi utilizada nas bases de dados PUBMED, EMBASE, Web of Science, Cochrane Library e Scopus, sem restrição dedata de publicação ou idioma. Resultados:ao final do processo de seleção dos artigos, 29 foram selecionados para a leitura e análise completa. Nesta revisão, foram abordados diferentes tipos de anticorpos monoclonais, os quais foram oportunamente agrupados de acordo com o seu mecanismo de ação. Conclusão: foi possível concluir que das cinco classes de anticorpos monoclonais tratadas neste trabalho, três potencialmente podem causar alterações nos níveis séricos de angiotensina II (AU).


Introduction:once the mechanisms of pathogenesis of SARS-CoV-2 are known, several methods of treatment for COVID-19 have been developed, among them the use of monoclonal antibodies for the context of patients in severe stages of the disease. Purpose:to understand whether the use of monoclonal antibodies for the treatment of severe COVID-19 interferes with serum angiotensin II levels. Methodology:For this research were selected through DeCS and MeSH the descriptors "COVID-19", "Angiotensin II" and "Antibodies, Monoclonal" and their respective entry "Terms" suggested by the MeSH database. Subsequently, using the boolean operators OR and AND, a search strategy was set up, which was used in the databases PUBMED, EMBASE, Web of Science, Cochrane Library and Scopus, without restriction of publication date or language. Results:at the end of the article selection process, 29 were selected for reading and full analysis. In this review, different types of monoclonal antibodies were addressed, which were opportunely grouped according to their mechanism of action. Conclusion:it was possible to conclude that of the five classes of monoclonal antibodies treated in this study, three potentially can cause changes in serum levels of angiotensin II (AU).


Introducción:Una vez conocidos los mecanismos de patogénesis del SARSCoV-2, se desarrollaron variosmétodos de tratamiento para el COVID-19, entre ellos, el uso de anticuerpos monoclonales para el contexto de pacientes en fases graves de la enfermedad. Objetivo:Comprender si el uso de anticuerpos monoclonales para el tratamiento de la COVID-19 grave interfiere en los niveles séricos de angiotensina II. Metodología:Los descriptores "COVID-19", "Angiotensina II", "Anticuerpos, Monoclonales" y sus respectivos "entry terms" (términos de entrada) sugeridos por el MeSH fueron seleccionados a través de DeCS yMeSH. Posteriormente, utilizando los operadores booleanos OR y AND, se estableció una estrategia de búsqueda que se utilizó en las bases de datos PUBMED, EMBASE, Web of Science, Cochrane Library y Scopus, sin restricción de fecha de publicación ni de idioma. Resultados:Al final del proceso de selección de artículos, se seleccionaron 29 artículos para su lectura y análisis completos. En esta revisión se han abordado diferentes tipos de anticuerpos monoclonales, que se han agrupado oportunamente según su mecanismo de acción. Conclusión:Se pudo concluir que de las cinco clases de anticuerpos monoclonales tratados en este trabajo, tres pueden potencialmente causar alteraciones en los niveles séricos de angiotensina II (AU).


Subject(s)
Angiotensin II , COVID-19/drug therapy , Immunologic Factors/therapeutic use , Antibodies, Monoclonal/therapeutic use , SARS-CoV-2/enzymology
2.
Int. j. cardiovasc. sci. (Impr.) ; 35(4): 476-485, July-Aug. 2022. tab, graf
Article in English | LILACS | ID: biblio-1385275

ABSTRACT

Abstract Background: Sarcopenia is a disease that involves skeletal muscle mass loss and is highly prevalent in the older adult population. Moreover, the incidence of sarcopenia is increased in patients with hypertension. Objectives: The study aimed to evaluate the association between the classes of the drugs used for arterial hypertension treatment and the presence or absence of sarcopenia. Methods: 129 older adults with hypertension were evaluated by the researchers who registered the participants medication for arterial hypertension treatment. Sarcopenia level was measured by anthropometric parameters, muscular strength, and functional capacity. The data were analyzed by one-way ANOVA followed by post-hoc test and Fisher's exact test; statistical significance was set at 0.05. Results: Age was not different between women with different levels of sarcopenia, but significant differences were observed between men with absent sarcopenia (66.8±4.2 years) and men with probable sarcopenia (77.0±10.2 years). Individuals with absent sarcopenia showed higher handgrip strength (men: 33.8±7.4, women: 23.2±4.6 Kgf) in comparison with those with sarcopenia (men with probable sarcopenia: 9.5±3.3 Kgf, women with probable, confirmed, and severe sarcopenia: 11.7±2.5, 12.2±3.0, 11.8±1.8 Kgf, respectively). The analysis showed an association between the type of medication and degree of sarcopenia; diuretics were significantly associated with probable sarcopenia, and angiotensin II receptor blockers (alone or in combination with diuretics) was associated with absence of sarcopenia. Conclusion: In conclusion, handgrip strength was a good method to diagnose sarcopenia, and diuretics were associated with increased risk of sarcopenia in older adults with hypertension.


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Diuretics/therapeutic use , Sarcopenia/complications , Hypertension/complications , Aging , Cross-Sectional Studies , Diuretics/adverse effects , Sarcopenia/etiology , Angiotensin Receptor Antagonists/adverse effects , Angiotensin Receptor Antagonists/therapeutic use
3.
Rev. bras. ginecol. obstet ; 44(7): 710-718, July 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1394810

ABSTRACT

Abstract Objective To describe the effects of combined oral contraceptives (COC) on the renin-angiotensin-aldosterone system (RAAS). Data sourcesThis is a systematic review according to the criteria of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), registered in PROSPERO under the ID: CRD42020200019. Searches were performed between August 2020 and December 2021, in the following databases: Medline via Pubmed, Cochrane Central Library, Scientific Electronic Library Online, and Latin American and Caribbean Literature in Health Sciences via Virtual Health Library. The effects of the combined oral contraceptive on plasma renin activity values, plasma renin values, angiotensinogen values— also known as plasma renin substrate— angiotensin, and/or aldosterone values. Study selectionA total of 877 studies were selected and, of these, 10 articles met the eligibility criteria and were included in this review. Data collectionData were combined through qualitative synthesis and included in a spreadsheet previously prepared by the authors. Data synthesisThe collected samples ranged from 18 to 137 participants, totaling 501 women aged between 18 and 49 years throughout all studies. The studies showed increased activity of plasma renin, plasma renin substrate, angiotensin II, and aldosterone in this population. Conclusion The findings of this study suggest that the COC promotes greater activation of the RAAS. Supporting the idea that its use is related to an increased risk of cardiovascular events, including systemic arterial hypertension.


Resumo Objetivo Descrever os efeitos do contraceptivo oral combinado (COC) no sistema renina-angiotensina-aldosterona (SRAA). Fontes dos dadosTrata-se de uma revisão sistemática de acordo com os critérios do Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), registrada no PROSPERO sob ID: CRD42020200019. As buscas foram realizadas entre agosto de 2020 e dezembro de 2021 nas bases de dados: Medline via Pubmed, Biblioteca Cochrane Central, Scientific Electronic Library Online, e Literatura Latino-americana e do Caribe em Ciências da Saúde via Biblioteca Virtual em Saúde. Consultado os artigos sobre os efeitos do contraceptivo oral combinado nos valores da atividade da renina plasmática, valores plasmáticos da renina, valores do angiotensinogênio - também conhecido como substrato da renina plasmática -, valores da angiotensina e/ou aldosterona. Seleção dos estudosForam selecionados 877 estudos e, destes, 10 artigos preencheram os critérios de elegibilidade e foram incluídos nesta revisão. Coleta de dadosOs dados foram combinados por meio de síntese qualitativa e inclusos em uma planilha elaborada previamente pelos autores. Síntese dos dadosAs amostras coletadas variavam entre 18 e 137 participantes, totalizando 501 mulheres com idade entre 18 e 49 anos em todos os estudos. Os estudos apresentaram aumento da atividade da renina plasmática, do substrato da renina plasmática, da angiotensina II e da aldosterona nessa população. Conclusão Os achados deste estudo sugerem que o COC promove maior ativação do SRAA. Apoiando a ideia de que o seu uso esteja relacionado ao aumento do risco de eventos cardiovasculares, incluindo a hipertensão arterial sistêmica.

5.
Arq. bras. cardiol ; 118(6): 1069-1082, Maio 2022. tab, graf
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1383706

ABSTRACT

Resumo Fundamento O tratamento adequado e a obtenção das metas na hipertensão arterial são importantes na redução dos desfechos cardiovasculares. Objetivos Descrever os bloqueadores do receptor de angiotensina (BRA) em monoterapia ou combinação dupla e a taxa de controle da hipertensão arterial. Métodos Estudo transversal que avaliou pacientes em uso de BRA entre 2017 e 2020. Foram excluídos aqueles em uso de três ou mais anti-hipertensivos. As variáveis analisadas foram: sexo, idade, índice de massa corporal, medidas válidas da medida residencial da pressão arterial (MRPA); pressão arterial sistólica (PAS) e diastólica (PAD) obtidas pela MRPA e de forma casual; variabilidade pressórica; classe dos anti-hipertensivos e dos BRAs. Foram utilizados testes de t pareado, qui-quadrado e Fisher, além de sobreposição dos intervalos de confiança de 95% com nível de significância de 5% (p < 0,05). Resultados Foram selecionados 17.013 pacientes; destes, 12.813 preencheram os critérios, dos quais 62,1% eram do sexo feminino. O número médio de medidas válidas foi de 23,3 (±2,0), com médias para a PAS de 126,8±15,8 mmHg e 133,5±20,1 mmHg (p < 0,001) e para a PAD de 79,1±9,7 mmHg e 83,6±11,9 mmHg (p < 0,001) pela MRPA e medida casual, respectivamente. Losartana foi o BRA mais utilizado e o que apresentou comportamentos mais elevados da pressão arterial. As combinações de BRA com diuréticos ou com antagonistas de canal de cálcio tiveram menores valores de pressão arterial. Conclusões Losartana foi utilizada em mais da metade dos pacientes, apesar de ser a menos eficiente na redução e no controle da pressão arterial.


Abstract Background Adequate treatment of arterial hypertension and achieving arterial hypertension goals in are important in reducing cardiovascular outcomes. Objectives To describe angiotensin receptor blockers in monotherapy or double combination therapy and the rate of arterial hypertension control. Methods This cross-sectional study evaluated patients who were using angiotensin receptor blockers between 2017 and 2020. Those using three or more antihypertensive drugs were excluded. The analyzed variables included sex, age, body mass index, valid home blood pressure monitoring (HBPM) measurements, casual and HBPM systolic and diastolic blood pressure measurements, blood pressure variability, and antihypertensive and angiotensin receptor blocker class. Paired t, chi-square, and Fisher's exact tests were used, as well as overlapping 95% confidence intervals and a significance level of 5% (p < 0.05). Results Of 17,013 patients, 12,813 met the inclusion criteria, 62.1% of whom were female. The mean number of valid measurements was 23.3 (SD, 2.0). The mean HBPM and casual measurements for systolic blood pressure were 126.8 (SD, 15.8) mmHg and 133.5 (SD, 20.1) mmHg (p <0.001), respectively, while those for diastolic blood pressure were 79.1 (SD, 9.7 mmHg) and 83.6 (SD, 11.9) mmHg (p <0.001), respectively. Losartan was the most common angiotensin receptor blocker and resulted in the highest blood pressure values. Combinations of angiotensin receptor blockers with diuretics or calcium channel antagonists resulted in lower blood pressure values. Conclusions More than half of the patients used losartan, although it was the least efficient drug for reducing and controlling blood pressure.

7.
J. bras. nefrol ; 44(1): 19-25, Jan-Mar. 2022. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1365037

ABSTRACT

Abstract Introduction: Studies have shown that the renin angiotensin aldosterone system (RAAS) and inflammation are related to kidney injury progression. The aim of this study was to evaluate RAAS molecules and chemokine (C-C motif) ligand 2 (CCL2) in 82 patients with chronic kidney disease (CKD). Methods: Patients were divided into two groups: patients diagnosed with CKD and patients without a CKD diagnosis. Glomerular filtration rate (GFR) and albumin/creatinine ratio (ACR) were determined, as well as plasma levels of angiotensin-(1-7) [Ang-(1-7)], angiotensin-converting enzyme (ACE)1, ACE2, and plasma and urinary levels of CCL2. Results: CCL2 plasma levels were significantly higher in patients with CKD compared to the control group. Patients with lower GFR had higher plasma levels of ACE2 and CCL2 and lower ratio ACE1/ACE2. Patients with higher ACR values had higher ACE1 plasma levels. Conclusion: Patients with CKD showed greater activity of both RAAS axes, the classic and alternative, and higher plasma levels of CCL2. Therefore, plasma levels of RAAS molecules and CCL2 seem to be promising prognostic markers and even therapeutic targets for CKD.


Resumo Introdução: Estudos têm mostrado que o sistema renina angiotensina aldosterona (SRAA) e a inflamação estão relacionados à progressão da lesão renal. O objetivo deste estudo foi avaliar moléculas do SRAA e o Ligante 2 de Quimiocina com Motivo C-C (CCL2) em 82 pacientes com doença renal crônica (DRC). Métodos: Os pacientes foram divididos em dois grupos: pacientes diagnosticados com DRC e pacientes sem diagnóstico de DRC. Foram determinadas a taxa de filtração glomerular (TFG) e a relação albumina/creatinina (RAC), assim como os níveis plasmáticos de angiotensina-(1-7) [Ang-(1-7)], enzima conversora de angiotensina (ECA)1, ECA2 e níveis plasmáticos e urinários de CCL2. Resultados: Os níveis plasmáticos de CCL2 foram significativamente mais altos em pacientes com DRC em comparação com o grupo controle. Pacientes com TFG mais baixa apresentaram níveis plasmáticos mais elevados de ECA2 e CCL2 e menor relação ECA1/ECA2. Pacientes com valores de RAC mais altos apresentaram níveis plasmáticos de ECA1 mais elevados. Conclusão: Pacientes com DRC mostraram maior atividade de ambos os eixos do SRAA, o clássico e o alternativo, e níveis plasmáticos mais altos de CCL2. Portanto, os níveis plasmáticos de moléculas do SRAA e CCL2 parecem ser marcadores prognósticos promissores e até mesmo alvos terapêuticos para a DRC.

8.
Hematol., Transfus. Cell Ther. (Impr.) ; 44(1): 26-31, Jan.-Mar. 2022. tab
Article in English | LILACS | ID: biblio-1364890

ABSTRACT

Abstract Introduction Coronavirus disease 2019 (COVID-19) may present with extrapulmonary manifestations, including hematologic changes. Previous studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) can interact with the renin-angiotensin system, ultimately causing increased production of angiotensin II. By reporting the cases of previously healthy young adults diagnosed with a hematologic malignancy after experiencing COVID-19, we raise the hypothesis that the SARS-Cov-2 infection could act as a trigger for leukemogenesis in predisposed individuals. Methods This was a case series performed through extraction of relevant clinical information from the medical records of three patients admitted to our Hematology unit between August 2020 and September 2020. Main Results Considering the relatively rapid development of cytopenias following recovery from COVID-19, it cannot be ruled out that SARS-Cov-2 played a role in leukemogenesis in those patients. Based on previous in vitro studies, the renin-angiotensin system imbalance induced by SARS-CoV-2 could potentially promote in vivo leukemogenesis through several mechanisms. Conclusion Despite the advances in pathophysiological and clinical characterization of COVID-19, the consequences of the pandemic to the incidence of hematologic diseases are still to be elucidated. In this context, future dissection of the status of the local bone marrow renin-angiotensin system in leukemogenesis is a clinically relevant basic research area.


Subject(s)
Humans , Male , Female , Adult , Hematologic Neoplasms , COVID-19 , Renin-Angiotensin System , Leukemia , SARS-CoV-2
9.
Braz. j. med. biol. res ; 55: e11635, 2022. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1360232

ABSTRACT

Hypovolemia induced by hemorrhage is a common clinical complication, which stimulates vasopressin (AVP) secretion by the neurohypophysis in order to retain body water and maintain blood pressure. To evaluate the role of brain L-glutamate and angiotensin II on AVP secretion induced by hypovolemia we induced hemorrhage (∼25% of blood volume) after intracerebroventricular (icv) administration of AP5, NBQX, or losartan, which are NMDA, AMPA, and AT1 receptor antagonists, respectively. Hemorrhage significantly increased plasma AVP levels in all groups. The icv injection of AP5 did not change AVP secretion in response to hemorrhage. Conversely, icv administration of both NBQX and losartan significantly decreased plasma AVP levels after hemorrhage. Therefore, the blockade of AMPA and AT1 receptors impaired AVP secretion in response to hemorrhage, suggesting that L-glutamate and angiotensin II acted in these receptors to increase AVP secretion in response to hemorrhage-induced hypovolemia.

10.
Asian Journal of Andrology ; (6): 139-146, 2022.
Article in English | WPRIM | ID: wpr-928531

ABSTRACT

The renin angiotensin system (RAS) appears to influence male fertility at multiple levels. In this work, we analyzed the relationship between the RAS and DNA integrity. Fifty male volunteers were divided into two groups (25 each): control (DNA fragmentation ≤20%) and pathological (DNA fragmentation >20%) cases. Activities of five peptidases controlling RAS were measured fluorometrically: prolyl endopeptidase (which converts angiotensin [A] I and A II to A 1-7), neutral endopeptidase (NEP/CD10: A I to A 1-7), aminopeptidase N (APN/CD13: A III to A IV), aminopeptidase A (A II to A III) and aminopeptidase B (A III to A IV). Angiotensin-converting enzyme (A I to A II), APN/CD13 and NEP/CD10 were also assessed by semiquantitative cytometry and quantitative flow cytometry assays, as were the receptors of all RAS components: A II receptor type 1 (AT1R), A II receptor type 2 (AT2R), A IV receptor (AT4R or insulin-regulated aminopeptidase [IRAP]), (pro)renin receptor (PRR) and A 1-7 receptor or Mas receptor (MasR) None of the enzymes that regulate levels of RAS components, except for APN/CD13 (decrease in fragmented cells), showed significant differences between both groups. Micrographs of RAS receptors revealed no significant differences in immunolabeling patterns between normozoospermic and fragmented cells. Labeling of AT1R (94.3% normozoospermic vs 84.1% fragmented), AT4R (96.2% vs 95.3%) and MasR (97.4% vs 87.2%) was similar between the groups. AT2R (87.4% normozoospermic vs 63.1% fragmented) and PRR (96.4% vs 48.2%) were higher in non-fragmented spermatozoa. These findings suggest that fragmented DNA spermatozoa have a lower capacity to respond to bioactive RAS peptides.


Subject(s)
Angiotensins , DNA Fragmentation , Humans , Insulin , Male , Renin-Angiotensin System/physiology , Spermatozoa
11.
Article in English | WPRIM | ID: wpr-923829

ABSTRACT

@#BACKGROUND: Acute pulmonary embolism (APE) with cardiac arrest (CA) is characterized by high mortality in emergency due to pulmonary arterial hypertension (PAH). This study aims to determine whether early pulmonary artery remodeling occurs in PAH caused by massive APE with CA and the protective effects of increasing angiotensin-converting enzyme (ACE) 2-angiotensin (Ang) (1-7)-Mas receptor axis and ACE-Ang II-Ang II type 1 receptor (AT1) axis (ACE2/ACE axes) ratio on pulmonary artery lesion after return of spontaneous circulation (ROSC). METHODS: To establish a porcine massive APE with CA model, autologous thrombus was injected into the external jugular vein until mean arterial pressure dropped below 30 mmHg (1 mmHg=0.133 kPa). Cardiopulmonary resuscitation and thrombolysis were delivered to regain spontaneous circulation. Pigs were divided into four groups of five pigs each: control group, APE-CA group, ROSC-saline group, and ROSC-captopril group, to examine the endothelial pathological changes and expression of ACE2/ACE axes in pulmonary artery with or without captopril. RESULTS: Histological analysis of samples from the APE-CA and ROSC-saline groups showed that pulmonary arterioles were almost completely occluded by accumulated endothelial cells. Western blotting analysis revealed a decrease in the pulmonary arterial ACE2/ACE axes ratio and increases in angiopoietin-2/angiopoietin-1 ratio and expression of vascular endothelial growth factor (VEGF) in the APE-CA group compared with the control group. Captopril significantly suppressed the activation of angiopoietin-2/angiopoietin-1 and VEGF in plexiform lesions formed by proliferative endothelial cells after ROSC. Captopril also alleviated endothelial cell apoptosis by increasing the B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X (Bax) ratio and decreasing cleaved caspase-3 expression. CONCLUSION: Increasing the ACE2/ACE axes ratio may ameliorate pulmonary arterial remodeling by inhibiting the apoptosis and proliferation of endothelial cells after ROSC induced by APE.

12.
China Pharmacy ; (12): 758-763, 2022.
Article in Chinese | WPRIM | ID: wpr-923015

ABSTRACT

The re gulators of renin-angiotensin system (RAS) include renin inhibitors ,angiotensin converting enzyme inhibitors,angiotensin Ⅱ receptor blockers ,angiotensin Ⅱ receptor agonists and angiotensin 1-7. This paper summarizes and analyzes the adjuvant effects of RAS regulators on antitumor drugs by searching the literature published from January 1992 to June 2021. The regulators of RAS can reduce the cardiotoxicity ,hematological toxicity and peripheral neurotoxicity of antitumor drugs , and has renal protective effect ;the regulators of RAS combined with other chemotherapy drugs show favorable effects on promoting chemotherapeutic drugs delivery ,improving anti-angiogenesis and bypass activation of targeted drugs ,enhancing tumor immune response of immune checkpoint inhibitors ,so as to improve therapeutic efficacy of antitumor drugs. The combination of RAS regulators with antitumor drugs is expected to reduce the side effects of antitumor drugs ,enhance its efficacy and improve the prognosis of patients.

13.
Braz. J. Pharm. Sci. (Online) ; 58: e19922, 2022. tab, graf
Article in English | LILACS | ID: biblio-1384022

ABSTRACT

Angiotensin-II (AgII) is thought to be crucial for tumor growth and progression. Moreover, hydrogen sulfide (H2S) performs a controversial action in cancer pathology. Zofenopril (ZF) is an angiotensin-converting enzyme (ACE) inhibitor with H2S donating properties. Hence, this study aims at investigating the tumor suppressor activity of ZF and elucidating the involved trajectories in Ehrlich's solid tumor (EST)-bearing mice. EST was induced by the intradermal injection of Ehrlich's ascites carcinoma cells into femoral region. All parameters were assessed after 28 days post-inoculation or one-week thereafter. ZF treatment resulted in significant reduction of tumor weights with marked decrease in IL-6 and VEGF levels in serum, and tumor Ag II and CEA contents. Additionally, the administration of ZF downregulated the tumor gene expression of cyclin-D, ACE-1, and Bcl2 and upregulated the proapoptotic gene, BAX. Moreover, ZF increased CBS gene expression, which is a major contributor to cellular H2S production. In addition, ZF was able to reduce the protein expression of PI3K, pAKT, pGSK-3ß, and NFκB. Our study has provided novel insights into the possible mechanisms by which ZF may produce its tumor defeating properties. These intersecting trajectories involve the interference between PI3K/Akt and CBS signaling pathways


Subject(s)
Animals , Male , Mice , Carcinoma, Ehrlich Tumor/pathology , Neoplasms , Angiotensin II/adverse effects , Carcinoma/pathology , Gene Expression , Vascular Endothelial Growth Factor A
14.
Article in Chinese | WPRIM | ID: wpr-933900

ABSTRACT

Objective:To investigate the effects of early-life (intrauterine and breastfeeding period) exposure to angiotensin Ⅱ type 1 receptor autoantibody (AT 1-AA) on lipid metabolism in offspring rats. Methods:Thirty-two AT 1-AA negative healthy nonpregnant specific pathogen free female Sprague Dawley rats weighing 150-170 g were randomly divided into two groups. Those in the immune group ( n=16) were subcutaneously injected with the mixture of an equal volume of Freund's adjuvant and the second extracellular loop of human-derived angiotensin Ⅱ receptor type 1 (AT1R-ECⅡ) repeatedly to establish the AT 1-AA-positive rat model by active immunization and those in the control group ( n=16) with normal saline solution. Before each immunization, blood samples were collected from the tail of rats to detect serum AT 1-AA levels of those rats in both groups, and the AT 1-AA-positive rat model was successfully established when the serum AT 1-AA was positive and its level reached a plateau. After eight weeks of immunization, the female rats in the two groups were mated with healthy AT 1-AA-negative male rats to conceive. Serum samples were collected from the maternal and offspring rats at the gestation of 18 days (G18), postnatal 21 days (P21), and from the normally fed offspring rats from the time of weaning to 12 weeks old (W12). Active immunization was not performed on the offspring throughout the experiment. The serum AT 1-AA levels of maternal and offspring rats were determined by enzyme-linked immunosorbent assay, and serum AT1-AA was positive when the ratio of AT1-AA level of the immune group over the control group ≥2.1. The blood lipid levels of maternal and offspring rats were measured by an automatic biochemical analyzer. Serum AT 1-AA levels, total cholesterol (TC), high-density lipoprotein-cholesterol [instead of high-density lipoprotein (HDL)], low-density lipoprotein-cholesterol, and free fatty acid levels of the offspring and maternal rats were determined for correlation analysis. Two independent sample t-test, linear regression analysis, and analysis of variance were adopted for statistical analysis. Results:(1) The serum levels of AT 1-AA in maternal rats at G18 and P21 in the immune group were significantly higher than those in the control group (G18: 1.170±0.190 vs 0.114±0.016, t=14.64; P21: 0.988±0.283 vs 0.084±0.006, t=9.57; both P<0.001). (2) The serum levels of AT 1-AA in the offspring at G18 and P21 in the immune group were significantly higher than those in the control group (offspring at G18: 0.948±0.220 vs 0.105±0.010, t=10.10; male offspring at P21: 0.758±0.273 vs 0.080±0.002, t=7.46; female offspring at P21: 0.774±0.274 vs 0.084±0.005, t=7.55; all P<0.001), which showed a positive correlation with those in maternal rats at the same period (offspring at G18: R=0.78; male offspring at P21: R=0.82; female offspring at P21: R=0.82; all P<0.05). However, there was no significant difference in the serum AT 1-AA level in offspring at W12 between the immune and control group ( P>0.05). (3) The serum levels of TC at G18 and P21, and HDL at P21 in maternal rats in the immune group were all higher than those in the control group [TC at G18: (2.36±0.32) vs (1.95±0.24) mmol/L, t=2.70; P21: (2.82±0.50) vs (2.18±0.26) mmol/L, t=3.41; HDL at P21: (1.94±0.33) vs (1.57±0.23) mmol/L, t=2.80; all P<0.05]. (4) Compared with the offspring in the control group, there was no significant change in lipid metabolism at G18 and W12 in the offspring in the immune group (both P>0.05). The serum levels of TC and HDL in male and female offspring at P21 in the immune group were higher than their counterparts in the control[TC in male offspring: (2.38±0.52) vs (1.83±0.30) mmol/L, t=2.73; HDL in male offspring: (1.44±0.32) vs (1.07±0.18) mmol/L, t=2.98; TC in female offspring: (2.50±0.72) vs (1.70±0.26) mmol/L, t=3.16; HDL in female offspring: (1.41±0.33) vs (1.00±0.14) mmol/L, t=3.41; all P<0.05]. (5) The serum levels of TC and HDL in male and female offspring at P21 in the immune group showed no correlation with those in maternal rats at P21 (all R<0.5, all P>0.05). The serum levels of HDL in male and female offspring at P21 in the immune group had a positive correlation with their own serum TC levels (male offspring: R=0.98; female offspring: R=0.97; both P<0.001) and also with their own serum AT 1-AA levels (male offspring: R=0.74, P=0.023; female offspring: R=0.91, P=0.001). The serum levels of TC in male and female offspring at P21 in the immune group had a positive correlation with their serum AT 1-AA levels (male offspring: R=0.72, P=0.030; female offspring: R=0.90, P=0.001). Conclusion:The early-life exposure to AT 1-AA may cause abnormal expression of TC and HDL in offspring rats.

15.
Article in Chinese | WPRIM | ID: wpr-931239

ABSTRACT

Natural products are great treasure troves for the discovery of bioactive components.Current bioassay guided fractionation for identification of bioactive components is time-and workload-consuming.In this study,we proposed a robust and convenient strategy for deciphering the bioactive profile of natural products by mass spectral molecular networking combined with rapid bioassay.As a proof-of-concept,the strategy was applied to identify angiotensin converting enzyme(ACE)inhibitors of Fangjihuangqi decoction(FJHQD),a traditional medicine clinically used for the treatment of heart failure.The chemical profile of FJHQD was comprehensively revealed with the assistance of tandem mass spectral molecular networking,and a total of 165 compounds were identified.With characterized constituents,potential clinical applications of FJHQD were predicted by Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine,and a range of cardiovascular related diseases were significantly enriched.ACE inhibitory activities of FJHQD and its constituents were then investigated with an aggregation-induced emission based fluorescent probe.FJHQD exhibited excellent ACE inhibitory effects,and a bioactive molecular network was established to elucidate the ACE inhibitory profile of constituents in FJHQD.This bioactive molecular network provided a panoramic view of FJHQD's ACE inhibitory ac-tivities,which demonstrated that flavones from Astragali Radix and Glycyrrhizae Radix et Rhizoma,saponins from Astragali Radix,and sesquiterpenoids from Atractylodis Macrocephalae Rhizoma were principal components responsible for this effect of FJHQD.Among them,four novel ACE inhibitors were the first to be reported.Our study indicated that the proposed strategy offers a useful approach to un-cover the bioactive profile of traditional medicines and provides a pragmatic workflow for exploring bioactive components.

16.
Article in Chinese | WPRIM | ID: wpr-930532

ABSTRACT

Objective:To investigate the correlation between serum indexes of children with simple obesity in Xinjiang area and the renin-angiotensin-aldosterone (RAS)system, thus providing evidence to clarify the pathogenesis of childhood obesity.Methods:It was a cross-sectional study involving 41 children with simple obesity (case group) and 41 age-matched healthy children (control group) through the cluster random sampling in Tacheng area of Xinjiang.The mean age of in both groups was (10.04±1.66) years and (10.12±1.68) years, respectively.Serum adipokines, insulin level and RAS indexes between groups were compared by the Student′s t test.The correlation between serum adipokines and RAS activity in children with simple obesity was assessed by the Pearson′ s correlation test. Results:The serum adiponectin(APN) level[(7.90±1.96) μg/L vs.(8.87±1.61) μg/L, P=0.017]was significantly lower in case group than that of control group, while leptin[(6.81±1.88) ng/L vs.(5.87±1.79) ng/L, P=0.023]and resistin levels[(12.61±3.63) ng/L vs.(10.18±3.07) ng/L, P=0.002] were significantly higher.RAS indexes, including the renin[(35.78±10.08) ng/L vs.(29.24±10.69) ng/L, P=0.007], aldosterone (ALD)[(106.90±20.18) ng/L vs.(97.68±17.60) ng/L, P=0.028] and angiotensin-Ⅱ (Ang-Ⅱ)[(55.65±10.37) ng/L vs.(48.78±9.26) ng/L, P=0.002] levels were significantly higher in case group than those of control group.In the case group, serum APN level was negatively correlated with renin, ALD and Ang-Ⅱ levels ( r=-0.646, -0.752, -0.839, all P<0.001), while serum leptin and resistin levels were positively correlated with renin, ALD and Ang-Ⅱ levels ( r=0.940, 0.871, 0.875; 0.877, 0.892, 0.914, all P<0.001). Conclusions:Serum adipokine in school-age children with simple obesity in Xinjiang area is dysregulated, which interferes with the activity of RAS.

17.
Acta Pharmaceutica Sinica B ; (6): 511-531, 2022.
Article in English | WPRIM | ID: wpr-929312

ABSTRACT

Aging is by far the most prominent risk factor for Alzheimer's disease (AD), and both aging and AD are associated with apparent metabolic alterations. As developing effective therapeutic interventions to treat AD is clearly in urgent need, the impact of modulating whole-body and intracellular metabolism in preclinical models and in human patients, on disease pathogenesis, have been explored. There is also an increasing awareness of differential risk and potential targeting strategies related to biological sex, microbiome, and circadian regulation. As a major part of intracellular metabolism, mitochondrial bioenergetics, mitochondrial quality-control mechanisms, and mitochondria-linked inflammatory responses have been considered for AD therapeutic interventions. This review summarizes and highlights these efforts.

18.
Acta Pharmaceutica Sinica B ; (6): 50-75, 2022.
Article in English | WPRIM | ID: wpr-929281

ABSTRACT

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling exert essential regulatory function in microbial-and onco-immunology through the induction of cytokines, primarily type I interferons. Recently, the aberrant and deranged signaling of the cGAS-STING axis is closely implicated in multiple sterile inflammatory diseases, including heart failure, myocardial infarction, cardiac hypertrophy, nonalcoholic fatty liver diseases, aortic aneurysm and dissection, obesity, etc. This is because of the massive loads of damage-associated molecular patterns (mitochondrial DNA, DNA in extracellular vesicles) liberated from recurrent injury to metabolic cellular organelles and tissues, which are sensed by the pathway. Also, the cGAS-STING pathway crosstalk with essential intracellular homeostasis processes like apoptosis, autophagy, and regulate cellular metabolism. Targeting derailed STING signaling has become necessary for chronic inflammatory diseases. Meanwhile, excessive type I interferons signaling impact on cardiovascular and metabolic health remain entirely elusive. In this review, we summarize the intimate connection between the cGAS-STING pathway and cardiovascular and metabolic disorders. We also discuss some potential small molecule inhibitors for the pathway. This review provides insight to stimulate interest in and support future research into understanding this signaling axis in cardiovascular and metabolic tissues and diseases.

19.
Acta Pharmaceutica Sinica B ; (6): 1523-1533, 2022.
Article in English | WPRIM | ID: wpr-929275

ABSTRACT

The spread of coronavirus disease 2019 (COVID-19) throughout the world has resulted in stressful healthcare burdens and global health crises. Developing an effective measure to protect people from infection is an urgent need. The blockage of interaction between angiotensin-converting enzyme 2 (ACE2) and S protein is considered an essential target for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drugs. A full-length ACE2 protein could be a potential drug to block early entry of SARS-CoV-2 into host cells. In this study, a therapeutic strategy was developed by using extracellular vesicles (EVs) with decoy receptor ACE2 for neutralization of SARS-CoV-2. The EVs embedded with engineered ACE2 (EVs-ACE2) were prepared; the EVs-ACE2 were derived from an engineered cell line with stable ACE2 expression. The potential effect of the EVs-ACE2 on anti-SARS-CoV-2 was demonstrated by both in vitro and in vivo neutralization experiments using the pseudovirus with the S protein (S-pseudovirus). EVs-ACE2 can inhibit the infection of S-pseudovirus in various cells, and importantly, the mice treated with intranasal administration of EVs-ACE2 can suppress the entry of S-pseudovirus into the mucosal epithelium. Therefore, the intranasal EVs-ACE2 could be a preventive medicine to protect from SARS-CoV-2 infection. This EVs-based strategy offers a potential route to COVID-19 drug development.

20.
Article in Chinese | WPRIM | ID: wpr-941014

ABSTRACT

OBJECTIVE@#To investigate the roles of angiotensin-converting enzyme 2 (ACE2) in ozone-induced pulmonary inflammation and airway remodeling in mice.@*METHODS@#Sixteen wild-type (WT) C57BL/6J mice and 16 ACE2 knock-out (KO) mice were exposed to either filtered air or ozone (0.8 ppm) for 3 h per day for 5 consecutive days. Masson's staining and HE staining were used to observe lung pathologies. Bronchoalveolar lavage fluid (BALF) was collected and the total cell count was determined. The total proteins and cytokines in BALF were determined by BCA and ELISA method. The transcription levels of airway remodeling-related indicators in the lung tissues were detected using real-time quantitative PCR. The airway resistance of the mice was measured using a small animal ventilator with methacholine stimulation.@*RESULTS@#Following ozoneexposure ACE2 KO mice had significantly higher lung pathological scores than WT mice (P < 0.05). Masson staining results showed that compared with ozone-exposed WT mice, ozone-exposed ACE2 KO mice presented with significantly larger area of collagen deposition in the bronchi [(19.62±3.16)% vs (6.49±1.34)%, P < 0.05] and alveoli [(21.63±3.78)% vs (4.44±0.99)%, P < 0.05]. The total cell count and total protein contents in the BALF were both higher in ozone-exposed ACE2 KO mice than in WT mice, but these differences were not statistically significant (P > 0.05). The concentrations of IL-6, IL-1β, TNF-α, CXCL1/KC and MCP-1 in the BALF were all higher in ozone-exposed ACE2 KO mice than in ozone-exposed WT mice, but only the difference in IL-1β was statistically significant (P < 0.05). The transcription levels of MMP-9, MMP-13, TIMP 4, COL1A1, and TGF-β in the lung tissues were all significantly higher in ozone-exposed ACE2 KO mice (P < 0.01). No significant difference was found in airway resistance between ozone-exposed ACE KO mice and WT mice after challenge with 0, 10, 25, or 100 mg/mL of methacholine.@*CONCLUSION@#ACE2 participates in ozone-induced lung inflammation and airway remodeling in mice.


Subject(s)
Airway Remodeling , Angiotensin-Converting Enzyme 2 , Animals , Methacholine Chloride , Mice , Mice, Inbred C57BL , Mice, Knockout , Ozone/adverse effects , Pneumonia
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