RESUMO
In brief: Impaired spermatogenesis resulting from disturbed cholesterol metabolism due to intake of high-fat diet (HFD) has been widely recognized, however, the role of preprotein invertase subtilin 9 (PCSK9), which is a negative regulator of cholesterol metabolism, has never been reported. This study aims to reveal the role of PCSK9 on spermatogenesis induced by HFD in mice. Abstract: Long-term consumption of a high-fat diet (HFD) is an important factor that leads to impaired spermatogenesis exhibiting poor sperm quantity and quality. However, the mechanism of this is yet to be elucidated. Disrupted cholesterol homeostasis is one of many crucial pathological factors which could contribute to impaired spermatogenesis. As a negative regulator of cholesterol metabolism, preprotein invertase subtilin 9 (PCSK9) mediates low density lipoprotein receptor (LDLR) degradation to the lysosome, thereby reducing the expression of LDLR on the cell membrane and increasing serum low-density lipoprotein cholesterol level, resulting in lipid metabolism disorders. Here, we aim to study whether PCSK9 is a pathological factor for impaired spermatogenesis induced by HFD and the underlying mechanism. To meet the purpose of our study, we utilized wild-type C57BL/6 male mice and PCSK9 knockout mice with same background as experimental subjects and alirocumab, a PCSK9 inhibitor, was used for treatment. Results indicated that HFD induced higher PCSK9 expression in serum, liver, and testes, and serum PCSK9 is negatively correlated with spermatogenesis, while both PCSK9 inhibitor treatment and PCSK9 knockout methodologies ameliorated impaired lipid metabolism and spermatogenesis in mice fed a HFD. This could be due to the overexpression of PCSK9 induced by HFD leading to dyslipidemia, resulting in testicular lipotoxicity, thus activating the Bcl-2-Bax-Caspase3 apoptosis signaling pathway in testes, particularly in Leydig cells. Our study demonstrates that PCSK9 is an important pathological factor in the dysfunction of spermatogenesis in mice induced by HFD. This finding could provide innovative ideas for the diagnosis and treatment of male infertility.
Assuntos
Dieta Hiperlipídica , Pró-Proteína Convertase 9 , Animais , Masculino , Camundongos , beta-Frutofuranosidase , Colesterol , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pró-Proteína Convertase 9/genética , SêmenRESUMO
BACKGROUND: Keloids represent one extreme of aberrant dermal wound healing and are characterized by fibroblast hyperproliferation and excessive deposition of extracellular matrix. Genetics is a major factor for predisposition to keloids and genome-wide association study has identified a single-nucleotide polymorphism (SNP) rs873549 at 1q41 as a susceptibility locus. The SNP rs873549, and the SNPs in strong linkage disequilibrium (LD) with rs873549, may be involved in keloid development. However, the functional significance of these SNPs in keloid pathogenesis remains elusive. OBJECTIVES: To investigate the function and mechanism of SNP rs873549 and the SNPs in strong LD with rs873549 in keloids. METHODS: SNPs in strong LD with rs873549 were analysed using Haploview. The expression levels of the genes near the susceptibility locus were analysed using quantitative real-time polymerase chain reaction. The interaction between rs1348270-containing enhancer and the long noncoding RNA down expressed in keloids (DEIK) (formerly RP11-400N13.1) promoter in fibroblasts was investigated using chromosome conformation capture. The enhancer activity of the rs1348270 locus was evaluated using luciferase reporter assay. Knockdown experiments were used to explore the function of DEIK in keloids. RNA-Seq was performed to investigate the mechanism by which DEIK regulates the expression of collagens POSTN and COMP. RESULTS: rs1348270, an enhancer-located SNP in strong LD with rs873549, mediated looping with the promoter of DEIK. The risk variant was associated with decreased enhancer-promoter interaction and DEIK down-expression in keloids. Mechanistically, downregulation of DEIK increased the expression of collagens POSTN and COMP through upregulating BMP2. Furthermore, correlation analysis revealed that DEIK expression was inversely correlated with BMP2, POSTN and COMP expression in both keloid and normal fibroblasts. CONCLUSIONS: Our findings suggest that the risk variant rs1348270 is located in an enhancer and is associated with the downregulation of DEIK in keloids, and that downregulation of DEIK increases the expression of collagens POSTN and COMP through BMP2 in keloid fibroblasts. These findings will help to provide a more thorough understanding of the role played by genetic factors in keloid development and may lead to new strategies for screening and therapy in keloid-susceptible populations.
Assuntos
Queloide , RNA Longo não Codificante , Humanos , Queloide/patologia , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/metabolismo , Estudo de Associação Genômica Ampla , Regiões Promotoras Genéticas , Fibroblastos/metabolismoRESUMO
Uterine receptivity to the embryo is crucial for successful implantation. The establishment of uterine receptivity requires a large amount of energy, and abnormal energy regulation causes implantation failure. Glucose metabolism in the endometrium is tissue specific. Glucose is largely stored in the form of glycogen, which is the main energy source for the endometrium. AMP-activated protein kinase (AMPK), an important energy-sensing molecule, is a key player in the regulation of glucose metabolism and its regulation is also tissue specific. However, the mechanism of energy regulation in the endometrium for the establishment of uterine receptivity remains to be elucidated. In this study, we aimed to investigate the energy regulation mechanism of mouse uterine receptivity and its significance in embryo implantation. The results showed that the AMPK, p-AMPK, glycogen synthase 1, and glycogen phosphorylase M levels and the glycogen content in mouse endometrial epithelium varied in a periodic manner under regulation by the ovarian hormone. Specifically, progesterone significantly activated AMPK, promoted glycogenolysis, and upregulated glycogen phosphorylase M expression. AMPK regulated glycogen phosphorylase M expression and promoted glycogenolysis. AMPK was also found to be activated by changes in the energy or glycogen of the endometrial epithelial cells. The inhibition of AMPK activity or glycogenolysis altered the uterine receptivity markers during the window of implantation and ultimately interfered with implantation. In summary, consistency and synchronization of AMPK and glycogen metabolism constitute the core regulatory mechanism in mouse endometrial epithelial cells involved in the establishment of uterine receptivity.
Assuntos
Proteínas Quinases Ativadas por AMP , Glicogênio , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Implantação do Embrião/fisiologia , Endométrio/metabolismo , Células Epiteliais/metabolismo , Feminino , Glicogênio/metabolismo , CamundongosRESUMO
The incidence of polycystic ovary syndrome (PCOS) due to high-fat diet (HFD) consumption has been increasing significantly. However, the mechanism by which a HFD contributes to the pathogenesis of PCOS has not been elucidated. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key protein that regulates cholesterol metabolism. Our previous study revealed abnormally high PCSK9 levels in serum from patients with PCOS and in serum and hepatic and ovarian tissues from PCOS model mice, suggesting that PCSK9 is involved in the pathogenesis of PCOS. However, the factor that induces high PCSK9 expression in PCOS remains unclear. In this study, Pcsk9 knockout mice were used to further explore the role of PCSK9 in PCOS. We also studied the effects of a HFD on the expression of PCSK9 and sterol regulatory element-binding protein 2 (SREBP2), a regulator of cholesterol homeostasis and a key transcription factor that regulates the expression of PCSK9, and the roles of these proteins in PCOS pathology. Our results indicated HFD may play an important role by inducing abnormally high PCSK9 expression via SREBP2 upregulation. We further investigated the effects of an effective SREBP inhibitor, fatostain, and found that it could reduce HFD-induced PCSK9 expression, ameliorate hyperlipidemia and improve follicular development in PCOS model mice. Our study thus further elucidates the important role of an HFD in the pathogenesis of PCOS and provides a new clue in the prevention and treatment of this disorder.
Assuntos
Síndrome do Ovário Policístico , Pró-Proteína Convertase 9 , Animais , Dieta Hiperlipídica/efeitos adversos , Feminino , Humanos , Camundongos , Camundongos Knockout , Síndrome do Ovário Policístico/etiologia , Pró-Proteína Convertase 9/genética , Pró-Proteína Convertase 9/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Regulação para CimaRESUMO
The study aims to observe the clinical efficacy of Baoerkang san on spleen-deficiency and dampness-obstructing diarrhea in children. Children diarrhea divided into acute diarrhea (group I) and chronic persistent diarrhea (group II). A randomized, double-blind, positive control test was conducted for dose finding. The 340 cases with acute diarrhea in group I were divided into three groups: the high dose group (112 patients), the low dose group (113 patients) and the positive control group (115 patients), which were treated for 3 days. Their clinical efficacies were compared to evaluate the clinical safety of Baoerkang san. The 167 patients with chronic persistent diarrhea in group If were divided into the high dose group (56 patients), the low dose group (55 patients) and the control group (56 patients), which were treated for 5 days. Their clinical efficacy were compared to evaluate the clinical safety of Baoerkang san. According to the results, the cure rate and the effective rate of acute diarrhea and chronic persistent diarrhea in the high dose group and the low dose group were significantly higher than that of the positive control group (P <0. 05, P < 0.01). In the treatment of spleen-deficiency and dampness-obstructing diarrhea with traditional Chinese medicines, the cure rate and the effective rate of acute diarrhea and chronic persistent diarrhea in the high dose group and the low dose group were significantly higher than that of the positive control group (P < 0.05, P < 0.01). During the test, all of the three groups did not suffer any adverse event, with no any abnormality in general physical indexes. In conclusion, Baoerkang san shows a significant efficacy in treating acute diarrhea and chronic persistent diarrhea (spleen-deficiency and dampness-obstructing) and safe clinical application.
Assuntos
Diarreia/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Criança , Pré-Escolar , Diarreia/fisiopatologia , Feminino , Humanos , Lactente , Masculino , Fitoterapia , Baço/efeitos dos fármacos , Baço/fisiopatologia , Resultado do TratamentoRESUMO
AIMS: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in the women of childbearing age. It is characterized by hyperandrogenism and abnormal follicular growth and ovulation. The polyol pathway is a glucose metabolism bypass pathway initiated by aldose reductase (ADR). Androgen induces the expression of ADR in the male reproductive tract, which has a general physiological significance for male reproductive function. Here we investigate whether hyperandrogenemia in PCOS leads to increased flux of the polyol pathway in ovarian tissue, which in turn affects follicular maturation and ovulation through oxidative stress. MAIN METHODS: We used clinical epidemiological methods to collect serum and granulosa cells from clinical subjects for a clinical case-control study. At the same time, cell biology and molecular biology techniques were used to conduct animal and cell experiments to further explore the mechanism of hyperandrogen-induced ovarian polyol pathway hyperactivity and damage to ovarian function. KEY FINDINGS: Here, we find that hyperandrogenism of PCOS can induce the expression of ovarian aldose reductase, which leads to the increase of the polyol pathway flux, and affects ovarian function through excessive oxidative stress. SIGNIFICANCE: Our research has enriched the pathological mechanism of PCOS and may provide a new clue for the clinical treatment of PCOS.
Assuntos
Hiperandrogenismo , Síndrome do Ovário Policístico , Humanos , Animais , Feminino , Masculino , Síndrome do Ovário Policístico/metabolismo , Hiperandrogenismo/metabolismo , Aldeído Redutase/metabolismo , Estudos de Casos e Controles , Estresse OxidativoRESUMO
Coronavirus is a family of viruses that can cause diseases such as the common cold, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS). The universal outbreak of coronavirus disease 2019 (COVID-19) caused by SARS coronaviruses 2 (SARS-CoV-2) has become a global pandemic. The ß-Coronaviruses, which caused SARS-CoV-2 (COVID-19), have spread in more than 213 countries, infected over 81 million people, and caused more than 1.79 million deaths. COVID-19 symptoms vary from mild fever, flu to severe pneumonia in severely ill patients. Difficult breathing, acute respiratory distress syndrome (ARDS), acute kidney disease, liver damage, and multi-organ failure ultimately lead to death. Researchers are working on different pre-clinical and clinical trials to prevent this deadly pandemic by developing new vaccines. Along with vaccines, therapeutic intervention is an integral part of healthcare response to address the ongoing threat posed by COVID-19. Despite the global efforts to understand and fight against COVID-19, many challenges need to be addressed. This article summarizes the current pandemic, different strains of SARS-CoV-2, etiology, complexities, surviving medications of COVID-19, and so far, vaccination for the treatment of COVID-19.
Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/genética , Variação Genética/genética , SARS-CoV-2/genética , Vacinação/tendências , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/genética , Antivirais/administração & dosagem , COVID-19/prevenção & controle , Vacinas contra COVID-19/genética , Surtos de Doenças/prevenção & controle , Humanos , Medicina Tradicional Chinesa/tendências , Vacinação/métodos , Tratamento Farmacológico da COVID-19RESUMO
Fibrotic skin disease represents a major global healthcare burden, characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix. Fibroblasts are found to be heterogeneous in multiple fibrotic diseases, but fibroblast heterogeneity in fibrotic skin diseases is not well characterized. In this study, we explore fibroblast heterogeneity in keloid, a paradigm of fibrotic skin diseases, by using single-cell RNA-seq. Our results indicate that keloid fibroblasts can be divided into 4 subpopulations: secretory-papillary, secretory-reticular, mesenchymal and pro-inflammatory. Interestingly, the percentage of mesenchymal fibroblast subpopulation is significantly increased in keloid compared to normal scar. Functional studies indicate that mesenchymal fibroblasts are crucial for collagen overexpression in keloid. Increased mesenchymal fibroblast subpopulation is also found in another fibrotic skin disease, scleroderma, suggesting this is a broad mechanism for skin fibrosis. These findings will help us better understand skin fibrotic pathogenesis, and provide potential targets for fibrotic disease therapies.
Assuntos
Colágeno/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Queloide/metabolismo , Mesoderma/citologia , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Colágeno/genética , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Fibroblastos/patologia , Regulação da Expressão Gênica/genética , Ontologia Genética , Humanos , Queloide/genética , Queloide/patologia , Ligantes , Mesoderma/metabolismo , Mesoderma/patologia , RNA-Seq , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/metabolismo , Escleroderma Sistêmico/patologia , Análise de Célula Única , Dermatopatias/genética , Dermatopatias/metabolismo , Dermatopatias/patologiaRESUMO
Many functional activities of endometrium epithelium are energy consuming which are very important for maintaining intrauterine environment needed by early embryonic development and establishment of implantation window. Glucose is a main energy supplier and one of the main components of intrauterine fluid. Obviously, glucose transports in endometrium epithelium involve in for these activities but their functions have not been elucidated. In this research, we observed a spatiotemporal pattern of sodium glucose transporter 1 (SGLT1) expression in the mouse endometrium. We also determined that progesterone can promote the expression of SGLT1 in the mouse endometrial epithelium in response to the action of oestrogen. Treatment with the SGLT1 inhibitor phlorizin or small interfering RNA specific for SGLT1 (SGLT1-siRNA) altered glucose uptake in primary cultured endometrial epithelial cells, which exhibited reduced ATP levels and AMPK activation. The injection of phlorizin or SGLT1-siRNA into one uterine horn of each mouse on day 2 of pregnancy led to an increased glucose concentration in the uterine fluid and decreased number of harvested normal blastocysts and decreased expression of integrin αVß3 in endometrial epithelium and increased expression of mucin 1 and lactoferrin in endometrial epithelium and the uterine homogenates exhibited activated AMPK, a decreased ATP level on day 4, and a decreased number of implantation sites on day 5. In embryo transfer experiments, pre-treatment of the uterine horn with phlorizin or SGLT1-siRNA during the implantation window led to a decreased embryo implantation rate on day 5 of pregnancy, even when embryos from normal donor mice were used. In conclusion, SGLT1, which participates in glucose transport in the mouse endometrial epithelium, inhibition and/or reduced expression of SGLT1 affects early embryo development by altering the glucose concentration in the uterine fluid. Inhibition and/or reduced expression of SGLT1 also affects embryo implantation by influencing energy metabolism in epithelial cells, which consequently influences implantation-related functional activities.
Assuntos
Implantação do Embrião/fisiologia , Desenvolvimento Embrionário/fisiologia , Endométrio/metabolismo , Epitélio/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Transportador 1 de Glucose-Sódio/biossíntese , Animais , Transferência Embrionária/métodos , Feminino , Glucose/metabolismo , Camundongos , Gravidez , Transportador 1 de Glucose-Sódio/genéticaRESUMO
Type 2 diabetes mellitus (T2DM) is a disease characterized by hyperglycemia resulting from insulin resistance. In recent years, the incidence of T2DM has been increasing. Women with T2DM often suffer from infertility and early miscarriage; however, the underlying mechanisms remain unclear. Insulin is the most important regulatory hormone of glycogen metabolism. In addition, 5' adenosine monophosphate-activated protein kinase (AMPK) is an important regulator of glycogen metabolism. Patients with T2DM have inhibited AMPK expression in the liver, which leads to impaired glucose metabolism. However, the role of AMPK in endometrial glycogen metabolism has not been reported. In this study, a mouse model of T2DM was established to investigate whether altered endometrial glucose metabolism affects early embryo implantation. Metformin and insulin were used for therapy; the resulting changes to glycogen metabolism and embryo implantation were examined. The results indicate that the concentrations of glycogen decreased significantly in T2DM mice, resulting in insufficient energy supplies for proper endometrial function, and thereby impeding embryonic implantation. Interestingly, endometrial AMPK was not found to be overactivated. Insulin treatment was found to partially resolve the embryo implantation defects in T2DM mice. Metformin improved blood glucose but did not have a significant effect on local endometrial glucose metabolism. This study explored the changes in endometrial glucose metabolism in T2DM mouse, and the effects of these changes on embryo implantation. We found that insulin, but not metformin, significantly resolved embryo implantation problems. These findings will help to increase our understanding of the pathomechanisms of infertility and early miscarriage in women with T2DM.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Implantação do Embrião , Endométrio/metabolismo , Infertilidade Feminina/etiologia , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Implantação do Embrião/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Endométrio/fisiopatologia , Feminino , Glicogênio/metabolismo , Homeostase , Hipoglicemiantes/farmacologia , Infertilidade Feminina/metabolismo , Infertilidade Feminina/fisiopatologia , Infertilidade Feminina/prevenção & controle , Insulina/farmacologia , Metformina/farmacologia , Camundongos Endogâmicos ICR , GravidezRESUMO
Resveratrol (RV) is a well-known polyphenolic compound in various plants, including grape, peanut, and berry fruits, which is quite famous for its association with several health benefits such as anti-obesity, cardioprotective neuroprotective, antitumor, antidiabetic, antioxidants, anti-age effects, and glucose metabolism. Significantly, promising therapeutic properties have been reported in various cancer, neurodegeneration, and atherosclerosis and are regulated by several synergistic pathways that control oxidative stress, cell death, and inflammation. Similarly, RV possesses a strong anti-adipogenic effect by inhibiting fat accumulation processes and activating oxidative and lipolytic pathways, exhibiting their cardioprotective effects by inhibiting platelet aggregation. The RV also shows significant antibacterial effects against various food-borne pathogens (Listeria, Campylobacter, Staphylococcus aureus, and E. coli) by inhibiting an electron transport chain (ETC) and F0F1-ATPase, which decreases the production of cellular energy that leads to the spread of pathogens. After collecting and analyzing scientific literature, it may be concluded that RV is well tolerated and favorably affects cardiovascular, neurological, and diabetic disorders. As such, it is possible that RV can be considered the best nutritional additive and a complementary drug, especially a therapeutic candidate. Therefore, this review would increase knowledge about the blend of RV as well as inspire researchers around the world to consider RV as a pharmaceutical drug to combat future health crises against various inhumane diseases. In the future, this article will be aware of discoveries about the potential of this promising natural compound as the best nutraceuticals and therapeutic drugs in medicine.
Assuntos
Suplementos Nutricionais , Compostos Fitoquímicos/uso terapêutico , Resveratrol/uso terapêutico , Animais , Suplementos Nutricionais/efeitos adversos , Humanos , Segurança do Paciente , Compostos Fitoquímicos/efeitos adversos , Compostos Fitoquímicos/farmacocinética , Resveratrol/efeitos adversos , Resveratrol/farmacocinética , Medição de RiscoRESUMO
GLUT4 is involved in rapid glucose uptake among various kinds of cells to contribute to glucose homeostasis. Prior data have reported that aberrant glucose metabolism by GLUT4 dysfunction in the uterus could be responsible for infertility and increased miscarriage. However, the expression and precise functions of GLUT4 in the endometrium under physiological conditions remain unknown or controversial. In this study, we observed that GLUT4 exhibits a spatiotemporal expression in mouse uterus on pregnant days 1-4; its expression especially increased on pregnant day 4 during the window of implantation. We also determined that estrogen, in conjunction with progesterone, promotes the expression of GLUT4 in the endometrial epithelium in vivo or in vitro. GLUT4 is an important transporter that mediates glucose transport in endometrial epithelial cells (EECs) in vitro or in vivo. In vitro, glucose uptake decreased in mouse EECs when the cells were treated with GLUT4 small interfering RNA (siRNA). In vivo, the injection of GLUT4-siRNA into one side of the mouse uterine horns resulted in an increased glucose concentration in the uterine fluid on pregnant day 4, although it was still lower than in blood, and impaired endometrial receptivity by inhibiting pinopode formation and the expressions of leukemia inhibitory factor (LIF) and integrin ανß3, finally affecting embryonic development and implantation. Overall, the obtained results indicate that GLUT4 in the endometrial epithelium affects embryo development by altering glucose concentration in the uterine fluid. It can also affect implantation by impairing endometrial receptivity due to dysfunction of GLUT4.
RESUMO
BACKGROUND: With the ageing of China's population, the incidence and mortality of coronary atherosclerotic heart disease (CAD) is increasing year by year, which brings a heavy burden to the family and society [1]. We aimed to analyse the strategy of coronary artery bypass grafting (CABG) in the right coronary artery and to compare the haemodynamic characteristics of the sequential grafts with those of single grafts and to observe the patency rate of those grafts for 1 week after the operation. METHODS: A total of 242 patients (178 men, mean age 62.6 ± 8.8 years) underwent right coronary artery bypass grafting in our hospital from October 2016 to January 2019. The blood flow (Q, ml/min), pulsatility index (PI) and related parameters of the grafts were measured and recorded by TTFM during the CABG. The patency of the grafts was evaluated by coronary computed tomography (CT) for 1 week after the operation. RESULTS: The most common material used for the graft in the right coronary system of CABG is the greater saphenous vein (92.3%), followed by the radial artery (5.5%) and the internal mammary artery (1.9%). The highest frequency target of the right coronary artery is the posterior descending artery (PDA) (47.6%), followed by the right main coronary artery (RCA) (29.1%) and the posterior branch of the left ventricle (PL) (23.3%). The proportion of single grafts was the highest for the right coronary artery in CABG (178 cases, 67.9%), followed by a graft of the PDA-PL (42 cases, 16.0%) and other sequential grafts among the different coronary artery systems (including the system of the left anterior descending artery (LAD) and the left circumflex (LCX)). Whether there were sequential grafts of the PDA-PL or other sequential grafts among the different systems of the coronary artery, the instantaneous flow of a group of sequential grafts was higher than that of a single graft, and the difference had statistical significance (P < 0.01). However, there were no significant differences in the flow between the groups of sequential grafts (P = 0.410). Diastolic flow (DF) in the group of sequential grafts of the right coronary system was better than that in the non-sequential group (P < 0.001), and the difference had statistical significance. There was no significant difference between the DF of the groups of the other system of sequential grafts and that of the right coronary sequential grafts. Coronary artery CT suggested that there were 11 cases of poorly developing grafts or stenosis and occlusion a week after the operation, and those phenomenon mainly occurred in the group with a single graft. There was only one case that was occluded in the group of other systems of sequential grafts, and statistically significant differences existed between the two groups (P < 0.01). CONCLUSIONS: In our centre, the most common form of CABG in the right coronary artery system is a non-sequential vein bridge to the PDA. Whether there are sequential grafts of the PDA-PL or other sequential grafts among the different coronary artery systems, the instantaneous flow of a group of sequential grafts is higher than that of a single graft. DF in the group of sequential grafts of the right coronary system was better than that in the non-sequential group.
Assuntos
Ponte de Artéria Coronária/métodos , Vasos Coronários/cirurgia , Idoso , Velocidade do Fluxo Sanguíneo , Circulação Coronária , Doença das Coronárias/cirurgia , Vasos Coronários/diagnóstico por imagem , Feminino , Coração , Hemodinâmica , Humanos , Masculino , Artéria Torácica Interna/transplante , Pessoa de Meia-Idade , Período Perioperatório , Fluxo Pulsátil , Artéria Radial/cirurgia , Estudos Retrospectivos , Veia Safena/transplante , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
The incidence of diabetes in women of childbearing age has been increasing recently and implantation failure and early abortion are important reasons for infertility in diabetic women. Glycogen synthesis and decomposition are the cores of glucose homeostasis in endometrium and AMPK is activated when cellular energy consumption increases. Embryo implantation is a complex process required huge energy. Yet the changes of glucose metabolism in endometrium and its impact on embryo implantation in diabetic women are still unclear. In this research, we established diabetic pregnancy mice model by intraperitoneal injecting streptozotocin on pregnant day 1. We first tested the changes of endometrial glucose homeostasis and embryo implantation. Next, we demonstrated abnormal activation of AMPK in the endometrium of diabetic mice and its affecting endometrial glucose homeostasis. Finally, we compared the endometrial glucose homeostasis and embryo implantation outcome in diabetic pregnant mice treated with insulin or insulin combined with metformin. The results indicated that there was disturbed glucose homeostasis associated with excessive activation of AMPK in endometrium of diabetic pregnant mice. AMPK inhibitor improved the over-activation of AMPK pathway in the endometrium, meanwhile, partially corrected the abnormal glycogen metabolism and improved the implantation. Insulin improved the disorder of endometrial glucose homeostasis and implantation of diabetic mice. Our research explores the causes of high abortion and infertility rate in diabetic women which is to provide a therapeutic reference for patients with diabetes complicated with infertility and early abortion.
Assuntos
Adenilato Quinase/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Gestacional/metabolismo , Implantação do Embrião/fisiologia , Endométrio/metabolismo , Glucose/metabolismo , Homeostase/fisiologia , Animais , Glicemia/metabolismo , Implantação do Embrião/efeitos dos fármacos , Feminino , Glicogênio/metabolismo , Hipoglicemiantes/administração & dosagem , Infertilidade Feminina/metabolismo , Insulina/administração & dosagem , Metformina/administração & dosagem , GravidezRESUMO
We have synthesized a number of novel Schiff's bases from 4-amino-3-(D-glucoheptonic-hexitol-1-yl)-1H-1,2,4-triazole-5-thione. By attaching D-glucoheptonic-hexitol-1-yl residues to 1,2,4-triazole at the 3-position, the solubility of the title compounds has been improved greatly. All the products have been characterized by elemental analysis, IR, 1H-NMR, 13C-NMR and MS. The plant-growth regulating effects of the title compounds were examined. From the biological activity results, we found that most compounds showed weak to moderate activities.
Assuntos
Bases de Schiff/síntese química , Triazóis/química , Desenvolvimento Vegetal , Plantas/efeitos dos fármacos , Bases de Schiff/farmacologia , Solubilidade , Análise EspectralRESUMO
To discover new 1,2,4-triazole derivatives which may possess significant biological activities, we synthesized a series of novel 6-aryl-3-(D-galactopentitol-1-yl)-7H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazines and 4-(arylmethylidene)amino-5-(D-galactopentitol-1-yl)-3-mercapto-4H-1,2,4-triazoles from 4-amino-3-(D-galactopentitol-1-yl)-5-mercapto-1,2,4-triazole. All the title compounds were characterized by elemental analysis, IR, 1H- and 13C-NMR. Plant growth-regulating activity tests showed that these compounds have remarkable effects on the growth of radish and wheat.
Assuntos
Raphanus/efeitos dos fármacos , Álcoois Açúcares/farmacologia , Triazóis/síntese química , Triazóis/farmacologia , Triticum/efeitos dos fármacos , Raphanus/crescimento & desenvolvimento , Triazóis/química , Triticum/crescimento & desenvolvimentoRESUMO
A series of 6-aryl-3-(3-hydroxypropyl)-7H-1,2,4-triazolo[3,4-b][1,3,4]-thiadiazines were synthesized by the reaction of 4-amino-3-(3-hydroxypropyl)-5-mercapto-1,2,4-triazole (1) with substituted omega-haloacetophenones. Their structures were confirmed by elemental analysis, IR, 1H-NMR, and 13C-NMR. Tests of plant growth regulating effects showed that the title compounds display remarkable inhibitory activities on the growth of radish and wheat.
Assuntos
Tiadiazinas/síntese química , Tiadiazinas/metabolismo , Triazóis/síntese química , Triazóis/metabolismo , Isótopos de Carbono , Germinação/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Reguladores de Crescimento de Plantas/farmacologia , Raízes de Plantas/efeitos dos fármacos , Brotos de Planta/efeitos dos fármacos , Raphanus/efeitos dos fármacos , Espectrofotometria Infravermelho , Tiadiazinas/química , Tiadiazinas/farmacologia , Triazóis/química , Triazóis/farmacologia , Triticum/efeitos dos fármacosRESUMO
AIM: To investigate the effects and underlying mechanisms of resveratrol and genistein on contractile responses of rat gastrointestinal smooth muscle. METHODS: Isolated strips of gastrointestinal smooth muscle from Spraque-Dawley rats were suspended in organ baths containing Kreb's solution, and the contractility of smooth muscles was measured before and after incubation with resveratrol and genistein, and the related mechanisms were studied by co-incubation with various inhibitors. RESULTS: Resveratrol and genistein dose-dependently decreased the resting tension, and also reduced the mean contractile amplitude of gastrointestinal smooth muscle. Estrogen receptor blockades (ICI 182780 and tamoxifen) failed to alter the inhibitory effects induced by resveratrol and genistein. However, their effects were attenuated by inhibitions of α-adrenergic receptor (phentolamine), nitric oxide synthase (levorotatory-NG-nitroarginine), ATP-sensitive potassium channels (glibenclamide), and cyclic adenosine monophosphate (SQ22536). In high K(+)/Ca(2+)-free Kreb's solution containing 0.01 mmol/L egtazic acid, resveratrol and genistein reduced the contractile responses of CaCl2, and shifted its cumulative concentration-response curves rightward. CONCLUSION: Resveratrol and genistein relax gastrointestinal smooth muscle via α-adrenergic receptors, nitric oxide and cyclic adenosine monophosphate pathways, ATP-sensitive potassium channels, and inhibition of L-type Ca(2+) channels.
Assuntos
Duodeno/efeitos dos fármacos , Motilidade Gastrointestinal/efeitos dos fármacos , Genisteína/farmacologia , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Fitoestrógenos/farmacologia , Estilbenos/farmacologia , Estômago/efeitos dos fármacos , Animais , Canais de Cálcio Tipo L/efeitos dos fármacos , Canais de Cálcio Tipo L/metabolismo , AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Duodeno/metabolismo , Feminino , Mucosa Gástrica/metabolismo , Técnicas In Vitro , Canais KATP/agonistas , Canais KATP/metabolismo , Músculo Liso/metabolismo , Óxido Nítrico/metabolismo , Ratos Sprague-Dawley , Receptores Adrenérgicos alfa/efeitos dos fármacos , Receptores Adrenérgicos alfa/metabolismo , Resveratrol , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: To observe and compare the effects of 17beta-estradiol (EST) on the phasic and tonic contractile activities of the uterine smooth muscles of SD rats in vitro. METHODS: Different concentrations of 17beta-estradiol were added into the perfusion muscular sockets containing uterine smooth muscles of SD rats, and the activities of muscle contraction were recorded at the same time. RESULTS: 17beta-estradiol had obvious depression effects on spontaneous rhythmic contraction of the uterine smooth muscles in a concentration-dependent manner, it could considerably decrease muscular tension, the mean amplitudes and frequencies of contractile waves (P < 0.01); it could also suppress the uterine contraction stimulated by KCl, CaCl2 or prostaglandin F2alpha (PGF2alpha). Based on the contraction of uterine smooth muscle stimulated by KCl, IC50 was 7.278 micromol/L and pD2 was -0.862 when calculated by linear regression method. 17beta-estradiol could also inhibit the maximal CaC12 contraction of uterine smooth muscle in the Ca2+ free Krebs solution, which the ECQ was 1.422 x 10(-3) mol/L, pD2 was 2.847 (control), but the E50 was 3.028 x 10(-3) mol/L, p2 was 2.519 (added with EST) when calculated by linear regression method. CONCLUSION: The depression effects of 17beta-estradiol on the spontaneous rhythmic contraction and activated contraction of the uterine smooth muscles of SD rats could be mediated through the blockage of C2+ influx through potential-dependent Ca2+ channels of plasma membrane.