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Eur J Neurosci ; : e14896, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32638449


The cellular and molecular mechanisms underlying leptin-mediated brain protection against cerebral ischemia were investigated at the blood-brain barrier (BBB) and neutrophil level. Through the ischemia/reperfusion (I/R) animal model, we found that leptin expression level was significantly decreased in ischemic hemisphere. Brain injection with leptin (15 µg/kg, intracisternally) could block the I/R-increased BBB permeability, activation of matrix metallopeptidase 9 (MMP-9) and brain infiltration of blood-borne neutrophils to reduce the infarct volume of ischemic brain. The brain expression level of tight junction protein ZO-1 as well as number and motility of neutrophils in blood was all increased by the same injection, indicating BBB stability (rather than reduction in neutrophils) played a major role in the leptin-inhibited brain infiltration of neutrophils. Leptin-mediated protection of BBB was further confirmed in vitro, through a BBB cellular model under the in vitro ischemic condition (G/R: glucose-oxygen-serum deprivation followed by GOS restoration). The results showed that leptin again could block the G/R-increased neutrophil adherence to EC layer as well as BBB permeability, likely by stimulating the endothelial expression of ZO-1 and VE-Cadherin. The study has demonstrated that leptin could protect ischemic brain via multiple ways (other than neuronal protection), by inhibiting the BBB permeability, brain infiltration of the blood-borne neutrophils and neutrophil adherence to vascular ECs. The role of leptin in vascular biology of stroke could further support its therapeutic potential in other neurodegenerative diseases, associated with BBB disorder.

Gynecol Minim Invasive Ther ; 9(2): 74-80, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32676284


Objectives: The objective of this study is to evaluate the efficacy of autocross-linked hyaluronic acid (HA) compared with intrauterine device (IUD) for preventing intrauterine adhesions (IUAs) in infertile patients after hysteroscopic adhesiolysis. Materials and Methods: A randomized clinical trial (ChiCTR-IOR-16007746). Upon completion of adhesiolysis, 3 ml of HA gel was placed into the uterine cavity in Group A; 3 ml of HA gel and an IUD were placed in Group B; and only an IUD was placed in Group C. A second hysteroscopic examination was performed in all patients at approximately 1 month postoperatively for the evaluation of IUA. The primary outcome measure was the effective rate of IUA prevention based on the American Fertility Society (AFS) scoring system. Results: Eighty-nine women were randomly distributed into two groups for intention to treat with 30 patients in Group A, 24 patients in Group B, and 35 patients in Group C. Patients were scored and stratified into three degrees and were enrolled using the simple random sampling method. The three groups were well balanced. There were no significant differences in age, endometrial thickness, the previous number of pregnancy, and the distribution of adhesion categories across mild, moderate, and severe between the three groups. The effective rate of IUA prevention, the AFS score after therapy, and the percentage improvements of Chinese score and AFS score before and after surgery were statistically significant difference between Groups A and C. The clinical pregnancy rate in Group A was higher than those in Groups B and C, but the difference was not statistically significant. Conclusion: HA gel has an advantage over an IUD in reducing IUA recurrence and decreasing adhesions.

Sleep Breath ; 24(4): 1767-1773, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32361960


PURPOSE: Obstructive sleep apnea (OSA) has been related to an increased risk of liver injury. Ferroptosis is a form of programmed cell death implicated in multiple physiological and pathological processes. This study aimed to explore the role of ferroptosis in chronic intermittent hypoxia (CIH)-induced liver injury as well as to uncover the underlying mechanisms using a CIH rat model. METHODS: Fourteen male Sprague-Dawley rats were randomly allocated to either the normal control (NC) (n = 7) or the CIH group (n = 7). Rats were exposed to intermittent hypoxia for 8 weeks in CIH group. Liver function, histological changes, and markers of oxidative stress were evaluated. The protein levels of hypoxia-inducible factor-1α, nuclear factor E2-related factor 2 (Nrf2), Acyl-CoA synthetase long-chain family member 4 (ACSL4), and glutathione peroxidase 4 (GPX4) in liver were examined by Western blot analysis. RESULTS: CIH treatment caused significant increase of serum alanine aminotransferase, aspartate aminotransferase, and malondialdehyde (MDA). Liver MDA was significantly higher in CIH group than that in NC group. Histology showed that CIH treatment induced discernible swelled, disordered hepatocytes, necrosis, and infiltrated inflammatory cells. CIH treatment significantly reduced the expression of GPX4, while markedly up-regulated expression of ACSL4, indicating elevation in hepatic ferroptosis. In addition, the protein expression of Nrf2 in CIH group was significantly lower than that in NC group. CONCLUSIONS: Ferroptosis played a crucial role in CIH-induced liver injury. The hepatic ferroptosis in CIH rat model might be mediated by the dysregulation of Nrf2. This highlights a potential therapeutic target for the treatment of OSA-related liver injury.

J Ethnopharmacol ; 254: 112713, 2020 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-32109545


ETHNOPHARMACOLOGICAL RELEVANCE: Zoujin pill (ZJP), a medication used to treat gastrointestinal disorders since the 15th Century in China, have been reported to exert anti-depressant effects in various models. STUDY AIM: To assess the effects of ZJP on gastrointestinal function and depressive behavior in rats under chronic unpredictable mild stress (CUMS), and to examine the underlying mechanisms related to brain-gut axis. METHODS: The rats suffered the stressor once daily for 5 weeks. ZJP (0.6 and 1.2 g/kg) and fluoxetine (15 mg/kg) as positive control were administered to the rats through gastric intubation once daily for 5 consecutive weeks. The anti-depression effects were compared by performing sucrose preference tests and open field tests. Gastrointestinal motility was investigated by determining the gastrointestinal transit rate and by electrogastrogram. The serum levels of the gastrointestinal hormone (GAS, MOT, VIP, SP), inflammatory cytokine (IL-1ß, IL-6; , TNFα) and glucagon-like peptide-1 (GLP-1) were assayed by enzyme-linked immunosorbent assay. For monoamine neurotransmitters (NE, 5-HT, DA), the levels were determined by high-performance liquid chromatography and electrochemical detection in conjunction, which was applied on the samples taken from the hypothalamus, hippocampus, and striatum. RESULTS: The depression-like symptoms among rats under CUMS were significantly relieved by ZJP administration (0.6 and 1.2 g/kg). Gastrointestinal motility was also improved by restoring gastric electrical rhythm and promoting gastrointestinal propulsion. The ZJP at 0.6 g/kg dosage obviously up-regulated 5-HT and DA levels in hippocampus. The ZJP at 1.2 g/kg dosage could increase 5-HT and DA levels in hypothalamus, striatum, and hippocampus, while down-regulated the NE level in hypothalamus and hippocampus. ZJP also reversed the alterations in serum gastrointestinal hormones. Furthermore, treatment with ZJP significantly reduced levels of IL-1ß, IL-6 and TNF-α and increased serum GLP-1 compared with the CUMS group. Fluoxetine also exerted similar anti-depressant effects in the absence of effects on gastrointestinal motility and the levels of serum hormone, inflammatory cytokine and GLP-1. CONCLUSION: ZJP imposed anti-depressant and gastrointestinal regulating functions in rats under CUMS, suggesting potential clinical application. .

Sleep Breath ; 24(2): 761-770, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31845084


PURPOSE: Obstructive sleep apnea (OSA) and OSA-associated chronic intermittent hypoxia (CIH) have been suggested to be associated with increased risk of liver disease. Little is known about the biological pathophysiology and underlying molecular mechanisms. Here we use whole-genome expression profiling to explore the transcriptomic changes induced by CIH in rat liver. METHODS: Rats (n = 3) were exposed to CIH for 8 weeks and were compared with rats exposed to normoxia (n = 3). Illumina HiSeq 4000 platform was used to examine differentially expressed genes (DEGs) in the liver between control group and CIH rat model. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate DEGs. Biological functions of DEGs were determined by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. RESULTS: Compared with control group, 318 genes were identified to be dysregulated in the liver of CIH rat model, with 211genes upregulated and 107 genes downregulated. Bioinformatics analysis showed that these genes were extensively related to various physiologic processes such as hepatic metabolism, apoptotic process, and oxidative stress. 10 genes with 5 upregulated and 5 downregulated were selected and further verified by qRT-PCR. CONCLUSIONS: CIH resulted in altered gene expression patterns in the liver of rat. The DEGs were related to various physiological and pathological processes in CIH rat liver. These data provide a better understanding of the mechanisms and underlying molecular changes of OSA-related liver disease.