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1.
Arch Gynecol Obstet ; 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33555431

RESUMO

OBJECTIVE: To observe the levels of leukemia inhibitory factor (LIF), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in blood, peritoneal fluid, ectopic endometrial tissue, and ectopic endometrial stromal cells of patients with endometriosis, and to compare expression of IL-6, LIF and VEGF expression between endometriotic and non-endometriotic patients underwent laparoscopic surgery. METHODS: Thirty-one patients who underwent laparoscopic surgery for endometriosis in our hospital from January 2018 to January 2020 were included in the observation group, and 32 patients who underwent laparoscopic surgery for uterine fibroids, ovarian serous cystadenoma, and ovarian teratomas, were included in the control group. The levels of LIF, IL-6 and VEGF in the blood and peritoneal fluid of the two groups of patients were detected. The levels of LIF, IL-6 and VEGF in ectopic endometrial tissue and self-paired eutopic endometrial tissue, ectopic endometrial stromal cells and self-paired eutopic endometrial stromal cells of patients in the observation group were detected. After treating the primary cultured ectopic endometrial stromal cells with LIF and IL-6 alone or in combination, the changes of VEGF mRNA of ectopic endometrial stromal cells and the VEGF levels in the supernatant were observed. RESULTS: The levels of LIF, IL-6 and VEGF in the blood and peritoneal fluid of the observation group were all higher than those of the control group (P < 0.05), and the levels of LIF, IL-6 and VEGF in the peritoneal fluid of the observation group were significantly higher than those in the blood (P < 0.05). In the observation group, the expression levels of LIF-mRNA and IL-6 mRNA in the ectopic endometrial tissue were higher than those in the self-paired eutopic endometrial tissues (P < 0.05), while the expression level of VEGF mRNA in the ectopic endometrial tissues was lower than that in the self-paired eutopic endometrial tissues (P < 0.05). Besides, the mRNA expression levels of LIF, IL-6 and VEGF in ectopic endometrial stromal cells of the observation group were all higher than those in the self-paired eutopic endometrial stromal cells (P < 0.05). After stimulating ectopic endometrial stromal cells with LIF, IL-6 and LIF + IL-6, respectively, the VEGF levels in the supernatant were all significantly higher than that in the blank control group (P < 0.05). CONCLUSION: The LIF, IL-6 and VEGF levels in blood and peritoneal fluid were increased in patients with endometriosis, and increased LIF and IL-6 in ectopic endometriosis stromal cells can play a synergistic role in increasing the VEGF levels, which may be involved in the occurrence and development of endometriosis.

2.
Aging (Albany NY) ; 13(2): 2294-2309, 2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-33318304

RESUMO

BACKGROUND: Recent studies have demonstrated a complex and dynamic neural crosstalk between the heart and brain. A heart-brain interaction has been described regarding cardiac ischemia, but the cerebral metabolic mechanisms involved are unknown. METHODS: Male Sprague Dawley rats were randomly allocated into 2 groups: those receiving myocardial ischemia-reperfusion surgery (IR group, n =10) and surgical controls (Con group, n=10). These patterns of metabolic abnormalities in different brain regions were assessed using proton magnetic resonance spectroscopy (PMRS). RESULTS: Results assessed by echocardiography showed resultant cardiac dysfunction following heart ischemia-reperfusion. Compared with the control group, the altered metabolites in the IR group were taurine and choline, and differences mainly occurred in the thalamus and brainstem. CONCLUSIONS: Alterations in cerebral taurine and choline are important findings offering new avenues to explore neuroprotective strategies for myocardial ischemia-reperfusion injury. These results provide preliminary evidence for understanding the cerebral metabolic process underlying myocardial ischemia-reperfusion injury in rats.

3.
Fetal Pediatr Pathol ; : 1-8, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33252287

RESUMO

Introduction: Genetically, complete hydatidiform mole (CHM) is androgenetic diploid, containing two sets of paternal chromosomes. In most cases, recurrent HM (RHM) is CHM but has diploid biparental chromosome constitution. Case report: We report a mother with RHM, both with biparental diploidy. The mother was compound heterozygous for two variants, c.1720dup, p.(C574Lfs*4) and c.2165A > G, p.(D722G) of the NLRP7 gene, as was a brother who fathered 2 normal pregnancies. Conclusion: The genotype study should be obtained for patients of CHM, even in their first pregnancy, followed by genetic screening for maternal-effect variants in those with biparental moles. This strategy will identify patients in their first pregnancy with HM that have a decreased chance for a normal pregnancy, to allow genetic counseling, perhaps utilizing a donor egg.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32677707

RESUMO

BACKGROUND AND AIM: Remimazolam tosilate (RT) is a new short-acting GABA(A) receptor agonist, having potential to be an effective option for procedural sedation. Here, we aimed to compare the efficacy and safety of RT with propofol in patients undergoing upper gastrointestinal endoscopy. METHODS: This positive-controlled, non-inferiority, phase III trial recruited patients at 17 centers, between September 2017 and November 2017. A total of 384 patients scheduled to undergo upper gastrointestinal endoscopy were randomly assigned to receive RT or propofol. Primary endpoint was the success rate of sedation. Adverse events (AEs) were recorded to evaluate safety. RESULTS: The success rate of sedation in the RT group was non-inferior to that in the propofol group (97.34% vs 100.00%; difference in rate -2.66%, 95% CI -4.96 to -0.36, meeting criteria for non-inferiority). Patients in the RT group had longer time to adequate sedation (P < 0.0001) but shorter time to fully alert (P < 0.0001) than that in the propofol group. The incidences of hypotension (13.04% vs 42.86%, P < 0.0001), treatment-related hypotension (0.54% vs 5.82%, P < 0.0001), and respiratory depression (1.09% vs 6.88%, P = 0.0064) were significantly lower in the RT group. AEs were reported in 74 (39.15%) patients in the RT group and 114 (60.32%) patients in the propofol group, with significant difference (P < 0.0001). CONCLUSION: This trial established non-inferior sedation success rate of RT compared with propofol. RT allows faster recovery from sedation compared with propofol. The safety profile is favorable and appears to be superior to propofol, indicating that it was feasible and well tolerated for patients.

5.
Rapid Commun Mass Spectrom ; 34(17): e8843, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32453886

RESUMO

RATIONALE: Gelsemium elegans (G. elegans) is highly toxic to humans and rats but has insecticidal and growth-promoting effects on pigs and goats. However, the mechanisms behind the toxicity differences of G. elegans are unclear. Gelsenicine, isolated from G. elegans, has been reported to be a toxic alkaloid. METHODS: In this study, the in vitro metabolism of gelsenicine was investigated and compared for the first time using human (HLM), pig (PLM), goat (GLM) and rat (RLM) liver microsomes and high-performance liquid chromatography/mass spectrometry (HPLC/MS). RESULTS: In total, eight metabolites (M1-M8) were identified by using high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (HPLC/QqTOF-MS). Two main metabolic pathways were found in the liver microsomes of the four species: demethylation at the methoxy group on the indole nitrogen (M1) and oxidation at different positions (M2-M8). M8 was identified only in the GLM. The degradation ratio of gelsenicine and the relative percentage of metabolites produced during metabolism were determined by high-performance liquid chromatography/tandem mass spectrometry (HPLC/QqQ-MS/MS). The degradation ratio of gelsenicine in liver microsomes decreased in the following order: PLM ≥ GLM > HLM > RLM. The production of M1 decreased in the order of GLM > PLM > RLM > HLM, the production of M2 was similar among the four species, and the production of M3 was higher in the HLM than in the liver microsomes of the other three species. CONCLUSIONS: Based on these results, demethylation was speculated to be the main gelsenicine detoxification pathway, providing vital information to better understand the metabolism and toxicity differences of G. elegans among different species.

6.
Toxicon ; 181: 28-35, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32335100

RESUMO

Gelsemium elegans Benth (G. elegans) is highly toxic to humans and rats, but has insecticides and growth promoting effects on pigs and goats. G. elegans is widely used in livestock, but its in vivo dynamics are entirely unknown. Hence, we investigated the toxicokinetic profiles of G. elegans alkaloids after a single oral dose of G. elegans to pigs (1.0 g/kg) and rats (0.1 g/kg). The results indicated that rats were more susceptible to the toxicity of G. elegans than pigs. The toxicokinetic parameters of 22 and 6 components were obtained in pigs and rats, respectively. The components included 9 and 5 gelsedine-type alkaloids in pigs and rats, respectively. The Tmax results of the 5 gelsedine-type alkaloids indicated that these alkaloids were rapidly absorbed in pigs and rats. The T1/2 values of the 5 gelsedine-type alkaloids indicated that the elimination rates of these alkaloids in pigs were slower than those in rats. In addition, the Cmax and AUC results indicated that the degrees of absorption and exposure of most alkaloids in pigs were higher than those in rats except GS-2. However, the Cmax value of GS-2 (11-methoxy-14-hydroxygelsenicine) in rats was greater than that of pigs, and the Cmax value of 14-hydroxygelsenicine in pigs was merely greater than 3 times that of rats. The present results suggested that the cause of the toxicological differences species of G. elegans might be related to the degrees of absorption and exposure of gelsedine-type alkaloids, especially for the 14-hydroxygelsenicine and GS-2 in different animals.


Assuntos
Gelsemium , Extratos Vegetais/toxicidade , Animais , Humanos , Extratos Vegetais/administração & dosagem , Ratos , Suínos , Toxicocinética
7.
J Anal Toxicol ; 44(4): 378-390, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-31993639

RESUMO

Gelsemium elegans (G. elegans) has been used in traditional Chinese medicine. This plant is highly toxic to humans, but can promote the growth of pigs and goats in the veterinary clinic. It is a very complex mixture containing tens or hundreds of different components. Therefore, multiple-component pharmacokinetic studies of G. elegans are a major challenge due to the lack of authentic standards of the components. The purpose of this study was to investigate the plasma pharmacokinetics of multiple components after a single oral dose of G. elegans in goat using a sensitive ultra-performance liquid chromatography coupled to tandem mass spectrometry method for the simultaneous semiquantification of multiple alkaloids without standards. The method was validated in terms of the specificity, LOD, LOQ, linearity, accuracy, precision and matrix effects. To validate the global pharmacokinetic characteristics, the results obtained from the semiquantitative analysis of three authentic compounds (gelsemine, koumine and humantenmine) were compared with the absolute quantification from our recently published method. The results showed that the two methods had similar analytical results, and the obtained values of Tmax, T1/2 and MRT0-t of the three alkaloids were similar between the two methods. In addition, the values of Cmax and AUC0-t of the three alkaloids after normalization were close to the real values, which indicated that this semiquantitative method could be used in the pharmacokinetic study of multiplecomponents. Then the pharmacokinetic parameters of 23 other G. elegans alkaloids in goats were obtained. The results suggested that the gelsedine-type alkaloids were the major active ingredients that predict and explain the efficacy and toxicity of G. elegans.


Assuntos
Gelsemium , Cabras/metabolismo , Extratos Vegetais/farmacocinética , Alcaloides/farmacocinética , Animais , Cromatografia Líquida , Humanos , Alcaloides Indólicos/farmacocinética , Suínos , Espectrometria de Massas em Tandem
8.
J Ethnopharmacol ; 252: 112617, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31988014

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Herbal medicine contains hundreds of natural products, and studying their absorption, metabolism, distribution, and elimination presents great challenges. Gelsemium elegans (G. elegans) is a flowering plants in the Loganiaceae family. The plant is known to be toxic and has been used for many years as a traditional Chinese herbal medicine for the treatment of rheumatoid arthritis, neuropathic pain, spasticity, skin ulcers and cancer. It was also used as veterinary drugs for deworming, promoting animal growth, and pesticides. At present, studies on the metabolism of G. elegans have primarily focused on only a few single available reference ingredients, such as koumine, gelsemine and gelsedine. MATERIAL AND METHODS: The goal of this work is to elucidate the overall metabolism of whole G. elegans powder in goats using high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC/QqTOF-MS). RESULTS: Analyses of plasma, urine and fecal samples identified or tentatively characterized a total of 44 absorbed natural products and 27 related produced metabolites. Gelsedine-type, sarpagine-type and gelsemine-type alkaloids were the compounds with the highest metabolite formation. In the present study, most natural products identified in G. elegans were metabolized through glucuronidation and oxidation. Hydrogenation, dehydrogenation and demethylation also occurred. CONCLUSION: To our knowledge, this is the first report of the metabolite profiling of the G. elegans crude extract in goats, which is of great significance for a safer and more rational application of this herbal medicine.


Assuntos
Gelsemium , Extratos Vegetais/farmacocinética , Animais , Cromatografia Líquida de Alta Pressão , Fezes/química , Cabras , Absorção Intestinal , Masculino , Espectrometria de Massas , Medicina Tradicional Chinesa , Extratos Vegetais/sangue , Extratos Vegetais/urina
10.
Sci Rep ; 9(1): 15756, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31673142

RESUMO

Gelsemium elegans is a flowering plant in the Loganiaceae. Because it can promote the growth of pigs and sheep, it is widely used, including in veterinary clinics, but little information is available about its biological effects. Here, we used high-throughput sequencing to characterize the differentially expressed genes (DEGs) in the ileums of pigs between a control group and a group fed Gelsemium elegans for 45 days. We found that Gelsemium elegans affected many inflammatory and immune pathways, including biological processes such as defense responses, inflammation and immune responses. Moreover, this study identified several important genes related to the anti-inflammatory activity of Gelsemium elegans (e.g., CXCL-8, IL1A, and CSF2), which will be beneficial for further study of the pharmacological mechanisms and clinical applications of Gelsemium elegans.


Assuntos
Ração Animal , Anti-Inflamatórios/farmacologia , Citocinas/imunologia , Gelsemium , Regulação da Expressão Gênica/imunologia , Íleo/imunologia , Transcriptoma/imunologia , Animais , Suínos
11.
Taiwan J Obstet Gynecol ; 58(6): 798-800, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31759530

RESUMO

OBJECTIVE: The aim of this study was to evaluate the usefulness of ultrasound in pregnancies with a positive non-invasive prenatal testing (NIPT) result for trisomy 18/13. MATERIALS AND METHODS: During a four-year period, the pregnant women who were referred for invasive genetic testing because of positive NIPT results for trisomy 18/13 were included in this study. An in-depth ultrasound was done for these patients before invasive procedures. The data of fetal ultrasound and cytogenetic results were collected. RESULTS: There were 81 patients with a positive NIPT result for trisomy 18/13, including 39 (30 positive for trisomy 18; 9 positive for trisomy 13) within 12-14 weeks of gestation, and 42 (31 positive for trisomy 18; 11 positive for trisomy 13) within 15-22 weeks. The PPV of NIPT was 60.7% for trisomy 18, and 30% for trisomy 13, respectively. When adding ultrasound to NIPT, the new PPV for trisomy 18 was 100%, and the negative predictive value (NPV) was 92.3%, with a NPV of 85.7% in the first trimester and a NPV of 100% in the second trimester, respectively. The new PPV and NPV for trisomy 13 were 100% and 100%, respectively. CONCLUSION: By adding ultrasound to the NIPT, we achieved much higher PPVs and NPVs for trisomy 18/13. A normal scan can help to alleviate stress in parents caused by false positive NIPT results.


Assuntos
Síndrome da Trissomia do Cromossomo 13/diagnóstico , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Ultrassonografia Pré-Natal/métodos , Adulto , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 18/genética , DNA/análise , Feminino , Seguimentos , Testes Genéticos/métodos , Idade Gestacional , Humanos , Recém-Nascido , Cariotipagem , Gravidez , Resultado da Gravidez , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Tempo
12.
Zhongguo Gu Shang ; 32(9): 785-791, 2019 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-31615171

RESUMO

OBJECTIVE: To assess the clinical efficacy of Tri-Lock bio-short prosthesis in artificial total hip arthroplasty(THA) in young patients with Dorr type C femoral medullary cavity. METHODS: From January 2010 to January 2014, 35 young patients(37 hips) with in the chimney-like femoral medullary cavity received Tri-Lock BPS prosthesis of THA, including 18 males(20 hips) and 17 females with an average age of (32.2±3.0) years old ranging from 21.2 to 38.5 years old. There were 16 cases of rheumatoid hip arthritis (17 hips), 8 cases of rheumatoid arthritis (9 hips), and 11 cases of aseptic necrosis of femoral head (11 hips). All cases were complicated with different degrees of osteoporosis. According to Singh index, 26 cases were classified as Grade III and 9 cases as Grade II. Biological prostheses were used for the acetabulum, with ceramic lining and full ceramic femoral head. The proximal femoral medullary cavity was Dorr type C on anteroposterior X-ray. After replacement, X-ray examination was performed to locate the prosthesis stem. Engh and Harris criteria were used to evaluate the stability of bone-prosthesis interface and hip function, respectively. Changes of hip movement pre-operation and at last follow-up were compared. RESULTS: All patients were followed up for 18 to 45 months(means 33.8 months). Harris hip scores in 35 cases (37 hips) increased significantly from preoperative 61.8±3.0 (51.2 to 73.5) to 93.3±6.5 (92.5 to 98.8) points at last follow-up (t=54.745, P<0.01). The hip mobility increased from (46.5±8.0)°(0° to 55°) before surgery to(101.2±10.5)°(85° to 130°) at the last follow-up, the difference was statistically significant(t=133.091, P<0.01). Immediately after surgery, the prostheses were tightly packed with the medullary cavity. At the final follow-up, 17 hips had significant femur cortical bone thickening;12 hips had varying degrees of stress occlusal bone resorption at proximal femoral, including 9 degree I(low femur density, round and blunt) and 3 degree II(involving small rotor) hips. Meanwhile, 15 hips had significant femur cortical bone thickening without thigh pain. CONCLUSIONS: The cone-shaped short Tri-lock biological short-stem can fill Dorr C chimney-like medullary cavity and effectively retain good proximal femoral bone mass. Titanium microporous coating on the surface can effectively increase the friction of the prosthesis. The short-stem end in the medullary cavity can effectively avoid the occurrence of coxa varus.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Acetábulo , Adulto , Feminino , Fêmur , Cabeça do Fêmur , Seguimentos , Humanos , Masculino , Resultado do Tratamento , Adulto Jovem
13.
Int J Mol Med ; 44(5): 1877-1887, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31545482

RESUMO

There is now substantial evidence that myocardial ischemia­reperfusion (IR) injury affects the spinal cord and brain, and that interactions may exist between these two systems. In the present study, the spinal cord proteomes were systematically analyzed after myocardial IR injury, in an attempt to identify the proteins involved in the processes. The myocardial IR injury rat model was first established by cross clamping the left anterior descending coronary artery for 30­min ischemia, followed by reperfusion for 2 h, which resulted in a significant histopathological and functional myocardial injury. Then using the stable isotope dimethyl labeling quantitative proteomics strategy, a total of 2,362 shared proteins with a good distribution and correlation were successfully quantified. Among these proteins, 33 were identified which were upregulated and 57 were downregulated in the spinal cord after myocardial IR injury, which were involved in various biological processes, molecular function and cellular components. Based on these proteins, the spinal cord protein interaction network regulated by IR injury, including apoptosis, microtubule dynamics, stress­activated signaling and cellular metabolism was established. These heart­spinal cord interactions help explain the apparent randomness of cardiac events and provide new insights into future novel therapies to prevent myocardial I/R injury.


Assuntos
Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/metabolismo , Proteoma/metabolismo , Traumatismo por Reperfusão/metabolismo , Medula Espinal/metabolismo , Animais , Apoptose/fisiologia , Regulação para Baixo/fisiologia , Coração/fisiopatologia , Masculino , Proteômica/métodos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia , Regulação para Cima/fisiologia
14.
J Pharm Biomed Anal ; 176: 112833, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31473492

RESUMO

The multicomponent pharmacokinetic study of herbal medicine is a great challenge due to the low plasma concentrations, large range of concentration scales, lack of authentic standards and uncertain interactions of the components. The aim of this work was to explore the in vivo pharmacokinetics of herbal medicine independently of authentic standards using an integrated analytical strategy. First, ion pairs of multiple components were tuned and selected, and then major parameters were optimized for derivative multiple reaction monitoring (DeMRM) by LC-MS/MS, which was combined with characterization of the chemical profiles of the herbal medicine by LC-QqTOF/MS. Second, different concentrations of herbal extracts were employed instead of authentic standards to construct calibration curves for the semiquantitative determination of multiple components in plasma. Taking Gelsemium elegans as an example, in addition to the fully validated and sufficient methodological results, a total of 27 alkaloid components, major bioactive constituents of Gelsemium elegans, were simultaneously monitored in pig plasma. The concentration-time profiles and pharmacokinetic properties of these 27 components were characterized. The absolute quantification of three components was compared with the results obtained using authentic standards, and the method showed very similar analytical characteristics, such as linearity, precision, accuracy, and the values of the pharmacokinetic parameters Tmax, Vd, Cl and MRT. This analytical strategy was found to be capable of assessing herbal pharmacokinetics independently of specific authentic compounds for each component. This study was the first attempt to systematically reveal the in vivo pharmacokinetics of Gelsemium elegans. This strategy and methodology will find widespread use in the quantitative pharmacokinetic analysis of multiple components independently of standards for herbal medicine, among other applications.


Assuntos
Alcaloides/análise , Medicamentos de Ervas Chinesas/farmacocinética , Gelsemium/química , Administração Oral , Alcaloides/farmacocinética , Animais , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Estudos de Viabilidade , Sus scrofa , Espectrometria de Massas em Tandem/métodos
16.
Biomed Environ Sci ; 32(7): 496-507, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31331434

RESUMO

OBJECTIVE: To explore the dynamic impacts of simulated microgravity (SM) on different vital brain regions of rats. METHODS: Microgravity was simulated for 7 and 21 days, respectively, using the tail-suspension rat model. Histomorphology, oxidative stress, inflammatory cytokines and the expression of some key proteins were determined in hippocampus, cerebral cortex and striatum. RESULTS: 21-day SM decreased brain derived neurotrophic factor and induced neuron atrophy in the cerebral cortex. Strong oxidative stress was triggered at day 7 and the oxidative status returned to physiological level at day 21. Inflammatory cytokines were gradually suppressed and in striatum, the suppression was regulated partially through c-Jun/c-Fos. CONCLUSION: The results revealed that the significant impacts of SM on rat brain tissue depended on durations and regions, which might help to understand the health risk and to prevent brain damage for astronauts in space travel.


Assuntos
Encéfalo/metabolismo , Citocinas/metabolismo , Simulação de Ausência de Peso , Animais , Encéfalo/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Masculino , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Distribuição Aleatória , Ratos
17.
Am J Transl Res ; 11(5): 3101-3108, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31217879

RESUMO

OBJECTIVES: The mechanism behind spinal metabolites and myocardial ischemia-reperfusion (IR) injury is not well understood. Proton magnetic resonance spectroscopic analysis of spinal cord extracts provides a quick evaluation of the specific metabolic activity in rats with myocardial IR injury. We investigated the relationship between the IR-related variables and the changes in spinal metabolites. METHODS: Proton magnetic resonance spectroscopy (1H-MRS) was used to assess the spinal metabolites of adult rats with and without myocardial IR injury (n = 6 per group). Myocardial IR injury was reproduced using intermittent occlusion of the left anterior descending coronary artery. We studied the relationship between the metabolite ratio measurement and IR-related variables. All rats underwent 1H-MRS, with the ratio of interest placed in different spinal cord segments to measure levels of twelve metabolites including N-acetylaspartate (NAA), taurine (Tau), glutamate (Glu), gamma amino acid butyric acid (GABA), creatine (Cr), and myoinositol (MI), etc. Results: Rats with myocardial IR injury had higher concentration of Tau in the upper thoracic spinal cord (P < 0.05), and lower concentration of Gly and Glu in the cervical segment of the spinal cord (P < 0.05), when compared to the Control group. The ratios of glutamate/taurine (Glu/Tau), Glu/(GABA + Tau) and Glu/Total were significantly different between the IR group and the Control group in the upper thoracic spinal cord (P < 0.05). So were the ratios of Glu/(GABA + Tau) in the cervical segment (P < 0.05), and Glu/Tau and Glu/(GABA + Tau) in the lower thoracic spinal cord (P < 0.05). CONCLUSIONS: These findings suggest that myocardial IR injury may be related to spinal biochemical alterations. It is speculated that these observed changes in the levels of spinal metabolites may be involved in the pathogenesis and regulation of myocardial IR injury.

18.
Int J Mol Med ; 43(6): 2361-2375, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30942426

RESUMO

The identification of the expression patterns of long non­coding RNAs (lncRNAs) and mRNAs in the spinal cord under normal and cardiac ischemia/reperfusion (I/R) conditions is essential for understanding the genetic mechanisms underlying the pathogenesis of cardiac I/R injury. The present study used high­throughput RNA sequencing to investigate differential gene and lncRNA expression patterns in the spinal cords of rats during I/R­induced cardiac injury. Male Sprague Dawley rats were assigned to the following groups: i) Control; ii) 2 h (2 h post­reperfusion); and iii)v0.5 h (0.5 h post­reperfusion). Further mRNA/lncRNA microarray analysis revealed that the expression profiles of lncRNA and mRNA in the spinal cords differed markedly between the control and 2 h groups, and in total 7,980 differentially expressed (>2­fold) lncRNAs (234 upregulated, 7,746 downregulated) and 3,428 mRNAs (767 upregulated, 2,661 downregulated) were identified. Reverse transcription­quantitative polymerase chain reaction analysis was performed to determine the expression patterns of several lncRNAs. The results indicated that the expression levels of lncRNA NONRATT025386 were significantly upregulated in the 2 and 0.5 h groups when compared with those in the control group, whereas the expression levels of NONRATT016113, NONRATT018298 and NONRATT018300 were elevated in the 2 h group compared with those in the control group; however, there was no statistically significant difference between the 0.5 h and control groups. Furthermore, the expression of lncRNA NONRATT002188 was significantly downregulated in the 0.5 and 2 h groups when compared with the control group. The present study determined the expression pattern of lncRNAs and mRNAs in rat spinal cords during cardiac I/R. It was suggested that lncRNAs and mRNAs from spinal cords may be novel therapeutic targets for the treatment of I/R­induced cardiac injury.


Assuntos
Perfilação da Expressão Gênica , Traumatismo por Reperfusão Miocárdica/genética , RNA Longo não Codificante/genética , Medula Espinal/metabolismo , Animais , Regulação para Baixo , Masculino , Traumatismo por Reperfusão Miocárdica/patologia , Ratos Sprague-Dawley , Medula Espinal/patologia , Regulação para Cima
19.
Pest Manag Sci ; 75(5): 1258-1269, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30324758

RESUMO

BACKGROUND: Diapause is the arrest of the development of insects and can be used for the development of effective agricultural pest management strategies. Heat shock protein 70 (Hsp70) is reported to be up-regulated during diapause to maintain survival in some insect species. However, its regulatory mechanism is unknown. RESULTS: Expression of hsp70 in Helicoverpa armigera was found to be up-regulated in diapause pupal brains. To elucidate the molecular regulatory mechanisms of hsp70, we focused our attention on its transcription factor, heat shock factor 1 (HSF1). Four alternative splicing variants of HSF1 from pupal brains of H. armigera were identified, and subcellular localization analysis indicated that these variants were exclusively expressed in the nucleus. Real-time PCR analysis showed that all of these variants were up-regulated in diapause pupal brains, and their expression patterns were consistent with that of hsp70. Finally, promoter activity assay and Western blotting detection demonstrated that hsp70 was activated and up-regulated by these variants. CONCLUSION: Expression of hsp70 in H. armigera during diapause is regulated by multiple alternatively spliced isoforms of HSF1. The results of this study may provide important information for understanding the regulatory mechanisms of hsps during insect diapause. © 2018 Society of Chemical Industry.


Assuntos
Processamento Alternativo , Encéfalo/crescimento & desenvolvimento , Diapausa/genética , Proteínas de Insetos/genética , Lepidópteros/crescimento & desenvolvimento , Lepidópteros/genética , Pupa/crescimento & desenvolvimento , Sequência de Aminoácidos , Animais , Encéfalo/metabolismo , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Espaço Intracelular/metabolismo , Lepidópteros/citologia , Regiões Promotoras Genéticas/genética , Transporte Proteico , Pupa/genética , Alinhamento de Sequência
20.
Int J Mol Med ; 42(5): 2469-2480, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30226564

RESUMO

Endometrial cancer is a life­threatening malignancy that affects women all over the world, and it has an increasing incidence. MicroRNAs (miRNAs/miRs) have been reported to be involved in cellular activities in endometrial cancer. The present study aimed to examine the effects of miR­183­5p on the epithelial­mesenchymal transition (EMT), proliferation, invasion, migration and apoptosis of human endometrial cancer cells by targeting Ezrin. Primary endometrial cancer tissues and adjacent normal tissues were obtained for the investigation. The protein expression of Ezrin in tissues was detected by immunohistochemistry. The expression level of miR­183­5p and the mRNA and protein expression levels of Ezrin and EMT­associated genes were determined by reverse transcription­quantitative polymerase chain reaction and western blot analyses. Endometrial cancer cells were treated with miR­183­5p inhibitors, small interfering RNA targeting Ezrin or miR­183­5p inhibitors. Cell proliferation, cell cycle, apoptosis, migration and invasion were then evaluated using an MTT assay, flow cytometry, scratch test and Transwell assay, respectively. Compared with normal adjacent tissues, the expression of miR­183­5p was decreased in endometrial cancer tissues, and the expression of Ezrin was significantly increased in endometrial cancer tissues. The protein expression of Ezrin was correlated with the severity and poor prognosis of endometrial cancer. Notably, the target prediction program and the luciferase reporter gene assay confirmed that miR­183­5p targeted and negatively regulated the expression of Ezrin. In vivo experiments revealed that the increased expression of miR­183­5p and decreased expression of Ezrin inhibited EMT, cell proliferation, migration and invasion, but promoted cell apoptosis in Ishikawa cells. These results suggested that the upregulated expression of miR­183­5p promoted apoptosis and suppressed the EMT, proliferation, invasion and migration of human endometrial cancer cells by downregulating Ezrin.


Assuntos
Proteínas do Citoesqueleto/genética , Neoplasias do Endométrio/genética , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Adulto , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação para Baixo , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Regulação para Cima
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