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Oxidative stress triggered by aging, radiation, or inflammation impairs ovarian function by inducing granulosa cell (GC) apoptosis. However, the mechanism inducing GC apoptosis has not been characterized. Here, we found that ovarian GCs from aging patients showed increased oxidative stress, enhanced reactive oxygen species activity, and significantly decreased expression of the known antiapoptotic factor sphingosine-1-phosphate/sphingosine kinase 1 (SPHK1) in GCs. Interestingly, the expression of Krüppel-like factor 12 (KLF12) was significantly increased in the ovarian GCs of aging patients. Furthermore, we determined that KLF12 was significantly upregulated in hydrogen peroxide-treated GCs and a 3-nitropropionic acid-induced in vivo model of ovarian oxidative stress. This phenotype was further confirmed to result from inhibition of SPHK1 by KLF12. Interestingly, when endogenous KLF12 was knocked down, it rescued oxidative stress-induced apoptosis. Meanwhile, supplementation with SPHK1 partially reversed oxidative stress-induced apoptosis. However, this function was lost in SPHK1 with deletion of the binding region to the KLF12 promoter. SPHK1 reversed apoptosis caused by hydrogen peroxide-KLF12 overexpression, a result further confirmed in an in vitro ovarian culture model and an in vivo 3-nitropropionic acid-induced ovarian oxidative stress model. Overall, our study reveals that KLF12 is involved in regulating apoptosis induced by oxidative stress in aging ovarian GCs and that sphingosine-1-phosphate/SPHK1 can rescue GC apoptosis by interacting with KLF12 in negative feedback.
Assuntos
Envelhecimento , Apoptose , Células da Granulosa , Peróxido de Hidrogênio , Fatores de Transcrição Kruppel-Like , Lisofosfolipídeos , Fosfotransferases (Aceptor do Grupo Álcool) , Esfingosina , Feminino , Humanos , Envelhecimento/metabolismo , Retroalimentação Fisiológica , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Peróxido de Hidrogênio/farmacologia , Técnicas In Vitro , Fatores de Transcrição Kruppel-Like/antagonistas & inibidores , Fatores de Transcrição Kruppel-Like/biossíntese , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Lisofosfolipídeos/biossíntese , Lisofosfolipídeos/metabolismo , Técnicas de Cultura de Órgãos , Estresse Oxidativo/efeitos dos fármacos , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Regiões Promotoras Genéticas , Esfingosina/biossíntese , Esfingosina/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Atherosclerosis is a major cause of death and disability in cardiovascular disease. Atherosclerosis associated with lipid accumulation and chronic inflammation leads to plaques formation in arterial walls and luminal stenosis in carotid arteries. Current approaches such as surgery or treatment with statins encounter big challenges in curing atherosclerosis plaque. The infiltration of proinflammatory M1 macrophages plays an essential role in the occurrence and development of atherosclerosis plaque. A recent study shows that TRIM24, an E3 ubiquitin ligase of a Trim family protein, acts as a valve to inhibit the polarization of anti-inflammatory M2 macrophages, and elimination of TRIM24 opens an avenue to achieve the M2 polarization. Proteolysis-targeting chimera (PROTAC) technology has emerged as a novel tool for the selective degradation of targeting proteins. But the low bioavailability and cell specificity of PROTAC reagents hinder their applications in treating atherosclerosis plaque. In this study we constructed a type of bioinspired PROTAC by coating the PROTAC degrader (dTRIM24)-loaded PLGA nanoparticles with M2 macrophage membrane (MELT) for atherosclerosis treatment. MELT was characterized by morphology, size, and stability. MELT displayed enhanced specificity to M1 macrophages as well as acidic-responsive release of dTRIM24. After intravenous administration, MELT showed significantly improved accumulation in atherosclerotic plaque of high fat and high cholesterol diet-fed atherosclerotic (ApoE-/-) mice through binding to M1 macrophages and inducing effective and precise TRIM24 degradation, thus resulting in the polarization of M2 macrophages, which led to great reduction of plaque formation. These results suggest that MELT can be considered a potential therapeutic agent for targeting atherosclerotic plaque and alleviating atherosclerosis progression, providing an effective strategy for targeted atherosclerosis therapy.
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Aterosclerose , Placa Aterosclerótica , Quimera de Direcionamento de Proteólise , Animais , Camundongos , Anti-Inflamatórios/uso terapêutico , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Inflamação/tratamento farmacológico , Macrófagos , Camundongos Endogâmicos C57BL , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/metabolismo , Quimera de Direcionamento de Proteólise/farmacologia , Quimera de Direcionamento de Proteólise/uso terapêutico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia , Nanopartículas/uso terapêuticoRESUMO
A novel Gram-stain-negative, aerobic strain, designated Y22T, was isolated from peanut field soil in Laoshan Mountain in China. Cells of strain Y22T were rod-shaped and motile by a single flagellum. The strain was found to be oxidase- and catalase-positive. 16S rRNA gene sequence based on phylogenetic analysis indicated that strain Y22T belonged to the genus Pseudomonas, and showed the highest 16S rRNA gene sequence similarity of 99.0% to Pseudomonas pelagia JCM 15562T, followed by Pseudomonas salina JCM 19469T (98.4%), Pseudomonas sabulinigri JCM 14963T (97.9%), Pseudomonas bauzanensis CGMCC 1.9095T (97.6%) and Pseudomonas litoralis KCTC23093T (97.5%). The phylogenetic analysis based on multilocus sequence analyses with concatenated 16S rRNA, gyrB, rpoD and rpoB genes indicated that strain Y22T belonged to Pseudomonas pertucinogena lineage. The average nucleotide identity scores between strain Y22T and closely related species were 74.6-82.8%, and the Genome-to-Genome Distance Calculator scores were 16.4-44.9%. The predominant cellular fatty acids of strain Y22T were C18:1ω7c (29.6%), C17:0 cyclo (17.5%) and summed feature 3 (C16:1ω7c and/or C16:1ω6c) (17.4%). The genomic DNA G+C content was 57.9 mol%. On the basis of phenotypic characteristics, phylogenetic analyses and in silico DNA-DNA relatedness, a novel species, Pseudomonas laoshanensis sp. nov. is proposed. The type strain is Y22T (= JCM 32580T = KCTC 62385T = CGMCC 1.16552T).
Assuntos
Filogenia , Pseudomonas/classificação , Microbiologia do Solo , Arachis , China , Genes Bacterianos/genética , Pseudomonas/genética , RNA Ribossômico 16S/genética , Especificidade da EspécieRESUMO
BACKGROUND: The blood saving efficacy of TXA in cardiac surgery has been proved in several studies, but TXA dosing regimens were varied in those studies. Therefore, we performed this study to investigate if there is a dose dependent in-vivo effect of TXA on fibrinolysis parameters by measurement of fibrinolysis markers in adults undergoing cardiac surgery with CPB. METHODS: A double-blind, randomized, controlled prospective trial was conducted from February 11, 2017 to May 05, 2017. Thirty patients undergoing cardiac valve surgery were identified and randomly divided into a placebo group, low-dose group and high-dose group by 1: 1: 1. Fibrinolysis parameters were measured by plasma levels of D-Dimers, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), plasmin-antiplasmin complex (PAP), tissue plasminogen activator (tPA) and thrombomodulin (TM). Those proteins were measured at five different sample times: preoperatively before the TXA injection (T1), 5 min after the TXA bolus (T2), 5 min after the initiation of CPB (T3), 5 min before the end of CPB (T4) and 5 min after the protamine administration (T5). A Thrombelastography (TEG) and standard coagulation test were also performed. RESULTS: Compared with the control group, the level of the D-Dimers decreased in the low-dose and high-dose groups when the patients arrived at the ICU and on the first postoperative morning. Over time, the concentrations of PAI-1, TAFI, and TM, but not PAP and tPA, showed significant differences between the three groups (P < 0.05). Compared with the placebo group, the plasma concentrations of PAI-1 and TAFI decreased significantly at the T3 and T4 (P < 0.05); TAFI concentrations also decreased at the T5 in low-dose group (P < 0.05). Compared with the low-dose group, the concentration of TM increased significantly at the T4 in high-dose group. CONCLUSIONS: The in-vivo effect of low dose TXA is equivalent to high dose TXA on fibrinolysis parameters in adults with a low bleeding risk undergoing valvular cardiac surgery with cardiopulmonary bypass, and a low dose TXA regimen might be equivalent to high dose TXA for those patients. TRIAL REGISTRATION: ChiCTR-IPR-17010303 , Principal investigator: Zhen-feng ZHOU, Date of registration: January 1, 2017.
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Antifibrinolíticos/farmacologia , Procedimentos Cirúrgicos Cardíacos/métodos , Ponte Cardiopulmonar/métodos , Fibrinólise/efeitos dos fármacos , Ácido Tranexâmico/farmacologia , Adulto , Antifibrinolíticos/administração & dosagem , Método Duplo-Cego , Valvas Cardíacas/cirurgia , Humanos , Projetos Piloto , Estudos Prospectivos , Ácido Tranexâmico/administração & dosagem , Resultado do TratamentoRESUMO
OBJECTIVES: To investigate the effects of etibatide combined with emergency percutaneous coronary intervention (PCI) on blood perfusion and cardiac function in acute myocardial infarction (AMI) patients. METHODS: This was a prospective, randomized, controlled study. From November 2015 to June 2019, 196 patients with ST-segment elevation myocardial infarction (STEMI) undergoing emergency PCI admitted to Baoding First Central Hospital were enrolled. The 196 STEMI patients were randomly divided into experimental group and control group. In the experimental group, STEMI patients were treated with emergency PCI + etibatide; while in the control group, only PCI was performed. Observation indexes included: general data, myocardial perfusion and cardiac function indexes and major adverse cardiac events (MACE). RESULTS: There was no significant difference in general data between the two groups (P > 0.05). The rate of ST-segment resolution (STR) in the experimental group was better than that in the control group (P < 0.05). In myocardial contrast echocardiography (MCE), higher peak intensity (PI) and shorter time-to-peak (TP) were observed in the experimental group compared with the control group (P < 0.05). The platelet aggregation rate was compared between the two group at the time points of before PCI, after PCI and two hour after drug withdrawal, and there was no significant change in the platelet aggregation rate of the control group between different time points (before PCI, after PCI and two hour after drug withdrawal); while the platelet aggregation rate of the experimental group was significantly lower after PCI and two hour after drug withdrawal than that before PCI (P < 0.05), and an obviously decreased platelet aggregation rate was found in the experimental group(P < 0.05). After three months of follow-up, there was one case of MACE in the experimental group and 1 case of MACE in the control group, without any difference in the incidence of MACE between the two groups (P > 0.05). CONCLUSION: Etibatide combined with emergency PCI could improve myocardial reperfusion and cardiac function in patients with acute STEMI without increasing the incidence of MACE.
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A Gram-stain-negative, aerobic, mobile, and rod-shaped bacterium, designated JJ3T, was isolated from peanut rhizospheric soil in Qingdao, Shandong Province, China, and was characterized using a polyphasic approach. Strain JJ3T grew at 4-40 °C, at pH 5.0-9.0 and 0-4% NaCl. The strain was positive for both catalase and oxidase tests, and was able to degrade aflatoxin B1. According to the 16S rRNA gene sequence comparisons, the strain JJ3T was identified as a member of the genus Pseudomonas and was most closely related to Pseudomonas japonica JCM 21532T and Pseudomonas alkylphenolica JCM 16553T with sequence similarity of 99.0% and 98.9%, respectively. A multilocus sequence analysis (MLSA) of concatenating 16S rRNA, gyrB and rpoD gene sequences showed that strain JJ3T belonged to the Pseudomonas putida subcluster. Genomic comparison of strain JJ3T with its closest phylogenetic type strain using average nucleotide index (ANI) and digital DNA-DNA relatedness revealed 76.7-82.9% and 20.2-37.1%, respectively. All values were distinctly lower than the thresholds established for species differentiation. The predominant cellular fatty acids of strain JJ3T were C17:0 cyclo (24.0%), C16:0 (21.4%), summed features 3 (C16:1ω7c and/or C16:1ω6c) (11.5%) and summed features 8 (C18:1ω7c and/or C18:1ω6c) (10.5%). The major polar lipids of strain JJ3T were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The physiological, biochemical, and genetic characteristics support the assignment of JJ3T to the genus Pseudomonas, but are different to those of phylogenetically neighboring species to represent a novel species. The name Pseudomonas qingdaonensis sp. nov. is proposed, with JJ3T (= JCM 32579T = KCTC 62384T = CGMCC 1.16493T) as the type strain.
Assuntos
Aflatoxina B1/metabolismo , Arachis/microbiologia , Pseudomonas/classificação , Pseudomonas/metabolismo , Técnicas de Tipagem Bacteriana , Composição de Bases/genética , Catalase/análise , China , DNA Bacteriano/genética , Ácidos Graxos/análise , Genes Bacterianos , Tipagem de Sequências Multilocus , Hibridização de Ácido Nucleico , Oxirredutases/análise , Fosfolipídeos/análise , Filogenia , Pseudomonas/genética , Pseudomonas/isolamento & purificação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Solo , Microbiologia do SoloRESUMO
BACKGROUND: Unsatisfactory analgesia would occur frequently during repeated cesarean section under epidural anesthesia. The aim of this study is to observe the effects of intravenous remifentanil on maternal comfort, maternal and neonatal safety during repeated cesarean section under epidural anesthesia. METHODS: A total of 80 parturients undergoing repeated cesarean section were involved in the study. The patients were randomly divided into the intravenous remifentanil- assisted epidural group (group R) and epidural group (group E), respectively (n = 40). In group R, the remifentanil was continuously intravenously infused as an adjuvant to epidural anesthesia. In group E, 0.75% ropivacaine epidural or intravenous ketamine was administered as needed. Parturient baseline characteristics, vital signs, VAS scores, and comfort scores during surgery were recorded. Adverse effects were also recorded. RESULTS: A total of 80 patients were enrolled in the current study and the final analyses included 39 patients in group R and 38 patients in group E. No differences in patients' baseline characteristics were found between the two groups (p > 0.05). Compared with group E, the comfort score was significantly higher in group R (9.1 ± 1.0 vs. 7.5 ± 1.3, p < 0.001), whereas the maximum VAS score was significantly lower in group R (1.8 ± 1.2 vs. 4.1 ± 1.0, p < 0.001). Maternal and neonatal adverse effects did not differ between the two groups during surgery (p > 0.05). CONCLUSIONS: Continuous intravenous infusion of low-dose remifentanil can significantly improve the experience of parturients undergoing repeated cesarean section under epidural anesthesia, without noticeable maternal or neonatal adverse effects. TRIAL REGISTRATION: This study was pre-registered at http://www.chictr.org.cn/index.aspx (ChiCTR1800018423) on 17/09/2018.
Assuntos
Anestesia Epidural/métodos , Anestesia Obstétrica/métodos , Recesariana/métodos , Remifentanil/administração & dosagem , Adulto , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Anestésicos Locais/administração & dosagem , Feminino , Humanos , Recém-Nascido , Infusões Intravenosas , Ketamina/administração & dosagem , Gravidez , Estudos Prospectivos , Remifentanil/efeitos adversos , Ropivacaina/administração & dosagem , Adulto JovemRESUMO
BACKGROUND: Perioperative allogenic transfusion is required in almost 50% of patients undergoing cardiac surgery and is associated with higher risk of mortality and morbidity (Xue et al., Lancet 387:1905, 2016; Ferraris et al., Ann Thorac Surg 91:944-82, 2011). Acute normovolemic hemodilution (ANH) is recommended as a potential strategy during cardiac surgery, but the blood conservation effect and the degree of ANH was still controversial. There is also an increasing concern about the improved outcomes associated with ANH. Therefore, a better understanding of the effect of mild volume ANH during cardiac surgery is urgently needed. METHODS: This retrospective study included 2058 patients who underwent cardiac surgery between 2010 and 2015. The study population was split into two groups (with and without mild volume ANH). Propensity score adjustment analysis was applied. We reported the association between the use of mild volume ANH and perioperative outcomes. RESULTS: A total of 1289 patients were identified. ANH was performed in 358 patients, and the remaining 931 patients did not receive any ANH. Five hundred of the total patients (38.8%) received perioperative RBC transfusions, 10% (129/1289) of patients received platelet, and 56.4% (727/1289) of patients received fresh frozen plasma transfusions. Mild volume ANH administration was significantly associated with decreased intraoperative RBC transfuse rate (8.5% vs. 14.4%; p = 0.013), number of RBC units (p = 0.019), and decreased postoperative pulmonary infection (6.8 vs. 11.3%; p = 0.036) during cardiac surgery. However, there was no significant difference regarding intraoperative fresh frozen plasma (FFP) and platelet concentrate transfusions, as well as postoperative and total perioperative allogeneic transfusions. Furthermore, there was no significant difference regarding postoperative outcomes including mortality, prolonged wound healing, stroke, atrial fibrillation, reoperation for postoperative bleeding and acute kidney injury. There was also no difference in postoperative ventilation time, length of ICU and hospital stay. CONCLUSION: Based on the 5-year experience of mild volume ANH in cardiac surgeries with CPB in our large retrospective cohort, mild volume ANH was associated with decreased intraoperative RBC transfusion and postoperative pulmonary infection in Chinese patients undergoing cardiac surgery. However, there was no significant difference regarding postoperative and total perioperative allogeneic transfusions.
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Transfusão de Sangue/estatística & dados numéricos , Hemodiluição/métodos , Pneumopatias/epidemiologia , Procedimentos Cirúrgicos Cardíacos , China/epidemiologia , Feminino , Humanos , Período Intraoperatório , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND: The analgesic potency of opioids is reduced in neuropathic pain. However, the molecular mechanism is not well understood. RESULTS: The present study demonstrated that increased methylation of the Mu opioid receptor (MOR) gene proximal promoter (PP) in dorsal root ganglion (DRG) plays a crucial role in the decreased morphine analgesia. Subcutaneous (s.c.), intrathecal (i.t.) and intraplantar (i.pl.), not intracerebroventricular (i.c.v.) injection of morphine, the potency of morphine analgesia was significantly reduced in nerve-injured mice compared with control sham-operated mice. After peripheral nerve injury, we observed a decreased expression of MOR protein and mRNA, accompanied by an increased methylation status of MOR gene PP, in DRG. However, peripheral nerve injury could not induce a decreased expression of MOR mRNA in the spinal cord. Treatment with 5-aza-2'-deoxycytidine (5-aza-dC), inhibited the increased methylation of MOR gene PP and prevented the decreased expression of MOR in DRG, thereby improved systemic, spinal and periphery morphine analgesia. CONCLUSIONS: Altogether, our results demonstrate that increased methylation of the MOR gene PP in DRG is required for the decreased morphine analgesia in neuropathic pain.
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Morfina/administração & dosagem , Neuralgia , Regiões Promotoras Genéticas/fisiologia , Receptores Opioides mu/genética , Receptores Opioides mu/metabolismo , Células Receptoras Sensoriais/metabolismo , Animais , Azacitidina/análogos & derivados , Azacitidina/farmacologia , Linhagem Celular Tumoral , Ilhas de CpG/efeitos dos fármacos , Decitabina , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Gânglios Espinais/citologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperalgesia/tratamento farmacológico , Metilação , Camundongos , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Neuralgia/patologia , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Medição da Dor , Limiar da Dor/efeitos dos fármacos , Regiões Promotoras Genéticas/efeitos dos fármacos , Células Receptoras Sensoriais/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismoRESUMO
Metastasis is the leading cause of cancer-related death in almost all types of cancers, including colorectal cancer (CRC). Metastasis is a complex, multistep, dynamic biological event, and epithelial-mesenchymal transition (EMT) is a critical process during the cascade. Ajuba family proteins are LIM domain-containing proteins and are reported to be transcription repressors regulating different kinds of physiological processes. However, the expression and pathological roles of Ajuba family proteins in tumors, especial in tumor metastasis, remain poorly studied. Here, we found that JUB, but not the other Ajuba family proteins, was highly upregulated in clinical specimens and CRC cell lines. Ectopic expression of JUB induced EMT and enhanced motility and invasiveness in CRC, and vice versa. Mechanistic study revealed that JUB induces EMT via Snail and JUB is also required for Snail-induced EMT. The expression of JUB shows an inverse correlation with E-cadherin expression in clinical specimens. Taken together, these findings revealed that the LIM protein JUB serves as a tumor-promoting gene in CRC by promoting EMT, a critical process of metastasis. Thus, the LIM protein JUB may provide a novel target for therapy of metastatic CRC.
Assuntos
Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal , Proteínas com Domínio LIM/metabolismo , Células CACO-2 , Caderinas/biossíntese , Movimento Celular , Neoplasias Colorretais/genética , Células HCT116 , Humanos , Proteínas com Domínio LIM/genética , Invasividade Neoplásica , Metástase Neoplásica , Interferência de RNA , RNA Interferente Pequeno , Transdução de Sinais , Fatores de Transcrição da Família Snail , Esferoides Celulares/patologia , Fatores de Transcrição/metabolismo , Células Tumorais Cultivadas , Regulação para CimaRESUMO
BACKGROUND: Pulmonary fibrosis is one of the main reasons for the high mortality rate among acute respiratory distress syndrome (ARDS) patients. Mesenchymal stromal cell-derived microvesicles (MSC-MVs) have been shown to exert antifibrotic effects in lung diseases. AIM: To investigate the effects and mechanisms of MSC-MVs on pulmonary fibrosis in ARDS mouse models. METHODS: MSC-MVs with low hepatocyte growth factor (HGF) expression (siHGF-MSC-MVs) were obtained via lentivirus transfection and used to establish the ARDS pulmonary fibrosis mouse model. Following intubation, respiratory mechanics-related indicators were measured via an experimental small animal lung function tester. Homing of MSC-MVs in lung tissues was investigated by near-infrared live imaging. Immunohistochemical, western blotting, ELISA and other methods were used to detect expression of pulmonary fibrosis-related proteins and to compare effects on pulmonary fibrosis and fibrosis-related indicators. RESULTS: The MSC-MVs gradually migrated and homed to damaged lung tissues in the ARDS model mice. Treatment with MSC-MVs significantly reduced lung injury and pulmonary fibrosis scores. However, low expression of HGF (siHGF-MSC-MVs) significantly inhibited the effects of MSC-MVs (P < 0.05). Compared with the ARDS pulmonary fibrosis group, the MSC-MVs group exhibited suppressed expression of type I collagen antigen, type III collagen antigen, and the proteins transforming growth factor-ß and α-smooth muscle actin, whereas the siHGF-MVs group exhibited significantly increased expression of these proteins. In addition, pulmonary compliance and the pressure of oxygen/oxygen inhalation ratio were significantly lower in the MSC-MVs group, and the effects of the MSC-MVs were significantly inhibited by low HGF expression (all P < 0.05). CONCLUSION: MSC-MVs improved lung ventilation functions and inhibited pulmonary fibrosis in ARDS mice partly via HGF mRNA transfer.
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Peripheral nerve injury induces the cleavage of CX3CL1 from the membrane of neurons, where the soluble CX3CL1 subsequently plays an important role in the transmission of nociceptive signals between neurons and microglia. Here we investigated whether CX3CL1 regulates microglia activation through the phosphorylation of extracellular signal-regulated protein kinase 5 (ERK5) in the spinal cord of rats with spinal nerve ligation (SNL). ERK5 and microglia were activated in the spinal cord after SNL. The knockdown of ERK5 by intrathecal injection of antisense oligonucleotides suppressed the hyperalgesia and nuclear impact of nuclear factor-κB induced by SNL. The blockage of CX3CR1, the receptor of CX3CL1, significantly reduced the level of ERK5 activation following SNL. In addition, the antisense knockdown of ERK5 reversed the CX3CL1-induced hyperalgesia and spinal microglia activation. Our study suggests that CX3CL1/CX3CR1 regulates nerve injury-induced pain hypersensitivity through the ERK5 signaling pathway.
Assuntos
Quimiocina CX3CL1/metabolismo , Hiperalgesia/metabolismo , Proteína Quinase 7 Ativada por Mitógeno/metabolismo , Neuralgia/metabolismo , Transdução de Sinais/fisiologia , Traumatismos da Medula Espinal/metabolismo , Animais , Quimiocina CX3CL1/genética , Hiperalgesia/etiologia , Hiperalgesia/fisiopatologia , Masculino , Proteína Quinase 7 Ativada por Mitógeno/genética , Neuralgia/complicações , Neuralgia/fisiopatologia , Oligodesoxirribonucleotídeos Antissenso , Fosforilação , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/fisiopatologia , Nervos Espinhais/lesões , Nervos Espinhais/metabolismoRESUMO
OBJECTIVE: To study the clinicopathological characteristics and diagnosis of true hermaphroditism complicated with seminoma. METHODS: We retrospectively analyzed the clinicopathological data of a case of true hermaphroditism complicated with seminoma and reviewed the related literature. RESULTS: The patient was a 42-year-old male, admitted for bilateral lower back pain and discomfort. CT showed a huge mass in the lower middle abdomen. Gross pathological examination revealed a mass of uterine tissue, 7 cm x 2 cm x 6 cm in size, with bilateral oviducts and ovarian tissue. There was a cryptorchidism (4.0 cm x 2.5 cm x 1.5 cm) on the left and a huge tumor (22 cm x9 cm x6 cm) on the right of the uterine tissue. The tumor was completely encapsulated, with some testicular tissue. Microscopically, the tumor tissue was arranged in nests or sheets divided and surrounded by fibrous tissue. The tumor cells were large, with abundant and transparent cytoplasm, deeply stained nuclei, coarse granular chromatins, visible mitosis, and infiltration of a small number of lymphocytes in the stroma. The karyotype was 46, XX. Immunohistochemistry showed that PLAP and CD117 were positive, while the AFP, Vimentin, EMA, S100, CK-LMW, Desmin, CD34 and CD30 were negative, and Ki-67 was 20% positive. A small amount of residual normal testicular tissue was seen in the tumor tissue. CONCLUSION: True hermaphroditism complicated with seminoma is rare. Histopathological analysis combined with immunohistochemical detection is of great value for its diagnosis and differential diagnosis.
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Transtornos Ovotesticulares do Desenvolvimento Sexual/patologia , Seminoma/patologia , Neoplasias Testiculares/patologia , Adulto , Humanos , Masculino , Transtornos Ovotesticulares do Desenvolvimento Sexual/complicações , Estudos Retrospectivos , Seminoma/complicações , Neoplasias Testiculares/complicaçõesRESUMO
BACKGROUND: Preoperative conditions in pediatric liver transplant recipients are understandably complex. Compared with adults, children have lesser compensatory abilities and demand greater precision during procedural executions. In the setting of end-stage liver disease, the heightened perioperative risk of coexistent cardiovascular pathology may impact graft survival as well. Requirements for anesthesia and perioperative management are thus more rigorous, calling for individualized treatments that reflect specific cardiovascular constraints and proposed surgical plans. CASE SUMMARY: Reports of perioperative anesthesia management and liver transplant prognostication in pediatric patients with concurrent atrial septal defects are scarce. Herein, we detail the course of liver transplantation in a child with dual afflictions, focusing on perioperative anesthesia management and the important contributions of the anesthesiologist (pre- and perioperatively) to a positive therapeutic outcome, despite the clinical hurdles imposed. CONCLUSION: Children with atrial septal defects bear substantially more than customary perioperative risk during orthotopic liver transplants, given their compromised cardiopulmonary reserves and functional states. Comprehensive preoperative cardiovascular assessments, including use of agitated-saline contrast echocardiography (to characterize intracardiac shunting) and multidisciplinary deliberation, may offer insights into structural cardiac pathophysiologic effects and transplant-related hemodynamic changes that impact new grafts. At the same time, active and effective monitoring and other measures should be taken to maintain hemodynamic stability in the perioperative period, avoid entry of bubbles into the circulation, and ease congestion in newly grafted livers. Such efforts are crucial for transplantation success and graft survival.
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This study aims to compare the prevalence of sexually transmitted infections (STIs) with semen quality in men from couples with primary and secondary infertility. Semen samples were collected from 133 men who requested fertility evaluation. Seminal tract infection with Ureaplasma spp. (UU), Mycoplasma hominis (MH), Mycoplasma genitalium (MG), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and herpes simplex virus-2 (HSV-2) was assessed by PCR-based diagnostic assays. Among all patients, the prevalence of STIs was higher in men from couples with primary infertility than that in men from couples with secondary infertility (39.7% vs 21.7%, P = 0.03). The prevalence of UU was 28.8% and 13.3% in men from couples with primary and secondary infertility, respectively. Men from couples with primary infertility were more likely to be positive for UU than men from couples with secondary infertility (P = 0.04). Regarding the UU subtype, the prevalence of Ureaplasma urealyticum (Uuu) and Ureaplasma parvum (Uup; including Uup1, Uup3, Uup6, and Uup14) did not differ between the two groups. No associations between the prevalence rates of MH, MG, and CT were found in men from either infertility group. A lower sperm concentration was associated with STI pathogen positivity in men with primary infertility according to the crude model (P = 0.04). The crude and adjusted models showed that semen volume (both P = 0.03) and semen leukocyte count (both P = 0.02) were independently associated with secondary infertility. These findings suggest the importance of classifying the type of infertility during routine diagnosis of seminal tract infections.
Assuntos
Infertilidade Masculina , Mycoplasma genitalium , Infecções Sexualmente Transmissíveis , Feminino , Humanos , Infertilidade Masculina/epidemiologia , Masculino , Mycoplasma hominis , Prevalência , Sêmen , Análise do Sêmen , Infecções Sexualmente Transmissíveis/complicações , Infecções Sexualmente Transmissíveis/epidemiologia , Ureaplasma urealyticumRESUMO
OBJECTIVE: To explore the effects of sevoflurane postconditioning on ischemic/reperfused myocardial apoptosis. METHODS: Isolated perfused rat hearts were randomly assigned into 3 groups: sham-operation (sham), ischemia/reperfusion (I/R) and sevoflurane postconditioning (SPC). Except for the sham group, the hearts were subjected to 40 min global myocardial ischemia and 120 min reperfusion. Left ventricular systolic pressure (LVSP), left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), maximum increase rate of LVDP (+dp/dt), maximum decrease rate of LVDP (-dp/dt), heart rate (HR) and coronary flow (CF) were measured at baseline, R (reperfusion) 30 min, R60 min, R90 min and R120 min. Creatine kinase (CK) and lactate dehydrogenase (LDH) were measured at 5 min and 10 min post-reperfusion. Infarct size was determined by triphenyltetrazolium chloride staining at the end of reperfusion. The expressions of Bcl-2 and Bax were determined by Western blot. RESULTS: The values of LVSP, LVDP, ± dp/dt and CF were higher while that of LVEDP was lower in the SPC group than the I/R group at all time points of reperfusion (P < 0.05). The releases of CK and LDH and infarct size were significantly reduced in the SPC group versus the I/R group (22.2% ± 2.8% vs I/R: 44.9% ± 6.6%, P < 0.05). The expression of Bcl-2 increased significantly while that of Bax decreased in the SPC group verus the I/R group. CONCLUSION: Sevoflurane postconditioning may improve myocardial functions, reduce infarct size and attenuate myocardial apoptosis. And the modulated expression of apoptotic proteins plays an important role in sevoflurane-induced myocardial protection.
Assuntos
Apoptose/efeitos dos fármacos , Éteres Metílicos/farmacologia , Miocárdio/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Animais , Técnicas In Vitro , Masculino , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Ratos , Ratos Sprague-Dawley , Sevoflurano , Proteína X Associada a bcl-2/metabolismoRESUMO
OBJECTIVE: To explore the effect of over-expression of tight junction protein claudin-6 upon the biological characters of breast cancer cell line MCF-7. METHODS: The MCF-7 subline expressing a high level of claudin-6 was established by transfection with a pcDNA3.1-claudin-6 expression vector. The expression of claudin-6 in mRNA and its protein level were confirmed by RT-PCR, Western blot and immunofluorescent assays. Then the effect of claudin-6 upon cell proliferation was examined by MTT assay. Colony-forming assays were used to examine 2-D and 3-D colony-forming capacities. Invasive and migratory traits of claudin-6 expressing cells were determined by Boyden chamber invasion assay and monolayer wound-healing assay. The structure and function of tight junctions in both parental and claudin-6 expression MCF-7 cells were evaluated by measuring transepithelial electrical resistance. RESULTS: Immunofluorescent assays showed that transfected cells expressed claudin-6 on their membrane. Cells with a high level expression of claudin-6 grew slowly than control cells. Anchorage-independent growth, invasive and migratory traits also decreased substantially in cells with claudin-6 expression; whereas the transepithelial electrical resistance increased in the claudin-6 transfected cells. CONCLUSION: The up-regulation of claudin-6 expression in MCF-7 breast cancer cells suppresses their malignant phenotypes with a correlation with the restoration of tight junction integrity. Claudin-6 may function as a cancer suppressor whose down-regulation contributes to the malignant progression of certain types of breast cancers.
Assuntos
Neoplasias da Mama/metabolismo , Proteínas de Membrana/metabolismo , Junções Íntimas/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Claudinas , Regulação para Baixo , Feminino , Humanos , Invasividade Neoplásica , Junções Íntimas/patologia , TransfecçãoRESUMO
OBJECTIVE: To explore the role of estrogen in the regulation of the expression of claudin-6 and biological behavior in MCF-7 cells. METHODS: RT-PCR and immunocytochemistry were conducted to analyze the expression and localization of claudin-6 in MCF-7 cells treated with 17ß-estradiol. CCK-8 kit assay and Scratch Test were conducted to analyze the capability of proliferation and migration of 17ß-estradiol treated MCF-7 cells. RESULTS: RT-PCR analysis and immunocytochemistry showed that 17ß-estradiol induced a concentration-and time-dependent effect on claudin-6. At 5 nmol/L and at 24 h, 17ß-estradiol treatment led to an increased level of claudin-6, which was located in the membrane of MCF-7 cells. CCK-8 analysis showed a significant decrease in the capability of proliferation of MCF-7 cells compared with the control group (P < 0.05). Cells Scratch Test showed decreased migration capability of MCF-7 cells compared with the control group (P > 0.05). CONCLUSIONS: 17ß-E2 might regulate the expression of claudin-6 and inhibit the proliferation and migration of MCF-7 cells. The inhibitory effects of 17ß-E2 on growth and migration of MCF-7 cells may be mediated by claudin-6 expression regulation.
Assuntos
Neoplasias da Mama/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Estradiol/farmacologia , Proteínas de Membrana/metabolismo , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Claudinas , Relação Dose-Resposta a Droga , Estradiol/administração & dosagem , Feminino , HumanosRESUMO
BACKGROUND: The influence of surgical delay on mortality and morbidity has been studied extensively among elderly hip fracture patients. However, most studies only focus on the timing of surgery when patients have already been hospitalized, without considering pre-admission waiting time. Therefore, the present study aims to explore the influence of admission delay on surgical outcomes. METHODS: In this retrospective study, we recorded admission timing and interval from admission to surgery for included patient. Other covariates were also collected to control confounding. The primary outcome was 1-year mortality. The secondary outcomes were 1-month mortality, 3-month mortality, ICU admission and postoperative pneumonia. We mainly used multivariate logistic regression to determine the effect of admission timing on postoperative outcomes. An additional survival analysis was also performed to assess the impact of admission delay on survival status in the first year after operation. RESULTS: The proportion of patients hospitalized on day 0, day 1, day 2 after injury was 25.4%, 54.7% and 66.3%, respectively. And 12.6% patients visited hospital one week later after injury. Mean time from admission to surgery was 5.2 days (standard deviation 2.8 days). Hospitalization at one week after injury was a risk factor for 1-year mortality (OR 1.762, 95% CI 1.026-3.379, P=0.041). CONCLUSION: Admission delay of more than one week is significantly associated with higher 1-year mortality. As a supplement to the current guidelines which emphasizes early surgery after admission, we also advocate early admission once patients get injured.