RESUMO
Rosacea and autoimmune liver diseases (AILDs) are diseases closely associated with immune system abnormalities. AILDs primarily includes autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). Currently, research on the association between these two conditions is limited. Therefore, this study employed the bidirectional Mendelian randomization (MR) method to investigate potential causal relationships between rosacea and AILDs based on genetic predictions. Summary data related to Rosacea, AIH, PSC, and PBC were obtained from public genome-wide association studies (GWAS). The inverse variance weighted (IVW) method was used as the primary analytical approach, supplemented by the MR-Egger, weighted mode method, weighted median, and simple mode. A series of sensitivity analyses were also conducted to identify heterogeneity and pleiotropy effects. The MR analysis results indicated a significant increase in the risk of rosacea being associated with PBC (OR = 1.09, 95% CI = 1.02-1.18, P = 0.014), but no such association was found with AIH or PSC. Furthermore, this study did not find a significant impact of rosacea on the risk of AILDs. This study represents the first in-depth exploration of the potential causal relationship between rosacea and AILDs using MR analysis. Thes findings suggest an increased risk of rosacea among PBC patients.
Assuntos
Colangite Esclerosante , Estudo de Associação Genômica Ampla , Hepatite Autoimune , Cirrose Hepática Biliar , Análise da Randomização Mendeliana , Rosácea , Humanos , Rosácea/genética , Rosácea/epidemiologia , Rosácea/diagnóstico , Colangite Esclerosante/genética , Colangite Esclerosante/epidemiologia , Cirrose Hepática Biliar/genética , Cirrose Hepática Biliar/epidemiologia , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/imunologia , Hepatite Autoimune/genética , Hepatite Autoimune/epidemiologia , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/imunologia , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Doenças Autoimunes/genética , Doenças Autoimunes/epidemiologiaRESUMO
OBJECTIVE: To evaluate the blood pressure (BP) lowering ability of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), in individuals with type-2 diabetes (T2D). METHODS: Randomized controlled trials (RCTs) comparing subcutaneous or oral semaglutide with placebo or other antihyperglycemic agents (AHAs) in T2D patients were identified by searching PubMed, Embase, Web of Science, ClinicalTrials.gov and Cochrane Library. These screened studies included the outcomes of interest: systolic and/or diastolic BP. Weighted mean differences (WMDs) and 95 % confidence intervals (CIs) were used to present the meta-analysis results. Pooled and sensitivity analyses were performed, and the risk of bias was evaluated. RESULTS: Twenty-nine RCTs with a total of 26985 participants were recruited in the final analysis. The WMD in change from baseline in systolic BP (SBP) of semaglutide versus placebo or other AHAs was -2.31 mmHg (95% CI: -3.11 to -1.51), while that for diastolic BP (DBP) was 0.09 mmHg (95% CI: -0.16 to 0.33). It also reduced glycated hemoglobin A1c (HbA1c) by 0.75% (95% CI: -0.92 to -0.58) and body weight loss by 2.80 kg (95% CI: -3.51 to -2.08). The reduction in SBP was similar for subcutaneous and oral administration of semaglutide, with -2.36 (95% CI: -3.38 to -1.35) and -2.50 (95% CI: -3.48 to -1.53), respectively. CONCLUSIONS: In T2D, SBP decreased significantly in the semaglutide group compared with placebo or other active controls. According to the efficacy results from this meta-analysis, subcutaneous and oral semaglutide have similar SBP-reducing effects. Therefore, the treatment of T2D patients with subcutaneous semaglutide or oral preparations is beneficial for reducing SBP.
Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Pressão Sanguínea , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Inositol requiring mutant 80 (INO80) is a chromatin remodeler that regulates pluripotency maintenance of embryonic stem cells and reprogramming of somatic cells into pluripotent stem cells. However, the roles and mechanisms of INO80 in porcine pre-implantation embryonic development remain largely unknown. Here, we show that INO80 modulates trophectoderm epithelium permeability to promote porcine blastocyst development. The INO80 protein is highly expressed in the nuclei during morula-to-blastocyst transition. Functional studies revealed that RNA interference (RNAi)-mediated knockdown of INO80 severely blocks blastocyst formation and disrupts lineage allocation between the inner cell mass and trophectoderm. Mechanistically, single-embryo RNA sequencing revealed that INO80 regulates multiple genes, which are important for lineage specification, tight junction assembly, and fluid accumulation. Consistent with the altered expression of key genes required for tight junction assembly, a permeability assay showed that paracellular sealing is defective in the trophectoderm epithelium of INO80 knockdown blastocysts. Importantly, aggregation of 8-cell embryos from the control and INO80 knockdown groups restores blastocyst development and lineage allocation via direct complementation of the defective trophectoderm epithelium. Taken together, these results demonstrate that INO80 promotes blastocyst development by regulating the expression of key genes required for lineage specification, tight junction assembly, and fluid accumulation.
Assuntos
ATPases Associadas a Diversas Atividades Celulares/metabolismo , Blastocisto/fisiologia , Cromatina/metabolismo , Proteínas de Ligação a DNA/metabolismo , Mórula/fisiologia , Suínos , ATPases Associadas a Diversas Atividades Celulares/genética , Animais , Proteínas de Ligação a DNA/genética , Técnicas de Cultura Embrionária/veterinária , Fertilização in vitro , Regulação da Expressão Gênica/fisiologia , Oócitos/fisiologia , PermeabilidadeRESUMO
Pre-implantation development is a dynamic, complex and precisely regulated process that is critical for mammalian development. There is currently no description of the role of the long noncoding RNAs (lncRNAs) during the pre-implantation stages in the goat. The in vivo transcriptomes of oocytes (n = 3) and pre-implantation stages (n=19) at seven developmental stages in the goat were analyzed by RNA sequencing (RNA-Seq). The major zygotic gene activation (ZGA) event was found to occur between the 8- and 16-cell stages in the pre-implantation stages. We identified 5,160 differentially expressed lncRNAs (DELs) in developmental stage comparisons and functional analyses of the major and minor ZGAs. Fourteen lncRNA modules were found corresponding to specific pre-implantation developmental stages by weighted gene co-expression network analysis (WGCNA). A comprehensive analysis of the lncRNAs at each developmental transition of high correlation modules was done. We also identified lncRNA-mRNA networks and hub-lncRNAs for the high correlation modules at each stage. The extensive association of lncRNA target genes with other embryonic genes suggests an important regulatory role for lncRNAs in embryonic development. These data will facilitate further exploration of the role of lncRNAs in the developmental transformation in the pre-implantation stage.
RESUMO
Fluid resuscitation is the first-line antishock treatment in severe acute pancreatitis (SAP). Currently, although mentions of complications related to aggressive fluid resuscitation are very frequent, a lack of proper handling of complications remains. One of the most important complications is intestinal barrier injury, including intestinal ischemia-reperfusion injury following aggressive fluid resuscitation. Once injured, the intestinal barrier may serve as the source of additional diseases, including systemic inflammatory response syndrome and multiple organ dysfunction syndrome, which aggravate SAP. This study focused on the underlying mechanisms of gut barrier dysfunction in rats induced by aggressive fluid resuscitation in SAP. This study further indicated the important role of necroptosis in intestinal barrier injury which could be relieved by using necroptosis-specific inhibitor Nec-1 before aggressive fluid resuscitation, thus reducing intestinal barrier damage. We also found pancreas damage after intestinal ischemia/reperfusion challenge and indicated the effects of high mobility group protein B1 in the vicious cycle between SAP and intestinal barrier damage.
Assuntos
Mucosa Intestinal , Necroptose , Pancreatite , Traumatismo por Reperfusão , Ressuscitação , Animais , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Pancreatite/etiologia , Pancreatite/metabolismo , Pancreatite/patologia , Pancreatite/terapia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/terapiaRESUMO
Intestinal ischaemia/reperfusion (I/R) severely disrupts gut barriers and leads to high mortality in the critical care setting. Transforming growth factor (TGF)-ß1 plays a pivotal role in intestinal cellular and immune regulation. However, the effects of TGF-ß1 on intestinal I/R injury remain unclear. Thus, we aimed to investigate the effects of TGF-ß1 on gut barriers after intestinal I/R and the molecular mechanisms. Intestinal I/R model was produced in mice by clamping the superior mesenteric artery for 1 hr followed by reperfusion. Recombinant TGF-ß1 was intravenously infused at 15 min. before ischaemia. The results showed that within 2 hrs after reperfusion, intestinal I/R disturbed intestinal immunoglobulin A class switch recombination (IgA CSR), the key process of mucosal IgA synthesis, and resulted in IgA dysfunction, as evidenced by decreased production and bacteria-binding capacity of IgA. Meanwhile, the disruptions of intestinal microflora and mucosal structure were exhibited. Transforming growth factor-ß1 activated IgA CSR as evidenced by the increased activation molecules and IgA precursors. Strikingly, TGF-ß1 improved intestinal mucosal IgA dysfunction, dysbiosis and epithelial damage at the early stage after reperfusion. In addition, SB-431542, a specific inhibitor of activating mothers against decapentaplegic homologue (SMAD) 2/3, totally blocked the inductive effect of TGF-ß1 on IgA CSR and almost abrogated the above protective effects on intestinal barriers. Taken together, our study demonstrates that TGF-ß1 protects intestinal mucosal IgA immunity, microbiota and epithelial integrity against I/R injury mainly through TGF-ß receptor 1/SMAD 2/3 pathway. Induction of IgA CSR may be involved in the protection conferred by TGF-ß1.
Assuntos
Disbiose/tratamento farmacológico , Imunoglobulina A/metabolismo , Mucosa Intestinal/irrigação sanguínea , Mucosa Intestinal/fisiopatologia , Traumatismo por Reperfusão/tratamento farmacológico , Fator de Crescimento Transformador beta1/farmacologia , Fator de Crescimento Transformador beta1/uso terapêutico , Animais , Bactérias/metabolismo , Disbiose/complicações , Disbiose/patologia , Humanos , Switching de Imunoglobulina/genética , Masculino , Camundongos Endogâmicos BALB C , Recombinação Genética/genética , Traumatismo por Reperfusão/complicações , Análise de SobrevidaRESUMO
BACKGROUND: Intestinal ischemia/reperfusion (I/R) injury can cause a high rate of mortality in the perioperative period. Remifentanil has been reported to provide protection for organs against I/R injury. We hypothesized that remifentanil preconditioning would attenuate the small intestinal injury induced by intestinal I/R. METHODS: We used both an in vivo rat model of intestinal I/R injury and a cell culture model using IEC-6 cells (the rat intestinal epithelial cell line) subjected to oxygen and glucose deprivation (OGD). Remifentanil was administered before ischemia or OGD, and 3 specific opioid receptors antagonists, naltrindole (a δ-OR selective antagonist), nor-binaltorphimine (nor-BNI, a κ-OR selective antagonist), and CTOP (a µ-OR selective antagonist), were administered before preconditioning to determine the role of opioid receptors in the intestinal protection mediated by remifentanil. RESULTS: In the in vivo rat model, intestinal I/R induced obvious intestinal injury as evidenced by increases in the Chiu score, serum diamine oxidase activity, the apoptosis index, and the level of cleaved caspase-3 protein expression, whereas remifentanil preconditioning significantly improved these changes in vivo. In the in vitro cell culture exposed to OGD, cell viability (MTT, ie, (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay and flow cytometric analysis showed that remifentanil preconditioning enhanced IEC-6 cell viability and decreased apoptosis. In both in vitro and in vivo models, the aforementioned protective effects of remifentanil preconditioning were abolished completely by previous administration of the δ- or µ-opioid markedly attentuated but not the κ-opioid receptor antagonist. CONCLUSION: Remifentanil preconditioning appears to act via δ- and µ-opioid receptors to protect the small intestine from intestinal I/R injury by attenuating apoptosis of the intestinal mucosal epithelial cells.
Assuntos
Intestino Delgado/irrigação sanguínea , Precondicionamento Isquêmico/métodos , Piperidinas/uso terapêutico , Substâncias Protetoras/uso terapêutico , Receptores Opioides delta/metabolismo , Receptores Opioides mu/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Mucosa Intestinal/irrigação sanguínea , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Masculino , Piperidinas/farmacologia , Substâncias Protetoras/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores Opioides delta/antagonistas & inibidores , Receptores Opioides kappa/antagonistas & inibidores , Receptores Opioides kappa/metabolismo , Receptores Opioides mu/antagonistas & inibidores , RemifentanilRESUMO
BACKGROUND: Intestinal ischemia/reperfusion (I/R) disrupts intestinal mucosal integrity and immunoglobulin A (IgA) generation. It has recently been shown that the programmed cell death-1 receptor (PD-1) plays a crucial role in regulating intestinal secreted IgA (sIgA). AIMS: To evaluate changes in PD-1 and PD-ligand 1 (PD-L1) expression on Peyer's patches (PP) CD4(+) T cells and to investigate the correlation between PD-1/PD-L1 and intestinal IgA production/mucosal integrity in mice following intestinal I/R. METHODS: I/R injury was induced by clamping the superior mesenteric artery for 1 h followed by 2-h reperfusion. PD-1/PD-L1 expression on PP CD4(+) T cells was measured in I/R and sham-operated mice. Additionally, transforming growth factor-ß1 (TGF-ß1) and interleukin-21 (IL-21) mRNA in CD4(+) T cells and IgA(+) and IgM(+) in PP B cells, as well as intestinal mucosal injury and sIgA levels, were assessed. RESULTS: PD-1/PD-L1, TGF-ß1, and IL-21 expression was down-regulated after intestinal I/R. Furthermore, IgA(+) B cells decreased and IgM(+) B cells increased in mice with intestinal I/R. Importantly, decreased PD-1/PD-L1 expression was correlated with increased mucosal injury and decreased IgA levels, as well as with decreased TGF-ß1 and IL-21 expression. CONCLUSIONS: Intestinal I/R inhibits PD-1/PD-L1 expression on PP CD4(+) T cells, which was associated with an impaired intestinal immune system and mechanical barriers. Our study indicates that PD-1/PD-L1 expression on CD4(+) T cells may be involved in the pathogenesis of intestinal I/R injury.
Assuntos
Antígeno B7-H1/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Imunoglobulina A/metabolismo , Mucosa Intestinal/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Linfócitos B/metabolismo , Imunoglobulina M/metabolismo , Interleucinas/genética , Mucosa Intestinal/irrigação sanguínea , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nódulos Linfáticos Agregados/patologia , RNA Mensageiro/metabolismo , Fator de Crescimento Transformador beta1/genéticaRESUMO
Intestinal ischemia/reperfusion (I/R) injury, in which macrophages play a key role, can cause high morbidity and mortality. The switch from classically (M1) to alternatively (M2) activated macrophages, which is dependent on the activation of STAT6 signaling, has been shown to protect organs from I/R injuries. In the current study, the effects of recombinant Trichinella spiralis cathepsin B-like protein (rTsCPB) on intestinal I/R injury and the potential mechanism related to macrophage phenotypes switch were investigated. In a mouse I/R model undergoing 60-min intestinal ischemia followed by 2-h or 7-d reperfusion, we demonstrated that intestinal I/R caused significant intestinal injury and induced a switch from M2 to M1 macrophages, evidenced by a decrease in levels of M2 markers (arginase-1 and found in inflammatory zone protein), an increase in levels of M1 markers (inducible NO synthase and CCR7), and a decrease in the ratio of M2/M1 macrophages. RTsCPB reversed intestinal I/R-induced M2-M1 transition and promoted M1-M2 phenotype switch evidenced by a significant decrease in M1 markers, an increase in M2 markers, and the ratio of M2/M1 macrophages. Meanwhile, rTsCPB significantly ameliorated intestinal injury and improved intestinal function and survival rate of animals, accompanied by a decrease in neutrophil infiltration and an increase in cell proliferation in the intestine. However, a selective STAT6 inhibitor, AS1517499, reversed the protective effects of rTsCPB by inhibiting M1 to M2 transition. These findings suggest that intestinal I/R injury causes a switch from M2 to M1 macrophages and that rTsCPB ameliorates intestinal injury by promoting STAT6-dependent M1 to M2 transition.
Assuntos
Antígenos de Helmintos/imunologia , Catepsina B/imunologia , Intestinos/efeitos dos fármacos , Macrófagos/imunologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Antígenos de Helmintos/administração & dosagem , Antígenos de Helmintos/genética , Arginase/genética , Arginase/imunologia , Catepsina B/administração & dosagem , Catepsina B/genética , Regulação da Expressão Gênica , Intestinos/imunologia , Intestinos/patologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/classificação , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/imunologia , Fenótipo , Pirimidinas/farmacologia , Receptores CCR7/genética , Receptores CCR7/imunologia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/mortalidade , Fator de Transcrição STAT6/antagonistas & inibidores , Fator de Transcrição STAT6/genética , Fator de Transcrição STAT6/imunologia , Transdução de Sinais , Análise de Sobrevida , Trichinella spiralis/química , Trichinella spiralis/imunologia , VacinaçãoRESUMO
The aim of this study was to present a comprehensive three-dimensional (3D) morphology of the petrous bone with computer image-processing technology, which could be beneficial for the teaching of anatomy and for surgical procedures. The unstained celloidin sections of human temporal bone were digitized with high resolution and quality, and then processed with Amira® software to include alignment, segmentation and reconstruction. The integral structure of the human inner ear was presented with computer modeling, including the petrous bone, bone labyrinth, internal carotid artery canal, internal jugular vein canal, sigmoid sinus, inferior petrosal sinus, glossopharyngeal meatus, vagal meatus, internal acoustic meatus, facial nerve canal, greater superficial petrosal nerve, vestibular aqueduct, extraosseous portion of the endolymphatic sac, round and oval window, processus cochleariformis and pyramidal eminence. The 3D model showed detailed structure of the external and internal petrous bone, as well as their spatial relationship. The present study suggests the feasibility of comprehensive 3D reconstruction of the petrous bone using unstained celloidin sections, which may provide advantages for future study.
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Fecundity improvement is one of the most important objectives for goat breeders as it greatly increases production efficiency. To investigate the genes associated with litter sizes in the Anhui White goat (AWG), gene expression differences in the ovaries of uniparous and multiparous AWG were assessed using the RNA-Seq (Quantification) method. This analysis generated 6,027,714 and 5,884,062 clean reads in uniparous and multiparous libraries, respectively. A total of 2201 differentially expressed genes (DEGs) were thereby identified (FDR≤0.001, |log2Ratio|≥1). There were 1583 up-regulated and 618 down-regulated genes in the multiparous samples compared with the uniparous samples. A large number of these DEGs were related to the terms cellular process, cell & cell part and binding. Twelve genes which may be associated with the high prolificacy of AWG were identified using a bioinformatic screen. In addition, pathway analysis revealed that these DEGs were significantly enriched in 11 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including ECM-receptor interactions, focal adhesion, and regulation of the actin cytoskeleton among others. This suggested a role for these pathways in the prolificacy of AWG. These results provide a list of new candidate genes for goat prolificacy.
Assuntos
Perfilação da Expressão Gênica/veterinária , Cabras/genética , Ovário/metabolismo , Análise de Sequência de RNA/métodos , Animais , Feminino , Ontologia Genética , Redes Reguladoras de Genes , Modelos Genéticos , Paridade , Gravidez , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/genéticaRESUMO
BACKGROUND: Remote ischemic preconditioning (RIPC) may confer the protection in critical organs. The authors hypothesized that limb RIPC would reduce lung injury in patients undergoing pulmonary resection. METHODS: In a randomized, prospective, parallel, controlled trial, 216 patients undergoing elective thoracic pulmonary resection under one-lung ventilation with propofol-remifentanil anesthesia were randomized 1:1 to receive either limb RIPC or conventional lung resection (control). Three cycles of 5-min ischemia/5-min reperfusion induced by a blood pressure cuff served as RIPC stimulus. The primary outcome was PaO2/FIO2. Secondary outcomes included other pulmonary variables, the incidence of in-hospital complications, markers of oxidative stress, and inflammatory response. RESULTS: Limb RIPC significantly increased PaO2/FIO2 compared with control at 30 and 60 min after one-lung ventilation, 30 min after re-expansion, and 6 h after operation (238 ± 52 vs. 192 ± 67, P = 0.03; 223 ± 66 vs. 184 ± 64, P = 0.01; 385 ± 61 vs. 320 ± 79, P = 0.003; 388 ± 52 vs. 317 ± 46, P = 0.001, respectively). In comparison with control, it also significantly reduced serum levels of interleukin-6 and tumor necrosis factor-α at 6, 12, 24, and 48 h after operation and malondialdehyde levels at 60 min after one-lung ventilation and 30 min after re-expansion (all P < 0.01). The incidence of acute lung injury and the length of postoperative hospital stay were markedly reduced by limb RIPC compared with control (all P < 0.05). CONCLUSION: Limb RIPC attenuates acute lung injury via improving intraoperative pulmonary oxygenation in patients without severe pulmonary disease after lung resection under propofol-remifentanil anesthesia.
Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Anestesia Intravenosa/métodos , Anestésicos Intravenosos , Precondicionamento Isquêmico/métodos , Pulmão/cirurgia , Piperidinas , Propofol , Idoso , Análise de Variância , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Citocinas/metabolismo , Feminino , Humanos , Inflamação/metabolismo , Inflamação/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Dor Pós-Operatória/epidemiologia , Estudos Prospectivos , Remifentanil , Testes de Função Respiratória , Tamanho da Amostra , Resultado do TratamentoRESUMO
STUDY OBJECTIVE: To identify the risk factors of, and develop a prediction model for, postoperative complications of patients undergoing infrarenal abdominal aortic aneurysm (IAAA) repair. DESIGN: Retrospective analysis. SETTING: Vascular surgery center of a university hospital. MEASUREMENTS: The clinical data of 316 IAAA cases were collected from January 2004 to October 2010 at a single vascular center in China. Postoperative complications were observed within 30 days after surgery. Patient-specific and operation-specific characteristics were analyzed in relation to postoperative complications using multiple logistic regression analysis. MAIN RESULTS: Overall incidence of postoperative complications and overall 30-day mortality of IAAA repair patients were 48.4% (153/316) and 8.8% (28/316), respectively. Postoperative complications involved pulmonary (18.9%), cardiac (14.2%), renal (7.3%), gastrointestinal (5.4%), neurologic (1.3%), and hepatic (0.9%) systems, and acute arterial embolism of the lower limb occurred in 1.3% of cases. Risk factors were age [> 65 yrs; odds ratio (OR) 1.6], aortic occlusion time (> 90 min; OR 2.4), history of chronic obstructive pulmonary disease (COPD; OR 4.4), emergency operation (OR 6.1), and history of cardiac dysfunction (OR 2.1). CONCLUSIONS: A combination of age, COPD, emergency operation, history of cardiac dysfunction and aortic occlusion time has significant impact on postoperative complications after open IAAA repair.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Modelos Estatísticos , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Emergências , Feminino , Hospitais Universitários , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/complicações , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversosRESUMO
BACKGROUND: Remote ischemic preconditioning (RIPC) may confer the cytoprotection in critical organs. The authors hypothesized that limb RIPC would reduce intestinal and pulmonary injury in patients undergoing open infrarenal abdominal aortic aneurysm repair. METHODS: In this single-center, prospective, double-blinded, randomized, parallel-controlled trial, 62 patients undergoing elective open infrarenal abdominal aortic aneurysm repair were randomly assigned in a 1:1 ratio by computerized block randomization to receive limb RIPC or conventional abdominal aortic aneurysm repair (control). Three cycles of 5-min ischemia/5-min reperfusion induced by a blood pressure cuff placed on the left upper arm served as RIPC stimulus. The primary endpoint was arterial-alveolar oxygen tension ratio. The secondary endpoints mainly included the intestinal injury markers (serum intestinal fatty acid-binding protein, endotoxin levels, and diamine oxidase activity), the markers of oxidative stress and systemic inflammatory response, and the scores of the severity of intestinal and pulmonary injury. RESULTS: In limb RIPC group, a/A ratio was significantly higher than that in control group at 8, 12, and 24 h after cross-clamp release (66 ± 4 vs. 45 ± 4, P = 0.003; 60 ± 6 vs. 37 ± 4, P = 0.002; and 60 ± 5 vs. 47 ± 6, P = 0.039, respectively). All biomarkers reflecting intestinal injury increased over time, and there was significant differences between limb RIPC and control group (P < 0.001). The severity of intestinal and pulmonary injury was decreased by limb RIPC (P = 0.014 and P = 0.001, respectively). CONCLUSIONS: Limb RIPC attenuates intestinal and pulmonary injury in patients undergoing elective open infrarenal abdominal aortic aneurysm repair without any potential risk.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Procedimentos Cirúrgicos Eletivos/métodos , Intestinos/irrigação sanguínea , Precondicionamento Isquêmico/métodos , Pulmão/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Idoso , Amina Oxidase (contendo Cobre)/sangue , Aorta Abdominal/cirurgia , Braço , Biomarcadores/sangue , China , Método Duplo-Cego , Endotoxinas/sangue , Proteínas de Ligação a Ácido Graxo/sangue , Feminino , Humanos , Enteropatias/sangue , Enteropatias/prevenção & controle , Pneumopatias/sangue , Pneumopatias/prevenção & controle , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Estudos Prospectivos , Síndrome de Resposta Inflamatória Sistêmica/sangueRESUMO
Enterotoxigenic Escherichia coli F18 is a major pathogen that causes postweaning diarrhoea and edema disease in piglets. The alpha(1,2)-fucosyltransferase (FUT1) gene has been identified as an ideal candidate gene for controlling the expression of the receptor for ECF18 bacteria. Therefore, the use of RNA interference (RNAi) to study the function of the FUT1 gene and to produce FUT1 knockdown transgenic pig would be highly beneficial. We developed an effective strategy for the expression of multiple small hairpin RNA simultaneously using multiple RNA polymerase III (hU6, hH1, mU6 and h7SK) promoters in a single vector to knockdown the FUT1 gene. Stable FUT1 knockdown transgenic fibroblast lines were generated by transfecting porcine fetal fibroblasts with the constructed vectors. Real-time RT-PCR indicated that the mRNA level of FUT1 in the transgenic fibroblast lines was significantly lower than that in the control, as much as 29 %. Finally, we successfully obtained transgenic SCNT porcine embryos. Overall, the results demonstrated that this vector-based RNAi expression system is an efficient approach to knockdown FUT1 gene expression in porcine fetal fibroblast cells, which could thereby provide donor cells for somatic cell nuclear cloning and the potential production of a marker-free transgenic pig resistant to F18 related diseases. Furthermore, it also provides strong evidence that this approach could be useful both in the production of transgenic livestock resistant to disease, and in the development of effective strategies for the suppression of gene expression in clinical gene therapy.
Assuntos
Fucosiltransferases/genética , Regulação da Expressão Gênica , Interferência de RNA , RNA Interferente Pequeno/genética , Animais , Animais Geneticamente Modificados , Fibroblastos/metabolismo , Fucosiltransferases/metabolismo , Expressão Gênica , Ordem dos Genes , Vetores Genéticos/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Suínos , Transfecção , Galactosídeo 2-alfa-L-FucosiltransferaseRESUMO
BACKGROUND: We demonstrated previously that ischemic postconditioning (IPo) attenuated intestinal injury induced by intestinal ischemia/reperfusion (I/R), and thereafter employed a proteomic method to identify aldose reductase (AR), a differentially expressed protein in intestinal mucosal tissue, which was downregulated by intestinal I/R and upregulated by IPo. This study aimed to further explore the possible role of AR in intestinal protection conferred by IPo. METHODS: Intestinal ischemia was induced by clamping the superior mesenteric artery (SMA) for 60 minutes in male adult rats. Then rats were allocated into 7 groups based on the random number table. The control group involved only sham operation; the control + AR inhibitor epalrestat group underwent sham operation and epalrestat administration; the I/R with and/or without epalrestat groups had SMA clamped for 60 minutes followed by 120 minutes of reperfusion with and/or without epalrestat given before index ischemia; the IPo group underwent 3 cycles of 30 seconds of reperfusion and 30 seconds of re-occlusion imposed immediately on reperfusion; and the epalrestat or vehicle control dimethylsulfoxide + IPo groups had the drugs administrated 10 minutes before ischemia. RESULTS: IPo resulted in significant intestinal protection evidenced as marked decreases in Chiu's score, reflecting changes intestinal histology, serum diamine oxidase activity, and intestinal mucosal levels of lactic acid, malondialdehyde, and myeloperoxidase, the apoptosis index, and downregulated cleaved caspase-3 protein expression; these changes were accompanied by an increase in superoxide dismutase activity and upregulation of AR protein levels. Epalrestat failed to protect against intestinal I/R insult, but abolished the protective effects of IPo. CONCLUSION: These findings suggest that IPo attenuates intestinal I/R-induced intestinal injury via AR-mediated oxidative defense and apoptosis suppression; AR inhibition reverses the protective effects of IPo. AR seems to be an innate protective factor in this model of intestinal I/R.
Assuntos
Aldeído Redutase/metabolismo , Apoptose , Íleo/irrigação sanguínea , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Pós-Condicionamento Isquêmico , Estresse Oxidativo , Traumatismo por Reperfusão/prevenção & controle , Aldeído Redutase/antagonistas & inibidores , Amina Oxidase (contendo Cobre)/sangue , Animais , Inibidores Enzimáticos/farmacologia , Ácido Láctico/metabolismo , Peroxidação de Lipídeos , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Rodanina/análogos & derivados , Rodanina/farmacologia , Tiazolidinas/farmacologiaRESUMO
Real-time quantitative PCR (qRT-PCR) is one of the important methods for investigating the changes in mRNA expression levels in cells and tissues. Selection of the proper reference genes is very important when calibrating the results of real-time quantitative PCR. Studies on the selection of reference genes in goat tissues are limited, despite the economic importance of their meat and dairy products. We used real-time quantitative PCR to detect the expression levels of eight reference gene candidates (18S, TBP, HMBS, YWHAZ, ACTB, HPRT1, GAPDH and EEF1A2) in ten tissues types sourced from Boer goats. The optimal reference gene combination was selected according to the results determined by geNorm, NormFinder and Bestkeeper software packages. The analyses showed that tissue is an important variability factor in genes expression stability. When all tissues were considered, 18S, TBP and HMBS is the optimal reference combination for calibrating quantitative PCR analysis of gene expression from goat tissues. Dividing data set by tissues, ACTB was the most stable in stomach, small intestine and ovary, 18S in heart and spleen, HMBS in uterus and lung, TBP in liver, HPRT1 in kidney and GAPDH in muscle. Overall, this study provided valuable information about the goat reference genes that can be used in order to perform a proper normalisation when relative quantification by qRT-PCR studies is undertaken.
RESUMO
OBJECTIVE: The mortality of critically ill patients associated with intestinal ischemia/reperfusion remains very high, which results from multiorgan dysfunction or failure due to intestinal injury induced by intestinal ischemia/reperfusion. This study was carried out to investigate whether intestinal ischemia/reperfusion can cause cerebral injury and concomitant memory dysfunction, and explore the potential mechanisms. DESIGN: Prospective, controlled, and randomized animal study. SETTING: University research laboratory. SUBJECTS: Male, adult Sprague-Dawley rats (weighing 250-300 g). INTERVENTIONS: Intestinal ischemia/reperfusion was established by clamping the superior mesenteric artery for 90 mins followed by different reperfusion durations (2, 6, 12, 24, or 48 hrs). The sham surgical preparation including isolation of the superior mesenteric artery without occlusion was performed as control. MEASUREMENTS AND MAIN RESULTS: In comparison with sham control, intestinal ischemia/reperfusion caused severe intestinal injury, accompanied by notable cerebral damage evidenced by increased wet-to-dry brain weight ratio reflecting brain edema and neuronal cell apoptosis manifested by increased apoptotic cell number and cleaved caspase-3 protein expressions. All these changes were concomitant with reduced survival rates as well as impaired memory function determined by Morris water maze test at 24 and 48 hrs after reperfusion. In addition, intestinal ischemia/reperfusion resulted in significant increases in the levels of tumor necrosis factor-α and interleukin-6 both in the serum and in cortices and hippocampal Cornu Ammonis area 1 regions, concomitant with the activation of microglia, a key cellular mediator involved in neuroinflammation and neurodegeneration, which was evidenced by increased protein expressions of ionized calcium binding adaptor molecule 1. Furthermore, the releases of reactive oxygen species evidenced by increased malondialdehyde levels and decreased superoxide dismutase activities in cortices and hippocampal Cornu Ammonis area 1 regions were found after reperfusion. CONCLUSIONS: These findings indicate that intestinal ischemia/reperfusion-induced intestinal injury can lead to cerebral damage and memory dysfunction partly via microglia activation which further facilitates oxidative injury, inflammatory response, and neuronal cell apoptosis.
Assuntos
Encefalopatias/etiologia , Intestinos/irrigação sanguínea , Isquemia/complicações , Transtornos da Memória/etiologia , Microglia/fisiologia , Traumatismo por Reperfusão/complicações , Animais , Apoptose , Encéfalo/enzimologia , Encéfalo/patologia , Química Encefálica , Encefalopatias/patologia , Encefalopatias/fisiopatologia , Caspase 3/metabolismo , Interleucina-6/análise , Interleucina-6/sangue , Isquemia/fisiopatologia , Masculino , Transtornos da Memória/fisiopatologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/análise , Fator de Necrose Tumoral alfa/análiseRESUMO
BACKGROUND: Intestinal ischemia-reperfusion (I/R) injury is a devastating complication in the perioperative period. Dexmedetomidine is commonly applied in the perioperative period. The authors aimed to determine the effects of different doses of dexmedetomidine (given before or after intestinal ischemia) on intestinal I/R injury and to explore the underlying mechanisms. METHODS: Intestinal I/R injury was produced in rat by clamping the superior mesenteric artery for 1 h followed by 2 h reperfusion. Intravenous infusion of dexmedetomidine was performed at 2.5, 5, and 10 µg · kg(-1) · h(-1) for 1 h before or after ischemic insult. In addition, yohimbine hydrochloride was administered intravenously to investigate the role of α2 adrenoreceptor in the intestinal protection conferred by dexmedetomidine. RESULTS: Intestinal I/R increased mortality of rats and caused notable intestinal injury, as evidenced by statistically significant increases in Chiu's scores; serum diamine oxidase and tumor necrosis factor-α concentration, accompanied by increases in the intestinal mucosal malondialdehyde concentration; myeloperoxidase activity; and epithelial cell apoptosis (all P < 0.05 vs. Sham). Except malondialdehyde and myeloperoxidase, all changes were improved by the administration of 5 µg · kg(-1) · h(-1) dexmedetomidine before ischemia (all P < 0.05 vs. Injury) but not after ischemia. Infusion of 2.5 µg · kg(-1) · h(-1) dexmedetomidine before or after ischemia produced no beneficial effects, and infusion of 10 µg · kg(-1) · h(-1) dexmedetomidine led to severe hemodynamic suppression. Yohimbine abolished the intestinal protective effect of the 5 µg · kg(-1) · h(-1) dexmedetomidine infusion before ischemia and was accompanied by the disappearance of its antiapoptotic and antiinflammatory effect. CONCLUSION: Dexmedetomidine administration before, but not after, ischemia dose-dependently protects against I/R-induced intestinal injury, partly by inhibiting inflammatory response and intestinal mucosal epithelial apoptosis via α2 adrenoreceptor activation.
Assuntos
Agonistas alfa-Adrenérgicos/uso terapêutico , Dexmedetomidina/uso terapêutico , Intestinos/lesões , Traumatismo por Reperfusão/tratamento farmacológico , Amina Oxidase (contendo Cobre)/sangue , Animais , Apoptose/efeitos dos fármacos , Gasometria , Caspase 3/biossíntese , Relação Dose-Resposta a Droga , Hemodinâmica/efeitos dos fármacos , Mucosa Intestinal/patologia , Intestinos/patologia , Ácido Láctico/sangue , Masculino , Malondialdeído/sangue , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Adrenérgicos alfa 2/efeitos dos fármacos , Receptores Adrenérgicos alfa 2/fisiologia , Traumatismo por Reperfusão/patologia , Análise de Sobrevida , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND: The precise relationship of the structures dorsal to the membranous urethra, including the rectourethralis muscle, the rhabdosphincter, the deep transverse perineal muscle (DTPM), the perineal body, and Denonvillier's fascia, remains controversial. OBJECTIVE: Our aim was to reexamine the detailed anatomy of the rectourethralis muscle and the deep transverse perineal muscle and their relationship with adjacent structures. DESIGN, SETTING, AND PARTICIPANTS: The pelvic viscera, including bladder, prostate, and rectum, were obtained from 20 formalin-fixed adult male cadavers. MEASUREMENTS: The pelvic viscera were embedded in celloidin and then cut into successive slices with an immersing-alcohol microtome. All slices were explored with anatomic microscopy. RESULTS AND LIMITATIONS: The longitudinal muscle of the anterior rectal wall was divided into anterior and posterior bundles at the junction of the rectum and anal canal. The intermediate fibers of the anterior bundle ended at the perineal body. The lateral fibers of the anterior bundle terminated at the posterior connective tissue of the bulbus penis. The DTPM occupied the space between the rhabdosphincter, rectum, and the bilateral levator ani muscle. Denonvillier's fascia terminated at the junction of the prostate and rhabdosphincter. Numerous slender nerves coming from the neurovascular bundle perforated the DTPM. CONCLUSIONS: The anterior bundle of the longitudinal muscle of the rectum inserts into the bulbus penis forming the rectourethralis muscle and ends at the perineal body forming the rectoperinealis muscle. The anterior bundle and DTPM together may contribute to the rectal angle of the anterior rectal wall, and they support the posterior border of the rhabdosphincter.