ABSTRACT
Vascular hypo-responsiveness to vasopressors in patients with obstructive jaundice (OJ) is a common anesthetic event, which leads to perioperative complications and increased mortality. The cause of this clinical issue remains unclear. In this study, we estimated the actin cytoskeleton and arterial protein level in the artery of OJ patients by proteomic analysis. Ten patients with OJ due to bile duct diseases or pancreatic head carcinoma were enrolled, while another ten non-jaundice patients with chronic cholecystitis or liver hemangioma as the control group. Vascular reactivity to noradrenaline was measured before anesthesia on the day of surgery. Artery samples in adjacent tissues of removed tumor were collected and evaluated by 2-dimensional electrophoresis. Proteins with differential expression were detected by MALDI-TOF mass spectrometry with immunoblot confirmation. The results confirmed the phenomenon of vascular hypo-reactivity in OJ patients as suppressed aortic response to noradrenaline were existed in these patients. We also found that actin cytoskeleton and several actin-binding proteins were up- or down-regulated in the artery of OJ patients. These proteins changed in OJ patents might be the basic mechanism of vascular hypo-reactivity, further studies to uncover the role of these proteins in OJ is critical for clinical treatment of these patients.
ABSTRACT
BACKGROUND: This study aimed to investigate the potential role and molecular mechanism of lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in cerebral ischemia/reperfusion injury. RESULTS: Using an oxygen-glucose deprivation/reoxygenation (OGD/R) cell model, we determined that the expression of MALAT1 was significantly increased during OGD/R. MALAT1 knockdown reversed OGD/R-induced apoptosis and ER stress. Mechanistically, MALAT1 promoted OGD/R-induced neuronal injury through sponging miR-195a-5p to upregulating high mobility group AT-hook1 (HMGA1). CONCLUSIONS: Collectively, these data demonstrate the mechanism underlying the invovlvement of MALAT1 in cerebral ischemia/reperfusion injury, thus providing translational evidence that MALAT1 may serve as a novel biomarker and therapeutic target for ischemic stroke.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , MicroRNAs , RNA, Long Noncoding , Reperfusion Injury , Apoptosis/genetics , Endoplasmic Reticulum Stress/genetics , Glucose , HMGA1a Protein , Humans , MicroRNAs/genetics , Oxygen , RNA, Long Noncoding/genetics , Reperfusion Injury/geneticsABSTRACT
BACKGROUND: This study aimed to investigate the potential role and molecular mechanism of lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in cerebral ischemia/reperfusion injury. RESULTS: Using an oxygen-glucose deprivation/reoxygenation (OGD/R) cell model, we determined that the expression of MALAT1 was significantly increased during OGD/R. MALAT1 knockdown reversed OGD/R-induced apoptosis and ER stress. Mechanistically, MALAT1 promoted OGD/R-induced neuronal injury through sponging miR-195a-5p to upregulating high mobility group AT-hook1 (HMGA1). CONCLUSIONS: Collectively, these data demonstrate the mechanism underlying the invovlvement of MALAT1 in cerebral ischemia/reperfusion injury, thus providing translational evidence that MALAT1 may serve as a novel biomarker and therapeutic target for ischemic stroke.
Subject(s)
Humans , Reperfusion Injury/genetics , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Adenocarcinoma of Lung , Lung Neoplasms , Oxygen , Apoptosis/genetics , HMGA1a Protein , Endoplasmic Reticulum Stress/genetics , GlucoseABSTRACT
The myodural bridge (MDB) is confirmed that connecting the most of suboccipital muscles to the cervical dura mater through the posterior intervertebral spaces and widely exists in mammals and birds. In order to reveal whether the MDB is universally existing in amniota of vertebrates, we explored the existence and the morphological features of the MDB in the Trachemys scripta elegans. Twenty fresh red-eared slider specimens were observed by the gross anatomy dissection and histological analysis. In the results, three kind of muscles in the postoccipital region of the red-eared slider were found. The rectus capitis dorsum minor muscle originated from the posterior margin of the occiput (C0) and terminated at the spinous process of the atlas (C1). The transversospinales muscle was attached to the vertebral arch and the postzygapophysis of the atlas and extended to the spinous process of the axis (C2). The C2-C3 intertransversales muscle were extended from the postzygapophysis of C2 and the one of C3. The three muscles covered the dorsal interspaces among C0-C3, and meantime they were closely connected with dense connective tissues, which filled in these interspaces. Each of these thick dense connective tissue membranes sent off several short and strong fibrous bundles ventrally to merge with the cervical spinal dura mater. Furthermore the connective tissues connecting these muscles with cervical spinal dura mater directly were revealed under the microscopy and they consisted of parallel and intensive collagen fibers with orientation from dorsal to ventral. In conclusion, this study for the first time demonstrated the existence of the MDB in the testudines, in all of the dorsal atlantooccipital, atlantoaxial and C2-C3 intervertebral spaces. Based on our results and comparative anatomical evidences in recent year, it could be inferred that the MDB might be its highly conserved structure in the evolution of amniota.
Se confirma que el puente miodural (PMD) conecta la mayoría de los músculos suboccipitales con la duramadre cervical a través de los espacios intervertebrales posteriores y existe ampliamente en mamíferos y aves. Para revelar si el MDB existe universalmente en la amniota de vertebrados, exploramos la existencia y las características morfológicas del PMD en Trachemys scripta elegans. Veinte muestras se observaron mediante disección anatómica y análisis histológico. En los resultados, se encontraron tres tipos de músculos en la región occipital. El músculo recto capitis dorsum minor se originó en el margen posterior del occipital (C0) y terminó en el proceso espinoso del atlas (C1). El músculo transverso espinal se unió al arco vertebral y el proceso del atlas y se extendió al proceso espinoso del axis (C2). El músculo intertransversario C2-C3 se extendió entre los procesos transversos de C2 y el de C3. Los tres músculos cubrían los espacios intermedios dorsales entre C0-C3 y, mientras tanto, estaban estrechamente conectados con tejidos conectivos densos, que rellenaban estos espacios. Cada una de estas membranas densas de tejido conectivo envían varios haces fibrosos cortos y fuertes ventralmente para fusionarse con la duramadre espinal cervical. Además, los tejidos conectivos que conectan estos músculos con la duramadre cervical y espinal se revelaron directamente bajo microscopía y consistían en intensas fibras de colágeno, paralelas, con orientación desde dorsal a ventral. En conclusión, este estudio demostró por primera vez la existencia del PMD en los estudios de prueba, en todos los espacios dorsales atlantooccipital, atlantoaxial e intervertebral C2-C3. Sobre la base de nuestros resultados y las evidencias anatómicas comparativas de los últimos años, se podría inferir que el PMD podría ser una estructura altamente conservada en la evolución de la amniota.
Subject(s)
Animals , Turtles/anatomy & histology , Dura Mater/anatomy & histology , Biological Evolution , Head/anatomy & histology , Neck/anatomy & histologyABSTRACT
To investigate the effects of sanguinarine (SAN) on acute radiation induced injury in mice, 45 mice were randomly divided into control, 10 Gy and SAN+10 Gy groups. Mice in the 10 Gy and SAN+10 Gy groups were exposed to single X-ray radiation with an accumulated dose of 10 Gy. Mice in the SAN+10 Gy group were administered intraperitoneally with 2.5 mg/kg body weight of SAN before radiation. Five days after radiation exposure, 5 mice from each group were sacrificed and samples of the small intestine, lung, spleen and liver were fixed for histopathological examinations. Compared with the 10 Gy group, radiation sickness was obviously delayed or attenuated in the SAN+10 Gy group. Survival analysis showed a significant difference between 2 radiation groups (P<0.05) and mean survival time was 3 days longer in the SAN+10 Gy group than in the 10 Gy group (7.21±0.19 vs. 4.20±0.13, P<0.001). Radiation-induced organ damage, based on histopathological examinations, was decreased by SAN pretreatment. Chiu’s pathology grading scores, which is an index of intestinal damage, was significantly lower in the SAN+10 Gy group than in the 10 Gy group (2.77±0.48 vs. 4.37±0.31, P<0.01). A similar result was obtained in the pathological score of lung (1.67±0.21 vs. 2.33±0.38, P<0.01). Our preliminary findings demonstrated that SAN protects animals against radiation-induced sickness and acute damage to organs and following animal death.
Para investigar os efeitos da sanguinarina (SAN) em lesões induzidas em ratos por radiação aguda, 45 ratos foram aleatoriamente divididos em grupo controle, grupo 10 Gy e grupo SAN+10 Gy. Os ratos dos grupos 10 Gy e SAN+10 Gy foram expostos à radiação de raio-X simples com uma dose acumulada de 10 Gy. Aos ratos do grupo SAN+10 Gy administraram-se, intraperitonealmente, 2.5 mg/kg de peso de SAN antes da radiação. Aos 5 dias de exposição à radiação, sacrificaram-se 5 ratos de cada grupo e retiraram-se amostras do intestino delgado, pulmões, baço e fígado para exames histopatológicos. Comparando com o grupo 10 Gy, a doença por radiação foi claramente atrasada e atenuada no grupo SAN+10 Gy. A análise de sobrevivência mostrou diferença significativa entre os dois grupos de radiação (P<0.05) e o tempo de sobrevivência média foi de mais 3 dias no grupo SAN+10 Gy do que no grupo 10 Gy (7.21±0.19 vs 4.20±0.13, P<0.001). Danos induzidos nos órgãos por radiação, baseados em exames histopatológicos, foram reduzidos pelo pré-tratamento com SAN. As pontuações de classificação da patologia Chiu, um índice para os danos intestinais, foi significativamente menor no grupo SAN+10 Gy do que no grupo 10 Gy (2.77±0.48 vs 4.37±0.31, P<0.01). Resultado semelhante foi obtido na pontuação patológica do pulmão (1.67±0.21 vs 2.33±0.38, P<0.01). As nossas descobertas preliminares mostram que SAN protege os animais contra doenças induzidas pela radiação e danos agudos nos órgãos seguidos de morte animal.
Subject(s)
Animals , Rats , /radiation effects , /radiation effects , Mice, Inbred BALB C , X-Rays/adverse effects , Radiation Exposure/analysis , Radiation Exposure ControlABSTRACT
BACKGROUND: Living donor liver transplantation (LDLT) for patients with high model for end-stage liver disease (MELD) scores is controversial due to its poor outcome. However, there is little information regarding which factor would negatively impact the outcome of patients with high MELD scores. The aim of this study was to identify factors associated with the in-hospital mortality of patients with high MELD scores after LDLT. MATERIAL AND METHODS: All patients with an MELD scores ≥ 20 who received LDLT from 2005 to 2011 were recruited for the present study. Pre- and intra-operative variables were retrospectively and statistically analyzed. RESULTS: A total of 61 patients were included in the current study. The overall 3-month survival rate was 82% for patients with high MELD scores. Preoperative renal dysfunction, hyponatremia, starting albumin level < 2.8 g/dL, preoperative renal replacement for severe renal failure, anhepatic period > 100 minutes and intraoperative red blood cell (RBC) transfusion ≥ 10 units were identified as potential risk factors by univariate analysis. However, only hyponatremia, preoperative dialysis and massive RBC transfusion were independent risk factors in a multivariate analysis. The 3-month survival rates of patients with two or more independent risk factors and patients with none or one risk factor were 91 and 25%, respectively. A significant difference was observed (P < 0.001). CONCLUSION: Hyponatremia, preoperative dialysis and massive RBC transfusion were related to poor outcome for sicker patients. Patients with two or more of the above-mentioned risk factors and high MELD scores may exhibit extremely poor short-term survival.