MicroRNA 181a-2-3p Alleviates the Apoptosis of Renal Tubular Epithelial Cells via Targeting GJB2 in Sepsis-Induced Acute Kidney Injury.

Acute kidney injury (AKI) is the most common complication of sepsis. MicroRNAs (miRNAs) play important roles in the sepsis-induced AKI. This paper aimed to explore the role of miRNA 181a-2-3p (miR-181a-2-3p) in the sepsis-induced AKI and the underlying mechanism. Our results revealed that miR-181a-2-3p showed low expression levels in patients with sepsis and mouse models undergoing cecal ligation and puncture (CLP). The addition of miR-181a-2-3p antagonists aggravated the sepsis-induced kidney injuries and inflammatory response in CLP mouse models, as suggested by hematoxylin and eosin (H&E) staining and quantitative real-time PCR (qRT-PCR). In addition, miR-181a-2-3p mimic alleviated the lipopolysaccharide (LPS)-induced inflammatory response, along with apoptosis of TCMK-1. Moreover, results from the GSE46955 data set indicated that GJB2 was highly expressed in septic patients but lowly expressed after recovery. Further, the dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were carried out, which confirmed that GJB2 was a target of miR-181a-2-3p, and overexpression of GJB2 reversed the anti-inflammatory and antiapoptotic effects of miR-181a-2-3p mimic on the LPS-induced sepsis cell models. In conclusion, miR-181a-2-3p alleviates the inflammatory response and cell apoptosis of septic patients and animal models by upregulating GJB2 expression, which may provide a new therapeutic strategy for sepsis.

Ideal target arterial pressure after control of bleeding in a rabbit model of severe traumatic hemorrhagic shock: results from volume loading-based fluid resuscitation.

BACKGROUND: Previously reported ideal target mean arterial pressure (MAP) after control of bleeding in traumatic hemorrhagic shock (THS) requires further verification in more clinically related models. The authors explored this issue via gradient volume loading without vasopressor therapy. As certain volume loading can induce secretion of atrial natriuretic peptide (ANP), which has been shown to be protective, the authors also observed its potential role. MATERIALS AND METHODS: Fifty male New Zealand rabbits were submitted to 1.5 h of uncontrolled THS (with another eight rabbits assigned to the sham group). After bleeding control, treated rabbits were randomly (n = 10, respectively) resuscitated with blood and Ringer lactate (1:2) to achieve target MAP of 50, 60, 70, 80, and 90 mm Hg within 1 h. During the following 2 h, they were resuscitated toward baseline MAP. Rabbits were observed until 7 h. RESULTS: After resuscitation, infused fluid was lower and oxidative stress injury was milder in the 70 mm Hg group. Fluid volume loaded during the initial hour after hemostasis was negatively correlated with pH, oxygen saturation, and base excess at the end of resuscitation. It also correlated positively with proinflammatory responses in bronchoalveolar lavage fluid at 7 h and 7-h mortality. Moreover, after volume loading, the 80 mm Hg group showed significantly increased serum ANP level, which correlated with the expression of Akt protein in the jejunum at 7 h. CONCLUSIONS: In rabbits the ideal target MAP during the initial resuscitation of severe THS after hemostasis was 70 mm Hg. ANP may have a critical role in gut protection.

Clinical and epidemiological characteristics of adult hand, foot, and mouth disease in northern Zhejiang, China, May 2008-November 2013.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is an infectious disease typically caused by enterovirus 71 (EV71) and Coxsackievirus A16. The incidence of HFMD appears to be increasing across the Asia Pacific region, with deaths occurring predominantly among children. Therefore, most HFMD reports focus on children and few have studied HFMD in adults. However, more adult HFMD cases may be seen in the foreseeable future as a result of global warming, continued viral evolution, and an increase in traveling. Thus, this study investigated the clinical and epidemiological characteristics of adult HFMD. METHODS: Case data of 49 adult HFMD patients who attended The First Affiliated Hospital of Jiaxing College, China from May 2008 to November 2013 were obtained. Socio-demographic data were collected through follow-up phone calls. Throat swab specimens were tested for enterovirus by quantitative reverse transcription-polymerase chain reaction and further confirmed by virus isolation assay. For 10 patients infected with EV71, the gene encoding the EV71 VP1 protein was sequenced and analyzed. Data from 8,354 child HFMD patients and 49 adult patients in the fever clinic of The First Affiliated Hospital of Jiaxing College during the same period were collected for comparison. RESULTS: This study revealed that close contact with HFMD patients and poor personal hygiene consciousness were risk factors for adult HFMD. This study also found that EV71 subgenotype C4a was the most common pathogen associated with adult HFMD in this area. Furthermore, this study demonstrated several unique epidemiological characteristics of adult HFMD compared to child HFMD, such as the geographic and gender distribution of adult HFMD patients and HFMD seasonality. CONCLUSIONS: The findings in this study showed the potential threat of adult HFMD.

Determination of protein phosphatase type 2A in monocytes from multiple trauma patients: a potential biomarker for sepsis.

BACKGROUND: Protein phosphatase type 2A (PP2A) can downregulate c-Jun N-terminal kinase (JNK) expression in monocytes stimulated by lipopolysaccharide. However, this effect has not been evaluated in patients with sepsis. We sought to determine whether PP2A/JNK pathway is involved in sepsis and whether PP2A expression can be associated with patient outcome. MATERIALS AND METHODS: We measured PP2A, c-Jun, and JNK protein as well as PP2A and c-Jun messenger RNA in monocytes from trauma patients with (n = 24) or without (n = 22) sepsis 1 and 7 d after major trauma and from healthy volunteers (n = 15) by Western blotting and quantitative real-time polymerase chain reaction. Patient outcomes, including intensive care unit length of stay, Sequential Organ Failure Assessment score, and Multiple Organ Dysfunction score were compared between groups. Correlations between PP2A and c-Jun/JNK expression as well as patient outcomes were analyzed. Receiver operating characteristic analysis was performed to determine the diagnostic efficiency of PP2A for sepsis. RESULTS: PP2A protein and messenger RNA expression were significantly higher in septic patients compared with nonseptic patients or healthy volunteers. Conversely, the expressions of JNK and c-Jun were significantly reduced in septic patients and correlated inversely with PP2A expression. Furthermore, PP2A expression was positively associated with LOS, Sequential Organ Failure Assessment and Multiple Organ Dysfunction score at day 1 and day 7. Receiver operating characteristic curve yielded a high sensitivity (87.5%) of PP2A in discriminating septic versus nonseptic patients. CONCLUSIONS: PP2A may serve as a negative regulator of the JNK pathway and a biomarker for sepsis.

Polymorphism of A133S and promoter hypermethylation in Ras association domain family 1A gene (RASSF1A) is associated with risk of esophageal and gastric cardia cancers in Chinese population from high incidence area in northern China.

BACKGROUND: The role of tumor suppressor gene RASSF1A in the esophageal and gastric cardia carcinogenesis is still inconclusive. In this study, the polymorphism, promoter methylation and gene expression of RASSF1A were characterized in esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA). METHODS: We firstly analyzed the prevalence of RASSF1A A133S in a total of 228 cancer patients with ESCC (n=112) and GCA (n=116) and 235 normal controls by polymerase chain reaction (PCR) and restriction enzyme-digestion assay. Then, the promoter methylation status of the RASSF1A in ESCC (n=143), GCA (n=92) and corresponding adjacent normal tissues were further investigated using methylation-specific PCR (MSP) approach. Finally, the RASSF1A protein expression were determined in ESCC (n=27), GCA (n=24) and the matched adjacent normal tissues by immunohistochemical method. RESULTS: The frequency of 133Ala/Se and Ser/Ser genotype was significantly higher in GCA patients than in normal controls (19.0% vs. 10.2%, P=0.02). Compared with Ala/Ala genotype, Ala/Se and Ser/Ser genotype significantly increased susceptibility to GCA (OR=2.06, 95% CI=1.09-3.97). However, this polymorphism had no association with ESCC (P=0.69). The promoter methylation of RASSF1A gene was significantly increased the risk to both ESCC (OR=5.90, 95% CI=2.78-12.52) and GCA (OR=7.50, 95% CI= 2.78-20.23). Promoter methylation of RASSF1A gene in ESCC was also associated with age and cancer cell differentiation (for age: OR=3.11, 95% CI=1.10-8.73; for differentiation: OR=0.29, 95% CI=0.12-0.69). RASSF1A positive expression was significantly decreased the risk of GCA (OR=0.16, 95% CI=0.03-0.83). In contrast, there was no statistical significance between RASSF1A positive expression and ESCC. The expression of RASSF1A protein trend to be positively related with older GCA patients (OR=16.20, 95% CI=1.57-167.74). CONCLUSIONS: The present findings suggest that alterations of RASSF1A may play an important role in gastric cardia carcinogenesis in terms of polymorphism, promoter hypermethylation and protein expression. Whereas, RASSF1A hypermethylation may probably also be involved in esophageal squamous cell carcinogenesis.

Expression of ATP7B in human gastric cardiac carcinomas in comparison with distal gastric carcinomas.

AIM: To analyze expression of ATP7B in gastric cardiac adenocarcinomas, its clinicopathologic significance, in comparison with distal gastric adenocarcinomas. METHODS: Immunohistochemical avidin-biotin peroxidase complex method was applied to detect the expression of ATP7B in 49 cases of cardiac carcinomas, the corresponding adjacent non-neoplastic epithelium and 55 cases of distal gastric carcinomas. RESULTS: The proportion of ATP7B positive samples in gastric cardiac carcinomas (51.0%, 25 of 49) was significantly higher than that in the corresponding adjacent non-neoplastic epithelium (22.4%, 11 of 49) (P = 0.003). ATP7B expression in poorly differentiated gastric cardiac carcinomas was significantly higher than that in well/moderately differentiated gastric cardiac carcinomas (P = 0.030). ATP7B expression in gastric cardiac carcinomas was independent of age, tumor size, nodal stage and metastasis status. ATP7B protein was detected in 30.9% (17/55 cases) of distal gastric carcinomas, markedly lower than that in gastric cardiac carcinomas (P = 0.037). CONCLUSION: ATP7B protein is frequently overexpressed in gastric cardiac carcinomas, and correlated with the differentiation of cardiac carcinoma. ATP7B expression in gastric cardiac carcinomas is significantly higher than that in distal gastric carcinomas, which might partially explain the difference of chemotherapy response and prognosis between these two gastric carcinomas.