PLK1 protects intestinal barrier function in sepsis: A translational research.

BACKGROUND: Sepsis and its related complications are very challenging in the intensive care unit, among which intestinal barrier injury is a general manifestation. Polo-like kinase 1 (PLK1) is widely studied in cancer, while its role in sepsis is poorly understood. In this study, the efficiency of PLK1 as a marker of intestinal barrier function as well as a predictor of mortality in sepsis was evaluated. METHODS: The level of serum PLK1 was measured in septic patients (n = 51) and controls (n = 20); subsequently, its correlation with serum diamine oxidase (DAO), d-lactate, and endotoxin levels and its ability topredict mortality were analysed. The survival rate and barrier injury degree were also assessed in septic mice. RESULTS: Serum PLK1 levels were elevated in septic patients, were negatively correlated with serum DAO, d-lactate, and endotoxin levels, and had a high predictive value for 28-day mortality in patients. The serum PLK1 level in non-survivors was lower. The expression of PLK1 in the intestine was decreased in septic mice, and overexpression or inhibition of PLK1 alleviated or aggravated intestinal barrier injury, respectively, as evaluated by Chiu's score, serum levels of DAO and d-lactate, and expression of tight junction proteins. Overexpressing PLK1 also decreased the 72-hour death rate of septic mice. Further study also revealed the negative correlation of PLK1 and IL-6 in patients, and increasing or interfering with PLK1 expression reduced or increased the serum IL-6 level in mice. CONCLUSIONS: PLK1 plays a critical role in intestinal barrier function during sepsis, providing a novel perspective for sepsis therapy in the clinic.

Ticagrelor Protects against Sepsis-Induced Acute Kidney Injury through an Adenosine Receptor-Dependent Pathway.

OBJECTIVE: Ticagrelor is a widely used anti-platelet drug. However, the mechanisms by which ticagrelor protects against sepsis-induced acute kidney injury (AKI) have not been clearly demonstrated. We designed this study to explore the protective effect of ticagrelor on sepsis-induced AKI and to explore the underlying mechanisms. METHODS: C57BL6J mice received oral ticagrelor (20 mg/kg and 50 mg/kg) for 7 days, and then caecal ligation and puncture (CLP) were performed. An adenosine receptor antagonist, CGS15943, was administered (10 mg/kg, intraperitoneal injection) to block the adenosine pathway 2 h before CLP. After 24 h, serum creatinine levels were measured. Periodic acid-Schiff (PAS) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining were employed to analyze pathological changes and cell apoptosis. Serum concentrations of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and mRNA expression of tissue TNF-α and IL-1ß were detected. Western blotting analysis was used to determine AKT and mammalian target of rapamycin (mTOR) protein expression in the kidney. RESULTS: PAS staining showed less swelling of renal tubules, and TUNEL staining revealed less cell apoptosis in the ticagrelor group than in the CLP group. Serum creatinine levels were significantly lower in the ticagrelor group than in the CLP group. Moreover, significantly lower serum and kidney levels of TNF-α and IL-1ß were observed in the ticagrelor group. CGS15943 blocked the effects of ticagrelor. Western blotting analysis showed increased phosphorylation of AKT and mTOR in the kidneys of the 50 mg/kg ticagrelor group. The adenosine receptor antagonist inhibited the activation of AKT and mTOR. CONCLUSION: This study demonstrates that the protective effect of ticagrelor on sepsis-induced AKI depends on adenosine receptor activation and the subsequent increase of AKT and mTOR phosphorylation.

Effect of Dexmedetomidine on Intestinal Barrier in Patients Undergoing Gastrointestinal Surgery-A Single-Center Randomized Clinical Trial.

INTRODUCTION: Gastrointestinal failure results in death in critically ill patients. This study aimed to explore the effect of dexmedetomidine (DEX) on intestinal barrier function and its mechanism in critically ill patients undergoing gastrointestinal surgery. METHODS: Patients undergoing gastrointestinal surgery were randomized into the DEX group (n = 21) or midazolam (MID) group (n = 21). Sufentanil was used for analgesia in both groups. In the DEX group, DEX was loaded (1 µg/kg) before sedation and infused (0.7 µg/kg/h) during sedation. In the MID group, MID was loaded (0.05 mg/kg) before sedation and infused (0.1 mg/kg/h) during sedation. The mean arterial pressure , heart rate , borborygmus resumption time , first defecation time, length of intensive care unit stay, and length of hospital stay were observed. The diamine oxidase (DAO), D-lactate , TNF-α, IL-6, and α7nAChR levels in plasma or hemocytes were detected before the start of sedation (0 h) and after sedation (24 h). RESULTS: No significant differences in age, sex, body mass index, Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were noted (P > 0.05). The mean arterial pressure between 0 h and 24 h showed no significant difference between the groups (P > 0.05), but the heart rate was significantly lower in the DEX group (P = 0.042). The borborygmus resumption time was significantly earlier in the DEX group (P = 0.034). The lengths of intensive care unit stay (P = 0.016) and hospital stay (P = 0.031) were significantly shorter in the DEX group. The TNF-α level in the DEX group was lower at 24 h than 0 h. The D-lactate level was significantly lower in the DEX group than the MID group at 24 h (P = 0.016). The expression of α7nAChR in the DEX group was significantly higher at 24 h than 0 h (P < 0.05). CONCLUSIONS: DEX maintained intestinal barrier integrity in patients undergoing gastrointestinal surgery through the cholinergic anti-inflammatory pathway.

Sepsis induces variation of intestinal barrier function in different phase through nuclear factor kappa B signaling.

The intestinal barrier function disrupted in sepsis, while little is known about the variation in different phases of sepsis. In this study, mouse models of sepsis were established by caecal ligation and puncture (CLP). The H&E staining of sections and serum diamine oxidase concentration were evaluated at different timepoint after CLP. TUNEL assay and EdU staining were performed to evaluate the apoptosis and proliferation of intestinal epithelium. Relative protein expression was assessed by Western blotting and serum concentrations of pro-inflammatory cytokines was measured by ELISA. The disruption of intestinal barrier worsened in the first 24 h after the onset of sepsis and gradually recovered over the next 24 h. The percentage of apoptotic cell increased in the first 24 h and dropped at 48 h, accompanied with the proliferative rate of intestinal epithelium inhibited in the first 6 h and regained in the later period. Furthermore, the activity of nuclear factor kappa B (NF-κB) presented similar trend with the intestinal barrier function, shared positive correction with apoptosis of intestinal epithelium. These findings reveal the conversion process of intestinal barrier function in sepsis and this process is closely correlated with the activity of NF-κB signaling.

[Effect of "one village, one control strategy" on schistosomiasis control in Qianjiang City].

OBJECTIVE: To evaluate the effect of "one village, one control strategy" on schistosomiasis control in Qianjiang City. METHODS: The villages with human and/or bovine schistosome infection rate being more than 1.5% in 2011 were chosen as the trial villages. According to the epidemic characteristics of schistosomiasis and control difficulties of the villages, the "one village, one control strategy" was performed and the control effects were evaluated. RESULTS: By the end of 2013, the infection rates of human and bovine in the trial villages decreased by 45.91% (χ2 = 469.19, P < 0.01) and 49.38% (χ2 = 11.46, P < 0.01), respectively, and all the infection rates of human and bovine in those villages were less than 1%. CONCLUSION: The "one village, one control strategy" is effective for schistosomiasis control, which can rapidly reduce the prevalence of schistosomiasis.

[Measures and effectiveness of comprehensive schistosomiasis control along Xinglong River in Qianjiang City].

OBJECTIVE: To evaluate the effect of comprehensive control of schistosomiasis along the Xinglong River in Qianjiang City, so as to provide the evidence for improving schistosomiasis control. METHODS: The comprehensive control measures including infection source control and Oncomelania hupensis snail eradication were surveyed along the Xinglong River in Qianjiang City. RESULTS: The prevalence of schistosomiasis was under control, that was the human and cattle infection rates decreased by 53.77% and 100% respectively, the snail area decreased by 26.9%, the mean density of living snails decreased by 25.5%, and no infected snails was found. CONCLUSIONS: The comprehensive control measures along the Xinglong River are effective, and the management and surveillance of snail environments still should be strengthened.

[Schistosomiasis haematobia misdiagnosed as urinary trace infection: one case report].

This paper reports one case of schistosomiasis haematobia that was misdiagnosed as urinary tract infection. It suggests that epidemiological data should be considered in the diagnosis and treatment of the patients with urinary tract infection symptoms coming back from Africa to avoid misdiagnosis.

[Molluscicidal effect of LDS in field in marshland areas].

The molluscicidal effects of salt of quinoid-2', 5-dichloro-4'-nitrosalicylanilide (LDS) and 50% wettable powder of niclosamide ethanolamine salt (WPN) were observed by three methods of immersion, insufflations and powdering. The results showed that there was no statistic difference between the snail control effects of LDS and WPN, which suggested that LDS had a good molluscicidal effect in marshland areas.

[One case of acute kidney injury caused by praziquantel].

This paper reported one case of acute kidney injury caused by praziquantel.