Association between serum HMGB1 elevation and early pediatric acute respiratory distress syndrome: a retrospective study of pediatric living donor liver transplant recipients with biliary atresia in China.

BACKGROUND: High mobility group box 1 (HMGB1) protein is one of the main risk factors for pediatric acute respiratory distress syndrome (PARDS) after living donor liver transplantation (LDLT). However, studies of the relationship between HMGB1 and PARDS are lacking. We evaluated the link between anomalies of intraoperative serum HMGB1 and PARDS in pediatric LDLT recipients with biliary atresia during the first week after transplant. METHODS: Data for 210 pediatric patients with biliary atresia who underwent LDLT between January 2018 and December 2021 were reviewed retrospectively. The main measure was serum HMGB1 levels 30 min after reperfusion, while the outcome was early PARDS after LDLT. Data including pretransplant conditions, laboratory indexes, variables of intraoperation, clinical complications, and outcomes after LDLT were analyzed for each patient. Univariate analysis of PARDS and multivariate logistic regression analyses of serum HMGB1 levels at 30 min in the neohepatic phase in the presence of PARDS were conducted to examine the potential associations. Subgroup interaction analyses and linear relationships between intraoperative serum HMGB1 levels and PARDS were also performed. RESULTS: Among the participants, 55 had PARDS during 7 days after LDLT, including four in the first HMGB1 tertile (4.3-8.1 pg/mL), 18 in the second tertile (8.2-10.6 pg/mL), and 33 in the third tertile (10.6-18.8 pg/mL). The nonadjusted association between intraoperative HMGB1 levels and PARDS was positive (odds ratio 1.41, 95% confidence intervals 1.24-1.61, P < 0.0001). The association remained unchanged after adjustment for age, weight, pretransplant total bilirubin, albumin, graft cold ischemia time, and intraoperative blood loss volume (odds ratio 1.28, 95% confidence interval 1.10-1.49, P = 0.0017). After controlling for potential confounders, the association between intraoperative HMGB1 levels and PARDS remained positive, as well as in the subgroup analyses. CONCLUSIONS: Serum HMGB1 levels at 30 min after reperfusion were positively associated with early PARDS among pediatric patients with biliary atresia who had undergone LDLT. Identifying such patients early may increase the efficacy of perioperative respiratory management.

Effective treatment of high-voltage pulsed radiofrequency combined with oxygen-ozone injection in acute zoster neuralgia.

INTRODUCTION: Postherpetic neuralgia (PHN) is the most common and severe complication of acute herpes zoster. Early treatment of herpes zoster neuralgia is of great significance to reduce the incidence of PHN. This retrospective study evaluated the efficacy and safety of the combination of high-voltage pulsed radiofrequency (PRF) and oxygen-ozone(O2-O3) injection in patients with acute zoster neuralgia (AZN) who failed to respond to conservative treatment. METHODS: One-hundred patients diagnosed with AZN were classified into two groups (high-voltage PRF group [HP group, n = 50] and high-voltage PRF combined with O2-O3 injection group [HPO group, n = 50]) based on different treatment methods. Therapeutic effectiveness was assessed using a numerical rating scale (NRS) and the Pittsburgh Sleep Quality Index (PSQI). The dosages of gabapentin and tramadol (mg/d) before treatment and after 1 week and 1, 3, and 6 months of treatment were measured. The incidence of clinically meaningful PHN after treatment was also recorded. RESULTS: Pain intensity and sleep quality in both groups at all time points improved after treatment compared to before treatment (P < 0.05). After 1 week and 1 month of treatment, NRS and PSQI scores in both groups decreased, but the differences were not statistically significant (P > 0.05). NRS, PSQI scores, and the dosages of gabapentin and tramadol decreased more significantly in the HPO group than those in the HP group after 3 months (P < 0.05). The incidence of PHN was significantly lower in the HPO group than in the HP group (P < 0.05). There were no significant differences in adverse events between the groups. CONCLUSIONS: High-voltage PRF is a safe and effective method for treating AZN. The combination of high-voltage PRF and O2-O3 injection is superior to high-voltage PRF alone for treating late-stage AZN. This approach could be recommended as an alternative treatment for patients with refractory AZN and could significantly reduce the risk of PHN.

Auditory event-related potentials based on name stimuli: A pilot study.

In recent years, diagnostic studies of brain disorders based on auditory event-related potentials (AERP) have become a hot topic. Research showed that AERP might help to detect patient consciousness, especially using the subjects' own name (SON). In this study, we conducted a preliminary analysis of the brain response to Chinese name stimuli. Twelve subjects participated in this study. SONs were used as target stimuli for each trial. The names used for non-target stimuli were divided into three Chinese character names condition (3CC) and two Chinese characters names condition (2CC). Thus, each subject was required to be in active (silent counting) and passive mode (without counting) with four conditions [(passive, active) × (3CC, 2CC)]. We analyzed the spatio-temporal features for each condition, and we used SVM for target vs. non-target classification. The results showed that the passive mode under 3CC conditions showed a similar brain response to the active mode, and when 3CC was used as a non-target stimulus, the brain response induced by the target stimulus would have a better interaction than 2CC. We believe that the passive mode 3CC may be a good paradigm to replace the active mode which might need more attention from subjects. The results of this study can provide certain guidelines for the selection and optimization of the paradigm of auditory event-related potentials based on name stimulation.

Screening and identification of biomarkers associated with the immune infiltration of intracerebral hemorrhage.

BACKGROUND: Recent studies showed that inflammation and immunity might play essential roles in the progression of intracerebral hemorrhage (ICH). However, the underlying mechanisms for changes at the cellular and molecular levels after ICH remain unclear. METHODS: We downloaded the microarray dataset of ICH from the Gene Expression Omnibus (GEO) database. The differential expression gene analysis was obtained by weighted gene co-expression network analysis (WGCNA). We got the hub genes and performed the biological functions and signaling pathways of these genes by Metascape. GSVA algorithm was used to evaluate the potential physical function of time-varying ICH samples. We used single-sample gene set enrichment analysis (ssGSEA) to assess the immune signatures infiltration and analyzed the correlation between hub genes and immune signatures. RESULTS: The data sets of all 22 ICH samples in GSE125512 were examined by the WGCNA R package. We finally screened five hub genes (GAPDH, PF4, SELP, APP, and PPBP) in the royal blue module. Metascape analysis displayed the biological processes related to inflammation and immunology. Cell adhesion molecule binding, myeloid leukocyte activation, CXCR chemokine receptor binding, and regulation of cytokine production were the most enriched pathophysiological process. The immune signatures infiltration analyses showed that ICH patients' early and late samples had different activity and abundance of immune-related cells and types. CONCLUSIONS: GAPDH, PF4, SELP, APP, and PPBP are identified as potential biomarkers for predicting the progression of ICH. This study may help us better understand the immunologic mechanism and shed new light on the promising approaches of immunotherapy for ICH patients.

Comparison of the success with two bending angles for lighted stylet intubation in children: A prospective randomised study.

BACKGROUND AND AIM: The bend angle of a lighted stylet is an important factor for successful orotracheal intubation. The aim of this study was to test the differences in the success of endotracheal intubation using lighted stylet with 70° versus 90° bend angles in children aged 4-6 years with normal airways. METHODS: A total of 136 children with normal airways required orotracheal intubation were enrolled and were randomly allocated to the 90° or 70° bend angle groups. The first-attempt success rate was assessed as the primary outcome. The intubation time, lighted stylet search time, lighted stylet withdrawal time, hemodynamic responses, and perioperative complications were recorded as secondary outcomes. RESULTS: All intubations were completed within three attempts (the 90° group, 63/5/0; the 70° group, 55/11/2). The first-attempt success rate was higher in the 90° group than that in the 70° group (92.6% [63/68 patients] versus 80.9% [55/68 patients], respectively; risk ratio, 1.15; 95% CI, 1.01-1.31; p = .04). Esophageal entry occurred in nine of 83 intubation attempts in the 70° group and two of 73 intubation attempts in the 90° group (risk ratio, 1.09; 95% CI, 1.01-1.19; p = .04). The intubation time and the lighted stylet search time were significantly shorter in the 90° group than that in the 70° group (intubation time: 12.2 ± 2.0 s versus 14.9 ± 2.6 s, respectively; mean difference, 2.65; 95% CI, 1.87-3.43; p < .01; effect size, 1.16; lighted stylet search time: 5.4 ± 1.0 s versus 8.0 ± 1.6 s, respectively; mean difference, 2.66; 95% CI, 2.21-3.12; p < .01; effect size, 1.95). CONCLUSIONS: Lighted stylet intubation with a 90° bend angle improved the first-attempt success rate and reduced esophageal intubation in children aged 4-6 years with normal airways.

Ketamine for Monitored Anesthesia Care During Transcatheter Aortic Valve Replacement.

PURPOSE: To study the feasibility and outcomes of ketamine as an anesthetic adjunct during monitored anesthesia care (MAC) in transcatheter aortic valve replacement (TAVR). DESIGN: This was a retrospective study. METHODS: Data from 155 consecutive TAVR patients at a tertiary care high-volume TAVR medical center were reviewed and analyzed. FINDINGS: Among the 155 TAVR cases under MAC, intravenous ketamine was administered as an adjunct in 126 patients. The most common ketamine dose was 20 mg. There was no significant difference for postoperative stroke, intraoperative conversion to general anesthesia, postoperative delirium, need for permanent pacemaker implantation, perivalvular leak and length of stay between the ketamine and non-ketamine groups. The ketamine group demonstrated a statistically significant lower 30-day mortality (P = .0381) and intraoperative cardiac arrest (P = .0025) rate when compared to the nonketamine group. CONCLUSIONS: Our results demonstrated that employing ketamine as an adjunct during MAC for TAVR is a feasible option.

Corrigendum to "Dexmedetomidine Ameliorates Hippocampus Injury and Cognitive Dysfunction Induced by Hepatic Ischemia/Reperfusion by Activating SIRT3-Mediated Mitophagy and Inhibiting Activation of the NLRP3 Inflammasome in Young Rats".

[This corrects the article DOI: 10.1155/2020/7385458.].

Dexmedetomidine had neuroprotective effects on hippocampal neuronal cells via targeting lncRNA SHNG16 mediated microRNA-10b-5p/BDNF axis.

Dexmedetomidine (DEX), a highly selective alpha2 adrenergic receptor agonist, is a commonly used anesthetic drug in surgical procedures. Previous studies have indicated that DEX exerts neuroprotective effects while the detailed mechanism has not been fully elucidated. Here, we aim to study the role of lncRNA SHNG16 in DEX-induced brain protection and its underlying molecular mechanism. The rats underwent middle cerebral artery occlusion (MCAO) surgery and oxygen-glucose deprivation (OGD)-treated HT22 hippocampal neurons were treated with DEX, respectively. CCK8 was used to evaluate cell viability. sh-SHNG16 as well as miR-10b-5p mimics were transfected into hippocampal neurons to further explore the bio-function of SNHG16 and miR-10b-5p in vitro. Furthermore, the interactions between SHNG16 and miR-10b-5p, miR-10b-5p and BDNF gene were confirmed by dual-luciferase report assay. Our data revealed that DEX attenuated neurological damage of the MCAO rats and also increased the cell viability of the neurons significantly. Besides, expression of SHNG16 and BDNF were both downregulated while miR-10b-5p was upregulated in MCAO brain tissues or OGD treated neurons. DEX inhibited miR-10b-5p expression but increased SHNG16 and BDNF levels with a dosage effect. After transfection with sh-SHNG16 or miR-10b-5p mimics, the expression of BDNF protein was downregulated, accompanied with decreased neuron viability. Dual-luciferase assay showed that SHNG16 targeted on miR-10b-5p, which also could bind directly to the 3'-UTR sites of BDNF and negatively regulate its expression. In conclusion, DEX exerts neuroprotective in ischemic stroke via improving neuron damage, the underlying mechanism may be upregulating SHNG16 and BDNF via sponging miR-10b-5p.

Dexmedetomidine Ameliorates Hippocampus Injury and Cognitive Dysfunction Induced by Hepatic Ischemia/Reperfusion by Activating SIRT3-Mediated Mitophagy and Inhibiting Activation of the NLRP3 Inflammasome in Young Rats.

Hepatic ischemia-reperfusion (HIR) has been proven to trigger oxidative stress and pyroptosis in the hippocampus. Sirtuin 3 (SIRT3) is an essential mitochondrial protein deacetylase regulating oxidative stress and mitophagy. Dexmedetomidine (Dex) has been demonstrated to confer neuroprotection in different brain injury models. However, whether the protective effects of Dex following HIR are orchestrated by activation of SIRT3-mediated mitophagy and inhibition of NOD-like receptor protein 3 (NLRP3) inflammasome activation remains unknown. Herein, two-week-old rats were treated with Dex or a selective SIRT3 inhibitor (3-TYP)/autophagy inhibitor (3-MA) and then subjected to HIR. The results revealed that Dex treatment effectively attenuated neuroinflammation and cognitive deficits via upregulating SIRT3 expression and activity. Furthermore, Dex treatment inhibited the activation of NLRP3 inflammasome, while 3-TYP and 3-MA eliminated the protective effects of Dex, suggesting that SIRT3-mediated mitophagy executes the protective effects of Dex. Moreover, 3-TYP treatment downregulated the expression level of SIRT3 downstream proteins: forkhead-box-protein 3α (FOXO3α), superoxide dismutase 2 (SOD2), peroxiredoxin 3 (PRDX3), and cyclophilin D (CYP-D), which were barely influenced by 3-MA treatment. Notably, both 3-TYP and 3-MA were able to offset the antioxidative and antiapoptosis effects of Dex, indicating that SIRT3-mediated mitophagy may be the last step and the major pathway executing the neuroprotective effects of Dex. In conclusion, Dex inhibits HIR-induced NLRP3 inflammasome activation mainly by triggering SIRT3-mediated mitophagy.

[A twenty-year review of clinical liver transplantation].

OBJECTIVE: To review the development of adult and pediatric liver transplantation in Tianjin First Center Hospital, and to enhance academic exchanges, improve technological innovation, and jointly promote the progress and maturity in the field of liver transplantation. METHODS: The development of liver transplantation in Tianjin First Center Hospital was analyzed. The clinical data of adult and pediatric liver transplantation from September 1998 to September 2018 were collected. The important events and technological innovation achievements of liver transplantation during the 20 years were summarized. RESULTS: The first clinical liver transplantation was attempted in Tianjin First Central Hospital in April 1980. The first long-term survival adult liver transplantation in China was completed in 1994 (11 years survival after the operation). The specialized team of liver transplantation was formally established in September 1998. The 20-year clinical exploration and progress reflected the characteristics of era changes and technological innovation during the rapid development of liver transplantation in China. Our center performed liver re-transplantation in January 1999, reduced-size pediatric liver transplantation in August 2000. In May 2001, we organized the formulation for the preventive and treatment plan for hepatitis B recurrence after liver transplantation. We performed combined liver and kidney transplantation in July 2002, split liver transplantation (SLT) in April 2004, the first domino liver transplantation (DLT) in August 2005. Pediatric living donor liver transplantation (LDLT) was initiated in October 2006, adult LDLT was carried out in August 2007. In September 2007, the first living donor combined liver and kidney transplantation from the same donor in Asia was performed. The first domino+living donor double grafts liver transplantation in the world was performed in January 2009. In March 2011, we performed laparoscopically assisted right hepatic lobe liver transplantation (LDLT) with middle hepatic vein. In May 2014, living donor laparoscopic left lateral lobe procurement was successfully established. In April 2016, simultaneous liver, pancreas and kidney multi-organ transplantation was completed. Domino donor-auxiliary liver transplantation was performed in February 2017. In December 2017, extracorporeal membrane oxygenation (ECMO)-supported liver transplantation in a patient with severe pulmonary hypertension was successfully completed. Liver transplantation combined with partial splenectomy was established in April 2018. Cross-domino liver transplantation (hypersensitive kidney transplantation with auxiliary liver transplantation+pediatric liver transplantation) was performed in May 2018. During the 20 years, the team has performed or assisted other centers in Beijing, Shanghai, Guangzhou and Shenzhen to carry out more than 10 000 cases of liver transplantations. A total of 7 043 cases of various types of liver transplantation were performed in the single center of the hospital (6 005 adult liver transplantations and 1 038 pediatric liver transplantations). Concerning adult liver transplantation, the cumulative 1-year, 3-year and 5-year survival rate from September 1998 to March 2003 were 83.1%, 73.0% and 69.0%, from April 2003 to March 2009 were 85.3%, 76.2% and 72.1% and from April 2009 to September 2018 were 87.5%, 79.2% and 75.1%, respectively. The cumulative 1-year, 3-year and 5-year survival rate for pediatric liver transplantation were 93.5%, 92.2% and 90.2%, respectively. The nucleoside (acid) analogue combined with low dose hepatitis B immunoglobulin (HBIG) was developed to prevent the recurrence of hepatitis B after liver transplantation, this plan has reduced the recurrence rate of hepatitis B and the 5-year re-infection rate of hepatitis B virus (HBV) after liver transplantation significantly. The risk assessment system for tumor recurrence after liver transplantation was established and individual treatment method was established based on this assessment system. Continuous exploration and improvement of liver transplantation for liver cancer, liver re-transplantation, liver transplantation with portal vein thrombosis, SLT, DLT and multi-organ combined transplantation have significantly improved the clinical efficacy of patients and the post-operative survival rate. CONCLUSIONS: The liver transplantation team of Tianjin First Center Hospital has carried out a scientific and technological exploration on the key problems and technical difficulties of clinical liver transplantation. This work strongly has initiated and promoted the rapid development of liver transplantation in China. The restrictive barrier of hepatitis B recurrence after liver transplantation has been overcome. The risk prevention and control system of tumor recurrence after liver transplantation has been established. A series of innovative achievements that can be popularized have been achieved in the field of complex liver transplantation and expansion of donor liver source. The iterative progress and sustainable development of liver transplantation have been realized.

Dephosphorylation by calcineurin regulates translocation of dynamin-related protein 1 to mitochondria in hepatic ischemia reperfusion induced hippocampus injury in young mice.

Hepatic ischemia reperfusion (HIR) has been found to induce brain injury and cognitive dysfunction. Dynamin-related protein 1 (Drp1) mediated mitochondrial fission involves oxidative stress, apoptosis and several neurological diseases. In this study, we investigated whether Drp1 translocation to mitochondria was implicated in HIR induced hippocampus injury in young mice, and further detected the role of calcineurin in the regulation of mitochondrial dynamics. 2-week C57BL/6 mice were chosen to make HIR model. Western blot was used to detect mitochondrial dynamics regulating proteins in whole hippocampal tissues and extracted mitochondria. Transmission electron microscopy was used to observe mitochondrial morphology. TUNEL staining and ELISA (serum S100ß/NSE concentrations) were used to evaluate neurons apoptosis and brain injury respectively. Drp1 inhibitor Mdivi-1 and calcineurin inhibitor FK506 were utilized to further confirm the role of Drp1 and calcineurin. Results showed that HIR affected mitochondrial dynamics in a fission-dominant manner with translocation of Drp1 to mitochondria in hippocampus of young mice. HIR induced increased expression of calcineurin and dephosphorylation of Drp1 at Ser637 in hippocampus. Treatment with Mdivi-1 and FK506 upregulated the phosphorylation of Drp1, inhibited Drp1 translocation to mitochondria, and alleviated mitochondrial fragmentation after HIR. What's more, Mdivi-1 and FK506 restrained cytochrome c release and cleaved caspase-3 expression, ameliorated hippocampal neurons apoptosis, and decreased serum S100ß/NSE concentrations as well. These data suggest that calcineurin mediated Drp1 dephosphorylation and translocation to mitochondria play a crucial role in HIR induced mitochondrial fragmentation and neurons apoptosis in hippocampus.

Src is Implicated in Hepatic Ischemia Reperfusion-Induced Hippocampus Injury and Long-Term Cognitive Impairment in Young Mice via NMDA Receptor Subunit 2A Activation.

Hepatic ischemia reperfusion (HIR) has been found to induce hippocampus injury and cognitive dysfunction. The N-methyl-d-aspartate (NMDA) receptor subunit 2A (NR2A) is an important factor mediating excitotoxicity and neurons injury, and autophosphorylation of Src can up-regulate tyrosine phosphorylation of NR2A to improve its activity. However, the role of Src and NR2A in HIR-induced hippocampus injury in young mice remains unknown. In this study, we found that serum biomarkers of brain injury (S100ß and NSE) increased significantly and reached highest after reperfusion of 3 days which had the same trend with the levels of p-Src and p-NR2A. Interactions between Src and NR2A or PSD95 were increased after HIR. Hippocampal neuron apoptosis was increased, and long-term cognitive impairment was found after reperfusion of 1 month. Inhibition of Src and NR2A with PP2 and NVP-AAM077 respectively not only down-regulated the levels of p-Src and p-NR2A, but also ameliorated hippocampal neurons apoptosis and long-term cognitive impairment after HIR. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ) and interleukin (IL)-6 were increased after reperfusion of 3 days, while PP2 and NVP-AAM077 treatment didn't attenuate the changes. And no difference was found in serum TNF-α, IFN-γ, IL-6 concentrations as well as the levels of Src, p-Src, NR2A, p-NR2A, PSD95 among the four groups after reperfusion of 1 month. In summary, HIR can lead to hippocampus injury and long-term cognitive dysfunction, and Src-PSD95-NR2A pathway plays an important role in the process.

The changes of intraoperative body temperature in adult liver transplantation: A retrospective study.

BACKGROUND: Body temperature is poorly regulated in patients with end-stage liver disease. Due to the prolonged surgery time and anhepatic time as well as the complex surgical procedures performed in liver transplantation, the body temperature fluctuates greatly. This study investigated the effect of intraoperative body temperature fluctuations on the prognosis of liver recipients. METHODS: The body temperatures of liver recipients recorded from the induction of anesthesia (T0) until the end of surgery (T14) were retrieved. The patients were divided into two groups: the hypothermia group (< 35 °C and ≥ 5 min) and the normothermia group (≥ 35 °C or < 35 °C but < 5 min). Intraoperative and postoperative variables were compared between the two groups, and the correlations between the duration of hypothermia and the medical variables were analyzed. RESULTS: Of the 107 patients, 67 patients were in the normothermia group, and 40 in the hypothermia group. The lowest body temperature was at 5 min after reperfusion for the whole cohort. Compared with the normothermia group, patients in the hypothermia group were more prone to bleeding, had a longer intubation time and increased rates of bacterial infection and acute pulmonary edema after liver transplantation (P < 0.05). Hypothermia time was positively correlated with bleeding volume, intubation time, units of blood transfusions and intensive care stay, but negatively correlated with urine output. CONCLUSIONS: The intraoperative body temperature exhibited a graphical "V" trend, and the lowest temperature was at 5 min after reperfusion. The longer the duration of hypothermia, the more unfavourable the prognosis.

Berberine protects renal tubular cells against hypoxia/reoxygenation injury via the Sirt1/p53 pathway.

Berberine (BBR) has been demonstrated to protect against renal ischemia/reperfusion injury; however, the underlying molecular mechanism is largely unknown. In the present study, we examined the role of silent information regulator 1 (Sirt1)/p53 in the protective effect of BBR on hypoxia/reoxygenation (H/R)-mediated mitochondrial dysfunction in rat renal tubular epithelial cells (NRK-52E cells). NRK-52E cells were preconditioned with small interfering RNA targeting Sirt1 (Sirt1-siRNA) and BBR before subjected to H/R. Cell damage was assessed by CCK8 assay and detection of oxidative parameters. The apoptotic rate was determined by flow cytometry and Hoechst 33258 staining. The expression of apoptotic markers, Sirt1, p53 and the translocation of p53 were examined by Western blotting assay. Nuclear p53 deacetylation by Sirt1 was detected using immunoprecipitation. Compared with the H/R group, BBR pretreatment increased cell viability and inhibited mitochondrial oxidative stress and apoptosis. Protein expression of Sirt1 was also enhanced along with a reduction of p53. Furthermore, both nuclear translocation of p53 and its acetylation were inhibited in NRK-52E cells pretreated with BBR. However, the knockdown of Sirt1 counteracted the renoprotection of BBR. BBR preconditioning protects rat renal tubular epithelial cells against H/R-induced mitochondrial dysfunction via regulating the Sirt1/p53 pathway.

Crocin Attenuates Oxidative Stress and Myocardial Infarction Injury in Rats.

Oxidative stress and excessive nitric oxide (NO) production play considerable roles in infarction-induced injury impairing cardiac functions. Crocin is the active constituent of Crocus sativus (saffron) with antioxidant properties and has protective effects against disturbances induced by ischemia in many organs. The present study aimed to investigate the protective effects and the underlying mechanisms of crocin on myocardial infarction (MI)-induced injury in rats in vivo. MI rats were intraperitoneally injected with crocin at different doses for seven successive days after coronary ligation. Infarct size, hemodynamic studies, and capillary density were evaluated. Levels of oxidative stress, inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and their corresponding phosphorylation expressions were then measured. Crocin decreased infarct size, left ventricular (LV) end-diastolic pressure, and LV minimum dP/dt while increased LV maximum dP/dt and percentage of LV fractional shortening dose dependently. Capillary density was markedly increased after crocin treatment. Crocin enhanced superoxide dismutase activity and reduced malondialdehyde levels as well as inhibited excessive production of NO through downregulating iNOS as well as upregulating eNOS during MI-induced injury. This study reveals that crocin improves MI-induced impairments in cardiac function, which is associated with its antioxidant properties.

Interferon regulatory factor-1 activates autophagy to aggravate hepatic ischemia-reperfusion injury via the P38/P62 pathway in mice.

Increasing evidence has linked autophagy to a detrimental role in hepatic ischemia- reperfusion (IR) injury (IRI). Here we focus on the role of interferon regulatory factor-1 (IRF-1) in regulating autophagy to aggravate hepatic IRI. We found that IRF-1 was up-regulated during hepatic IRI and was associated with an activation of the autophagic signaling. This increased IRF-1 expression, which was allied with high autophagic activity, amplified liver damage to IR, an effect which was abrogated by IRF-1 depletion. Moreover, IRF-1 contributed to P38 induced autophagic and apoptotic cell death, that can play a key role in liver dysfunction. The levels of P62 mRNA and protein were increased when P38 was activated and decreased when P38 was inhibited by SB203580. We conclude that IRF-1 functioned as a trigger to activate autophagy via P38 activation and that P62 was required for this P38-mediated autophagy. IRF-1 appears to exert a pivotal role in hepatic IRI, by predisposing hepatocytes to activate an autophagic pathway. Such an effect promotes autophagic cell death through the P38/P62 pathway. The identification of this novel pathway, that links expression levels of IRF-1 with autophagy, may provide new insights for the generation of novel protective therapies directed against hepatic IRI.

Predictive Value of Intraoperative Troponin I Elevation in Pediatric Living Donor Liver Transplant Recipients With Biliary Atresia.

BACKGROUND: Pediatric living donor liver transplantation is associated with slight alteration in cardiac enzymes without ongoing acute cardiac injury, but available information about the significance of these changes is limited. The aims of this study were to analyze the link between the anomalies of intraoperative serum cardiac troponin I (cTnI) and acute lung injury during the first week after liver transplantation. METHODS: In this retrospective study, 123 children suffering from biliary atresia were enrolled. Several perioperative variables, particularly cTnI before operation and at 30 minutes of neohepatic phase were recorded. Sixty-four recipients were divided into high cTnI group (≥0.07 ng/mL) and 59 recipients composed normal cTnI group (<0.07 ng/mL). The clinical data between 2 groups were compared and the association between serum cTnI level and acute lung injury after living donor liver transplantation were evaluated by univariate and multivariate logistic regression analyses. RESULTS: The percentage of acute lung injury after pediatric living donor liver transplantation among high cTnI group and normal cTnI group was 34.3% and 11.9%, respectively. Intratransplant cTnI ≥ 0.07 ng/mL (odds ratio [OR], 3.475; 95% confidence interval [CI], 1.114-10.842) was the risk factors for acute lung injury after transplantation. The value of cTnI showed the close correlation with preoperative bilirubin (OR, 1.005; 95% CI, 1.002-1.008) and pretransplant albumin (OR, 0.915; 95% CI, 0.849-0.986). CONCLUSIONS: Intraoperative cTnI elevation was the significant prognostic risk factor in acute lung injury after pediatric living-donor liver transplantation for children with biliary atresia. And the value of cTnI was associated with preoperative bilirubin and albumin level.

Berberine protects against ischemia/reperfusion injury after orthotopic liver transplantation via activating Sirt1/FoxO3α induced autophagy.

The effects and mechanism of berberine (BBR) on hepatic injury after orthotopic liver transplantation (OLT) have not been well characterized. We examined the role of Sirt1/FoxO3α axis in the protective effect of BBR on ischemia/reperfusion injury after OLT. Adult male Wistar rats were randomly allocated into four groups: Sham, OLT, OLT with BBR pretreatment (BBR), OLT with BBR and Sirt1 inhibitor (EX527) pretreatment group (EX527). The liver function and oxidative stress level were measured by biochemical and histopathologic examinations. The formation of autophagosome was observed by transmission electron microscopy. The apoptotic rate was determined by TUNEL analysis and the apoptotic mRNA expression. The expression of Sirt1, FoxO3α, Beclin-1, LC3-II/LC3-I, p62 and the acetylation of FoxO3α were assayed by western blot assay and immunoprecipitation. Compared with the OLT group, BBR dramatically attenuated the histopathologic damage, restored the liver function, and decreased the oxidative stress level. Simultaneously, BBR significantly ameliorated apoptosis by decreasing the apoptotic rate and the expression of apoptotic mRNA in rats subjected to OLT. The level of Beclin-1 and LC3-II/LC3-I were upregulated with the inhibition of p62. The deacetylation of FoxO3α by Sirt1 was enhanced in the nuclear of liver after pretreated with BBR. However, the inhibition of Sirt1 by EX527 counteracted the protective effects of BBR. Thus, BBR preconditioning promotes liver transplant ischemia/reperfusion injury partly via activating Sirt1/FoxO3α mediated autophagy.

Propofol postconditioning attenuates hippocampus ischemia-reperfusion injury via modulating JAK2/STAT3 pathway in rats after autogenous orthotropic liver transplantation.

Liver transplantation has been a routine treatment for the end stage liver diseases. Severe changes in circulation system and internal environment may occur during transplant surgery and cause injury to many organs including brain. Specific mechanisms of brain injury associated with liver transplantation are not yet elucidated. Previous studies have shown that the JAK/STAT signal transduction pathways are involved in the development of the central nervous system, such as nerve cell proliferation, survival, differentiation, and it also have a role in the disease processes, including brain tumor, brain ischemia and other diseases of the central nervous system. In this study we investigate whether propofol plays an important role in protecting the hippocampus through JAK2/STAT3 pathway. Thirty-two healthy male Sprague-Dawley rats, were randomly divided into four groups (n=8). Sham operation group (group S), autogenous orthotropic liver transplantation group (group I), autogenous orthotropic liver transplantation+propofol treatment group (group P) and autogenous orthotropic liver transplantation+propofol+AG490 treatment group (group A). We evaluated histological damage, inflammation, oxidative stress and apoptosis in hippocampus using HE staining, light microscope, real-time PCR and western blot. The results showed that there was a significant damage of hippocampus in group I compared to the sham group as demonstrated by increased serum levels of S100ß, NSE and the histological changes. However, an induction of propofol reduced the levels of MDA, TNFα, S100ß, NSE and increased activity of SOD, IL-10, and attenuated the expression of JAK2 and STAT3, meanwhile. Consistently, pretreatment with JAK2/STAT3 pathway inhibitor AG490, decreased the levels of MDA, TNFα, S100ß, NSE and increased activity of SOD, IL-10, and attenuated the expression of JAK2 and STAT3. These results reveal that autogenous orthotropic liver transplantation induces the activation of JAK2/STAT3 signaling pathway in hippocampus. Pretreatment with propofol attenuates autogenous orthotropic liver transplantation induces hippocampal injury via JAK2/STAT3 pathway.