LPS-TLR4 pathway exaggerates alcoholic hepatitis via provoking NETs formation / La vía LPS-TLR4 exagera la hepatitis alcohólica al provocar la formación de NET

Background Intrahepatic infiltration of neutrophils is a character of alcoholic hepatitis (AH) and neutrophil extracellular traps (NETs) are an important strategy for neutrophils to fix and kill invading microorganisms. The gut-liver axis has been thought to play a critical role in many liver diseases also including AH. However, whether NETs appear in AH and play role in AH is still unsure. Methods Serum samples from AH patients were collected and LPS and MPO-DNA were detected. WT, NE KO, and TLR4 KO mice were used to build the AH model, and the intestinal bacteria were eliminated at the same time and LPS was given. Then the formation of NETs and AH-related markers were detected. Results The serum MPO-DNA and LPS concentration was increased in AH patients and a correlation was revealed between these two indexes. More intrahepatic NETs formed in AH mice. NETs formation decreased with antibiotic intervention and restored with antibiotic intervention plus LPS supplement. While NETs formation failed to change with gut microbiome or combine LPS supplement in TLR4 KO mice. As we tested AH-related characters, liver injury, intrahepatic fat deposition, inflammation, and fibrosis alleviated with depletion of NE. These related marks were also attenuated with gut sterilization by antibiotics and recovered with a combined treatment with antibiotics plus LPS. But the AH-related markers did show a difference in TLR4 KO mice when they received the same treatment. Conclusion Intestinal-derived LPS promotes NETs formation in AH through the TLR4 pathway and further accelerates the AH process by NETs (AU)

Antecedentes La infiltración intrahepática de neutrófilos es una característica de la hepatitis alcohólica (AH, por sus siglas en inglés) y las trampas extracelulares de neutrófilos (NET, por sus siglas en inglés) son una estrategia importante para que los neutrófilos fijen y maten microorganismos invasores. Se ha pensado que el eje intestino/hígado desempeña un papel crítico en muchas enfermedades hepáticas, incluida la AH. Sin embargo, aún no está claro si las NET aparecen en la AH y desempeñan un papel en la misma. Métodos Se recogieron muestras de suero de pacientes con AH, y se detectaron LPS y MPO-ADN. Se utilizaron ratones WT, NE KO y TLR4 KO para construir el modelo de la AH, y las bacterias intestinales se eliminaron al mismo tiempo y se administró LPS. Luego se detectó la formación de NET y los marcadores relacionados con la AH. Resultados La concentración sérica de MPO-ADN y LPS aumentó en los pacientes con HA, y se reveló una correlación entre estos 2 índices. Se formaron más NET intrahepáticos en ratones con AH. La formación de las NET disminuyó con la intervención antibiótica, y se restauró con la intervención antibiótica más suplemento de LPS. Mientras que la formación de NET no pudo cambiar con el microbioma intestinal o combinar el suplemento de LPS en ratones TLR4 KO. A medida que probamos los caracteres relacionados con la AH, la lesión hepática, la deposición de grasa intrahepática, la inflamación y la fibrosis se aliviaron con el agotamiento de las NET. Estas marcas relacionadas también se atenuaron con la esterilización intestinal con antibióticos, y se recuperaron con un tratamiento combinado con antibióticos más LPS. Pero los marcadores relacionados con la AH mostraron una diferencia en los ratones TLR4 KO cuando recibieron el mismo tratamiento. Conclusión El LPS de origen intestinal promueve la formación de NET en la AH a través de la vía TLR4, y acelera aún más el proceso de AH por NET (AU)

LPS-TLR4 pathway exaggerates alcoholic hepatitis via provoking NETs formation.

BACKGROUND: Intrahepatic infiltration of neutrophils is a character of alcoholic hepatitis (AH) and neutrophil extracellular traps (NETs) are an important strategy for neutrophils to fix and kill invading microorganisms. The gut-liver axis has been thought to play a critical role in many liver diseases also including AH. However, whether NETs appear in AH and play role in AH is still unsure. METHODS: Serum samples from AH patients were collected and LPS and MPO-DNA were detected. WT, NE KO, and TLR4 KO mice were used to build the AH model, and the intestinal bacteria were eliminated at the same time and LPS was given. Then the formation of NETs and AH-related markers were detected. RESULTS: The serum MPO-DNA and LPS concentration was increased in AH patients and a correlation was revealed between these two indexes. More intrahepatic NETs formed in AH mice. NETs formation decreased with antibiotic intervention and restored with antibiotic intervention plus LPS supplement. While NETs formation failed to change with gut microbiome or combine LPS supplement in TLR4 KO mice. As we tested AH-related characters, liver injury, intrahepatic fat deposition, inflammation, and fibrosis alleviated with depletion of NE. These related marks were also attenuated with gut sterilization by antibiotics and recovered with a combined treatment with antibiotics plus LPS. But the AH-related markers did show a difference in TLR4 KO mice when they received the same treatment. CONCLUSION: Intestinal-derived LPS promotes NETs formation in AH through the TLR4 pathway and further accelerates the AH process by NETs.

Preliminary report on a novel technique for endoscopic transaxillary thyroidectomy: a case-control study.

BACKGROUND: Endoscopic transaxillary approaches to thyroidectomy have been well described and gasless transaxillary endoscopic thyroidectomy (GTET) is the most popular method. However, this require a single long axillary incision which is longer than most remote access thyroidectomy procedures. The authors improved the GTET and provided a novel way to access the thyroid. The purpose of this study was to test the feasibility of our novel transaxillary thyroidectomy procedure and to attempt to reduce the size of the scar and reduce the flap creation area. METHODS: One hundred sixteen patients who underwent our novel transaxillary thyroidectomy procedure were compared with the patients who underwent open and GTET procedures. The patients' demographics, outcomes, and complications were analyzed. RESULTS: Although the operation time (121.48±23.91 mins) was longer in the novel endoscopic group compare to the open group, it was shorter than GTET group. Intraoperative blood loss was similar between the groups. However, the novel procedure group had more drainage volume within 48 postoperative hours compare to other two groups. Despite the VAS pain score did not reveal a difference between the open and novel endoscopic procedure, it was lower in the novel procedure than GTET. The hospital stay days did not show a difference between the two groups. The number of resected central lymph nodes was similar between the groups. Differences did not reveal between the groups regarding to the complications rate. CONCLUSION: Our results showed that our novel transaxillary thyroidectomy procedure is feasible and safe. This procedure can be an alternative endoscopic transaxillary method for thyroidectomy.

Endoscopic total thyroidectomy using a unilateral transaxillary approach: A case report.

Endoscopic transaxillary thyroidectomy is a common method for remote-access thyroidectomy. The approach typically uses a gasless method, and a long incision to insert a special retractor. In addition, it is considered only suitable for unilateral lobectomy because of problems accessing contralateral parts of the thyroid gland. We describe here, a case of a young woman who had a total thyroidectomy performed using an endoscopic approach. We reduced the non-inflated 4-6 cm incision that is usually required, into three holes, and performed unilateral transaxillary thyroidectomy; this was verified by radioactive iodine uptake and thyroglobulin levels during follow-up. The approach was clinically successful and resulted in minimal scarring. More studies are required to optimize this promising technique.

Evaluation of a new method of calculating breast tumor volume based on automated breast ultrasound.

Objective: To evaluate the effectiveness and advantages of a new method for calculating breast tumor volume based on an automated breast ultrasound system (ABUS). Methods: A total of 42 patients (18-70 years old) with breast lesions were selected for this study. The Ivenia ABUS 2.0 (General Electric Company, USA) was used, with a probe frequency of 6-15 MHz. Adobe Photoshop CS6 software was used to calculate the pixel ratio of each ABUS image, and to draw an outline of the tumor cross-section. The resulting area (in pixels) was multiplied by the pixel ratio to yield the area of the tumor cross-section. The Wilcoxon signed rank test and Bland-Altman plot were used to compare mean differences and mean values, respectively, between the two methods. Results: There was no significant difference between the tumor volumes calculated by pixel method as compared to the traditional method (P>0.05). Repeated measurements of the same tumor volume were more consistent with the pixel method. Conclusion: The new pixel method is feasible for measuring breast tumor volume and has good validity and measurement stability.

Gut-derived lipopolysaccharide promotes alcoholic hepatosteatosis and subsequent hepatocellular carcinoma by stimulating neutrophil extracellular traps through toll-like receptor 4.

BACKGROUND/AIMS: Binge drinking leads to many disorders, including alcoholic hepatosteatosis, which is characterized by intrahepatic neutrophil infiltration and increases the risk of hepatocellular carcinoma (HCC). Molecular mechanisms may involve the migration of bacterial metabolites from the gut to the liver and the activation of neutrophil extracellular traps (NETs). METHODS: Serum samples from both binge drinking and alcohol-avoiding patients were analyzed. Mouse models of chronic plus binge alcohol-induced hepatosteatosis and HCC models were used. RESULTS: A marker of NETs formation, lipopolysaccharide (LPS), was significantly higher in alcoholic hepatosteatosis and HCC patients and mice than in controls. Intrahepatic inflammation markers and HCC-related cytokines were decreased in mice with reduced NET formation due to neutrophil elastase (NE) deletion, and liver-related symptoms of alcohol were also alleviated in NE knockout mice. Removal of intestinal bacteria with antibiotics led to decreases in markers of NETs formation and inflammatory cytokines upon chronic alcohol consumption, and development of alcoholic hepatosteatosis and HCC was also attenuated. These functions were restored upon supplementation with the bacterial product LPS. When mice lacking toll-like receptor 4 (TLR4) received chronic alcohol feeding, intrahepatic markers of NETs formation decreased, and hepatosteatosis and HCC were alleviated. CONCLUSION: Formation of NETs following LPS stimulation of TLR4 upon chronic alcohol use leads to increased alcoholic steatosis and subsequent HCC.

Magnolol Suppresses Pancreatic Cancer Development In Vivo and In Vitro via Negatively Regulating TGF-ß/Smad Signaling.

Magnolol, a hydroxylated biphenyl extracted from Magnolia officinalis, has recently drawn attention due to its anticancer potential. The present study was aimed to explore the effects of Magnolol on restraining the proliferation, migration and invasion of pancreatic cancer in vivo and in vitro. Magnolol showed significant anti-growth effect in an orthotopic xenograft nude mouse model, and immunohistochemical staining of the xenografts revealed that Magnolol suppressed vimentin expression and facilitated E-cadherin expression. The cytoactive detection using CCK-8 assay showed Magnolol inhibited PANC-1 and AsPC-1 concentration-dependently. Scratch healing assay and the Transwell invasion assay proved the inhibiting effects of Magnolol on cellular migration and invasion at a non-cytotoxic concentration. Western blot and rt-PCR showed that Magnolol suppressed epithelial-mesenchymal-transition by increasing the expression level of E-cadherin and decreasing those of N-cadherin and vimentin. Magnolol suppressed the TGF-ß/Smad pathway by negatively regulating phosphorylation of Smad2/3. Moreover, TGF-ß1 impaired the antitumor effects of Magnolol in vivo. These results demonstrated that Magnolol can inhibit proliferation, migration and invasion in vivo and in vitro by suppressing the TGF-ß signal pathway and EMT. Magnolol could be a hopeful therapeutic drug for pancreatic malignancy.

Timed Up and Go Test can predict recurrent falls: a longitudinal study of the community-dwelling elderly in China.

PURPOSE: Falling is a major health problem in community-dwelling elderly individuals. The aim of the present study was to conduct a prospective investigation to evaluate the accuracy of the Timed Up and Go Test (TUGT), 4-meter walking test, and grip strength test to screen for the risk of falls and to determine a cutoff point to be used clinically. PATIENTS AND METHODS: This was a prospective study that included 541 participants. The fall data were obtained via face-to-face interview, and the date, site, and circumstances of any falls were recorded. TUGTs were recorded as part of a comprehensive geriatric assessment. We collected the same data at baseline and after follow-up via comprehensive geriatric assessment. RESULTS: The incidence of falls of our study subjects was 20.8%. The recurrent-fall group had a fall rate of 6.8% during the follow-up year. The standard area under the curve (AUC) of our screening tool was >0.70, and hence our tool can be used for clinical purposes. After adjusting for age and gender, the AUC of TUGT became 0.642, so it cannot be used as a predictive tool for measuring any types of falls. However, when recurrent falls were adjusted for age and gender, the TUGT's AUC improved to 0.733 and a score of 15.96 seconds is used as a cut-point to screen recurrent falls in community-dwelling elderly Chinese individuals. CONCLUSION: Future falls were best predicted by TUGT in recurrent fallers at baseline. A score of 15.96 seconds is used as a cut-point to screen recurrent falls in community-dwelling elderly Chinese individuals.

Effects of protease-treated royal jelly on muscle strength in elderly nursing home residents: A randomized, double-blind, placebo-controlled, dose-response study.

Although we have found that protease-treated royal jelly (pRJ) benefit for the skeletal muscle mass and strength in the aged animals, the potential beneficial effects have not been evaluated in humans. The aim of this study was to determine whether pRJ intake had beneficial effects on muscle strength in elderly nursing home residents. One hundred and ninety-four subjects enrolled into this multicenter, randomized, double-blind, placebo-controlled study. Subjects received either placebo(Group 1), pRJ 1.2 g/d(Group 2), or 4.8 g/d(Group 3). Data through 1 year are reported for 163 subjects. The primary outcome measure is handgrip strength. Secondary outcomes include several physical performance tests (six-minute walk test, timed up and go test, and standing on one leg with eyes closed). The dropout rate was 16.0%. The means (95% confidence interval) of change in handgrip strength for placebo, low-dose, and high-dose groups are -0.98(-2.04,0.08), 0.50(-0.65,1.65) and 1.03(-0.37,2.44) kg (P = 0.06, P for trend = 0.02), respectively. No significant effects of the interventions were observed for physical performances. These findings suggest that pRJ treatment might not improve, but rather attenuate the progression of decrease in muscle strength in elderly people. In addition, we have not found that pRJ intervention can achieve improvement or attenuating the decrease in physical performance.

Effect of HSP27 and Cofilin in the injury of hypoxia/reoxygenation on hepatocyte membrane F-actin microfilaments.

Hypoxia-reoxygenation (H/R) injury hepatocyte models were established to simulate the ischemia/reperfusion injury of transplanted organ. Through the study of the molecular mechanism of H/R on the F-actin damage of the liver cytomembrane, the mechanism of F-actin damage induced by ischemia and reperfusion was studied from the level of cell and molecule.The hypoxic environment of cells in vitro was simulated by chemical hypoxia agent CoCl2. Liver cells were detected by MTT, H/R group was subdivided into 3 subgroups: H/R 2, 4, and 6 h. Changes of cell shape and the growth state, apoptosis, ultrastructural changes, and the changes in F-actin microfilament content were observed. Heat shock protein 27 (HSP27), Cofilin, and F-actin gene and protein levels were determined by real-time polymerase chain reaction and western blot assay, respectively.Cells showed circular adherence growth under normal circumstances, while the spindle cells and shedding cells were significantly increased in H/R groups. Apoptosis cells in H/R group were increased significantly with the extension of hypoxia time. The number of endoplasmic reticulum was decreased significantly in the H/R group, the mitochondrion hydropic was degenerated and the glycogen was disappeared. The F-actin fibers in the H/R group were disordered, the morphology of the fibers was obviously decreased, and the fluorescence staining decreased obviously (P < .05). The transcription and expression levels of HSP27, Cofilin, and F-actin were significantly lower than those in the control group (P < .05).These results demonstrate that H/R can affect the correct assembly of F-actin microfilaments and weakens the normal cycle of F-actin microfilaments through inhibiting the protein expression and gene transcription of HSP27 and Cofilin in hepatocytes, thereby changing the skeleton of F-actin microfilaments.

Both muscle mass and muscle strength are inversely associated with depressive symptoms in an elderly Chinese population.

OBJECTIVE: Few population studies have examined the association between skeletal muscle and depressive symptoms. The aim of this study was to examine whether low muscle mass and muscle strength were associated with the depressive symptoms in elderly Chinese. METHODS: A cross-sectional study was conducted with 1046 elderly in Tianjin, China. Depressive symptoms were examined using the 30-item Geriatric Depression Scale. A Geriatric Depression Scale score of ≥11 was used to indicate depressive symptoms. Skeletal muscle mass was indicated using a skeletal muscle mass index (SMI) that was measured by bioimpedance analysis and muscle strength was measured by dynamometer. RESULTS: In a multiple logistic regression analysis, subjects in the lowest quartile of SMI or muscle strength had a significantly higher risk for depressive symptoms compared with those in the fourth quartile. The odds ratios and 95% confidence interval for depressive symptoms risk in the lowest quartile of SMI compared with the highest after adjusting for potential confounding factors were 10.1 (2.25, 58.3) in men and 3.17 (1.07, 9.95) in women. The odds ratios (95% confidence interval) for depressive symptoms risk in the lowest quartile of muscle strength compared with the highest after adjusting for potential confounding factors were 2.55 (1.02, 6.67) in men and 4.18 (1.83, 10.2) in women. CONCLUSIONS: Both muscle mass and muscle strength are inversely associated with depressive symptoms in elderly Chinese. These findings may provide novel insights linking skeletal muscle and depressive symptoms. Copyright © 2016 John Wiley & Sons, Ltd.

Synergy of subgroup J avian leukosis virus and Eimeria tenella to increase pathogenesis in specific-pathogen-free chickens.

To investigate the effects of co-infections of subgroup J avian leukosis virus (ALV-J) and Eimeria tenella on the pathogenesis in specific-pathogen-free (SPF) white leghorn chickens, groups of chickens were infected with ALV-J strain NX0101 at one day of age or with E. tenella at 14 days of age or both. The control group was left uninfected and was mock-inoculated with phosphate buffer saline (PBS). Mortality rates, body weights, cecal lesions, and viremia of infected chickens in each group were evaluated. Immune status was evaluated by measuring several parameters: immune organ weight/body weight index, specific humoral responses to inactivated NDV vaccine and to inoculated E. tenella, proportions of blood CD3+CD4+ and CD3+CD8α+ lymphocytes and transcriptional levels of cytokines in blood and cecal tonsils. The results show that co-infections of ALV-J and E. tenella induced a higher mortality rate and a lower body weight in SPF chickens compared to single-pathogen infection. In co-infected chickens, ALV-J accelerated the disease symptoms induced by E. tenella, and the E. tenella extended the ALV-J viremia. Thymus atrophy, decrease in the humoral response levels to pathogens and the NDV vaccine, modifications in the blood lymphocyte sub-populations and transcriptional cytokine disorders were found in co-infected chickens compared to chickens infected with one pathogen alone and to controls. We underline a synergy between ALV-J and E. tenella that results in increasing pathogenesis in SPF chickens.

Mobility and Muscle Strength Together are More Strongly Correlated with Falls in Suburb-Dwelling Older Chinese.

Falls are common in older adults and result in adverse outcomes. Impaired mobility and poor muscle strength have been consistently identified as the main contributors to falls. We choose three easy-to-perform tests (i.e. Timed Up and Go test (TUGT), walking speed (WS) and grip strength (GS)) in order to assess mobility and muscle strength to further define their relationship with falls. This study is cross-sectional, consisting of 1092 residents over 60-year-old; 589 were female. 204 (18.68%) participants reported falling at least once in the past year. It was found that, of the three tests evaluated independently, a TUGT < 9.1750 s had the strongest association with fewer falls. When evaluating these tests as pairs, the combination of a TUGT < 9.1750 s and a WS < 0.9963 m/s was the best protective indicator of falls after adjusting for age, sex and other variables. When evaluating all three tests in conjunction with each other, the combination of a TUGT < 9.1750 s, a WS < 0.9963 m/s, and a GS > 0.3816 was most correlated with less possibility of falls. The combination of a better TUGT performance, a stronger GS, and a slower WS is the most strongly correlated with less possibility of falls.

Prevalence and Factors Associated With Sarcopenia in Suburb-dwelling Older Chinese Using the Asian Working Group for Sarcopenia Definition.

BACKGROUND: Sarcopenia is a common condition in older people. The aim of the present study was to examine the prevalence and factors associated with sarcopenia in an elderly Chinese suburb-dwelling population. METHODS: This study was conducted on 1,069 Chinese suburb-dwelling participants aged ≥60 years to evaluate sarcopenia using the Asian Working Group for Sarcopenia criteria. Sociodemographic and behavioral characteristics, as well as medical conditions, were considered independent variables to determine factors associated with sarcopenia using a logistic regression model. RESULTS: The prevalence of sarcopenia was 6.4% in men and 11.5% in women. Age was a significant factor in both sexes. In addition, presence of sarcopenia was inversely associated with BMI for both sexes. The odds ration and 95% confidence interval for factors statistically significantly associated with sarcopenia were 5.04 (1.70-14.89) and 2.36 (1.06-5.25) for diabetes in males and females, respectively; 10.60 (1.75-64.24) for daily consumption of alcohol (daily drinkers), 5.58 (2.13-14.59) for peptic ulcer in female (not statistically significant in males). CONCLUSIONS: The Asian Working Group for Sarcopenia criterion is useful for defining sarcopenia, and our data suggest that the prevalence of sarcopenia in the general elderly suburb-dwelling Chinese population is high. Moreover, we find that high body mass index is inversely associated with the likelihood of being sarcopenic and that several others factors such as diabetes, peptic ulcer, and drinking habits increase the prevalence of sarcopenia.

Clinical Relevance of Different Handgrip Strength Indexes and Mobility Limitation in the Elderly Adults.

BACKGROUND: More efficient clinical indexes are needed to identify older people most likely to present mobility impairments. The aim of the present study was to determine which handgrip strength (HS) indexes are clinically relevant to detect risk of mobility limitation in the elderly adults. In addition, we attempted to determine an optimal cutoff point for the most relevant index. METHODS: Data are from 469 men and 609 women aged 60 years and older recruited in the Hangu area of Tianjin, China. Participants scoring in the top 20% on the Timed Up and Go Test or in the slowest 20% for the 4-m walk test were defined as having mobility limitation. RESULTS: The prevalence of mobility limitation was 27.6% in women and 24.5% in men. The area under the receiver-operating characteristic curve for HS/body fat mass was 0.723 (95% confidence interval [CI] = 0.658-0.788) in men and for HS/weight was 0.684 (95% CI = 0.628-0.739) in women. These values were indicated higher levels of mobility limitation compared with HS and other relative HS indexes. The cutoffs of the most relevant index in men and women that effectively identified individuals at risk of mobility limitation were 1.884 and 0.281, respectively. CONCLUSION: HS/body fat mass and HS/weight appear to be the indices best associated with mobility limitation for men and women, respectively. Optimal cutoffs for clinically relevant index have the potential to identify elderly adults at risk of mobility limitation.

Hepatic artery bridging lessens temporary ischemic injury to bile canaliculi.

AIM: To study whether transfer of blood between the right gastroepiploic artery and gastroduodenal artery could lessens the damage to bile canaliculi. METHODS: Forty male Bama miniature pigs were divided into four groups as follows: a control group, two hepatic artery ischemia groups (1 h and 2 h), and a hepatic artery bridging group. The hemodynamics of the hepatic artery in the hepatic artery bridging group was measured using color Doppler ultrasound. Morphological changes in the bile canaliculus were observed by transmission electron microscopy. Cofilin, heat shock protein 27 and F-actin expression was detected by immunohistochemistry, Western blot, and real-time polymerase chain reaction. Terminal deoxynucleotidyl transferase-mediated nick end-labeling method was used to evaluate liver injury. RESULTS: The hemodynamics was not changed in the hepatic artery bridging group. The microvilli in the bile canaliculus were impaired in the two hepatic artery ischemia groups. The down-regulation of cofilin and F-actin and up-regulation of heat shock protein 27 were observed in the two hepatic artery ischemia groups, while there were no significant differences between the control group and hepatic artery bridging group. CONCLUSION: Hepatic artery ischemia aggravates damage to bile canaliculi, and this damage can be diminished by a hepatic artery bridging duct.

MicroRNA-130a and -130b enhance activation of hepatic stellate cells by suppressing PPARγ expression: A rat fibrosis model study.

Hepatic stellate cells (HSCs) are the primary sources of extracellular matrix (ECM) in normal and fibrotic liver. Peroxisome proliferator-activated receptor gamma (PPARγ) maintains HSCs in a quiescent state, and its downregulation induces HSC activation. MicroRNAs (miRNAs) can induce PPARγ mRNA degradation, but the mechanism by which miRNAs regulate PPARγ in rat HSCs is unclear. This study aimed to investigate some miRNAs which putatively bind to the 3'-untranslated region (3'-UTR) of PPARγ mRNA, and increase expression of ECM genes in rat HSCs. In carbon tetrachloride injection (CCl4) and common bile duct ligation (CBDL) liver fibrosis models, miRNAs miR-130a, miR-130b, miR-301a, miR-27b and miR-340 levels were found to be increased and PPARγ expression decreased. Overexpression of miR-130a and miR-130b enhanced cell proliferation by involving Runx3. MiR-130a and miR-130b decreased PPARγ expression by targeting the 3'-UTR of PPARγ mRNA in rat HSC-T6 cells. Transforming growth factor-ß1 (TGF-ß1) may mediate miR-130a and miR-130b overexpression, PPARγ downregulation, and ECM genes overexpression in cell culture. These findings suggest that miR-130a and miR-130b are involved in downregulation of PPARγ in liver fibrosis.

Sequential vs simultaneous revascularization in patients undergoing liver transplantation: A meta-analysis.

AIM: We undertook this meta-analysis to investigate the relationship between revascularization and outcomes after liver transplantation. METHODS: A literature search was performed using MeSH and key words. The quality of the included studies was assessed using the Jadad Score and the Newcastle-Ottawa Scale. Heterogeneity was evaluated by the χ(2) and I (2) tests. The risk of publication bias was assessed using a funnel plot and Egger's test, and the risk of bias was assessed using a domain-based assessment tool. A sensitivity analysis was conducted by reanalyzing the data using different statistical approaches. RESULTS: Six studies with a total of 467 patients were included. Ischemic-type biliary lesions were significantly reduced in the simultaneous revascularization group compared with the sequential revascularization group (OR = 4.97, 95%CI: 2.45-10.07; P < 0.00001), and intensive care unit (ICU) days were decreased (MD = 2.00, 95%CI: 0.55-3.45; P = 0.007) in the simultaneous revascularization group. Although warm ischemia time was prolonged in simultaneous revascularization group (MD = -25.84, 95%CI: -29.28-22.40; P < 0.00001), there were no significant differences in other outcomes between sequential and simultaneous revascularization groups. Assessment of the risk of bias showed that the methods of random sequence generation and blinding might have been a source of bias. The sensitivity analysis strengthened the reliability of the results of this meta-analysis. CONCLUSION: The results of this study indicate that simultaneous revascularization in liver transplantation may reduce the incidence of ischemic-type biliary lesions and length of stay of patients in the ICU.

Delayed rearterialization unlikely leads to nonanastomotic stricture but causes temporary injury on bile duct after liver transplantation.

Nonanastomotic strictures (NAS) are common biliary complications after liver transplantation (LT). Delayed rearterialization induces biliary injury in several hours. However, whether this injury can be prolonged remains unknown. The correlation of this injury with NAS occurrence remains obscure. Different delayed rearterialization times were compared using a porcine LT model. Morphological and functional changes in bile canaliculus were evaluated by transmission electron microscopy and real-time PCR. Immunohistochemistry and TUNEL were performed to validate intrahepatic bile duct injury. Three months after LT was performed, biliary duct stricture was determined by cholangiography; the tissue of common bile duct was detected by real-time PCR. Bile canaliculi were impaired in early postoperative stage and then exacerbated as delayed rearterialization time was prolonged. Nevertheless, damaged bile canaliculi could fully recover in subsequent months. TNF-α and TGF-ß expressions and apoptosis cell ratio increased in the intrahepatic bile duct only during early postoperative period in a time-dependent manner. No abnormality was observed by cholangiography and common bile duct examination after 3 months. Delayed rearterialization caused temporary injury to bile canaliculi and intrahepatic bile duct in a time-dependent manner. Injury could be fully treated in succeeding months. Solo delayed rearterialization cannot induce NAS after LT.

Duration of exercise as a key determinant of improvement in insulin sensitivity in type 2 diabetes patients.

Exercise duration and intensity are important parameters in exercise prescription and play a major role in improving insulin sensitivity (including transient and persistent improvement effects following cessation of training) in patients with type 2 diabetes mellitus (T2DM). However, whether duration or intensity of exercise is the more important factor has yet to be established. Therefore, we aimed to determine whether exercise prescriptions differing in duration and intensity differ in their ability to aid T2DM patients to retain insulin sensitivity following the conclusion of a period of training. Sedentary T2DM patients (age 51.2 ± 1.3 years) were assigned to either a low-intensity (50% VO(2peak), n = 27) or a high-intensity exercise group (75% VO(2peak), n = 28), and followed a 12-week exercise program of 5 sessions/week and 240 kcal/session. Insulin sensitivity (oral glucose tolerance test, ISI) was measured when subjects were sedentary and at 16-24 h and 15 days after the final training bout. The low-intensity group spent more training time to training per exercise session than the high-intensity group (56.1 ± 3.0 min/session vs. 34.3 ± 2.4 min/session) (P < 0.01), but the total amount of energy expended was the same. ISI was increased in both groups 16-24 h after the final training session, but only the low-intensity group still had elevated ISI 15 days after the cessation of training. These findings suggest that in T2DM patients, the persistent training-induced improvements in insulin sensitivity may be more dependent on exercise duration than exercise intensity in regimens with the same level of energy expenditure.