circRNADisease v2.0: an updated resource for high-quality experimentally supported circRNA-disease associations.

circRNADisease v2.0 is an enhanced and reliable database that offers experimentally verified relationships between circular RNAs (circRNAs) and various diseases. It is accessible at http://cgga.org.cn/circRNADisease/ or http://cgga.org.cn:9091/circRNADisease/. The database currently includes 6998 circRNA-disease entries across multiple species, representing a remarkable 19.77-fold increase compared to the previous version. This expansion consists of a substantial rise in the number of circRNAs (from 330 to 4246), types of diseases (from 48 to 330) and covered species (from human only to 12 species). Furthermore, a new section has been introduced in the database, which collects information on circRNA-associated factors (genes, proteins and microRNAs), molecular mechanisms (molecular pathways), biological functions (proliferation, migration, invasion, etc.), tumor and/or cell line and/or patient-derived xenograft (PDX) details, and prognostic evidence in diseases. In addition, we identified 7 159 865 relationships between mutations and circRNAs among 30 TCGA cancer types. Due to notable enhancements and extensive data expansions, the circRNADisease 2.0 database has become an invaluable asset for both clinical practice and fundamental research. It enables researchers to develop a more comprehensive understanding of how circRNAs impact complex diseases.

Gut Microbiota Control the Bioavailability and Metabolism of Organoarsenicals of Seaweeds in Mice after Oral Ingestion.

Edible seaweed consumption is an essential route of human exposure to complex organoarsenicals, including arsenosugars and arsenosugar phospholipids. However, the effects of gut microbiota on the metabolism and bioavailability of arsenosugars in vivo are unknown. Herein, two nori and two kelp samples with phosphate arsenosugar and sulfonate arsenosugar, respectively, as the predominant arsenic species, were administered to normal mice and gut microbiota-disrupted mice treated with the broad-spectrum antibiotic cefoperazone for 4 weeks. Following exposure, the community structures of the gut microbiota, total arsenic concentrations, and arsenic species in excreta and tissues were analyzed. Total arsenic excreted in feces and urine did not differ significantly between normal and antibiotic-treated mice fed with kelp samples. However, the total urinary arsenic of normal mice fed with nori samples was significantly higher (p < 0.05) (urinary arsenic excretion factor, 34-38 vs 5-7%), and the fecal total arsenic was significantly lower than in antibiotic-treated mice. Arsenic speciation analysis revealed that most phosphate arsenosugars in nori were converted to arsenobetaine (53.5-74.5%) when passing through the gastrointestinal tract, whereas a large portion of sulfonate arsenosugar in kelp was resistant to speciation changes and was excreted in feces intact (64.1-64.5%). Normal mice exhibited greater oral bioavailability of phosphate arsenosugar from nori than sulfonate arsenosugar from kelp (34-38 vs 6-9%). Our work provides insights into organoarsenical metabolism and their bioavailability in the mammalian gut.

Loneliness, Stress, and Depressive Symptoms Among the Chinese Rural Empty Nest Elderly: A Moderated Mediation Analysis.

This study aimed to explore the relationship of loneliness, perceived stress, and depressive symptoms among the Chinese rural empty nest elderly. The role of sense of coherence (SOC) as a moderating variable was investigated in a representative sample of older adults in Henan, China, from November 2016 to February 2017. Results indicated that perceived stress mediated the relationship between loneliness and depressive symptoms, and SOC acted as a moderator on this mediating model. The mediation effect of perceived stress was significant only when SOC was lower. The results emphasized the importance of perceived stress in older adults. SOC was a protective factor with regard to depressive symptoms, and improving SOC should be a focus of health promotion with the elderly.

Psychometric Assessment of the Depressive Cognition Scale Among Older Chinese People.

The study aimed to translate the Depressive Cognition Scale (DCS) into Chinese and to test its reliability and validity among Chinese older people. Using a cross-sectional design, a demographic questionnaire and Chinese versions of the Depressive Cognition Scale (DCS-CHI) and the Center for Epidemiological Studies-Depression Scale (CES-D) were administered. The sample consisted of 1673 older people who were from communities and hospitals. The Cronbach's alpha (α) of DCS-CHI was 0.91, and the test-retest correlation coefficient was 0.91 (95% CI, 0.86-0.95, p<0.001). The Content Validity Index (CVI) was found to be good. Exploratory factor analysis (EFA) resulted in a single factor that explained 58.46% of the total variance and all 8 items had strong factor loadings ranging from 0.62 to 0.83; confirmatory factory analysis (CFA) indicated all measurements of the structural model exceeded the recommended criteria, and the single factor solution of DCS-CHI had a good fit (χ2/df=2.45, GFI=0.99, AGFI=0.97, CFI=0.99, TLI=0.99, RMSEA=0.04, RMR=0.01, PCLOSE=0.79). The strong correlation of 0.81 (p<0.01) between the DCS-CHI and CES-D suggested good concurrent validity. Specifying the CES-D as the criterion, the area under the receiver operator characteristic (ROC) curve of the DCS-CHI for the optimal cut-point was 0.941(95%CI:0.919-0.963, p=0.000), the sensitivity and the specificity were 84.7% and 90.7% respectively, suggesting good predictive validity. The findings support the reliability and validity of the DCS-CHI as a measure of depressive cognitions that typically proceed more serious depressive symptoms among Chinese older adults.

Antifungal Activity of Eucalyptus Oil against Rice Blast Fungi and the Possible Mechanism of Gene Expression Pattern.

Eucalyptus oil possesses a wide spectrum of biological activity, including anti-microbial, fungicidal, herbicidal, acaricidal and nematicidal properties. We studied anti-fungal activities of the leaf oil extracted from Eucalyptus. grandis × E. urophylla. Eleven plant pathogenic fungi were tested based on the mycelium growth rates with negative control. The results showed that Eucalyptus oil has broad-spectrum inhibitory effects toward these fungi. Remarkable morphological and structural alterations of hypha have been observed for Magnaporthe grisea after the treatment. The mRNA genome array of M. grisea was used to detect genes that were differentially expressed in the test strains treated by the Eucalyptus oil than the normal strains. The results showed 1919 genes were significantly affected, among which 1109 were down-regulated and 810 were up-regulated (p < 0.05, absolute fold change >2). According to gene ontology annotation analysis, these differentially expressed genes may cause abnormal structures and physiological function disorders, which may reduce the fungus growth. These results show the oil has potential for use in the biological control of plant disease as a green biopesticide.

Transplanted neural stem cells modulate regulatory T, γδ T cells and corresponding cytokines after intracerebral hemorrhage in rats.

The immune system, particularly T lymphocytes and cytokines, has been implicated in the progression of brain injury after intracerebral hemorrhage (ICH). Although studies have shown that transplanted neural stem cells (NSCs) protect the central nervous system (CNS) from inflammatory damage, their effects on subpopulations of T lymphocytes and their corresponding cytokines are largely unexplored. Here, rats were subjected to ICH and NSCs were intracerebrally injected at 3 h after ICH. The profiles of subpopulations of T cells in the brain and peripheral blood were analyzed by flow cytometry. We found that regulatory T (Treg) cells in the brain and peripheral blood were increased, but γδT cells (gamma delta T cells) were decreased, along with increased anti-inflammatory cytokines (IL-4, IL-10 and TGF-ß) and decreased pro-inflammatory cytokines (IL-6, and IFN-γ), compared to the vehicle-treated control. Our data suggest that transplanted NSCs protect brain injury after ICH via modulation of Treg and γδT cell infiltration and anti- and pro-inflammatory cytokine release.

Interaction of tetracycline and copper co-intake in inducing antibiotic resistance genes and potential pathogens in mouse gut.

The widespread use of copper and tetracycline as growth promoters in the breeding industry poses a potential threat to environmental health. Nevertheless, to the best of our knowledge, the potential adverse effects of copper and tetracycline on the gut microbiota remain unknown. Herein, mice were fed different concentrations of copper and/or tetracycline for 6 weeks to simulate real life-like exposure in the breeding industry. Following the exposure, antibiotic resistance genes (ARGs), potential pathogens, and other pathogenic factors were analyzed in mouse feces. The co-exposure of copper with tetracycline significantly increased the abundance of ARGs and enriched more potential pathogens in the gut of the co-treated mice. Copper and/or tetracycline exposure increased the abundance of bacteria carrying either ARGs, metal resistance genes, or virulence factors, contributing to the widespread dissemination of potentially harmful genes posing a severe risk to public health. Our study provides insights into the effects of copper and tetracycline exposure on the gut resistome and potential pathogens, and our findings can help reduce the risks associated with antibiotic resistance under the One Health framework.

Ultrafast power Doppler imaging for ischemic encephalopathy: A case report.

BACKGROUND: Severely elevated intracranial pressure due to various reasons, such as decreased cerebral perfusion, can lead to devastating neurological outcomes, such as brain herniation. Decompression craniectomy is a life-saving procedure that is commonly performed for such a critical situation, but the changes in cerebral microvessels after brain herniation and decompression are unclear. Ultrafast power Doppler imaging (uPDI) is a new microvascular imaging technology that utilizes high frame rate plane/diverging wave transmission and advanced clutter filters. uPDI significantly improves Doppler sensitivity and can detect microvessels, which are usually invisible using traditional ultrasound Doppler imaging. CASE SUMMARY: In this report, uPDI was used for the first time to observe the brain blood flow of a hypoperfusion area in a 4-year-old girl who underwent decompression craniectomy due to refractory intracranial hypertension (ICP) after malignant brain tumor surgery. B-mode imaging was used to verify the increased densities of the cerebral cortex and basal ganglia that were observed by computed tomography. CONCLUSION: uPDI showed the local blood supplies and anatomical structures of the patient after decompressive craniectomy. uPDI is potentially a more intuitive and noninvasive method for evaluating the effects of severe ICP on cerebral microvessels.

A network pharmacology-based study on Alzheimer disease prevention and treatment of Qiong Yu Gao.

BACKGROUND AND OBJECTIVE: As the pathological mechanisms of AD are complex, increasing evidence have demonstrated Chinese Medicine with multi-ingredients and multi-targets may be more suitable for the treatment of diseases with complex pathogenesis. Therefore, the study was to preliminarily decipher the bioactive compounds and potential mechanisms of Qiong Yu Gao (QYG) for AD prevention and treatment by an integrated network pharmacology approach. METHODS: Putative ingredients of QYG and significant genes of AD were retrieved from public database after screening. Then QYG ingredients target proteins/genes were obtained by target fishing. Compound-target-disease network was constructed using Cytoscape to decipher the mechanism of QYG for AD. KEGG pathway and GO enrichment analysis were performed to investigate the molecular mechanisms and pathways related to QYG for AD treatments. RESULTS: Finally, 70 compounds and 511 relative drug targets were collected. In which, 17 representative direct targets were found. Gene ontology enrichment analysis revealed that the adenylate cyclase-inhibiting G-protein coupled acetylcholine receptor signaling pathway was the key biological processes and were regulated simultaneously by the 17 direct targets. The KEGG pathway enrichment analysis found that three signaling pathways were closely related to AD prevention and treatment by QYG, including PI3K-Akt signaling pathway, regulation of actin cytoskeleton pathway and insulin resistance pathway. CONCLUSION: This study demonstrated that QYG exerted the effect of preventing and treating AD by regulating multi-targets with multi-components. Furthermore, the study demonstrated that a network pharmacology-based approach was useful for elucidation of the interrelationship between complex diseases and interventions of Chinese herbal medicines.

The susceptibility of three strains of Chinese minipigs to diet-induced type 2 diabetes mellitus.

Researchers have extensively used animal models to study diabetes mellitus. In this study, the authors determined the susceptibility of three strains of Chinese minipigs to diet-induced type 2 diabetes mellitus. For 8 months, the researchers fed Nongda control minipigs (n=4) a normal diet and fed Bama, Wuzhishan and Nongda minipigs (n=6 per group) a high-sucrose, high-fat diet. They measured the minipigs' body weights, fasting serum glucose concentrations and insulin concentrations each month. Every 2 months, they measured serum triglyceride, cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels and carried out intravenous glucose tolerance tests (IVGTTs). The Bama and Wuzhishan minipigs were relatively susceptible to diabetes induced by the high-sucrose, high-fat diet, though susceptibility differed among individual animals in the same strain. On the other hand, Nongda minipigs were relatively resistant to diet-induced diabetes. These results provide a foundation for diabetes-related genetic analyses in minipigs with high and low susceptibility to diet-induced type 2 diabetes.

Locomotive function and quality of life among older people in Liaoning, China: Falls efficacy as mediator or moderator?

OBJECTIVES: This study aimed to examine the role of falls efficacy in the relationship between the locomotive function and quality of life. METHODS: From March to May in 2016, we conducted a cross-sectional survey among 830 community residents aged ≥60 years from Jinzhou,China.GLFS-25 (25-question Geriatric Locomotive Function Scale), FES-I(International edition of Falls Efficacy Scale),and SF-12 (12-item Short Form Health Survey) were used to estimate locomotive function, falls efficacy and quality of life, respectively. The higher score of GLFS-25, the worse the locomotive function. RESULTS: Median age was 68.69 years (ranges 60-88). Locomotive function, falls efficacy and quality of life all presented a linear relationship within each other, locomotive function score was negatively correlated with falls efficacy score (-0.461, P < 0.01). locomotive function score was negatively correlated with quality of life score (-0.523, P < 0.01).Falls efficacy score was positively correlated with quality of life score (0.415, P < 0.01).Falls efficacy exerted both a mediating and moderating role between locomotive function and quality of life, and the mediation effect accounted for 45.5% of the total effect. CONCLUSIONS: Poorer locomotive function was associated with poorer quality of life, and greater falls efficacy was associated with better quality of life. In addition, falls efficacy was demonstrated to be both a mediator and moderator variable in the linkage between locomotive function and quality of life. Aged care professional practitioners and our policy makers should strengthen the awareness of the psychological role of the elderly falls efficacy.

[Effects of lung protective ventilation in prone or supine position on inhibiting adrenomedullin release in acute respiratory distress syndrome caused by pulmonary and extra-pulmonary insults in dog].

OBJECTIVE: To investigate the changes in adrenomedullin release in bronchial alveolar lavage fluid (BALF) from different lung areas in acute respiratory distress syndrome (ARDS) of produced dogs, by pulmonary and extra-pulmonary causes, with low tidal volume and positive end expiratory pressure (PEEP) treatment under supine and prone position. METHODS: Twenty-four male mongrel dogs were randomly divided into ARDSp (ARDS caused by pulmonary causes) supine group, ARDSp prone group, ARDSexp (ARDS caused by extra-pulmonary causes) supine group, and ARDSexp prone group. A detergent to cause lung injury in ARDSp dogs, and intravenous oleic acid was given in ARDSexp dogs. The results of adrenomedullin in different areas of dog's lung (upper lobe, middle lobe, and lower lobe) and arterial blood gas under lung protective ventilation treatment were measured. RESULTS: After lung injury, the arterial oxygenation index was lowered, and the levels of adrenomedullin in the upper lobe and middle lobe of ARDSp dogs were higher than that of ARDSexp dogs. After receiving low tidal volume and PEEP ventilation, the conditions of all the dogs were gradually getting ameliorated, and prone position ventilation gave better effects on lung injury dogs by inhibiting adrenomedullin release. CONCLUSION: There are statistical differences in adrenomedullin release in different lung areas between ARDSp dogs and ARDSexp dogs, and in both ARDSexp dogs and ARDSp dogs low tidal volume and PEEP treatment under prone position ventilation give better results compared to supine position.

Comparative pharmacokinetics and bile transformation of R-enantiomer and racemic bambuterol after single-dose intravenous, oral administration in rats and beagle dogs.

This study was to compare pharmacokinetics and bile transformation of R-enantiomer bambuterol with its racemate. Pharmacokinetics of R-enantiomer was investigated after single-dose intravenous and three doses of oral administration to rats and beagle dogs. To compare the pharmacokinetics with racemic bambuterol, the same oral doses of racemic bambuterol were also administrated; the blood and bile samples were collected by cannulation. A validated LC-MS/MS method was used to assess the level of bambuterol in plasma and bile. After single intravenous administration, no significant differences were observed between the two drugs in pharmacokinetic data. After oral dosing of R-bambuterol, the AUCs of R-enantiomer presented linear correlation. After same oral dosing of R-enantiomer and its racemate, all the pharmacokinetic parameters were equivalent. However, the clearance and apparent distribution had different results due to species and administration route difference. The bile transformation of these two compounds was similar and implicated that liver transformation accounted for the major metabolism of them. The bioavailability of R-enantiomer and racemate were comparative and relatively high in beagle dogs. Thus, R-enantiomer had a comparative pharmacokinetic profile and bile transformation with racemic bambuterol in rats and beagle dogs. These findings provided references for further clinical study.

[Effects of prone position ventilation on inflammatory factors in blood and bronchial alveolar lavage fluid of acute respiratory distress syndrome dogs caused by pulmonary and extrapulmonary insults].

OBJECTIVE: To observe the changes of inflammatory factors in blood and bronchial alveolar lavage fluid (BALF) of different lung areas of acute respiratory distress syndrome (ARDS) dogs caused by pulmonary and extra-pulmonary causes with low tidal volume and positive end expiratory pressure (PEEP) treatment under prone position ventilation. METHODS: 24 male mongrel dogs were randomly divided into 4 equal groups:ARDSp (ARDS caused by pulmonary causes) experimental group, ARDSp control group, ARDSexp (ARDS caused by extra-pulmonary causes) experimental group, and ARDSexp control group. The ARDSp dogs inspired detergent to cause lung injury, and the ARDSexp dogs were injected with oleic acid through central vein. The results of TNF-alpha, IL-1beta, and IL-6 of blood and BALF in different areas of dog's lung (upper lobe, heart lobe, and diaphragm lobe) and arterial blood gas under lung protective ventilation treatment were measured. RESULTS: After lung injury, the arterial oxygenation index as decreased, and the values of TNF-alpha, IL-1beta, and IL-6 in plasma were obviously getting higher in all groups. The values of inflammatory factors in the BALF from upper lobe and heart lobe of ARDSp dogs were significantly higher than those of the ARDSexp dogs. After receiving low tidal volume and PEEP ventilation under prone position, all dogs were gradually getting ameliorated. CONCLUSION: There are statistically those of the differences in inflammatory factor releasing in different lung areas between the ARDSp dogs and ARDSexp dogs, and low tidal volume and PEEP treatment under prone position ventilation shows good effects both on ARDSexp dogs and ARDSp dogs.

[Experiment study of infusing tPA in retinal vein for treatment of retinal vein occlusion].

OBJECTIVE: To Investigate the effectiveness and complications of injection of tissue plasminogen activator into a retinal vein for treatment of retinal vein occlusion via micropuncture of the retinal vein. METHODS: Thirty miniature pigs (one eye of each pig) were produced photodynamic thrombi of retinal vein by injecting Rose bengal (20 mg/kg) into the ear vein, and randomly divided into three groups: 1. control (n = 8), 2. infusion of sterile water (n = 8) or 3. infusion of tissue-type plasminogen activator (n = 14) in obstructed retinal vein. In the first group no micropuncture of retinal vein was performed. In the others micropuncture of retinal vein were performed by a micromanipulator that we designed and sterile water was infused in retinal vein in the second group or tissue-type plasminogen activator was infused in the third one. Fluorescent angiography and histological study were performed to document the morphological alterations with clinical observations. RESULTS: 18 eyes were successfully performed micropuncture of retinal vein in the 22 eyes (81.4%). Except stopping operation due to surgical accident, there were 7 eyes that the thrombi were lysed in 9 eyes by infusion of tissue-type plasminogen activator in obstructed retinal vein (77.8%). If the micropipette was not accurate for puncturing the vessels, the vessels' wall could be ruptured and hemorrhage appeared. If thrombi of retinal veins were lysed, no bleeding and no leakage of the infused drug were observed from the site of micropuncture after micropipette was withdrawn from the vessel. Sterile water failed to flush the clot downstream. When the thrombus failed to be dislodged, the infusion fluid would back flow into the distal retinal vein and, an exudative retinal detachment would occur. In the first group, the retina exhibited hemorrhages and edema due to the vein occluded. In the second group, sterile water resulted in exaggerated retinal edema and exudative retinal detachment. In the third group, after thrombi of retinal veins were lysed, the hemorrhages and edema of retinal tissues were reduced significantly in few days. CONCLUSIONS: Infusing thrombolytic agents into the thrombosed retinal vein is a new method for treatment of retinal vein occlusion. This surgery must performed accurately by a special design. This study demonstrated that the rate and dose of thrombolytic agents infused in retinal vein should be limited in case of injuring retina tissues.

[Experimental retinal vein occlusion induced by photodynamic approach].

OBJECTIVE: To develop a new photochemical method of experimental retinal vein occlusion and investigate the morphologic and histologic changes in the retina. METHODS: After intravenous injection of rose Bengal, the vessels next to the disc of miniature pigs in the experiment group (n = 15) were exposed to an endo-illuminator for 15 minutes. As a control group, the vessels next to the disc of each pig were exposed to the endo-illuminator without rose Bengal injection. After complete vascular occlusion, the eyes were observed at following times: one hour, and 1, 3, 7, 14, 21, and 28 days. After the 28th day, the eyes were enucleated and prepared for light and electron microscope examination. RESULTS: Histopathologic features were consistent with changes of retinal vein occlusion and formation of retinal vein thrombi was reliable. CONCLUSIONS: Photodynamic method combined with endo-illuminator was a simple, reliable and definitive experimental technique to produce retinal vein occlusion.

Immune responses of orange-spotted grouper, Epinephelus coioides, against virus-like particles of betanodavirus produced in Escherichia coli.

Betanodaviruses are the causative agents of viral nervous necrosis (VNN), a serious disease of cultured marine fish worldwide. Virus-like particles (VLPs) are one of the good novel vaccine candidates to control this disease. Until now, betanodavirus vaccine studies mainly focused on the humoral immune response and mortality after virus challenge. However, little is known about the activation of genes responsible for cellular and innate immunity by vaccines. In the present study, VLPs of orange-spotted grouper nervous necrosis virus (OGNNV) were produced in prokaryotes and their ability to enter Asian sea bass cells was the same as native virus, suggesting that they possess a similar structure to OGNNV. VLPs immunogenicity was then determined by intramuscularly vaccinating Epinephelus coioides at different concentrations (1.5 or 15 µg g(-1) fish body weight, FBW) and immunizing frequencies (administration once, twice and thrice). A single vaccination with the dosage of 1.5 µg g(-1) FBW is enough to provoke high titer antibodies (average 3 fold higher than that of negative control) with strong neutralizing antibody titer as early as 1 week post immunization. Furthermore, quantitative PCR analysis revealed that eleven genes associated with humoral, cellular and innate immunities were up-regulated in the liver, spleen and head kidney at 12h post immunization, correlating with the early antibody response. In conclusion, we demonstrated that VLP vaccination induced humoral immune responses and activated genes associated with cellular and innate immunity against betanodavirus infection in orange-spotted grouper.

Genome-wide analyses of proliferation-important genes of Iridovirus-tiger frog virus by RNAi.

Tiger frog virus (TFV), a species of genus Ranavirus in the family Iridoviridae, is a nuclear cytoplasmic large DNA virus that infects aquatic vertebrates such as tiger frog (Rana tigrina rugulosa) and Chinese soft-shelled turtle (Trionyx sinensis). Based on the available genome sequences of TFV, the well-developed RNA interference (RNAi) technique, and the reliable cell line for infection model, we decided to analyze the functional importance of all predicted genes. Firstly, a relative quantitative cytopathogenic effect (Q-CPE) assay was established to monitor the viral proliferation in fish cells. Then, genome-wide RNAi screens of 95 small interference (si) RNAs against TFV were performed to characterize the functional importance of nearly all (95%) predicted TFV genes by Q-CPE scaling system. We identified 32 (33.7%) genes as essential, 50 (52.6%) genes as semi-essential and 13 (13.7%) genes as nonessential for TFV proliferation. Quantitative RT-PCR and titer assays of selected genes were performed to verify the screen results. Furthermore, the screened essential genes were analyzed for their genome distribution and conservative comparison within Ranavirus. Such a systematic screen for viral functional genes by cell phenotypes should provide further insights into understanding of the information in antiviral targets, and in viral replication and pathogenesis of iridovirus.

Effects of γ-synuclein on the tumorigenicity and metastasis of colon cancer SW1116 cells in vitro and in vivo.

Recent evidence suggests the involvement of γ-synuclein in tumorigenesis and tumor progression. The present study was designed to further clarify the effects of γ-synuclein on the biological features of colon cancer cells in vitro and in vivo. We constructed the eukaryotic expression vector and siRNA vector and selected stable transfectants to respectively upregulate and downregulate γ-synuclein expression in SW1116 cells. we found that silencing of γ-synuclein significantly attenuated SW1116 cell growth and colony formation in vitro (P<0.05), and overexpression of γ-synuclein moderately enhanced cell growth and colony formation, but not significantly when compared with the parental SW1116 cells and empty vector-transfected cells (P>0.05). Meanwhile, overexpression of γ-synuclein significantly facilitated SW1116 cell migration, invasion and adhesion to human liver sinusoidal endothelial cells (HLSECs) in vitro (P<0.05), and the effects were less attenuated by γ-synuclein knockdown (P>0.05). Furthermore, γ-synuclein promoted these malignant phenotypes in a γ-synuclein expression quantity-dependent manner not only in vitro but also in the in vivo expression. stable cells were injected subcutaneously into the right flank, and injected intrasplenically in nude mice. γ-synuclein knockdown suppressed the tumorigenicity of SW1116 cells in mice, which presented significantly smaller tumor masses on day 6 over a 30-day period, compared with empty vector cells (P<0.05). Meanwhile, overexpression of γ-synuclein led to a profound augmentation of liver metastasis in nude mice, not only in macroscopic appearance but also in the size and weight of livers (P<0.05). These results provide strong evidence that suggests γ-synuclein plays a positive role in the progression of colorectal cancer.

Inhalation of hydrogen gas reduces liver injury during major hepatotectomy in swine.

AIM: To study the effect of H2 gas on liver injury in massive hepatectomy using the intermittent Pringle maneuver in swine. METHODS: Male Bama pigs (n = 14) treated with ketamine hydrochloride and Sumianxin II as induction drugs followed by inhalation anesthesia with 2% isoflurane, underwent 70% hepatotectomy with loss of bleeding less than 50 mL, and with hepatic pedicle occlusion for 20 min, were divided into two groups: Hydrogen-group (n = 7), the pigs with inhalation of 2% hydrogen by the tracheal intubation during major hepatotectomy; contrast-group (n = 7), underwent 70% hepatotectomy without inhalation of hydrogen. Hemodynamic changes and plasma concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and malondialdehyde (MDA) in liver tissue were measured at pre-operation, post-hepatotectomy (PH) 1 h and 3 h. The apoptosis and proliferating cell nuclear antigen (PCNA) expression in liver remnant were evaluated at PH 3 h. Then we compared the two groups by these marks to evaluate the effect of the hydrogen in the liver injury during major hepatotectomy with the Pringle Maneuver in the swine. RESULTS: There were no significant differences in body weight, blood loss and removal liver weight between the two groups. There was no significant difference in changes of portal vein pressure between two groups at pre-operation, PH 30 min, but in hydrogen gas treated-group it slightly decrease and lower than its in contrast-group at PH 3 h, although there were no significant difference (P = 0.655). ALT and AST in Hydrogen-group was significantly lower comparing to contrast-group (P = 0.036, P = 0.011, vs. P = 0.032, P = 0.013) at PH 1 h and 3 h, although the two groups all increased. The MDA level increased between the two group at PH 1 h and 3 h. In the hydrogen gas treated-group, the MDA level was not significantly significant at pre-operation and significantly low at PH 1 h and 3 h comparing to Contrast-group (P = 0.0005, P = 0.0004). In Hydrogen-group, the HA level was also significantly low to contrast-group (P = 0.0005, P = 0.0005) although the two groups all increased at PH 1 h and 3 h. The expression of cluster of differentiation molecule 31 molecules Hydrogen-group was low to Contrast-group. However, PCNA index (%) was not statistically significant between the two groups (P = 0.802). Microphotometric evaluation of apoptotic index (AI) in terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-stained tissue after hepatotectomy for 3h, the AI% level in the hydrogen was significantly low to contrast-group (P = 0.012). There were no significant difference between Hydrogen-group and contrast-group at pre-operation (P = 0.653, P = 0.423), but after massive hepatotectomy, the TNF-α and IL-6 levels increase, and its in Hydrogen-group was significantly low compared with contrast-group (P = 0.022, P = 0.013, vs. P = 0.016, P = 0.012), respectively. Hydrogen-gas inhalation reduce levels of these markers and relieved morphological liver injury and apoptosis. CONCLUSION: H2 gas attenuates markedly ischemia and portal hyperperfusion injury in pigs with massive hepatotectomy, possibly by the reduction of inflammation and oxidative stress, maybe a potential agent for treatment in clinic.