Objective To explore the effect and mechanism of ursolic acid (UA) extracted from Hippophae rhamnoides L.on alcohol-induced liver disease in rats. Methods Fifty male Wistar rats (SPF)were randomly divided into five groups:normal control group,model control group,low-,medium- and high-dose UA group,10 rats in each group.The rats were administered by intragastric administration for eight consecutive weeks.After 12 hours of last administration,blood was collected by abdominal aorta and the liver was obtained for histopathological and biochemical assays.The levels of ALT and AST in serum was detected.The content of TG in liver homogenate was determined.The morphological changes of hepatic tissue in rats were observed by HE staining.The apoptotic rate of rat liver cells was detected by TUNEL method.The protein expressions of Bcl-2,Bax and cleaved caspase-3 in liver tissue were detected by Western blotting. Results In model control group,HE staining showed that the hepatic cord was arranged disorderly,and there were lots of vacuoles in the cytoplasm of hepatocytes.The inflammatory cells in the liver tissue gathered,and the hepatocytes showed flake necrosis in model control group. Compared with model control group,ursolic acid significantly improved the steatosis of the liver.In the UA group,infiltration and necrosis of inflammatory cells were significantly decreased,the tissue structure tended to be normal,and the activity of serum ALT,AST,and the content of TG in the medium- and high-dose UA group liver tissue were significantly decreased (P<0.05).TUNEL results showed that the number of positive cells and the apoptosis index of hepatocytes in the high dose of UA group were significantly lower than in model control group (P<0.05).Western blotting results showed that the protein expression of Bcl-2 in liver tissue of UA groups was significantly increased,the protein expression of Bax was significantly decreased,and the protein expression of cleaved caspase-3 was increased,compared with model control group. Conclusion Ursolic acid extracted from Hippophae rhamnoides L.could improve the liver injury induced by alcohol.The mechanism might be related to the regulation the protein expressions of Bcl-2,Bax and cleaved caspase-3,key proteins of apoptosis,thereby inhibiting the abnormal apoptosis of hepatocytes.
Fig.1
Histopathological structure of the livers(×400) A.normal control group;B.model control group;C.high-dose ursolic acid group;D.medium-dose ursolic acid group;E.low-dose ursolic acid group.
①Compared with normal control group,t=-8.752--3.912,P<0.05;②Compared with model control group,t=2.107-7.785,P<0.05;③Compared with low-dose ursolic acid group,t=1.762-3.388,P<0.05.
表1
5组大鼠血清ALT、AST及肝脏TG含量比较
Tab.1
Comparison of the serum levels of ALT,AST and hepatic TG contents among five groups of rats $\overline{x}$±s,n=10
Fig.2
Hepatocyte apoptosis in five groups of rats(TUNEL,×200) A.normal control group;B.model control group;C.high-dose ursolic acid group;D.medium-dose ursolic acid group;E.low-dose ursolic acid group.
Fig.3
Comparison of hepatocyte apoptosis rate among five groups of rats($\overline{x}$±s,n=10) A.normal control group;B.model control group;C.high-dose ursolic acid group;D.medium-dose ursolic acid group;E.low-dose ursolic acid group.①Compared with normal control group,t=-69.823--9.457,P<0.05;②Compared with model control group,t=3.561-17.611,P<0.05;③Compared with low-dose ursolic acid group,t=-6.767,P<0.05.
Fig.4
Comparison of Bcl-2,Bax and cleaved caspase-3 protein expression in liver tissue among five groups of rats($\overline{x}$±s,n=10) A.normal control group;B.model control group;C.high-dose ursolic acid group;D.medium-dose ursolic acid group;E.low-dose ursolic acid group.①Compared with normal control group,t=-19.682-12.778,P<0.05;②Compared with model control group,t=-14.409-20.195,P<0.05;③Compared with low-dose ursolic acid group,t=-11.288-15.734,P<0.05.
PEACOCKA,LEUNGJ,LARNEYS.Global statistics on alcohol,tobacco and illicit drug use:2017 status report[J].Addiction,2018,113(10):1905-1926.
AIMS: This review provides an up-to-date curated source of information on alcohol, tobacco and illicit drug use and their associated mortality and burden of disease. Limitations in the data are also discussed, including how these can be addressed in the future. METHODS: Online data sources were identified through expert review. Data were obtained mainly from the World Health Organization, United Nations Office on Drugs and Crime and Institute for Health Metrics and Evaluation. RESULTS: In 2015, the estimated prevalence among the adult population was 18.4% for heavy episodic alcohol use (in the past 30 days); 15.2% for daily tobacco smoking; and 3.8, 0.77, 0.37 and 0.35% for past-year cannabis, amphetamine, opioid and cocaine use, respectively. European regions had the highest prevalence of heavy episodic alcohol use and daily tobacco use. The age-standardized prevalence of alcohol dependence was 843.2 per 100 000 people; for cannabis, opioids, amphetamines and cocaine dependence it was 259.3, 220.4, 86.0 and 52.5 per 100 000 people, respectively. High-income North America region had among the highest rates of cannabis, opioid and cocaine dependence. Attributable disability-adjusted life-years (DALYs) were highest for tobacco smoking (170.9 million DALYs), followed by alcohol (85.0 million) and illicit drugs (27.8 million). Substance-attributable mortality rates were highest for tobacco smoking (110.7 deaths per 100 000 people), followed by alcohol and illicit drugs (33.0 and 6.9 deaths per 100 000 people, respectively). Attributable age-standardized mortality rates and DALYs for alcohol and illicit drugs were highest in eastern Europe; attributable age-standardized tobacco mortality rates and DALYs were highest in Oceania. CONCLUSIONS: In 2015 alcohol use and tobacco smoking use between them cost the human population more than a quarter of a billion disability-adjusted life years, with illicit drugs costing further tens of millions. Europeans suffered proportionately more, but in absolute terms the mortality rate was greatest in low- and middle-income countries with large populations and where the quality of data was more limited. Better standardized and rigorous methods for data collection, collation and reporting are needed to assess more accurately the geographical and temporal trends in substance use and its disease burden.
XIAOJ,WANGF,WONG NK,et al.Global liver disease burdens and research trends:analysis from a China perspective[J].J Hepatol,2019,71(1):212-221.
Liver diseases affect millions of people worldwide. In most developed countries, the incidence of viral hepatitis is waning as a result of modern advances in disease prevention, diagnosis, and therapies. Expanded programmes for systematic immunisation against hepatitis B virus have also significantly brought down the number of new cases in many countries, including China. In contrast, with the improvement in living standards, the prevalence of metabolic liver diseases including non-alcoholic fatty liver disease and alcohol-related liver disease is set to rise, ultimately leading to more cases of end-stage liver diseases (liver failure, cirrhosis, and liver cancer). Over the past 30years, visionary governments of major nations have provided strong incentives for basic/clinical research, vaccination programmes, and drug discovery and development in the field of hepatology. To get rid of her unflattering title as the
OLASB,KONTEKB,SZCZESNAM,et al.Inhibition of blood platelet adhesion by phenolics' rich fraction of Hippophae rhamnoides L.fruits[J].J Physiol Pharmacol,2017,68:223-229.
Beneficial influence of fruits on human health may be their ability to prevent the hyperactivation of blood platelets and cardiovascular disorders. Effects of the phenolic fraction from Hippophae rhamnoides fruit on different stages of blood platelet activation (platelet adhesion and aggregation) were studied in vitro. We also examined effects of the H. rhamnoides fraction on metabolism of thiol groups, which plays an important role in platelet functions. The effects of the H. rhamnoides fraction on adhesion of blood platelets to collagen and fibrinogen were determined with Tuszynski's and Murphy's method. The platelet aggregation was determined with turbidimetry. The action of the H. rhamnoides fraction on the level of thiol groups in platelet proteins and a level of glutathione (GSH) in platelets was estimated with 5,5'-dithio-bis(2-nitro-benzoic acid). The tested fraction of H. rhamnoides (0.5 - 50 mug/ml; 30 min of the incubation time 30 min) inhibited blood platelets adhesion to collagen and fibrinogen. The effect of the tested fraction on blood platelet adhesion depended on concentration of fraction. In presence of the highest tested concentration which was 50 mug/ml, inhibition of platelet adhesion for thrombin-activated platelets was about 55%. On the other hand, tested plant fraction had no anti-aggregatory properties. Our results showed anti-adhesive properties of phenolic fraction from H. rhamnoides fruit and we suggest that it may be beneficial for prevention of cardiovascular diseases.
SEO DY,LEE SR,HEO JW,et al.Ursolic acid in health and disease[J].Korean J Physiol Pharmacol,2018,22(3):235-248.
Ursolic acid (UA) is a natural triterpene compound found in various fruits and vegetables. There is a growing interest in UA because of its beneficial effects, which include anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-carcinogenic effects. It exerts these effects in various tissues and organs: by suppressing nuclear factor-kappa B signaling in cancer cells, improving insulin signaling in adipose tissues, reducing the expression of markers of cardiac damage in the heart, decreasing inflammation and increasing the level of anti-oxidants in the brain, reducing apoptotic signaling and the level of oxidants in the liver, and reducing atrophy and increasing the expression levels of adenosine monophosphate-activated protein kinase and irisin in skeletal muscles. Moreover, UA can be used as an alternative medicine for the treatment and prevention of cancer, obesity/diabetes, cardiovascular disease, brain disease, liver disease, and muscle wasting (sarcopenia). In this review, we have summarized recent data on the beneficial effects and possible uses of UA in health and disease managements.
OSNA NA,DONOHUET M J R,KHARBANDAK K.Alcoholic liver disease:pathogenesis and current management[J].Alcohol Res,2017,38(2):147-161.
Excessive alcohol consumption is a global healthcare problem. The liver sustains the greatest degree of tissue injury by heavy drinking because it is the primary site of ethanol metabolism. Chronic and excessive alcohol consumption produces a wide spectrum of hepatic lesions, the most characteristic of which are steatosis, hepatitis, and fibrosis/cirrhosis. Steatosis is the earliest response to heavy drinking and is characterized by the deposition of fat in hepatocytes. Steatosis can progress to steatohepatitis, which is a more severe, inflammatory type of liver injury. This stage of liver disease can lead to the development of fibrosis, during which there is excessive deposition of extracellular matrix proteins. The fibrotic response begins with active pericellular fibrosis, which may progress to cirrhosis, characterized by excessive liver scarring, vascular alterations, and eventual liver failure. Among problem drinkers, about 35 percent develop advanced liver disease because a number of disease modifiers exacerbate, slow, or prevent alcoholic liver disease progression. There are still no FDA-approved pharmacological or nutritional therapies for treating patients with alcoholic liver disease. Cessation of drinking (i.e., abstinence) is an integral part of therapy. Liver transplantation remains the life-saving strategy for patients with end-stage alcoholic liver disease.
GEN,LIANGH,ZHAO YY,et al.Aplysin protects against alcohol-induced liver injury via alleviating oxidative damage and modulating endogenous apoptosis-related genes expression in rats[J].J Food Sci,2018,83(10):2612-2621.
We investigated the protective effects and possible mechanisms of Aplysin against alcohol-induced liver injury. Rats were given daily either alcohol only (alcohol model group; 8 to 12 mL/kg body weight), one of three doses of Aplysin (50, 100, or 150 mg/kg Aplysin) plus alcohol, or volume-matched saline. After 6 weeks, the effects of Aplysin were assessed in terms of changes in histology, biochemical indices, and DNA oxidative damage. Potential mechanisms were analyzed through measurements of lipid peroxidation, antioxidant defense systems, expression of cytochrome P450 2E1, and expression of apoptosis-related genes. We found that Aplysin significantly protected the liver against alcohol-induced oxidative injury, evidenced by improved hepatic histological structure, inhibited alcohol-induced elevation of serum biochemical indices, attenuated extents of hepatocellular DNA damage. At a mechanistic level, Aplysin alleviated alcohol-induced oxidative stress as illustrated by the revivification of erythrocyte membrane fluidity, the attenuation of glutathione depletion, the restoration of antioxidase activities, and reduced malondialdehyde overproduction. Furthermore, the mRNA levels of Bax, cytochrome c, and cytochrome P450 2E1 were significantly down-regulated, whereas those of Bcl-2 and caspase-9 and caspase-3 were markedly up-regulated. These findings suggest that Aplysin provides significant protection against alcohol-induced liver injury, possibly through alleviating oxidative damage and modulating endogenous apoptosis-related genes expression. PRACTICAL APPLICATION: Many natural components derived from alga have been used in the food, cosmetics, and biomedicine industries. Aplysin, a marine bromosesquiterpene, was extracted from the red alga Laurencia tristicha, which could effectively protect against alcohol-induced liver injury, might be a potential natural sources for preventing alcoholic liver damage.
SZABOG,PETRASEKJ.Gut-liver axis and sterile signals in the development of alcoholic liver disease[J].Alcohol Alcohol,2017,52(4):414-424.
Background: Innate immunity plays a critical role in the development of alcohol-induced liver inflammation. Understanding the inter-relationship of signals from within and outside of the liver that trigger liver inflammation is pivotal for development of novel therapeutic targets of alcoholic liver disease (ALD). Aim: The aim of this paper is to review recent advances in the field of alcohol-induced liver inflammation. Methods: A detailed literature review was performed using the PubMed database published between January 1980 and December 2016. Results: We provide an update on the role of intestinal microbiome, metabolome and the gut-liver axis in ALD, discuss the growing body of evidence on the diversity of liver macrophages and their differential contribution to alcohol-induced liver inflammation, and highlight the crucial role of inflammasomes in integration of inflammatory signals in ALD. Studies to date have identified a multitude of new therapeutic targets, some of which are currently being tested in patients with severe alcoholic hepatitis. These treatments aim to strengthen the intestinal barrier, ameliorate liver inflammation and augment hepatocyte regeneration. Conclusion: Given the complexity of inflammation in ALD, multiple pathobiological mechanisms may need to be targeted at the same time as it seems unlikely that there is a single dominant pathogenic pathway in ALD that would be easily targeted using a single target drug approach. Short summary: Here, we focus on recent advances in immunopathogenesis of alcoholic liver disease (ALD), including gut-liver axis, hepatic macrophage activation, sterile inflammation and synergy between bacterial and sterile signals. We propose a multiple parallel hit model of inflammation in ALD and discuss its implications for clinical trials in alcoholic hepatitis.
CARTER AR,BORGES MC,BENNM,et al.Combined association of body mass index and alcohol consumption with biomarkers for liver injury and incidence of liver disease:a mendelian randomization study[J].JAMA Netw Open,2019,2(3):e190305.
Importance: Individually, higher body mass index (BMI) and alcohol consumption increase the risk of liver disease. Evidence of a joint association is mixed; however, previous studies have not used causal inference methods robust to confounding and reverse causation. Understanding any true effect is key to developing effective interventions to reduce liver disease. Objective: To investigate the joint association of BMI and alcohol consumption with liver injury biomarkers and incident liver disease using factorial mendelian randomization (MR). Design, Setting, and Participants: A population-based cohort study (Copenhagen General Population Study) recruited a random sample of Copenhagen, Denmark, residents aged 20 years or older of white, Danish descent (N = 98 643) between November 25, 2003, and July 1, 2014. Data were also obtained from ongoing links to national registers, and then analyzed from September 30, 2016, to April 23, 2018. Exposures: High and low BMI and alcohol consumption categories from baseline-measured or self-reported observational data and genetic variants predicting BMI and alcohol consumption. Main Outcomes and Measures: Plasma biomarkers of liver injury (alanine aminotransferase [ALT] and gamma-glutamyltransferase [GGT]) and incident cases of liver disease from hospital records were the outcomes. Results: Of the 98643 individuals recruited, 91552 (54 299 [45.2%] women; mean [SD] age, 58 [13.05] years) with no baseline liver disease were included in main analyses. Individuals had a mean (SD) BMI of 26.2 (4.3) and consumed a mean (SD) of 10.6 (10.2) U/wk of alcohol. In factorial MR analyses, considering the high BMI/high alcohol group as the reference, mean circulating ALT and GGT levels were lowest in the low BMI/low alcohol group (ALT: -2.32%; 95% CI, -4.29% to -0.35%, and GGT: -3.56%; 95% CI, -5.88% to -1.24%). Individuals with low BMI/high alcohol use and high BMI/low alcohol use also had lower mean circulating ALT levels (low BMI/high alcohol use: -1.31%; 95% CI, -1.88% to -0.73%, and high BMI/low alcohol use: -0.81%; 95% CI, -2.86% to 1.22%) and GGT levels (low BMI/high alcohol use: -0.91%; 95% CI, -1.60% to -0.22%, and high BMI/low alcohol use: -1.13%; 95% CI, -3.55% to 1.30%) compared with the high BMI/high alcohol use reference group. These patterns were similar in multivariable factorial analyses. For incident liver disease (N = 580), factorial MR results were less conclusive (odds ratio of liver disease vs high BMI/high alcohol group: 1.01; 95% CI, 0.84 to 1.18, for the low BMI/high alcohol group, 1.22; 95% CI, 0.56 to 1.88 for the high BMI/low alcohol group, and 0.99 (95% CI, 0.41 to 1.56 for the low BMI/low alcohol group). Conclusions and Relevance: Interventions to reduce both BMI and alcohol consumption might reduce population levels of biomarkers of liver injury more than interventions aimed at either BMI or alcohol use alone. However, it is not clear whether this intervention will directly translate to a reduced risk of liver disease.
SINGHS,OSNA NA,KHARBANDA KK.Treatment options for alcoholic and non-alcoholic fatty liver disease:A review[J].World J Gastroenterol,2017,23(36):6549-6570.
Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are serious health problems worldwide. These two diseases have similar pathological spectra, ranging from simple steatosis to hepatitis to cirrhosis and hepatocellular carcinoma. Although most people with excessive alcohol or calorie intake display abnormal fat accumulation in the liver (simple steatosis), a small percentage develops progressive liver disease. Despite extensive research on understanding the pathophysiology of both these diseases there are still no targeted therapies available. The treatment for ALD remains as it was 50 years ago: abstinence, nutritional support and corticosteroids (or pentoxifylline as an alternative if steroids are contraindicated). As for NAFLD, the treatment modality is mainly directed toward weight loss and co-morbidity management. Therefore, new pathophysiology directed therapies are urgently needed. However, the involvement of several inter-related pathways in the pathogenesis of these diseases suggests that a single therapeutic agent is unlikely to be an effective treatment strategy. Hence, a combination therapy towards multiple targets would eventually be required. In this review, we delineate the treatment options in ALD and NAFLD, including various new targeted therapies that are currently under investigation. We hope that soon we will be having an effective multi-therapeutic regimen for each disease.
ZWOLAKA,SURDACKAA,DANILUKJ.Bcl-2 and Fas expression in peripheral blood leukocytes of patients with alcoholic and autoimmune liver disorders[J].Human Exp Toxicol,2016,35(8):799-807.
KNIGHTT,LUEDTKED,EDWARDSH,et al.A delicate balance-the Bcl-2 family and its role in apoptosis,oncogenesis,and cancer therapeutics[J].Biochem Pharmaco,2019,162:250-261.
LIAOW,LIUJ,LIUB,et al.JIB04 induces cell apoptosis via activation of the p53/Bcl2/caspase pathway in MHCC97H and HepG2 cells[J].Oncol Rep,2018,40(6):3812-3820.
JIB04 is a structurally unique small molecule, known to exhibit anticancer activity and to inhibit the growth of human lung cancer and prostate cancer cell lines. However, the anticancer effect of JIB04 against human hepatic carcinoma, and its underlying mechanisms, are still unclear. In the present study, MHCC97H and HepG2 cells were employed to investigate the anticancer effects of JIB04 on cell viability and apoptosis. Annexin V/PI staining, a CCK8 assay and western blot analysis demonstrated that JIB04 induced apoptosis in MHCC97H and HepG2 cells, which was evidenced by the expression of proapoptotic and apoptotic proteins including p53, Bak, Bax, caspase3 and caspase9. Subsequently, the expression trends of Bcl2 and p53 were reversed after cotreatment with pifithrinalpha (PFTalpha, a p53 inhibitor). The results revealed that JIB04 suppressed the cell viability of MHCC97H and HepG2 cells in a concentrationdependent manner. Meanwhile, it was also demonstrated that JIB04 effectively triggered MHCC97H and HepG2 cell apoptosis by downregulating Bcl2/Bax expression, and upregulating proapoptotic and apoptotic protein expression via the p53/Bcl2/caspase signaling pathway. JIB04 had effects on the inhibition of cell viability and the induction of apoptosis in MHCC97H and HepG2 cells. The underlying mechanism of action of JIB04 was associated with the p53/Bcl2/caspase signaling pathway. Our findings provide a foundation for understanding the anticancer effect of JIB04 on MHCC97H and HepG2 cells, and suggested that JIB04 may be a promising therapeutic agent in human liver cancer.
KALEJ,OSTERLUND EJ,ANDREWS DW.Bcl-2 family proteins:changing partners in the dance towards death[J].Cell Death Differ,2018,25(1):65-80.
The BCL-2 family of proteins controls cell death primarily by direct binding interactions that regulate mitochondrial outer membrane permeabilization (MOMP) leading to the irreversible release of intermembrane space proteins, subsequent caspase activation and apoptosis. The affinities and relative abundance of the BCL-2 family proteins dictate the predominate interactions between anti-apoptotic and pro-apoptotic BCL-2 family proteins that regulate MOMP. We highlight the core mechanisms of BCL-2 family regulation of MOMP with an emphasis on how the interactions between the BCL-2 family proteins govern cell fate. We address the critical importance of both the concentration and affinities of BCL-2 family proteins and show how differences in either can greatly change the outcome. Further, we explain the importance of using full-length BCL-2 family proteins (versus truncated versions or peptides) to parse out the core mechanisms of MOMP regulation by the BCL-2 family. Finally, we discuss how post-translational modifications and differing intracellular localizations alter the mechanisms of apoptosis regulation by BCL-2 family proteins. Successful therapeutic intervention of MOMP regulation in human disease requires an understanding of the factors that mediate the major binding interactions between BCL-2 family proteins in cells.
WANGX,CHENJ,WANGH,et al.Memantine can reduce ethanol-induced caspase-3 activity and apoptosis in H4 cells by decreasing intracellular calcium[J].J Mol Neurosci,2017,62(3/4):402-411.
ZHANGY,YANGX,GE XH,et al.Puerarin attenuates neurological deficits via Bcl-2/Bax/cleaved caspase-3 and Sirt3/SOD2 apoptotic pathways in subarachnoid hemorrhage mice[J].Biomed Pharmacother,2019,109:726-733.
BACKGROUND: Subarachnoid hemorrhage (SAH) results in many brain dysfunctions and the neuroprotective function of puerarin after brain damage has been demonstrated in several studies. But whether puerarin can reduce brain nerve damage after SAH is not clear.In this study, we hypothesized that puerarin had the neuroprotective effect after SAH, and this protection could be mediated by bothBcl-2/Bax/Cleaved caspase-3 and SIRT3/SOD2 apoptotic signaling pathways. METHODS: First, we used neurological score, brain water content and so on to detect the neurological deficits after SAH. Then apoptosis neuron rate was detected by TUNEL staining. Western blot was carried out to explore the alteration of Blc-2, Bax, cleaved caspase-3 and Sirt3.Also, ROS acitivity and As-lysine level of SOD2 should be detected with assays. RESULTS: We demonstrate that puerarin attenuated the neurological deficits, effectively relieves cerebral edema, and reduce BBB disruption in SAH mice.And we revealed that a reduced rate of apoptosis neuron has been found out in puerarin treatment after SAH. In addition, obviously higher ratio of Blc-2/Bax and decreased expression of cleaved caspase-3 in puerarin-treated SAH micecomparing with vehicle-treated SAH animals had been found. Furthermore, puerarin effectively reversed these alterations in expression and inhibits ROSproduction induced by SAH. Also, puerarin can increase SOD activation after SAH and protect the expression of Sirt3 after SAH. CONCLUSIONS: In coclusion, puerarin can provide potential neuroprotection from the SAH damages, and can be act as a novel therapy for SAH.
WANGY,SONGQ,HUANGX,et al.Long noncoding RNA GAS5 promotes apoptosis in primary nucleus pulposus cells derived from the human intervertebral disc via Bcl-2 downregulation and caspase-3 upregulation[J].Mol Med Rep,2019,19(3):2164-2172.
Nucleus pulposus cell (NPC) apoptosis serves an important role in intervertebral disc degeneration (IDD); however, the roles of long noncoding RNAs (lncRNAs) in this process remain unknown. The present study aimed to determine the effects of the lncRNA growth arrestspecific transcript 5 (GAS5) on the apoptosis of primary human NPCs derived from the intervertebral disc, and to investigate the underlying mechanisms. TargetScan was used to predict the lncRNAs targeted by microRNA155 (miR155). Then, NPCs were subjected to lentivirusmediated transduction of miR155 or GAS5. A human lncRNA and mRNA array was used to screen differentially expressed lncRNAs following miR155 overexpression. GAS5 and miR155 expression levels were determined by reverse transcriptionquantitative polymerase chain reaction. After GAS5 overexpression, apoptosis was assessed by flow cytometry via Annexin V/propidium iodide staining. Western blotting was employed to determine the expression of apoptosisassociated proteins, including caspase3 and B cell lymphoma 2 (Bcl2). TargetScan indicated GAS5 had one binding site for miR155. Following exogenous transfection of miR155 mimics, GAS5 expression levels in NPCs were significantly decreased (P<0.05). Interestingly, miR155 overexpression in NPCs resulted in 721 differentially expressed lncRNAs compared with the negative control group (P<0.05), including 492 and 229 upregulated and downregulated lncRNAs respectively. In addition, 18 transcripts of GAS5 exhibited a downregulated expression profile. GAS5 overexpression in NPCs resulted in enhanced caspase3 decreased Bcl2 expression levels; the apoptosis of NPCs was significantly increased (P<0.05). The results of the present study revealed that overexpression of lncRNA GAS5 may promotes NPC apoptosis via Bcl2 downregulation and caspase3 upregulation, which may be associated with miR155. The results of the present study suggest that lncRNA GAS5silenced NPCs, or lentivirusmediated lncRNA GAS5 knockdown may be precise and effective therapeutic strategies in the treatment of IDD.
Aplysin protects against alcohol-induced liver injury via alleviating oxidative damage and modulating endogenous apoptosis-related genes expression in rats
Combined association of body mass index and alcohol consumption with biomarkers for liver injury and incidence of liver disease:a mendelian randomization study
Long noncoding RNA GAS5 promotes apoptosis in primary nucleus pulposus cells derived from the human intervertebral disc via Bcl-2 downregulation and caspase-3 upregulation
, 张男男
