The liver is the largest internal organ of the body, which may suffer acute or chronic injury induced by many factors, leading to cirrhosis and hepatocarcinoma. Cirrhosis is the irreversible end result of fibrous scar...The liver is the largest internal organ of the body, which may suffer acute or chronic injury induced by many factors, leading to cirrhosis and hepatocarcinoma. Cirrhosis is the irreversible end result of fibrous scarring and hepatocellular regeneration, characterized by diffuse disorganization of the normal hepatic structure, regenerative nodules and fibrotic tissue. Cirrhosis is associated with a high co-morbidity and mortality without effective treatment, and much research has been aimed at developing new therapeutic strategies to guarantee recovery. Liver-based gene therapy has been used to downregulate specific genes, to block the expression of deleterious genes, to delivery therapeutic genes, to prevent allograft rejection and to augment liver regeneration. Viral and non-viral vectors have been used, with viral vectors proving to be more efficient. This review provides an overview of the main strategies used in liver-gene therapy represented by non-viral vectors, viral vectors, novel administration methods like hydrodynamic injection, hybrids of two viral vectors and blocking molecules, with the hope of translating findings from the laboratory to the patient′s bed-side.展开更多
AIM: To investigate the role of genes and kinetics of specific transcription factors in liver regeneration, and to analyze the gene expression and the activity of some molecules crucially involved in hepatic regenerat...AIM: To investigate the role of genes and kinetics of specific transcription factors in liver regeneration, and to analyze the gene expression and the activity of some molecules crucially involved in hepatic regeneration. METHODS: USING gel-shift assay and RT-PCR, transcription factors, such as NF-κB, STAT-3, SMAD3 and AP-1, and gene expression of inducible nitric oxide synthase (iNOS), hepatocyte growth factor (HGF) and c-met were analyzed in an animal model of chemically induced hepatectomy. RESULTS: Gene expression of HGF and its receptor c-met peaked at 3 h and 24 h after acute CCl4 intoxi- cation. iNOS expression was only observed from 6 to 48 h. Transcriptional factor NF-κB had an early activation at 30 min after acute liver damage. STAT-3 peaked 3 h post- intoxication, while AP-1 displayed a peak of activation at 48 h. SMAD3 showed a high activity at all analyzed times. CONCLUSION: TNF-α and IL-6 play a central role in hepatic regeneration. These two molecules are responsible for triggering the cascade of events and switch-on of genes involved in cell proliferation, such as growth factors, kinases and cyclins which are direct participants of cell proliferation.展开更多
AIM To determine a potential relationship between serum undercarboxylated(uc OC) concentration and cardiovascular risk factors in type 2 diabetes(T2D) patients and healthy subjects(HS).METHODS A cross-sectional study ...AIM To determine a potential relationship between serum undercarboxylated(uc OC) concentration and cardiovascular risk factors in type 2 diabetes(T2D) patients and healthy subjects(HS).METHODS A cross-sectional study was conducted on 140 subjects classified into two groups, 70 with T2D and 70 HS. Medical history and physical examination with anthropometric measurements were obtained from all subjects. Body fat percentage was determined by bioelectrical impendency analysis. Serum uc OC concentration was determined by enzyme immunoassay,while serum levels of insulin and hsC RP were obtained using high sensitivity enzyme-linked immunosorbent assay. Insulin resistance was determined using the homeostasis model assessment-IR. Lipid profile [triglycerides,total cholesterol(TC), high-density lipoproteins(HDL-c),low density lipoproteins(LDL-c), very low-density lipoproteins] was determined by spectrophotometry and standard formulas when applicable. RESULTS The T2D patient group showed significantly higher values of waist circumference, waist-to-hip ratio, systolic blood pressure(SBP), diastolic blood pressure(DBP),current smoking, and alcohol use when compared to the HS group(P < 0.05). We observed a significantly lower serum ucO C concentration in T2D than in HS(1.5 ± 1.4vs 2.3 ± 1.8, P < 0.05). In the whole study population,ucO C concentration was inversely correlated with body mass index(BMI)(r =-0.236, P < 0.05), fasting plasma glucose(r =-0.283, P < 0.01) and HDL-c(r =-0.255,P < 0.05); and positively correlated with LDL-c/HDL-c ratio(r = 0.306, P < 0.05) and TC/HDL-c ratio(r =0.284, P < 0.05). In the T2D group, serum uc OC concentration was inversely correlated with BMI(r =-0.310, P < 0.05) and body-fat percentage(r =-0.311,P < 0.05), and positively correlated with DBP(r = 0.450,P < 0.01). In HS group a positive correlation between serum levels of uc OC and SBP(r = 0.277, P < 0.05)was observed. CONCLUSION Serum uc OC is a potential marker for cardiovascular risk in Mexicans because it is related to adiposity parameters, blood pressure and lipid profile.展开更多
AIM To study the effect of 18-hydroxy-eicosapentaenoic acid(18-HEPE) and 17-hydroxy-docosahexaenoic acid(17-HDHA) in a murine model of obesity/nonalcoholic fatty liver disease.METHODS C57 BL/6 mice were fed with stand...AIM To study the effect of 18-hydroxy-eicosapentaenoic acid(18-HEPE) and 17-hydroxy-docosahexaenoic acid(17-HDHA) in a murine model of obesity/nonalcoholic fatty liver disease.METHODS C57 BL/6 mice were fed with standard chow diet(CD) or high-fat, fructose-enriched diet(HFD) for 16 wk. Then, three groups were treated for 14 d with either, diet switch(HFD for CD), 18-HEPE, or 17-HDHA. Weightand fasting glucose were recorded on a weekly basis. Insulin tolerance test was performed at the end of treatment. Histological analysis(HE and Masson's trichrome stain) and determination of serum insulin, glucagon, glucagon-like peptide 1(GLP-1), glucose-dependent insulinotropic polypeptide, adiponectin and resistin were carried out as well as liver proteins by western blot.RESULTS Mice treated with hydroxy-fatty acids 18-HEPE and 17-HDHA displayed no weight loss or improved insulin sensitivity. However, these mice groups showed a significant amelioration on serum GLP-1, adiponectin and resistin levels. Also, a significant reduction on inflammatory infiltrate was observed at both portal and lobular zones. Furthermore, up-regulation of PPARα/γ protein levels was observed in liver tissue and it was associated with decreased levels of NF-κB also determined by western blot analysis. On the other hand, diet switch regimen resulted in a marked improvement in most parameters including: weight loss, increased insulin sensitivity, decreased steatosis, restored levels of insulin, glucagon, leptin, adiponectin and resistin. However, no significant changes were observed regarding inflammatory infiltrate in this last group.CONCLUSION 18-HEPE and 17-HDHA differentially exert hepatoprotective effects through up-regulation of nuclear receptors PPARα/γ and amelioration of serum adipokines profile.展开更多
Hepatocellular carcinoma(HCC)is the most common cancer associated with chronic liver disease and cirrhosis.The most common cause of HCC is chronic hepatitis C virus infection and many studies in Europe,Asia and North ...Hepatocellular carcinoma(HCC)is the most common cancer associated with chronic liver disease and cirrhosis.The most common cause of HCC is chronic hepatitis C virus infection and many studies in Europe,Asia and North America have focused on its etiology,epidemiology,diagnostic tools,and therapeutic options.However,little is known about these issues in Latin America.The aim of this review is to address these aspects of HCC in Latin America.The main risk factors associated with developing HCC in this region are:age,concomitant cirrhosis,hepatitis C infection,obesity and hereditary disease such as hemochromatosis.On the other hand,screening tests and diagnostic methods of HCC are mostly serum alpha fetoprotein quantification,liver ultrasound,computed tomography,magnetic resonance,and histopathology.Novel diagnostic methods include gut microbiota analysis and the use of nanotechnology and they continue to be tested.Finally,according to the Barcelona Clinic Liver Cancer,curative treatments used in HCC patients are mainly liver resection,liver transplantation,and local ablation,each with advantages and disadvantages.In conclusion,clear strategies are urgently needed to understand the extent of HCC and related problems in this part of the world.This review provides greater knowledge of HCC for the proper design of preventive programs by taking into consideration specific characteristics of our population.Also,this review allows for an understanding of individualizing treatments according to the patient’s needs.展开更多
文摘The liver is the largest internal organ of the body, which may suffer acute or chronic injury induced by many factors, leading to cirrhosis and hepatocarcinoma. Cirrhosis is the irreversible end result of fibrous scarring and hepatocellular regeneration, characterized by diffuse disorganization of the normal hepatic structure, regenerative nodules and fibrotic tissue. Cirrhosis is associated with a high co-morbidity and mortality without effective treatment, and much research has been aimed at developing new therapeutic strategies to guarantee recovery. Liver-based gene therapy has been used to downregulate specific genes, to block the expression of deleterious genes, to delivery therapeutic genes, to prevent allograft rejection and to augment liver regeneration. Viral and non-viral vectors have been used, with viral vectors proving to be more efficient. This review provides an overview of the main strategies used in liver-gene therapy represented by non-viral vectors, viral vectors, novel administration methods like hydrodynamic injection, hybrids of two viral vectors and blocking molecules, with the hope of translating findings from the laboratory to the patient′s bed-side.
基金Supported by CONACyT grant # 28827-M to Adriana Salazar-Montes and, in part, by COECyTJal grant # 08-2004 to Juan Armendariz-Borunda
文摘AIM: To investigate the role of genes and kinetics of specific transcription factors in liver regeneration, and to analyze the gene expression and the activity of some molecules crucially involved in hepatic regeneration. METHODS: USING gel-shift assay and RT-PCR, transcription factors, such as NF-κB, STAT-3, SMAD3 and AP-1, and gene expression of inducible nitric oxide synthase (iNOS), hepatocyte growth factor (HGF) and c-met were analyzed in an animal model of chemically induced hepatectomy. RESULTS: Gene expression of HGF and its receptor c-met peaked at 3 h and 24 h after acute CCl4 intoxi- cation. iNOS expression was only observed from 6 to 48 h. Transcriptional factor NF-κB had an early activation at 30 min after acute liver damage. STAT-3 peaked 3 h post- intoxication, while AP-1 displayed a peak of activation at 48 h. SMAD3 showed a high activity at all analyzed times. CONCLUSION: TNF-α and IL-6 play a central role in hepatic regeneration. These two molecules are responsible for triggering the cascade of events and switch-on of genes involved in cell proliferation, such as growth factors, kinases and cyclins which are direct participants of cell proliferation.
文摘AIM To determine a potential relationship between serum undercarboxylated(uc OC) concentration and cardiovascular risk factors in type 2 diabetes(T2D) patients and healthy subjects(HS).METHODS A cross-sectional study was conducted on 140 subjects classified into two groups, 70 with T2D and 70 HS. Medical history and physical examination with anthropometric measurements were obtained from all subjects. Body fat percentage was determined by bioelectrical impendency analysis. Serum uc OC concentration was determined by enzyme immunoassay,while serum levels of insulin and hsC RP were obtained using high sensitivity enzyme-linked immunosorbent assay. Insulin resistance was determined using the homeostasis model assessment-IR. Lipid profile [triglycerides,total cholesterol(TC), high-density lipoproteins(HDL-c),low density lipoproteins(LDL-c), very low-density lipoproteins] was determined by spectrophotometry and standard formulas when applicable. RESULTS The T2D patient group showed significantly higher values of waist circumference, waist-to-hip ratio, systolic blood pressure(SBP), diastolic blood pressure(DBP),current smoking, and alcohol use when compared to the HS group(P < 0.05). We observed a significantly lower serum ucO C concentration in T2D than in HS(1.5 ± 1.4vs 2.3 ± 1.8, P < 0.05). In the whole study population,ucO C concentration was inversely correlated with body mass index(BMI)(r =-0.236, P < 0.05), fasting plasma glucose(r =-0.283, P < 0.01) and HDL-c(r =-0.255,P < 0.05); and positively correlated with LDL-c/HDL-c ratio(r = 0.306, P < 0.05) and TC/HDL-c ratio(r =0.284, P < 0.05). In the T2D group, serum uc OC concentration was inversely correlated with BMI(r =-0.310, P < 0.05) and body-fat percentage(r =-0.311,P < 0.05), and positively correlated with DBP(r = 0.450,P < 0.01). In HS group a positive correlation between serum levels of uc OC and SBP(r = 0.277, P < 0.05)was observed. CONCLUSION Serum uc OC is a potential marker for cardiovascular risk in Mexicans because it is related to adiposity parameters, blood pressure and lipid profile.
文摘AIM To study the effect of 18-hydroxy-eicosapentaenoic acid(18-HEPE) and 17-hydroxy-docosahexaenoic acid(17-HDHA) in a murine model of obesity/nonalcoholic fatty liver disease.METHODS C57 BL/6 mice were fed with standard chow diet(CD) or high-fat, fructose-enriched diet(HFD) for 16 wk. Then, three groups were treated for 14 d with either, diet switch(HFD for CD), 18-HEPE, or 17-HDHA. Weightand fasting glucose were recorded on a weekly basis. Insulin tolerance test was performed at the end of treatment. Histological analysis(HE and Masson's trichrome stain) and determination of serum insulin, glucagon, glucagon-like peptide 1(GLP-1), glucose-dependent insulinotropic polypeptide, adiponectin and resistin were carried out as well as liver proteins by western blot.RESULTS Mice treated with hydroxy-fatty acids 18-HEPE and 17-HDHA displayed no weight loss or improved insulin sensitivity. However, these mice groups showed a significant amelioration on serum GLP-1, adiponectin and resistin levels. Also, a significant reduction on inflammatory infiltrate was observed at both portal and lobular zones. Furthermore, up-regulation of PPARα/γ protein levels was observed in liver tissue and it was associated with decreased levels of NF-κB also determined by western blot analysis. On the other hand, diet switch regimen resulted in a marked improvement in most parameters including: weight loss, increased insulin sensitivity, decreased steatosis, restored levels of insulin, glucagon, leptin, adiponectin and resistin. However, no significant changes were observed regarding inflammatory infiltrate in this last group.CONCLUSION 18-HEPE and 17-HDHA differentially exert hepatoprotective effects through up-regulation of nuclear receptors PPARα/γ and amelioration of serum adipokines profile.
文摘Hepatocellular carcinoma(HCC)is the most common cancer associated with chronic liver disease and cirrhosis.The most common cause of HCC is chronic hepatitis C virus infection and many studies in Europe,Asia and North America have focused on its etiology,epidemiology,diagnostic tools,and therapeutic options.However,little is known about these issues in Latin America.The aim of this review is to address these aspects of HCC in Latin America.The main risk factors associated with developing HCC in this region are:age,concomitant cirrhosis,hepatitis C infection,obesity and hereditary disease such as hemochromatosis.On the other hand,screening tests and diagnostic methods of HCC are mostly serum alpha fetoprotein quantification,liver ultrasound,computed tomography,magnetic resonance,and histopathology.Novel diagnostic methods include gut microbiota analysis and the use of nanotechnology and they continue to be tested.Finally,according to the Barcelona Clinic Liver Cancer,curative treatments used in HCC patients are mainly liver resection,liver transplantation,and local ablation,each with advantages and disadvantages.In conclusion,clear strategies are urgently needed to understand the extent of HCC and related problems in this part of the world.This review provides greater knowledge of HCC for the proper design of preventive programs by taking into consideration specific characteristics of our population.Also,this review allows for an understanding of individualizing treatments according to the patient’s needs.
