Hepatocellular carcinoma (HCC) is a major cause of cancer death worldwide, accounting for over half a million deaths per year. The geographic pattern of HCC incidence is parallel to exposure to viral etiologic factors...Hepatocellular carcinoma (HCC) is a major cause of cancer death worldwide, accounting for over half a million deaths per year. The geographic pattern of HCC incidence is parallel to exposure to viral etiologic factors. Its incidence is increasing, ranging between 3% and 9% annually depending on the geographical location, and variability in the incidence rates correspond closely to the prevalence and pattern of the primary etiologic factors. Chronic infections with hepatitis B viruses or hepatitis C viruses have both been recognized as human liver carcinogens with a combined attributable fraction of at least 75% of all HCC cases. Multiple non-viral factors have been implicated in the development of HCC. Increased body mass index and diabetes with subsequent development of non-alcoholic steatohepatitis represent significant risk factors for HCC. Other non-viral causes of HCC include iron overload syndromes, alcohol use, tobacco, oral contraceptive, aflatoxin, pesticides exposure and betel quid chewing, a prevalent habit in the developing world. Wilson disease, α-1 antitrypsin deficiency, Porphyrias, autoimmune hepatitis, Schistosoma japonicum associated with positive hepatitis B surface antigen, and thorotrastray are also contributing hepatocellualar carcinoma. In addition, primary biliary cirrhosis, congestive liver disease and family history of liver cancer increase the risk of HCC incident. In conclusion,clarification of relevant non-viral causes of HCC will help to focus clinicians on those risk factors that are modifiable. The multilevel preventative approach will hopefully lead to a reduction in incidence of non-viral HCC, and a decrease in the patient morbidity and mortality as well as the societal economic burden associated with HCC.展开更多
Before a pathogen even enters a cell, intrinsic immune defenses are active. This first-line defense is mediated by a variety of constitutively expressed cell proteins collectively termed "restriction factors"...Before a pathogen even enters a cell, intrinsic immune defenses are active. This first-line defense is mediated by a variety of constitutively expressed cell proteins collectively termed "restriction factors"(RFs), and they form a vital element of the immune response to virus infections. Over time, however, viruses have evolved in a variety ways so that they are able to overcome these RF defenses via mechanisms that are specific for each virus. This review provides a summary of the universal characteristics of RFs, and goes on to focus on the strategies employed by some of the most important RFs in their attempt to control human cytomegalovirus(HCMV) infection. This is followed by a discussion of the counter-restriction mechanisms evolved by viruses to circumvent the host cell's intrinsic immune defenses. RFs include nuclear proteins IFN-γ inducible protein 16(IFI16)(a Pyrin/HIN domain protein), Sp100, promyelocytic leukemia, and h Daxx; the latter three being the keys elements of nuclear domain 10(ND10). IFI16 inhibits the synthesis of virus DNA by downregulating UL54 transcription- a gene encoding a CMV DNA polymerase; in response, the virus antagonizes IFI16 via a process involving viral proteins UL97 and pp65(p UL83), which results in the mislocalizing of IFI16 into the cytoplasm. In contrast, viral regulatory proteins, including pp71 and IE1, seek to modify or disrupt the ND10 proteins and thus block or reverse their inhibitory effects upon virus replication. All in all, detailed knowledge of these HCMV counter-restriction mechanisms will be fundamental for the future development of new strategies for combating HCMV infection and for identifying novel therapeutic agents.展开更多
Previous studies have confirmed that the anti-virus effects of Shuanghuanglian injection may be associated with nuclear factor-kappa B activity. This study observed nuclear factor-kappa B expression in mice with viral...Previous studies have confirmed that the anti-virus effects of Shuanghuanglian injection may be associated with nuclear factor-kappa B activity. This study observed nuclear factor-kappa B expression in mice with viral encephalitis, and showed significant decreases in nuclear factor-kappa B protein and mRNA levels following Shuanghuanglian injection. The inhibitory effect was more significant with prolonged intervention duration and increased treatment dose. These findings verify that Shuanghuanglian injection plays a therapeutic role in viral encephalitis by reducing expression of nuclear factor-kappa B in a time- and dose-dependent manner.展开更多
Purpose: To evaluate the serological status of hepatitis B and C and to identify the risk factors for viral B and C infection in health workers at the university hospital. Material and Method: Mono-centric cross-secti...Purpose: To evaluate the serological status of hepatitis B and C and to identify the risk factors for viral B and C infection in health workers at the university hospital. Material and Method: Mono-centric cross-sectional study carried out at Bouaké University Hospital from March 2nd to May 16th, 2016, concerning the health staff of the Bouaké University Hospital. Cross-sectional study mono-centric concerning the serological status of viral hepatitis B and C from the period from March 2nd to May 16th, 2016 of the health staff of the University Hospital of Bouaké. It has benefited from data from PNLHVi (national program against viral hepatitis) as part of its awareness campaign. The data were analyzed by SPSS software version 20.0. Results: Of the 1107 health workers, 632 had been included, representing a participation rate of 57.1%. The average age of the staff was 37.8 years with extremes ranging from 18 to 66 years. The sex ratio (H/F) was 0.8. Accidents with blood exposure were noted in 52.4% of cases. The maximum vaccine coverage was 16.1%. The prevalence of HBsAg was 8.4%. Contact with HBV was present in 3/4 of the staff. Anti HCV Ab was positive in 1.4% of the staff. Males, age over 50 and over 20 years of seniority were associated with HBV. Also, HBV infection was significantly higher in boys and girls (81.7%), nurses (78.3%) and nursing aides (73.8%), (p = 0.022). HCV infection was significantly correlated with emergency services. Conclusion: Age, gender, seniority, paramedic qualification, and high risk of exposure to body fluids were correlated with viral B infection while emergency department membership was a factor risk of HCV infection.展开更多
A mouse model of viral encephalitis was induced by intracranial injection of a Coxsackie virus B3 suspension. Quantitative real-time reverse transcription-PCR and western blot assay were applied to detect mRNA and pro...A mouse model of viral encephalitis was induced by intracranial injection of a Coxsackie virus B3 suspension. Quantitative real-time reverse transcription-PCR and western blot assay were applied to detect mRNA and protein expression of intelectin-2 and nuclear factor-kappa B in the viral encephalitis and control groups. Nuclear factor-kappa B and intelectin-2 mRNA and protein expression were significantly increased in mice with viral encephalitis. After intraperitoneal injection of Shuanghuanglian at a dose of 1.5 mg/kg for 5 successive days, intelectin-2 and nuclear factor-kappa B protein and mRNA expression were significantly decreased. To elucidate the relationship between intelectin-2 and nuclear factor-kappa B, mice with viral encephalitis were administered an intracerebral injection of 107 pfu recombinant lentivirus expressing intelectin shRNA. Both protein and mRNA levels of intelectin and nuclear factor-kappa B in brain tissue of mice were significantly decreased. Experimental findings suggest that Shuanghuanglian injection may downregulate nuclear factor-kappa B production via suppression of intelectin production, thus inhibiting inflammation associated with viral encephalitis.展开更多
<strong>Introduction:</strong> <span style="font-family:""><span style="font-family:Verdana;">Unsuppressed viral load (VL) in immunocompromised children on antiretrovir...<strong>Introduction:</strong> <span style="font-family:""><span style="font-family:Verdana;">Unsuppressed viral load (VL) in immunocompromised children on antiretroviral therapy (ART) increases the risk of child morbidity and death. The aim of the study was to identify factors associated with unsuppressed viral load in children on ART for the improvement of prognosis. </span><b><span style="font-family:Verdana;">Patients and Methods: </span></b><span style="font-family:Verdana;">this is a retrospective, descriptive and analytical study carried out from July 2015 to December 2019 in the 28 pediatric HIV/AIDS treatment centers supervised by the NGO IRAA in the region of Gbêkê. It Included children from 0 to 15 years who were HIV positive, on ART for at least 6 months with at least one viral load. The variables studied were socio-demographic, diagnostic and evolutionary. Data analysis was descriptive and analytical with a significance level of p < 0.05. </span><b><span style="font-family:Verdana;">Results</span></b><span style="font-family:Verdana;">: out of 329 children included, 118 (62 boys, 53 girls) had a non-suppressed VL,</span><i><span style="font-family:Verdana;"> i.e.</span></i><span style="font-family:Verdana;"> a prevalence of 36%. The mean age at diagnosis was 61 months. The mother was a small trader (36.4%), illiterate (45.8%). Unsuppressed viral load was significantly associated with poor nutritional status at the start of treatment (p < 0.001), non-compliance with treatment (p < 0.001), poor maternal education (p = 0.011) and the lack of follow-up of the mother in the context of PMTCT (p = 0.03). </span><b><span style="font-family:Verdana;">Conclusion</span></b><span style="font-family:Verdana;">: Unsuppressed viral load is common in children on ART in the Gbêkê region. It mainly concerns the child who did not comply with ART, and whose mother was not followed within the framework of PMTCT. Strengthening early detection, early initiation of ART, PMTCT and increased therapeutic education strategies would improve the prognosis of children infected with HIV.</span></span>展开更多
Epidemiological and clinical data point to a close association between chronic hepatitis B virus infection or chronic hepatitis C virus infection and development of hepatocellular carcinoma (HCC). HCC develops over se...Epidemiological and clinical data point to a close association between chronic hepatitis B virus infection or chronic hepatitis C virus infection and development of hepatocellular carcinoma (HCC). HCC develops over several decades and is associated with fibrosis. This sequence suggests that persistent viral infection and chronic inflammation can synergistically induce liver fibrosis and hepatocarcinogenesis. The transforming growth factor-β (TGF-β) signaling pathway plays a pivotal role in diverse cellular processes and contributes to hepatic fibro-carcinogenesis under inflammatory microenvironments during chronic liver diseases. The biological activities of TGF-β are initiated by the binding of the ligand to TGF-β receptors, which phosphorylate Smad proteins. TGF-β type I receptor activates Smad3 to create COOH-terminally phosphorylated Smad3 (pSmad3C), while pro-inflammatory cytokine-activated kinases phosphorylates Smad3 to create the linker phosphorylated Smad3 (pSmad3L). During chronic liver disease progression, virus components, together with pro-inflammatory cytokines and somatic mutations, convert the Smad3 signal from tumor-suppressive pSmad3C to fibro-carcinogenic pSmad3L pathways, accelerating liver fibrosis and increasing the risk of HCC. The understanding of Smad3 phosphorylation profiles may provide new opportunities for effective chemoprevention and personalized therapy for patients with hepatitis virus-related HCC in the future.展开更多
Hepatocyte nuclear factor 4-alpha(HNF4α)is a highly conserved member of nuclear receptor superfamily of ligand-dependent transcription factors that is expressed in liver and gastrointestinal organs(pancreas,stomach,a...Hepatocyte nuclear factor 4-alpha(HNF4α)is a highly conserved member of nuclear receptor superfamily of ligand-dependent transcription factors that is expressed in liver and gastrointestinal organs(pancreas,stomach,and intestine).In liver,HNF4αis best known for its role as a master regulator of liver-specific gene expression and essential for adult and fetal liver function.Dysregulation of HNF4αexpression has been associated with many human diseases such as ulcerative colitis,colon cancer,maturity-onset diabetes of the young,liver cirrhosis,and hepatocellular carcinoma.However,the precise role of HNF4αin the etiology of these human pathogenesis is not well understood.Limited information is known about the role of HNF4αisoforms in liver and gastrointestinal disease progression.There is,therefore,a critical need to know how disruption of the expression of these isoforms may impact on disease progression and phenotypes.In this review,we will update our current understanding on the role of HNF4αin human liver and gastrointestinal diseases.We further provide additional information on possible use of HNF4αas a target for potential therapeutic approaches.展开更多
AIM: To detect immunohistochemically the presence of oval cells in chronic viral hepatitis with antibody against c-kit. METHODS: We detected oval cells in paraffin embedded liver sections of 3 normal controls and 26 l...AIM: To detect immunohistochemically the presence of oval cells in chronic viral hepatitis with antibody against c-kit. METHODS: We detected oval cells in paraffin embedded liver sections of 3 normal controls and 26 liver samples from patients with chronic viral hepatitis, using immunohistochemistry with antibodies against c-kit, piclass glutathione S-transferase (pi-GST) and cytokeratins 19 (CK19). RESULTS: Oval cells were not observed in normal livers. In chronic viral hepatitis, hepatic oval cells were located predominantly in the periportal region and fibrosis septa,characterized by an ovoid nucleus, small size,and scant cytoplasm. Antibody against stem cell factor receptor, c-kit, had higher sensitivity and specificity than pi-GST and CK19. About 50%-70% of c-kit positive oval cells were stained positively for either pi-GST or CK19. CONCLUSION: Oval cells are frequently detected in human livers with chronic viral hepatitis, suggesting that oval cell proliferation is associated with the liver regeneration in this condition.展开更多
Viral hepatitis C is a type of illness, which is transmitted to patients by different methods in world. Here we will identify the different common risk factors for transmission of viral hepatitis C in our setup. Aim o...Viral hepatitis C is a type of illness, which is transmitted to patients by different methods in world. Here we will identify the different common risk factors for transmission of viral hepatitis C in our setup. Aim of study was to determine frequency of various risk factors in HCV positive patients. This study was cross sectional and conducted Department of Medicine PMC Hospital at Nawabshah. Duration of this study was one year from April 2016 to March 2017. After taking informed written consent, 243 diseased persons with positive anti Hepatitis C Antibodies were incorporated in this research. Frequency of variables i.e. Hepatitis C virus risk factors and different other demographic results was collected on preformed proforma. In total of 243 subjects there were 165 (67.9%) male and 78 (32.1%) females respectively. Most of the subjects have more than one risk factor. 19 (7.8%) had history of blood and blood products transfusion. IV drug abuse was detected in 08 (3.3%). Homosexuality and heterosexuality were observed in 14 (5.8%) and 12 (4.9%) subjects respectively. History of dental procedure was seen in 31 (12.8%). 228 (93.8%) had history of needle pricking in different ways. History of different surgical procedures was observed in 33 (13.8%). Calculated Mean and Standard Deviation for age was 39.2 ± 10.3 years. It was concluded that proper implementation of precautionary measures should be carried out for every human being to reduce burden of HCV illness in far near future.展开更多
The characteristics of viral hepatitis B and D co-infection are poorly documented in Chad. The aim of our study was to determine the prevalence of HBV/HDV co-infection and the characteristics of this co-infection. Mat...The characteristics of viral hepatitis B and D co-infection are poorly documented in Chad. The aim of our study was to determine the prevalence of HBV/HDV co-infection and the characteristics of this co-infection. Materials and Methods: This was a retrospective study including all patients with chronic HBsAg carriers referred in our department from January 2014 to December 2018. Non-inclusion criteria were: absence of anti-HDV testing, presence of anti-viral hepatitis C or Human Immunodeficiency Virus antibodies or excessive alcohol consumption. The variables studied were age, sex, blood transaminase level, HBV DNA level, HDV RNA level, and liver fibrosis and activity score (Actitest Fibrotest). The prevalence of HDV and the characteristics of HDV/HBV co-infection were determined. Results: During the study period, 403 patients were seen in these two hospitals for chronic HBsAg carriage. Of these, 378 (75%) had performed the anti HDV assay. Anti-HDV antibodies were positive in 53 patients (14%). In multivariate analysis, HBV/HDV co-infected patients were less frequently HBeAg positive (5.4% vs. 28.1%;p = 0.0001), older (35 years vs. 32 years;p = 0.001), and more frequently had significant necrotic-inflammatory activity (3.9% vs. 3.2%;p = 0.031) compared with mono infected patients. Neither gender (76.9% male vs. 77.4% male;p = ns), nor viral load (median 530 IU/ml vs. 195 IU/ml;p = ns), nor significant liver fibrosis (35.1% vs. 47.1%;p = ns), nor transaminases (median 26 vs. 32 IU/ml) were different with mono infected patients. Conclusion: VHD is common in Chad. It is associated with increased hepatic necrotic-inflammatory activity.展开更多
Characterization of genes related to sweetpotato viral disease resistance is critical for understanding plant-pathogen interactions, especially with feathery mottle virus infection. For example, genes encoding eukaryo...Characterization of genes related to sweetpotato viral disease resistance is critical for understanding plant-pathogen interactions, especially with feathery mottle virus infection. For example, genes encoding eukaryotic translation initiation factor (eIF)4E, its isoforms, eIF(iso)4E, and the cap-binding protein (CBP) in plants, have been implicated in viral infections aside from their importance in protein synthesis. Full-length cDNA encoding these putative eIF targets from susceptible/resistant and unknown hexaploid sweetpotato (Ipomoea batatas L. Lam) were amplified based on primers designed from the diploid wild-type relative Ipomoea trifida consensus sequences, and designated IbeIF4E, IbeIF(iso)4E and IbCBP. Comparative analyses following direct-sequencing of PCR-amplified cDNAs versus the cloned cDNA sequences identified multiple homeoalleles: one to four IbeIF4E, two to three IbeIF(iso)4E, and two IbCBP within all cultivars tested. Open reading frames were in the length of 696 bp IbeIF4E, 606 bp IbeIF(iso)4E, and 675 bp IbCBP. The encoded single polypeptide lengths were 232, 202, and 225 amino acids for IbeIF4E, IbeIF(iso)4E, and IbCBP, with a calculated protein molecular mass of 26 kDa, 22.8 kDa, and 25.8 kDa, while their theoretical isoelectric points were 5.1, 5.57, and 6.6, respectively. Although the homeoalleles had similar sequence lengths, single nucleotide polymorphisms and multi-allelic variations were detected within the coding sequences. The multi-sequence alignment performed revealed a 66.9% - 96.7% sequence similarity between the predicted amino acid sequences obtained from the homeoalleles and closely related species. Furthermore, phylogenetic analysis revealed ancestral relationships between the eIF4E homeoalleles and other species. The outcome herein on the eIF4E superfamily and its correlation in sequence variations suggest opportunities to decipher the role of eIF4E in hexaploid sweetpotato feathery mottle virus infection.展开更多
文摘Hepatocellular carcinoma (HCC) is a major cause of cancer death worldwide, accounting for over half a million deaths per year. The geographic pattern of HCC incidence is parallel to exposure to viral etiologic factors. Its incidence is increasing, ranging between 3% and 9% annually depending on the geographical location, and variability in the incidence rates correspond closely to the prevalence and pattern of the primary etiologic factors. Chronic infections with hepatitis B viruses or hepatitis C viruses have both been recognized as human liver carcinogens with a combined attributable fraction of at least 75% of all HCC cases. Multiple non-viral factors have been implicated in the development of HCC. Increased body mass index and diabetes with subsequent development of non-alcoholic steatohepatitis represent significant risk factors for HCC. Other non-viral causes of HCC include iron overload syndromes, alcohol use, tobacco, oral contraceptive, aflatoxin, pesticides exposure and betel quid chewing, a prevalent habit in the developing world. Wilson disease, α-1 antitrypsin deficiency, Porphyrias, autoimmune hepatitis, Schistosoma japonicum associated with positive hepatitis B surface antigen, and thorotrastray are also contributing hepatocellualar carcinoma. In addition, primary biliary cirrhosis, congestive liver disease and family history of liver cancer increase the risk of HCC incident. In conclusion,clarification of relevant non-viral causes of HCC will help to focus clinicians on those risk factors that are modifiable. The multilevel preventative approach will hopefully lead to a reduction in incidence of non-viral HCC, and a decrease in the patient morbidity and mortality as well as the societal economic burden associated with HCC.
基金Supported by Italian Ministry of Education,University and Research--MIUR(PRIN 2012)to S.Landolfo(2012SNMJRL)and V.Dell’Oste(20127MFYBR)University of Turin,Research Funding 2014 to S.Landolfo,M.De Andrea,and V.Dell’OsteRegione Piemonte to S.Landolfo(PAR-FCS 2007/2013)
文摘Before a pathogen even enters a cell, intrinsic immune defenses are active. This first-line defense is mediated by a variety of constitutively expressed cell proteins collectively termed "restriction factors"(RFs), and they form a vital element of the immune response to virus infections. Over time, however, viruses have evolved in a variety ways so that they are able to overcome these RF defenses via mechanisms that are specific for each virus. This review provides a summary of the universal characteristics of RFs, and goes on to focus on the strategies employed by some of the most important RFs in their attempt to control human cytomegalovirus(HCMV) infection. This is followed by a discussion of the counter-restriction mechanisms evolved by viruses to circumvent the host cell's intrinsic immune defenses. RFs include nuclear proteins IFN-γ inducible protein 16(IFI16)(a Pyrin/HIN domain protein), Sp100, promyelocytic leukemia, and h Daxx; the latter three being the keys elements of nuclear domain 10(ND10). IFI16 inhibits the synthesis of virus DNA by downregulating UL54 transcription- a gene encoding a CMV DNA polymerase; in response, the virus antagonizes IFI16 via a process involving viral proteins UL97 and pp65(p UL83), which results in the mislocalizing of IFI16 into the cytoplasm. In contrast, viral regulatory proteins, including pp71 and IE1, seek to modify or disrupt the ND10 proteins and thus block or reverse their inhibitory effects upon virus replication. All in all, detailed knowledge of these HCMV counter-restriction mechanisms will be fundamental for the future development of new strategies for combating HCMV infection and for identifying novel therapeutic agents.
基金the Health Research Fund from Health Department of Shaanxi Province,China,No. 04015
文摘Previous studies have confirmed that the anti-virus effects of Shuanghuanglian injection may be associated with nuclear factor-kappa B activity. This study observed nuclear factor-kappa B expression in mice with viral encephalitis, and showed significant decreases in nuclear factor-kappa B protein and mRNA levels following Shuanghuanglian injection. The inhibitory effect was more significant with prolonged intervention duration and increased treatment dose. These findings verify that Shuanghuanglian injection plays a therapeutic role in viral encephalitis by reducing expression of nuclear factor-kappa B in a time- and dose-dependent manner.
文摘Purpose: To evaluate the serological status of hepatitis B and C and to identify the risk factors for viral B and C infection in health workers at the university hospital. Material and Method: Mono-centric cross-sectional study carried out at Bouaké University Hospital from March 2nd to May 16th, 2016, concerning the health staff of the Bouaké University Hospital. Cross-sectional study mono-centric concerning the serological status of viral hepatitis B and C from the period from March 2nd to May 16th, 2016 of the health staff of the University Hospital of Bouaké. It has benefited from data from PNLHVi (national program against viral hepatitis) as part of its awareness campaign. The data were analyzed by SPSS software version 20.0. Results: Of the 1107 health workers, 632 had been included, representing a participation rate of 57.1%. The average age of the staff was 37.8 years with extremes ranging from 18 to 66 years. The sex ratio (H/F) was 0.8. Accidents with blood exposure were noted in 52.4% of cases. The maximum vaccine coverage was 16.1%. The prevalence of HBsAg was 8.4%. Contact with HBV was present in 3/4 of the staff. Anti HCV Ab was positive in 1.4% of the staff. Males, age over 50 and over 20 years of seniority were associated with HBV. Also, HBV infection was significantly higher in boys and girls (81.7%), nurses (78.3%) and nursing aides (73.8%), (p = 0.022). HCV infection was significantly correlated with emergency services. Conclusion: Age, gender, seniority, paramedic qualification, and high risk of exposure to body fluids were correlated with viral B infection while emergency department membership was a factor risk of HCV infection.
基金funded by the Health Research Fund from the Health Department of Shanxi Province, China, No.04015
文摘A mouse model of viral encephalitis was induced by intracranial injection of a Coxsackie virus B3 suspension. Quantitative real-time reverse transcription-PCR and western blot assay were applied to detect mRNA and protein expression of intelectin-2 and nuclear factor-kappa B in the viral encephalitis and control groups. Nuclear factor-kappa B and intelectin-2 mRNA and protein expression were significantly increased in mice with viral encephalitis. After intraperitoneal injection of Shuanghuanglian at a dose of 1.5 mg/kg for 5 successive days, intelectin-2 and nuclear factor-kappa B protein and mRNA expression were significantly decreased. To elucidate the relationship between intelectin-2 and nuclear factor-kappa B, mice with viral encephalitis were administered an intracerebral injection of 107 pfu recombinant lentivirus expressing intelectin shRNA. Both protein and mRNA levels of intelectin and nuclear factor-kappa B in brain tissue of mice were significantly decreased. Experimental findings suggest that Shuanghuanglian injection may downregulate nuclear factor-kappa B production via suppression of intelectin production, thus inhibiting inflammation associated with viral encephalitis.
文摘<strong>Introduction:</strong> <span style="font-family:""><span style="font-family:Verdana;">Unsuppressed viral load (VL) in immunocompromised children on antiretroviral therapy (ART) increases the risk of child morbidity and death. The aim of the study was to identify factors associated with unsuppressed viral load in children on ART for the improvement of prognosis. </span><b><span style="font-family:Verdana;">Patients and Methods: </span></b><span style="font-family:Verdana;">this is a retrospective, descriptive and analytical study carried out from July 2015 to December 2019 in the 28 pediatric HIV/AIDS treatment centers supervised by the NGO IRAA in the region of Gbêkê. It Included children from 0 to 15 years who were HIV positive, on ART for at least 6 months with at least one viral load. The variables studied were socio-demographic, diagnostic and evolutionary. Data analysis was descriptive and analytical with a significance level of p < 0.05. </span><b><span style="font-family:Verdana;">Results</span></b><span style="font-family:Verdana;">: out of 329 children included, 118 (62 boys, 53 girls) had a non-suppressed VL,</span><i><span style="font-family:Verdana;"> i.e.</span></i><span style="font-family:Verdana;"> a prevalence of 36%. The mean age at diagnosis was 61 months. The mother was a small trader (36.4%), illiterate (45.8%). Unsuppressed viral load was significantly associated with poor nutritional status at the start of treatment (p < 0.001), non-compliance with treatment (p < 0.001), poor maternal education (p = 0.011) and the lack of follow-up of the mother in the context of PMTCT (p = 0.03). </span><b><span style="font-family:Verdana;">Conclusion</span></b><span style="font-family:Verdana;">: Unsuppressed viral load is common in children on ART in the Gbêkê region. It mainly concerns the child who did not comply with ART, and whose mother was not followed within the framework of PMTCT. Strengthening early detection, early initiation of ART, PMTCT and increased therapeutic education strategies would improve the prognosis of children infected with HIV.</span></span>
文摘Epidemiological and clinical data point to a close association between chronic hepatitis B virus infection or chronic hepatitis C virus infection and development of hepatocellular carcinoma (HCC). HCC develops over several decades and is associated with fibrosis. This sequence suggests that persistent viral infection and chronic inflammation can synergistically induce liver fibrosis and hepatocarcinogenesis. The transforming growth factor-β (TGF-β) signaling pathway plays a pivotal role in diverse cellular processes and contributes to hepatic fibro-carcinogenesis under inflammatory microenvironments during chronic liver diseases. The biological activities of TGF-β are initiated by the binding of the ligand to TGF-β receptors, which phosphorylate Smad proteins. TGF-β type I receptor activates Smad3 to create COOH-terminally phosphorylated Smad3 (pSmad3C), while pro-inflammatory cytokine-activated kinases phosphorylates Smad3 to create the linker phosphorylated Smad3 (pSmad3L). During chronic liver disease progression, virus components, together with pro-inflammatory cytokines and somatic mutations, convert the Smad3 signal from tumor-suppressive pSmad3C to fibro-carcinogenic pSmad3L pathways, accelerating liver fibrosis and increasing the risk of HCC. The understanding of Smad3 phosphorylation profiles may provide new opportunities for effective chemoprevention and personalized therapy for patients with hepatitis virus-related HCC in the future.
文摘Hepatocyte nuclear factor 4-alpha(HNF4α)is a highly conserved member of nuclear receptor superfamily of ligand-dependent transcription factors that is expressed in liver and gastrointestinal organs(pancreas,stomach,and intestine).In liver,HNF4αis best known for its role as a master regulator of liver-specific gene expression and essential for adult and fetal liver function.Dysregulation of HNF4αexpression has been associated with many human diseases such as ulcerative colitis,colon cancer,maturity-onset diabetes of the young,liver cirrhosis,and hepatocellular carcinoma.However,the precise role of HNF4αin the etiology of these human pathogenesis is not well understood.Limited information is known about the role of HNF4αisoforms in liver and gastrointestinal disease progression.There is,therefore,a critical need to know how disruption of the expression of these isoforms may impact on disease progression and phenotypes.In this review,we will update our current understanding on the role of HNF4αin human liver and gastrointestinal diseases.We further provide additional information on possible use of HNF4αas a target for potential therapeutic approaches.
文摘AIM: To detect immunohistochemically the presence of oval cells in chronic viral hepatitis with antibody against c-kit. METHODS: We detected oval cells in paraffin embedded liver sections of 3 normal controls and 26 liver samples from patients with chronic viral hepatitis, using immunohistochemistry with antibodies against c-kit, piclass glutathione S-transferase (pi-GST) and cytokeratins 19 (CK19). RESULTS: Oval cells were not observed in normal livers. In chronic viral hepatitis, hepatic oval cells were located predominantly in the periportal region and fibrosis septa,characterized by an ovoid nucleus, small size,and scant cytoplasm. Antibody against stem cell factor receptor, c-kit, had higher sensitivity and specificity than pi-GST and CK19. About 50%-70% of c-kit positive oval cells were stained positively for either pi-GST or CK19. CONCLUSION: Oval cells are frequently detected in human livers with chronic viral hepatitis, suggesting that oval cell proliferation is associated with the liver regeneration in this condition.
文摘Viral hepatitis C is a type of illness, which is transmitted to patients by different methods in world. Here we will identify the different common risk factors for transmission of viral hepatitis C in our setup. Aim of study was to determine frequency of various risk factors in HCV positive patients. This study was cross sectional and conducted Department of Medicine PMC Hospital at Nawabshah. Duration of this study was one year from April 2016 to March 2017. After taking informed written consent, 243 diseased persons with positive anti Hepatitis C Antibodies were incorporated in this research. Frequency of variables i.e. Hepatitis C virus risk factors and different other demographic results was collected on preformed proforma. In total of 243 subjects there were 165 (67.9%) male and 78 (32.1%) females respectively. Most of the subjects have more than one risk factor. 19 (7.8%) had history of blood and blood products transfusion. IV drug abuse was detected in 08 (3.3%). Homosexuality and heterosexuality were observed in 14 (5.8%) and 12 (4.9%) subjects respectively. History of dental procedure was seen in 31 (12.8%). 228 (93.8%) had history of needle pricking in different ways. History of different surgical procedures was observed in 33 (13.8%). Calculated Mean and Standard Deviation for age was 39.2 ± 10.3 years. It was concluded that proper implementation of precautionary measures should be carried out for every human being to reduce burden of HCV illness in far near future.
文摘The characteristics of viral hepatitis B and D co-infection are poorly documented in Chad. The aim of our study was to determine the prevalence of HBV/HDV co-infection and the characteristics of this co-infection. Materials and Methods: This was a retrospective study including all patients with chronic HBsAg carriers referred in our department from January 2014 to December 2018. Non-inclusion criteria were: absence of anti-HDV testing, presence of anti-viral hepatitis C or Human Immunodeficiency Virus antibodies or excessive alcohol consumption. The variables studied were age, sex, blood transaminase level, HBV DNA level, HDV RNA level, and liver fibrosis and activity score (Actitest Fibrotest). The prevalence of HDV and the characteristics of HDV/HBV co-infection were determined. Results: During the study period, 403 patients were seen in these two hospitals for chronic HBsAg carriage. Of these, 378 (75%) had performed the anti HDV assay. Anti-HDV antibodies were positive in 53 patients (14%). In multivariate analysis, HBV/HDV co-infected patients were less frequently HBeAg positive (5.4% vs. 28.1%;p = 0.0001), older (35 years vs. 32 years;p = 0.001), and more frequently had significant necrotic-inflammatory activity (3.9% vs. 3.2%;p = 0.031) compared with mono infected patients. Neither gender (76.9% male vs. 77.4% male;p = ns), nor viral load (median 530 IU/ml vs. 195 IU/ml;p = ns), nor significant liver fibrosis (35.1% vs. 47.1%;p = ns), nor transaminases (median 26 vs. 32 IU/ml) were different with mono infected patients. Conclusion: VHD is common in Chad. It is associated with increased hepatic necrotic-inflammatory activity.
文摘Characterization of genes related to sweetpotato viral disease resistance is critical for understanding plant-pathogen interactions, especially with feathery mottle virus infection. For example, genes encoding eukaryotic translation initiation factor (eIF)4E, its isoforms, eIF(iso)4E, and the cap-binding protein (CBP) in plants, have been implicated in viral infections aside from their importance in protein synthesis. Full-length cDNA encoding these putative eIF targets from susceptible/resistant and unknown hexaploid sweetpotato (Ipomoea batatas L. Lam) were amplified based on primers designed from the diploid wild-type relative Ipomoea trifida consensus sequences, and designated IbeIF4E, IbeIF(iso)4E and IbCBP. Comparative analyses following direct-sequencing of PCR-amplified cDNAs versus the cloned cDNA sequences identified multiple homeoalleles: one to four IbeIF4E, two to three IbeIF(iso)4E, and two IbCBP within all cultivars tested. Open reading frames were in the length of 696 bp IbeIF4E, 606 bp IbeIF(iso)4E, and 675 bp IbCBP. The encoded single polypeptide lengths were 232, 202, and 225 amino acids for IbeIF4E, IbeIF(iso)4E, and IbCBP, with a calculated protein molecular mass of 26 kDa, 22.8 kDa, and 25.8 kDa, while their theoretical isoelectric points were 5.1, 5.57, and 6.6, respectively. Although the homeoalleles had similar sequence lengths, single nucleotide polymorphisms and multi-allelic variations were detected within the coding sequences. The multi-sequence alignment performed revealed a 66.9% - 96.7% sequence similarity between the predicted amino acid sequences obtained from the homeoalleles and closely related species. Furthermore, phylogenetic analysis revealed ancestral relationships between the eIF4E homeoalleles and other species. The outcome herein on the eIF4E superfamily and its correlation in sequence variations suggest opportunities to decipher the role of eIF4E in hexaploid sweetpotato feathery mottle virus infection.