Association of UGT1A1 gene variants, expression levels, and enzyme concentrations with 2,3,7,8-TCDD exposure in individuals exposed to Agent Orange/Dioxin.

Among the congener of dioxin, 2,3,7,8-TCDD is the most toxic, having a serious long-term impact on the environment and human health. UDP-glucuronosyltransferase 1A1 (UGT1A1) plays a crucial role in the detoxification and excretion of endogenous and exogenous lipophilic compounds, primarily in the liver and gastrointestinal tract. This study aimed to investigate the association of UGT1A1 gene polymorphisms, expression levels, and enzyme concentration with Agent Orange/Dioxin exposure. The study included 100 individuals exposed to Agent Orange/Dioxin nearby Da Nang and Bien Hoa airports in Vietnam and 100 healthy controls. UGT1A1 SNP rs10929303, rs1042640 and rs8330 were determined by Sanger sequencing, mRNA expression was quantified by RT-qPCR and plasma UGT1A1 concentrations were measured by ELISA. The results showed that UGT1A1 polymorphisms at SNPs rs10929303, rs1042640 and rs8330 were associated with Agent Orange/Dioxin exposure (OR = 0.55, P = 0.018; OR = 0.55, P = 0.018 and OR = 0.57, P = 0.026, respectively). UGT1A1 mRNA expression levels and enzyme concentration were significantly elevated in individuals exposed to Agent Orange/Dioxin compared to controls (P < 0.0001). Benchmark dose (BMD) analyses showed that chronic exposure to 2,3,7,8-TCDD contamination affects the UGT1A1 mRNA and protein levels. Furthermore, UGT1A1 polymorphisms affected gene expression and enzyme concentrations in individuals exposed to Agent Orange/Dioxin. In conclusion, UGT1A1 gene polymorphisms, UGT1A gene expression levels and UGT1A1 enzyme concentrations were associated with Agent Orange/Dioxin exposure. The metabolism of 2,3,7,8-TCDD may influence UGT1A gene expression and enzyme concentrations.

Clinical association and diagnostic significance of miRNA-29a and miRNA-147b in type 2 diabetes mellitus.

Background: Micro RNAs (miRs) expression is involved in the pathogenesis of type 2 diabetes mellitus (T2DM). This study investigates the expression levels of plasma miR-29a, miR-146a, and miR-147b and their correlations with clinical parameters in patients with T2DM. Methods: 105 patients with T2DM who categorized either as newly diagnosed T2DM (n=52) or treated T2DM (n=53) and 93 healthy individuals were included in this study. The expression levels of miR-29a, miR-146a, and miR-147b were quantified by real-time PCR and analyzed for possible association with T2DM. Results: The expressions of miR-29a and miR-147b were significantly increased in T2DM patients compared with healthy controls (P<0.0001). The expression levels of miR-29a in newly diagnosed T2DM patients were higher than that in the group of treated T2DM (P=0.002). The expression of studied miRs was correlated with several clinical parameters such as blood glucose levels, HbA1C, microalbuminuria, C-peptide, triglyceride levels as well as the HOMA-ß index. The expression levels of miR-29a and miR-147b show a potential diagnostic performance to discriminate newly diagnostic T2DM (AUCs=0.77 and 0.84, respectively) and beta-cell dysfunction (AUCs= 0.62 and 0.75, respectively). Conclusions: The plasma miR-29a and miR-147b expression levels in T2DM patients are significantly associated with T2DM while miR-146a shows poor evidence in relation to T2DM. miR-147b shows potential as a biomarker for the diagnosis of T2DM and pancreatic beta cell dysfunction.

Custom gene expression panel for evaluation of potential molecular markers in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. It is a highly heterogeneous disease with poor prognosis and limited treatment options, which highlights the need for reliable biomarkers. This study aims to explore molecular markers that allow stratification of HCC and may lead to better prognosis and treatment prediction. MATERIALS AND METHODS: We studied 20 candidate genes (HCC hub genes, potential drug target genes, predominant somatic mutant genes) retrieved from literature and public databases with potential to be used as the molecular markers. We analysed expression of the genes by RT-qPCR in 30 HCC tumour and adjacent non-tumour paired samples from Vietnamese patients. Fold changes in expression were then determined using the 2-∆∆CT method, and unsupervised hierarchical clustering was generated using Cluster v3.0 software. RESULTS: Clustering of expression data revealed two subtypes of tumours (proliferative and normal-like) and four clusters for genes. The expression profiles of the genes TOP2A, CDK1, BIRC5, GPC3, IGF2, and AFP were strongly correlated. Proliferative tumours were characterized by high expression of the c-MET, ARID1A, CTNNB1, RAF1, LGR5, and GLUL1 genes. TOP2A, CDK1, and BIRC5 HCC hub genes were highly expressed (> twofold) in 90% (27/30), 83% (25/30), and 83% (24/30) in the tissue samples, respectively. Among the drug target genes, high expression was observed in the GPC3, IGF2 and c-MET genes in 77% (23/30), 63% (19/30), and 37% (11/30), respectively. The somatic mutant Wnt/ß-catenin genes (CTNNB1, GLUL and LGR5) and TERT were highly expressed in 40% and 33% of HCCs, respectively. Among the HCC marker genes, a higher percentage of tumours showed GPC3 expression compared to AFP expression [73% (23/30) vs. 43% (13/30)]. CONCLUSION: The custom panel and molecular markers from this study may be useful for diagnosis, prognosis, biomarker-guided clinical trial design, and prediction of treatment outcomes.

Antimicrobial resistance in colonizing group B Streptococcus among pregnant women from a hospital in Vietnam.

Few studies have been conducted on group B Streptococcus (GBS) in Vietnam. We determined the GBS colonization and antimicrobial resistance vaginal-rectal profile of 3863 Vietnamese pregnant women over 5 years. Maternal GBS colonization was characterized by antibiotic susceptibility. Overall, the GBS colonization rate was 8.02% (95% CI: 7.20-8.94%). Compared to sampling ≥ 35 weeks of gestation, the GBS colonization rate was statistically higher (p = 0.004) with sampling < 35 weeks. Among 272 antimicrobial susceptibility testing isolates, all were susceptible to ampicillin, penicillin, ceftriaxone, cefotaxime, vancomycin, and quinupristin/dalfopristin. Resistance was highest for tetracycline (89.66%), followed by erythromycin (76.23%) and clindamycin (58.21%). Multidrug resistance and resistance to ≥ 6 different antibiotics were 60.66% and 8.82%, respectively. Resistance to clindamycin but not erythromycin (L phenotype) was 2.2%. The clindamycin resistance rate was significantly increased (p = 0.005) during the study period. These data demonstrate a low rate of maternal GBS colonization. The high rate of erythromycin, clindamycin, and multidrug resistance to GBS that can be transmitted to neonates is an important risk factor to consider. ß-lactams continue to be appropriate for first-line treatment and prophylaxis in the study area. Ongoing monitoring should be considered in the future.

Maternal Vaginal Colonization and Extended-Spectrum Beta-Lactamase-Producing Bacteria in Vietnamese Pregnant Women.

Extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) resistance to commonly prescribed drugs is increasing in Vietnam. During pregnancy, ESBL-E may predispose women to reproductive tract infections and increases the risk for neonatal morbidity. Vaginal colonization and infections by Escherichia coli and Klebsiella pneumoniae are seldom studied in Vietnam. In this study, we investigated ESBL-producing Enterobacterales in the birth canal of pregnant women. Between 2016 and 2020, vaginal swabs were collected from 3104 pregnant women (mean gestational age of 31 weeks) and inoculated onto MacConkey agar plates. Colonies were subjected to direct identification and antimicrobial susceptibility testing using the VITEK®-2 automated compact system and disk diffusion. ESBL production was determined phenotypically. E. coli, Klebsiella species were identified in 30% (918/3104) of the vaginal swabs, with E. coli being the most common (73%; 667/918). ESBL-production was detected in 47% (432/918) of Enterobacterales, with frequent multidrug-resistant phenotype. The overall prevalence of carbapenem resistance was low (8%). Over 20% of Klebsiella spp. were carbapenem-resistant. Pregnant women had a high prevalence of colonization and may transmit ESBL-E to neonates at birth, an important risk factor to be considered. The high rate of ESBL-producers and carbapenem resistance in Enterobacterales in Vietnam emphasizes the need for consequent surveillance and access to molecular typing.

Impact of VSIG4 gene polymorphisms on susceptibility and functional status of rheumatoid arthritis.

The complement receptor of the immunoglobulin superfamily (CRIg, encoded by the VSIG4 gene) is a macrophage receptor involved in the clearance of immune complexes and autologous cells. Our results suggest that the VSIG4 rs1044165T allele is a risk factor for severe functional status of rheumatoid arthritis in women, possibly by affecting VSIG4 gene expression.

Predominant secondary dengue infection among Vietnamese adults mostly without warning signs and severe disease.

BACKGROUND: The morbidity in dengue fever is dependent on the dengue virus (DENV) serotypes, the patient age, predisposing immunogenic markers and the frequency of primary and secondary infections. This study aims to distinguish acute primary from secondary dengue infections of Vietnamese adults and to assess the association of viremia and anti-dengue immunoglobulin levels with clinical outcomes. STUDY DESIGN: Viral RNA, dengue serotypes and levels of anti-dengue IgM and IgG of hospitalized adult cases were determined in EDTA-plasma samples prospectively collected during three consecutive years of dengue infection in Hanoi. Patients admitted to hospital within 7 days of their 1st reported fever were included. Primary infections were anti-dengue IgG enzyme-linked immunosorbent assay (ELISA) negative on both day of hospital entry (day 0) and day two or three of hospitalization (day 2 or 3) with a positive anti-dengue IgM on either day 0 or day 2 or 3 hospitalization. The secondary infections were anti-dengue IgG ELISA positive on both day 0 and day 2 or 3 with positive anti-dengue IgM ELISA on either day 0 or day 2 or 3. RESULTS: The hospitalized dengue fever cases between October 2016 and March 2019 were predominantly secondary infections (74%, 68% and 77%, respectively) with DENV-1 (60% and 65%) and DENV-2 (22% and 26%) serotypes determined in the latter two years. The viremia in primary infection was significantly higher than that in secondary infection (P < 0.01) and positively correlated with the days of hospital stay. In secondary infections, platelet counts were lower than in primary infections (P = 0.04) and IgG levels in secondary infection negatively correlated with platelet counts (Spearman's r = -0.22, P < 0.01). CONCLUSIONS: Our results indicate high rates of secondary infection with DENV1 and DENV2 serotypes. Anti-dengue immunoglobulins negatively correlate with hospital stay and platelet counts with few warning signs or severe disease. Further investigations of specific antibodies in adults which predict auto-inflammatory activity after the recovery from dengue infection are warranted.

Complement protein levels and MBL2 polymorphisms are associated with dengue and disease severity.

The complement system may be crucial during dengue virus infection and progression to severe dengue. This study investigates the role of MBL2 genetic variants and levels of MBL in serum and complement proteins in Vietnamese dengue patients. MBL2 genotypes (- 550L/H, MBL2 codon 54), MBL2 diplotypes (XA/XO, YA/XO) and MBL2 haplotypes (LXPB, HXPA, XO) were associated with dengue in the study population. The levels of complement factors C2, C5, and C5a were higher in dengue and dengue with warning signs (DWS) patients compared to those in healthy controls, while factor D levels were decreased in dengue and DWS patients compared to the levels determined in healthy controls. C2 and C5a levels were associated with the levels of AST and ALT and with WBC counts. C9 levels were negatively correlated with ALT levels and WBC counts, and factor D levels were associated with AST and ALT levels and with platelet counts. In conclusions, MBL2 polymorphisms are associated with dengue in the Vietnamese study population. The levels of the complement proteins C2, C4b, C5, C5a, C9, factor D and factor I are modulated in dengue patients during the clinical course of dengue.

Clinical significance of combined circulating TERT promoter mutations and miR-122 expression for screening HBV-related hepatocellular carcinoma.

Telomerase reverse-transcriptase (TERT) gene promoter mutations in circulating cell-free DNA (cfDNA) as well as the levels of circulating microRNA-122 (miR-122) have been reported as potential noninvasive biomarkers for several. This study evaluates the diagnostic performance of potent biomarker-based panels composing of serological AFP, miR-122 and circulating TERT promoter mutations for screening HBV-related HCC. TERT promoter mutations (C228T and C250T) and miR-122 expression were assessed in the plasma samples from 249 patients with HBV-related liver diseases by nested PCR and qRT-PCR assays, respectively. The diagnostic values of TERT promoter mutations, miR-122 expression and biomarker-based panels were assessed by computation of the area under the curve (AUC). Nested-PCR assays were optimized to detect C228T and C250T mutations in TERT promoter with detection limit of 1%. The common hotspot C228T was observed in 22 HCC cases. The triple combinatory panel (AFP@TERT@miR-122) acquired the best diagnostic value to distinguish HCC from CHB (AUC = 0.98), LC (AUC = 0.88) or non-HCC (LC + CHB, AUC = 0.94) compared to the performance of double combinations or single biomarkers, respectively. Notably, among patients with AFP levels≤20 ng/µl, the double combination panel (TERT@miR-122) retains satisfactory diagnostic performance in discriminating HCC from the others (HCC vs. CHB, AUC = 0.96; HCC vs. LC, AUC = 0.88, HCC vs. non-HCC, AUC = 0.94). The triple combination panel AFP@TERT@miR-122 shows a better diagnostic performance for screening HCC in HBV patients, regardless of AFP levels. The newly established panels can be a potential application in clinical practice in Vietnamese setting.

Proinflammatory Cytokines Are Modulated in Vietnamese Patients with Dengue Fever.

The clinical outcome of dengue is due to a complex interplay between dengue virus (DENV) and host immune factors, including complement and cytokine systems. Proinflammatory cytokines are mainly produced by monocytes in response to infectious pathogens. This study investigated the levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1ß), and IL-12 in Vietnamese patients with dengue, and their correlations with the clinical outcome of dengue infection in 156 patients clinically classified as dengue without warning signs (DWS-, n = 87), dengue with warning signs (DWS+, n = 62), and severe dengue (SD, n = 7) patients as well as in 60 healthy controls (HCs). Serum TNF-α, IL-1ß, and IL-12 levels were quantified by enzyme-linked immunosorbent assay (ELISA). The results showed that TNF-α, IL-1ß, and IL-12 levels were significantly increased in dengue patients compared with HCs (p < 0.0001). TNF-α levels were significantly correlated with white blood cells and platelet counts (rs = 0.52, 0.2; p < 0.0001, p = 0.018, respectively). IL-1ß levels were correlated with red blood cells counts and the levels of aspartate aminotransferase and alanine aminotransferase (rs = 0.23, 0.21, 0.23; p = 0.004, 0.012, 0.005, respectively). The results suggest that these three proinflammatory cytokines are associated with the clinical outcome of dengue and could play roles in the pathogenesis of the disease.

Neopterin levels and Kyn/Trp ratios were significantly increased in dengue virus patients and subsequently decreased after recovery.

OBJECTIVES: During dengue fever, a pronounced gamma-interferon immune response produces neopterin and promotes tryptophan degradation by the enzyme indoleamine-2,3-dioxygenase 1 (IDO-1). Activated IDO-1 is indicated by an increased kynurenine to tryptophan ratio (Kyn/Trp) in patients. METHODS: Plasma levels of neopterin, kynurenine, and tryptophan were measured in 72 hospitalized dengue virus (DENV) patients and 100 healthy individuals. Plasma levels of neopterin, kynurenine, and tryptophan were also measured prospectively in a second cohort of 13 DENV patients; on the day of hospitalization, on day 2-3 at discharge, and 7-10 days after discharge. DENV RNA positivity was determined by qualitative and quantitative methodologies. RESULTS: DENV RNA-positive patients presented significantly higher levels of neopterin (mean 36.5nmol/l) and Kyn/Trp ratios (mean 102µmol/mmol) compared to DENV RNA-negative individuals. A significant correlation between neopterin levels and Kyn/Trp ratios was observed in both DENV RNA-positive (Spearman's rho=0.37, p< 0.01) and DENV RNA-negative (Spearman's rho=0.89, p<0.001) patients. Kyn/Trp ratios were negatively correlated with platelet counts (Spearman's rho=-0.43, p<0.01) and positively correlated with liver enzymes: AST (Spearman's rho=0.68, p<0.01) and ALT (Spearman's rho=0.51, p<0.05). In addition, the follow-up data presented a significant decrease in neopterin levels and Kyn/Trp ratios within 10 days after hospital entry. CONCLUSIONS: Neopterin levels and Kyn/Trp ratios were significantly increased in DENV patients and subsequently decreased after recovery.

Molecular surveillance and temporal monitoring of malaria parasites in focal Vietnamese provinces.

BACKGROUND: While the World Health Organization (WHO) Southeast Asia region has the second highest incidence of malaria worldwide, malaria in Vietnam is focal to few provinces, where delayed parasite clearance to anti-malarial drugs is documented. This study aims to understand Plasmodium species distribution and the genetic diversity of msp1 and msp2 of parasite populations using molecular tools. METHODS: A total of 222 clinical isolates from individuals with uncomplicated malaria were subjected to Plasmodium species identification by nested real-time PCR. 166 isolates positive for Plasmodium falciparum mono infections were further genotyped for msp1 (MAD20, K1, and RO33), and msp2 allelic families (3D7 and FC27). Amplicons were resolved through capillary electrophoresis in the QIAxcel Advanced system. RESULTS: Mono-infections were high and with 75% P. falciparum, 14% Plasmodium vivax and 9% P. falciparum/P. vivax co-infections, with less than 1% Plasmodium malariae identified. For msp1, MAD20 was the most prevalent (99%), followed by K1 (46%) allelic family, with no sample testing positive for RO33 (0%). For msp2, 3D7 allelic family was predominant (97%), followed by FC27 (10%). The multiplicity of infection of msp1 and msp2 was 2.6 and 1.1, respectively, and the mean overall multiplicity of infection was 3.7, with the total number of alleles ranging from 1 to 7. CONCLUSIONS: Given the increasing importance of antimalarial drugs in the region, the genetic diversity of P. falciparum msp1 and msp2 should be regularly monitored with respect to treatment outcomes and/or efficacy studies in regions, where there are ongoing changes in the malaria epidemiology.

Combination of Vaccine Strain Measles Virus and Nimotuzumab in the Treatment of Laryngeal Cancer.

BACKGROUND/AIM: This study aims to investigate whether the combination of oncolytic viruses with chemoradiotherapy or other therapies is a promising strategy for cancer treatment. MATERIALS AND METHODS: The anticancer effects of measles virus (MeV) in combination with nimotuzumab in the treatment of laryngeal cancer were evaluated in vitro and in nude mice inoculated with Hep2 tumors. MTT assay and flow cytometry were used to examine cell death. RESULTS: Laryngeal cancer cells treated with MeV+nimotuzumab combination had a significantly lower survival rate compared to those treated with MeV or nimotuzumab alone (p<0.0001). In an animal model bearing human laryngeal tumor, the treated group had a higher survival rate (60%) compared to a untreated group (20%) (p<0.05), and the survival rate of the group treated with MeV+nimotuzumab combination was higher compared to the groups received single treatment. CONCLUSION: The MeV+nimotuzumab combination has greater anticancer activities in both laryngeal cancer cells and an animal model.

NTCP S267F variant associates with decreased susceptibility to HBV and HDV infection and decelerated progression of related liver diseases.

OBJECTIVES: To determine potential associations of the rs2296651 variant (c.800C>T, S267F) of NTCP with HBV and HBV plus concomitant HDV infection as well as with the progression of related liver diseases. METHODS: The S267F variant was genotyped by DNA sequencing in 620 HBV-infected patients and 214 healthy controls (HCs). Among the patients, 450 individuals were tested for HDV by a nested PCR assay. Logistic regression was applied to examine the association. RESULTS: The S267F variant was found more frequently among HCs (16%) compared to HBV-infected (6%) and HBV-HDV co-infected patients (3%) (HBV patients vs HC: OR=0.32, P=0.00002 and HDV patients vs. HC: OR=0.17, P=0.018). The frequency of S267F variant was inversely correlated with CHB, LC or HCC patients compared with HCs (OR=0.31, P=0.001; OR=0.32, P=0.013; OR=0.34, P=0.002, respectively). S267F variant was also associated with decreased risk of the development of advanced liver cirrhosis (LC) and hepatocellular carcinoma (HCC) (Child B and C vs. Child A, OR=0.26, adjusted P=0.016; BCLC B,C,D vs. BCLC A, OR=0.038, P=0.045, respectively). In addition, patients with the genotype CT had lower levels of AST, ALT, total and direct bilirubin as well as higher platelet counts, indicating an association with a more favorable clinical outcome. CONCLUSION: The NTCP S267F variant of the SLC10A1 gene exhibits protective effects against HBV and HDV infection and is associated with a reduced risk of developing to advanced stages of LC and HCC.

The blood transcriptome of childhood malaria.

BACKGROUND: Transcriptomic research of blood cell lineages supports the understanding of distinct features of the immunopathology in human malaria. METHODS: We used microarray hybridization, validated by real-time RT-PCR to analyze whole blood gene expression in healthy Gabonese children and children with various conditions of Plasmodium falciparum infection, including i) asymptomatic infection, ii) uncomplicated malaria, iii) malaria associated with severe anemia and iv) cerebral malaria. FINDINGS: Our data indicate that the expression profile of 22 genes significantly differed among the investigated groups. Immunoglobulin production, complement regulation and IFN beta signaling, in particular IRF7 and ISRE binding signatures in the corresponding genes, were most conspicuous. Down-regulation in cerebral malaria seems to rely on AhRF, GABP and HIF1 hypoxia transcription factors. ARG1, BPI, CD163, IFI27, HP and TNFAIP6 transcript levels correlated positively with lactatemia, and negatively with hemoglobin concentrations. INTERPRETATION: Differences in gene expression profile reflect distinct immunopathological mechanisms of P. falciparum infection. They emerge as potential prognostic markers for early therapeutic measures and need to be validated further. FUND: This work was supported by a grant of the NGFN (Nationales Genomforschungsnetz 01GS0114) and by a CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil) PhD scholarship for A. B. W. Boldt. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Soluble fibrinogen-like protein 2 levels in patients with hepatitis B virus-related liver diseases.

BACKGROUND: Clinical progression of HBV-related liver diseases is largely associated with the activity of HBV-specific T cells. Soluble fibrinogen-like protein 2 (sFGL2), mainly secreted by T cells, is an important effector molecule of the immune system. METHODS: sFGL2 levels were determined by ELISA assays in sera of 296 HBV patients clinically classified into the subgroups of acute hepatitis B (AHB), chronic hepatitis B (CHB), liver cirrhosis (LC), hepatocellular carcinoma (HCC) and patients with LC plus HCC. As control group, 158 healthy individuals were included. FGL2 mRNA was quantified by qRT-PCR in 32 pairs of tumor and adjacent non-tumor liver tissues. RESULTS: sFGL2 levels were elevated in HBV patients compared to healthy controls (P <  0.0001). In the patient group, sFGL2 levels were increased in AHB compared to CHB patients (P = 0.017). sFGL2 levels were higher in LC patients compared to those without LC (P = 0.006) and were increased according to the development of cirrhosis as staged by Child-Pugh scores (P = 0.024). Similarly, HCC patients had increased sFGL2 levels compared to CHB patients (P = 0.033) and FGL2 mRNA was up-regulated in tumor tissues compared to adjacent non-tumor tissues (P = 0.043). In addition, sFGL2 levels were positively correlated with HBV-DNA loads and AST (Spearman's rho = 0.21, 0.25 and P = 0.006, 0.023, respectively), but reversely correlated with platelet counts and albumin levels (Spearman's rho = - 0.27, - 0.24 and P = 0.014, 0.033, respectively). CONCLUSIONS: sFGL2 levels are induced by HBV infection and correlated with the progression and clinical outcome of HBV-related liver diseases. Thus, sFGL2 may serve as a potential indicator for HBV-related liver diseases.

Interferon-stimulated gene 20 kDa protein serum levels and clinical outcome of hepatitis B virus-related liver diseases.

Interferon-stimulated gene 20 kDa protein (ISG20) with 3' to 5' exonuclease activity mainly targeting single-stranded RNA plays an important role in immune responses against various infectious pathogens, including hepatitis viruses. ISG20 levels were measured by ELISA assays in sera of 339 hepatitis B-virus (HBV) infected patients and 71 healthy individuals and were correlated with clinical and laboratory parameters. ISG20 mRNA was quantified by qRT-PCR in 30 pairs of hepatocellular carcinoma (HCC) tumour and adjacent non-tumour liver tissues. ISG20 levels were significantly elevated in HBV patients compared to healthy controls (P<0.0001). In the patient group, varying ISG20 levels were associated with different forms of HBV-related liver diseases. ISG20 levels were higher in patients with HCC compared to those without HCC (P<0.0001), and increased according to the stages of HCC (P<0.0001). ISG20 mRNA expression was up-regulated in tumour tissues compared to the expression in adjacent non-tumour tissues (P=0.017). Importantly, ISG20 levels were strongly correlated with the levels of AST, ALT, total and direct bilirubin among HCC patients (Pearson's r = 0.43, 0.35, 0.34, 0.3; P<0.0001, respectively). Although differences between liver cirrhosis (LC) and non-LC patients were not observed, ISG20 levels were elevated according to the progression of cirrhosis in patients with LC plus HCC (P=0.005). In conclusions, ISG20 levels are induced by HBV infection and significantly associated with progression and clinical outcome of HBV-related liver diseases, especially in patients with HCC. ISG20 might be a potential indicator for liver injury and the clinical outcome in HBV-related HCC.

HDV infection rates in northern Vietnam.

Hepatitis D caused by the hepatitis delta virus (HDV) is a serious health problem in many regions of the world. A total of 546 HBV-infected patients were enrolled from 2013 to 2015 and classified clinically into the subgroups of chronic hepatitis B (CHB, n = 191), liver cirrhosis (LC, n = 147) and hepatocellular carcinoma (HCC, n = 208). The patients were screened for HDV-RNA by nested PCR assays. HDV genotypes were assessed by direct sequencing, followed by phylogenetic analysis. HDV-RNA was identified in 13% (71/546) of HBV-infected patients. The highest HDV prevalence was found in the LC group (19.7%), followed by the HCC (12%) and CHB (8.9%) groups (P = 0.017). HDV/HBV coinfections were significantly associated with a rather unfavourable clinical outcome, in particular with LC development compared to HBV monoinfection. Phylogenetic analyses indicated that the genotype HDV1 was, with a prevalence of 91%, by far the most common genotype in Vietnam, followed by HDV2 with 9%. Other HDV genotypes were not observed. In accordance with previous data obtained a decade ago, our results confirm a continuing high prevalence of HDV infection in hepatitis B patients in northern Vietnam with the HDV1 genotype still being the predominant genotype. HDV nucleic acid testing to minimize the associated risk should be considered.

Adipose tissue-derived cytokines and their correlations with clinical characteristics in Vietnamese patients with type 2 diabetes mellitus.

BACKGROUND: Adipokines are involved in the pathogenesis of metabolic disorders including obesity and type 2 diabetes mellitus (T2DM). This study investigates the levels of leptin, resistin, visfatin, secreted frizzled-related protein 5 (SFRP5), monocyte chemoattractant protein-1 (MCP-1) and retinol-binding protein 4 (RBP4) and their correlations with clinical parameters of overweight and T2DM. METHODS: We recruited overweight 50 patients with T2DM, 88 non-overweight patients with T2DM, 29 overweight and 100 non-overweight individuals devoid of T2DM for this study. The levels of studied adipokines were measured by enzyme-linked immunosorbent assay and correlated with clinical parameters. RESULTS: The levels of MCP-1 and SFRP5 were decreased while visfatin and RBP4 levels were increased in patients with T2DM compared to those in the control individuals (P < 0.01). Among patients with T2DM, leptin and resistin levels were higher while RBP4 levels were lower in patients with overweight T2DM compared to those in patients with non-overweight T2DM (P < 0.0001, 0.019 and 0.05, respectively). Leptin and MCP-1 levels were correlated with HOMA-IR, QUICKI and HOMA-ß. Leptin/MCP-1 ratio was correlated with insulin levels, HOMA-IR and HOMA-ß indexes. Resistin/RBP4, visfatin/MCP-1 and MCP-1/RBP4 ratios were strongly correlated with the levels of fasting glucose, HbA1c and HOMA-ß. In addition, ROC curve analyses indicated a diagnostic potential of resistin/RBP4 and MCP-1/RBP4 indexes for T2DM (AUC = 0.81 and 0.83, respectively) and ß-cell function (AUC = 0.76 and 0.74, respectively). CONCLUSIONS: Adipokines (leptin, resistin, visfatin, SFRP5, MCP-1, and RBP4) are associated with overweight and T2DM and may serve as a potential prognostic marker and therapeutic intervention for overweight-related T2DM.

Combination of Vaccine-Strain Measles and Mumps Viruses Enhances Oncolytic Activity against Human Solid Malignancies.

Oncolytic measles and mumps viruses (MeV, MuV) have a potential for anti-cancer treatment. We examined the anti-tumor activity of MeV, MuV, and MeV-MuV combination (MM) against human solid malignancies (HSM). MeV, MuV, and MM targeted and significantly killed various cancer cell lines of HSM but not normal cells. MM demonstrated a greater anti-tumor effect and prolonged survival in a human prostate cancer xenograft tumor model compared to MeV and MuV. MeV, MuV, and MM significantly induced the expression of immunogenic cell death markers and enhanced spleen-infiltrating immune cells. In conclusion, MM combination significantly improves the treatment of human solid malignancies.