Association of Plasma DPP4 Activity and Brain-Derived Neurotrophic Factor With Moderate to Severe Depressive Symptoms in Patients With Type 2 Diabetes: Results From a Cross-Sectional Study.

OBJECTIVE: The objective of this study was to assess the association of plasma dipeptidyl peptidase-4 (DPP4) activity, brain-derived neurotrophic factor (BDNF), and the DPP4/BDNF ratio (DBR) with moderate to severe depressive symptoms in patients with type 2 diabetes mellitus. Increased DPP4 activity and decreased BDNF in peripheral circulation have been implicated in the pathophysiology of depression. METHODS: We performed a cross-sectional study using data from 1535 patients with type 2 diabetes mellitus. The main outcome measures were plasma DPP4 activity, BDNF levels, DBR, inflammation markers, and oxidative stress parameters. Depressive symptoms were assessed using the nine-item Patient Health Questionnaire. RESULTS: DPP4 activity and BDNF were negatively correlated in patients with and without moderate to severe depressive symptoms (p < .001). Oxidative stress partially mediated the inverse correlation between DPP4 and BDNF. Nitrotyrosine, 8-iso-PGF2a, interleukin-6, C-reactive protein, and the nine-item Patient Health Questionnaire score increased significantly with rising quartiles of DBR. Patients in the highest quartile of DPP4 activity and DBR and lowest quartile of BDNF more often had moderate to severe depressive symptoms compared with those in the lowest quartile of DPP4 activity and DBR and the highest quartile of BDNF, respectively (p < .05). The likelihood of having moderate to severe depressive symptoms increased more with higher DPP4 activity and lower BDNF. CONCLUSIONS: Our hypothesis-generating study demonstrates that oxidative stress might partially play a mediating role in the negative relationship between DPP4 activity and BDNF. DBR is positively related to moderate to severe depressive symptoms and thus might be used as a novel biological measure associated with depressive symptoms in patients with type 2 diabetes mellitus.

Association between plasma dipeptidyl peptidase-4 activity to brain-derived neurotrophic factor ratio and depressive symptoms in middle-aged and older adults with normal glucose tolerance: A cross-sectional study.

Objectives: Attenuation of brain-derived neurotrophic factor (BDNF) availability and increased dipeptidyl peptidase-4 (DPP4) activity have both been reported to link to the pathogenesis of depression. The aim of this study was to test the correlation between depressive symptoms and plasma DPP4 activity to BDNF ratio (DBR).Methods: We evaluated DPP4 activity, BDNF, oxidative stress parameters and inflammatory markers and calculated DBR in a cross-sectional sample of 1640 non-diabetic participants.Results: DPP4 activity was negatively related to BDNF in participants with and without depressive symptoms (r= -0.351 and r= -0.404, p<.001). Nitrotyrosine and 8-iso-PGF2a mediated 18.4 and 12.6% of the total effect of DPP4 activity on BDNF, respectively. 8-iso-PGF2a, nitrotyrosine, C-reactive protein, interleukin-6 and PHQ-9 score progressively increased across DBR quartiles. Participants whose DBRs were in the highest quartile had 2.64-fold increased odds (OR = 3.03) of depressive symptoms. The depressive symptoms risk increased more with lower levels of BDNF and higher levels of DPP4 activity (p<.05).Conclusions: Our data suggested inverse correlation between DPP4 activity and BDNF through the oxidative stress mediator. The positive relationship between DBR and depressive symptoms risk raises feasibility of identifying DBR as a novel biological marker or even a possible therapeutic target for depression.

The Relationship Between Plasma DPP4 Activity to BDNF Ratio and Mild Cognitive Impairment in Elderly Population With Normal Glucose Tolerance.

Objective: Since decreased brain-derived neurotrophic factor (BDNF) and increased dipeptidyl peptidase-4 (DPP4) activity have both been implicated in the pathogenesis of mild cognitive impairment (MCI), the aim of our study was to evaluate the association of MCI with plasma DPP4 activity to BDNF ratio (DBR) in an elderly population with normal glucose tolerance. Methods: We cross-sectionally measured C-reactive protein, interleukin-6, nitrotyrosine, 8-iso-PGF2a, DPP4 activity BDNF and calculated the DBR in a total of 1,066 elderly participants in China. MCI was determined by the Montreal Cognitive Assessment and finally confirmed by neurologists. Results: An inverse correlation was found between DPP4 activity and BDNF (r = -0.456, P < 0.001) and this inverse correlation was partly mediated by nitrotyrosine and 8-iso-PGF2a. Across rising quartiles of DBR, nitrotyrosine, 8-iso-PGF2a, C-reactive protein and interleukin-6 progressively increased, whereas the Montreal Cognitive Assessment score progressively decreased. Subjects in the lowest quartile of BDNF and highest quartiles of DBR and DPP4 activity, had higher MCI risk compared with subjects in the highest quartile of the BDNF and lowest quartiles of DBR and DPP4 activity, respectively (all P < 0.05). The odds ratio for MCI became more pronounced with decreased BDNF and increased DPP4. Conclusion: In conclusion, a negative correlation was found between DPP4 activity and BDNF, and this negative correlation was partly mediated by oxidative stress, not inflammation. The DBR was positively associated with MCI and thus may be used as a novel risk biomarker for MCI in an elderly population with normal glucose tolerance.

Association of Serum Angiopoietin-Like Protein 8 With Albuminuria in Type 2 Diabetic Patients: Results From the GDMD Study in China.

Background: Hyperglycemia, insulin resistance and hypertriglyceridesmia are risk factors for albuminuria in type 2 diabetes. Angiopoietin-like Protein 8(ANGPTL8) is a newly identified liver-derived hormone related to these risk factors. Hence, we aimed to explore the relationship between ANGPTL8 and albuminuria in type 2 diabetes. Methods: Serum ANGPTL8 levels were determined in groups of control (n = 50) and type 2 diabetic patients with normoalbuminuria (A1, n = 100), microalbuminuria (A2, n = 45), and macroalbuminuria (A3, n = 33). Results: Serum levels of ANGPTL8 and triglycerides were significantly increased in type 2 diabetic patients with albuminuria as compared with controls (P < 0.001). ANGPTL8 levels were positively correlated with triglycerides, duration of diabetes, and urine albumin-to-creatinine ratio (ACR) and negatively correlated with estimated glomerular filtration rate in type 2 diabetic patients with A2 and A3 (all P < 0.05). Logistic regression analysis indicated that ANGPTL8 had higher odds of having A2 (OR = 2.52, 95% CI 1.16-5.48, P = 0.019) and A3 (OR = 4.89, 95% CI 2.10-11.39, P < 0.001) in type 2 diabetes. Mediation analysis indicated that triglycerides might act as a partial mediator in the relationship between ANGPTL8 and ACR. Conclusions: Triglycerides might partially mediate the correlation between ANGPTL8 and ACR. Our data provide the evidence for a strong link between ANGPTL8 and albuminuria, indicating that ANGPTL8 may be a new biomarker for diabetic kidney disease in type 2 diabetes. TRIAL REGISTRATION NUMBER: ChiCTR-EPC-14005273.

[Distribution of hepatitis B virus genotypes and its clinical significance in Guangxi].

OBJECTIVE: To understand the distribution of hepatitis B virus genotype in Guangxi and its clinical significance. METHODS: Nested polymerase chain reaction (nPCR) was used for amplification of HBV DNA in sera of asymptomatic carrier (ASC) of hepatitis B virus (HBV) and patients with different liver diseases from southern and northern Guangxi. Specimens from 161 subjects were positive for HBV DNA and HBV genotype was determined by using restriction fragment length polymorphism analysis, direct sequencing or cloning sequencing. RESULTS: The prevalence of genotype A was 3.7% in all samples and that of genotype B, C and D was 21.7%, 72.7% and 1.2%, respectively. No other genotypes (such as genotype E, F, G, H) were found. The prevalence of genotype C showed an increasing trend in ASC, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC) group; in contrast, the prevalence of genotype B showed an opposite trend, although no statistically significant difference was observed, except between ASC and HCC (P=0.05). The HBeAg positive rate was higher, and the anti-HBe positive rate was lower in patients with chronic genotype C infection than in those with genotype B (P<0.05 for both). Liver function test (ALT) abnormality was more severe in genotype C group than in genotypes A and B groups having acute or chronic infection (P<0.01 for all comparisons). The prevalence of genotype C in southern Guangxi was higher than that in northern Guangxi. In contrast, the prevalence of genotype B in southern Guangxi was lower than that in northern Guangxi. CONCLUSIONS: 1. The predominant HBV genotypes in Guangxi were genotypes B and C. The major genotype in southern Guangxi was genotype C; while that in northern Guangxi was genotype B, which implied that the distribution of HBV genotype C was consistent with the incidence of HCC in Guangxi. 2. Genotype C maybe associated with development of severe liver diseases including HCC. 3. Genotype A,D and B+C were mostly found in acute, hepatitis and chronic hepatitis group.

[Preliminary evidence that a hepatitis E virus (HEV) ORF2 recombinant protein protects cynomolgus macaques against challenge with wild-type HEV].

BACKGROUND: To observe the protective effect of hepatitis E virus (HEV) ORF2 recombinant protein expressed in prokaryote cell cynomolgus macaques (cynos) against challenging with wild-type HEV. METHODS: Cynos were immunized with HEV ORF2 recombinant protein and then challenged with wild-type HEV, the unimmunized cynos were used as control. Blood samples were collected and tested to see if there were dynamic changes of ALT and antibody to HEV before and after challenge with wild-type HEV. RESULTS: All the five unimmunized cynos re-presented hepatitis 3 weeks after challenging with wild-type HEV. However, all the five immunized cynos showed no hepatitis and pathological changes. CONCLUSIONS: Cynos can be efficiently protected by immunization with HEV ORF2 recombinant protein against wild-type HEV. This protein can be a promising candidate for HEV vaccine.

[Nucleotide sequence analysis of new genotype of hepatitis G virus in population at high risk for HCV infection in Guangxi].

OBJECTIVE: To examine the prevalence and the sequence of the genes of new genotypes of hepatitis G virus (HGV) in Guangxi, China. METHODS: Serum samples were collected from 85 intravenous drug abusers (IVDAs), 80 patients with liver diseases (PLDs) and 50 blood donors (BDs). All sera (n=215) were tested by using EIA for HBsAg, anti-HCV and anti-HIV, and by using nested PCR for HGV RNA. In 62 subjects positive for HGV, HGV RNA was sequenced, and a phylogenetic tree was constructed for analyzing genotypes of HGV. RESULTS: HGV RNA was detected in 85 of 215 serum samples (39.53%). The positivity rates for HBsAg, anti-HCV and anti-HIV were 39.07%, 42.79% and 0, respectively. First, 11 nucleotide sequences were determined and the isolates were grouped into three clusters with HGV. 5 of 11 HGV isolates clustered in a distinct phylogenetic branch (genotype Asia) which was different from the described GBV-C and HGV sequences, suggesting the presence of a new genotype of HGV in this locality. Second, 51 nucleotide sequences were determined and analyzed for their genotypes of HGV, and showed genotype GBV-C (3.23%), genotype HGV 30-65% and new genotype (genotype Asia) 64.51%, respectively. CONCLUSIONS: There were subgenotypes in 3 genotypes of HGV; The predominant genotypes of HGV were genotype Asia and genotype HGV among IVDAs, PLDs, and BDs patients in Guangxi, China.