Metabolic disorders induced by PNPLA3 and TM6SF2 gene variants affect chronic kidney disease in patients infected with non-genotype 3 hepatitis C virus.

BACKGROUND: Patients with chronic hepatitis C virus (HCV) infections differ in their risk for metabolic disorders and chronic kidney disease (CKD). The aim of this study was to investigate the effect of metabolic disorders induced by genetic factors on CKD in HCV-infected patients. METHODS: Patients with chronic non-genotype 3 HCV infection with or without CKD were examined. PNPLA3 and TM6SF2 variants were determined using high-throughput sequencing. The relationships of variants and different combinations with metabolic disorders were analyzed in CKD patients. Univariate and multivariate analyses were used to identify factors associated with CKD. RESULTS: There were 1022 patients with chronic HCV infection, 226 with CKD and 796 without CKD. The CKD group had more severe metabolic disorders, and also had higher prevalences of liver steatosis, the PNPLA3 rs738409 non-CC genotype, and the TM6SF2 rs58542926 CC genotype (all P < 0.05). Relative to patients with the PNPLA3 rs738409 CC genotype, patients with the non-CC genotype had a significantly decreased eGFR and a greater prevalence of advanced CKD (CKD G4-5). Patients with the TM6SF2 rs58542926 CC genotype had a lower eGFR and a higher prevalence of CKD G4-5 than those with the non-CC genotype. Multivariable analysis indicated that multiple metabolic abnormalities, including liver steatosis and the PNPLA3 rs738409 C > G variant, increased the risk of CKD, but the TM6SF2 rs58542926 C > T variant decreased the risk of CKD. CONCLUSION: Specific PNPLA3 rs738409 and TM6SF2 rs58542926 variants are independent risk factors for CKD in patients with chronic HCV infections and are associated with the severity of renal injury.

Mexicanolide limonoids from the seeds of Khaya ivorensis with antimicrobial activity.

The methanol extract of the seeds of Khaya ivorensis afforded two new mexicanolide limonoids, ivorensines A and B (1 and 2), together with one known compound, ruageanin D (3). The structures of the isolated compounds were established based on 1 D and 2 D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated limonoids were tested in vitro for antimicrobial potentials against 5 pathogenic microorganisms. As a result, compounds 1-3 exhibited antimicrobial activity against the tested Gram negative bacteria at the minimum inhibitory concentration values less than 50 µg/ml.

Femtosecond laser hybrid processing strategy of transparent hard and brittle materials.

With high hardness, high thermal stability, chemical inertness and excellent optoelectronic properties, transparent hard and brittle materials have drawn significant attentions in frontier domains such as aerospace, photoelectric detection, and high-intensity lasers. Femtosecond laser processing technology demonstrates great potential for transparent hard and brittle materials processing due to its outstanding advantages such as non-contact, true 3D processing and programmable design. However, high-energy laser ablation usually causes severe damage to the surface of the materials, resulting in low processing accuracy, low processing efficiency and poor surface quality. Femtosecond laser hybrid processing strategies have been proven to be an effective solution to solve the above problems. This mini-review summarizes the fundamentals and research progress of femtosecond laser hybrid processing strategies of transparent hard and brittle materials in recent years. Moreover, the challenges and application prospects of these techniques are discussed.

Texture Features of Computed Tomography Image under the Artificial Intelligence Algorithm and Its Predictive Value for Colorectal Liver Metastasis.

The aim of this research was to investigate the predictive role of texture features in computed tomography (CT) images based on artificial intelligence (AI) algorithms for colorectal liver metastases (CRLM). A total of 150 patients with colorectal cancer who were admitted to the hospital were selected as the research objects and randomly divided into three groups with 50 cases in each group. The patients who were found to suffer from the CRLM in the initial examination were included in group A. Patients who were found with CRLM in the follow-up were assigned to group B (B1: metastasis within 0.5 years, 16 cases; B2: metastasis within 0.5-1.0 years, 17 cases; and B3: metastasis within 1.0-2.0 years, 17 cases). Patients without liver metastases during the initial examination and subsequent follow-up were designated as group C. Image textures were analyzed for patients in each group. The prediction accuracy, sensitivity, and specificity of CRLM in patients with six classifiers were calculated, based on which the receiver operator characteristic (ROC) curves were drawn. The results showed that the logistic regression (LR) classifier had the highest prediction accuracy, sensitivity, and specificity, showing the best prediction effect, followed by the linear discriminant (LD) classifier. The prediction accuracy, sensitivity, and specificity of the LR classifier were higher in group B1 and group B3, and the prediction effect was better than that in group B2. The texture features of CT images based on the AI algorithms showed a good prediction effect on CRLM and had a guiding significance for the early diagnosis and treatment of CRLM. In addition, the LR classifier showed the best prediction effect and high clinical value and can be popularized and applied.

Study on the mechanism of curcumin to reduce the inflammatory response of temporal lobe in Alzheimer's disease by regulating miR-146a.

BACKGROUND: To explore the potential mechanism of curcumin in the treatment of Alzheimer's disease (AD) and clarify the role of miR-146a in the neuroinflammatory response to AD. METHODS: Clinical case study: 20 AD patients and 20 age-gender matched non-inflammatory and non-dementia patients in the department of neurology of our hospital were included, peripheral venous blood and cerebrospinal fluid were collected, and mir-146a levels in peripheral blood and cerebrospinal fluid were detected by real-time fluorescence quantitative PCR. Animal experimental study group: There were 3 groups, including APP/PS1 mice control group, APP/PS1 mice low-dose curcumin treatment group, and C57BL/6J mice wild-type (WT) control group, with 10 mice in each group. mir-146a levels in mice brain tissue were detected by quantitative real-time PCR. Aß, APP, complement factor H (CFH) and M1 microglia labeled IL-1 ß and iNOS in temporal lobe tissues of mice were detected by using Westernblot method. RESULTS: The plasma miRNA-146a level in AD group was 39.10±12.97 fmol/L, and that in control group was 60.54±13.16 fmol/L. The plasma miRNA-146a level in AD group was significantly lower than that in control group. The level of miRNA-146a in cerebrospinal fluid of AD group (25.16±5.16 fmol/L) was significantly higher than that of control group (11.35±3.58 fmol/L). After treatment with low dose curcumin, the level of miRNA-146a in APP/PS1 mice decreased significantly, and the expression of A ß and APP/PS1 in temporal lobe of mice detected by Western blot decreased significantly, the levels of IL-1 ß and iNOS protein decreased significantly, and the protein of CFH increased significantly. CONCLUSIONS: miRNA-146a can be used as one of the potential biomarkers of AD. Low dose curcumin can significantly reduce the level of neuropro-inflammatory miR-146A, up-regulate the expression of CFH protein, inhibit the phenotype of M1 microglia, and play a role in the treatment of AD by promoting the phagocytosis and clearance mechanism of A ß.

Regulatory polymorphism of CXCL10 rs1439490 in seronegative occult hepatitis C virus infection.

AIM: To examine the relationship between the single nucleotide polymorphism CXCL10 rs1439490 and seronegative occult hepatitis C virus (HCV) infection (OCI). METHODS: One hundred and three cases of seronegative OCI and 155 cases of seropositive chronic HCV infection (CHC) were diagnosed at five Liver Centers in Northeastern China, from 2012 to 2016. CXCL10 rs1439490, rs1440802, and IL-28B rs12979860 were analyzed by sequencing. Serum CXCL10 was measured by ELISA. Intrahepatic CXCL10 was determined by quantitative PCR and immunohistochemical semi-quantitative scoring. Liver necroinflammation and fibrosis were scored according to the METAVIR system. RESULTS: CXCL10 rs1439490 G/G was more prevalent in OCI patients (n = 93/103; 90.3%) than in CHC patients (n = 116/155; 74.8%; P = 0.008). OCI patients had lower serum CXCL10 levels than CHC patients (192.91 ± 46.50 pg/mL vs 354.78 ± 102.91 pg/mL, P < 0.0001). Of IL-28B rs12979860 C/C patients, OCI patients with rs1439490 G/G had lower serum and liver levels of CXCL10 and lower levels of liver necroinflammation and fibrosis than non-G/G patients. OCI patients had higher alanine aminotransferase normalization rates after Peg-interferon treatment than CHC patients (P < 0.05) and serum CXCL10 decreased significantly (P < 0.0001). Liver necroinflammation and fibrosis were alleviated in 8 OCI patients after treatment. Multivariate analysis indicated that rs1439490 G/G significantly influenced the occurrence of OCI in HCV infection (OR = 0.31, 95%CI: 0.15-0.66, P = 0.002). CONCLUSION: CXCL10 rs1439490 G/G is positively associated with OCI in HCV infection and antiviral outcome.

The relationship between ITPA rs1127354 polymorphisms and efficacy of antiviral treatment in Northeast Chinese CHC patients.

This prospective study investigated the relationship between 2 inosine triphosphatase (ITPA) polymorphisms (rs7270101 and rs1127354) and the efficacy of ribavirin-based antiviral therapy in hepatitis C virus (HCV)-infected Chinese patients.A total of 906 patients diagnosed with chronic hepatitis C receiving pegylated interferon (PEG-IFN) plus ribavirin combination therapy between January 2011 and January 2014 from 5 hepatitis centers in Northeast China were enrolled. The patients were divided into genotype 1 and non-genotype 1 groups according to the genotype of infected HCV. ITPA single nucleotide polymorphism (SNP) genotyping was performed for all patients. Ribavirin-induced hemolytic anemia and virological response (VR) were monitored during treatment and follow-up. Multivariate regression analysis was used to analyze the predictors for sustained virological response (SVR).IPTA rs7270101 variants were not detected. IPTA rs1127354 variants were detected and showed no difference between the genotype 1 and non-genotype 1 groups. IPTA rs1127354 genotype CC was related to a higher incidence of ribavirin-induced hemolytic anemia. For patients who received >80% of the planned ribavirin dose, rs1127354 variants and related ITPase were related to better SVR. Multivariate analysis showed that IPTA rs1127354 non-genotype CC, HCV genotype, a baseline HCV RNA level <4 × 10 IU/mL, IL-28B rs12979860 genotype CC, and low liver fibrosis were independent predictors for SVR during the combination therapy.IPTA rs1127354 variants and related ITPase were not only related with ribavirin-induced hemolytic anemia but also directly affected the SVR to PEG-IFN plus ribavirin combination therapy in Chinese HCV-infected patients.

Genetic Polymorphism of CYP27B1-1260 as Associated With Impaired Fasting Glucose in Patients With Chronic Hepatitis C Undergoing Antiviral Therapy.

BACKGROUND: Recent studies have indicated that abnormal glucose levels and diabetes are negatively associated with the prognosis of patients with chronic hepatitis C virus (HCV) infection. The genetic polymorphism of the promoter region -1260 of a gene encoding the enzyme 1-alpha-hydroxylase (CYP27B1-1260) has been shown to have an impact on the signaling pathways involved in insulin secretion. OBJECTIVES: The aim is to investigate the effect of CYP27B1-1260 polymorphism on the fasting plasma glucose (FPG) levels in patients with chronic HCV undergoing antiviral therapy. PATIENTS AND METHODS: A total of 461 patients with chronic HCV infection and 300 volunteers without HCV infection were enrolled in an observational cohort study in the China-Japan Union hospital of Jilin University and the Second Hospital of Daqing, Changchun, Jilin Province. Both groups were further divided into normal and abnormal FPG subgroups. The frequencies of the three CYP27B1-1260 genotypes (AA, AC, and CC) were determined in each subgroup. FPG levels were monitored at baseline in HCV and control participants, and both during and after antiviral therapy in HCV infected patients. The frequency of each genotype was determined. Logistic regression analysis was performed to evaluate the risk factors associated with abnormal FPG levels in HCV infected patients undergoing antiviral therapy. RESULTS: In HCV infected patients with abnormal FPG levels, the frequency of the genotype CC was significantly higher than that in patients with normal FPG levels (19% vs. 7%, P < 0.001). In contrast, in the control participants, the CC genotype was not significantly different between FPG groups. At baseline, the CC genotype was associate with four times more risk of IFG after adjusting for multiple variables (OR: 4.11; 95%CI: 1.98 - 8.52, P = 0.0001). During 24 weeks of anti-HCV treatment, 38 HCV participants developed newly-diagnosed impaired fasting glucose. The CC genotype markedly increased the risk for newly developed IFG (OR: 26.54; 95%CI: 7.80 - 90.32, P < 0.0001). Other risk factors included age and body mass index. CONCLUSIONS: CYP27B1-1260 polymorphism is associated with abnormal glucose metabolism in HCV infected patients. HCV infected individuals with CYP27B1-1260 genotype CC appeared to have an increased risk of developing abnormal FPG levels.

Interactions between CYP1A1 polymorphisms and cigarette smoking are associated with the risk of hepatocellular carcinoma: evidence from epidemiological studies.

The Cytochrome P-450 1A1 (CYP1A1) gene has been implicated in the etiology of hepatocellular carcinoma (HCC). However, the results have been inconsistent. In this study, a meta-analysis was performed to clarify the associations of polymorphisms in CYP1A1 gene with HCC risk. Published literature from PubMed, Embase, CNKI and Wanfang Data were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Eight studies (1,752 cases and 2,279 controls) for Ile-Val polymorphism and eight studies (933 cases and 1,449 controls) for MspI polymorphism were identified. The results showed that there was no statistically significant association between the Ile-Val polymorphism and HCC risk under all genetic models (co-dominant model: Val/Val vs. Ile/Ile: OR = 1.62, 95% CI 0.96-2.72 and Ile/Val vs. Ile/Ile: OR = 1.15, 95% CI 0.87-1.52; dominant model: OR = 1.25, 95% CI 0.92-1.70; recessive model: OR = 1.48, 95% CI 0.99-2.21). The MspI polymorphism was also not associated with HCC risk (co-dominant model: m2m2 vs. m1m1: OR = 1.09, 95% CI 0.83-1.42 and m1m2 vs. m1m1: OR = 1.30, 95% CI 1.05-1.61; dominant model: OR = 1.20, 95% CI 0.99­1.45; recessive model: OR = 0.94, 95% CI 0.74-1.18). However, the significant associations were found between both the Ile­Val and MspI polymorphisms and HCC risk among the cigarette smoking subjects (Ile-Val: OR = 1.40, 95% CI 1.06-1.85; MspI: OR = 2.65, 95% CI 1.47-4.77). The present meta-analysis indicated that the MspI and Ile-Val polymorphisms of CYP1A1 may play important roles in increasing susceptibility to smoking-related HCC.