LINC00460 contributes to colorectal cancer cell invasion.

RESEARCH BACKGROUND: Colorectal cancer (CRC) is one of the most prevalent malignant tumors in the world. Research on long noncoding RNAs (LncRNAs) may illuminate tumorigenesis and progression of CRC. METHODS: We screened long non-coding RNA LINC00460 as a new candidate, which promoted the development of CRC in two independent datasets (GSE39582 and GSE21510) from the Gene Expression Omnibus (GEO). In 98 CRC tissues, expression levels of LINC00460 were significantly increased in cancerous tissues compared to paired adjacent normal tissues (P < 0.001). In addition, in the most common CRC cell lines. LINC00460 expression was up-regulated compared to normal human intestinal epithelial cell line NCM460. siRNA was transfected into CRC cell lines. LINC00460 knockdown reduced cell invasion ability and did not affect cell proliferation. The association between LINC00460 expression and clinical pathological features and prognosis were also analyzed. RESULTS: This increased expression was found to significantly correlate with lymph node metastasis (P = 0.002), distant metastasis (P = 0.045) and TNM stage (P < 0.001); but not related to age, gender, location of tumor, and histological grade. The overall survival (OS) in CRC patients with overexpression of LINC00460 was inferior to that with low expression (P = 0.0167). Multivariate Cox regression analyses indicated that LINC00460 expression, as well as TNM stage was an independent prognostic risk factor for patients with CRC. CONCLUSION: These results showed that a higher expression level of LINC00460 might play an oncogenic role in colorectal cancer invasion and metastasis. It also proved that LINC00460 might be used as a potential diagnostic and prognostic biomarker in CRC patients.

Activating IL-6/STAT3 Enhances Protein Stability of Proteasome 20S α+ß in Colorectal Cancer by miR-1254.

A widely recognized feature of colorectal cancer (CRC) is an increase in cytokine levels, which result in an inflammatory environment in the tumor. Interleukin-6 (IL-6) is a robust protumor cytokine. Several studies suggest that IL-6 plays a role in the development of tumors. Most intracellular protein breakdown occurs in eukaryotes via the ubiquitin-proteasome pathway; this mechanism may also be involved in cancer pathogenesis. The tumor tissues and paracancerous tissues were collected from 90 patients with colorectal cancer. The expressions of pSTAT3, proteasome 20S α+ß, miR-1254, and PSMD1 in tissues were detected by immunohistochemistry, ELISA, and qRT-PCR, and the effects of pSTAT3 and proteasome 20s α+ß expressions on the survival of patients were studied. HCT116 and HCT116-R cells were cultured and added IL-6, AG490, STAT3 plasmid, or overexpression/knockdown of miR-1254 in cells. Immunofluorescence, western blot, qRT-PCR, double luciferase gene reporter assay, and flow cytometry were used to detect the expression of pSTAT3, STAT3, proteasome 20s α+ß, miR-1254, and PSMD1 and cell cycle. The nude mouse xenograft model was constructed and divided into 3 groups: PBS group, IL-6 treatment group, and IL-6+miR-1254 mimic group. After 28 days, the tumor tissues were collected, and the expressions of miR-1254, pSTST3, proteasome 20s α+ß, and PSMD1 in the tissues were detected by qRT-PCR and immunohistochemistry, respectively. Our study discovered that the level of proteasome 20S α+ß had a strong connection with pSTAT3 in CRC patients. They were also linked to the development and clinical outcome of CRC. In addition, we found that IL-6 dramatically increased the expression of proteasome 20S α+ß and pSTAT3; however, it did not affect the proteasome 20S α+ß mRNA synthesis. Circulating proteasome concentration correlated with tumor tissue proteasome 20S α+ß. STAT3 could occupy the miR-1254 promoter to inhibit transcription, and it could suppressed miR-1254 which targeted PSMD10, promoting proteasome 20S α+ß protein stability. This is a prospective target for developing a new colorectal cancer therapy strategy.

Hsa_circ_0026628 promotes the development of colorectal cancer by targeting SP1 to activate the Wnt/ß-catenin pathway.

Circular RNAs (circRNAs) have been reported to play crucial roles in the progression of various cancers, including colorectal cancer (CRC). SP1 (Sp1 transcription factor) is a well-recognized oncogene in CRC and is deemed to trigger the Wnt/ß-catenin pathway. The present study was designed to investigate the role of circRNAs which shared the same pre-mRNA with SP1 in CRC cells. We identified that hsa_circ_0026628 (circ_0026628), a circular RNA that originated from SP1 pre-mRNA, was upregulated in CRC cells. Sanger sequencing and agarose gel electrophoresis verified the circular characteristic of circ_0026628. Functional assays including CCK-8, colony formation, transwell, immunofluorescence staining, and sphere formation assay revealed the function of circ_0026628. RNA pull-down and mass spectrometry disclosed the proteins interacting with circ_0026628. Mechanistic assays including RIP, RNA pull-down, CoIP, ChIP, and luciferase reporter assays demonstrated the interplays between molecules. The results depicted that circ_0026628 functioned as a contributor to CRC cell proliferation, migration, EMT, and stemness. Mechanistically, circ_0026628 served as the endogenous sponge of miR-346 and FUS to elevate SP1 expression at the post-transcriptional level, thus strengthening the interaction between SP1 and ß-catenin to activate the Wnt/ß-catenin pathway. In turn, the downstream gene of Wnt/ß-catenin signaling, SOX2 (SRY-box transcription factor 2), transcriptionally activated SP1 and therefore boosted circ_0026628 level. On the whole, SOX2-induced circ_0026628 sponged miR-346 and recruited FUS protein to augment SP1, triggering the downstream Wnt/ß-catenin pathway to facilitate CRC progression.

Cytochrome P450-Mediated Bioactivation: Implication for the Liver Injury Induced by Fraxinellone, A Bioactive Constituent from Dictamni Cortex.

Fraxinellone, a furanoid, is one of the bioactive and potentially hepatotoxic constituents from Dictamnus dasycarpus Turcz, which is extensively spread throughout Asian countries. This herb was reported to cause liver injury in clinical application. However, the mechanism behind is still not fully understood. This study mainly focused on the hepatotoxicity of fraxinellone and the underlying mechanism. The current study demonstrated that fraxinellone resulted in a significant elevation of serum alanine aminotransferase and aspartate aminotransferase in a dose-dependent manner in mice after oral administration. Pretreatment with ketoconazole for three successive days could significantly alleviate the hepatotoxicity of fraxinellone. Considering that fraxinellone has a structural alert of furan ring, it is believed that the hepatotoxicity caused by fraxinellone required cytochrome P450-mediated bioactivation. Bioactivation studies were subsequently carried out in vitro and in vivo. Fraxinellone was metabolized into cis-enedial intermediate, an electrophile that was prone to react with glutathione or N-acetyl-lysine through 1,2- or 1,4-addition to form stable conjugates. Ketoconazole significantly inhibited the formation of the glutathione conjugates (M1 and M2) in microsomal incubation and similar finding was obtained in vivo. Phenotyping study indicated that CYP3A4 was the principal enzyme responsible for the bioactivation of fraxinellone. This study suggested that CYP3A4-mediated bioactivation plays an indispensable role in fraxinellone-induced hepatotoxicity. The work performed herein enables us to better understand the hepatotoxicity of fraxinellone as well as the mechanism behind.

FAM225A facilitates colorectal cancer progression by sponging miR-613 to regulate NOTCH3.

Colorectal cancer (CRC) is a fatal disease ranking the third among the commonplace cancer types around the world. It is extremely significant to exploit effective treatments against CRC. FAM225A was proved to influence cell progression and forecast unfavorable prognosis in nasopharyngeal carcinoma. The role and function mechanism of FAM225A are still unclear in CRC. In this research, FAM225A was discovered presenting much higher expression in CRC tissues and cell lines. In addition, depleting FAM225A was capable of inhibiting cell proliferation, migration, and epithelial-to-mesenchymal transition (EMT) progress, and enhancing cell apoptosis ability. Furthermore, miR-613 exerted important effects as a mediator between FAM225A and NOTCH3. NOTCH3 was negatively correlated with miR-613, whereas was positively associated with FAM225A. Via competitively binding with miR-613, FAM225A positively regulated NOTCH3 expression. FAM225A facilitated CRC occurrence and development through positively regulating NOTCH3 expression by binding with miR-613. In a word, FAM225A/miR-613/NOTCH3 axis may play a tumor-facilitator in CRC cell progression. These data manifested the pivotal effect of FAM225A/miR-613/NOTCH3 pathway in CRC cell proliferation, apoptosis, and migration process. The findings may provide some theoretical basis and different perspective for CRC treatment.

Effect of NLRC5 on activation and reversion of hepatic stellate cells by regulating the nuclear factor-κB signaling pathway.

BACKGROUND: The formation of liver fibrosis is mainly caused by the activation of hepatic stellate cells (HSCs) and the imbalance of extracellular matrix (ECM) production and degradation. The treatment of liver fibrosis mainly includes removing the cause, inhibiting the activation of HSCs, and inhibiting inflammation. NOD-like receptor (NLR) family, caspase activation and recruitment domain (CARD) domain containing 5/NOD27/CLR16.1 (NLRC5) is a highly conserved member of the NLR family and is involved in inflammation and immune responses by regulating various signaling pathways such as nuclear factor-κB (NF-κB) signaling. It has been found that NLRC5 plays an important role in liver fibrosis, but its specific effect and possible mechanism remain to be fully elucidated. AIM: To investigate the role of NLRC5 in the activation and reversion of HSCs induced with transforming growth factor-ß (TGF-ß) and MDI, and to explore its relationship with liver fibrosis. METHODS: A total of 24 male C57BL/6 mice were randomly divided into three groups, including normal, fibrosis, and recovery groups. Twenty-four hours after a liver fibrosis and spontaneous reversion model was established, the mice were sacrificed and pathological examination of liver tissue was performed to observe the degree of liver fibrosis in each group. LX-2 cells were cultured in vitro and treated with TGF-ß1 and MDI. Real-time quantitative PCR (qPCR) and Western blot were used to analyze the expression levels of NLRC5, α-smooth muscle actin (α-SMA), and collagen type I alpha1 (Col1a1) in each group. The activity of NF-κB in each group of cells transfected with NLRC5-siRNA was detected. RESULTS: Compared with the normal mice, the expression level of NLRC5 increased significantly (P < 0.01) in the fibrosis group, but decreased significantly in the recovery group (P < 0.01). In in vitro experiments, the content of NLRC5 was enhanced after TGF-ß1 stimulation and decreased to a lower level when treated with MDI (P < 0.01). The expression of α-SMA and Col1a1 proteins and mRNAs in TGF-ß1-mediated cells was suppressed by transfection with NLRC5-siRNA (P < 0.01). Western blot analysis showed that the expression of NF-κB p65 protein and phosphorylated IκBα (p-IκBα) was increased in the liver of mice in the fibrosis group but decreased in the recovery group (P < 0.01), and the protein level of nuclear p65 and p-IκBα was significantly increased after treatment with NLRC5-siRNA (P < 0.01). CONCLUSION: NLRC5 may play a key role in the development and reversal of hepatic fibrosis through the NF-κB signaling pathway, and it is expected to be one of the clinical therapeutic targets.

Discovery and anticancer evaluation of a formononetin derivative against gastric cancer SGC7901 cells.

Background Gastric cancer (GC) is the second most common cause of cancer-related death worldwide. Novel anticancer drugs against gastric cancer are urgently needed. Methods Compound 10 was designed and synthesized via a molecular hybridization strategy based on the natural product formononetin. It was evaluated for their antiproliferative activity against three gastric cancer cell lines (SGC7901, MKN45 and MGC803). Results Derivative 10 displayed potently antiproliferative activity with an IC50 value of 1.07 µM against SGC7901 cells. Derivative 10 could inhibit the growth and migration against gastric cancer SGC7901 cells through the Wnt/ß-Catenin and AKT/mTOR pathways. From the in vivo expremints, it could effectively inhibited SGC7901 xenograft tumor growth in vivo without significant loss of the body weight. Conclusion Derivative 10 is an novel antitumor agent with potential for further clinical applications to treat gastric cancer. Graphical abstract.

LncRNA TINCR/microRNA-107/CD36 regulates cell proliferation and apoptosis in colorectal cancer via PPAR signaling pathway based on bioinformatics analysis.

The present study aims to determine the potential biomarkers and uncover the regulatory mechanisms of the long-noncoding RNA (lncRNA) TINCR/miR-107/CD36 axis in colorectal cancer (CRC). Aberrantly-expressed lncRNAs and differential-expressed genes were identified by analyzing the dataset GSE40967. Gene set enrichment analysis was employed, and Cytoscape software helped in establishing the co-expression network between lncRNAs and genes. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis contributes to examining the expression levels of lncRNA TINCR, miR-107 and CD36. The dual luciferase assay was used to validate the association between miR-107 and lncRNA TINCR or CD36. The EdU incorporation assay was employed, and flow cytometry was employed to detect cell apoptosis with the tumor xenograft model being utilized. Significantly dysregulated lncRNAs and mRNAs were identified. The peroxisome proliferator-activated receptor (PPAR) signaling pathway in CRC tissues was down-regulated. The loss of TINCR expression was associated with CRC progression. The expression levels of the TINCR and CD36 were down-regulated. We identified miR-107 as an inhibitory target of TINCR and CD36. Overexpression of TINCR could inhibit cell proliferation and promote apoptosis. MiR-107 overexpression in CRC cells induced proliferation and impeded apoptosis. A regulatory function of the lncRNA TINCR/miR-107/CD36 axis in CRC was revealed. LncRNA TINCR overexpression exerted suppressive influence on CRC progression through modulating the PPAR signaling pathway via the miR-107/CD36 axis.

Silencing TRIP13 inhibits cell growth and metastasis of hepatocellular carcinoma by activating of TGF-ß1/smad3.

BACKGROUND: TRIP13 is highly expressed in several cancers and is closely connected with cancer progression. However, its roles on the growth and metastasis of hepatocellular carcinoma (HCC), and the underlying mechanism are still unclear. METHODS: Combining bioinformatics with previous studies, the correlation between TRIP13 and HCC was predicted. TRIP13 expressions from 52 HCC patients and several cell lines were determined. The effects of silencing TRIP13 on cell viability, apoptosis, migration and invasion were respectively detected using CCK-8, flow cytometry and Transwell. qRT-PCR and western blot were performed to reveal associated mechanism. A HCC model was established in BALB/c-nu mice by transplanting HepG2 cells. TRIP13 protein expression and apoptosis in mice tissues were accordingly detected by Immunohistochemistry and TUNEL. RESULTS: High expression of TRIP13 in HCC affected the survival rate and it was enriched in RNA degradation and fatty acid metabolism according to bioinformatics and prediction from previous literature. Increased expression of TRIP13 in HCC patient tissues was associated with the progression of HCC. Silencing TRIP13 inhibited cell viability, migration and invasion, and induced cell apoptosis. TRIP13 knockdown also suppressed the formation of tumor in vivo. Meanwhile, silencing TRIP13 decreased the expressions of Ki67 and MMP-2 and increased the expressions of TIMP-2, active-caspase-3 and TGF-ß1/smad3 signaling- related genes. CONCLUSIONS: Silencing TRIP13 acts as a tumor suppresser of HCC to repress cell growth and metastasis in vitro and in vivo, and such a phenomenon possibly involved activation of TGF-ß1/smad3 signaling.

Current progress in host innate and adaptive immunity against hepatitis C virus infection.

Hepatitis C virus (HCV) infects more than 170 million people worldwide and is the main cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Although the newly developed direct-acting antivirals (DAAs) have transformed the treatment of HCV infection, controlling HCV infection on a global scale remains a challenge because of the high cost, low resistance barrier of DAAs and lack of HCV vaccine. The host immune responses associated with HCV infection, especially HCV-specific T cellular immunity, determine the outcome of HCV infection: either acute or chronic infection. It is important to fully interpret the immunopathogenesis of HCV infection and consequently to exploit effective strategies to eliminate HCV. Here, we review the current progress in HCV immunology, which will deepen our understanding of the spectrum of HCV infection and immunity in humans.

Interleukin-21 is associated with the severity of psoriasis vulgaris through promoting CD4+ T cells to differentiate into Th17 cells.

Interleukin-21 (IL-21) and T helper 17 (Th17) cells are known to be involved in the pathogenesis of psoriasis, but little is known about their relationship in psoriasis. Herein, we investigated whether IL-21 could regulate Th17 cell induction in patients with psoriasis vulgaris. 32 patients with psoriasis vulgaris and 13 healthy controls were recruited. Flow cytometry was used to detect the frequencies of cells mainly secreting IL-21 (including IL-21+CD4+ T and IL-21+ Th17 cells) and Th17 cells. An enzyme-linked immunosorbent assay (ELISA) was used to determine the serum content of IL-21. Severity of the psoriasis was evaluated by a Psoriasis Area and Severity Index (PASI) score. In addition, the differentiation of CD4+ T cells with IL-21 and the different frequencies of IL-21+CD4+ T cells, IL-21+ Th17 cells and Th17 cells were assessed, as were serum levels of IL-21 in patients with moderate to severe psoriasis before and after treatment. Our results showed that the levels of IL-21, IL-21+CD4+ T cells, IL-21+ Th17 cells and Th17 cells were significantly increased in patients and positively associated with PASI score (P < 0.01). Moreover, the levels of IL-21, IL-21+CD4+ T cells and IL-21+ Th17 cells were positively correlated with the frequency of Th17 cells (P < 0.01). In vitro experiments demonstrated that IL-21 could promote CD4+ T cells to differentiate into Th17 cells. After a 4-week treatment of acitretin and a topical therapy, all the immune markers observed in patients decreased significantly (P < 0.01), but the levels remained higher than those in healthy controls (P < 0.01). These findings indicate that IL-21 might promote Th17 cell induction in psoriasis and might be a potential immune marker for targeting this disease.

Clinical Model for Predicting Hepatocellular Carcinomas in Patients with Post-Sustained Virologic Responses of Chronic Hepatitis C: A Case Control Study.

BACKGROUND/AIMS: No clinical model exists to predict the occurrence of hepatocellular carcinoma in sustained virologic response-achieving (HCC after SVR) patients with chronic hepatitis C (CHC). METHODS: We performed a case-control study using a clinical database to research the risk factors for HCC after SVR. A predictive model based on risk factors was established, and the area under the receiver operating characteristic curve (AUC) was calculated. RESULTS: In the multivariate model, an initial diagnosis of compensated cirrhosis and post-SVR albumin reductions of 1 g/L were associated with 21.7-fold (95% CI, 4.2 to 112.3; p<0.001) and 1.3-fold (95% CI, 1.1 to 1.7; p=0.004) increases in the risk of HCC after SVR, respectively. A predictive model based on an initial diagnosis of compensated cirrhosis (yes, +1; no, 0) and post-SVR albumin ≤36.0 g/L (yes, +1; not, 0) predicted the occurrence of HCC after SVR with a cutoff value of >0, an AUC of 0.880, a sensitivity of 0.833, a specificity of 0.896, and a negative predictive value of 0.956. CONCLUSIONS: An initial diagnosis of compensated cirrhosis combined with a post-SVR albumin value of ≤36.0 g/L predicts the occurrence of HCC after SVR in patients with CHC.

Interferon-α plus ribavirin yields 98 % sustained virologic response in children aged 1-5 years with iatrogenic chronic hepatitis C.

BACKGROUND AND OBJECTIVES: The clinical features and efficacies of antivirals for children with hepatitis C virus (HCV) infections that are acquired through different transmission routines are poorly understood worldwide. This study investigated the clinical characteristics of children who were infected via iatrogenic means and analyzed the efficacy of antiviral therapy in children with chronic hepatitis C (CHC). METHODS: In total, 256 children with HCV infections aged 1 to 5 years were enrolled and surveyed. Interferon-α plus ribavirin was administered to 162 children with CHC for 24 or 48 weeks. The sustained virologic response (SVR) at 24 weeks post-treatment was determined. RESULTS: The median duration of infection was 11.5 (range 6-24) months. The median age was 2.7 years, and 64.5 % of the subjects were male. Ninety-three children (36.3 %, 93/256) exhibited spontaneous resolution of the HCV infection. The remaining 163 (63.7 %) were HCV RNA-positive and had HCV genotypes 1b and 2a, which were identified in 42 and 58 %, respectively, of the 133 tested children. Liver biopsies were performed in all HCV RNA-detectable children. A total of 23.9 % cases exhibited grade 2 activity, and 30.1 % exhibited stage 2/3 liver fibrosis. The serum HCV RNA levels were positively correlated with the aminotransferases. Of the 162 treated CHC children, 158 (97.5 %) achieved SVR. The side effects were mild, and 158 (97.5 %) of the treated patients tolerated the treatment well. CONCLUSIONS: This study revealed that histological liver disease can be present within 6-24 months of acquiring an HCV infection in children aged 1-5 years. Interferon-α plus ribavirin therapy is a highly effective and cost-effective means of managing children with early-stage chronic HCV infection.

Primary biliary cirrhosis-associated hepatocellular carcinoma in Chinese patients: incidence and risk factors.

AIM: To investigate the incidence, characteristics, and risk factors for hepatocellular carcinoma (HCC) in Chinese patients with primary biliary cirrhosis (PBC). METHODS: We reviewed the data of 52 PBC-associated HCC patients treated at Beijing 302 Hospital from January 2002 to December 2013 and analyzed its incidence and characteristics between the two genders. The risk factors for PBC-associated HCC were analyzed via a case-control study comprising 20 PBC patients with HCC and 77 matched controls without HCC. The matched factors included gender, age, follow-up period and Child-Pugh scores. Conditional logistic regression was used to evaluate the odds ratios of potential risk factors for HCC development. A P < 0.05 was considered statistically significant. RESULTS: The incidence of HCC in Chinese PBC patients was 4.13% (52/1255) and was significantly higher in the males (9.52%) than in the females (3.31%). Among the 52 PBC patients with HCC, 55.76% (29/52) were diagnosed with HCC and PBC simultaneously, and 5.76% (3/52) were diagnosed with HCC before PBC. The males with PBC-associated HCC were more likely than the females to have undergone blood transfusion (18.75% vs 8.33%, P = 0.043), consumed alcohol (31.25% vs 8.33%, P = 0.010), smoked (31.25% vs 8.33%, P = 0.010), had a family history of malignancy (25% vs 5.56%, P = 0.012), and had serious liver inflammation, as indicated by the elevated levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase (P < 0.05). Conditional logistic regression analysis revealed that body mass index (BMI) ≥ 25 [adjusted odds ratio (AOR) = 1.116, 95%CI: 1.002-1.244, P = 0.045] and history of alcohol intake (AOR = 10.294, 95%CI: 1.108-95.680, P = 0.040) were significantly associated with increased odds of HCC development in PBC patients. CONCLUSION: HCC is not rare in Chinese PBC patients. Risk factors for PBC-associated HCC include BMI ≥ 25 and a history of alcohol intake. In addition to regular monitoring, PBC patients may benefit from abstinence from alcohol and body weight control.

[CD160 characterization and its association with disease progression in patients with chronic HIV-1 infection].

OBJECTIVE: To explore the expression of CD160, a costimulator, on CD4(+) and CD8(+) T cells in chronic human immunodeficiency virus-1 (HIV-1) infected patients. METHODS: A total of 23 chronic HIV-1 infected patients were enrolled into 302 Hospital of People's Liberation Army from January 2010 to December 2011. Meanwhile, 20 healthy individuals were selected as healthy controls (HC). Peripheral blood was collected, peripheral blood mononuclear cells (PBMC) were isolated by density gradient centrifugation and CD160 was stained with fluorescent antibody. The expressions of CD160 on CD4(+) and CD8(+) T cell subsets were detected by flow cytometry and its correlation with CD4(+) T cell absolute number and HIV RNA viral load were analyzed. RESULTS: The expressions of CD160 on CD4(+) and CD8(+) T cell increased versus HC (on CD4(+) T cells, percentage: (14.3 ± 7.5)% vs (3.9 ± 2.2)%, median fluorescent intensity (MFI): 26.4 ± 11.0 vs 12.4 ± 2.9; on CD8(+) T cells, percentage: (40.9 ± 13.2)% vs (12.9 ± 6.6)%, MFI: 52.5 ± 17.4 vs 18.2 ± 5.0). Furthermore, the expression of CD160 on CD4(+) T cells was negatively correlated with CD4(+) T cell absolute number (r = -0.550, P = 0.010) and positively with HIV RNA load (r = 0.522, P = 0.015). However, the expression of CD160 on CD8(+) T cells was not correlated with CD4(+) T cell absolute number or HIV RNA load. The expressions of CD160 on CD8(+) T cell subsets Tn, Tcm and Tem in patients with chronic HIV-1 infection increased compared with HC (25.3 ± 17.6 vs 5.0 ± 3.1, 45.8 ± 13.0 vs 20.4 ± 4.3, 37.0 ± 13.6 vs 20.0 ± 10.8). In addition, Tn subset decreased while Tcm subset increased in CD160(+) CD8(+) T cell subset distribution in patients with HIV-1 infection compared with HC subjects. CONCLUSION: CD160 may contribute to the exhaustion of CD4(+) and CD8(+) T cells and influence the distribution of memory CD8(+) T cell subsets.

Risk factors for liver-related mortality in chronic hepatitis C patients: a deceased case-living control study.

AIM: To investigate the risk factors for liver-related mortality in chronic hepatitis C (CHC) patients. METHODS: All deceased CHC inpatient data were collected from the Beijing 302 Hospital clinical database, which includes more than 8250 CHC inpatients during the period from 2002 to 2012. The controls were matched to cases by age (± 2 years), sex and date of hospital admission (within the same year). Potential risk factors were included for the evaluation, and odds ratios (OR) and 95%CI were estimated using univariate (unadjusted) and multivariate (adjusted OR, AOR) conditional logistic regression. All statistical tests were two-sided. P values < 0.05 were considered statistically significant. RESULTS: Based on examinations of 144 CHC-related deceased cases and 576 controls, we found that antiviral therapy with interferon-α was associated with a 47% decrease in the risk of hepatic mortality (AOR = 0.53, 95%CI: 0.28-0.99, P = 0.048). Additionally, the initial diagnostic stage of the disease (AOR = 2.89, 95%CI: 1.83-4.56 and P < 0.001 for liver cirrhosis/AOR = 8.82, 95%CI: 3.99-19.53 and P < 0.001 for HCC compared with CHC), diabetes (AOR = 2.35, 95%CI: 1.40-3.95, P = 0.001), hypertension (AOR = 1.76, 95%CI: 1.09-2.82, P = 0.020), alcohol consumption (AOR = 1.73, 95%CI: 1.03-2.81, P = 0.037) and HBsAg positivity (AOR = 22.28, 95%CI: 5.58-89.07, P < 0.001) were associated with a significant increase in the risk of liver-related mortality in CHC patients. CONCLUSION: This study indicates that interferon-α treatment, the stage at the initial diagnosis of the disease and comorbidities are all independent risk factors for liver-related mortality in CHC patients.