SIRT6 Inhibits Anoikis of Colorectal Cancer Cells by Down-Regulating NDRG1.

Anoikis, a form of apoptosis resulting from the loss of cell-extracellular matrix interaction, is a significant barrier to cancer cell metastasis. However, the epigenetic regulation of this process remains to be explored. Here, we demonstrate that the histone deacetylase sirtuin 6 (SIRT6) plays a pivotal role in conferring anoikis resistance to colorectal cancer (CRC) cells. The protein level of SIRT6 is negatively correlated with anoikis in CRC cells. The overexpression of SIRT6 decreases while the knockdown of SIRT6 increases detachment-induced anoikis. Mechanistically, SIRT6 inhibits the transcription of N-myc downstream-regulated gene 1 (NDRG1), a negative regulator of the AKT signaling pathway. We observed the up-regulation of SIRT6 in advanced-stage CRC samples. Together, our findings unveil a novel epigenetic program regulating the anoikis of CRC cells.

Comprehensive analysis of disulfidptosis-related lncRNAs for predicting prognosis and response of immunotherapy in pancreatic adenocarcinoma.

Background: Pancreatic adenocarcinoma (PAAD) is a common and deadly tumor. Currently, there is a severe lack of therapeutic options. As a novel mode of cell death, increasing evidence reveals the important role of the disulfidptosis in cancer. However, few studies have utilized disulfidptosis-related long-stranded non-coding RNAs (DRlncRNAs) to investigate the prognosis of PAAD. Methods: We comprehensively analyzed the expression and prognostic value of 958 DRlncRNAs in PAAD using data from The Cancer Genome Atlas (TCGA). We established and validated a new DRlncRNAs-related prognostic index by least absolute shrinkage and selection operator (LASSO) and COX regression analysis. In addition, we built a nomogram consisting of risk score, age, gender, tumor grade and stage to validate the clinical feasibility of the index. We further evaluated the value of the index in terms of PAAD functional pathways, tumor microenvironment (TME) and tumor mutations. Results: We designed a risk model for five DRlncRNAs and demonstrated its accuracy using receiver operating characteristic (ROC) curves. COX regression suggested that the model may be an independent predictor of cancer prognosis. Tumor immune infiltration analysis revealed that low-risk subgroups had higher extent of immune infiltration, higher sensitivity to immunotherapy and a higher TME score. This is helpful for us to discover more precise immunotherapy for PAAD patients. Conclusions: In conclusion, we established a DRlncRNA index comprising of five DRlncRNAs, which may provide new insights for clinical diagnosis and precision therapy.

An intelligent ratiometric fluorescent assay based on MOF nanozyme-mediated tandem catalysis that guided by contrary logic circuit for highly sensitive sarcosine detection and smartphone-based portable sensing application.

As the well-known test-indicator for early prostate cancer (PCa), sarcosine (SA) is closely related to the differential pathological process, which makes its accurate determination increasingly significant. Herein, we for the first time expanded the peroxidase (POD)-like property of facile-synthesized Zn-TCPP(Fe) MOF to fluorescent substrates and exploited it to ratiometric fluorescent (RF) sensing. By harnessing the effective catalytic oxidation of MOF nanozyme toward two fluorescent substrates (Scopoletin, SC; Amplex Red, AR) with contrary changes, and target-responsive (SA + SOx)/MOF/(SC + AR) tandem catalytic reaction, we constructed the first MOF nanozyme-based RF sensor for the quantitative determination of SA. Superior to previous works, the operation of this RF sensor is under the guidance of AND-(AND^NAND) contrary logic circuit. The dual-channel binary output changes (from 1/0 to 0/1) not only enable the intelligent logical recognition of SA, bringing strengthened reliability and accuracy, but also manifest the proof-of-concept discrimination of PCa individuals and healthy ones. Through recording the fluorescence alterations of SC (F465) and AR (F585), two segments of linear relationships between ratiometric values (F585/F465) and varied contents of SA are realized successfully. The LOD for SA could reach to as low as 39.98 nM, which outperforms all nanozyme-originated SA sensors reported till now. Moreover, this sensor also demonstrates high selectivity and satisfactory performance in human serum samples. Furthermore, the portable sensing of SA is realized under the assistance of smartphone-based RGB analysis, demonstrating the potential of point-of-care diagnostics of PCa in the future.

Activation of METTL3 Promotes White Adipose Tissue Beiging and Combats Obesity.

The induction of beige adipocytes in white adipose tissue (WAT), also known as WAT beiging, improves glucose and lipid metabolism. However, the regulation of WAT beiging at the posttranscriptional level remains to be studied. Here, we report that METTL3, the methyltransferase of N6-methyladenosine (m6A) mRNA modification, is induced during WAT beiging in mice. Adipose-specific depletion of the Mettl3 gene undermines WAT beiging and impairs the metabolic capability of mice fed with a high-fat diet. Mechanistically, METTL3-catalyzed m6A installation on thermogenic mRNAs, including Krüppel-like factor 9 (Klf9), prevents their degradation. Activation of the METTL3 complex by its chemical ligand methyl piperidine-3-carboxylate promotes WAT beiging, reduces body weight, and corrects metabolic disorders in diet-induced obese mice. These findings uncover a novel epitranscriptional mechanism in WAT beiging and identify METTL3 as a potential therapeutic target for obesity-associated diseases. ARTICLE HIGHLIGHTS: METTL3, the methyltransferase of N6-methyladenosine (m6A) mRNA modification, is induced during WAT beiging. Depletion of Mettl3 undermines WAT beiging and impairs thermogenesis. METTL3-mediated m6A installation promotes the stability of Krüppel-like factor 9 (Klf9). KLF9 rescues impaired beiging elicited by Mettl3 depletion. Pharmaceutical activation of the METTL3 complex by its chemical ligand methyl piperidine-3-carboxylate induces WAT beiging. Methyl piperidine-3-carboxylate corrects obesity-associated disorders. The METTL3-KLF9 pathway may serve as a potential therapeutic target for obesity-associated diseases.

Elabela, a Novel Peptide, Exerts Neuroprotective Effects Against Ischemic Stroke Through the APJ/miR-124-3p/CTDSP1/AKT Pathway.

Elabela (ELA), which is the second endogenous peptide ligand of the apelin receptor (APJ) to be discovered, has been widely studied for potential use as a therapeutic peptide. However, its role in ischemic stroke (IS), which is a leading cause of disability and death worldwide and has limited therapeutic options, is uncertain. The aim of the present study was to investigate the beneficial effects of ELA on neuron survival after ischemia and the underlying molecular mechanisms. Primary cortical neurons were isolated from the cerebral cortex of pregnant C57BL/6J mice. Flow cytometry and immunofluorescence showed that ELA inhibited oxygen-glucose deprivation (OGD) -induced apoptosis and axonal damage in vitro. Additionally, analysis of the Gene Expression Omnibus database revealed that the expression of microRNA-124-3p (miR-124-3p) was decreased in blood samples from patients with IS, while the expression of C-terminal domain small phosphatase 1 (CTDSP1) was increased. These results indicated that miR-124-3p and CTDSP1 were related to ischemic stroke, and there might be a negative regulatory relationship between them. Then, we found that ELA significantly elevated miR-124-3p expression, suppressed CTDSP1 expression, and increased p-AKT expression by binding to the APJ receptor under OGD in vitro. A dual-luciferase reporter assay confirmed that CTDSP1 was a direct target of miR-124-3p. Furthermore, adenovirus-mediated overexpression of CTDSP1 exacerbated neuronal apoptosis and axonal damage and suppressed AKT phosphorylation, while treatment with ELA or miR-124-3p mimics reversed these effects. In conclusion, these results indicated that ELA could alleviate neuronal apoptosis and axonal damage by upregulating miR-124-3p and activating the CTDSP1/AKT signaling pathway. This study, for the first time, verified the protective effect of ELA against neuronal injury after ischemia and revealed the underlying mechanisms. We demonstrated the potential for the use of ELA as a therapeutic agent in the treatment of ischemic stroke.

Protective properties of extracellular vesicles in sepsis models: a systematic review and meta-analysis of preclinical studies.

BACKGROUND: Multiple preclinical studies have reported a beneficial effect of extracellular vesicles (EVs), especially mesenchymal stem cells derived EVs (MSC-EVs), in the treatment of sepsis. However, the therapeutic effect of EVs is still not universally recognized. Therefore, we conducted this meta-analysis by summarizing data from all published studies that met certain criteria to systematically review the association between EVs treatment and mortality in animal models of sepsis. METHODS: Systematic retrieval of all studies in PubMed, Cochrane and Web of Science that reported the effects of EVs on sepsis models up to September 2022. The primary outcome was animal mortality. After screening the eligible articles according to inclusion and exclusion criteria, the inverse variance method of fixed effect model was used to calculate the joint odds ratio (OR) and 95% confidence interval (CI). Meta-analysis was performed by RevMan version 5.4. RESULTS: In total, 17 studies met the inclusion criteria. Meta-analysis of those studies showed that EVs treatment was associated with reduced mortality in animal models of sepsis (OR 0.17 95% CI: 0.11,0.26, P < 0.001). Further subgroup analysis showed that the mode of sepsis induction, the source, dose, time and method of injection, and the species and gender of mice had no significant effect on the therapeutic effect of EVs. CONCLUSION: This meta-analysis showed that MSC-EVs treatment may be associated with lower mortality in animal models of sepsis. Subsequent preclinical studies will need to address the standardization of dose, source, and timing of EVs to provide comparable data. In addition, the effectiveness of EVs in treating sepsis must be studied in large animal studies to provide important clues for human clinical trials.

Adipocyte YTH N(6)-methyladenosine RNA-binding protein 1 protects against obesity by promoting white adipose tissue beiging in male mice.

Obesity, one of the most serious public health issues, is caused by the imbalance of energy intake and energy expenditure. N(6)-methyladenosine (m6A) RNA modification has been recently identified as a key regulator of obesity, while the detailed mechanism is elusive. Here, we find that YTH RNA binding protein 1 (YTHDF1), an m6A reader, acts as an essential regulator of white adipose tissue metabolism. The expression of YTHDF1 decreases in adipose tissue of male mice fed a high-fat diet. Adipocyte-specific Ythdf1 deficiency exacerbates obesity-induced metabolic defects and inhibits beiging of inguinal white adipose tissue (iWAT) in male mice. By contrast, male mice with WAT-specific YTHDF1 overexpression are resistant to obesity and shows promotion of beiging. Mechanistically, YTHDF1 regulates the translation of diverse m6A-modified mRNAs. In particular, YTHDF1 facilitates the translation of bone morphogenetic protein 8b (Bmp8b) in an m6A-dependent manner to induce the beiging process. Here, we show that YTHDF1 may be an potential therapeutic target for the management of obesity-associated diseases.

Cholesterol and C-reactive protein prognostic score predicted prognosis of immune checkpoint inhibitors based interventional therapies for intermediate-to-advanced hepatocellular carcinoma patients.

Serum cholesterol (CHO) and C-reactive protein (CRP) have been successfully used as prognostic predictors for several malignancies, respectively. However, the clinicopathological significance of CHO and CRP levels in hepatocellular carcinoma (HCC) patients treated with ICIs-based hepatic artery infusion chemotherapy (HAIC) remains unclear. Serum CHO and CRP levels were measured for a total of 152 HCC patients that had been treated with ICIs-based HAIC from February 2019 to April 2020. Efficacy was evaluated according to tumor response and survival. The median OS was not reached in the CHO-low subgroup and 17.7 months in the CHO-high subgroup (P = 0.015). The median OS was not reached in the CRP-low subgroup and 20.0 months in the CRP-high subgroup (P = 0.010). Univariate and multivariate Cox regression analysis demonstrated that both serum CHO and CRP levels were independent risk factors for the OS of HCC patients treated with ICIs-based HAIC (P < 0.05). Moreover, Cox regression analysis after Propensity Score Matching showed the similar results. CHO and CRP prognostic score (CCPS) combining CHO and CRP levels could significantly stratify HCC patients receiving ICIs-based HAIC into low-, intermediate-, and high-risk subgroups (P < 0.001). Patients in the risk subgroups reported similar disease control rates (P = 0.121) and significantly different overall response rates (low- vs intermediate- vs high-risk groups: 70.6 % vs 46.6 % vs 44.1 %, respectively, P = 0.038) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). The results of this study support the association between CCPS high risk with the response and OS for HCC patients receiving ICIs-based HAIC.

Levels of pretreatment serum lipids predict responses to PD-1 inhibitor treatment in advanced intrahepatic cholangiocarcinoma.

BACKGROUND: It has been identified that serum lipids can be used as prognostic biomarkers in several types of cancer and are associated with patient survival. We aimed to clarify the prognostic value of the serum lipids and to establish a novel effective nomogram for overall survival (OS) in intrahepatic cholangiocarcinoma (iCCA) patients receiving anti-PD1 therapy. METHODS: Pretreatment serum lipids were retrospectively analyzed for prognostic value, including apolipoprotein B (APOB), apolipoproteinA-1 (APOA1), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), which were assessed for prediction accuracy using Kaplan-Meier survival curves and time-dependent receiver operating characteristic (ROC). Cox regression analysis with univariate and multivariate factors was used to identify prognostic factors predictive of OS, and prognostic nomograms were constructed. RESULTS: All the serum lipids showed good discriminatory ability in terms of OS (all P < 0.05), the higher the lipid levels, the better the prognosis, while APOA1 and TG were remarkable independent predictors for OS in multivariate analysis (hazard ratio, 2.177,2.035; confidence interval, 1.393-3.402, 1.184-3.498; P = 0.001, P = 0.01). Four (CA19-9, APOA1, tumor number and TG) independent prognostic factors were chosen to generate the nomogram for OS. The area under the ROC curve at 1-year and 2-year consistently demonstrated that the predictive value of the nomogram was superior to serum lipids. CONCLUSION: In our study, serum lipid levels were used as a prognostic nomogram in the prediction of anti-PD-1 therapy efficacy in patients with iCCA.

LncRNA STK4 antisense RNA 1 (STK4-AS1) promoted osteosarcoma by inhibiting p53 expression.

BACKGROUND: LncRNA STK4 antisense RNA 1 (STK4-AS1) has been identified as a potential biomarker associated with multiple cancers. We proposed that STK4-AS1 plays a role in the proliferation of osteosarcoma by regulating the cell cycle. METHODS: We compared the expression of STK4-AS1, p53, and p21 in osteosarcoma vs normal samples in clinical tissues and cell lines. We determined the effect of overexpression and knockdown of STK4-AS1 in p53 expressing osteosarcoma cells U2OS, p53 muted osteosarcoma cells MG63, and osteoblast cells hFOB on p53 and p21 expression and the cell viability. For U2OS and MG63, the cell cycle was analyzed and the expression of cyclin proteins was determined. We overexpressed p53 or p21 in STK4-AS1 overexpressed cells to explore the association of STK4-AS1 and p53 in U2OS. RESULTS: The STK4-AS1 expression was higher and p53 and p21 expression were lower in osteosarcoma tissue and cells than in their non-cancer counterparts. The expression of STK4-AS1 was negatively correlated with the expression of p53 or p21. Knockdown of STK4-AS1 in U2OS decreased the cell viability, increased cells in the G0/G1 phase, decreased cells in the S and G2/M phase, decreased expression of cyclin A and B, increased p53 and p21, and had no effect on cyclin D and cyclin E, while overexpression of STK4-AS1 did the opposes. Overexpression of p53 or p21 recovered some changes caused by STK4-AS1 overexpression in U2OS. MG63 expressed no p53 and the expression of p21, cyclin A, and cyclin B, cell viability, and cell cycle were not affected by altered STK4-AS1 levels. In hFOB cells, the expression of p53 and p21 was decreased and the cell viability was increased when STK4-AS1 was overexpressed, but they were not affected when STK4-AS1 was knocked down. CONCLUSION: LncRNA STK4-AS1 promoted the cell cycle of osteosarcoma cells by inhibiting p53 expression.

Bi-dimensional principal gene feature selection from big gene expression data.

Gene expression sample data, which usually contains massive expression profiles of genes, is commonly used for disease related gene analysis. The selection of relevant genes from huge amount of genes is always a fundamental process in applications of gene expression data. As more and more genes have been detected, the size of gene expression data becomes larger and larger; this challenges the computing efficiency for extracting the relevant and important genes from gene expression data. In this paper, we provide a novel Bi-dimensional Principal Feature Selection (BPFS) method for efficiently extracting critical genes from big gene expression data. It applies the principal component analysis (PCA) method on sample and gene domains successively, aiming at extracting the relevant gene features and reducing redundancies while losing less information. The experimental results on four real-world cancer gene expression datasets show that the proposed BPFS method greatly reduces the data size and achieves a nearly double processing speed compared to the counterpart methods, while maintaining better accuracy and effectiveness.

Dynamic base stations selection method for passive location based on GDOP.

For the problem of passive location in mobile cellular network, base stations (BSs) selection can improve positioning accuracy. Through the analysis of base station layout in cellular networks, using Geometric Dilution of Precision (GDOP) as the optimization objective, we propose a Dynamic Base Stations Selection (DBSS) method in a cellular unit. This method enables the system to dynamically select the positioning base station when positioning target in the detection area. DBSS mainly include three steps: nearest base station calculation, layout of base stations analysis, and base station selection based on the target location. We mainly focus on the derivation of four-base station dynamic selection (DBSS4) and five-base station dynamic selection (DBSS5) algorithms. In simulation experiments, DBSS4 algorithm and DBSS5algorithm were compared with the state-of-the-art of BSs selection methods. The results show that our proposed method can achieve the exhaustive search in cellular cells and reduce more than 20% of the GDOP cumulative positioning error compared with the fixed four-base station selection algorithm. Meanwhile, the proposed method is more efficient, requires less running time and floating-point operations (FLOPs) than other comparison algorithm, and is independent of localization algorithms.

Real-Life Experience of Regorafenib in Patients With Advanced Hepatocellular Carcinoma.

Background: The RESORCE trial reported that regorafenib was effective as the second-line treatment for patients with hepatocellular carcinoma (HCC) after progression on sorafenib. Real-world data are needed to assess clinical outcomes and adverse events in the setting of daily practice. Objective: We aimed to evaluate the efficacy and safety of regorafenib after disease progression with sorafenib in Chinese patients with advanced HCC. Patients and Methods: A total of 41 patients with advanced HCC who did not respond to sorafenib and followed a regorafenib regimen were enrolled in this retrospective study. Overall survival (OS), progression-free survival (PFS), radiological responses, and adverse events (AEs) were evaluated. Survival curves were compared by using the log-rank test and constructed with the Kaplan-Meier method. Results: The median PFS with regorafenib was 6.6 months (range: 5.0-8.2 months), and the median OS with regorafenib was not reached. The 1-year OS rate of regorafenib was 66.4%. The median OS of sequential sorafenib to regorafenib treatment was 35.3 months [95% confidence interval (CI), 24.3-46.3], and the 2-year OS rate of sequential sorafenib to regorafenib treatment was 74.4%. The most common AEs of regorafenib treatment were elevated aspartate aminotransferase [17/41 patients (41.5%)], elevated alanine aminotransferase [16/41 patients (39%)] and hand-foot syndrome [14/41 patients (34.1%)]. Conclusion: Regorafenib appears to be safe and clinically effective in patients with advanced HCC who progressed on first-line sorafenib.

LncRNA CBR3-AS1 promotes osteosarcoma progression through the network of miR-140-5p/DDX54-NUCKS1-mTOR signaling pathway.

Long noncoding RNA (lncRNA) CBR3-AS1 (termed as CBR3-AS1) has been reported to be upregulated in several cancers including osteosarcoma. Its positive impact on the proliferation, migration, and invasion of osteosarcoma cells has been unveiled; nevertheless, whether it also affects the stemness and epithelial-mesenchymal transition (EMT) of osteosarcoma cells is unclear. The purpose for this study was to explore the effects of CBR3-AS1 on the stemness and EMT of osteosarcoma cells as well as its underlying mechanism. qRT-PCR and western blot were applied to detect target gene expression. Function assays were conducted to evaluate the effect of genes on the stemness and EMT of osteosarcoma cells. Mechanism assays were done to verify the association among different genes. In vivo assays were also performed. The obtained data showed that CBR3-AS1 demonstrated a high expression in osteosarcoma cells. CBR3-AS1 could promote stemness and EMT of osteosarcoma cells as well as osteosarcoma tumor growth. Mechanically, CBR3-AS1 sponged miR-140-5p and recruited DDX54 to upregulate NUCKS1, thus activating the mTOR signaling pathway. Furthermore, NUCKS1 could facilitate stemness and EMT of osteosarcoma cells. In summary, this study reveals that CBR3-AS1 exerts an oncogenic role in osteosarcoma through modulating the network of the miR-140-5p/DDX54-NUCKS1-mTOR signaling pathway.

Antiviral Treatments Eliminate the Adverse Impacts of High Baseline HBV Loads on the Survival of HBV-Related HCC Patients.

Background: In consideration of no standard exclusion criteria for hepatitis B virus (HBV) loads in hepatocellular carcinoma (HCC)-related clinical trials, this study aimed to investigate the prevalence of HBV-related exclusion criteria among current clinical trials and evaluate whether antiviral treatments could eliminate the adverse effects from high HBV loads for HCC patients. Methods: This is a retrospective study including 772 HCC clinical trials on ClinicalTrials.gov and 1784 HCC patients receiving antiviral treatment. The Kaplan-Meier (K-M) method was used to compare the progression-free survival (PFS) and overall survival (OS) between different groups, and Cox regression analyses were performed to validate possible risk factors on PFS and overall survival OS. Results: Among 772 clinical trials, 58.3% did not adopt baseline HBV loads as exclusion criteria, 18.0% was 2000 IU/mL, and 10.5% was receiving antiviral therapy. We observed baseline HBV loads had no significant impact on PFS (p = 0.491, 0.155, 0.119, 0.788, 0.280, 0.683 respectively) and OS (p = 0.478, 0.741, 0.263, 0.039, 0.999, 0.581 respectively) in all patients or each treatment group including hepatectomy, radiofrequency ablation, interventional therapy, targeted drugs and anti-programmed cell death immunotherapy, except for the OS of interventional therapy group, where patients with high HBV loads had higher BCLC stage, serum AFP level and ALBI grade (p = 0.009, 0.015 and 0.003, respectively). Conclusion: Antiviral treatments could eliminate the adverse impacts of high HBV loads on the survival of HCC patients. Simplified eligibility criteria can be adopted for HCC patients with HBV infection where regular antiviral therapy should be enough.

Tenofovir vs. Entecavir on Outcomes of Hepatitis B Virus-Related Hepatocellular Carcinoma after Radiofrequency Ablation.

For patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) treated with curative radiofrequency ablation (RFA), the effect of entecavir (ETV) vs. tenofovir disoproxil fumarate (TDF) on recurrence-free survival (RFS) and overall survival (OS) remains unclear. We aimed to compare the outcomes of patients receiving ETV or TDF after RFA. This study consecutively collected patients who were treated with ETV (n = 202) or TDF (n = 102) for chronic hepatitis B (CHB) after curative RFA of HCC from December 2015 to January 2021 at Sun Yat-sen University Cancer Center. There were 130 patients in the ETV group and 77 patients in the TDF group after we performed 1-to-n propensity score matching. Kaplan−Meier and Cox regression analyses were performed to validate possible risk factors for RFS and OS. In addition, we estimated the curative effect of ETV and TDF for HBV-related hepatitis by recording the change in serum HBV DNA and ALBI grade after RFA. During the study period (median 34.1 (interquartile range: 19.6−47.4 months) months), 123 (40.5%) patients suffered HCC recurrence, and 15 (4.9%) died. In the full cohort, the probability of HCC recurrence (41.6% vs. 37.3%, p = 0.49) and overall survival (95% vs. 95.1%, p = 0.39) at 5 years were similar between the ETV and TDF groups. In the matched cohort, HCC recurrence (40.8% vs. 40.3%, p = 0.35) and overall survival (96.9% vs. 93.5%, p = 0.12) at 5 years were similar between the ETV and TDF groups. Furthermore, the early RFS (<2 years) did not differ significantly between the two groups in the full and matched cohorts (p = 0.26, p = 0.13). Compared with the ALBI grade before RFA, the ALBI grade of 80 patients (41%) remained stable or improved in the ETV group and 64 patients (64%) in the TDF group (p < 0.001). The mean time of serum HBV DNA reduction to 0 was 9.13 (95% CI: 5.92−12.33) and 2.75 (95% CI: 2.01−3.49) months in the ETV and TDF groups, respectively (p = 0.015). The RFS and OS of patients after curative RFA for HCC were not significantly different between the ETV and TDF groups. TDF therapy was associated with a better effect of protecting liver function and reducing the load of HBV. Further validation studies are needed.

A novel isoform of hydroxyacyl-CoA dehydrogenase inhibits cell proliferation.

Hydroxyacyl-CoA dehydrogenase (HADH) catalyzes the third reaction of mitochondrial ß-oxidation cascade, while the regulation of its expression and function remains to be elucidated. Using the quantitative translation initiation sequencing (QTI-seq), we have identified that murine Hadh mRNA has two alternative translation start codons. We demonstrated that translation from upstream start codon encodes the mitochondrial isoform of HADH, while translation from downstream start codon produces a short isoform (HADH-S) with predominant nuclear localization. Moreover, overexpression of HADH-S inhibits the proliferation of mouse embryonic fibroblasts. Overall, our results identify a novel isoform of HADH participating in cell proliferation.

Tenofovir vs. entecavir on prognosis of hepatitis B virus-related hepatocellular carcinoma after curative resection.

BACKGROUND: Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are recommended as first-line choices regarding the treatment of chronic hepatits B. The impact of the two antiviral agents on prognosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative liver resection remains to be explored. We aimed to assess the effect of antiviral therapy with ETV or TDF after curative resection on the prognosis of patients with HBV-related HCC. METHODS: A total of 1173 consecutive patients who were treated with ETV or TDF after curative liver resection for HCC were enrolled in the study. HCC recurrence, overall survival, postoperative liver function reserve, and early virologic (VR) and biochemical responses (BR) of patients were compared between the ETV and TDF groups by propensity score matching (PSM) from the date of liver resection for HCC. RESULTS: No difference was observed with recurrence-free survival between TDF and ETV in the PSM cohort (hazard ratio [HR], 0.91; 95% confidence interval [CI] 0.70-1.17; P = 0.45). No difference was observed with early VR and BR between TDF and ETV in the PSM cohort. Compared with ETV, TDF therapy was associated with significantly better protection of liver function and higher overall survival rates in the PSM cohort (HR, 0.37; 95% CI 0.20-0.71; P = 0.002). After PSM, 69 (40.8%) patients in the ETV group and 63 (57.3%) patients in the TDF group had single tumor recurrence, while the TDF group had significantly more patients with single tumor recurrence in the PSM cohort (P = 0.007). CONCLUSIONS: For patients who underwent curative resection for HBV-related HCC, TDF treatment had a significantly better overall survival and better protection of liver function, but no difference in the incidences of HCC recurrence than ETV treatment.