Research progress of lncRNA and miRNA in hepatic ischemia-reperfusion injury

BackgroundHepatic ischemia-reperfusion injury (HIRI) is a common complication of liver surgeries, such as hepatectomy and liver transplantation. In recent years, several non-coding RNAs (ncRNAs) including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been identified as factors involved in the pathological progression of HIRI. In this review, we summarized the latest research on lncRNAs, miRNAs and the lncRNA-miRNA regulatory networks in HIRI.Data sourcesThe PubMed and Web of Science databases were searched for articles published up to December 2021 using the following keywords: “hepatic ischemia-reperfusion injury”, “lncRNA”, “long non-coding RNA”, “miRNA” and “microRNA”. The bibliography of the selected articles was manually screened to identify additional studies.ResultsThe mechanism of HIRI is complex, and involves multiple lncRNAs and miRNAs. The roles of lncRNAs such as AK139328, CCAT1, MALAT1, TUG1 and NEAT1 have been established in HIRI. In addition, numerous miRNAs are associated with apoptosis, autophagy, oxidative stress and cellular inflammation that accompany HIRI pathogenesis. Based on the literature, we conclude that four lncRNA-miRNA regulatory networks mediate the pathological progression of HIRI. Furthermore, the expression levels of some lncRNAs and miRNAs undergo significant changes during the progression of HIRI, and thus are potential prognostic markers and therapeutic targets.ConclusionsComplex lncRNA-miRNA-mRNA networks regulate HIRI progression through mutual activation and antagonism. It is necessary to screen for more HIRI-associated lncRNAs and miRNAs in order to identify novel therapeutic targets.     

Potential Gains in Health-Adjusted Life Expectancy by Reducing Burden of Noncommunicable Diseases in 188 Countries: A Population-Based Study

ObjectivesThis article quantifies the potential gains in health-adjusted life expectancy for people aged 30 to 70 years (HALE_[30-70]) by examining the reductions in disability in addition to premature mortality from noncommunicable diseases (NCDs).MethodsWe extracted data from the Global Burden of Disease Study 2019 for 4 major NCDs (cancers, cardiovascular diseases, chronic respiratory diseases, and diabetes mellitus) in 188 countries from 2010 to 2019. Estimates of the potential gains in HALE_[30-70] were based on a counterfactual analysis involving 3 alternative future scenarios: (1) achieve Sustainable Development Goals target 3.4 but do not make any progress on disability reduction, (2) achieve Sustainable Development Goals target 3.4 and eliminate NCD-related disability, and (3) eliminate all NCD-related mortality and disability.ResultsIn all scenarios, the high-income group has the greatest potential gains in HALE_[30-70], above the global average. For all specific causes, potential gains in HALE_[30-70] decrease as income levels fall. Across these 3 scenarios, the potential gains in HALE_[30-70] globally of reducing premature mortality for 4 major NCDs are 3.13 years, 4.53 years, and 7.32 years, respectively. In scenario A, all income groups have the greatest potential gains in HALE_[30-70] from diabetes and chronic respiratory diseases. In scenarios B and C, the high-income group has the greatest potential gains in HALE_[30-70] from cancer intervention, and the other income groups have the greatest potential gains in HALE_[30-70] from cardiovascular diseases intervention.ConclusionReducing premature death and disability from 4 major NCDs at once and attaching equal importance to each lead to a sizable improvement in HALE_[30-70].     

A novel xenograft model of human hepatocellular carcinoma in immunocompetent mice based on the microcarrier-6

BackgroundHepatocellular carcinoma (HCC) is one of the most common malignant tumors that threaten human health; thus, the establishment of an animal model with clinical features similar to human hepatocellular carcinoma is of important practical significance.MethodsTaking advantage of the novel microcarrier-6, human HCC cells were injected into immunocompetent mice to establish a novel human HCC patient-derived xenograft (PDX) model. Primary HCC cells were isolated from fresh hepatocellular carcinoma tissues, which were subsequently co-cultured with microcarrier-6 to construct a three-dimensional tumor cell culture model in vitro. The HCC-microcarrier complex was implanted into mice by subcutaneous inoculation, and the tumor formation time, tumor formation rate, and pathological manifestation were recorded. Changes of immune parameters in mice were detected by flow cytometry.ResultsThe success rate was 60% (6/10) in the establishment of hepatocellular carcinoma PDX mouse model, and the total tumor formation rate of the tumor-forming model is 90–100%. H&E staining and immunohistochemical experiments indicate that the model well retained the characteristics of the primary tumor. Interestingly, M2 macrophages in tumor-bearing mice increased significantly, and the levels of CD4⁺ T cells were significantly reduced.ConclusionsThrough the application of the microcarrier-6 in immunocompetent mice, we successfully established a novel human HCC PDX model, which can be used to better study and further elucidate the occurrence and pathogenic mechanism of HCC, improve the predictability of toxicity and drug sensitivity in HCC.     

Risk factors for acute rejection in liver transplantation and its impact on the outcomes of recipients

ObjectiveTo determine the risk factors for acute rejection in liver transplantation and its impact on the outcomes of the recipients.MethodsClinicopathological data of 290 patients who underwent liver transplantation from January 2012 to December 2021 at our center were retrospectively evaluated. Patients were grouped into an acute rejection (AR) group and a normal (NM) group based on the confirmed histopathological diagnosis of acute rejection. Univariate and multivariate logistic regression were used to determine the risk factors for acute rejection.Results244 patients were included in the study. Acute rejection occurred in 27 (11.1%) of the patients. Warm ischemia time (P = 0.137), cold ischemia time (P = 0.064) and chronic liver failure (P = 0.001) were potential risk factors for acute rejection. Chronic liver failure (P < 0.001, OR = 8.22, 95% CI = 2.47–27.32) was the independent risk factor. There was no significant difference in overall survival between recipients with acute rejection and those without it (P = 0.985). The 1-, 3- and 5-year overall survival in the NM group was 98.1%, 85.7% and 78.6% respectively vs 88.9%, 82.5% and 82.5% respectively in the AR group.ConclusionAcute rejection does not appear to affect the long-term survival of the recipients. Only chronic liver failure was an independent risk factor for acute rejection. Our findings further illustrate that contradictions still exist on which factors influence acute rejection in liver transplant recipients.SummaryClinicopathological data of 290 liver transplant recipients at our center between January 2012 and December 2021 were retrospectively evaluated to determine the risk factors for acute rejection and its impact on the outcomes of the recipients. 244 patients were included in the analysis. 27 of the 244 experienced acute rejection. Propensity score matching was performed to reduce the confounding effect. Patients were assigned to an acute rejection group (n = 27) and a normal group (n = 54). Chronic liver failure (P < 0.001, OR = 8.22, 95% CI = 2.47–27.32) was the determined to be independent risk factor for acute rejection. Acute rejection did not appear to affect the long-term survival of the recipients and there was no significant difference in overall survival between the patients with acute rejection and those without it.     

Changes in abdominal adipose tissue depots assessed by MRI correlate with hepatic histologic improvement in non-alcoholic steatohepatitis

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The latest research progress on minimally invasive treatments for hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. Due to the high prevalence of hepatitis B virus (HBV) infection in China, the incidence of HCC in China is high, and liver cirrhosis caused by chronic hepatitis also brings great challenges to treatment. This paper reviewed the latest research progress on minimally invasive treatments for HCC, including percutaneous thermal ablation and new nonthermal ablation techniques, and introduced the principles, advantages, and clinical applications of various therapeutic methods in detail.Data sourcesThe data of treatments for HCC were systematically collected from the PubMed, ScienceDirect, American Chemical Society and Web of Science databases published in English, using “minimally invasive” and “hepatocellular carcinoma” or “liver cancer” as the keywords.ResultsPercutaneous thermal ablation is still a first-line strategy for the minimally invasive treatment of HCC. The effect of microwave ablation (MWA) on downgrading treatment before liver transplantation is better than that of radiofrequency ablation (RFA), while RFA is more widely used in the clinical practice. High-intensity focused ultrasound (HIFU) is mainly used for the palliative treatment of advanced liver cancer. Electrochemotherapy (ECT) delivers chemotherapeutic drugs to the target cells while reducing the blood supply around HCC. Irreversible electroporation (IRE) uses a microsecond-pulsed electric field that induces apoptosis and necrosis and triggers a systemic immune response. The nanosecond pulsed electric field (nsPEF) has achieved a good response in the ablation of mice with HCC, but it has not been reported in China for the treatment of human HCC.ConclusionsA variety of minimally invasive treatments provide a sufficient survival advantage for HCC patients. Nonthermal ablation will lead to a new wave with its unique advantage of antitumor recurrence and metastasis.