Mesenchymal stem cell-based Smad7 gene therapy for experimental liver cirrhosis

BackgroundBone mesenchymal stem cells (MSCs) can promote liver regeneration and inhibit inflammation and hepatic fibrosis. MSCs also can serve as a vehicle for gene therapy. Smad7 is an essential negative regulatory gene in the TGF-β1/Smad signalling pathway. Activation of TGF-β1/Smad signalling accelerates liver inflammation and fibrosis; we therefore hypothesized that MSCs overexpressing the Smad7 gene might be a new cell therapy approach for treating liver fibrosis via the inhibition of TGF-β1/Smad signalling.MethodsMSCs were isolated from 6-week-old Wistar rats and transduced with the Smad7 gene using a lentivirus vector. Liver cirrhosis was induced by subcutaneous injection of carbon tetrachloride (CCl4) for 8 weeks. The rats with established liver cirrhosis were treated with Smad7-MSCs by direct injection of cells into the main lobes of the liver. The expression of Smad7, Smad2/3 and fibrosis biomarkers or extracellular matrix proteins and histopathological change were assessed by quantitative PCR, ELISA and Western blotting and staining.ResultsThe mRNA and protein level of Smad7 in the recipient liver and serum were increased after treating with Smad-MSCs for 7 and 21 days (P

I. S. Turgenev’s Novel “Fathers and Sons” in Chinese Translation and Research Reception

The previously not considered question of the reception of the novel “Fathers and Sons” by Ivan Sergeyevich Turgenev in the Chinese research tradition and in translations is considered. The novelty of the work is seen in the fact that at present in the Russian and Chinese literary environment there is no detailed study devoted to the perception of the novel “Fathers and Sons” in China. The relevance of the article is due to the need to study the significance of I.S. Turgenev for the Chinese cultural process in order to understand the specifics of Russian-Chinese literary relations, which corresponds to the trends of modern comparative literature. The most important issues are those related to the study of Russian literature in the Chinese context. It is noted that, based on the work of Chinese researchers and translators, it is possible to draw conclusions, firstly, about the popularity of the work “Fathers and Sons” in the Chinese readership, and secondly, about the special merits of the translations of Ba Jin, Li Ni, Zheng Bin and other translators to distribute the works of I. S. Turgenev in China. It is shown that not only scientists and translators, but also cinematographers turn to the work of the classic, which also testifies to the great interest of the Chinese audience in the classical heritage of Russian literature

Accelerating L 1 -penalized expectation maximization algorithm for latent variable selection in multidimensional two-parameter logistic models

© 2023 Shang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/One of the main concerns in multidimensional item response theory (MIRT) is to detect the relationship between observed items and latent traits, which is typically addressed by the exploratory analysis and factor rotation techniques. Recently, an EM-based L1-penalized log-likelihood method (EML1) is proposed as a vital alternative to factor rotation. Based on the observed test response data, EML1 can yield a sparse and interpretable estimate of the loading matrix. However, EML1 suffers from high computational burden. In this paper, we consider the coordinate descent algorithm to optimize a new weighted log-likelihood, and consequently propose an improved EML1 (IEML1) which is more than 30 times faster than EML1. The performance of IEML1 is evaluated through simulation studies and an application on a real data set related to the Eysenck Personality Questionnaire is used to demonstrate our methodologies.Peer reviewe

Caspase-3 suppresses diethylnitrosamine-induced hepatocyte death, compensatory proliferation and hepatocarcinogenesis through inhibiting p38 activation

It is critical to understand the molecular mechanisms of hepatocarcinogenesis in order to prevent or treat hepatocellular carcinoma (HCC). The development of HCC is commonly associated with hepatocyte death and compensatory proliferation. However, the role of Caspase-3, a key apoptotic executor, in hepatocarcinogenesis is unknown. In this study, we used Caspase-3-deficient mice to examine the role of Caspase-3 in hepatocarcinogenesis in a chemical (diethylnitrosamine, DEN)-induced HCC model. We found that Caspase-3 deficiency significantly increased DEN-induced HCC. Unexpectedly, Caspase-3 deficiency increased apoptosis induced by DEN and the subsequent compensatory proliferation. Intriguingly, we discovered that Caspase-3 deficiency increased the activation of p38 with and without DEN treatment. Moreover, we demonstrated that TNFα and IL1α stimulated increased activation of p38 in Caspase-3 KO hepatocytes compared with wild-type hepatocytes. Finally, we found that inhibition of p38 by SB202190 abrogated enhanced hepatocyte death, compensatory proliferation and HCC induced by DEN in Caspase-3-deficient mice. Overall, our data suggest that Caspase-3 inhibits chemical-induced hepatocarcinogenesis by suppressing p38 activation and hepatocyte death

An update on the functional roles of long non‑coding RNAs in ischemic injury (Review)

Ischemic injuries result from ischemia and hypoxia in cells. Tissues and organs receive an insufficient supply of nutrients and accumulate metabolic waste, which leads to the development of inflammation, fibrosis and a series of other issues. Ischemic injuries in the brain, heart, kidneys, lungs and other organs can cause severe adverse effects. Acute renal ischemia induces acute renal failure, heart ischemia induces myocardial infarction and cerebral ischemia induces cerebrovascular accidents, leading to loss of movement, consciousness and possibly, life-threatening disabilities. Existing evidence suggests that long non-coding RNAs (lncRNAs) are regulatory sequences involved in transcription, post-transcription, epigenetic regulation and multiple physiological processes. lncRNAs have been shown to be differentially expressed following ischemic injury, with the severity of the ischemic injury being affected by the upregulation or downregulation of certain types of lncRNA. The present review article provides an extensive summary of the functional roles of lncRNAs in ischemic injury, with a focus on the brain, heart, kidneys and lungs. The present review mainly summarizes the functional roles of lncRNA MALAT1, lncRNA MEG3, lncRNA H19, lncRNA TUG1, lncRNA NEAT1, lncRNA AK139328 and lncRNA CAREL, among which lncRNA MALAT1, in particular, plays a crucial role in ischemic injury and is currently a hot research topic

Quarterly GDP forecast based on coupled economic and energy feature WA-LSTM model

Existing macroeconomic forecasting methods primarily focus on the characteristics of economic data, but they overlook the energy-related features concealed behind these economic characteristics, which may lead to inaccurate GDP predictions. Therefore, this paper meticulously analyzes the relationship between energy big data and economic data indicators, explores the coupling feature mining of energy big data and economic data, and constructs features coupling economic and energy data. Targeting the nonlinear variation coupling features in China’s quarterly GDP data and using the long short-term memory (LSTM) neural network model based on deep learning, we employ wavelet analysis technology (WA) to decompose selected macroeconomic variables and construct a prediction model combining LSTM and WA, which is further compared with multiple benchmark models. The research findings show that, in terms of quarterly GDP data prediction, the combined deep learning model and wavelet analysis significantly outperform other methods. When processing structurally complex, nonlinear, and multi-variable data, the LSTM and WA combined prediction model demonstrate better generalization capabilities, with its prediction accuracy generally surpassing other benchmark models

A novel anti-virulence gene revealed by proteomic analysis in Shigella flexneri 2a

<p>Abstract</p> <p>Background</p> <p><it>Shigella flexneri </it>is a gram-negative, facultative pathogen that causes the majority of communicable bacterial dysenteries in developing countries. The virulence factors of <it>S. flexneri </it>have been shown to be produced at 37 degrees C but not at 30 degrees C. To discover potential, novel virulence-related proteins of <it>S. flexneri</it>, we performed differential in-gel electrophoresis (DIGE) analysis to measure changes in the expression profile that are induced by a temperature increase.</p> <p>Results</p> <p>The ArgT protein was dramatically down-regulated at 37 degrees C. In contrast, the ArgT from the non-pathogenic <it>E. coli </it>did not show this differential expression as in <it>S. flexneri</it>, which suggested that <it>argT </it>might be a potential anti-virulence gene. Competitive invasion assays in HeLa cells and in BALB/c mice with <it>argT </it>mutants were performed, and the results indicated that the over-expression of ArgT_Y225Dwould attenuate the virulence of <it>S. flexneri</it>. A comparative proteomic analysis was subsequently performed to investigate the effects of ArgT in <it>S. flexneri </it>at the molecular level. We show that HtrA is differentially expressed among different derivative strains.</p> <p>Conclusion</p> <p>Gene <it>argT </it>is a novel anti-virulence gene that may interfere with the virulence of <it>S. flexneri </it>via the transport of specific amino acids or by affecting the expression of the virulence factor, HtrA.</p