Mycn ameliorates cardiac hypertrophy-induced heart failure in mice by mediating the USP2/JUP/Akt/ß-catenin cascade.

BACKGROUND: Pathological cardiac hypertrophy is associated with cardiac dysfunction and is a key risk factor for heart failure and even sudden death. This study investigates the function of Mycn in cardiac hypertrophy and explores the interacting molecules. METHODS: A mouse model of cardiac hypertrophy was induced by isoproterenol (ISO). The cardiac dysfunction was assessed by the heart weight-to-body weight ratio (HW/BW), echocardiography assessment, pathological staining, biomarker detection, and cell apoptosis. Transcriptome alteration in cardiac hypertrophy was analyzed by bioinformatics analysis. Gain- or loss-of-function studies of MYCN proto-oncogene (Mycn), ubiquitin specific peptidase 2 (USP2), and junction plakoglobin (JUP) were performed. The biological functions of Mycn were further examined in ISO-treated cardiomyocytes. The molecular interactions were verified by luciferase assay or immunoprecipitation assays. RESULTS: Mycn was poorly expressed in ISO-treated mice, and its upregulation reduced HW/BW, cell surface area, oxidative stress, and inflammation while improving cardiac function of mice. It also reduced apoptosis of cardiomyocytes in mice and those in vitro induced by ISO. Mycn bound to the USP2 promoter to activate its transcription. USP2 overexpression exerted similar myocardial protective functions. It stabilized JUP protein by deubiquitination modification, which blocked the Akt/ß-catenin pathway. Knockdown of JUP restored phosphorylation of Akt and ß-catenin protein level, which negated the protective effects of USP2. CONCLUSION: This study demonstrates that Mycn activates USP2 transcription, which mediates ubiquitination and protein stabilization of JUP, thus inactivating the Akt/ß-catenin axis and alleviating cardiac hypertrophy-induced heart failure.

Evolving policies, enduring impacts: Cross-sectional surveys of mental health, risk-related perceptions, and coping behaviors throughout China's U-turn in its stringent zero-COVID policy.

OBJECTIVE: China's early encounter with COVID-19 and protracted prevention policies, presents an ideal case to study psychological changes during a prolonged and evolving crisis. This study aims to examine the shifts in mental health symptoms, risk-related perceptions, and associated coping behaviors within two large-scale samples of Chinese respondents, spanning from the pandemic's onset to the relaxation of the zero-COVID policy. Moreover, the study strives to identify protective factors that could potentially mitigate the pandemic's impact. METHODS: Two online surveys were conducted during China's initial pandemic phase (February 25-28, 2020) and the relaxation of the zero-COVID policy (March 30-April 18, 2023). Participants' mental health indicators, risk-related perceptions, and coping behaviors were assessed using the Depression, Anxiety, and Stress Scale-21 Items, the 9-item Bergen Burnout Inventory, and other adopted scales. Multivariable linear models were employed to examine the enduring psychological impact of the pandemic and identify potential protective factors. RESULTS: Analysis of two datasets comprising 1946 and 1878 participants from the onset and the remission of China's COVID-19 pandemic revealed an upward trend in various mental health indicators of Chinese respondents between 2020 and 2023. Similarly, risk-related perceptions, encompassing perceived severity, susceptibility, and self-efficacy, and risk-related information sharing witnessed an increase. Being female, single, residing in rural areas, having higher education, and lacking acquaintances with COVID-19 are protective factors against mental health risks. Additionally, being female, married, over 30, living in big cities, having higher education, and lacking personal or acquaintances' infection history are associated with engaging in protective behaviors and reduced information avoidance. CONCLUSION: The study investigated the changes in mental health symptoms, risk-related perceptions, and coping behaviors of Chinese respondents between 2020 and 2023 and identified protective factors against the pandemic's impact, including demographic (gender, age), social (education, marital status, residence), and exposure (infection history) elements. Understanding these fluctuations and protective elements is crucial for policymakers, as it can inform the development of targeted strategies to alleviate negative psychological impacts while effectively managing future pandemics.

FBXW7 promotes pathological cardiac hypertrophy by targeting EZH2-SIX1 signaling.

F-box and WD repeat domain-containing 7 (FBXW7) is an E3-ubiquitin ligase, which serves as one of the components of the SKP1, CUL1, and F-box protein type ubiquitin ligase (SCF) complex. Previous studies reveal that FBXW7 participates in cancer, inflammation and Parkinson's disease. FBXW7 also contributes to angiogenesis of endothelial cells. However, the function of FBXW7 in cardiac homeostasis remains to elucidate. Here we identified the critical role of FBXW7 during cardiac hypertrophy in humans and rodents. Quantitative real-time PCR (qRT-PCR) and Western blot revealed that the mRNA and protein levels of FBXW7 were upregulated significantly in hypertrophic hearts in human and mouse as well as Angiotensin II (Ang II)-induced hypertrophic neonatal rat cardiomyocytes (NRCM). Gain-of-function (adenovirus) and loss-of-function (siRNA) experiments provided evidence that FBXW7 promoted Ang II-induced cardiomyocyte hypertrophy as demonstrated by the increase in the size of cardiomyocytes and overexpression of hypertrophic fetal genes myosin heavy chain 7 (Myh7) natriuretic peptide a (Nppa), brain natriuretic peptide (Nppb). Further mechanism study revealed that FBXW7 promoted the expression of sine oculis homeobox homolog 1 (SIX1) in cardiomyocytes, which relied on regulation of the stability of the histone methyltransferase EZH2 (Enhancer of zeste homolog 2). Previous work revealed the pro-hypertrophic role of the EZH2-SIX1 axis in rodents. Indeed, our genetic and pharmacological evidence showed that the EZH2-SIX1 signaling was critically involved in FBXW7 functions in Ang II-induced cardiomyocyte hypertrophy. Therefore, we identified FBWX7 as an important regulator of cardiac hypertrophy via modulating the EZH2-SIX1 axis.

Effectiveness and Safety of Combination Therapy of Transarterial Chemoembolization and Apatinib for Unresectable Hepatocellular Carcinoma in the Chinese Population: A Meta-Analysis.

BACKGROUND: The combination of transarterial chemoembolization (TACE) and apatinib has been used in the treatment of intermediate or advanced hepatocellular carcinoma (HCC). However, its effectiveness and safety are also argued. METHODS: Eligible studies were collected from a computer search of literatures published from the database establishment to May 2019 in PubMed, Web of Science, EMBASE, Ovid, the Cochrane Library, Wanfang Database, China National Knowledge Infrastructure, and China Biology Medicine Disc. The objective response rate (ORR), the disease control rate (DCR), survival rate (SR), and the incidences of treatment-related adverse effects (AEs) were collected as the relevant outcomes. Data were analyzed through fixed/random effects of meta-analysis models with RevMan 5.3 software. RESULTS: Eight randomized controlled clinical trials comprising 528 patients and 4 cohort studies comprising 226 patients were eventually included. Compared to the control group treated with TACE solely, combination therapy group, in which intermediate or advanced HCC patients were treated with TACE and apatinib, significantly enhanced ORR (relative risk [RR] 2.06, 95% CI 1.63-2.61, p < 0.001), DCR (RR 1.65, 95% CI 1.24-2.20, p < 0.001), and whole SRs of 6-month (RR 1.52, 95% CI 1.08-2.14, p = 0.02), 1-year (RR 1.52, 95% CI 1.25-1.84, p < 0.001), and 2-year (RR 1.84, 95% CI 1.34-2.54, p < 0.001). The incidence of hand foot syndrome, proteinuria, hypertension, and diarrhea was significantly increased in the combination therapy group compared with the control group (p < 0.05), and the incidence of nausea and vomiting, fever, and myelosuppression, respectively, was similar in 2 groups (p > 0.05). CONCLUSIONS: The combination therapy of TACE and apatinib can enhance the clinical effectiveness better than TACE solely in patients with intermediate or advanced HCC, while increase in the AEs is usually tolerable.

iATC-mISF: a multi-label classifier for predicting the classes of anatomical therapeutic chemicals.

Motivation: Given a compound, can we predict which anatomical therapeutic chemical (ATC) class/classes it belongs to? It is a challenging problem since the information thus obtained can be used to deduce its possible active ingredients, as well as its therapeutic, pharmacological and chemical properties. And hence the pace of drug development could be substantially expedited. But this problem is by no means an easy one. Particularly, some drugs or compounds may belong to two or more ATC classes. Results: To address it, a multi-label classifier, called iATC-mISF, was developed by incorporating the information of chemical­chemical interaction, the information of the structural similarity, and the information of the fingerprintal similarity. Rigorous cross-validations showed that the proposed predictor achieved remarkably higher prediction quality than its cohorts for the same purpose, particularly in the absolute true rate, the most important and harsh metrics for the multi-label systems. Availability and Implementation: The web-server for iATC-mISF is accessible at http://www.jci-bioinfo.cn/iATC-mISF. Furthermore, to maximize the convenience for most experimental scientists, a step-by-step guide was provided, by which users can easily get their desired results without needing to go through the complicated mathematical equations. Their inclusion in this article is just for the integrity of the new method and stimulating more powerful methods to deal with various multi-label systems in biology. Contact: xxiao@gordonlifescience.org Supplementary Information: Supplementary data are available at Bioinformatics online.

pLoc-mAnimal: predict subcellular localization of animal proteins with both single and multiple sites.

MOTIVATION: Cells are deemed the basic unit of life. However, many important functions of cells as well as their growth and reproduction are performed via the protein molecules located at their different organelles or locations. Facing explosive growth of protein sequences, we are challenged to develop fast and effective method to annotate their subcellular localization. However, this is by no means an easy task. Particularly, mounting evidences have indicated proteins have multi-label feature meaning that they may simultaneously exist at, or move between, two or more different subcellular location sites. Unfortunately, most of the existing computational methods can only be used to deal with the single-label proteins. Although the 'iLoc-Animal' predictor developed recently is quite powerful that can be used to deal with the animal proteins with multiple locations as well, its prediction quality needs to be improved, particularly in enhancing the absolute true rate and reducing the absolute false rate. RESULTS: Here we propose a new predictor called 'pLoc-mAnimal', which is superior to iLoc-Animal as shown by the compelling facts. When tested by the most rigorous cross-validation on the same high-quality benchmark dataset, the absolute true success rate achieved by the new predictor is 37% higher and the absolute false rate is four times lower in comparison with the state-of-the-art predictor. AVAILABILITY AND IMPLEMENTATION: To maximize the convenience of most experimental scientists, a user-friendly web-server for the new predictor has been established at http://www.jci-bioinfo.cn/pLoc-mAnimal/, by which users can easily get their desired results without the need to go through the complicated mathematics involved. CONTACT: xxiao@gordonlifescience.org or kcchou@gordonlifescience.org. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Antitumor activity of a sulfated polysaccharide from Enteromorpha intestinalis targeted against hepatoma through mitochondrial pathway.

A sulfated polysaccharide (EI-SP), extracted from Enteromorpha intestinalis that is a kind of algae, is found to have anticancer activity. This study was designed to investigate the anti-tumor effect of EI-SP on human hepatoma HepG2 cell line and its possible mechanisms. An MTT assay showed that EI-SP could specifically inhibit the growth of human hepatoma HepG2 cells in a dose-dependent manner. Analysis by flow cytometry indicated that the apoptosis of tumor cells increased after treatment with EI-SP in range of 100-400 µg/ml. Furthermore, Western blot analysis showed that EI-SP treatment led to decreased protein expression of Bcl-2 and an increase in Bax, cleaved caspase-3, cleaved caspase-9 and cleaved poly(ADP-ribose) polymerase (PARP). Moreover, it was found that EI-SP caused a loss of mitochondrial membrane potential (Δψ m) and the release of cytochrome c to the cytosol. Collectively, our results showed that the EI-SP induces apoptosis in HepG2 cells involving a caspases-mediated mitochondrial signalling pathway.

Efficient removal of high concentration dyes from water by functionalized in-situ N-doped porous biochar derived from waste antibiotic fermentation residue.

Using biochar for dye wastewater treatment is attracting interest due to its excellent adsorption properties and low costs. In this work, a novel biochar derived from oxytetracycline fermentation residue (functionalized OFR biochar, FOBC) was investigated as a efficient adsorbent for typical dyes removal. At 25 °C, the maximum adsorption capacity calculated by Langmuir model of FOBC-3-600 for methylene blue (MB), malachite green (MG), and methyl orange (MO) reached 643.97, 617.89, and 521.03 mg/g, respectively. The kinetics and isotherm model fitting showed that the chemisorption and physisorption both occurred during the adsorption process. Dyes were efficiently adsorbed through pore filling, electrostatic attraction, π-π interactions, and surface complexation. And the cycling experiment and environmental risk assessment indicated that the FOBC-3-600 had excellent recyclability and utilization safety. Overall, this study provides a practical method to simultaneously treat the dyeing wastewater and utilize the antibiotic fermentation residue.

Efficient Removal of Tetracycline from Water by One-Step Pyrolytic Porous Biochar Derived from Antibiotic Fermentation Residue.

The disposal and treatment of antibiotic residues is a recognized challenge due to the huge production, high moisture content, high processing costs, and residual antibiotics, which caused environmental pollution. Antibiotic residues contained valuable components and could be recycled. Using a one-step controllable pyrolysis technique in a tubular furnace, biochar (OSOBs) was produced without the preliminary carbonization step, which was innovative and time- and cost-saving compared to traditional methods. The main aim of this study was to explore the adsorption and removal efficiency of tetracycline (TC) in water using porous biochar prepared from oxytetracycline fermentation residues in one step. A series of characterizations were conducted on the prepared biochar materials, and the effects of biochar dosage, initial tetracycline concentration, reaction time, and reaction temperature on the adsorption capacity were studied. The experimental results showed that at 298 K, the maximum adsorption capacity of OSOB-3-700 calculated by the Langmuir model reached 1096.871 mg/g. The adsorption kinetics fitting results indicated that the adsorption of tetracycline on biochar was more consistent with the pseudo-second-order kinetic model, which was a chemical adsorption. The adsorption isotherm fitting results showed that the Langmuir model better described the adsorption process of tetracycline on biochar, indicating that tetracycline was adsorbed in a monolayer on specific homogeneous active sites through chemical adsorption, consistent with the kinetic conclusions. The adsorption process occurred on the surface of the biochar containing rich active sites, and the chemical actions such as electron exchange promoted the adsorption process.

Biomechanical comparison of the therapeutic effect of a novel proximal femoral bionic intramedullary nail and traditional inverted triangle hollow screw on femoral neck fracture.

OBJECTIVE: A novel Proximal Femoral Bionic Nail (PFBN) has been developed by a research team for the treatment of femoral neck fractures. This study aims to compare the biomechanical properties of the innovative PFBN with those of the conventional Inverted Triangular Cannulated Screw (ITCS) fixation method through biomechanical testing. METHODS: Sixteen male femoral specimens preserved in formalin were selected, with the donors' age at death averaging 56.1 ± 6.3 years (range 47-64 years), and a mean age of 51.4 years. The femurs showed no visible damage and were examined by X-rays to exclude diseases affecting bone quality such as tumors, severe osteoporosis, and deformities. The 16 femoral specimens were randomly divided into an experimental group (n = 8) and a control group (n = 8). All femurs were prepared with Pauwels type III femoral neck fractures, fixed with PFBN in the experimental group and ITCS in the control group. Displacement and stress limits of each specimen were measured through cyclic compression tests and failure experiments, and vertical displacement and strain values under a 600 N vertical load were measured in all specimens through vertical compression tests. RESULTS: In the vertical compression test, the average displacement at the anterior head region of the femur was 0.362 mm for the PFBN group, significantly less than the 0.480 mm for the ITCS group (p < 0.001). At the fracture line area, the average displacement for the PFBN group was also lower than that of the ITCS group (0.196 mm vs. 0.324 mm, p < 0.001). The difference in displacement in the shaft area was smaller, but the average displacement for the PFBN group (0.049 mm) was still significantly less than that for the ITCS group (0.062 mm, p = 0.016). The situation was similar on the posterior side of the femur. The average displacements in the head area, fracture line area, and shaft area for the PFBN group were 0.300 mm, 0.168 mm, and 0.081 mm, respectively, while those for the ITCS group were 0.558 mm, 0.274 mm, and 0.041 mm, with significant differences in all areas (p < 0.001). The average strain in the anterior head area for the PFBN group was 4947 µm/m, significantly less than the 1540 µm/m for the ITCS group (p < 0.001). Likewise, in the fracture line and shaft areas, the average strains for the PFBN group were significantly less than those for the ITCS group (p < 0.05). In the posterior head area, the average strain for the PFBN group was 4861 µm/m, significantly less than the 1442 µm/m for the ITCS group (p < 0.001). The strain conditions in the fracture line and shaft areas also showed the PFBN group was superior to the ITCS group (p < 0.001). In cyclic loading experiments, the PFBN fixation showed smaller maximum displacement (1.269 mm vs. 1.808 mm, p < 0.001), indicating better stability. In the failure experiments, the maximum failure load that the PFBN-fixated fracture block could withstand was significantly higher than that for the ITCS fixation (1817 N vs. 1116 N, p < 0.001). CONCLUSION: The PFBN can meet the biomechanical requirements for internal fixation of femoral neck fractures. PFBN is superior in biomechanical stability compared to ITCS, particularly showing less displacement and higher failure resistance in cyclic load and failure experiments. While there are differences in strain performance in different regions between the two fixation methods, overall, PFBN provides superior stability.

Construction of chiral tertiary alcohol stereocenters via the [2,3]-Meisenheimer rearrangement: enantioselective synthesis of the side-chain acids of homoharringtonine and harringtonine.

For the first time, the [2,3]-Meisenheimer rearrangement has been developed into a general strategy for the construction of chiral tertiary alcohols. The effectiveness and practicality of this methodology are illustrated by the successful synthesis of (R)-20 and (R)-30, the side chain acids of homoharringtonine and harringtonine, respectively.

Attentive immobility: Investigating the emotional-cognitive mechanism underlying conspiracy mentality and Covid-19 preventive behaviors.

While conspiracy theories have received extensive attention in the realm of misinformation, there has been limited research exploring the impact of conspiracy mentality on individuals' preventive behaviors during acute public health crises. This study investigates how conspiracy mentality may affect compliance with preventive health measures necessary to fight the COVID-19 pandemic, and the underlying emotional and cognitive mediators. Data was collected through a survey among 1878 Chinese respondents at the conclusion of the pandemic. The results indicate that individuals with higher levels of conspiracy mentality are significantly less engaged in preventive behaviors. Furthermore, this correlation is mediated by a sequence of mediating factors, starting from anger leading to institutional distrust and fear leading to perceived risk. Conspiracists' response mode can be described as a state of "attentive immobility," in which the impact of heightened institutional distrust outweighs their perceptions of risk, ultimately reducing engagement in preventive behaviors during crises. These findings underscore the importance of debunking initiatives that aim to address and mitigate the negative consequences of conspiracy mentality by targeting the mediating psychological processes during future pandemic threats.

Dispersion and Tunable Alignment of Colloidal Silver Nanowires in a Nematic Liquid Crystal for Applications in Electric-Optic Devices.

The dispersion and tunable alignment of colloidal nanomaterials is desirable for practical applications in electric-optic (E-O) devices; however, it remains challenging for large one-dimensional nanomaterials with a large aspect ratio. Here, we demonstrate a large-scale, simple, multi-microdomain, and noncontact photoalignment technology to align colloidal silver nanowires (AgNWs, length ∼4.5 µm, diameter ∼70.6 nm) in a liquid crystal (LC) with a high two-dimensional order parameter (about 0.9). The AgNWs are precisely self-assembled via photomasks with twisted nematic and planar alignment models in microdomain regions. The AgNW orientation is tuned with an electric field, through the rotation of an LC director n, which allows three-dimensional (3D) tunable orientation combined with photoalignment. The colloidal dispersions of AgNWs in the LC cell influenced the ion transfer, elastic constant, dielectric anisotropy, and near LC alignment, changing the E-O properties of the LC devices. The 3D tunable orientation of an AgNW by photoalignment and an electric field could provide a new way to assemble large colloidal nanomaterials and fabricate functional E-O devices.

Intestinal Cckbr-specific knockout mouse as a novel model of salt-sensitive hypertension via sodium over-absorption.

OBJECTIVES: To investigate the value of CCKBRfl/fl villin-Cre mice as a mouse model of salt-sensitive hypertension (SSH). METHODS: In the first part, 2-month-old CCKBRfl/fl villin-Cre mice (CKO) and control CCKBRfl/fl mice (WT) were fed with normal diet (0.4% NaCl) or high salt diet (4% NaCl), separately for 6 weeks. In the rescue study, one week of hydrochlorothiazide or saline injection were treated with the CKO mice fed high salt diet. The blood pressure, biochemical indexes, and the expression of small intestinal sodium transporters (NHE3, NKCC1, eNaC) was detected. The organ injury markers (MMP2/MMP9) and the histopathological changes of kidneys were observed, whereas the changes of duodenal sodium absorption were detected by small intestinal perfusion in vivo. RESULTS: The CCKBRfl/fl villin-Cre mice with high salt intake exhibited high blood pressure, increased duodenal sodium absorption and urinary sodium excretion, and with renal injury. The protein expression of NHE3, NKCC1 and eNaC were also significant increase in the intestine of CKO-HS mice. Treatment with hydrochlorothiazide remarkably attenuated the elevated blood pressure by high salt absorption in the CCKBRfl/fl villin-Cre mice, but no significant histopathological changes were observed. CONCLUSIONS: These results support a crucial role of intestinal Cckbr deficiency on SSH development and the diuretic antihypertension effect in CCKBRfl/fl villin-Cre mice. The CCKBRfl/fl villin-Cre mice with the high salt intake may serve as a stable model of salt-sensitive hypertensive induced by sodium overloading.

Infamous Gaming: The Intergroup Bias of Non-gamers in the Chinese Marriage Market.

The link between gaming and negative outcomes has been explored by previous research and has led to the widespread adverse attitude toward gaming (ATG) and gamers, especially from those who are unfamiliar with this activity. By implementing an audit study with gamers and non-gamers as participants (N = 1,280), we found that non-gamer participants rated gamers less as similar to their ideal marriage partners compared to non-gamers, while gamer participants did not differentiate between gamers and non-gamers in the ideal marriage partners similarity rating (IMPSR). The findings also revealed that the difference in IMPSR between gamer and non-gamer participants toward gamers was completely mediated by their ATG. These results imply that non-gamers consider gaming as an undesired characteristic, and this is due to the relatively negative attitude of non-gamers toward gaming. Current study provides a new perspective on exploring the effect of gaming by investigating the social interaction between gamers and non-gamers in real-world and suggests that the unfamiliarity of gaming can lead to the negative ATG, which may, ultimately, place gamers at a disadvantage in the context of mate selection.

CapsNet-COVID19: Lung CT image classification method based on CapsNet model.

The outbreak of the Corona Virus Disease 2019 (COVID-19) has posed a serious threat to human health and life around the world. As the number of COVID-19 cases continues to increase, many countries are facing problems such as errors in nucleic acid testing (RT-PCR), shortage of testing reagents, and lack of testing personnel. In order to solve such problems, it is necessary to propose a more accurate and efficient method as a supplement to the detection and diagnosis of COVID-19. This research uses a deep network model to classify some of the COVID-19, general pneumonia, and normal lung CT images in the 2019 Novel Coronavirus Information Database. The first level of the model uses convolutional neural networks to locate lung regions in lung CT images. The second level of the model uses the capsule network to classify and predict the segmented images. The accuracy of our method is 84.291% on the test set and 100% on the training set. Experiment shows that our classification method is suitable for medical image classification with complex background, low recognition rate, blurred boundaries and large image noise. We believe that this classification method is of great value for monitoring and controlling the growth of patients in COVID-19 infected areas.

GM-CSF-mediated inducement of bone marrow MDSCs by TSA and effect on survival of graft in mice.

OBJECTIVE: This study analyzed the effect of HDAC inhibitor, trichostatin A (TSA), in inducing granulocyte-macrophage colony-stimulating factor (GM-CSF)-mediated bone marrow (BM) cell differentiation to myeloid-derived suppressor cells (MDSCs) in vitro and in vivo. METHODS: BM cell differentiation to CD11b + GR-1 + MDSCs was achieved by in vitro culture with TSA and GM-CSF, and the collected cells were analyzed by mixed lymphocyte culture to identify suppressive actions against effector T cells. RT-PCR and ELISA were conducted to analyze the CCL5 mRNA and protein levels in TSA + GM-CSF + BM, GR-1 + MDSCs and GR-1 + MDSC + CCL5 groups. The survival of cardiac grafts was compared between groups. RESULTS: TSA was beneficial for the GM-CSF-mediated BM differentiation to CD11b + GR-1 + MDSCs. Adoptive transfer of GR-1 + MDSCs was powerful in suppressing CD4 + CD25-T cell proliferation and the effect was mediated by iNOS and HO-1; it also increased CCL5 gradient concentration between grafts and plasma to recruit Treg to grafts and prolong the survival of the grafts. Survival analysis revealed that the survival of grafts after adoptive transfer of GR-1 + MDSCs could be prolonged. CONCLUSION: This study helps in further research on the application value of MDSCs in the field of transplant, and may provide a new thought for the cell therapy in inducing immune tolerance in organ transplant.

Laparoscopy vs. Laparotomy for the Management of Abdominal Trauma: A Systematic Review and Meta-Analysis.

Background: There is still no consensus regarding the role of laparoscopy in trauma cases. The purpose of this paper is to assess the value of diagnostic and therapeutic laparoscopy for patients with blunt or penetrating abdominal trauma by performing a systematic review and meta-analysis. Methods: PubMed, Embase, and the Cochrane library were systemically searched for the randomized controlled trials (RCTs) and non-RCT comparative studies on effectiveness and safety of laparoscopy vs. laparotomy for the two authors independently performed the search, data extraction, and quality assessment. Results: A total of 5,517 patients were enrolled in 23 eligible studies that were published in English. Meta-analysis results suggest that there is no significant difference in the incidence of missed injury and mortality between abdominal trauma patients receiving laparoscopy and those receiving laparotomy. Concerning postoperative complications, compared with patients in the open surgery group, those in the laparoscopy group are at a similar risk of intra-abdominal abscesses, thromboembolism, and ileus, while there is a decreased incidence of wound infection and pneumonia. Besides, patients in the laparoscopy group experience shorter hospitalization times and procedure times. For most outcomes, the sensitivity analysis yielded similar results to the primary analysis. Conclusion: Laparoscopic surgery is a practical alternative to laparotomy for appropriate patients. The decision to perform laparoscopy should be based on the experience of the surgeon and the resources available.

Curcumin attenuates insulin resistance in hepatocytes by inducing Nrf2 nuclear translocation.

BACKGROUND/AIMS: NF-E2-Related Factor-2 (Nrf2) is a transcription factor that plays a crucial role in the cellular protection against oxidative stress. Curcumin has been reported to induce Nrf2 nuclear translocation and upregulate the expression of numerous reactive oxygen species (ROS) detoxifying and antioxidant genes in hepatocytes. This study was designed to investigate whether curcumin-induced Nrf2 nuclear translocation could reduce ROS-mediated insulin resistance in cultured LO2 hepatocytes. METHODOLOGY: Human LO2 hepatocytes were incubated with curcumine and glucose oxidase (GO) in the presence/absence of wortmannin (a phosphatidyinositol 3-kinase (PI3K) inhibitor), oxidative stress, cellular damage, Nrf2 nuclear translocation and insulin resistance were measured. RESULTS: GO exposure significantly increased intracellular ROS, glutathione (GSH) depletion, malondialdehyde (MDA) formation, and increased activities of cellular lactate dehydrogenase (LDH) and aspartate amino transferase (AST), as well as causing insulin resistance. Curcumin pretreatment significantly attenuated these disturbances in intracellular ROS, liver enzyme activity and significantly antagonized the lipid peroxidation, GSH depletion and insulin resistance induced by GO in LO2 hepatocytes. These effects paralleled Nrf2 nuclear translocation induced by curcumin. Wortmannin partially blocked curcumin-induced Nrf2 nuclear translocation. In addition, wortmannin prevented curcumin-induced improvements in intracellular ROS, MDA formation, GSH depletion, liver enzyme activity and insulin resistance in cultured LO2 hepatocytes. CONCLUSIONS: These findings suggest that curcumin could reduce ROS-mediated insulin resistance in hepatocytes, at least in part through nuclear translocation of Nrf2.