Identification of immune feature genes and intercellular profiles in diabetic cardiomyopathy

BACKGROUND Diabetic cardiomyopathy(DCM)is a multifaceted cardiovascular disorder in which immune dysregulation plays a pivotal role.The immunological molecular mechanisms underlying DCM are poorly understood.AIM To examine the immunological molecular mechanisms of DCM and construct diagnostic and prognostic models of DCM based on immune feature genes(IFGs).METHODS Weighted gene co-expression network analysis along with machine learning methods were employed to pinpoint IFGs within bulk RNA sequencing(RNA-seq)datasets.Single-sample gene set enrichment analysis(ssGSEA)facilitated the analysis of immune cell infiltration.Diagnostic and prognostic models for these IFGs were developed and assessed in a validation cohort.Gene expression in the DCM cell model was confirmed through real time-quantitative polymerase chain reaction and western blotting techniques.Additionally,single-cell RNA-seq data provided deeper insights into cellular profiles and interactions.RESULTS The overlap between 69 differentially expressed genes in the DCM-associated module and 2483 immune genes yielded 7 differentially expressed immune-related genes.Four IFGs showed good diagnostic and prognostic values in the validation cohort:Proenkephalin(Penk)and retinol binding protein 7(Rbp7),which were highly expressed,and glucagon receptor and inhibin subunit alpha,which were expressed at low levels in DCM patients(all area under the curves>0.9).SsGSEA revealed that IFG-related immune cell infiltration primarily involved type 2 T helper cells.High expression of Penk(P<0.0001)and Rbp7(P=0.001)was detected in cardiomyocytes and interstitial cells and further confirmed in a DCM cell model in vitro.Intercellular events and communication analysis revealed abnormal cellular phenotype transformation and signaling communication in DCM,especially between mesenchymal cells and macrophages.CONCLUSION The present study identified Penk and Rbp7 as potential DCM biomarkers,and aberrant mesenchymal-immune cell phenotype communication may be an important aspect of DCM pathogenesis.

Novel intervention for alcohol-associated liver disease

A recently published article in the World Journal of Gastroenterology clarified that elafibranor,a dual peroxisome proliferator activated receptorα/δ(PPARα/δ)agonist,reduced inflammation and fibrosis in alcohol-associated liver disease(ALD).This letter aims to discuss the findings presented in that article.ALD is a global health problem,and no effective drugs has been approved by the Food and Drug Administration to cure it.Thus,finding targeted therapies is of great urgency.Herein,we focus on the pathogenesis of ALD and the role of PPARα/δin its development.Consistent with the conclusion of the article of interest,we think that elafibranor may be a promising therapeutic option for ALD,due to the pivotal involvement of PPARα/δin the pathogenesis of the disease.However,its treatment dose,timing,and side effects need to be further investigated in future studies.

Innovative mesenchymal stem cell treatments for fatty liver disease

The incidence of non-alcoholic fatty liver disease(NAFLD)and alcohol-associated liver disease(ALD)is increasing year by year due to changes in the contemporary environment and dietary structure,and is an important public health problem worldwide.There is an urgent need to continuously improve the understanding of their disease mechanisms and develop novel therapeutic strategies.Mesenchymal stem cells(MSCs)have shown promise as a potential therapeutic strategy in therapeutic studies of NAFLD and ALD.NAFLD and ALD have different triggers and their specific mechanisms of disease progression are different,but both involve disease processes such as hepatocellular steatosis and potential fibrosis,cirrhosis,and even hepatocellular carcinoma.MSCs have metabolic regulatory,anti-apoptotic,antioxidant,and immunomodulatory effects that together promote liver injury repair and functional recovery,and have demonstrated positive results in preclinical studies.This editorial is a continuum of Jiang et al’s review focusing on the advantages and limitations of MSCs and their derivatives as therapeutics for NAFLD and ALD.They detail how MSCs attenuate the progression of NAFLD by modulating molecular pathways involved in glucolipid metabolism,inflammation,oxidative stress,endoplasmic reticulum stress,and fibrosis.Based on recent advances,we discuss MSCs and their derivatives as therapeutic strategies for NAFLD and ALD,providing useful information for their clinical application.

Endoscopy dissection of small stromal tumors emerged from the muscularis propria in the upper gastrointestinal tract:Preliminary study

AIM:To investigate the feasibility and safety of the treatment of an upper gastrointestinal(GI) submucosal tumor with endoscopic submucosal dissection(ESD).METHODS:A total of 20 patients with esophageal and gastric submucosal tumors emerged from the muscular layer identified by endoscopic ultrasonography were collected from January 2009 to June 2010.Extramural or dumbbell-like lesions were excluded by an enhanced computerized tomography(CT) scan.All patients had intravenous anesthesia with propofol and then underwent the ESD procedure to resect these submucosal tumors.The incision was closed by clips as much as possible to decrease complications,such as bleeding or perforation,after resection of the tumor.All the specimens were collected and evaluated by hematoxylin,eosin and immunohistochemical staining,with antibodies against CD117,CD34,desmin,α-smooth muscle actin and vimentin to identify the characteristics of the tumors.Fletch's criteria was used to evaluate the risk of gastrointestinal stromal tumors(GISTs).All patients underwent a follow-up endoscopy at 3,6 and 12 mo and CT scan at 6 and 12 mo.RESULTS:The study group consisted of 5 men and 15 women aged 45-73 years,with a mean age of 60.2 years.Three tumors were located in the esophagus,9 in the gastric corpus,4 in the gastric fundus,3 lesions in the gastric antrum and 1 in the gastric angulus.Apart from the one case in the gastric angulus which was abandoned due to being deeply located in the serosa,94.7%(18/19) achieved complete gross dissection by ESD with operation duration of 60.52±30.32 min.The average maximum diameter of tumor was 14.8±7.6 mm,with a range of 6 to 30 mm,and another lesion was ligated by an endoscopic ligator after most of the lesion was dissected.After pathological and immunohistochemical analysis,12 tumors were identified as a GI stromal tumor and 6 were leiomyoma.Mitotic count of all 12 GIST lesions was fewer than 5 per 50 HPF and all lesions were at very low(9/12,75.0%) or low risk(3/12,25.0%) according to Fletch's criteria.Procedure complications mainly included perforation and GI bleeding;perforation occurred in 1 patient and conservative treatment succeeded by a suturing clip and no post-operative GI bleeding occurred.All patients were followed up for 6.5±1.8 mo(range,3-12 mo) by endoscopy and abdominal CT.Local recurrence and metastasis did not occur in any patient.CONCLUSION:ESD shows promise as a safe and feasible technique to resect esophageal and gastric submucosal tumors and the incidence of complications was very low.Clinical studies with more subjects and longer follow-up are needed to confirm its treatment value.

Evaluation of prognostic markers in severe drug-induced liver disease

AIM: To analyze the outcome of patients with severe drug-induced liver disease (DILD) associated with jaundice classified as hepatocellular, cholestatic or mixed liver injury and to evaluate the validity of Hy’s rule and the most important predictors for outcome. METHODS: The Adverse Drug Reaction Advisory Committee was set up in 1997 in our hospital to identify all suspicions of DILD following a structured prospective report form. Liver damage was divided into hepatocellular, cholestatic, and mixed types according to laboratory and histologic criteria when available. Further evaluation of causality assessment was performed. RESULTS: From January 1997 to December 2004, 265 patients were diagnosed with DILD,and 140 (52.8%) of them were female. hepatocellular damage was the most common (72.1%), the incidence of death was 9.9% in patients with hepatocellular damage and 9.5% in patients with cholestatic/mixed damage (P < 0.05). There was no difference in age of dead and recovered patients. The proportion of females and males was similar in recovered and dead patients, no difference was observed in duration of treatment between the two groups. The serum total bilirubin (P < 0.001), direct bilirubin (P < 0.001) and aspartate transaminase (AST) (P = 0.013) values were higher in dead patients than in recovered patients. Chinese herbal medicine was the most frequently prescribed, accounting for 24.2% of the whole series. However, antitubercular drugs (3.4%) were found to be the primary etiological factor for fetal DILD. Factors associated with the development of fulminanthepatic failure were hepatic encephalopathy (OR = 43.66, 95% CI = 8.47-224.95, P < 0.0001), ascite (OR = 28.48, 95% CI = 9.26-87.58, P < 0.0001), jaundice (OR = 11.43, 95% CI = 1.52-85.96, P = 0.003), alcohol abuse (OR = 3.83, 95% CI = 1.26-11.67, P = 0.035) and direct bilirubin (OR = 1.93, 95% CI = 1.25-2.58, P = 0.012). CONCLUSION: Death occurs in 9.8% of patients with DILD. Chinese herbal medicine stands out as the most common drug for DILD. While antitubercular drugs are found to be the primary etiological factor for fetal DILD, hepatic encephalopathy, ascites, jaundice, alcohol abuse and direct bilirubin levels are associated with the death of DILD patients.

Comparison on Clinical Characteristics of Multifocal Choroiditis and Punctate Inner Choroidopathy

Purpose:To compare the differences in the clinical characteristics of multifocal choroiditis(MFC) and punctate inner choriodopathy(PIC).Methods:A cross-sectional study,consisting of 22 cases(37 eyes) with MFC and 11 cases(18 eyes) with PIC,was carried out.Multiple indexes were measured and analysed to compare the differences in clinical characteristics of the subjects between two groups,including BCVA,avergae age,sex composition,presence of intraocular inflammation,choroidal neovascularization(CNV),and intraocular inflammation complications,such as cataract,cystoid macular edema(CME) and epiretinal membrane(ERM).Results:The avergae age of the MFC and PIC patients were(48.1±13.9) years and(32.1±10.2) years with a significant difference(P=0.043).CNV occurred more frequently in patients with PIC(PIC,55.6%;MFC,21.6%;P=0.016) compared with those with MFC.MFC patients had a higher frequency of intraocular inflammation complications,such as,cataract(27.0%),CME(35.1%),ERM(5.4%).PIC patients presented none of these complications.MFC subjects presented with more visual impairments than PIC patients.Totally 51.4% of MFC patients had visual impairments and 22.2% of PIC patients had BCVA < 0.3(P=0.047).Conclusion:Both MFC and PIC are categorized into the umbrella term of "white spot syndromes".Although sharing similar ocular expressions,they present with different clinical characteristics.Patients with PIC had a higher frequency of CNV but a lower frequency of structural complications caused by intraocular inflammation and lower frequency of visual impairments compared with MFC counterparts.

The current status and reflections on 3D in vitro modeling of liver metastasis in colorectal cancer

Colorectal cancer(CRC)ranks as the third most prevalent cancer worldwide and is identified as the second leading cause of cancer-related fatalities(1).The liver is the most common site for distant metastasis in CRC,with approximately 20%to 25%of newly diagnosed patients experiencing liver metastasis.As the disease progresses,this proportion can increase to as high as 50%(2),making it a primary cause of death in CRC patients.

LncRNA DPP10-AS1 promotes malignant processes through epigenetically activating its cognate gene DPP10 and predicts poor prognosis in lung cancer patients

Objective:The purpose of this study was to explore the function and gene expression regulation of the newly identified lnc RNA DPP10-AS1 in lung cancer,and its potential value as a prognostic biomarker.Methods:q RT-PCR and Western blot were conducted to detect the expression of DDP10-AS1 and DPP10 in lung cancer cell lines and tissues.The effects of DDP10-AS1 on DPP10 expression,cell growth,invasion,apoptosis,and in vivo tumor growth were investigated in lung cancer cells by Western blot,rescue experiments,colony formation,flow cytometry,and xenograft animal experiments.Results:The novel antisense lnc RNA DPP10-AS1 was found to be highly expressed in cancer tissues(P<0.0001),and its upregulation predicted poor prognosis in patients with lung cancer(P=0.0025).Notably,DPP10-AS1 promoted lung cancer cell growth,colony formation,and cell cycle progression,and repressed apoptosis in lung cancer cells by upregulating DPP10 expression.Additionally,DPP10-AS1 facilitated lung tumor growth via upregulation of DPP10 protein in a xenograft mouse model.Importantly,DPP10-AS1 positively regulated DPP10 gene expression,and both were coordinately upregulated in lung cancer tissues.Mechanically,DPP10-AS1 was found to associate with DPP10 m RNA but did not enhance DPP10 m RNA stability.Hypomethylation of DPP10-AS1 and DPP10 contributed to their coordinate upregulation in lung cancer.Conclusions:These findings indicated that the upregulation of the antisense lnc RNA DPP10-AS1 promotes lung cancer malignant processes and facilitates tumorigenesis by epigenetically regulating its cognate sense gene DPP10.DPP10-AS1 may serve as a candidate prognostic biomarker and a potential therapeutic target in lung cancer.

Fascaplysin sensitizes cells to TRAIL-induced apoptosis through upregulating DR5 expression

This study investigated the molecular mechanism of anti-tumor effect of fascaplysin, a nitrogenous red pigment firstly isolated from a marine sponge. Microarray analysis show that the TNF and TNF receptor superfamily in human umbilical vein endothelial cells (HUVEC) and human hepatocarcinoma cells (BEL-7402) were significantly regulated by fascaplysin. Western Blot results reveal that fascaplysin increased the expression of cleaved caspase-9, active caspase-3, and decreased the level of procaspase-8 and Bid. Flow cytometry and cytotoxicity tests indicate that fascaplysin sensitized cells to tumor necrosis-related apoptosis-inducing ligand-(TRAIL) induced apoptosis, which was markedly blocked by TRAIL R2/Fc chimera, a dominant negative form of TRAIL receptor DR5. Therefore, our results demonstrate that fascaplysin promotes apoptosis through the activation of TRAIL signaling pathway by upregulating DR5 expression.

Fluorescent Organohydrogel with Thermal-Induced Color Change for Anti-counterfeiting

Smart fluorescent patterns enable dynamic color variation under external stimuli,showing a much higher security level in the field of anti-counterfeiting.However,there is still lacking of a simple and convenient way to achieve dynamic fluorescence changes.Herein,a fluorescent organohydrogel made up of a poly(N,/N-dimethylacrylamide-co-isopropylacrylamide)(p(DMA-NIPAM))hydrogel network and a polyflauryl methacrylate)(PLMA)organogel network was fabricated via a two-step interpenetrating technique.The former network bears naphthalimide moieties(DEAN,green fluorescent monomer)and the later contains 6-acrylamidopicolinic acid(6APA,fluorescent ligand),leading to emitting green fluorescence.When Eu^(3+) was introduced and coordinated with 6APA,the organohydrogel displays red fluorescence,which can further emit yellow after applying thermal stimulus.Furthermore,by adjusting the proportion of comonomers,various organohydrogels can be obtained,which can be programmed and act as an effective platform for the encryption and decryption of secret information.

Decellularized small intestine submucosa/polylactic-co-glycolic acid composite scaffold for potential application in hypopharyngeal and cervical esophageal tissue repair

There has been an increase in the incidence of hypopharyngeal and cervical esophageal cancer worldwide,and hence growing needs for hypopharyngeal and cervical esophageal tissue repair.This work produced a bi-layer composite scaffold with decellularized small intestine submucosa and polylactic-co-glycolic acid,which resembled the layered architectures of its intended tissues.The decellularized small intestine submucosa contained minimal residual DNA(52.5±61.2 ng/mg)and the composite scaffold exhibited satisfactory mechanical properties(a tensile modulus of 21.1±64.8 MPa,an ultimate tensile strength of 14.0±62.9MPa and a failure strain of 26.9±65.1%).The interactions between cells and the respective layers of the scaffold were characterized by CCK-8 assays,immunostaining and Western blotting.Desirable cell proliferation and phenotypic behaviors were observed.These results have provided an important basis for the next-step in vivo studies of the scaffold,and bode well for its future clinical applications.