Liver transplantation remains the most effective treatment for end-stage liver disease(ESLD),but it is fraught with challenges such as immunosuppression,high risk and cost,and donor shortage.In recent years,stem cell transplantation has emerged as a promising new strategy for ESLD treatment,with mesenchymal stem cells(MSCs)gaining significant attention because of their unique properties.MSCs can regulate signaling pathways,including hepatocyte growth factor/c-Met,Wnt/beta(β)-catenin,Notch,transforming growth factor-β1/Smad,interleukin-6/Janus kinase/signal transducer and activator of transcription 3,and phosphatidylinositol 3-kinase/PDK/Akt,thereby influencing the progression of liver fibrosis and regeneration.As a promising stem cell type,MSCs offer numerous advantages in liver disease treatment,including low immunogenicity;ease of acquisition;unlimited proliferative ability;pluripotent differentiation potential;immunomodulatory function;and anti-inflammatory,antifibrotic,and anti-apoptotic biological characteristics.This review outlines the mechanisms by which MSCs reverse liver fibrosis and promote liver regeneration.MSCs are crucial in reversing liver fibrosis and repairing liver damage through the secretion of growth factors,regulation of signaling pathways,and modulation of immune responses.MSCs have shown good therapeutic effects in preclinical and clinical studies,providing new strategies for liver disease treatment.However,challenges still exist in the clinical application of MSCs,including low differentiation efficiency and limited sources.This review provides a reference for MSC application in liver disease treatment.With the continuous progress in MSC research,MSCs are expected to achieve breakthroughs in liver disease treatment,thereby improving patient treatment outcomes.

Objective:To investigate the effect of methylene blue (MB) on motor dysfunction and its mechanism in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse models.Methods:Forty healthy male C57BL/6 mice were randomly divided into 4 groups: control group, model group, low-dose treatment group and medium-dose treatment group ( n=10); PD mouse models were established by intraperitoneal injection of 25 mg/kg/d MPTP for a consecutive 7 d; low-dose treatment group and medium-dose treatment group were pretreated intraperitoneally with MB 2 mg/kg/d or MB 10 mg/kg/d for a consecutive 3 d, respectively; and then, MPTP 25 mg/kg/d+MB 2 mg/kg/d or MPTP 25 mg/kg/d+MB 10 mg/kg/d were injected intraperitoneally into the low-dose treatment group or medium-dose treatment group for a consecutive 7 d (MPTP and MB were given at 12 h of interval). Eight d after modeling, open field experiment, pole climbing experiment and rod rotating experiment were carried out to evaluate the spontaneous movement, coordination, endurance and motor ability. And then, the mice were sacrificed; immunofluorescent staining was used to observe tyrosine hydroxylase (TH) expression in the substantia nigra; Western blotting was used to detect the expressions of TH, α-synuclein, nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), cleaved-Caspase-1 and Gasdermin D (GSDMD) in the striatum and substantia nigra of mice. Contents of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-18 in the substantia nigra and striatum of mice were detected by ELISA. Results:Compared with the control group, the model group had shortened residence time in rod rotating, prolonged descent time in rod climbing, reduced total movement distance in open field, decreased number of TH-positive cells in the substania nigra, decreased TH protein levels in the substania nigra and striatum, and increased NLRP3, ASC, cleaved-Caspase-1, GSDMD and GSDMD-N protein levels in the substania nigra and striatum, and increased TNF-α, IL-1β and IL-18 contents in the substania nigra and striatum, with significant differences ( P<0.05). Compared with the model group, low-dose treatment group and medium-dose treatment group had prolonged residence time in rod rotating, shortened descent time in rod climbing, increased total movement distance in open field, increased number of TH-positive cells in the substania nigra, and increased TH protein levels in the substania nigra and striatum, decreased NLRP3, ASC, and cleaved-Caspase-1 levels in the substania nigra and striatum, and decreased TNF-α, IL-1β and IL-18 contents in the substania nigra and striatum, with significant differences ( P<0.05). No statistical differences in the above indexes were noted between the low-dose treatment group and medium-dose treatment group ( P>0.05). Conclusion:Low-/medium-dose MB can ameliorate motor dysfunction in PD mouse models, whose mechanism may be related to downregulate NLRP3 inflammasome and inhibit neuroinflammatory response to reduce dopaminergic neuron pyroptosis.

Objective By analyzing the relevant factors of drug-resistant epilepsy(DRE),to screen out the high-risk factors,and to built the risk prediction model for guiding clinical treatment.Methods The medical records of 404 patients with epilepsy admitted to department of Neurosurgery of Xijing Hospital from January 2015 to December 2019 were collected.According to the definition of DRE,patients were divided into DRE group(n=85)and the drug treatment effective group(n=319).Univariate and multivariate Logistic regression analysis were performed on the relevant factors such as the initial onset and treatment conditions of patients,respectively.According to the results,the risk prediction model of DRE was established and verified.Results Univariate Logistic regression analysis showed that there were no significant differences in gender,neurological dysfunction,cluster attacks,history of cranial infection,EEG abnormalities,and the time from onset to standardized treatment between the two groups(all P＞0.05).Meanwhile,there were statistically significant differences in age,age of first onset,perinatal events,history of febrile convulsion,brain imaging changes,etiological classification,attack type,frequency of initial onset and curative effect after initial treatment between the two groups(all P＜0.05).Multivariate Logistic regression analysis showed that young age of initial onset,brain imaging changes,symptomatic epilepsy and high frequency of initial onset were independent risk factors for DRE(all P＜0.05).The risk prediction model of DRE was successfully constructed and the ROC curve was drawn,in which the area under the training set curve was 0.873 and the area under the verification set curve was 0.851.Both curves showed good clinical consistency,confirming the accuracy of the prediction model.Conclusion Attention and intervention should be paid to epilepsy patients with independent risk factors such as young age of initial onset,brain imaging changes,symptomatic epilepsy and high frequency of initial onset as early as possible to predict and diagnose DRE and improve the prognosis of patients.

Objective By analyzing the relevant factors of drug-resistant epilepsy(DRE),to screen out the high-risk factors,and to built the risk prediction model for guiding clinical treatment.Methods The medical records of 404 patients with epilepsy admitted to department of Neurosurgery of Xijing Hospital from January 2015 to December 2019 were collected.According to the definition of DRE,patients were divided into DRE group(n=85)and the drug treatment effective group(n=319).Univariate and multivariate Logistic regression analysis were performed on the relevant factors such as the initial onset and treatment conditions of patients,respectively.According to the results,the risk prediction model of DRE was established and verified.Results Univariate Logistic regression analysis showed that there were no significant differences in gender,neurological dysfunction,cluster attacks,history of cranial infection,EEG abnormalities,and the time from onset to standardized treatment between the two groups(all P＞0.05).Meanwhile,there were statistically significant differences in age,age of first onset,perinatal events,history of febrile convulsion,brain imaging changes,etiological classification,attack type,frequency of initial onset and curative effect after initial treatment between the two groups(all P＜0.05).Multivariate Logistic regression analysis showed that young age of initial onset,brain imaging changes,symptomatic epilepsy and high frequency of initial onset were independent risk factors for DRE(all P＜0.05).The risk prediction model of DRE was successfully constructed and the ROC curve was drawn,in which the area under the training set curve was 0.873 and the area under the verification set curve was 0.851.Both curves showed good clinical consistency,confirming the accuracy of the prediction model.Conclusion Attention and intervention should be paid to epilepsy patients with independent risk factors such as young age of initial onset,brain imaging changes,symptomatic epilepsy and high frequency of initial onset as early as possible to predict and diagnose DRE and improve the prognosis of patients.

Objective : To investigate the effects of D ⁃allose on the restoration of neurological function , Galectin⁃3 (Gal⁃3) , adenosine monophosphate⁃activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) and the expression of some inflammatory factors in ischemia⁃reperfusion injury ( CIRI) mice . Methods : A total of 50 male mice were randomly divided into control group (Con group) , sham group (Sham group) , cerebral ischemia⁃reperfusion injury group (MCAO group) , cerebral ischemia⁃reperfusion injury + D ⁃alolose group (MCAO + D ⁃allose group) and cerebral ischemia⁃reperfusion injury + modified citrus pectin group (MCAO + MCP group) . The middle cerebral artery occlusion/reperfusion (MCAO/R) model (reperfusion after 2 hours of MCA ischemia) was established by thread embolism . After successful modeling , the neurological function of mice was evaluated Longa score and rotated rod walking . TTC staining was used to observe the volume of cerebral infarction foci . The expression levels of Gal⁃3 and autophagy⁃related molecules were detected by Western blot and RT⁃PCR . Immunofluorescence was applied to detect the distribution of Gal⁃3 in brain tissue , and TNF⁃α , IL⁃8 secretion was detected with ELISA KIT . Results : Compared with Con group and Sham group , the MCAO model represented significant increase in the Longa neurofunction score (P < 0. 01) , cerebral infarction volume ( P < 0. 01) , Gal⁃3 expression and manifasted enhanced autophagy (P < 0. 01) . After treatment with D ⁃allose , it could significantly improve neurological dysfunction , reduce cerebral infarction volume (P < 0. 01) , reduce the expression of Gal⁃3 ( P < 0. 01) , inhibit AMPK phosphorylation , promote mTOR phosphorylation , and inhibit autophagy (P < 0. 01) . The use of the Gal⁃3 inhibitor MCP alone could also achieve the effect of inhibiting autophagy . Conclusion D ⁃allose can effectively promote the recovery of neurological function and reduce the volume of infarct foci in CIRI mice . The mechanism may involve inhibiting excessive cell autophagy by downregulating the expression of Gal⁃3 , and reducing the release of inflammatory factors such as TNF⁃α and IL⁃8 , thereby exerting neuroprotective effects .

We assessed the effects of pulsatile flow shear stress on the gene expression profiles of human umbilical artery smooth muscle cells (HUASMCs) in vitro using the Express Chip DNA microarray method and investigated the difference between pulsatile and steady shear stress on differentially expressed genes of HUASMCs. In a modified pulsatile flow chamber system, HUASMCs were exposed to pulsatile and steady fluid shear stress (5.52 dyne/cm2) for 6 h respectively, and normal static cultured HUASMCs were selected as a control. The total cellular RNA was extracted by TRIzol Reagent (Life Technologies, Inc) according to the manufacturer's manual. Conversion of mRNA to single strand cDNA and double strand cDNA template was synthesized by Reverse Transcription from the total RNA. cRNA probe was transcribed with biotin labeling. After hybridization of probe with microarray, the binding of streptavidin to biotin was performed and amplified with the first antibody and further amplified with Cy3-conjugated second antibody. Then detection of Cy3 dye was carried out with ScanArray 5000. The results showed that a total of 1,330 genes revealed differential expression in HUASMCs exposed on pulsatile shear stress (5.52 dyne/cm2, 6 h); however, 2,676 genes revealed differential expression in HUASMCs exposed on steady shear stress. Comparsion of HUASMCs exposed to pulsatile with the HUASMCs exposed to steady shear stress showed there were 2,297 genes revealing differential expression. The transcriptional profile of fluidally induced genes in HUASMCs suggested a different response to pulsatile and steady shear stress.
Cells, Cultured ; Gene Expression Profiling ; Humans ; Muscle, Smooth, Vascular ; cytology ; metabolism ; Oligonucleotide Array Sequence Analysis ; Pulsatile Flow ; RNA, Messenger ; biosynthesis ; genetics ; Stress, Mechanical ; Umbilical Arteries ; cytology