IGF-1介导的丰富环境对成年弱视小鼠视皮层可塑性的影响

目的:检测丰富环境干预对单眼剥夺成年弱视小鼠视皮质中IGF-1及其受体的表达变化,初步探讨其对成年弱视小鼠初级视皮质突触可塑性的影响及分子机制。方法:将正常新生昆明小鼠随机分为正常组(Nor),单眼剥夺+标准环境组(MD+SE),单眼剥夺+丰富环境组(MD+EE),单眼剥夺+氟西汀组(MD+FLX)。在小鼠21日龄时构建单眼剥夺模型,确定模型建立成功后,每组选取18只小鼠按照预先分组放置在标准环境或丰富环境中饲养4wk,单眼剥夺+氟西汀组小鼠饮水中加入氟西汀。通过前爪触地反射实验检测小鼠视敏度,闪光视觉诱发电位检测客观视功能;小鼠处死后取材,使用电镜检测视皮层神经元的突触间隙宽度、突触活性区长度及突触后致密物厚度,Western Blot法检测视皮层中IGF-1、IGF-1R及IGFBP5蛋白表达。结果:(1)视敏度检测结果:MD+SE组小鼠前爪触地成功率明显低于Nor组(P<0.001);MD+EE组及MD+FLX组小鼠前爪触地成功率明显高于MD+SE组(均P<0.001);与MD+FLX组比较,MD+EE组小鼠前爪触地成功率无差异(P=0.816)。(2)闪光视觉诱发电位检测结果:与Nor组比较,MD+SE组小鼠剥夺眼闪光视觉诱发电位P2波潜伏期延长、波幅降低(均P<0.01);丰富环境饲养后,MD+EE组较MD+SE组小鼠剥夺眼闪光视觉诱发电位P2波潜伏期缩短、波幅增加(均P<0.01);与MD+FLX组比较,MD+EE组小鼠剥夺眼闪光视觉诱发电位P2波的潜伏期和波幅变化无差异(P>0.05)。(3)电镜检测视皮层神经细胞突触超微结构:与N or组比较,M D+SE组小鼠剥夺眼对侧视皮层神经细胞突触间隙增宽(P <0.01),突触活性区长度缩短(P <0.01),突触后致密物厚度变薄(P <0.01);丰富环境饲养后,MD+EE组小鼠较MD+SE组突触间隙变窄(P=0.0035),突触活性区长度延长(P<0.01),突触后致密物厚度增加(P<0.01),MD+EE组突触超微结构各项指标较MD+FLX组比较无差异(P>0.05)。(4)Western blot检测视皮层中IGF-1、IGF-1R及IGFBP5蛋白表达:MD+SE组小鼠IGF-1及IGF-1R蛋白表达明显低于Nor组(均P<0.01);MD+EE组小鼠IGF-1及IGF蛋白的表达明显高于MD+SE组(均P<0.01),然而仍显著低于Nor组(均P<0.01)。各组间小鼠IGFBP5蛋白表达异常无差异(P>0.05)。结论:丰富环境能重新激活成年单眼剥夺弱视小鼠视皮质可塑性,改善弱视小鼠视觉功能,其机制可能与调控IGF-1及受体的表达有关。

Laparoscopic approach for managing intussusception in children:Analysis of 65 cases

BACKGROUND Intussusception can be managed by pneumatic reduction,ultrasound-guided hydrostatic reduction,open or laparoscopic surgery,but laparoscopy in such cases remains controversial.AIM To explore the clinical characteristics,effectiveness,and complications of surgical reduction for intussusception using laparoscopy in children.METHODS This study was a retrospective case series of pediatric patients with intussusception who underwent surgical reduction by laparoscopy from May 2011 to April 2016 at Taizhou Hospital of Zhejiang Province.Clinical characteristics(operation time,intraoperative blood loss,conversion rate of laparotomy,reasons for conversion,postoperative hospital stay,and adverse events)were described.RESULTS The 65 patients included 45 boys and 20 girls.The average age was 2.3 years(27.5±24.5 mo).Of the 65 patients,61 underwent surgical reduction by laparoscopy after a failed enema reduction of intussusception,and four underwent the procedure directly.All patients were treated successfully and 57(87.7%)patients underwent successful laparoscopic surgery,two of which had a spontaneous reduction.Among the remaining cases,one was converted to open surgery via right upper quadrant incision,and seven required enlarged umbilical incisions.Intestinal resection was performed in 5 patients because of abnormal bowel lesions.There were no complications(intestinal perforations,wound infections,or intestinal adhesions)during the follow-up of 3 years to 8 years.Two patients experienced a recurrence of intussusception;one was resolved with pneumatic reduction,and the other underwent a second laparoscopic surgery.CONCLUSION Laparoscopic approach for pediatric intussusception is feasible and safe.Bowel resection if required can be performed by extending umbilical incision without the conventional laparotomy.

Recombinant protein Schistosoma japonicum-derived molecule attenuates dextran sulfate sodium-induced colitis by inhibiting miRNA-217-5p to alleviate apoptosis

BACKGROUND Inflammatory bowel disease(IBD)affects millions of people worldwide and has emerged as a growing problem in industrialized nations.The lack of therapeutic targets has limited the treatment of IBD.Studies found that parasitic nematode infections can ameliorate clinical and experimental colitis.Our previous study found that rSj16,a 16-kDa secreted protein of Schistosoma japonicum produced by Escherichia coli,has protective effects on dextran sulfate sodium(DSS)-induced colitis in mice.Apoptosis is an important factor in the pathogenesis of colitis.However,it is not clear whether the effect of rSj16 on colitis is related to apoptosis.AIM To investigate whether the protective effects of rSj16 on colitis is related to apoptosis and its mechanism.METHODS In-vivo,colitis was induced by DSS.The severity of colitis was assessed.WB was used to detect the changes of apoptosis-related genes in colon tissues.Q-PCR was used to detect the changes of miRNA-217-5p and HNF1B.In-vitro,WB was used to detect the changes of apoptosis-related genes in intestinal epithelial cells.TUNNEL staining and flow cytometry were used to detect cell apoptosis.RESULTS rSj16 attenuates clinical activity in DSS-induced colitis mice.TUNNEL staining and WB results showed that apoptosis was increased in colon tissue after treatment with DSS,and the apoptosis of colon tissue was significantly reduced after treatment with rSj16.Compared with normal mice,the expression of miR-217-5p was increased in colon tissue of DSS-induced colitis mice.In addition,the miR-217-5p target gene hnf1b was decreased after administration of DSS.After treatment with rSj16,the expression of miR-217-5p was decreased and the expression of HNF1B was increased compared with the DSS-treated group.When Etoposide was used in combination with miR-217-5p mimic on MODE-K cells,the expression of cleaved-Caspase-3 and Bax was increased,and Bcl-2 was decreased compared with only Etoposide treatment,the expression of HNF1B was significantly reduced,suggesting that miR-217-5p acts as a pro-apoptotic in colon epithelial cells and down-regulates the target gene hnf1b.After rSj16 administration in MODE-K cells,miR-217-5p expression was significantly decreased,HNF1B expression was increased,and apoptosis was reduced.CONCLUSION The protective effects of rSj16 on colitis is related to apoptosis and miRNA-217-5p may be a further target for therapeutic intervention against IBD.

Differentiation of human embryonic stem cells derived mesenchymal stem cells into corneal epithelial cells after being seeded on decellularized SMILE-derived lenticules

AIM: To evaluate the feasibility of mesenchymal stem cells(MSCs) to differentiate into corneal epithelial cells after being seeded on the decellularized small incision lenticule extraction(SMILE)-derived lenticules. METHODS: The fresh lenticules procured from patients undergoing SMILE for the correction of myopia were decellularized. The MSCs were subsequently cultivated on those denuded lenticules. The MSCs without lenticules were used as a control. The proliferation activity of the MSCs after seeding 24 h was quantitatively determined with the Cell Counting Kit-8(CCK-8) assay. Immunofluorescence staining and quantitative reverse transcription polymerase chain reaction(qRT-PCR) were used to assess the marker expression in differentiated MSCs. RESULTS: The data showed that both fresh and decellularized lenticules could significantly promote the proliferation of MSCs, compared to that in control(P=0.02 for fresh lenticules, P=0.001 for decellularize ones, respectively). The MSCs seeded on both lenticules were positive for cytokeratin 3(CK3) staining. The expression of CK3 increased 5-fold in MSCs seeded on fresh lenticules and 18-fold on decellularized ones, compared to that in control. There was a significant difference in the expression of CK3 in MSCs seeded on fresh and decellularized lenticules(P<0.001). The expression of CK8 and CK18 was similar in pure MSCs and MSCs seeded on fresh lenticules(P>0.05), while the expression of these markers was decreased in MSCs seeded on decellularized ones. CONCLUSION: These results suggest that the decellularized lenticules might be more suitable for MSCs to differentiate into corneal epithelial cells, which offersthe prospect of a novel therapeutic modality of SMILEderived lenticules in regenerative corneal engineering.

Study of liver cirrhosis over twenty consecutive years in adults in Southern China

BACKGROUND Liver cirrhosis(LC)is a prevalent and severe disease in China.The burden of LC is changing with widespread vaccination of hepatitis B virus(HBV)and antiviral therapy.However,the recent transition in etiologies and clinical features of LC cases requiring hospitalization is unclear.AIM To identify the transition in etiologies and clinical characteristics of hospitalized LC patients in Southern China.METHODS In this retrospective,cross-sectional study we included LC inpatients admitted between January 2001 and December 2020.Medical data indicating etiological diagnosis and LC complications,and demographic,laboratory,and imaging data were collected from our hospital-based dataset.The etiologies of LC were mainly determined according to the discharge diagnosis,and upper gastrointestinal bleeding,ascites,hepatic encephalopathy,spontaneous bacterial peritonitis,hepatocellular carcinoma(HCC),portal vein thrombosis,hepatorenal syndrome,and acute-on-chronic liver failure(ACLF)were considered LC-related complications in our study.Changing trends in the etiologies and clinical characteristics were investigated using logistic regression,and temporal trends in proportions of separated years were investigated using the Cochran-Armitage test.In-hospital prognosis and risk factors associated with in-hospital mortality were also invest igated.RESULTS A total of 33143 patients were included in the study[mean(SD)age,51.7(11.9)years],and 82.2%were males.The mean age of the study population increased from 51.0 years in 2001-2010 to 52.0 years in 2011-2020(P<0.001),and the proportion of female patients increased from 16.7%in 2001-2010 to 18.2%in 2011-2020(P=0.003).LC patients in the decompensated stage at diagnosis decreased from 68.1%in 2001-2010 to 64.6%in 2011-2020(P<0.001),and the median score of model for end-stage liver disease also decreased from 14.0 to 11.0(P<0.001).HBV remained the major etiology of LC(75.0%)and the dominant cause of viral hepatitis-LC(94.5%)during the study period.However,the proportion of HBV-LC decreased from 82.4%in 2001-2005 to 74.2%in 2016-2020,and the proportion of viral hepatitis-LC decreased from 85.2%in 2001-2005 to 78.1%in 2016-2020(both P for trend<0.001).Meanwhile,the proportions of LC caused by alcoholic liver disease,autoimmune hepatitis and mixed etiology increased by 2.5%,0.8%and 4.5%,respectively(all P for trend<0.001).In-hospital mortality was stable at 1.0%in 2011-2020,whereas HCC and ACLF manifested the highest increases in prevalence among all LC complications(35.8%to 41.0%and 5.7%to 12.4%,respectively)and were associated with 6-fold and 4-fold increased risks of mortality(odds ratios:6.03 and 4.22,respectively).CONCLUSION LC inpatients have experienced changes in age distribution and etiologies of cirrhosis over the last 20 years in Southern China.HCC and ACLF are associated with the highest risk of in-hospital mortality among LC complications.

Anodal transcranial direct current stimulation alleviates cognitive impairment in an APP/PS1 model of Alzheimer’s disease in the preclinical stage

Anodal transcranial direct current stimulation(AtDCS)has been shown to alleviate cognitive impairment in an APP/PS1 model of Alzheimer’s disease in the preclinical stage.However,this enhancement was only observed immediately after AtDCS,and the long-term effect of AtDCS remains unknown.In this study,we treated 26-week-old mouse models of Alzheimer’s disease in the preclinical stage with 10 AtDCS sessions or sham stimulation.The Morris water maze,novel object recognition task,and novel object location test were implemented to evaluate spatial learning memory and recognition memory of mice.Western blotting was used to detect the relevant protein content.Morphological changes were observed using immunohistochemistry and immunofluorescence staining.Six weeks after treatment,the mice subjected to AtDCS sessions had a shorter escape latency,a shorter path length,more platform area crossings,and spent more time in the target quadrant than sham-stimulated mice.The mice subjected to AtDCS sessions also performed better in the novel object recognition and novel object location tests than sham-stimulated mice.Furthermore,AtDCS reduced the levels of amyloid-β42 and glial fibrillary acidic protein,a marker of astrocyte activation,and increased the level of neuronal marker NeuN in hippocampal tissue.These findings suggest that AtDCS can improve the spatial learning and memory abilities and pathological state of an APP/PS1 mouse model of Alzheimer’s disease in the preclinical stage,with improvements that last for at least 6 weeks.

Clinical efficacy of the partial rectus muscle transportation procedure for paralytic strabismus

AIM:To analyze the clinical efficacy of the partial rectus muscle transportation(PRT)procedure for paralytic strabismus due to single rectus muscle palsy.METHODS:In total,28 patients(31 eyes)who underwent the PRT procedure for paralytic strabismus due to single rectus muscle palsy were retrospectively examined.The following data were collected pre-and postoperatively:angle of deviation in the primary position,presence of diplopia in the primary position,presence of compensatory head posture,and motility of the affected eye.The follow-up period was 6 mo.RESULTS:Based on the preoperative and intraoperative findings,different operations were performed:2 eyes were treated with PRT,26 eyes were treated with PRT combined with the recession of the antagonist muscle(Am)of the paralytic rectus muscle,and 3 eyes were treated with PRT along with the recession of the Am and the yoke muscle(Ym).On the first day after the operation,24 patients were found to be orthophoric in the primary position,without diplopia or abnormal head posture.Moreover,2 patients with monocular lateral rectus muscle palsy had mild overcorrection to 5 prism diopters(PD)and 8 PD,respectively,whereas 2 patients with binocular lateral rectus muscle palsy had mild undercorrection to 8 PD and 10 PD,respectively.During the 6-month follow-up period,the mean deviation was rectified from 96.79±41.21 PD to 0.64±2.38 PD(t=12.48,P<0.001),whereas the deviations in the 2 patients with mild overcorrection were corrected to orthotropia.The mean preoperative limitation of motility improved from-4.55±0.51 to-2.65±0.61(t=-15.13,P<0.001)after 6 mo postoperatively.CONCLUSION:PRT is an effective treatment for complete paralytic strabismus due to single rectus muscle palsy,and can achieve stable clinical efficacy.

菟丝子提取物UPLC指纹图谱建立及抗氧化谱效关系研究

目的 建立菟丝子提取物的超高效液相色谱(UPLC)指纹图谱,分析其与抗氧化活性的谱效关系。方法 采用UPLC法测定11批菟丝子提取物的指纹图谱,以1,1-二苯基-2-苦基肼自由基、2,2-联氮-二(3-乙基-苯并噻唑-6-磺酸)二铵盐法测定菟丝子体外抗氧化活性,结合正交偏最小二乘法(OPLS)以及灰色关联度法分析指纹图谱与抗氧化活性的关联度,筛选出对抗氧化活性贡献较大的关键物质。结果 菟丝子提取物相似度均在0.97以上,共有21个共有峰,通过与对照品对比,指认了10个峰,其中峰5为新绿原酸,峰8为绿原酸,峰9为隐绿原酸,峰10为咖啡酸,峰12为对香豆酸,峰15为金丝桃苷,峰16为异槲皮苷,峰17为紫云英苷,峰20为槲皮素,峰21为山奈素。灰色关联度以及OPLS结果表明,峰8、15、16、18与抗氧化活性呈现正相关,为主要药效成分。结论 菟丝子抗氧化活性是多组分联合效应的结果,通过指纹图谱与抗氧化谱效分析,可为后面菟丝子的进一步研究提供数据参考。

Clinical study on the effect of simvastatin on the bone healing in elderly patients with femoral intertrochanteric fracture merged with type 2 diabetes mellitus

Objective:To explore the effect of simvastatin on the bone mineral density (BMD) and bone metabolism in elderly patients with femoral intertrochanteric fracture merged with type 2 diabetes mellitus (T2DM).Methods: A total of 120 patients with femoral intertrochanteric fracture merged with T2DM who were admitted in our hospital from June, 2014 to October, 2016 were included in the study and randomized into the observation group and the control group (n=60). The patients in the two groups were given minimally invasive PFNA, and blood sugar and blood pressure reducing. The patients in the control group were given alendronate sodium, 70 mg/time, 1 time/week. On this basis, the patients in the observation group were given simvastatin, 40 mg/time,1 time/every night. After 6-month treatment, the efficacy was evaluated. The morning fasting peripheral venous blood before and after treatment in the two groups was collected. The full automatic biochemical analyzer was used to detect the serum Ca, P, and GHb. ECLI was used to detect the serum OC and BAP. ELISA was used to detect the serum TRACP-5b and s-CTX. The dual energy X-ray absorptiomery was used to detect BMD level of the forearm, femoral neck, and anterial position of lumbar spine.Results:Ca, P, and GHb levels after treatment in the two groups were not significantly changed (P>0.05). BMD level of the forearm, femoral neck, and anterial position of lumbar spine after treatment in the observation group was significantly higher than that in the control group (P<0.05). OC and BAP levels after treatment in the observation group were significantly higher than those in the control group (P<0.05), while s-CTX and TRACP-5b levels were significantly lower than those in the control group (P<0.05).Conclusions:Simvastatin can significantly improve the bone metabolism abnormality in elderly patients with femoral intertrochanteric fracture merged with T2DM, enhance BMD, and promote the bone formation and fracture healing;therefore, it deserves to be widely recommended in the clinic.

DEL RBC transfusion should be avoided in particular blood recipient in East Asia due to allosensitization and ineffectiveness

Previously, both primary and secondary anti-D alloimmunizations induced by "Asian type" DEL (RHD1227A allele) were observed in two incidents. We investigated how often these alloimmunization events occur. The transfusions of any D-negative patients were investigated in the First Affiliated Hospital of Xi'an Jiaotong University Medical College, China, during the entire 2009. The antigens of D, C, c, E, and e were routinely serotyped. The "Asian type" DEL variant was genotyped and the RHD heterozygote was determined through two published methods. The changes in anti-D levels were monitored by the indirect antiglobulin test (IAT) and flow cytometry. Thirty D-negative transfused patients were included in the study. We focused on 11 recipients who were transfused with packed red blood cells (RBCs) from DEL donors at least one time. Of those 11 recipients, seven were anti-D negative before transfusion and four were anti-D positive (one patient with an autoantibody). One of the seven pre-transfusion anti-D negative patients produced a primary-response anti-D after being transfused with 400 ml of DEL blood twice. All four pre-transfusion antibody positive patients were not observed hemoglobin (Hb) levels increased, as expected after transfusions. Two patients had an increase in anti-D from 1:8 to 1:64 by IAT, which was also shown by flow cytometry. None of the patients experienced an acute hemolytic episode. Our data indicated that the primary anti-D induced by DEL transfusion or the secondary anti-D elevated by DEL in a truly D-negative patient might not be unusual. We suggest that a truly D-negative childbearing-aged woman should avoid DEL transfusion to protect her from primary anti-D allosensitization. In addition, anti-D positive recipients should also avoid DEL red cell transfusion due to the delayed hemolytic transfusion reaction (DHTR).

Imported parasitic diseases in China's Mainland:current status and perspectives for better control and prevention

Background:The high prevalence of parasitic diseases leads to millions of deaths and disabilities each year in developing countries.China has also been greatly affected by parasitic infections,including filariasis,leishmaniasis,malaria,schistosomiasis,and soil-transmitted nematodosis.However,the situation in China improved dramatically after comprehensive parasitic disease control efforts were strengthened,leading to the elimination of filariasis in 2006 and to significant control over other diseases.However,imported parasitic disease cases are inevitable,and such cases have increasingly been reported as a result of enhanced globalization and international or regional cooperation.These imported diseases represent a major obstacle to the elimination of several parasitoses,such as malaria.Main text:This paper reviews imported cases of parasitic diseases in China's Mainland,particularly malaria and schistosomiasis,based on data reported separately by the Chinese annual reports and from other published papers.We summarize the new challenges that face parasitic disease control efforts in China's Mainland and perspectives regarding better control.We argue that both the provision of professional education and updated training for medical care personnel and the management and surveillance of people entering China are essential.We recommend that Chinese migrant workers should be considered a priority group for health education and that public awareness of imported diseases should be emphasized.Furthermore,we underscore the importance of investigating the distribution of introduced/potential vectors,parasite susceptibility,and improvements in diagnostic techniques and drug stocks.Conclusions:Imported cases have become the main challenge to the elimination of several parasitoses,such as malaria and schistosomiasis,in China's Mainland.China should act to meet these challenges,which are closely associated with national biological safety.

Lnc-TCL6 is a potential biomarker for early diagnosis and grade in liver-cirrhosis patients

Background:Long non-coding RNAs(lncRNAs)have been applied as biomarkers in many diseases.However,scarce biomarkers are available in single lncRNA differential expression associated with different clinical stages of liver cirrhosis(LC).The aim of the study is to identify some lncRNAs that can serve as non-invasive sensitive biomarkers for early diagnosis and grade of LC.Methods:Blood lncRNA expression was evaluated in three independent cohorts with 305 participants including healthy controls,hepatitis B virus(HBV)carriers,and patients with chronic hepatitis B(CHB)or LC.First,candidate lncRNAs were screened by CapitalBiotech microarray to diagnose cirrhosis.Quantitative reverse-transcriptase polymerase chain reaction was then used to investigate the expression of selected lncRNAs in the whole group of cirrhosis and different Child–Pugh classes.Ultimately,the diagnostic accuracy of the promising biomarker was examined and validated via Mann–Whitney test and receiver-operating characteristics analysis.Results:Lnc-TCL6 was identified as a sensitive biomarker for early diagnosis of LC(Child–Pugh A)compared with healthy controls(area under the ROC curve[AUC]=0.636),HBV carriers(AUC=0.671),and CHB patients(AUC=0.672).Furthermore,lnc-TCL6 showed a favourable capacity in discriminating among different Child–Pugh classes(AUC:0.711–0.837).Compared with healthy controls,HBV carriers,and CHB patients,the expression of lnc-TCL6 was obviously up-regulated in Child–Pugh A patients and,conversely,significantly down-regulated in Child–Pugh C patients.Conclusions:Lnc-TCL6 is a novel potential biomarker for early diagnosis of LC and is a possible predictor of disease progression.

Sodium butyrate protects against lipopolysaccharideinduced liver injury partially via the GPR43/b-arrestin-2/NF-кB network

Background Butyrate acts as a regulator in multiple inflammatory organ injuries.However,the role of butyrate in acute liver injury has not yet been fully explored.In the present study,we aimed to investigate the association between butyrate and lipopolysaccharide(LPS)-induced acute liver injury and the signaling pathways involved.Methods LPS-induced acute liver injury was induced by intraperitoneal injection of LPS(5 mg/kg)in G-protein-coupled receptor 43(GPR43)-knockout(KO)and wild-type female C57BL/6 mice.Sodium butyrate(500mg/kg)was administered intraperitoneally 30min prior to LPS exposure.Liver injury was detected by serum markers,tissue morphology,and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL).Pro-inflammatory-factor levels were detected by enzyme-linked immunosorbent assay and real-time polymerase chain reaction(RT-PCR).Cell models were first treated with sodium butyrate(4μmol/mL),followed by LPS(1μg/mL)half an hour later in GPR43 small interfering RNA(siRNA)-transfected or control RAW264.7 cells.Cell-inflammation status was evaluated through detecting pro-inflammatory-factor expression by RT-PCR and also through checking toll-like receptor 4/nuclear factor-кB(TLR4/NF-кB)-element levels including TLR4,TRAF6,IKKb,IкBα,phospho-IкBα,p65,and phospho-p65 by Western blot.The interaction between GPR43 and barrestin-2 was tested by co-immunoprecipitation.Results Sodium butyrate reversed the LPS-induced tissue-morphology changes and high levels of serum alanine aminotransferase,aspartate transaminase,myeloperoxidase,TUNEL,and pro-inflammatory cytokines such as tumor necrosis factor-a and interleukin-6.The ameliorating effect of sodium butyrate was weakened in GPR43-KO mice and GPR43 siRNA RAW264.7 cells,compared with those of GPR43-positive controls.Sodium butyrate downregulated some elements of the TLR4/NF-кB pathway,including phospho-IкBαand phospho-p65,in RAW264.7 cells.Increased interactions between GPR43 and b-arrestin-2,and between b-arrestin-2 and IrBa were observed.Conclusion Sodium butyrate significantly attenuated LPS-induced liver injury by reducing the inflammatory response partially via the GPR43/b-arrestin-2/NF-кB signaling pathway.

Modulation of Wnt/β-catenin signaling affects the directional differentiation of hair follicle stem cells

Aim:The differentiation of hair follicle stem cells(HFSCs)into hair follicle cells has potential clinical applications for cutaneous burns.However,the mechanisms regulating the differentiation of HFSCs into hair follicular papilla or epidermal cells are currently not clear.This study investigated the role of the Wnt/β-catenin pathway and its crosstalk with other signaling components during this differentiation process.Methods:Lithium chloride(LiCl,10 mmol/L)and keratinocyte growth factor(KGF,10μg/L)were used to induce HFSC differentiation,validated by immunofluorescence analysis.The mRNA expression ofβ-catenin,adenomatous polyposis coli,glycogen synthase kinase-3β(GSK-3β),axin,and lymphoid enhancer factor-1 after 3,5,7,and 9 days were measured to evaluate the role of the Wnt/β-catenin pathway.Results:During LiCl-induced HFSC differentiation into hair follicle cells,the Wnt/β-catenin signaling pathway was activated and the expression of GSK-3β,a vital component of the degradation compound,was inhibited.This led to increased cytoplasmicβ-catenin expression,nuclear translocation,and subsequent target gene transcription.By contrast,KGF induced the differentiation of HFSCs into epidermal cells and did not affect the expression ofβ-catenin.This data indicates that LiCl and KGF distinctly regulate the differentiation of HFSCs into hair follicle and epidermal cells,respectively.Furthermore,the Wnt/β-catenin signaling pathway is predominantly involved in hair follicle differentiation.Conclusion:these results demonstrate that LiCl can be used to differentiate HFSCs into hair follicle cells in vitro,which has important therapeutic applications for treating patients with cutaneous damage.