BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse symptoms.Identifying its risk factors is crucial to understanding the etiology,prevention,and management of the disease.The occurrence...BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse symptoms.Identifying its risk factors is crucial to understanding the etiology,prevention,and management of the disease.The occurrence of reflux esophagitis may be associated with food reactions,Helicobacter pylori(H.pylori)infection,and metabolic syndromes.AIM To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin(Ig)G-mediated food intolerance,H.pylori infection,and metabolic syndrome on reflux esophagitis.METHODS Outpatients attending the Second Medical Center of the PLA General Hospital between 2017 and 2021 were retrospectively enrolled.The patients’basic information,test results,gastroscopy results,H.pylori test results,and IgG-mediated food intolerance results were collected.Multivariate logistic regression analysis was used to analyze risk factors for reflux esophagitis.Statistical mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on H.pylori infection affecting reflux esophagitis.RESULTS A total of 7954 outpatients were included;the prevalence of reflux esophagitis,IgG-mediated food intolerance,H.pylori infection,and metabolic syndrome were 20.84%,61.77%,35.91%,and 60.15%,respectively.Multivariate analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance(OR=1.688,95%CI:1.497-1.903,P<0.00001)and metabolic syndrome(OR=1.165,95%CI:1.030-1.317,P=0.01484),and the independent protective factor for reflux esophagitis was H.pylori infection(OR=0.400,95%CI:0.351-0.456,P<0.00001).IgG-mediated food intolerance had a partially positive mediating effect on H.pylori infection as it was associated with reduced occurrence of reflux esophagitis(P=0.0200).Metabolic syndrome had a partially negative mediating effect on H.pylori infection and reduced the occurrence of reflux esophagitis(P=0.0220).CONCLUSION Patients with IgG-mediated food intolerance and metabolic syndrome were at higher risk of developing reflux esophagitis,while patients with H.pylori infection were at lower risk.IgG-mediated food intolerance reduced the risk of reflux esophagitis pathogenesis in patients with H.pylori infection;however,metabolic syndrome increased the risk of patients with H.pylori infection developing reflux esophagitis.展开更多
This letter comments on the article that developed and tested a machine learning model that predicts lymphovascular invasion/perineural invasion status by combining clinical indications and spectral computed tomograph...This letter comments on the article that developed and tested a machine learning model that predicts lymphovascular invasion/perineural invasion status by combining clinical indications and spectral computed tomography characteristics accurately.We review the research content,methodology,conclusions,strengths and weaknesses of the study,and introduce follow-up research to this work.展开更多
Hypoxia can get more ability to inhibit inflammation.But how it impact on survival time of mesenchymal stem cells(MSCs)is confusing and how preconditioned MSCs inhibiting inflammation are partially known.Those issues ...Hypoxia can get more ability to inhibit inflammation.But how it impact on survival time of mesenchymal stem cells(MSCs)is confusing and how preconditioned MSCs inhibiting inflammation are partially known.Those issues decided the value of preconditioned MSCs by hypoxia.展开更多
This letter comments on the article which reported that tenofovir alafenamide may increase blood lipid levels compared with entecavir in patients with chronic hepatitis B published on World J Hepatol 2023 August 27.We...This letter comments on the article which reported that tenofovir alafenamide may increase blood lipid levels compared with entecavir in patients with chronic hepatitis B published on World J Hepatol 2023 August 27.We review the related research content,topic selection,methodology,conclusions,strengths and weaknesses of this article.And evaluate it in relation to other published relevant articles.展开更多
Neurotrophic factors,particularly nerve growth factor,enhance neuronal regeneration.However,the in vivo applications of nerve growth factor are largely limited by its intrinsic disadvantages,such as its short biologic...Neurotrophic factors,particularly nerve growth factor,enhance neuronal regeneration.However,the in vivo applications of nerve growth factor are largely limited by its intrinsic disadvantages,such as its short biological half-life,its contribution to pain response,and its inability to cross the blood-brain barrier.Considering that let-7(human miRNA)targets and regulates nerve growth factor,and that let-7 is a core regulator in peripheral nerve regeneration,we evaluated the possibilities of let-7 application in nerve repair.In this study,anti-let-7a was identified as the most suitable let-7 family molecule by analyses of endogenous expression and regulatory relationship,and functional screening.Let-7a antagomir demonstrated biosafety based on the results of in vivo safety assessments and it entered into the main cell types of the sciatic nerve,including Schwann cells,fibroblasts and macrophages.Use of hydrogel effectively achieved controlled,localized,and sustained delivery of let-7a antagomir.Finally,let-7a antagomir was integrated into chitosan conduit to construct a chitosan-hydrogel scaffold tissue-engineered nerve graft,which promoted nerve regeneration and functional recovery in a rat model of sciatic nerve transection.Our study provides an experimental basis for potential in vivo application of let-7a.展开更多
BACKGROUND Intrahepatic cholestasis of pregnancy(ICP)is a liver disorder that occurs in pregnant women and can lead to a range of adverse pregnancy outcomes.The condition is typically marked by pruritus(itching)and el...BACKGROUND Intrahepatic cholestasis of pregnancy(ICP)is a liver disorder that occurs in pregnant women and can lead to a range of adverse pregnancy outcomes.The condition is typically marked by pruritus(itching)and elevated levels of liver enzymes and bile acids.The standard treatment for ICP has generally been ursodeoxycholic acid and ademetionine 1,4-butanedisulfonate,but the efficacy of this approach remains less than optimal.Recently,polyene phosphatidylcholine has emerged as a promising new therapeutic agent for ICP due to its potential hepatoprotective effects.AIM To evaluate the effect of polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate on bile acid levels,liver enzyme indices,and pregnancy outcomes in patients with ICP.METHODS From June 2020 to June 2021,600 patients with ICP who were diagnosed and treated at our hospital were recruited and assigned at a ratio of 1:1 via randomnumber table method to receive either ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate(control group,n=300)or polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate(combined group,n=300).Outcome measures included bile acids levels,liver enzyme indices,and pregnancy outcomes.RESULTS Prior to treatment,no significant differences were observed between the two groups(P>0.05).Post-treatment,patients in both groups had significantly lower pruritus scores,but the triple-drug combination group had lower scores than the dual-drug combination group(P<0.05).The bile acid levels decreased significantly in both groups,but the decrease was more significant in the triple-drug group(P<0.05).The triple-drug group also exhibited a greater reduction in the levels of certain liver enzymes and a lower incidence of adverse pregnancy outcomes compared to the dual-drug group(P<0.05).CONCLUSION Polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate effectively relieves pruritus and reduces bile acid levels and liver enzyme indices in patients with ICP,providing a positive impact on pregnancy outcome and a high safety profile.Further clinical trials are required prior to clinical application.展开更多
AIM: To investigate the potential therapeutic effects of mesenchymal stem cells (MSCs) in inflammatory bowel disease (IBD), we transplanted MSCs into an experimental model of IBD. METHODS: A rectal enema of trinitrobe...AIM: To investigate the potential therapeutic effects of mesenchymal stem cells (MSCs) in inflammatory bowel disease (IBD), we transplanted MSCs into an experimental model of IBD. METHODS: A rectal enema of trinitrobenzene sulfonic acid (TNBS) (100 mg/kg body weight) was administered to female BALB/c mice. Bone marrow mesenchymal stem cells (BMSCs) were derived from male green fluorescent protein (GFP) transgenic mice and were transplanted intravenously into the experimental animals after disease onset. Clinical activity scores and histological changes were evaluated. GFP and Sex determining region Y gene (SRY ) expression were used for cell tracking. Ki67 positive cells and Lgr5-expressing cells were determined to measure proliferative activity. Inflammatory response was determined by mea-suring the levels of different inflammatory mediators in the colon and serum. The inflammatory cytokines included tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-6, IL-17, IL-4, IL-10, and transforming growth factor (TGF-β). Master regulators of Th1 cells (T-box expressed in T cells, T-bet), Th17 cells (retinoid related orphan receptor gamma(t), RORγt), Th2 cells (GATA family of transcription factors 3, GATA3) and regulatory T cells (forkhead box P3, Foxp3) were also determined. RESULTS: Systemic infusion of GFP-BMSCs ameliorated the clinical and histopathologic severity of colitis, including body weight loss, diarrhea and inflammation, and increased survival (P < 0.05). The cell tracking study showed that MSCs homed to the injured colon. MSCs promoted proliferation of intestinal epithelial cells and differentiation of intestinal stem cells (P < 0.01). This therapeutic effect was mainly mediated by downregulation of both Th1-Th17-driven autoimmune and inflammatory responses (IL-2, TNF-α, IFN-γ, T-bet; IL-6, IL-17, RORγt), and by up-regulation of Th2 activities (IL-4, IL-10, GATA-3) (P < 0.05). MSCs also induced activated CD4 + CD25 + Foxp3 + regulatory T cells (TGF-β, IL-10, Foxp3) with a suppressive capacity on Th1-Th17 effecter responses and promoted Th2 differentiation in vivo (P < 0.05). CONCLUSION: MSCs are key regulators of immune and inflammatory responses and may be an attractive candidate for cell-based therapy of IBD.展开更多
AIM To investigate whether mesenchymal stem cells(MSCs) from adipose-derived stromal cells(ADSCs) and bone marrow stromal cells(BMSCs) have similar hepatic differentiation potential.METHODS Mouse ADSCs and BMSCs were ...AIM To investigate whether mesenchymal stem cells(MSCs) from adipose-derived stromal cells(ADSCs) and bone marrow stromal cells(BMSCs) have similar hepatic differentiation potential.METHODS Mouse ADSCs and BMSCs were isolated and cultured. Their morphological and phenotypic characteristics, as well as their multiple differentiation capacity were compared. A new culture system was established to induce ADSCs and BMSCs into functional hepatocytes. Reverse transcription polymerase chain reaction, Western blot, and immunofluorescence analyses were performed to identify the induced hepatocytelike cells. CM-Dil-labeled ADSCs and BMSCs were then transplanted into a mouse model of CCl4-induced acute liver failure. fluorescence microscopy was used to track the transplanted MSCs. Liver function was tested by an automatic biochemistry analyzer, and liver tissue histology was observed by hematoxylin and eosin(HE) staining.RESULTS ADSCs and BMSCs shared a similar morphology and multiple differentiation capacity, as well as a similar phenotype(with expression of CD29 and CD90 and no expression of CD11 b or CD45). Morphologically, ADSCs and BMSCs became round and epithelioid following hepatic induction. These two cell types differentiated into hepatocyte-like cells with similar expression of albumin, cytokeratin 18, cytokeratin 19, alpha fetoprotein, and cytochrome P450. fluorescence microscopy revealed that both ADSCs and BMSCs were observed in the mouse liver at different time points. Compared to the control group, both the function of the injured livers and HE staining showed significant improvement in the ADSC-and BMSC-transplanted mice. There was no significant difference between the two MSC groups.CONCLUSION ADSCs share a similar hepatic differentiation capacity and therapeutic effect with BMSCs in an acute liver failure model. ADSCs may represent an ideal seed cell type for cell transplantation or a bio-artificial liver support system.展开更多
AIM To assess the efficiency of endoscopic trans-esophageal submucosal tunneling surgery(EESTS) technique for diseases located around the aorta ventralis.METHODS Nine pigs were assigned to EESTs. The procedures were a...AIM To assess the efficiency of endoscopic trans-esophageal submucosal tunneling surgery(EESTS) technique for diseases located around the aorta ventralis.METHODS Nine pigs were assigned to EESTs. The procedures were as follows: First, a long esophageal submucosal tunnel was established. Second, full-thickness myotomy was created. Third, an endoscope was entered into the abdominal cavity through a muscle incision and the endoscope was around the aorta ventralis. Eventually,celiac trunk ganglion neurolysis, partial hepatectomy and splenectomy, partial tissue resection in the area of the posterior peritoneum, and endoscopic submucosal dissection(ESD) combined with lymph node dissection were performed. The animals were given antibiotics for 5 d and necropsied 7 d after surgery.RESULTS In all surgeries, one pig died from intraperitoneal hemorrhage after doing partial splenectomy, while the other pigs were alive after successfully operating other surgeries. For surgery of celiac trunk ganglion damage, at necropsy, there was no exudation in the abdominal cavity. Regarding surgery of partial hepatectomy, the wound with part healing was observed in the left hepatic lobe, and no bleeding or obvious exudation was seen. In surgery of partial splenectomy, massive hemorrhage was observed on the splenic wound surface, and the metal clips could not stop bleeding. After surgery of retroperitoneal tissue resection, mild tissue adhesion was observed in the abdominal cavity of one animal, and another one suffered from severe infection. For surgery of ESD and lymph node dissection, a moderate tissue adhesion was observed.CONCLUSION EESTS is a feasible and safe technique for diseases located around the aorta ventralis.展开更多
The reduction of geraniol to citronellol is the first step for the synthesis of natural phytol in the production of tocopherols and natural vitamin K.Baker's yeast was used in the bioreduction described above as a...The reduction of geraniol to citronellol is the first step for the synthesis of natural phytol in the production of tocopherols and natural vitamin K.Baker's yeast was used in the bioreduction described above as a whole-cell biocatalyst.However,the enzyme responsible for the reduction of geraniol to citronellol is not yet known.Four old yellow enzyme(OYE)genes were cloned from yeast and plants,and expressed in Escherichia coli for a high level of recombinant proteins.The recombinant protein displayed a catalytic activity of converting geraniol to citronellol as a sole product verified by GC-MS analyses.The recombinant OYE2 intact cells were found to show 3.7 and 1.9-fold higher activity than that of yeast cells and the recombinant crude extracts,respectively.Compared to the recombinant fusion enzyme,the entrokinase-cleaved enzyme displayed nearly identical activity for geraniol reduction.To our knowledge,this is the first enzyme identified to catalyze the formation of citronellol from geraniol by reducing the allylic alcohol double bond,which is normally known as inactivating group for the old yellow enzymes.展开更多
The earth-abundant transition metal based nanomaterials are regarded as state-of-the-art oxygen evolution reaction(OER) electrocatalyst. Recent studies have shown that amorphous materials are more active than their cr...The earth-abundant transition metal based nanomaterials are regarded as state-of-the-art oxygen evolution reaction(OER) electrocatalyst. Recent studies have shown that amorphous materials are more active than their crystalline forms. Herein, we demonstrate a facile and rapid substrate participation method to fabricate amorphous NiFe nanosheets on iron foam(a-NiFe NS/IF) at ambient temperature as a highly efficient electrocatalyst for OER. This method only takes 200 s to fabricate the a-NiFe NS/IF and the electrocatalyst possesses excellent catalytic activities which only needs overpotentials of about 211 and 240 m V to reach 10 and 100 mA cm-2 current densities in 1.0 M KOH.展开更多
Parkinson’s disease is characterized by dopaminergic neuron loss and intracellular inclusions composed mainly of alpha synuclein(α-syn),but the mechanism of pathogenesis is still obscure.In recent years,more attenti...Parkinson’s disease is characterized by dopaminergic neuron loss and intracellular inclusions composed mainly of alpha synuclein(α-syn),but the mechanism of pathogenesis is still obscure.In recent years,more attention has been given to the gut as a key player in the initiation and progression of PD pathology.Several studies characterizing changes in the microbiome,particularly the gut microbiome,have been conducted.Although many studies found a decrease in the bacterial family Prevotellaceae and in butyrate-producing bacterial genera such as Roseburia and Faecalibacteria,and an increase in the genera Akkermansia many of the studies reported contradictory findings.In this review,we highlight the findings from the different studies and reflect on the future of microbiome studies in PD research.展开更多
Herein,we first describe the physical mixture of Cu(OH)_2/Fe(OH)_3 as a composite catalyst precursor for the dehydrogenation of ammonia borane(AB)in methanol.During the initial period of catalytic reaction,Cu nanopart...Herein,we first describe the physical mixture of Cu(OH)_2/Fe(OH)_3 as a composite catalyst precursor for the dehydrogenation of ammonia borane(AB)in methanol.During the initial period of catalytic reaction,Cu nanoparticles were formed in-situ.The catalytic activity of Cu nanoparticles can be significantly enhanced with the assistance of Fe species and OH~à.A maximum turnover frequency(TOF)of 50.3 mol_(H2)mol^(à1)_(total metal)min^(à1)(135.6 mol_(H2)mol_(Cu)^(à1)min^(à1))was achieved at ambient temperature,which is superior to those of previously reported Fe or Cu based systems.展开更多
The enteric nervous system (ENS) controls the function of the gastrointestinal tract and has been impli- cated in various diseases, including Parkinson's disease (PD). PD is a neurodegenerative disease with Lewy ...The enteric nervous system (ENS) controls the function of the gastrointestinal tract and has been impli- cated in various diseases, including Parkinson's disease (PD). PD is a neurodegenerative disease with Lewy bodies (LBs) and Lewy neurites (LNs) as the main pathological features. In addition to the typical motor symptoms in PD, attention has been drawn to non-motor symptoms, such as constipation, implying dysfunction of the ENS. In the present study, we characterized the age-dependent mor- phological alterations and aggregation of α-synuclein (α- syn), the primary protein component in LBs and LNs, in the ENS in an α-syn transgenic mouse model. We found that the expression and accumulation of α-syn increased gradually in neurons of Meissner's and Auerbach's plexuses of the gastrointestinal tract with age (from 1 week to 2 years). In addition, α-syn was increasingly phosphorylated at the serine 129 residue, reflecting patho- logical alterations of the protein over time. Furthermore,α- syn was present in different subtypes of neurons expressing vasoactive intestinal polypeptide, neuronal nitric oxide synthase, or calretinin. The results indicated that BAC-α- Syn-GFP transgenic mice provide a unique model in which to study the relationship between ENS and PD pathogenesis.展开更多
Background:Parkinson’s disease(PD)is one of the most common neurodegenerative diseases,neuropathologically characterized by misfolded protein aggregation,called Lewy bodies and Lewy neurites.PD is a slow-progressive ...Background:Parkinson’s disease(PD)is one of the most common neurodegenerative diseases,neuropathologically characterized by misfolded protein aggregation,called Lewy bodies and Lewy neurites.PD is a slow-progressive disease with colonic dysfunction appearing in the prodromal stage and lasting throughout the course of the disease.Methods:In order to study PD pathology in the colon,we examined the age-dependent morphological and pathological changes in the colon of a PD mouse model expressing human wildtype α-synuclein(α-syn)fused with the green fluorescent protein(GFP),under the endogenous mouse α-syn promoter.Results:We observed an age-dependent progressive expression and accumulation of α-syn-GFP in the enteric neurons of Meissner’s(submucosal)and Auerbach’s(myenteric)plexuses of the colon.Additionally,the phosphorylation of α-syn at serine 129 also increased with age and the aggregation ofα-syn-GFP coincided with the appearance of motor deficits at 9 months of age.Furthermore,α-syn(-GFP)distinctly co-localized with different subtypes of neurons,as identified by immunohistochemical labeling of vasoactive intestinal peptide(VIP),neuronal nitric oxide synthase(nNOS),and calretinin.Conclusions:Our results show the development of α-syn pathology in the enteric neurons of the colon in a PD mouse model,which coincide with the appearance of motor deficits.Our mouse model possesses the potential and uniqueness for studying PD gastrointestinal dysfunction.展开更多
Monodispersed palladium phosphide(Pd_(3)P)(5.2 ± 0.5 nm) was firstly applied to photocatalytic Suzuki coupling reaction under visible light irradiation with CdS nanoflake as a photo sensitizer.This heterogeneous ...Monodispersed palladium phosphide(Pd_(3)P)(5.2 ± 0.5 nm) was firstly applied to photocatalytic Suzuki coupling reaction under visible light irradiation with CdS nanoflake as a photo sensitizer.This heterogeneous system exhibited high yields to corresponding products and excellent stability in alcohol solvent at room temperature.展开更多
基金This study was reviewed and approved by the Ethics Committee of the PLA General Hospital(Ethics audits No.S2022-414-01).
文摘BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse symptoms.Identifying its risk factors is crucial to understanding the etiology,prevention,and management of the disease.The occurrence of reflux esophagitis may be associated with food reactions,Helicobacter pylori(H.pylori)infection,and metabolic syndromes.AIM To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin(Ig)G-mediated food intolerance,H.pylori infection,and metabolic syndrome on reflux esophagitis.METHODS Outpatients attending the Second Medical Center of the PLA General Hospital between 2017 and 2021 were retrospectively enrolled.The patients’basic information,test results,gastroscopy results,H.pylori test results,and IgG-mediated food intolerance results were collected.Multivariate logistic regression analysis was used to analyze risk factors for reflux esophagitis.Statistical mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on H.pylori infection affecting reflux esophagitis.RESULTS A total of 7954 outpatients were included;the prevalence of reflux esophagitis,IgG-mediated food intolerance,H.pylori infection,and metabolic syndrome were 20.84%,61.77%,35.91%,and 60.15%,respectively.Multivariate analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance(OR=1.688,95%CI:1.497-1.903,P<0.00001)and metabolic syndrome(OR=1.165,95%CI:1.030-1.317,P=0.01484),and the independent protective factor for reflux esophagitis was H.pylori infection(OR=0.400,95%CI:0.351-0.456,P<0.00001).IgG-mediated food intolerance had a partially positive mediating effect on H.pylori infection as it was associated with reduced occurrence of reflux esophagitis(P=0.0200).Metabolic syndrome had a partially negative mediating effect on H.pylori infection and reduced the occurrence of reflux esophagitis(P=0.0220).CONCLUSION Patients with IgG-mediated food intolerance and metabolic syndrome were at higher risk of developing reflux esophagitis,while patients with H.pylori infection were at lower risk.IgG-mediated food intolerance reduced the risk of reflux esophagitis pathogenesis in patients with H.pylori infection;however,metabolic syndrome increased the risk of patients with H.pylori infection developing reflux esophagitis.
文摘This letter comments on the article that developed and tested a machine learning model that predicts lymphovascular invasion/perineural invasion status by combining clinical indications and spectral computed tomography characteristics accurately.We review the research content,methodology,conclusions,strengths and weaknesses of the study,and introduce follow-up research to this work.
文摘Hypoxia can get more ability to inhibit inflammation.But how it impact on survival time of mesenchymal stem cells(MSCs)is confusing and how preconditioned MSCs inhibiting inflammation are partially known.Those issues decided the value of preconditioned MSCs by hypoxia.
文摘This letter comments on the article which reported that tenofovir alafenamide may increase blood lipid levels compared with entecavir in patients with chronic hepatitis B published on World J Hepatol 2023 August 27.We review the related research content,topic selection,methodology,conclusions,strengths and weaknesses of this article.And evaluate it in relation to other published relevant articles.
基金supported by the National Natural Science Foundation of China,No.31970968(to SYL)the Collegiate Natural Science Foundation of Jiangsu Province,No.16KJA310005(to SYL)+1 种基金Priority Academic Program Development of Jiangsu Higher Education Institutions[PAPD]the Natural Science Foundation of Jiangsu Province,No.BK20200976(to XHW).
文摘Neurotrophic factors,particularly nerve growth factor,enhance neuronal regeneration.However,the in vivo applications of nerve growth factor are largely limited by its intrinsic disadvantages,such as its short biological half-life,its contribution to pain response,and its inability to cross the blood-brain barrier.Considering that let-7(human miRNA)targets and regulates nerve growth factor,and that let-7 is a core regulator in peripheral nerve regeneration,we evaluated the possibilities of let-7 application in nerve repair.In this study,anti-let-7a was identified as the most suitable let-7 family molecule by analyses of endogenous expression and regulatory relationship,and functional screening.Let-7a antagomir demonstrated biosafety based on the results of in vivo safety assessments and it entered into the main cell types of the sciatic nerve,including Schwann cells,fibroblasts and macrophages.Use of hydrogel effectively achieved controlled,localized,and sustained delivery of let-7a antagomir.Finally,let-7a antagomir was integrated into chitosan conduit to construct a chitosan-hydrogel scaffold tissue-engineered nerve graft,which promoted nerve regeneration and functional recovery in a rat model of sciatic nerve transection.Our study provides an experimental basis for potential in vivo application of let-7a.
文摘BACKGROUND Intrahepatic cholestasis of pregnancy(ICP)is a liver disorder that occurs in pregnant women and can lead to a range of adverse pregnancy outcomes.The condition is typically marked by pruritus(itching)and elevated levels of liver enzymes and bile acids.The standard treatment for ICP has generally been ursodeoxycholic acid and ademetionine 1,4-butanedisulfonate,but the efficacy of this approach remains less than optimal.Recently,polyene phosphatidylcholine has emerged as a promising new therapeutic agent for ICP due to its potential hepatoprotective effects.AIM To evaluate the effect of polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate on bile acid levels,liver enzyme indices,and pregnancy outcomes in patients with ICP.METHODS From June 2020 to June 2021,600 patients with ICP who were diagnosed and treated at our hospital were recruited and assigned at a ratio of 1:1 via randomnumber table method to receive either ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate(control group,n=300)or polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate(combined group,n=300).Outcome measures included bile acids levels,liver enzyme indices,and pregnancy outcomes.RESULTS Prior to treatment,no significant differences were observed between the two groups(P>0.05).Post-treatment,patients in both groups had significantly lower pruritus scores,but the triple-drug combination group had lower scores than the dual-drug combination group(P<0.05).The bile acid levels decreased significantly in both groups,but the decrease was more significant in the triple-drug group(P<0.05).The triple-drug group also exhibited a greater reduction in the levels of certain liver enzymes and a lower incidence of adverse pregnancy outcomes compared to the dual-drug group(P<0.05).CONCLUSION Polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate effectively relieves pruritus and reduces bile acid levels and liver enzyme indices in patients with ICP,providing a positive impact on pregnancy outcome and a high safety profile.Further clinical trials are required prior to clinical application.
基金Supported by The National Natural Science Foundation of China, No. 81050027
文摘AIM: To investigate the potential therapeutic effects of mesenchymal stem cells (MSCs) in inflammatory bowel disease (IBD), we transplanted MSCs into an experimental model of IBD. METHODS: A rectal enema of trinitrobenzene sulfonic acid (TNBS) (100 mg/kg body weight) was administered to female BALB/c mice. Bone marrow mesenchymal stem cells (BMSCs) were derived from male green fluorescent protein (GFP) transgenic mice and were transplanted intravenously into the experimental animals after disease onset. Clinical activity scores and histological changes were evaluated. GFP and Sex determining region Y gene (SRY ) expression were used for cell tracking. Ki67 positive cells and Lgr5-expressing cells were determined to measure proliferative activity. Inflammatory response was determined by mea-suring the levels of different inflammatory mediators in the colon and serum. The inflammatory cytokines included tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-6, IL-17, IL-4, IL-10, and transforming growth factor (TGF-β). Master regulators of Th1 cells (T-box expressed in T cells, T-bet), Th17 cells (retinoid related orphan receptor gamma(t), RORγt), Th2 cells (GATA family of transcription factors 3, GATA3) and regulatory T cells (forkhead box P3, Foxp3) were also determined. RESULTS: Systemic infusion of GFP-BMSCs ameliorated the clinical and histopathologic severity of colitis, including body weight loss, diarrhea and inflammation, and increased survival (P < 0.05). The cell tracking study showed that MSCs homed to the injured colon. MSCs promoted proliferation of intestinal epithelial cells and differentiation of intestinal stem cells (P < 0.01). This therapeutic effect was mainly mediated by downregulation of both Th1-Th17-driven autoimmune and inflammatory responses (IL-2, TNF-α, IFN-γ, T-bet; IL-6, IL-17, RORγt), and by up-regulation of Th2 activities (IL-4, IL-10, GATA-3) (P < 0.05). MSCs also induced activated CD4 + CD25 + Foxp3 + regulatory T cells (TGF-β, IL-10, Foxp3) with a suppressive capacity on Th1-Th17 effecter responses and promoted Th2 differentiation in vivo (P < 0.05). CONCLUSION: MSCs are key regulators of immune and inflammatory responses and may be an attractive candidate for cell-based therapy of IBD.
基金Supported by the National Natural Science foundation of China,No.30900669 and No.81473271Technology Nova Plan of Beijing City,No.2011117China Postdoctoral Science foundation,No.2016T90994
文摘AIM To investigate whether mesenchymal stem cells(MSCs) from adipose-derived stromal cells(ADSCs) and bone marrow stromal cells(BMSCs) have similar hepatic differentiation potential.METHODS Mouse ADSCs and BMSCs were isolated and cultured. Their morphological and phenotypic characteristics, as well as their multiple differentiation capacity were compared. A new culture system was established to induce ADSCs and BMSCs into functional hepatocytes. Reverse transcription polymerase chain reaction, Western blot, and immunofluorescence analyses were performed to identify the induced hepatocytelike cells. CM-Dil-labeled ADSCs and BMSCs were then transplanted into a mouse model of CCl4-induced acute liver failure. fluorescence microscopy was used to track the transplanted MSCs. Liver function was tested by an automatic biochemistry analyzer, and liver tissue histology was observed by hematoxylin and eosin(HE) staining.RESULTS ADSCs and BMSCs shared a similar morphology and multiple differentiation capacity, as well as a similar phenotype(with expression of CD29 and CD90 and no expression of CD11 b or CD45). Morphologically, ADSCs and BMSCs became round and epithelioid following hepatic induction. These two cell types differentiated into hepatocyte-like cells with similar expression of albumin, cytokeratin 18, cytokeratin 19, alpha fetoprotein, and cytochrome P450. fluorescence microscopy revealed that both ADSCs and BMSCs were observed in the mouse liver at different time points. Compared to the control group, both the function of the injured livers and HE staining showed significant improvement in the ADSC-and BMSC-transplanted mice. There was no significant difference between the two MSC groups.CONCLUSION ADSCs share a similar hepatic differentiation capacity and therapeutic effect with BMSCs in an acute liver failure model. ADSCs may represent an ideal seed cell type for cell transplantation or a bio-artificial liver support system.
基金Scientific Research Support Fund for Chinese PLA General Hospital,No.2012FCTSYS-3035
文摘AIM To assess the efficiency of endoscopic trans-esophageal submucosal tunneling surgery(EESTS) technique for diseases located around the aorta ventralis.METHODS Nine pigs were assigned to EESTs. The procedures were as follows: First, a long esophageal submucosal tunnel was established. Second, full-thickness myotomy was created. Third, an endoscope was entered into the abdominal cavity through a muscle incision and the endoscope was around the aorta ventralis. Eventually,celiac trunk ganglion neurolysis, partial hepatectomy and splenectomy, partial tissue resection in the area of the posterior peritoneum, and endoscopic submucosal dissection(ESD) combined with lymph node dissection were performed. The animals were given antibiotics for 5 d and necropsied 7 d after surgery.RESULTS In all surgeries, one pig died from intraperitoneal hemorrhage after doing partial splenectomy, while the other pigs were alive after successfully operating other surgeries. For surgery of celiac trunk ganglion damage, at necropsy, there was no exudation in the abdominal cavity. Regarding surgery of partial hepatectomy, the wound with part healing was observed in the left hepatic lobe, and no bleeding or obvious exudation was seen. In surgery of partial splenectomy, massive hemorrhage was observed on the splenic wound surface, and the metal clips could not stop bleeding. After surgery of retroperitoneal tissue resection, mild tissue adhesion was observed in the abdominal cavity of one animal, and another one suffered from severe infection. For surgery of ESD and lymph node dissection, a moderate tissue adhesion was observed.CONCLUSION EESTS is a feasible and safe technique for diseases located around the aorta ventralis.
基金This work was supported by grants from the Ministry of Science and Technology of China(2007CB108802)State Key Laboratory of Phytochemistry and Plant Resources in West China(P2008-ZZ16,P2009-ZZ02).
文摘The reduction of geraniol to citronellol is the first step for the synthesis of natural phytol in the production of tocopherols and natural vitamin K.Baker's yeast was used in the bioreduction described above as a whole-cell biocatalyst.However,the enzyme responsible for the reduction of geraniol to citronellol is not yet known.Four old yellow enzyme(OYE)genes were cloned from yeast and plants,and expressed in Escherichia coli for a high level of recombinant proteins.The recombinant protein displayed a catalytic activity of converting geraniol to citronellol as a sole product verified by GC-MS analyses.The recombinant OYE2 intact cells were found to show 3.7 and 1.9-fold higher activity than that of yeast cells and the recombinant crude extracts,respectively.Compared to the recombinant fusion enzyme,the entrokinase-cleaved enzyme displayed nearly identical activity for geraniol reduction.To our knowledge,this is the first enzyme identified to catalyze the formation of citronellol from geraniol by reducing the allylic alcohol double bond,which is normally known as inactivating group for the old yellow enzymes.
基金the financial support from the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB17000000)the National Natural Science Foundation of China(21773275)CAS-Croucher Funding Scheme for Joint Laboratories
文摘The earth-abundant transition metal based nanomaterials are regarded as state-of-the-art oxygen evolution reaction(OER) electrocatalyst. Recent studies have shown that amorphous materials are more active than their crystalline forms. Herein, we demonstrate a facile and rapid substrate participation method to fabricate amorphous NiFe nanosheets on iron foam(a-NiFe NS/IF) at ambient temperature as a highly efficient electrocatalyst for OER. This method only takes 200 s to fabricate the a-NiFe NS/IF and the electrocatalyst possesses excellent catalytic activities which only needs overpotentials of about 211 and 240 m V to reach 10 and 100 mA cm-2 current densities in 1.0 M KOH.
基金This work was supported by grants from the Swedish Research Council(K2015-61X-22297-03-4),EU-JPND(aSynProtec)and EU-JPND(REfreAME),EU H2020-MSCA-ITN-2016(Syndegen)the Strong Research Environment Multi-Park(Multidisciplinary research on Parkinson’s disease)+2 种基金the Swedish Parkinson Foundation(Parkinsonfonden),Torsten Söderbergs Foundation and Olle Engkvist Byggmästere FoundationAcknowledgements are also to the supports of the National Natural Science Foundation of China(No.81430025 and U1801681)the Key Field Research Development Program of Guangdong Province(2018B030337001).
文摘Parkinson’s disease is characterized by dopaminergic neuron loss and intracellular inclusions composed mainly of alpha synuclein(α-syn),but the mechanism of pathogenesis is still obscure.In recent years,more attention has been given to the gut as a key player in the initiation and progression of PD pathology.Several studies characterizing changes in the microbiome,particularly the gut microbiome,have been conducted.Although many studies found a decrease in the bacterial family Prevotellaceae and in butyrate-producing bacterial genera such as Roseburia and Faecalibacteria,and an increase in the genera Akkermansia many of the studies reported contradictory findings.In this review,we highlight the findings from the different studies and reflect on the future of microbiome studies in PD research.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB17000000)the National Natural Science Foundation of China (21773275)
文摘Herein,we first describe the physical mixture of Cu(OH)_2/Fe(OH)_3 as a composite catalyst precursor for the dehydrogenation of ammonia borane(AB)in methanol.During the initial period of catalytic reaction,Cu nanoparticles were formed in-situ.The catalytic activity of Cu nanoparticles can be significantly enhanced with the assistance of Fe species and OH~à.A maximum turnover frequency(TOF)of 50.3 mol_(H2)mol^(à1)_(total metal)min^(à1)(135.6 mol_(H2)mol_(Cu)^(à1)min^(à1))was achieved at ambient temperature,which is superior to those of previously reported Fe or Cu based systems.
基金supported by the National Natural Science Foundation of China (81430025)Northeastern University, China, as well as the Swedish Research Council (K201561X-22297-03-4)+5 种基金the EU Joint Programme-Neurodegenerative Disease Research (aSyn Protec and REfre AME),EU H2020-MSCAITN-2016 (Syndegen)Basal Ganglia Disorders Linnaeus Consortium-Excellence in Parkinson and Huntington Researchthe Strong Research Environment Multi Park (Multidisciplinary Research on Parkinson's disease)the Swedish Parkinson Foundation (Parkinsonfonden)the Torsten Sderbergs Foundation, and the Olle Engkvist Byggmstere Foundationsupported by a scholarship from the China Scholarship Council
文摘The enteric nervous system (ENS) controls the function of the gastrointestinal tract and has been impli- cated in various diseases, including Parkinson's disease (PD). PD is a neurodegenerative disease with Lewy bodies (LBs) and Lewy neurites (LNs) as the main pathological features. In addition to the typical motor symptoms in PD, attention has been drawn to non-motor symptoms, such as constipation, implying dysfunction of the ENS. In the present study, we characterized the age-dependent mor- phological alterations and aggregation of α-synuclein (α- syn), the primary protein component in LBs and LNs, in the ENS in an α-syn transgenic mouse model. We found that the expression and accumulation of α-syn increased gradually in neurons of Meissner's and Auerbach's plexuses of the gastrointestinal tract with age (from 1 week to 2 years). In addition, α-syn was increasingly phosphorylated at the serine 129 residue, reflecting patho- logical alterations of the protein over time. Furthermore,α- syn was present in different subtypes of neurons expressing vasoactive intestinal polypeptide, neuronal nitric oxide synthase, or calretinin. The results indicated that BAC-α- Syn-GFP transgenic mice provide a unique model in which to study the relationship between ENS and PD pathogenesis.
基金This work was supported by the National Natural Science Foundation(81430025)also to the supports of the Swedish Research Council(K2015-61X-22297-03-4),EU-JPND(aSynProtec)and EU-JPND(REfreAME),EU H2020-MSCA-ITN-2016(Syndegen),BAGADILICO-Excellence in Parkinson and Huntington Research,the Strong Research Environment MultiPark(Multidisciplinary research on Parkinson’s disease)+1 种基金the Swedish Parkinson Foundation(Parkinsonfonden),Torsten Söderbergs Foundation,Olle Engkvist Byggmästere FoundationW.L.is supported by a scholarship from the China Scholarship Council.
文摘Background:Parkinson’s disease(PD)is one of the most common neurodegenerative diseases,neuropathologically characterized by misfolded protein aggregation,called Lewy bodies and Lewy neurites.PD is a slow-progressive disease with colonic dysfunction appearing in the prodromal stage and lasting throughout the course of the disease.Methods:In order to study PD pathology in the colon,we examined the age-dependent morphological and pathological changes in the colon of a PD mouse model expressing human wildtype α-synuclein(α-syn)fused with the green fluorescent protein(GFP),under the endogenous mouse α-syn promoter.Results:We observed an age-dependent progressive expression and accumulation of α-syn-GFP in the enteric neurons of Meissner’s(submucosal)and Auerbach’s(myenteric)plexuses of the colon.Additionally,the phosphorylation of α-syn at serine 129 also increased with age and the aggregation ofα-syn-GFP coincided with the appearance of motor deficits at 9 months of age.Furthermore,α-syn(-GFP)distinctly co-localized with different subtypes of neurons,as identified by immunohistochemical labeling of vasoactive intestinal peptide(VIP),neuronal nitric oxide synthase(nNOS),and calretinin.Conclusions:Our results show the development of α-syn pathology in the enteric neurons of the colon in a PD mouse model,which coincide with the appearance of motor deficits.Our mouse model possesses the potential and uniqueness for studying PD gastrointestinal dysfunction.
基金the financial support from the Strategic Priority Research Program of the Chinese Academy of Sciences (No. XDB17000000)the National Natural Science Foundation of China (Nos.21773275 and 21971250)the financial support from K.C.Wong Education Foundation and the CAS-Croucher Funding Scheme for Joint Laboratories。
文摘Monodispersed palladium phosphide(Pd_(3)P)(5.2 ± 0.5 nm) was firstly applied to photocatalytic Suzuki coupling reaction under visible light irradiation with CdS nanoflake as a photo sensitizer.This heterogeneous system exhibited high yields to corresponding products and excellent stability in alcohol solvent at room temperature.