BACKGROUND Deoxycholic acid(DCA),a secondary bile acid,is associated with colorectal carcinogenesis,but its mechanisms remain unclear.AIM To investigate how DCA regulates apoptosis in colorectal cancer(CRC)cells.METHO...BACKGROUND Deoxycholic acid(DCA),a secondary bile acid,is associated with colorectal carcinogenesis,but its mechanisms remain unclear.AIM To investigate how DCA regulates apoptosis in colorectal cancer(CRC)cells.METHODS SW480 and DLD-1 CRC cell lines were used to investigate the mechanism of apoptosis by western blotting,flow cytometry,confocal microscopy,and other methods.RESULTS DCA significantly induced apoptosis,with rates increasing to 7.2%±1.5%in SW480 cells and 14.3%±0.6%in DLD-1 cells after treatment,compared to 4.7%±1.0%and 11.6%±0.8%in controls(P<0.05).Western blot analysis showed upregulation of pro-apoptotic proteins Bax and Cleaved-PARP,with a significant increase in the Cleaved-PARP/PARP ratio(P<0.001).DCA treatment also increased the intracellular reactive oxygen species(ROS)levels of SW480 and DLD-1 cells to 1.2-fold and 1.3-fold,respectively(P<0.01),while the increase of mitochondrial ROS levels in these cells was statistically significant under confocal microscopy.Additionally,cytosolic and mitochondrial Ca^(2+)levels increased 1.3-fold and 1.2-fold,respectively,in SW480 cells(P<0.01),and 1.1-fold and 1.1-fold,respectively,in DLD-1 cells compared with controls(P<0.05).p-CaMKII protein levels were also elevated(P<0.01),indicating activation of the Ca^(2+)-CaMKII signaling pathway.Pharmacological inhibition with BAPTAAM(1μM)reduced mitochondrial Ca^(2+)accumulation and ROS levels in SW480 cells(P<0.05),and suppressed apoptosis.CONCLUSION DCA activates the Ca^(2+)-CaMKII pathway,leading to ROS-mediated apoptosis in CRC cells,providing insights for potential therapeutic targets.展开更多
AIM:To detect the expression of tumor necrosis factor-a(TNF-a)in colorectal cancer(CRC)cells among Saudi patients,and correlate its expression with clinical stages of cancer.METHODS:Archival tissue specimens were coll...AIM:To detect the expression of tumor necrosis factor-a(TNF-a)in colorectal cancer(CRC)cells among Saudi patients,and correlate its expression with clinical stages of cancer.METHODS:Archival tissue specimens were collected from 30 patients with CRC who had undergone surgical intervention at King Khalid University Hospital.Patient demographic information,including age and gender,tumor sites,and histological type of CRC,was recorded.To measure TNF-a m RNA expression in CRC,total RNA was extracted from tumor formalin-fixed,paraffinembedded,and adjacent normal tissues.Reverse transcription and reverse transcription polymerase chain reaction were performed.Colorectal tissue microarrays were constructed to investigate the protein expression of TNF-a by immunohistochemistry.RESULTS:The relative expression of TNF-a m RNA in colorectal cancer was significantly higher than that seen in adjacent normal colorectal tissue.High TNF-a gene expression was associated with StageⅢandⅣneoplasms when compared with earlier tumor stages(P=0.004).Eighty-three percent of patients(25/30)showed strong TNF-a positive staining,while only 10%(n=3/30)of patients showed weak staining,and 7%(n=2/30)were negative.We showed the presence of elevated TNF-a gene expression in cancer cells,which strongly correlated with advanced stages of tumor.CONCLUSION:High levels of TNF-a expression could be an independent diagnostic indicator of colorectal cancer,and targeting TNF-a might be a promising prognostic tool by assessment of the clinical stages of CRC.展开更多
AIM： To systematically review the literature for studies investigating the potential effect of gender of dialysis patients on the immunogenicity of hepatitis B virus vaccines. METHODS： Literature searches were condu...AIM： To systematically review the literature for studies investigating the potential effect of gender of dialysis patients on the immunogenicity of hepatitis B virus vaccines. METHODS： Literature searches were conducted by the MEDLINE and Google Scholar. The key words used included “hepatitis B （HB）”, “vaccine”, “dialysis”, “hemodialysis”, “sex”, “male” and “female”. Data of seroresponse to HB vaccine in clinical trials regarding sex of the recipients have been achieved and analyzed. Finally data from 19 clinical trials have been pooled and analyzed.RESULTS： Analysis of response to HB vaccination in our dialysis population showed males significantly res-pond less to hepatitis B vaccination （P = 0.002, Z = 3.08） with no significant heterogeneity detected [P = 0.766; heterogeneity χ2 = 14.30 （df = 19）; I2 = 0%]. A reanalysis of the pooled data was conducted regarding the dialysis mode to evaluate potential differential impact of sex on HB vaccine response. Hemodialysis was the only subgroup that showed a signifcant difference regarding dialysis mode in response to HB vaccination regarding sex （ P = 0.042, Z = 2.03）.CONCLUSION： This Meta-analysis showed significant effect for the sex of chronic kidney disease and dialysis patients on the immunogenicity of HB vaccine. This sex discrimination was most prominent among hemodialysis patients.展开更多
Objective: To determine whether permutation scan statistics was more efficient in finding prospective spatial-temporal outbreaks for cutaneous leishmaniasis(CL) or for malaria in Fars province, Iran in 2016. Methods: ...Objective: To determine whether permutation scan statistics was more efficient in finding prospective spatial-temporal outbreaks for cutaneous leishmaniasis(CL) or for malaria in Fars province, Iran in 2016. Methods: Using time-series data including 29 177 CL cases recorded during 2010-2015 and 357 malaria cases recorded during 2010-2015, CL and malaria cases were predicted in 2016. Predicted cases were used to verify if they followed uniform distribution over time and space using space-time analysis. To testify the uniformity of distributions, permutation scan statistics was applied prospectively to detect statistically significant and non-significant outbreaks. Finally, the findings were compared to determine whether permutation scan statistics worked better for CL or for malaria in the area. Prospective permutation scan modeling was performed using SatScan software. Results: A total of 5 359 CL and 23 malaria cases were predicted in 2016 using time-series models. Applied timeseries models were well-fitted regarding auto correlation function, partial auto correlation function sample/model, and residual analysis criteria(Pv was set to 0.1). The results indicated two significant prospective spatial-temporal outbreaks for CL(P<0.5) including Most Likely Clusters, and one non-significant outbreak for malaria(P>0.5) in the area. Conclusions: Both CL and malaria follow a space-time trend in the area, but prospective permutation scan modeling works better for detecting CL spatial-temporal outbreaks. It is not far away from expectation since clusters are defined as accumulation of cases in specified times and places. Although this method seems to work better with finding the outbreaks of a high-frequency disease; i.e., CL, it is able to find non-significant outbreaks. This is clinically important for both high-and low-frequency infections; i.e., CL and malaria.展开更多
Objective: To determine the endemic values of cutaneous leishmaniasis in different cities of Fars province, Iran. Methods: Totally, 29 201 cases registered from 2010 to 2015 in Iranian Fars province were selected, and...Objective: To determine the endemic values of cutaneous leishmaniasis in different cities of Fars province, Iran. Methods: Totally, 29 201 cases registered from 2010 to 2015 in Iranian Fars province were selected, and the endemic values of cutaneous leishmaniasis were determined by retrospective clusters derived from spatiotemporal permutation modeling on a time-series design. The accuracy of the values was assessed using receiver operating characteristic(ROC) curve. SPSS version 22, Arc GIS, and ITSM 2002 software tools were used for analysis. Results: Nine statistically significant retrospective clusters(P<0.05) resulted in finding seven significant and accurate endemic values(P<0.1). These valid endemic scores were generalized to the other 18 cities based on 6 different climates in the province. Conclusions: Retrospectively detected clusters with the help of ROC curve analysis could help determine cutaneous leishmaniasis endemic values which are essential for future prediction and prevention policies in the area.展开更多
Objective:To establish an early warning system for cutaneous leishmaniasis in Fars province,Iran in 2016.Methods:Time-series data were recorded from 29 201 cutaneous leishmaniasis cases in 25 cities of Fars province f...Objective:To establish an early warning system for cutaneous leishmaniasis in Fars province,Iran in 2016.Methods:Time-series data were recorded from 29 201 cutaneous leishmaniasis cases in 25 cities of Fars province from 2010 to 2015 and were used to fit and predict the cases using time-series models.Different models were compared via Akaike information criterion/Bayesian information criterion statistics,residual analysis,autocorrelation function,and partial autocorrelation function sample/model.To decide on an outbreak,four endemic scores were evaluated including mean,median,mean+ 2 standard deviations,and median+ interquartile range of the past five years.Patients whose symptoms of cutaneous leishmaniasis began from 1 January 2010 to 31 December 2015 were included,and there were no exclusion criteria.Results:Regarding four statistically significant endemic values,four different cutaneous leishmaniasis space-time outbreaks were detected in 2016.The accuracy of all four endemic values was statistically significant(P<0.05).Conclusions:This study presents a protocol to set early warning systems regarding time and space features of cutaneous leishmaniasis in four steps:(i)to define endemic values based on which we could verify if there is an outbreak,(ii)to set different time-series models to forecast cutaneous leishmaniasis in future,(iii)to compare the forecasts with endemic values and decide on space-time outbreaks,and(iv)to set an alarm to health managers.展开更多
Alginate scaffold has been considered as an appropriate biomaterial for promoting the differentiation of embryonic stem cells toward neuronal cell lineage. We hypothesized that alginate scaffold is suitable for cultur...Alginate scaffold has been considered as an appropriate biomaterial for promoting the differentiation of embryonic stem cells toward neuronal cell lineage. We hypothesized that alginate scaffold is suitable for culturing Wharton’s jelly mesenchymal stem cells（WJMSCs） and can promote the differentiation of WJMSCs into neuron-like cells. In this study, we cultured WJMSCs in a three-dimensional scaffold fabricated by 0.25% alginate and 50 m M Ca Cl2 in the presence of neurogenic medium containing 10 μM retinoic acid and 20 ng/m L basic fibroblast growth factor. These cells were also cultured in conventional two-dimensional culture condition in the presence of neurogenic medium as controls. After 10 days, immunofluorescence staining was performed for detecting β-tubulin（marker for WJMSCs-differentiated neuron） and CD271（motor neuron marker）. β-Tubulin and CD271 expression levels were significantly greater in the WJMSCs cultured in the three-dimensional alginate scaffold than in the conventional two-dimensional culture condition. These findings suggest that three-dimensional alginate scaffold cell culture system can induce neuronal differentiation of WJMSCs effectively.展开更多
Objective:The plastic role of regulatory factor X1(RFX1)in colon cancer progression and its impact on the tumor microenvironment remain poorly understood.The study aimed to clarify the molecular and clinical role of R...Objective:The plastic role of regulatory factor X1(RFX1)in colon cancer progression and its impact on the tumor microenvironment remain poorly understood.The study aimed to clarify the molecular and clinical role of RFX1 in colon cancer.Methods:We classified colon cancers into subgroups with high and low RFX1 expression and characterized their immune profiles,mutational profiles,cancer immunotherapy and drug sensitivity.By combining RFX1 expression with persistent tumor mutational burden,we proposed a novel nomogram clinical prediction model and validated its predictive performance,and the correlation between high expression and poor prognosis.Results:Compared to tumor mutational burden(TMB),persistent tumor mutational burden(pTMB)is an independent predictor of prognosis in patients with colon cancer.The predictive efficacy of the combination of RFX1 expression and pTMB was superior to and sensitive than the combination of RFX1 expression with TMB.Among them,patients in the RFX1^(high)/pTMB^(high) subgroup had the worst quality of survival and prognosis,whereas those in the RFX1low/pTMBlow subgroup had a relatively better prognosis(p<0.0001).Univariate Cox regression revealed a significant association between high RFX1 expression and increased risk in colon cancer patients(Hazard Ratio[HR]=1.58,95%Confidence Interval[CI]:1.10–2.25,p=0.012),which remained independently predictive in multivariate analysis after covariate adjustment(HR=1.52,95%CI:1.04–2.22,p=0.031).Conclusion:A nomogram model based on RFX1 combined with pTMB provides an alternative approach for the diagnosis and treatment of colon cancer.展开更多
Background:Exosome administration is a novel medical approach that promises excellent immunomodulatory properties without the conventional side effects of current antitumor necrosis factor drugs and stemcells.This stu...Background:Exosome administration is a novel medical approach that promises excellent immunomodulatory properties without the conventional side effects of current antitumor necrosis factor drugs and stemcells.This study aimed to assess the safety and efficacy of usingmesenchymal stemcell(MSC)exosomes to treat refractory fistulas in patients with inflammatory bowel disease.Methods:MSCs were derived from the umbilical cords and their exosomes were isolated.Five patients with refractory perianal Crohn’s disease fistulas with amedian age of 35 years(range 31–47 years)were enrolled in the study.Exosome injections were administered in the operating roomto patients with refractory fistula(fistulas that are irresponsive to anti-tumor necrosis factor-αadministration within 6months).Sixmonths later,a physical examination,face-to-face interviews,andmagnetic resonance imaging were employed to evaluate the therapy responses of patients.Results:The outcomes within 6 months after initiation of therapy showed that four patients had responded to therapy.Three patients who received exosome injections exhibited complete healing,while one reported no improvement and active discharge from the fistula site.In addition,five patients(100%)reported neither systemic nor local adverse effects.Conclusions:Injection of exosomes extracted from MSCs demonstrates safety and a satisfactory therapeutic effect,as evidenced in this and other studies,and may play a significant role in the future treatment of gastrointestinal fistulas.展开更多
Background:Lgr5-positive cells located in the basal layer of crypts have self-regenerative and proliferative differentiation potentials of intestinal stem cells(ISCs),maintaining a balance of regeneration-repair in mu...Background:Lgr5-positive cells located in the basal layer of crypts have self-regenerative and proliferative differentiation potentials of intestinal stem cells(ISCs),maintaining a balance of regeneration-repair in mucosal epithelium.However,the mechanisms of mucosal repair that are regulated by ISCs in ulcerative colitis(UC)remain unclear.Method:Colon tissues from patients with UC were collected to testβ-catenin and Notch1 expression by using Western blot and quantitative real-time polymerase chain reaction(PCR).β-catenin^(fl/fl) mice,β-cateninTg mice,and Dll1tm1 Gos mice were used to cross with Lgr5-EGFP-IRES-creERT2 mice to generate mice of different genotypes,altering the activation of Wnt/β-catenin and Dll1-mediated Notch signaling in ISCs in vivo.Dextran sulfate sodium(DSS)was used to induce a colitis mice model.Intestinal organoids were isolated and cultured to observe the proliferation and differentiation levels of ISCs.Result:β-catenin and Notch1 expression were significantly increased in the inflamed colon tissues from patients with UC.Wnt/β-catenin activation and Dll1-mediated Notch pathway inhibition in Lgr5-positive stem cells promoted the expressions of E-cadherin,CK20,and CHGA in colonic organoids and epithelium,implying the promotion of colonic epithelial integrity.Activation of Wnt/β-catenin and suppression of Dll1-mediated Notch pathway in Lgr5-positive ISCs alleviated the DSS-induced intestinal mucosal inflammation in mice.Conclusions:Lgr5-positive ISCs are characterized by self-renewal and high dividend potential,which play an important role in the injury and repair of intestinal mucosa.More importantly,the Wnt/β-catenin signaling pathway cooperates with the Notch signaling pathway to maintain the function of the Lgr5-positive ISCs.展开更多
The proper differentiation and reorganization of the intestinal epithelial cell population is critical to mucosal regeneration post injury.Label retaining cells(LRCs)expressing SRY-box transcription factor 9(SOX9)prom...The proper differentiation and reorganization of the intestinal epithelial cell population is critical to mucosal regeneration post injury.Label retaining cells(LRCs)expressing SRY-box transcription factor 9(SOX9)promote epithelial repair by replenishing LGR5 t intestinal stem cells(ISCs).While,LRCs are also considered precursor cells for enteroendocrine cells(EECs)which exacerbate mucosal damage in inflammatory bowel disease(IBD).The factors that determine LRC-EEC differentiation and the effect of intervening in LRC-EEC differentiation on IBD remain unclear.In this study,we investigated the effects of a natural anthraquinone called aloe emodin(derived from the Chinese herb rhubarb)on mucosal healing in IBD models.Our findings demonstrated that aloe emodin effectively interfered with the differentiation to EECs and preserved a higher number of SOX9t LRCs,thereby promoting mucosal healing.Furthermore,we discovered that aloe emodin acted as an antagonist of free fatty acid receptors(FFAR1),suppressing the FFAR1-mediated Gbg/serine/threonine-protein kinase(AKT)pathway and promoting the translocation of forkhead box protein O1(FOXO1)into the nucleus,ultimately resulting in the intervention of differentiation fate.These findings reveal the effect of free fatty acid accessibility on EEC differentiation and introduce a strategy for promoting mucosal healing in IBD by regulating the FFAR1/AKT/FOXO1 signaling pathway.展开更多
基金Supported by the Key Discipline of Zhejiang Province in Medical Technology(First Class,Category A)Wenzhou Science&Technological Project,No.Y20240103.
文摘BACKGROUND Deoxycholic acid(DCA),a secondary bile acid,is associated with colorectal carcinogenesis,but its mechanisms remain unclear.AIM To investigate how DCA regulates apoptosis in colorectal cancer(CRC)cells.METHODS SW480 and DLD-1 CRC cell lines were used to investigate the mechanism of apoptosis by western blotting,flow cytometry,confocal microscopy,and other methods.RESULTS DCA significantly induced apoptosis,with rates increasing to 7.2%±1.5%in SW480 cells and 14.3%±0.6%in DLD-1 cells after treatment,compared to 4.7%±1.0%and 11.6%±0.8%in controls(P<0.05).Western blot analysis showed upregulation of pro-apoptotic proteins Bax and Cleaved-PARP,with a significant increase in the Cleaved-PARP/PARP ratio(P<0.001).DCA treatment also increased the intracellular reactive oxygen species(ROS)levels of SW480 and DLD-1 cells to 1.2-fold and 1.3-fold,respectively(P<0.01),while the increase of mitochondrial ROS levels in these cells was statistically significant under confocal microscopy.Additionally,cytosolic and mitochondrial Ca^(2+)levels increased 1.3-fold and 1.2-fold,respectively,in SW480 cells(P<0.01),and 1.1-fold and 1.1-fold,respectively,in DLD-1 cells compared with controls(P<0.05).p-CaMKII protein levels were also elevated(P<0.01),indicating activation of the Ca^(2+)-CaMKII signaling pathway.Pharmacological inhibition with BAPTAAM(1μM)reduced mitochondrial Ca^(2+)accumulation and ROS levels in SW480 cells(P<0.05),and suppressed apoptosis.CONCLUSION DCA activates the Ca^(2+)-CaMKII pathway,leading to ROS-mediated apoptosis in CRC cells,providing insights for potential therapeutic targets.
文摘AIM:To detect the expression of tumor necrosis factor-a(TNF-a)in colorectal cancer(CRC)cells among Saudi patients,and correlate its expression with clinical stages of cancer.METHODS:Archival tissue specimens were collected from 30 patients with CRC who had undergone surgical intervention at King Khalid University Hospital.Patient demographic information,including age and gender,tumor sites,and histological type of CRC,was recorded.To measure TNF-a m RNA expression in CRC,total RNA was extracted from tumor formalin-fixed,paraffinembedded,and adjacent normal tissues.Reverse transcription and reverse transcription polymerase chain reaction were performed.Colorectal tissue microarrays were constructed to investigate the protein expression of TNF-a by immunohistochemistry.RESULTS:The relative expression of TNF-a m RNA in colorectal cancer was significantly higher than that seen in adjacent normal colorectal tissue.High TNF-a gene expression was associated with StageⅢandⅣneoplasms when compared with earlier tumor stages(P=0.004).Eighty-three percent of patients(25/30)showed strong TNF-a positive staining,while only 10%(n=3/30)of patients showed weak staining,and 7%(n=2/30)were negative.We showed the presence of elevated TNF-a gene expression in cancer cells,which strongly correlated with advanced stages of tumor.CONCLUSION:High levels of TNF-a expression could be an independent diagnostic indicator of colorectal cancer,and targeting TNF-a might be a promising prognostic tool by assessment of the clinical stages of CRC.
基金Supported by Grant from the Baqiyatallah University of Medical Sciences
文摘AIM： To systematically review the literature for studies investigating the potential effect of gender of dialysis patients on the immunogenicity of hepatitis B virus vaccines. METHODS： Literature searches were conducted by the MEDLINE and Google Scholar. The key words used included “hepatitis B （HB）”, “vaccine”, “dialysis”, “hemodialysis”, “sex”, “male” and “female”. Data of seroresponse to HB vaccine in clinical trials regarding sex of the recipients have been achieved and analyzed. Finally data from 19 clinical trials have been pooled and analyzed.RESULTS： Analysis of response to HB vaccination in our dialysis population showed males significantly res-pond less to hepatitis B vaccination （P = 0.002, Z = 3.08） with no significant heterogeneity detected [P = 0.766; heterogeneity χ2 = 14.30 （df = 19）; I2 = 0%]. A reanalysis of the pooled data was conducted regarding the dialysis mode to evaluate potential differential impact of sex on HB vaccine response. Hemodialysis was the only subgroup that showed a signifcant difference regarding dialysis mode in response to HB vaccination regarding sex （ P = 0.042, Z = 2.03）.CONCLUSION： This Meta-analysis showed significant effect for the sex of chronic kidney disease and dialysis patients on the immunogenicity of HB vaccine. This sex discrimination was most prominent among hemodialysis patients.
文摘Objective: To determine whether permutation scan statistics was more efficient in finding prospective spatial-temporal outbreaks for cutaneous leishmaniasis(CL) or for malaria in Fars province, Iran in 2016. Methods: Using time-series data including 29 177 CL cases recorded during 2010-2015 and 357 malaria cases recorded during 2010-2015, CL and malaria cases were predicted in 2016. Predicted cases were used to verify if they followed uniform distribution over time and space using space-time analysis. To testify the uniformity of distributions, permutation scan statistics was applied prospectively to detect statistically significant and non-significant outbreaks. Finally, the findings were compared to determine whether permutation scan statistics worked better for CL or for malaria in the area. Prospective permutation scan modeling was performed using SatScan software. Results: A total of 5 359 CL and 23 malaria cases were predicted in 2016 using time-series models. Applied timeseries models were well-fitted regarding auto correlation function, partial auto correlation function sample/model, and residual analysis criteria(Pv was set to 0.1). The results indicated two significant prospective spatial-temporal outbreaks for CL(P<0.5) including Most Likely Clusters, and one non-significant outbreak for malaria(P>0.5) in the area. Conclusions: Both CL and malaria follow a space-time trend in the area, but prospective permutation scan modeling works better for detecting CL spatial-temporal outbreaks. It is not far away from expectation since clusters are defined as accumulation of cases in specified times and places. Although this method seems to work better with finding the outbreaks of a high-frequency disease; i.e., CL, it is able to find non-significant outbreaks. This is clinically important for both high-and low-frequency infections; i.e., CL and malaria.
文摘Objective: To determine the endemic values of cutaneous leishmaniasis in different cities of Fars province, Iran. Methods: Totally, 29 201 cases registered from 2010 to 2015 in Iranian Fars province were selected, and the endemic values of cutaneous leishmaniasis were determined by retrospective clusters derived from spatiotemporal permutation modeling on a time-series design. The accuracy of the values was assessed using receiver operating characteristic(ROC) curve. SPSS version 22, Arc GIS, and ITSM 2002 software tools were used for analysis. Results: Nine statistically significant retrospective clusters(P<0.05) resulted in finding seven significant and accurate endemic values(P<0.1). These valid endemic scores were generalized to the other 18 cities based on 6 different climates in the province. Conclusions: Retrospectively detected clusters with the help of ROC curve analysis could help determine cutaneous leishmaniasis endemic values which are essential for future prediction and prevention policies in the area.
基金funded by Shiraz University of Medical Sciences(12439)
文摘Objective:To establish an early warning system for cutaneous leishmaniasis in Fars province,Iran in 2016.Methods:Time-series data were recorded from 29 201 cutaneous leishmaniasis cases in 25 cities of Fars province from 2010 to 2015 and were used to fit and predict the cases using time-series models.Different models were compared via Akaike information criterion/Bayesian information criterion statistics,residual analysis,autocorrelation function,and partial autocorrelation function sample/model.To decide on an outbreak,four endemic scores were evaluated including mean,median,mean+ 2 standard deviations,and median+ interquartile range of the past five years.Patients whose symptoms of cutaneous leishmaniasis began from 1 January 2010 to 31 December 2015 were included,and there were no exclusion criteria.Results:Regarding four statistically significant endemic values,four different cutaneous leishmaniasis space-time outbreaks were detected in 2016.The accuracy of all four endemic values was statistically significant(P<0.05).Conclusions:This study presents a protocol to set early warning systems regarding time and space features of cutaneous leishmaniasis in four steps:(i)to define endemic values based on which we could verify if there is an outbreak,(ii)to set different time-series models to forecast cutaneous leishmaniasis in future,(iii)to compare the forecasts with endemic values and decide on space-time outbreaks,and(iv)to set an alarm to health managers.
基金the research deputy of Shiraz University of Medical Sciences, Iran for offering student research grant (No. 5959)
文摘Alginate scaffold has been considered as an appropriate biomaterial for promoting the differentiation of embryonic stem cells toward neuronal cell lineage. We hypothesized that alginate scaffold is suitable for culturing Wharton’s jelly mesenchymal stem cells（WJMSCs） and can promote the differentiation of WJMSCs into neuron-like cells. In this study, we cultured WJMSCs in a three-dimensional scaffold fabricated by 0.25% alginate and 50 m M Ca Cl2 in the presence of neurogenic medium containing 10 μM retinoic acid and 20 ng/m L basic fibroblast growth factor. These cells were also cultured in conventional two-dimensional culture condition in the presence of neurogenic medium as controls. After 10 days, immunofluorescence staining was performed for detecting β-tubulin（marker for WJMSCs-differentiated neuron） and CD271（motor neuron marker）. β-Tubulin and CD271 expression levels were significantly greater in the WJMSCs cultured in the three-dimensional alginate scaffold than in the conventional two-dimensional culture condition. These findings suggest that three-dimensional alginate scaffold cell culture system can induce neuronal differentiation of WJMSCs effectively.
基金sponsored by the National Natural Science Foundation of China(82002507)Shanghai Sailing Program(20YF1430100)Shanghai Hospital Development Center(SHDC2023CRT004).
文摘Objective:The plastic role of regulatory factor X1(RFX1)in colon cancer progression and its impact on the tumor microenvironment remain poorly understood.The study aimed to clarify the molecular and clinical role of RFX1 in colon cancer.Methods:We classified colon cancers into subgroups with high and low RFX1 expression and characterized their immune profiles,mutational profiles,cancer immunotherapy and drug sensitivity.By combining RFX1 expression with persistent tumor mutational burden,we proposed a novel nomogram clinical prediction model and validated its predictive performance,and the correlation between high expression and poor prognosis.Results:Compared to tumor mutational burden(TMB),persistent tumor mutational burden(pTMB)is an independent predictor of prognosis in patients with colon cancer.The predictive efficacy of the combination of RFX1 expression and pTMB was superior to and sensitive than the combination of RFX1 expression with TMB.Among them,patients in the RFX1^(high)/pTMB^(high) subgroup had the worst quality of survival and prognosis,whereas those in the RFX1low/pTMBlow subgroup had a relatively better prognosis(p<0.0001).Univariate Cox regression revealed a significant association between high RFX1 expression and increased risk in colon cancer patients(Hazard Ratio[HR]=1.58,95%Confidence Interval[CI]:1.10–2.25,p=0.012),which remained independently predictive in multivariate analysis after covariate adjustment(HR=1.52,95%CI:1.04–2.22,p=0.031).Conclusion:A nomogram model based on RFX1 combined with pTMB provides an alternative approach for the diagnosis and treatment of colon cancer.
文摘Background:Exosome administration is a novel medical approach that promises excellent immunomodulatory properties without the conventional side effects of current antitumor necrosis factor drugs and stemcells.This study aimed to assess the safety and efficacy of usingmesenchymal stemcell(MSC)exosomes to treat refractory fistulas in patients with inflammatory bowel disease.Methods:MSCs were derived from the umbilical cords and their exosomes were isolated.Five patients with refractory perianal Crohn’s disease fistulas with amedian age of 35 years(range 31–47 years)were enrolled in the study.Exosome injections were administered in the operating roomto patients with refractory fistula(fistulas that are irresponsive to anti-tumor necrosis factor-αadministration within 6months).Sixmonths later,a physical examination,face-to-face interviews,andmagnetic resonance imaging were employed to evaluate the therapy responses of patients.Results:The outcomes within 6 months after initiation of therapy showed that four patients had responded to therapy.Three patients who received exosome injections exhibited complete healing,while one reported no improvement and active discharge from the fistula site.In addition,five patients(100%)reported neither systemic nor local adverse effects.Conclusions:Injection of exosomes extracted from MSCs demonstrates safety and a satisfactory therapeutic effect,as evidenced in this and other studies,and may play a significant role in the future treatment of gastrointestinal fistulas.
基金supported by the National Natural Science Foundation of China[No.82000481,81570474,and 82270549].
文摘Background:Lgr5-positive cells located in the basal layer of crypts have self-regenerative and proliferative differentiation potentials of intestinal stem cells(ISCs),maintaining a balance of regeneration-repair in mucosal epithelium.However,the mechanisms of mucosal repair that are regulated by ISCs in ulcerative colitis(UC)remain unclear.Method:Colon tissues from patients with UC were collected to testβ-catenin and Notch1 expression by using Western blot and quantitative real-time polymerase chain reaction(PCR).β-catenin^(fl/fl) mice,β-cateninTg mice,and Dll1tm1 Gos mice were used to cross with Lgr5-EGFP-IRES-creERT2 mice to generate mice of different genotypes,altering the activation of Wnt/β-catenin and Dll1-mediated Notch signaling in ISCs in vivo.Dextran sulfate sodium(DSS)was used to induce a colitis mice model.Intestinal organoids were isolated and cultured to observe the proliferation and differentiation levels of ISCs.Result:β-catenin and Notch1 expression were significantly increased in the inflamed colon tissues from patients with UC.Wnt/β-catenin activation and Dll1-mediated Notch pathway inhibition in Lgr5-positive stem cells promoted the expressions of E-cadherin,CK20,and CHGA in colonic organoids and epithelium,implying the promotion of colonic epithelial integrity.Activation of Wnt/β-catenin and suppression of Dll1-mediated Notch pathway in Lgr5-positive ISCs alleviated the DSS-induced intestinal mucosal inflammation in mice.Conclusions:Lgr5-positive ISCs are characterized by self-renewal and high dividend potential,which play an important role in the injury and repair of intestinal mucosa.More importantly,the Wnt/β-catenin signaling pathway cooperates with the Notch signaling pathway to maintain the function of the Lgr5-positive ISCs.
基金National Natural Science Foundation of China(Nos.82030113,82130108,and 82204717)China Postdoctoral Science Foundation(Nos.BX20220069 and 2021M700864).
文摘The proper differentiation and reorganization of the intestinal epithelial cell population is critical to mucosal regeneration post injury.Label retaining cells(LRCs)expressing SRY-box transcription factor 9(SOX9)promote epithelial repair by replenishing LGR5 t intestinal stem cells(ISCs).While,LRCs are also considered precursor cells for enteroendocrine cells(EECs)which exacerbate mucosal damage in inflammatory bowel disease(IBD).The factors that determine LRC-EEC differentiation and the effect of intervening in LRC-EEC differentiation on IBD remain unclear.In this study,we investigated the effects of a natural anthraquinone called aloe emodin(derived from the Chinese herb rhubarb)on mucosal healing in IBD models.Our findings demonstrated that aloe emodin effectively interfered with the differentiation to EECs and preserved a higher number of SOX9t LRCs,thereby promoting mucosal healing.Furthermore,we discovered that aloe emodin acted as an antagonist of free fatty acid receptors(FFAR1),suppressing the FFAR1-mediated Gbg/serine/threonine-protein kinase(AKT)pathway and promoting the translocation of forkhead box protein O1(FOXO1)into the nucleus,ultimately resulting in the intervention of differentiation fate.These findings reveal the effect of free fatty acid accessibility on EEC differentiation and introduce a strategy for promoting mucosal healing in IBD by regulating the FFAR1/AKT/FOXO1 signaling pathway.
