Objective The effect of the functionally unknown gene C6orf120 on autoimmune hepatitis was investigated on C6orf120 knockout rats(C6orf120^(-/-))and THP-1 cells.Method Six–eight-week-old C6orf120^(-/-)and wild-type(W...Objective The effect of the functionally unknown gene C6orf120 on autoimmune hepatitis was investigated on C6orf120 knockout rats(C6orf120^(-/-))and THP-1 cells.Method Six–eight-week-old C6orf120^(-/-)and wild-type(WT)SD rats were injected with Con A(16 mg/kg),and euthanized after 24 h.The sera,livers,and spleens were collected.THP-1 cells and the recombinant protein(rC6ORF120)were used to explore the mechanism in vitro.The frequency of M1 and M2 macrophages was analyzed using flow cytometry.Western blotting and PCR were used to detect macrophage polarization-associated factors.Results C6orf120 knockout attenuated Con A-induced autoimmune hepatitis.Flow cytometry indicated that the proportion of CD68^(+)CD86^(+)M1 macrophages from the liver and spleen in the C6orf120^(-/-)rats decreased.C6orf120 knockout induced downregulation of CD86 protein and the mRNA levels of related inflammatory factors TNF-α,IL-1β,and IL-6 in the liver.C6orf120 knockout did not affect the polarization of THP-1 cells.However,rC6ORF120 promoted the THP-1 cells toward CD68^(+)CD80^(+)M1 macrophages and inhibited the CD68^(+)CD206^(+)M2 phenotype.Conclusion C6orf120 knockout alleviates Con A-induced autoimmune hepatitis by inhibiting macrophage polarization toward M1 macrophages and reducing the expression of related inflammatory factors in C6orf120^(-/-)rats.展开更多
Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased states.In lower vertebrates like zebrafish,these cells assume respon...Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased states.In lower vertebrates like zebrafish,these cells assume responsibility for spontaneous retinal regeneration,wherein endogenous Müller glia undergo proliferation,transform into Müller glia-derived progenitor cells,and subsequently regenerate the entire retina with restored functionality.Conversely,Müller glia in the mouse and human retina exhibit limited neural reprogramming.Müller glia reprogramming is thus a promising strategy for treating neurodegenerative ocular disorders.Müller glia reprogramming in mice has been accomplished with remarkable success,through various technologies.Advancements in molecular,genetic,epigenetic,morphological,and physiological evaluations have made it easier to document and investigate the Müller glia programming process in mice.Nevertheless,there remain issues that hinder improving reprogramming efficiency and maturity.Thus,understanding the reprogramming mechanism is crucial toward exploring factors that will improve Müller glia reprogramming efficiency,and for developing novel Müller glia reprogramming strategies.This review describes recent progress in relatively successful Müller glia reprogramming strategies.It also provides a basis for developing new Müller glia reprogramming strategies in mice,including epigenetic remodeling,metabolic modulation,immune regulation,chemical small-molecules regulation,extracellular matrix remodeling,and cell-cell fusion,to achieve Müller glia reprogramming in mice.展开更多
Despite its often illegal nature, artisanal gold mining in Burkina Faso contributes to the economic and social development of the country. However, the rudimentary techniques used in gold panning have a significant im...Despite its often illegal nature, artisanal gold mining in Burkina Faso contributes to the economic and social development of the country. However, the rudimentary techniques used in gold panning have a significant impact on the environment due to inappropriate practices and the use of various chemical substances. This study aims to assess the impact of artisanal gold mining on the quality of water resources in a rural community at Méguet, Burkina Faso. To this end, surface and groundwater samples were collected and analyzed at the BUMIGEB laboratory. Field results show that the waters are slightly alkaline (6.97 < pH < 8.1), weakly mineralized and conductive (124 < EC < 543 μS/cm), with temperatures ranging from 24.6˚C to 31.6˚C. In addition, trace metals (TMEs) analyzed from surface and subsurface waters show very high levels, generally deviating from the levels recommended by WHO guidelines for Burkina Faso. Trace metals contamination of water resources in the commune of Méguet is mainly due to Fe (3.78 - 11.12 mg/kg), Hg (0.03 - 0.29 mg/kg), As (0.01- 6.31 mg/kg) and Pb (0.01 - 3.8 mg/kg). This study can serve as a basis for guiding national environmental policies to protect the water resources of the Méguet mine.展开更多
BACKGROUND Oncostatin M(OSM)is a pleiotropic cytokine which is implicated in the path-ogenesis of inflammatory bowel disease(IBD).AIM To evaluate the prognostic role of OSM in IBD patients.METHODS Literature search wa...BACKGROUND Oncostatin M(OSM)is a pleiotropic cytokine which is implicated in the path-ogenesis of inflammatory bowel disease(IBD).AIM To evaluate the prognostic role of OSM in IBD patients.METHODS Literature search was conducted in electronic databases(Google Scholar,Embase,PubMed,Science Direct,Springer,and Wiley).Studies were selected if they reported prognostic information about OSM in IBD patients.Outcome data were synthesized,and meta-analyses were performed to estimate standardized mean differences(SMDs)in OSM levels between treatment responders and non-res-ponders and to seek overall correlations of OSM with other inflammatory bio-markers.RESULTS Sixteen studies(818 Crohn’s disease and 686 ulcerative colitis patients treated with anti-tumor necrosis factor-based therapies)were included.OSM levels were associated with IBD severity.A meta-analysis found significantly higher OSM levels in non-responders than in responders to therapy[SMD 0.80(0.33,1.27);P=0.001],in non-remitters than in remitters[SMD 0.75(95%CI:0.35 to 1.16);P<0.0001]and in patients with no mucosal healing than in those with mucosal heal-ing[SMD 0.63(0.30,0.95);P<0.0001].Area under receiver operator curve values showed considerable variability between studies but in general higher OSM levels were associated with poor prognosis.OSM had significant correlations with Simple Endoscopic Score of Crohn’s disease[r=0.47(95%CI:0.25 to 0.64);P<0.0001],Mayo Endoscopic Score[r=0.35(95%CI:0.28 to 0.41);P<0.0001],fecal calprotectin[r=0.19(95%CI:0.08 to 0.3);P=0.001],C-reactive protein[r=0.25(95%CI:0.11 to 0.39);P<0.0001],and platelet count[r=0.28(95%CI:0.17 to 0.39);P<0.0001].CONCLUSION OSM is a potential candidate for determining the severity of disease and predicting the outcomes of anti-tumor necrosis factor-based therapies in IBD patients.展开更多
Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in ...Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in neuroinflammation in the cerebrum.However,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown.In our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion injury.For in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller cells.We found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion injury.Furthermore,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte rleukin-18.The opposite results we re observed with Homerla ove rexpression.Finally,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion injury.Taken together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.展开更多
目的探讨甲基转移酶5(methyltransferase-like 5,METTL5)在三阴乳腺癌(triple-negative breast cancer,TNBC)中的作用和潜在机制。方法采用免疫组织化学方法和Western blot检测TNBC肿瘤组织和细胞系中METTL5的表达情况。用靶向METTL5的s...目的探讨甲基转移酶5(methyltransferase-like 5,METTL5)在三阴乳腺癌(triple-negative breast cancer,TNBC)中的作用和潜在机制。方法采用免疫组织化学方法和Western blot检测TNBC肿瘤组织和细胞系中METTL5的表达情况。用靶向METTL5的shRNA(shRNA-METTL5)转染TNBC细胞后,用CCK-8、集落形成、伤口愈合以及Transwell实验分别检测细胞增殖活性、迁移与侵袭,Western blot检测Wnt/β-catenin信号关键蛋白的表达。构建异种移植瘤模型,验证敲降METTL5对TNBC细胞在体内生长以及Wnt/β-catenin信号活性的影响。结果METTL5在TNBC肿瘤组织和细胞系中表达上调(P<0.01)。敲降METTL5可抑制TNBC细胞的增殖、迁移和侵袭并降低了Wnt/β-catenin信号分子β-catenin、细胞周期蛋白(Cyclin)D1、基质金属蛋白酶(MMP)-2和MMP-7的表达(均P<0.01)。体内实验显示,敲降METTL5减缓了移植瘤生长和Wnt/β-catenin信号活性。结论敲降METTL5能抑制TNBC细胞的增殖、迁移与侵袭,其作用可能与抑制Wnt/β-catenin信号通路有关。展开更多
基金supported by the Dengfeng Talent Support Program of Beijing Municipal Administration of Hospitals[Grant No.DFL20221601]the Natural Science Foundation of Beijing[Grant No.7212053]Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine[Grant No.ZYYCXTD-C-202006].
文摘Objective The effect of the functionally unknown gene C6orf120 on autoimmune hepatitis was investigated on C6orf120 knockout rats(C6orf120^(-/-))and THP-1 cells.Method Six–eight-week-old C6orf120^(-/-)and wild-type(WT)SD rats were injected with Con A(16 mg/kg),and euthanized after 24 h.The sera,livers,and spleens were collected.THP-1 cells and the recombinant protein(rC6ORF120)were used to explore the mechanism in vitro.The frequency of M1 and M2 macrophages was analyzed using flow cytometry.Western blotting and PCR were used to detect macrophage polarization-associated factors.Results C6orf120 knockout attenuated Con A-induced autoimmune hepatitis.Flow cytometry indicated that the proportion of CD68^(+)CD86^(+)M1 macrophages from the liver and spleen in the C6orf120^(-/-)rats decreased.C6orf120 knockout induced downregulation of CD86 protein and the mRNA levels of related inflammatory factors TNF-α,IL-1β,and IL-6 in the liver.C6orf120 knockout did not affect the polarization of THP-1 cells.However,rC6ORF120 promoted the THP-1 cells toward CD68^(+)CD80^(+)M1 macrophages and inhibited the CD68^(+)CD206^(+)M2 phenotype.Conclusion C6orf120 knockout alleviates Con A-induced autoimmune hepatitis by inhibiting macrophage polarization toward M1 macrophages and reducing the expression of related inflammatory factors in C6orf120^(-/-)rats.
基金supported by the National Natural Science Foundation of China,No.31930068National Key Research and Development Program of China,Nos.2018YFA0107302 and 2021YFA1101203(all to HX).
文摘Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased states.In lower vertebrates like zebrafish,these cells assume responsibility for spontaneous retinal regeneration,wherein endogenous Müller glia undergo proliferation,transform into Müller glia-derived progenitor cells,and subsequently regenerate the entire retina with restored functionality.Conversely,Müller glia in the mouse and human retina exhibit limited neural reprogramming.Müller glia reprogramming is thus a promising strategy for treating neurodegenerative ocular disorders.Müller glia reprogramming in mice has been accomplished with remarkable success,through various technologies.Advancements in molecular,genetic,epigenetic,morphological,and physiological evaluations have made it easier to document and investigate the Müller glia programming process in mice.Nevertheless,there remain issues that hinder improving reprogramming efficiency and maturity.Thus,understanding the reprogramming mechanism is crucial toward exploring factors that will improve Müller glia reprogramming efficiency,and for developing novel Müller glia reprogramming strategies.This review describes recent progress in relatively successful Müller glia reprogramming strategies.It also provides a basis for developing new Müller glia reprogramming strategies in mice,including epigenetic remodeling,metabolic modulation,immune regulation,chemical small-molecules regulation,extracellular matrix remodeling,and cell-cell fusion,to achieve Müller glia reprogramming in mice.
文摘Despite its often illegal nature, artisanal gold mining in Burkina Faso contributes to the economic and social development of the country. However, the rudimentary techniques used in gold panning have a significant impact on the environment due to inappropriate practices and the use of various chemical substances. This study aims to assess the impact of artisanal gold mining on the quality of water resources in a rural community at Méguet, Burkina Faso. To this end, surface and groundwater samples were collected and analyzed at the BUMIGEB laboratory. Field results show that the waters are slightly alkaline (6.97 < pH < 8.1), weakly mineralized and conductive (124 < EC < 543 μS/cm), with temperatures ranging from 24.6˚C to 31.6˚C. In addition, trace metals (TMEs) analyzed from surface and subsurface waters show very high levels, generally deviating from the levels recommended by WHO guidelines for Burkina Faso. Trace metals contamination of water resources in the commune of Méguet is mainly due to Fe (3.78 - 11.12 mg/kg), Hg (0.03 - 0.29 mg/kg), As (0.01- 6.31 mg/kg) and Pb (0.01 - 3.8 mg/kg). This study can serve as a basis for guiding national environmental policies to protect the water resources of the Méguet mine.
文摘BACKGROUND Oncostatin M(OSM)is a pleiotropic cytokine which is implicated in the path-ogenesis of inflammatory bowel disease(IBD).AIM To evaluate the prognostic role of OSM in IBD patients.METHODS Literature search was conducted in electronic databases(Google Scholar,Embase,PubMed,Science Direct,Springer,and Wiley).Studies were selected if they reported prognostic information about OSM in IBD patients.Outcome data were synthesized,and meta-analyses were performed to estimate standardized mean differences(SMDs)in OSM levels between treatment responders and non-res-ponders and to seek overall correlations of OSM with other inflammatory bio-markers.RESULTS Sixteen studies(818 Crohn’s disease and 686 ulcerative colitis patients treated with anti-tumor necrosis factor-based therapies)were included.OSM levels were associated with IBD severity.A meta-analysis found significantly higher OSM levels in non-responders than in responders to therapy[SMD 0.80(0.33,1.27);P=0.001],in non-remitters than in remitters[SMD 0.75(95%CI:0.35 to 1.16);P<0.0001]and in patients with no mucosal healing than in those with mucosal heal-ing[SMD 0.63(0.30,0.95);P<0.0001].Area under receiver operator curve values showed considerable variability between studies but in general higher OSM levels were associated with poor prognosis.OSM had significant correlations with Simple Endoscopic Score of Crohn’s disease[r=0.47(95%CI:0.25 to 0.64);P<0.0001],Mayo Endoscopic Score[r=0.35(95%CI:0.28 to 0.41);P<0.0001],fecal calprotectin[r=0.19(95%CI:0.08 to 0.3);P=0.001],C-reactive protein[r=0.25(95%CI:0.11 to 0.39);P<0.0001],and platelet count[r=0.28(95%CI:0.17 to 0.39);P<0.0001].CONCLUSION OSM is a potential candidate for determining the severity of disease and predicting the outcomes of anti-tumor necrosis factor-based therapies in IBD patients.
基金supported by the Youth Development Project of Air Force Military Medical University,No.21 QNPY072Key Project of Shaanxi Provincial Natural Science Basic Research Program,No.2023-JC-ZD-48(both to FF)。
文摘Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in neuroinflammation in the cerebrum.However,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown.In our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion injury.For in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller cells.We found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion injury.Furthermore,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte rleukin-18.The opposite results we re observed with Homerla ove rexpression.Finally,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion injury.Taken together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.
