【背景】猪圆环病毒2型(porcine circovirus type 2,PCV2)是引发猪群多种临床表现疾病的重要病原,对养猪业造成了重大经济损失。【目的】建立更适合PCV2感染的动物模型,分析一株PCV2d型毒株对C57BL/6小鼠的致病性。【方法】腹腔注射PCV...【背景】猪圆环病毒2型(porcine circovirus type 2,PCV2)是引发猪群多种临床表现疾病的重要病原,对养猪业造成了重大经济损失。【目的】建立更适合PCV2感染的动物模型,分析一株PCV2d型毒株对C57BL/6小鼠的致病性。【方法】腹腔注射PCV2感染C57BL/6小鼠,观察小鼠的临床症状及组织病理变化;qPCR测定组织中的病毒载量;血常规分析外周血中白细胞、红细胞和血小板的变化,流式细胞术分析外周血淋巴细胞的变化;RT-qPCR测定脾脏中IL-10、IL-6、TNF-α和IFN-αmRNA的表达。【结果】PCV2感染导致小鼠精神萎靡、体重下降,所有小鼠脾脏均出现肿大、坏死,部分肝脏色泽变浅、肺脏有出血;组织病理切片显示,脾脏均出现多核巨细胞浸润,感染第14天后含铁血黄素明显增多;脾脏中病毒载量约为(2.19±0.93)×10^(2)copies/mg;PCV2感染诱导小鼠外周血中红细胞、血小板数量显著减少,流式细胞术分析表明,在感染后第3、7、14天,小鼠外周血均出现淋巴细胞数量减少,主要涉及CD_(8)^(+)T细胞和CD_(4)^(+)T细胞。PCV2感染促进了小鼠脾脏中IL-10、IL-6、TNF-αmRNA的表达,而IFN-αmRNA的表达只在感染后第3天和第21天显著降低。【结论】本研究鉴定了一株PCV2d型毒株对C57BL/6小鼠的致病性,为PCV2小鼠模型建立及其致病性研究提供了参考。展开更多
Objective This study aimed to comprehensively investigate the potential protective effects and underlying mechanisms of taurine against dihydrotestosterone(DHT)-induced androgenetic alopecia(AGA)in male C57BL/6 mice,w...Objective This study aimed to comprehensively investigate the potential protective effects and underlying mechanisms of taurine against dihydrotestosterone(DHT)-induced androgenetic alopecia(AGA)in male C57BL/6 mice,with a focus on hair follicle cycle modulation,cellular proliferation/apoptosis,and key related signaling pathways.Methods Six-week-old female C57BL/6 mice were initially used to assess the hair growth-promoting potential of taurine.After acclimatization,they were randomly assigned to three groups(n=8):control(regular drinking water),taurine(drinking water containing 1%taurine),and minoxidil(topical 2%minoxidil,positive control).For the AGA study,male C57BL/6 mice were randomly divided into five groups(n=8):control(physiological saline),DHT(model group,1 mg/d DHT),DHT+low-dose taurine(1 mg/d DHT+2 mg/d taurine),DHT+high-dose taurine(1 mg/d DHT+10 mg/d taurine),and DHT+minoxidil(positive control,1 mg/d DHT+topical 2%minoxidil).One day before treatment initiation,dorsal hair was shaved with scissors,and residual hair was removed using a depilatory cream.DHT and taurine were administered via daily intraperitoneal injection.Hair regrowth was assessed by photographing the depilated area at regular intervals and quantified using a four-point grading system(0-3).Dorsal skin samples were collected on day 14 for histological analysis(H&E staining),immunofluorescence staining(Ki67 for proliferation,TUNEL for apoptosis),ELISA(DHT quantification),RT-qPCR,and Western blot analysis to evaluate the expression of key genes and proteins(androgen receptor(AR),transforming growth factor(TGF)‑β1,TGF‑β2,Dickkopf-1(DKK1)).Results In female mice,taurine supplementation significantly accelerated hair growth,with effects comparable to minoxidil.This was evidenced by an earlier transition from pink(telogen)to black(anagen)skin and increased hair growth scores.Histological analysis showed that taurine increased hair follicle count and dermal thickness.Immunofluorescence confirmed enhanced keratinocyte proliferation in the hair matrix.In the DHTinduced AGA model,DHT significantly extended the telogen phase,inhibited hair growth,increased skin DHT content,and induced hair follicle miniaturization.Taurine treatment,particularly at the high dose,effectively counteracted these effects:it promoted the telogen-to-anagen transition and improved hair growth scores.Histomorphometric analysis showed that taurine significantly restored DHT-induced reductions in dermal thickness,hair follicle count,hair bulb depth,and follicle size.Taurine treatment also reduced apoptosis and promoted the proliferation of hair follicle cells,as demonstrated by Ki67 and TUNEL assays.Crucially,RT-qPCR and Western blot analyses revealed that DHT significantly up-regulated the expression of AR,TGF‑β1,TGF‑β2,and DKK1 at both mRNA and protein levels in dorsal skin.Taurine administration markedly down-regulated the expression of these pathogenic factors,bringing them closer to the levels observed in the control group.Conclusion Taurine demonstrates significant efficacy in alleviating DHT-induced AGA in male C57BL/6 mice.Its protective effects are mediated through multi-faceted mechanisms.(1)Promoting hair follicle cycle progression:it accelerates the transition from telogen to anagen,counteracting DHT-induced prolongation of the telogen phase.(2)Modulating cellular dynamics:it stimulates the proliferation of hair matrix keratinocytes and reduces DHT-induced apoptosis within hair follicle cells.(3)Suppressing androgen-driven pathogenic pathways:it downregulates the expression of critical molecules in the AGA pathway,including AR,the cytokines TGF-β1 and TGF-β2,and the Wnt pathway inhibitor DKK1.Given its favorable safety profile and multi-targeted action,taurine emerges as a promising novel therapeutic candidate or adjunct for treating AGA.Further investigation into its clinical potential and precise molecular mechanisms is warranted.This study provides a robust preclinical foundation for considering taurine supplementation or topical application in hair loss management strategies.展开更多
Experimental mice play a critical role in biomedical research.The phenotype and application of different substrains vary due to genetic differentiation and variation.To ensure validity and reliability of results,it is...Experimental mice play a critical role in biomedical research.The phenotype and application of different substrains vary due to genetic differentiation and variation.To ensure validity and reliability of results,it is imperative to adhere to standardized experiments and controls.This paper objectively reviews the origin,differentiation,and phenotypic and genetic differences between the C57BL/6 and BALB/c mouse substrains.Furthermore,an optimal selection strategy is proposed based on the genetic quality control technology to facilitate the precise application of these two mouse substrains.展开更多
文摘【背景】猪圆环病毒2型(porcine circovirus type 2,PCV2)是引发猪群多种临床表现疾病的重要病原,对养猪业造成了重大经济损失。【目的】建立更适合PCV2感染的动物模型,分析一株PCV2d型毒株对C57BL/6小鼠的致病性。【方法】腹腔注射PCV2感染C57BL/6小鼠,观察小鼠的临床症状及组织病理变化;qPCR测定组织中的病毒载量;血常规分析外周血中白细胞、红细胞和血小板的变化,流式细胞术分析外周血淋巴细胞的变化;RT-qPCR测定脾脏中IL-10、IL-6、TNF-α和IFN-αmRNA的表达。【结果】PCV2感染导致小鼠精神萎靡、体重下降,所有小鼠脾脏均出现肿大、坏死,部分肝脏色泽变浅、肺脏有出血;组织病理切片显示,脾脏均出现多核巨细胞浸润,感染第14天后含铁血黄素明显增多;脾脏中病毒载量约为(2.19±0.93)×10^(2)copies/mg;PCV2感染诱导小鼠外周血中红细胞、血小板数量显著减少,流式细胞术分析表明,在感染后第3、7、14天,小鼠外周血均出现淋巴细胞数量减少,主要涉及CD_(8)^(+)T细胞和CD_(4)^(+)T细胞。PCV2感染促进了小鼠脾脏中IL-10、IL-6、TNF-αmRNA的表达,而IFN-αmRNA的表达只在感染后第3天和第21天显著降低。【结论】本研究鉴定了一株PCV2d型毒株对C57BL/6小鼠的致病性,为PCV2小鼠模型建立及其致病性研究提供了参考。
基金supported by grants from The National Natural Science Foundation of China(31772690)the Natural Science Foundation of Shanxi Province(201701D121106)PhD Research Startup Foundation of Changzhi Medical College(BS202308)。
文摘Objective This study aimed to comprehensively investigate the potential protective effects and underlying mechanisms of taurine against dihydrotestosterone(DHT)-induced androgenetic alopecia(AGA)in male C57BL/6 mice,with a focus on hair follicle cycle modulation,cellular proliferation/apoptosis,and key related signaling pathways.Methods Six-week-old female C57BL/6 mice were initially used to assess the hair growth-promoting potential of taurine.After acclimatization,they were randomly assigned to three groups(n=8):control(regular drinking water),taurine(drinking water containing 1%taurine),and minoxidil(topical 2%minoxidil,positive control).For the AGA study,male C57BL/6 mice were randomly divided into five groups(n=8):control(physiological saline),DHT(model group,1 mg/d DHT),DHT+low-dose taurine(1 mg/d DHT+2 mg/d taurine),DHT+high-dose taurine(1 mg/d DHT+10 mg/d taurine),and DHT+minoxidil(positive control,1 mg/d DHT+topical 2%minoxidil).One day before treatment initiation,dorsal hair was shaved with scissors,and residual hair was removed using a depilatory cream.DHT and taurine were administered via daily intraperitoneal injection.Hair regrowth was assessed by photographing the depilated area at regular intervals and quantified using a four-point grading system(0-3).Dorsal skin samples were collected on day 14 for histological analysis(H&E staining),immunofluorescence staining(Ki67 for proliferation,TUNEL for apoptosis),ELISA(DHT quantification),RT-qPCR,and Western blot analysis to evaluate the expression of key genes and proteins(androgen receptor(AR),transforming growth factor(TGF)‑β1,TGF‑β2,Dickkopf-1(DKK1)).Results In female mice,taurine supplementation significantly accelerated hair growth,with effects comparable to minoxidil.This was evidenced by an earlier transition from pink(telogen)to black(anagen)skin and increased hair growth scores.Histological analysis showed that taurine increased hair follicle count and dermal thickness.Immunofluorescence confirmed enhanced keratinocyte proliferation in the hair matrix.In the DHTinduced AGA model,DHT significantly extended the telogen phase,inhibited hair growth,increased skin DHT content,and induced hair follicle miniaturization.Taurine treatment,particularly at the high dose,effectively counteracted these effects:it promoted the telogen-to-anagen transition and improved hair growth scores.Histomorphometric analysis showed that taurine significantly restored DHT-induced reductions in dermal thickness,hair follicle count,hair bulb depth,and follicle size.Taurine treatment also reduced apoptosis and promoted the proliferation of hair follicle cells,as demonstrated by Ki67 and TUNEL assays.Crucially,RT-qPCR and Western blot analyses revealed that DHT significantly up-regulated the expression of AR,TGF‑β1,TGF‑β2,and DKK1 at both mRNA and protein levels in dorsal skin.Taurine administration markedly down-regulated the expression of these pathogenic factors,bringing them closer to the levels observed in the control group.Conclusion Taurine demonstrates significant efficacy in alleviating DHT-induced AGA in male C57BL/6 mice.Its protective effects are mediated through multi-faceted mechanisms.(1)Promoting hair follicle cycle progression:it accelerates the transition from telogen to anagen,counteracting DHT-induced prolongation of the telogen phase.(2)Modulating cellular dynamics:it stimulates the proliferation of hair matrix keratinocytes and reduces DHT-induced apoptosis within hair follicle cells.(3)Suppressing androgen-driven pathogenic pathways:it downregulates the expression of critical molecules in the AGA pathway,including AR,the cytokines TGF-β1 and TGF-β2,and the Wnt pathway inhibitor DKK1.Given its favorable safety profile and multi-targeted action,taurine emerges as a promising novel therapeutic candidate or adjunct for treating AGA.Further investigation into its clinical potential and precise molecular mechanisms is warranted.This study provides a robust preclinical foundation for considering taurine supplementation or topical application in hair loss management strategies.
基金National Key R&D Program of China,Grant/Award Number:2021YFF0703200Key Technology Fund of the National Institutes for Food and Drug Control,Grant/Award Number:GJJS-2022-1-5。
文摘Experimental mice play a critical role in biomedical research.The phenotype and application of different substrains vary due to genetic differentiation and variation.To ensure validity and reliability of results,it is imperative to adhere to standardized experiments and controls.This paper objectively reviews the origin,differentiation,and phenotypic and genetic differences between the C57BL/6 and BALB/c mouse substrains.Furthermore,an optimal selection strategy is proposed based on the genetic quality control technology to facilitate the precise application of these two mouse substrains.
