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
bHLH transcription factors,widely exist in various plants,and are vital for the growth and development of these plants.Among them,many have been implicated in anthocyanin biosynthesis across various plants.In the pres...bHLH transcription factors,widely exist in various plants,and are vital for the growth and development of these plants.Among them,many have been implicated in anthocyanin biosynthesis across various plants.In the present study,a PdbHLH57 gene,belonging to the bHLH IIIf group,was characterized,which was isolated and cloned from the colored-leaf poplar‘Zhongshancaiyun’(ZSCY).The cDNA sequence of PdbHLH57 was 1887 base pairs,and the protein encoded by PdbHLH57 had 628 amino acids,the isoelectric point and molecular weight of which were 6.26 and 69.75 kDa,respectively.Through bioinformatics analysis,PdbHLH57 has been classified into the IIIf bHLH subgroup,with many members of this subgroup known to participate in anthocyanin biosynthesis.The subcellular localization analysis conducted in the leaf protoplasts of‘ZSCY’revealed that the PdbHLH57 protein is specifically localized in the nucleus.The transcription activation analysis was also conducted,and the results showed that the PdbHLH57 protein had self-transcription activation.To better explore the functions of the PdbHLH57 protein,two parts of this protein(PdbHLH57-1,PdbHLH57-2)were split to detect their transcriptional activation activity.The results indicated that PdbHLH57-1(1-433aa)had self-transcription activation,and PdbHLH57-2(433-628aa)had no transcription activation.The expression of PdbHLH57 peaked in June during different developmental stages in‘ZSCY’,and it was most highly expressed in the phloem among various tissues.These findings offer a basis for understanding the role of PdbHLH57 in colored-leaf poplar.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
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supported by the Natural Science Foundation of Jiangsu Province,China(BK20242007)the Natural Science Foundation of China(32271916)the Jiangsu Agricultural Science and Technology Innovation Fund[CX(24)3048].
文摘bHLH transcription factors,widely exist in various plants,and are vital for the growth and development of these plants.Among them,many have been implicated in anthocyanin biosynthesis across various plants.In the present study,a PdbHLH57 gene,belonging to the bHLH IIIf group,was characterized,which was isolated and cloned from the colored-leaf poplar‘Zhongshancaiyun’(ZSCY).The cDNA sequence of PdbHLH57 was 1887 base pairs,and the protein encoded by PdbHLH57 had 628 amino acids,the isoelectric point and molecular weight of which were 6.26 and 69.75 kDa,respectively.Through bioinformatics analysis,PdbHLH57 has been classified into the IIIf bHLH subgroup,with many members of this subgroup known to participate in anthocyanin biosynthesis.The subcellular localization analysis conducted in the leaf protoplasts of‘ZSCY’revealed that the PdbHLH57 protein is specifically localized in the nucleus.The transcription activation analysis was also conducted,and the results showed that the PdbHLH57 protein had self-transcription activation.To better explore the functions of the PdbHLH57 protein,two parts of this protein(PdbHLH57-1,PdbHLH57-2)were split to detect their transcriptional activation activity.The results indicated that PdbHLH57-1(1-433aa)had self-transcription activation,and PdbHLH57-2(433-628aa)had no transcription activation.The expression of PdbHLH57 peaked in June during different developmental stages in‘ZSCY’,and it was most highly expressed in the phloem among various tissues.These findings offer a basis for understanding the role of PdbHLH57 in colored-leaf poplar.
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.
