Hair graying is a common phenomenon associated with aging, and the excessive differentiation of melanocyte stem cells in hair follicles has gradually gained attention for its role in the occurrence and development of hair graying. The cyclical nature of hair follicles provides an excellent model for studying stem cells. With the continuous development of mouse models and cell transplantation technologies, the understanding of hair graying and aging has been steadily deepening, though many questions remain unanswered. This review focuses on the origins and biological characteristics of melanocyte stem cells and their related signaling pathways. It further explains the relationship between melanocyte stem cells and hair graying, as well as the role of some drugs in hair repigmentation.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Hair graying is a common phenomenon associated with aging, and the excessive differentiation of melanocyte stem cells in hair follicles has gradually gained attention for its role in the occurrence and development of hair graying. The cyclical nature of hair follicles provides an excellent model for studying stem cells. With the continuous development of mouse models and cell transplantation technologies, the understanding of hair graying and aging has been steadily deepening, though many questions remain unanswered. This review focuses on the origins and biological characteristics of melanocyte stem cells and their related signaling pathways. It further explains the relationship between melanocyte stem cells and hair graying, as well as the role of some drugs in hair repigmentation.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Humans ; Pedigree ; Rosacea ; pathology

Objective To analyze the expression characteristics of annexin A2 in dermal papilla cells (DPCs) with aggregative behavior.Methods Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot were performed to measure the mRNA and protein expressions of annexin A2 respectively in DPCs with or without aggregative behavior.Results The mRNA expression level of annexin A2 was significantly higher in DPCs with aggregative behavior than in those without aggregative behavior (0.50 ± 0.15 vs.0.35 ± 0.19, t =8.26, P ＜ 0.05).Western blot showed that annexin A2 had two isoforms, including one isoform with a relative molecular mass of 40 000 and the other one with a relative molecular mass of 36 000.The annexin A2 isoform with a relative molecular mass of 40 000 was highly expressed in both DPCs with aggregative behavior and those without aggregative behavior, while the other isoform was only expressed in DPCs with aggregative behavior.Conclusion Annexin A2 may be closely related to the aggregative growth of DPCs.

Adult ; Female ; Humans ; Keratin-1 ; genetics ; Keratin-9 ; genetics ; Keratoderma, Palmoplantar ; genetics ; Male ; Middle Aged ; Pedigree

Objective To study the expression ot secreted proteins in aggregated dermal papilla cells (DPCs).Methods DPCs were isolated from human scalp tissue and subjected to primary culture and subculture.Aggregated and non-aggregated DPCs served as the subject of this study.Secreted proteins were prepared from these cells and subjected to two-dimensional polyacrylamide gel electrophoresis.Differentially expressed proteins were screened by the PDQuest image analysis software.Protein spots were digested and identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry,and finally analyzed using the National Center for Biotechnology Information (NCBI) non-redundant (Nr) protein database.Results Two-dimensional electrophoresis maps with good repeatability and high resolution were established.Image analysis of 2-D gels revealed that the average number of detected protein spots was 1 134 ± 52 and 1 078 ± 36 in aggregated and nonaggregated DPCs respectively,and the majority of these protein spots were matched between aggregated and nonaggregated DPCs.Twenty-eight protein spots showed more than 5-fold difference between the two groups of cells,and 10 proteins were preliminarily identified as differentially expressed proteins by peptide-mass fingerprinting.Of these differentially expressed proteins,8 proteins including Rhogdi 1,filamin A,cystatin C,fibronectin,cyclophilin A,procollagen C proteinase enhancer 1,tissue inhibitor of metalloproteinase and tissue inhibitor of metalloproteinase-2 were up-regulated,and 2 proteins including neuropolypeptide h3 and matrix metalloproteinase-3/tissue inhibitor of metalloproteinase-1 complex were down-regulated in aggregated DPCs compared with non-aggregated DPCs.Conclusions Differentially expressed proteins between aggregated and non-aggregated DPCs are mainly implicated in cell signaling pathway,cellular proliferation and differentiation,extracellular matrix synthesis and degradation,and so on.

Objective To detect the expression and function of cysteinyl leukotriene receptors (CysLTRs)in keratinocytes.Methods Human keratinocytes were isolated from the tissue of foreskin by digestion with dispase Ⅱ and trypsin,and subjected to primary culture.By using confocal laser scanning microscopy and reverse transcriptase PCR,the localization and expression of CysLTRs were studied in kemtinocytes.respectively.Some primarily cultured keratinocytes were pretreated with leukotriene D4 (30 nmoi/L),MK571(300 nmol/L),and BAYu9773 for 5 minutes followed by the detection of intmcellular calcium level using the Ca2+ indicator dye Fura-2/AM as well as cell proliferation bv MTT assay.Results The expressions of CysLTR1 and CysLTR2 were observed in cultured keratinocytes,and they were mainly located on cell membrane,partly in cytoplasm and nuclei.Compared with non.stimulated cells,a significant increase Was noted in the expression of CysLTRs,especially in the nuclei of keratinocytes stimulated by LTD4(P＜0.05),together with an elevation in intracellular calcium level(42.27±3.00 mmol/L,P＜0.01)and acceleration in cell proliferation (P＜0.01).However,both MK571 and BAYu9773 could completely block the effect of LTD4 on intmcellular calcium level and cell proliferation.and there was no significant difference in the blocking effect between MK571 and BAYu9773.Conclusions Functional CysLTRs are expressed in human keratinocytes.and they carl increase the intracellular calcium level in,and cell proliferation of,keratinocytes.