T‐helper (Th) 17 and the more recently identified Th22 cells are of great importance in host defense against pathogens, but can also be responsible for chronic inflammatory disorders. However, the roles of the two cell subsets in syphilis remain elusive. In this study, we show that the frequencies of Th17 and Th22 cells are significantly increased in the peripheral blood of patients with secondary syphilis (SS). A significant positive correlation is observed between Th17 and Th22 cells, whereas a negative correlation exists between Th17 and Th1 cells. Moreover, the frequency of Th17 cells has a significant positive correlation with the plasma interleukin 6 (IL‐6) or IL‐1β levels, and the frequency of Th22 cells is positively correlated with the IL‐6 or IL‐23 levels. Finally, the elevated frequencies of Th17 and Th22 cells are positively associated with plasma C‐reactive protein levels. Our results suggest that Th17 and Th22 cells may be implicated in the pathogenesis of the SS.
Human melanocyte stem cells (MSCs) or melanoblasts are not well-investigated owing to the devoid of suitable culture system. Establishing cell lines of MSCs and/or their progenies from human hair follicles will provide a better opportunity to satisfy clinical needs and to enable a deeper understanding of hair-related diseases. In the present study, we cultured melanocytes derived from human fetal hair follicles, perform immunocytochemistry and Fontana Masson staining on them, and employed atomic force microscopy (AFM) and scanning electron microscopy to observe their subtle morphologies. The results show that the cultured melanocytes have a bipolar or tripolar appearance, which obviously differ from cultured epidermal melanocytes. Compared to cells derived from adult human hair follicles, these cells display a high proliferative capability and exhibit a clonal growth behavior. At the second passage, all these cells were positive for immunocytochemical staining with the NKI/beteb monoclonal antibody and Fontana Masson staining. Under AFM, the cells exhibited rounded, oval, triangular, or quadrangular perikarya, from which two or three dendrites arose. The dendritic arbor was not homogeneous but appeared as spindle-shaped dendritic swellings, knob-like processes, without any filopodia arising from the dendrites or the cell body. Without using a feeder layer, we successfully obtained the clonal growth of melanocytes from human fetal HFs, suggesting that the medium was suitable for the growth of MSCs and their progenies.
Objectives To evaluate the safety, tolerability, immunogenicity, and induced expression of skin biomarkers of AK111 injection after multiple administrations in subjects with moderate-to-severe plaque psoriasis. Methods This study is a randomized, double-blinded, placebo-parallel-controlled study using a dose escalation mode of multiple doses. A total of 48 subjects were sequentially randomized to receive each AK111 dose regimen (75 mg, 150 mg, 300 mg, 450 mg) or the corresponding placebo. All subjects were treated with the study drug at weeks 0, 1, 4, and 8 and were unblinded at week 12, with the placebo group ending and the AK111 group being followed up to 20 weeks. Results At week 12, compared with placebo, the percentage of subjects achieving Psoriasis Area and Severity Index 75 (PASI75) and static Physician Global Assessment (sPGA) 0/1 in the AK111 75 mg–450 mg dose groups was significantly increased, and higher PASI90 was achieved in the 150 mg, 300 mg, and 450 mg dose groups than in the 75 mg group. All efficacy indicators were maintained at week 20. The incidence of treatment-emergent anti-drug antibodies (ADAs) was 0% (0/48). Neutralizing antibodies (NAbs) were not detected in any subject. The proportion of subjects who reported any treatment-emergent adverse event (TEAE) was 75.0% in the AK111 group, similar to the 66.7% in the placebo group. The most commonly reported adverse events were hyperglycemia, elevated blood pressure, and hypokalemia. The AK111 pharmacokinetics showed approximate dose proportionality with regard to the maximum observed concentration ( C max ) and area under the curve from 0 to the time of the last quantifiable concentration (AUC 0– t ) following subcutaneous injection doses of 150–450 mg. Conclusions After moderate-to-severe plaque psoriasis subjects received multiple subcutaneous AK111 injections of 150–450 mg, AK111 exposure increased in a roughly dose-proportional relationship. AK111 was safe and tolerable. In subjects with moderate-to-severe plaque psoriasis, AK111 demonstrated encouraging preliminary efficacy, which was sustained for a relatively long time after the last dose administration. Clinical trial registration The clinical trial identification number is NCT05504317.
Objectives To evaluate the safety, tolerability, immunogenicity, pharmacokinetics (PK), pharmacodynamics (PD), and the expression of skin biomarkers of AK111 injection after multiple administration in subjects with moderate to severe plaque psoriasis, and to evaluate the preliminary clinical efficacy in the trial. Methods This study is a randomized, double-blind, placebo-parallel controlled study using a dose escalation mode of multiple doses. 48 subjects were sequentially randomized to receive each of AK111 dose regimens (75mg, 150mg, 300mg, 450mg) or corresponding placebo. All subjects were treated with the study drug at week 0/1/4/8 and were unblinded at week 12 with the placebo group being ended, and AK111 group being followed up to 20 weeks. Results A total of 48 subjects were randomized. At week 12, compared with placebo, the percentage of subjects achieving PASI75 and sPGA0/1 in AK111 75mg, 150mg, 300mg, and 450mg dose groups was significantly increased, and higher PASI90 was achieved in 150mg, 300mg, and 450mg dose groups than in 75mg group. All efficacy indicators were maintained at week 20. The incidence of treatment-emergent Anti-Drug Antibody (ADA) was 0%(0/48). Neutralizing antibodies (Nabs) were not detected in any subject. The proportion of subjects with any reported treatment-emergent adverse event (TEAE) was 75.0% in the AK111 group, similar to 66.7% in the placebo group, and there was no obvious dose relationship. The most commonly reported adverse events were hyperglycemia, elevated blood pressure and hypokalemia. Additionally, the AK111 PK showed approximate dose proportionalitywith regard to the PK parameters of the Cmax and AUC0-tfollowing subcutaneous injection doses of 150mg,300mg and 450 mg. Conclusion After moderate to severe plaque psoriasis subjects received multiple subcutaneous AK111 injections,the dose range of 150mg-450mg, AK111 exposure increased in an approximate dose-proportional relationship. AK111 was demonstrated to be safe and tolerable. In subjects with moderate to severe plaque psoriasis, AK111 demonstrated encouraging preliminary efficacy which was sustained in a relatively long period after the last dose administration. Clinical trial registration Clinical trial identification number is NCT05504317 and was registered in August 2022
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.