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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

Positively charged chitosan-dissolving microneedles promote follicular accumulation of finasteride nanocrystals to treat androgenetic alopecia

Jingru Zhao,Hong Xiang,Yurong Liu,Xiaoqing Miao

An imbalance of androgens and changes in the follicular microenvironment are the hallmarks of androgenetic alopecia (AGA), a complex disorder that causes follicular shrinkage and progressive hair loss. Although the main goal of finasteride (FIN) monotherapy is androgen control, it has systemic drawbacks such as psychiatric side effects and sexual dysfunction. FIN nanocrystals (NCs) stabilized by cationic chitosan (CS) were added to dissolving microneedles (MNs) to improve follicle targeting while reducing systemic exposure. When CS was applied to the 167.20 ± 0.01 nm FIN-NCs, which had a zeta potential of −49.70 ± 2.00 mV, the outcome was positively charged CS-FIN-NCs that ranged in size from 200 to 300 nm. This alteration resulted in improved accumulation in hair follicles (2.65-fold fluorescence enhancement) and an enlarged passive diffusion area (1.48-fold increase). CS-FIN-NCs markedly enhanced folliculogenesis and hair regrowth in a mouse model of AGA. This formulation mechanistically enhances the migration of human umbilical vein endothelial cells by inhibiting TGF-β1, upregulating β-catenin, and promoting angiogenesis. These results demonstrate that CS-FIN-NCs delivered transcutaneously via MNs produce dual therapeutic benefits for the treatment of localized AGA by modulating follicular niches and acting pharmacologically.

CAS / MDL: 98319-26-7
研究领域: 皮肤病学 · 纳米医学 · 药剂学 · 生物医学工程 · 毛发生物学 · 药物递送
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

Fabrication of carboxymethyl cellulose/hyaluronic acid/polyvinylpyrrolidone composite pastes incorporation of minoxidil-loaded ferulic acid-derived lignin nanoparticles and valproic acid for treatment of androgenetic alopecia

Peixin Li,Yanfang Sun,Lei Nie,Amin Shavandi,Khaydar E. Yunusov,Yinjian Hua,Guohua Jiang

Androgenetic alopecia (AGA) is a transracial and cross-gender disease worldwide with a higher prevalence among young individuals. Traditional oral or subcutaneous injections are often used to treat AGA, however, they may cause severe side-effects and therefore effective treatments for AGA are currently lacking. In this work, to treat AGA, we developed a composite paste system based on minoxidil (MXD)-loaded nanoparticles and valproic acid (VPA) with the assistance of roller-microneedles (roller-MNs). The matrix of composite paste systems is carboxymethyl cellulose (CMC), hyaluronic acid (HA) and polyvinylpyrrolidone (PVP). The roller-MNs can create microchannels in the skin to enhance drug transdermal efficiency. With the combined effects of the stimulation hair follicle (HF) regrowth by upregulating Wnt/beta-catenin of VPA and the mechanical microchannels induced by roller-MNs, the as-prepared composite paste systems successfully boost perifollicular vascularization, and activate hair follicle stem cells, thereby inducing notably faster hair regeneration at a lower administration frequency on AGA mouse model compared with minoxidil. This approach offers several benefits, including the avoidance of efficacy loss due to the liver's first-pass effect associated with oral drug, reduction in the risk of infection from subcutaneous injection, and significant decrease in the side effects of lower-dose MXD.

研究领域: 药学 · 生物医学工程 · 皮肤科 · 纳米技术 · 药物递送系统
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FREE RADICAL BIOLOGY AND MEDICINE · 2025 · IF 8.2

Ergothioneine regulates the paracrine of dermal papilla cells through SIRT1/Nrf2 pathway to antagonize oxidative stress and natural hair follicle aging

Hailin Wang,Yueying Wang,Xin Li,Jiayang Ma,Zhiqi Hu,Qian Qu,Yong Miao

Hair graying and loss are significant indicators of aging, and oxidative stress plays an essential role in this progression. Ergothioneine (EGT), potent antioxidant from edible fungi and certain prokaryotes, regulates the antioxidant defense system. However, its anti-aging effects on hair follicles (HFs) are remain obscure. We used dermal papilla cells (DPCs) co-culture system, HFs organ culture system, aged mice and H 2 O 2 -induced gray hair mice to explore the antioxidative functions and mechanisms of EGT on HFs. Research demonstrated that EGT mitigated H 2 O 2 -induced DPCs damage, reduced the secretion of inflammatory factors (IL-6, IL-1β, and TNF-α) and enhanced the production of pigmentation promoting factors (SCF and SDF1) through the SIRT1/Nrf2 pathway in DPCs. In vitro experiments of co-culture system indicated that EGT-treated DPCs remarkably alleviated oxidative damages and promoted cell proliferation in A-375 and HaCaT. Furthermore, it increased tyrosinase activity, melanin content and the expression of key melanin synthesis genes in A-375. Meanwhile, it promoted the expression of K19 and K14 in HaCaT. In vivo experiments revealed that EGT exhibited excellent effects on reducing pigmentation disfunction and hair loss in aged mice and H 2 O 2 -induced gray hair mice. In the HFs organ culture, the EGT promoted hair growth and pigmentation via SIRT1/Nrf2 partly. Our research indicated that EGT had potent antioxidant and anti-aging functions for HFs. This not only provided new applications for EGT but also opened up new therapeutic avenues for hair aging.

CAS / MDL: 616-91-1
研究领域: 细胞生物学 · 医学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CELL · 2024 · IF 45.5

Intermittent fasting triggers interorgan communication to suppress hair follicle regeneration

Han Chen,Chao Liu,Shiyao Cui,Yingqian Xia,Ke Zhang,Hanxiao Cheng,Jingyu Peng,Xiaoling Yu,Luyang Li,Hualin Yu,Jufang Zhang,Ju-Sheng Zheng,Bing Zhang

Intermittent fasting has gained global popularity for its potential health benefits, although its impact on somatic stem cells and tissue biology remains elusive. Here, we report that commonly used intermittent fasting regimens inhibit hair follicle regeneration by selectively inducing apoptosis in activated hair follicle stem cells (HFSCs). This effect is independent of calorie reduction, circadian rhythm alterations, or the mTORC1 cellular nutrient-sensing mechanism. Instead, fasting activates crosstalk between adrenal glands and dermal adipocytes in the skin, triggering the rapid release of free fatty acids into the niche, which in turn disrupts the normal metabolism of HFSCs and elevates their cellular reactive oxygen species levels, causing oxidative damage and apoptosis. A randomized clinical trial (NCT05800730) indicates that intermittent fasting inhibits human hair growth. Our study uncovers an inhibitory effect of intermittent fasting on tissue regeneration and identifies interorgan communication that eliminates activated HFSCs and halts tissue regeneration during periods of unstable nutrient supply.

CAS / MDL: 7722-84-1
研究领域: 干细胞生物学 · 组织再生 · 营养科学 · 细胞代谢 · 器官间通讯
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Animal Bioscience · 2025 ·Vol. 38 ·期 7 ·1356 · IF 2.5

Spatial variation and associated genes of total hair follicle density in goats

Jipan Zhang,Ziyi Chen,Siyuan Zhang,Guoqiu Li,Xingqiang Fang,Yongju Zhao

Objective Improving total hair follicle density (THFD) can directly result in increased fiber yield in cashmere goats. However, its phenotypic and genetic characteristics remain poorly understood. This study aimed to investigate the spatial distribution and associated genes of THFD in goats. Methods A large-scale histological image analysis was conducted on 791 skin samples to characterize the spatial distribution of THFD at the local-site (n = 7), body-side (32 sites, n = 224), and whole-body (14 sites, n = 560) levels. Additionally, transcriptome sequencing was performed on 18 skin samples to identify genes associated with THFD. Results The unique structure of the hair follicle group leads to an uneven distribution of hair follicles, resulting variation in THFD at the local-site. THFD exhibited a gradient pattern throughout the body, characterized by elevated values in the scapular region and decreased values in the abdominal region. THFD showed uneven distribution across the whole-body, with a consistent pattern observed in Inner Mongolia cashmere goats, Dazu black goats and their F1 hybrids (DBG♂ × IMCG♀). Through the integration of differential gene expression analysis, trend analysis, weighted correlation network analysis, Venn analysis, and literature review, four core genes ( GJA1 , DSP , CDH3 , and PER1 ) were identified. These genes showed high and specific expression in skin tissue and demonstrated a significant response to changes in THFD. Conclusion This study thoroughly characterized the spatial variation of THFD at the local-site, body-side, and whole-body levels in order to gain a better understanding of genetic characterization, associated genes and spatial variation. Additionally, we have identified four genes that are associated with THFD. These findings provide an important reference for the subsequent development and utilization of THFD genes in cashmere goats.

研究领域: 生物学 · 遗传学 · 畜牧学
✓ 已验证 DOI PubMed 高影响因子
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS · 2025 · IF 2.2

MafB regulates hair follicle stem cell activation and hair regeneration through NFATc1 signaling pathway

Qiuni Gao,Shangyu Zeng,Yupeng Chen,Ying Bao,Haiyan Cui

Alopecia, a prevalent condition driven by abnormal hair follicle cycling and stem cell (HFSCs) dysregulation, underscores the need to elucidate molecular mechanisms governing HFSCs activation. While the nuclear factor of activated T cells c1 (NFATc1) is known to maintain HFSCs quiescence by suppressing cyclin-dependent kinase 4 (CDK4), the upstream regulators of this pathway remain unclear. Here, we identify MafB as a key modulator of HFSCs dynamics through NFATc1 signaling. Transcriptome sequencing of murine skin revealed elevated MafB expression during active hair regeneration. Adenoviral overexpression of MafB in depilated mice accelerated hair regrowth, increased hair follicle diameter, and enhanced HFSCs proliferation. Conversely, MafB knockdown suppressed regeneration and reduced the prolifiration ability of HFSCs. In vitro , MafB overexpression promoted HFSCs proliferation, migration, and differentiation, while mechanistic studies demonstrated MafB inhibits NFATc1 transcription, thereby relieving CDK4 repression and activating Wnt/β-catenin signaling. Rescue experiments confirmed NFATc1 restoration abrogated MafB-induced HFSCs activation. These findings establish MafB as a critical regulator of hair follicle cycling through the NFATc1/CDK4 axis, offering novel therapeutic avenues for alopecia.

研究领域: 分子生物学 · 发育生物学 · 皮肤科学
✓ 已验证 DOI PubMed 高影响因子
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Pharmaceutics · 2024 · IF 4.9

Engineered Exosomes Biopotentiated Hydrogel Promote Hair Follicle Growth via Reprogramming the Perifollicular Microenvironment

Hairui Zhang,Jiali Yao,Qianyang Jiang,Yurou Shi,Weihong Ge,Xiaoling Xu

Androgenetic alopecia (AGA) is a highly prevalent condition in contemporary society. The conventional treatment of minoxidil tincture is hindered by issues such as skin irritation caused by ethanol, non-specific accumulation in hair follicles, and short retention due to its liquid form. Herein, we have developed a novel minoxidil-incorporated engineered exosomes biopotentiated hydrogel (Gel@MNs) that has the capability to modulate the perifollicular microenvironment for the treatment of AGA. Leveraging the exceptional skin penetration abilities of flexible liposomes and the targeting properties of exosomes, the encapsulated minoxidil can be effectively delivered to the hair follicles. In comparison to free minoxidil, Gel@MNs demonstrated accelerated hair regeneration in an AGA mouse model without causing significant skin irritation. This was evidenced by an increase in both the number and size of hair follicles within the dermal layer, enhanced capillary formation surrounding the follicles, and the regulation of the transition of hair follicle cells from the telogen phase to the anagen growth phase. Therefore, this safe and microenvironment-modifying hybrid exosome-embedded hydrogel shows promising potential for clinical treatment of AGA.

研究领域: 皮肤病学 · 药学 · 生物技术 · 组织工程
✓ 已验证 DOI PubMed 高影响因子
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Cellular and Molecular Bioengineering · 2025 · IF 5

Acteoside-Loaded Self-Healing Hydrogel Enhances Skin Wound Healing through Modulation of Hair Follicle Stem Cells

Liu Junyu,Wang Hua,Zhang Caihua

Background Skin wound healing is a complex biological process involving cellular, molecular, and physiological events. Traditional treatments often fail to provide optimal outcomes, particularly for chronic wounds. Objectives This study aimed to develop a self-healing hydrogel loaded with Acteoside, a bioactive compound with antioxidant and anti-inflammatory properties, to enhance skin wound healing. Methods Using transcriptomic analysis, Rab31 was identified as a key target of Acteoside in regulating hair follicle stem cells (HFSCs). In vitro assays demonstrated that Acteoside promotes HFSC proliferation, migration, and differentiation by upregulating Rab31 expression. The self-healing hydrogel was prepared using quaternized chitosan derivatives, which exhibited excellent mechanical properties, antibacterial, and antioxidant activities. Results In vivo studies in a mouse model showed that Acteoside-loaded hydrogel significantly accelerated wound healing, promoting skin regeneration and improving wound closure. Conclusions This research highlights the potential of Acteoside-loaded self-healing hydrogels as an innovative therapeutic strategy for enhancing skin wound healing. By modulating HFSC activity, this hydrogel offers a promising solution for improving healing outcomes in challenging wound environments. Graphical Schematic representation of an injectable self-healing hydrogel loaded with the phenylethanoid compound acteoside for regulating the proliferation and differentiation of HFSCs to mediate the healing of skin wounds.

研究领域: 生物材料学 · 分子生物学 · 皮肤修复
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Journal of Materials Chemistry B · 2025 · IF 5.7

ROS-Scavenging CuxO Nanozyme-Functionalized Microneedle Patch for Androgenetic Alopecia Treatment

Yudie Lv,Yang Yang,Jiaxin Niu,Xu Sun,Han Zhang,Xiangdong Kong

Oxidative stress is closely linked to androgenetic alopecia (AGA). However, research on antioxidants specifically targeting hair follicle tissue has been limited. The utilization of nanomaterials that possess superior reactive oxygen species (ROS)-scavenging capabilities and biocompatibility is a promising approach for the treatment of AGA. The microneedle-mediated transdermal delivery system can overcome the limitations of the stratum corneum and effectively deliver functional nanomaterials to the vicinity of hair follicles. In this study, we report a degradable microneedle patch loaded with ROS-scavenging CuxO nanozyme (CuxO-MNs) for targeted treatment of AGA. Tiny CuxO nanozymes were synthesized using a robust and eco-friendly method, demonstrating effective ROS-scavenging ability at both in vitro and cellular levels. With the penetration and dissolution of sodium hyaluronate microneedles, CuxO can be rapidly released and effectively reach the area around the hair follicle, enabling targeted removal of ROS. In the AGA model, CuxO-MNs effectively alleviate oxidative stress, restore the hair follicle microenvironment, and stimulate the transition of hair follicles from the telogen to the anagen. These combined effects significantly enhance hair regeneration and exhibit therapeutic efficacy comparable to the clinical drug minoxidil, suggesting the safety and translational potential of this strategy for AGA treatment.

研究领域: 生物医学工程 · 皮肤病学 · 纳米技术 · 药剂学
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AAPS PHARMSCITECH · 2024 ·Vol. 25 ·期 6 ·1-14 · IF 3.4

Effects and Action Mode of Oleic Acid and Azone on Release and Penetration Process of Levothyroxine Sodium Patches

Li Xing,Liang Kaili,Dong Yingying,Li Shen,Gao Zhengnan,Wang Qing

In recent years, there has been a significant increase in the prevalence of thyroid diseases, particularly hypothyroidism. In this study, we investigated the impact and mechanisms of Chemical permeation enhancement(CPE) on transdermal permeation of levothyroxine sodium (L-T4) patches.We found that the combination of oleic acid (OA) and Azone (NZ) yielded the best transdermal permeation effect for L-T4.Subsequently, we also investigated the relevant propermeability mechanism.The results demonstrate that the combined application of OA and NZ significantly enhances the transdermal permeation of L-T4 compared to individual applications,it is attributed to two mechanisms: firstly, OA improves drug release by increasing the flowability of the pressure-sensitive adhesive (PSA) matrix; secondly, both OA and NZ act on the stratum corneum, especially facilitating L-T4 permeation through the hair follicle pathway. No skin irritation or cytotoxicity is observed with these final patches, which exhibit a remarkable therapeutic effect on hypothyroidism. this study contributes to the development of transdermal formulations of L-T4. Graphical Abstract

CAS / MDL: 112-80-1
研究领域: 药剂学 · 皮肤科学 · 内分泌学
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LIFE SCIENCES · 2020 · IF 3.647

Pantothenic acid promotes dermal papilla cell proliferation in hair follicles of American minks via inhibitor of DNA Binding 3/Notch signaling pathway

Zhuo Wang,Weixiao Nan,Huazhe Si,Shiyong Wang,Haihua Zhang,Guangyu Li

Aims Pantothenic acid (PA) has been applied to treat alopecia, but the underlying mechanism is still unclear. Our study aims to explore the underlying mechanism of PA in regulating hair follicle (HF) growth. Main methods Mink HFs and dermal papilla (DP) cells were isolated and cultured in vitro . HFs and DP cells were treated with 0, 10, 20, 40 μg/ml PA. The effect of PA on HF growth, DP cell proliferation, cell cycle distribution, cell migration, and insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) expressions in DP cells was measured. Moreover, the effect of PA on inhibitor of DNA binding 3 (ID3)/Notch signaling pathway was analyzed. Subsequently, ID3 was silenced to validate whether ID3/Notch signaling pathway was involved in regulating DP cell proliferation by PA. Key findings Both 20 μg/ml and 40 μg/ml PA promoted HF growth, G1/S transition of DP cells and IGF-1 and VEGF expressions in DP cells, while only 20 μg/ml PA promoted cell viability and the migration of DP cells. Thus 20 μg/ml PA was chosen for the following experiments. PA treatment was found to up-regulate ID3 expression but down-regulate Notch receptor 1 (Notch1) and Notch signaling targets expressions. Furthermore, ID3 knockdown reversed PA-induced cell proliferation and inhibition of Notch1 and Notch signaling targets expressions, indicating that PA-induced DP cell proliferation and inhibition of Notch signaling were mediated via up-regulation of ID3. Significance This study provides an underlying mechanism related to the effect of PA on stimulating DP cell proliferation.

CAS / MDL: 137-08-6
研究领域: 皮肤科 · 分子生物学 · 细胞生物学
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Nature Communications · 2022 ·Vol. 13 ·期 1 ·1-21 · IF 17.694

Bead-jet printing enabled sparse mesenchymal stem cell patterning augments skeletal muscle and hair follicle regeneration

Cao Yuanxiong,Tan Jiayi,Zhao Haoran,Deng Ting,Hu Yunxia,Zeng Junhong,Li Jiawei,Cheng Yifan,Tang Jiyuan,Hu Zhiwei,Hu Keer,Xu Bing,Wang Zitian,Wu Yaojiong,Lobie Peter E.,Ma Shaohua

Transplantation of mesenchymal stem cells (MSCs) holds promise to repair severe traumatic injuries. However, current transplantation practices limit the potential of this technique, either by losing the viable MSCs or reducing the performance of resident MSCs. Herein, we design a “bead-jet” printer, specialized for high-throughput intra-operative formulation and printing of MSCs-laden Matrigel beads. We show that high-density encapsulation of MSCs in Matrigel beads is able to augment MSC function, increasing MSC proliferation, migration, and extracellular vesicle production, compared with low-density bead or high-density bulk encapsulation of the equivalent number of MSCs. We find that the high-density MSCs-laden beads in sparse patterns demonstrate significantly improved therapeutic performance, by regenerating skeletal muscles approaching native-like cell density with reduced fibrosis, and regenerating skin with hair follicle growth and increased dermis thickness. MSC proliferation within 1-week post-transplantation and differentiation at 3 − 4 weeks post-transplantation are suggested to contribute therapy augmentation. We expect this “bead-jet” printing system to strengthen the potential of MSC transplantation.

研究领域: 生物医学工程 · 再生医学 · 干细胞生物学
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