Cell Communication and Signaling
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2024
·Vol. 22
·期 1
·1-16
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IF 8.2
Zhai Wenhui,Tian Hairui,Liang Xuemei,Wu Yunqiang,Wen Jian,Liu Zhipeng,Zhao Xiaodong,Tao Li,Zou Kang
Background Androgens are essential hormones for testicular development and the maintenance of male fertility. Environmental factors, stress, aging, and psychological conditions can disrupt androgen production, impacting the androgen signaling pathway and consequently spermatogenesis. Within the testes, testosterone is produced by Leydig cells and acts on Sertoli cells by activating the androgen receptor (AR), which then translocates to the nucleus to function as a transcription factor. Despite clinical correlations between low testosterone levels and diminished sperm quality, the precise mechanism remains unclear. Methods This study explores the hypothesis that reduced androgen levels impair Sertoli cell function by disrupting AR transcriptional regulation. Using an androgen blockade model with enzalutamide, we investigated the impact of low androgen levels on AR target genes in Sertoli cells through ChIP-seq and RNA-seq assays. Results Our results reveal that androgen blockage increases AR enrichment on the promoter region of Wee1 , promoting Wee1 expression, while decreasing binding to the promoter region of Lfng , inhibiting its expression. Increased WEE1 protein inhibits Sertoli cell proliferation, whereas reduced LFNG affects Notch modification, leading to decreased production of glial cell line-derived neurotrophic factor (GDNF), a key growth factor for spermatogonial stem cell self-renewal. Conclusions These findings provide new insights into the molecular mechanisms by which low androgen levels interfere with Sertoli cell functions, offering novel perspectives for the clinical treatment of male reproductive disorders.
研究领域:
生殖生物学
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内分泌学
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DOI
PubMed
高影响因子
MOLECULAR BIOLOGY REPORTS
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2022
·Vol. 49
·期 6
·4607-4617
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IF 2.742
Zhang Yimin,Chen Jingqin,Fang Wenxuan,Liang Kaoyun,Li Xiaoning,Zhang Fan,Pang Yuzhou,Fang Gang,Wang Xueni
Purpose Kaempferol is a natural flavonoid that has been reported to be active against many cancers, including prostate cancer, breast cancer and colon cancer. In our previous study, we found kaempferol could act as a selective androgen receptor modulator, thereby suppress development of benign prostatic hyperplasia. This finding inspired us to further explore the effect and the mechanism of action of kaempferol on prostate cancer. Methods Plate clone formation assay was performed to detect the effect of kaempferol on cell proliferation. Flow cytometry was used to detect the impact of kaempferol on cell apoptosis and cell cycle distribution. qPCR, immunofluorescence staining, and enzyme-linked immunosorbent assay were used to detect the expression of gene and protein of Ki67 which is a biomarker of cell proliferation. Results In the present study, we found kaempferol could dramatically suppress androgen-dependent and androgen-independent prostate cancer cells proliferation and induce their apoptosis. Furthermore, we found that kaempferol induced cell cycle to be arrested at G1 phase in 22Rv1 cells but at S and G2 phase in PC-3 cells. In addition, we detected the mRNA and protein of Ki67 which is corresponding to the cell proliferation and found that kaempferol could significantly inhibit Ki67 expression at mRNA level but increase its expression at protein levels in both androgen-dependent and androgen-independent prostate cancer cells. Conclusion Taken together, kaempferol inhibited the proliferation of androgen-dependent and androgen-independent prostate cancer cells by regulating the expression of Ki67. These findings further shed light on the mechanism of action of kaempferol on anti-prostate cancer.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
MICROCHIMICA ACTA
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2024
·Vol. 191
·期 5
·1-11
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IF 5.3
Li Heming,Tu Yuxin,Xie Wen,Shi Xinye,Zhang Qiuting,Lin Juan,Zhong Yanhui,Lin Zian,Cai Zongwei
Solid-phase microextraction (SPME) coupled with electrospray ionization mass spectrometry (ESI-MS) was developed for rapid and sensitive determination of endogenous androgens. The SPME probe is coated with covalent organic frameworks (COFs) synthesized by reacting 1,3,5-tri(4-aminophenyl)benzene (TPB) with 2,5-dioctyloxybenzaldehyde (C8PDA). This COFs-SPME probe offers several advantages, including enhanced extraction efficiency and stability. The analytical method exhibited wide linearity (0.1–100.0 µg L −1 ), low limits of detection (0.03–0.07 µg L −1 ), high enrichment factors (37–154), and satisfactory relative standard deviations (RSDs) for both within one probe (4.0–14.8%) and between different probes (3.4–12.7%). These remarkable performance characteristics highlight the reliability and precision of the COFs-SPME-ESI-MS method. The developed method was successfully applied to detect five kinds of endogenous androgens in female serum samples, indicating that the developed analytical method has great potential for application in preliminary clinical diagnosis. Graphical abstract
研究领域:
分析化学
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生物分析化学
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质谱分析
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生物医学分析
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Jie Gao,Zhenzhen Weng,Ze Zhang,Yuanyuan Liu,Zikang Liu,Xinyue Pu,Simin Yu,Yanhua Zhong,Danmeng Bai,Hongbo Xin,Xiaolei Wang
Androgenetic alopecia (AGA) is a prevalent systemic disease caused by diverse factors, for which effective treatments are currently limited. Herein, the oleogel (OG) containing copper-curcumin (CuR) nanoparticles is developed, designated as CuRG, which is also combined with traditional naturopathic scraping (Gua Sha, SCR) as a multifunctional therapy for AGA. With the assistance of lipophilic OG and SCR, CuR can efficaciously penetrate the epidermal and dermal regions where most hair follicles (HFs) reside, thereby releasing curcumin (CR) and copper ions (Cu 2+ ) subcutaneously to facilitate hair regeneration. Concomitantly, the mechanical stimulation induced by SCR promotes the formation of new blood vessels, which is conducive to reshaping the microenvironment of HFs. This study validates that the combination of CuRG and SCR is capable of systematically interfering with different pathological processes, ranging from improvement of perifollicular microenvironment (oxidative stress and insufficient vascularization), regulation of inflammatory responses to degradation of androgen receptor (AR), thus potentiating hair growth. Compared with minoxidil, a widely used clinical drug for AGA therapy, the designed synergistic system displays augmented hair regeneration in the AGA mouse model. This article is protected by copyright. All rights reserved
研究领域:
皮肤科
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纳米技术
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传统医学
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药学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
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2022
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IF 6.064
Xiangru Chen,Peiyu Yan,Wenqiang Zhang,Xin He,Rihua Jiang,Yulin Li,Jing Sun,Jinlan Jiang
Androgenic alopecia (AGA) is a common disease that negatively affects patients’ physical and mental health. AGA can be treated with drugs that improve the perifollicular microenvironment, such as 5α-reductase inhibitors (e.g., dutasteride [DUT]), androgen receptor blockers, and minoxidil. However, the efficacy of these treatments is limited. Therefore, this study aimed to show that nanoparticles are effective as stable carriers with high curative benefits and little adverse effects. The in vitro study showed that PLGA-DUT/siAR@DPCM NPs could deliver both DUT and siAR to dermal papilla cells. They could successfully suppress 5α-reductase and knock down androgen receptor, respectively, and thereby promote cell proliferation. In the in vivo study, PLGA-DUT/siAR@DPCM NPs showed a significant therapeutic effect in an AGA mouse model. They successfully penetrated the stratum corneum and showed a clear targeting effect on hair follicles and surrounding tissues. PLGA-DUT/siAR@DPCM NPs could enable the targeted delivery of DUT and siAR through percutaneous penetration, enhancing phagocytosis and decreasing adverse effects. Thus, they have great potential in the clinical treatment of AGA.
研究领域:
药学
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纳米技术
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皮肤科
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分子生物学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2021
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IF 6.53
Danlan Fu,Junfei Huang,Kaitao Li,Yuxin Chen,Ye He,Yang Sun,Yilong Guo,Lijuan Du,Qian Qu,Yong Miao,Zhiqi Hu
Androgenic alopecia (AGA), also known as male pattern baldness, is one of the most common hair loss diseases worldwide. The main treatments of AGA include hair transplant surgery, oral medicines, and LDL laser irradiation, although no treatment to date can fully cure this disease. Animal models play important roles in the exploration of potential mechanisms of disease development and in assessing novel treatments. The present study describes androgen receptor (AR) in C57BL/6 mouse hair follicles that can be activated by dihydrotestosterone (DHT) and translocate to the nucleus. This led to the design of a mouse model of androgen-induced AGA in vivo and in vitro. DHT was found to induce early hair regression, hair miniaturization, hair density loss, and changes in hair morphology in male C57BL/6 mice. These effects of DHT could be partly reversed by the AR antagonist bicalutamide. DHT had similar effects in an ex vivo model of hair loss. Evaluation of histology, organ culture, and protein expression could explain the mechanism by which DHT delayed hair regrowth.
研究领域:
皮肤科
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药理学
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分子生物学
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DOI
PubMed
高影响因子
CELLULAR AND MOLECULAR LIFE SCIENCES
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2024
·Vol. 81
·期 1
·1-24
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IF 6.2
Hong Ling,Xiao Shan,Diao Lianghui,Lian Ruochun,Chen Cong,Zeng Yong,Liu Su
Polycystic ovary syndrome (PCOS) is a complex common endocrine disorder affecting women of reproductive age. Ovulatory dysfunction is recognized as a primary infertile factor, however, even when ovulation is medically induced and restored, PCOS patients continue to experience reduced cumulative pregnancy rates and a higher spontaneous miscarriage rate. Hyperandrogenism, a hallmark feature of PCOS, affects ovarian folliculogenesis, endometrial receptivity, and the establishment and maintenance of pregnancy. Decidualization denotes the transformation that the stromal compart of the endometrium must undergo to accommodate pregnancy, driven by the rising progesterone levels and local cAMP production. However, studies on the impact of hyperandrogenism on decidualization are limited. In this study, we observed that primary endometrial stromal cells from women with PCOS exhibit abnormal responses to progesterone during in vitro decidualization. A high concentration of testosterone inhibits human endometrial stromal cells (HESCs) decidualization. RNA-Seq analysis demonstrated that pyruvate dehydrogenase kinase 4 (PDK4) expression was significantly lower in the endometrium of PCOS patients with hyperandrogenism compared to those without hyperandrogenism. We also characterized that the expression of PDK4 is elevated in the endometrium stroma at the mid-secretory phase. Artificial decidualization could enhance PDK4 expression, while downregulation of PDK4 leads to abnormal decidualization both in vivo and in vitro. Mechanistically, testosterone excess inhibits IGFBP1 and PRL expression, followed by phosphorylating of AMPK that stimulates PDK4 expression. Based on co-immunoprecipitation analysis, we observed an interaction between SIRT1 and PDK4, promoting glycolysis to facilitate decidualization. Restrain of AR activation resumes the AMPK/SIRT1/PDK4 pathway suppressed by testosterone excess, indicating that testosterone primarily acts on decidualization through AR stimulation. Androgen excess in the endometrium inhibits decidualization by disrupting the AMPK/SIRT1/PDK4 signaling pathway. These data demonstrate the critical roles of endometrial PDK4 in regulating decidualization and provide valuable information for understanding the underlying mechanism during decidualization.
研究领域:
生殖内分泌学
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分子生物学
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细胞生物学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
Communications Biology
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2025
·Vol. 8
·期 1
·1-15
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IF 5.1
Wang Xue,Yan Guangqi,Li Hao,Wang Chunyu,Kang Ye,Wang Shengli,Liu Wei,Lin Lin,Zou Renlong,Zeng Kai,Wang Manlin,Luan Ruina,Zhou Baosheng,Bai Yu,Yang Dongjun,Ning Bolin,Sun Ge,Zhao Yue
Oral squamous cell carcinoma (OSCC) progresses from epithelial cell proliferation to malignancy. Given the higher proportion of male patients compared to female patients, the androgen signaling pathway is believed to play a significant role in promoting epithelial cell proliferation. However, the underlying molecular mechanisms remain unclear. Here, we identified RBAP48 as a novel androgen receptor (AR) co-activator in OSCC cells. Our results show that RBAP48 was highly expressed in OSCC tumor tissues from patients with a poor prognosis. Further, RBAP48 knockdown decreased genome-wide oncogene transcription. RBAP48 and AR interacted to activate CCND1 and RAB31 transcription, and upregulated RELA and CCNE1 mRNA expression through an AR-independent pathway. Additionally, RBAP48 promoted OSCC cell proliferation and was involved in the cellular response to drugs and external compounds in vitro, ultimately driving cancer progression. Our results indicate that RBAP48 is a novel oncogene and a promising target for predicting and treating OSCC progression.
研究领域:
肿瘤学
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分子生物学
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医学遗传学
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DOI
PubMed
高影响因子
LANGMUIR
·
2024
·
IF 3.7
Wenzuo Luo,Xingui Zhang,Yingying Chu,Tiantian Chen,Huixuan Sun,Jiadong Liu,Guoxing Zhang,Lihong Fan,Haixing Xu,Yue Zhang,Ming Yang
Although finasteride (FNS) tablets are considered the most effective drug for the treatment of androgenetic alopecia (AGA), their clinical applications are limited due to the associated side effects including decreased libido, breast enlargement, and liver dysfunction. In this study, we have developed a personalized microneedle (PMN) with a double-layer structure that incorporates FNS-loaded microspheres (MPs) to accommodate irregular skin surfaces. This design enables the sustained release of FNS, thereby reducing potential side effects. The needle body was synthesized with high-strength hyaluronic acid (HA) as the base material substrate. The backing layer utilized methacrylate gelatin (GelMA) with specific toughness, enabling PMN to penetrate the skin while adapting to various skin environments. The length of PMN needles (10 × 10) was approximately 600 μm, with the bottom of the needles measuring about 330 μm × 330 μm. The distance between adjacent tips was around 600 μm, allowing the drug to penetrate the stratum corneum of the skin. The results of the drug release investigation indicated the sustained and regulated release of FNS from PMN, as compared to that of pure FNS and FNS-MPs. Further, the cytotoxicity assay demonstrates that PMS displays good cytocompatibility. Altogether, this mode of administration has immense potential for the development of delivery of other drugs, as well as in the medical field.
CAS / MDL:
研究领域:
药剂学
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皮肤科学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
Advanced Composites and Hybrid Materials
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2025
·Vol. 8
·期 2
·1-17
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IF 21.8
Mbituyimana Bricard,Fu Lina,Wang Hao,Qi Fuyu,Jiang Yuchi,Meng Fanbo,Wu Min,Shi Zhijun,Yang Guang
Androgenetic alopecia (AGA) is the most common type of hair loss frequently observed in clinics. Right now, there are no effective treatments for AGA. Here, we developed a biodegradable microneedle (MN) patch made of polylactic-co-glycolic acid (PLGA) loaded with glutamic acid (GA) that improves sustainable drug release and effective hair regeneration treatment. Once the patch has penetrated the skin, the GA-loaded MNs (GA-MNs) are quickly separated from their base and enter the skin. These MNs then serve as drug storage tanks inside the skin, releasing the therapeutics gradually for over 4 weeks. The sustained release of GA from long-acting biodegradable needles could lead to endocytosis by dermal papilla cells (DPCs), promoting the proliferation of cells. Compared with topical minoxidil, which requires daily treatment, animal studies have shown that GA-MNs can increase hair regeneration more effectively with lower dose frequency; the number of hair follicles in the GA-MNs group reached 83.68 ± 4.52%, which was significantly higher than that of the minoxidil group (56.93 ± 3.21%). This transdermal technology of biodegradable MNs shows considerable promise in clinical applications and offers a straightforward, safe, and effective therapy approach for clinical hair regeneration treatment.
研究领域:
生物医学工程
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皮肤病学
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药物递送系统
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产品关联
DOI
高影响因子
Journal of Environmental Chemical Engineering
·
2022
·
IF 7.968
Congcong He,Zhiming Yin,Jun He,Jungang Lv,Chengjun Wang
The occurrence and distribution of typical estrogenic and androgenic steroid hormones including estrone, 17β-estradiol, estriol, 17α-ethynylestradiol and testosterone in surface water from nine lakes across the Wuhan City, China were investigated. The concentrations of studied steroids in surface water samples from different lakes were ranged from less than detection limits to hundreds nanomolarity and there were significant positive correlations among the concentrations of target steroids, indicating that these chemicals have the common sources and similar environmental behavior. Detection frequencies and abundance of steroids in lakes located in residential area were generally higher than those in remote lakes, and the levels of detected steroids in the identical lake varied in sampling locations with the highest concentration being observed around outlet of wastewater effluent. All these results indicated that anthropogenic factors play important roles in steroids contamination in urban surface water. Photodegradation data of the steroid hormones in natural lake water and deionized water demonstrated that only indirect photosensitive decomposition of steroids occurred in real lake surface water under simulated sunlight irradiation. Reactive species characterization and quenching experimental results revealed that photo-generated triplet 3 DOM* , • OH and 1 O 2 contribute to the indirect degradation of steroids in natural lake water. This study provided important reference for better understanding the sources and transformation of steroid hormones in urban lake surface water.
研究领域:
环境科学
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生态学
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产品关联
DOI
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Jianxing Liu,Shanshan Chen,Wenjing Yan,Jiakun Liu,Qianqian Jin,Yanfeng Zhang,Fangfang Zhang,Yi Pan,Wenjun Hu,Liang Jin
Background Dihydrotestosterone-induced androgen receptor activation and nuclear translocation was identified as the key event in androgen alopecia, which led to dermal papilla cell damage and hair growth cycle arrest. Inhibiting androgen receptor activation or nuclear translocation thus represents a potential therapeutic strategy for reducing dermal papilla cell damage and treating androgen alopecia. Purpose To evaluate the effects of obacunone androgen alopecia and explore the potential underlying mechanisms. Methods The effects of obacunone on androgen receptor activation and changes in the properties of dermal papilla cells were investigated. Meanwhile, the effects of obacunone on transforming growth factor-β-induced hair follicle stem cell damage and on androgen alopecia mice induced by dihydrotestosterone were evaluated. Results Obacunone can competitively bind to androgen receptors with dihydrotestosterone, thereby alleviating the androgen receptor dimerization and nuclear translocation. The negative effects of dihydrotestosterone on dermal papilla cell apoptosis, senescence, and cycle arrest were alleviated by obacunone. Obacunone also counteracted the proliferation and apoptosis of transforming growth factor-β-mediated hair follicle stem cells. In mice with androgen alopecia, treatment with obacunone promoted mice hair growth and inhibited TGF-β/smad signaling. Conclusion Thus, inhibiting androgen receptor dimerization was found to be an effective strategy for alleviating androgen alopecia. Obacunone follows a novel mechanism and holds potential as a drug candidate for androgen alopecia through inhibition of the dimerization of the androgen receptor. This targeting strategy may provide a new avenue for the development of new drugs different from the existing therapeutic approaches.
研究领域:
药理学
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皮肤病学
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分子生物学
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DOI
PubMed
高影响因子
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