Food Bioscience
·
2024
·
IF 4.8
Yiming Ren,Liang Li
Probiotics have numerous biological functions and clinical studies have reported that consuming probiotic foods could promote hair growth and hair follicle health. Bifidobacterium longum BB536 was selected to investigate the possibility of treating hair loss with Cell-Free Supernatant (CFS) of B. longum BB536 and the alleviation mechanism of CFS on dihydrotestosterone (DHT)-damaged human dermal papilla cells (HDPCs). The results showed that HDPCs treated with 10% CFS of B. longum BB536 for 24 h could significantly promote cell proliferation, repair cell damage, accelerate the process of cell cycle and increase the secretion of VEGF. The CFS of B. longum BB536 reduced the apoptosis rate of DHT-damaged HDPCs. In addition, it could reduce the level of pro-inflammatory factors and improve the alkaline phosphatase (ALP) activity. Metabolites of B. longum BB536 may increase the protein expression of Wnt10b, β-catenin and LEF-1 by activating Wnt/β-catenin signaling pathway and inhibit the expression of DHT-induced negative feedback factors DKK1 and GSK-3β, which alleviates the damage of DHT on HDPCs, some protein expression levels such as LEF-1 are close to minoxidil (common drugs for hair loss). So, metabolites of B. longum BB536 can be used as new treatment for hair loss due to its safety. This study provides theoretical basis for probiotics to prevent androgenic alopecia.
研究领域:
微生物学
·
细胞生物学
·
药理学
·
皮肤病学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Pharmaceutical Analysis
·
2023
·
IF 8.8
Tingting Yang,Jiayu Yuan,Yuting Peng,Jiale Pang,Zhen Qiu,Shangxiu Chen,Yuhan Huang,Zhenzhou Jiang,Yilin Fan,Junjie Liu,Tao Wang,Xueyan Zhou,Sitong Qian,Jinfang Song,Yi Xu,Qian Lu,Xiaoxing Yin
The occurrence of benign prostate hyperplasia (BPH) was related to disrupted sex steroid hormones, and metformin (Met) had a clinical response to sex steroid hormone-related gynaecological disease. However, whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear. Here, our clinical study showed that along with prostatic epithelial cell (PEC) proliferation, sex steroid hormones were dysregulated in the serum and prostate of BPH patients. As the major contributor to dysregulated sex steroid hormones, elevated DHT had a significant positive relationship with the clinical characteristics of BPH patients. Activation of AMPK by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor (AR)-mediated YAP1-TEAD4 heterodimers. Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells. Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.
研究领域:
泌尿学
·
内分泌学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Ovarian Research
·
2025
·Vol. 18
·期 1
·1-14
·
IF 4.2
Zheng Xiufen,Chen Zikai,Liang Miao,Zhou Liting,Wang Miaoru,Zhang Silin,Zhang Shuyun,Ma Lei,Yi Wei,Liu Xiawen
Background Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder among women of reproductive age. It is characterized by hyperandrogenism, ovulatory dysfunction, and the presence of polycystic ovarian morphology (PCOM) on ultrasound, often accompanied by metabolic disturbances such as insulin resistance and obesity. Current treatments, including oral contraceptives and anti-androgen medications, often yield limited efficacy and undesirable side effects. This study investigates the role of UGT2B15, an essential enzyme for androgen metabolism, in PCOS pathogenesis and its potential as a therapeutic target.Methods We used RNA sequencing to examine the effects of UGT2B15 knockdown in KGN cells. To modulate UGT2B15 expression, we employed siRNA and (R)/(S)-NAF (naftopidil), a chemical inducer of UGT2B15 identified in our previous studies on a prostate hyperplasia model. The effects of siRNA and (R)/(S)-NAF on dihydrotestosterone (DHT) levels, cell apoptosis, and the expression of apoptosis-related proteins in KGN cells were evaluated. In a PCOS mouse model, we assessed the effects of (R)-NAF and (S)-NAF on serum androgen levels, menstrual cycles, ovarian morphology, and UGT2Bs expression. Additionally, luciferase reporter and ChIP assays were utilized to study UGT2B15 regulation by NR1H4.Results Elevated androgens were found to suppress UGT2B15 expression in ovarian granulosa cells, leading to DHT accumulation and apoptosis. (R)-NAF and (S)-NAF treatments reversed these effects, alleviating PCOS symptoms in mice such as hyperandrogenism, irregular menstrual cycles, and the presence of ovarian cysts. NR1H4 negatively regulated the transcription of UGT2B15 in KGN cells. (R)-NAF and (S)-NAF disrupted NR1H4 binding to the UGT2B15 promoter without affecting its protein levels, indicating direct interference with its regulation.Conclusion sUGT2B15 represents a promising target for novel PCOS therapies by modulating androgen metabolism and protecting ovarian granulosa cells from apoptosis. (R)-NAF and (S)-NAF regulate UGT2B15 by disrupting NR1H4's binding to its promoter, implying potential therapeutic compounds for PCOS treatment.
研究领域:
内分泌学
·
生殖医学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL
·
2025
·
IF 42.5
Zhao Yang,Yu-Qi Ping,Ming-Wei Wang,Chao Zhang,Shu-Hua Zhou,Yue-Tong Xi,Kong-Kai Zhu,Wei Ding,Qi-Yue Zhang,Zhi-Chen Song,Ru-Jia Zhao,Zi-Lu He,Meng-Xin Wang,Lei Qi,Christian Ullmann,Albert Ricken,Torsten Schöneberg,Zhen-Ji Gan,Xiao Yu,Peng Xiao,Fan Yi,Ines Liebscher,Jin-Peng Sun
Androgens, such as 5α-dihydrotestosterone (5α-DHT), regulate numerous functions by binding to nuclear androgen receptors (ARs) and potential unknown membrane receptors. Here, we report that the androgen 5α-DHT activates membrane receptor GPR133 in muscle cells, thereby increasing intracellular cyclic AMP (cAMP) levels and enhancing muscle strength. Further cryoelectron microscopy (cryo-EM) structural analysis of GPR133-Gs in complex with 5α-DHT or its derivative methenolone (MET) reveals the structural basis for androgen recognition. Notably, the presence of the “Φ(F/L) 2.64 -F 3.40 -W 6.53 ” and the “F 7.42 ××N/D 7.46 ” motifs, which recognize the hydrophobic steroid core and polar groups, respectively, are common in adhesion GPCRs (aGPCRs), suggesting that many aGPCRs may recognize different steroid hormones. Finally, we exploited in silico screening methods to identify a small molecule, AP503, which activates GPR133 and separates the beneficial muscle-strengthening effects from side effects mediated by AR. Thus, GPR133 represents an androgen membrane receptor that contributes to normal androgen physiology and has important therapeutic potentials.
研究领域:
药理学
·
分子生物学
·
结构生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2019
·Vol. 24
·期 12
·2266
·
IF 3.06
Xueying Liu,Xiaoku Ran,Muhammad Riaz,Haixue Kuang,Deqiang Dou,Decheng Cai
The major objective of this study was to investigate the anti-chronic nonbacterial prostatitis (CNP) mechanism ofT. patulaby metabolomics and network pharmacology. The study demonstrated that the flavonoids and polysaccharides ofT. patulacould alleviate prostatitis by improving the level of DHT, reducing the secretion of PSA and TNF-α. Besides, both could enhance Na+/K+-ATPase activity, decrease the O2consumption, CO2production, heat production, energy expenditure of rats and promote respiratory exchange ratio of rats. Up to 28 potential biomarkers and 8 key metabolic pathways related to the treatment of CNP were elucidated by the metabolomics analysis, including phenylalanine metabolism, taurine and hypotaurine metabolism, tryptophan metabolism etc. Network pharmacology prediction also reflected the potential mechanism was associated with tryptophan metabolism and energy pathway. Generally, the potential anti-CNP mechanism of flavonoids and polysaccharides ofT. patulamight be through reducing the expression of inflammation factors, adjusting the level of hormone and regulating the amino acid metabolism, energy metabolism and glucose and lipid metabolism.Keywords:Tagetes patulaL.;chronic nonbacterial prostatitis;metabolomics;energy metabolism;network pharmacology
研究领域:
药理学
·
代谢组学
·
传统医学
·
前列腺疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）