NBMA Promotes Spermatogenesis by Mediating Oct4 Pathway

Yang, Jinfei; Lin, Dengfeng; Yao, Weiwei; Yun, Damin; Zhou, Li-Wei; Gao, Sheng; Sun, Fei

doi:10.1002/open.202100219

Cited by 6 publications

(1 citation statement)

References 37 publications

(39 reference statements)

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“…Surgical intervention and sophisticated auxiliary technology serve as treatment modalities for some oligospermia patients, albeit their exorbitant cost coupled with suboptimal outcomes ( Jiang et al, 2017 ). In clinical practice, some patients with oligospermia choose medication treatment through empirical therapy, while the therapeutic effect is still ideal ( Yang et al, 2022 ; Yilmaz et al, 2018 ). Therefore, the development of novel pharmaceuticals to treat male infertility caused by oligospermia holds substantial practical significance.…”

Section: Introductionmentioning

confidence: 99%

Ursolic acid attenuates oligospermia in busulfan-induced mice by promoting motor proteins

Dong,

Ye,

Dong

et al. 2024

PeerJ

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Background Oligospermia is one of the most common reasons for male infertility which is troubling numerous couples of child-bearing age. This investigation scrutinizes the implications and mechanistic underpinnings of ursolic acid’s effect on busulfan-induced oligospermia in mouse models. Methods A singular intraperitoneal injection of busulfan at a dosage of 30 mg/kg induced oligospermia. Two weeks subsequent to this induction, mice were subjected to various dosages of ursolic acid (10, 30, and 50 mg/kg body weight, respectively) on a daily basis for four consecutive weeks. Following this treatment period, a meticulous analysis of epididymal sperm parameters, encompassing concentration and motility, was conducted using a computer-assisted sperm analysis system. The histopathology of the mice testes was performed utilizing hematoxylin and eosin staining, and the cytoskeleton regeneration of the testicular tissues was analyzed via immunofluorescent staining. Serum hormone levels, including testosterone, luteinizing hormone, and follicle-stimulating hormone, as well as reactive oxygen species levels (inclusive of reactive oxygen species and malondialdehyde), were gauged employing specific enzyme-linked immunosorbent assay kits. Differentially expressed genes of testicular mRNA between the oligospermia-induced group and the various ursolic acid treatment groups were identified through RNA sequencing analysis. Results The results revealed that a dosage of 50 mg/kg ursolic acid treatment could increase the concentration of epididymal sperm in oligospermia mice, promote the recovery of testicular morphology, regulate hormone levels and ameliorate oxidative damage. The mechanism research results indicated that ursolic acid increased the expression level of genes related to motor proteins in oligospermia mice.

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Section: Introductionmentioning

confidence: 99%

Ursolic acid attenuates oligospermia in busulfan-induced mice by promoting motor proteins

Dong,

Ye,

Dong

et al. 2024

PeerJ

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NBMA Promotes Spermatogenesis by Mediating Oct4 Pathway

et al. 2022

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Non‐obstructive azoospermia is one of the most common causes of male infertility, but there is still no specific treatment drug. Given that the Oct4 (Octamer‐binding transcription factor 4) has an important regulatory effect on spermatogenesis, activating it can effectively promote spermatogenesis, so it is of great value to develop Oct4‐targeted drug design and elucidating its mechanism of action. Here, we screened out the Oct4‐targeted drug molecule NBMA ( N ‐benzyl‐4‐methoxy‐2‐(1‐(4‐(trifluoromethyl)phenyl)vinyl)aniline) by computer‐assisted technology, and found that it has a significant promoting effect on spermatogenesis in the established mouse azoospermia model. Subsequently, through transcriptome sequencing and enrichment analysis, real‐time fluorescent quantitative PCR (qPCR) and western blot experiments revealed that NBMA promotes the differentiation of spermatogonial stem cells by activating the Oct4 pathway, thereby promoting spermatogenesis. This study proves that NBMA is a molecule with great potential to be developed as a therapeutic drug for azoospermia. It also shows that computer‐assisted, chemical and biological multidisciplinary methods play a very important role in innovative drug discovery.

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Development of Potent ERα Inhibitors: Effectively Inhibit the Growth of Breast Cancer Cells

Yao¹,

Wang

Yang³

et al. 2022

ChemistrySelect

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Breast cancer is the highest incidence among female cancers in the world, but the approved clinical drugs have strong side effects, and some even have carcinogenic effects. Lonidamine has attracted much attention due to its stronger inhibitory effect and smaller side effects for breast cancer, but its low bioavailability limits its clinical application. To overcome this challenge, we hope to further enhance its effect of inhibiting cancer cell proliferation and increase its bioavailability by modifying the structure of lonidamine. After continuous efforts, we designed and synthesized two drug molecules 18a (YRL‐01) and 18b (YRL‐02) with higher inhibitory activity than lonidamine based on the structure‐based drug design strategy, with IC50 values of 45 μM and 53 μM, respectively. Subsequent molecular docking experiments showed that these two molecules should act by targeting the estrogen receptoralpha (ERα). We believe that the research results will provide meaningful guidance for the design and development of innovative drugs against breast cancer in the future.

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NBMA Promotes Spermatogenesis by Mediating Oct4 Pathway

Cited by 6 publications

References 37 publications

Ursolic acid attenuates oligospermia in busulfan-induced mice by promoting motor proteins

Ursolic acid attenuates oligospermia in busulfan-induced mice by promoting motor proteins

NBMA Promotes Spermatogenesis by Mediating Oct4 Pathway

Development of Potent ERα Inhibitors: Effectively Inhibit the Growth of Breast Cancer Cells

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