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JOURNAL OF CELLULAR PHYSIOLOGY · 2024 · IF 4.5

Regulation of spermatogonial stem cell differentiation by Sertoli cells-derived exosomes through paracrine and autocrine signaling

Hairui Tian,Xingju Wang,Xiaoxiao Li,Weixiang Song,Jiaqi Mi,Kang Zou

In the orchestrated environment of the testicular niche, the equilibrium between self-renewal and differentiation of spermatogonial stem cells (SSCs) is meticulously maintained, ensuring a stable stem cell reserve and robust spermatogenesis. Within this milieu, extracellular vesicles, specifically exosomes, have emerged as critical conveyors of intercellular communication. Despite their recognized significance, the implications of testicular exosomes in modulating SSC fate remain incompletely characterized. Given the fundamental support and regulatory influence of Sertoli cells (SCs) on SSCs, we were compelled to explore the role of SC-derived exosomes (SC-EXOs) in the SSC-testicular niche. Our investigation hinged on the hypothesis that SC-EXOs, secreted by SCs from the testes of 5-day-old mice—a developmental juncture marking the onset of SSC differentiation—participate in the regulation of this process. We discovered that exposure to SC-EXOs resulted in an upsurge of PLZF, MVH, and STRA8 expression in SSC cultures, concomitant with a diminution of ID4 and GFRA1 levels. Intriguingly, obstructing exosomal communication in a SC-SSC coculture system with the exosome inhibitor GW4869 attenuated SSC differentiation, suggesting that SC-EXOs may modulate this process via paracrine signaling. Further scrutiny revealed the presence of miR-493-5p within SC-EXOs, which suppresses Gdnf mRNA in SCs to indirectly restrain SSC differentiation through the modulation of GDNF expression—an indication of autocrine regulation. Collectively, our findings illuminate the complex regulatory schema by which SC-EXOs affect SSC differentiation, offering novel perspectives and laying the groundwork for future preclinical and clinical investigations.

研究领域: 生殖生物学 · 干细胞生物学 · 分子生物学
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Signal Transduction and Targeted Therapy · 2025 ·Vol. 10 ·期 1 ·1-19 · IF 52.7

Piezo1 activation suppresses bone marrow adipogenesis to prevent osteoporosis by inhibiting a mechanoinflammatory autocrine loop

Wang Baile,Liu Jie,Wang Qin,Arhatte Malika,Cheong Lai Yee,Glogowska Edyta,Jiang Xue,Chung Sookja Kim,Jin Leigang,Hu Qianxing,Wang Yu,Honoré Eric,Xu Aimin

With aging or osteoporosis, bone marrow adipogenesis is increased and inversely correlates with the loss of bone mass. Bone marrow adipocytes are derived from multipotent bone marrow mesenchymal stem cells (BMMSCs), which can differentiate into either fat or bone. BMMSCs are mechanosensitive cells, but how mechanical loading is implicated in the in vivo regulation of bone marrow adipogenesis and its impact on bone remodeling remain poorly understood. Here, we identify the mechanosensitive cationic channel Piezo1 in BMMSCs as a key suppressor of bone marrow adipogenesis by preventing local inflammation, thereby enhancing osteoblast differentiation and bone formation. Mice with a specific Piezo1 invalidation in BMMSCs exhibit osteoporosis and marrow adiposity, together with resistance to the beneficial effects of exercise on bone health. Accordingly, Piezo1-deficient BMMSCs in vitro preferentially differentiate into adipocytes rather than osteoblasts. Invalidation of Piezo1 in BMMSCs enhances the autocrine activation of CCR2 by Ccl2, which further induces lipocalin-2 (Lcn2) production via NF-κB activation, thereby promoting adipocyte differentiation. Conversely, Piezo1 opening induces Klf2 expression through CaMKII, preventing c-Jun activation, Ccl2 production and bone marrow adipogenesis. These findings demonstrate that Piezo1 activation in BMMSCs suppresses bone marrow adipogenesis to maintain bone strength by preventing the Ccl2-Lcn2 inflammatory autocrine loop, thus uncovering a previously unrecognized link between mechanotransduction, inflammation, and cell fate determination.

CAS / MDL: 134-03-2
研究领域: 骨生物学 · 干细胞生物学 · 机械转导 · 炎症与免疫 · 代谢性骨病 · 分子细胞生物学 · 转化医学
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ACS Applied Materials & Interfaces · 2025 · IF 8.2

Self-Secreting Organohydrogels with Adaptive Lubrication for Extreme Environments

Li Wang,Yi Zeng,Wenbing Zhou,Fang Yang,Jun Qu,Yi Zhong,Lihua Zhou,Guilong Yan,Zhenyu Li,Jingyu Chen,Jingjuan Lai,Dong Li,Dong Xiang,Chunxia Zhao,Hui Li,Bo Yu,Xuezhong Zhang,Han Li,Xungai Wang,Yuanpeng Wu

Autonomous lubrication mechanisms in nature inspire the development of self-secreting materials to address tribological challenges in extreme environments. Traditional hydrogels rely heavily on hydration lubrication, which is ineffective in dry conditions and severely compromised in subzero environments due to water loss and freezing. In this study, we present a novel organohydrogel (OHG) system that integrates supramolecular organogels within a hydrogel matrix, enabling temperature-responsive and shear-responsive self-secretion for lubrication in dry, wet, and subzero conditions. Experimental results demonstrate that OHGs exhibit effective lubrication even in completely dry conditions, overcoming reliance on hydration lubrication seen in traditional hydrogels. In dry conditions, the friction coefficient (COF) of OHGs decreases from 0.4 to 0.1 due to thermally or shear induced self-secretion of the lubricating phase. Additionally, OHGs maintain low-temperature lubrication at −10 °C, retaining flexibility and achieving a stable COF of 0.1. In aqueous environments, OHGs not only exhibit hydration lubrication like traditional hydrogels but also benefit from oil-phase secretion, further reducing the COF to 0.07. Furthermore, self-secretion-controlled hydration swelling behavior was observed, resulting in a swelling equilibrium time eight times greater than that of conventional hydrogels. This controlled swelling behavior enables prolonged migration and enhanced sealing performance, making OHGs particularly suited for deep profile control in oilfield applications. These findings highlight the potential of OHGs as a next-generation self-lubricating material that overcomes the limitations of hydration-based hydrogels, offering enhanced lubrication functionality with promising applications in oilfield development, robotics, and biomedical engineering.

研究领域: 材料科学 · 化学工程 · 摩擦学 · 高分子科学 · 应用物理学 · 生物医学工程 · 石油工程
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Biofilm regulation through biological autocrine signaling molecules and its deuterogenic benefits on gaseous dichloromethane degradation

Lichao Lu,Yangdan Fang,Weixi Zhang,Qi Qi,Tuo Ju,Jianmeng Chen,Dong-zhi Chen

Biofilm regulation based on quorum sensing is an effective bioaugmentation method for air purification; however, it has uncertain stability and obscure deuterogenic mechanisms. A biological autocrine signaling molecule (SMH13) with a C6-HSL component was prepared based on a dichloromethane (DCM) degrader— Methylobacterium rhodesianum H13—that enhanced DCM removal by 16% and maximally shortened the startup time by 39% in labscale biotrickling filters with substantially robust responses to shock loads and starvation resistance. Bioaugmentation closely correlated with increased microbial viability and activated metabolism, especially the enhanced degradation of a metabolic intermediate—HCOOH. Thus, the deuterogenic benefits of initial SMH13 addition on performance improvement was uncovered via the regulation of the microbial community and enrichment of functional genes, including the ones related to DCM removal, such as dcmA . These findings offer an innovative approach for the efficient and economical treatment of chlorinated volatile organic compounds.

CAS / MDL: 75-09-2
研究领域: 环境工程 · 微生物学 · 生物技术
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INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE · 2016 ·Vol. 37 ·期 4 ·998-1004 · IF 2.348

Silencing of phosphoglucose isomerase/autocrine motility factor decreases U87 human glioblastoma cell migration

Yang Li,Zhenqing Wei,Bin Dong,Zhigang Lian,Yinghui Xu

Phosphoglucose isomerase/autocrine motility factor (PGI/AMF) is secreted by tumors and influences tumor growth and metastasis. In order to investigate the effects of silencing PGI/AMF on the migration and the sphere forming abilities of human glioblastoma U87 cells, as well as on the side population cells (SPCs), PGI/AMF was silenced using siRNA. Western blot analysis and RT-qPCR were used to assess the expression of PGI/AMF, Akt and SRY (sex determining region Y)-box 2 (SOX2). Wound healing, migration and tumorsphere formation assays were performed to assess invasion and metastatic potential. The proportion of SPCs was determined using Hoechst 33342 dye and flow cytometric analysis. PGI/AMF silencing inhibited the wound healing capacity and migration ability of U87 cells by 52.6 and 80.4%, respectively, compared with the scrambled siRNA (both P<0.001). Silencing of PGI/AMF decreased the proportion of SPCs in the U87 cells by 80.9% (P<0.01). The silencing of PGI/AMF decreased the number and size of tumorspheres by 53.1 and 39.9%, respectively, compared with the scrambled siRNA (both P<0.01). The silencing of PGI/AMF decreased the levels of phosphorylated Akt (-71.9%, P<0.001) compared with the scrambled siRNA, as well as the levels of the stemness marker, SOX2 (-61.7%, P<0.01). Taken together, these findings suggest that PGI/AMF silencing decreases migration, tumorsphere formation as well as the proportion of SPCs in glioblastoma U87 cells. We suggest that the Akt pathway is involved, and our results provide a potential new target for the treatment of glioblastoma.

CAS / MDL: 50-55-5
研究领域: 肿瘤学 · 分子生物学 · 细胞生物学
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Reproductive Sciences · 2023 · IF 2.9

The Mechanism of IL-17 Regulating Neutrophils Participating in Host Immunity of RVVC Mice

Shao Mingkun,Hou Mengyao,Li Sainan,Qi Wenjin

Vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis (RVVC) are the most common lower genital tract infections in reproductive women. In recent years, the research on its pathogenesis mainly focuses on vaginal local immunity and IL-17 as key factors in adaptive immunity, attracting much attention. However, the role of IL-17 in local immunity in VVC and RVVC is poorly understood. At the same time, neutrophils are considered the most effective way to control and eliminate candidal infection and have a controversial role in VVC and RVVC. In this study, we built a mouse RVVC model. After analyzing the vaginal lavage solution of RVVC mice with an inflammatory factor antibody chip and ELISA, we found that IL-17 may play a protective role in RVVC. The experiment of constructing RVVC mice with different concentrations of IL-17 using halofuginone and comparing the vaginal fungi load and vaginal epithelial damage verified that IL-17 had a protective effect in RVVC. In addition, in vitro and in vivo studies found that IL-17 can promote neutrophil apoptosis and recruit neutrophils in the vagina. The neutrophils in the vagina can secrete IL-17 in an autocrine manner. These two may be why IL-17 plays a protective role in RVVC. In summary, the study suggests that IL-17-mediated regulation of neutrophil function is involved in host immune response to RVVC, which helps us to further understand the potential mechanism of IL-17 in RVVC.

CAS / MDL: 979-32-8
研究领域: 免疫学 · 微生物学 · 传染病学 · 分子生物学
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