BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2025
·
IF 2.2
Rongyan Zhu,Liu Yang,Yulan Li
Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age and is frequently associated with impaired glucose metabolism. Thioredoxin-interacting protein (TXNIP) plays a critical role in cellular metabolic regulation; however, its involvement in PCOS pathogenesis remains unclear. Bioinformatics analysis revealed significantly increased TXNIP expression in both PCOS patients and mouse ovarian granulosa cells (GCs). In vivo experiments using dehydroepiandrosterone (DHEA)-induced PCOS mouse models showed that TXNIP knockdown restored the expression of glycolysis-related enzymes, including HK2, PFKM, and PKM2. This restoration enhanced glycolytic function by suppressing IRS-1 phosphorylation and activating the PI3K signaling pathway. In vitro, dihydrotestosterone (DHT)treatment elevated TXNIP expression and suppressed glycolytic activity in KGN cells. Silencing TXNIP restored glycolytic metabolites such as pyruvate and lactate and promoted glycolytic flux, while TXNIP overexpression further impaired these functions. Additionally, treatment with the IRS-1 inhibitor NT157 confirmed that TXNIP regulates glycolysis in GCs through the IRS-1/PI3K signaling axis. This study is the first to demonstrate that TXNIP contributes to glycolytic dysfunction in PCOS GCs via the IRS-1/PI3K pathway, highlighting a potential target for PCOS diagnosis and therapy.
研究领域:
生殖生物学
·
代谢病学
·
内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale Advances
·
2025
·
IF 4.6
Weibo Xu,Xiaohan Li,Fujin He,Han Zhao,Jing Wu,Mengyu Li,Xiaoying Dai,Yanmin Li,Xiaojiao Hu,Xiao-Dong Li,Juan Cen,Peng Guo,Shaofeng Duan
Prostate cancer (PCa) is the most common cancer in men and the leading cause of cancer death worldwide. Overactivation of PI3K signaling has been reported to be associated with PCa. TGX221 is an effective specific inhibitor of PI3K, but its clinical application is greatly limited due to its poor solubility. Herein, by using folic acid-PEG-cholesterol semi-succinate (FA-PEG-CHEMS) as the targeting component, we developed a folate receptor-targeted pH-sensitive liposomal delivery system loaded with TGX221 (FA-Lip-TGX221) that could realize effective delivery and controlled release of drugs in the tumor. The prepared liposomes exhibited a uniform particle size and high stability. In addition, FA-Lip-TGX221 could be effectively internalized by PC-3 cells due to its ability to target folate receptors, thereby accumulating in tumor issues. Meanwhile, in vitro and in vivo experiments suggested that FA-Lip-TGX221 could activate PERK-ATF4-CHOP signaling pathway by inhibiting PI3K/110β signaling in PCa, thus significantly promoting endoplasmic reticulum (ER) stress-mediated cancer cell death. In conclusion, FA-Lip-TGX221 is a promising nano delivery vehicle for the treatment of PCa, and also provides new ideas for all tumors overexpressing folate receptors.
研究领域:
肿瘤学
·
药剂学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2024
·
IF 4.6
Wang Ajun,Li Nan,Zhang Nan,Liu Jian,Yang Tao,Li Dongxue,Li Changwen,Li Rui,Jiang Tongcui,Xia Chengyu
The pathogenesis and development of Moyamoya disease are still unclear. This study aimed to investigate the effect of desmoglein-2 (DSG2) on Moyamoya disease and determine the inhibitory effect of DSG2 in vascular remodeling in Moyamoya disease. RNA sequencing, immunohistochemistry (IHC), and western blotting were used to detect the expression of DSG2 in the superficial temporal artery (STA) tissues of Moyamoya disease. The association between DSG2 and endothelial cells’ biological activities was investigated by cell counting kit-8 (CCK-8), migration assay, tube formation assay, flow cytometry with Annexin V-FITC/PI staining, and TUNEL apoptotic cell detection kit. Pathways affected by overexpression or knockdown of DSG2 were identified in endothelial cells. The expression of DSG2 in the STA tissues of Moyamoya disease was lower than that in normal controls. Overexpression of DSG2 inhibits the proliferation and migration but promotes apoptosis in endothelial cells, and low DSG2 levels result in impaired angiogenesis. In addition, there was an interaction between DSG2 and MMP-9, and DSG2 acted through the PI3K signaling in endothelial cells. Our results indicate that DSG2 affects PI3K signaling in vascular endothelial cells, and MMP-9 is involved in DSG2-mediated vascular changes in Moyamoya disease.
研究领域:
神经病学
·
血管生物学
·
细胞信号
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Today
·
2024
·
IF 13.2
Yanjie Han,Haifeng Lu,Zikuan Gu,Peixin Guan,Zhen Liu
In situ reprogramming of tumor associated macrophages (TAMs) to resurge their phagocytic ability holds great potential in cancer treatment. However, most of currently existing TAMs-reshaping approaches fail to effectively reprogram TAMs due to low efficiency, poor specificity, and potential immune side effects. Herein, we report a strategy called molecularly imprinted lysosomal nanodegrader (MILND) for resurging the phagocytosis of macrophages and reversing the "don't eat me" CD47-SIRPα signal via degrading SIRPα in lysosomes. The MILND, which was rationally engineered by controllable molecular imprinting using the N-terminal epitope of SIRPα as template, could specifically bind SIPRα on TAMs. Upon being engulfed by TAMs via endocytosis, the MILND-SIRPα complex was transferred to lysosomes for degradation. The degradation of SIRPα induced a cascade reaction of the downstream PI3K signaling pathway to resurging the phagocytic and recognition capability of TAMs towards cancer cells. Ultimately, MILND resulted in a subsequent series of anti-tumor effects. Benefiting from this, MILND effectively sensitized the immune microenvironment and amplified CD8+ T cell responses, leading to substantial tumor growth inhibition in tumor-bearing mouse model. Thus, this work provides an efficient and versatile immunomodulatory strategy for enhanced antitumor immunotherapy.
研究领域:
癌症生物学
·
免疫治疗
·
纳米技术
·
细胞信号传导
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）