Testicular structural and functional impairment is a serious complication in male diabetes mellitus (DM) patients that leads to impaired fertility in adulthood. In contrast to other endocrine therapies, islet transplantation (IT) can effectively prevent and even reverse diabetic nephropathy and myocardial damage. However, whether IT can alleviate diabetes-induced testicular injury remains unclear. In this study, we sought to investigate the effect of IT on diabetes-induced testicular damage. A diabetic rat model was established by streptozotocin injection. DM, IT, and insulin treatment (INS) groups were compared after 4 weeks of respective treatment. We confirmed that IT could effectively attenuate diabetes-induced testicular damage and recover sperm counts more extensively compared with INS in diabetic rats. In addition, significantly higher levels of superoxide dismutase (SOD) activity and lower contents of malondialdehyde (MDA) were detected in the testes of the IT group versus diabetic rats. Mechanism studies revealed that IT significantly activates the expression of Nrf-2, HO-1, and NQO-1 and inhibits upregulation of the NF-κB expression in response to DM, while INS only exhibit slight impact on the protein expression. Therefore, we speculate that IT may prevent the progression of testicular damage by downregulating oxidative stress and inhibiting inflammation via Nrf-2/HO-1 and NF-κB pathways.
Most hepatocellular carcinoma (HCC)-associated mortalities are related to the metastasis of cancer cells. The localization of mRNAs and their products to cell protrusions has been reported to play a crucial role in the metastasis. Our previous findings demonstrated that STAT3 mRNA accumulated in the protrusions of metastatic HCC cells. However, the underlying mechanism and functional significance of this localization of STAT3 mRNA has remained unexplored. Here we show that fragile X mental retardation protein (FMRP) modulates the localization and translation of STAT3 mRNA, accelerating HCC metastasis. The results of molecular analyses reveal that the 3′UTR of STAT3 mRNA is responsible for the localization of STAT3 mRNA to cell protrusions. FMRP is able to interact with the 3′UTR of STAT3 mRNA and facilitates its localization to protrusions. Importantly, FMRP could promote the IL-6-mediated translation of STAT3, and serine 114 of FMRP is identified as a potential phosphorylation site required for IL-6-mediated STAT3 translation. Furthermore, FMRP is highly expressed in HCC tissues and FMRP knockdown efficiently suppresses HCC metastasis in vitro and in vivo. Collectively, our findings provide further insights into the mechanism of HCC metastasis associated with the regulation of STAT3 mRNA localization and translation.
Malignant ascites (MA) is a common symptom of peritoneal
metastasis
in liver cancer. Cancer immunotherapy can modulate immune cells to
induce antitumor immune efficiency. Reprogramming tumor immune microenvironment
(TIME) is a momentous strategy to overcome immunosuppression and achieve
immune functional normalization. Inspired by the inherent apoptotic
bodies and vesicles, we proposed and systematically studied engineered
apoptosis-bioinspired nanoparticles (EBN) for cancer immunotherapy
of MA. Using both in vitro and in vivo experimental validations, we
elucidated that EBN could be efficiently engulfed by the tumor-associated
macrophages (TAMs) and manipulate their polarization. Moreover, a
boosted immune cascade response as a result of heightening cytotoxic
T-lymphocytes (CTLs) activity was investigated. Based on these results,
EBN was confirmed to have strong immune cascade activation capability.
Remarkably, the injection of EBN further reduced ascites volume and
reformed immune cell subtypes, compared to the injection of either
PBS or free TMP195 alone. In short, this novel nanodrug delivery system
(NDDS) represents a prospective immunotherapeutic approach for clinical
therapeutics of hepatoma ascites and other malignant effusion.
A highly selective and sensitive split molecular beacon (SMB)-based SNP genotyping biosensing system was developed by combining the selectivity of ligation detection reaction (LDR) with the efficient signal amplification of target recycling.
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