TXNIP overexpression in mice enhances streptozotocin-induced diabetes severity.

Thioredoxin-interacting protein (TXNIP) is a key player in the endocrine pancreas; it induces beta cell apoptosis, such that TXNIP deficiency promotes beta cell survival. To study its function in more detail, we generated transgenic mice with ubiquitous overexpression of TXNIP. CBATXNIP/+ mice were investigated under basal conditions and after being challenged in diet-induced obesity (DIO) and streptozotocin-induced type 1 diabetes mellitus (T1DM) models. TXNIP overexpression caused no effect in the DIO model, contrasting to the already reported TXNIP-deficient mice. However, in the T1DM background, CBATXNIP/+ animals showed significantly enhanced blood glucose and increased glucose levels in a glucose tolerance test. Finally, the beta cell mass of CBATXNIP/+ transgenic animals in the T1DM model was significantly reduced compared to control littermates. Our study demonstrates that overexpression of TXNIP doesn't affect blood glucose parameters under basal conditions. However, overexpression of TXNIP in a T1DM model enhances the severity of the disease.

Regular aspirin intake and prognosis of TxN2-3M0 nasopharyngeal carcinoma: A cohort study based on propensity score matching.

OBJECTIVES: Distant metastasis is the leading cause of death in patients with N2-3 nasopharyngeal carcinoma (NPC). And aspirin is found to reduce metastasis and improve prognosis in some other malignancies, such as colorectal cancer. This study aimed to evaluate the clinical value of regular aspirin intake (RAI) in N2-3 NPC treated with standard chemoradiotherapy. MATERIALS AND METHODS: Totally 2064 patients diagnosed with TxN2-3M0 NPC from Jan. 2008 to Dec. 2015 and treated with neoadjuvant chemotherapy followed by concurrent chemoradiotherapy were involved. According to RAI, these patients were divided into 2 groups between which a propensity score matching was made, with a ratio of 1:3 and a series of clinical characteristics (age, gender, T stage, N stage and EBV DNA) as covariates. Then survivals and acute toxicities were compared in the 464 matched patients. RESULTS: RAI appeared to bring better overall (87.7% vs. 79.6%, P = 0.031), metastasis-free (87.8% vs. 76.5%, P = 0.017) and disease-free (85.9% vs. 75.5%, P = 0.033) survivals. It simultaneously increased total incidences of myelosuppression (55.2% vs. 32.2%, P < 0.001), oral mucositis (60.3% vs. 38.2%, P < 0.001), cervical dermatitis (60.3% vs. 38.5%, P < 0.001) and xerostomia (49.1% vs. 33.3%, P = 0.002). But RAI failed to affect incidence of any grade 3/4 toxicity. CONCLUSIONS: Post-diagnosis RAI might be a tolerable approach to control distant metastasis and provide survival benefit for N2-3 NPC in combination with standard chemoradiotherapy.

Topical application of recombinant calreticulin peptide, vasostatin 48, alleviates laser-induced choroidal neovascularization in rats.

PURPOSE: Vasostatin 48 (VS48) is a peptide of 48 amino acids derived from calreticulin. This study aimed to investigate the effects of topical application of VS48 eyedrops on experimental choroidal neovascularization (CNV). METHODS: Recombinant VS48 was expressed and purified as a thioredoxin (TRX)-fused protein, TRX-VS48. The anti-angiogenic effects of TRX-VS48 were validated by migration and tube formation assays performed on cultured endothelial cells, and by rat aorta ring assays. CNV lesions were created in Brown Norway rats by laser-induced photocoagulation at day 1. After topical TRX-VS48 application for 21 days, the CNV lesions were monitored via either choroidal flat mounts on day 21 or by fluorescent angiography on days 21, 28, 35, and 42. CNV lesions were evaluated by histological analysis. The retinal function of animals was examined by electroretinogram (ERG) to evaluate the safety and therapeutic efficacy of TRX-VS48. RESULTS: Application of TRX-VS48 inhibited the migration and tube formation of endothelial cells. TRX-VS48 inhibited the growth of sprouting vessels in aorta rings. ERG analysis revealed that topical TRX-VS48 application for 21 days had no effect on rat retinal functions. After CNV induction, topical TRX-VS48 application for 21 days significantly reduced the size of CNV, as assayed by flat mounts. Fluorescent angiography revealed that the CNV areas in TRX-VS48-treated eyes were significantly reduced compared with TRX-treated eyes on days 21, 28, 35, and 42. Histological analysis also revealed attenuated CNV lesions in TRX-VS48-treated eyes. Topical TRX-VS48 treatment significantly reversed the CNV-induced alterations in ERG parameters on day 35. CONCLUSIONS: Topical TRX-VS48 application suppressed laser-induced CNV in rats, thereby constituting a possible modality for ocular diseases due to excessive angiogenesis.