Cascade-Catalyzed Nanogel for Amplifying Starvation Therapy by Nitric Oxide-Mediated Hypoxia Alleviation.

Glucose oxidase (Gox)-mediated starvation therapy offers a prospective advantage for malignancy treatment by interrupting the glucose supply to neoplastic cells. However, the negative charge of the Gox surface hinders its enrichment in tumor tissues. Furthermore, Gox-mediated starvation therapy infiltrates large amounts of hydrogen peroxide (H2O2) to surround normal tissues and exacerbate intracellular hypoxia. In this study, a cascade-catalyzed nanogel (A-NE) was developed to boost the antitumor effects of starvation therapy by glucose consumption and cascade reactive release of nitric oxide (NO) to relieve hypoxia. First, the surface cross-linking structure of A-NE can serve as a bioimmobilization for Gox, ensuring Gox stability while improving the encapsulation efficiency. Then, Gox-mediated starvation therapy efficiently inhibited the proliferation of tumor cells while generating large amounts of H2O2. In addition, covalent l-arginine (l-Arg) in A-NE consumed H2O2 derived from glucose decomposition to generate NO, which augmented starvation therapy on metastatic tumors by alleviating tumor hypoxia. Eventually, both in vivo and in vitro studies indicated that nanogels remarkably inhibited in situ tumor growth and hindered metastatic tumor recurrence, offering an alternative possibility for clinical intervention.

Treatment of diabetic foot during the COVID-19 pandemic: A systematic review.

BACKGROUND: In the context of the novel coronavirus disease 2019 (COVID-19) pandemic, people have had to stay at home more and make fewer trips to the hospital. Furthermore, hospitals give priority to the treatment of COVID-19 patients. These factors are not conducive to the treatment of diabetic foot, and even increase the risk of amputation. Therefore, how to better treat patients with diabetic foot during the COVID-19 epidemic, prevent further aggravation of the disease and reduce the risk of amputation in patients with diabetic foot has become an urgent problem for doctors around the world. METHODS: The researchers searched PubMed, the Cochrane Library, and the Embase database. The retrieval time was set from the database establishment to October 2021. All studies on treatment of diabetic foot in the COVID-19 pandemic were included in our study. RESULTS: A total of 6 studies were included in this study. In the 6 protocols for treating patients with diabetic foot, the researchers classified patients according to the condition of their diabetic foot. Diabetic foot patients with general conditions received treatment at home, and doctors can guide the wound dressing change and medication treatment of patients through telemedicine. Patients with severe conditions of diabetic foot were admitted to hospital for treatment. Patients were screened for COVID-19 before hospitalization, those infected or suspected of COVID-19 were treated in isolation, and those not infected with COVID-19 were treated in a general ward. CONCLUSION: Through this systematic review, we proposed a new protocol for the treatment of patients with diabetic foot in the context of the COVID-19 pandemic. It provided reference for the treatment of diabetic foot in the context of COVID-19 epidemic. However, the global applicability of the treatment protocol for diabetic foot in the context of COVID-19 epidemic proposed in this study needs further clinical testing.

Gestational diabetes mellitus alters DNA methylation profiles in pancreas of the offspring mice.

Gestational diabetes mellitus (GDM), which has an increasing global prevalence, contributes to the susceptibility to metabolic dysregulation and obesity in the offspring via epigenetic modifications. However, the underlying mechanism remains largely obscure. The current study established a GDM mice model to investigate the alternations in the metabolic phenotypes and genomic DNA methylation in the pancreas of the offspring. We found that in the GDM offspring, intrauterine hyperglycemia induced dyslipidemia, insulin resistance, and glucose intolerance. Meanwhile, altered DNA methylation patterns were exhibited in the pancreas and many differentially methylated regions (DMRs)-related genes were involved in glycolipids metabolism and related signaling pathways, including Agap2, Plcbr, Hnf1b, Gnas, Fbp2, Cdh13, Wnt2, Kcnq1, Lhcgr, Irx3, etc. Additionally, the overall hypermethylation of Agap2, verified by bisulfite sequencing PCR (BSP), was negatively correlated with its mRNA expression level. In conclusion, these findings suggest that the DNA methylation changes in the pancreatic genome of the GDM offspring may be associated with the glycolipid metabolism abnormalities, T2DM susceptibility, and obesity in the adult GDM offspring.