Carcinoma, Papillary ; genetics ; Humans ; Mutation ; Proto-Oncogene Proteins B-raf ; genetics ; Thyroid Neoplasms ; genetics

AIM To explore the effects of Sangtong alkaloids (total alkaloids and total flavones from Mori folium,STA) on the random blood glucose,starch tolerance and hepatic insulin resistance in db/db mice with type 2 diabetes mellitus.METHODS Eight-week-old db/db mice were divided into model group (normal saline),acarbose group (39 mg/kg) and Sangtong alkaloids groups (105,210 and 420 mg/kg),db/m mice were used as control group (normal saline).The mice were given by intragastric administration for one hundred days.The random blood glucose of mice was determined every ten days.The starch tolerance was determined in the 100th day,together with the determination of serum insulin level,insulin resistance index and insulin sensitivity index.Histopathology changes of pancreas were observed by HE staining.Protein expressions of P-IRS1,P-PI3 K,P-AKT and GLUT2 were detected by Western blot.RESULTS Sangtong alkaloids significantly decreased the random blood glucose,serum insulin level and insulin resistance index,and increased the insulin sensitivity index in db/db mice.Meanwhile,Sangtong alkaloids ameliorated the pancreas histopathological damage and up-regulated the protein expressions of P-IRS1,P-PI3K,P-AKT and GLUT2 in liver.CONCLUSION Sangtong alkaloids can decrease the random blood glucose and improve the insulin resistance of liver in db/db mice with type 2 diabetes mellitus,whose mechanism may be associated with the regulation of hepatic insulin signal pathway.

AIM To observe the effects of Sangtongjian Mixture (STJ) on glucose and lipid metabolism,insulin resistance and fat cytokines in type 2 diabetic rats,and their mechanisms of action.METHODS One hundred and forty rats fed on the combination of STZ and high fat diet were established as the type 2 diabetic models.Fasting blood glucose (FBG) level reached more than 16.7 mmol/L and then the rats were randomly divided into model group,metformin (180 mg/kg) group,STJ (73.5,147 and 294 mg/kg) groups.Ten rats were set as the blank group.Each treatment group was intragastrically given the corresponding agents for twelve weeks.The fasting blood glucose levels of rats were measured once every two weeks after the administration.After a 12-week administration period,glycosylated serum protein (GSP),glycosylated hemoglobin (GHb) and lipid profile indices (TC,TG,HDL-C and LDL-C) were determined.The serum insulin level was measured by radioimmunoassay,and homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity index (ISI) were calculated.The levels of serum adiponectin and leptin were detected by ELISA.RESULTS STJ remarkably decreased the levels of FBG,GSP,GHb,TC,TG,LDL-C,leptin and HOMR-IR in type 2 diabetic rats.Furthermore,STJ also significantly increased the levels of HDL-C,adiponectin and ISI.CONCLUSION STJ can improve glucose and lipid metabolism in type 2 diabetic rats by ameliorating insulin resistance and regulating fat cytokine levels.

Tumor-targeted immunotherapy is a remarkable breakthrough, offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity. However, existing platforms suffer from low efficacy, inability to induce strong immunogenic cell death (ICD), and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones. Here, an innovative platform, perfluorooctyl bromide (PFOB) nanoemulsions holding MnO₂ nanoparticles (MBP), was developed to orchestrate cancer immunotherapy, serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD. By simultaneously depleting the GSH and eliciting the ICD effect via high-intensity focused ultrasound (HIFU) therapy, the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells (DCs) and facilitating the activation of CD8⁺ and CD4⁺ T cells. The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis. Together, these findings inaugurate a new strategy of tumor-targeted immunotherapy, realizing a novel therapeutics paradigm with great clinical significance.