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Cancer immunotherapy is impaired by the intrinsic and adaptive immune resistance. Herein, a bispecific prodrug nanoparticle was engineered for circumventing immune evasion of the tumor cells by targeting multiple immune resistance mechanisms. A disulfide bond-linked bispecific prodrug of NLG919 and JQ1 (namely NJ) was synthesized and self-assembled into a prodrug nanoparticle, which was subsequently coated with a photosensitizer-modified and tumor acidity-activatable diblock copolymer PHP for tumor-specific delivery of NJ. Upon tumor accumulation via passive tumor targeting, the polymeric shell was detached for facilitating intracellular uptake of the bispecific prodrug. NJ was then activated inside the tumor cells for releasing JQ1 and NLG919 via glutathione-mediated cleavage of the disulfide bond. JQ1 is a bromodomain-containing protein 4 inhibitor for abolishing interferon gamma-triggered expression of programmed death ligand 1. In contrast, NLG919 suppresses indoleamine-2,3-dioxygenase 1-mediated tryptophan consumption in the tumor microenvironment, which thus restores robust antitumor immune responses. Photodynamic therapy (PDT) was performed to elicit antitumor immunogenicity by triggering immunogenic cell death of the tumor cells. The combination of PDT and the bispecific prodrug nanoparticle might represent a novel strategy for blockading multiple immune evasion pathways and improving cancer immunotherapy.
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OBJECTIVE:To study the effects of Tanshinone capsules on glucose and lipid metabolism and serum sex hormone level in rats with polycystic ovary syndrome (PCOS). METHODS:90 female SD rats were randomly divided into normal group (distilled water),model group (distilled water),positive control group (metformin 200 mg/kg) and Tanshinone capsules low-dose,medium-dose and high-dose groups(30,60,90 mg/kg),with 15 rats in each group. Those groups were induced PCOS mod-el except for normal group;after modeling,those groups were given relevant medicine intragastrically for consecutive 28 d,once a day. The ovulation rate was compared before intervention and 28 d after intervention. Body weight,fat wet weight,fasting insulin (FINS),fasting blood-glucose (FPG),AUC of glucose,HOMA-IR,ISI,serum levels of FSH,LH and T were detected. RE-SULTS:Compared with normal group,anovulation,body weight,fat wet weight,FINS,FPG,AUC of glucose,HOMA-IR, FSH,LH and T were all increased significantly in model group,while ISI decreased significantly(P<0.05). Compared with mod-el group,ovulation rate and ISI of positive control group and Tanshinone capsules groups were increased significantly after interven-tion, while body weight (except for Tanshinone capsules low-dose group), fat wet weight (except for Tanshinone capsules low-dose group),FINS,FPG,AUC of glucose,HOMA-IR,FSH,LH and T were all decreased significantly(P<0.05),especial-ly in Tanshinone capsules high-dose group and positive control group. CONCLUSIONS:Tanshinone capsules can regulate glucose and lipid metabolism and serum sex hormone secretion disorder in PCOS rats.
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Objective To investigate the value of KIM-1 and NGAL in predicting the early diabetes nephropathy(DN).Meth-ods 132 cases of type 1 and type 2 diabetic patients were recruited in this study,patients were divided into four groups based on the urine albumin/creatinine and serum creatinine levels,as follows:normal albuminuria group (45 cases),mi-croalbuminuria group (36 cases),clinical albuminuria group (30 cases),renal failure group (21 cases),65 healthy subjects were recruited as control group.Urinary KIM-1 and NGAL levels were measured by enzyme linked immunosorbent assay (ELISA).Results With the progress of DN,urinary KIM-1 and NGAL levels gradually increased (P<0.05),the urinary KIM-1/Ucr level was positively correlated with ACR (r=0.822,P<0.01),and the urinary NGAL/Ucr was positively cor-related with ACR (r=0.842,P<0.01).Conclusion The urinary KIM-1 and NGAL level can predict the occurrence of ear-ly DN,and also monitor the progression of DN.
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Objective: To Study the effects and feasibility of life quality list for idiopathic pulmonary fibrosis(IPF) patients.Methods: Applying the self-made life quality evaluating list,life qualities of 36 cases of IPF patients were analyzed and compared before and after the intervention of traditional Chinese medicine.Results: The evaluating list of life quality is available for IPF patients.Conclusion: The evaluation of life quality is an available method for the observations of clinical therapeutic effect and health status on IPF patients and it is worth further investigation.