Although anti-PD-1 immunotherapy is widely used to treat melanoma, its efficacy still has to be improved. In this work, we present a therapeutic method that combines immunotherapy and starvation therapy to achieve better antitumor efficacy. We designed the CMSN-GOx method, in which mesoporous silica nanoparticles (MSN) are loaded with glucose oxidase (GOx) and then encapsulate the surfaces of cancer cell membranes to realize starvation therapy. By functionalizing the MSN’s biomimetic surfaces, we can synthesize nanoparticles that can escape the host immune system and homologous target. These attributes enable the nanoparticles to have improved cancer targeting ability and enrichment in tumor tissues. Our synthetic CMSN-GOx complex can ablate tumors and induce dendritic cell maturity to stimulate an antitumor immune response. We performed an in vivo analysis of these nanoparticles and determined that our combined therapy CMSN-GOx plus PD-1 exhibits a better antitumor therapeutic effect than therapies using CMSN-GOx or PD-1 alone. Additionally, we used the positron emission tomography imaging to measuring the level of glucose metabolism in tumor tissues, for which we investigate the effect with the cancer therapy in vivo.

Breast cancer is the most common cancer in women. Bisphenol A (BPA), as a known endocrine disrupter, is closely related to the development of breast cancer. Curcumin has been clinically used in chemopreventation and treatment of cancer; however, it remains unknown whether microRNAs are involved in curcumin-mediated protection from BPA-associated promotive effects on breast cancer. In the present study, we showed that BPA exhibited estrogenic activity by increasing the proliferation of estrogen-receptor-positive MCF-7 human breast cancer cells and triggering transition of the cells from G1 to S phase. Curcumin inhibited the proliferative effects of BPA on MCF-7 cells. Meanwhile, BPA-induced upregulation of oncogenic miR-19a and miR-19b, and the dysregulated expression of miR-19-related downstream proteins, including PTEN, p-AKT, p-MDM2, p53, and proliferating cell nuclear antigen, were reversed by curcumin. Furthermore, the important role of miR-19 in BPA-mediated MCF-7 cell proliferation was also illustrated. These results suggest for the first time that curcumin modulates miR-19/PTEN/AKT/p53 axis to exhibit its protective effects against BPA-associated breast cancer promotion. Findings from this study could provide new insights into the molecular mechanisms by which BPA exerts its breast-cancer-promoting effect as well as its target intervention.

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Long-term treatment with mid-dose UDCA can improve liver biochemistry and survival free of liver transplantation in patients with PBC. In addition, UDCA therapy can delay the histological progression in the early-stage patients.

Owing to their versatile functionality and tunable energy dissipation, aggregation-induced emission luminogens (AIEgens) have emerged as ap otential platform for multimodal theranostics.N evertheless,t he construction of AIEactive phototheranostic agents in the second near-infrared window (NIR-II, 1000-1700 nm), which allows superior resolution and minimized photodamage,i ss till af ormidable challenge.H erein, benzo[c]thiophene serves as an electronrich and bulky donor (D)/p-bridge,w hich can enlarge the conjugation length and distort the backbone of an AIEgen. By precise D/p-bridge engineering,h ighly stable NIR-II AIEgen DPBTA-DPTQ nanoparticles are obtained with acceptable NIR-II fluorescence quantum yield and excellent photothermal conversion efficiency.Inaddition, the spatial conformation of DPBTA-DPTQ is determined for the first time by X-ray single crystal diffraction and theoretical simulations.DPBTA-DPTQ NPs have good biocompatibility and show efficient photothermal therapeutic effects in in vitro tests.F urthermore, DPBTA-DPTQ NPs were used in fluorescence-photoacoustic-photothermal trimodal imaging-guided photothermal eradication of tumors in HepG2 and B16-F10 tumor-xenografted mice.

Edited by Barry HalliwellKeywords: Angiotensin II Glycogen synthase kinase 3b Tau Alzheimer disease a b s t r a c t Growing evidence suggests that Alzheimer disease (AD) origins in vascular lesions. As the crucial mediator of vascular pathology, angiotensin II-induced significant amyloid production in our laboratory, although amyloid neurotoxicity depended on phosphorylated tau (p-tau) in recent studies. In the present study, p-tau levels were significantly elevated by central angiotensin II via glycogen synthase kinase 3b (GSK 3b) and other tau kinases. Moreover, angiotensin II-induced cognitive impairment and tau phosphorylation was attenuated by losartan and a GSK 3b inhibitor. These findings implicate Ang II as a crucial mediator of AD pathology and a link between cardiovascular events and AD.

Our study demonstrated that MCT was efficacious in suppressing body fat accumulation, insulin resistance, inflammatory response, and NF-κB and p38 MAPK activation in high fat diet-fed mice. These data suggest that MCT may exert beneficial effects against high fat diet-induced insulin resistance and inflammation.

Recently, RBC membrane coated nanoparticles have attracted much attention because of their excellent immune escape ability; meanwhile, Au nanocages (AuNs) have been extensively used for cancer therapy due to its photothermal effect and drug delivery capability. The combination of RBC membrane coating and Au nanocages may provide an effective approach for targeted cancer therapy. However, few reports have shown the utilization of combining these two technologies. Here, we present the development of Erythrocyte membrane-coated Gold nanocages for targeted cancer photothermal and chemical therapy. First, anti-EpCam antibodies are used to modify RBC membranes to target 4T1 cancer cells. Second, the antitumor drug paclitaxel is encapsulated into AuNs. Then, the AuNs are coated with the modified RBC membranes. This new nanoparticles are termed EpCam-RPAuNs. We characterize the capability of EpCam-RPAuNs for selective tumor targeting via exposure to the near-infrared irradiation. Experimental results demonstrate that EpCam-RPAuNs can effectively generate hyperthermia and precisely deliver the antitumor drug PTX to targeted cells. We also validate the biocompatibility of our EpCam-RPAuNs in vitro. By combining the targeting moleculars modified RBC membrane and AuNs, our approach provides a new way to design biomimetic nanoparticles to enhance the surface functionality of nanoparticles. We believe that EpCam-RPAuNs can be potentially applied for cancer diagnoses and therapies.