In the era of the rapid development of cancer immunotherapy, there is a high level of interest in the application of cell-released small vesicles that stimulate the immune system. As cell-derived ...nanovesicles, exosomes show great promise in cancer immunotherapy because of their immunogenicity and molecular transfer function. The cargoes carried on exosomes have been recently identified with improved technological advances and play functional roles in the regulation of immune responses. In particular, exosomes derived from tumor cells and immune cells exhibit unique composition profiles that are directly involved in anticancer immunotherapy. More importantly, exosomes can deliver their cargoes to targeted cells and thus influence the phenotype and immune-regulation functions of targeted cells. Accumulating evidence over the last decade has further revealed that exosomes can participate in multiple cellular processes contributing to cancer development and therapeutic effects, showing the dual characteristics of promoting and suppressing cancer. The potential of exosomes in the field of cancer immunotherapy is huge, and exosomes may become the most effective cancer vaccines, as well as targeted antigen/drug carriers. Understanding how exosomes can be utilized in immune therapy is important for controlling cancer progression; additionally, exosomes have implications for diagnostics and the development of novel therapeutic strategies. This review discusses the role of exosomes in immunotherapy as carriers to stimulate an anti-cancer immune response and as predictive markers for immune activation; furthermore, it summarizes the mechanism and clinical application prospects of exosome-based immunotherapy in human cancer.
The coronavirus disease 19 (COVID-19) is quickly spreading across China and globally. Pharmacy services are an important pillar in public health to prevent and contain the COVID-19 pandemic. Chinese ...pharmacists have acted swiftly in the public health response in China, such as drafting professional service guidance to pharmacists and pharmacies, establishing emergency drug formularies, monitoring and resolving drug shortages, establishing remote pharmacy services to prevent human-to-human infections, providing event-driven pharmaceutical care, educating the public on infection prevention and disease management, and participating in clinical trials and drug evaluation. This commentary reviews the unique needs of pharmacy services in the COVID-19 pandemic, and shares our experiences with the international pharmacy community in the response to these needs.
Temozolomide (TMZ), an alkylating agent, is widely used for treating primary and recurrent high-grade gliomas. However, the efficacy of TMZ is often limited by the development of resistance. ...Recently, studies have found that TMZ treatment could induce autophagy, which contributes to therapy resistance in glioma. To enhance the benefit of TMZ in the treatment of glioblastomas, effective combination strategies are needed to sensitize glioblastoma cells to TMZ. In this regard, as autophagy could promote cell survival or autophagic cell death, modulating autophagy using a pharmacological inhibitor, such as chloroquine, or an inducer, such as rapamycin, has received considerably more attention. To understand the effectiveness of regulating autophagy in glioblastoma treatment, this review summarizes reports on glioblastoma treatments with TMZ and autophagic modulators from in vitro and in vivo studies, as well as clinical trials. Additionally, we discuss the possibility of using autophagy regulatory compounds that can sensitive TMZ treatment as a chemotherapy for glioma treatment.
The novel coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly evolved into a global pandemic. The substantial morbidity and mortality ...associated with the infection has prompted us to understand potential risk factors that can predict patient outcomes. Hypertension has been identified as the most prevalent cardiovascular comorbidity in patients infected with COVID-19 that demonstrably increases the risk of hospitalization and death. Initial studies implied that renin-angiotensin-aldosterone system inhibitors might increase the risk of viral infection and aggravate disease severity, thereby causing panic given the high global prevalence of hypertension. Nonetheless, subsequent evidence supported the administration of antihypertensive drugs and noted that they do not increase the severity of COVID-19 infection in patients with hypertension, rather may have a beneficial effect. To date, the precise mechanism by which hypertension predisposes to unfavorable outcomes in patients infected with COVID-19 remains unknown. In this mini review, we elaborate on the pathology of SARS-CoV-2 infection coexisting with hypertension and summarize potential mechanisms, focusing on the dual roles of angiotensin-converting enzyme 2 and the disorders of renin-angiotensin-aldosterone system in COVID-19 and hypertension. The effects of proinflammatory factors released because of immune response and gastrointestinal dysfunction in COVID-19 are also discussed.
Abstract
Gliomas, especially glioblastomas, represent one of the most aggressive and difficult-to-treat human brain tumors. In the last few decades, clinical immunotherapy has been developed and has ...provided exceptional achievements in checkpoint inhibitors and vaccines for cancer treatment. Immunization with cellular vaccines has the advantage of containing specific antigens and acceptable safety to potentially improve cancer therapy. Based on T cells, dendritic cells (DC), tumor cells and natural killer cells, the safety and feasibility of cellular vaccines have been validated in clinical trials for glioma treatment. For TAA engineered T cells, therapy mainly uses chimeric antigen receptors (IL13Rα2, EGFRvIII and HER2) and DNA methylation-induced technology (CT antigen) to activate the immune response. Autologous dendritic cells/tumor antigen vaccine (ADCTA) pulsed with tumor lysate and peptides elicit antigen-specific and cytotoxic T cell responses in patients with malignant gliomas, while its pro-survival effect is biased. Vaccinations using autologous tumor cells modified with TAAs or fusion with fibroblast cells are characterized by both effective humoral and cell-mediated immunity. Even though few therapeutic effects have been observed, most of this therapy showed safety and feasibility, asking for larger cohort studies and better guidelines to optimize cellular vaccine efficiency in anti-glioma therapy.
Identification of long non-coding RNAs (lncRNAs) has provided a substantial increase in our understanding of the non-coding transcriptome. Studies have revealed a crucial function of lncRNAs in the ...modulation of cell autophagy in vitro and in vivo, further contributing to the hallmarks of disease phenotypes. These findings have profoundly altered our understanding of disease pathobiology, and may lead to the emergence of new biological concepts underlying autophagy-associated diseases, such as the carcinomas. Studies on the molecular mechanism of the lncRNA-autophagy axis may offer additional avenues for therapeutic intervention and biomarker assessment. In this review, we discuss recent findings on the multiple molecular roles of regulatory lncRNAs in the signaling pathways of cell autophagy. The emerging knowledge in this rapidly advancing field will offer novel insights into human diseases, especially cancers.
► DPPH-HPLC was developed to screen antioxidants from Eucommia ulmoides leaves. ► HSCCC with three runs was used to isolate target antioxidants. ► Seven antioxidants with high purity were purified ...and identified. ► Antioxidant activities of isolated compounds have been evaluated.
Seven antioxidants were purified from Eucommia ulmoides Oliv. leaves using HSCCC guided by DPPH-HPLC experiment. HSCCC was successfully used to separate target antioxidants by three runs with different solvent systems after D101 column chromatography fractionation. Ethyl acetate–n-butanol–water (1:2:3, v/v/v) was selected as the optimum solvent system to purify geniposidic acid. Ethyl acetate–ethanol–water (4:1:5, v/v/v) was used to isolate caffeic acid, chlorogenic acid and ferulic acid. While three flavonoids, quercetin-3-O-sambubioside, rutin and isoquercitrin were purified by petroleum ether–ethyl acetate–methanol–water (1:5:1:5, v/v/v/v). The structures were identified by MS and NMR. Antioxidant activities were assessed, and compounds 2–7 showed strong antioxidant activities. This is the first report about separation of antioxidants from E. ulmoides leaves by HSCCC. The results indicated that the combinative methods using DPPH-HPLC and HSCCC could be widely applied for screening and isolation of antioxidants from complex extracts.
Ferroptosis is an iron-dependent cell death process that plays important regulatory roles in the occurrence and development of cancers, including hepatocellular carcinoma (HCC). Moreover, the ...molecular events surrounding aberrantly expressed long non-coding RNAs (lncRNAs) that drive HCC initiation and progression have attracted increasing attention. However, research on ferroptosis-related lncRNA prognostic signature in patients with HCC is still lacking. In this study, the association between differentially expressed lncRNAs and ferroptosis-related genes, in 374 HCC and 50 normal hepatic samples obtained from The Cancer Genome Atlas (TCGA), was evaluated using Pearson's test, thereby identifying 24 ferroptosis-related differentially expressed lncRNAs. The least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression model were used to construct and validate a prognostic risk score model from both TCGA training dataset and GEO testing dataset (GSE40144). A nine-lncRNA-based signature (CTD-2033A16.3, CTD-2116N20.1, CTD-2510F5.4, DDX11-AS1, LINC00942, LINC01224, LINC01231, LINC01508, and ZFPM2-AS1) was identified as the ferroptosis-related prognostic model for HCC, independent of multiple clinicopathological parameters. In addition, the HCC patients were divided into high-risk and low-risk groups according to the nine-lncRNA prognostic signature. The gene set enrichment analysis enrichment analysis revealed that the lncRNA-based signature might regulate the HCC immune microenvironment by interfering with tumor necrosis factor α/nuclear factor kappa-B, interleukin 2/signal transducers and activators of transcription 5, and cytokine/cytokine receptor signaling pathways. The infiltrating immune cell subtypes, such as resting memory CD4(+) T cells, follicular helper T cells, regulatory T cells, and M0 macrophages, were all significantly different between the high-risk group and the low-risk group as indicated in Spearman's correlation analysis. Moreover, a substantial increase in the expression of B7H3 immune checkpoint molecule was found in the high-risk group. Our findings provided a promising insight into ferroptosis-related lncRNAs in HCC and a personalized prediction tool for prognosis and immune responses in patients.
Health literacy is essential to population health, yet few studies have described the geographic variation in health literacy in China. This study aimed to investigate the level of health literacy, ...its regional heterogeneities, as well as influencing factors of health literacy in 25 provinces or municipalities in China.
The study was conducted among residents aged 15-69 years from 25 provinces or municipalities in China in 2017. Health literacy was measured using the Chinese Health Literacy Scale. MapInfo software was used to map the geographic distribution. Multiple logistic regression was used to adjust for the factors associated with the health literacy level in the overall and regional samples.
A total of 3,482 participants were included in the study, comprising 1,792 (51.5%) males and 1,690 (48.5%) females. Notable geographic variation was observed in health literacy levels. The proportion of respondents with adequate health literacy was 22.3% overall, 33.0% in the eastern region, 23.1% in the central region, and 17.6% in the western region. The proportion of adequate health literacy in the different provinces and municipalities ranged from 10.5% (Xinjiang) to 47.0% (Beijing). Being a female odds ratio (OR) = 1.353; 95% confidence interval (CI): 1.146-1.597, having a high education level OR ranging from 2.794 (CI: 1.469-5.314) to 9.458 (CI: 5.251-17.036), having a high economic status OR ranging from 1.537 (CI: 1.248-1.891) to 1.850 (CI: 1.498-2.284), having a good self-rated health status OR ranging from 2.793 (CI: 1.534-5.083) to 3.003 (CI: 1.672-5.395), and having frequent community health education (OR = 1.588; 95% CI: 1.066-2.365) were independently associated with adequate health literacy.
The health literacy level in the 25 provinces or municipalities of China is relatively low compared to the developed countries, and there are heterogeneities among different regions, between urban and rural areas, and among different social groups. Tailored health education and promotion strategies are needed for different subgroups of residents.
FoxO transcription factors have been reported to play pivotal roles in tumorigenesis and drug resistance. The mechanisms underlying the tumor suppression function of FoxOs in human cancers remain ...largely unknown. Aberrant expression and activation of Nrf2 often correlate with chemoresistance and poor prognosis. Here, we report that FoxO3 directs the basal transcription of Kelch‐like ECH‐associated protein 1 (Keap1), an adaptor protein that bridges Nrf2 to Cul3 for degradation. FoxO3 depletion resulted in Keap1 down‐regulation, thereby activating Nrf2 signaling. We further demonstrated that inhibition of the FoxO3‐Keap1 axis accounts for Nrf2 induction and activation induced by constitutively active AKT signaling or tumor necrosis factor α treatment. Unlike previous findings, FoxO3 silencing led to decreased reactive oxygen species production, therefore protecting cells from oxidative stress‐induced killing in an Nrf2‐dependent manner. Importantly, FoxO3 deficiency strongly potentiated tumor formation in nude mice and rendered cholangiocarcinoma xenografts resistant to cisplatin‐induced cell death by activating Nrf2. Additionally, we found that clinical cholangiocarcinoma samples displayed FoxO3‐Keap1 down‐regulation and Nrf2 hyperactivation, underscoring the essential roles of these proteins in cholangiocarcinoma development. Conclusion: Our results unravel a unique mechanism underlying the tumor suppressor function of FoxO3 through constraining Nrf2 signaling. (Hepatology 2016;63:1914‐1927)
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