Chemodynamic therapy (CDT), enabling selective therapeutic effects and low side effect, attracts increasing attention in recent years. However, limited intracellular content of H 2 O 2 and acid at the tumor site restrains the lasting Fenton reaction and thus the anticancer efficacy of CDT. Herein, a nanoscale Co-ferrocene metal-organic framework (Co-Fc NMOF) with high Fenton activity is synthesized and combined with glucose oxidase (GOx) to construct a cascade enzymatic/Fenton catalytic platform (Co-Fc@GOx) for enhanced tumor treatment. In this system, Co-Fc NMOF not only acts as a versatile and effective delivery cargo of GOx molecules to modulate the reaction conditions, but also possesses excellent Fenton effect for the generation of highly toxic •OH. In the tumor microenvironment, GOx delivered by Co-Fc NMOF catalyzes endogenous glucose to gluconic acid and H 2 O 2 . The intracellular acidity and the on-site content of H 2 O 2 are consequently promoted, which in turn favors the Fenton reaction of Co-Fc NMOF and enhances the generation of reactive oxygen species (ROS). Both in vitro and in vivo results demonstrate that this cascade enzymatic/Fenton catalytic reaction triggered by Co-Fc@GOx nanozyme enables remarkable anticancer properties.
Background: The recent outbreak of coronavirus disease 2019 (COVID-19) has been rapidly spreading on a global scale and poses a great threat to human health. Acute respiratory distress syndrome, characterized by a rapid onset of generalized inflammation, is the leading cause of mortality in patients with COVID-19. We thus aimed to explore the effect of risk factors on the severity of the disease, focusing on immune-inflammatory parameters, which represent the immune status of patients. Methods: A comprehensive systematic search for relevant studies published up to April 2020 was performed by using the PubMed, Web of Science, EMBASE, and China National Knowledge Internet (CNKI) databases. After extracting all available data of immune-inflammatory indicators, we statistically analyzed the risk factors of severe and non-severe COVID-19 patients with a meta-analysis. Results: A total of 4,911 patients from 29 studies were included in the final meta-analysis. The results demonstrated that severe patients tend to present with increased white blood cell (WBC) and neutrophil counts, neutrophil-lymphocyte ratio (NLR), procalcitonin (PCT), C-reaction protein (CRP), erythrocyte sedimentation rate (ESR), and Interleukin-6 (IL-6) and a decreased number of total lymphocyte and lymphocyte subtypes, such as CD4+ T lymphocyte and CD8+ T lymphocyte, compared to the non-severe patients. In addition, the WBC count>10 × 10 9 /L, lymphocyte count<1 × 10 9 /L, PCT>0.5 ng/mL, and CRP>10 mg/L were risk factors for disease progression in patients with COVID-19 (WBC count>10 × 10 9 /L: OR = 2.92, 95% CI: 1.96-4.35; lymphocyte count<1 × 10 9 /L: OR = 4.97, 95% CI: 3.53-6.99; PCT>0.5 ng/mL: OR = 6.33, 95% CI: 3.97-10.10; CRP>10 mg/L: OR = 3.51, 95% CI: 2.38-5.16). Furthermore, we found that NLR, as a novel marker of systemic inflammatory response, can also help predict clinical severity in patients with COVID-19 (OR = 2.50, 95% CI: 2.04-3.06). Conclusions: Immune-inflammatory parameters, such as WBC, lymphocyte, PCT, CRP, and NLR, could imply the progression of COVID-19. NLR has taken both the levels Feng et al. Immune-Inflammatory Parameters in COVID-19 of neutrophil and lymphocyte into account, indicating a more complete, accurate, and reliable inspection efficiency; surveillance of NLR may help clinicians identify high-risk COVID-19 patients at an early stage.
Cancer has always been an enormous threat to human health and survival. Surgery, radiotherapy, and chemotherapy could improve the survival of cancer patients, but most patients with advanced cancer usually have a poor survival or could not afford the high cost of chemotherapy. The emergence of oncolytic viruses provided a new strategy for us to alleviate or even cure malignant tumors. An oncolytic virus can be described as a genetically engineered or naturally existing virus that can selectively replicate in cancer cells and then kill them without damaging the healthy cells. There have been many kinds of oncolytic viruses, such as herpes simplex virus, adenovirus, and Coxsackievirus. Moreover, they have different clinical applications in cancer treatment. This review focused on the clinical application of oncolytic virus and predicted the prospect by analyzing the advantages and disadvantages of oncolytic virotherapy.
The conversion of endogenous H 2 O 2 into toxic hydroxyl radical ( • OH) via catalytic nanoparticles is explored for tumor therapy and received considerable success. The intrinsic characteristics of microenvironment in tumor cells, such as limited H 2 O 2 and overexpressed glutathione (GSH), hinder the intracellular • OH accumulation and thus weaken therapeutic efficacy considerably. In this study, fine CaO 2 nanoparticles with Cu-ferrocene molecules at the surface (CaO 2 /Cu-ferrocene) are successfully designed and synthesized. Under an acidic condition, the particles release Ca 2+ ions and H 2 O 2 in a rapid fashion, while they can remain stable in neutral. In addition, agitated production of • OH occurs following the Fenton reaction of H 2 O 2 and ferrocene molecules, and GSH is consumed by Cu 2+ ions to avoid the potential • OH consumption. More interestingly, in addition to the exogenous Ca 2+ released by the particles, the enhanced • OH production facilitates intracellular calcium accumulation by regulating Ca 2+ channels and pumps of tumor cells. It turns out that promoted • OH induction and intracellular calcium overload enable significant in vitro and in vivo antitumor phenomena.
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