Causal effects of COVID-19 on cancer risk: A Mendelian randomization study.

In contemporary literature, little attention has been paid to the association between coronavirus disease-2019 (COVID-19) and cancer risk. We performed the Mendelian randomization (MR) to investigate the causal associations between the three types of COVID-19 exposures (critically ill COVID-19, hospitalized COVID-19, and respiratory syndrome coronavirus 2 (SARS-CoV-2) infection) and 33 different types of cancers of the European population. The results of the inverse-variance-weighted model indicated that genetic liabilities to critically ill COVID-19 had suggestive causal associations with the increased risk for HER2-positive breast cancer (odds ratio [OR] = 1.0924; p-value = 0.0116), esophageal cancer (OR = 1.0004; p-value = 0.0226), colorectal cancer (OR = 1.0010; p-value = 0.0242), stomach cancer (OR = 1.2394; p-value = 0.0331), and colon cancer (OR = 1.0006; p-value = 0.0453). The genetic liabilities to hospitalized COVID-19 had suggestive causal associations with the increased risk for HER2-positive breast cancer (OR = 1.1096; p-value = 0.0458), esophageal cancer (OR = 1.0005; p-value = 0.0440) as well as stomach cancer (OR = 1.3043; p-value = 0.0476). The genetic liabilities to SARS-CoV-2 infection had suggestive causal associations with the increased risk for stomach cancer (OR = 2.8563; p-value = 0.0019) but with the decreasing risk for head and neck cancer (OR = 0.9986, p-value = 0.0426). The causal associations of the above combinations were robust through the test of heterogeneity and pleiotropy. Together, our study indicated that COVID-19 had causal effects on cancer risk.

Exosome-Autophagy Crosstalk in Enveloped Virus Infection.

Exosomes, which are extracellular vesicles (EVs) predominantly present in bodily fluids, participate in various physiological processes. Autophagy, an intracellular degradation mechanism, eliminates proteins and damaged organelles by forming double-membrane autophagosomes. These autophagosomes subsequently merge with lysosomes for target degradation. The interaction between autophagy and endosomal/exosomal pathways can occur at different stages, exerting significant influences on normal physiology and human diseases. The interplay between exosomes and the autophagy pathway is intricate. Exosomes exhibit a cytoprotective role by inducing intracellular autophagy, while autophagy modulates the biogenesis and degradation of exosomes. Research indicates that exosomes and autophagy contribute to the infection process of numerous enveloped viruses. Enveloped viruses, comprising viral nucleic acid, proteins, or virions, can be encapsulated within exosomes and transferred between cells via exosomal transport. Consequently, exosomes play a crucial role in the infection of certain viral diseases. This review presents recent findings on the interplay between exosomes and autophagy, as well as their implications in the infection of enveloped viruses, thereby offering valuable insights into the pathogenesis and vaccine research of enveloped virus infection.

The Role of Exosome and the ESCRT Pathway on Enveloped Virus Infection.

The endosomal sorting complex required for transport (ESCRT) system consists of peripheral membrane protein complexes ESCRT-0, -I, -II, -III VPS4-VTA1, and ALIX homodimer. This system plays an important role in the degradation of non-essential or dangerous plasma membrane proteins, the biogenesis of lysosomes and yeast vacuoles, the budding of most enveloped viruses, and promoting membrane shedding of cytokinesis. Recent results show that exosomes and the ESCRT pathway play important roles in virus infection. This review mainly focuses on the roles of exosomes and the ESCRT pathway in virus assembly, budding, and infection of enveloped viruses. The elaboration of the mechanism of exosomes and the ESCRT pathway in some enveloped viruses provides important implications for the further study of the infection mechanism of other enveloped viruses.

Baicalein suppress EMT of breast cancer by mediating tumor-associated macrophages polarization.

Tumor associated macrophages (TAMs) are the main infiltrating component in the tumor microenvironment and play an important role in cancer progression. Baicalein has a wide range of pharmacological properties. This study explores the potential effect of baicalein on macrophages polarization and epithelial-mesenchymal transition (EMT) of breast cancer. Co-culture system was established to evaluate the interaction between TAMs and breast cancer cells. Then the role of baicalein in modulating TAMs function was assessed. Finally, breast cancer mouse model was established to study the underlying mechanism. In vitro experiments showed that co-culture with M2 macrophages significantly enhanced EMT of both MDA-MB-231 and MCF-7 breast cancer cells. Baicalein could regulate polarization of M2 and attenuate TGF-ß1 secretion. In vivo experiments showed that compared with the MDA-MB-231 + M2 group, tumor growth and metastasis of baicalein + MDA-MB-231 + M2 group was significantly inhibited, with smaller tumor size and decreased lung metastasis lesions. Our findings suggest that the regulation of TAMs may be a novel mechanism underlying the anti-tumor effects of baicalein in breast cancer.