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Abnormalities in vascular smooth muscle cells (VSMCs) are pivotal in the pathogenesis of cardiovascular pathologies such as atherosclerosis and hypertension. Scutellarin (Scu), a flavonoid derived from marigold flowers, exhibits a spectrum of biological activities including anti‐inflammatory, antioxidant, antitumor, immunomodulatory and antimicrobial effects. Notably, Scu has demonstrated the capacity to mitigate vascular endothelial damage and prevent atherosclerosis via its antioxidative properties. Nevertheless, the influence of Scu on the formation of VSMC‐derived foam cells remains underexplored. In this study, Scu was evidenced to efficaciously attenuate oleic acid (OA)‐induced lipid accumulation and the upregulation of adipose differentiation‐associated protein Plin2 in a dose‐ and time‐responsive manner. We elucidated that Scu effectively diminishes OA‐provoked VSMC foam cell formation. Further, it was established that Scu pretreatment augments the protein expression of LC3B‐II and the mRNA levels of Map1lc3b and Becn1, concurrently diminishing the protein levels of the NLRP3 inflammasome compared to the OA group. Activation of autophagy through rapamycin attenuated NLRP3 inflammasome protein expression, intracellular lipid droplet content and Plin2 mRNA levels. Scu also counteracted the OA‐induced decrement of LC3B‐II levels in the presence of bafilomycin‐a1, facilitating the genesis of autophagosomes and autolysosomes. Complementarily, in vivo experiments revealed that Scu administration substantially reduced arterial wall thickness, vessel wall cross‐sectional area, wall‐to‐lumen ratio and serum total cholesterol levels in comparison to the high‐fat diet model group. Collectively, our findings suggest that Scu attenuates OA‐induced VSMC foam cell formation through the induction of autophagy and the suppression of NLRP3 inflammasome activation. [ABSTRACT FROM AUTHOR]

Aims: COVID‐19 patients with type 2 diabetes mellitus (T2DM) show both poorer clinical outcomes and have an increased risk of death. SARS‐CoV‐2 virus infection requires simultaneous expression of the SARS‐CoV‐2 cell entry factors angiotensin‐converting enzyme 2 (ACE2) and transmembrane protease serine type 2 (TMPRSS2) in the same cell. The aim of the study was to explore the underlying mechanisms of a COVID‐19 infection in patients with T2DM. Methods: The distribution and expression of AEC2 and TMPRSS2 in different pancreatic cell types in clinical samples of T2DM patients and diabetic mouse models were analysed by single‐cell sequencing, bioinformatics analysis and basic experiments. Results: The results showed that ACE2 and TMPRSS2 are expressed in the ducts of the human pancreas. These findings suggest that SARS‐CoV‐2 can infect ductal cells in vivo through ACE2 and TMPRSS2. T2DM can promote the co‐expression of ACE2 and TMPRSS2 in exocrine ducts, including in the human pancreas. We hypothesize that ACE2 expression levels are associated with increased numbers of lymphocytes in vivo. Conclusions: Increased blood glucose levels are associated with increased ACE2 expression and an increased number of lymphocytes. At the same time, lymphocytes can promote ACE2 expression. [ABSTRACT FROM AUTHOR]

Vascular dementia (VaD) is the second most common type of dementia and has become a major public health challenge as the global population ages. VaD is caused by cerebrovascular disease, and most patients with VaD have been reported to also have Alzheimer's pathologies, which is the formation of neurofibrillary tangles and amyloid plaques that are mainly composed of hyperphosphorylated Tau and amyloid β (Aβ) respectively. However, the mechanisms of VaD are not completely understood, and very few drugs are available to treat this condition. Gastrodin (Gas) is the main bioactive component of the traditional Chinese herbal plant named Tian Ma (Gastrodia elata), and it has been used to treat neurasthenia in the clinical practice of Chinese Medicine for many years. Here, we hypothesize that Gas alleviates VaD in a rat model of permanent bilateral common carotid artery occlusion (2-VO)-induced VaD. Based on the results of the Morris water maze test and attention set shift test, either 22.5 or 90 mg/kg/day Gas improved the executive dysfunction and memory impairment of 2-VO rats following an intragastric administration for 4 weeks. Both 22.5 and 90 mg/kg/day Gas reduced Aβ1–40 and Aβ1–42 plaques in plasma and hippocampus of 2-VO rats. Mechanistically, in 2-VO rats, treatment with Gas (90 mg/kg/day) suppressed Aβ plaque deposition by decreasing the hippocampus levels of phosphorylated Tau. Thus, Gas ameliorated the cognitive deficits of 2-VO rats by inhibiting the abnormal phosphorylation of Aβ and Tau. [ABSTRACT FROM AUTHOR]

• Protein 4.1R may be involved in the process of Zika virus entering host cells. • The deletion of protein 4.1R will significantly reduce Zika virus titer and viral protein synthesis. • Protein 4.1R interacts with Axl/Zika virus envelope (E) protein to promote Zika entry. Zika virus (ZIKV) is a typical mosquito-borne flavivirus known to cause severe fetal microcephaly and adult Guillain-Barré syndrome. Currently, there are no specific drugs or licensed vaccines available for ZIKV infection, and further research is required to identify host cell proteins involved in the virus's life cycle. Viruses are known to use host cell membrane skeletal proteins, such as actin and spectrin, to complete cell entry, transportation, and release. Here, based on immunoprecipitation, the Axl and ZIKV envelope (E) protein were shown to interact with the cell membrane skeleton protein 4.1R. Furthermore, deletion of 4.1R significantly reduced virus titer and viral protein synthesis. Our study showed that 4.1R is an important host cell protein during ZIKV infection and may be involved in the process of viral entry into host cells. [ABSTRACT FROM AUTHOR]