Platelets mediate inflammatory monocyte activation by SARS-CoV-2 spike protein.

Infection with SARS-CoV-2, the causative agent of COVID-19, causes mild to moderate disease in most patients but carries a risk of morbidity and mortality. Seriously affected individuals manifest disorders of hemostasis and a cytokine storm, but it is not understood how these manifestations of severe COVID-19 are linked. Here, we showed that the SARS-CoV-2 spike protein engaged the CD42b receptor to activate platelets via 2 distinct signaling pathways and promoted platelet-monocyte communication through the engagement of P selectin/PGSL-1 and CD40L/CD40, which led to proinflammatory cytokine production by monocytes. These results explain why hypercoagulation, monocyte activation, and a cytokine storm are correlated in patients severely affected by COVID-19 and suggest a potential target for therapeutic intervention.

Association of metabolic syndrome and benign prostatic hyperplasia in Chinese patients of different age decades.

OBJECTIVES: To evaluate the relationship between metabolic syndrome (MetS) and annual prostate growth rates in Chinese patients of different age decades with benign prostatic hyperplasia (BPH). METHODS: We retrospectively analyzed the clinical data obtained from 1,052 Chinese men with BPH. Overnight fasting venous blood specimens were collected and serum levels of prostate-specific antigen, fasting blood glucose, high-density lipoprotein cholesterol, total cholesterol and triglyceride were recorded. We divided age into four groups: 50 ≤ age ≤ 60, 60 < age ≤ 70, 70 < age ≤ 80 and 80 < age ≤ 90. Pearson's correlation coefficient was used to test the linearity of the relationships between each of the MetS components and prostate volume and annual prostate growth rates generally and in different age decades. RESULTS: The median total prostate volume (69.01 ml) and median annual prostate growth rate (1.92 ml/year) were significantly higher in the MetS group compared with the non-MetS group (57.26 ml and 1.23 ml/year). Significant positive correlations were also found in total prostate volume and different age decades, while negative correlations were seen in annual prostate growth rate and different age decades. CONCLUSIONS: MetS is associated with an increased risk of total volume and annual prostate growth rate in BPH patients of different age decades.

The adeno-associated virus-mediated HSV-TK/GCV suicide system: a potential strategy for the treatment of bladder carcinoma.

Novel treatment strategies such as gene therapy are warranted in view of the failure of current treatment approaches to cure a high percentage of patients with advanced bladder cancers. The emergence of cancer gene therapy potentially offers a number of exciting treatments. The majority of approaches involve strategies to suppress the function of activated oncogenes to restore the expression of functional tumour suppressor genes or to initiate tumour self-destruction. One gene therapy approach against tumours that holds great promise is suicide gene therapy. Herpes simplex virus thymidine kinase (HSV-TK) phosphorylates ganciclovir (GCV), which in turn interacts with cellular DNA polymerase and interferes with DNA synthesis to cause death of rapidly dividing cells. The development of an effective delivery system is absolutely critical to the usefulness and safety of gene therapy. At present, the adeno-associated virus (AAV) vector has the most promising potential in view of its non-pathogenicity, wide tropisms and long-term transgene expression in vivo. Gene therapy studies using different serotypes of recombinant AAV (rAAV) as delivery vehicles have proved rAAVs to be an effective modality of cancer gene therapy. In the present study, we investigated the suppression effect of AAV-mediated HSV-TK/GCV system on the bladder cancer cells and in mice xenograft models of bladder cancer. Our data demonstrate that rAAV-HSV-TK system controlled tumour cell growth and achieves strong antitumour efficacy in vivo. These findings provide a foundation for the development of potential targeted clinical therapies for bladder cancer in humans.