Aim: To study the effect of peroxisome proliferator-actived receptor γ (PPARγ) ligands on cell proliferation and apoptosis in human renal carcinoma cell lines. Methods: The expression of PPARγ was investigated by reverse transcriptase polymerase chain reaction (RT-PCR), Western blot and immunohistochemistry. The effect of thiazolidinedione (TZD) PPARγ ligands on growth of renal cell carcinoma (RCC) cells was measured by MTT assay and flow cytometric analysis. Cell death ELISA, Hoechst 33342 fluorescent staining and DNA ladder assay were used to observe the effects of PPARγ ligands on apoptosis. Regulatory proteins of cell cycle and apoptosis were detected by Western blot analysis. Results: PPARγ was expressed at much higher levels in renal tumors than in the normal kidney (2.16±0.85 vs 0.90±0.73; P<0.01). TZD PPARγ ligands inhibited RCC cell growth in a dose-dependent manner with IC 50 values of 7.08 µmol/L and 11.32 µmol/L for pioglitazone, and 5.71 µmol/L and 8.38 µmol/L for troglitazone in 786-O and A498 cells, respectively. Cell cycle analysis showed a G 0 /G 1 arrest in human RCC cells following 24-h exposure to TZD. Analysis of cell cycle regulatory proteins revealed that TZD decreased the protein levels of proliferating cell nuclear antigen, pRb, cyclin D 1 , and Cdk4 but increased the levels of p21 and p27 in a timedependent manner. Furthermore, high doses of TZD induced massive apoptosis in renal cancer cells, with increased Bax expression and decreased Bcl-2 expression. Conclusion: TZD PPARγ ligands showed potent inhibitory effect on proliferation, and could induce apoptosis in RCC cells. These results suggest that ligands for PPARγ have potential antitumor effects on renal carcinoma cells.

The outbreak of COVID-19 has become a global crisis, and brought severe disruptions to societies and economies. Until now, effective therapeutics against COVID-19 are in high demand. Along with our improved understanding of the structure, function, and pathogenic process of SARS-CoV-2, many small molecules with potential anti-COVID-19 effects have been developed. So far, several antiviral strategies were explored. Besides directly inhibition of viral proteins such as RdRp and Mpro, interference of host enzymes including ACE2 and proteases, and blocking relevant immunoregulatory pathways represented by JAK/STAT, BTK, NF-κB, and NLRP3 pathways, are regarded feasible in drug development. The development of small molecules to treat COVID-19 has been achieved by several strategies, including computer-aided lead compound design and screening, natural product discovery, drug repurposing, and combination therapy. Several small molecules representative by remdesivir and paxlovid have been proved or authorized emergency use in many countries. And many candidates have entered clinical-trial stage. Nevertheless, due to the epidemiological features and variability issues of SARS-CoV-2, it is necessary to continue exploring novel strategies against COVID-19. This review discusses the current findings in the development of small molecules for COVID-19 treatment. Moreover, their detailed mechanism of action, chemical structures, and preclinical and clinical efficacies are discussed.

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Objectives The co-occurrence of chronic diseases in the elderly is a common problem. However, the relationship between comorbidities and the prognosis of elderly patients with COVID-19 was not clear. This study was supposed to describe the clinical characteristics of elderly patients with COVID-19 infection from Sichuan province and the effects of comorbidity. Design A retrospective study. Settings and participants COVID-19 patients from Public Health Clinical Center of Chengdu between December 16, 2019 and February 26, 2020 were included in this study. Patients were divided into elderly group (≥60 years old) and non-elderly group (< 60 years old). Results Elderly patients with COVID-19 indicated relatively higher proportion of comorbidities, and the most common were atherosclerotic cardiovascular disease (56.5%), hypertension (43.5%) and chronic pulmonary disease (21.7%). The proportion of severe cases was higher in elderly group than that in non-elderly group (73.9% and 42.2%, respectively, P=0.012). During hospitalization, elderly patients indicated relatively higher proportion of complications, such as shock (21.7%), respiratory failure (21.7%). The proportion of patients with a decreased number of CD8+ lymphocytes (82.6%) and B lymphocytes (77.8%) in elderly patients was significantly higher than that in non-elderly group (48.9% and 44.8%, respectively). All 3 deaths were elderly patients with comorbidities and the cell counts of T lymphocyte subsets, B and NK cells of them were significantly decreased at admission. Conclusions Elderly patients with COVID-19 had a high proportion of severe cases and comorbidities, more likely to show low immune function, and indicate higher proportion of complications.

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