Recombinant interleukin-2 stimulates lymphocyte recovery in patients with severe COVID-19.

A recently identified type of pneumonia, referred to as coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2, has rapidly spread worldwide. Lymphopenia and a proinflammatory cytokine storm frequently occur in patients with severe COVID-19. However, to the best of our knowledge, no specific immunomodulatory therapy for COVID-19 has been reported to date. In the present retrospective case-control study, the potential therapeutic effect of recombinant human interleukin-2 (rIL-2) in patients with severe COVID-19 was demonstrated. A total of 59 patients with severe COVID-19 were admitted to the Union Hospital of Tongji Medical College (Wuhan, China) between 29th January 2020 and 29th February 2020 and were included in the present study. In total, 20 patients received subcutaneous injection of rIL-2 (1 million IU per day) for 7-10 days in addition to regular treatment and were classified as the rIL-2 group. Furthermore, 20 of the 39 patients receiving regular treatment, without the intervention of rIL-2, were matched as the control group. Patients in these two groups were subjected to propensity score matching in terms of clinical characteristics such as age, sex, symptoms, signs, laboratory data and comorbidities. Changes in the lymphocyte count, as well as IL-6 and C-reactive protein (CRP) levels, were analyzed at the time of admission and discharge and any differences between the rIL-2 and non-rIL-2 groups were determined. The results demonstrated an increase in the lymphocyte count and a decrease in CRP levels in the rIL-2 group compared with that in the non-rIL-2 group. The difference in the change of the lymphocyte count between the rIL-2 group and non-rIL-2 group was statistically significant (P<0.01). Although CRP levels were decreased to a greater extent in the rIL-2 group, the difference between the two groups was not statistically significant (P>0.05). Collectively, the present results suggested that administration of rIL-2 may be a prospective adjuvant therapy for patients with severe COVID-19 and its effects may be mediated by increasing lymphocyte numbers.

Baicalin Attenuates Cardiac Dysfunction and Myocardial Remodeling in a Chronic Pressure-Overload Mice Model.

BACKGROUND/AIMS: Baicalin has been shown to be effective for various animal models of cardiovascular diseases, such as pulmonary hypertension, atherosclerosis and myocardial ischaemic injury. However, whether baicalin plays a role in cardiac hypertrophy remains unknown. Here we investigated the protective effects of baicalin on cardiac hypertrophy induced by pressure overload and explored the potential mechanisms involved. METHODS: C57BL/6J-mice were treated with baicalin or vehicle following transverse aortic constriction or Sham surgery for up to 8 weeks, and at different time points, cardiac function and heart size measurement and histological and biochemical examination were performed. RESULTS: Mice under pressure overload exhibited cardiac dysfunction, high mortality, myocardial hypertrophy, increased apoptosis and fibrosis markers, and suppressed cardiac expression of PPARα and PPARß/δ. However, oral administration of baicalin improved cardiac dysfunction, decreased mortality, and attenuated histological and biochemical changes described above. These protective effects of baicalin were associated with reduced heart and cardiomyocyte size, lower fetal genes expression, attenuated cardiac fibrosis, lower expression of profibrotic markers, and decreased apoptosis signals in heart tissue. Moreover, we found that baicalin induced PPARα and PPARß/δ expression in vivo and in vitro. Subsequent experiments demonstrated that long-term baicalin treatment presented no obvious cardiac lipotoxicity. CONCLUSIONS: The present results demonstrated that baicalin attenuates pressure overload induced cardiac dysfunction and ventricular remodeling, which would be due to suppressed cardiac hypertrophy, fibrosis, apoptosis and metabolic abnormality.

Indirect co­culture of vascular smooth muscle cells with bone marrow mesenchymal stem cells inhibits vascular calcification and downregulates the Wnt signaling pathways.

Vascular calcification (VC) is widely considered to be a crucial clinical indicator of cardiovascular disease. Recently, certain properties of mesenchymal stem cells (MSCs) have been hypothesized to have potential in treating cardiovascular diseases. However, their effect on the initiation and progression of VC remains controversial. The present study aimed to investigate whether MSCs indirectly mediate VC and their impact on the Wnt signaling pathways. A Transwell system was selected to establish the indirect co­culture environment, and hence, vascular smooth muscle cells (VSMCs) were indirectly co­cultured in the presence or absence of MSCs at a ratio of 1:1. Osteogenic medium (OS) was added to imitate a calcifying environment. Fourteen days later, VSMCs in the lower layers of the Transwell plates were harvested. Alkaline phosphatase activity and calcium nodules were markedly increased in calcific VSMCs induced by OS. However, these parameters were significantly decreased in VSMCs by indirectly co­culturing with MSCs in the same medium. Furthermore, the messenger RNA expression levels of osteopontin and osteoprotegerin were notably increased in VSMCs cultured in OS, but reduced by indirect interaction with MSCs. In addition, the activities of canonical and noncanonical Wnt ligands, wingless­type MMTV integration site family, number 5A (Wnt5a), receptor tyrosine kinase­like orphan receptor 2 (Ror2) and ß­catenin, which are important in the process of VC, were downregulated by indirect contact with MSCs in OS. Thus, indirect co­culture with MSCs inhibits VC and downregulates the Wnt signaling pathways.