Unique molecular signatures sustained in circulating monocytes and regulatory T cells in Convalescent COVID-19 patients

Over two years into the COVID-19 pandemic, the human immune response to SARS-CoV-2 during the active disease phase has been extensively studied. However, the long-term impact after recovery, which is critical to advance our understanding SARS-CoV-2 and COVID-19-associated long-term complications, remains largely unknown. Herein, we characterized multi-omic single-cell profiles of circulating immune cells in the peripheral blood of 100 patients, including covenlesent COVID-19 and sero-negative controls. The reduced frequencies of both short-lived monocytes and long-lived regulatory T (Treg) cells are significantly associated with the patients recovered from severe COVID-19. Consistently, sc-RNA seq analysis reveals seven heterogeneous clusters of monocytes (M0-M6) and ten Treg clusters (T0-T9) featuring distinct molecular signatures and associated with COVID-19 severity. Asymptomatic patients contain the most abundant clusters of monocyte and Treg expressing high CD74 or IFN-responsive genes. In contrast, the patients recovered from a severe disease have shown two dominant inflammatory monocyte clusters with S100 family genes: S100A8 & A9 with high HLA-I whereas S100A4 & A6 with high HLA-II genes, a specific non-classical monocyte cluster with distinct IFITM family genes, and a unique TGF-{beta} high Treg Cluster. The outpatients and seronegative controls share most of the monocyte and Treg clusters patterns with high expression of HLA genes. Surprisingly, while presumably short-ived monocytes appear to have sustained alterations over 4 months, the decreased frequencies of long-lived Tregs (high HLA-DRA and S100A6) in the outpatients restore over the tested convalescent time (>= 4 months). Collectively, our study identifies sustained and dynamically altered monocytes and Treg clusters with distinct molecular signatures after recovery, associated with COVID-19 severity.

Protective effect of betulinic acid on Freund's complete adjuvant-induced arthritis in rats.

The purpose of the experiment was to study the effects of betulinic acid (BA) on adjuvant-induced arthritis in rats. The rat model of rheumatoid arthritis (AA) was established by Freund's complete adjuvant. Arthritis index, joint pathology, toe swelling, hemorheology, related cytokines and ROCK/NF-κB signaling pathway were measured in rats. BA can significantly inhibit the arthritis index, improve joint pathology, reduce toe swelling, improve blood rheology, improve synovial cell apoptosis, and restore related cytokine negative regulation of ROCK/NF-κB signaling pathways. BA has an obvious therapeutic effect on joint inflammation of toes in AA model rats, which may be due to the regulation of ROCK/NF-κB signaling pathway.

Effect of miRNA-409-3p expression on proliferation of cervical cancer cells and chemotherapy sensitivity of cisplatin / 实用肿瘤学杂志

Objective The objective of this study was to investigate the effect of microRNA-409-3p(miRNA-409-3p) expression on proliferation of cervical cancer Hela cells and chemotherapy sensitivity of cisplatin. Methods HeLa cells were divided into normal control,miRNA-409-3p mimic and RNA control groups. The mRNA expression of miRNA-409-3p was detected by RT-qPCR. The cell viability was detected by CCK-8 assay,and the expression of Fip200,LC3 and Caspase-3 was detected by Western blot. Results The relative expression level of microRNA-409-3p mRNA in cervical cancer tissues was significantly lower than that in normal cervical tissues and adjacent tissues(P<0. 05). After transfection of microRNA-409-3p mimic,the relative ex-pression level of microRNA-409-3p mRNA in the microNA-409-3p mimic group was significantly up-regulated compared with the normal control group(P<0. 05). The relative expression level of miRNA-409-3p mRNA in the RNA control group was not dif-ferent from that in the normal control group(P>0. 05). The proliferative rate of HeLa cells int the microRNA-409 mimic group was significantly lower than that in normal control and RNA control groups(P<0. 05). After cisplatin treatment,the proliferation of Hela cells was significantly inhibited in the miRNA-409-3p mimic group(P<0. 05);the expression of Fip200 protein and LC3II/LC3I ratio in the microRNA-409-3p mimic group were significantly lower than those in the normal control and RNA control groups(P<0. 05). Conclusion The low expression of microRNA-409-3p in cervical cancer tissue may be related to the occurrence and de-velopment of cervical cancer. Upregulation of microRNA-409-3p level can inhibit the proliferation of HeLa cells and increase the sensitivity of HeLa cells to cisplatin.

Expressions of LYVE-1 and PROX-1 in Breast Carcinoma and Their Clinical Significance / 华中科技大学学报(医学版)

Objective To investigate the expressions of LYVE-1 and PROX-1 in human breast carcinoma and the clinical significance of lymphatic vessel density.Methods Immunohistochemistry (SP method)was used to detect the expressions of LYVE-1 and PROX-1 in 80 specimens of breast invasive ductal carcinoma and 35 specimens of breast hyperplasia.Results The density of lymphatic vessels positive for LYVE-1 or PROX-1 was significantly higher in breast carcinoma than in breast hyper-plasia (P<0.01).There was a significant correlation between lymphatic vessel density and lymph node metastasis (P<0.01). A negative correlation was noted between the PROX-1 expression in carcinoma cells and tumor grade (P<0.01)or TNM stage (P < 0.01 ).Conclusion Lymphangiogenesis is increased in breast carcinoma,which is associated with lymph node metastasis.PROX-1 may be involved in tumorigenesis,progression and lymphatic metastasis in breast cancer.