The potential use of microRNAs as a therapeutic strategy for SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, there is no effective therapeutic approach for treating SARS-CoV-2 infections. MicroRNAs (miRNAs) have been recognized to target the viral genome directly or indirectly, thereby inhibiting viral replication. Several studies have demonstrated that host miRNAs target different sites in SARS-CoV-2 RNA and constrain the production of essential viral proteins. Furthermore, miRNAs have lower toxicity, are more immunogenic, and are more diverse than protein-based and even plasmid-DNA-based therapeutic agents. In this review, we emphasize the role of miRNAs in viral infection and their potential use as therapeutic agents against COVID-19 disease. The potential of novel miRNA delivery strategies, especially EDV™ nanocells, for targeting lung tissue for treatment of SARS-CoV-2 infection is also discussed.

[Effects of Wenyang Huazhuo Tongluo Recipe Containing Serum on Transforming Growth Factor ß1/ Smad Signaling Pathway of Skin Fibroblasts in Systemic Sclerosis].

OBJECTIVE: To explore the effects of Wenyang Huazhuo Tongluo Recipe (WYHZTLR) containing serum on transforming growth factor ß1 (TGF-ß1)/Smad signaling pathway of skin fibroblasts in systemic sclerosis (SSc). METHODS: Totally 36 SSc patients were randomly assigned to Chinese medicine (CM) group, Western medicine (WM) group, and integrative medicine (IM) group according to random digit table, 12 in each group. Patients in the CM group took WYHZTLR decoction (one dose per day). Patients in the WM group took penicillamine tablet (0. 125 g each time, bid) and Prednisone Acetate Tablet (PAT 20 mg, qd). Patients in the IM group took penicillamine, PAT, and WYHZTLR decoction (in the same dosage of corresponding drugs as aforesaid). All patients were treated for one month to get drug containing serum. Besides, 10 untreated SSc patients' serum was taken as the control group. Healthy subjects' skin fibroblasts were originated from healthy skin tissue of the upper arms of 2 female patients undergoing plastic surgery. Corresponding serum of each group was added in the culture system of SSc patients' and healthy subjects' dermal fibroblasts respectively. Expression levels of TGF-ß1 receptor type I (TGF-ß1 RI), TGF-ß1 receptor II (TGF-ß1 RII), p-Smad2/3 and Smad7 protein were examined by Western blot. Expression levels of collagen type I and collagen type III (Col-I, Col-III) mRNA were examined by reverse transcription PCR. Contents of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in the supernatant of SSc, skin fibroblasts were examined by ELISA. RESULTS: Compared with the control group, expression levels of TGF-ß1 R I and p-Smad2/3 protein significantly decreased, but expression levels of Smad7 protein significantly increased in skin fibroblasts of SSc patients and healthy subjects of WM, CM, and IM groups (P <0.05, P <0. 01). Meanwhile, the expression level of TGF-ß1 RII decreased in the IM group (P <0. 05, P <0. 01). Compared with the WM group, expression levels of TGF-ß1 RI and p-Smad2/ 3 protein significantly decreased, but that of Srnad7 protein significantly increased in IM groups (P <0. 01). mRNA expression levels of Col-I and Col-II in SSc skin fibroblasts significantly decreased more in WM, CM, and IM groups than in the control group (P <0. 05, P <0. 01). Besides, the expression level of Col-III mRNA was significantly lower in the IM group than in the WM group (P <0.01). Compared with the control group, serum levels of MMP-9 and MMP-9/TIMP-1 ratios increased more obviously in WM, CM, and IM groups (P <0.05, P <0.01). But expression levels of TIMP-1 decreased significantly in CM and IM groups (P <0.01). Expression levels of MMP-9 and MMP-9/TIMP-1 ratios increased more in the IM group than in the WM group (P <0. 01). Expression levels of TIMP-1 decreased more in CM and IM groups than in the WM group (P <0.01). CONCLUSION: WYHZTLR containing serum could reduce expression levels of Col-I and Col-III possibly through regulating key signal molecules, such as TGF-ß1 RI, p-Smad2/3, and Smad7 in TGF-ß1/Smad signaling pathway of SSc skin fibroblasts, and inhibiting transduction of TGF-ß1/Smad signaling pathway.

[Effect of Wenyang Huazhuo Tongluo Recipe on Peripheral Blood Thl7/Treg Cell Balance in Systemic Sclerosis Patients].

OBJECTIVE: To observe the effect of Wenyang Huazhuo Tongluo Recipe (WYHZTLR) on the proportion of T helper 17 cells (Thl7)/regulatory T cells (Treg), and serum levels of IL-17 and IL-10 in peripheral blood of systemic sclerosis (SSc) patients with yang qi insufficiency and turbidity induced collaterals blockage syndrome (YQITICBS). METHODS: Totally 82 SSc patients were randomly assigned to the Western medicine group (as the control group) and the integrated Chinese and Western medicine group (as the treatment group), 41 cases in each group. All patients took methotrexate (MTX) tablet and prednisone tablet. Patients in the treatment group additionally took WYHZTLR. The treatment course for all was six consecutive months. Besides, another 70 healthy volunteers were recruited as a healthy control group (as the healthy group). Percentages of Th17 and Treg in peripheral blood were detected by flow cytometry. Serum levels of IL-17, IL-10, von Willebrand factor (vWF), aminoterminal propeptide of type l procollagen (PIIINP), and cross-linked carboxyterminal telopeptide of type I collagen ( I CTP) were measured by double antibody sandwich ELISA. The correlations between Th17/Treg and levels of vWF, PIIINP, I CTP, skin score, and disease activity index were observed by Pearson correlation analysis. RESULTS: The percentage of Th17 in peripheral blood, ratios of Th17/Treg, and the serum level of IL-17 were significantly higher, but the percentage of Treg and the serum level of IL-10 were significantly lower in SSc patients, when compared with those of the healthy group (P <0. 05, P <0. 01). Compared with the same group before treatment, the percentage of Thl7, ratios of Thl7/Treg, and levels of IL-17, vWF, and PIIINP all decreased in the two groups after treatment (P <0.05, P <0.01), but the percentage of Treg and the IL-10 level increased (P <0. 05, P <0. 01). Meanwhile,the level of I CTP was higher in the treatment group after treatment (P <0. 05). The improvement of all indices except the percentage of Th17 was more obvious in the treatment group than in the control group (P <0. 05, P <0. 01). The ratio of Th17/Treg was positively correlated with levels of vWF, PIIINP, skin score, and disease activity index before and after treatment respectively (P <0. 01), but with no obvious correlation with the level of I CTP (P >0. 05). CONCLUSION: WYHZTLR could achieve its therapeutic effect on SSc patients by regulating Th17/Treg imbalance, lowering levels of vWF and PIIINP, and elevating the level of I CTP.

The complete chloroplast genome sequence of the medicinal plant Cercis chinensis and phylogenetic analysis.

Cercis chinensis is a deciduous shrub or small landscape tree with exceptional ornamental characteristics. Here, we report the complete chloroplast genome of C. chinensis to provide a foundation for further phylogenetic studies of the Leguminosae. The chloroplast (cp) genome was 158,999 bp in size containing a large single-copy (LSC) region 88,176 bp in length, a small single-copy (SSC) region 19,583 bp in length, and two inverted repeat (IR) regions that were 25,620 bp each. The total GC content of the cp genome was 42.9% with the LSC, SSC, and IR regions 36.2, 33.8, and 29.4%, respectively. The cp genome contains 129 genes, including 85 protein-coding, 36 tRNA, and 8 rRNA genes. The phylogenetic analysis revealed that C. chinensis is closely related to Cercis glabra. These results provide valuable information about the evolutionary processes and conservation genetics of C. chinensis.

The complete chloroplast genome sequence of Salvia miltiorrhiza, a medicinal plant for preventing and treating vascular dementia.

S. miltiorrhiza is a perennial herb of the genus Salvia (Lamiaceae), which is an important medicinal plant for preventing and treating vascular dementia. The complete chloroplast genome sequence of Salvia miltiorrhiza was characterized from Illumina pair-end sequencing. The chloroplast genome of S. miltiorrhiza was 152,680 bp in length, containing a large single-copy region (LSC) of 84,104 bp, a small single-copy region (SSC) of 17,638 bp, and two inverted repeat (IR) regions of 25,469 bp. The overall GC content is 38.70%, while the correponding values of the LSC, SSC, and IR regions are 36.2%, 31.9%, and 43.2%, respectively. The genome contains 131 complete genes, including 86 protein-coding genes (62 protein-coding gene species), 37 tRNA genes (29 tRNA species) and 8 rRNA genes (4 rRNA species). The Neighbour-joining phylogenetic analysis showed that S. miltiorrhiza and Salvia przewalskii clustered together as sisters to other Salvia species.