Ligustrazine Attenuates Liver Fibrosis by Targeting miR-145 Mediated Transforming Growth Factor-ß/Smad Signaling in an Animal Model of Biliary Atresia.

To investigate therapeutic target for ligustrazine during liver fibrosis in an ethanol-induced biliary atresia rat model and transforming growth factor-ß (TGF-ß) induced hepatic stellate cell activation cell model, and the underlying mechanism, a total of 30 rats were randomly assigned into five groups (n = 6 per group): control, sham, ethanol-induced biliary atresia model, model plus pirfenidone, and model plus ligustrazine groups. The liver changes were assessed using H&E and Masson staining and transmission electron microscopy. Expression of miR-145 and mRNA and protein levels of TGF-ß/smads pathway-related proteins were detected. HSC-T6 cells were infected with LV-miR or rLV-miR-145 in the presence or absence of SMAD3 inhibitor SIS3 and treated with 2.5 ng/ml TGF-ß1 and then with ligustrazine. Collected cells were subjected to detect the expression of miR-145 and mRNA and protein expression levels of TGF-ß/smads pathway-related proteins. Ligustrazine rescued liver fibrogenesis and pathology for ethanol-caused bile duct injury, revealed by decreased α-smooth muscle actin and collagen I expression and liver tissue and cell morphology integrity. Further experiments showed that ligustrazine inhibited intrinsic and phosphorylated Smad2/3 protein expression and modification. Similar results were obtained in cells. In addition, ligustrazine altered miR-145 expression in both animal and cell models. Lentivirus mediated miR-145 overexpression and knockdown recombinant virus showed that miR-145 enhanced the TGF-ß/Smad pathway, which led to hepatic stellate cell activation, and ligustrazine blocked this activation. This work validated that ligustrazine-regulated miR-145 mediated TGF-ß/Smad signaling to inhibit the progression of liver fibrosis in a biliary atresia rat model and provided a new therapeutic strategy for liver fibrosis. SIGNIFICANCE STATEMENT: With an ethanol-induced biliary atresia rat model, ligustrazine was found to rescue liver fibrogenesis and pathology for ethanol caused bile duct injury, revealed by decreased α-smooth muscle actin and collagen I expression and liver tissue and cell morphology integrity. Furthermore, we found ligustrazine upregulated miR-145 expression and inhibited TGF-ß/SMAD signaling pathway both in vivo and in vitro. In addition, overexpression and knockdown of miR-145 confirmed that miR-145 is involved in the ligustrazine inhibition of liver fibrosis through the TGF-ß/SMAD signaling pathway.

Efficacy and safety of azithromycin combined with glucocorticoid on refractory Mycoplasma pneumoniae pneumonia in children: A PRISMA-compliant systematic review and meta-analysis.

INTRODUCTION: The aim of this study was to evaluate the efficacy and safety of azithromycin (AZI) combined with glucocorticoid (GC) in the treatment of children with refractory Mycoplasma pneumoniae. METHODS: Computer search for PubMed, EMbase, Cochrane Library, China Biomedical Literature Database (CBMdisc), China Knowledge Network (CNKI), Wanfang, VIP (VIP), and a randomized controlled trial (RCT) of AZI combined with GC in the treatment of children with refractory Mycoplasma pneumoniae pneumonia test (RCT), the search time limit is built until March 20, 2019. Two researchers independently performed literature screening, data extraction, and literature risk bias, and meta-analysis was performed using RevMan 5.3 software. RESULTS: A total of 12 RCTs were included, including 1130 patients. Meta-analysis showed that AZI combined with GC therapy significantly improved the total effective rate of the disease compared with the conventional treatment group (odds ratio [OR] = 6.37; 95% confidence interval [CI] 4.03, 10.07; P < .00001; I = 0%), effectively shortened the antipyretic time (SMD = -2.29; 95% CI -2.70, -1.88; P < .0001); promoted lung inflammation absorption (SMD = -1.89; 95% CI -2.38, -1.40; P < .0001), reduced cough time (SMD = -2.39; 95% CI -2.80, -1.99; P < .0001); shortened hospital stay (SMD = -2.19; 95% CI -3.21, -1.17; P < .0001); improved imaging findings (OR = 5.38; 95% CI 1.09, 26.51, P = .04); reduced inflammation index (SMD = -3.15; 95% CI -4.93, -1.36; P = .004); improved immune function (SMD = 1.29; 95% CI -0.02, 2.60; P < .0001); had no significant adverse reactions (OR = 1.18; 95% CI 0.71, 1.98; P = .53). CONCLUSIONS: According to the current limited research evidence, the addition of GCs to the conventional treatment of refractory Mycoplasma pneumoniae in children can improve the clinical efficacy to a certain extent, and the safety is better. However, due to the quality and quantity of the included literature, the conclusions of this study need to be confirmed by more high-quality studies.

The complete mitochondrial genome of the white-tailed tropicbird, Phaethon lepturus.

The white-tailed tropicbird, Phaethon lepturus (Pelecaniformes, Phaethontidae) is a tropicbird, smallest of three closely related seabirds of the tropical oceans and smallest member of the order Pelecaniformes. Here, we first determined the complete mitochondrial genome of while-tailed tropicbird. The mitogenome (17,773 bp) was composed of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and 1 putative control region. Most protein-coding genes started with a traditional ATG codon except for COX1, COX2, and ND3, which initiated with non-typical start codon GTG, GTG, and ATA instead, respectively, and terminated with the mitochondria stop codon (TAA/TCC/AGG/AGA). The mitogenome structural organization was identical to the same genus species Phaethon rubricauda. The overall AT content was 52.04%, which was higher than GC. To obtain the phylogenetic status of Phaethon lepturus, we constructed the species phylogenetic tree together with the 12 protein-coding genes of nine other closely species. We expected that the complete mitogenome of while-tailed tropicbird would contribute to address taxonomic issues and study the related evolution events.

The complete mitochondrial genome of large flying fox, Pteropus vampyrus (Pteropus, Pteropodidae).

The large flying fox (Pteropus vampyrus) is named after its fox-like face and noted for being one of the largest bats. Here, we reported the complete mitogenome sequence of P. vampyrus, which was 16,554 bp and composed of 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and one control region, with a base composition of lower G+C content (41.5%). Like other bats, all genes were located on H-strand except for eight tRNA and ND6 genes. Most protein-coding genes started with an ATG codon except for ND2, ND3, and ND5, which initiated with ATA or ATT instead, and terminated with the typical stop codon (TAA/TAG) or a single T or an unexpected codon of AGG. Within the control region, 6 bp repeat (TACGCA) was appeared only nine times, much lower than other published Pteropus species. These results provided basic information for researching Pteropus vampyrus on genetics, phylogeny, and adaptive evolution.

Complete mitochondrial genome of the Saker falcon, Falco cherrug (Falco, Falconidae).

The Falco cherrug (Saker falcon) is a large bird of prey. In this article, the complete mitochondrial genome of F. cherrug has been determined for the first time. The mitogenome (18,059 bp) comprised 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and 1 control region. Most protein-coding genes started with an ATG or ATA codon except for COI, which initiated with nontypical start codon of GTG instead, and terminated with the typical stop codon (TAA/TAG/AGA/AGG) or a single T. Two tandem repeats were identified in the control region, which was almost identical to Falco peregrinus, and the length of these two repeats are 204 bp and 291 bp, respectively.

The complete mitochondrial genome of Astatotilapia burtoni.

Astatotilapia burtoni is a species of fish in the Cichlidae family. Astatotilapia burtoni has been used as a model organism to research the behaviors and physical systems of cichlids. Here, we reported the complete mitogenome sequence of A. burtoni, which was 16,583 bp and composed of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and 1 control region, with a base composition of lower G + C content (45.5%). Similar to Astatotilapia calliptera, all genes were located on H-strand except for eight tRNAs and ND6 genes. Most protein-coding genes started with an ATG codon except for COX1, ATP6 and ND3, which initiated with GTG or ATC instead, and terminated with the typical stop condon (TAA/TAG)or a single T. In this article, 12 protein-coding genes of other 10 closely species were used to construct the species phylogenetic tree to convince the mitogenome sequences. These results provided basic information for researching A. burtoni on genetics, phylogeny and adaptive evolution.