Network Pharmacology and Molecular Docking Analysis of the Mechanism Underlying Yikunyin's Therapeutic Effect on Menopausal Syndrome.

Objective: Yikunyin is an empirical prescription that exhibits good efficacy in the clinical treatment of menopausal syndrome; however, its underlying mechanism remains unclear. This study investigates the mechanism implicated in the therapeutic effect of Yikunyin by identifying its hub genes, central pathways, and key active ingredients. Method: The active ingredients and targets of Yikunyin were obtained from the Traditional Chinese Medicine Systems Pharmacology database, whereas the targets related to menopausal syndrome were obtained from GeneCards, PharmGKB, Therapeutic Target Database (TTD), and Comparative Toxicogenomics Database (CTD). To reveal the pharmacological mechanism, the component-target and the intersecting protein-protein interaction (PPI) networks were constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Finally, molecular docking was carried out to assess the strength of binding between the key active ingredients and key targets. Results: A total of 418 targets and 121 active ingredients were identified in Yikunyin. The intersection of Yikunyin's 418 targets with the 2822 targets related to menopausal syndrome shows that there are 247 common targets that can be considered potential targets of Yikunyin in the treatment of menopausal syndrome. The topology analysis of the constructed PPI network conducted using the Cytoscape software shows that there are 15 hub genes implicated in the therapeutic effect of Yikunyin: AKT1, PRKCA, TLR9, CXCL10, PRKCD, PARP1, ABCB1, TP53, CAV1, MAPK8, PPARA, GRB2, EGFR, IL-6, and JAK2. Moreover, the key active components acting on these genes are paeoniflorin, luteolin, quercetin, beta-sitosterol, and kaempferol. GO and KEGG analyses indicate that Yikunyin can treat menopausal syndrome by regulating cellular response to chemical stress (GO:0062197), cellular response to oxidative stress (GO:0034599), phosphatase binding (GO:0019902), cytokine receptor binding (GO:0005126), PI3K-Akt signaling (hsa04151), lipid and atherosclerosis (hsa05417), and hepatitis B (hsa05161). Finally, the results of molecular docking suggest that the key active ingredients and key targets can bind well, with binding energies of less than -5 kJ/mol. Conclusion: The research conducted herein reveals that Yikunyin treats menopausal syndrome by targeting AKT1 and IL-6 and by regulating the PI3K-Akt signaling pathway. Moreover, it provides a new idea for understanding the therapeutic effects of traditional Chinese medicines.

Mitochondrial analysis of oribatid mites provides insights into their atypical tRNA annotation, genome rearrangement and evolution.

BACKGROUND: The mitochondrial (mt) genomes of Sarcoptiformes mites typically contain 37 genes. Although the loss of genes is rare in Sarcoptiformes mite mitogenomes, two of the six previously reported oribatid mites (Acariforms: Sarcoptiformes) are reported to have lost parts of their tRNA genes. To confirm whether the tRNA genes were indeed lost and whether the loss is universal, we re-annotated the available oribatid mite sequences and sequenced the mitogenome of Oribatula sakamorii. METHODS: The mitogenome of O. sakamorii was sequenced using an Illumina HiSeq sequencer. The mt tRNA gene was annotated using multi-software combined with a manual annotation approach. Phylogenetic analyses were performed using the maximum likelihood and Bayesian inference methods with concatenated nucleotide and amino acid sequences. RESULTS: The mitogenomes of O. sakamorii contained 37 genes, including 22 tRNA genes. We identified all mt tRNA genes that were reported as "lost" in Steganacarus magnus and Paraleius leontonychus and revealed certain atypical tRNA annotation errors in oribatid mite sequences. Oribatid mite mitogenomes are characterized by low rates of genetic rearrangement, with six or seven gene blocks conserved between the mitogenome of all species and that of ancestral arthropods. Considering the relative order of the major genes (protein-coding genes and rRNAs), only one or two genes were rearranged with respect to their positions in the ancestral genome. We explored the phylogenetic relationships among the available oribatid mites, and the results confirmed the systematic position of Hermannia in the Crotonioidea superfamily. This was also supported by the synapomorphic gene-derived boundaries. CONCLUSIONS: The tRNA "lost" phenomenon is not universal in oribatid mites. Rather, highly atypical secondary structure of the inferred mt tRNA genes made them unidentifiable using a single type of tRNA search program. The use of multi-software combined with a manual annotation approach can improve the accuracy of tRNA gene annotation. In addition, we identified the precise systematic position of Hermannia and validated that Astigmata is nested in Oribatida.

De novo sequence of the mitochondrial genome of Tyrophagus putrescentiae (Acari: Sarcoptiformes) including 22 tRNA sequences and the largest non-coding region.

In this study, we de novo sequenced and analyzed the circular mitochondrial genome (mitogenome) of Tyrophagus putrescentiae. It was 14,156 bp long and contained a complete set of 37 genes, contrary to the initial published sequences; it included 22 tRNA sequences and the largest non-coding region. The mtDNA gene order of T. putrescentiae was found to be identical to that of Aleuroglyphus ovatus, Caloglyphus berlesei, and Rhizoglyphus robini (all Acaroidea). Most tRNAs of T. putrescentiae lack at least a D-arm or T-arm. Tyrophagus putrescentiae tRNAs also shared considerable structural and sequence similarity with the tRNAs of other reported Acaroidea species that have the full set of tRNAs. The largest non-coding region was located between trnF and trnS1, and it contained a microsatellite-like (AT)n sequence, short palindromic sequences, and several hairpin loops, as observed in other reported Acaroidea species (excepting Tyrophagus longior).

[A multi-center, randomized, double-blind, placebo-controlled trial of glyceryl trinitrate ointment in the treatment of anal fissure].

OBJECTIVE: To evaluate the clinical efficacy and safety of glyceryl trinitrate (GTN) ointment in the treatment of anal fissure. METHODS: In this multi-center, randomized, double-blind and placebo-controlled trial, 240 chronic anal fissure patients from 7 clinical centers were randomized to receive eight-week treatment with GTN ointment (treatment group) or vaseline ointment (control group) respectively. Healing rate, visual analogue score (VAS), maximum anal resting pressure (MARP) and adverse reactions were recorded and compared. RESULTS: A total of 221 patients (92.1%) finished the trial, including 114 patients in treatment group (95.0%, 114/120) and 107 in control group (89.2%, 107/120). At the endpoint of treatment (56 d), 90 patients in treatment group (78.9%, 90/114) healed completely compared to 31 patients in control group (29.0%, 31/107), and decrease rates of VAS in the two groups were (94.8±15.7)% and (61.2±35.7)% respectively, both differences were statistically significant (P<0.01). MARP after first administration was (20.2±18.5) mm Hg in treatment group (n=12) and (7.1±14.7) mm Hg in control group (n=6), which was not significantly different (P=0.152). Adverse reaction incidence was higher in treatment group (42.1% vs. 9.3%, P<0.05), while these adverse reactions were mainly headache and fullness in head, which were self-limiting. CONCLUSION: GTN ointment can effectively promote healing and relieve pain in anal fissure with safety and tolerance.