Formononetin improves the inflammatory response and bone destruction in knee joint lesions by regulating the NF-kB and MAPK signaling pathways.

Formononetin (FMN) is a phytoestrogen that belongs to the isoflavone family. It has antioxidant and anti-inflammatory effects, as well as, many other biological activities. Existing evidence has aroused interest in its ability to protect against osteoarthritis (OA) and promote bone remodeling. To date, research on this topic has not been thorough and many issues remain controversial. Therefore, the purpose of our study was to explore the protective effect of FMN against knee injury and clarify the possible molecular mechanisms. We found that FMN inhibited osteoclast formation induced by receptor activator of NF-κB ligand (RANKL). Inhibition of the phosphorylation and nuclear translocation of p65 in the NF-κB signaling pathway plays a role in this effect. Similarly, during the inflammatory response of primary knee cartilage cells activated by IL-1ß, FMN inhibited the NF-κB signaling pathway and the phosphorylation of the ERK and JNK proteins in the MAPK signaling pathway to suppress the inflammatory response. In addition, in vivo experiments showed that both low- and high-dose FMN had a clear protective effect against knee injury in the DMM (destabilization of the medial meniscus) model, and the therapeutic effect of high-dose FMN was stronger. In conclusion, these studies provide evidence of the protective effect of FMN against knee injury.

Evaluation of the effect of the capitation compensation mechanism among pulmonary tuberculosis patients with a full period of treatment.

BACKGROUND: PTB is an infectious disease, which not only seriously affects people's health, but also causes a heavier disease economic burden on patients. At present, reform of the medical insurance payment can be an effective method to control medical expenses. Therefore, our study is to explore the compensation mechanism for pulmonary tuberculosis (PTB) patients with a full period of treatment, to alleviate the financial burden of PTB patients and provide a reference and basis for the reform of PTB payment methods in other regions and countries. METHODS: The quantitative data of PTB patients was collected from the first half of 2015 to the first half of 2018 in Dehui Tuberculosis Hospital in Jilin Province, and medical records of PTB patients registered in the first half of 2018 (n = 100) from the hospital was randomly selected. Descriptive analysis of these quantitative data summarized the number, cost, medication and compliance. Semi-structured in depth interviews with policymakers and physicians were conducted to understand the impact of interventions and its causes. RESULTS: After implementation of the compensation mechanism, the number of PTB patient visits in 2018 was increased by 14.2%, average medical costs for outpatients and inpatients were significantly reduced by 31.8% and 47.0%, respectively, and the auxiliary medication costs was reduced by 36.5%. Moreover, the hospital carried out standardized management of tuberculosis, and the patient compliance was very high, reaching almost 90%. CONCLUSIONS: The capitation compensation mechanism with a full period of treatment was a suitable payment method for PTB, and it is worthy of promotion and experimentation. In addition, the model improved patient compliance and reduced the possibility of drug-resistant PTB. However, due to the short implementation time of the model in the pilot areas, the effect remains to be further observed and demonstrated.

Genome-wide analysis of DNA methylation in soybean.

Cytosine methylation is an important mechanism for dynamical regulation of gene expression and transposable element (TE) mobility during plant developmental processes. Here, we identified the transcription start sites of genes using high-throughput sequencing and then analyzed the DNA methylation status in soybean roots, stems, leaves, and cotyledons of developing seeds at single-base resolution. Profiling of DNA methylation in different organs revealed 2162 differentially methylated regions among organs, and a portion of hypomethylated regions were correlated with high expression of neighboring genes. Because of the different distribution of class I TEs (retrotransposons) and class II TEs (DNA transposons), the promoters of the lowest-expressed genes showed higher levels of CG and CHG methylation but a lower level of CHH methylation. We further found that the CHH methylation level of class II TEs was higher than class I TEs, possibly due to the presence of more smRNAs in class II TEs. In cotyledons of developing seeds, smRNA abundance was roughly positively correlated with hypermethylated regions but negatively related to hypomethylated regions. These studies provide significant insights into the complicated interplays among DNA methylation, smRNA abundance, TE distribution, and gene expression in soybean.

Identification of miRNAs and their target genes in developing soybean seeds by deep sequencing.

BACKGROUND: MicroRNAs (miRNAs) regulate gene expression by mediating gene silencing at transcriptional and post-transcriptional levels in higher plants. miRNAs and related target genes have been widely studied in model plants such as Arabidopsis and rice; however, the number of identified miRNAs in soybean (Glycine max) is limited, and global identification of the related miRNA targets has not been reported in previous research. RESULTS: In our study, a small RNA library and a degradome library were constructed from developing soybean seeds for deep sequencing. We identified 26 new miRNAs in soybean by bioinformatic analysis and further confirmed their expression by stem-loop RT-PCR. The miRNA star sequences of 38 known miRNAs and 8 new miRNAs were also discovered, providing additional evidence for the existence of miRNAs. Through degradome sequencing, 145 and 25 genes were identified as targets of annotated miRNAs and new miRNAs, respectively. GO analysis indicated that many of the identified miRNA targets may function in soybean seed development. Additionally, a soybean homolog of Arabidopsis suppressor of gene silencing 3 (AtSGS3) was detected as a target of the newly identified miRNA Soy_25, suggesting the presence of feedback control of miRNA biogenesis. CONCLUSIONS: We have identified large numbers of miRNAs and their related target genes through deep sequencing of a small RNA library and a degradome library. Our study provides more information about the regulatory network of miRNAs in soybean and advances our understanding of miRNA functions during seed development.