BpAFP, a Broussonetia papyrifera latex chitinase, exhibits a dual role in resisting to both Verticillium wilt disease and lepidopterous pests, Plutella xylostella and Prodenia litura.

Paper mulberry (Broussonetia papyrifera) is a fast-growing tree known for its tolerance to diverse biotic and abiotic stresses. To explore genes combating Verticillium wilt, a devasting and formidable disease damage to cotton and many economically significant crops, we purified an antifungal protein, named BpAFP, from the latex of paper mulberry. Based on peptide fingerprint, we cloned the full cDNA sequence of BpAFP and revealed that BpAFP belongs to Class I chitinases, sharing 74 % identity with B. papyrifera leaf chitinase, PMAPII. We further introduced BpAFP into Arabidopsis, tobacco, and cotton. Transgenic plants exhibited significant resistance to Verticillium wilt. Importantly, BpAFP also demonstrated insecticidal activity against herbivorous pests, Plutella xylostella, and Prodenia litura, when feeding the larvae with transgenic leaves. Our finding unveils a dual role of BpAFP in conferring resistance to both plant diseases and lepidopterous pests.

Identifying potential biomarkers of idiopathic pulmonary fibrosis through machine learning analysis.

Idiopathic pulmonary fibrosis (IPF) is the most common and serious type of idiopathic interstitial pneumonia, characterized by chronic, progressive, and low survival rates, while unknown disease etiology. Until recently, patients with idiopathic pulmonary fibrosis have a poor prognosis, high mortality, and limited treatment options, due to the lack of effective early diagnostic and prognostic tools. Therefore, we aimed to identify biomarkers for idiopathic pulmonary fibrosis based on multiple machine-learning approaches and to evaluate the role of immune infiltration in the disease. The gene expression profile and its corresponding clinical data of idiopathic pulmonary fibrosis patients were downloaded from Gene Expression Omnibus (GEO) database. Next, the differentially expressed genes (DEGs) with the threshold of FDR < 0.05 and |log2 foldchange (FC)| > 0.585 were analyzed via R package "DESeq2" and GO enrichment and KEGG pathways were run in R software. Then, least absolute shrinkage and selection operator (LASSO) logistic regression, support vector machine-recursive feature elimination (SVM-RFE) and random forest (RF) algorithms were combined to screen the key potential biomarkers of idiopathic pulmonary fibrosis. The diagnostic performance of these biomarkers was evaluated through receiver operating characteristic (ROC) curves. Moreover, the CIBERSORT algorithm was employed to assess the infiltration of immune cells and the relationship between the infiltrating immune cells and the biomarkers. Finally, we sought to understand the potential pathogenic role of the biomarker (SLAIN1) in idiopathic pulmonary fibrosis using a mouse model and cellular model. A total of 3658 differentially expressed genes of idiopathic pulmonary fibrosis were identified, including 2359 upregulated genes and 1299 downregulated genes. FHL2, HPCAL1, RNF182, and SLAIN1 were identified as biomarkers of idiopathic pulmonary fibrosis using LASSO logistic regression, RF, and SVM-RFE algorithms. The ROC curves confirmed the predictive accuracy of these biomarkers both in the training set and test set. Immune cell infiltration analysis suggested that patients with idiopathic pulmonary fibrosis had a higher level of B cells memory, Plasma cells, T cells CD8, T cells follicular helper, T cells regulatory (Tregs), Macrophages M0, and Mast cells resting compared with the control group. Correlation analysis demonstrated that FHL2 was significantly associated with the infiltrating immune cells. qPCR and western blotting analysis suggested that SLAIN1 might be a signature for the diagnosis of idiopathic pulmonary fibrosis. In this study, we identified four potential biomarkers (FHL2, HPCAL1, RNF182, and SLAIN1) and evaluated the potential pathogenic role of SLAIN1 in idiopathic pulmonary fibrosis. These findings may have great significance in guiding the understanding of disease mechanisms and potential therapeutic targets in idiopathic pulmonary fibrosis.

Multiform-based Baduanjin exercise prevention and treatment for idiopathic pulmonary fibrosis: study protocol for a randomized controlled trial.

INTRODUCTION: In this study, we will combine the traditional Baduanjin with Yijin Jing and Wuqinxi to create an optimized Baduanjin exercise program with three different forms (vertical, sitting, and horizontal) to adapt to idiopathic pulmonary fibrosis (IPF) patients in vairous stages of the disease. The purpose of this study is to explore and compare the therapeutic effects of this multi-form Baduanjin, traditional Baduanjin, and resistance training on lung function and limb motor function in IPF patients. The goal of this study is to prove a novel optimal exercise prescription strategy of Baduanjin exercise for improving and protecting lung function in IPF patients. METHODS/DESIGN: A single-blind and randomized controlled trial is used to conduct this study, while the randomization list will be generated using a computerized random number generator and opaque sealed envelopes with group allocation will be prepared. It will be strictly followed to blind the outcome assessors. and until the experiment's conclusion, participants won't know which group they are enrolled in. Patients between the ages of 35 and 80 who have stable diseases and have not regularly practiced Baduanjin exercise in the past will be included. They are divvied up into the following five groups at random: (1) The conventional care group (control group, CG), (2) The traditional Baduanjin exercise group (TG), (3) The modified Baduanjin exercise group (IG), (4) The resistance exercise group (RG) (5) The modified Baduanjin exercise combined with resistance exercise group (IRG). Those CG participants only received the usual treatment, while TC, IG, and RG participants exercised 1 h twice a day for 3 months. MRG participants will have a 3-month intervention with 1 h of Modified Baduanjin Exercise and 1 H of Resistance Training for each day. Every week, all groups underwent will supervis one-day training, with the exception of the control group. The Pulmonary Function Testing (PFT), HRCT, and 6MWT are the main outcome variables. The St. George Respiratory Questionnaire and mMRC are used as secondary outcome measures. DISCUSSION: This study may produce a new Baduanjin exercise prescription that is user-friendly, simple to execute, more targeted, and adaptable. Because it consists of three forms, including vertical, sitting, and horizontal, it is more adaptable to the various disease stages and actual situations of IPF patients and may compensate for the shortcomings of conventional pulmonary rehabilitation and traditional Baduanjin. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200055559 . Registered on 12 January 2022.

Quantification of 3-bromopyruvate in rat plasma by HPLC-MS/MS employing precolumn derivatization and the application to a pharmacokinetics study.

A simple high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been developed for the determination of 3-bromopyruvate (3-BrPA) in rat plasma for the first time. The analytes were separated on a C18 column (100 × 2.1 mm, 1.7 µm) and a triple-quadrupole mass spectrometry equipped with an electrospray ionization source was applied for detection. 3-BrPA was extracted from rat plasma with protein precipitation, and then derivatized with 4-nitro-1,2-phenylenediamine to obtain the mass signal because 3-BrPA could not be detected in mass spectrometry. The method was fully validated according to the US Food and Drug Administration guidance. The method was linear over the concentration range 0.5-1,000.0 ng/ml for 3-BrPA. The precision and accuracy, extraction recovery, and matrix effect were within acceptable limits. The method was then applied to support a pharmacokinetic study after 3-BrPA and 3-BrPA-l-Val-l-Ile (a dipeptide prodrug of 3-BrPA, 3-BrPA-l-Valine-l-isoleucine) had been administered to the Sprague-Dawley rats, respectively.

Renal Protective Mechanisms of Shenyuan Particle in Db/Db Mice: A Study Based on Network Pharmacology.

Aim: The renal protective mechanisms of Shenyuan particle (SYP) in the treatment of diabetic kidney disease (DKD) were investigated, focusing on the main targets and pathways. Materials and Methods: In this study, the potential targets of compounds identified in SYP were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and a "herb-compound-target" network was constructed via Cytoscape. Next, the Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were dissected using R language. A protein-protein interaction network was fabricated using STRING to obtain the main target information. In addition, db/db mice were used as the DKD models to explore the renal protective effects of SYP. Transmission electron microscopy, western blot, pathological staining, TUNEL staining, and biochemical methods were used to identify the apoptotic pathways and establish the primary mechanism of SYP. Results: Network pharmacology analysis revealed 67 potential targets based on the analysis of different databases. The targets of SYP were primarily associated with apoptosis. The network hub genes included caspase 3, caspase 7, caspase 8, caspase 9, Bax, and Bcl-2. In vivo, SYP materially improved renal function and inhibited apoptosis in the db/db mouse kidneys by improving the mitochondrial health. In addition, our results showed that SYP significantly decreased the expression of Bax, caspase 3, and Cyto-c and increased the expression of Bcl-2. Conclusions: Network pharmacology analysis and experimental results suggest that SYP ameliorates DKD mediated via multiple components, targets, and pathways. Our study further demonstrates that SYP inhibits apoptosis in the kidneys of db/db mice by improving the mitochondrial health and thereby alleviating renal damage.

Identification of key genes and microRNAs for multiple sclerosis using bioinformatics analysis.

ABSTRACT: To better understand the molecular mechanism underlying the pathogenesis of multiple sclerosis (MS), we aimed to identify the key genes and microRNAs (miRNA) associated with MS and analyze their interactions. Differentially expressed genes (DEGs) and miRNAs (DEMs) based on the gene miRNA dataset GSE17846 and mRNA dataset GSE21942 were determined using R software. Next, we performed functional enrichment analysis and constructed a protein-protein interaction network. Data validation was performed to ensure the reliability of hub genes. The miRNA-mRNA regulatory network was constructed. In total, 47 DEMs and 843 DEGs were identified. Protein-protein interaction network analysis identified several hub genes, including JUN, FPR2, AKT1, POLR2L, LYZ, CXCL8, HBB, CST3, CTSZ, and MMP9, especially LYZ and CXCL8. We constructed an miRNA-mRNA regulatory network and found that hsa-miR-142-3p, hsa-miR-107, hsa-miR-140-5p, and hsa-miR-613 were the most important miRNAs. This study reveals some key genes and miRNAs that may be involved in the pathogenesis of MS, providing potential targets for the diagnosis and treatment of MS.

Fourteen small molecule and biological agents for psoriatic arthritis: A network meta-analysis of randomized controlled trials.

BACKGROUND: The comparative efficacy and safety of small molecule and biological agents in the treatment of psoriatic arthritis (PsA) remain unknown. OBJECTIVES: To compare the efficacy and safety of 14 small molecule and biological agents by network meta-analysis (NMA). METHODS: Relevant randomized controlled trials involving biological treatments for PsA were identified by searching PubMed, Cochrane Library, EMBASE, Web of Science, and Clinicaltrials.gov and by manual retrieval, up to June 2018. NMA was conducted with Stata 14.0 based on the frequentist method. Effect measures were odds ratios (ORs) with 95% confidence intervals (CIs). Intervention efficacy and safety were ranked according to the surface under the cumulative ranking curve (SUCRA). RESULTS: A total of 30 studies involving 10,191 adult subjects were included. According to NMA, ≥ 20% improvement in modifed American College of Rheumatology response criteria (ACR20) response, Psoriasis Area and Severity Index 75 (PASI75) response, and serious adverse events rate (SAEs) were observed. In direct comparisons, most of the biologics performed better than placebo in terms of ACR20 response rate and PASI75 response rate. Additionally, all medicines were comparable to placebo in terms of SAEs except secukinumab. In terms of mixed comparisons, with regard to the ACR20 response, etanercept (ETN) and infliximab (IFX) were more effective than golimumab (GOL), with ORs of 3.33 (95% CI: 1.17-9.48) and 1.24 (95% CI: 0.61-2.52), respectively. For PASI75 response, IFX was superior to certolizumab pegol (OR = 10.08, 95% CI: 1.54-75.48). In addition, these medicines were comparable to each other in terms of SAEs. ETN and IFX were shown to have the most favorable SUCRA for achieving improved ACR20 and PASI75 responses, respectively, while ABT-122 exhibited the best safety according to the SUCRA for SAEs. Considering both the efficacy (ACR20, PASI75) and safety (SAEs), GOL, ETN, and IFX are the top 3 treatments. CONCLUSIONS AND IMPLICATIONS: Direct and indirect comparisons and integrated results suggested that the 3 anti- tumor necrosis factor -α biologics (GOL, ETN, and IFX) can be considered the best treatments for PsA after comprehensive consideration of efficacy and safety.

lncRNA­MM2P downregulates the production of pro­inflammatory cytokines in acute gouty arthritis.

Acute gouty arthritis (AGA) is characterized by the accumulation of pro­inflammatory cytokines, which are immunological responses to monosodium urate (MSU) crystals. It has been demonstrated that long non­coding RNA (lncRNA)­MM2P is a novel regulator of M2 polarization of macrophages. The aim of the present study was to investigate whether lncRNA­MM2P regulates the MSU­induced inflammatory process. In cell models of RAW 264.7 and THP­1­derived macrophages, decreased expression of lncRNA­MM2P was observed in lipopolysaccharide­ and MSU­treated macrophages, which was accompanied with obvious inflammatory responses. Using small interfering RNA to knockdown lncRNA­MM2P led to the upregulation of MSU­mediated inflammatory responses, both in RAW 264.7 and THP­1­derived macrophages. In conclusion, lncRNA­MM2P could be an important regulator of MSU­induced inflammation, and therefore could be involved in the development of AGA.

Correction to: Effects of miR-150-5p on the growth and SOCS1 expression of rheumatoid arthritis synovial fibroblasts.

The first name of the co-author of the above article was presented incorrect in the published version. The author name "Miangliang Qiu" should read "Mingliang Qiu" as mentioned above.

Effects of miR-150-5p on the growth and SOCS1 expression of rheumatoid arthritis synovial fibroblasts.

OBJECTIVE: miR-150-5p has been implicated in the regulation and onset of immune diseases. We investigated the effects of miR-150-5p on the functions of RA synovial fibroblasts (RASFs). METHOD: The binding site between suppressor of cytokine signaling 1 (SOCS1) and miR-150-5p was analyzed using European Bioinformatics Institute database, and the 3' UTR of SOCS1 mRNA, including the binding site, was amplified and ligated to the 3'-end of LUC2 gene in the pmirGL0 dual-luciferase vector. The pmirGL0 vector and corresponding mimics were subsequently co-transfected into 293T cells to compare the relative fluorescence intensity of LUC2 between the miR-150-5p mimics and the negative control (NC) mimics groups. Further, the RASF cell line MH7A was transfected with miR-150-5p or NC mimics and subjected to flow cytometric analysis, cell counting kit-8 assay, western blot analysis, qPCR, and enzyme-linked immunosorbent (ELISA) assay 48 h after transfection. RESULTS: miR-150-5p mimics resulted in a lower cell apoptotic rate and proportion of cells in the S phase. Using a dual-luciferase reporter gene assay, we then found that SOCS1 is a potential target of miR-150-5p. Compared with NC mimics, miR-150-5p mimics significantly decreased the protein and mRNA expression levels of SOCS1. ELISA assay showed that miR-150-5p mimics increased interleukin-6 level in the cell culture medium but did not influence tumor necrosis factor-alpha levels. CONCLUSIONS: Overall, the growth-promoting effect of miR-150-5p on MH7A cells may be attributed to the miR-150-5p-induced degradation of SOCS1 mRNA, suggesting a potential therapeutic target for RA.Key Points• SOCS1 is a potential target of miR-150-5p.• miR-150-5p promoted the growth of RASF cell line MH7A.• miR-150-5p increased the secretion of IL-6 but did not significantly affect TNF-α levels in MH7A cells.