Multiomics Reveals the Effect of Root Rot on Polygonati Rhizome and Identifies Pathogens and Biocontrol Strain.

Root (rhizome) rot of Polygonatum plants has received substantial attention because it threatens yield and sustainable utilization in the polygonati rhizome industry. However, the potential pathogens that cause rhizome rot as well as the direct and indirect (via root-associated microbes) strategies by which Polygonatum defends against pathogens remain largely unknown. Herein, we used integrated multiomics of plant-targeted metabolomics and transcriptomics, microbiome, and culture-based methods to systematically investigate the interactions between the Polygonatum cyrtonema Hua root-associated microbiota and pathogens. We found that root rot inhibited P. cyrtonema rhizome growth and that the fresh weight significantly decreased (P < 0.001). The transcriptomic and metabonomic results showed that the expression of differentially expressed genes (DEGs) related to specialized metabolic and systemic resistance pathways, such as glycolysis/gluconeogenesis and flavonoid biosynthesis, cycloartenol synthase activity (related to saponin synthesis), mitogen-activated protein kinase (MAPK) signaling, and plant hormone signal transduction, was particularly increased in diseased rhizomes. Consistently, the contents of lactose, d-fructose, sarsasapogenin, asperulosidic acid, botulin, myricadoil, and other saponins, which are functional medicinal compounds present in P. cyrtonema rhizomes, were also increased in diseased plants infected with rhizome rot. The microbiome sequencing and culture results showed that root rot disrupted the P. cyrtonema bacterial and fungal communities and reduced the microbial diversity in the rhizomes and rhizosphere soil. We further found that a clear enrichment of Streptomyces violascens XTBG45 (HJB-XTBG45) in the healthy rhizosphere could control the root rot caused by Fusarium oxysporum and Colletotrichum spaethianum. Taken together, our results indicate that P. cyrtonema can modulate the plant immune system and metabolic processes and enrich beneficial root microbiota to defend against pathogens. IMPORTANCE Root (rhizome or tuber) reproduction is the main method for the agricultural cultivation of many important cash crops, and infected crop plants rot, exhibit retarded growth, and experience yield losses. While many studies have investigated medicinal plants and their functional medicinal compounds, the occurrence of root (rhizome) rot of plant and soil microbiota has received little attention. Therefore, we used integrated multiomics and culture-based methods to systematically study rhizome rot on the famous Chinese medicine Polygonatum cyrtonema and identify pathogens and beneficial microbiota of rhizome rot. Rhizome rot disrupted the Polygonatum-associated microbiota and reduced microbial diversity, and rhizome transcription and metabolic processes significantly changed. Our work provides evidence that rhizome rot not only changes rhizome transcription and functional metabolite contents but also impacts the microbial community diversity, assembly, and function of the rhizome and rhizosphere. This study provides a new friendly strategy for medicinal plant breeding and agricultural utilization.

Therapeutic Effect and Mechanism Study of Rhodiola wallichiana var. cholaensis Injection to Acute Blood Stasis Using Metabolomics Based on UPLC-Q/TOF-MS.

In traditional Chinese medicine theory, blood stasis syndrome (BSS), characterized by blood flow retardation and blood stagnation, is one of the main pathologic mechanisms and clinical syndromes of cardiovascular diseases (CVDs). Rhodiola wallichiana var. cholaensis injection (RWCI) is made from dry roots and stems of RWC via the processes of decoction, alcohol precipitation, filtration, and dilution. Studies indicated the extracts of RWC could alleviate CVDs; however, the mechanism had not been illustrated. In the present study, the acute blood stasis rat model was established to investigate the pathogenesis of BSS and the therapeutic mechanism of RWCI against BSS. Hemorheological parameters (whole blood viscosity and plasma viscosity) and inflammatory factors (TNF-α and IL-6) were used to evaluate the success of the BSS rat model and RWCI efficacy. 14 and 33 differential metabolites were identified from plasma and urine samples using the metabolomics approach based on ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The results of multivariate analysis displayed that there were significant separations among model, control, and treatment groups, but the high-dose RWCI treatment group was closer to the control group. 9 perturbed metabolic pathways were related to BSS's development and RWCI intervention. 5 metabolic pathways (arachidonic acid metabolism, linoleic acid metabolism, alpha-linolenic acid metabolism, retinol metabolism, and steroid hormone biosynthesis) showed apparent correlations. These differential metabolites and perturbed metabolic pathways might provide a novel view to understand the pathogenesis of BSS and the pharmacological mechanism of RWCI.

Phenotype-Specific Therapeutic Effect of Rhodiola wallichiana var. cholaensis Combined with Dexamethasone on Experimental Murine Asthma and Its Comprehensive Pharmacological Mechanism.

The heterogeneity of asthma involves complex pathogenesis leading to confusion regarding the choice of therapeutic strategy. In the clinic, asthma is commonly classified as having either eosinophilic asthma (EA) or non-eosinophilic asthma (NEA) phenotypes. Microbiota colonizing in airways has been demonstrated to induce distinct phenotypes of asthma and the resistance to steroids. Rhodiola wallichiana var. cholaensis (RWC) has the potential to alleviate asthmatic inflammation according to recent studies, but its pharmacological mechanisms remain unclarified. In our study, murine asthmatic phenotypes were established and treated with RWC and/or dexamethasone (DEX). Combined treatment with RWC and DEX could improve spirometry and airway hyperresponsiveness (AHR) in asthmatic phenotypes, alleviate steroid resistance in NEA, and reduce the inflammatory infiltration of the both phenotypes. The combined treatment increased Th1, regulated the imbalance of Th2/Th1, and decreased the related cytokines in EA. As for NEA, the combined treatment reduced Th17 and promoted the accumulation of regulatory T cells (Tregs) in lung. A microbiome study based on 16S rDNA sequencing technique revealed the significantly changed structure of the lower airway microbiota after combined treatment in NEA, with 4 distinct genera and 2 species identified. OPLS-DA models of metabolomics analysis based on UPLC-Q/TOF-MS technique identified 34 differentiated metabolites and 8 perturbed metabolic pathways. A joint multiomics study predicted that the colonized microbiota in airways might be associated with susceptibility of asthma and steroid resistance, which involved systematic and pulmonary metabolic perturbation. In summary, the pharmacological network of RWC included the complicated interaction mechanisms of immune regulation, microbiota change, and metabolic perturbation.

Protective effect of amygdalin on epithelial-mesenchymal transformation in experimental chronic obstructive pulmonary disease mice.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory pulmonary disease characterized by continuous, progressive limitation of airflow. Airway remodelling, which is correlated with epithelial-mesenchymal transitions (EMTs), is a typical pathophysiological change of COPD. Amygdalin, an active ingredient in the traditional Chinese medicine bitter almond with extensive pharmacological effects, was shown to inhibit tissue fibrosis in recent studies. In this study, a human bronchial epithelial cell line (BEAS-2B) and mice were exposed to cigarette smoke, and EMT levels were investigated after treatment with different concentrations of amygdalin. Morphology was assessed by immunohistochemical staining. Evaluation of the expression of TGF-ß1, smad2/3, and p-smad2/3 in lung tissue was conducted out via ELISA, Western blot, and real-time PCR. The results showed that E-cadherin expression was significantly increased, whereas vimentin, TGF-ß1, and phosphorylated smad2/3 (p-smad2/3) expression was markedly decreased in the amygdalin-treated groups compared with the model group. Therefore, our study demonstrated a protective role of amygdalin in the murine EMT process after COPD.

Inhibitory Effect of Methotrexate on Rheumatoid Arthritis Inflammation and Comprehensive Metabolomics Analysis Using Ultra-Performance Liquid Chromatography-Quadrupole Time of Flight-Mass Spectrometry (UPLC-Q/TOF-MS).

Rheumatoid arthritis (RA) is a common autoimmune disease. The inflammation in joint tissue and system endanger the human health seriously. Methotrexate have exhibited a satisfactory therapeutic effect in clinical practice. The aim of this research was to establish the pharmacological mechanism of methotrexate on RA therapy. Collagen induced arthritic rats were used to identify how methotrexate alleviates inflammation in vivo. Lipopolysaccharide-induced inflammatory proliferation in macrophages was also be detected in vitro. The activation level of Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Nucleotide binding domain and leucine-rich repeat pyrin 3 domain (NLRP3)/Caspase-1 and related cytokines were examined by real-time PCR and western blotting or quantified with the enzyme-linked immunosorbent assay. Comprehensive metabolomics analysis was performed to identify the alteration of metabolites. Results showed that treating with methotrexate could alleviate the inflammatory condition, downregulate the activation of NF-κB and NLRP3/Caspase-1 inflammatory pathways and reduce the level of related cytokines. Docking interaction between methotrexate and caspase-1 was visualized as six H-bonds indicating a potential inhibitory effect. Metabolomics analysis reported three perturbed metabolic inflammation related pathways including arachidonic acid, linoleic acid and sphingolipid metabolism. These findings indicated that methotrexate could inhibit the onset of inflammation in joint tissue by suppressing the activation of NF-κB and NLRP3/Caspase-1 pathways and regulating the inflammation related metabolic networks.

Obesity-Related Asthma: Immune Regulation and Potential Targeted Therapies.

Obesity, one of the most severe public health problems of the 21st century, is a common metabolic syndrome due to excess body fat. The incidence and severity of obesity-related asthma have undergone a dramatic increase. Because obesity-related asthma is poorly controlled using conventional therapies, alternative and complementary therapies are urgently needed. Lipid metabolism may be abnormal in obesity-related asthma, and immune modulation therapies need to be investigated. Herein, we describe the immune regulators of lipid metabolism in obesity as well as the interplay of obesity and asthma. These lay the foundations for targeted therapies in terms of direct and indirect immune regulators of lipid metabolism, which ultimately help provide effective control of obesity-related asthma with a feasible treatment strategy.

Improved refining properties of pulps pretreated with ionic liquids under mild conditions.

Imidazolium-based ionic liquids (ILs), including 1-butyl-3-methylimidazolium chloride (BmimCl) and 1-allyl-3-methylimidazolium chloride (AmimCl), were used to improve the refining properties of pulps under mild conditions. Results showed that the macro appearance of pulps was virtually unchanged after pretreatment with ILs under mild conditions. In addition, chemical pulps pretreated with ILs are more suitable for pretreatment than chemimechanical pulps. Pretreatment with ILs facilitates the refining process by destroying hydrogen bonds, which exist extensively in fiber. At the same refining energy input, the Canada standard freeness (CSF) of refined pulp decreased with improved fiber quality. At identical CSF values, the energy consumed during refining significantly decreased because ILs pretreatment facilitated swelling and fibrillation. The viscosity of cellulose changed slightly after IL pretreatment. However, the crystallinity index and fines content decreased, and the micro appearance of the fiber surface changed. BmimCl has a stronger swelling influence on pulp than AmimCl under optimal conditions.