Banxia Xiexin decoction promotes gastric lymphatic pumping by regulating lymphatic smooth muscle cell contraction and energy metabolism in a stress-induced gastric ulceration rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) formula Banxia Xiexin decoction (BXD) has definite therapeutic effect in treating stress-induced gastric ulceration (SIGU) and many other gastrointestinal diseases, but its effect on gastric lymphatic pumping (GLP) remains unclear. AIM OF THE STUDY: Elucidating the role of GLP in SIGU and BXD treatment, and exploring the molecular mechanisms of GLP regulation. MATERIALS AND METHODS: In vivo GLP imaging were performed on SIGU rat model, and the lymphatic dynamic parameters were evaluated. Gastric antrum tissues and serum were collected for macroscopic, histopathological and ulcerative parameters analysis. Gastric lymphatic vessel (GLV) tissues were collected for RNA-Seq assays. Differentially expressed genes (DEGs) were screened from RNA-Seq result and submitted for transcriptomic analysis. Key DEGs and their derivative proteins were measured by qRT-PCR and WB. RESULTS: GLP was significantly suppressed in SIGU rats. BXD could recover GLP, ameliorate stomach lymphostasis, and alleviate the ulcerative damage. Transcriptome analysis of GLV showed the top up-DEGs were concentrated in smooth muscle contraction signaling pathway, while the top the down-DEGs were concentrated in energy metabolism pathways especially fatty acid degradation pathway, which indicated BXD can promote lymphatic smooth muscle contraction, regulate energy metabolism, and reduce fatty acid degradation. The most possible target of these mechanisms was the lymphatic smooth muscle cells (LSMCs) which drove the GLP. This speculation was further validated by the qRT-PCR and WB assessments for the level of key genes and proteins. CONCLUSIONS: By activating the smooth muscle contraction signaling pathway, restoring energy supply, modulating energy metabolism program and reducing fatty acid degradation, BXD effectively recovered GLP, mitigated the accumulation of inflammatory cytokines and metabolic wastes in the stomach, which importantly contributes to its efficacy in treating SIGU.

Hydration and properties of hydrogen-based mineral phase transformation iron ore tailings as supplementary cementitious material.

Almost all iron ore tailings (IOTs) required activation prior to use as SCMs, which limited their application in building materials. This study investigated HMPT-IOTs and discovered that they possess latent hydraulic and pozzolanic properties. In order to better utilize as SCM, mechanical properties, hydration reactions, hydration products, microstructure, and pores were comprehensively studied through mechanical tests, hydration heat tests, XRD, SEM, TG, and MIP. The results show that when HMPT-IOTs replace cement at 10 wt%, 20 wt% and 30 wt%, the compressive strength at 28 days is 41.9 MPa, 47.9 MPa and 37.5 MPa, respectively. When the substitution amount reaches 30 wt%, it will reduce the cumulative heat of hydration and promote early hydration reactions. The main hydration products are ettringite and Ca(OH)2. As the nucleation site of C-S-H, hydration products are interconnected, making the microstructure denser. At this substitution level, Ca(OH)2 consumption was about 2% at 28 days of age. Simultaneously, the total pore volume was only 0.01 mL/g greater than that of the control group, and the number of micropores and transition pores decreased by approximately 3%.

Inhibitory effects and mechanisms of insoluble humic acids on internal phosphorus release from the sediments.

Release of phosphorus (P) from the sediments plays a critical role in the eutrophication of aquatic environments. Humic acids (HA), as the main form of carbon storage in the sediments, has essential impacts on the biogeochemical cycle of phosphorus in aquatic systems. Nevertheless, previous studies mainly concentrated on the competitive adsorption of HA solution and P on metal oxides and soils, with little attention paid to the effects of insoluble humic acids (IHA) on P sorption by and release from the sediments. Herein, an investigation on the rivers and lakes in Sichuan Province, China, found that there was a significantly positive correlation between the maximum P adsorption capacity (Qmax) of sediments and IHA contents (p < 0.01), but a significantly negative correlation between the zero equilibrium P concentration (EPC0) and IHA concentrations (p < 0.01). This indicated that IHA might have an inhibitory effect on the release of P from the sediments, which was verified by batch adsorption experiments and static incubation experiments. Adsorption experiments indicated that IHA can promote P adsorption by sediments. With the increase of IHA addition (from 0 to 20 mg/g) in the sediments, Qmax of sediments increased (from 0.516 to 0.911 mg/g), while EPC0 decreased greatly (from 0.264 to 0.005 mg/L). Increases in Fe (Ⅲ) bound-P, Al bound-P and humic bound-P caused by IHA were responsible for this promoting effect. Incubation experiments illustrated that IHA addition can efficiently inhibit P release from the sediments. After 32 days incubation, P concentration in the overlying water of control group (without IHA addition) was 0.651 mg/L, which was 13.29-40.69 times higher than those (0.016-0.049 mg/L) in the test groups (with 5 %-20 % IHA addition). The analysis of P species in sediments showed that transformation from loosely adsorbed-P and Fe (Ⅲ) bound-P to Al bound-P and humic bound-P was responsible for this inhibition of P release by IHA. This study demonstrated that IHA, differing from readily degradable or dissolved organic matter, have great inhibitory effects on internal P release, which provided a novel insight into the association between carbon burial and internal P release and even the management of water eutrophication.

[Exploration of transcriptome SSR markers and its application in genetic diversity assessment of Asarum sieboldii].

To explore the genetic diversity of Asarum sieboldii this study developed SSR markers based on transcriptome sequencing results and five populations of A.sieboldii from different regions were used as samples for genetic diversity assessment using software such as GenALEx 6.5, NTSYS 2.1, and Structure 2.3.4. The results showed that 16 SSR markers with high polymorphism and good repeatability were selected from the A.sieboldii transcriptome. Primers designed based on the flanking sequences of these markers successfully amplified 56 polymorphic fragments from 150 individual samples of the five A.sieboldii populations. On average, each primer amplified 3.5 polymorphic fragments, ranging from 2 to 8. The mean values of expected heterozygosity(H_e), Shannon's diversity index(I), Nei's gene diversity index(H), and the polymorphic information content(PIC) were 0.172, 0.281, 0.429, and 0.382, respectively. The mean population differentiation coefficient(F_(ST)) was 0.588, consistent with the analysis of molecular variance(AMOVA) results, which indicated greater genetic variation among A.sieboldii populations(69%) than that within populations(31%). The percentage of polymorphic loci(PPL) ranged from highest to lowest as SNJ>LN>SY>SZ>TB. Principal coordinate analysis(PCoA) and UPGMA clustering analysis further revealed genetic clustering of A.sieboldii individuals based on their geographical distribution, consistent with the results of the structure clustering analysis. In summary, the SSR markers developed from the transcriptome effectively assessed the genetic differentiation and population structure of natural A.sieboldii populations, revealing a relatively low genetic diversity in A.sieboldii, with genetic variation primarily observed at the population level and a correlation between population differentiation and geographic distance.

Qili Qiangxin (QLQX) capsule as a multi-functional traditional Chinese medicine in treating chronic heart failure (CHF): A review of ingredients, molecular, cellular, and pharmacological mechanisms.

Chronic heart failure (CHF) is a key part of cardiovascular continuum. Under the guidance of the theory of vessel-collateral doctrine, the present study proposes therapeutic benefits of Qili Qiangxin (QLQX) capsules, an innovative Chinese medicine, on chronic heart failure. The studies show that multiple targets of the drug on CHF, including enhancing myocardial systole, promoting urine excretion, inhibiting excessive activation of the neuroendocrine system, preventing ventricular remodeling by inhibiting inflammatory response, myocardial fibrosis, apoptosis and autophagy, enhancing myocardial energy metabolism, promoting angiogenesis, and improving endothelial function. Investigation on the effects and mechanism of the drug is beneficial to the treatment of chronic heart failure (CHF) through multiple targets and/or signaling pathways. Meanwhile, it provides new insights to further understand other refractory diseases in the cardiovascular continuum, and it also has an important theoretical and practical significance in enhancing prevention and therapeutic effect of traditional Chinese medicine for these diseases.

The facilitating role of phycospheric heterotrophic bacteria in cyanobacterial phosphonate availability and Microcystis bloom maintenance.

BACKGROUND: Phosphonates are the main components in the global phosphorus redox cycle. Little is known about phosphonate metabolism in freshwater ecosystems, although rapid consumption of phosphonates has been observed frequently. Cyanobacteria are often the dominant primary producers in freshwaters; yet, only a few strains of cyanobacteria encode phosphonate-degrading (C-P lyase) gene clusters. The phycosphere is defined as the microenvironment in which extensive phytoplankton and heterotrophic bacteria interactions occur. It has been demonstrated that phytoplankton may recruit phycospheric bacteria based on their own needs. Therefore, the establishment of a phycospheric community rich in phosphonate-degrading-bacteria likely facilitates cyanobacterial proliferation, especially in waters with scarce phosphorus. We characterized the distribution of heterotrophic phosphonate-degrading bacteria in field Microcystis bloom samples and in laboratory cyanobacteria "phycospheres" by qPCR and metagenomic analyses. The role of phosphonate-degrading phycospheric bacteria in cyanobacterial proliferation was determined through coculturing of heterotrophic bacteria with an axenic Microcystis aeruginosa strain and by metatranscriptomic analysis using field Microcystis aggregate samples. RESULTS: Abundant bacteria that carry C-P lyase clusters were identified in plankton samples from freshwater Lakes Dianchi and Taihu during Microcystis bloom periods. Metagenomic analysis of 162 non-axenic laboratory strains of cyanobacteria (consortia cultures containing heterotrophic bacteria) showed that 20% (128/647) of high-quality bins from eighty of these consortia encode intact C-P lyase clusters, with an abundance ranging up to nearly 13%. Phycospheric bacterial phosphonate catabolism genes were expressed continually across bloom seasons, as demonstrated through metatranscriptomic analysis using sixteen field Microcystis aggregate samples. Coculturing experiments revealed that although Microcystis cultures did not catabolize methylphosphonate when axenic, they demonstrated sustained growth when cocultured with phosphonate-utilizing phycospheric bacteria in medium containing methylphosphonate as the sole source of phosphorus. CONCLUSIONS: The recruitment of heterotrophic phosphonate-degrading phycospheric bacteria by cyanobacteria is a hedge against phosphorus scarcity by facilitating phosphonate availability. Cyanobacterial consortia are likely primary contributors to aquatic phosphonate mineralization, thereby facilitating sustained cyanobacterial growth, and even bloom maintenance, in phosphate-deficient waters. Video Abstract.

Effects of Banxia Xiexin Decoction on apoptosis of interstitial cells of Cajal via regulation of MiR-451-5p: An in vivo and in vitro study.

ETHNOPHARMACOLOGICAL RELEVANCE: Banxia Xiexin Decoction (BXD) is a traditional Chinese medical formula applied to gastrointestinal (GI) motility disorders. Previous studies showed that miR-451-5p was down-regulated in rats with GI motility disorders induced by gastric electrical dysrhythmia. Interstitial cells of Cajal (ICCs) are pacemakers for GI motility, while loss of ICCs is responsible for GI motility disturbance. Thus, the underlying interaction mechanisms for BXD regulating ICCs apoptosis via miR-451-5p remain to be explored. AIM OF THE STUDY: In this work, the main objectives were to examine the efficacy of BXD on ICCs via miR-451-5p both in GI motility disorders rats model and in vitro, as well as the potential contributions of SCF/c-kit signaling. MATERIALS AND METHODS: Rats with gastric electrical dysrhythmia were established in male SD rats by using a single-day diet and a double fasting method (drinking diluted hydrochloric acid water during the period) for 4 weeks. The gastric slow wave (GSW) recording, RT-qPCR, and western blot were performed to examine the effects of BXD on ICCs apoptosis in rats with GED and miR-451-5p expression. In vitro assays included CCK-8, flow cytometry analysis, RT-qPCR, and western blot were applied to investigate the potential molecular mechanism of BXD on ICCs apoptosis via miR-451-5p. RESULTS: BXD promoted gastric motility, reduced ICCs apoptosis, and elevated miR-451-5p in GED rats. In addition, miR-451-5p was significantly up-regulated in ICCs after BXD treatment compared with that in ICCs with miR-451-5p inhibitor transfection. Meanwhile, high miR-451-5p expression with either BXD treatment or miRNA mimics enhanced ICCs proliferation and inhibit apoptosis. Moreover, overexpression of miR-451-5p can reverse G0/G1 arrest in ICCs by BXD treatment. Further, SCF and c-kit protein levels were detected to demonstrate that modulation of miR-451-5p by BXD treatment was involved in this signaling. CONCLUSIONS: Through this study, we demonstrated that BXD could promote ICCs proliferation and inhibit apoptosis via miR-451-5p and may involve the modulations of SCF/c-kit signaling, thus suggesting a new therapy basis for GI motility dysfunction from the perspective of modulation of ICCs apoptosis by targeting miR-451-5p.

Diversified cassane family diterpenoids from the leaves of Caesalpinia minax exerting anti-neuroinflammatory activity through suppressing MAPK and NF-κB pathways in BV-2 microglia.

ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia minax Hance, whose seeds are known as "Ku-shi-lian" in China, have been used in Chinese folk medicine for treatment of rheumatism, dysentery, and skin itching. However, the anti-neuroinflammatory constituents of its leaves and their mechanism are rarely reported. AIM OF THE STUDY: To search for new anti-neuro-inflammatory compounds from the leaves of C. minax and elucidate their mechanism on anti-neuroinflammatory effect. MATERIALS AND METHODS: The main metabolites of the ethyl acetate fraction from C. minax were analyzed and purified via HPLC and various column chromatography techniques. Their structures were elucidated on the basis of 1D and 2D NMR, HR-ESI-MS, and single crystal X-ray diffraction analysis. Anti-neuroinflammatory activity was evaluated in BV-2 microglia cells induced by LPS. The expression levels of molecules in NF-κB and MAPK signaling pathways were analyzed through western blotting. Meanwhile, the time- and dose-dependent expression of associated proteins such as iNOS and COX-2 were detected by western blotting. Furthermore, Compounds 1 and 3 were performed on the NF-κB p65 active site using molecular docking simulation to elucidate the molecular level inhibition mechanism. RESULTS: 20 cassane diterpenoids, including two novel ones (caeminaxins A and B) were isolated from the leaves of C. minax Hance. Caeminaxins A and B possessed a rare unsaturated carbonyl moiety in their structures. Most of the metabolites exhibited potent inhibition effects with IC50 values ranging from 10.86 ± 0.82 to 32.55 ± 0.47 µM. Among them, caeminaxin A inhibited seriously the expression of iNOS and COX-2 proteins and restrained the phosphorylation of MAPK and the activation of NF-κB signaling pathways in BV-2 cells. The anti-neuro-inflammatory mechanism of caeminaxin A has been studied systematically for the first time. Furthermore, biosynthesis pathways for compounds 1-20 were discussed. CONCLUSIONS: The new cassane diterpenoid, caeminaxin A, alleviated the expression of iNOS and COX-2 protein and down-regulated of intracellular MAPK and NF-κB signaling pathways. The results implied that cassane diterpenoids had potential to be developed into therapeutic agents for neurodegenerative disorders such as Alzheimer's disease.

Psoralen induces liver injury and affects hepatic bile acids metabolism in female and male C57BL/6J mice.

Psoralen is a major component of Fructus Psoraleae that could induce liver injury. In this study, C57BL/6J mice were administered with psoralen at doses of 80 mg/kg for 3, 7 and 14 days. Blood and liver samples were collected for serum biochemistry and histopathology examinations, respectively. Psoralen led to liver injury with significantly increased liver weight and liver coefficient and up regulated serum ALT, AST and TG but down regulated serum TC and TP. The expression of bile acid-associated transporters and enzymes was detected by western blot, and the results showed that psoralen significantly down-regulates the expressions of CYP7A1, CYP27A1, BSEP and OSTα protein while up-regulates the expressions of HMGCR and FASN, resulting in the obstacles of bile acid efflux in the liver. The contents of 24 kinds of bile acids in the liver were measured by LC-MS/MS, and the results showed that psoralen led to the accumulation of unconjugated bile acids in the liver, such as ALCA and CA, which were more severe in male mice than female mice. It was indicated that psoralen may disrupt the balance of bile acid metabolism by inhibiting the expression of the efflux transporter, which then leads to liver damage.

[Effects of electroacupuncture pretreatment on NLRP3 inflammasome in mice with ventilator-induced lung injury].

OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment on inflammatory response in ven-tilator-induced lung injury (VILI) mice, so as to explore the underlying mechanism of EA pretreatment on prevention of VILI. METHODS: C57BL/6 mice were randomly divided into sham-operation group, model group, EA group and sham-acupoint group，with 8 mice in each group. The VILI model was established by ventilation with high tidal volume. Mice in the EA group and sham-acupoint group were given EA at "Zusanli" (ST36)and "Feishu"(BL13) or non-acupoints (located at 1-2 cm on both sides of the tail root of the proximal trunk) before mechanical ventilation, 30 min each time, once a day for 5 days. Arterial blood was collec-ted for blood gas analysis, the total protein content in bronchoalveolar lavage fluid (BALF) was detected by BCA method. The contents of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in BALF were detected by ELISA. Lung injury score was determined after HE staining. The protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and Caspase-1 in lung tissue was detected by Western blot. RESULTS: Compared with the sham-operation group, the arterial partial pressure of oxygen and oxygenation index were decreased(P<0.05), the levels of total protein, IL-1ß and IL-18 in BALF, the W/D value and the pathological injury score of lung tissue and the protein expression levels of NLRP3, Caspase-1 and ASC were increased(P<0.05)in the model group. Following the interventions, the above mentioned increased or decreased indicators were reversed(P<0.05) in the EA group rather than in the sham-acupoint group. CONCLUSION: EA pretreatment of ST36 and BL13 can reduce the damage of lung tissue caused by mechanical ventilation, which may be related to its effect in reducing the expression of NLPR3 inflammasome related proteins, reducing the activation of inflammasome, and thereby reducing the inflammatory response.

Oridonin employs interleukin 1 receptor type 2 to treat noise-induced hearing loss by blocking inner ear inflammation.

NOD-like receptor protein 3 (NLRP3) inflammasomes trigger the inflammatory cascades and participate in various inflammatory diseases, including noise-induced hearing loss (NIHL) caused by oxidative stress. Recently, the anti-inflammatory traditional medicine oridonin (Ori) has been reported to provide hearing protection in mice after noise exposure by blocking the NLRP3-never in mitosis gene A-related kinase 7 (NEK7)-inflammasome complex assembly. Using RNA sequencing analysis, we further elucidated that interleukin 1 receptor type 2 (IL1R2) may be another crucial factor regulated by Ori to protect NIHL. We observed that IL1R2 expression was localized in spiral ganglion neurons, inner and outer hair cells, in Ori-treated mouse cochleae. Additionally, we confirmed that ectopic overexpression of IL1R2 in the inner ears of healthy mice using an adeno-associated virus delivery system significantly reduced noise-induced ribbon synapse lesions and hearing loss by blocking the "cytokine storm" in the inner ear. This study provides a novel theoretical foundation for guiding the clinical treatment of NIHL.

Interaction between Changan Granule and its main components in the plasma and CYP450 enzymes.

ETHNOPHARMACOLOGICAL RELEVANCE: Changan Granule (CAG) is a Chinese patent drug developed based on an empirical prescription in accordance with the formulation theory of Traditional Chinese Medicine. The prescription is composed of eight herbal drugs which have been traditionally used by Chinese people for a long history. It has effects of invigorating spleen and supplementing qi, as well as regulating liver and ceasing diarrhea, and is indicated for the treatment of irritable bowel syndrome (IBS). AIM OF THE STUDY: This study was aimed to investigate the interaction between CAG and its main components and cytochrome P450 (CYP450) enzymes so as to characterize the major metabolites and metabolic enzymes and evaluate the safety concerns to its clinical use. MATERIALS AND METHODS: Both in vivo and in vitro experiments using such as diarrhea-predominant IBS (IBS-D) rat model, HepG2 cells, and human liver microsomes (HLM) were carried out to investigate the interaction between CAG and its main components and CYP450 enzymes. Real-time quantitative PCR (qPCR), ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and cocktail probes were employed to qualitatively or quantitatively measure the metabolites and metabolic enzymes. RESULTS: CAG inhibited the enzyme activities of CYP1A2, CYP2E1, CYP2D6, CYP2C9, and CYP3A4 and the mRNA expressions of CYP2E1, CYP2C9, CYP3A4, and CYP2D6 in vitro. CAG down-regulated the increased expression of CYP1A2 and up-regulated the decreased expression of CYP3A1 in vivo. Twenty-two metabolites were characterized from the main components of CAG after incubation with HLM in vitro. CYP2D6, CYP2E1, CYP3A4 and CYP2C9 were identified as the characteristic metabolic enzymes. CONCLUSIONS: This study provides a reference for clinical application of CAG in safety. CAG and CYP450 enzymes are interacted. CAG is mainly metabolized by CYP2E1 and CYP2D6. The expression of CYP2E1 and CYP2D6 are more susceptible to be influenced by CAG in comparison with that of CYP3A4, CYP2C9 and CYP1A2. It implies the potential risk of interaction when CAG is taken together with the drugs metabolized by CYP2E1 and CYP2D6.

Apigenin ameliorates non-eosinophilic inflammation, dysregulated immune homeostasis and mitochondria-mediated airway epithelial cell apoptosis in chronic obese asthma via the ROS-ASK1-MAPK pathway.

BACKGROUND: Obese asthma is one of the important asthma phenotypes that have received wide attention in recent years. Excessive oxidative stress and different inflammatory endotypes may be important reasons for the complex symptoms, frequent aggravation, and resistance to traditional treatments of obese asthma. Apigenin (API), is a flavonoid natural small molecule compound with good anti-inflammatory and antioxidant activity in various diseases and proved to have the potential efficacy to combat obese asthma. METHODS: In vivo, this study fed C57BL/6 J mice with high-fat diets(HFD)for 12 weeks and then stimulated them with OVA for 6 weeks to establish a model of chronic obese asthma, while different doses of oral API or dexamethasone were used for therapeutic interventions. In vitro, this study used HDM to stimulate human bronchial cells (HBEs) to establish the model and intervened with API or Selonsertib (SEL). RESULTS: This study clarified that OVAinduced a type of mixed granulocytic asthma with elevated neutrophils and eosinophils in obese male mice fed with long-term HFD, which also exhibited mixed TH17/TH1/TH2 inflammation. Apigenin effectively suppressed this complex inflammation and acted as a regulator of immune homeostasis. Meanwhile, apigenin reduced AHR, inflammatory cell infiltration, airway epithelial cell apoptosis, airway collagen deposition, and lung oxidative stress via the ROS-ASK1-MAPK pathway in an obese asthma mouse model. In vitro, this study found that apigenin altered the binding status of TRAF6 to ASK1, inhibited ASK1 phosphorylation, and protected against ubiquitin-dependent degradation of ASK1, suggesting that ROS-activated ASK1 may be an important target for apigenin to exert anti-inflammatory and anti-apoptotic effects. To further verify the intervention mechanism, this study clarified that apigenin improved cell viability and mitochondrial function and inhibited apoptosis by interfering with the ROS-ASK1-MAPK pathway. CONCLUSIONS: This study demonstrates for the first time the therapeutic effect of apigenin in chronic obese asthma and further clarifies its potential therapeutic targets. In addition, this study clarifies the specificity of chronic obese asthma and provides new options for its treatment.

Metabolomics reveals the defense mechanism of histidine supplementation on high-salt exposure-induced hepatic oxidative stress.

AIMS: This study mainly evaluated the protective mechanism of histidine against the hepatic oxidative stress after high-salt exposure (HSE) through combined analysis of non-targeted metabolomics and biological metabolic networks. MATERIALS AND METHODS: Dahl salt-sensitive (SS) rats were fed with normal-salt diet or HSE ± histidine in addition to drinking water for 14 days. Gas chromatography-mass spectrometry was used to analyze the hepatic metabolites. The metabolic profile was analyzed by SIMCA-14.1, the metabolic correlation network was performed using Gephi-0.9.2, and pathway enrichment was analyzed using MetaboAnalyst 5.0 online website. KEY FINDINGS: Results indicated that HSE disturbed the hepatic metabolic profile, generated abnormal liver metabolism and exacerbated oxidative stress. Histidine supplementation significantly reversed the hepatic metabolic profile. Of note, 14 differential metabolic pathways were enriched after histidine supplementation, most of which played an important role in ameliorating redox and nitric oxide (NO) metabolism. Histidine administration decreased the levels of hydroperoxide and malondialdehyde, and increased the activities of antioxidant enzymes (Catalase, Superoxide Dismutase, Glutathione S-transferase and Glutathione reductases). Histidine effectively enhanced the endogenous synthesis of glutathione by increasing the levels of glutamate and cysteine, thereby enhancing the antioxidant capacity of the glutathione system. After histidine administration, lysine, glutamate, and hypotaurine owned a higher metabolic centrality in the correlation network. In addition, histidine could also effectively increase the endogenous synthesis of NO by enhancing the L-arginine/NO pathway. SIGNIFICANCE: This study offers new insights into the metabolic mechanisms underlying the antioxidant protective effect of histidine on the liver.

Species mixing enhances the resistance of Robinia pseudoacacia L. to drought events in semi-arid regions: Evidence from China's Loess Plateau.

As a potential planting strategy, species mixing increases biomass production, improves ecosystem service functions, and mitigates climate change. However, the effect of species mixing on tree growth and drought resilience in semi-arid areas remains unclear. Hence, we established tree-ring chronologies of Robinia pseudoacacia L. in pure Robinia pseudoacacia L. plantation (RP) and mixed plantations with Hippophae rhamnoides L. and Populus simonii Carr. at different proportions of 8:2 and 5:5 (RH 8:2, RH 5:5, RC 8:2, RC 5:5) in the typical semi-arid region of the Loess Plateau (LP), China. The mean annual growth, climate-growth relationships, and tree resilience (Rs) to drought, including resistance (Rt) and recovery (Rc), were analyzed using dendrochronological methods. The results showed that the growth of R. pseudoacacia L. in mixed plantations was lower when Palmer Drought Severity Index (PDSI) >0, but much higher than that in monoculture under drought stress (PDSI <0 or after drought event). Meanwhile, the relationship between PDSI and tree growth was significantly positive in the pure plantation, but weakened in the mixed plantations, indicating that species mixing alleviated drought stress to some extent. The resilience results showed that, although the Rc was higher in monoculture after drought events, species mixing could enhance Rt and mitigate the growth decline of R. pseudoacacia L. during drought events. Moreover, the Rt varied significantly among mixing species and proportions and was also affected by the magnitude and timing of drought. The RC 5:5 and RH 8:2 had higher resistance to moderate and severe drought stress. However, RC 8:2 and RH 5:5 could cope better with mild drought stress. These results indicate that species mixing can alleviate drought stress and improve the drought resistance. Therefore, it is necessary to expand species mixing to maximize plantation functions and minimize the potential impacts of warming and drought in semi-arid regions.

Production of ginsenoside compound K by microbial cell factory using synthetic biology-based strategy: a review.

Ginsenoside compound K (CK) is a major intestinal bacterial metabolite of the protopanaxadiol-type ginsenoside family that can be absorbed in the systemic circulation. CK possesses diverse and important pharmacological properties. The low production and high cost of traditional manufacturing methods based on the extraction and biotransformation of total ginsenosides from ginseng have limited their medical application. However, considerable progress has been made in the area of de novo CK production via microbial cell factories using synthetic biology-based strategies. By introducing key enzymes responsible for CK biosynthesis into microbial cells, CK was produced via a series of in vivo enzymatic reactions that utilize the inherent precursors in microbial cells. After systematic optimization using various metabolic engineering strategies, the yield of CK increased significantly and exceeded the traditional plant extraction-biotransformation method, implying the commercial feasibility of this approach. This review summarizes recent novel advancements in the production of CK using microbial cell factories.

Iron-catalyzed regioselective synthesis of (E)-vinyl sulfones mediated by unprotected hydroxylamines.

An Fe-catalyzed unprotected hydroxylamine mediated Heck-type coupling between sulfinic acids and alkenes for the regioselective synthesis of (E)-vinyl sulfones has been developed. Mechanism studies indicated for the first time that a radical process may be involved and that hydroxylamines play multiple roles, including those of a mild oxidant and an in situ base. It was found for the first time that this transformation not only realizes C-S bond construction promoted by unprotected hydroxylamines, but also provides a practical and complementary method for the preparation of structurally important (E)-vinyl sulfones.

Benincasa hispida extracts positively regulated high salt-induced hypertension in Dahl salt-sensitive rats: Impact on biochemical profile and metabolic patterns.

Salt-induced hypertension is one of the major issues worldwide and one of the main factors involved in heart and kidney failure. The objective of this study was to investigate the potential role of Benincasa hispida extracts on high salt-induced hypertension in Dahl-salt sensitive (D-SS) rats and to find out the metabolic and biochemical pattern involved in the reduction of hypertension. Twenty-six Dahl salt-sensitive (D-SS) rats were selected and divided into four groups. The metabolic strategy was applied to test the extracts on salt-sensitive hypertension in kidney. Gas Chromatography-Mass spectrometry (GC-MS) was used to identify the potent biochemical profile in renal medulla and cortex of rat kidneys. The differential metabolites of cortex and medulla, enrichment analysis and pathway analysis were performed using metabolomics data. The GC-MS data revealed that 24 different antihypertensive metabolites was detected in renal cortex, while 16 were detected in renal medulla between different groups. The significantly metabolic pathways namely citrate cycle, glutathione metabolism, glycine, serine, and threonine metabolism, glyoxylate and dicarboxylate metabolism, glycerolipid metabolism, alanine, aspartate and glutamate metabolism in renal cortex and glycerolipid metabolism, pentose phosphate pathway, citrate cycle, glycolysis, glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis in renal medulla were involved in the process of Hypertension. The results suggest that the extract mainly alter the metabolic pathways of amino acid in Dahl salt-sensitive rats and its antioxidant potential reduced the hypertension patterns of Salt-sensitive rat. The antihypertensive components malic acid, aspartic acid, and glycine of extract can be used as therapeutic drugs to protect kidneys from salt-induced hypertension. PRACTICAL APPLICATIONS: Hypertension is a multifactorial disease and one of the risk factors for heart and kidney failure. Benincasa hispida is a widely used vegetable in China, which belongs to the Cucurbitaceae family. Benincasa hispida (wax gourd) has been used in traditional Chinese medicine for the treatment of inflammation and hypertension. The Benincasa hispida contains many compounds such as amino acids, carbohydrates, volatile compounds, vitamins, and minerals. The amino acid present in the pulp of Benincasa hispida are ornithine, threonine, aspartate, glutamate, serine, glycine, proline, alanine, valine, cysteine, isoleucine, tyrosine, leucine, lysine, phenylalanine, histidine, arginine, and γ-aminobutyric acid. Our results showed that Benincasa hispida is one of the potent natural antioxidants and can maintain normal blood pressure in Dahl salt-sensitive rats (D-SS). In conclusion, the current results provide good theoretical basis for the development and research using Benincasa hispida as an effective natural antioxidant for hypertension.

Conventional disease-modifying anti-rheumatic drugs combined with Chinese Herbal Medicines for rheumatoid arthritis: A systematic review and meta-analysis.

Rheumatoid Arthritis (RA) remains a major global public health challenge. Disease-modifying anti-rheumatic drugs (DMARDs) are standard therapeutic drugs for RA. Conventional DMARDs (c-DMARDs) are a subgroup of approved synthetic DMARDs. The c-DMARDs experienced lesser response with longer disease duration or drug exposure, and unwanted adverse events (AEs). The combination treatments (CTs) of c-DMARDs and Chinese Herbal Medicines (CHMs) were often used in RA clinical trials for increasing the therapeutic effectiveness and reducing the AEs. This systematic review aimed to evaluate the efficacy and safety of the CTs for RA. Databases were searched from inception to October 2020 for identification of randomized controlled trials (RCTs) that investigated the CTs in the management of RA. Twenty-three RCTs with 2,441 participants were included. The assessments and analyses found CTs improved American College of Rheumatology (ACR) 20 (RR: 1.33, 95% CI [1.21, 1.45], 10 studies, n=1,075) and alleviated AEs (RR: -0.40, 95% CI [-0.30, -0.53], 19 studies, n=2,011) in comparison with c-DMARDs. The CTs also significantly improved RA symptoms and patient-reported outcomes; reduced disease activity score (DAS) 28, serum acute-phase reactants and RA biomarkers. The five most commonly used herbs in included studies were Angelicae Sinensis Radix, Paeoniae Radix Alba, Cinnamomi Ramulus, Glycyrrhizae Radix et Rhizoma, and Clematidis Radix et Rhizoma. Pharmacological studies indicated these CHMs could contribute to the outcomes. The integrated CHMs potentially increased the overall effectiveness of c-DMARDs and alleviated AEs in management of RA. Large sample and rigorously designed RCTs are required for future studies.