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The influence of maternal vitamin D supplementation on infant vitamin D status: A systematic review and meta-analyses

Zhong X, Xiong Y, Wei D, Wang S, Xiao Z, Liu M, et al.

Complement Ther Med, 2020 Aug;52:102491.
PMID: 32951740 DOI: 10.1016/j.ctim.2020.102491

BACKGROUND: Inconsistencies exist with regard to effect of maternal vitamin D supplementation on infant vitamin D status. The inconsistencies could be attributed to numerous factors, such as duration of intervention and dosage, among others. In this work, we conducted a systematic review and meta-analysis to determine the influence of maternal vitamin D supplementation on infant vitamin D status.
METHODS: A comprehensive systematic search was performed in Scopus, EMBASE, Web of Science, and PubMed/MEDLINE, by investigators, from database inception until November 2019, without using any restrictions. Weighted mean difference (WMD) with the 95 % CI was used for assessing the effects of maternal vitamin D supplementation on 25(OH) D levels in infants.
RESULTS: Overall results from 14 studies revealed a non-significant effect of maternal vitamin D administration on the level of 25(OH) D in breastfeeding infants (WMD: -0.464 ng/mL, 95 % CI: -6.68 to 5.75, p = 0.884, I2 = 98 %). Subgroup analyses demonstrated that vitamin D supplementation dosage ≥2000 IU/day (WMD: 9 ng/mL, 95 % CI: 8.19, 9.82, I2 = 99 %) and intervention duration ≥20 weeks (WMD: 16.20 ng/mL, 95 % CI: 14.89, 17.50, I2 = 99 %) significantly increased 25(OH) D.
CONCLUSIONS: The main results indicate a non-significant increase in infant vitamin D following maternal vitamin D supplementation. Additionally, vitamin D supplementation dosage ≥2000 IU/day and intervention duration ≥20 weeks significantly increased infant 25(OH) D.
Tissue-specific and maturity-dependent distribution of pyridine alkaloids in Areca triandra

Wu J, Zhang H, Wang S, Yuan L, Grünhofer P, Schreiber L, et al.

J Plant Res, 2019 Jul;132(4):531-540.
PMID: 31127431 DOI: 10.1007/s10265-019-01115-9

Areca nuts (seeds of Areca catechu L.) are a traditional and popular masticatory in India, Bangladesh, Malaysia, certain parts of China, and some other countries. Four related pyridine alkaloids (arecoline, arecaidine, guvacoline, and guvacine) are considered being the main functional ingredients in areca nut. Until now, A. catechu is the only known species producing these alkaloids in the Arecaceae family. In the present study, we investigated alkaloid contents in 12 Arecaceae species and found that only Areca triandra Roxb. contained these pyridine alkaloids. We further analyzed in more detail tissue-specific and development-related distribution of these alkaloids in leaves, male and female flowers and fruits in different stages of maturity in A. triandra by ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry. Results revealed that the alkaloids were most abundant in young leaves, the pericarp of ripe fruits and the endosperm of unripe fruits in developmental stage 2. Abundance of the 4 different alkaloids in A. triandra fruits varied during maturation. Pericarps of ripe fruits had the highest arecaidine concentration (4.45 mg g-1) and the lowest guvacoline concentration (0.0175 mg g-1), whereas the endosperm of unripe fruits of developmental stage 2 contained the highest guvacoline concentration (3.39 mg g-1) and the lowest guvacine concentration (0.245 mg g-1). We conclude that A. triandra is useful in future as a further valuable source of Areca alkaloids.
Fulltext MUSiC: a model-unspecific search for new physics in proton-proton collisions at s = 13 TeV

CMS Collaboration, Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, et al.

Eur Phys J C Part Fields, 2021;81(7):629.
PMID: 34727144 DOI: 10.1140/epjc/s10052-021-09236-z

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV , corresponding to an integrated luminosity of 35.9 fb - 1 , are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.
Fulltext Search for dark matter produced in association with a leptonically decaying Z boson in proton-proton collisions at s = 13 Te

Sirunyan AM, CMS Collaboration, Tumasyan A, Adam W, Bergauer T, Dragicevic M, et al.

Eur Phys J C Part Fields, 2021;81(1):13.
PMID: 33493254 DOI: 10.1140/epjc/s10052-020-08739-5

A search for dark matter particles is performed using events with a Z boson candidate and large missing transverse momentum. The analysis is based on proton-proton collision data at a center-of-mass energy of 13 Te , collected by the CMS experiment at the LHC in 2016-2018, corresponding to an integrated luminosity of 137 fb - 1 . The search uses the decay channels Z → e e and Z → μ μ . No significant excess of events is observed over the background expected from the standard model. Limits are set on dark matter particle production in the context of simplified models with vector, axial-vector, scalar, and pseudoscalar mediators, as well as on a two-Higgs-doublet model with an additional pseudoscalar mediator. In addition, limits are provided for spin-dependent and spin-independent scattering cross sections and are compared to those from direct-detection experiments. The results are also interpreted in the context of models of invisible Higgs boson decays, unparticles, and large extra dimensions.
Fulltext Measurements of production cross sections of the Higgs boson in the four-lepton final state in proton-proton collisions at s = 13 TeV

CMS Collaboration, Sirunyan AM, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, et al.

Eur Phys J C Part Fields, 2021;81(6):488.
PMID: 34727143 DOI: 10.1140/epjc/s10052-021-09200-x

Production cross sections of the Higgs boson are measured in the H → Z Z → 4 ℓ ( ℓ = e , μ ) decay channel. A data sample of proton-proton collisions at a center-of-mass energy of 13 TeV , collected by the CMS detector at the LHC and corresponding to an integrated luminosity of 137 fb - 1 is used. The signal strength modifier μ , defined as the ratio of the Higgs boson production rate in the 4 ℓ channel to the standard model (SM) expectation, is measured to be μ = 0.94 ± 0.07 (stat) - 0.08 + 0.09 (syst) at a fixed value of m H = 125.38 GeV . The signal strength modifiers for the individual Higgs boson production modes are also reported. The inclusive fiducial cross section for the H → 4 ℓ process is measured to be 2 . 84 - 0.22 + 0.23 (stat) - 0.21 + 0.26 (syst) fb , which is compatible with the SM prediction of 2.84 ± 0.15 fb for the same fiducial region. Differential cross sections as a function of the transverse momentum and rapidity of the Higgs boson, the number of associated jets, and the transverse momentum of the leading associated jet are measured. A new set of cross section measurements in mutually exclusive categories targeted to identify production mechanisms and kinematical features of the events is presented. The results are in agreement with the SM predictions.
Fulltext Myocardial injury after noncardiac surgery: a large, international, prospective cohort study establishing diagnostic criteria, characteristics, predictors, and 30-day outcomes

Botto F, Alonso-Coello P, Chan MT, Villar JC, Xavier D, Srinathan S, et al.

Anesthesiology, 2014 Mar;120(3):564-78.
PMID: 24534856 DOI: 10.1097/ALN.0000000000000113

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The study's four objectives were to determine the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS.
METHODS: In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated "abnormal" laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria.
RESULTS: An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors' diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96-5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6-41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom.
CONCLUSION: Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.
Fulltext Multiple Genome Sequences of Helicobacter pylori Strains of Diverse Disease and Antibiotic Resistance Backgrounds from Malaysia

Rehvathy V, Tan MH, Gunaletchumy SP, Teh X, Wang S, Baybayan P, et al.

Genome Announc, 2013;1(5).
PMID: 24051312 DOI: 10.1128/genomeA.00687-13

Helicobacter pylori causes human gastroduodenal diseases, including chronic gastritis and peptic ulcer disease. It is also a major microbial risk factor for the development of gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. Twenty-one strains with different ethnicity, disease, and antimicrobial susceptibility backgrounds were sequenced by use of Illumina HiSeq and PacBio RS platforms.
Fulltext The complete methylome of Helicobacter pylori UM032

Lee WC, Anton BP, Wang S, Baybayan P, Singh S, Ashby M, et al.

BMC Genomics, 2015;16:424.
PMID: 26031894 DOI: 10.1186/s12864-015-1585-2

The genome of the human gastric pathogen Helicobacter pylori encodes a large number of DNA methyltransferases (MTases), some of which are shared among many strains, and others of which are unique to a given strain. The MTases have potential roles in the survival of the bacterium. In this study, we sequenced a Malaysian H. pylori clinical strain, designated UM032, by using a combination of PacBio Single Molecule, Real-Time (SMRT) and Illumina MiSeq next generation sequencing platforms, and used the SMRT data to characterize the set of methylated bases (the methylome).
Fulltext Comparing the genomes of Helicobacter pylori clinical strain UM032 and Mice-adapted derivatives

Khosravi Y, Rehvathy V, Wee WY, Wang S, Baybayan P, Singh S, et al.

Gut Pathog, 2013;5:25.
PMID: 23957912 DOI: 10.1186/1757-4749-5-25

Helicobacter pylori is a Gram-negative bacterium that persistently infects the human stomach inducing chronic inflammation. The exact mechanisms of pathogenesis are still not completely understood. Although not a natural host for H. pylori, mouse infection models play an important role in establishing the immunology and pathogenicity of H. pylori. In this study, for the first time, the genome sequences of clinical H. pylori strain UM032 and mice-adapted derivatives, 298 and 299, were sequenced using the PacBio Single Molecule, Real-Time (SMRT) technology.
Tough, adhesive biomimetic hyaluronic acid methacryloyl hydrogels for effective wound healing

Peng Z, Xue H, Liu X, Wang S, Liu G, Jia X, et al.

Front Bioeng Biotechnol, 2023;11:1222088.
PMID: 37539434 DOI: 10.3389/fbioe.2023.1222088

The development of cost-effective, biocompatible soft wound dressings is highly desirable; however, conventional dressings are only designed for flat wounds, which creates difficulty with promising healing efficiency in complex practical conditions. Herein, we developed a tough, adhesive biomimetic hyaluronic acid methacryloyl hydrogels composed of chemically crosslinked hyaluronic acid methacryloyl (HAMA) network and poly(N-hydroxyethyl acrylamide) (PHEAA) network rich in multiple hydrogen bonding. Due to the multiple chemical crosslinking sites (acrylamide groups) of HAMA; the bulk HEMA/PHEAA hydrogels presented significant enhancements in mechanical properties (∼0.45 MPa) than common hyaluronic acid hydrogels (<0.1 MPa). The abundant hydrogen bonding also endowed the resultant hydrogels with extremely high adhesiveness on many nonporous substrates, including glass and biological tissues (e.g., heart, liver, lung, kidney, stomach, and muscle), with a considerable interfacial toughness of ∼1432 J m-2. Accordingly, since both natural hyaluronic acid derivative polymers and hydrophilic PHEAA networks are highly biocompatible, the hydrogel matrix possesses good blood compatibility (<5% of hemolysis ratio) and satisfies the general dressing requirements (>99% of cell viability). Based on these physicochemical features, we have demonstrated that this adhesive hydrogel, administered in the form of a designed patch, could be applied to wound tissue healing by promoting epithelialization, angiogenesis, and collagen deposition. We believe that our proposed biomimetic hydrogel design holds great potential for wound repair and our developed HAMA/PHEAA hydrogels are extremely promising for the next-generation tissue healings in emergency situations.
Unusual case of lipoma arborescens in the subacromial-subdeltoid bursa

Lim MC, See PL, Wang SY, Wee AT, Tee UL

Med J Malaysia, 2018 12;73(6):400-402.
PMID: 30647212

A 38-year-old female presented with a 10-month history of right shoulder pain with impingement symptoms. She was diagnosed on magnetic resonance (MR) imaging to have supraspinatus tendon tear and degenerative changes contributing to subacromial impingement. She also had lipoma arborescens of the subacromial-subdeltoid bursa, an uncommon condition in a particularly rare location. Lipoma arborescens is a benign intra-articular condition characterized by lipomatous proliferation of synovium with replacement of subsynovial tissue by mature adipocytes. It is typically a monoarticular process affecting the knee. Due to the presence of pathognomonic fat, diagnosis is usually straightforward with MR as the preferred imaging modality.
Fulltext Effect of (R)-salbutamol on the switch of phenotype and metabolic pattern in LPS-induced macrophage cells

Wang S, Liu F, Tan KS, Ser HL, Tan LT, Lee LH, et al.

J Cell Mol Med, 2020 01;24(1):722-736.
PMID: 31680470 DOI: 10.1111/jcmm.14780

Evidence demonstrates that M1 macrophage polarization promotes inflammatory disease. Here, we discovered that (R)-salbutamol, a β2 receptor agonist, inhibits and reprograms the cellular metabolism of RAW264.7 macrophages. (R)-salbutamol significantly inhibited LPS-induced M1 macrophage polarization and downregulated expressions of typical M1 macrophage cytokines, including monocyte chemotactic protein-1 (MCP-1), interleukin-1β (IL-1β) and tumour necrosis factor α (TNF-α). Also, (R)-salbutamol significantly decreased the production of inducible nitric oxide synthase (iNOS), nitric oxide (NO) and reactive oxygen species (ROS), while increasing the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio. In contrast, (S)-salbutamol increased the production of NO and ROS. Bioenergetic profiles showed that (R)-salbutamol significantly reduced aerobic glycolysis and enhanced mitochondrial respiration. Untargeted metabolomics analysis demonstrated that (R)-salbutamol modulated metabolic pathways, of which three metabolic pathways, namely, (a) phenylalanine metabolism, (b) the pentose phosphate pathway and (c) glycerophospholipid metabolism were the most noticeably impacted pathways. The effects of (R)-salbutamol on M1 polarization were inhibited by a specific β2 receptor antagonist, ICI-118551. These findings demonstrated that (R)-salbutamol inhibits the M1 phenotype by downregulating aerobic glycolysis and glycerophospholipid metabolism, which may propose (R)-salbutamol as the major pharmacologically active component of racemic salbutamol for the treatment of inflammatory diseases and highlight the medicinal value of (R)-salbutamol.
The Attenuation of Chronic Ulcerative Colitis by (R)-salbutamol in Repeated DSS-Induced Mice

Deng L, Guo H, Wang S, Liu X, Lin Y, Zhang R, et al.

Oxid Med Cell Longev, 2022;2022:9318721.
PMID: 35178163 DOI: 10.1155/2022/9318721

Racemic salbutamol ((RS)-sal), which consist of the same amount of (R)-sal and (S)-sal, has been used for asthma and COPD due to its bronchodilation effect. However, the effect of (R)-sal on repeated dextran sulfate sodium (DSS)-induced chronic colitis has not yet been investigated. In this study evaluated the potential effect of (R)-, (S)-, and (RS)-sal in mice with repeated DSS-induced chronic colitis and investigated the underlying mechanisms. Here, we verified that chronic colitis was significantly attenuated by (R)-sal, which was evidenced by notably mitigated body weight loss, disease activity index (DAI), splenomegaly, colonic lengths shortening, and histopathological scores. (R)-sal treatment noticeably diminished the levels of inflammatory cytokines (such as TNF-α, IL-6, IL-1β, and IFN-γ). Notably, the efficacy of (R)-sal was better than that of (RS)-sal. Further research revealed that (R)-sal mitigated colonic CD4 leukocyte infiltration, decreased NF-κB signaling pathway activation, improved the Nrf-2/HO-1 signaling pathway, and increased the expression of ZO-1 and occludin. In addition, (R)-sal suppressed the levels of TGF-β1, α-SMA, and collagen in mice with chronic colitis. Furthermore, the 16S rDNA sequences analyzed of the intestinal microbiome revealed that (R)-sal could mitigate the intestinal microbiome structure and made it more similar to the control group, which mainly by relieving the relative abundance of pathogens (such as Bacteroides) and increasing the relative abundance of probiotics (such as Akkermansia). Therefore, (R)-sal ameliorates repeated DSS-induced chronic colitis in mice by improving inflammation, suppressing oxidative stress, mitigating intestinal barrier function, relieving intestinal fibrosis, and regulating the intestinal microbiome community. These results indicate that (R)-sal maybe a novel treatment alternative for chronic colitis.
(RS)-bambuterol and its enantiomers: Potential improvement of (R)-bambuterol in mice with colitis

Deng L, Wang S, Guo H, Liu X, Zou X, Zhang R, et al.

Int Immunopharmacol, 2022 Feb;103:108501.
PMID: 34974400 DOI: 10.1016/j.intimp.2021.108501

Bambuterol (BMB) has been used clinically to treat asthma due to its bronchodilation activity. However, the effect of BMB on ulcerative colitis (UC) has not been examined. The present work focused on the effects of enantiomeric BMB on UC. Acute UC was induced in mice by 3% dextran sulfate sodium (DSS), and (R)-, (S) and (RS)-BMB were orally administered. Body weight loss and the disease activity index (DAI) were measured once a day. Inflammatory factors were detected by ELISA and qRT-PCR. Histological evaluations of colon samples were performed. IL-6, STAT3, and RORγt pathway-related proteins were analyzed by western blotting. The results verified that colitis severity was dramatically ameliorated by (R)-BMB, which was significantlybetter than the effect of (RS)-BMB or (S)-BMB, as evidenced by body weight loss, DAI, colon length, spleen/body weight ratio and histopathological manifestations. Furthermore, (R)-BMB treatment significantly diminished the levels of inflammatory cytokines and macrophages infiltration in mice with colitis. Besides, treated with (R)-BMB obviously elevated the level of β2AR. In addition, (R)-BMB decreased the expression of IL-6, IL-17, retinoic acid receptor-related orphan receptor-gamma t (RORt), and phosphorylated STAT3 (p-STAT3) in a dose-dependent manner in the colon tissues. The efficacy of (R)-BMB was more notable than aminosalicylic acid (5-ASA). (R)-BMB is either butyrilcholinesterase inhibitor or β2AR agonist which offers new treatment of colitis.
Fulltext Isosteviol Sodium Ameliorates Dextran Sodium Sulfate-Induced Chronic Colitis through the Regulation of Metabolic Profiling, Macrophage Polarization, and NF-κB Pathway

Wang S, Huang J, Tan KS, Deng L, Liu F, Tan W

Oxid Med Cell Longev, 2022;2022:4636618.
PMID: 35126813 DOI: 10.1155/2022/4636618

Inflammatory bowel diseases (IBDs) constitute a group of chronic intestinal conditions prominently featuring deranged metabolism. Effective pharmacological treatments for IBDs are lacking. Isosteviol sodium (STV-Na) exhibits anti-inflammatory activity and may offer therapeutic benefits in chronic colitis. However, the associated mechanism remains unclear. This study is aimed at exploring the therapeutic effects of STV-Na against chronic colitis in terms of metabolic reprogramming and macrophage polarization. Results show that STV-Na attenuated weight loss and colonic pathological damage and restored the hematological and biochemical parameters in chronic colitis mice models. STV-Na also restored intestinal permeability by increasing the goblet cell numbers, which was accompanied by lowered plasma lipopolysaccharide and diamine oxidase levels. Metabolomic analysis highlighted 102 candidate biomarkers and 5 vital pathways that may be crucial in the potential pharmacological mechanism of STV-Na in regulating intestinal inflammation and oxidative stress. These pathways were glycerophospholipid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, the pentose phosphate pathway, and phosphonate and phosphinate metabolism. Furthermore, STV-Na significantly decreased M1 macrophage polarization in the spleen and colon. The mRNA and protein levels of IL-1β, TNF-α, and NF-κB/p65 in colonic tissue from the colitis mice were decreased after the STV-Na treatment. Overall, STV-Na could alleviate chronic colitis by suppressing oxidative stress and inflammation levels, reprogramming the metabolic profile, inhibiting macrophage polarization, and suppressing the NF-κB/p65 signaling pathway. STV-Na remains a promising candidate drug for treating IBDs.
Effects of R-salbutamol on the inflammatory response and acute lung injury in endotoxemic mice

Beng H, Hu J, Wang S, Liang X, Qin H, Tan W

Int Immunopharmacol, 2023 Aug;121:110482.
PMID: 37364330 DOI: 10.1016/j.intimp.2023.110482

Salbutamol, which consists of an R-isomer and S-isomer, is an effective and widely used β2 adrenoreceptor agonist that may possess anti-inflammatory properties in addition to its bronchodilator activity. Whether the salbutamol R-isomer has advantages over its racemic mixture and effectiveness in treating endotoxemia and endotoxin-induced lung injury has not been well studied. In this study, we investigated the preventive and therapeutic effects of R-salbutamol (R-sal), S-salbutamol (S-sal), and their racemic mixture (Rac-sal) on a mouse model of lipopolysaccharide (LPS)-induced endotoxemia. Dexamethasone (Dex) was used for comparison. The results showed that R-sal markedly improved the 7-day survival rate of endotoxic mice when administered before and after LPS treatment. Dex was toxic and accelerated the death of endotoxic mice when administered before LPS injection. Histological examination of the lungs revealed that the LPS challenge resulted in acute lung damage, including inflammatory cell infiltration, thickened alveolar septa, and congestion. R-sal pre-treatment effectively inhibited these changes, accompanied by markedly reduced lung myeloperoxidase levels, serum cytokine levels, and lactate release, significant restoration of lymphocyte count, and reduction of monocyte count. This may have occurred through inhibition of M1 macrophage inflammatory responses by enhancement of β-arrestin2 expression and suppression of NF-κB activation. Rac-sal exhibited diminished effects compared to that of R-sal, while S-sal showed enhanced release of some inflammatory cytokines. In addition, R-sal pre-treatment showed a better improvement in prognostic pulmonary function on day 4 compared to that by Rac-sal. Collectively, our results indicate the potential benefits of R-sal in regulating inflammatory responses to endotoxemia and endotoxin-induced lung injury.
Protective effect of isosteviol sodium against LPS-induced multiple organ injury by regulating of glycerophospholipid metabolism and reducing macrophage-driven inflammation

Wang S, Tan KS, Beng H, Liu F, Huang J, Kuai Y, et al.

Pharmacol Res, 2021 Oct;172:105781.
PMID: 34302975 DOI: 10.1016/j.phrs.2021.105781

Sepsis is a severe inflammatory disorder that can lead to multiple organ injury. Isosteviol sodium (STV-Na) is a terpenoid derived from stevioside that exerts anti-inflammatory, antioxidant and antiapoptotic activities. However, the influence of STV-Na on sepsis remains unknown. Here, we assessed the potential effects of STV-Na on sepsis and multiple organ injury induced by lipopolysaccharide (LPS). We found that STV-Na increased the survival rate of mice treat with LPS, significantly improved the functions of the heart, lung, liver, and kidney, reduced the production of inflammatory cytokines and decreased macrophage infiltration. Moreover, Multiorgan metabolomics analysis demonstrated that glutathione metabolism, purine metabolism, glycerophospholipid metabolism and pantothenate and CoA biosynthesis, were significantly altered by STV-Na. This study provides novel insights into the metabolite changes of multiple organ injury in septic mice, which may help characterize the underlying mechanism and provide an improved understanding of the therapeutic effects of STV-Na on sepsis.
Fulltext (R)-Salbutamol Improves Imiquimod-Induced Psoriasis-Like Skin Dermatitis by Regulating the Th17/Tregs Balance and Glycerophospholipid Metabolism

Liu F, Wang S, Liu B, Wang Y, Tan W

Cells, 2020 02 24;9(2).
PMID: 32102363 DOI: 10.3390/cells9020511

Psoriasis is a skin disease that is characterized by a high degree of inflammation caused by immune dysfunction. (R)-salbutamol is a bronchodilator for asthma and was reported to alleviate immune system reactions in several diseases. In this study, using imiquimod (IMQ)-induced mouse psoriasis-like dermatitis model, we evaluated the therapeutic effects of (R)-salbutamol in psoriasis in vivo, and explored the metabolic pathway involved. The results showed that, compared with IMQ group, (R)-salbutamol treatment significantly ameliorated psoriasis, reversed the suppressive effects of IMQ on differentiation, extreme keratinocyte proliferation, and infiltration of inflammatory cells. Enzyme-linked immunosorbent assays (ELISA) showed that (R)-salbutamol markedly reduced the plasma levels of IL-17. Cell analysis using flow cytometry showed that (R)-salbutamol decreased the proportion of CD4+ Th17+ T cells (Th17), whereas it increased the percentage of CD25+ Foxp3+ regulatory T cells (Tregs) in the spleens. (R)-salbutamol also decreased the weight ratio of spleen to body. Furthermore, untargeted metabolomics showed that (R)-salbutamol affected three metabolic pathways, including (i) arachidonic acid metabolism, (ii) sphingolipid metabolism, and (iii) glycerophospholipid metabolism. These results demonstrated that (R)-salbutamol can alleviate IMQ-induced psoriasis through regulating Th17/Tregs cell response and glycerophospholipid metabolism. It may provide a new use of (R)-salbutamol in the management of psoriasis.
Fulltext Isosteviol Sodium Exerts Anti-Colitic Effects on BALB/c Mice with Dextran Sodium Sulfate-Induced Colitis Through Metabolic Reprogramming and Immune Response Modulation

Wang S, Huang J, Liu F, Tan KS, Deng L, Lin Y, et al.

J Inflamm Res, 2021;14:7107-7130.
PMID: 34992409 DOI: 10.2147/JIR.S344990

PURPOSE: Inflammatory bowel diseases (IBDs) are global health problems that are associated with immune regulation, but clinical IBDs treatment is currently inadequate. Effective preventive or therapeutic methods for immune disorders rely on controlling the function of immune cells. Isosteviol sodium (STV-Na) has antioxidant activity, but the therapeutic effect of STV-Na against IBD remain undocumented. Herein, we investigated the therapeutic effect of STV-Na in mice models with IBDs.
METHODS: Mice received 3.5% DSS for 7 days to establish IBD models. Intraperitoneal STV-Na was given 2 days before DSS and lasted for 9 days. Commercially available drugs used in treating IBDs (5-aminosalicylic acid, dexamethasone, and infliximab) were used as positive controls. Samples were collected 7 days after colitis induction. Histopathological score, biochemical parameters, molecular biology methods, and metabolomics were used for evaluating the therapeutic effect of STV-Na.
RESULTS: Our data revealed that STV-Na could significantly alleviate colon inflammation in mice with colitis. Specifically, STV-Na treatment improved body weight loss, increased colon length, decreased histology scores, and restored the hematological parameters of mice with colitis. The untargeted metabolomics analysis revealed that metabolic profiles were restored by STV-Na treatment. Furthermore, STV-Na therapy suppressed the number of CD68 macrophages and F4/80 cell infiltration. And STV-Na suppressed M1 and M2 macrophage numbers along with the mRNA expressions of proinflammatory cytokines. Moreover, STV-Na administration increased the number of regulatory T (Treg) cells while decreasing Th1/Th2/Th17 cell counts in the spleen. Additionally, STV-Na treatment restored intestinal barrier disruption in DSS-triggered colitis tissues by ameliorating the TJ proteins, increasing goblet cell proportions, and mucin protein production, and decreasing the permeability to FITC-dextran, which was accompanied by decreased plasma LPS and DAO contents.
CONCLUSION: These results indicate that STV-Na can ameliorate colitis by modulating immune responses along with metabolic reprogramming, and could therefore be a promising therapeutic strategy for IBDs.
Fulltext Exploring the efficacy of 1-amino-cyclopropane-1-carboxylic acid (ACCA) as a natural compound in strengthening maize resistance against biotic and abiotic stressors: an empirical computational study

Debnath S, Elgorban AM, Bahkali AH, Eswaramoorthy R, Verma M, Tiwari P, et al.

Front Microbiol, 2023;14:1232086.
PMID: 37637126 DOI: 10.3389/fmicb.2023.1232086

OBJECTIVE: This study aims to understand plant-bacteria interactions that enhance plant resistance to environmental stressors, with a focus on maize (Zea mays L.) and its vulnerability to various pathogenic organisms. We examine the potential of 1-amino-cyclopropane-1-carboxylic acid (ACCA) as a compound to boost maize's resilience against stressors and pathogens.
BACKGROUND: With the growing global population and increased food demand, the study of endophytes, comprising bacteria and fungi, becomes crucial. They reside within plant tissues, affecting their hosts either beneficially or detrimentally. Agrobacteria are of specific interest due to their potential to contribute to developing strategies for plant resistance enhancement.
METHODS: We conducted exhaustive research on the defense-related proteins and mechanisms involved in maize-pathogen interactions. The efficacy of ACCA as a natural-compound that could enhance maize's resistance was examined.
RESULTS: Our research indicates that ACCA, having a binding energy of -9.98 kcal/mol, successfully strengthens maize resistance against pathogenic assaults and drought stress. It plays a crucial protective role in maize plants as they mature, outperforming other ligands in its effectiveness to improve productivity and increase yield.
CONCLUSION: Applying ACCA to maize plants has considerable potential in enhancing their resilience and tolerance to stress, proving to be an effective strategy to boost crop yield and productivity. This could help address the increasing global food demand. However, more research is needed to optimize ACCA application methods and to gain a comprehensive understanding of its long-term effects on maize cultivations and the environment.

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