PubMed

Br J Pharmacol. 2024 Jun 16. doi: 10.1111/bph.16432. Online ahead of print.ABSTRACTBACKGROUND AND PURPOSE: Ulcerative colitis (UC) is a refractory inflammatory disease associated with immune dysregulation. Elevated levels of heat shock protein (HSP) 90 in the β but not α subtype were positively associated with disease status in UC patients. This study validated the possibility that pharmacological inhibition or reduction of HSP90β would alleviate colitis, induced by dextran sulfate sodium, in mice and elucidated its mechanisms.EXPERIMENTAL APPROACH: Histopathological and biochemical analysis assessed disease severity, and bioinformatics and correlation analysis explained the association between the many immune cells and HSP90β. Flow cytometry was used to analyse the homeostasis and transdifferentiation of Th17 and Treg cells. In vitro inhibition and adoptive transfer assays were used to investigate functions of the phenotypically transformed Th17 cells. Metabolomic analysis, DNA methylation detection and chromatin immunoprecipitation were used to explore these mechanisms.KEY RESULTS: The selective pharmacological inhibitor (HSP90βi) and shHSP90β significantly mitigated UC in mice and promoted transformation of Th17 to Treg cell phenotype, via Foxp3 transcription. The phenotypically-transformed Th17 cells by HSP90βi or shHSP90β were able to inhibit lymphocyte proliferation and colitis in mice. HSP90βi and shHSP90β selectively weakened glycolysis by stopping the direct association of HSP90β and GLUT1, the key glucose transporter, to accelerate ubiquitination degradation of GLUT1, and enhance the methylation of Foxp3 CNS2 region. Then, the mediator path was identified as the "lactate-STAT5-TET2" cascade.CONCLUSION AND IMPLICATIONS: HSP90β shapes the fate of Th17 cells via glycolysis-controlled methylation modification to affect UC progression, which provides a new therapeutic target for UC.PMID:38881036 | DOI:10.1111/bph.16432

Cancer Control. 2024 Jan-Dec;31:10732748241261539. doi: 10.1177/10732748241261539.ABSTRACTCervical cancer is the fourth most common cancer in women. Advanced stage and metastatic disease are often associated with poor clinical outcomes. This substantiates the absolute necessity for high-throughput diagnostic and treatment platforms that are patient and tumour specific. Cervical cancer treatment constitutes multimodal intervention. Systemic treatments such as chemotherapy and/or focal radiotherapy are typically applied as neoadjuvant and/or adjuvant strategies. Cisplatin constitutes an integral part of standard cervical cancer treatment approaches. However, despite initial patient response, de novo or delayed/acquired treatment resistance is often reported, and toxicity is of concern. Chemotherapy resistance is associated with major alterations in genomic, metabolomic, epigenetic and proteomic landscapes. This results in imbalanced homeostasis associated with pro-oncogenic and proliferative survival, anti-apoptotic benefits, and enhanced DNA damage repair processes. Although significant developments in cancer diagnoses and treatment have been made over the last two decades, drug resistance remains a major obstacle to overcome.PMID:38881031 | DOI:10.1177/10732748241261539

Diabetol Metab Syndr. 2024 Jun 16;16(1):131. doi: 10.1186/s13098-024-01365-1.ABSTRACTBACKGROUND: Type 2 diabetes is an endocrine disorder characterized by compromised insulin sensitivity that eventually leads to overt disease. Adipose stem cells (ASCs) showed promising potency in improving type 2 diabetes and its complications through their immunomodulatory and differentiation capabilities. However, the hyperglycaemia of the diabetic microenvironment may exert a detrimental effect on the functionality of ASCs. Herein, we investigate ASC homeostasis and regenerative potential in the diabetic milieu.METHODS: We conducted data collection and functional enrichment analysis to investigate the differential gene expression profile of MSCs in the diabetic microenvironment. Next, ASCs were cultured in a medium containing diabetic serum (DS) or normal non-diabetic serum (NS) for six days and one-month periods. Proteomic analysis was carried out, and ASCs were then evaluated for apoptosis, changes in the expression of surface markers and DNA repair genes, intracellular oxidative stress, and differentiation capacity. The crosstalk between the ASCs and the diabetic microenvironment was determined by the expression of pro and anti-inflammatory cytokines and cytokine receptors.RESULTS: The enrichment of MSCs differentially expressed genes in diabetes points to an alteration in oxidative stress regulating pathways in MSCs. Next, proteomic analysis of ASCs in DS revealed differentially expressed proteins that are related to enhanced cellular apoptosis, DNA damage and oxidative stress, altered immunomodulatory and differentiation potential. Our experiments confirmed these data and showed that ASCs cultured in DS suffered apoptosis, intracellular oxidative stress, and defective DNA repair. Under diabetic conditions, ASCs also showed compromised osteogenic, adipogenic, and angiogenic differentiation capacities. Both pro- and anti-inflammatory cytokine expression were significantly altered by culture of ASCs in DS denoting defective immunomodulatory potential. Interestingly, ASCs showed induction of antioxidative stress genes and proteins such as SIRT1, TERF1, Clusterin and PKM2.CONCLUSION: We propose that this deterioration in the regenerative function of ASCs is partially mediated by the induced oxidative stress and the diabetic inflammatory milieu. The induction of antioxidative stress factors in ASCs may indicate an adaptation mechanism to the increased oxidative stress in the diabetic microenvironment.PMID:38880916 | DOI:10.1186/s13098-024-01365-1

BMC Plant Biol. 2024 Jun 17;24(1):567. doi: 10.1186/s12870-024-05278-z.ABSTRACTCadmium (Cd) is a nonessential element in plants and has adverse effects on the growth and development of plants. However, the molecular mechanisms of Cd phytotoxicity, tolerance and accumulation in hyperaccumulators Solanum nigrum L. has not been well understood. Here, physiology, transcriptome, and metabolome analyses were conducted to investigate the influence on the S. nigrum under 0, 25, 50, 75 and 100 µM Cd concentrations for 7 days. Pot experiments demonstrated that compared with the control, Cd treatment significantly inhibited the biomass, promoted the Cd accumulation and translocation, and disturbed the balance of mineral nutrient metabolism in S. nigrum, particularly at 100 µM Cd level. Moreover, the photosynthetic pigments contents were severely decreased, while the content of total protein, proline, malondialdehyde (MDA), H2O2, and antioxidant enzyme activities generally increased first and then slightly declined with increasing Cd concentrations, in both leaves and roots. Furthermore, combined with the previous transcriptomic data, numerous crucial coding-genes related to mineral nutrients and Cd ion transport, and the antioxidant enzymes biosynthesis were identified, and their expression pattern was regulated under different Cd stress. Simultaneously, metabolomic analyses revealed that Cd treatment significantly changed the expression level of many metabolites related to amino acid, lipid, carbohydrate, and nucleotide metabolism. Metabolic pathway analysis also showed that S. nigrum roots activated some differentially expressed metabolites (DEMs) involved in energy metabolism, which may enhance the energy supply for detoxification. Importantly, central common metabolism pathways of DEGs and DEMs, including the "TCA cycle", "glutathione metabolic pathway" and "glyoxylate and dicarboxylate metabolism" were screened using conjoint transcriptomics and metabolomics analysis. Our results provide some novel evidences on the physiological and molecular mechanisms of Cd tolerance in hyperaccumulator S. nigrum plants.PMID:38880885 | DOI:10.1186/s12870-024-05278-z

Plant Sci. 2024 Jun 14:112158. doi: 10.1016/j.plantsci.2024.112158. Online ahead of print.ABSTRACTArtemisia argyi is an herbaceous plant of the genus Artemisia. Its young and mature leaves are used as food and medicine, respectively. Glandular trichomes (GTs) are distributed on the leaf surface in A. argyi and are generally considered the location of flavonoid biosynthesis and accumulation. However, the mechanism of flavonoid biosynthesis and accumulation in A. argyi remains unclear. In this study, the coregulatory genes involved in flavonoid biosynthesis and trichome development in this species were screened and evaluated, and the biosynthetic pathways for key flavonoids in A. argyi were uncovered. AaMYB1 and AaYABBY1 were screened using weighted gene co-expression network analysis, and both genes were then genetically transformed into Nicotiana tabacum L. cv. K326 (tobacco). Simultaneously, AaYABBY1 was also genetically transformed into Arabidopsis thaliana. The total flavonoid and rutin contents were increased in tobacco plants overexpressing AaMYB1 and AaYABBY1, and the expression levels of genes participating in the flavonoid synthesis pathway, such as PAL, FLS, and F3H, were significantly up-regulated in plants overexpressing these genes. These results indicated that AaMYB1 and AaYABBY1 promote flavonoid biosynthesis in tobacco. Furthermore, compared to that in the wild-type, the trichome density was significantly increased in tobacco and A. thaliana plants overexpressing AaYABBY1. These results confirm that AaYABBY1 might be involved in regulating trichome formation in A. argyi. This indicates the potential genes involved in and provides new insights into the development of trichome cellular factories based on the "development-metabolism" interaction network and the cultivation of high-quality A. argyi.PMID:38880338 | DOI:10.1016/j.plantsci.2024.112158

Genomics. 2024 Jun 14:110886. doi: 10.1016/j.ygeno.2024.110886. Online ahead of print.ABSTRACTBACKGROUND: Fibre diameter is an important economic trait of wool fibre. As the fibre diameter decreases, the economic value of wool increases. Therefore, understanding the mechanism of wool fibre diameter regulation is important in improving the value of wool.RESULTS: In this study, we used non-targeted metabolome and reference transcriptome data to detect differences in metabolites and genes in groups of Alpine Merino sheep with different wool fibre diameter gradients, and integrated metabolome and transcriptome data to identify key genes and metabolites that regulate wool fibre diameter. We found 464 differentially abundant metabolites (DAMs) and 901 differentially expressed genes (DEGs) in four comparisons of groups with different wool fibre diameters. Approximately 25% of the differentially abundant metabolites were lipid and lipid-like molecules. These molecules were predicted to be associated with skin development and keratin filament by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. Key genes, including COL5A2, COL5A3, CREB3L4, COL1A1, and SFRP4, were identified by gene set enrichment analysis.CONCLUSIONS: Key genes regulating wool fibre diameter were identified, the effects of lipid molecules on wool performance were investigated, and potential synergies between genes and metabolites were postulated, providing a theoretical framework for fine wool sheep breeding.PMID:38880312 | DOI:10.1016/j.ygeno.2024.110886

Chemosphere. 2024 Jun 14:142619. doi: 10.1016/j.chemosphere.2024.142619. Online ahead of print.ABSTRACTThe present study aims to compare and assess the toxicity induced by aged (irradiated with ultraviolet radiation for 120 days) polyethylene microplastics (PE-MPs) in comparison to virgin (non-irradiated) ones, after feeding the freshwater fish Perca fluviatilis. To this end, MPs mediated genotoxicity was assessed by the investigation of micronucleus nuclear abnormalities frequency in fish blood, and the degree of DNA damage in the liver and muscle tissues, while metabolic alterations were also recorded in both tissues. Results showed that both virgin and aged PE-MPs induced signaling pathways leading to DNA damage and nuclear abnormalities, as well as metabolites changes in all tissues studied. Metabolic changes revealed that the metabolism of nucleic acids, energy, amino acids, and neurotransmitters was more disrupted in the liver and by aged PE-MPs compared to muscles. Fish fed with aged PE-MPs exhibited greater DNA damage, while blood cells of fish fed with virgin PE-MPs seemed to be more vulnerable to nuclear abnormalities in relation to those fed with aged PE-MPs. Moreover, aged PE-MPs induced more acute overall effects on the metabolic profiles of fish tissues, and initiated stronger stress responses, inflammation, and cellular damages in fish tissues in relation to virgin ones. Characterization of both virgin and aged MPs revealed that the latter exhibited lower crystallinity and melting point, more irregular shapes and higher moiety of oxygen and carbonyl groups, which could be attributed for their observed higher toxicity. The research outcomes provide significant insights for advancing toxicological investigations in this field.PMID:38880257 | DOI:10.1016/j.chemosphere.2024.142619

Dev Comp Immunol. 2024 Jun 14:105213. doi: 10.1016/j.dci.2024.105213. Online ahead of print.ABSTRACTRegulation of neuroimmune interactions varies across avian species. Little is presently known about the interplay between periphery and central nervous system (CNS) in parrots, birds sensitive to neuroinflammation. Here we investigated the systemic and CNS responses to dextran sulphate sodium (DSS)- and lipopolysaccharide (LPS)-induced subclinical acute peripheral inflammation in budgerigar (Melopsittacus undulatus). Three experimental treatment groups differing in DSS and LPS stimulation were compared to controls. Individuals treated with DSS showed significant histological intestinal damage. Through quantitative proteomics we described changes in plasma (PL) and cerebrospinal fluid (CSF) composition. In total, we identified 180 proteins in PL and 978 proteins in CSF, with moderate co-structure between the proteomes. Between treatments we detected differences in immune, coagulation and metabolic pathways. Proteomic variation was associated with the levels of pro-inflammatory cytokine mRNA expression in intestine and brain. Our findings shed light on systemic impacts of peripheral low-grade inflammation in birds.PMID:38880215 | DOI:10.1016/j.dci.2024.105213

Sci Total Environ. 2024 Jun 14:173913. doi: 10.1016/j.scitotenv.2024.173913. Online ahead of print.ABSTRACTThe globally distributed harmful algal blooms (HAB) species, Heterosigma akashiwo, has been found to exhibit ichthyotoxicity. Previous studies have shown that H. akashiwo achieves a competitive edge during bloom occurrences by inhibiting the growth of a coexisting diatom, Skeletonema costatum, through allelopathy. However, the specific allelopathic mechanisms underlying the allelopathic effects of H. akashiwo on S. costatum remain unknown. To bridge this gap, our study utilized a combination of quantitative real-time PCR and metabolomics to examine the allelopathic processes of H. akashiwo on S. costatum. Our results demonstrate that the growth of S. costatum is hindered when co-cultured with H. akashiwo (initial cell concentration, 2 × 104 cell/mL). Gene expression investigation showed a substantial reduction in the mRNA levels of cytochrome b6, ribulose bisphosphate carboxylase large chain, and silicon transporter in S. costatum when grown in co-culture conditions. Furthermore, metabolic pathway analysis suggested that the allelopathic effects of H. akashiwo disrupted several vital metabolic pathways in S. costatum, including a reduction in purine and pyrimidine metabolism and an increase in fatty acid biosynthesis. Our investigation has revealed the intricate and substantial involvement of allelopathy in the formation of H. akashiwo blooms, demonstrating the complexity of the allelopathic interaction between H. akashiwo and S. costatum. These insights also contribute significantly to our understanding of the dynamics within HAB species.PMID:38880157 | DOI:10.1016/j.scitotenv.2024.173913

Sci Total Environ. 2024 Jun 14:174014. doi: 10.1016/j.scitotenv.2024.174014. Online ahead of print.ABSTRACTThe threat of neonicotinoids to insect pollinators, particularly honeybees (Apis mellifera), is a global concern, but the risk of chiral neonicotinoids to insect larvae remains poorly understood. In the current study, we evaluated the acute and chronic toxicity of dinotefuran enantiomers to honeybee larvae in vitro and explored the mechanism of toxicity. The results showed that the acute median lethal dose (LD50) of S-dinotefuran to honeybee larvae was 30.0 μg/larva after oral exposure for 72 h, which was more toxic than rac-dinotefuran (92.7 μg/larva) and R-dinotefuran (183.6 μg/larva). Although the acute toxicity of the three forms of dinotefuran to larvae was lower than that to adults, chronic exposure significantly reduced larval survival, larval weight, and weight of newly emerged adults. Analysis of gene expression and hormone titer indicated that dinotefuran affects larval growth and development by interfering with nutrient digestion and absorption and the molting system. Analysis of hemolymph metabolome further revealed that disturbances in the neuroactive ligand-receptor interaction pathway and energy metabolism are the key mechanisms of dinotefuran toxicity to bee larvae. In addition, melatonin and vitellogenin are used by larvae to cope with dinotefuran-induced oxidative stress. Our results contribute to a comprehensive understanding of dinotefuran damage to bees and provide new insights into the mechanism of enantioselective toxicity of insecticides to insect larvae.PMID:38880156 | DOI:10.1016/j.scitotenv.2024.174014

J Chromatogr B Analyt Technol Biomed Life Sci. 2024 Jun 3;1242:124189. doi: 10.1016/j.jchromb.2024.124189. Online ahead of print.ABSTRACTGrape and grape derived products contain many bioactive phenolics which have a variety of impacts on health. Following oral ingestion, the phenolic compounds and their metabolites may be detectable in human urine. However, developing a reliable method for the analysis of phenolic compounds in urine is challenging. In this work, we developed and validated a new high-throughput, sensitive and reproducible analytical method for the simultaneous analysis of 31 grape phenolic compounds and metabolites using Oasis PRiME HLB cleanup for sample preparation combined with ultra-performance liquid chromatography with triple quadrupole tandem mass spectrometry (UHPLC-QqQ-MS/MS). Using this new method, the accuracy achieved was 69.3 % ∼ 134.9 % (except for six compounds), and the recovery achieved was 52.4 % ∼ 134.7 % (except for two very polar compounds). For each of the 31 target analytes, the value of intra-day precision was less than 14.3 %. The value of inter-day precision was slightly higher than intra-day precision, with a range of 0.7 % ∼ 19.1 %. We report for the first time on the effect of gender and BMI on the accuracy and recovery of human urine samples, and results from analysis of variance (ANOVA), and principal component analysis (PCA) indicated there was no difference in the value of accuracy and recovery between different gender or BMI (>30) using our purposed cleanup and UHPLC-QqQ-MS/MS method. Overall, this newly developed method could serve as a powerful tool for analyzing grape phenolic compounds and metabolites in human urine samples.PMID:38880055 | DOI:10.1016/j.jchromb.2024.124189

Plant Physiol Biochem. 2024 Jun 15;213:108843. doi: 10.1016/j.plaphy.2024.108843. Online ahead of print.ABSTRACTHibiscus hamabo Siebold & Zuccarini is one of the few semi-mangrove plants in the genus Hibiscus that can survive in saline-alkali soil and flooded land, but the mechanism underlying its adaptation to salt soil remains unknown. Here, to uncover this unsolved mystery, we characterized the changes in the accumulation of specific metabolites under salt stress in H. hamabo by integrating physiological, metabolic, and transcriptomic data, and found that osmotic adjustment and abscisic acid (ABA) is highly associated with the salt stress response. Further, a weighted gene co-expression network analysis was performed on the root transcriptome data, which identified three key candidate transcription factors responsive to salt stress. Among them, the expression HhERF9 was significantly upregulated under salt stress and ABA treatment and was involved in regulating the expression of genes related to the salt stress response. Further research indicated that HhERF9 enhances the accumulation of proline and soluble sugars by regulating the expression of genes such as NHX2 and P5CS. These findings provide a reference for improving H. hamabo through targeted genetic engineering and lay a theoretical foundation for its future promotion and cultivation in saline-alkali areas.PMID:38879985 | DOI:10.1016/j.plaphy.2024.108843

Metabolomics. 2024 Jun 16;20(4):65. doi: 10.1007/s11306-024-02134-x.ABSTRACTBACKGROUND: Preeclampsia is a pregnancy-specific clinical syndrome and can be subdivided into early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE) according to the gestational age of delivery. Patients with preeclampsia have aberrant lipid metabolism. This study aims to compare serum lipid profiles of normal pregnant women with EOPE or LOPE and screening potential biomarkers to diagnose EOPE or LOPE.METHODS: Twenty normal pregnant controls (NC), 19 EOPE, and 19 LOPE were recruited in this study. Untargeted lipidomics based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to compare their serum lipid profiles.RESULTS: The lipid metabolism profiles significantly differ among the NC, EOPE, and LOPE. Compared to the NC, there were 256 and 275 distinct lipids in the EOPE and LOPE, respectively. Furthermore, there were 42 different lipids between the LOPE and EOPE, of which eight were significantly associated with fetal birth weight and maternal urine protein. The five lipids that both differed in the EOPE and LOPE were DGTS (16:3/16:3), LPC (20:3), LPC (22:6), LPE (22:6), PC (18:5e/4:0), and a combination of them were a potential biomarker for predicting EOPE or LOPE. The receiver operating characteristic analysis revealed that the diagnostic power of the combination for distinguishing the EOPE from the NC and for distinguishing the LOPE from the NC can reach 1.000 and 0.992, respectively. The association between the lipid modules and clinical characteristics of EOPE and LOPE was investigated by the weighted gene co-expression network analysis (WGCNA). The results demonstrated that the main different metabolism pathway between the EOPE and LOPE was enriched in glycerophospholipid metabolism.CONCLUSIONS: Lipid metabolism disorders may be a potential mechanism of the pathogenesis of preeclampsia. Lipid metabolites have the potential to serve as biomarkers in patients with EOPE or LOPE. Furthermore, lipid metabolites correlate with clinical severity indicators for patients with EOPE and LOPE, including fetal birth weight and maternal urine protein levels.PMID:38879866 | DOI:10.1007/s11306-024-02134-x

Sci Rep. 2024 Jun 15;14(1):13862. doi: 10.1038/s41598-024-64586-4.ABSTRACTAcute kidney injury (AKI) is a systemic disease that affects energy metabolism in various remote organs in murine models of ischemic AKI. However, AKI-mediated effects in the liver have not been comprehensively assessed. After inducing ischemic AKI in 8-10-week-old, male C57BL/6 mice, mass spectrometry metabolomics revealed that the liver had the most distinct phenotype 24 h after AKI versus 4 h and 7 days. Follow up studies with in vivo [13C6]-glucose tracing on liver and kidney 24 h after AKI revealed 4 major findings: (1) increased flux through glycolysis and the tricarboxylic (TCA) cycle in both kidney and liver; (2) depleted hepatic glutathione levels and its intermediates despite unchanged level of reactive oxygen species, suggesting glutathione consumption exceeds production due to systemic oxidative stress after AKI; (3) hepatic ATP depletion despite unchanged rate of mitochondrial respiration, suggesting increased ATP consumption relative to production; (4) increased hepatic and renal urea cycle intermediates suggesting hypercatabolism and upregulation of the urea cycle independent of impaired renal clearance of nitrogenous waste. Taken together, this is the first study to describe the hepatic metabolome after ischemic AKI in a murine model and demonstrates that there is significant liver-kidney crosstalk after AKI.PMID:38879688 | DOI:10.1038/s41598-024-64586-4

Cardiovasc Diabetol. 2024 Jun 15;23(1):205. doi: 10.1186/s12933-024-02296-x.ABSTRACTBACKGROUND: There has been a substantial increase in the use of laparoscopic sleeve gastrectomy (SG) to treat morbid obesity despite observational evidence demonstrating the superiority of Roux-en-Y gastric bypass (RYGB) for reducing low-density lipoprotein (LDL) cholesterol. The main aim was to ascertain whether high LDL cholesterol levels should be considered when selecting the most appropriate surgical procedure for each patient (RYGB or SG).METHODS: In this single-center, randomized clinical trial using intention-to-treat analysis, 38 patients with severe obesity and elevated levels of LDL cholesterol were randomly assigned to undergo RYGB or SG. The primary outcome was LDL cholesterol remission at 12 months, defined as LDL cholesterol < 3.36 nmol/l without lipid-lowering medications. Secondary outcomes included changes in weight, other comorbidities, qualitative lipoprotein traits, cholesterol esters, glycoproteins, cholesterol absorption and synthesis metabolites and complications.RESULTS: Intention-to-treat analysis revealed that LDL cholesterol remission occurred in 66.6% of RYGB patients compared to 27.8% of SG patients (p = 0.019). Among patients completing follow-up, RYGB demonstrated superior remission (80.0% vs. 29.4%, p = 0.005). Exclusive benefits of RYGB included a reduction in large, medium, and small LDL particles. Cholesterol absorption markers showed differential behavior after both techniques: campesterol (Δ -15.2 µg/mg, 95% CI -30.2 to -0.1) decreased after RYGB, and sitosterol (Δ 21.1 µg/mg, 95% CI 0.9 to 41.2), cholestanol (Δ 30.6 µg/mg, 95% CI 14.8 to 57.9) and campesterol (Δ 18.4 µg/mg, 95% CI 4.4 to 32.3) increased after SG. No differences in weight loss, cholesterol esters, glycoproteins, cholesterol synthesis metabolites or postoperative complications were observed between techniques.CONCLUSION: In conclusion, RYGB is superior to SG in terms of short-term of high LDL cholesterol remission. Furthermore, RYGB also led to a greater improvement in lipoprotein parameters that confer an atherogenic profile. Therefore, the presence of elevated levels of LDL cholesterol should be considered when determining the optimal bariatric surgery procedure for each patient.TRIAL REGISTRATION: Clinicaltrials.gov number, NCT03975478).PMID:38879559 | DOI:10.1186/s12933-024-02296-x

Cell Biosci. 2024 Jun 15;14(1):80. doi: 10.1186/s13578-024-01253-1.ABSTRACTBACKGROUND: About 1/3 of primary biliary cholangitis (PBC) patients suffered from poor response worldwide. And these patients present intestinal disturbances. We aimed to identify signatures of microbiota and metabolites in PBC patients with poor response, comparing to patients with response.METHODS: This study enrolled 25 subjects (14 PBC patients with response and 11 PBC patients with poor response). Metatranscriptomics and metabolomics analysis were carried out on their fecal.RESULTS: PBC patients with poor response had significant differences in the composition of bacteria, characterized by decreased Gemmiger etc. and increased Ruminococcus etc. The differential microbiota functions characterized by decreased abundance of elongation factor Tu and elongation factor G base on the KO database, as well as decreased abundance of Replicase large subunit etc. based on the SWISS-PROT database. PBC with poor response also had significant differences in 17 kinds of bacterial metabolites, characterized by decreased level of metabolites vital in bile acids metabolism pathway (L-Cysteine etc.) and the all-trans-Retinoic acid, a kind of immune related metabolite. The altered microbiota was associated with the differential expressed metabolites and clinical liver function indicators. 1 bacterial genera, 2 bacterial species and 9 metabolites simultaneously discriminated PBC with poor response from PBC with response with high accuracy.CONCLUSION: PBC patients with poor response exhibit unique changes in microbiota and metabolite. Gut microbiota and metabolite-based algorithms could be used as additional tools for differential prediction of PBC with poor prognosis.PMID:38879547 | DOI:10.1186/s13578-024-01253-1

Chin Med. 2024 Jun 15;19(1):87. doi: 10.1186/s13020-024-00958-2.ABSTRACTBACKGROUND: Shaoyao Decoction (SYD) is a widely recognized herbal formula utilized in traditional Chinese medicine for the treatment of diarrhea. Although it has demonstrated significant effectiveness in clinical practice for treating ulcerative colitis, the precise mechanisms by which it operates remain largely elusive.METHODS: The active ingredients of SYD were obtained by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), which were used to explore the potential pharmacological mechanism based on TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and PANTHER (Protein Analysis Through Evolutionary Relationships) classification system. In a mouse model of dextran sulfate sodium (DSS)-induced colitis, mRNA sequencing, 16S rDNA sequencing and targeted metabolomics techniques were used to elucidate the mechanisms of SYD, and immunohistochemistry, immunofluorescence, enzyme linked immunosorbent assay, real time quantitative polymerase chain reaction and western blot were used to test the key targets. In addition, QGP-1 and H9 cells were performed to validate the discoveries from the animal experiments.RESULTS: In the mouse model of DSS-induced colitis, SYD effectively alleviated symptoms such as bloody stool, tissue damage, inflammation, intestinal flora dysbiosis and abnormal gene expression. Analyses of both differential expressed genes in colonic tissue and predicted 16S rDNA genes, as well as the analyses of targeted genes from TCMSP based on the active ingredients in UPLC-MS/MS of SYD, uncovered the enrichment of pathways involved in the biosynthesis and degredation of 5-hydroxytryptamine (5-HT). Interestingly, SYD suppressed the relative abundance of key genes in 5-HT synthesis, Tph1(Tryptophan hydroxylase 1) and Ddc (Dopa decarboxylase), in faeces from DSS-induced mice, leading to a reduction in the concentration of fecal 5-HT. Moreover, SYD augmented the production of butyric acid. Subsequently, increasing butyric acid influenced the metabolism of 5-HT in the organism through G protein-coupled receptor 43 by impeding its synthesis, facilitating its transport and degredation. These findings were additionally corroborated in a model utilizing enterochromaffin cell (QGP-1 cells). Furthermore, reduced levels of 5-HT hindered the activation of T lymphocytes (H9 cells) via the PKC (Protein kinase C) and NF-κB (Nuclear factor kappa-B) signaling pathways, by means of HTR1A (5-HT receptor 1A) and HTR3 (5-HT receptor 3). Additionally, diminished secretion of 5-HT resulted in reduced secretion of associated cytokines, thereby alleviating inflammation in the colon.CONCLUSION: Through modulation of T lymphocyte activation mediated by 5-HT metabolism in the local colon via the intestinal flora and its metabolite, SYD effectively mitigated colonic inflammation in DSS-induced mice.PMID:38879471 | DOI:10.1186/s13020-024-00958-2

BMC Plant Biol. 2024 Jun 15;24(1):563. doi: 10.1186/s12870-024-05286-z.ABSTRACTBACKGROUND: Drought is a leading environmental factor affecting plant growth. To explore the drought tolerance mechanism of asparagus, this study analyzed the responses of two asparagus varieties, namely, 'Jilv3' (drought tolerant) and 'Pacific Early' (drought sensitive), to drought stress using metabolomics and transcriptomics.RESULTS: In total, 2,567 and 7,187 differentially expressed genes (DEGs) were identified in 'Pacific Early' and 'Jilv3', respectively, by comparing the transcriptome expression patterns between the normal watering treatment and the drought stress treatment. These DEGs were significantly enriched in the amino acid biosynthesis, carbon metabolism, phenylpropanoid biosynthesis, and plant hormone signal transduction pathways. In 'Jilv3', DEGs were also enriched in the following energy metabolism-related pathways: citrate cycle (TCA cycle), glycolysis/gluconeogenesis, and pyruvate metabolism. This study also identified 112 and 254 differentially accumulated metabolites (DAMs) in 'Pacific Early' and 'Jilv3' under drought stress compared with normal watering, respectively. The amino acid, flavonoid, organic acid, and soluble sugar contents were more significantly enhanced in 'Jilv3' than in 'Pacific Early'. According to the metabolome and transcriptome analysis, in 'Jilv3', the energy supply of the TCA cycle was improved, and flavonoid biosynthesis increased. As a result, its adaptability to drought stress improved.CONCLUSIONS: These findings help to better reveal the molecular mechanism underlying how asparagus responds to drought stress and improve researchers' ability to screen drought-tolerant asparagus varieties as well as breed new varieties.PMID:38879466 | DOI:10.1186/s12870-024-05286-z

Trends Immunol. 2024 Jun 14:S1471-4906(24)00122-4. doi: 10.1016/j.it.2024.05.008. Online ahead of print.ABSTRACTMammalian innate-like T cells (ILTCs), including mucosal-associated invariant T (MAIT), natural killer T (NKT), and γδ T cells, are abundant tissue-resident lymphocytes that have recently emerged as orchestrators of hepatic inflammation, tissue repair, and immune homeostasis. This review explores the involvement of different ILTC subsets in liver diseases. We explore the mechanisms underlying the pro- and anti-inflammatory effector functions of ILTCs in a context-dependent manner. We highlight latest findings regarding the dynamic interplay between ILTC functional subsets and other immune and parenchymal cells which may inform candidate immunomodulatory strategies to achieve improved clinical outcomes in liver diseases. We present new insights into how distinct gene expression programs in hepatic ILTCs are induced, maintained, and reprogrammed in a context- and disease stage-dependent manner.PMID:38879436 | DOI:10.1016/j.it.2024.05.008

Pestic Biochem Physiol. 2024 Jun;202:105969. doi: 10.1016/j.pestbp.2024.105969. Epub 2024 May 26.ABSTRACTPopulus pseudo-cathayana × Populus deltoides is a crucial artificial forest tree species in Northeast China. The presence of the fall webworm (Hyphantria cunea) poses a significant threat to these poplar trees, causing substantial economic and ecological damage. This study conducted an insect-feeding experiment with fall webworm on P. pseudo-cathayana × P. deltoides, examining poplar's physiological indicators, transcriptome, and metabolome under different lengths of feeding times. Results revealed significant differences in phenylalanine ammonia-lyase activity, total phenolic content, and flavonoids at different feeding durations. Transcriptomic analysis identified numerous differentially expressed genes, including AP2/ERF, MYB, and WRKY transcription factor families exhibiting the highest expression variations. Differential metabolite analysis highlighted flavonoids and phenolic acid compounds of poplar's leaves as the most abundant in our insect-feeding experiment. Enrichment analysis revealed significant enrichment in the plant hormone signal transduction and flavonoid biosynthetic pathways. The contents of jasmonic acid and jasmonoyl-L-isoleucine increased with prolonged fall webworm feeding. Furthermore, the accumulation of dihydrokaempferol, catechin, kaempferol, and naringenin in the flavonoid biosynthesis pathway varied significantly among different samples, suggesting their crucial role in response to pest infestation. These findings provide novel insights into how poplar responds to fall webworm infestation.PMID:38879313 | DOI:10.1016/j.pestbp.2024.105969