PubMed
Immunogenic Cell Stress and Death Sensitize Tumors to Immunotherapy
Cells. 2023 Dec 15;12(24):2843. doi: 10.3390/cells12242843.ABSTRACTThe efficacy of chemotherapy with cytotoxicants and that of targeted therapies with more sophisticated agents is limited due to the plasticity of malignant cells, which leads to the inevitable development of resistance [...].PMID:38132163 | DOI:10.3390/cells12242843
Blood-Derived Lipid and Metabolite Biomarkers in Cardiovascular Research from Clinical Studies: A Recent Update
Cells. 2023 Dec 8;12(24):2796. doi: 10.3390/cells12242796.ABSTRACTThe primary prevention, early detection, and treatment of cardiovascular disease (CVD) have been long-standing scientific research goals worldwide. In the past decades, traditional blood lipid profiles have been routinely used in clinical practice to estimate the risk of CVDs such as atherosclerotic cardiovascular disease (ASCVD) and as treatment targets for the primary prevention of adverse cardiac events. These blood lipid panel tests often fail to fully predict all CVD risks and thus need to be improved. A comprehensive analysis of molecular species of lipids and metabolites (defined as lipidomics and metabolomics, respectively) can provide molecular insights into the pathophysiology of the disease and could serve as diagnostic and prognostic indicators of disease. Mass spectrometry (MS) and nuclear magnetic resonance (NMR)-based lipidomics and metabolomics analysis have been increasingly used to study the metabolic changes that occur during CVD pathogenesis. In this review, we provide an overview of various MS-based platforms and approaches that are commonly used in lipidomics and metabolomics workflows. This review summarizes the lipids and metabolites in human plasma/serum that have recently (from 2018 to December 2022) been identified as promising CVD biomarkers. In addition, this review describes the potential pathophysiological mechanisms associated with candidate CVD biomarkers. Future studies focused on these potential biomarkers and pathways will provide mechanistic clues of CVD pathogenesis and thus help with the risk assessment, diagnosis, and treatment of CVD.PMID:38132115 | DOI:10.3390/cells12242796
Radiotherapy-Triggered In Situ Tumor Vaccination Boosts Checkpoint Blockaded Immune Response via Antigen-Capturing Nanoadjuvants
ACS Nano. 2023 Dec 22. doi: 10.1021/acsnano.3c10225. Online ahead of print.ABSTRACTIn situ vaccination (ISV) formed with the aid of intratumorally injected adjuvants has shed bright light on enhancing the abscopal therapeutic effects of radiotherapy. However, the limited availability of antigens resulting from the radiotherapy-induced immunogenic cell death largely hampers the clinical outcome of ISV. To maximally utilize the radiotherapy-induced antigen, we herein developed a strategy by capturing the radiotherapy-induced antigen in situ with a nanoadjuvant comprised of CpG-loaded Fe3O4 nanoparticles. The highly efficient click reaction between the maleimide residue on the nanoadjuvant and sulfhydryl group on the antigen maximized the bioavailability of autoantigens and CpG adjuvant in vivo. Importantly, combined immune checkpoint blockade can reverse T cell exhaustion after treatment with radiotherapy-induced ISV, thereby largely suppressing the treated and distant tumor. Mechanistically, metabolomics reveals the intratumorally injected nanoadjuvants disrupt redox homeostasis in the tumor microenvironment, further inducing tumor ferroptosis after radiotherapy. Overall, the current study highlights the immense potential of the innovative antigen-capturing nanoadjuvants for synergistically enhancing the antitumor effect.PMID:38131289 | DOI:10.1021/acsnano.3c10225
Plant Sample Collection and Shipment for Multi-omic Analyses and Phytosanitary Evaluation
Curr Protoc. 2023 Dec;3(12):e952. doi: 10.1002/cpz1.952.ABSTRACTPlant sample preparation for analyses is a fundamental step in high-throughput omics strategies. Especially for plant metabolomics, quenching of hydrolytic enzymes able to affect metabolite concentrations is crucial for the accuracy of results. Given that DNA is usually less labile than metabolites, most sampling and shipment procedures able to preserve the metabolome are also suitable for preventing the degradation of plant DNA or of DNA of pathogens in the plant tissue. In this article, we describe all the steps of sample collection, shipment (including the phytosanitary issues of moving plant samples), and processing for combined genomics and metabolomics from a single sample, as well as the protocols used in our laboratories for downstream approaches for crop plants, allowing collection of multi-omic datasets in large experimental setups. The protocols have been adjusted to apply to both freeze-dried and fresh-frozen material to allow the processing of crop plant samples that will require long-distance transport. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Preparation of freeze-dried leaf disks for multiplexed PCR or DArT-Seq genotyping Basic Protocol 2: Medium-throughput preparation of pathogen-free nucleic acids for most genotyping-resequencing applications or pathogen detection Alternate Protocol: Low-throughput extraction of high-quality DNA for resequencing using commercial kits Support Protocol: DNA quality control Basic Protocol 3: Preparation of freeze-dried plant material for metabolomics Basic Protocol 4: Preparation of fresh-frozen plant material for metabolomics Basic Protocol 5: Preparation and shipment of metabolite extracts for metabolomic analyses Basic Protocol 6: Sample shipping and long-term storage.PMID:38131272 | DOI:10.1002/cpz1.952
Integration of lipidomics and metabolomics reveals plasma and urinary profiles associated with pediatric Mycoplasma pneumoniae infections and its severity
Biomed Chromatogr. 2023 Dec 22:e5817. doi: 10.1002/bmc.5817. Online ahead of print.ABSTRACTMycoplasma pneumoniae is a significant contributor to lower respiratory infections in children. However, the lipidomics and metabolics bases of childhood M. pneumoniae infections remain unclear. In this study, lipidomics and metabolomics analyses were conducted using UHPLC-LTQ-Orbitrap XL mass spectrometry and gas chromatography-triple quadrupole mass spectrometry on plasma (n = 65) and urine (n = 65) samples. MS-DIAL software, in combination with LipidBlast and Fiehn BinBase DB, identified 163 lipids and 104 metabolites in plasma samples, as well as 208 metabolites in urine samples. Perturbed lipid species (adjusted p < 0.05) were observed, including lysophosphatidylethanolamines, phosphatidylinositols, phosphatidylcholines, phosphatidylethanol amines, and triglycerides. Additionally, differential metabolites (adjusted p < 0.05) exhibited associations with amino acid metabolism, nucleotide metabolism, and energy metabolism. Thirteen plasma metabolites, namely l-hydroxyproline, 3-phosphoglycerate, citric acid, creatine, inosine, ribitol, α tocopherol, cholesterol, cystine, serine, uric acid, tagatose, and glycine, showed significant associations with disease severity (p < 0.05) and exhibited distinct separation patterns in M. pneumoniae-infected bronchitis and pneumonia, with an area under the curve of 0.927. Nine of them exhibited either positive or negative correlations with neutrophil or lymphocyte percentages. These findings indicated significant systemic metabolic shifts in childhood M. pneumoniae infections, offering valuable insights into the associated metabolic alterations and their relationship with disease severity.PMID:38131121 | DOI:10.1002/bmc.5817
Action Mechanisms of Metformin Combined with Exenatide and Metformin Only in the Treatment of PCOS in Obese Patients
Int J Endocrinol. 2023 Dec 14;2023:4288004. doi: 10.1155/2023/4288004. eCollection 2023.ABSTRACTBACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine disease in women of reproductive age, whose clinical characteristics are hyperandrogenism (HA), ovulatory dysfunction, and polycystic ovary, often accompanied by insulin resistance (IR) and metabolic abnormalities. Glucagon-like peptide (GLP)-1 receptor agonists (GLP-1Ra), such as exenatide, can bind to specific receptors on tissues such as the ovaries to improve the clinical phenotype of PCOS, while insulin-sensitizing agents, such as metformin, can also benefit to metabolic abnormalities in PCOS. Liquid chromatography-mass spectrometry (LC/MS) metabolomics revealed differences between the mechanisms of exenatide and metformin treatment of PCOS to some extent.METHODS: In this study, 50 obese subjects with PCOS were randomly divided into the exenatide combined with metformin group (COM group, n = 28) and the metformin group (MF group, n = 22) for 12-week treatment. Before and after, serum samples were subjected to LC/MS analysis.RESULTS: After treatment, there were 153 named differential metabolites in the COM group and 99 in the MF group. Most phosphatidylcholines (PC) and deoxycholic acid 3-glucuronide (DA3G) were significantly upregulated, while most glycerophosphoethanolamine (PE-NMe2), glycerophosphocholine (GPC), and threonine were downregulated in both groups. Only the decrease of neuromedin B, glutamate, and glutamyl groups and the increase of chenodeoxycholic acid sulfate docosadienoate (22: 2n6), and prostaglandin E2 have been observed in the COM group. In addition, salicylic acid and spisulosine increased and decanoylcarnitine decreased in the MF group. Both groups were enriched in glycerophospholipid, choline, and sphingolipid metabolism, while the COM group was especially superior in the glutamine and glutamate, bile secretion, and amino acid metabolism.CONCLUSION: Compared with metformin alone in the treatment of PCOS, the differential metabolites of the exenatide combined with metformin group are more extensive. The COM group may act on the hypothalamic-pituitary-gonadal axis (HPO) and its bypass, regulate multiple metabolism pathways such as phospholipids, amino acids, fatty acids, carnitine, bile acids, and glucose directly or indirectly in obese PCOS patients.PMID:38131036 | PMC:PMC10735721 | DOI:10.1155/2023/4288004
Mulberry leaf supplementation inhibits skatole deposition by regulating gut microbiota and upregulating liver cytochrome P450 1A1 expression in finishing pigs
Anim Nutr. 2023 Oct 19;16:34-44. doi: 10.1016/j.aninu.2023.05.018. eCollection 2024 Mar.ABSTRACTSkatole, a strong fecal odor substance, is generated through microbial degradation of tryptophan in the animal hindgut. It easily accumulates in adipose tissue and affects meat quality. In this study, the effect of mulberry leaf supplementation on skatole in finishing pigs was studied. In a 35-day trial, 20 finishing pigs (barrows and gilts) were fed with a basal diet or basal diet with 6% mulberry leaves. Growth performance of the pigs (n = 10) was automatically recorded by a performance-testing feeder system and 8 pigs in each treatment were slaughtered and sampled for the remaining tests. Skatole and short-chain fatty acids were detected using HPLC and gas chromatography, respectively. Fecal microbiota were analyzed using 16S rRNA gene sequencing. The metabolomics analysis of feces and serum was performed with UHPLC-MS/MS. The major cytochrome P450 (CYP) enzymes that catalyze skatole degradation in the liver were tested by using RT-PCR and Western blot. Effects of major bioactive compounds in mulberry leaves on the CYP genes were verified in the hepatic cell line HepG2 in an in vitro test (n = 3). In finishing pigs, mulberry leaf supplementation had no significant effect on the average daily gain, average daily feed intake, and feed conversion ratio (P > 0.05), but reduced skatole levels in feces, serum, and backfat (P < 0.05), and increased acetic acid levels in feces (P = 0.027). Mulberry leaf supplementation decreased the relative abundance of the skatole-producing bacteria Megasphaera and Olsenella (P < 0.05). Indole-3-acetic acid, the intermediate that is essential for skatole production, was significantly reduced in feces by mulberry leaf supplementation (P < 0.05) and was positively correlated with skatole content in feces (P = 0.004). In pigs treated with mulberry leaves, liver CYP1A1 expression was increased (P < 0.05) and was negatively correlated with skatole content in backfat (P = 0.045). The in vitro test demonstrated that mulberry leaf polyphenols and polysaccharides could directly stimulate CYP1A1 expression in hepatic cells. These findings suggest that mulberry leaf supplementation reduces skatole production and deposition in finishing pigs by regulating the gut microbiota and promoting skatole degradation in liver.PMID:38131029 | PMC:PMC10730352 | DOI:10.1016/j.aninu.2023.05.018
Integrated transcriptome and metabolome revealed the drought responsive metabolic pathways in Oriental Lily <em>(Lilium L.)</em>
PeerJ. 2023 Dec 18;11:e16658. doi: 10.7717/peerj.16658. eCollection 2023.ABSTRACTOBJECTIVE: Lily is an essential ornamental flowering species worldwide. Drought stress is a major constraint affecting the morphology and physiology and lily leaves and flowers. Therefore, understanding the molecular mechanism underlying lily response to drought stress is important.METHOD: Transcriptome and metabolome analysis were performed on Oriental Lily subjected to drought stress.RESULT: Most transcription factors and metabolites yielded by the conjoint analysis displayed a downregulated expression pattern. Differential genes and metabolites mainly co-enriched in glycolic pathways related to sugars, such as galactose, and sucrose, glycolysis and gluconeogenesis, indicating that drought stress reduced the sugar metabolism level of Oriental Lily. Combined with transcriptome and metabolome data, nine pairs of differentially expressed metabolites and the genes (p < 0.05) were obtained. Interestingly, a gene named TRINITY_DN2608 (encoding a type of alpha-D-glucose) cloned and its overexpression lines in Arabidopsis thaliana was generated. Overexpression of TRINITY_DN2608 gene elevated the susceptibility to drought stress possibly by suppressing the glucose level.CONCLUSION: The enrichment of sugar-related pathways advocates the potential role of glucose metabolism in drought stress. Our study provides theoretical information related to the glucose-mediated drought response and would be fruitful in future lily breeding programs.PMID:38130923 | PMC:PMC10734436 | DOI:10.7717/peerj.16658
Biomarkers of aging through the life course: A Recent Literature Update
Curr Opin Epidemiol Public Health. 2023 Jun;2(2):7-17. doi: 10.1097/pxh.0000000000000018.ABSTRACTPURPOSE OF REVIEW: The development of biomarkers of aging has greatly advanced epidemiological studies of aging processes. However, much debate remains on the timing of aging onset and the causal relevance of these biomarkers. In this review, we discuss the most recent biomarkers of aging that have been applied across the life course.RECENT FINDINGS: The most recently developed aging biomarkers that have been applied across the life course can be designated into three categories: epigenetic clocks, epigenetic markers of chronic inflammation, and mitochondrial DNA copy number. While these have been applied at different life stages, the development, validation, and application of these markers has been largely centered on populations of older adults. Few studies have examined trajectories of aging biomarkers across the life course. As the wealth of molecular and biochemical data increases, emerging biomarkers may be able to capture complex and system-specific aging processes. Recently developed biomarkers include novel epigenetic clocks; clocks based on ribosomal DNA, transcriptomic profiles, proteomics, metabolomics, and inflammatory markers; clonal hematopoiesis of indeterminate potential gene mutations; and multi-omics approaches.SUMMARY: Attention should be placed on aging at early and middle life stages to better understand trajectories of aging biomarkers across the life course. Additionally, novel biomarkers will provide greater insight into aging processes. The specific mechanisms of aging reflected by these biomarkers should be considered when interpreting results.PMID:38130910 | PMC:PMC10732539 | DOI:10.1097/pxh.0000000000000018
<em>OsDWARF10</em>, transcriptionally repressed by <em>OsSPL3</em>, regulates the nutritional metabolism of polished rice
Front Plant Sci. 2023 Dec 7;14:1322463. doi: 10.3389/fpls.2023.1322463. eCollection 2023.ABSTRACTStrigolactone (SL) plays essential roles in plant development and the metabolism of rice leaves. However, the impact of SL on the accumulation of nutritional metabolites in polished rice, as well as the transcription factors directly involved in SL synthesis, remains elusive. In this study, we performed a metabolome analysis on polished rice samples from mutants of an SL biosynthetic gene, OsDWARF10 (OsD10). Compared with those in the wild type plants, primary and secondary metabolites exhibited a series of alterations in the d10 mutants. Notably, the d10 mutants showed a substantial increase in the amino acids and vitamins content. Through a yeast one-hybridization screening assay, we identified OsSPL3 as a transcription factor that binds to the OsD10 promoter, thereby inhibiting OsD10 transcription in vivo and in vitro. Furthermore, we conducted a metabolic profiling analysis in polished rice from plants that overexpressed OsSPL3 and observed enhanced levels of amino acids and vitamins. This study identified a novel transcriptional repressor of the SL biosynthetic gene and elucidated the regulatory roles of OsSPL3 and OsD10 on the accumulation of nutritional metabolites in polished rice.PMID:38130489 | PMC:PMC10733476 | DOI:10.3389/fpls.2023.1322463
The neonatal blood spot metabolome in retinoblastoma
EJC Paediatr Oncol. 2023 Dec;2:100123. doi: 10.1016/j.ejcped.2023.100123. Epub 2023 Nov 10.ABSTRACTBACKGROUND: Retinoblastoma is rare but nevertheless the most common pediatric eye cancer that occurs in children under age 5. High-resolution metabolomics (HRM) is a powerful analytical approach to profile metabolic features and pathways or identify metabolite biomarkers. To date, no studies have used pre-diagnosis blood samples from retinoblastoma cases and compared them to healthy controls to elucidate early perturbations in tumor pathways.OBJECTIVES: Here, we report on metabolic profiles of neonatal blood comparing cases later in childhood diagnosed with retinoblastoma and controls.METHODS: We employed untargeted metabolomics analysis using neonatal dried blood spots for 1327 children (474 retinoblastoma cases and 853 healthy controls) born in California from 1983 to 2011. Cases were selected from the California Cancer Registry and controls, frequency matched to cases by birth year, from California birth rolls. We performed high-resolution metabolomics to extract metabolic features, partial least squares discriminant analysis (PLS-DA) and logistic regression to identify features associated with disease, and Mummichog pathway analysis to characterize enriched biological pathways.RESULTS: PLS-DA identified 1917 discriminative features associated with retinoblastoma and Mummichog identified 14 retinoblastoma-related enriched pathways including linoleate metabolism, pentose phosphate pathway, pyrimidine metabolism, fructose and mannose metabolism, vitamin A metabolism, as well as fatty acid and lipid metabolism.INTERPRETATION: Our findings linked a retinoblastoma diagnosis in early life to newborn blood metabolome perturbations indicating alterations in inflammatory pathways and energy metabolism. Neonatal blood spots may provide a venue for early detection for this or potentially other childhood cancers.PMID:38130370 | PMC:PMC10735245 | DOI:10.1016/j.ejcped.2023.100123
Ultrasound-guided extracorporeal shock wave lithotripsy with minimal x-ray exposure prevented genitourinary tract injury patients with urolithiasis in Taiwan
Sci Prog. 2023 Oct-Dec;106(4):368504231220988. doi: 10.1177/00368504231220988.ABSTRACTBACKGROUND: This study investigated the use of ultrasound-guided extracorporeal shock wave lithotripsy (ESWL) to break stones in the genitourinary tract and prevent genitourinary injury. Our goals were to achieve accurate focusing and minimal X-ray exposure for the benefit of the patients.METHODS: The LiteMed LM-9200 lithotripter with ultrasonography and fluoroscopy was used for two different procedures: autoaimed and autoperiodical. These procedures enabled dual focusing on stone localization and tracking.RESULTS: Out of 108 patients who underwent autoperiodical procedures, 29 had no gross hematuria. Among the 335 patients who received autoaimed procedures, 194 had no gross hematuria. The average duration of X-ray exposure during autoperiodical and autoaimed procedures was 120 and 50 s, respectively.CONCLUSION: The ultrasound-guided ESWL with minimal X-ray exposure was found to be useful in treating genitourinary upper-tract urolithiasis in the autoaimed procedure. Patients who underwent the autoaimed procedure experienced less gross hematuria compared to those who underwent the autoperiodical procedure.PMID:38130182 | DOI:10.1177/00368504231220988
Comparative genomic and metabolomic study of three Streptomyces sp. differing in biological activity
Microbiologyopen. 2023 Dec;12(6):e1389. doi: 10.1002/mbo3.1389.ABSTRACTThe Streptomyces genus is known to produce many specialized metabolites of value for medicine, but the potential of these metabolites in agronomy remains largely unexplored. In this study, we investigated three phylogenetically closely related Streptomyces strains (B5, B91, and B135) isolated from three distinct soil samples in Sudan. Despite belonging to the same species, these strains exhibited different ranges of Phytophthora infestans inhibition. The objective of this work was to identify the active compound(s) responsible for the inhibition of P. infestans and of other plant pathogens by comparing the genomes and metabolomes of the three strains which showed distinct activity patterns: B5 was the strongest inhibitor of oomycetes, B5 and B91 both inhibited most fungi and B135 was the only strain showing antibacterial activity. Our comparative genomic and metabolomic analysis identified borrelidin as the bioactive compound underlying B5's strong anti-oomycete activity and highlighted a few other metabolites as putative candidates underlying the strains' antifungal and antibacterial activities. This study illustrates the power of comparative genomics and metabolomics on phylogenetically closely related strains of differing activities to highlight bioactive compounds that could contribute to new sustainable crop protection strategies.PMID:38129981 | DOI:10.1002/mbo3.1389
Succinate-induced macrophage polarization and RBP4 secretion promote vascular sprouting in ocular neovascularization
J Neuroinflammation. 2023 Dec 21;20(1):308. doi: 10.1186/s12974-023-02998-1.ABSTRACTPathological neovascularization is a pivotal biological process in wet age-related macular degeneration (AMD), retinopathy of prematurity (ROP) and proliferative diabetic retinopathy (PDR), in which macrophages (Mφs) play a key role. Tip cell specialization is critical in angiogenesis; however, its interconnection with the surrounding immune environment remains unclear. Succinate is an intermediate in the tricarboxylic acid (TCA) cycle and was significantly elevated in patients with wet AMD by metabolomics. Advanced experiments revealed that SUCNR1 expression in Mφ and M2 polarization was detected in abnormal vessels of choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR) models. Succinate-induced M2 polarization via SUCNR1, which facilitated vascular endothelial cell (EC) migration, invasion, and tubulation, thus promoting angiogenesis in pathological neovascularization. Furthermore, evidence indicated that succinate triggered the release of RBP4 from Mφs into the surroundings to regulate endothelial sprouting and pathological angiogenesis via VEGFR2, a marker of tip cell formation. In conclusion, our results suggest that succinate represents a novel class of vasculature-inducing factors that modulate Mφ polarization and the RBP4/VEGFR2 pathway to induce pathological angiogenic signaling through tip cell specialization.PMID:38129891 | DOI:10.1186/s12974-023-02998-1
Longitudinal multi-omics study reveals common etiology underlying association between plasma proteome and BMI trajectories in adolescent and young adult twins
BMC Med. 2023 Dec 21;21(1):508. doi: 10.1186/s12916-023-03198-7.ABSTRACTBACKGROUND: The influence of genetics and environment on the association of the plasma proteome with body mass index (BMI) and changes in BMI remains underexplored, and the links to other omics in these associations remain to be investigated. We characterized protein-BMI trajectory associations in adolescents and adults and how these connect to other omics layers.METHODS: Our study included two cohorts of longitudinally followed twins: FinnTwin12 (N = 651) and the Netherlands Twin Register (NTR) (N = 665). Follow-up comprised 4 BMI measurements over approximately 6 (NTR: 23-27 years old) to 10 years (FinnTwin12: 12-22 years old), with omics data collected at the last BMI measurement. BMI changes were calculated in latent growth curve models. Mixed-effects models were used to quantify the associations between the abundance of 439 plasma proteins with BMI at blood sampling and changes in BMI. In FinnTwin12, the sources of genetic and environmental variation underlying the protein abundances were quantified by twin models, as were the associations of proteins with BMI and BMI changes. In NTR, we investigated the association of gene expression of genes encoding proteins identified in FinnTwin12 with BMI and changes in BMI. We linked identified proteins and their coding genes to plasma metabolites and polygenic risk scores (PRS) applying mixed-effects models and correlation networks.RESULTS: We identified 66 and 14 proteins associated with BMI at blood sampling and changes in BMI, respectively. The average heritability of these proteins was 35%. Of the 66 BMI-protein associations, 43 and 12 showed genetic and environmental correlations, respectively, including 8 proteins showing both. Similarly, we observed 7 and 3 genetic and environmental correlations between changes in BMI and protein abundance, respectively. S100A8 gene expression was associated with BMI at blood sampling, and the PRG4 and CFI genes were associated with BMI changes. Proteins showed strong connections with metabolites and PRSs, but we observed no multi-omics connections among gene expression and other omics layers.CONCLUSIONS: Associations between the proteome and BMI trajectories are characterized by shared genetic, environmental, and metabolic etiologies. We observed few gene-protein pairs associated with BMI or changes in BMI at the proteome and transcriptome levels.PMID:38129841 | DOI:10.1186/s12916-023-03198-7
Effect of beinaglutide combined with metformin versus aspart 30 with metformin on metabolic profiles and antidrug antibodies in patients with type 2 diabetes: a randomized clinical trial
Front Endocrinol (Lausanne). 2023 Dec 6;14:1267503. doi: 10.3389/fendo.2023.1267503. eCollection 2023.ABSTRACTOBJECTIVE: This prospective study aimed to evaluate the effect of beinaglutide combined with metformin versus aspart 30 with metformin on metabolic profiles and antidrug antibodies (ADAs) in patients with type 2 diabetes (T2D).METHODS: A total of 134 eligible participants were randomly assigned to the test group and the control group. Patients in the test group were treated with beinaglutide and metformin, whereas patients in the control group were randomly treated with aspart 30 and metformin, with a follow-up period of 6 months. The metabolic profiles and ADAs over 6 months were evaluated.RESULTS: After 6 months, 101 (75.37%) patients completed the study. Compared with the control group, the beinaglutide group had significant reductions in 2-h postprandial blood glucose (2hBG) and low blood glucose index (LBGI). Glycated hemoglobin (HbA1c) decreased in both groups relative to baseline. In the test group, one had treatment-emergent beinaglutide ADAs. Significant reductions in triglycerides (TG), non-fasting TG, weight, waist circumference (WC), and body mass index (BMI) were observed. The values of insulin sensitivity index (HOMA-IR) were decreased to a statistically higher degree with beinaglutide treatment.CONCLUSION: Beinaglutide reduces metabolic dysfunction, LBGI, and weight in patients of T2D with a low risk of ADAs. Beinaglutide may offer the potential for a disease-modifying intervention in cardiovascular disease (CVD).CLINICAL TRIAL REGISTRATION: www.chictr.org.cn, identifier ChiCTR2200061003.PMID:38125788 | PMC:PMC10731293 | DOI:10.3389/fendo.2023.1267503
Multi-omic approaches provide insights into the molecular mechanisms of Sojae semen germinatum water extract against overactive bladder
Food Res Int. 2024 Jan;175:113746. doi: 10.1016/j.foodres.2023.113746. Epub 2023 Nov 26.ABSTRACTSojae semen germinatum (SSG) is derived from mature soybean seeds that have been germinated and dried, typically with sprouts measuring approximately 0.5 cm in length. SSG is traditionally known for its properties in clearing heat and moisture. Nevertheless, limited information was reported on the effects and mechanisms of SSG in alleviating urinary symptoms. This study employed urodynamic parameters to investigate the therapeutic effect of SSG water extract on overactive bladder (OAB) in the rat model with benign prostatic hyperplasia. Through a combination of transcriptomic and metabolomic analyses, the pathways and key proteins of the SSG treatment for OAB were identified and validated by ELISA and Western blotting. Furthermore, network pharmacology elucidated the roles of SSG's isoflavones acting on the target which was identified by above-mentioned multi-omics analysis. Our results indicate that SSG water extract significantly mitigated OAB by down-regulating the PGE2/EP1/PLCβ2/p-MLC signaling pathway. It was speculated that the active ingredient in the SSG on EP1 was genistein. This study provided valuable insights into the molecular mechanisms of SSG water extract, emphasizing the multi-target characteristics and critical pathways in improving OAB. Furthermore, this study contributes to the potential utilization of SSG as a functional food.PMID:38129051 | DOI:10.1016/j.foodres.2023.113746
Effect of oxygen supplement on post-mortem metabolic profile of shrimp during cold storage
Food Res Int. 2024 Jan;175:113734. doi: 10.1016/j.foodres.2023.113734. Epub 2023 Nov 24.ABSTRACTShrimp, renowned for its exceptional nutritional value, holds a pivotal position within the realm of aquatic products. The supplementation of extra oxygen to shrimp throughout the entire supply chain has found application within the commercial seafood market. In this study, a dual-platform metabolic analysis, coupled with multivariate data analysis, was employed to discern the impact of supplementary oxygen. Furthermore, this approach facilitated the construction of the post-mortem metabolic profile of shrimp during cold storage. A noticeable decrease of alcohols, ketones and carbohydrates which are related to the energy metabolism in shrimp has been found during cold storage, compared to the fresh shrimp. The degradation of nutritional amino acids was alleviated in shrimp after 4 h of extra oxygen supplement. Furthermore, a higher concentration of identified fatty acids, integral to lipid metabolism and functioning as flavor compounds was observed in shrimp subsequent to oxygen supplementation. Therefore, the additional oxygen supplementation exerted influence on multiple metabolic pathways, including nitrogen metabolism, amino acid and peptide metabolism, nucleotide metabolism, carbohydrate metabolism, and lipid metabolism. This study has constructed a comprehensive post-mortem metabolic profile of shrimp during cold storage, thereby establishing a theoretical foundation for the utilization of oxygen supplements in the preservation of seafood.PMID:38129045 | DOI:10.1016/j.foodres.2023.113734
Integrated analysis of the metabolome and transcriptome provides insights into anthocyanin biosynthesis of cashew apple
Food Res Int. 2024 Jan;175:113711. doi: 10.1016/j.foodres.2023.113711. Epub 2023 Nov 28.ABSTRACTThe cashew apple remains an underutilized agricultural product despite its abundance as a by-product of cashew nut production. Anthocyanins are water-soluble pigments responsible for red, purple, and blue hues in plant tissues and have various health-promoting properties. To investigate the anthocyanin biosynthesis in cashew apples, fruits with varying peel colors from three cultivars were subjected to integrative analyses with metabolomics and transcriptomics. Through a UPLC-ESI-MS/MS-based targeted metabolomics analysis, a total of 26 distinct anthocyanin compounds were identified in the fruits of the three cashew cultivars. Subsequent quantification revealed that Pelargonidin-3-O-galactoside, Petunidin-3-O-arabinoside, and Cyanidin-3-O-galactoside were the primary contributors responsible for the red pigmentation in cashew apple peels. Following transcriptomic analysis showed that the expression levels of anthocyanin biosynthetic genes were predominantly higher in the red cashew apples as compared to the other two cultivars. Moreover, correlation analysis revealed that eight potential transcription factors implicated in the regulation of anthocyanin biosynthesis. Among these, four transcription factors exhibited positive correlations with both anthocyanin contents and anthocyanin biosynthetic gene expression, while the remaining four transcription factors displayed negative correlations. These findings provide a comprehensive understanding of the molecular basis of anthocyanin biosynthesis in cashew apple peels.PMID:38129034 | DOI:10.1016/j.foodres.2023.113711
Comprehensive metabolite and biological profile of "Sulmona Red Garlic" ecotype's aerial bulbils
Food Res Int. 2024 Jan;175:113654. doi: 10.1016/j.foodres.2023.113654. Epub 2023 Nov 2.ABSTRACT"Sulmona Red Garlic" is a well-known Italian traditional product. Bulbs, used for culinary purposes, have been largely investigated for their medicinal properties whereas aerial bulbils are usually removed as waste material. Here, for the first time, chemical composition and biological properties of the hydroalcoholic extract from aerial bulbils were investigated. Complementary information on metabolite composition were obtained using both NMR based untargeted and HPLC-DAD targeted methodologies. The NMR analysis revealed the presence of sugars, organic acids, amino acids, organosulphur compounds (methiin, alliin, allicin and cycloalliin), and other secondary metabolites. In particular, methiin and alliin were identified for the first time in the NMR spectra of aerial bulbil garlic extracts. Polyphenol content was determined by HPLC-DAD analysis: catechin, chlorogenic acid, and gallic acid turned out to be the most abundant phenolics. Hydroalcoholic extract blocked cell proliferation of colon cancer cell line HCT116 with an IC50 of 352.07 µg/mL, while it was non-toxic to myoblast cell line C2C12. In addition, it caused seedling germination reduction of two edible and herbaceous dicotyledon species, namely Cichorium intybus and C. endivia. Moreover, the same extract reduced the gene expression of TNF-α (tumor necrosis factor), HIF1-α (hypoxia-inducible factor), VEGFA (vascular endothelial growth factor), and transient receptor potential (TRP) M8 (TRPM8) indicating the ability to contrast cancer development through the angiogenic pathway. Final, in silico experiments were also carried out supporting the biological effects of organosulphur compounds, particularly alliin, which may directly interact with TRPM8. The results here reported suggest the potential use of garlic aerial bulbils often considered a waste product as a source in phytotherapeutic remedies.PMID:38129017 | DOI:10.1016/j.foodres.2023.113654