PubMed

J Ethnopharmacol. 2023 May 15:116640. doi: 10.1016/j.jep.2023.116640. Online ahead of print.ABSTRACTETHNOPHARMACOLOGY RELEVANCE: San Hua Tang (SHT) was first mentioned in the book "The Collection of Plain Questions about Pathogenesis, Qi, and Life." SHT has the effect of dispelling wind and dredging collaterals, dredging viscera, and guiding stagnation, and is used in the treatment of ischemic stroke (IS). SHT is composed of Rheum palmatum L., Magnolia officinalis Rehder & E.H.Wilson, Citrus assamensis S.Dutta & S.C.Bhattacharya, and Notopterygium tenuifolium M.L.Sheh & F.T.Pu, which is the traditional prescription of the Tongxia method for the treatment of stroke. Tongxia is one of the "eight methods" used in traditional Chinese medicine, which plays a role in treating diseases by promoting gastrointestinal peristalsis and defecation. Studies have demonstrated a close relationship between gut microbiota metabolism and cerebral stroke; however, the role of SHT in IS treatment through gut microbiota or intestinal metabolites is unclear.AIM OF THE STUDY: To explore the connotation of the Xuanfu theory and clarify the mechanism underlying SHT-mediated opening Xuanfu methods. Through metabolomics, 16S rRNA gene sequencing, and molecular biology techniques, research on the changes in the gut microbiota and blood-brain barrier (BBB) will highlight greater strategies for the treatment of stroke.MATERIALS AND METHODS: We used pseudo-germ-free (PGF) rats combined with an ischemia/reperfusion (I/R) rat model for the follow-up experimental research. PGF rats were prepared by the intragastric administration of an antibiotic cocktail for 6 days, following which SHT was administered for 5 consecutive days. The I/R model was performed 1 day following the concluding administration of SHT. We detected the neurological deficit score, cerebral infarct volume, serum inflammatory factor levels (interleukin IL-6, IL-10, IL-17, and tumor necrosis factor alpha), tight junction-related proteins (Zonula occludens-1, Occludin, and Claudin-5), and small glue plasma cell-associated proteins (Cluster of Differentiation 16/Cluster of Differentiation 206, Matrix metalloproteinase, ionized calcium-binding adapter molecule 1, and C-X3-C Motif Chemokine Ligand 1) 24 h following I/R. Using 16S rRNA gene sequencing and non-targeted metabolomics analysis, we explored the relationship between fecal microecology and serum metabolites. Eventually, we analyzed the correlation between the gut microbiota and plasma metabolic profile as well as the mechanism underlying the SHT-mediated regulation of gut microbiota to protect the BBB following stroke.RESULTS: In IS treatment, SHT is principally involved in reducing neurological injury and the volume of cerebral infarction; protecting the intestinal mucosal barrier; increasing the levels of acetic acid, butyric acid, and propionic acid; promoting the transformation of microglia to the M2 state; reducing inflammatory reactions; and enhancing tight junctions. These therapeutic effects were not observed in the group treated with antibiotics alone or that treated with SHT in combination with antibiotics, thereby indicating SHT plays a therapeutic role through the gut microbiota.CONCLUSION: SHT regulates the gut microbiota, inhibits pro-inflammatory factors in rats with IS, alleviates an inflammatory injury of the BBB, and plays a protective role in the brain.PMID:37196812 | DOI:10.1016/j.jep.2023.116640

Biochem Pharmacol. 2023 May 15:115599. doi: 10.1016/j.bcp.2023.115599. Online ahead of print.ABSTRACTEmerging evidence suggests an association of dysbiotic gut microbiota (GM) with atrial fibrillation (AF). The current study aimed to determine whether aberrant GM promotes AF development. A fecal microbiota transplantation (FMT) mouse model demonstrated that dysbiotic GM is sufficient to enhance AF susceptibility assessed by transesophageal burst pacing. Compared with recipients transplanted with GM obtained from healthy subjects (FMT-CH), the prolonged P wave duration and an enlarging tendency for the left atrium were detected in recipients transplanted with AF GM (FMT-AF). Meanwhile, the disrupted localizations of connexin 43 and N-cadherin and increased expression levels of phospho-CaMKII and phospho-RyR2, were observed in the atrium of FMT-AF, which indicated aggravated electrical remodeling caused by the altered gut flora. Specifically, exacerbated fibrosis disarray, collagen deposition, α-SMA expression, and inflammation in the atrium were also confirmed to be transmissible by the GM. Furthermore, deteriorated intestinal epithelial barrier and intestinal permeability, accompanied by disturbing metabolomic features in both feces and plasma, especially decreased linoleic acid (LA), were identified in FMT-AF mice. Subsequently, the anti-inflammatory role of LA among the imbalanced SIRT1 signaling discovered in the atrium of FMT-AF was confirmed in mouse HL-1 cells treated with LPS/nigericin, LA, and SIRT1 knockdown. This study provides preliminary insights into the causal role of aberrant GM in the pathophysiology of AF, suggesting the GM-intestinal barrier-atrium axis might participate in the vulnerable substrates for AF development, and the GM could be utilized as an environmental target in AF management.PMID:37196685 | DOI:10.1016/j.bcp.2023.115599

Cell Rep Med. 2023 May 16;4(5):101045. doi: 10.1016/j.xcrm.2023.101045.ABSTRACTPost-traumatic stress disorder (PTSD) is a multisystem syndrome. Integration of systems-level multi-modal datasets can provide a molecular understanding of PTSD. Proteomic, metabolomic, and epigenomic assays are conducted on blood samples of two cohorts of well-characterized PTSD cases and controls: 340 veterans and 180 active-duty soldiers. All participants had been deployed to Iraq and/or Afghanistan and exposed to military-service-related criterion A trauma. Molecular signatures are identified from a discovery cohort of 218 veterans (109/109 PTSD+/-). Identified molecular signatures are tested in 122 separate veterans (62/60 PTSD+/-) and in 180 active-duty soldiers (PTSD+/-). Molecular profiles are computationally integrated with upstream regulators (genetic/methylation/microRNAs) and functional units (mRNAs/proteins/metabolites). Reproducible molecular features of PTSD are identified, including activated inflammation, oxidative stress, metabolic dysregulation, and impaired angiogenesis. These processes may play a role in psychiatric and physical comorbidities, including impaired repair/wound healing mechanisms and cardiovascular, metabolic, and psychiatric diseases.PMID:37196634 | DOI:10.1016/j.xcrm.2023.101045

Cell Rep Med. 2023 May 16;4(5):101051. doi: 10.1016/j.xcrm.2023.101051.ABSTRACTAlterations in the microbiome correlate with improved metabolism in patients following bariatric surgery. While fecal microbiota transplantation (FMT) from obese patients into germ-free (GF) mice has suggested a significant role of the gut microbiome in metabolic improvements following bariatric surgery, causality remains to be confirmed. Here, we perform paired FMT from the same obese patients (BMI > 40; four patients), pre- and 1 or 6 months post-Roux-en-Y gastric bypass (RYGB) surgery, into Western diet-fed GF mice. Mice colonized by FMT from patients' post-surgery stool exhibit significant changes in microbiota composition and metabolomic profiles and, most importantly, improved insulin sensitivity compared with pre-RYGB FMT mice. Mechanistically, mice harboring the post-RYGB microbiome show increased brown fat mass and activity and exhibit increased energy expenditure. Moreover, improvements in immune homeostasis within the white adipose tissue are also observed. Altogether, these findings point to a direct role for the gut microbiome in mediating improved metabolic health post-RYGB surgery.PMID:37196633 | DOI:10.1016/j.xcrm.2023.101051

Phytomedicine. 2023 Apr 27;116:154841. doi: 10.1016/j.phymed.2023.154841. Online ahead of print.ABSTRACTBACKGROUND: Plantaginis Herba (Plantago asiatica L.) has the effects of clearing heat and diuresis, oozing wet and drenching. As the main active components of Plantaginis Herba (Plantago asiatica L.), plantamajoside have a wide range of antitumor activities but very low bioavailability. The process of interacting between plantamajoside and gut microbiota remains unclear.PURPOSE: To illustrate the process of interacting between plantamajoside and gut microbiota based on high-resolution mass spectrometry and targeted metabolomics methods.STUDY DESIGN AND METHODS: This experiment was divided into two parts. First, metabolites produced from plantamajoside by gut microbiota were identified and quantified based on high-resolution mass spectrometry and LC-MS/MS. Additionally, stimulation of plantamajoside on gut microbiota-derived metabolites was determined by targeted metabolomics and gas chromatography.RESULTS: We first found that plantamajoside was rapidly metabolized by gut microbiota. Then, we identified metabolites of plantamajoside by high-resolution mass spectrometry and speculated that plantamajoside was metabolized into five metabolites including calceolarioside A, dopaol glucoside, hydroxytyrosol, 3-(3-hydroxyphenyl) propionic acid (3-HPP) and caffeic acid. Among them, we quantitatively analyzed four possible metabolites based on LC‒MS/MS and found that hydroxytyrosol and 3-HPP were final products by the gut microbiota. In addition, we studied whether plantamajoside could affect the short-chain fatty acid (SCFA) and amino acid metabolites. We found that plantamajoside could inhibit the acetic acid, kynurenic acid (KYNA) and kynurenine (KN) produced by intestinal bacteria and promote the indole propionic acid (IPA) and indole formaldehyde (IALD) produced by intestinal bacteria.CONCLUSION: An interaction between plantamajoside and gut microbiota was revealed in this study. Unlike the traditional metabolic system, the special metabolic characteristics of plantamajoside in gut microbiota was found. Plantamajoside was metabolized into the following active metabolites: calceolarioside A, dopaol glucoside, hydroxytyrosol, caffeic acid and 3-HPP. Besides, plantamajoside could affect SCFA and tryptophan metabolism by gut microbiota. Especially, the exogenous metabolites hydroxytyrosol, caffeic acid and endogenous metabolites IPA may have potential association with the antitumor activity of plantamajoside.PMID:37196513 | DOI:10.1016/j.phymed.2023.154841

Nature. 2023 May 17. doi: 10.1038/s41586-023-06073-w. Online ahead of print.ABSTRACTPancreatic ductal adenocarcinoma (PDA) is a lethal disease notoriously resistant to therapy1,2. This is mediated in part by a complex tumour microenvironment3, low vascularity4, and metabolic aberrations5,6. Although altered metabolism drives tumour progression, the spectrum of metabolites used as nutrients by PDA remains largely unknown. Here we identified uridine as a fuel for PDA in glucose-deprived conditions by assessing how more than 175 metabolites impacted metabolic activity in 21 pancreatic cell lines under nutrient restriction. Uridine utilization strongly correlated with the expression of uridine phosphorylase 1 (UPP1), which we demonstrate liberates uridine-derived ribose to fuel central carbon metabolism and thereby support redox balance, survival and proliferation in glucose-restricted PDA cells. In PDA, UPP1 is regulated by KRAS-MAPK signalling and is augmented by nutrient restriction. Consistently, tumours expressed high UPP1 compared with non-tumoural tissues, and UPP1 expression correlated with poor survival in cohorts of patients with PDA. Uridine is available in the tumour microenvironment, and we demonstrated that uridine-derived ribose is actively catabolized in tumours. Finally, UPP1 deletion restricted the ability of PDA cells to use uridine and blunted tumour growth in immunocompetent mouse models. Our data identify uridine utilization as an important compensatory metabolic process in nutrient-deprived PDA cells, suggesting a novel metabolic axis for PDA therapy.PMID:37198494 | DOI:10.1038/s41586-023-06073-w

Sci Rep. 2023 May 17;13(1):8051. doi: 10.1038/s41598-023-35272-8.ABSTRACTQuercetin (QR) has significant anti-respiratory syncytial virus (RSV) effects. However, its therapeutic mechanism has not been thoroughly explored. In this study, a lung inflammatory injury model caused by RSV was established in mice. Untargeted lung tissue metabolomics was used to identify differential metabolites and metabolic pathways. Network pharmacology was used to predict potential therapeutic targets of QR and analyze biological functions and pathways modulated by QR. By overlapping the results of the metabolomics and the network pharmacology analyses, the common targets of QR that were likely to be involved in the amelioration of RSV-induced lung inflammatory injury by QR were identified. Metabolomics analysis identified 52 differential metabolites and 244 corresponding targets, while network pharmacology analysis identified 126 potential targets of QR. By intersecting these 244 targets with the 126 targets, hypoxanthine-guanine phosphoribosyltransferase (HPRT1), thymidine phosphorylase (TYMP), lactoperoxidase (LPO), myeloperoxidase (MPO), and cytochrome P450 19A1 (CYP19A1) were identified as the common targets. The key targets, HPRT1, TYMP, LPO, and MPO, were components of purine metabolic pathways. The present study demonstrated that QR effectively ameliorated RSV-induced lung inflammatory injury in the established mouse model. Combining metabolomics and network pharmacology showed that the anti-RSV effect of QR was closely associated with purine metabolism pathways.PMID:37198253 | DOI:10.1038/s41598-023-35272-8

Sci Rep. 2023 May 17;13(1):8044. doi: 10.1038/s41598-023-34902-5.ABSTRACTAnlotinib, as a promising oral small-molecule antitumor drug, its role in glioma has been only reported in a small number of case reports. Therefore, anlotinib has been considered as a promising candidate in glioma. The aim of this study was to investigate the metabolic network of C6 cells after exposure to anlotinib and to identify anti-glioma mechanism from the perspective of metabolic reprogramming. Firstly, CCK8 method was used to evaluate the effects of anlotinib on cell proliferation and apoptosis. Secondly, ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS)-based metabolomic and lipidomic were developed to characterize the metabolite and lipid changes in cell and cell culture medium (CCM) caused by anlotinib in the treatment of glioma. As a result, anlotinib had concentration-dependent inhibitory effect with the concentration range. In total, twenty-four and twenty-three disturbed metabolites in cell and CCM responsible for the intervention effect of anlotinib were screened and annotated using UHPLC-HRMS. Altogether, seventeen differential lipids in cell were identified between anlotinib exposure and untreated groups. Metabolic pathways, including amino acid metabolism, energy metabolism, ceramide metabolism, and glycerophospholipid metabolism, were modulated by anlotinib in glioma cell. Overall, anlotinib has an effective treatment against the development and progression of glioma, and these remarkable pathways can generate the key molecular events in cells treated with anlotinib. Future research into the mechanisms underlying the metabolic changes is expected to provide new strategies for treating glioma.PMID:37198251 | DOI:10.1038/s41598-023-34902-5

J Agric Food Chem. 2023 May 17. doi: 10.1021/acs.jafc.3c01010. Online ahead of print.ABSTRACTl-Theanine is the most abundant free amino acid present in tea. Several tea components have been studied for their impact on male fertility, but little is known about the effects of l-theanine. Cyclophosphamide (CP) is an antineoplastic and immunosuppressive agent that reduces fertility in males. In the present study, we evaluated the effect of l-theanine on CP-induced testicular toxicity in male mice. A single dosage of 50 mg/kg saline or CP was administered intraperitoneally over the course of 5 days. Mice were administered l-theanine (80 mg/kg) or saline by gavage for 30 days. Animals were euthanized 24 h after the last l-theanine administration, and the testes were removed for histopathological and transmission electron microscopy analysis. Histological evaluation and transmission electron microscopy showed that administration of l-theanine alleviated CP-induced damage to the testicles, including spermatogonial cells, epithelial cells, seminiferous tubules, and basement membrane. An integrated proteomics and metabolomics investigation of testes revealed that l-theanine therapy substantially affected the quantity of 719 proteins (395 upregulated and 324 downregulated) and 196 metabolites (75 upregulated and 111 downregulated). The top three enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for these proteins and metabolites were purine metabolism, choline metabolism in cancer, and arachidonic acid metabolism. This is the first study to reveal the protective effect of l-theanine on CP-induced testicular toxicity. l-Theanine could be a potential natural active substance for resistance to the testis toxicity induced by CP.PMID:37198140 | DOI:10.1021/acs.jafc.3c01010

J Pharm Biomed Anal. 2023 May 12;232:115450. doi: 10.1016/j.jpba.2023.115450. Online ahead of print.ABSTRACTWine/zingiberis rhizoma recens/euodiae fructus processed Coptidis Rhizoma (wCR/zCR/eCR) are the major processed products of CR in clinic, and the role of CR is highlighted in different aspects after being processed with different excipients. To explore the mechanism and material basis for the highlighted efficacy of wCR/zCR/eCR, the metabolomics strategy was introduced to the comparative study between wCR/zCR/eCR and CR. Firstly, the metabolomics approach was applied to compare the chemical profiling and differential components between wCR/zCR/eCR and CR extract. Secondly, the rats were treated with CR/wCR/zCR/eCR extracts and a serum metabolomics approach was adopted to compare the metabolic profiling and significantly changed metabolites in CR/wCR/zCR/eCR groups, base on which the metabolic pathways were enriched, the metabolic network was constructed and the highlighted efficacy wCR/zCR/eCR was investigated. Lastly, the pathological and biochemical assessments (VIP, COX, HSL and HMGR) were implemented to validate the results inferred from metabolomics study. In chemical research, 23 differential components between wCR/zCR/eCR and CR extracts were identified. Thereinto, the content of alkaloids and organic acids decreased in wCR extract, the content of partial alkaloids and most organic acids increased in zCR extract, the content of alkaloids decreased, and partial organic acids increased in eCR extract. In serum metabolomics study, wCR had no outstanding effect, zCR played a more prominent role in resisting inflammation of gastrointestinal tissue by interfering with arachidonic acid metabolism, eCR exhibited the hottest drug property and the strongest effect on smoothing the liver and harmonizing the stomach by interfering with of bile acids biosynthesis. Based on the changes in chemical composition and efficacy before and after processing, as well as biochemical validation, it can be concluded that the above activity of zCR might be related to the increased alkaloids and organic acids in zCR extract, and the prominent role of eCR may be related to the increased organic acids in eCR extract. In brief, hot processing excipients could alleviate the cold property of CR, and different excipients have different effects on the chemical composition and efficacy mechanism. The present study fully reflects the advantage of metabolomics and provides guidance for the rational use of CR.PMID:37196375 | DOI:10.1016/j.jpba.2023.115450

Plant Physiol Biochem. 2023 May 11;200:107739. doi: 10.1016/j.plaphy.2023.107739. Online ahead of print.ABSTRACTBlack mung bean is rich in anthocyanin, however, the accumulation and the molecular mechanism of anthocyanin synthesis in black mung bean are unclear. In this study, anthocyanin metabolomics and transcriptomics on the seed coats of two different colors of mung bean were performed to clarify the composition of anthocyanins, and identify transcription factors involved in regulating anthocyanin biosynthesis. In the mature stage, 23 kinds of anthocyanin compounds were identified. All anthocyanin components contents were significantly higher in seed coat of black mung bean compare with green mung bean. Transcriptome analysis suggested that most of the structural genes for anthocyanin biosynthesis and some potential regulatory genes were significantly differentially expressed. WGCNA suggested VrMYB90 was an important regulatory gene in anthocyanin biosynthesis. Arabidopsis thaliana overexpressing VrMYB90 showed significant accumulation of anthocyanins. PAL, 4CL, DFR, F3'5'H, LDOX, F3'H and UFGT were up-regulated in 35S:VrMYB90 Arabidopsis thaliana. These findings provide valuable information for understanding the synthesis mechanism of anthocyanins in black mung bean seed coats.PMID:37196373 | DOI:10.1016/j.plaphy.2023.107739

Annu Rev Biomed Data Sci. 2023 May 17. doi: 10.1146/annurev-biodatasci-020722-094144. Online ahead of print.ABSTRACTPrenatal screening using sequencing of circulating cell-free DNA has transformed obstetric care over the past decade and significantly reduced the number of invasive diagnostic procedures like amniocentesis for genetic disorders. Nonetheless, emergency care remains the only option for complications like preeclampsia and preterm birth, two of the most prevalent obstetrical syndromes. Advances in noninvasive prenatal testing expand the scope of precision medicine in obstetric care. In this review, we discuss advances, challenges, and possibilities toward the goal of providing proactive, personalized prenatal care. The highlighted advances focus mainly on cell-free nucleic acids; however, we also review research that uses signals from metabolomics, proteomics, intact cells, and the microbiome. We discuss ethical challenges in providing care. Finally, we look to future possibilities, including redefining disease taxonomy and moving from biomarker correlation to biological causation. Expected final online publication date for the Annual Review of Biomedical Data Science, Volume 6 is August 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.PMID:37196360 | DOI:10.1146/annurev-biodatasci-020722-094144

Sci Adv. 2023 May 19;9(20):eade7236. doi: 10.1126/sciadv.ade7236. Epub 2023 May 17.ABSTRACTDuring therapy, adaptations driven by cellular plasticity are partly responsible for driving the inevitable recurrence of glioblastoma (GBM). To investigate plasticity-induced adaptation during standard-of-care chemotherapy temozolomide (TMZ), we performed in vivo single-cell RNA sequencing in patient-derived xenograft (PDX) tumors of GBM before, during, and after therapy. Comparing single-cell transcriptomic patterns identified distinct cellular populations present during TMZ therapy. Of interest was the increased expression of ribonucleotide reductase regulatory subunit M2 (RRM2), which we found to regulate dGTP and dCTP production vital for DNA damage response during TMZ therapy. Furthermore, multidimensional modeling of spatially resolved transcriptomic and metabolomic analysis in patients' tissues revealed strong correlations between RRM2 and dGTP. This supports our data that RRM2 regulates the demand for specific dNTPs during therapy. In addition, treatment with the RRM2 inhibitor 3-AP (Triapine) enhances the efficacy of TMZ therapy in PDX models. We present a previously unidentified understanding of chemoresistance through critical RRM2-mediated nucleotide production.PMID:37196077 | DOI:10.1126/sciadv.ade7236

Sci Transl Med. 2023 May 17;15(696):eade6509. doi: 10.1126/scitranslmed.ade6509. Epub 2023 May 17.ABSTRACTDisruption of mitochondrial function and protein homeostasis plays a central role in aging. However, how these processes interact and what governs their failure in aging remain poorly understood. Here, we showed that ceramide biosynthesis controls the decline in mitochondrial and protein homeostasis during muscle aging. Analysis of transcriptome datasets derived from muscle biopsies obtained from both aged individuals and patients with a diverse range of muscle disorders revealed that changes in ceramide biosynthesis, as well as disturbances in mitochondrial and protein homeostasis pathways, are prevalent features in these conditions. By performing targeted lipidomics analyses, we found that ceramides accumulated in skeletal muscle with increasing age across Caenorhabditis elegans, mice, and humans. Inhibition of serine palmitoyltransferase (SPT), the rate-limiting enzyme of the ceramide de novo synthesis, by gene silencing or by treatment with myriocin restored proteostasis and mitochondrial function in human myoblasts, in C. elegans, and in the skeletal muscles of mice during aging. Restoration of these age-related processes improved health and life span in the nematode and muscle health and fitness in mice. Collectively, our data implicate pharmacological and genetic suppression of ceramide biosynthesis as potential therapeutic approaches to delay muscle aging and to manage related proteinopathies via mitochondrial and proteostasis remodeling.PMID:37196064 | DOI:10.1126/scitranslmed.ade6509

Inflamm Bowel Dis. 2023 May 17:izad080. doi: 10.1093/ibd/izad080. Online ahead of print.ABSTRACTBACKGROUND: A distinctive metabolic phenotype provides the opportunity to discover noninvasive biomarkers for the diagnosis of Crohn's disease (CD) and for differentiating it from other intestinal inflammatory diseases. The study sought to identify new biomarkers for CD diagnosis.METHODS: Serum metabolites from 68 newly diagnosed and treatment-naïve patients with CD and 56 healthy control (HC) subjects were profiled using targeted liquid chromatography-mass spectrometry. Five metabolic biomarkers were identified to distinguish patients with CD from the HC subjects and validated in a separate cohort consisting of 110 patients with CD and 90 HC subjects using a combination of univariate analysis, orthogonal partial least-squares discriminant analysis, and receiver-operating characteristic curve analysis. Differences in the 5 metabolites were evaluated among patients with CD and patients with ulcerative colitis (n = 62), intestinal tuberculosis (n = 48), and Behçet's disease (n = 31).RESULTS: Among the 185 quantified metabolites, a panel of 5 (pyruvate, phenylacetylglutamine, isolithocholic acid, taurodeoxycholic acid, and glycolithocholic acid) were found to distinguish patients with CD with high accuracy from HC subjects, with an area under the curve of 0.861 (P < .001). The performance of the model in assessing clinical disease activity was comparable to that of the present biomarkers: C-reactive protein and erythrocyte sedimentation rate. The 5 metabolites were significantly different among the patients and were valuable in the differentiation between CD and other chronic intestinal inflammatory diseases.CONCLUSIONS: The combination of 5 serum metabolite biomarkers for the diagnosis of CD has the potential to provide an accurate, noninvasive, and inexpensive alternative to conventional tests and might be valuable for the differentiation from other diagnostically challenging intestinal inflammatory diseases.PMID:37195904 | DOI:10.1093/ibd/izad080

Anal Bioanal Chem. 2023 May 17. doi: 10.1007/s00216-023-04730-7. Online ahead of print.ABSTRACTEarly, express, and reliable detection of cancer can provide a favorable prognosis and decrease mortality. Tumor biomarkers have been proven to be closely related to tumor occurrence and development. Conventional tumor biomarker detection based on genomic, proteomic, and metabolomic methods is time and equipment-consuming and always needs a specific target marker. Surface-enhanced Raman scattering (SERS), as a non-invasive ultrasensitive and label-free vibrational spectroscopy technique, can detect cancer-related biomedical changes in biofluids. In this paper, 110 serum samples were collected from 30 healthy controls and 80 cancer patients (including 30 bladder cancer (BC), 30 adrenal cancer (AC), and 20 acute myeloid leukemia (AML)). One microliter of blood serum was mixed with 1 μl silver colloid and then was air-dried for SERS measurements. After spectral data augmentation, one-dimensional convolutional neural network (1D-CNN) was proposed for precise and rapid identification of healthy and three different cancers with high accuracy of 98.27%. After gradient-weighted class activation mapping (Grad-CAM) based spectral interpretation, the contributions of SERS peaks corresponding to biochemical substances indicated the most potential biomarkers, i.e., L-tyrosine in bladder cancer; acetoacetate and riboflavin in adrenal cancer and phospholipids, amide-I, and α-Helix in acute myeloid leukemia, which might provide an insight into the mechanism of intelligent diagnosis of different cancers based on label-free serum SERS. The integration of label-free SERS and deep learning has great potential for the rapid, reliable, and non-invasive detection of cancers, which may significantly improve the precise diagnosis in clinical practice.PMID:37195443 | DOI:10.1007/s00216-023-04730-7

Geroscience. 2023 May 17. doi: 10.1007/s11357-023-00823-4. Online ahead of print.ABSTRACTWith the exponential growth in the older population in the coming years, many studies have aimed to further investigate potential biomarkers associated with the aging process and its incumbent morbidities. Age is the largest risk factor for chronic disease, likely due to younger individuals possessing more competent adaptive metabolic networks that result in overall health and homeostasis. With aging, physiological alterations occur throughout the metabolic system that contribute to functional decline. In this cross-sectional analysis, a targeted metabolomic approach was applied to investigate the plasma metabolome of young (21-40y; n = 75) and older adults (65y + ; n = 76). A corrected general linear model (GLM) was generated, with covariates of gender, BMI, and chronic condition score (CCS), to compare the metabolome of the two populations. Among the 109 targeted metabolites, those associated with impaired fatty acid metabolism in the older population were found to be most significant: palmitic acid (p < 0.001), 3-hexenedioic acid (p < 0.001), stearic acid (p = 0.005), and decanoylcarnitine (p = 0.036). Derivatives of amino acid metabolism, 1-methlyhistidine (p = 0.035) and methylhistamine (p = 0.027), were found to be increased in the younger population and several novel metabolites were identified, such as cadaverine (p = 0.034) and 4-ethylbenzoic acid (p = 0.029). Principal component analysis was conducted and highlighted a shift in the metabolome for both groups. Receiver operating characteristic analyses of partial least squares-discriminant analysis models showed the candidate markers to be more powerful indicators of age than chronic disease. Pathway and enrichment analyses uncovered several pathways and enzymes predicted to underlie the aging process, and an integrated hypothesis describing functional characteristics of the aging process was synthesized. Compared to older participants, the young group displayed greater abundance of metabolites related to lipid and nucleotide synthesis; older participants displayed decreased fatty acid oxidation and reduced tryptophan metabolism, relative to the young group. As a result, we offer a better understanding of the aging metabolome and potentially reveal new biomarkers and predicted mechanisms for future study.PMID:37195387 | DOI:10.1007/s11357-023-00823-4

J Phys Chem B. 2023 May 17. doi: 10.1021/acs.jpcb.3c01443. Online ahead of print.ABSTRACTCoherent anti-Stokes Raman scattering (CARS) microscopy is an emerging nonlinear vibrational imaging technique that delivers label-free chemical maps of cells and tissues. In narrowband CARS, two spatiotemporally superimposed picosecond pulses, pump and Stokes, illuminate the sample to interrogate a single vibrational mode. Broadband CARS (BCARS) combines narrowband pump pulses with broadband Stokes pulses to record broad vibrational spectra. Despite recent technological advancements, BCARS microscopes still struggle to image biological samples over the entire Raman-active region (400-3100 cm-1). Here, we demonstrate a robust BCARS platform that answers this need. Our system is based on a femtosecond ytterbium laser at a 1035 nm wavelength and a 2 MHz repetition rate, which delivers high-energy pulses used to produce broadband Stokes pulses by white-light continuum generation in a bulk YAG crystal. Combining such pulses, pre-compressed to sub-20 fs duration, with narrowband pump pulses, we generate a CARS signal with a high (<9 cm-1) spectral resolution in the whole Raman-active window, exploiting both the two-color and three-color excitation mechanisms. Aided by an innovative post-processing pipeline, our microscope allows us to perform high-speed (≈1 ms pixel dwell time) imaging over a large field of view, identifying the main chemical compounds in cancer cells and discriminating tumorous from healthy regions in liver slices of mouse models, paving the way for applications in histopathological settings.PMID:37195090 | DOI:10.1021/acs.jpcb.3c01443

Plant Physiol. 2023 May 17:kiad288. doi: 10.1093/plphys/kiad288. Online ahead of print.ABSTRACTCell polarity is intimately linked to numerous biological processes, such as oriented plant cell division, particular asymmetric division, cell differentiation, cell and tissue morphogenesis, and transport of hormones and nutrients. Cell polarity is typically initiated by a polarizing cue that regulates the spatiotemporal dynamic of polarity molecules, leading to the establishment and maintenance of polar domains at the plasma membrane (PM). Despite considerable progress in identifying key polarity regulators in plants, the molecular and cellular mechanisms underlying cell polarity formation have yet to be fully elucidated. Recent work suggests a critical role for membrane protein/lipid nanodomains in polarized morphogenesis in plants. One outstanding question is how the spatiotemporal dynamics of signaling nanodomains are controlled to achieve robust cell polarization. In this review, we first summarize the current state of knowledge on potential regulatory mechanisms of nanodomain dynamics, with a special focus on RHO GTPases of Plants (ROPs). We then discuss the pavement cell system as an example of how cells may integrate multiple signals and nanodomain-involved feedback mechanisms to achieve robust polarity. A mechanistic understanding of nanodomains' roles in plant cell polarity is still in the early stages and will remain an exciting area for future investigations.PMID:37194569 | DOI:10.1093/plphys/kiad288

Environ Sci Technol. 2023 May 16. doi: 10.1021/acs.est.3c01877. Online ahead of print.ABSTRACTThe eco-corona on microplastics refers to the initial layer of biomolecular compounds adsorbed onto the surface after environmental exposure. The formation and composition of the eco-corona in soils have attracted relatively little attention; however, the eco-corona has important implications for the fate and impacts of microplastics and co-occurring chemical contaminants. Here, it was demonstrated that the formation of the eco-corona on polyethylene microplastics exposed to water-extractable soil metabolites (WESMs) occurs quite rapidly via two pathways: direct adsorption of metabolites on microplastics and bridging interactions mediated by macromolecules. The main eco-corona components were common across all soils and microplastics tested and were identified as lipids and lipid-like molecules, phenylpropanoids and polyketides, nucleosides, nucleotides, and their analogues. WESMs were found to reduce the adsorption of co-occurring organic contaminants to microplastics by two pathways: reduced adsorption to the eco-corona surface and co-solubilization in the surrounding water. These impacts from the eco-corona and the soil metabolome should be considered within fate and risk assessments of microplastics and co-occurring contaminants.PMID:37194262 | DOI:10.1021/acs.est.3c01877