PubMed

Biomark Res. 2023 Jul 20;11(1):71. doi: 10.1186/s40364-023-00497-2.ABSTRACTBACKGROUND: For early screening and diagnosis of non-small cell lung cancer (NSCLC), a robust model based on plasma proteomics and metabolomics is required for accurate and accessible non-invasive detection. Here we aim to combine TMT-LC-MS/MS and machine-learning algorithms to establish models with high specificity and sensitivity, and summarize a generalized model building scheme.METHODS: TMT-LC-MS/MS was used to discover the differentially expressed proteins (DEPs) in the plasma of NSCLC patients. Plasma proteomics-guided metabolites were selected for clinical evaluation in 110 NSCLC patients who were going to receive therapies, 108 benign pulmonary diseases (BPD) patients, and 100 healthy controls (HC). The data were randomly split into training set and test set in a ratio of 80:20. Three supervised learning algorithms were applied to the training set for models fitting. The best performance models were evaluated with the test data set.RESULTS: Differential plasma proteomics and metabolic pathways analyses revealed that the majority of DEPs in NSCLC were enriched in the pathways of complement and coagulation cascades, cholesterol and bile acids metabolism. Moreover, 10 DEPs, 14 amino acids, 15 bile acids, as well as 6 classic tumor biomarkers in blood were quantified using clinically validated assays. Finally, we obtained a high-performance screening model using logistic regression algorithm with AUC of 0.96, sensitivity of 92%, and specificity of 89%, and a diagnostic model with AUC of 0.871, sensitivity of 86%, and specificity of 78%. In the test set, the screening model achieved accuracy of 90%, sensitivity of 91%, and specificity of 90%, and the diagnostic model achieved accuracy of 82%, sensitivity of 77%, and specificity of 86%.CONCLUSIONS: Integrated analysis of DEPs, amino acid, and bile acid features based on plasma proteomics-guided metabolite profiling, together with classical tumor biomarkers, provided a much more accurate detection model for screening and differential diagnosis of NSCLC. In addition, this new mathematical modeling based on plasma proteomics-guided metabolite profiling will be used for evaluation of therapeutic efficacy and long-term recurrence prediction of NSCLC.PMID:37475010 | DOI:10.1186/s40364-023-00497-2

Zhongguo Zhong Yao Za Zhi. 2023 Jul;48(13):3664-3677. doi: 10.19540/j.cnki.cjcmm.20230226.502.ABSTRACTBased on the metabolomics, this paper systematically analyzed the metabolic substance basis of Zuogui Pills and Yougui Pills in syndrome differentiation and treatment of diminished ovarian reserve(DOR), so as to provide a scientific basis for the traditional Chinese medicine(TCM) syndrome differentiation and treatment of DOR. Patients with DOR of kidney-Yin deficiency syndrome were collected from outpatient department of hospitals and treated with Zuogui Pills for 12 weeks. And kidney-Yang deficiency syndrome were treated with Yougui Pills for 12 weeks. Based on the non-targeted metabolomic research techniques, the potential biomarkers of Zuogui Pills and Yougui Pills in the treatment of DOR with kidney-Yin deficiency and kidney-Yang deficiency, respectively, were screened out, and metabolic pathways of biomarkers were analyzed. The pregnancy rate, basic serum hormone levels [basal follicle-stimulating hormone(bFSH), basal-luteinizing hormone(bLH), basal-estradiol(bE_2), and anti-Müllerian hormone(AMH)], TCM syndrome type score, and Kupperman score were recorded and statistically analyzed after treatment. The results showed that 23 patients with DOR of kidney-Yin deficiency syndrome and 25 patients of kidney-Yang deficiency syndrome were collected. Twenty-six differential metabolites, including L-carnitine, acetyl-CoA, coenzyme A, and coenzyme Q_(10)(CoQ10), were mapped to 12 metabolic pathways in patients with kidney-Yin deficiency treated with Zuogui Pills. Twenty-two differential metabolites, such as adipoyl-CoA, L-lysine, lysine arginine, and α-tocopherol, were mapped to 11 metabolic pathways in patients with kidney-Yang deficiency. After treatment, bFSH and bLH of patients with DOR were significantly lower than those before treatment(P<0.05). Although the comparison of bE_2 and AMH had no significant differences, there was a improvement trend. The TCM syndrome type score and Kupperman score of patients with DOR after TCM treatment were significantly lower than those before treatment(P<0.05).PMID:37474998 | DOI:10.19540/j.cnki.cjcmm.20230226.502

Zhongguo Zhong Yao Za Zhi. 2023 Jul;48(13):3612-3622. doi: 10.19540/j.cnki.cjcmm.20230413.705.ABSTRACTThis study aimed to analyze the effect of Bletilla striata polysaccharide(BSP) on endogenous metabolites in serum of tumor-bearing mice treated with 5-fluorouracil(5-FU) by untargeted metabolomics techniques and explore the mechanism of BSP in alleviating the toxic and side effects induced by 5-FU. Male BALB/C mice were randomly divided into a normal group, a model group, a 5-FU group, and a 5-FU + BSP group, with eight mice in each group. Mouse colon cancer cells(CT26) were transplanted into the mice except for those in the normal group to construct the tumor-bearing mouse model by subcutaneous injection, and 5-FU chemotherapy and BSP treatment were carried out from the second day of modeling. The changes in body weight, diarrhea, and white blood cell count in the peripheral blood were recorded. The mice were sacrificed and sampled when the tumor weight of mice in the model group reached approximately 1 g. TUNEL staining was used to detect the cell apoptosis in the small intestine of each group. The proportions of hematopoietic stem cells and myeloid progenitor cells in bone marrow were measured by flow cytometry. Five serum samples were selected randomly from each group for untargeted metabolomics analysis. The results showed that BSP was not effective in inhibiting colon cancer in mice, but diarrhea, leukopenia, and weight loss caused by 5-FU chemotherapy were significantly improved after BSP intervention. In addition, apoptotic cells decreased in the small intestinal tissues and the percentages of hematopoietic stem cells and myeloid progenitor cells in bone marrow were significantly higher after BSP treatment. Metabolomics results showed that the toxic and side effects of 5-FU resulted in significant decrease in 29 metabolites and significant increase in 22 metabolites in mouse serum. Among them, 19 disordered metabolites showed a return to normal levels in the 5-FU+BSP group. The results of pathway enrichment indicated that metabolic pathways mainly involved pyrimidine metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis. Therefore, BSP may ameliorate the toxic and side effects of 5-FU in the intestinal tract and bone marrow presumably by regulating nucleotide synthesis, inflammatory damage, and hormone production.PMID:37474994 | DOI:10.19540/j.cnki.cjcmm.20230413.705

Zhongguo Zhong Yao Za Zhi. 2023 Jul;48(13):3602-3611. doi: 10.19540/j.cnki.cjcmm.20230411.401.ABSTRACTRheumatoid arthritis(RA), a chronic autoimmune disease, is featured by persistent joint inflammation. The development of RA is associated with the disturbance of endogenous metabolites and intestinal microbiota. Gardeniae Fructus(GF), one of the commonly used medicinal food in China, is usually prescribed for the prevention and treatment of jaundice, inflammation, ache, fever, and skin ulcers. GF exerts an effect on ameliorating RA, the mechanism of which remains to be studied. In this study, ultra-perfor-mance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)-based serum non-target metabolomics and 16S rDNA high-throughput sequencing were employed to elucidate the mechanism of GF in ameliorating RA induced by complete Freund's adjuvant in rats. The results showed that GF alleviated the pathological conditions in adjuvant arthritis(AA) rats. The low-and high-dose GF lo-wered the serum levels of interleukin(IL)-6, tumor necrosis factor-α(TNF-α), IL-1β, and prostaglandin E2 in the rats(P<0.05, P<0.01). Pathways involved in metabolomics were mainly α-linolenic acid metabolism and glycerophospholipid metabolism. The results of 16S rDNA sequencing showed that the Streptococcus, Facklamia, Klebsiella, Enterococcus, and Kosakonia were the critical gut microorganisms for GF to treat AA in rats. Spearman correlation analysis showed that the three differential metabolites PE-NMe[18:1(9Z)/20:0], PC[20:1(11Z)/18:3(6Z,9Z,12Z)], and PC[20:0/18:4(6Z,9Z,12Z,15Z)] were correlated with the differential bacteria. In conclusion, GF may ameliorate RA by regulating the composition of intestinal microbiota, α-linolenic acid metabolism, and glycerophospholipid metabolism. The findings provide new ideas and data for elucidating the mechanism of GF in relieving RA.PMID:37474993 | DOI:10.19540/j.cnki.cjcmm.20230411.401

Zhongguo Zhong Yao Za Zhi. 2023 Jul;48(13):3535-3545. doi: 10.19540/j.cnki.cjcmm.20230411.203.ABSTRACTThis study aims to evaluate the quality consistency of Saposhnikoviae Radix based on carbohydrates, and explore the potential of carbohydrates as the internal quality control indicators of Saposhnikoviae Radix. The total polysaccharides were quantified by UV-Vis spectrophotometry and the molecular weight range of the polysaccharides was determined by high performance gel-permeation chromatography-evaporative light scattering detection(HPGPC-ELSD). The monosaccharides in polysaccharides and the free monosaccharides were quantified by high performance liquid chromatography-UV detection(HPLC-UV), and the oligosaccharides and fructose were quantified by high performance liquid chromatography-evaporative light scattering detection(HPLC-ELSD). The carbohydrate-based quality of Saposhnikoviae Radix was compared among 45 batches of commercial samples and 13 batches of self-collected samples. The results showed that the molecular weight distribution, monosaccharide composition, oligosaccharide, and free monosaccharide composition were similar in the 58 batches of samples. The average content of total polysaccharides, oligosaccharides, and total free monosaccharides in commercial samples were 39.66, 148.79, and 68.62 mg·g~(-1), respectively. The content showed significant differences among batches, with the highest differences of 3.51, 1.75, and 2.58 times, respectively. The RSD of the relative ratios of monosaccharides in the polysaccharides in commercial samples reached 28%-45%. The average content of total polysaccharides, oligosaccharides, and total free monosaccharides in self-collected samples were 68.07, 145.76, and 42.04 mg·g~(-1), respectively, with the inter-region differences of 2.88, 1.88, and 1.07 times, respectively. The RSD of the relative ratios of monosaccharides in polysaccharides in self-collected samples ranged from 8.2% to 59%. The total polysaccharides and total free monosaccharides in self-collected samples were 1.72 times higher and 1.63 times lower, respectively, than those in commercial samples. The content of oligosaccharides was similar between self-collected samples and commercial samples. To sum up, carbohydrates are one of the material bases for the internal quality consistency of Saposhnikoviae Radix. The qualitative characteristics of polysaccharides and the quantitative characteristics of polysaccharides and oligosaccharides are related to the origin of medicinal materials. Moreover, the quantitative characteristics of polysaccharides and free monosaccharides may be related to the storage conditions. Carbohydrates are potential indicators for the quality control of Saposhnikoviae Radix and deserve attention.PMID:37474987 | DOI:10.19540/j.cnki.cjcmm.20230411.203

Nat Genet. 2023 Jul 20. doi: 10.1038/s41588-023-01452-5. Online ahead of print.ABSTRACTTransposable elements (TEs) are parasitic DNA sequences accounting for over half of the human genome. Tight control of the repression and activation states of TEs is critical for genome integrity, development, immunity and diseases, including cancer. However, precisely how this regulation is achieved remains unclear. Here we develop a targeted proteomic proximity labeling approach to capture TE-associated proteins in human embryonic stem cells (hESCs). We find that the RNA N6-methyladenosine (m6A) reader, YTHDC2, occupies genomic loci of the primate-specific TE, LTR7/HERV-H, specifically through its interaction with m6A-modified HERV-H RNAs. Unexpectedly, YTHDC2 recruits the DNA 5-methylcytosine (5mC)-demethylase, TET1, to remove 5mC from LTR7/HERV-H and prevent epigenetic silencing. Functionally, the YTHDC2/LTR7 axis inhibits neural differentiation of hESCs. Our results reveal both an underappreciated crosstalk between RNA m6A and DNA 5mC, the most abundant regulatory modifications of RNA and DNA in eukaryotes, and the fact that in hESCs this interplay controls TE activity and cell fate.PMID:37474847 | DOI:10.1038/s41588-023-01452-5

Nat Commun. 2023 Jul 20;14(1):4367. doi: 10.1038/s41467-023-39683-z.ABSTRACTThe codependency of cholesterol metabolism sustains the malignant progression of glioblastoma (GBM) and effective therapeutics remain scarce. In orthotopic GBM models in male mice, we identify that codependent cholesterol metabolism in tumors induces phagocytic dysfunction in monocyte-derived tumor-associated macrophages (TAMs), resulting in disease progression. Manipulating cholesterol efflux with apolipoprotein A1 (ApoA1), a cholesterol reverse transporter, restores TAM phagocytosis and reactivates TAM-T cell antitumor immunity. Cholesterol metabolomics analysis of in vivo-sorted TAMs further reveals that ApoA1 mediates lipid-related metabolic remodeling and lowers 7-ketocholesterol levels, which directly inhibits tumor necrosis factor signaling in TAMs through mitochondrial translation inhibition. An ApoA1-armed oncolytic adenovirus is also developed, which restores antitumor immunity and elicits long-term tumor-specific immune surveillance. Our findings provide insight into the mechanisms by which cholesterol metabolism impairs antitumor immunity in GBM and offer an immunometabolic approach to target cholesterol disturbances in GBM.PMID:37474548 | DOI:10.1038/s41467-023-39683-z

Tree Physiol. 2023 Jul 20:tpad090. doi: 10.1093/treephys/tpad090. Online ahead of print.NO ABSTRACTPMID:37471649 | DOI:10.1093/treephys/tpad090

Anal Chem. 2023 Jul 20. doi: 10.1021/acs.analchem.3c02353. Online ahead of print.ABSTRACTGut microbiota-host co-metabolites serve as essential mediators of communication between the host and gut microbiota. They provide nutrient sources for host cells and regulate gut microenvironment, which are associated with a variety of diseases. Analysis of gut microbiota-host co-metabolites is of great significance to explore the host-gut microbiota interaction. In this study, we integrated chemical derivatization, liquid chromatography-mass spectrometry, and molecular networking (MN) to establish a novel CD-MN strategy for the analysis of carboxylated metabolites in gut microbial-host co-metabolism. Using this strategy, 261 carboxylated metabolites from mouse feces were detected, which grouped to various classes including fatty acids, bile acids, N-acyl amino acids, benzoheterocyclic acids, aromatic acids, and other unknown small-scale molecular clusters in MN. Based on the interpretation of the bile acid cluster, a novel type of phenylacetylated conjugates of host bile acids was identified, which were mediated by gut microbiota and exhibited a strong binding ability to Farnesoid X receptor and Takeda G protein-coupled receptor 5. Our proposed strategy offers a promising platform for uncovering carboxylated metabolites in gut microbial-host co-metabolism.PMID:37471289 | DOI:10.1021/acs.analchem.3c02353

Int J Neural Syst. 2023 Jul 21:2350041. doi: 10.1142/S0129065723500417. Online ahead of print.ABSTRACTParkinson's Disease (PD) is the second most prevalent neurodegenerative disorder among adults. Although its triggers are still not clear, they may be due to a combination of different types of biomarkers measured through medical imaging, metabolomics, proteomics or genetics, among others. In this context, we have proposed a Computer-Aided Diagnosis (CAD) system that combines structural and functional imaging data from subjects in Parkinson's Progression Markers Initiative dataset by means of an Ensemble Learning methodology trained to identify and penalize input sources with low classification rates and/or high-variability. This proposal improves results published in recent years and provides an accurate solution not only from the point of view of image preprocessing (including a comparison between different intensity preservation techniques), but also in terms of dimensionality reduction methods (Isomap). In addition, we have also introduced a bagging classification schema for scenarios with unbalanced data. As shown by our results, the CAD proposal is able to detect PD with [Formula: see text] of balanced accuracy, and opens up the possibility of combining any number of input data sources relevant for PD.PMID:37470777 | DOI:10.1142/S0129065723500417

Mol Plant Microbe Interact. 2023 Jul 20. doi: 10.1094/MPMI-05-23-0071-R. Online ahead of print.ABSTRACTPseudomonas simiae WCS417 is a plant growth-promoting rhizobacterium that improves plant health and development. In this study, we investigate the early leaf responses of Arabidopsis thaliana to WCS417 exposure and the possible involvement of formate dehydrogenase (FDH) in such responses. In vitro-grown A. thaliana seedlings expressing a FDH::GUS reporter show a significant increase in FDH promoter activity in their roots and shoots after 7 days of indirect exposure (without contact) to WCS417. After root exposure to WCS417, the leaves of FDH::GUS plants grown in the soil also show an increased FDH promoter activity in hydathodes. To elucidate early foliar responses to WCS417, as well as FDH involvement, the roots of A. thaliana wt Col and atfdh1-5 knock-out mutant plants grown in soil were exposed to WCS417 and proteins from rosette leaves were subjected to proteomic analysis. The results reveal that chloroplasts, in particular several components of the photosystems PSI and PSII, as well as members of the Glutathione S-transferase GST family, are among the early targets of the metabolic changes induced by WCS417. Taken together, the alterations in the foliar proteome, as observed in the atfdh1-5 mutant, especially after exposure to WCS417 and involving stress-responsive genes, suggest that FDH is a node in the early events triggered by the interactions between A. thaliana and the rhizobacterium WCS417.PMID:37470457 | DOI:10.1094/MPMI-05-23-0071-R

Environ Technol. 2023 Jul 20:1-39. doi: 10.1080/09593330.2023.2238930. Online ahead of print.ABSTRACTElectrochemical-assisted microbial degradation technology was considered a crucial strategy to reduce micropollutants, but the mechanism of the pulsed electric field (PEF) in affecting biodegradation had not been systematically studied. This study aimed to construct a bio-electrochemical system (BES) using PEF to investigate its effect on the degradation of triclosan (TCS) by the aerobic bacterium Bacillus sp. DL4. The operating optimal parameters for the BES (i.e., 0.01 A of the pulsed current, 1000 Hz of the pulse frequency, Fe (+) - C (-) of the plate materials, 4 cm of the plate spacing) were obtained by batch experiments. The maximum biomass (OD600 = 1.0 ± 0.05) was achieved and the removal efficiency of TCS reached above 95% in 24 h under the obtained operating conditions. Meanwhile, a thorough and methodical investigation of the metabolites in strain DL4 stimulated by PEF using untargeted Liquid Chromatography - Mass Spectrometry (LC-MS). In multivariate analysis, the experimental groups showed a notable separation in Principal Components Analysis (PCA) and Orthogonal Partial Least Squares Analysis discriminant analysis (OPLS-DA) score plots. A total of 3181 differential metabolites were obtained, and the up-regulated metabolites were mainly related to "Aminoacyl-tRNA biosynthesis", "Arginine and proline metabolism", "Lysine degradation", "ABC transporters", and "TCA cycle", implying that PEF enhanced the degradation efficiency of TCS by enriching functional genes with transport ability and ion migration ability in cells. This study illuminated how PEF can affect TCS biodegradation and gives insights into the application prospect of electrochemical-assisted biodegradation technology in water environment treatment.PMID:37470412 | DOI:10.1080/09593330.2023.2238930

J Exp Bot. 2023 Jul 20:erad276. doi: 10.1093/jxb/erad276. Online ahead of print.ABSTRACTThe surrounding gene networks of Nod factor receptors that govern the symbiotic process remain largely unexplored. In the present study, we identified 13 novel GmNFR1α-associated proteins by Y2H screening, and a potential interacting protein GmBI-1α was described. GmBI-1α had the highst positive correlation with GmNFR1α in the co-expression network analysis, and its expression at the mRNA level in roots was enhanced by rhizobial infection. Moreover, GmBI-1α- GmNFR1α interaction was shown to occur in vitro and in vivo. The GmBI-1α protein was localized to multiple subcellular locations, including the Endoplasmic Reticulum (ER) and Plasma Membrane (PM). Overexpression of GmBI-1α increased the nodule number in transgenic hairy roots or transgenic soybean, whereas down-regulation of GmBI-1α transcripts by RNA interference (RNAi) reduced the nodule number. Besides, the nodules in GmBI-1α-OX plants became smaller in size and infected area with reduced nitrogenase activity. In GmBI-1α-OX transgenic soybean, the elevated GmBI-1α level also promoted plant growth and suppressed the expression of defense signaling-related genes. IT analysis of GmBI-1α-OX showed that GmBI-1α promoted rhizobial infection. Collectively, our current findings supported a GmNFR1α-associated protein in the Nod factor signaling pathway and shed new light on the regulatory mechanism of GmNFR1α in rhizobial symbiosis.PMID:37470327 | DOI:10.1093/jxb/erad276

Food Funct. 2023 Jul 20. doi: 10.1039/d3fo02246c. Online ahead of print.ABSTRACTSucrose and fructose are the most commonly used sweeteners in the modern food industry, but there are few comparative studies on the mechanisms by which fructose and sucrose affect host health. The aim of the present study was to explain the different effects of fructose and sucrose on host metabolism from the perspective of gut microbiota. Mice were fed for 16 weeks with normal drinking water (CON), 30% fructose drinking water (CF) and 30% sucrose drinking water (SUC). Compared with fructose treatment, sucrose caused significantly higher weight gain, epididymal fat deposition, hepatic steatosis, and jejunum histological injury. Sucrose increased the abundance of LPS-producing bacteria which was positively correlated with obesity traits, while fructose increased the abundance of Lactobacillus. An in vitro fermentation experiment also showed that fructose increased the abundance of Lactobacillus, while sucrose increased the abundance of Klebsiella and Escherichia. In addition, combined with microbial functional analysis and metabolomics data, fructose led to the enhancement of carbohydrate metabolism and TCA cycle capacity, and increased the production of glutamate. The cross-cooperation network greatly influenced the microbiota (Klebsiella, Lactobacillus), metabolites (glutamate, fructose 1,6-biosphosphate, citric acid), and genes encoding enzymes (pyruvate kinase, 6-phosphofructokinase 1, fructokinase, lactate dehydrogenase, aconitate hydratase, isocitrate dehydrogenase 3), suggesting that they may be the key differential factors in the process of fructose and sucrose catabolism. Therefore, the changes in gut microbiome mediated by fructose and sucrose are important reasons for their differential effects on host health and metabolism.PMID:37470119 | DOI:10.1039/d3fo02246c

Front Vet Sci. 2023 Jul 4;10:1231996. doi: 10.3389/fvets.2023.1231996. eCollection 2023.ABSTRACTThis research aimed to assess the impact of fermented Citri Sarcodactylis Fructus by-products (FCSF) on the growth performance, gut digestive enzyme activity, nutrient utilization efficiency, gut microbiota, and their metabolites in broiler chickens. A total of 1,080 male broiler chickens were allocated into four groups (T1-T4) consisting of 6 replicates per group, each containing 45 chickens. The basal diet was provided to group T1, while groups T2, T3, and T4 were supplemented with 1%, 3%, and 5% FCSF in the basal diet, respectively. The experimental period was 42 days. The findings revealed that supplementing FCSF improved the FW and ADG of broiler chickens, and led to a reduction in the F/G, ADFI, and mortality rate of broiler chickens (p < 0.05). Furthermore, supplementation with 3% and 5% FCSF improved the thigh yield, semi-eviscerated carcass yield, slaughter yield, and lipase activity in the duodenum and ileum of birds (p < 0.05). Additionally, supplementing 3% FCSF enhanced the activity of protease in the duodenum of broilers (p < 0.05). Moreover, supplementing 3% FCSF enhanced the utilization of total phosphorus, dry matter, crude protein, and crude ash in the feed by broilers (p < 0.05). Compared with the control group, supplementation of 3% and 5% FCSF reduced the serine content in broiler chicken breast meat (p < 0.05). Supplementing 1% FCSF significantly increased the C14:0, C14:1, and C20:1 content in the breast meat compared to the other experimental groups (p < 0.05). The levels of C20:4n6 and C23:0 in the breast meat of birds of FCSF supplemented groups were lower than in T1 (p < 0.05). Furthermore, the content of ∑ω-3PUFA decreased after supplementing with 3% and 5% FCSF (p < 0.05). 16SrDNA showed that supplementing 3% FCSF reduced the ACE, Chao1, and Shannon indices in the cecum of birds (p < 0.05). Supplementing 3% FCSF also decreased the abundance of the phylum Desulfobacterota and improved genera Coprobacter and Prevotella in the cecum of broiler chickens (p < 0.05). Metabolomic analysis of the gut microbiota revealed that supplementing 3% FCSF upregulated 6 metabolites and downregulated 16 metabolites (p < 0.05). Moreover, supplementing 3% FCSF downregulated 12 metabolic pathways and upregulated 3 metabolic pathways (p < 0.05). In summary our findings indicate that supplementing FCSF can improve the growth performance of broiler chickens by enhancing intestinal digestive enzyme activity, nutrient utilization, improving gut microbial diversity, and influencing the metabolism of gut microbiota.PMID:37470069 | PMC:PMC10352846 | DOI:10.3389/fvets.2023.1231996

PNAS Nexus. 2023 Jul 18;2(7):pgad216. doi: 10.1093/pnasnexus/pgad216. eCollection 2023 Jul.ABSTRACTEnhancing crop yields is a major challenge because of an increasing human population, climate change, and reduction in arable land. Here, we demonstrate that long-lasting growth enhancement and increased stress tolerance occur by pretreatment of dark grown Arabidopsis seedlings with ethylene before transitioning into light. Plants treated this way had longer primary roots, more and longer lateral roots, and larger aerial tissue and were more tolerant to high temperature, salt, and recovery from hypoxia stress. We attributed the increase in plant growth and stress tolerance to ethylene-induced photosynthetic-derived sugars because ethylene pretreatment caused a 23% increase in carbon assimilation and increased the levels of glucose (266%), sucrose/trehalose (446%), and starch (87%). Metabolomic and transcriptomic analyses several days posttreatment showed a significant increase in metabolic processes and gene transcripts implicated in cell division, photosynthesis, and carbohydrate metabolism. Because of this large effect on metabolism, we term this "ethylene-mediated metabolic priming." Reducing photosynthesis with inhibitors or mutants prevented the growth enhancement, but this was partially rescued by exogenous sucrose, implicating sugars in this growth phenomenon. Additionally, ethylene pretreatment increased the levels of CINV1 and CINV2 encoding invertases that hydrolyze sucrose, and cinv1;cinv2 mutants did not respond to ethylene pretreatment with increased growth indicating increased sucrose breakdown is critical for this trait. A model is proposed where ethylene-mediated metabolic priming causes long-term increases in photosynthesis and carbohydrate utilization to increase growth. These responses may be part of the natural development of seedlings as they navigate through the soil to emerge into light.PMID:37469928 | PMC:PMC10353721 | DOI:10.1093/pnasnexus/pgad216

Front Pharmacol. 2023 Jul 4;14:1164425. doi: 10.3389/fphar.2023.1164425. eCollection 2023.ABSTRACTObjective: Traditional Chinese medicine (TCM) has been used as a complementary treatment for cancer patients, but there has been no quantitative comprehensive analysis of TCM's efficacy. The purpose of this paper is to explore the current status and hotspots of TCM in cancer research from 2002 to 2022 and to provide a reference for future research. Methods: We retrieved articles published between 2002 and 2022 from the Web of Science database and analyzed them using R software, VOSviewer, and CiteSpace software. Results: A total of 7,129 articles were included in this study. The publication rate of TCM cancer research increased steadily from 2002 to 2022, with a rapid increase from 2010 to 2021. China was the country with the most published articles, followed by the United States, Republic of Korea, Germany, and Japan. China was also the country with the most international collaborations, and China Medical University and Shanghai University of Traditional Chinese Medicine were the most representative cooperation centers. The Journal of Ethnopharmacology was the most published and cited journal. Apoptosis, expression, in vitro, activation, and other related keywords were commonly used in these articles. Breast cancer, colorectal cancer, gastric cancer, liver cancer, and lung cancer were the most studied cancer types in TCM research. Pathway-related apoptosis, anti-inflammation, and oxidative stress were the hotspots and trends of TCM's anti-cancer mechanism. Metabolomics combined with network pharmacology was the main research method. Conclusion: Traditional Chinese medicine as an anti-cancer drug has received increasing attention from researchers worldwide, and it is expected to be a hotspot for developing new anti-cancer drugs in the future. Our study provides a comprehensive analysis of the current status and hotspots of TCM cancer research, which could serve as a valuable reference for future studies.PMID:37469862 | PMC:PMC10352617 | DOI:10.3389/fphar.2023.1164425

Front Mol Biosci. 2023 Jul 4;10:1218518. doi: 10.3389/fmolb.2023.1218518. eCollection 2023.ABSTRACTThe tRNA adaptation index (tAI) is a translation efficiency metric that considers weighted values (S ij values) for codon-tRNA wobble interaction efficiencies. The initial implementation of the tAI had significant flaws. For instance, generated S ij weights were optimized based on gene expression in Saccharomyces cerevisiae, which is expected to vary among different species. Consequently, a species-specific approach (stAI) was developed to overcome those limitations. However, the stAI method employed a hill climbing algorithm to optimize the S ij weights, which is not ideal for obtaining the best set of S ij weights because it could struggle to find the global maximum given a complex search space, even after using different starting positions. In addition, it did not perform well in computing the tAI of fungal genomes in comparison with the original implementation. We developed a novel approach named genetic tAI (gtAI) implemented as a Python package (https://github.com/AliYoussef96/gtAI), which employs a genetic algorithm to obtain the best set of S ij weights and follows a new codon usage-based workflow that better computes the tAI of genomes from the three domains of life. The gtAI has significantly improved the correlation with the codon adaptation index (CAI) and the prediction of protein abundance (empirical data) compared to the stAI.PMID:37469707 | PMC:PMC10352787 | DOI:10.3389/fmolb.2023.1218518

Front Public Health. 2023 Jul 4;11:1217237. doi: 10.3389/fpubh.2023.1217237. eCollection 2023.ABSTRACTAIMS: Gestational diabetes mellitus (GDM) stands as a prevalent obstetric complication bearing consequential health implications for both mother and child. While existing studies have probed the alterations in acylcarnitines during GDM, an updated systematic meta-analysis is needed to consolidate these findings. Hence, this study endeavours to furnish a comprehensive systematic review and meta-analysis delineating the association between acylcarnitines and GDM, aimed at bolstering diagnostic accuracy and preventive measures against GDM.METHODS: To extract pertinent studies for this meta-analysis, we meticulously scoured databases such as PubMed, Web of Science, Embase, and Cochrane Library up until May 2023. The inclusion criteria were studies contrasting plasma metabolomics between two cohorts: women diagnosed with GDM and normoglycemic pregnant women. Weighted mean differences (SMDs) and 95% confidence intervals (CIs) were calculated using random-effects models. The I2 index was employed to quantify heterogeneity amongst the studies. All meta-analyses were executed using Stata version 12.0.RESULTS: Our meta-analysis included eight studies encompassing 878 pregnant women. The analysis disclosed that relative to normoglycemic pregnant women, women with GDM exhibited significantly elevated levels of Short-Chain Acylcarnitines (SCAC) (SMD: 0.19, 95% CI: 0.02-0.36, I2 = 71.3%). No substantial difference was discerned in fasting total carnitine levels (SMD: 0.15, 95% CI: -0.16-0.31, I2 = 68.2%), medium-chain acylcarnitines (MCAC) (SMD: 0.08, 95% CI: -0.02-0.36, I2 = 79.0%), and long-chain acylcarnitines (LCAC) (SMD: 0.04, 95% CI: -0.06-0.15, I2 = 0%). Neither funnel plot assessment nor Egger's regression and Begg's rank correlation tests indicated any evidence of publication bias.CONCLUSION: Our meta-analysis suggests that elevated levels of SCAC may heighten the risk of GDM onset. Given GDM's deleterious impact on pregnant women and their offspring, these findings underscore the clinical imperative of managing this condition. Early surveillance of plasma metabolomic profiles, particularly serum acylcarnitine concentrations, may equip clinicians with a valuable tool for timely diagnosis and intervention in GDM.PMID:37469690 | PMC:PMC10352491 | DOI:10.3389/fpubh.2023.1217237

Parkinsons Dis. 2023 Jul 10;2023:8848642. doi: 10.1155/2023/8848642. eCollection 2023.ABSTRACTOBJECTIVE: To investigate the role of aberrant Dyrk1a expression in phosphorylation modification at the α-synuclein serine 129 (Ser129) site to analyze its molecular mechanism in mediating apoptosis of PD.METHODS: The protein level of P-α-synuclein (Ser129), α-synuclein, Bcl-2, Bax, active caspase 3, GSK3β, PI3K, AKT, and cyclinD1 were detected. The mRNA transcript levels of Dyrk1a and DAT and protein levels of IL-1β, IL-6, COX-2, and TNF-α were detected.RESULTS: P-α-synuclein (Ser129), α-synuclein, Bax, active caspase 3, GSK3β, and cyclinD1 expressions were decreased in Dyrk1a-AAV-ShRNA (P < 0.05), and Bcl-2, AKT, and PI3K expressions were increased (P < 0.05). Increased TH protein expression was shown in Dyrk1a-AAV-ShRNA (P < 0.05). Dyrk1a mRNA was decreased in the Dyrk1a-AAV-ShRNA group (P < 0.05), and DAT mRNA was increased (P < 0.05). IL-1β, IL-6, COX-2, and TNF-α protein levels were decreased in Dyrk1al-AAV-Sh-RNA (P < 0.05). Transcriptome sequencing showed that Fam220a, which was expected to activate STAT family protein binding activity and participate in the negative regulation of transcription through RNA polymerase II and protein dephosphorylation showed differentially upregulated expression. The untargeted metabolome showed that the major compounds in the Dyrk1a-AAV-ShRNA group were hormones and transmission mediators and the most metabolism-related pathways. Fam220a showed differentially upregulated expression, and differentially expressed genes were enriched for the neuroactive ligand-receptor interaction, vascular smooth muscle contraction, and melanogenesis-related pathways.CONCLUSION: Abnormal Dyrk1a expression can affect α-synuclein phosphorylation modifications, and dyrk1a knockdown activates the PI3K/AKT pathway and reduces dopaminergic neuron apoptosis. It provides a theoretical basis for the group to further investigate the molecular mechanism.PMID:37469393 | PMC:PMC10352525 | DOI:10.1155/2023/8848642