Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Combined effects of salinity and polystyrene microplastics exposure on the Pacific oysters Crassostrea gigas: Oxidative stress and energy metabolism

Fri, 16/06/2023 - 12:00
Mar Pollut Bull. 2023 Jun 14;193:115153. doi: 10.1016/j.marpolbul.2023.115153. Online ahead of print.ABSTRACTMicroplastics (MPs) pollution and salinity variation are two environmental stressors, but their combined effects on marine mollusks are rarely known. Oysters (Crassostrea gigas) were exposed to 1 × 104 particles L-1 spherical polystyrene MPs (PS-MPs) of different sizes (small polystyrene MPs (SPS-MPs): 6 μm, large polystyrene MPs (LPS-MPs): 50-60 μm) under three salinity levels (21, 26, and 31 psu) for 14 days. Results demonstrated that low salinity reduced PS-MPs uptake in oysters. Antagonistic interactions between PS-MPs and low salinity mainly occurred, and partial synergistic effects were mainly induced by SPS-MPs. SPS-MPs induced higher lipid peroxidation (LPO) levels than LPS-MPs. In digestive glands, low salinity decreased LPO levels and glycometabolism-related gene expression, which was related to salinity levels. Low salinity instead of MPs mainly affected metabolomics profiles of gills through energy metabolism and osmotic adjustment pathway. In conclusion, oysters can adapt to combined stressors through energy and antioxidative regulation.PMID:37327720 | DOI:10.1016/j.marpolbul.2023.115153

Fibroblast phenylalanine concentration as a surrogate biomarker of cellular number

Fri, 16/06/2023 - 12:00
J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Jun 10;1226:123787. doi: 10.1016/j.jchromb.2023.123787. Online ahead of print.ABSTRACTMetabolomics studies in human dermal fibroblasts can elucidate the biological mechanisms associated with some diseases, but several methodological issues that increase variability have been identified. We aimed to quantify the amino acid levels in cultured fibroblasts and to apply different sample-based normalization approaches. Forty-four skin biopsies from control subjects were collected. Amino acids were measured in fibroblasts supernatants by UPLC-MS/MS. Statistical supervised and unsupervised studies were used. Spearman's test showed that phenylalanine displayed the second highest correlation with the remaining amino acids (mean r = 0.8), whereas the total protein concentration from the cell pellet showed a mean of r = 0.67. The lowest percentage of variation was obtained when amino acids were normalized by phenylalanine values, with a mean of 42% vs 57% when normalized by total protein values. When amino acid levels were normalized by phenylalanine, Principal Component Analysis and clustering analyses identified different fibroblasts groups. In conclusion, phenylalanine may be a suitable biomarker to estimate cellular content in cultured fibroblasts.PMID:37327517 | DOI:10.1016/j.jchromb.2023.123787

The mechanism of action of Ophiocordyceps sinensis mycelia for prevention of acute lung injury based on non-targeted serum metabolomics

Fri, 16/06/2023 - 12:00
PLoS One. 2023 Jun 16;18(6):e0287331. doi: 10.1371/journal.pone.0287331. eCollection 2023.ABSTRACTOphiocordyceps sinensis is a fungus with medicinal value in treating lung diseases, but no study has reported how to prevent acute lung injury using this fungus. The mice were divided into normal, model, positive control, and O. sinensis groups to observe lung histopathological sections and transmission electron microscopy, along with liquid chromatography-mass spectrometry and hematoxylin and eosin (H&E) staining to closely identify structural differences resulting from destruction between the groups. The results of the H&E staining showed that, compared with the normal group, the model group showed alveolar collapse. Compared with the model group, the infiltration of inflammatory cells in the alveolar cavity of the O. sinensis group was significantly reduced. Mitochondrial plate-like cristae were observed in type II alveolar cells of the normal group, with normal coloration of the mitochondrial matrix. Type II alveolar cells in the model group showed obvious edema. The statuses of type II alveolar cells in the O. sinensis and positive groups were similar to that in the normal group. Twenty-nine biomarkers and 10 related metabolic pathways were identified by serum metabolomics screening. The results showed that O. sinensis mycelia had a significant effect on the prevention of lipopolysaccharide-induced inflammation.PMID:37327224 | DOI:10.1371/journal.pone.0287331

Lactate Decreases Bortezomib Sensitivity and Predicts Poor Clinical Outcomes of Multiple Myeloma

Fri, 16/06/2023 - 12:00
Curr Med Sci. 2023 Jun 16. doi: 10.1007/s11596-023-2747-0. Online ahead of print.ABSTRACTOBJECTIVE: Metabolic disorders are regarded as hallmarks of multiple myeloma (MM) and are responsible for rapid cancer cell proliferation and tumor growth. However, the exact biological roles of metabolites in MM cells have not been fully explored. This study aimed to explore the feasibility and clinical significance of lactate for MM and investigate the molecular mechanism of lactic acid (Lac) in the proliferation of myeloma cells and cell sensitivity to bortezomib (BTZ).METHODS: Metabolomic analysis of the serum was carried out to obtain metabolites expression and clinical characteristics in MM patients. The CCK8 assay and flow cytometry were used to detect cell proliferation, apoptosis, and cell cycle changes. Western blotting was used to detect the potential mechanism and apoptosis- and cycle-related protein changes.RESULTS: Lactate was highly expressed in both the peripheral blood and bone marrow of MM patients. It was significantly correlated with Durie-Salmon Staging (DS Staging) and the International Staging System (ISS Staging) and the serum and urinary involved/uninvolved free light chain ratios. Patients with relatively high lactate levels had a poor treatment response. Moreover, in vitro experiments showed that Lac could promote the proliferation of tumor cells and decrease the proportion of G0/G1-phase cells, which was accompanied by an increased proportion of S-phase cells. In addition, Lac could decrease tumor sensitivity to BTZ by disrupting the expression of nuclear factor kappa B subunit 2 (NFkB2) and RelB.CONCLUSION: Metabolic changes are important in MM cell proliferation and treatment response; lactate could be used as a biomarker in MM and as a therapeutic target to overcome cell resistance to BTZ.PMID:37326888 | DOI:10.1007/s11596-023-2747-0

Competition between p53 and YY1 determines PHGDH expression and malignancy in bladder cancer

Fri, 16/06/2023 - 12:00
Cell Oncol (Dordr). 2023 Jun 16. doi: 10.1007/s13402-023-00823-8. Online ahead of print.ABSTRACTPURPOSE: Serine metabolism is frequently dysregulated in many types of cancers and the tumor suppressor p53 is recently emerging as a key regulator of serine metabolism. However, the detailed mechanism remains unknown. Here, we investigate the role and underlying mechanisms of how p53 regulates the serine synthesis pathway (SSP) in bladder cancer (BLCA).METHODS: Two BLCA cell lines RT-4 (WT p53) and RT-112 (p53 R248Q) were manipulated by applying CRISPR/Cas9 to examine metabolic differences under WT and mutant p53 status. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and non-targeted metabolomics analysis were adopted to identify metabolomes changes between WT and p53 mutant BLCA cells. Bioinformatics analysis using the cancer genome atlas and Gene Expression Omnibus datasets and immunohistochemistry (IHC) staining was used to investigate PHGDH expression. Loss-of-function of PHGDH and subcutaneous xenograft model was adopted to investigate the function of PHGDH in mice BLCA. Chromatin immunoprecipitation (Ch-IP) assay was performed to analyze the relationships between YY1, p53, SIRT1 and PHGDH expression.RESULTS: SSP is one of the most prominent dysregulated metabolic pathways by comparing the metabolomes changes between wild-type (WT) p53 and mutant p53 of BLCA cells. TP53 gene mutation shows a positive correlation with PHGDH expression in TCGA-BLCA database. PHGDH depletion disturbs the reactive oxygen species homeostasis and attenuates the xenograft growth in the mouse model. Further, we demonstrate WT p53 inhibits PHGDH expression by recruiting SIRT1 to the PHGDH promoter. Interestingly, the DNA binding motifs of YY1 and p53 in the PHGDH promoter are partially overlapped which causes competition between the two transcription factors. This competitive regulation of PHGDH is functionally linked to the xenograft growth in mice.CONCLUSION: YY1 drives PHGDH expression in the context of mutant p53 and promotes bladder tumorigenesis, which preliminarily explains the relationship between high-frequency mutations of p53 and dysfunctional serine metabolism in bladder cancer.PMID:37326803 | DOI:10.1007/s13402-023-00823-8

Omics technologies towards sesame improvement: a review

Fri, 16/06/2023 - 12:00
Mol Biol Rep. 2023 Jun 16. doi: 10.1007/s11033-023-08551-w. Online ahead of print.ABSTRACTGenetic improvement of sesame (Sesamum indicum L.), one of the most important oilseed crops providing edible oil, proteins, minerals, and vitamins, is important to ensure a balanced diet for the growing world population. Increasing yield, seed protein, oil, minerals, and vitamins is urgently needed to meet the global demand. The production and productivity of sesame is very low due to various biotic and abiotic stresses. Therefore, various efforts have been made to combat these constraints and increase the production and productivity of sesame through conventional breeding. However, less attention has been paid to the genetic improvement of the crop through modern biotechnological methods, leaving it lagging behind other oilseed crops. Recently, however, the scenario has changed as sesame research has entered the era of "omics" and has made significant progress. Therefore, the purpose of this paper is to provide an overview of the progress made by omics research in improving sesame. This review presents a number of efforts that have been made over past decade using omics technologies to improve various traits of sesame, including seed composition, yield, and biotic and abiotic resistant varieties. It summarizes the advances in genetic improvement of sesame using omics technologies, such as germplasm development (web-based functional databases and germplasm resources), gene discovery (molecular markers and genetic linkage map construction), proteomics, transcriptomics, and metabolomics that have been carried out in the last decade. In conclusion, this review highlights future directions that may be important for omics-assisted breeding in sesame genetic improvement.PMID:37326753 | DOI:10.1007/s11033-023-08551-w

Predicting chronic postsurgical pain: current evidence and a novel program to develop predictive biomarker signatures

Fri, 16/06/2023 - 12:00
Pain. 2023 Jun 15. doi: 10.1097/j.pain.0000000000002938. Online ahead of print.ABSTRACTChronic pain affects more than 50 million Americans. Treatments remain inadequate, in large part, because the pathophysiological mechanisms underlying the development of chronic pain remain poorly understood. Pain biomarkers could potentially identify and measure biological pathways and phenotypical expressions that are altered by pain, provide insight into biological treatment targets, and help identify at-risk patients who might benefit from early intervention. Biomarkers are used to diagnose, track, and treat other diseases, but no validated clinical biomarkers exist yet for chronic pain. To address this problem, the National Institutes of Health Common Fund launched the Acute to Chronic Pain Signatures (A2CPS) program to evaluate candidate biomarkers, develop them into biosignatures, and discover novel biomarkers for chronification of pain after surgery. This article discusses candidate biomarkers identified by A2CPS for evaluation, including genomic, proteomic, metabolomic, lipidomic, neuroimaging, psychophysical, psychological, and behavioral measures. Acute to Chronic Pain Signatures will provide the most comprehensive investigation of biomarkers for the transition to chronic postsurgical pain undertaken to date. Data and analytic resources generated by A2CPS will be shared with the scientific community in hopes that other investigators will extract valuable insights beyond A2CPS's initial findings. This article will review the identified biomarkers and rationale for including them, the current state of the science on biomarkers of the transition from acute to chronic pain, gaps in the literature, and how A2CPS will address these gaps.PMID:37326643 | DOI:10.1097/j.pain.0000000000002938

Untargeted metabonomic analysis of non-alcoholic fatty liver disease with iron overload in rats via UPLC/MS

Fri, 16/06/2023 - 12:00
Free Radic Res. 2023 Jun 16:1-15. doi: 10.1080/10715762.2023.2226315. Online ahead of print.ABSTRACTBACKGROUND/AIMS: In recent years, many metabolites specific to nonalcoholic fatty liver disease (NAFLD) have been identified thanks to the application of metabolomics techniques. This study aimed to investigate the candidate targets and potential molecular pathways involved in NAFLD in the presence of iron overload.METHODS: Male Sprague Dawley rats were fed with control or high-fat diet with or without excess iron. After 8,16,20 weeks of treatment, urine samples of rats were collected for metabolomics analysis using ultra-performance liquid chromatography/mass spectrometry (UPLC-MS). Blood and liver samples were also collected.RESULTS: High-fat, high-iron diet resulted in increased triglyceride accumulation and increased oxidative damage. A total of 13 metabolites and four potential pathways were identified. Compared to the control group, the intensities of adenine, cAMP, hippuric acid, kynurenic acid, xanthurenic acid, uric acid, and citric acid were significantly lower (P < 0.05) and the concentration of other metabolites was significantly higher in the high-fat diet group. In the high-fat, high-iron group, the differences in the intensities of the above metabolites were amplified.CONCLUSION: Our findings suggest that NAFLD rats have impaired antioxidant system and liver function, lipid disorders, abnormal energy, and glucose metabolism, and that iron overload may further exacerbate these disorders.PMID:37326040 | DOI:10.1080/10715762.2023.2226315

Multi-omics analysis reveals the mechanism of torularhodin accumulation in the mutant <em>Rhodosporidium toruloides</em> A1-15 under nitrogen-limited conditions

Fri, 16/06/2023 - 12:00
Food Funct. 2023 Jun 16. doi: 10.1039/d3fo01097j. Online ahead of print.ABSTRACTA carotenoid production strain Rhodosporidium toruloides NP11 and its mutant strain R. toruloides A1-15 were studied under chemostat nitrogen-limited cultivation. Multi-omics analysis (metabolomics, lipidomics and transcriptomics) was used to investigate the different mechanisms of torularhodin accumulation between NP11 and A1-15. The results showed that the carotenoid synthesis pathway was significantly enhanced in A1-15 compared to NP11 under nitrogen limitation, due to the significant increase of torularhodin. Under nitrogen-limited conditions, higher levels of β-oxidation were present in A1-15 compared to those in NP11, which provided sufficient precursors for carotenoid synthesis. In addition, ROS stress accelerated the intracellular transport of iron ions, promoted the expression of CRTI and CRTY genes, and reduced the transcript levels of FNTB1 and FNTB2 in the bypass pathway, and these factors may be responsible for the regulation of high torularhodin production in A1-15. This study provided insights into the selective production of torularhodin.PMID:37325941 | DOI:10.1039/d3fo01097j

Diets, Gut Microbiota and Metabolites

Fri, 16/06/2023 - 12:00
Phenomics. 2023 Mar 2;3(3):268-284. doi: 10.1007/s43657-023-00095-0. eCollection 2023 Jun.ABSTRACTThe gut microbiota refers to the gross collection of microorganisms, estimated trillions of them, which reside within the gut and play crucial roles in the absorption and digestion of dietary nutrients. In the past decades, the new generation 'omics' (metagenomics, transcriptomics, proteomics, and metabolomics) technologies made it possible to precisely identify microbiota and metabolites and describe their variability between individuals, populations and even different time points within the same subjects. With massive efforts made, it is now generally accepted that the gut microbiota is a dynamically changing population, whose composition is influenced by the hosts' health conditions and lifestyles. Diet is one of the major contributors to shaping the gut microbiota. The components in the diets vary in different countries, religions, and populations. Some special diets have been adopted by people for hundreds of years aiming for better health, while the underlying mechanisms remain largely unknown. Recent studies based on volunteers or diet-treated animals demonstrated that diets can greatly and rapidly change the gut microbiota. The unique pattern of the nutrients from the diets and their metabolites produced by the gut microbiota has been linked with the occurrence of diseases, including obesity, diabetes, nonalcoholic fatty liver disease, cardiovascular disease, neural diseases, and more. This review will summarize the recent progress and current understanding of the effects of different dietary patterns on the composition of gut microbiota, bacterial metabolites, and their effects on the host's metabolism.PMID:37325710 | PMC:PMC10260722 | DOI:10.1007/s43657-023-00095-0

Lipid metabolism and rheumatoid arthritis

Fri, 16/06/2023 - 12:00
Front Immunol. 2023 May 31;14:1190607. doi: 10.3389/fimmu.2023.1190607. eCollection 2023.ABSTRACTAs a chronic progressive autoimmune disease, rheumatoid arthritis (RA) is characterized by mainly damaging the synovium of peripheral joints and causing joint destruction and early disability. RA is also associated with a high incidence rate and mortality of cardiovascular disease. Recently, the relationship between lipid metabolism and RA has gradually attracted attention. Plasma lipid changes in RA patients are often detected in clinical tests, the systemic inflammatory status and drug treatment of RA patients can interact with the metabolic level of the body. With the development of lipid metabolomics, the changes of lipid small molecules and potential metabolic pathways have been gradually discovered, which makes the lipid metabolism of RA patients or the systemic changes of lipid metabolism after treatment more and more comprehensive. This article reviews the lipid level of RA patients, as well as the relationship between inflammation, joint destruction, cardiovascular disease, and lipid level. In addition, this review describes the effect of anti-rheumatic drugs or dietary intervention on the lipid profile of RA patients to better understand RA.PMID:37325667 | PMC:PMC10264672 | DOI:10.3389/fimmu.2023.1190607

HIV-1 activates oxidative phosphorylation in infected CD4 T cells in a human tonsil explant model

Fri, 16/06/2023 - 12:00
Front Immunol. 2023 May 30;14:1172938. doi: 10.3389/fimmu.2023.1172938. eCollection 2023.ABSTRACTINTRODUCTION: Human immunodeficiency virus type 1 (HIV-1) causes a chronic, incurable infection leading to immune activation and chronic inflammation in people with HIV-1 (PWH), even with virologic suppression on antiretroviral therapy (ART). The role of lymphoid structures as reservoirs for viral latency and immune activation has been implicated in chronic inflammation mechanisms. Still, the specific transcriptomic changes induced by HIV-1 infection in different cell types within lymphoid tissue remain unexplored.METHODS: In this study, we utilized human tonsil explants from healthy human donors and infected them with HIV-1 ex vivo. We performed single-cell RNA sequencing (scRNA-seq) to analyze the cell types represented in the tissue and to investigate the impact of infection on gene expression profiles and inflammatory signaling pathways.RESULTS: Our analysis revealed that infected CD4+ T cells exhibited upregulation of genes associated with oxidative phosphorylation. Furthermore, macrophages exposed to the virus but uninfected showed increased expression of genes associated with the NLRP3 inflammasome pathway.DISCUSSION: These findings provide valuable insights into the specific transcriptomic changes induced by HIV-1 infection in different cell types within lymphoid tissue. The activation of oxidative phosphorylation in infected CD4+ T cells and the proinflammatory response in macrophages may contribute to the chronic inflammation observed in PWH despite ART. Understanding these mechanisms is crucial for developing targeted therapeutic strategies to eradicate HIV-1 infection in PWH.PMID:37325659 | PMC:PMC10266353 | DOI:10.3389/fimmu.2023.1172938

Advances in gut microbiome in metabonomics perspective: based on bibliometrics methods and visualization analysis

Fri, 16/06/2023 - 12:00
Front Cell Infect Microbiol. 2023 May 30;13:1196967. doi: 10.3389/fcimb.2023.1196967. eCollection 2023.ABSTRACTBACKGROUND AND AIMS: Gastrointestinal microbial metabolomics is closely related to the state of the organism and has significant interaction with the pathogenesis of many diseases. Based on the publications in Web of Science Core Collection(WoSCC) from 2004 to 2022, this study conducted a bibliometric analysis of this field, aiming to understand its development trend and frontier, and provide basic information and potential points for in-depth exploration of this field.METHODS: All articles on gastrointestinal flora and metabolism published from 2004 to 2022 were collected and identified in WoCSS. CiteSpace v.6.1 and VOSviewer v.1.6.15.0 were used to calculate bibliometric indicators, including number of publications and citations, study categories, countries/institutions, authors/co-cited authors, journals/co-cited journals, co-cited references, and keywords. A map was drawn to visualize the data based on the analysis results for a more intuitive view.RESULTS: There were 3811 articles in WoSCC that met our criteria. Analysis results show that the number of publications and citations in this field are increasing year by year. China is the country with the highest number of publications and USA owns the highest total link strength and citations. Chinese Acad Sci rank first for the number of institutional publications and total link strength. Journal of Proteome Research has the most publications. Nicholson, Jeremy K. is one of the most important scholars in this field. The most cited reference is "Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease". Burst detection indicates that Urine, spectroscopy, metabonomic and gut microflora are long-standing hot topics in this field, while autism spectrum disorder and omics are likely to be at the forefront of research. The study of related metabolic small molecules and the application of gastrointestinal microbiome metabolomics in various diseases are currently emerging research directions and frontier in this field.CONCLUSION: This study is the first to make a bibliometric analysis of the studies related to gastrointestinal microbial metabolomics and reveal the development trends and current research hotspots in this field. This can contribute to the development of the field by providing relevant scholars with valuable and effective information about the current state of the field.PMID:37325519 | PMC:PMC10266355 | DOI:10.3389/fcimb.2023.1196967

Exploring the effects of palm kernel meal feeding on the meat quality and rumen microorganisms of Qinghai Tibetan sheep

Fri, 16/06/2023 - 12:00
Food Sci Nutr. 2023 Apr 5;11(6):3516-3534. doi: 10.1002/fsn3.3340. eCollection 2023 Jun.ABSTRACTPalm kernel meal (PKM) has been shown to be a high-quality protein source in ruminant feeds. This study focused on the effects of feed, supplemented with different amounts of PKM (ZL-0 as blank group, and ZL-15, ZL-18, and ZL-21 as treatment group), on the quality and flavor profile of Tibetan sheep meat. Furthermore, the deposition of beneficial metabolites in Tibetan sheep and the composition of rumen microorganisms on underlying regulatory mechanisms of meat quality were studied based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry as well as 16S rDNA sequencing. The results of the study showed that Tibetan sheep in the ZL-18 group exhibited superior eating quality and flavor profile while depositing more protein and fat relative to the other groups. The ZL-18 group also changed significantly in terms of the concentration and metabolic pathways of meat metabolites, as revealed by metabolomics. Metabolomics and correlation analyses finally showed that PKM feed mainly affected carbohydrate metabolism in muscle, which in turn affects meat pH, tenderness, and flavor. In addition, 18% of PKM increased the abundance of Christensenellaceae R-7 group, Ruminococcaceae UCG-013, Lachnospiraceae UCG-002, and Family XIII AD3011 group in the rumen but decreased the abundance of Prevotella 1; the above bacteria groups regulate meat quality by regulating rumen metabolites (succinic acid, DL-glutamic acid, etc.). Overall, the addition of PKM may improve the quality and flavor of the meat by affecting muscle metabolism and microorganisms in the rumen.PMID:37324863 | PMC:PMC10261763 | DOI:10.1002/fsn3.3340

A systematic overexpression approach reveals native targets to increase squalene production in <em>Synechocystis</em> sp. PCC 6803

Fri, 16/06/2023 - 12:00
Front Plant Sci. 2023 May 30;14:1024981. doi: 10.3389/fpls.2023.1024981. eCollection 2023.ABSTRACTCyanobacteria are a promising platform for the production of the triterpene squalene (C30), a precursor for all plant and animal sterols, and a highly attractive intermediate towards triterpenoids, a large group of secondary plant metabolites. Synechocystis sp. PCC 6803 natively produces squalene from CO2 through the MEP pathway. Based on the predictions of a constraint-based metabolic model, we took a systematic overexpression approach to quantify native Synechocystis gene's impact on squalene production in a squalene-hopene cyclase gene knock-out strain (Δshc). Our in silico analysis revealed an increased flux through the Calvin-Benson-Bassham cycle in the Δshc mutant compared to the wildtype, including the pentose phosphate pathway, as well as lower glycolysis, while the tricarboxylic acid cycle predicted to be downregulated. Further, all enzymes of the MEP pathway and terpenoid synthesis, as well as enzymes from the central carbon metabolism, Gap2, Tpi and PyrK, were predicted to positively contribute to squalene production upon their overexpression. Each identified target gene was integrated into the genome of Synechocystis Δshc under the control of the rhamnose-inducible promoter Prha. Squalene production was increased in an inducer concentration dependent manner through the overexpression of most predicted genes, which are genes of the MEP pathway, ispH, ispE, and idi, leading to the greatest improvements. Moreover, we were able to overexpress the native squalene synthase gene (sqs) in Synechocystis Δshc, which reached the highest production titer of 13.72 mg l-1 reported for squalene in Synechocystis sp. PCC 6803 so far, thereby providing a promising and sustainable platform for triterpene production.PMID:37324717 | PMC:PMC10266222 | DOI:10.3389/fpls.2023.1024981

Integrated metabolome and transcriptome analyses provide insight into the effect of red and blue LEDs on the quality of sweet potato leaves

Fri, 16/06/2023 - 12:00
Front Plant Sci. 2023 May 30;14:1181680. doi: 10.3389/fpls.2023.1181680. eCollection 2023.ABSTRACTRed and blue light-emitting diodes (LEDs) affect the quality of sweet potato leaves and their nutritional profile. Vines cultivated under blue LEDs had higher soluble protein contents, total phenolic compounds, flavonoids, and total antioxidant activity. Conversely, chlorophyll, soluble sugar, protein, and vitamin C contents were higher in leaves grown under red LEDs. Red and blue light increased the accumulation of 77 and 18 metabolites, respectively. Alpha-linoleic and linolenic acid metabolism were the most significantly enriched pathways based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A total of 615 genes were differentially expressed between sweet potato leaves exposed to red and blue LEDs. Among these, 510 differentially expressed genes were upregulated in leaves grown under blue light compared with those grown under red light, while the remaining 105 genes were expressed at higher levels in the latter than in the former. Among the KEGG enrichment pathways, blue light significantly induced anthocyanin and carotenoid biosynthesis structural genes. This study provides a scientific reference basis for using light to alter metabolites to improve the quality of edible sweet potato leaves.PMID:37324670 | PMC:PMC10266350 | DOI:10.3389/fpls.2023.1181680

Gut and reproductive tract microbiota: Insights into the pathogenesis of endometriosis (Review)

Fri, 16/06/2023 - 12:00
Biomed Rep. 2023 May 29;19(1):43. doi: 10.3892/br.2023.1626. eCollection 2023 Jul.ABSTRACTEndometriosis is characterized by the presence of endometrial-like tissue outside the uterus and is associated with an inflammatory immune response. The gut and reproductive tract microbiota constitute a protective barrier against infection by pathogens and regulate inflammatory and immune functions. This review summarizes microbiota imbalance (i.e., dysbiosis) in endometriosis and discusses how dysbiosis influences disease development. The literature was searched for studies published from inception to March 2022 in the PubMed and Google Scholar databases using a combination of specific terms. An altered gut and reproductive tract microbiome has been reported in numerous conditions, such as inflammatory bowel disease, allergies, autoimmunity, cancer and reproductive disorders (e.g., endometriosis). Furthermore, microbial dysbiosis is a hallmark of endometriosis and is characterized by a decrease in beneficial probiotics and an increase in pathogenic microbes, which leads to a series of estrobolomic and metabolomic changes. Gut or reproductive tract microbiome dysbiosis was reported in mice, nonhuman primates, and females with endometriosis. Animal models of endometriosis demonstrated the effects of the gut microbiome on lesion growth and vice versa. The immune system mediated by the microbiota-gut-reproductive tract axis triggers an inflammatory response that damages reproductive tract tissue, which possibly leads to endometriosis. However, whether the alteration of eubiosis (a balanced microbiota) to dysbiosis is a cause or a result of endometriosis is unclear. In conclusion, this review provides an overview of the relationship between the gut and reproductive tract microbiome and endometriosis, focusing on the mechanisms by which dysbiosis may increase the risk of disease.PMID:37324168 | PMC:PMC10265574 | DOI:10.3892/br.2023.1626

The predictive value of chest computed tomography images, tumor markers, and metabolomics in the identification of benign and malignant pulmonary nodules

Fri, 16/06/2023 - 12:00
J Thorac Dis. 2023 May 30;15(5):2668-2679. doi: 10.21037/jtd-23-250. Epub 2023 May 24.ABSTRACTBACKGROUND: Invasive puncture biopsy is currently the main method of identifying benign and malignant pulmonary nodules (PNs). This study aimed to investigate the application effect of chest computed tomography (CT) images, tumor markers (TMs), and metabolomics in the identification of benign and malignant PNs (MPNs).METHODS: A total of 110 patients with PNs who were hospitalized in Dongtai Hospital of Traditional Chinese Medicine from March 2021 to March 2022 were selected as the study cohort. A retrospective analysis study of chest CT imaging, serum TMs testing, and plasma fatty acid (FA) metabolomics was performed on all participants.RESULTS: According to the pathological results, participants were divided into a MPN group (n=72) and a benign PN (BPN) group (n=38). The morphological signs of CT images, the levels and positive rate of serum TMs, and the plasma FA indicator were compared between groups. There were significant differences between the MPN group and the BPN group in the CT morphological signs, including location of PN and the number of patients with or without lobulation sign, spicule sign, and vessel convergence sign (P<0.05). Serum carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA 21-1), neuron-specific enolase (NSE), and squamous cell carcinoma antigen (SCC-Ag) were not significantly different between the 2 groups. The serum contents of CEA and CYFRA 21-1 in the MPN group were remarkably higher than those in the BPN group (P<0.05). The plasma levels of palmitic acid, total omega-3 polyunsaturated FA (W3), nervonic acid, stearic acid, docosatetraenoic acid, linolenic acid, eicosapentaenoic acid, total saturated FA, and total FA were much higher in the MPN group than the BPN group (P<0.05).CONCLUSIONS: In conclusion, chest CT images and TMs, combined with metabolomics, has a good application effect in the diagnosis of BPNs and MPNs, and is worthy of further promotion.PMID:37324101 | PMC:PMC10267948 | DOI:10.21037/jtd-23-250

Changes in targeted metabolomics in lung tissue of chronic obstructive pulmonary disease

Fri, 16/06/2023 - 12:00
J Thorac Dis. 2023 May 30;15(5):2544-2558. doi: 10.21037/jtd-22-1731. Epub 2023 May 22.ABSTRACTBACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common chronic lung disease and its incidence is steadily increasing. COPD patients and mouse models of COPD share some similarities in lung pathology and physiology. We performed this study to explore the potential metabolic pathways involved in the pathogenesis of COPD and to discover the COPD-associated biomarkers. Furthermore, we aimed to examine how much the mouse model of COPD was similar and different to human COPD in terms of the altered metabolites and pathways.METHODS: Twenty human lung tissue samples (ten COPD and ten controls) and twelve mice lung tissue samples (six COPD and six controls) were analyzed by targeted HM350 metabolomics, and multivariate and pathway analysis were performed by Kyoto Encyclopedia of Genes and Genomes (KEGG) database.RESULTS: The counts of many metabolites such as amino acids, carbohydrates and carnitines were changed in both COPD patients and mice compared to controls, respectively. While lipid metabolism was changed only in COPD mice. After KEGG analysis, we found these altered metabolites involved in COPD through aging, apoptosis, oxidative stress and inflammation pathways.CONCLUSIONS: The expressions of metabolites changed in both COPD patients and cigarette smoke exposed (CS-exposed) mice. And there were also some differences between COPD patients and mouse models due to the differences between species. Our study suggested the dysregulation in amino acid metabolism, energy production pathway and perhaps lipid metabolism may be significantly related to the pathogenesis of COPD.PMID:37324094 | PMC:PMC10267913 | DOI:10.21037/jtd-22-1731

Editorial: Bacterial metabolomics approach towards antimicrobials and resistance

Fri, 16/06/2023 - 12:00
Front Microbiol. 2023 May 30;14:1222594. doi: 10.3389/fmicb.2023.1222594. eCollection 2023.NO ABSTRACTPMID:37323916 | PMC:PMC10265112 | DOI:10.3389/fmicb.2023.1222594

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