Metabolic Profile Research Articles

Endocrinological and metabolic profile of Gaucher disease patients treated with enzyme replacement therapy.

Gaucher Disease (GD) is a lysosomal storage disease caused by glucocerebrosidase (GCase) enzyme deficiency. Gaucher cells transformed from the macrophages by progressive sphingolipid accumulation and infiltrate bone marrow, spleen, liver, and other organs. The accumulation of substrate causes inflammation, compromised cellular homeostasis, and disturbed autophagy. It has been hypothesized that this proinflammatory state of GD leads cytokines and chemokines release. As a result of inflammatory process, the cellular dysfunction caused by disruption of cellular signaling, organelle dysfunction, or autoimmune antibodies may affect endocrine profile of GD patients such as hormone levels, lipid profile, and bone mineral density status. A total of 13 patients confirmed to have GD, 12 non-neuronopathic type and one subacute neuronopathic type, were enrolled in our study. The median treatment duration in the enzyme therapy was 13.33 years (9-26 years). At least one endocrinological abnormality was detected in blood tests of nine patients. Hyperinsulinism was the most common finding although fasting blood glucose levels HgbA1c levels were normal in all patients. Two patients had osteopenia, and osteoporosis was detected in two patients. Low HDL levels were detected in six patients, but HDL levels below 23 mg/dL associated with disease severity have been detected in two patients who have not receiving enzyme replacement therapy. None of patients had thyroidal dysfunction. This study had revealed endocrinological abnormalities in GD patients that have not led any severe morbidity in our patients. However, thyroid hormone abnormalities, insulin resistance, or lipid profile abnormalities may cause unpredictable comorbidities. Endocrinological assessment in GD patients in routine follow-up may prevent possible clinical manifestation in long term as well as can define efficacy of ERT on endocrine abnormalities.

The synergism of Lactobacillaceae, inulin, polyglucose, and aerobic exercise ameliorates hyperglycemia by modulating the gut microbiota community and the metabolic profiles in db/db mice.

This study aimed to assess the impact of Lactobacillaceae (L or H represents a low or high dose), inulin (I), and polydextrose (P) combined with aerobic exercise (A) on the composition of the gut microbiota and metabolic profiles in db/db mice. After a 12-week intervention, LIP, LIPA, and HIPA groups exhibited significant improvements in hyperglycemia, glucose tolerance, insulin resistance, inflammatory response, and short-chain fatty acid (SCFA) and blood lipid levels compared to type 2 diabetes mice (MC). After treatment, the gut microbiota composition shifted favorably in the treatment groups which significantly increased the abundance of beneficial bacteria, such as Bacteroides, Blautia, Akkermansia, and Faecalibaculum, and significantly decreased the abundance of Proteus. Metabolomics analysis showed that compared to the MC group, the contents of 5-hydroxyindoleacetic acid, 3-hydroxysebacic acid, adenosine monophosphate (AMP), xanthine and hypoxanthine were significantly decreased, while 3-ketosphinganine, sphinganine, and sphingosine were significantly increased in the LIP and LIPA groups, respectively. Additionally, LIP and LIPA not only improved sphingolipid metabolism and purine metabolism pathways but also activated AMP-activated protein kinase to promote β-oxidation by increasing the levels of SCFAs. Faecalibaculum, Blautia, Bacteroides, and Akkermansia exhibited positive correlations with sphingosine, 3-ketosphinganine, and sphinganine, and exhibited negative correlations with hypoxanthine, xanthine and AMP. Faecalibaculum, Blautia, Bacteroides, and Akkermansia may have the potential to improve sphingolipid metabolism and purine metabolism pathways. These findings suggest that the synergism of Lactobacillaceae, inulin, polydextrose, and aerobic exercise provides a promising strategy for the prevention and management of type 2 diabetes.

Metabolic profiling of peri-implant crevicular fluid in peri-implantitis.

This study aims to explore the etiology of peri-implantitis by comparing the metabolic profiles in peri-implant crevicular fluid (PICF) from patients with healthy implants (PH) and those with peri-implantitis (PI). Fifty-six patients were enrolled in this cross-sectional study. PICF samples were collected and analyzed using both non-targeted and targeted metabolomics approaches. The relationship between metabolites and clinical indices including probing depth (PD), bleeding on probing (BOP), and marginal bone loss (MBL) was examined. Additionally, submucosal microbiota was collected and analyzed using 16S rRNA gene sequencing to elucidate the association between the metabolites and microbial communities. Significant differences in metabolic profiles were observed between the PH and PI groups, with 179 distinct metabolites identified. In the PI group, specific amino acids and fatty acids were significantly elevated compared to the PH group. Organic acids including succinic acid, fructose-6-phosphate, and glucose-6-phosphate were markedly higher in the PI group, showing positive correlations with mean PD, BOP, and MBL. Metabolites that increased in the PI group positively correlated with the presence of Porphyromonas and Treponema and negatively with Streptococcus and Haemophilus. This study establishes a clear association between metabolic compositions and peri-implant condition, highlighting enhanced metabolite activity in peri-implantitis. These findings open avenues for further research into metabolic mechanisms of peri-implantitis and their potential therapeutic implications.

Combined Metabolomics and Biochemical Analyses of Serum and Milk Revealed Parity-Related Metabolic Differences in Sanhe Dairy Cattle

The production performance of dairy cattle is closely related to their metabolic state. This study aims to provide a comprehensive understanding of the production performance and metabolic features of Sanhe dairy cattle across different parities, with a specific focus on evaluating variations in milk traits and metabolites in both milk and serum. Sanhe dairy cattle from parities 1 to 4 (S1, n = 10; S2, n = 9; S3, n = 10; and S4, n = 10) at mid-lactation were maintained under the same feeding and management conditions. The milk traits, hydrolyzed milk amino acid levels, serum biochemical parameters, and serum free amino acid levels of the Sanhe dairy cattle were determined. Multiparous Sanhe dairy cattle (S2, S3, and S4) had a greater milk protein content, lower milk lactose content, and lower solids-not-fat content than primiparous Sanhe dairy cattle (S1). Moreover, S1 had a higher ratio of essential to total amino acids (EAAs/TAAs) in both the serum and milk. The serum biochemical results showed the lower glucose and total protein levels in S1 cattle were associated with milk quality. Furthermore, ultra-high-resolution high-performance liquid chromatography with tandem MS analysis (UPLC-MS/MS) identified 86 and 105 differential metabolites in the serum and milk, respectively, and these were mainly involved in amino acid, carbohydrate, and lipid metabolism. S1 and S2/S3/S4 had significantly different metabolic patterns in the serum and milk, and more vitamin B-related metabolites were significantly higher identified in S1 than in multiparous cattle. Among 36 shared differential metabolites in the serum and milk, 10 and 7 metabolites were significantly and strongly correlated with differential physiological indices, respectively. The differential metabolites identified were enriched in key metabolic pathways, illustrating the metabolic characteristics of the serum and milk from Sanhe dairy cattle of different parities. L-phenylalanine, dehydroepiandrosterone, and linoleic acid in the milk and N-acetylornithine in the serum could be used as potential marker metabolites to distinguish between Sanhe dairy cattle with parities of 1–4. In addition, a metabolic map of the serum and milk from the three aspects of carbohydrates, amino acids, and lipids was created for the further analysis and exploration of their relationships. These results reveal significant variations in milk traits and metabolites across different parities of Sanhe dairy cattle, highlighting the influence of parity on the metabolic profiles and production performance. Tailored nutritional strategies based on parity-specific metabolic profiles are recommended to optimize milk production and quality in Sanhe cattle.

Exploring Anticancer Properties of Medicinal Plants against Breast Cancer by Downregulating Human Epidermal Growth Factor Receptor 2.

Plants have a history of being employed in managing breast cancer. However, no scientific evidence supports the idea that these plants can effectively reduce the level of HER2 expression. In this study, extracts from 10 medicinal plants were evaluated for their anticancer properties against HER2-positive breast cancer cells through various methods, including the SRB assay, comet assay, annexin V-FITC dual staining, and immunoblotting. All extracts exerted antiproliferative activity against HER2-positive breast cancer cells. Furthermore, Terminalia chebula (T. chebula), Berberis aristata (B. aristata), and Mucuna pruriens (M. pruriens) reduced HER2 expression in tested cell lines. In addition, an increased Bax/Bcl-2 ratio was observed after the treatment. A comparative proteomics study showed modulation in the proteome profile of breast cancer cells after treatment with T. chebula, B. aristata, Punica granatum, M. pruriens, and Acorus calamus. Metabolic profiling of lead plants revealed the existence of multiple anticancer compounds. Our study demonstrates the considerable potential of the mentioned plants as innovative therapies for HER2-positive breast cancer.

The Obese Taste Bud study: Objectives and study design.

Taste modifies eating behaviour, impacting body weight and potentially obesity development. The Obese Taste Bud (OTB) Study is a prospective cohort study launched in 2020 at the University of Leipzig Obesity Centre in cooperation with the HI-MAG Institute. OTB will test the hypothesis that taste cell homeostasis and taste perception are linked to obesity. Here, we provide the study design, data collection process and baseline characteristics. Participants presenting overweight, obesity or normal weight undergo taste and smell tests, anthropometric, and taste bud density (TBD) assessment on Day 1. Information on physical and mental health, eating behaviour, physical activity, and dental hygiene are obtained, while biomaterial (saliva, tongue swap, blood) is collected in the fasted state. Further blood samples are taken during a glucose tolerance test. A stool sample is collected at home prior to Day 2, on which a taste bud biopsy follows dental examination. A subsample undergoes functional magnetic resonance imaging while exposed to eating-related cognitive tasks. Follow-up investigations after conventional weight loss interventions and bariatric surgery will be included. Initial results show that glycated haemoglobin levels and age are negatively associated with TBD, while an unfavourable metabolic profile, current dieting, and vegan diet are related to taste perception. Olfactory function negatively correlates with age and high-density lipoprotein cholesterol. Initial findings suggest that metabolic alterations are relevant for taste and smell function and TBD. By combining omics data from collected biomaterial with physiological, metabolic and psychological data related to taste perception and eating behaviour, the OTB study aims to strengthen our understanding of taste perception in obesity.

Overexpression of oilseed rape trehalose-6-phosphate synthesis gene BnaC02.TPS8 confers sensitivity to low nitrogen and high sucrose-induced anthocyanin accumulation in Arabidopsis.

Overexpression of BnaC02.TPS8 increased low N and high sucrose-induced anthocyanin accumulation. Anthocyanin plays a crucial role in safeguarding photosynthetic tissues against high light, UV radiation, and oxidative stress. Their accumulation is triggered by low nitrogen (N) stress and elevated sucrose levels in Arabidopsis. Trehalose-6-phosphate (T6P) serves as a pivotal signaling molecule, sensing sucrose availability, and carbon (C) metabolism. However, the mechanisms governing the regulation of T6P synthase (TPS) genes responsible for anthocyanin accumulation under conditions of low N and high sucrose remain elusive. In a previous study, we demonstrated the positive impact of a cytoplasm-localized class II TPS protein 'BnaC02.TPS8' on photosynthesis and seed yield improvement in Brassica napus. The present research delves into the biological role of BnaC02.TPS8 in response to low N and high sucrose. Ectopic overexpression of BnaC02.TPS8 in Arabidopsis seedlings resulted in elevated shoot T6P levels under N-sufficient conditions, as well as an increased carbon-to-nitrogen (C/N) ratio, sucrose accumulation, and starch storage under low N conditions. Overexpression of BnaC02.TPS8 in Arabidopsis heightened sensitivity to low N stress and high sucrose levels, accompanied by increased anthocyanin accumulation and upregulation of genes involved in flavonoid biosynthesis and regulation. Metabolic profiling revealed increased levels of intermediate products of carbon metabolism, as well as anthocyanin and flavonoid derivatives in BnaC02.TPS8-overexpressing Arabidopsis plants under low N conditions. Furthermore, yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) analyses demonstrated that BnaC02.TPS8 interacts with both BnaC08.TPS9 and BnaA01.TPS10. These findings contribute to our understanding of how TPS8-mediated anthocyanin accumulation is modulated under low N and high sucrose conditions.

A Mechanistic Action of Salicylic acid on Metabolic Profiling, Antioxidative Potential, and Growth Pattern of Amaranthus hybridus

This study has been conducted to investigate the effects of salicylic acid application on the growth and biomass of Amaranthus hybridus. The crop was grown in pots during July-August 2023, under natural weather conditions in the botanical garden of Banaras Hindu University, Varanasi. Different doses of SA (0.69 ppm – 13.8 ppm) was sprayed on the shoot of the plants. Compared to the control group, SA application at 0.69 ppm, 1.38 ppm, and 2.76 ppm showed increased growth and yield of the plants. SA applied at 1.38 ppm concentration, particularly, gave maximum increments in the length and biomass of the crop. SA application reduced the formation of oxidative stress markers (H2O2, SOR, MDA) by increasing the activities of antioxidants like SOD, POD, APX, total phenol, and proline. Salicylic acid treatment also increased the nutritive value of the crop by increasing the level of Ca, Mg, Fe, Zn, and protein, while reduced the levels of oxalic acid. The photosynthetic efficiency of the PSII was strengthened better with 1.38 ppm SA application by increasing chlorophyll content, allocation of absorbed light energy to drive the photochemical process, and quenching of the heat energy. The metabolic profiling via UHPLC-Q-TOF-MS/MS revealed increase in the number and proportion of secondary metabolites belonging to phenolic, alkaloids, terpenoid, flavonoids, betalains, and coumarins group by 240%, 127%, 37%, 182%, 83%, and 90% respectively.  Hence, 1.38 ppm of SA has been considered as the suitable dose for spraying on Amaranthus hybridus for increased growth and biomass.

Integration of omics technologies for the identification of predictive biomarkers in type 2 diabetes: a comprehensive analysis of recent literature

Background. Omics technologies, such as genomics, proteomics, metabolomics, and Transcriptomics are being used for identifying biomarkers. These biomarkers are unraveling the molecular mechanisms underlying type 2 diabetes mellitus (T2DM), which can help to promote more personalized treatment strategies and advance our understanding of disease pathogenesis. Omics approaches enable the examination of genetic, protein, metabolic, and gene expression profiles more comprehensively while offering insights into T2DM risk, progression, and potential therapeutic targets. Methods: This review follows a systematic methodology, aimed at evaluating omics technology’s role in diabetes research. Utilizing literature searches, we got an initial pool of 257 studies with a rigorous selection process and narrowed the selection to 10 high-quality studies. Our methodology approach ensured the inclusion of relevant, peer-reviewed articles that contribute significantly to understanding the application of omics technologies in predicting biomarkers for type 2 diabetes. Results: The systematic review identifies ten high-quality studies illuminating substantial omics technology’s role in advancing our understanding of type 2 diabetes (T2D). Collectively, these studies demonstrate how genomics, proteomics, metagenomics, metabolomics, and Transcriptomics have uncovered novel biomarkers and molecular pathways for T2D. Our findings underscore all the omics potentials specifically for developing predictive biomarkers, enhancing diagnostics, and tailoring personalized treatment strategies. Genetic variations, metabolic alterations, and protein and RNA expression profiles were highlighted as key areas where omics technologies offer insights into the pathophysiology and management of T2D.

Deciphering Bisphenol A degradation by Coelastrella sp. M60: Unravelling metabolic insights through metabolomics analysis

Microalgae, owing to their efficacy and eco-friendliness have emerged as a promising solution for mitigating Bisphenol A (BPA), a hazardous environmental pollutant. This study mainly investigated the BPA degradation by Coelastrella sp. M60 at various concentrations (10 to 50 mg/L) using GC–MS analysis. Further, the metabolic profiling of Coelastrella sp. M60 was performed via the MetaboAnalyst and results revealed that BPA exposure modulated the metabolites profile with the presence of intermediates like 4-hydroxybenzoic acid and benzene. Moreover, the highest lipid (54 %) and pigment content (40 %) at 10 mg/L of BPA exposure. Fatty acid methyl esters were quantified in Coelastrellasp. M60, with enhanced recovery facilitated by Cuprous oxide nanoparticle (Cu2O NPs) synthesized from Spatoglossum asperum. Thus, this study persuades a potential of Coelastrella sp. M60 for effective BPA degradation, suggesting avenues to enhance the degradation efficiency of emerging contaminants in polluted water bodies via targeted metabolite expression modulation in microalgae

Effects of triglyceride and ethyl ester forms of EPA on hepatic lipid metabolism in mice with non-alcoholic fatty liver disease

In this study, the beneficial effects of EPA in ethyl esters (EE) and triacylglycerides (TAG) forms on high fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) were studied and compared. Results indicated that both EPA-TAG and EPA-EE can alleviate pathological features of NAFLD, such as hepatic lipid accumulation and lobular inflammation, with a more pronounced protective effects observed in EPA-TAG treated mice. The integrated hepatic transcriptomic, metabolic and gut microbiota profiles suggest that EPA-TAG and EPA-EE improved hepatic steatosis by suppression of food intake and lipogenesis, promotion of lipid and phospholipid PUFA remodeling, ketogenesis and fatty acids oxidation, possibly via activating the AMPK/adipocytokine signaling pathway. The protective effect of EPA was also associated with the regulation of intestinal flora structure. In general, EPA-TAG was found to be more effective than EPA-EE in preventing HFD-induced NAFLD by reducing appetite, improving hepatic lipid metabolism, increasing energy expenditure, and enhancing gut-liver cross-talk.

Integrated proteogenomic and metabolomic characterization of papillary thyroid cancer with different recurrence risks

Although papillary thyroid cancer (PTC) has a good prognosis, its recurrence rate is high and remains a core concern in the clinic. Molecular factors contributing to different recurrence risks (RRs) remain poorly defined. Here, we perform an integrative proteogenomic and metabolomic characterization of 102 Chinese PTC patients with different RRs. Genomic profiling reveals that mutations in MUC16 and TERT promoter as well as multiple gene fusions like NCOA4-RET are enriched by the high RR. Integrative multi-omics analyses further describe the multi-dimensional characteristics of PTC, especially in metabolism pathways, and delineate dominated molecular patterns of different RRs. Moreover, the PTC patients are clustered into four subtypes (CS1: low RR and BRAF-like; CS2: high RR and metabolism type, worst prognosis; CS3: high RR and immune type, better prognosis; CS4: high RR and BRAF-like) based on the omics data. Notably, the subtypes display significant differences considering BRAF and TERT promoter mutations, metabolism and immune pathway profiles, epithelial cell compositions, and various clinical factors (especially RRs and prognosis) as well as druggable targets. This study can provide insights into the complex molecular characteristics of PTC recurrences and help promote early diagnosis and precision treatment of recurrent PTC.

Metabolic profiling of Verbena bonariensis L. extract by LC/MS and evaluation of the hepatoprotective potential with isoniazid- and rifampicin-induced hepatotoxicity in rats.

The study explored the hepatoprotective activity and metabolic profile of Verbena bonariensis L. methanol extract (VBM) and fractions using isoniazid as well as rifampicin-triggered liver toxicity in Wistar albino rats. Metabolite profiling of VBM using HPLC-PDA-ESI-MS identified 12 compounds, mainly iridoids, phenylpropanoids, and flavonoids, where verbascoside represents the major compound. Different biochemical parameters such as aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP), bilirubin, and total protein levels were used to assess liver functions. All the evaluated samples exhibited hepatoprotective potential, but VBM exhibited maximum activity and a notable decline in ALP (p < 0.05, significant), even better than the standard drug (silymarin). VBM significantly reduced the elevated ALT, AST, ALP, and total bilirubin. It also triggered a significant elevation in total proteins compared with diseased animals. This was further consolidated by histopathological studies. Verbena bonariensis L. could serve as a potent hepatoprotective agent and may alleviate liver ailments.

LC/MS-Based Metabolomics Reveals Chemical Variations of Two Broccoli Varieties in Relation to Their Anticholinesterase Activity: In vitro and In silico Studies.

Broccoli is commonly consumed as food and as medicine. However, comprehensive metabolic profiling of two broccoli varieties, Romanesco broccoli (RB) and purple broccoli (PB), in relation to their anticholinergic activity has not been fully disclosed. A total of 110 compounds were tentatively identified using UPLC-Q-TOF-MS metabolomics. Distinctively different metabolomic profiles of the two varieties were revealed by principal component analysis (PCA). Furthermore, by volcano diagram analysis, it was found that PB had a significantly higher content of phenolic acids, flavonoids, and glucosinolates, indicating the different beneficial health potentials of PB that demonstrated higher antioxidant and anticholinergic activities. Moreover, Pearson's correlation analysis revealed 18 metabolites, mainly phenolic and sulfur compounds, as the main bioactive. The binding affinity of these biomarkers to the active sites of acetyl- and butyryl-cholinesterase enzymes was further validated using molecular docking studies. Results emphasize the broccoli significance as a functional food and nutraceutical source and highlight its beneficial effects against Alzheimer's disease.

Impact of detraining on the health of individuals with spinal cord injury: a systematic review

Introduction: Spinal cord injury (SCI) is a debilitating condition that causes motor, physiological, and sensory impairments, potentially leading to permanent disability, increased morbidity, and mortality, ultimately impacting an individual's quality of life (QoL). Physical exercise emerges as an effective alternative to mitigate these consequences and uphold the autonomy and QoL for this population. Detraining (DT), defined as the partial or total loss of adaptations induced by physical training in response to its complete interruption or insufficient stimulus, represents a significant concern. The objective of this systematic review was to conduct a comprehensive literature review regarding the current state of knowledge on the potential impacts of DT on the health of individuals with SCI. Method: The search was conducted on PubMed, Web of Science, Embase, SPORTDiscus, and Cochrane databases using relevant English terms (("Detraining") AND ("Spinal Cord Injury")) and their synonyms. Due to the limited number of studies addressing this topic, no specific time frame was set for study eligibility. Results: The literature search was performed in November 2023, yielding 42 results, from which 15 remained after removing duplicates. Two articles were excluded following title analysis. Thirteen abstracts were reviewed, and 7 were excluded, leaving 6 articles for full analysis. Due to the nature of the studies, a meta-analysis was not conducted. Conclusion: DT resulted in alterations in body composition (BC), including increased body fat and reduced muscle mass, especially following the interruption of testosterone-associated training. Additionally, the cessation of training impacted the metabolic profile, leading to changes in glucose, lipids, and insulin sensitivity. Furthermore, hemodynamic variables, such as blood pressure (BP) and heart rate (HR), underwent changes, elevating the risk of cardiovascular complications. Regarding cardiorespiratory components, there was a decline in peak oxygen consumption (VO2peak) following the DT period. Halting exercise can lead to detrimental health consequences, underscoring the imperative of maintaining consistent physical training for these individuals.

Dysregulations of amino acid metabolism and lipid metabolism in urine of children and adolescents with major depressive disorder: a case-control study.

The mechanisms underlying major depressive disorder (MDD) in children and adolescents are unclear. Metabolomics has been utilized to capture metabolic signatures of various psychiatric disorders; however, urinary metabolic profile of MDD in children and adolescents has not been studied. We analyzed urinary metabolites in children and adolescents with MDD to identify potential biomarkers and metabolic signatures. Here, liquid chromatography-mass spectrometry was used to profile metabolites in urine samples from 192 subjects, comprising 80 individuals with antidepressant-naïve MDD (AN-MDD), 37 with antidepressant-treated MDD (AT-MDD) and 75 healthy controls (HC). We performed orthogonal partial least squares discriminant analysis to identify differential metabolites and employed logistic regression and receiver operating characteristic analysis to establish a diagnostic panel. In total, 143 and 71 differential metabolites were identified in AN-MDD and AT-MDD, respectively. These were primarily linked to lipid metabolism, molecular transport, and small molecule biochemistry. AN-MDD additionally exhibited dysregulated amino acid metabolism. Compared to HC, a diagnostic panel of seven metabolites displayed area under the receiver operating characteristic curves of 0.792 for AN-MDD, 0.828 for AT-MDD, and 0.799 for all MDD. Furthermore, the urinary metabolic profiles of children and adolescents with MDD significantly differed from those of adult MDD. Our research suggests dysregulated amino acid metabolism and lipid metabolism in the urine of children and adolescents with MDD, similar to results in plasma metabolomics studies. This contributes to the comprehension of mechanisms underlying children and adolescents with MDD.

Metabolomics assisted by transcriptomics analysis to reveal metabolic characteristics and potential biomarkers associated with treatment response of neoadjuvant therapy with TCbHP regimen in HER2 + breast cancer

BackgroundThis study aimed to explore potential indicators associated with the neoadjuvant efficacy of TCbHP regimen (taxane, carboplatin, trastuzumab, and pertuzumab) in HER2 + breast cancer (BrCa) patients.MethodsA total of 120 plasma samples from 40 patients with HER2 + BrCa were prospectively collected at three treatment times of neoadjuvant therapy (NAT) with TCbHP regimen. Serum metabolites were analyzed based on LC-MS and GC-MS data. Random forest was used to establish predictive models based on pre-therapeutic differentially expressed metabolites. Time series analysis was used to obtain potential monitors for treatment response. Transcriptome analysis was performed in nine available pre‑therapeutic specimens of core needle biopsies. Integrated analyses of metabolomics and transcriptomics were also performed in these nine patients. qRT-PCR was used to detect altered genes in trastuzumab-sensitive and trastuzumab-resistant cell lines.ResultsTwenty-one patients achieved pCR, and 19 patients achieved non-pCR. There were significant differences in plasma metabolic profiles before and during treatment. A total of 100 differential metabolites were identified between pCR patients and non-pCR patients at baseline; these metabolites were markedly enriched in 40 metabolic pathways. The area under the curve (AUC) values for discriminating the pCR and non-PCR groups from the NAT of the single potential metabolite [sophorose, N-(2-acetamido) iminodiacetic acid, taurine and 6-hydroxy-2-aminohexanoic acid] or combined panel of these metabolites were greater than 0.910. Eighteen metabolites exhibited potential for monitoring efficacy. Several validated genes might be associated with trastuzumab resistance. Thirty-nine altered pathways were found to be abnormally expressed at both the transcriptional and metabolic levels.ConclusionSerum-metabolomics could be used as a powerful tool for exploring informative biomarkers for predicting or monitoring treatment efficacy. Metabolomics integrated with transcriptomics analysis could assist in obtaining new insights into biochemical pathophysiology and might facilitate the development of new treatment targets for insensitive patients.

Systemic arterial hypertension and metabolic profile: a systematic review

Introduction: Systemic arterial hypertension (SAH) is a significant cause of morbidity and mortality worldwide. Despite the difficulty in diagnosing SAH in the early stages, the rapid detection and management of SAH are essential in preventing the development of target organ injuries. Newer technologies such as metabolomics have been revealed as promising alternatives for SAH diagnoses. Objectives: The purpose of this study is to evaluate, through a systematic review, the metabolomic profile of individuals with and without SAH. Methods: This review followed the PRISMA guidelines on reporting items. It analyses articles selected from the EMBASE and MEDLINE databases that compares metabolites in a hypertensive group with a non-hypertensive group. Results: The differences that reached statistical significance were a higher prevalence of lipids and lactic acid in the hypertensive group, as well as a reduction in methionine. Conclusion: Future research should be conducted to establish a possible clinical implication to this metabolite alteration, by linking it to a potential target organ injury for SAH, such as atherosclerosis, renal failure, retinopathy our ventricular hypertrophy.

Microbiome and lipidomic analysis reveal the interplay between skin bacteria and lipids in a cohort study

Human skin acts as a protective barrier between the body and the external environment. Skin microbiome and intercellular lipids in the stratum corneum (SC) are essential for maintaining skin barrier function. However, the interplay between skin bacteria and the lipids is not fully understood. In this study, we characterized the skin microbiome and SC lipid profiles from the forearm and face in a cohort of 57 healthy participants. 16S rRNA gene sequencing showed the skin microbial composition is significantly different between body locations and genders. Female forearm samples have the highest microbial diversity. The relative abundance of Staphylococcus hominis, Micrococcus luteus, Corynebacterium tuberculostearicum, Finegoldia magna, and Moraxellaceae sp. are significantly higher in the forearm than the face. The predictive functional analysis of 16S rRNA gene sequencing by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2) and ANCOM-BC showed different bacterial metabolic pathway profiles between body locations or genders, and identified 271 differential pathways, including arginine and polyamine biosynthesis, chorismate biosynthesis pathways, which are more abundant in the female forearm, and sulfur oxidation pathway, which is more abundant in the male face. The SC lipid profiles differ between the body locations as well. Total free fatty acids (FFA), cholesterol sulfate and sphingosine are more abundant in the face. Dihydro-/6-hydroxy/phyto-ceramides are more abundant in the forearm. The correlation analysis of 16S rRNA gene sequencing and lipids revealed novel interplay between the bacteria and skin lipids. Shannon entropy and S. hominis negatively correlated with FFA, cholesterol sulfate and sphingosine; while positively correlated with dihydro-/6-hydroxy/phyto-ceramides. The correlation of predictive pathway profiles and lipids identified pathways involved in amino acids metabolism, carbohydrates degradation, aromatic compounds metabolism and fatty acid degradation metabolism are positively correlated with dihydro-/6-hydroxy/phyto-ceramides and negatively correlated with FFA, cholesterol sulfate and sphingosine. This study provides insights on the potential correlation between skin microbiome and lipids.

Metabolomic profiling of embryo culture media in patients with repeated implantation failure during assisted reproductive technology cycles.

This study investigated the metabolic status of the spent culture media from embryos of patients with repeated implantation failure (RIF) undergoing in vitro fertilization-intracytoplasmic sperm injection cycles in comparison with the embryos from healthy fertile women. Metabolite levels in spent culture media were assessed and compared between embryos from RIF patients (n=35) and oocyte donors as controls (n=15). Protein levels of insulin-like growth factor 1 (IGF-1) were determined using Western blotting. Concentrations of glucose, pyruvate, and lactate were measured using spectrophotometry. Ionic colorimetric assay kits were utilized to analyze the concentrations of sodium, chloride, calcium, and magnesium ions. High-performance liquid chromatography was employed to measure the concentrations of glutamic acid, aspartic acid, methionine, phenylalanine, and histidine. Glucose consumption and lactate secretion were higher in the control group than in the RIF group. The magnesium concentration was significantly higher in the control group than in the RIF group, but glutamic acid and aspartic acid concentrations were lower in the control group than in the RIF patients (p<0.05). The levels of IGF-1, sodium, calcium, chloride, methionine, histidine, and phenylalanine did not show statistically significant differences between the two groups. The metabolic profile of the culture medium of the embryos in the RIF group differed from that of the control group. These findings suggest potential factors that may affect implantation capacity in RIF patients and provide a new perspective on embryo selection.