PubMed

Ther Drug Monit. 2023 Jan 10. doi: 10.1097/FTD.0000000000001063. Online ahead of print.ABSTRACTBACKGROUND: The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, palbociclib, ribociclib, and abemaciclib, are standard-of-care agents for patients with hormone receptor-positive human epidermal growth factor receptor 2-negative metastatic breast cancer. In support of therapeutic drug monitoring and clinical pharmacokinetic studies, a liquid chromatography coupled with tandem mass spectrometry assay for the simultaneous quantitation of CDK4/6 inhibitors and the major active metabolite M2 of abemaciclib in human plasma has been developed.METHODS: Analytes were extracted from 50 μL of human plasma by precipitating proteins with methanol and then collecting the supernatant. Reversed-phase high-performance liquid chromatography was performed for analyte separation using a biphasic gradient at a flow rate of 0.25-0.5 mL/min. The total run time was 9.5 minutes. The analytes were detected using MS/MS with electrospray ionization operating in positive ion mode.RESULTS: Validation according to the US Food and Drug Administration's guidance showed that the new assay produced accurate (94.7%-107%) and precise (within-run: 1.2%-8.2%; between-run: 0.6%-7.5%) measurements of all analytes over a concentration range of 5-2000 ng/mL. Overall, analyte recoveries were consistent (mean values: 110%-129%). The analytes were also stable in human plasma and the final extract under various storage conditions. Finally, the clinical applicability of the assay was confirmed by quantitation of all analytes in plasma samples obtained from patients treated with CDK4/6 inhibitors. Reproducibility of the measured analyte concentrations in study samples was confirmed successfully by incurred sample reanalysis.CONCLUSIONS: A sensitive liquid chromatography coupled with tandem mass spectrometry method to measure CDK4/6 inhibitors was developed and validated according to the Food and Drug Administration criteria. Quantitation of all analytes in clinical plasma samples confirmed that the assay is suitable for therapeutic drug monitoring and clinical pharmacokinetic studies of CDK4/6 inhibitors.PMID:36728357 | DOI:10.1097/FTD.0000000000001063

J Cell Physiol. 2023 Feb 2. doi: 10.1002/jcp.30953. Online ahead of print.ABSTRACTA common adverse response to the clinical use of glucocorticoids (GCs) is elevated intraocular pressure (IOP) which is a major risk factor for glaucoma. Elevated IOP arises due to impaired outflow of aqueous humor (AH) through the trabecular meshwork (TM). Although GC-induced changes in actin cytoskeletal dynamics, contractile characteristics, and cell adhesive interactions of TM cells are believed to influence AH outflow and IOP, the molecular mechanisms mediating changes in these cellular characteristics are poorly understood. Our studies focused on evaluating changes in the cytoskeletal and cytoskeletal-associated protein (cytoskeletome) profile of human TM cells treated with dexamethasone (Dex) using label-free mass spectrometric quantification, identified elevated levels of specific proteins known to regulate actin stress fiber formation, contraction, actin networks crosslinking, cell adhesion, and Wnt signaling, including LIMCH1, ArgBP2, CNN3, ITGBL1, CTGF, palladin, FAT1, DIAPH2, EPHA4, SIPA1L1, and GPC4. Several of these proteins colocalized with the actin cytoskeleton and underwent alterations in distribution profile in TM cells treated with Dex, and an inhibitor of Abl/Src kinases. Wnt/Planar Cell Polarity (PCP) signaling agonists-Wnt5a and 5b were detected prominently in the cytoskeletome fraction of TM cells, and studies using siRNA to suppress expression of glypican-4 (GPC4), a known modulator of the Wnt/PCP pathway revealed that GPC4 deficiency impairs Dex induced actin stress fiber formation, and activation of c-Jun N-terminal Kinase (JNK) and Rho kinase. Additionally, while Dex augmented, GPC4 deficiency suppressed the formation of actin stress fibers in TM cells in the presence of Dex and Wnt5a. Taken together, these results identify the GPC4-dependent Wnt/PCP signaling pathway as one of the crucial upstream regulators of Dex induced actin cytoskeletal reorganization and cell adhesion in TM cells, opening an opportunity to target the GPC4/Wnt/PCP pathway for treatment of ocular hypertension in glaucoma.PMID:36727620 | DOI:10.1002/jcp.30953

Arterioscler Thromb Vasc Biol. 2023 Feb 2. doi: 10.1161/ATVBAHA.122.318871. Online ahead of print.ABSTRACTBACKGROUND: Acute myocardial infarction (AMI) is a leading cause of death and disability. Diabetes is an important risk factor and a common comorbidity in AMI patients. The higher mortality risk of diabetes-AMI relative to nondiabetes-AMI indicates a need for specific treatment to improve clinical outcome. However, the global metabolic dysregulation of AMI complicated with diabetes is still unclear. We aim to systematically interrogate changes in the metabolic microenvironment immediate to AMI episodes in the absence or presence of diabetes.METHODS: In this work, quantitative metabolomics was used to investigate plasma metabolic differences between diabetes-AMI (n=59) and nondiabetes-AMI (n=59) patients. A diverse array of perturbed metabolic pathways involving carbohydrate metabolism, lipid metabolism, glycolysis, tricarboxylic acid cycle, and amino acid metabolism emerged.RESULTS: In all, our omics-oriented approach defined a metabolic signature of afflicted mitochondrial function aggravated by concurrent diabetes in AMI patients. In particular, our analyses uncovered N-lactoyl-phenylalanine and lysophosphatidylcholines as key functional metabolites that skewed the metabolic picture of diabetes-AMI relative to nondiabetes-AMI. N-lactoyl-phenylalanine was strongly associated with metabolic indicators reflective of mitochondrial overload and negatively correlated with HbA1c specifically in hyperglycemic AMI, suggestive of its central role in glucose utilization and mitochondrial energy production instrumental to the clinical outcome of diabetes-AMI. Reductions in lysophosphatidylcholines, which were negatively correlated with blood glucose and inflammatory markers, might further compromise glucose expenditure and aggravate inflammation leading to poorer prognosis in diabetes-AMI.CONCLUSIONS: As circulating metabolite levels are amenable to therapeutic intervention, such shifts in metabolic signatures provide new clues and potential therapeutic targets specific to the treatment of diabetes-AMI.PMID:36727520 | DOI:10.1161/ATVBAHA.122.318871

Arterioscler Thromb Vasc Biol. 2023 Feb 2. doi: 10.1161/ATVBAHA.122.318334. Online ahead of print.ABSTRACTDespite devastating clinical sequelae of calcific aortic valve disease that range from left ventricular remodeling to arrhythmias, heart failure, and early death, the molecular insights into disease initiation and progression are limited and pharmacotherapies remain unavailable. The pathobiology of calcific aortic valve disease is complex and comprehensive studies are challenging valvular calcification is heterogeneous and occurs preferentially on the aortic surface, along a fibrocalcific spectrum. Here, we review efforts to study (epi-)genomic, transcriptomic, proteomic, and metabolomic aspects of aortic valve calcification in combination with network medicine-/systems biology-based strategies to integrate multilayered omics datasets and prioritize druggable targets for experimental validation studies. Ultimately, such holistic approach efforts may open therapeutic avenues that go beyond invasive and costly valve replacement therapy.PMID:36727519 | DOI:10.1161/ATVBAHA.122.318334

J Appl Toxicol. 2023 Feb 1. doi: 10.1002/jat.4440. Online ahead of print.ABSTRACTIn recent years, chromium (Cr) has been found to induce neurotoxicity. However, the underlying mechanism remains unclear. This study aimed to investigate the effects of chromium exposure on the metabolome and microbiome that may contribute to neurotoxicity in juvenile zebrafish. Zebrafish embryos were exposed to 1mg/L Cr (III) and 1mg/L Cr (VI) for seven days, respectively. Swimming distance and locomotor behavior was decreased, and acetylcholinesterase activity was reduced in Cr-exposed groups. Total cholesterol levels were decreased in Cr-exposed groups. The differential-expressed metabolites due to Cr exposure were mainly enriched in primary bile acid biosynthesis, which indicated that Cr exposure may promote cholesterol conversion. The abundance of Bacteroidetes decreased and the abundance of Actinomycetes increased in Cr- exposed groups, as compared to that in the control group. At the genus level, the abundance of Acinetobacter, Acidophorax, Mycobacterium, Aeromonas, Hydrophagophaga and Brevundimonas increased, whereas Chryseobacterium, Pseudomonas, Delftia and Ancylobacter decreased in the Cr-exposed groups. Analysis of the correlation between gut microbiota and bile acid metabolites showed that changes of gut microbial community due to Cr exposure may be related to secondary bile acid metabolism. Collectively, chromium exposure may disturb cholesterol metabolism, including primary bile acid and microbiota-related secondary bile acid metabolism. This study provides potential mechanism of the effects of chromium on neurotoxicity based on modulation of metabolome and gut microbiota diversity, which needs further verification.PMID:36727205 | DOI:10.1002/jat.4440

Front Nutr. 2023 Jan 16;9:1065188. doi: 10.3389/fnut.2022.1065188. eCollection 2022.ABSTRACTINTRODUCTION: Metabolic flexibility (MetF) is the capacity of an organism to oxidate substrate according to substrate availability or demand. The mismatch of substrate availability and oxidation may cause ectopic fat accumulation in the muscle and the liver. The objectives of the study are to examine the effect of 12 weeks of combined exercise on hepatic fat reduction and investigate metabolites related to MetF before and after the high-fat diet between individuals with NAFLD and healthy control with an active lifestyle.METHODS: This study is an open-label, single-center trial randomized controlled clinical study plus a cross-sectional comparison between individuals with NAFLD and healthy control. Individuals with NAFLD were allocated into two groups receiving resistance training (RT) combined with high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT). Anthropometric indicators, clinical blood markers about glucose, lipid metabolism, and hepatic fat content (HFC) were assessed before and after the intervention. The metabolomics was also used to investigate the discrepant metabolites and mechanisms related to MetF.DISCUSSION: Metabolic flexibility reflects the capacity of an organism to switch the oxidation substrates flexibly, which is associated with ectopic fat accumulation. Our study aimed to explore the discrepant metabolites related to MetF before and after a high-fat diet between individuals with NAFLD and healthy control. In addition, the study also examined the effectiveness of RT combined with HIIT or MICT on hepatic fat reduction and quantificationally analyzed the metabolites related to MetF before and after the intervention. Our results provided a perspective on fatty liver-associated metabolic inactivity.TRIAL REGISTRATION: ClinicalTrials.gov: ChiCTR2200055110; Registered 31 December 2021, http://www.chictr.org.cn/index.aspx.PMID:36726820 | PMC:PMC9884837 | DOI:10.3389/fnut.2022.1065188

Front Nutr. 2023 Jan 16;9:1092846. doi: 10.3389/fnut.2022.1092846. eCollection 2022.ABSTRACTINTRODUCTION: Esports is a category of competitive video games that, in many aspects, may be similar to traditional sports; however, the gut microbiota composition of players has not been yet studied.MATERIALS AND METHODS: Here, we investigated the composition and function of the gut microbiota, as well as short chain fatty acids (SCFAs), and amino acids, in a group of 109 well-characterized Polish male esports players. The results were compared with two reference groups: 25 endurance athletes and 36 healthy students of physical education. DNA and metabolites isolated from fecal samples were analyzed using shotgun metagenomic sequencing and mass spectrometry, respectively. Physical activity and nutritional measures were evaluated by questionnaire.RESULTS: Although anthropometric, physical activity and nutritional measures differentiated esports players from students, there were no differences in bacterial diversity, the Bacteroidetes/Firmicutes ratio, the composition of enterotype clusters, metagenome functional content, or SCFA concentrations. However, there were significant differences between esports players and students with respect to nine bacterial species and nine amino acids. By contrast, all of the above-mentioned measures differentiated professional athletes from esports players and students, with 45 bacteria differentiating professional athletes from the former and 31 from the latter. The only species differentiating all three experimental groups was Parabacteroides distasonis, showing the lowest and highest abundance in esports players and athletes, respectively.CONCLUSION: Our study confirms the marked impact of intense exercise training on gut microbial structure and function. Differences in lifestyle and dietary habits between esports players and physical education students appear to not have a major effect on the gut microbiota.PMID:36726816 | PMC:PMC9884692 | DOI:10.3389/fnut.2022.1092846

Front Nutr. 2023 Jan 16;9:1070223. doi: 10.3389/fnut.2022.1070223. eCollection 2022.ABSTRACTINTRODUCTION: Recent evidence supports a role for the gut microbe-metabolites in longevity. However, the phenomenon of hypertension is more common in the longevity area and whether hypertension is associated with longevity remains unclear. Here, we hypothesize that the levels of gut microbiota, SCFAs, and urine metabolites were different between hypertension elderly and hypertension longevity.METHODS: We recruited 46 elderly volunteers from Donglan County, Guangxi, and 32 were selected and included in the experiment. The subjects with hypertension were divided into two groups according to age, Hypertension Elderly (HTE, aged 70.5 ± 8.59, n = 19) and Hypertension Longevity (HTL, aged 100 ± 5.72, n = 13). The gut microbiota, SCFAs, and urine metabolites were determined by three-generation 16S rRNA full-length sequencing, GC-MS, and 1H-NMR, respectively.RESULTS: Compared with the HTL group, the HTE group had higher levels of hypertension-related genera Klebsiella and Streptococcus, while having lower levels of the SCFA-producing genera Bacteroides, Faecalibacterium, and Alistipes. Based on LEFse analysis, Klebsiella pneumoniae, Lactobacillus gasseri, Streptococcus salivarius, Ruminococcus, Actinomyces, Rikenellaceae, f_Saccharimonadaceae, Clostridium perfringens, and Bacteroids, Faecalibacterium prausnitzii, Parabacteroides, Alistipes were biomarkers that showed significant differences between the groups. In addition, the microbial pathways associated with K. pneumoniae and E. coli may promote hypertension, while A. muciniphila may play a role in reversing the development of hypertension in long-lived elderly. Metabolomics revealed that HTL contained a lower concentration of fecal acetate and propionate than HTE, while it contained a higher concentration of serum acetate and urine acetate. Furthermore, their immune cells exhibited no significant changes in SCFAs receptors.CONCLUSION: Although long-lived elderly have extremely high systolic blood pressure, their unique gut microbiota composition and efficient acetate absorption in the colon may offset the damages caused by hypertension and maintain healthy homeostasis.PMID:36726815 | PMC:PMC9884688 | DOI:10.3389/fnut.2022.1070223

Front Nutr. 2023 Jan 16;10:1114880. doi: 10.3389/fnut.2023.1114880. eCollection 2023.ABSTRACTINTRODUCTION: Huangjiu is an important Chinese alcoholic beverage, usually prepared from rice. Although its unique flavor improves with prolonged storage in traditional pottery jars, knowledge of the aging mechanism, necessary for commercialization of an optimum product, remains unclear.METHODS: Here, volatile aroma compounds from forced aged samples exposed to different temperatures and oxygen treatments were measured by GC/MS. After retention time alignment and normalization, the peak vectors were compared over storage time using Pearson's correlation, and a correlation network was established. Marker compounds, representative of traditionally aged Huangjiu, were then monitored and compared to similar compounds in the forced aged product.RESULTS AND DISCUSSION: Correlation network analysis revealed the following: Temperature had little effect on most aroma compounds; alcohols, acids, and esters all increased with increasing dissolved oxygen, while polyphenols, lactones, and ketones were readily oxidized; aldehydes (e.g., furfural and benzaldehyde) were highly dependent on both temperature and dissolved oxygen. Dynamic changes in the targeted aging-markers showed that a higher initial oxygen concentration intensified the "aging-aroma" of Huangjiu in the early and middle stages of storage. Consequently, careful control of oxygen supplementation and storage temperature could be beneficial in controlling the desirable flavor of Huangjiu in the artificially aged product.PMID:36726696 | PMC:PMC9884831 | DOI:10.3389/fnut.2023.1114880

Front Plant Sci. 2023 Jan 16;13:1125003. doi: 10.3389/fpls.2022.1125003. eCollection 2022.ABSTRACTBarley is a major cereal crop for temperate climates, and a diploid genetic model for polyploid wheat. Cereal straw biomass is an attractive source of feedstock for green technologies but lignin, a key determinant of feedstock recalcitrance, complicates bio-conversion processes. However, manipulating lignin content to improve the conversion process could negatively affect agronomic traits. An alternative approach is to manipulate lignin composition which influences the physical and chemical properties of straw. This study validates the function of a barley ferulate 5-hydroxylase gene and demonstrates that its downregulation using the RNA-interference approach substantially impacts lignin composition. We identified five barley genes having putative ferulate 5-hydroxylase activity. Downregulation of HvF5H1 substantially reduced the lignin syringyl/guaiacyl (S/G) ratio in straw while the lignin content, straw mechanical properties, plant growth habit, and grain characteristics all remained unaffected. Metabolic profiling revealed significant changes in the abundance of 173 features in the HvF5H1-RNAi lines. The drastic changes in the lignin polymer of transgenic lines highlight the plasticity of barley lignification processes and the associated potential for manipulating and improving lignocellulosic biomass as a feedstock for green technologies. On the other hand, our results highlight some differences between the lignin biosynthetic pathway in barley, a temperate climate grass, and the warm climate grass, rice, and underscore potential diversity in the lignin biosynthetic pathways in grasses.PMID:36726680 | PMC:PMC9886061 | DOI:10.3389/fpls.2022.1125003

Front Plant Sci. 2023 Jan 16;13:1072782. doi: 10.3389/fpls.2022.1072782. eCollection 2022.ABSTRACTClimate change and abiotic stress challenges in crops are threatening world food production. Among others, salinity affects the agricultural sector by significantly impacting yield losses. Plant biostimulants have received increasing attention in the agricultural industry due to their ability to improve health and resilience in crops. The main driving force of these products lies in their ability to modulate plant metabolic processes involved in the stress response. This study's purpose was to investigate the effect of two biostimulant products, including a protein hydrolysate (Clever HX®) and a seaweed extract with high amino acids content (Ascovip®), and their combination, on the metabolomics profile of tomato crops grown under salt stress (150 mM NaCl). Several stress indicators (leaf relative water content, membrane stability index, and photosynthesis activity) and leaf mineral composition after salinity stress exposure were assessed to evaluate stress mitigation, together with growth parameters (shoot and root biomasses). After that, an untargeted metabolomics approach was used to investigate the mechanism of action of the biostimulants and their link with the increased resilience to stress. The application of the biostimulants used reduced the detrimental effect of salinity. In saline conditions, protein hydrolysate improved shoot dry weight while seaweed extracts improved root dry weight. Regarding stress indicators, the application of the protein hydrolysate was found to alleviate the membrane damage caused by salinity stress compared to untreated plants. Surprisingly, photosynthetic activity significantly improved after treatment with seaweed extracts, suggesting a close correlation between root development, root water assimilation capacity and photosynthetic activity. Considering the metabolic reprogramming after plant biostimulants application, protein hydrolysates and their combination with seaweed extracts reported a distinctive metabolic profile modulation, mainly in secondary metabolite, lipids and fatty acids, and phytohormones biosynthetic pathways. However, treatment with seaweed extract reported a similar metabolic reprogramming trend compared to salinity stress. Our findings indicate a different mechanism of action modulated by protein hydrolysate and seaweed extract, suggesting stronger activity as a stress mitigator of protein hydrolysate in tomato crops under salinity stress.PMID:36726679 | PMC:PMC9884811 | DOI:10.3389/fpls.2022.1072782

Front Microbiol. 2023 Jan 16;13:1076499. doi: 10.3389/fmicb.2022.1076499. eCollection 2022.ABSTRACTINTRODUCTION: Italian ryegrass is less studied in northern China due to high-quality forage grass has not been fully utilized. Full utilization of high-quality forage grass helps to alleviate the shortage of forage grass in winter and spring season and guarantee stable development of livestock production. Consequently, this study was aimed to evaluate the effects of different regions in northern China on the fermentative products, bacterial community compositions, and metabolic pathways and metabolites of Italian ryegrass silage.METHODS: The Italian ryegrass was harvested from three regions (Ordos-WK; Hohhot-AK; Ulanqab-SYK) and ensiled for 60 days. Single molecule real-time (SMRT) sequencing and ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) were used to analyze bacterial communities and metabolites, respectively.RESULTS: After 60 d of fermentation, the SYK group had the lowest pH (4.67), the highest lactic acid contents (95.02 g/kg DM) and largest lactic acid bacteria populations (6.66 log10 cfu/g FM) among the treatment groups. In addition, the SYK group had the highest abundance of Lactiplantibacillus plantarum (63.98%). In SYK group, isoquinoline alkaloid biosynthesis was the significantly enriched (p < 0.05) and high-impact value (0.0225) metabolic pathway. In AK group, tryptophan metabolism the was the significantly enriched (p < 0.001) and high-impact value (0.1387) metabolic pathway. In WK group, citrate cycle (TCA cycle) was the significantly enriched (p < 0.001) and high-impact value (0.1174) metabolic pathway. Further, Lactiplantibacillus plantarum was positively correlated with cinnamic acid, tetranor 12-HETE, D-Mannitol, (2S)-2-amino-4-methylpentanoic acid L-Leucine, guanine, isoleucyl-aspartate and 3,4-Dihydroxyphenyl propanoate, but negatively correlated with isocitrate and D-mannose.DISCUSSION: In conclusion, this study can improve our understanding of the ensiling microbiology and metabolomics in different regions to further regulate the fermentation products and promote livestock production.PMID:36726558 | PMC:PMC9885166 | DOI:10.3389/fmicb.2022.1076499

Infect Drug Resist. 2023 Jan 26;16:581-594. doi: 10.2147/IDR.S394779. eCollection 2023.ABSTRACTPURPOSE: Community-acquired pneumonia (CAP) is one of the most frequently encountered infectious diseases worldwide. Few studies have explored the microbial composition of the lower respiratory tract (LRT) and host metabolites of CAP. We analyzed the microbial composition of the LRT and levels of host metabolites to explore new biomarkers for CAP.PATIENTS AND METHODS: Bronchoalveolar lavage fluid (BALF) was collected from 28 CAP patients and 20 healthy individuals. Following centrifugation, BALF pellets were used for amplicon sequencing of a variable region of the bacterial 16S rDNA gene to characterize the microbial composition. Non-targeted metabolomics was used to detect host's metabolites in the supernatant.RESULTS: Compared with healthy individuals, the bacterial alpha diversity in the LRT of CAP patients was significantly lower in CAP patients (p<0.05). On the bacterial genus level, over 20 genera were detected with lower relative abundance (p<0.05), while the relative abundance of Ruminiclostridium-6 was significantly higher in CAP patients. The levels of the host metabolites dimethyldisulfide, choline, pyrimidine, oleic acid and N-acetyl-neuraminic acid were all increased in BALF of CAP patients (p<0.05), while concentrations of lysophosphatidylcholines (LPC (12:0/0:0)) and phosphatidic acid (PA (20:4/2:0)) were decreased (p<0.05). Furthermore, the relative abundance of Parvimonas, Treponema-2, Moraxella, Aggregatibacter, Filifactor, Fusobacterium, Lautropia and Neisseria negatively correlated with concentrations of oleic acid (p<0.05). A negative correlation between the relative abundance of Treponema-2, Moraxella, Filifactor, Fusobacterium and dimethyldisulfide concentrations was also observed (p<0.05). In contrast, the relative abundance of Treponema-2, Moraxella, Filifactor, and Fusobacterium was found to be positively associated with concentrations of LPC (12:0/0:0) and PA (20:4/2:0) (p<0.05).CONCLUSION: The composition of the LRT microbiome differed between healthy individuals and CAP patients. We propose that some respiratory microbial components and host metabolites are potentially novel diagnostic markers of CAP.PMID:36726385 | PMC:PMC9885967 | DOI:10.2147/IDR.S394779

Front Microbiol. 2023 Jan 16;14:1112328. doi: 10.3389/fmicb.2023.1112328. eCollection 2023.ABSTRACTINTRODUCTION: With the purpose to evaluate the effects of dietary olive cake, a source of bioactive phenolic compounds, as feed supplementation of lactating dairy cows on fatty acid composition, volatile organic compounds, and microbiological profiles of Provola cheese, we performed a two-arm study where control and experimental administered cows derived dairy have been compared.METHODS: Our panel of analyses include metabolomics, physicochemical detected variables, culture dependent and independent analyses, and a stringent statistical approach aimful at disclosing only statistically significant results.RESULTS AND DISCUSSION: Looking at the physicochemical variable's profiles, a higher content of unsaturated fatty acids, polyunsaturated fatty acid, and conjugated linoleic acids as well of proteins were observed in experimental cheese samples, indicating the beneficial effect of dietary supplementation. Furthermore, based on volatilome composition, a clear cluster separation between control and experimental cheeses was obtained, mainly related to terpenes degradation, able of influencing their aroma and taste. Microbiological results showed a decrease of some spoilage related microbial groups in experimental cheeses, probably due to the inhibitory effect exerted by polyphenols compounds, that contrarily did not affect the core taxa of all cheese samples. This paper confirmed the promising utilization of olive by-product in farming practices to obtain more sustainable and safe dairy food products with lower environmental impact, mainly in Sicily and Mediterranean area, where waste disposal poses serious environmental and economic problems.PMID:36726372 | PMC:PMC9885796 | DOI:10.3389/fmicb.2023.1112328

Reprod Biol Endocrinol. 2023 Feb 1;21(1):16. doi: 10.1186/s12958-023-01056-y.ABSTRACTOwing to its difficulty in degrading and ease of accumulation in the body, perfluorooctanoic acid (PFOA) has a detrimental effect on reproduction. This study aimed to examine the effect of PFOA concentration in follicular fluid during ovulation stimulation on embryo quality and the impact of PFOA exposure on the metabolic components of follicular fluid. This was a single-center prospective study that included 25 patients with diminished ovarian reserve (DOR), 25 with normal ovarian reserve (NOR), and 25 with polycystic ovary syndrome (PCOS). Follicular fluid samples were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry. We demonstrated that the PFOA levels of follicular fluid in the DOR group were higher than those in the NOR group and PCOS group (P < 0.05). PFOA concentration in the PCOS group was negatively correlated with high-quality embryos (P < 0.05). To gain more insight into the impact of PFOA on the metabolic composition of follicular fluid, we classified the DOR group based on the PFOA concentration, for which metabolomic analysis was performed. In the high-concentration PFOA group, there was an increase and a decrease in three and nine metabolites, respectively, compared to that in the low-concentration group. These results suggest that PFOA may alter the metabolic composition of follicular fluid, thus, affecting ovarian reserve function.PMID:36726108 | DOI:10.1186/s12958-023-01056-y

BMC Plant Biol. 2023 Feb 1;23(1):69. doi: 10.1186/s12870-023-04079-0.ABSTRACTBACKGROUND: Green manure (GM) is a crop commonly grown during fallow periods, which has been applied in agriculture as a strategy to regulate nutrient cycling, improve organic matter, and enhance soil microbial biodiversity, but to date, few studies have examined the effects of GM treatments on rhizosphere soil bacterial community and soil metabolites from continuous cropping peanut field.RESULTS: In this study, we found that the abundances of several functionally significant bacterial groups containing Actinobacteria, Acidobacteria, and genus Sphingomonas, which are associated with nitrogen cycling, were dramatically increased in GM-applied soils. Consistent with the bacterial community results, metabolomics analysis revealed a strong perturbation of nitrogen- or carbon-related metabolisms in GM-applied soils. The substantially up-regulated beneficial metabolites including sucrose, adenine, lysophosphatidylcholine (LPC), malic acid, and betaines in GM-applied soils may contribute to overcome continuous cropping obstacle. In contrast to peanut continuous cropping, planting winter wheat and oilseed rape in winter fallow period under continuous spring peanut production systems evidently improved the soil quality, concomitantly with raised peanut pod yield by 32.93% and 25.20%, in the 2020 season, respectively.CONCLUSIONS: GMs application is an effective strategy to overcome continuous cropping obstacle under continuous peanut production systems by improving nutrient cycling, soil metabolites, and rhizobacterial properties.PMID:36726076 | DOI:10.1186/s12870-023-04079-0

Sci Rep. 2023 Feb 1;13(1):1870. doi: 10.1038/s41598-023-27958-w.ABSTRACTThe use of alternative tobacco products, particularly medwakh, has expanded among youth in the Middle East and around the world. The present study is conducted to investigate the biochemical and pathophysiological changes caused by medwakh smoking, and to examine the salivary metabolomics profile of medwakh smokers. Saliva samples were collected from 30 non-smokers and 30 medwakh smokers and subjected to metabolomic analysis by UHPLC-ESI-QTOF-MS. The CRP and Glutathione Peroxidase 1 activity levels in the study samples were quantified by ELISA and the total antioxidant capacity (TAC) by TAC assay kits. Statistical measurements and thorough validation of data obtained from untargeted metabolomics identified 37 uniquely and differentially abundant metabolites in saliva of medwakh smokers. The levels of phthalate, L-sorbose, cytosine, uridine, alpha-hydroxy hippurate, and L-nicotine were noticeably high in medwakh smokers. Likewise, 20 metabolic pathways were differentially altered in medwakh smokers. This study identified a distinctive saliva metabolomics profile in medwakh smokers associated with altered redox homeostasis, metabolic pathways, antioxidant system, and CRP levels. The impact of the altered metabolites in medwakh smokers and their diagnostic utility require further research in large cohorts.PMID:36725974 | DOI:10.1038/s41598-023-27958-w

Curr Drug Targets. 2023 Feb 1. doi: 10.2174/1389450124666230201144605. Online ahead of print.ABSTRACTBone morphogenetic proteins are a center of serious concern and are known to execute various cancer-related issues. The BMP signaling cascades have become more unpredictable as a result of their pleiotropic and risky characteristics, particularly when it comes to cancer responses. This perspective discusses the current therapeutic implications, emphasizes different cellular aspects that impact the failures of the current drug treatments, and speculates on future research avenues that include novel strategies like metabolomic studies and bio-mimetic peptide therapeutics to mitigate cancerous outcomes.PMID:36725830 | DOI:10.2174/1389450124666230201144605

Atherosclerosis. 2023 Jan 21:S0021-9150(23)00024-2. doi: 10.1016/j.atherosclerosis.2023.01.012. Online ahead of print.NO ABSTRACTPMID:36725416 | DOI:10.1016/j.atherosclerosis.2023.01.012

Gut. 2023 Feb 1:gutjnl-2022-329312. doi: 10.1136/gutjnl-2022-329312. Online ahead of print.NO ABSTRACTPMID:36725314 | DOI:10.1136/gutjnl-2022-329312