PubMed

Int J Mol Sci. 2022 Dec 23;24(1):270. doi: 10.3390/ijms24010270.ABSTRACTEffective prevention and risk prediction are important for peripheral artery disease (PAD) due to its poor prognosis and the huge disease burden it produces. Circulating amino acids (AA) and their metabolites may serve as biomarkers of PAD risk, but they have been scarcely investigated. The objective was to prospectively analyze the associations of baseline levels of plasma AA (and their pathways) with subsequent risk of PAD and the potential effect modification by a nutritional intervention with the Mediterranean diet (MedDiet). A matched case-control study was nested in the PREDIMED trial, in which participants were randomized to three arms: MedDiet with tree nut supplementation group, MedDiet with extra-virgin olive oil (EVOO) supplementation group or control group (low-fat diet). One hundred and sixty-seven PAD cases were matched with 250 controls. Plasma AA was measured with liquid chromatography/mass spectrometry at the Broad Institute. Baseline tryptophan, serine and threonine were inversely associated with PAD (ORfor 1 SD increase = 0.78 (0.61-0.99); 0.67 (0.51-0.86) and 0.75 (0.59-0.95), respectively) in a multivariable-adjusted conditional logistic regression model. The kynurenine/tryptophan ratio was directly associated with PAD (ORfor 1 SD increase = 1.50 (1.14-1.98)). The nutritional intervention with the MedDiet+nuts modified the association between threonine and PAD (p-value interaction = 0.018) compared with the control group. However, subjects allocated to the MedDiet+EVOO group were protected against PAD independently of baseline threonine. Plasma tryptophan, kynurenine/tryptophan ratio, serine and threonine might serve as early biomarkers of future PAD in subjects at a high risk of cardiovascular disease. The MedDiet supplemented with EVOO exerted a protective effect, regardless of baseline levels of threonine.PMID:36613713 | DOI:10.3390/ijms24010270

Int J Mol Sci. 2022 Dec 22;24(1):210. doi: 10.3390/ijms24010210.ABSTRACTWith the rising incidence of hepatocellular carcinoma (HCC) from non-alcoholic steatohepatitis (NASH), identifying new metabolic readouts that function in metabolic pathway perpetuation is still a demand. The study aimed to compare the metabolic signature between NASH and NASH-HCC patients to explore novel reprogrammed metabolic pathways that might modulate cancer progression in NASH patients. NASH and NASH-HCC patients were recruited and screened for metabolomics, and isotope-labeled lipidomics were targeted and profiled using the EXION-LCTM system equipped with a Triple-TOFTM 5600+ system. Results demonstrated significantly (p ≤ 0.05) higher levels of triacylglycerol, AFP, AST, and cancer antigen 19-9 in NASH-HCC than in NASH patients, while prothrombin time, platelet count, and total leukocyte count were decreased significantly (p ≤ 0.05). Serum metabolic profiling showed a panel of twenty metabolites with 10% FDR and p ≤ 0.05 in both targeted and non-targeted analysis that could segregate NASH-HCC from NASH patients. Pathway analysis revealed that the metabolites are implicated in the down-regulation of necroptosis, amino acid metabolism, and regulation of lipid metabolism by PPAR-α, biogenic amine synthesis, fatty acid metabolism, and the mTOR signaling pathway. Cholesterol metabolism, DNA repair, methylation pathway, bile acid, and salts metabolism were significantly upregulated in NASH-HCC compared to the NASH group. Metabolite-protein interactions network analysis clarified a set of well-known protein encoding genes that play crucial roles in cancer, including PEMT, IL4I1, BAAT, TAT, CDKAL1, NNMT, PNP, NOS1, and AHCYL. Taken together, reliable metabolite fingerprints are presented and illustrated in a detailed map for the most predominant reprogrammed metabolic pathways that target HCC development from NASH.PMID:36613653 | DOI:10.3390/ijms24010210

Int J Mol Sci. 2022 Dec 21;24(1):101. doi: 10.3390/ijms24010101.ABSTRACTColorectal cancer (CRC) is one of the major public health and socio-economic problems, which management demands the development of non-invasive screening tests. Assessment of circulating polyamines could be a valuable tool, although analytical problems still preclude its clinical practice. We exploited ultra-high-resolution liquid chromatography and mass spectrometry, as a highly sensitive and innovative method, to profile eleven polyamines, including spermine and spermidine with their acetylated forms. These data together with an evaluation of the inflammatory indexes might represent suitable biomarkers for the identification of CRC patients. The statistical models revealed good discrimination in distinguishing CRC patients from healthy subjects. The plasma assessment of ornithine and acetylspermine, as well as lymphocyte/platelet ratio, revealed helpful information on the progression of CRC. The combined profiles of circulating polyamines and inflammatory indexes, together with the application of an innovative technology, could represent a valuable tool for discriminating patients from different clinical groups.PMID:36613539 | DOI:10.3390/ijms24010101

Int J Mol Sci. 2022 Dec 20;24(1):10. doi: 10.3390/ijms24010010.ABSTRACTFollicular fluid is an important component of follicle growth and development. Negative effects of COVID-19 on follicular function are still open. The aim of this work was to study the features of the lipid profile of follicular fluid and evaluate the results of the in vitro fertilization (IVF) program in women after COVID-19 to identify biomarkers with prognostic potential. The study involved samples of follicular fluid collected from 237 women. Changes in the lipid composition of the follicular fluid of patients who underwent COVID-19 in mild and severe forms before entering the IVF program and women who did not have COVID-19 were studied by mass spectrometry. Several lipids were identified that significantly changed their level. On the basis of these findings, models were developed for predicting the threat of miscarriage in patients who had a severe course of COVID-19 and models for predicting the success of the IVF procedure, depending on the severity of COVID-19. Of practical interest is the possibility of using the developed predictive models in working with patients who have undergone COVID-19 before entering the IVF program. The results of the study suggest that the onset of pregnancy and its outcome after severe COVID-19 may be associated with changes in lipid metabolism in the follicular fluid.PMID:36613453 | DOI:10.3390/ijms24010010

Foods. 2022 Dec 27;12(1):143. doi: 10.3390/foods12010143.ABSTRACTIn this work, untargeted metabolomics was used to shed light on the impact of different pasture-based diets on the chemical profile of Sarda sheep milk. The study considered 11 dairy sheep farms located in Sardinia, and milk samples were collected in 4 different periods, namely January, March, May, and July 2019, when all sheep had 58, 98, 138, and 178 days in milk, respectively. The animal diet composition was based on the intake of grazed herbage in natural pasture, hay, and concentrate. Overall, the combination of two comprehensive databases on food, namely the Milk Composition Database and Phenol-Explorer, allowed the putative identification of 406 metabolites, with a significant (p < 0.01) enrichment of several metabolite classes, namely amino acids and peptides, monosaccharides, fatty acids, phenylacetic acids, benzoic acids, cinnamic acids, and flavonoids. The multivariate statistical approach based on supervised orthogonal projections to latent structures (OPLS-DA) allowed us to predict the chemical profile of sheep milk samples as a function of the high vs no fresh herbage intake, while the prediction model was not significant when considering both hay and concentrate intake. Among the discriminant markers of the herbage intake, we found five phenolic metabolites (such as hippuric and coumaric acids), together with lutein and cresol (belonging to carotenoids and their metabolites). Additionally, a high discriminant power was outlined for lipid derivatives followed by sugars, amino acids, and peptides. Finally, a pathway analysis revealed that the herbage intake affected mainly five biochemical pathways in milk, namely galactose metabolism, phenylalanine metabolism, alpha-linolenic acid metabolism, linoleic acid metabolism, and aromatic amino acids involved in protein synthesis (namely tyrosine, phenylalanine, and tryptophan).PMID:36613358 | DOI:10.3390/foods12010143

Foods. 2022 Dec 22;12(1):33. doi: 10.3390/foods12010033.ABSTRACTChronic diseases have been a leading cause of death worldwide, and polysaccharide supplementation is an effective therapeutic strategy for chronic diseases without adverse effects. In this study, the beneficial effect of Laminaria japonica fucoidan (LJF) on type 2 diabetes mellitus (T2DM) was evaluated in streptozocin-treated mice. LJF ameliorated the symptoms of T2DM in a dose-dependent manner, involving reduction in weight loss, water intake, triglyceride, blood glucose, cholesterol and free fatty acids, and increases in high-density lipoprotein cholesterol, catalase, glucagon-like peptide-1, and superoxide dismutase. In addition, LJF regulated the balance between insulin resistance and insulin sensitivity, reduced islet necrosis and β-cell damage, and inhibited fat accumulation in T2DM mice. The protective effect of LJF on T2DM can be associated with modulation of the gut microbiota and metabolites, e.g., increases in Lactobacillus and Allobaculum. Untargeted and targeted metabolomics analysis showed that the microbiota metabolite profile was changed with LJF-induced microbiota alterations, mainly involving amino acids, glutathione, and glyoxylate and dicarboxylate metabolism pathways. This study indicates that LJF can be used as a prebiotic agent for the prevention and treatment of diabetes and microbiota-related diseases.PMID:36613249 | DOI:10.3390/foods12010033

Foods. 2022 Dec 20;12(1):5. doi: 10.3390/foods12010005.ABSTRACTThe Bama Xiang pig (BM) is a unique pig species in Guangxi Province, China. Compared to other breeds of domestic pig, such as the Debao pig (DB), it is smaller in size, better in meat quality, resistant to rough feeding and strong in stress resistance. These unique advantages of Bama Xiang pigs make them of great edible value and scientific research value. However, the differences in muscle metabolites between Bama Xiang pigs (BM) and Debao pigs (DB) are largely unexplored. Here, we identified 214 differential metabolites between these two pig breeds by LC-MS. Forty-one such metabolites are enriched into metabolic pathways, and these metabolites correspond to 11 metabolic pathways with significant differences. In Bama pigs, the abundance of various metabolites such as creatine, citric acid, L-valine and hypoxanthine is significantly higher than in Debao pigs, while the abundance of other metabolites, such as carnosine, is significantly lower. Among these, we propose six differential metabolites: L-proline, citric acid, ribose 1-phosphate, L-valine, creatine, and L-arginine, as well as four potential differential metabolites (without the KEGG pathway), alanyl-histidine, inosine 2'-phosphate, oleoylcarnitine, and histidinyl hydroxyproline, as features for evaluating the meat quality of Bama pigs and for differentiating pork from Bama pigs and Debao pigs. This study provides a proof-of-concept example of distinguishing pork from different pig breeds at the metabolite level and sheds light on elucidating the biological processes underlying meat quality differences. Our pork metabolites data are also of great value to the genomics breeding community in meat quality improvement.PMID:36613221 | DOI:10.3390/foods12010005

Int J Environ Res Public Health. 2022 Dec 28;20(1):503. doi: 10.3390/ijerph20010503.ABSTRACTPulmonary arterial hypertension (PAH) is a rare disease with a serious prognosis. The aim of this study was to identify biomarkers for PAH in the breath phase and to prepare an automatic classification method to determine the changing metabolome trends and molecular mapping. A group of 37 patients (F/M: 8/29 women, mean age 60.4 ± 10.9 years, BMI 27.6 ± 6.0 kg/m2) with diagnosed PAH were enrolled in the study. The breath phase of all the patients was collected on a highly porous septic material using a special patented holder PL230578, OHIM 002890789-0001. The collected air was then examined with gas chromatography coupled with mass spectrometry (GC/MS). The algorithms of Spectral Clustering, KMeans, DBSCAN, and hierarchical clustering methods were used to perform the cluster analysis. The identification of the changes in the ratio of the whole spectra of biomarkers allowed us to obtain a multidimensional pathway for PAH characteristics and showed the metabolome differences in the four subgroups divided by the cluster analysis. The use of GC/MS, supported with novel porous polymeric materials, for the breath phase analysis seems to be a useful tool in selecting bio-fingerprints in patients with PAH. The four metabolome classes which were obtained constitute novel data in the PAH population.PMID:36612835 | DOI:10.3390/ijerph20010503

Cancers (Basel). 2022 Dec 31;15(1):287. doi: 10.3390/cancers15010287.ABSTRACTRenal cell carcinoma (RCC) is among the 15 most common cancers worldwide, with rising incidence. In most cases, this is a silent disease until it reaches advance stages, demanding new effective biomarkers in all domains, from detection to post-therapy monitoring. Circulating tumor cells (CTC) have the potential to provide minimally invasive information to guide assessment of the disease's aggressiveness and therapeutic strategy, representing a special pool of neoplastic cells which bear metastatic potential. In some tumor models, CTCs' enumeration has been associated with prognosis, but there is a largely unexplored potential for clinical applicability encompassing screening, diagnosis, early detection of metastases, prognosis, response to therapy and monitoring. Nonetheless, lack of standardization and high cost hinder the translation into clinical practice. Thus, new methods for collection and analysis (genomic, proteomic, transcriptomic, epigenomic and metabolomic) are needed to ascertain the role of CTC as a RCC biomarker. Herein, we provide a critical overview of the most recently published data on the role and clinical potential of CTCs in RCC, addressing their biology and the molecular characterization of this remarkable set of tumor cells. Furthermore, we highlight the existing and emerging techniques for CTC enrichment and detection, exploring clinical applications in RCC. Notwithstanding the notable progress in recent years, the use of CTCs in a routine clinical scenario of RCC patients requires further research and technological development, enabling multimodal analysis to take advantage of the wealth of information they provide.PMID:36612281 | DOI:10.3390/cancers15010287

Cancers (Basel). 2022 Dec 29;15(1):210. doi: 10.3390/cancers15010210.ABSTRACTGut bacterial/viral dysbiosis, changes in circulating metabolites, and plasma cytokines/chemokines have been previously associated with various liver diseases. Here, we analyzed the associations between fecal microbial composition, circulating metabolites, and plasma cytokines/chemokines in patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC). We recruited 10 HCC patients, 18 LC patients, and 17 healthy individuals. Their stool samples were used for gene sequencing of bacterial 16S rRNA and viral genomes, while plasma samples were utilized for the determination of endotoxin, zonulin, metabolite, and cytokine/chemokine levels. Dysbiosis was observed among gut bacteria and viruses, with significant changes in abundance at the genus and species levels, respectively. However, no differences were found between cohorts in the alpha and beta diversity. Plasma lipopolysaccharides and zonulin, but not trimethylamine N-oxide, were progressively increased in LC and HCC subjects. Profiling plasma metabolites and selected cytokines/chemokines revealed differential changes in the LC and HCC cohorts. Following joint correlation and correlation network analyses, regardless of etiology, common network signatures shared by LC and HCC patients were characterized by the gut virus Stenotrophomonas virus DLP5 and the uncultured Caudovirales phage, plasma metabolites pyruvic acid and acetic acid, and plasma cytokines/chemokines eotaxin and PDGF-AB/BB, respectively. Additionally, LC- and HCC-specific correlation networks were also identified. This study provides novel insights into altered gut microbial/viral composition that may contribute to pre-HCC disorders, metabolic reprogramming, or inflammatory microenvironments for hepatocarcinogenesis.PMID:36612207 | DOI:10.3390/cancers15010210

Cancers (Basel). 2022 Dec 26;15(1):140. doi: 10.3390/cancers15010140.ABSTRACTEarly diagnostics significantly improves the survival of patients with renal cell carcinoma (RCC), which is the prevailing type of adult kidney cancer. However, the absence of clinically obvious symptoms and effective screening strategies at the early stages result to disease progression and survival rate reducing. The study was focused on revealing of potential low molecular biomarkers for early-stage RCC. The untargeted direct injection mass spectrometry-based metabolite profiling of blood plasma samples from 51 non-cancer volunteers (control) and 78 patients with different RCC subtypes and stages (early stages of clear cell RCC (ccRCC), papillary RCC (pRCC), chromophobe RCC (chrRCC) and advanced stages of ccRCC) was performed. Comparative analysis of the blood plasma metabolites between the control and cancer groups provided the detection of metabolites associated with different tumor stages. The designed model based on the revealed metabolites demonstrated high diagnostic power and accuracy. Overall, using the metabolomics approach the study revealed the metabolites demonstrating a high value for design of plasma-based test to improve early ccRCC diagnosis.PMID:36612136 | DOI:10.3390/cancers15010140

Cells. 2022 Dec 30;12(1):163. doi: 10.3390/cells12010163.ABSTRACTGreen plant regeneration efficiency (GPRE) via in vitro anther culture results from biochemical pathways and cycle dysfunctions that may affect DNA and histone methylation, with gene expression influencing whole cell functioning. The reprogramming from gametophytic to sporophytic fate is part of the phenomenon. While DNA methylation and sequence changes related to the GPRE have been described, little attention was paid to the biochemical aspects of the phenomenon. Furthermore, only a few theoretical models that describe the complex relationships between biochemical aspects of GPRE and the role of Cu(II) ions in the induction medium and as cofactors of enzymatic reactions have been developed. Still, none of these models are devoted directly to the biochemical level. Fourier transform infrared (FTIR) spectroscopy was used in the current study to analyze triticale regenerants derived under various in vitro tissue culture conditions, including different Cu(II) and Ag(I) ion concentrations in the induction medium and anther culture times. The FTIR spectra of S-adenosyl-L-methionine (SAM), glutathione, and pectins in parallel with the Cu(II) ions, as well as the evaluated GPRE values, were put into the structural equation model (SEM). The data demonstrate the relationships between SAM, glutathione, pectins, and Cu(II) in the induction medium and how they affect GPRE. The SEM reflects the cell functioning under in vitro conditions and varying Cu(II) concentrations. In the presented model, the players are the Krebs and Yang cycles, the transsulfuration pathway controlled by Cu(II) ions acting as cofactors of enzymatic reactions, and the pectins of the primary cell wall.PMID:36611956 | DOI:10.3390/cells12010163

Cells. 2022 Dec 28;12(1):124. doi: 10.3390/cells12010124.ABSTRACTPrevious studies have demonstrated an involvement of chromatin-remodelling SWI/SNF complexes in the development of prostate cancer, suggesting both tumor suppressor and oncogenic activities. SMARCD1/BAF60A, SMARCD2/BAF60B, and SMARCD3/BAF60C are mutually exclusive accessory subunits that confer functional specificity and are components of all known SWI/SNF subtypes. To assess the role of SWI/SNF in prostate tumorigenesis, we studied the functions and functional relations of the SMARCD family members. Performing RNA-seq in LnCAP cells grown in the presence or absence of dihydrotestosterone, we found that the SMARCD proteins are involved in the regulation of numerous hormone-dependent AR-driven genes. Moreover, we demonstrated that all SMARCD proteins can regulate AR-downstream targets in androgen-depleted cells, suggesting an involvement in the progression to castration-resistance. However, our approach also revealed a regulatory role for SMARCD proteins through antagonization of AR-signalling. We further demonstrated that the SMARCD proteins are involved in several important cellular processes such as the maintenance of cellular morphology and cytokinesis. Taken together, our findings suggest that the SMARCD proteins play an important, yet paradoxical, role in prostate carcinogenesis. Our approach also unmasked the complex interplay of paralogue SWI/SNF proteins that must be considered for the development of safe and efficient therapies targeting SWI/SNF.PMID:36611918 | DOI:10.3390/cells12010124

Animals (Basel). 2022 Dec 31;13(1):160. doi: 10.3390/ani13010160.ABSTRACTThe aim of this study was to investigate the impacts of inulin and Chinese gallotannin on the meat fatty acids and urinary metabolites in sheep. Twenty-four healthy (25.80 ± 3.85 kg) weaned Hu lambs of approximately 4.5 months old were equally divided into four groups: control group (basal diet), treatment group I (basal diet + 0.1% inulin), treatment group II (basal diet + 0.1% inulin + 2% Chinese gallotannin), and treatment group III (basal diet + 0.1% inulin + 2% Chinese gallotannin + 4% PEG). The contents of myristic acid (C14:0) and palmitic acid (C16:0) were found to be lower in treatment group II than in the control group (p < 0.05). Moreover, the palmitoleic acid (C16:1) content in treatment group II was notably higher than that in the control group (p < 0.05), while the elaidic acid (C18:1n9t) content in treatment group II was higher than that in other groups (p < 0.05). Besides, the linoleic acid (C18:2n6c) content was higher in the treatment II and control groups than in the treatment I and III groups. Furthermore, compared with the control group, both 4-pyridoxic acid and creatinine in treatment groups I and II were upregulated (p < 0.05), while other metabolites, such as nicotinuric acid, l-threonine, palmitic acid, and oleic acid, were drastically downregulated (p < 0.05). These differential metabolites were found to be mainly involved in nicotinate and nicotinamide metabolism (ko00760), vitamin B6 metabolism (ko00750), and the fatty acid biosynthesis pathway (ko00061). It is concluded that the combination of inulin and Chinese gallotannin in the diet could improve the energy and lipid metabolism of sheep, which may improve both mutton quality and production performance.PMID:36611769 | DOI:10.3390/ani13010160

Animals (Basel). 2022 Dec 29;13(1):131. doi: 10.3390/ani13010131.ABSTRACTInduction of FGF21 expression in the liver and a significant increase in plasma FGF21 concentration have been demonstrated in cows during early lactation, but knowledge about the function of FGF21 in dairy cows remains limited. In order to improve the understanding of the physiological role of FGF21 in dairy cows, the present study aimed to investigate differences in metabolic pathways between dairy cows with high and low hepatic expression of FGF21 at week 1 of lactation (n = 8/group) by liver transcriptomics, targeted plasma metabolomics, and analysis of inflammatory and oxidative stress-related parameters. Dry matter intake, energy balance, milk yield, and energy-corrected milk yield at days 8-14 postpartum did not differ between cows with high and low hepatic FGF21 expression. However, cows with high FGF21 expression showed an upregulation of genes involved in endoplasmic reticulum stress, inflammation, and nuclear factor E2-related factor 2 (Nrf2)-dependent cytoprotection compared to cows with low FGF21 expression at week 1 postpartum (p < 0.05). Concentrations of important antioxidants (tocopherols, β-carotene, and glutathione) in the liver and plasma, trolox equivalent antioxidant capacity in plasma, concentrations of oxidative stress-related compounds (thiobarbituric acid-reactive substances and protein carbonyls), and levels of most acute phase proteins at week 1 postpartum did not differ between cows with high or low FGF21 expression. Moreover, among a total of >200 metabolites assayed in the plasma, concentrations of only 7 metabolites were different between cows with high or low FGF21 expression (p < 0.05). Overall, the results showed that cows with high and low FGF21 hepatic expression had only moderate differences in metabolism, but FGF21 might be important in the adaptation of dairy cows to stress conditions during early lactation.PMID:36611740 | DOI:10.3390/ani13010131

Diagnostics (Basel). 2022 Dec 30;13(1):133. doi: 10.3390/diagnostics13010133.ABSTRACTCOVID-19 infection triggered a global public health crisis during the 2020-2022 period, and it is still evolving. This highly transmissible respiratory disease can cause mild symptoms up to severe pneumonia with potentially fatal respiratory failure. In this cross-sectional study, 41 PCR-positive patients for SARS-CoV-2 and 42 healthy controls were recruited during the first wave of the pandemic in Mexico. The plasmatic expression of five circulating miRNAs involved in inflammatory and pathological host immune responses was assessed using RT-qPCR (Reverse Transcription quantitative Polymerase Chain Reaction). Compared with controls, a significant upregulation of miR-146a, miR-155, and miR-221 was observed; miR-146a had a positive correlation with absolute neutrophil count and levels of brain natriuretic propeptide (proBNP), and miR-221 had a positive correlation with ferritin and a negative correlation with total cholesterol. We found here that CDKN1B gen is a shared target of miR-146a, miR-221-3p, and miR-155-5p, paving the way for therapeutic interventions in severe COVID-19 patients. The ROC curve built with adjusted variables (miR-146a, miR-221-3p, miR-155-5p, age, and male sex) to differentiate individuals with severe COVID-19 showed an AUC of 0.95. The dysregulation of circulating miRNAs provides new insights into the underlying immunological mechanisms, and their possible use as biomarkers to discriminate against patients with severe COVID-19. Functional analysis showed that most enriched pathways were significantly associated with processes related to cell proliferation and immune responses (innate and adaptive). Twelve of the predicted gene targets have been validated in plasma/serum, reflecting their potential use as predictive prognosis biomarkers.PMID:36611425 | DOI:10.3390/diagnostics13010133

Diagnostics (Basel). 2022 Dec 27;13(1):79. doi: 10.3390/diagnostics13010079.ABSTRACTLipopolysaccharide (LPS) or endotoxin, the major cell wall component of Gram-negative bacteria, plays a pivotal role in the pathogenesis of sepsis. It is able to activate the host defense system through interaction with Toll-like receptor 4, thus triggering pro-inflammatory mechanisms. A large amount of LPS induces inappropriate activation of the immune system, triggering an exaggerated inflammatory response and consequent extensive organ injury, providing the basis of sepsis damage. In this review, we will briefly describe endotoxin's molecular structure and its main pathogenetic action during sepsis. In addition, we will summarize the main different available methods for endotoxin detection with a special focus on the wider spectrum offered by omics technologies (genomics, transcriptomics, proteomics, and metabolomics) and promising applications of these in the identification of specific biomarkers for sepsis.PMID:36611371 | DOI:10.3390/diagnostics13010079

NanoImpact. 2023 Jan 4:100449. doi: 10.1016/j.impact.2022.100449. Online ahead of print.ABSTRACTMacro- or micro-nutrients are essential for crop yield and nutritional quality. In this work, selenium engineering nanomaterials (Se ENMs, 0.5 mg‧kg-1) significantly increased the yield and nutritional quality of lettuce, which was better than that of selenite (Na2SeO3). Under the treatment of Se ENMs, macro-nutrients including nitrogen (N), phosphorus (P), potassium (K), calcium (Ca), and magnesium (Mg) were increased by 15.8%, 98.5%, 42.8%, 146.9%, and 62.5%, respectively, and micro-nutrients including manganese (Mn), iron (Fe), copper (Cu), and zinc (Zn) were also increased by 87.4%, 78.0%, 61.1%, and 56.1%, respectively. As a result, the improved nutritional status of lettuce leaves increased photosynthesis (59.2%) and yield (37.6%). Root diameters and root tips of lettuce were increased by 23.9% and 18.6%, respectively, upon exposure to Se ENMs, which may be responsible for facilitating the absorption of macro and micro nutrients from the soil. These effects were significantly better than SeO32- treated group. Metabolome results indicated that Se ENMs could improve the shikimic acid, phenylalanine, and tyrosine pathway, resulting in an enhancement of the beneficial compounds, including quercetin, rutin, and coumarin, by 2.9, 2.7, and 2.4-fold, respectively. Besides, pyruvic acid and TCA cycle were also improved by Se ENMs. These results provide new insight into the positive effect of Se ENMs on crop yield and nutritional quality, which demonstrate that the Se ENMs-enabled agriculture practices have a promising prospect as a sustainable crop strategy.PMID:36610662 | DOI:10.1016/j.impact.2022.100449

J Affect Disord. 2023 Jan 4:S0165-0327(22)01527-0. doi: 10.1016/j.jad.2022.12.166. Online ahead of print.ABSTRACTBACKGROUND: The anti-depressant effect of berberine (BBR) has been widely reported. However, the underlying mechanism remains unclear. The microbiota-gut-brain (MGB) axis plays a key role in the pathogenesis of depression. Therefore, we aimed to explore the anti-depressant mechanisms of BBR involving the association of the gut microbiota, neurotransmitters, BDNF, and SCFAs in chronic unpredictable mild stress (CUMS)-induced depressive rats.METHODS: The antidepressant effects of BBR were detected by open-field test, 1 % sucrose preference test and body weight test in CUMS-induced depressive rats. 16S rDNA sequencing was performed to identify the change of gut microbiota. The concentrations of fecal SCFAs were analyzed by GC-MS targeted metabolomics. At the same time, neurotransmitters and BDNF expression were measured by enzyme linked immunosorbent assay (ELISA).RESULTS: BBR improved depression-like behaviors in CUMS rats by increasing the expression of serotonin (5-HT), norepinephrine (NE), dopamine (DA), and BDNF in the hippocampus. BBR regulates Firmicutes, Bacteroidetes, and Lachnospiraceae in depressive rats, resulting in the alteration of the synthesis and metabolism of SCFAs, including acetic, propanoic, and isovaleric acids.LIMITATIONS: Direct evidence that BBR improves depressive behaviors via gut microbiota-SCFAs-brain axis is lacking, and only male rats were investigated in the present study.CONCLUSION: The anti-depressant mechanism of BBR is related to the regulation of the MGB axis via modulating the gut microbiota-SCFAs-monoamine neurotransmitters/BDNF.PMID:36610597 | DOI:10.1016/j.jad.2022.12.166

J Appl Lab Med. 2023 Jan 4;8(1):53-66. doi: 10.1093/jalm/jfac100.ABSTRACTBACKGROUND: Ultra-performance liquid chromatography (UPLC)-MSE/quadrupole time-of-flight (QTOF) high-resolution mass spectrometry employs untargeted, data-independent acquisition in a dual mode that simultaneously collects precursor ions and product ions at low and ramped collision energies, respectively. However, algorithmic analysis of large-scale multivariate data of comprehensive drug screening as well as the positivity criteria of drug identification have not been systematically investigated. It is also unclear whether ion ratio (IR), the intensity ratio of a defined product ion divided by the precursor ion, is a stable parameter that can be incorporated into the MSE/QTOF data analysis algorithm.METHODS: IR of 91 drugs were experimentally determined and variation of IR was investigated across 5 concentrations measured on 3 different days. A data-driven machine learning approach was employed to develop multivariate linear regression (MLR) models incorporating mass error, retention time, number of detected fragment ions and IR, accuracy of isotope abundance, and peak response using drug-supplemented urine samples. Performance of the models was evaluated in an independent data set of unknown clinical urine samples in comparison with the results of manual analysis.RESULTS: IR of most compounds acquired by MSE/QTOF were low and concentration-dependent (i.e., IR increased at higher concentrations). We developed an MLR model with composite score outputs incorporating 7 parameters to predict positive drug identification. The model achieved a mean accuracy of 89.38% in the validation set and 87.92% agreement in the test set.CONCLUSIONS: The MLR model incorporating all contributing parameters can serve as a decision-support tool to facilitate objective drug identification using UPLC-MSE/QTOF.PMID:36610415 | DOI:10.1093/jalm/jfac100