PubMed

Front Plant Sci. 2024 Apr 16;15:1353352. doi: 10.3389/fpls.2024.1353352. eCollection 2024.ABSTRACTAmong tropical fruit trees, coconut holds significant edible and economic importance. The natural growth of coconuts faces a challenge in the form of low temperatures, which is a crucial factor among adverse environmental stresses impacting their geographical distribution. Hence, it is essential to enhance our comprehension of the molecular mechanisms through which cold stress influences various coconut varieties. We employed analyses of leaf growth morphology and physiological traits to examine how coconuts respond to low temperatures over 2-hour, 8-hour, 2-day, and 7-day intervals. Additionally, we performed transcriptome and metabolome analyses to identify the molecular and physiological shifts in two coconut varieties displaying distinct sensitivities to the cold stress. As the length of cold stress extended, there was a prominent escalation within the soluble protein (SP), proline (Pro) concentrations, the activity of peroxidase (POD) and superoxide dismutase (SOD) in the leaves. Contrariwise, the activity of glutathione peroxidase (GSH) underwent a substantial reduction during this period. The widespread analysis of metabolome and transcriptome disclosed a nexus of genes and metabolites intricately cold stress were chiefly involved in pathways centered around amino acid, flavonoid, carbohydrate and lipid metabolism. We perceived several stress-responsive metabolites, such as flavonoids, carbohydrates, lipids, and amino acids, which unveiled considerably, lower in the genotype subtle to cold stress. Furthermore, we uncovered pivotal genes in the amino acid biosynthesis, antioxidant system and flavonoid biosynthesis pathway that presented down-regulation in coconut varieties sensitive to cold stress. This study broadly enriches our contemporary perception of the molecular machinery that contributes to altering levels of cold stress tolerance amid coconut genotypes. It also unlocks several unique prospects for exploration in the areas of breeding or engineering, aiming to identifying tolerant and/or sensitive coconut varieties encompassing multi-omics layers in response to cold stress conditions.PMID:38689842 | PMC:PMC11058665 | DOI:10.3389/fpls.2024.1353352

World J Hepatol. 2024 Apr 27;16(4):601-611. doi: 10.4254/wjh.v16.i4.601.ABSTRACTBACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver condition that typically arises in the middle and late stages of pregnancy. Short-chain fatty acids (SCFAs), prominent metabolites of the gut microbiota, have significant connections with various pregnancy complications, and some SCFAs hold potential for treating such complications. However, the metabolic profile of SCFAs in patients with ICP remains unclear.AIM: To investigate the metabolic profiles and differences in SCFAs present in the maternal and cord blood of patients with ICP and determine the clinical significance of these findings.METHODS: Maternal serum and cord blood samples were collected from both patients with ICP (ICP group) and normal pregnant women (NP group). Targeted metabolomics was used to assess the SCFA levels in these samples.RESULTS: Significant differences in maternal SCFAs were observed between the ICP and NP groups. Most SCFAs exhibited a consistent declining trend in cord blood samples from the ICP group, mirroring the pattern seen in maternal serum. Correlation analysis revealed a positive correlation between maternal serum SCFAs and cord blood SCFAs [r (Pearson) = 0.88, P = 7.93e-95]. In both maternal serum and cord blood, acetic and caproic acids were identified as key metabolites contributing to the differences in SCFAs between the two groups (variable importance for the projection > 1). Receiver operating characteristic analysis demonstrated that multiple SCFAs in maternal blood have excellent diagnostic capabilities for ICP, with caproic acid exhibiting the highest diagnostic efficacy (area under the curve = 0.97).CONCLUSION: Compared with the NP group, significant alterations were observed in the SCFAs of maternal serum and cord blood in the ICP group, although they displayed distinct patterns of change. Furthermore, the SCFA levels in maternal serum and cord blood were significantly positively correlated. Notably, certain maternal serum SCFAs, specifically caproic and acetic acids, demonstrated excellent diagnostic efficiency for ICP.PMID:38689740 | PMC:PMC11056904 | DOI:10.4254/wjh.v16.i4.601

Hortic Res. 2024 Mar 2;11(4):uhae064. doi: 10.1093/hr/uhae064. eCollection 2024 Apr.ABSTRACTRubus rosaefolius is a kind of red raspberry possessing high nutritional and pharmaceutical value. Here we present a chromosome-level draft genome of R. rosaefolius. Of the total 131 assembled scaffolds, 70 with a total size of 219.02 Mb, accounting for 99.33% of the estimated genome size, were anchored to seven pseudochromosomes. We traced a whole-genome duplication (WGD) event shared among members of the Rosaceae family, from which were derived 5090 currently detectable duplicated gene pairs (dgps). Of the WGD-dgps 75.09% underwent purifying selection, and approximately three-quarters of informative WGD-dgps expressed their two paralogs with significant differences. We detected a wide variety of anthocyanins in the berries of R. rosaefolius, and their total concentration remained relatively stable during berry development but increased rapidly during the ripening stage, mainly because of the contributions of pelargonidin-3-O-glucoside and pelargonidin-3-O-(6″-O-malonyl)glucoside. We identified many structural genes that encode enzymes, such as RrDFR, RrF3H, RrANS, and RrBZ1, and play key roles in anthocyanin biosynthesis. The expression of some of these genes significantly increased or decreased with the accumulation of pelargonidin-3-O-glucoside and pelargonidin-3-O-(6″-O-malonyl)glucoside. We also identified some transcription factors and specific methylase-encoding genes that may play a role in regulating anthocyanin biosynthesis by targeting structural genes. In conclusion, our findings provide deeper insights into the genomic evolution and molecular mechanisms underlying anthocyanin biosynthesis in berries of R. rosaefolius. This knowledge may significantly contribute to the targeted domestication and breeding of Rubus species.PMID:38689697 | PMC:PMC11060340 | DOI:10.1093/hr/uhae064

J Cachexia Sarcopenia Muscle. 2024 Apr 30. doi: 10.1002/jcsm.13433. Online ahead of print.ABSTRACTBACKGROUND: Sarcopenia is characterized by loss of skeletal muscle mass and function, and is a major risk factor for disability and independence in the elderly. Effective medication is not available. Dietary restriction (DR) has been found to attenuate aging and aging-related diseases, including sarcopenia, but the mechanism of both DR and sarcopenia are incompletely understood.METHODS: In this study, mice body weight, fore and all limb grip strength, and motor learning and coordination performance were first analysed to evaluate the DR effects on muscle functioning. Liquid chromatography-mass spectrometry (LC-MS) was utilized for the metabolomics study of the DR effects on sarcopenia in progeroid DNA repair-deficient Ercc1∆/- and Xpg-/- mice, to identify potential biomarkers for attenuation of sarcopenia.RESULTS: Muscle mass was significantly (P < 0.05) decreased (13-20%) by DR; however, the muscle quality was improved with retained fore limbs and all limbs grip strength in Ercc1∆/- and Xpg-/- mice. The LC-MS results revealed that metabolites and pathways related to oxidative-stress, that is, GSSG/GSH (P < 0.01); inflammation, that is, 9-HODE, 11-HETE (P < 0.05), PGE2, PGD2, and TXB2 (P < 0.01); and muscle growth (PGF2α) (P < 0.01) and regeneration stimulation (PGE2) (P < 0.05) are significantly downregulated by DR. On the other hand, anti-inflammatory indicator and several related metabolites, that is, β-hydroxybutyrate (P < 0.01), 14,15-DiHETE (P < 0.0001), 8,9-EET, 12,13-DiHODE, and PGF1 (P < 0.05); consumption of sources of energy (i.e., muscle and liver glycogen); and energy production pathways, that is, glycolysis (glucose, glucose-6-P, fructose-6-P) (P < 0.01), tricarboxylic acid cycle (succinyl-CoA, malate) (P < 0.001), and gluconeogenesis-related metabolite, alanine (P < 0.01), are significantly upregulated by DR. The notably (P < 0.01) down-modulated muscle growth (PGF2α) and regeneration (PGE2) stimulation metabolite and the increased consumption of glycogen in muscle and liver may be related to the significantly (P < 0.01) lower body weight and muscle mass by DR. The downregulated oxidative stress, pro-inflammatory mediators, and upregulated anti-inflammatory metabolites resulted in a lower energy expenditure, which contributed to enhanced muscle quality together with upregulated energy production pathways by DR. The improved muscle quality may explain why grip strength is maintained and motor coordination and learning performance are improved by DR in Ercc1∆/- and Xpg-/- mice.CONCLUSIONS: This study provides fundamental supporting information on biomarkers and pathways related to the attenuation of sarcopenia, which might facilitate its diagnosis, prevention, and clinical therapy.PMID:38689513 | DOI:10.1002/jcsm.13433

Brain Behav Evol. 2024 Apr 30. doi: 10.1159/000539128. Online ahead of print.ABSTRACTINTRODUCTION: The octopus peduncle complex is an agglomeration of neural structures with remarkably diverse functional roles. The complex rests on the optic tract, between the optic lobe and the central brain, and comprises the peduncle lobe proper, the olfactory lobe, and the optic gland. The peduncle lobe regulates visuomotor behaviors, the optic glands control sexual maturation and maternal death, and the olfactory lobe is thought to receive input from the olfactory organ. Recent transcriptomic and metabolomic studies have identified candidate peptide and steroid ligands in the Octopus bimaculoides optic gland.METHODS: With gene expression for these ligands and their biosynthetic enzymes, we show that optic gland neurochemistry extends beyond the traditional optic gland secretory tissue and into lobular territories.RESULTS: A key finding is that the classically defined olfactory lobe is itself a heterogenous territory and includes steroidogenic territories that overlap with cells expressing molluscan neuropeptides and the synthetic enzyme dopamine beta-hydroxylase.CONCLUSION: Our study reveals the neurochemical landscape of the octopus peduncle complex, highlighting the unexpected overlap between traditionally defined regions.PMID:38688255 | DOI:10.1159/000539128

Protist. 2024 Apr 18;175(3):126035. doi: 10.1016/j.protis.2024.126035. Online ahead of print.ABSTRACTThe protist Euglena gracilis has various trophic modes including heterotrophy and photoheterotrophy. To investigate how cultivation mode influences metabolic regulation, the chemical composition of cellular metabolites of Euglena gracilis grown under heterotrophic and photoheterotrophic conditions was monitored from the early exponential phase to the mid-stationary phase using two different techniques, i.e, nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HRMS). The combined metabolomics approach allowed an in-depth understanding of the mechanism of photoheterotrophic and heterotrophic growth for biomolecule production. Heterotrophic conditions promoted the production of polar amino and oxygenated compounds such as proteins and polyphenol compounds, especially at the end of the exponential phase while photoheterotrophic cells enhanced the production of organoheterocyclic compounds, carbohydrates, and alkaloids.PMID:38688055 | DOI:10.1016/j.protis.2024.126035

J Anim Sci Biotechnol. 2024 May 1;15(1):58. doi: 10.1186/s40104-024-01017-4.ABSTRACTFinding out how diet impacts health and metabolism while concentrating on the functional qualities and bioactive components of food is the crucial scientific objective of nutritional research. The complex relationship between metabolism and nutrition could be investigated with cutting-edge "omics" and bioinformatics techniques. This review paper provides an overview of the use of omics technologies in nutritional research, with a particular emphasis on the new applications of transcriptomics, proteomics, metabolomics, and genomes in functional and biological activity research on ruminant livestock and products in the tropical regions. A wealth of knowledge has been uncovered regarding the regulation and use of numerous physiological and pathological processes by gene, mRNA, protein, and metabolite expressions under various physiological situations and guidelines. In particular, the components of meat and milk were assessed using omics research utilizing the various methods of transcriptomics, proteomics, metabolomics, and genomes. The goal of this review is to use omics technologies-which have been steadily gaining popularity as technological tools-to develop new nutritional, genetic, and leadership strategies to improve animal products and their quality control. We also present an overview of the new applications of omics technologies in cattle production and employ nutriomics and foodomics technologies to investigate the microbes in the rumen ecology. Thus, the application of state-of-the-art omics technology may aid in our understanding of how species and/or breeds adapt, and the sustainability of tropical animal production, in the long run, is becoming increasingly important as a means of mitigating the consequences of climate change.PMID:38689368 | DOI:10.1186/s40104-024-01017-4

BMC Complement Med Ther. 2024 Apr 30;24(1):178. doi: 10.1186/s12906-024-04479-1.ABSTRACTBACKGROUND: Gastrointestinal cancer (GIC) ranks as the highest cause of cancer-related deaths globally. GIC patients are often diagnosed at advanced stages, limiting effective treatment options. Chemotherapy, the common GIC recommendation, has significant disadvantages such as toxicity and adverse effects. Natural products contain substances with diverse pharmacological characteristics that promise for use in cancer therapeutics. In this study, the flower of renowned Asian medicinal plant, Shorea roxburghii was collected and extracted to investigate its phytochemical contents, antioxidant, and anticancer properties on GIC cells.METHODS: The phytochemical contents of Shorea roxburghii extract were assessed using suitable methods. Phenolic content was determined through the Folin-Ciocalteu method, while flavonoids were quantified using the aluminum chloride (AlCl3) method. Antioxidant activity was evaluated using the FRAP and DPPH assays. Cytotoxicity was assessed in GIC cell lines via the MTT assay. Additionally, intracellular ROS levels and apoptosis were examined through flow cytometry techniques. The correlation between GIC cell viability and phytochemicals, 1H-NMR analysis was conducted.RESULTS: Among the four different solvent extracts, ethyl acetate extract had the highest phenolic and flavonoid contents. Water extract exhibited the strongest reducing power and DPPH scavenging activity following by ethyl acetate. Interestingly, ethyl acetate extract demonstrated the highest inhibitory activity against three GIC cell lines (KKU-213B, HepG2, AGS) with IC50 values of 91.60 µg/ml, 39.38 µg/ml, and 35.59 µg/ml, while showing less toxicity to normal fibroblast cells. Ethyl acetate extract induced reactive oxygen species and apoptosis in GIC cell lines by downregulating anti-apoptotic protein Bcl-2. Metabolic profiling-based screening revealed a positive association between reduced GIC cell viability and phytochemicals like cinnamic acid and its derivatives, ferulic acid and coumaric acid.CONCLUSIONS: This study highlights the potential of natural compounds in Shorea roxburghii in the development of more effective and safer anticancer agents as options for GIC as well as shedding light on new avenues for cancer treatment.PMID:38689275 | DOI:10.1186/s12906-024-04479-1

BMC Pregnancy Childbirth. 2024 Apr 30;24(1):333. doi: 10.1186/s12884-024-06538-4.ABSTRACTBACKGROUND: Lower socioeconomic position (SEP) associates with adverse pregnancy and perinatal outcomes and with less favourable metabolic profile in nonpregnant adults. Socioeconomic differences in pregnancy metabolic profile are unknown. We investigated association between a composite measure of SEP and pregnancy metabolic profile in White European (WE) and South Asian (SA) women.METHODS: We included 3,905 WE and 4,404 SA pregnant women from a population-based UK cohort. Latent class analysis was applied to nineteen individual, household, and area-based SEP indicators (collected by questionnaires or linkage to residential address) to derive a composite SEP latent variable. Targeted nuclear magnetic resonance spectroscopy was used to determine 148 metabolic traits from mid-pregnancy serum samples. Associations between SEP and metabolic traits were examined using linear regressions adjusted for gestational age and weighted by latent class probabilities.RESULTS: Five SEP sub-groups were identified and labelled 'Highest SEP' (48% WE and 52% SA), 'High-Medium SEP' (77% and 23%), 'Medium SEP' (56% and 44%) 'Low-Medium SEP' (21% and 79%), and 'Lowest SEP' (52% and 48%). Lower SEP was associated with more adverse levels of 113 metabolic traits, including lower high-density lipoprotein (HDL) and higher triglycerides and very low-density lipoprotein (VLDL) traits. For example, mean standardized difference (95%CI) in concentration of small VLDL particles (vs. Highest SEP) was 0.12 standard deviation (SD) units (0.05 to 0.20) for 'Medium SEP' and 0.25SD (0.18 to 0.32) for 'Lowest SEP'. There was statistical evidence of ethnic differences in associations of SEP with 31 traits, primarily characterised by stronger associations in WE women e.g., mean difference in HDL cholesterol in WE and SA women respectively (vs. Highest-SEP) was -0.30SD (-0.41 to -0.20) and -0.16SD (-0.27 to -0.05) for 'Medium SEP', and -0.62SD (-0.72 to -0.52) and -0.29SD (-0.40 to -0.20) for 'Lowest SEP'.CONCLUSIONS: We found widespread socioeconomic differences in metabolic traits in pregnant WE and SA women residing in the UK. Further research is needed to understand whether the socioeconomic differences we observe here reflect pre-conception differences or differences in the metabolic pregnancy response. If replicated, it would be important to explore if these differences contribute to socioeconomic differences in pregnancy outcomes.PMID:38689215 | DOI:10.1186/s12884-024-06538-4

Metabolomics. 2024 Apr 30;20(3):49. doi: 10.1007/s11306-024-02115-0.ABSTRACTINTRODUCTION: Untargeted metabolomics studies are expected to cover a wide range of compound classes with high chemical diversity and complexity. Thus, optimizing (pre-)analytical parameters such as the analytical liquid chromatography (LC) column is crucial and the selection of the column depends primarily on the study purpose.OBJECTIVES: The current investigation aimed to compare six different analytical columns. First, by comparing the chromatographic resolution of selected compounds. Second, on the outcome of an untargeted toxicometabolomics study using pooled human liver microsomes (pHLM), rat plasma, and rat urine as matrices.METHODS: Separation and analysis were performed using three different reversed-phase (Phenyl-Hexyl, BEH C18, and Gold C18), two hydrophilic interaction chromatography (HILIC) (ammonium-sulfonic acid and sulfobetaine), and one porous graphitic carbon (PGC) columns coupled to high-resolution mass spectrometry (HRMS). Their impact was evaluated based on the column performance and the size of feature count, amongst others.RESULTS: All three reversed-phase columns showed a similar performance, whereas the PGC column was superior to both HILIC columns at least for polar compounds. Comparing the size of feature count across all datasets, most features were detected using the Phenyl-Hexyl or sulfobetaine column. Considering the matrices, most significant features were detected in urine and pHLM after using the sulfobetaine and in plasma after using the ammonium-sulfonic acid column.CONCLUSION: The results underline that the outcome of this untargeted toxicometabolomic study LC-HRMS metabolomic study was highly influenced by the analytical column, with the Phenyl-Hexyl or sulfobetaine column being the most suitable. However, column selection may also depend on the investigated compounds as well as on the investigated matrix.PMID:38689195 | DOI:10.1007/s11306-024-02115-0

J Nephrol. 2024 Apr 30. doi: 10.1007/s40620-024-01923-w. Online ahead of print.ABSTRACTBACKGROUND: Glomerulonephritis inherently leads to the development of chronic kidney disease. It is the second most common diagnosis in patients requiring renal replacement therapy in the United Kingdom. Metabolomics and proteomics can characterise, identify and quantify an individual's protein and metabolite make-up. These techniques have been optimised and can be performed on samples including kidney tissue, blood and urine. Utilising omic techniques in nephrology can uncover disease pathophysiology and transform the diagnostics and treatment options for glomerulonephritis.OBJECTIVES: To evaluate the utility of metabolomics and proteomics using mass spectrometry and nuclear magnetic resonance in glomerulonephritis.METHODS: The systematic review was registered on PROSPERO (CRD42023442092). Standard and extensive Cochrane search methods were used. The latest search date was March 2023. Participants were of any age with a histological diagnosis of glomerulonephritis. Descriptive analysis was performed, and data presented in tabular form. An area under the curve or p-value was presented for potential biomarkers discovered.RESULTS: Twenty-seven studies were included (metabolomics (n = 9)), and (proteomics (n = 18)) with 1818 participants. The samples analysed were urine (n = 19) blood (n = 4) and biopsy (n = 6). The typical outcome themes were potential biomarkers, disease phenotype, risk of progression and treatment response.CONCLUSION: This review shows the potential of metabolomic and proteomic analysis to discover new disease biomarkers that may influence diagnostics and disease management. Further larger-scale research is required to establish the validity of the study outcomes, including the several proposed biomarkers.PMID:38689160 | DOI:10.1007/s40620-024-01923-w

Nat Metab. 2024 Apr 30. doi: 10.1038/s42255-024-01038-3. Online ahead of print.ABSTRACTThe oxidative phosphorylation system1 in mammalian mitochondria plays a key role in transducing energy from ingested nutrients2. Mitochondrial metabolism is dynamic and can be reprogrammed to support both catabolic and anabolic reactions, depending on physiological demands or disease states. Rewiring of mitochondrial metabolism is intricately linked to metabolic diseases and promotes tumour growth3-5. Here, we demonstrate that oral treatment with an inhibitor of mitochondrial transcription (IMT)6 shifts whole-animal metabolism towards fatty acid oxidation, which, in turn, leads to rapid normalization of body weight, reversal of hepatosteatosis and restoration of normal glucose tolerance in male mice on a high-fat diet. Paradoxically, the IMT treatment causes a severe reduction of oxidative phosphorylation capacity concomitant with marked upregulation of fatty acid oxidation in the liver, as determined by proteomics and metabolomics analyses. The IMT treatment leads to a marked reduction of complex I, the main dehydrogenase feeding electrons into the ubiquinone (Q) pool, whereas the levels of electron transfer flavoprotein dehydrogenase and other dehydrogenases connected to the Q pool are increased. This rewiring of metabolism caused by reduced mtDNA expression in the liver provides a principle for drug treatment of obesity and obesity-related pathology.PMID:38689023 | DOI:10.1038/s42255-024-01038-3

Brief Funct Genomics. 2024 Apr 30:elae019. doi: 10.1093/bfgp/elae019. Online ahead of print.ABSTRACTAs the demographic structure shifts towards an aging society, strategies aimed at slowing down or reversing the aging process become increasingly essential. Aging is a major predisposing factor for many chronic diseases in humans. The hematopoietic system, comprising blood cells and their associated bone marrow microenvironment, intricately participates in hematopoiesis, coagulation, immune regulation and other physiological phenomena. The aging process triggers various alterations within the hematopoietic system, serving as a spectrum of risk factors for hematopoietic disorders, including clonal hematopoiesis, immune senescence, myeloproliferative neoplasms and leukemia. The emerging single-cell technologies provide novel insights into age-related changes in the hematopoietic system. In this review, we summarize recent studies dissecting hematopoietic system aging using single-cell technologies. We discuss cellular changes occurring during aging in the hematopoietic system at the levels of the genomics, transcriptomics, epigenomics, proteomics, metabolomics and spatial multi-omics. Finally, we contemplate the future prospects of single-cell technologies, emphasizing the impact they may bring to the field of hematopoietic system aging research.PMID:38688725 | DOI:10.1093/bfgp/elae019

Sci Signal. 2024 Apr 30;17(834):eadj6603. doi: 10.1126/scisignal.adj6603. Epub 2024 Apr 30.ABSTRACTThe localization, number, and function of postsynaptic AMPA-type glutamate receptors (AMPARs) are crucial for synaptic plasticity, a cellular correlate for learning and memory. The Hippo pathway member WWC1 is an important component of AMPAR-containing protein complexes. However, the availability of WWC1 is constrained by its interaction with the Hippo pathway kinases LATS1 and LATS2 (LATS1/2). Here, we explored the biochemical regulation of this interaction and found that it is pharmacologically targetable in vivo. In primary hippocampal neurons, phosphorylation of LATS1/2 by the upstream kinases MST1 and MST2 (MST1/2) enhanced the interaction between WWC1 and LATS1/2, which sequestered WWC1. Pharmacologically inhibiting MST1/2 in male mice and in human brain-derived organoids promoted the dissociation of WWC1 from LATS1/2, leading to an increase in WWC1 in AMPAR-containing complexes. MST1/2 inhibition enhanced synaptic transmission in mouse hippocampal brain slices and improved cognition in healthy male mice and in male mouse models of Alzheimer's disease and aging. Thus, compounds that disrupt the interaction between WWC1 and LATS1/2 might be explored for development as cognitive enhancers.PMID:38687825 | DOI:10.1126/scisignal.adj6603

PLoS Biol. 2024 Apr 30;22(4):e3002607. doi: 10.1371/journal.pbio.3002607. Online ahead of print.ABSTRACTUnbiased data-driven omic approaches are revealing the molecular heterogeneity of Alzheimer disease. Here, we used machine learning approaches to integrate high-throughput transcriptomic, proteomic, metabolomic, and lipidomic profiles with clinical and neuropathological data from multiple human AD cohorts. We discovered 4 unique multimodal molecular profiles, one of them showing signs of poor cognitive function, a faster pace of disease progression, shorter survival with the disease, severe neurodegeneration and astrogliosis, and reduced levels of metabolomic profiles. We found this molecular profile to be present in multiple affected cortical regions associated with higher Braak tau scores and significant dysregulation of synapse-related genes, endocytosis, phagosome, and mTOR signaling pathways altered in AD early and late stages. AD cross-omics data integration with transcriptomic data from an SNCA mouse model revealed an overlapping signature. Furthermore, we leveraged single-nuclei RNA-seq data to identify distinct cell-types that most likely mediate molecular profiles. Lastly, we identified that the multimodal clusters uncovered cerebrospinal fluid biomarkers poised to monitor AD progression and possibly cognition. Our cross-omics analyses provide novel critical molecular insights into AD.PMID:38687811 | DOI:10.1371/journal.pbio.3002607

PLoS One. 2024 Apr 30;19(4):e0302976. doi: 10.1371/journal.pone.0302976. eCollection 2024.ABSTRACT[This corrects the article DOI: 10.1371/journal.pone.0300319.].PMID:38687752 | DOI:10.1371/journal.pone.0302976

J Anal Toxicol. 2024 Mar 29:bkae022. doi: 10.1093/jat/bkae022. Online ahead of print.ABSTRACTHexahydrocannabinol (HHC), 6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-1-ol, is a semi-synthetic cannabinoid that has presented challenges to analytical laboratories due to its emergence and spread in the drug market. The lack of information on human pharmacokinetics hinders the development and application of presumptive and confirmatory tests for reliably detecting HHC consumption. To address this knowledge gap, we report the analytical results obtained from systematic forensic toxicological analysis of body-fluid samples collected from three individuals suspected of drug-impaired driving after HHC consumption. Urine and plasma samples were analyzed using non-targeted liquid chromatography-high-resolution tandem mass spectrometry. The results provided evidence that HHC undergoes biotransformation reactions similar to other well-characterized cannabinoids, such as ∆9-tetrahydrocannabinol or cannabidiol. Notably, HHC itself was only detectable in plasma samples, not in urine samples. The observed Phase I reactions involved oxidation of C11 and the pentyl side chain, leading to corresponding hydroxylated and carboxylic acid species. Additionally, extensive glucuronidation of HHC and its Phase I metabolites was evident.PMID:38687640 | DOI:10.1093/jat/bkae022

Med Sci Sports Exerc. 2024 May 1. doi: 10.1249/MSS.0000000000003475. Online ahead of print.ABSTRACTPURPOSE: Human skeletal muscle has the profound ability to hypertrophy in response to resistance training (RT). Yet, this has a high energy and protein cost and is presumably mainly restricted to recruited muscles. It remains largely unknown what happens with non-recruited muscles during RT. This study investigated the volume changes of 17 recruited and 13 non-recruited muscles during a 10-week single-joint RT program targeting upper arm and upper leg musculature.METHODS: Muscle volume changes were measured by manual or automatic 3D segmentation in 21 RT novices. Subjects ate ad libitum during the study and energy and protein intake were assessed by self-reported diaries.RESULTS: Post-training, all recruited muscles increased in volume (range: +2.2% to +17.7%, p < 0.05) while the non-recruited adductor magnus (mean: -1.5 ± 3.1%, p = 0.038) and soleus (-2.4 ± 2.3%, p = 0.0004) decreased in volume. Net muscle growth (r = 0.453, p = 0.045) and changes in adductor magnus volume (r = 0.450, p = 0.047) were positively associated with protein intake. Changes in total non-recruited muscle volume (r = 0.469, p = 0.037), adductor magnus (r = 0.640, p = 0.002), adductor longus (r = 0.465, p = 0.039) and soleus muscle volume (r = 0.481, p = 0.032) were positively related to energy intake (p < 0.05). When subjects were divided into a HIGH or LOW energy intake group, overall non-recruited muscle volume (-1.7 ± 2.0%), adductor longus (-5.6 ± 3.7%), adductor magnus (-2.8 ± 2.4%) and soleus volume (-3.7 ± 1.8%) decreased significantly (p < 0.05) in the LOW but not the HIGH group.CONCLUSIONS: To our knowledge, this is the first study documenting that some non-recruited muscles significantly atrophy during a period of resistance training. Our data therefore suggest muscle mass reallocation, i.e., that hypertrophy in recruited muscles takes place at the expense of atrophy in non-recruited muscles, especially when energy and protein availability are limited.PMID:38687626 | DOI:10.1249/MSS.0000000000003475

Clin Cancer Res. 2024 Apr 30. doi: 10.1158/1078-0432.CCR-23-2934. Online ahead of print.ABSTRACTPURPOSE: Endometrial cancer is highly prevalent and lacking non-invasive diagnostic techniques. Diagnosis depends on histological investigation of biopsy samples. Serum biomarkers for endometrial cancer have lacked sensitivity and specificity. The objective of this study was to investigate the cervicovaginal environment to improve understanding of metabolic reprogramming related to endometrial cancer and identify potential biomarker candidates for non-invasive diagnostic and prognostic tests.EXPERIMENTAL DESIGN: Cervicovaginal lavages were collected from 192 participants with endometrial cancer (n=66) and non-malignant conditions (n=108), and global untargeted metabolomics was performed. Using the metabolite data (n=920), we completed a multivariate biomarker discovery analysis.RESULTS: We analyzed grade 1/2 endometrioid carcinoma (n=53) and other endometrial cancer subtypes (n=13) to identify shared and unique metabolic signatures between the subtypes. When compared to non-malignant conditions, downregulation of proline (p<0.0001), tryptophan (p<0.0001), and glutamate (p<0.0001) was found among both endometrial cancer groups, relating to key hallmarks of cancer including immune suppression and redox balance. Upregulation (q<0.05) of sphingolipids, fatty acids, and glycerophospholipids was observed in endometrial cancer in a type-specific manner. Furthermore, cervicovaginal metabolites related to tumor characteristics, including tumor size and myometrial invasion.CONCLUSIONS: Our findings provide insights into understanding the endometrial cancer metabolic landscape and improvement into diagnosis. The metabolic dysregulation described in this paper linked specific metabolites and pathophysiological mechanisms including cellular proliferation, energy supply, and invasion of neighbouring tissues. Furthermore, cervicovaginal metabolite levels related to tumor characteristics, which are used for risk stratification. Overall, development of non-invasive diagnostic can improve both the acceptability and accessibility of diagnosis.PMID:38687603 | DOI:10.1158/1078-0432.CCR-23-2934

Bioprocess Biosyst Eng. 2024 Apr 30. doi: 10.1007/s00449-024-03013-4. Online ahead of print.ABSTRACTEicosapentaenoic acid (EPA) is a vital ɷ-3 polyunsaturated fatty acid (PUFA) for human body with various physiological functions. In this study, we proposed an adaptive evolutionary strategy based on high-temperature and high-oxygen two-factor stress to increase the EPA production capacity of Schizochytrium. High-temperature stress was used to increase EPA yield, and high oxygen was implemented to continuously stimulate cell growth and lipid accumulation. The biomass and EPA production of ALE-D50 reached 35.33 g/L and 1.54 g/L, which were 43.85% and 71.11% higher than that of the original strain, respectively. Lower in vivo reactive oxygen species levels indicated that the evolved strain possessed stronger antioxidant activity. Liquid chromatography-mass spectrometry metabolomics showed that enhanced glucose consumption and glycolysis metabolism, as well as a weakened tricarboxylic acid cycle and reduced amino acid metabolic tributaries in the evolved strain, might be associated with increased growth and EPA synthesis. Finally, the lipid production and EPA production in a fed-batch fermentation were further increased to 48.93 g/L and 3.55 g/L, improving by 54.30% and 90.86%, respectively. This study provides a novel pathway for promoting EPA biosynthesis in Schizochytrium.PMID:38687387 | DOI:10.1007/s00449-024-03013-4