PubMed

Front Endocrinol (Lausanne). 2023 Mar 2;14:1168700. doi: 10.3389/fendo.2023.1168700. eCollection 2023.NO ABSTRACTPMID:36936168 | PMC:PMC10019277 | DOI:10.3389/fendo.2023.1168700

Front Physiol. 2023 Mar 2;14:1127294. doi: 10.3389/fphys.2023.1127294. eCollection 2023.ABSTRACTBackground: Cigarette smoking is an important environmental risk factor for cardiovascular events of hypertension (HTN). Existing studies have provided evidence supporting altered gut microbiota by cigarette smoking, especially in hypertensive patients. Metabolic biomarkers play a central role in the functional potentials of the gut microbiome but are poorly characterized in hypertensive smokers. To explore whether serum metabolomics signatures and compositions of HTN patients were varied in smokers, and investigate their connecting relationship to gut microbiota, the serum metabolites were examined in untreated hypertensive patients using untargeted liquid chromatography-mass spectrometry (LC/MS) analysis. Results: A dramatic difference and clear separation in community features of circulating metabolomics members were seen in smoking HTN patients compared with the non-smoking controls, according to partial least squares discrimination analysis (PLS-DA) and orthogonal partial least squares discrimination analysis (OPLS-DA). Serum metabolic profiles and compositions of smoking patients with HTN were significantly distinct from the controls, and were characterized by enrichment of 12-HETE, 7-Ketodeoxycholic acid, Serotonin, N-Stearoyl tyrosine and Deoxycholic acid glycine conjugate, and the depletion of Tetradecanedioic acid, Hippuric acid, Glyceric acid, 20-Hydroxyeicosatetraenoic acid, Phenylpyruvic acid and Capric acid. Additionally, the metabolome displayed prominent functional signatures, with a majority proportion of the metabolites identified to be discriminating between groups distributed in Starch and sucrose metabolism, Caffeine metabolism, Pyruvate metabolism, Glycine, serine and threonine metabolism, and Phenylalanine metabolic pathways. Furthermore, the observation of alterations in metabolites associated with intestinal microbial taxonomy indicated that these metabolic members might mediate the effects of gut microbiome on the smoking host. Indeed, the metabolites specific to smoking HTNs were strongly organized into co-abundance networks, interacting with an array of clinical parameters, including uric acid (UA), low-denstiy lipoprotein cholesterol (LDLC) and smoking index. Conclusions: In conclusion, we demonstrated disparate circulating blood metabolome composition and functional potentials in hypertensive smokers, showing a linkage between specific metabolites in blood and the gut microbiome.PMID:36935758 | PMC:PMC10018148 | DOI:10.3389/fphys.2023.1127294

Aging Cell. 2023 Mar 19:e13813. doi: 10.1111/acel.13813. Online ahead of print.ABSTRACTUntargeted metabolomics is the study of all detectable small molecules, and in geroscience, metabolomics has shown great potential to describe the biological age-a complex trait impacted by many factors. Unfortunately, the sample sizes are often insufficient to achieve sufficient power and minimize potential biases caused by, for example, demographic factors. In this study, we present the analysis of biological age in ~10,000 toxicologic routine blood measurements. The untargeted screening samples obtained from ultra-high pressure liquid chromatography-quadruple time of flight mass spectrometry (UHPLC- QTOF) cover + 300 batches and + 30 months, lack pooled quality controls, lack controlled sample collection, and has previously only been used in small-scale studies. To overcome experimental effects, we developed and tested a custom neural network model and compared it with existing prediction methods. Overall, the neural network was able to predict the chronological age with an rmse of 5.88 years (r2 = 0.63) improving upon the 6.15 years achieved by existing normalization methods. We used the feature importance algorithm, Shapley Additive exPlanations (SHAP), to identify compounds related to the biological age. Most importantly, the model returned known aging markers such as kynurenine, indole-3-aldehyde, and acylcarnitines along with a potential novel aging marker, cyclo (leu-pro). Our results validate the association of tryptophan and acylcarnitine metabolism to aging in a highly uncontrolled large-s cale sample. Also, we have shown that by using robust computational methods it is possible to deploy large LC-MS datasets for metabolomics studies to reduce the risk of bias and empower aging studies.PMID:36935524 | DOI:10.1111/acel.13813

Prim Care Diabetes. 2023 Mar 14:S1751-9918(23)00065-7. doi: 10.1016/j.pcd.2023.03.004. Online ahead of print.ABSTRACTPURPOSE: The study aim was to evaluate the effects of public lockdown during the covid-19 pandemic on glucose and metabolic parameters as well as body weight control in type 2 diabetic patients.METHODS: This study was conducted in two outpatient Diabetes Clinics and analyzed data available in database of Diabetes Clinic. Data related to a year before covid-19 pandemic and a year during covid-19 pandemic was collected from the database and analyzed. Patients with type 2 diabetes included in the analysis if they had referred to Diabetes Clinics both before and during covid-19 pandemic. Demographic information and data about metabolic status were collected from the records of previous outpatient Clinic visits and compared RESULTS: Finally 9440 patients with mean age of 61.08 ± 11.62 referred to Diabetes Clinics in both the year before and the year of the corona pandemic. Mean FBS and HbA1c in diabetes patients reduced significantly from 155.37 ± 62.93 and 7.97 ± 1.74 before pandemic, respectively to 138.77 ± 45.39 and 7.54 ± 1.34, respectively during covid-19 outbreak. During covid-19 pandemic, all metabolic parameters including glycemic and lipid profile (except for triglyceride) and BMI (body mass index) reduced significantly statistically, but, these changes were not clinically significant. However, triglyceride level increased statistically significantly but again it was not significant clinically.CONCLUSION: During COVID-19 lockdown, glycemic and metabolic control of diabetes patients have improved significantly except for triglycerides.PMID:36935271 | DOI:10.1016/j.pcd.2023.03.004

J Dairy Sci. 2023 Mar 17:S0022-0302(23)00125-X. doi: 10.3168/jds.2022-22209. Online ahead of print.ABSTRACTMetabolic disorders as ketosis are manifestations of the animal's inability to manage the increase in energy requirement during early lactation. Generally, buffaloes show a different response to higher metabolic demands than other ruminants with a lower incidence of metabolic problems, although ketosis is one of the major diseases that may decrease the productivity in buffaloes. The aim of this study was to characterize the metabolic profile of Mediterranean buffaloes (MB) associated with 2 different levels of β-hydroxybutyrate (BHB). Sixty-two MB within 50 days in milk (DIM) were enrolled and divided into 2 groups according to serum BHB concentration: healthy group (37 MB; BHB <0.70 mmol/L; body condition score: 5.00; parity: 3.78; and DIM: 30.70) and group at risk of hyperketonemia (25 MB; BHB ≥0.70 mmol/L; body condition score: 4.50; parity: 3.76; and DIM: 33.20). The statistical analysis was conducted by one-way ANOVA and unpaired 2-sample Wilcoxon tests. Fifty-seven metabolites were identified and among them, 12 were significant or tended to be significant. These metabolites were related to different metabolic changes such as mobilization of body resources, ruminal fermentations, urea cycle, thyroid hormone synthesis, inflammation, and oxidative stress status. These findings are suggestive of metabolic changes related to subclinical ketosis status that should be further investigated to better characterize this disease in the MB.PMID:36935234 | DOI:10.3168/jds.2022-22209

Anal Chim Acta. 2023 Apr 29;1252:341028. doi: 10.1016/j.aca.2023.341028. Epub 2023 Feb 27.ABSTRACTA facile and rapid skin metabolomics protocol is proposed. The liquid microjunction-surface sampling probe system has been partly automated, and used in conjunction with hydrogel probes for skin metabolite analysis. A control device was built to precisely control the segmented solvent flow and analyte re-extraction into the liquid microjunction. This mode provides rapid online re-extraction of the analytes from hydrogel probes. Humectant was added to the hydrogel, and moist heat treatment was used to make the hydrogel probes rugged for sampling in the clinical setting. The developed method was validated for the analysis of choline - a putative biomarker of psoriasis. A linear relationship over six calibration levels from 3.18 × 10-5 to 3.18 × 10-4 mol m-2 has been obtained. The limit of detection was 6.6 × 10-6 mol m-2, while the recoveries range from 92 to 109%. The within-run and between-run precision were evaluated and the coefficients of variation range from 1.84 to 7.13%. Furthermore, the developed method has been used to screen patients (n = 10) and healthy participants (control group; n = 10) for psoriasis-related skin metabolites. Metabolomic profiling of the skin excretion-related signals identified potential biomarkers of psoriasis: choline, pipecolic acid, ornithine, urocanic acid, and methionine.PMID:36935144 | DOI:10.1016/j.aca.2023.341028

Sci Total Environ. 2023 Mar 17:162928. doi: 10.1016/j.scitotenv.2023.162928. Online ahead of print.ABSTRACTCompared with the effect of a single substance on arsenic plant toxicity, the effect of coexisting pyrite and natural organic matter can better reflect actual environmental conditions. In this study, the interaction between pyrite and glutamic acid in arsenite solution was explored, the influence of pyrite and glutamic acid on arsenite plant toxicity was evaluated, and the metabolic regulation mechanism of pyrite and glutamic acid on the arsenite phytotoxic effect was clarified by metabolomics analysis. Combined pyrite and glutamic acid treatment fixed more arsenic by forming chemical bonds such as AsS, AsO, and As-O-OH in culture solution and reduced inorganic arsenic levels in plants. Compared with glutamic acid alone and pyrite alone, the combined treatment reduced the inorganic arsenic concentration in plants by 4.7 % and 40.0 %, respectively. The combined treatment limited plant ROS accumulation and maintained the leaf chlorophyll content by increasing SOD synthesis. Compared with the effect of As(III) alone, the chlorophyll content increased by 15.1-21.0 % on average under the combined treatment. The combined treatment promoted the absorption of Ca, Cu, Fe, Mo and Zn in lettuce, enhanced plant adaptation to As(III) and significantly improved plant nutritional quality. Compared with glutamic acid alone, the combined treatment increased the VC, fiber and protein contents by 128.9 %, 202.8 % and 36.7 %, respectively. Metabolomics analysis indicated that in the combined treatment group, the upregulation of tyrosine, pyruvate and N metabolism increased the plant chlorophyll content. The upregulation of S metabolism increases VC synthesis in plants and inhibits ROS accumulation, thus maintaining normal plant growth and development. The upregulation of glutathione and glycine metabolism enhances plant stress resistance. This study will provide a new way to scientifically and rationally evaluate the ecological risk of arsenic and regulate its toxicity.PMID:36934948 | DOI:10.1016/j.scitotenv.2023.162928

Sci Total Environ. 2023 Mar 17:162887. doi: 10.1016/j.scitotenv.2023.162887. Online ahead of print.ABSTRACTToxic heavy metals are common contaminants and will most likely interact with ubiquitous natural nanocolloids (Ncs) in the soil environment. However, the effect of soil Ncs on the fate and health risk of cadmium (Cd) have not been well addressed. Here, the interaction between Ncs and Cd is investigated using two-dimensional correlation spectroscopy (2DCOS) combined with synchronous fluorescence and Fourier transform infrared spectroscopy. Our results reveal that Cd binding to the soil Ncs surface is mainly driven through strong hydrophilic effects and π - π interactions, which contribute to a high adsorption capacity (366-612 mg/g) and strong affinity (KL = 4.3-9.7 L/mg) of Cd to soil Ncs. Interestingly, soil Ncs and Cd coexposure can significantly mediate the phytotoxicity (e.g., uptake, root growth, and oxidative stress) of Cd to rice (Oryza sativa L.) roots after 7 days of exposure. At the molecular level, metabolomic analysis reveals that the downregulated metabolic pathways (e.g., isoquinoline alkaloid and aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism) may contribute to the above adverse phytotoxicity. This study provides new insight into the effect of natural Ncs on the fate and health risks of toxic heavy metals in soil environments.PMID:36934947 | DOI:10.1016/j.scitotenv.2023.162887

Sci Total Environ. 2023 Mar 17:162898. doi: 10.1016/j.scitotenv.2023.162898. Online ahead of print.ABSTRACTUntargeted Nuclear Magnetic Resonance metabolomics was employed to study the effects of warming conditions (17-21 °C) and exposure to 17-α-ethinylestradiol (EE2) on the polar metabolome of Ruditapes philippinarum clams, to identify metabolic markers for monitoring/prediction of deviant environmental conditions. Warming alone triggered changes in alanine/aspartate/glutamate, aromatic amino acids, taurine/hypotaurine and homarine/trigonelline pathways, as well as in energy metabolism, suggesting osmoregulatory adaptations and glycolytic/tricarboxylic acid (TCA) cycle activation, possibly accompanied to some extent by gluconeogenesis to preserve glycogen reserves. At 17 °C, the lowest EE2 concentration (5 ng/L) specifically engaged branched-chain and aromatic amino acids to activate the glycolysis/TCA cycle. Notably, a partial metabolic recovery was observed at 25 ng/L, whereas higher EE2 concentrations (125 and 625 ng/L) again induced significant metabolic disturbances. These included enhanced glycogen biosynthesis and increased lipid reserves, sustained by low-level glutathione-based antioxidative mechanisms that seemed active. At 21 °C, response to EE2 was notably weak at low/intermediate concentrations, becoming particularly significant at the highest EE2 concentration (625 ng/L), suggesting higher protection capacity of Ruditapes philippinarum clams under warming conditions. At 625 ng/L, disturbances in alanine/aspartate/glutamate and taurine/hypotaurine metabolisms were observed, with no evidence of enhanced carbohydrate/protein catabolism. This low energy function profile was accompanied by marked antioxidative mechanisms and choline compounds modulation for cell membrane protection/repair. These results help monitor clams´ response to temperature rise and EE2 exposure, paving the way for future effective guidance and prediction of environmental damaging effects.PMID:36934939 | DOI:10.1016/j.scitotenv.2023.162898

Food Chem. 2023 Mar 8;417:135867. doi: 10.1016/j.foodchem.2023.135867. Online ahead of print.ABSTRACTTasmanian-farmed Atlantic salmon populations exhibit starvation followed by a reduced growth rate alongside reduced flesh pigmentation in response to elevated summer temperatures, which at times can exceed their optimum threshold. Here we investigated fatty acids and carotenoids of Atlantic salmon displaying three different flesh color phenotypes, using metabolomic and chemical analyses of lipids and pigments in six key tissues. Astaxanthin is mainly responsible for flesh pigmentation, while canthaxanthin is associated with carotenoid catabolism in the liver, as our findings indicate. Reduced flesh pigmentation correlated with lower levels of carotenoids across all tested tissues and clear evidence of a correlation between carotenoid and fatty acid levels in all detected fatty acid classes was observed. The reduced growth performance and flesh pigmentation are most likely due to the impact of varying levels of starvation on fatty acids and carotenoid profiles supporting the link between carotenoids and fatty acid metabolic processes.PMID:36934706 | DOI:10.1016/j.foodchem.2023.135867

J Hazard Mater. 2023 Mar 17;452:131226. doi: 10.1016/j.jhazmat.2023.131226. Online ahead of print.ABSTRACTCadmium (Cd) is highly toxic to all organisms including plants, and recently tryptophan (Trp) pretreatment of plant seedlings is shown to improve Cd tolerance. But the underlying mechanism remains largely unknown. In this study, we used Arabidopsis (Arabidopsis thaliana) to determine the physiological relevance of Trp pretreatment in alleviating Cd toxicity in plants and explore its molecular mechanism with a focus on the metabolic pathways. The results showed that Trp pretreatment maintained the biomass and root lengths, relieved Cd-induced lipid peroxidation, and reduced Cd transport to the shoots, and eventually improved the response against Cd in Arabidopsis seedlings. The integrative analyses of the transcriptome and metabolome further revealed that Trp pretreatment alleviated Cd toxicity not only through a known mechanism of producing a major auxin indole-3-acetic acid and maintaining its levels, but also through two previously unrecognized mechanisms: increasing the area and strength of cell walls by promoting lignification to further reduce Cd entry, and fine-tuning Cd detoxification products derived from sulfur-containing amino acid metabolism. Our findings thereby provide deep mechanical insights into how Trp alleviates Cd toxicity in plants.PMID:36934628 | DOI:10.1016/j.jhazmat.2023.131226

Nat Commun. 2023 Mar 18;14(1):1530. doi: 10.1038/s41467-023-37200-w.ABSTRACTEven in the setting of optimal resuscitation in high-income countries severe sepsis and septic shock have a mortality of 20-40%, with antibiotic resistance dramatically increasing this mortality risk. To develop a reference dataset enabling the identification of common bacterial targets for therapeutic intervention, we applied a standardized genomic, transcriptomic, proteomic and metabolomic technological framework to multiple clinical isolates of four sepsis-causing pathogens: Escherichia coli, Klebsiella pneumoniae species complex, Staphylococcus aureus and Streptococcus pyogenes. Exposure to human serum generated a sepsis molecular signature containing global increases in fatty acid and lipid biosynthesis and metabolism, consistent with cell envelope remodelling and nutrient adaptation for osmoprotection. In addition, acquisition of cholesterol was identified across the bacterial species. This detailed reference dataset has been established as an open resource to support discovery and translational research.PMID:36934086 | DOI:10.1038/s41467-023-37200-w

Phytomedicine. 2023 Feb 26;113:154732. doi: 10.1016/j.phymed.2023.154732. Online ahead of print.ABSTRACTBACKGROUND: New therapeutic approaches are required to improve the outcomes of lung cancer (LC), a leading cause of cancer-related deaths worldwide. Chinese herbal medicine formulae widely used in China provide a unique opportunity for improving LC treatment, and the Shuang-Huang-Sheng-Bai (SHSB) formula is a typical example. However, the underlying mechanisms of action remains unclear.PURPOSE: This study aimed to confirm the efficacy of SHSB against lung adenocarcinoma (LUAD), which is a major histological type of LC, unveil the downstream targets of this formula, and assess the clinical relevance and biological roles of the newly identified target.METHODS: An experimental metastasis mouse model and a subcutaneous xenograft mouse model were used to evaluate the anti-cancer activity of SHSB. Multi-omics profiling of subcutaneous tumors and metabolomic profiling of sera were performed to identify downstream targets, especially the metabolic targets of SHSB. A clinical trial was conducted to verify the newly identified metabolic targets in patients. Next, the metabolites and enzymes engaged in the metabolic pathway targeted by SHSB were measured in clinical samples. Finally, routine molecular experiments were performed to decipher the biological functions of the metabolic pathways targeted by SHSB.RESULTS: Oral SHSB administration showed overt anti-LUAD efficacy as revealed by the extended overall survival of the metastasis model and impaired growth of implanted tumors in the subcutaneous xenograft model. Mechanistically, SHSB administration altered protein expression in the post-transcriptional layer and modified the metabolome of LUAD xenografts. Integrative analysis demonstrated that SHSB markedly inhibited acetyl-CoA synthesis in tumors by post-transcriptionally downregulating ATP-citrate lyase (ACLY). Consistently, our clinical trial showed that oral SHSB administration declined serum acetyl-CoA levels of patients with LC. Moreover, acetyl-CoA synthesis and ACLY expression were both augmented in clinical LUAD tissues of patients, and high intratumoral ACLY expression predicted a detrimental prognosis. Finally, we showed that ACLY-mediated acetyl-CoA synthesis is essential for LUAD cell growth by promoting G1/S transition and DNA replication.CONCLUSION: Limited downstream targets of SHSB for LC treatment have been reported in previous hypothesis-driven studies. In this study, we conducted a comprehensive multi-omics investigation and demonstrated that SHSB exerted its anti-LUAD efficacy by actively and post-transcriptionally modulating protein expression and particularly restraining ACLY-mediated acetyl-CoA synthesis.PMID:36933457 | DOI:10.1016/j.phymed.2023.154732

Food Chem. 2023 Mar 13;417:135873. doi: 10.1016/j.foodchem.2023.135873. Online ahead of print.ABSTRACTTraditionally in Northern China, Acer truncatum leaves (ATL) have been used as herbal tea, now consumed worldwide. Few studies have reported ATL metabolites from different areas and their correlation with the environment. Thus, metabolomic analyses were conducted on ATL collected from twelve locations throughout four environmental zones in Northern China to understand the phytochemical differences with regards to environmental conditions. Sixty-four compounds, mostly flavonoids (FLAs) and gallic acid-containing natural products (GANPs), were characterized, including 34 previously unreported constituents from A. truncatum. Twenty-two markers were useful to differentiate ATL from the four environmental zones. Humidity, temperature, and sunshine duration are the predominant factors affecting FLAs and GANPs levels. Sunshine duration was positively correlated with eriodictyol (r = 0.994, p < 0.01), and humidity negatively with epicatechin gallate (r = -0.960, p < 0.05). These findings provide insights into ATL phytochemistry, aiding cultivation of A. truncatum tea with higher potential health benefits.PMID:36933422 | DOI:10.1016/j.foodchem.2023.135873

J Plant Physiol. 2023 Mar 7;284:153961. doi: 10.1016/j.jplph.2023.153961. Online ahead of print.ABSTRACTThe tubers of the widely distributed Cyperus esculentus are rich in oil, and therefore, the plant is considered to have a high utilization value in the vegetable oil industry. Oleosins and caleosins are lipid-associated proteins found in oil bodies of seeds; however oleosins and caleosins genes have not been identified in C. esculentus. In this study, we performed transcriptome sequencing and lipid metabolome analysis of C. esculentus tubers at four developmental stages to obtain the information on their genetic profile, expression trends, and metabolites in oil accumulation pathways. Overall, 120,881 non-redundant unigenes and 255 lipids were detected; 18 genes belonged to the acetyl-CoA carboxylase (ACC), malonyl-CoA:ACP transacylase (MCAT), β-ketoacyl-ACP synthase (KAS), and fatty acyl-ACP thioesterase (FAT) gene families involved in fatty acid biosynthesis, and 16 genes belonged to the glycerol-3-phosphate acyltransferase (GPAT), diacylglycerol acyltransferase 3 (DGAT3), phospholipid:diacylglycerol acyltransferase (PDAT), FAD2, and lysophosphatidic acid acyltransferase (LPAAT) gene families playing important roles in triacylglycerol synthesis. We also identified 9 oleosin- and 21 caleosin-encoding genes in C. esculentus tubers. These results provide detailed information on the C. esculentus transcriptional and metabolic profiles, which can be used as reference for the development of strategies to increase oil content in C. esculentus tubers.PMID:36933340 | DOI:10.1016/j.jplph.2023.153961

Anal Bioanal Chem. 2023 Mar 18. doi: 10.1007/s00216-023-04651-5. Online ahead of print.ABSTRACTThe determination of sudden cardiac death (SCD) is one of the difficult tasks in the forensic practice, especially in the absence of specific morphological changes in the autopsies and histological investigations. In this study, we combined the metabolic characteristics from corpse specimens of cardiac blood and cardiac muscle to predict SCD. Firstly, ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS)-based untargeted metabolomics was applied to obtain the metabolomic profiles of the specimens, and 18 and 16 differential metabolites were identified in the cardiac blood and cardiac muscle from the corpses of those who died of SCD, respectively. Several possible metabolic pathways were proposed to explain these metabolic alterations, including the metabolism of energy, amino acids, and lipids. Then, we validated the capability of these combinations of differential metabolites to distinguish between SCD and non-SCD through multiple machine learning algorithms. The results showed that stacking model integrated differential metabolites featured from the specimens showed the best performance with 92.31% accuracy, 93.08% precision, 92.31% recall, 91.96% F1 score, and 0.92 AUC. Our results revealed that the SCD metabolic signature identified by metabolomics and ensemble learning in cardiac blood and cardiac muscle has potential in SCD post-mortem diagnosis and metabolic mechanism investigations.PMID:36933055 | DOI:10.1007/s00216-023-04651-5

New Phytol. 2023 Mar 17. doi: 10.1111/nph.18886. Online ahead of print.ABSTRACTOne model of a disease-suppressive soil predicts that the confrontation of plant with a phytopathogen can lead to the recruitment and accumulation of beneficial microorganisms. However, more information is need to be deciphered regarding which beneficial microbes become enriched, and how the disease suppression is achieved. Here, we conditioned soil by continuously growing eight generations of cucumber inoculated with Fusarium oxysporum f.sp. cucumerinum in a split-root- system. Disease incidence was found to decrease gradually upon pathogen infection accompanied with higher quantity of reactive oxygen species (ROS mainly OH·) in roots and accumulation of Bacillus and Sphingomonas. These key microbes were proven to protect the cucumber from pathogen infection by inducing high ROS level in the roots through enrichment of pathways, including a two-component system, a bacterial secretion system and flagellar assembly revealed by metagenomics sequencing. Untargeted metabolomics analysis combined with in vitro application assays suggested that threonic acid and lysine were pivotal to recruit Bacillus and Sphingomonas. Collectively, our study deciphered a "cry for help" case wherein cucumber releases particular compounds to enrich beneficial microbes that raise the ROS level of host to prevent pathogen attack. More importantly, this may be one of the fundamental mechanisms underpinning disease-suppressive soil formation.PMID:36932631 | DOI:10.1111/nph.18886

BMC Infect Dis. 2023 Mar 17;23(1):164. doi: 10.1186/s12879-023-08123-0.ABSTRACTHIV-1 remains a global health concern and to date, nearly 38 million people are living with HIV. The complexity of HIV-1 pathogenesis and its subsequent prevalence is influenced by several factors including the HIV-1 subtype. HIV-1 subtype variation extends to sequence variation in the amino acids of the HIV-1 viral proteins. Of particular interest is the transactivation of transcription (Tat) protein due to its key function in viral transcription. The Tat protein predominantly functions by binding to the transactivation response (TAR) RNA element to activate HIV-1 transcriptional elongation. Subtype-specific Tat protein sequence variation influences Tat-TAR binding affinity. Despite several studies investigating Tat-TAR binding, it is not clear which regions of the Tat protein and/or individual Tat amino acid residues may contribute to TAR binding affinity. We, therefore, conducted a scoping review on studies investigating Tat-TAR binding. We aimed to synthesize the published data to determine (1) the regions of the Tat protein that may be involved in TAR binding, (2) key Tat amino acids involved in TAR binding and (3) if Tat subtype-specific variation influences TAR binding. A total of thirteen studies met our inclusion criteria and the key findings were that (1) both N-terminal and C-terminal amino acids outside the basic domain (47-59) may be important in increasing Tat-TAR binding affinity, (2) substitution of the amino acids Lysine and Arginine (47-59) resulted in a reduction in binding affinity to TAR, and (3) none of the included studies have investigated Tat subtype-specific substitutions and therefore no commentary could be made regarding which subtype may have a higher Tat-TAR binding affinity. Future studies investigating Tat-TAR binding should therefore use full-length Tat proteins and compare subtype-specific variations. Studies of such a nature may help explain why we see differential pathogenesis and prevalence when comparing HIV-1 subtypes.PMID:36932337 | DOI:10.1186/s12879-023-08123-0

Nutr Neurosci. 2023 Mar 17:1-10. doi: 10.1080/1028415X.2023.2188639. Online ahead of print.ABSTRACTNutrition is a modifiable risk factor for ischemic stroke. As people age their ability to absorb some nutrients decreases, a primary example is vitamin B12. Older individuals with a vitamin B12 deficiency are at a higher risk for ischemic stroke and have worse stroke outcome. However, the mechanisms through which these occur remain unknown. The aim of the study was to investigate the role of vitamin B12 deficiency in ischemic stroke outcome and mechanistic changes in a mouse model. Ten-month-old male and female mice were put on control or vitamin B12 deficient diets for 4 weeks prior to and after ischemic stroke to the sensorimotor cortex. Motor function was measured, and tissues were collected to assess potential mechanisms. All deficient mice had increased levels of total homocysteine in plasma and liver tissues. After ischemic stroke, deficient mice had impaired motor function compared to control mice. There was no difference between groups in ischemic damage volume. However, within the ischemic damage region, there was an increase in total apoptosis of male deficient mice compared to controls. Furthermore, there was an increase in neuronal survival in ischemic brain tissue of the vitamin B12 deficient mice compared to controls. Additionally, there were changes in choline metabolites in ischemic brain tissue because of a vitamin B12 deficiency. The data presented in this study confirms that a vitamin B12 deficiency worsens stroke outcome in male and female mice. The mechanisms driving this change may be a result of neuronal survival and compensation in choline metabolism within the damaged brain tissue.PMID:36932327 | DOI:10.1080/1028415X.2023.2188639

Sci China Life Sci. 2023 Mar 14. doi: 10.1007/s11427-022-2279-5. Online ahead of print.ABSTRACTThe gut microbiome of plant-eaters is affected by the food they eat, but it is currently unclear how the plant metabolome and microbiome are influenced by the substrate the plant grows in and how this subsequently impacts the feeding behavior and gut microbiomes of insect herbivores. Here, we use Plutella xylostella caterpillars and show that the larvae prefer leaves of cabbage plants growing in a vermiculite substrate to those from plants growing in conventional soil systems. From a plant metabolomics analysis, we identified 20 plant metabolites that were related to caterpillar feeding performance. In a bioassay, the effects of these plant metabolites on insects' feeding were tested. Nitrate and compounds enriched with leaves of soilless cultivation promoted the feeding of insects, while compounds enriched with leaves of plants growing in natural soil decreased feeding. Several microbial groups (e.g., Sporolactobacillus, Haliangium) detected inside the plant correlated with caterpillar feeding performance and other microbial groups, such as Ramlibacter and Methylophilus, correlated with the gut microbiome. Our results highlight the role of growth substrates on the food metabolome and microbiome and on the feeding performance and the gut microbiome of plant feeders. It illustrates how belowground factors can influence the aboveground properties of plant-animal systems, which has important implications for plant growth and pest control.PMID:36932313 | DOI:10.1007/s11427-022-2279-5