Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Effects of Pera Orange Juice and Moro Orange Juice in Healthy Rats: A Metabolomic Approach

Fri, 25/08/2023 - 12:00
Metabolites. 2023 Aug 2;13(8):902. doi: 10.3390/metabo13080902.ABSTRACTCardiovascular disease is a leading cause of death worldwide. Heart failure is a cardiovascular disease with high prevalence, morbidity, and mortality. Several natural compounds have been studied for attenuating pathological cardiac remodeling. Orange juice has been associated with cardiovascular disease prevention by attenuating oxidative stress. However, most studies have evaluated isolated phytochemicals rather than whole orange juice and usually under pathological conditions. In this study, we evaluated plasma metabolomics in healthy rats receiving Pera or Moro orange juice to identify possible metabolic pathways and their effects on the heart.METHODS: Sixty male Wistar rats were allocated into 3 groups: control (C), Pera orange juice (PO), and Moro orange juice (MO). PO and MO groups received Pera orange juice or Moro orange juice, respectively, and C received water with maltodextrin (100 g/L). Echocardiogram and euthanasia were performed after 4 weeks. Plasma metabolomic analysis was performed by high-resolution mass spectrometry. Type I collagen was evaluated in picrosirius red-stained slides and matrix metalloproteinase (MMP)-2 activity by zymography. MMP-9, tissue inhibitor of metalloproteinase (TIMP)-2, TIMP-4, type I collagen, and TNF-α protein expression were evaluated by Western blotting.RESULTS: We differentially identified three metabolites in PO (N-docosahexaenoyl-phenylalanine, diglyceride, and phosphatidylethanolamine) and six in MO (N-formylmaleamic acid, N2-acetyl-L-ornithine, casegravol isovalerate, abscisic alcohol 11-glucoside, cyclic phosphatidic acid, and torvoside C), compared to controls, which are recognized for their possible roles in cardiac remodeling, such as extracellular matrix regulation, inflammation, oxidative stress, and membrane integrity. Cardiac function, collagen level, MMP-2 activity, and MMP-9, TIMP-2, TIMP-4, type I collagen, and TNF-α protein expression did not differ between groups.CONCLUSION: Ingestion of Pera and Moro orange juice induces changes in plasma metabolites related to the regulation of extracellular matrix, inflammation, oxidative stress, and membrane integrity in healthy rats. Moro orange juice induces a larger number of differentially expressed metabolites than Pera orange juice. Alterations in plasma metabolomics induced by both orange juice are not associated with modifications in cardiac extracellular matrix components. Our results allow us to postulate that orange juice may have beneficial effects on pathological cardiac remodeling.PMID:37623846 | DOI:10.3390/metabo13080902

Metabolomic Profiling of Aqueous Humor from Pathological Myopia Patients with Choroidal Neovascularization

Fri, 25/08/2023 - 12:00
Metabolites. 2023 Jul 30;13(8):900. doi: 10.3390/metabo13080900.ABSTRACTChoroidal neovascularization (CNV) is a severe complication observed in individuals with pathological myopia (PM). Our hypothesis is that specific metabolic alterations occur during the development of CNV in patients with PM. To investigate this, an untargeted metabolomics analysis was conducted using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) on aqueous humor (AH) samples obtained from meticulously matched PM patients, including those with CNV (n = 11) and without CNV (n = 11). The analysis aimed to identify differentially expressed metabolites between the two groups. Furthermore, the discriminative ability of each metabolite was evaluated using the area under the receiver operating characteristic curve (AUC). Enriched metabolic pathways were determined using the KEGG and MetaboAnalyst databases. Our results revealed the detection of 272 metabolites using GC-MS and 1457 metabolites using LC-MS in AH samples. Among them, 97 metabolites exhibited significant differential expression between the CNV and non-CNV groups. Noteworthy candidates, including D-citramalic acid, biphenyl, and isoleucylproline, demonstrated high AUC values ranging from 0.801 to 1, indicating their potential as disease biomarkers. Additionally, all three metabolites showed a strong association with retinal cystoid edema in CNV patients. Furthermore, the study identified 12 altered metabolic pathways, with five of them related to carbohydrate metabolism, suggesting their involvement in the occurrence of myopic CNV. These findings provide possible disease-specific biomarkers of CNV in PM and suggest the role of disturbed carbohydrate metabolism in its pathogenesis. Larger studies are needed to validate these findings.PMID:37623844 | DOI:10.3390/metabo13080900

Untargeted Metabolomics and Body Mass in Adolescents: A Cross-Sectional and Longitudinal Analysis

Fri, 25/08/2023 - 12:00
Metabolites. 2023 Jul 30;13(8):899. doi: 10.3390/metabo13080899.ABSTRACTObesity in children and adolescents has increased globally. Increased body mass index (BMI) during adolescence carries significant long-term adverse health outcomes, including chronic diseases such as cardiovascular disease, stroke, diabetes, and cancer. Little is known about the metabolic consequences of changes in BMI in adolescents outside of typical clinical parameters. Here, we used untargeted metabolomics to assess changing BMI in male adolescents. Untargeted metabolomic profiling was performed on urine samples from 360 adolescents using UPLC-QTOF-MS. The study includes a baseline of 235 subjects in a discovery set and 125 subjects in a validation set. Of them, a follow-up of 81 subjects (1 year later) as a replication set was studied. Linear regression analysis models were used to estimate the associations of metabolic features with BMI z-score in the discovery and validation sets, after adjusting for age, race, and total energy intake (kcal) at false-discovery-rate correction (FDR) ≤ 0.1. We identified 221 and 16 significant metabolic features in the discovery and in the validation set, respectively. The metabolites associated with BMI z-score in validation sets are glycylproline, citrulline, 4-vinylsyringol, 3'-sialyllactose, estrone sulfate, carnosine, formiminoglutamic acid, 4-hydroxyproline, hydroxyprolyl-asparagine, 2-hexenoylcarnitine, L-glutamine, inosine, N-(2-Hydroxyphenyl) acetamide glucuronide, and galactosylhydroxylysine. Of those 16 features, 9 significant metabolic features were associated with a positive change in BMI in the replication set 1 year later. Histidine and arginine metabolism were the most affected metabolic pathways. Our findings suggest that obesity and its metabolic outcomes in the urine metabolome of children are linked to altered amino acids, lipid, and carbohydrate metabolism. These identified metabolites may serve as biomarkers and aid in the investigation of obesity's underlying pathological mechanisms. Whether these features are associated with the development of obesity, or a consequence of changing BMI, requires further study.PMID:37623843 | DOI:10.3390/metabo13080899

Metabolome Mining of <em>Curcuma longa</em> L. Using HPLC-MS/MS and Molecular Networking

Fri, 25/08/2023 - 12:00
Metabolites. 2023 Jul 29;13(8):898. doi: 10.3390/metabo13080898.ABSTRACTTurmeric, Curcuma longa L., is a type of medicinal plant characterized by its perennial nature and rhizomatous growth. It is a member of the Zingiberaceae family and is distributed across the world's tropical and subtropical climates, especially in South Asia. Its rhizomes have been highly valued for food supplements, spices, flavoring agents, and yellow dye in South Asia since ancient times. It exhibits a diverse array of therapeutic qualities that encompass its ability to combat diabetes, reduce inflammation, act as an antioxidant, exhibit anticancer properties, and promote anti-aging effects. In this study, organic extracts of C. longa rhizomes were subjected to HPLC separation followed by ESI-MS and low-energy tandem mass spectrometry analyses. The Global Natural Product Social Molecular Networking (GNPS) approach was utilized for the first time in this ethnobotanically important species to conduct an in-depth analysis of its metabolomes based on their fragments. To sum it up, a total of 30 metabolites including 16 diarylheptanoids, 1 diarylpentanoid, 3 bisabolocurcumin ethers, 4 sesquiterpenoids, 4 cinnamic acid derivatives, and 2 fatty acid derivatives were identified. Among the 16 diarylheptanoids identified in this study, 5 of them are reported for the first time in this species.PMID:37623841 | DOI:10.3390/metabo13080898

The Impact of Acute Low-Dose Gamma Irradiation on Biomass Accumulation and Secondary Metabolites Production in <em>Cotinus coggygria</em> Scop. and <em>Fragaria × ananassa</em> Duch. Red Callus Cultures

Fri, 25/08/2023 - 12:00
Metabolites. 2023 Jul 28;13(8):894. doi: 10.3390/metabo13080894.ABSTRACTCotinus coggygria Scop. (smoketree) and Fragaria × ananassa Duch. (strawberry) are two industrially important species due to their composition in bioactive compounds. In this study, we investigated the effects of acute low-dose gamma irradiation (15, 20, 25, 30, 35 and 40 Gy) on two red callus cultures established in smoketree and strawberry. The biomass production, dry weight, content of phenols, flavonoids, monomeric anthocyanins', index of anthocyanins polymerization and antioxidant activity were evaluated. For the smoketree callus, a negative correlation between irradiation doses and callus biomass accumulation was observed. For the strawberry callus, irradiation did not significantly affect the accumulation of the biomass. An increased dry weight was observed in irradiated smoketree callus, while for treated strawberry callus, a decrease was recorded. Irradiation with 30 Gy was stimulative for polyphenols' accumulation in both cultures; however, the increase was significant only in the strawberry callus. The flavonoids increased in the 30 Gy strawberry variants, while it significantly decreased in smoketree callus irradiated with 35 and 40 Gy. In irradiated strawberry callus, except for the 25 Gy variant (1.65 ± 0.4 mg C-3-GE/g DW), all treatments caused an increase in anthocyanins' accumulation. In smoketree, except for the 15 Gy variant (2.14 ± 0.66 mg C-3-GE/g DW), the irradiation determined an increase in anthocyanins synthesis, with the highest value being seen in the 20 Gy variant (2.8 ± 0.94 mg C-3-GE/g DW). According to UPLC-HRMS investigations, an unidentified compound increased by 99% at the 30 Gy dose in strawberry callus, while in smoketree, maslinic acid increased by 51% after irradiation with 40 Gy. The results of this study showed, for the first time, the differential response of two performant callus cultures to low-dose gamma irradiation, a biotechnological method that can be used to stimulate the synthesis of important flavonoids and triterpenes.PMID:37623838 | DOI:10.3390/metabo13080894

Metabolites Potentially Derived from Gut Microbiota Associated with Podocyte, Proximal Tubule, and Renal and Cerebrovascular Endothelial Damage in Early Diabetic Kidney Disease in T2DM Patients

Fri, 25/08/2023 - 12:00
Metabolites. 2023 Jul 28;13(8):893. doi: 10.3390/metabo13080893.ABSTRACTComplications due to type 2 diabetes mellitus (T2DM) such as diabetic kidney disease (DKD) and cerebral small vessel disease (CSVD) have a powerful impact on mortality and morbidity. Our current diagnostic markers have become outdated as T2DM-related complications continue to develop. The aim of the investigation was to point out the relationship between previously selected metabolites which are potentially derived from gut microbiota and indicators of endothelial, proximal tubule (PT), and podocyte dysfunction, and neurosonological indices. The study participants were 20 healthy controls and 90 T2DM patients divided into three stages: normoalbuminuria, microalbuminuria, and macroalbuminuria. Serum and urine metabolites were determined by untargeted and targeted metabolomic techniques. The markers of endothelial, PT and podocyte dysfunction were assessed by ELISA technique, and the neurosonological indices were provided by an ultrasound device with high resolution (MYLAB 8-ESAOTE Italy). The descriptive statistical analysis was followed by univariable and multivariable linear regression analyses. In conclusion, in serum, arginine (sArg), butenoylcarnitine (sBCA), and indoxyl sulfate (sIS) expressed a biomarker potential in terms of renal endothelial dysfunction and carotid atherosclerosis, whereas sorbitol (sSorb) may be a potential biomarker of blood-brain barrier (BBB) dysfunction. In urine, BCA and IS were associated with markers of podocyte damage, whereas PCS correlated with markers of PT dysfunction.PMID:37623837 | DOI:10.3390/metabo13080893

Integration of Metabolome and Transcriptome Reveals the Major Metabolic Pathways and Potential Biomarkers in Response to Freeze-Stress Regulation in Apple (<em>Malus domestica</em>)

Fri, 25/08/2023 - 12:00
Metabolites. 2023 Jul 27;13(8):891. doi: 10.3390/metabo13080891.ABSTRACTFreezing stress is the main factor affecting the normal growth and distribution of plants. The safe overwintering of a perennial deciduous plant is a crucial link to ensuring its survival and yield. However, little is known about the molecular mechanism of its gene regulation metabolites as related to its freeze-tolerance. In order to enhance our comprehension of freeze-tolerance metabolites and gene expression in dormant apple trees, we examined the metabolic and transcriptomic differences between 'Ralls' and 'Fuji', two apple varieties with varying degrees of resistance to freezing. The results of the freezing treatment showed that 'Ralls' had stronger freeze-tolerance than 'Fuji'. We identified 302, 334, and 267 up-regulated differentially accumulated metabolites (DAMs) and 408, 387, and 497 down-regulated DAMs between 'Ralls' and 'Fuji' under -10, -15, and -20 °C treatment, respectively. A total of 359 shared metabolites were obtained in the upward trend modules, of which 62 metabolites were associated with 89 pathways. The number of up-regulated genes accounted for 50.2%, 45.6%, and 43.2% of the total number of differentially expressed genes (DEGs), respectively, at -10, -15, and -20 °C. Through combined transcriptome and metabolome analysis, we identified 12 pathways that included 16 DAMs and 65 DEGs. Meanwhile, we found that 20 DEGs were identified in the phenylpropanoid biosynthesis pathway and its related pathways, involving the metabolism of p-Coumaroyl-CoA, 7, 4'-Dihydroxyflavone, and scolymoside. These discoveries advance our comprehension of the molecular mechanism underlying apple freeze-tolerance and provide genetic material for breeding apple cultivars with enhanced freeze-tolerance.PMID:37623835 | DOI:10.3390/metabo13080891

Evaluation of Metabolomics as Diagnostic Targets in Oral Squamous Cell Carcinoma: A Systematic Review

Fri, 25/08/2023 - 12:00
Metabolites. 2023 Jul 27;13(8):890. doi: 10.3390/metabo13080890.ABSTRACTIn recent years, high-throughput technologies have facilitated the widespread use of metabolomics to identify biomarkers and targets for oral squamous cell carcinoma (OSCC). As a result, the primary goal of this systematic review is to identify and evaluate metabolite biomarkers and their pathways for OSCC that featured consistently across studies despite methodological variations. Six electronic databases (Medline, Cochrane, Web of Science, CINAHL, ProQuest, and Embase) were reviewed for the longitudinal studies involving OSCC patients and metabolic marker analysis (in accordance with PRISMA 2020). The studies included ranged from the inception of metabolomics in OSCC (i.e., 1 January 2007) to 30 April 2023. The included studies were then assessed for their quality using the modified version of NIH quality assessment tool and QUADOMICS. Thirteen studies were included after screening 2285 studies. The majority of the studies were from South Asian regions, and metabolites were most frequently derived from saliva. Amino acids accounted for more than quarter of the detected metabolites, with glutamate and methionine being the most prominent. The top dysregulated metabolites indicated dysregulation of six significantly enriched pathways including aminoacyl-tRNA biosynthesis, glutathione metabolism and arginine biosynthesis with the false discovery rate (FDR) <0.05. Finally, this review highlights the potential of metabolomics for early diagnosis and therapeutic targeting of OSCC. However, larger studies and standardized protocols are needed to validate these findings and make them a clinical reality.PMID:37623834 | DOI:10.3390/metabo13080890

Non-Targeted Metabolomics Combined with Chemometrics by UHPLC-Orbitrap-HRMS and Antioxidant Activity of <em>Atractylodes chinensis</em> (DC.) Koidez. from Eight Origins

Fri, 25/08/2023 - 12:00
Metabolites. 2023 Jul 27;13(8):888. doi: 10.3390/metabo13080888.ABSTRACTAtractylodes chinensis (DC.) Koidez. (AC) is a type of Atractylodis Rhizoma that is widely used in China to treat diarrhea and arthritis, as well as a nutritional supplement. The objective of this study was to investigate and identify the phytochemicals in the aqueous extract of AC using an ultra-high-performance liquid chromatography (UHPLC)-Orbitrap-HRMS platform based on a non-targeted metabolomic approach. There were 76 compounds in the AC, the majority of which were phenylpropanoids (16) and terpenoids (15). The hierarchical clustering analysis (HCA) and principal component analysis (PCA) results revealed variations across eight AC samples and classified them into four groups. Using Pareto modeling, the orthogonal partial least squares-discriminant analysis (OPLS-DA) identified 11 distinct AC compounds. Furthermore, the antioxidant activity of eight AC samples was assessed using ABTS, DPPH, and OH· methods. The AC samples with concentrations ranging from 0 to 25 mg/mL had no toxic effects on A549 cells. They have a strong therapeutic potential against oxidation-related diseases, and further research on AC is warranted.PMID:37623832 | DOI:10.3390/metabo13080888

Integrated Analysis of Metabolomics Combined with Network Pharmacology and Molecular Docking Reveals the Effects of Processing on Metabolites of <em>Dendrobium officinale</em>

Fri, 25/08/2023 - 12:00
Metabolites. 2023 Jul 26;13(8):886. doi: 10.3390/metabo13080886.ABSTRACTDendrobium officinale (D. officinale) is a precious medicinal species of Dendrobium Orchidaceae, and the product obtained by hot processing is called "Fengdou". At present, the research on the processing quality of D. officinale mainly focuses on the chemical composition indicators such as polysaccharides and flavonoids content. However, the changes in metabolites during D. officinale processing are still unclear. In this study, the process was divided into two stages and three important conditions including fresh stems, semiproducts and "Fengdou" products. To investigate the effect of processing on metabolites of D. officinale in different processing stages, an approach of combining metabolomics with network pharmacology and molecular docking was employed. Through UPLC-MS/MS analysis, a total of 628 metabolites were detected, and 109 of them were identified as differential metabolites (VIP ≥ 1, |log2 (FC)| ≥ 1). Next, the differential metabolites were analyzed using the network pharmacology method, resulting in the selection of 29 differential metabolites as they have a potential pharmacological activity. Combining seven diseases, 14 key metabolites and nine important targets were screened by constructing a metabolite-target-disease network. The results showed that seven metabolites with potential anticoagulant, hypoglycemic and tumor-inhibiting activities increased in relative abundance in the "Fengdou" product. Molecular docking results indicated that seven metabolites may act on five important targets. In general, processing can increase the content of some active metabolites of D. officinale and improve its medicinal quality to a certain extent.PMID:37623830 | DOI:10.3390/metabo13080886

The Impacts of Slc19a3 Deletion and Intestinal SLC19A3 Insertion on Thiamine Distribution and Brain Metabolism in the Mouse

Fri, 25/08/2023 - 12:00
Metabolites. 2023 Jul 26;13(8):885. doi: 10.3390/metabo13080885.ABSTRACTThe Thiamine Transporter 2 (THTR2) encoded by SLC19A3 plays an ill-defined role in the maintenance of tissue thiamine, thiamine monophosphate, and thiamine diphosphate (TDP) levels. To evaluate the impact of THTR2 on tissue thiamine status and metabolism, we expressed the human SLC19A3 transgene in the intestine of total body Slc19a3 knockout (KO) mice. Male and female wildtype (WT) and transgenic (TG) mice were fed either 17 mg/kg (1×) or 85 mg/kg (5×) thiamine hydrochloride diet, while KOs were only fed the 5× diet. Thiamine vitamers in plasma, red blood cells, duodenum, brain, liver, kidney, heart, and adipose tissue were measured. Untargeted metabolomics were performed on the brain tissues of groups with equivalent plasma thiamine. KO mice had ~two- and ~three-fold lower plasma and brain thiamine levels than WT on the 5× diet. Circulating vitamers were sensitive to diet and equivalent in TG and WT mice. However, TG had 60% lower thiamine but normal brain TDP levels regardless of diet, with subtle differences in the heart and liver. The loss of THTR2 reduced levels of nucleic acid and amino acid derivatives in the brain. Therefore, mutation or inhibition of THTR2 may alter the brain metabolome and reduce the thiamine reservoir for TDP biosynthesis.PMID:37623829 | DOI:10.3390/metabo13080885

An Integrated Multi-OMICS Approach Highlights Elevated Non-Esterified Fatty Acids Impact BeWo Trophoblast Metabolism and Lipid Processing

Fri, 25/08/2023 - 12:00
Metabolites. 2023 Jul 25;13(8):883. doi: 10.3390/metabo13080883.ABSTRACTMaternal obesity and gestational diabetes mellitus (GDM) are linked with impaired placental function and early onset of non-communicable cardiometabolic diseases in offspring. Previous studies have highlighted that the dietary non-esterified fatty acids (NEFAs) palmitate (PA) and oleate (OA), key dietary metabolites associated with maternal obesity and GDM, are potential modulators of placental lipid processing. Using the BeWo cell line model, the current study integrated transcriptomic (mRNA microarray), metabolomic, and lipidomic readouts to characterize the underlying impacts of exogenous PA and OA on placental villous trophoblast cell metabolism. Targeted gas chromatography and thin-layer chromatography highlighted that saturated and monounsaturated NEFAs differentially impact BeWo cell lipid profiles. Furthermore, cellular lipid profiles differed when exposed to single and multiple NEFA species. Additional multi-omic analyses suggested that PA exposure is associated with enrichment in β-oxidation pathways, while OA exposure is associated with enrichment in anti-inflammatory and antioxidant pathways. Overall, this study further demonstrated that dietary PA and OA are important regulators of placental lipid metabolism. Encouraging appropriate dietary advice and implementing dietary interventions to maintain appropriate placental function by limiting excessive exposure to saturated NEFAs remain crucial in managing at-risk obese and GDM pregnancies.PMID:37623828 | DOI:10.3390/metabo13080883

Influence of Maternal Immune Activation and Stressors on the Hippocampal Metabolome

Fri, 25/08/2023 - 12:00
Metabolites. 2023 Jul 25;13(8):881. doi: 10.3390/metabo13080881.ABSTRACTPrenatal stress often results in maternal immune activation (MIA) that can impact prenatal brain development, molecular processes, and substrates and products of metabolism that participate in physiological processes at later stages of life. Postnatal metabolic and immunological stressors can affect brain metabolites later in life, independently or in combination with prenatal stressors. The effects of prenatal and postnatal stressors on hippocampal metabolites were studied using a pig model of viral MIA exposed to immunological and metabolic stressors at 60 days of age using gas chromatography mass spectrometry. Postnatal stress and MIA elicited effects (FDR-adjusted p-value < 0.1) on fifty-nine metabolites, while eight metabolites exhibited an interaction effect. The hippocampal metabolites impacted by MIA or postnatal stress include 4-aminobutanoate (GABA), adenine, fumarate, glutamate, guanine, inosine, ornithine, putrescine, pyruvate, and xanthine. Metabolites affected by MIA or postnatal stress encompassed eight significantly (FDR-adjusted p-value < 0.1) enriched Kyoto Encyclopedia of Genes and Genomes Database (KEGG) pathways. The enriched arginine biosynthesis and glutathione metabolism pathways included metabolites that are also annotated for the urea cycle and polyamine biosynthesis pathways. Notably, the prenatal and postnatal challenges were associated with disruption of the glutathione metabolism pathway and changes in the levels of glutamic acid, glutamate, and purine nucleotide metabolites that resemble patterns elicited by drugs of abuse and may underlie neuroinflammatory processes. The combination of MIA and postnatal stressors also supported the double-hit hypothesis, where MIA amplifies the impact of stressors later in life, sensitizing the hippocampus of the offspring to future challenges. The metabolites and pathways characterized in this study offer evidence of the role of immunometabolism in understanding the impact of MIA and stressors later in life on memory, spatial navigation, neuropsychiatric disorders, and behavioral disorders influenced by the hippocampus.PMID:37623825 | DOI:10.3390/metabo13080881

Improving rice eating and cooking quality by enhancing endogenous expression of a nitrogen-dependent floral regulator

Fri, 25/08/2023 - 12:00
Plant Biotechnol J. 2023 Aug 25. doi: 10.1111/pbi.14160. Online ahead of print.ABSTRACTImproving rice eating and cooking quality (ECQ) is one of the primary tasks in rice production to meet the rising demands of consumers. However, improving grain ECQ without compromising yield faces a great challenge under varied nitrogen (N) supplies. Here, we report the approach to upgrade rice ECQ by native promoter-controlled high expression of a key N-dependent floral and circadian clock regulator Nhd1. The amplification of endogenous Nhd1 abundance alters rice heading date but does not affect the entire length of growth duration, N use efficiency and grain yield under both low and sufficient N conditions. Enhanced expression of Nhd1 reduces amylose content, pasting temperature and protein content while increasing gel consistence in grains. Metabolome and transcriptome analyses revealed that increased expression of Nhd1 mainly regulates the metabolism of carbohydrates and amino acids in the grain filling stage. Moreover, expression level of Nhd1 shows a positive relationship with grain ECQ in some local main cultivars. Thus, intensifying endogenous abundance of Nhd1 is a promising strategy to upgrade grain ECQ in rice production.PMID:37623700 | DOI:10.1111/pbi.14160

Prospective of Pancreatic Cancer Diagnosis Using Cardiac Sensing

Fri, 25/08/2023 - 12:00
J Imaging. 2023 Jul 25;9(8):149. doi: 10.3390/jimaging9080149.ABSTRACTPancreatic carcinoma (Ca Pancreas) is the third leading cause of cancer-related deaths in the world. The malignancies of the pancreas can be diagnosed with the help of various imaging modalities. An endoscopic ultrasound with a tissue biopsy is so far considered to be the gold standard in terms of the detection of Ca Pancreas, especially for lesions <2 mm. However, other methods, like computed tomography (CT), ultrasound, and magnetic resonance imaging (MRI), are also conventionally used. Moreover, newer techniques, like proteomics, radiomics, metabolomics, and artificial intelligence (AI), are slowly being introduced for diagnosing pancreatic cancer. Regardless, it is still a challenge to diagnose pancreatic carcinoma non-invasively at an early stage due to its delayed presentation. Similarly, this also makes it difficult to demonstrate an association between Ca Pancreas and other vital organs of the body, such as the heart. A number of studies have proven a correlation between the heart and pancreatic cancer. The tumor of the pancreas affects the heart at the physiological, as well as the molecular, level. An overexpression of the SMAD4 gene; a disruption in biomolecules, such as IGF, MAPK, and ApoE; and increased CA19-9 markers are a few of the many factors that are noted to affect cardiovascular systems with pancreatic malignancies. A comprehensive review of this correlation will aid researchers in conducting studies to help establish a definite relation between the two organs and discover ways to use it for the early detection of Ca Pancreas.PMID:37623681 | DOI:10.3390/jimaging9080149

Strategies for the Development of Industrial Fungal Producing Strains

Fri, 25/08/2023 - 12:00
J Fungi (Basel). 2023 Aug 8;9(8):834. doi: 10.3390/jof9080834.ABSTRACTThe use of microorganisms in industry has enabled the (over)production of various compounds (e.g., primary and secondary metabolites, proteins and enzymes) that are relevant for the production of antibiotics, food, beverages, cosmetics, chemicals and biofuels, among others. Industrial strains are commonly obtained by conventional (non-GMO) strain improvement strategies and random screening and selection. However, recombinant DNA technology has made it possible to improve microbial strains by adding, deleting or modifying specific genes. Techniques such as genetic engineering and genome editing are contributing to the development of industrial production strains. Nevertheless, there is still significant room for further strain improvement. In this review, we will focus on classical and recent methods, tools and technologies used for the development of fungal production strains with the potential to be applied at an industrial scale. Additionally, the use of functional genomics, transcriptomics, proteomics and metabolomics together with the implementation of genetic manipulation techniques and expression tools will be discussed.PMID:37623605 | DOI:10.3390/jof9080834

Light-Induced Changes in Secondary Metabolite Production of <em>Trichoderma atroviride</em>

Fri, 25/08/2023 - 12:00
J Fungi (Basel). 2023 Jul 26;9(8):785. doi: 10.3390/jof9080785.ABSTRACTMany studies aim at maximizing fungal secondary metabolite production but the influence of light during cultivation has often been neglected. Here, we combined an untargeted isotope-assisted liquid chromatography-high-resolution mass spectrometry-based metabolomics approach with standardized cultivation of Trichoderma atroviride under three defined light regimes (darkness (PD), reduced light (RL) exposure, and 12/12 h light/dark cycle (LD)) to systematically determine the effect of light on secondary metabolite production. Comparative analyses revealed a similar metabolite profile upon cultivation in PD and RL, whereas LD treatment had an inhibiting effect on both the number and abundance of metabolites. Additionally, the spatial distribution of the detected metabolites for PD and RL was analyzed. From the more than 500 detected metabolites, only 25 were exclusively produced upon fungal growth in darkness and 85 were significantly more abundant in darkness. The majority were detected under both cultivation conditions and annotation revealed a cluster of substances whose production followed the pattern observed for the well-known T. atroviride metabolite 6-pentyl-alpha-pyrone. We conclude that cultivation of T. atroviride under RL can be used to maximize secondary metabolite production.PMID:37623556 | DOI:10.3390/jof9080785

Editorial for the Special Issue "Advanced Research in Plant Metabolomics"

Fri, 25/08/2023 - 12:00
Curr Issues Mol Biol. 2023 Aug 14;45(8):6701-6703. doi: 10.3390/cimb45080423.ABSTRACTThe study of plant metabolome and the role of cellular pathway end products has gained increased attention [...].PMID:37623242 | DOI:10.3390/cimb45080423

Boldine Alters Serum Lipidomic Signatures after Acute Spinal Cord Transection in Male Mice

Fri, 25/08/2023 - 12:00
Int J Environ Res Public Health. 2023 Aug 17;20(16):6591. doi: 10.3390/ijerph20166591.ABSTRACTTraumatic spinal cord injury (SCI) results in wide-ranging cellular and systemic dysfunction in the acute and chronic time frames after the injury. Chronic SCI has well-described secondary medical consequences while acute SCI has unique metabolic challenges as a result of physical trauma, in-patient recovery and other post-operative outcomes. Here, we used high resolution mass spectrometry approaches to describe the circulating lipidomic and metabolomic signatures using blood serum from mice 7 d after a complete SCI. Additionally, we probed whether the aporphine alkaloid, boldine, was able to prevent SCI-induced changes observed using these 'omics platforms'. We found that SCI resulted in large-scale changes to the circulating lipidome but minimal changes in the metabolome, with boldine able to reverse or attenuate SCI-induced changes in the abundance of 50 lipids. Multiomic integration using xMWAS demonstrated unique network structures and community memberships across the groups.PMID:37623175 | DOI:10.3390/ijerph20166591

Biosensors with Boronic Acid-Based Materials as the Recognition Elements and Signal Labels

Fri, 25/08/2023 - 12:00
Biosensors (Basel). 2023 Aug 3;13(8):785. doi: 10.3390/bios13080785.ABSTRACTIt is of great importance to have sensitive and accurate detection of cis-diol-containing biologically related substances because of their important functions in the research fields of metabolomics, glycomics, and proteomics. Boronic acids can specifically and reversibly interact with 1,2- or 1,3-diols to form five or six cyclic esters. Based on this unique property, boronic acid-based materials have been used as synthetic receptors for the specific recognition and detection of cis-diol-containing species. This review critically summarizes the recent advances with boronic acid-based materials as recognition elements and signal labels for the detection of cis-diol-containing biological species, including ribonucleic acids, glycans, glycoproteins, bacteria, exosomes, and tumor cells. We also address the challenges and future perspectives for developing versatile boronic acid-based materials with various promising applications.PMID:37622871 | DOI:10.3390/bios13080785

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