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

Daily Vinegar Ingestion Improves Depression and Enhances Niacin Metabolism in Overweight Adults: A Randomized Controlled Trial

Sat, 27/07/2024 - 12:00
Nutrients. 2024 Jul 18;16(14):2305. doi: 10.3390/nu16142305.ABSTRACTDepressive disorders are the most prevalent mental health conditions in the world. The commonly prescribed antidepressant medications can have serious side effects, and their efficacy varies widely. Thus, simple, effective adjunct therapies are needed. Vinegar, a fermented acetic acid solution, is emerging as a healthful dietary supplement linked to favorable outcomes for blood glucose management, heart disease risk, and adiposity reduction, and a recent report suggests vinegar may improve symptoms of depression. This randomized controlled study examined the 4-week change in scores for the Center for Epidemiological Studies Depression (CES-D) questionnaire and the Patient Health Questionnaire (PHQ-9) in healthy overweight adults ingesting 2.95 g acetic acid (4 tablespoons vinegar) vs. 0.025 g acetic acid (one vinegar pill) daily. A secondary objective explored possible underlying mechanisms using metabolomics analyses. At week 4, mean CES-D scores fell 26% and 5% for VIN and CON participants respectively, a non-significant difference between groups, and mean PHQ-9 scores fell 42% and 18% for VIN and CON participants (p = 0.036). Metabolomics analyses revealed increased nicotinamide concentrations and upregulation of the NAD+ salvage pathway for VIN participants compared to controls, metabolic alterations previously linked to improved mood. Thus, daily vinegar ingestion over four weeks improved self-reported depression symptomology in healthy overweight adults, and enhancements in niacin metabolism may factor into this improvement.PMID:39064748 | DOI:10.3390/nu16142305

Does Microbiome Matter in Chronic Intestinal Failure Due to Type 1 Short Bowel Syndrome in Adults?

Sat, 27/07/2024 - 12:00
Nutrients. 2024 Jul 16;16(14):2282. doi: 10.3390/nu16142282.ABSTRACTThe exact microbiome composition and function of patients with Short Bowel Syndrome (SBS) and Chronic Intestinal Failure (CIF) are still unknown. Patients with type I SBS-CIF (end-jejunostomy/ileostomy) are little represented in available studies. The aim of this study is to evaluate the microbiome characteristics of adult type 1 SBS-CIF patients according to their clinical features. Fecal microbiota was studied by amplicon-based sequencing and volatile organic compounds (VOCs) were assessed by solid-phase microextraction and gas chromatography-mass spectrometry. A total of 44 adult type 1 SBS-CIF patients were enrolled. At the family level, Lactobacillaceae (38% of the relative frequency) and Streptococcaceae (24%) were predominant; at the genus level, Streptococcus (38% of the relative frequency) and Lactobacillus (24%) were the dominant amplicon sequence variants (ASVs). Patients with increased stomal output showed higher ASVs for Lactobacillus (Rho = +0.38; p = 0.010), which was confirmed after adjusting for small bowel length (OR = 1.04; 95% CI 1.01-1.07, p = 0.023). Hyperphagia was associated with higher concentrations of short-chain fatty acid (SCFA) esters, such as butanoic acid ethyl ester (p = 0.005) and hexanoic acid ethyl ester (p = 0.004). Dietary fiber intake was directly correlated with most VOCs. Hyperphagia was associated with dietary fiber, after adjusting for small bowel length (OR = 1.35; 95% CI 1.01-1.81; p = 0.040). In type 1 SBS-CIF patients, a greater frequency of Lactobacilli was associated with increased stomal outputs, while increased fiber intake and concentrations of SCFA esters were associated with hyperphagia. These results might have implications for clinical practice.PMID:39064725 | DOI:10.3390/nu16142282

Diet Supplemented with Special Formula Milk Powder Promotes the Growth of the Brain in Rats

Sat, 27/07/2024 - 12:00
Nutrients. 2024 Jul 9;16(14):2188. doi: 10.3390/nu16142188.ABSTRACTThis investigation was to study the effects of different formula components on the brain growth of rats. Fifty male SD rats were randomly divided into five groups: a basic diet group; a 20% ordinary milk powder group; a 20% special milk powder group; a 30% ordinary milk powder group; and a 30% special milk powder group by weight. LC-MS was used to detect brain lipidomics. After 28 days of feeding, compared with the basic diet group, the brain/body weights of rats in the 30% ordinary milk powder group were increased. The serum levels of 5-HIAA in the 30% ordinary milk powder group were lower than in the 20% ordinary milk powder group. Compared with the basic diet group, the expressions of DLCL, MePC, PI, and GM1 were higher in the groups with added special milk powder, while the expressions of LPE, LdMePE, SM, and MGTG were higher in the groups with added ordinary milk powder. The expression of MBP was significantly higher in the 20% ordinary group. This study found that different formula components of infant milk powder could affect brain growth in SD rats. The addition of special formula infant milk powder may have beneficial effects on rat brains by regulating brain lipid expression.PMID:39064631 | DOI:10.3390/nu16142188

Progranulin and Vaspin as Potential Novel Markers in the Etiology of Type 1 Diabetes in Children

Sat, 27/07/2024 - 12:00
Medicina (Kaunas). 2024 Jul 19;60(7):1165. doi: 10.3390/medicina60071165.ABSTRACTBackground and Objectives: Diabetes is a significant health problem, prompting the search for new therapeutic strategies. Recently, researchers have focused on identifying novel markers for the progression of this condition. It is well established that adipokines, such as progranulin and vaspin, play crucial roles in regulating lipid and carbohydrate metabolism. Materials and Methods: This single-center cross-sectional study aimed to assess serum progranulin and vaspin levels in 80 children diagnosed with type 1 diabetes (T1D) and to examine their correlation with body mass index (BMI), glycated hemoglobin, and lipid profile. The cohort included 40 children newly diagnosed with diabetes, 40 children with long-term diabetes (20 well-controlled and 20 poorly controlled), and 14 non-diabetic children as a control group. Progranulin and vaspin levels were determined using a sandwich enzyme-linked immunosorbent assay. Results: There were no significant differences in the progranulin and vaspin concentrations in the studied groups (p = 0.246 and p = 0.095, respectively). No statistically significant differences were noted in the levels of both adipokines among boys and girls within the T1D, well-controlled T1D, and poorly controlled T1D groups. We did not find any differences in the progranulin and vaspin levels among all children with T1D and healthy controls when divided based on BMI percentiles. A negative correlation was observed between progranulin concentration and the age of children in the T1D, well-controlled T1D, and healthy groups. Furthermore, progranulin correlated negatively with BMI among children with T1D. In contrast, vaspin concentration correlated positively with age among healthy children. Conclusions: Our study provides novel insights into the status of progranulin and vaspin among pediatric participants with varying levels of type 1 diabetes control. However, further research involving larger patient cohorts and different stages of sexual maturation is warranted.PMID:39064594 | DOI:10.3390/medicina60071165

Bioinformatics in Neonatal/Pediatric Medicine-A Literature Review

Sat, 27/07/2024 - 12:00
J Pers Med. 2024 Jul 18;14(7):767. doi: 10.3390/jpm14070767.ABSTRACTBioinformatics is a scientific field that uses computer technology to gather, store, analyze, and share biological data and information. DNA sequences of genes or entire genomes, protein amino acid sequences, nucleic acid, and protein-nucleic acid complex structures are examples of traditional bioinformatics data. Moreover, proteomics, the distribution of proteins in cells, interactomics, the patterns of interactions between proteins and nucleic acids, and metabolomics, the types and patterns of small-molecule transformations by the biochemical pathways in cells, are further data streams. Currently, the objectives of bioinformatics are integrative, focusing on how various data combinations might be utilized to comprehend organisms and diseases. Bioinformatic techniques have become popular as novel instruments for examining the fundamental mechanisms behind neonatal diseases. In the first few weeks of newborn life, these methods can be utilized in conjunction with clinical data to identify the most vulnerable neonates and to gain a better understanding of certain mortalities, including respiratory distress, bronchopulmonary dysplasia, sepsis, or inborn errors of metabolism. In the current study, we performed a literature review to summarize the current application of bioinformatics in neonatal medicine. Our aim was to provide evidence that could supply novel insights into the underlying mechanism of neonatal pathophysiology and could be used as an early diagnostic tool in neonatal care.PMID:39064021 | DOI:10.3390/jpm14070767

Immature Surfactant Protein Type B and Surfactant Protein Type D Correlate with Coronary Heart Disease in Patients with Type 2 Diabetes

Sat, 27/07/2024 - 12:00
Life (Basel). 2024 Jul 17;14(7):886. doi: 10.3390/life14070886.ABSTRACTBACKGROUND: Different specific surfactant proteins (SPs) have been associated with various pathological conditions, not only of the respiratory system, but also more recently with cardiovascular diseases, such as heart failure. The aim of the present study was to evaluate the role of SP-A, SP-D, and the precursor protein of SP-B (proSP-B) in the pathogenesis of cardiovascular damage in patients affected by type 2 diabetes (T2D).METHODS: The study considered 31 patients with T2D (DN group), 34 patients with both T2D and coronary heart disease (CHD) (DC group), and 30 patients without diabetes but with a diagnosis of CHD (NC group). SP-A, SP-D, and proSP-B concentrations were determined in plasma samples, and were statistically compared using parametric and multivariate methods.RESULTS: Higher plasma concentrations of SP-D and proSP-B were found in patients affected by both T2D and CHD (DC group), and in patients with CHD without diabetes (NC group), in comparison to T2D patients (DN group). A significant correlation, both with linear regression (r = 0.3565, p = 0.001) and Principal Component Analysis (PCA), was found between the plasma levels of SP-D and proSP-B in the overall cohort of patients. No differences in SP-A were observed among the three groups of subjects.CONCLUSION: The present study extends the knowledge on the role of plasma SPs' levels as possible indicators of the risk of CHD being linked to T2D disease progression.PMID:39063639 | DOI:10.3390/life14070886

Technology and Future of Multi-Cancer Early Detection

Sat, 27/07/2024 - 12:00
Life (Basel). 2024 Jun 29;14(7):833. doi: 10.3390/life14070833.ABSTRACTCancer remains a significant global health challenge due to its high morbidity and mortality rates. Early detection is essential for improving patient outcomes, yet current diagnostic methods lack the sensitivity and specificity needed for identifying early-stage cancers. Here, we explore the potential of multi-omics approaches, which integrate genomic, transcriptomic, proteomic, and metabolomic data, to enhance early cancer detection. We highlight the challenges and benefits of data integration from these diverse sources and discuss successful examples of multi-omics applications in other fields. By leveraging these advanced technologies, multi-omics can significantly improve the sensitivity and specificity of early cancer diagnostics, leading to better patient outcomes and more personalized cancer care. We underscore the transformative potential of multi-omics approaches in revolutionizing early cancer detection and the need for continued research and clinical integration.PMID:39063587 | DOI:10.3390/life14070833

Light Flux Density and Photoperiod Affect Growth and Secondary Metabolism in Fully Expanded Basil Plants

Sat, 27/07/2024 - 12:00
Foods. 2024 Jul 18;13(14):2273. doi: 10.3390/foods13142273.ABSTRACTIndoor production of basil (Ocimum basilicum L.) is influenced by light spectrum, photosynthetic photon flux density (PPFD), and the photoperiod. To investigate the effects of different lighting on growth, chlorophyll content, and secondary metabolism, basil plants were grown from seedlings to fully expanded plants in microcosm devices under different light conditions: (a) white light at 250 and 380 μmol·m-2·s-1 under 16/8 h light/dark and (b) white light at 380 μmol·m-2·s-1 under 16/8 and 24/0 h light/dark. A higher yield was recorded under 380 μmol·m-2·s-1 compared to 250 μmol·m-2·s-1 (fresh and dry biomasses 260.6 ± 11.3 g vs. 144.9 ± 14.6 g and 34.1 ± 2.6 g vs. 13.2 ± 1.4 g, respectively), but not under longer photoperiods. No differences in plant height and chlorophyll content index were recorded, regardless of the PPFD level and photoperiod length. Almost the same volatile organic compounds (VOCs) were detected under the different lighting treatments, belonging to terpenes, aldehydes, alcohols, esters, and ketones. Linalool, eucalyptol, and eugenol were the main VOCs regardless of the lighting conditions. The multivariate data analysis showed a sharp separation of non-volatile metabolites in apical and middle leaves, but this was not related to different PPFD levels. Higher levels of sesquiterpenes and monoterpenes were detected in plants grown under 250 μmol·m-2·s-1 and 380 μmol·m-2·s-1, respectively. A low separation of non-volatile metabolites based on the photoperiod length and VOC overexpression under longer photoperiods were also highlighted.PMID:39063357 | DOI:10.3390/foods13142273

Dietary Energy and Protein Levels Influence the Mutton Quality and Metabolomic Profile of the Yunshang Black Goat

Sat, 27/07/2024 - 12:00
Foods. 2024 Jul 18;13(14):2271. doi: 10.3390/foods13142271.ABSTRACTThis study aimed to evaluate the impact of dietary energy and protein levels on the meat quality and metabolomic profile of Yunshang black goats. For this, 80 Yunshang black goats (male, 6 months old, with a mean live body weight of 35.82 ± 2.79 kg) were used in a completely randomized design with a 2 × 2 factorial dietary arrangement. The dietary treatments were (1) high energy (9.74 MJ/kg) with high protein (12.99%) (HEHP), (2) high energy (9.76 MJ/kg) with low protein (10.01%) (HELP), (3) low energy (8.18 MJ/kg) with high protein (13.04%) (LEHP), and (4) low energy (8.14 MJ/kg) with low protein (10.05%) (LELP). The experiment lasted 64 days, including 14 days for dietary adaptation and a 50-day feeding trial. At the end of the experiment, four animals from each treatment were slaughtered to assess their meat quality and metabolomic profiles. The pH value was greater for the goats fed the LELP diet compared with the other treatments. The LEHP-fed group's meat was brighter (L*) than that of the other three groups. The HEHP-fed group had considerably more tender meat (p < 0.05) compared with the LEHP-fed group. Moreover, 72 and 183 differentiated metabolites were detected in the longissimus muscle samples by using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry, respectively. The hydropathy and volatilities of raw meat were different (p < 0.05), suggesting changes in the meat flavor because of the dietary treatments. Based on the results, it can be concluded that feeding a high-energy- and high-protein-containing diet improved the tenderness, flavor, and fatty acid contents of mutton.PMID:39063355 | DOI:10.3390/foods13142271

Step-by-Step Metagenomics for Food Microbiome Analysis: A Detailed Review

Sat, 27/07/2024 - 12:00
Foods. 2024 Jul 14;13(14):2216. doi: 10.3390/foods13142216.ABSTRACTThis review article offers a comprehensive overview of the current understanding of using metagenomic tools in food microbiome research. It covers the scientific foundation and practical application of genetic analysis techniques for microbial material from food, including bioinformatic analysis and data interpretation. The method discussed in the article for analyzing microorganisms in food without traditional culture methods is known as food metagenomics. This approach, along with other omics technologies such as nutrigenomics, proteomics, metabolomics, and transcriptomics, collectively forms the field of foodomics. Food metagenomics allows swift and thorough examination of bacteria and potential metabolic pathways by utilizing foodomic databases. Despite its established scientific basis and available bioinformatics resources, the research approach of food metagenomics outlined in the article is not yet widely implemented in industry. The authors believe that the integration of next-generation sequencing (NGS) with rapidly advancing digital technologies such as artificial intelligence (AI), the Internet of Things (IoT), and big data will facilitate the widespread adoption of this research strategy in microbial analysis for the food industry. This adoption is expected to enhance food safety and product quality in the near future.PMID:39063300 | DOI:10.3390/foods13142216

Metabolomics and Biochemical Benefits of Multivitamin and Multimineral Supplementation in Healthy Individuals: A Pilot Study

Sat, 27/07/2024 - 12:00
Foods. 2024 Jul 13;13(14):2207. doi: 10.3390/foods13142207.ABSTRACTScientific evidence regarding the effectiveness of vitamin and mineral supplements in healthy individuals remains scarce. In a randomized, double-blind study, 30 healthy individuals were assigned to receive a single daily dose of multivitamin and multimineral supplementation or a double daily dose for 30 days. Before and after the intake, an untargeted metabolomics assay for serum metabolites was conducted by hydrophilic interaction liquid chromatography-mass spectrometry, and clinical assessments of peripheral blood samples were performed. A paired t-test for metabolic analysis, adjusted using the false discovery rate (FDR) and p-value correction method (rate of change > 2 and FDR < 0.05), the Shapiro-Wilk test, Student's t-test, and the Mann-Whitney U test were applied depending on the variable, with a 5% significance level. An impact on oxidative stress was observed, with a significant reduction in homocysteine levels and an increment of pyridoxic acid (vitamin B6). The effect on energy metabolism was shown by a significant increase in diverse metabolites, such as linoleoylcarnitine. Serum iron and calcium levels were also impacted. Overall, we observed a nutritional balance compatible with a good state of health. In conclusion, beneficial effects on adult health were demonstrated in relation to oxidative stress, energy metabolism, and nutritional balance.PMID:39063291 | DOI:10.3390/foods13142207

A Comparison Analysis of Quality and Metabolic Compounds in Lilies with Different Drying Treatments

Sat, 27/07/2024 - 12:00
Foods. 2024 Jul 13;13(14):2206. doi: 10.3390/foods13142206.ABSTRACTThe present study aimed to investigate the variations in the nutritional composition, antioxidant capacity, and metabolite profile of lilies subjected to different drying treatments, including vacuum freeze drying (VFD), hot air drying (HAD), vacuum drying (VD), and infrared drying (ID). The results show that VFD provided better preservation of the original coloration and displayed the highest levels of total amino acid content, total phenolic content, total flavonoid content, and polysaccharide and alkaloid content. Our results reveal that VFD treatment can be employed to obtain high-quality lilies with desirable appearance characteristics and nutrient compositions. Metabolomics analysis identified a total of 464 metabolites from various dried lilies. Differential metabolite screening found 150 differential metabolites across all pairwise comparisons. Hierarchical clustering analysis (HCA) indicated that lilies subjected to VFD treatment exhibited a higher abundance of steroids, saponin, flavonoids, and phenolic glycoside, whereas those subjected to HAD, VD, or ID treatments showed relatively elevated levels of specific amino acids or derivatives. This study elucidates the significant impact of various drying treatments on the quality and metabolic profile of lilies, thereby providing valuable insights for enhancing the nutritional quality of processed lilies.PMID:39063290 | DOI:10.3390/foods13142206

The Mechanism of Action of L-Tyrosine Derivatives against Chikungunya Virus Infection In Vitro Depends on Structural Changes

Sat, 27/07/2024 - 12:00
Int J Mol Sci. 2024 Jul 21;25(14):7972. doi: 10.3390/ijms25147972.ABSTRACTAlthough the disease caused by chikungunya virus (CHIKV) is of great interest to public health organizations around the world, there are still no authorized antivirals for its treatment. Previously, dihalogenated anti-CHIKV compounds derived from L-tyrosine (dH-Y) were identified as being effective against in vitro infection by this virus, so the objective of this study was to determine the mechanisms of its antiviral action. Six dH-Y compounds (C1 to C6) dihalogenated with bromine or chlorine and modified in their amino groups were evaluated by different in vitro antiviral strategies and in silico tools. When the cells were exposed before infection, all compounds decreased the expression of viral proteins; only C4, C5 and C6 inhibited the genome; and C1, C2 and C3 inhibited infectious viral particles (IVPs). Furthermore, C1 and C3 reduce adhesion, while C2 and C3 reduce internalization, which could be related to the in silico interaction with the fusion peptide of the E1 viral protein. Only C3, C4, C5 and C6 inhibited IVPs when the cells were exposed after infection, and their effect occurred in late stages after viral translation and replication, such as assembly, and not during budding. In summary, the structural changes of these compounds determine their mechanism of action. Additionally, C3 was the only compound that inhibited CHIKV infection at different stages of the replicative cycle, making it a compound of interest for conversion as a potential drug.PMID:39063216 | DOI:10.3390/ijms25147972

Circulating Liquid Biopsy Biomarkers in Glioblastoma: Advances and Challenges

Sat, 27/07/2024 - 12:00
Int J Mol Sci. 2024 Jul 21;25(14):7974. doi: 10.3390/ijms25147974.ABSTRACTGliomas, particularly glioblastoma (GBM), represent the most prevalent and aggressive tumors of the central nervous system (CNS). Despite recent treatment advancements, patient survival rates remain low. The diagnosis of GBM traditionally relies on neuroimaging methods such as magnetic resonance imaging (MRI) or computed tomography (CT) scans and postoperative confirmation via histopathological and molecular analysis. Imaging techniques struggle to differentiate between tumor progression and treatment-related changes, leading to potential misinterpretation and treatment delays. Similarly, tissue biopsies, while informative, are invasive and not suitable for monitoring ongoing treatments. These challenges have led to the emergence of liquid biopsy, particularly through blood samples, as a promising alternative for GBM diagnosis and monitoring. Presently, blood and cerebrospinal fluid (CSF) sampling offers a minimally invasive means of obtaining tumor-related information to guide therapy. The idea that blood or any biofluid tests can be used to screen many cancer types has huge potential. Tumors release various components into the bloodstream or other biofluids, including cell-free nucleic acids such as microRNAs (miRNAs), circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), proteins, extracellular vesicles (EVs) or exosomes, metabolites, and other factors. These factors have been shown to cross the blood-brain barrier (BBB), presenting an opportunity for the minimally invasive monitoring of GBM as well as for the real-time assessment of distinct genetic, epigenetic, transcriptomic, proteomic, and metabolomic changes associated with brain tumors. Despite their potential, the clinical utility of liquid biopsy-based circulating biomarkers is somewhat constrained by limitations such as the absence of standardized methodologies for blood or CSF collection, analyte extraction, analysis methods, and small cohort sizes. Additionally, tissue biopsies offer more precise insights into tumor morphology and the microenvironment. Therefore, the objective of a liquid biopsy should be to complement and enhance the diagnostic accuracy and monitoring of GBM patients by providing additional information alongside traditional tissue biopsies. Moreover, utilizing a combination of diverse biomarker types may enhance clinical effectiveness compared to solely relying on one biomarker category, potentially improving diagnostic sensitivity and specificity and addressing some of the existing limitations associated with liquid biomarkers for GBM. This review presents an overview of the latest research on circulating biomarkers found in GBM blood or CSF samples, discusses their potential as diagnostic, predictive, and prognostic indicators, and discusses associated challenges and future perspectives.PMID:39063215 | DOI:10.3390/ijms25147974

Metabolic Shift in Porcine Spermatozoa during Sperm Capacitation-Induced Zinc Flux

Sat, 27/07/2024 - 12:00
Int J Mol Sci. 2024 Jul 19;25(14):7919. doi: 10.3390/ijms25147919.ABSTRACTMammalian spermatozoa rely on glycolysis and mitochondrial oxidative phosphorylation for energy leading up to fertilization. Sperm capacitation involves a series of well-regulated biochemical steps that are necessary to give spermatozoa the ability to fertilize the oocyte. Additionally, zinc ion (Zn2+) fluxes have recently been shown to occur during mammalian sperm capacitation. Semen from seven commercial boars was collected and analyzed using image-based flow cytometry before, after, and with the inclusion of 2 mM Zn2+ containing in vitro capacitation (IVC) media. Metabolites were extracted and analyzed via Gas Chromatography-Mass Spectrometry (GC-MS), identifying 175 metabolites, with 79 differentially abundant across treatments (p < 0.05). Non-capacitated samples showed high levels of respiration-associated metabolites including glucose, fructose, citric acid, and pyruvic acid. After 4 h IVC, these metabolites significantly decreased, while phosphate, lactic acid, and glucitol increased (p < 0.05). With zinc inclusion, we observed an increase in metabolites such as lactic acid, glucitol, glucose, fructose, myo-inositol, citric acid, and succinic acid, while saturated fatty acids including palmitic, dodecanoic, and myristic acid decreased compared to 4 h IVC, indicating regulatory shifts in metabolic pathways and fatty acid composition during capacitation. These findings underscore the importance of metabolic changes in improving artificial insemination and fertility treatments in livestock and humans.PMID:39063161 | DOI:10.3390/ijms25147919

The Link between Inflammation, Lipid Derivatives, and Microbiota Metabolites in COVID-19 Patients: Implications on Eating Behaviors and Nutritional Status

Sat, 27/07/2024 - 12:00
Int J Mol Sci. 2024 Jul 19;25(14):7899. doi: 10.3390/ijms25147899.ABSTRACTExtreme inflammation that continues even after infections can lead to a cytokine storm. In recent times, one of the most common causes of cytokine storm activation has been SARS-CoV-2 infection. A cytokine storm leads to dysregulation and excessive stimulation of the immune system, producing symptoms typical of post-COVID syndrome, including chronic fatigue, shortness of breath, joint pain, trouble concentrating (known as "brain fog"), and even direct organ damage in the heart, lungs, kidneys, and brain. This work summarizes the current knowledge regarding inflammation and the cytokine storm related to SARS-CoV-2 infection. Additionally, changes in lipid metabolism and microbiota composition under the influence of inflammation in COVID-19, along with the possible underlying mechanisms, are described. Finally, this text explores potential health implications related to changes in eating behaviors and nutritional status in COVID-19 patients. Although research on the cytokine storm is still ongoing, there is convincing evidence suggesting that severe immune and inflammatory responses during the acute phase of COVID-19 may lead to long-term health consequences. Understanding these links is key to developing treatment strategies and supporting patients after infection.PMID:39063142 | DOI:10.3390/ijms25147899

Comparative Analysis of Breast Cancer Metabolomes Highlights Fascin's Central Role in Regulating Key Pathways Related to Disease Progression

Sat, 27/07/2024 - 12:00
Int J Mol Sci. 2024 Jul 18;25(14):7891. doi: 10.3390/ijms25147891.ABSTRACTOmics technologies provide useful tools for the identification of novel biomarkers in many diseases, including breast cancer, which is the most diagnosed cancer in women worldwide. We and others have reported a central role for the actin-bundling protein (fascin) in regulating breast cancer disease progression at different levels. However, whether fascin expression promotes metabolic molecules that could predict disease progression has not been fully elucidated. Here, fascin expression was manipulated via knockdown (fascinKD+NORF) and rescue (fascinKD+FORF) in the naturally fascin-positive (fascinpos+NORF) MDA-MB-231 breast cancer cells. Whether fascin dysregulates metabolic profiles that are associated with disease progression was assessed using untargeted metabolomics analyses via liquid chromatography-mass spectrometry. Overall, 12,226 metabolic features were detected in the tested cell pellets. Fascinpos+NORF cell pellets showed 2510 and 3804 significantly dysregulated metabolites compared to their fascinKD+NORF counterparts. Fascin rescue (fascinKD+FORF) revealed 2710 significantly dysregulated cellular metabolites compared to fascinKD+NORF counterparts. A total of 101 overlapped cellular metabolites between fascinKD+FORF and fascinpos+NORF were significantly dysregulated in the fascinKD+NORF cells. Analysis of the significantly dysregulated metabolites by fascin expression revealed their involvement in the metabolism of sphingolipid, phenylalanine, tyrosine, and tryptophan biosynthesis, and pantothenate and CoA biosynthesis, which are critical pathways for breast cancer progression. Our findings of fascin-mediated alteration of metabolic pathways could be used as putative poor prognostic biomarkers and highlight other underlying mechanisms of fascin contribution to breast cancer progression.PMID:39063133 | DOI:10.3390/ijms25147891

P38α MAPK Coordinates Mitochondrial Adaptation to Caloric Surplus in Skeletal Muscle

Sat, 27/07/2024 - 12:00
Int J Mol Sci. 2024 Jul 16;25(14):7789. doi: 10.3390/ijms25147789.ABSTRACTExcessive calorie intake leads to mitochondrial overload and triggers metabolic inflexibility and insulin resistance. In this study, we examined how attenuated p38α activity affects glucose and fat metabolism in the skeletal muscles of mice on a high-fat diet (HFD). Mice exhibiting diminished p38α activity (referred to as p38αAF) gained more weight and displayed elevated serum insulin levels, as well as a compromised response in the insulin tolerance test, compared to the control mice. Additionally, their skeletal muscle tissue manifested impaired insulin signaling, leading to resistance in insulin-mediated glucose uptake. Examination of muscle metabolites in p38αAF mice revealed lower levels of glycolytic intermediates and decreased levels of acyl-carnitine metabolites, suggesting reduced glycolysis and β-oxidation compared to the controls. Additionally, muscles of p38αAF mice exhibited severe abnormalities in their mitochondria. Analysis of myotubes derived from p38αAF mice revealed reduced mitochondrial respiratory capacity relative to the myotubes of the control mice. Furthermore, these myotubes showed decreased expression of Acetyl CoA Carboxylase 2 (ACC2), leading to increased fatty acid oxidation and diminished inhibitory phosphorylation of pyruvate dehydrogenase (PDH), which resulted in elevated mitochondrial pyruvate oxidation. The expected consequence of reduced mitochondrial respiratory function and uncontrolled nutrient oxidation observed in p38αAF myotubes mitochondrial overload and metabolic inflexibility. This scenario explains the increased likelihood of insulin resistance development in the muscles of p38αAF mice compared to the control mice on a high-fat diet. In summary, within skeletal muscles, p38α assumes a crucial role in orchestrating the mitochondrial adaptation to caloric surplus by promoting mitochondrial biogenesis and regulating the selective oxidation of nutrients, thereby preventing mitochondrial overload, metabolic inflexibility, and insulin resistance.PMID:39063031 | DOI:10.3390/ijms25147789

Platelet Storage-Problems, Improvements, and New Perspectives

Sat, 27/07/2024 - 12:00
Int J Mol Sci. 2024 Jul 16;25(14):7779. doi: 10.3390/ijms25147779.ABSTRACTPlatelet transfusions are routine procedures in clinical treatment aimed at preventing bleeding in critically ill patients, including those with cancer, undergoing surgery, or experiencing trauma. However, platelets are susceptible blood cells that require specific storage conditions. The availability of platelet concentrates is limited to five days due to various factors, including the risk of bacterial contamination and the occurrence of physical and functional changes known as platelet storage lesions. In this article, the problems related to platelet storage lesions are categorized into four groups depending on research areas: storage conditions, additive solutions, new testing methods for platelets (proteomic and metabolomic analysis), and extensive data modeling of platelet production (mathematical modeling, statistical analysis, and artificial intelligence). This article provides extensive information on the challenges, potential improvements, and novel perspectives regarding platelet storage.PMID:39063021 | DOI:10.3390/ijms25147779

Dissection of Metabolome and Transcriptome-Insights into Capsaicin and Flavonoid Accumulation in Two Typical Yunnan Xiaomila Fruits

Sat, 27/07/2024 - 12:00
Int J Mol Sci. 2024 Jul 16;25(14):7761. doi: 10.3390/ijms25147761.ABSTRACTPepper is an economically important vegetable worldwide, containing various specialized metabolites crucial for its development and flavor. Capsaicinoids, especially, are genus-specialized metabolites that confer a spicy flavor to Capsicum fruits. In this work, two pepper cultivars, YB (Capsicum frutescens L.) and JC (Capsicum baccatum L.) pepper, showed distinct differences in the accumulation of capsaicin and flavonoid. However, the molecular mechanism underlying them was still unclear. Metabolome analysis showed that the JC pepper induced a more abundant accumulation of metabolites associated with alkaloids, flavonoids, and capsaicinoids in the red ripening stages, leading to a spicier flavor in the JC pepper. Transcriptome analysis confirmed that the increased expression of transcripts associated with phenylpropanoid and flavonoid metabolic pathways occurred in the JC pepper. Integrative analysis of metabolome and transcriptome suggested that four structural genes, 4CL7, 4CL6, CHS, and COMT, were responsible for the higher accumulation of metabolites relevant to capsaicin and flavonoids. Through weighted gene co-expression network analyses, modules related to flavonoid biosynthesis and potential regulators for candidate genes were identified. The promoter analysis of four candidate genes showed they contained several cis-elements that were bonded to MYB, bZIP, and WRKY transcription factors. Further RT-qPCR examination verified three transcription factors, MYB, bZIP53, and WRKY25, that exhibited increased expression in the red ripening stage of the JC pepper compared to YB, which potentially regulated their expression. Altogether, our findings provide comprehensive understanding and valuable information for pepper breeding programs in the future.PMID:39063003 | DOI:10.3390/ijms25147761

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