Amino Acid Metabolic Pathways Research Articles

Nontargeted metabolomics reveals sequential changes in amino acid and ferroptosis-related metabolism in Parkinson's disease.

Parkinson's disease (PD) is inseparable from metabolic disorders but lacks assessment of specific metabolite alteration. To explore the sequential metabolic changes in PD progression, we evenly divided 78 C57BL/6 mice (10weeks) into six groups (one control group and five experimental groups) and collected the hippocampus tissue of mice after treating with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and probenecid (twice a week) at five periods (1, 2, 3, 4, and 5weeks) for metabolome analysis. Our study identified 567 differentially abundant metabolites (DAMs) (total 4348 metabolites). Compared with controls, 145, 146, 171, 208, and 213 DAMs were obtained from the five experimental groups, respectively. Notably, 40 shared DAMs were present in five experimental groups, of which 22 shared DAMs formed a new metabolic network based on amino acid metabolism. Compared with group W3, 84 DAMs were identified in group W5, including 12 unique DAMs. DAMs in different stages of PD were significantly enriched in amino acid metabolism pathway, lipid metabolism pathway, and ferroptosis pathway. l-Glutamine, spermidine, and l-tryptophan were the key hubs in the whole metabolic process of PD. N-Formyl-l-methionine gradually increased in abundance with PD progression, whereas 5-methylcytosine gradually decreased. The study emphasized the sequential changes in DAMs in PD progression, stimulating subsequent studies.

Metabolomic interference induced by short-chain chlorinated paraffins in human normal hepatic cells

Short-chain chlorinated paraffins (SCCPs) are an emerging class of persistent organic pollutants (POPs) that are widely detected in environmental matrices and human samples. Because of their environmental persistence, long-range transport potential, bioaccumulation potential, and biotoxicity, SCCPs pose a significant threat to human health. In this study, metabolomics technology was applied to reveal the metabolomic interference in human normal hepatic (L02) cells after exposure to low (1 μg/L), moderate (10 μg/L), and high (100 μg/L) doses of SCCPs. Principal component analysis (PCA) and metabolic effect level index (MELI) values showed that all three SCCP doses caused notable metabolic perturbations in L02 cells. A total of 72 metabolites that were annotated by MS/MS and matched with the experimental spectra in the Human Metabolome Database (HMDB) or validated by commercially available standards were selected as differential metabolites (DMs) across all groups. The low-dose exposure group shared 33 and 36 DMs with the moderate- and high-dose exposure groups, respectively. The moderate-dose exposure group shared 46 DMs with the high-dose exposure group. In addition, 33 DMs were shared among the three exposure groups. Among the 72 DMs, 9, 9, and 45 metabolites participated in the amino acid, nucleotide, and lipid metabolism pathways, respectively. The results of pathway enrichment analysis showed that the most relevant metabolic pathways affected by SCCPs were the lipid metabolism, fatty acid β-oxidation, and nucleotide metabolism pathways, and that compared with low-dose exposure, moderate- and high-dose SCCP exposures caused more notable perturbations of these metabolic pathways in L02 cells. Exposure to SCCPs perturbed glycerophospholipid and sphingolipid metabolism. Significant alterations in the levels of phosphatidylcholines, phosphatidylethanolamines, and sphingomyelins indicated SCCP-induced biomembrane damage. SCCPs inhibited fatty acid β-oxidation by decreasing the levels of short- and medium-chain acylcarnitines in L02 cells, indicating that the energy supplied by fatty acid oxidation was reduced in these cells. Furthermore, compared with low- and moderate-dose SCCPs, high-dose SCCPs produced a significantly stronger inhibition of fatty acid β-oxidation. In addition, SCCPs perturbed nucleotide metabolism. The higher hypoxanthine levels observed in L02 cells after SCCP exposures indicate that SCCPs may induce several adverse effects, including hypoxia, reactive oxygen species production, and mutagenesis in L02 cells.

Effect of Lactiplantibacillus plantarum CCFM8661 on serum metabolites and gut microbiota in a lead-exposed population

In this study, we investigated the impact of Lactiplantibacillus plantarum (L. plantarum) CCFM8661 on the gut microbiota, and the serum and fecal metabolomes in lead (Pb)-exposed individuals. The volunteers recruited for this study were divided into two treatment groups, (i) the placebo (control) and (ii) the L. plantarum CCFM8661 treatment groups. The analysis revealed that probiotic intervention reversed some of the changes in Pb exposure-induced intestinal bacterial abundance, including the abundance of Parabacteroides, Bacteroides, Clostridiaceae, and Erysipelotrichaceae. An analysis of the fecal metabolome identified 26 differential metabolites involved in purine metabolism, unsaturated fatty acid metabolism, and other pathways. Serum metabolite analysis showed that L. plantarum CCFM8661 treatment altered the serum metabolite levels of various metabolic pathways, such as the glycerophospholipid, amino acid, and glutathione metabolism pathways. These results suggest that L. plantarum CCFM8661 may have beneficial effects on Pb-exposed populations by modulating the gut microbiota, host serum metabolism, and the metabolism of the gut microbiota.

Insights into the mechanism of L-malic acid on drip loss of chicken meat under commercial conditions

BackgroundA deterioration in the meat quality of broilers has attracted much more attention in recent years. L-malic acid (MA) is evidenced to decrease meat drip loss in broilers, but the underlying molecular mechanisms are still unclear. It’s also not sure whether the outputs obtained under experimental conditions can be obtained in a commercial condition. Here, we investigated the effects and mechanisms of dietary MA supplementation on chicken meat drip loss at large-scale rearing.ResultsResults showed that the growth performance and drip loss were improved by MA supplementation. Meat metabolome revealed that L-2-aminoadipic acid, β-aminoisobutyric acid, eicosapentaenoic acid, and nicotinamide, as well as amino acid metabolism pathways connected to the improvements of meat quality by MA addition. The transcriptome analysis further indicated that the effect of MA on drip loss was also related to the proper immune response, evidenced by the enhanced B cell receptor signaling pathway, NF-κB signaling pathway, TNF signaling pathway, and IL-17 signaling pathway.ConclusionsWe provided evidence that MA decreased chicken meat drip loss under commercial conditions. Metabolome and transcriptome revealed a comprehensive understanding of the underlying mechanisms. Together, MA could be used as a promising dietary supplement for enhancing the water-holding capacity of chicken meat.

Dietary Paper Mulberry Silage Supplementation Improves the Growth Performance, Carcass Characteristics, and Meat Quality of Yangzhou Goose

There have been few investigations into the health benefits and meat quality of supplementing Yangzhou geese with paper mulberry silage. One hundred and twenty 28-day-old Yangzhou geese were selected for the experiment and randomly divided into two groups: a control group (CON) and a paper mulberry silage group (PM), with six replicates in each group. The experiment lasted for a total of 6 weeks. The experiment found that compared with CON, PM had a promoting effect on the average daily weight gain of Yangzhou geese (p = 0.056). Sensory and nutritional analysis of breast muscles revealed a decrease in a* value (p < 0.05) and an increase in protein content (p < 0.05) following PM treatment. Through untargeted metabolomics analysis of breast muscle samples, it was found that 11 different metabolites, including guanidinoacetic acid and other substances, had a positive effect on amino acid metabolism and lipid antioxidant pathways of PM treatment. Overall, the strategy of feeding Yangzhou geese with paper mulberry silage is feasible, which can improve the sensory quality and nutritional value of goose meat. The experiment provides basic data for the application form of goose breeding, so exploring the impact of substances within paper mulberry on goose meat should be focused on in the future.

Dietary selenium levels affect mineral absorbability, rumen fermentation, microbial composition and metabolites of the grazing sheep

Selenium (Se) is an essential trace element for the growth of all livestock. However, little is known about the effects of dietary selenium levels on production metrics, nutrient digestion and absorption, ruminal microbiota, and metabolites in grazing sheep. Therefore, in this research, 28 individually-housed grazing sheep were randomly divided into a low-Se feeding group (LSe) and a control group for the low-Se feeding phase (LCG), supplemented with multi-nutrient salts containing 0 mg Se and 0.63 mg Se, respectively, for 53 days. After 53 days of feeding, a 7-day digestion test was conducted, then seven sheep in each group were randomly slaughtered. Then, the remaining sheep in LSe and LCG were transferred to a high-Se supplementation group (SSe) and a control group for the high-Se feeding phase (SCG), supplemented with multi-nutrient salts containing 1.90 mg and 0.63 mg Se, respectively. This phase consisted of a 34-day diet adaptation period, a 7-day digestive test, and eventual slaughter. LSe reduced and elevated ruminal Se and copper (Cu) content, respectively, and decreased Se apparent absorbability compared to LCG (P < 0.05). Conversely, SSe reduced and increased ruminal Cu and Se content, respectively, and increased Se apparent absorption in comparison to SCG (P < 0.05). It also increased the ruminal NH3-N concentration (P < 0.05). Amplicon sequencing analysis revealed a decrease in Lentimicrobium and Treponema abundance and an increase in Lawsonibacter and Sporobacter abundance (P < 0.05) in LSe group. Metabolomic analysis confirmed an elevated level of ruminal citrulline, ornithine and glutathione affecting amino acid and glutathione metabolic pathways (P < 0.05) in LSe group. In SSe group, Alistipes were significantly reduced (P < 0.05) with metabolomics showing elevated levels of L-carnitine and arginine, affecting ruminal antioxidant capacity and arginine biosynthesis pathways (P < 0.05). Notably, both treatments had no significant effect on production metrics and apparent digestibility of organic nutrients (P > 0.05). In conclusion, Se deficiency affects Se absorption and amino acid metabolism in grazing sheep, while supplementing Se in diet effectively ameliorates these deficiencies and improves ruminal antioxidant capacity.

Citrus p-Synephrine Improves Energy Homeostasis by Regulating Amino Acid Metabolism in HFD-Induced Mice.

p-Synephrine is a common alkaloid widely distributed in citrus fruits. However, the effects of p-synephrine on the metabolic profiles of individuals with energy abnormalities are still unclear. In the study, we investigated the effect of p-synephrine on energy homeostasis and metabolic profiles using a high fat diet (HFD)-induced mouse model. We found that p-synephrine inhibited the gain in body weight, liver weight and white adipose tissues weight induced by HFD. p-Synephrine supplementation also reduced levels of serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) but not to a statistically significant degree. Histological analysis showed that HFD induced excessive lipid accumulation and glycogen loss in the liver and adipocyte enlargement in perirenal fat tissue, while p-synephrine supplementation reversed the changes induced by HFD. Moreover, HFD feeding significantly increased mRNA expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and reduced the mRNA expression level of interleukin-10 (IL-10) compared to the control group, while p-synephrine supplementation significantly reversed these HFD-induced changes. Liver and serum metabolomic analysis showed that p-synephrine supplementation significantly altered small molecule metabolites in liver and serum in HFD mice and that the changes were closely associated with improvement of energy homeostasis. Notably, amino acid metabolism pathways, both in liver and serum samples, were significantly enriched. Our study suggests that p-synephrine improves energy homeostasis probably by regulating amino acid metabolism in HFD mice, which provides a novel insight into the action mechanism of p-synephrine modulating energy homeostasis.

The metabolic pathway regulation in kidney injury and repair.

Kidney injury and repair are accompanied by significant disruptions in metabolic pathways, leading to renal cell dysfunction and further contributing to the progression of renal pathology. This review outlines the complex involvement of various energy production pathways in glucose, lipid, amino acid, and ketone body metabolism within the kidney. We provide a comprehensive summary of the aberrant regulation of these metabolic pathways in kidney injury and repair. After acute kidney injury (AKI), there is notable mitochondrial damage and oxygen/nutrient deprivation, leading to reduced activity in glycolysis and mitochondrial bioenergetics. Additionally, disruptions occur in the pentose phosphate pathway (PPP), amino acid metabolism, and the supply of ketone bodies. The subsequent kidney repair phase is characterized by a metabolic shift toward glycolysis, along with decreased fatty acid β-oxidation and continued disturbances in amino acid metabolism. Furthermore, the impact of metabolism dysfunction on renal cell injury, regeneration, and the development of renal fibrosis is analyzed. Finally, we discuss the potential therapeutic strategies by targeting renal metabolic regulation to ameliorate kidney injury and fibrosis and promote kidney repair.

Silencing of crustacean hyperglycemic hormone gene expression reveals the characteristic energy and metabolic changes in the gills and epidermis of crayfish Procambarus clarkii.

The crustacean hyperglycemic hormone (CHH) is a multifaceted neuropeptide instrumental in regulating carbohydrate and lipid metabolism, reproduction, osmoregulation, molting, and metamorphosis. Despite its significance, there is a dearth of research on its metabolic impact on the gills and epidermis-key organs in osmoregulation and molting processes. This study employed CHH dsRNA injections to silence CHH gene expression in Procambarus clarkii, followed by a metabolomic analysis of the gills and epidermis using nuclear magnetic resonance spectroscopy. Metabolic profiling through principal component analysis revealed the most pronounced changes at 24h post-injection (hpi) in the epidermis and at 48hpi in the gills. At 24hpi, the epidermis exhibited significant modulation in 25 enrichment sets and 20 KEGG pathways, while at 48hpi, 5 metabolite sets and 6 KEGG pathways were prominently regulated. Notably, pathways associated with amino acid metabolism, carbohydrate metabolism, and cofactor and vitamin metabolism were affected. A marked decrease in glucose and other carbohydrates suggested a compromised carbohydrate supply, whereas increased levels of citrate cycle intermediates implied a potential boost in energy provision. The silencing of CHH gene expression hampered the carbohydrate supply, which was possibly the main energy derived substrates. Conversely, the gills displayed significant alterations in 15 metabolite sets and 16 KEGG pathways at 48 hpi, with no significant changes at 24hpi. These changes encompassed amino acid, carbohydrate, and lipid metabolism pathways. The decline in TCA cycle intermediates pointed to a potential downregulation of the cycle, whereas a decrease in ketone bodies indicated a shift towards lipid metabolism for energy production. Additionally, increased levels of nicotinate, nicotinamide, and quinolinate were observed in both organs. Overall, CHH's impact on the epidermis was prominent at 24hpi and diminished thereafter, whereas its influence on metabolism in gills was delayed but intensified at 48hpi. This differential CHH effect between gills and epidermis in P. clarkii provides new insights into the organ-specific regulatory mechanisms of CHH on energy metabolism and osmoregulation, warranting further comparative studies to elucidate the distinct roles of CHH in these organs.

Comparative genomics and fermentation flavor characterization of five selected lactic acid bacteria provide predictions for flavor biosynthesis metabolic pathways in fermented muskmelon puree

AbstractFive species of plant‐derived lactic acid bacteria (LAB), including Pediococcus pentosaceus, Lactococcus garvieae, Lactiplantibacillus paraplantarum, Weissella paramesenteroides, and Lactococcus lactis, were used for muskmelon fermentation to improve flavor characteristics. Comparative genomic analysis showed that a high proportion of annotated genes were related to carbohydrate metabolism and amino acid metabolism in all five strains. L. lactis P‐1 (Ll1) contained the highest proportion (2.02%) of genes from the glycoside hydrolase family associated with carbohydrate metabolism. Gas chromatography–mass spectrometry results showed that 89 volatile compounds in muskmelon purees were identified; the largest number of volatile compounds was detected in fermented muskmelon puree (FMP) inoculated with W. paramesenteroides FL3, followed by L. paraplantarum FL‐8. A total of 25 key volatile compounds were screened in muskmelon puree, and some unique key volatile compounds (e.g., β‐damascenone, phenylacetaldehyde, and 3‐penten‐2‐one) and taste compounds (e.g., mannitol) were produced by different LAB strains. L. garvieae Pa‐2 and Ll1 were considered to have greater potential due to their ability to produce a greater category of pleasant key aromas. Based on the correlations of potential pathways analyzed using comparative genomics and detected flavor profiles, flavor synthesis pathways in FMP were predicted. Some carbohydrate, amino acid, and fatty acid metabolism pathways, including tricarboxylic acid cycle, glycolysis, and cysteine and methionine metabolism pathways, are common to all five LAB strains. Furthermore, differences in the predicted flavor biosynthesis metabolic pathways in monoterpenoid biosynthesis, phenylalanine metabolism, fatty acid biosynthesis, and fructose and mannose metabolism pathways explained the differences in volatile profiles produced by different strains.

Endosymbiont Tremblaya phenacola influences the reproduction of cotton mealybugs by regulating the mechanistic target of rapamycin pathway.

The intricate evolutionary dynamics of endosymbiotic relationships result in unique characteristics among the genomes of symbionts, which profoundly influence host insect phenotypes. Here, we investigated an endosymbiotic system in Phenacoccus solenopsis, a notorious pest of the subfamily Phenacoccinae. The endosymbiont, "Candidatus Tremblaya phenacola" (T. phenacola PSOL), persisted throughout the complete life cycle of female hosts and was more active during oviposition, whereas there was a significant decline in abundance after pupation in males. Genome sequencing yielded an endosymbiont genome of 221.1kb in size, comprising seven contigs and originating from a chimeric arrangement between betaproteobacteria and gammaproteobacteria. A comprehensive analysis of amino acid metabolic pathways demonstrated complementarity between the host and endosymbiont metabolism. Elimination of T. phenacola PSOL through antibiotic treatment significantly decreased P. solenopsis fecundity. Weighted gene coexpression network analysis demonstrated a correlation between genes associated with essential amino acid synthesis and those associated with host meiosis and oocyte maturation. Moreover, altering endosymbiont abundance activated the host mechanistic target of rapamycin pathway, suggesting that changes in the amino acid abundance affected the host reproductive capabilities via this signal pathway. Taken together, these findings demonstrate a mechanism by which the endosymbiont T. phenacola PSOL contributed to high fecundity in P. solenopsis and provide new insights into nutritional compensation and coevolution of the endosymbiotic system.

UV-ARTP compound mutagenesis breeding improves macrolactins production of Bacillus siamensis and reveals metabolism changes by proteomic

Macrolactins are a type of compound with complex macrolide structure which mainly be obtained through microbiological fermentation now. They have excellent antifungal, antibacterial and antitumor activity. In order to improve macrolactins production, Bacillus siamensis YB304 was used as the research object, and a mutant Mut-K53 with stable genetic characters was selected by UV-ARTP compound mutagenesis. The yield of macrolactins was 156.46 mg/L, 3.95 times higher than original strain. The metabolic pathway changes and regulatory mechanism of macrolactins were analyzed by quantitative proteomics combined with parallel reaction monitoring. This study revealed that 1794 proteins were extracted from strain YB304 and strain Mut-K53, most of them were related to metabolism. After UV-ARTP compound mutagenesis treatment, the expression of 628 proteins were significantly changed, of which 299 proteins were significantly up-regulated. KEGG pathway analysis showed that differentially expression proteins mainly distributed in biological process, cellular component, and molecular function processing pathways. Such as utilization of carbon sources, glycolysis pathway, and amino acid metabolism pathway. Furthermore, key precursor substances such as acyl-CoA and amino acids of macrolactin biosynthesis are mostly up-regulated, which are one of the main reasons for increased production of macrolactin.This study will provide a new way to increase the yield of macrolactins through mutagenesis breeding and proteomics.

Developing the novel diagnostic model and potential drugs by integrating bioinformatics and machine learning for aldosterone-producing adenomas.

Background: Aldosterone-producing adenomas (APA) are a common cause of primary aldosteronism (PA), a clinical syndrome characterized by hypertension and electrolyte disturbances. If untreated, it may lead to serious cardiovascular complications. Therefore, there is an urgent need for potential biomarkers and targeted drugs for the diagnosis and treatment of aldosteronism. Methods: We downloaded two datasets (GSE156931 and GSE60042) from the GEO database and merged them by de-batch effect, then screened the top50 of differential genes using PPI and enriched them, followed by screening the Aldosterone adenoma-related genes (ARGs) in the top50 using three machine learning algorithms. We performed GSEA analysis on the ARGs separately and constructed artificial neural networks based on the ARGs. Finally, the Enrich platform was utilized to identify drugs with potential therapeutic effects on APA by tARGseting the ARGs. Results: We identified 190 differential genes by differential analysis, and then identified the top50 genes by PPI, and the enrichment analysis showed that they were mainly enriched in amino acid metabolic pathways. Then three machine learning algorithms identified five ARGs, namely, SST, RAB3C, PPY, CYP3A4, CDH10, and the ANN constructed on the basis of these five ARGs had better diagnostic effect on APA, in which the AUC of the training set is 1 and the AUC of the validation set is 0.755. And then the Enrich platform identified drugs tARGseting the ARGs with potential therapeutic effects on APA. Conclusion: We identified five ARGs for APA through bioinformatic analysis and constructed Artificial neural network (ANN) based on them with better diagnostic effects, and identified drugs with potential therapeutic effects on APA by tARGseting these ARGs. Our study provides more options for the diagnosis and treatment of APA.

The transmembrane protein TMEM182 promotes fat deposition and alters metabolomics and lipidomics

TMEM182, a transmembrane protein highly expressed in muscle and adipose tissues, plays a crucial role in muscle cell differentiation, metabolism, and signaling. However, its role in fat deposition and metabolism is still unknown. In this study, we used overexpression and knockout models to examine the impact of TMEM182 on fat synthesis and metabolism. Our results showed that TMEM182 overexpression increased the expression of fat synthesis-related genes and promoted the differentiation of preadipocytes into fat cells. In TMEM182 knockout mice, there was a significant decrease in abdominal fat deposition. RNA sequencing results showed that TMEM182 overexpression in preadipocytes enhanced the activity of pathways related to fat formation, ECM-receptor interaction, and cell adhesion. Furthermore, our analysis using UPLC-MS/MS showed that TMEM182 significantly altered the metabolite and lipid content and composition in chicken breast muscle. Specifically, TMEM182 increased the content of amino acids and their derivatives in chicken breast muscle, promoting amino acid metabolic pathways. Lipidomics also revealed a significant increase in the content of glycerophospholipids, sphingolipids, and phospholipids in the breast muscle after TMEM182 overexpression. These findings suggest that TMEM182 plays a crucial role in regulating fat deposition and metabolism, making it a potential target for treating obesity-related diseases and animal breeding.

Abnormal expression of natural mating behaviour of captive adult giant pandas is related to physiological stress.

During ex situ conservation, the adaptability of giant pandas to environmental changes is greatly challenged. The issue of natural reproduction in captive giant pandas remains unresolved both domestically and internationally. It hypothesized that the restricted natural reproductive capacity may be linked to abnormal mating behavior expression due to physiological stress resulting from incompatible pairings in confined environments. To test this hypothesis, we utilized ultra-high performance liquid chromatographytandem quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) to analyse urine metabolites in captive adult giant pandas during their breeding period. Simultaneously, enzyme-linked immunosorbent assay was employed to measure the levels of cortisol and epinephrine in urine, providing insight into the psychological state of captive giant pandas during mate selection by examining all metabolites and related biochemical pathways. This comprehensive approach aims to fully elucidate the physiological mechanisms underlying the decline in natural reproductive capacity. The metabolomics findings indicate that the aberrant expression of natural mating behaviour in captive adult male and female giant pandas may be associated with dysfunction in amino acid metabolic pathways. The activation of these metabolic pathways is linked to psychological stress, such as the tryptophan metabolic pathway and GABAergic synapse pathway. The results of physiological indicators indicate a significant correlation between the expression of natural mating behaviour in captive adult pandas and the hormone urine cortisol, which is associated with physiological stress. These findings indicate that the atypical manifestation of natural mating behaviour in captive adult giant pandas may be associated with physiological stress induced by incompatible pairings within confined environments.

Unbalanced redox status network as an early pathological even in congenital cataracts

Aims/Purpose: The lens proteome undergoes dramatic composition changes during development and maturation. Defective developmental processes lead to congenital cataracts that account for about 30% of cases of childhood blindness. Gene mutations are associated with approximately 50% of early‐onset forms of lens opacity, with the remainder being of unknown aetiology. To gain a better understanding of congenital cataractogenesis, we utilized a transgenic mouse model expressing a mutant ubiquitin protein in the lens (K6W‐Ub) that recapitulates many of the early pathological changes seen in human congenital cataracts.Methods: We performed MS‐based tandem‐mass‐tag quantitative proteomics (TMT), computational molecular phenotyping (CMP), high‐performance liquid chromatography (HPLC), western blotting and immunohistochemical analysis in E15, P1 and P30 control or K6W‐Ub lenses.Results: TMT identified proteins that were altered during normal lens differentiation, some of which were also altered in cataractous lenses. These included proteins in glutathione and amino acid metabolic pathways. CMP revealed that glutathione and taurine were reduced spatially altered in the K6W‐Ub cataractous lens. HPLC revealed that both the ratio GSH/GSSG and taurine, two indicators of redox status, were differentially compromised in K6W‐Ub cataractous lenses.Conclusions: Our findings shed light on the molecular mechanisms associated with congenital cataracts and point out that unbalanced redox status due to reduced levels of taurine and glutathione, metabolites already linked to age‐related cataract, could be a major underlying mechanism behind lens opacities that appear early in life.Funding: Funding was provided by grants RYC 2018‐024434‐I, MINECO PID 2020‐119466RB‐I00, FUSP‐PPC‐19‐B53C4C64, NIH RO1EY026979 (to AT), USDA 8050‐51000‐089‐01S (to AT).

Spatially resolved multi-omics unravels region-specific responses, microenvironment remodeling and metabolic reprogramming in aristolochic acid nephropathy

&lt;p&gt;Aristolochic acid nephropathy (AAN), primarily caused by overexposure to aristolochic acid I (AAI), is characterized by acute renal injury, interstitial nephritis, and metabolic dysfunction. Previous studies have revealed the cell-specific responses to AAI and its role in inducing metabolic dysfunction. However, the lack of structural information in these datasets hinders our full understanding of the spatially specific pathological mechanisms of AAN. To address this limitation, we propose an integration of spatial transcriptomics with spatial metabolomics methods to establish a spatial multi-omics analysis, which allows for deciphering region-specific responses, microenvironmental remodeling, and metabolic reprogramming &lt;i&gt;in situ&lt;/i&gt; in AAN. The pathological differences between renal regions indicate that AAI-induced renal injury exhibits spatial heterogeneity. With prolonged AAI treatment, we observed an increased proportion and co-localization of the injured proximal tubule (PT-inj) and immune cells in the cortex region, accompanied by intercellular crosstalk involving the MHC-I and CCL pathways. In addition, we identified a divergent cellular response along nephron segments, with up-regulation of multiple renal stress markers and pathways after AAI treatment. Regional heterogeneity of metabolic activities was also observed, with PT-inj cells exhibiting dysregulation of carbohydrate, lipid, and amino acid metabolic pathways, as well as increased purine and pyrimidine metabolism after AAI treatment. These findings provide a more comprehensive understanding of the cellular and molecular mechanisms of AAN in a spatial context, and suggest potential intervention pathways to alleviate the global burden of AAN.&lt;/p&gt;

Broadening horizons: the role of ferroptosis in polycystic ovary syndrome.

Polycystic ovarian syndrome (PCOS) is a common heterogeneous reproductive endocrine metabolic disorder in women of reproductive age characterized by clinical and biochemical hyperandrogenemia, ovulation disorders, and polycystic ovarian morphology. Ferroptosis is a novel type of cell death driven by iron accumulation and lipid peroxidation. Ferroptosis plays a role in maintaining redox balance, iron metabolism, lipid metabolism, amino acid metabolism, mitochondrial activity, and many other signaling pathways linked to diseases. Iron overload is closely related to insulin resistance, decreased glucose tolerance, and the occurrence of diabetes mellitus. There is limited research on the role of ferroptosis in PCOS. Patients with PCOS have elevated levels of ferritin and increased reactive oxygen species in ovarian GCs. Studying ferroptosis in PCOS patients is highly important for achieving personalized treatment. This article reviews the progress of research on ferroptosis in PCOS, introduces the potential connections between iron metabolism abnormalities and oxidative stress-mediated PCOS, and provides a theoretical basis for diagnosing and treating PCOS.

The regulatory mechanism of garlic skin improving the growth performance of fattening sheep through metabolism and immunity.

Garlic skin (GAS) has been proven to improve the growth performance of fattening sheep. However, the mechanism by which GAS affects fattening sheep is not yet clear. The aim of this study is to investigate the effects of adding GAS to feed on the growth performance, rumen and fecal microbiota, serum and urine metabolism, and transcriptomics of rumen epithelial cells in fattening sheep. GAS with 80 g/kg dry matter (DM) was added to the diet of fattening sheep to study the effects of GAS on gut microbiota, serum and urine metabolism, and transcriptome of rumen epithelial tissue in fattening sheep. Twelve Hu sheep (body weights; BW, 23.0 ± 2.3 kg and ages 120 ± 3.5 d) were randomly divided into two groups. The CON group was the basal diet, while the GAS group was supplemented with GAS in the basal diet. The trial period was 10 weeks, with the first 2 weeks being the pre-trial period. The daily average weight gain of fattening sheep in the GAS group was significantly higher than that in the CON group (p < 0.05), and the serum GSH-Px of the GAS group fattening sheep was significantly increased, while MDA was significantly reduced (p < 0.05). Based on the genus classification level, the addition of garlic peel in the diet changed the intestinal microbial composition, and the relative abundance was significantly upregulated by Metanobrevibater (p < 0.05), while significantly downregulated by Akkermansia, Parasutterella, and Guggenheimella (p < 0.05). Metabolomics analysis found that there were 166 significantly different metabolites in serum and 68 significantly different metabolites in urine between the GAS and CON groups (p < 0.05). GAS had an impact on amino acid metabolism, pyrimidine metabolism, methane metabolism, riboflavin metabolism, and unsaturated fatty acid synthesis pathways (p < 0.05). Transcriptome sequencing showed that differentially expressed genes were mainly enriched in immune regulatory function, improving the health of fattening sheep. Adding GAS can improve the energy metabolism and immune function of fattening sheep by altering gut microbiota, metabolome, and transcriptome, thereby improving the growth performance of fattening sheep.

Monascus-fermented quinoa alleviates hyperlipidemia in mice by regulating the amino acid metabolism pathway.

Monascus has the ability to produce secondary metabolites, such as monacolin K (MK), known for its physiological functions, including lipid-lowering effects. Widely utilized in industries such as health food and medicine, MK is a significant compound derived from Monascus. Quinoa, recognized by the Food and Agriculture Organization of the United Nations as "the only plant food that can meet human basic nutritional needs by itself", possesses dual advantages of high nutritional value and medicinal food homology. This study employed animal experiments to investigate the hypolipidemic activity of Monascus-fermented quinoa (MFQ) and explored the molecular mechanism underlying the lipid-lowering effect of MFQ on hyperlipidemic mice through transcriptomic and metabolomic analyses. The results demonstrated that high-dose MFQ intervention (1600 mg kg-1 d-1) effectively decreased weight gain in hyperlipidemic mice without significant changes in cardiac index, renal index, or spleen index. Moreover, hepatic steatosis in mice was significantly improved. Serum levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol were markedly reduced, demonstrating that the lipid-lowering effect of MFQ was comparable to the drug control lovastatin. Conversely, both low-dose MFQ (400 mg kg-1 d-1) and unfermented quinoa exhibited no significant lipid-lowering effect. Integrated analysis of the transcriptome and metabolome suggested that MFQ may regulate amino acid levels in hyperlipidemic mice by influencing metabolic pathways such as phenylalanine, tyrosine, and tryptophan metabolism. This regulation alleviates hyperlipidemia induced by a high-fat diet, resulting in a significant reduction in blood lipid levels in mice.