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Keywords = gluconeogenesis metabolism

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18 pages, 3976 KiB  
Article
Impact of Salinity Stress on Antioxidant Enzyme Activity, Histopathology, and Gene Expression in the Hepatopancreas of the Oriental River Prawn, Macrobrachium nipponense
by Shubo Jin, Zhenghao Ye, Hongtuo Fu, Yiwei Xiong, Hui Qiao, Wenyi Zhang and Sufei Jiang
Animals 2025, 15(15), 2319; https://doi.org/10.3390/ani15152319 - 7 Aug 2025
Abstract
Macrobrachium nipponense represents a commercial decapod species that predominantly inhabits freshwater ecosystems or environments with low salinity. However, the species exhibits normal survival and reproductive capacity in natural aquatic habitats with salinity levels up to 10 parts per thousand (ppt). The present study [...] Read more.
Macrobrachium nipponense represents a commercial decapod species that predominantly inhabits freshwater ecosystems or environments with low salinity. However, the species exhibits normal survival and reproductive capacity in natural aquatic habitats with salinity levels up to 10 parts per thousand (ppt). The present study aimed to elucidate the molecular mechanisms underlying salinity acclimation in M. nipponense by investigating alterations in oxidative stress, morphological adaptations, and hepatopancreatic gene expression profiles following exposure to a salinity level of 10 ppt. The present study demonstrates that glutathione peroxidase and Na+/K+-ATPase play critical roles in mitigating oxidative stress induced by elevated salinity in M. nipponense. Furthermore, histological analysis revealed distinct pathological alterations in the hepatopancreas of M. nipponense following 7-day salinity exposure, including basement-membrane disruption, luminal expansion, vacuolization, and a marked reduction in storage cells. Transcriptomic profiling of M. nipponense hepatopancreas suggested coordinated activation of both immune (lysosome and protein processing in endoplasmic reticulum pathways) and energy (pyruvate metabolism, glycolysis/gluconeogenesis, and citrate cycle) metabolic processes during salinity acclimation in M. nipponense. Quantitative real-time PCR validation confirmed the reliability of RNA-seq data. This study provides molecular insights into the salinity adaptation mechanisms in M. nipponense, offering potential applications for improving cultivation practices in brackish water environments. Full article
(This article belongs to the Special Issue Developmental Genetics of Adaptation in Aquatic Animals)
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19 pages, 3457 KiB  
Article
Transcriptome Analysis Revealed the Immune and Metabolic Responses of Grass Carp (Ctenopharyngodon idellus) Under Acute Salinity Stress
by Leshan Ruan, Baocan Wei, Yanlin Liu, Rongfei Mu, Huang Li and Shina Wei
Fishes 2025, 10(8), 380; https://doi.org/10.3390/fishes10080380 - 5 Aug 2025
Viewed by 135
Abstract
Freshwater salinization, an escalating global environmental stressor, poses a significant threat to freshwater biodiversity, including fish communities. This study investigates the grass carp (Ctenopharyngodon idellus), a species with the highest aquaculture output in China, to elucidate the molecular underpinnings of its [...] Read more.
Freshwater salinization, an escalating global environmental stressor, poses a significant threat to freshwater biodiversity, including fish communities. This study investigates the grass carp (Ctenopharyngodon idellus), a species with the highest aquaculture output in China, to elucidate the molecular underpinnings of its physiological adaptations to fluctuating salinity gradients. We used high-throughput mRNA sequencing and differential gene expression profiling to analyze transcriptional dynamics in intestinal and kidney tissues of grass carp exposed to heterogeneous salinity stressors. Concurrent serum biochemical analyses showed salinity stress significantly increased Na+, Cl, and osmolarity, while decreasing lactate and glucose. Salinity stress exerted a profound impact on the global transcriptomic landscape of grass carp. A substantial number of co-regulated differentially expressed genes (DEGs) in kidney and intestinal tissues were enriched in immune and metabolic pathways. Specifically, genes associated with antigen processing and presentation (e.g., cd4-1, calr3b) and apoptosis (e.g., caspase17, pik3ca) exhibited upregulated expression, whereas genes involved in gluconeogenesis/glycolysis (e.g., hk2, pck2) were downregulated. KEGG pathway enrichment analyses revealed that metabolic and cellular structural pathways were predominantly enriched in intestinal tissues, while kidney tissues showed preferential enrichment of immune and apoptotic pathways. Rigorous validation of RNA-seq data via qPCR confirmed the robustness and cross-platform consistency of the findings. This study investigated the core transcriptional and physiological mechanisms regulating grass carp’s response to salinity stress, providing a theoretical foundation for research into grass carp’s resistance to salinity stress and the development of salt-tolerant varieties. Full article
(This article belongs to the Special Issue Adaptation and Response of Fish to Environmental Changes)
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22 pages, 4596 KiB  
Article
Gut Microbiota Dysbiosis Remodels the Lysine Acetylome of the Mouse Cecum in Early Life
by Yubing Zeng, Jinying Shen, Xuejia He, Fan Liu, Yi Wang, Yi Wang, Yanan Qiao, Pei Pei and Shan Wang
Biology 2025, 14(8), 917; https://doi.org/10.3390/biology14080917 - 23 Jul 2025
Viewed by 288
Abstract
The interaction between epigenetic mechanisms and the gut microbiome is potentially crucial for the development and maintenance of intestinal health. Lysine acetylation, an important post-translational modification, plays a complex and critical role in the epigenetic regulation of the host by the gut microbiota. [...] Read more.
The interaction between epigenetic mechanisms and the gut microbiome is potentially crucial for the development and maintenance of intestinal health. Lysine acetylation, an important post-translational modification, plays a complex and critical role in the epigenetic regulation of the host by the gut microbiota. However, there are currently no reports on how gut microbiota dysbiosis affects host physiology in early life through global lysine acetylation. In this study, we constructed a mouse model of gut microbiota dysbiosis using antibiotic cocktail therapy (ABX). Using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the cecum, we analyzed the cecal lysine acetylome and proteome. As a result, we profiled the lysine acetylation landscape of the cecum and identified a total of 16,579 acetylation sites from 5218 proteins. Differentially acetylated proteins (DAPs) are involved in various metabolic pathways, including the citrate cycle (TCA cycle), butanoate metabolism, pyruvate metabolism, glycolysis/gluconeogenesis, and fatty acid biosynthesis. Moreover, both glycolysis and gluconeogenesis are significantly enriched in acetylation and protein modifications. This study aimed to provide valuable insights into the epigenetic molecular mechanisms associated with host protein acetylation as influenced by early-life gut microbiota disturbances. It reveals potential therapeutic targets for metabolic disorders linked to gut microbiota dysbiosis, thereby establishing a theoretical foundation for the clinical prevention and treatment of diseases arising from such dysbiosis. Full article
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23 pages, 3556 KiB  
Article
Transcriptomic and Metabolomic Joint Analysis Revealing Different Metabolic Pathways and Genes Dynamically Regulating Bitter Gourd (Momordica charantia L.) Fruit Growth and Development in Different Stages
by Boyin Qiu, Dazhong Li, Qianrong Zhang, Hui Lin, Yongping Li, Qingfang Wen and Haisheng Zhu
Plants 2025, 14(14), 2248; https://doi.org/10.3390/plants14142248 - 21 Jul 2025
Viewed by 383
Abstract
Insights into dynamic regulatory factors in various stages of growth and development can guide strategies for precision and targeted breeding. Bitter gourd, as a vegetable product with medicinal value, plays a role in both agricultural and medical fields. In this study, phenotypic observations, [...] Read more.
Insights into dynamic regulatory factors in various stages of growth and development can guide strategies for precision and targeted breeding. Bitter gourd, as a vegetable product with medicinal value, plays a role in both agricultural and medical fields. In this study, phenotypic observations, metabolomic and transcriptomic analyses, and differential gene expression patterns, along with a correlation analysis, were conducted in different stages of fruit growth and development. The results revealed that the growth rate of fruit’s fresh weight, length, diameter, and flesh thickness during the first seven days was slow, and that it then rapidly increased after the seventh day, and finally slowed once more after 17 days, indicating that the overall process followed a “slow–fast–slow” pattern. Transcriptomic and metabolomic analyses identified several differentially expressed genes and metabolites, and joint analyses revealed that each of the glycolysis/gluconeogenesis, fructose and mannose metabolism and flavonoid biosynthesis pathways individually play significant roles in the dynamic regulation of fruit growth and development during the early, middle, and late stages. Among these, 53 differentially expressed genes (DEGs) and 12 differentially expressed metabolites (DEMs) were found in these pathways. A total of 12 randomly selected DEGs were analyzed using quantitative PCR, and the results showed that gene expression levels were generally consistent with transcriptomic sequencing results, exhibiting dynamic changes with varying expression levels. Correlation analysis revealed that 11 DEMs were positively correlated with four traits except for arbutin, while eight DEGs were related to all traits, including six significantly positive and two significantly negative correlations. These findings enhance our understanding of the regulatory network governing yield and quality and provide substantial evidence to support improvements in breeding programs. Full article
(This article belongs to the Section Plant Physiology and Metabolism)
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20 pages, 7380 KiB  
Article
Copper Pyrithione Induces Hepatopancreatic Apoptosis and Metabolic Disruption in Litopenaeus vannamei: Integrated Transcriptomic, Metabolomic, and Histopathological Analysis
by Jieyu Guo, Yang Yang, Siying Yu, Cairui Jiang, Xianbin Su, Yongfeng Zou and Hui Guo
Animals 2025, 15(14), 2134; https://doi.org/10.3390/ani15142134 - 18 Jul 2025
Viewed by 261
Abstract
Copper pyrithione (CuPT), an emerging biocide used in ship antifouling coatings, may accumulate in marine sediments and pose risks to non-target organisms. However, current research on CuPT toxicity remains limited. Litopenaeus vannamei, one of the world’s most important aquaculture shrimp species, relies [...] Read more.
Copper pyrithione (CuPT), an emerging biocide used in ship antifouling coatings, may accumulate in marine sediments and pose risks to non-target organisms. However, current research on CuPT toxicity remains limited. Litopenaeus vannamei, one of the world’s most important aquaculture shrimp species, relies heavily on its hepatopancreas for energy metabolism, detoxification, and immune responses. Due to their benthic habitat, these shrimps are highly vulnerable to contamination in sediment environments. This study investigated the toxicological response in the hepatopancreas of L. vannamei exposed to CuPT (128 μg/L) for 3 and 48 h. Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) fluorescence staining revealed increased apoptosis, deformation of hepatic tubule lumens, and the loss of stellate structures in the hepatopancreas after CuPT 48 h exposure. A large number of differentially expressed genes (DEGs) were identified by transcriptomics analysis at 3 and 48 h, respectively. Most of these DEGs were related to detoxification, glucose transport, and immunity. Metabolomic analysis identified numerous significantly different metabolites (SDMs) at both 3 and 48 h post-exposure, with most SDMs associated with energy metabolism, fatty acid metabolism, and related pathways. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of metabolomics and transcriptome revealed that both DEGs and SDMs were enriched in arachidonic acid metabolism, fatty acid biosynthesis, and glycolysis/gluconeogenesis pathways at 3 h, while at 48 h they were enriched in the starch and sucrose metabolism, amino sugar and nucleotide sugar metabolism, and galactose metabolism pathways. These results suggested that CuPT disrupts the energy and lipid homeostasis of L. vannamei. This disruption compelled L. vannamei to allocate additional energy toward sustaining basal physiological functions and consequently caused the accumulation of large amounts of reactive oxygen species (ROS) in the body, leading to apoptosis and subsequent tissue damage, and ultimately suppressed the immune system and impaired the health of L. vannamei. Our study elucidates the molecular mechanisms of CuPT-induced metabolic disruption and immunotoxicity in L. vannamei through integrated multi-omics analyses, providing new insights for ecological risk assessment of this emerging antifoulant. Full article
(This article belongs to the Special Issue Ecology of Aquatic Crustaceans: Crabs, Shrimps and Lobsters)
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25 pages, 1538 KiB  
Review
Lipid Hormones at the Intersection of Metabolic Imbalances and Endocrine Disorders
by Maria-Zinaida Dobre, Bogdana Virgolici and Ruxandra Cioarcă-Nedelcu
Curr. Issues Mol. Biol. 2025, 47(7), 565; https://doi.org/10.3390/cimb47070565 - 18 Jul 2025
Viewed by 559
Abstract
Lipid hormone imbalances involving glucocorticoids, thyroid hormones (THs), and sex hormones have widespread metabolic consequences, contributing to the global increase in obesity and insulin resistance. This review examines the complex role of disrupted lipid hormone pathways in the development of metabolic disorders, particularly [...] Read more.
Lipid hormone imbalances involving glucocorticoids, thyroid hormones (THs), and sex hormones have widespread metabolic consequences, contributing to the global increase in obesity and insulin resistance. This review examines the complex role of disrupted lipid hormone pathways in the development of metabolic disorders, particularly metabolic dysfunction-associated steatotic liver disease (MASLD). Endocrine disorders such as hypercortisolism, hypothyroidism, and polycystic ovary syndrome (PCOS) are closely linked to MASLD through shared metabolic pathways. Mechanisms include glucocorticoid-induced gluconeogenesis and lipolysis, impaired lipid clearance in hypothyroidism, and the hyperandrogenism-induced downregulation of hepatic low-density lipoprotein (LDL) receptors. PCOS-related factors—such as central obesity, adipocyte hypertrophy, low adiponectin levels, and genetic predisposition—further promote hepatic steatosis. Thyroid dysfunction may also impair the hepatic deiodination of T4, contributing to lipid accumulation and inflammation. Given the overlapping pathophysiology among endocrine, hepatic, and reproductive disorders, multidisciplinary collaboration is essential to optimize diagnosis, treatment, and long-term cardiometabolic outcomes. Full article
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14 pages, 2210 KiB  
Article
Proteomic Analysis Reveals the Protective Effects of Selenomethionine Against Liver Oxidative Injury in Piglets
by Kai Zhang, Shuhui Yan, Junhong Miao, Wen Li and Zhenxu Li
Animals 2025, 15(13), 1989; https://doi.org/10.3390/ani15131989 - 7 Jul 2025
Viewed by 324
Abstract
This study investigated the protective effects of high selenomethionine (SeMet) supplementation on liver injury caused by oxidative stress in piglets and explored the underlying mechanisms. A total of 18 piglets were randomly assigned to three groups, with six replicates in each group. The [...] Read more.
This study investigated the protective effects of high selenomethionine (SeMet) supplementation on liver injury caused by oxidative stress in piglets and explored the underlying mechanisms. A total of 18 piglets were randomly assigned to three groups, with six replicates in each group. The control (CON) and diquat (DQ) groups were fed a basal diet supplemented with 0.3 mg Se/kg Se, while the SeMet group received a basal diet supplemented with 1.0 mg Se/kg. The results indicated that SeMet supplementation significantly improved growth performance and increased the serum and liver activities of antioxidant enzymes. Additionally, it reduced the serum and liver levels of malondialdehyde and protein carbonyls in piglets exposed to DQ. Selenoprotein transcriptome analysis showed that the mRNA levels of five selenoprotein genes (GPX1/3, DIO2, and SELENOF/M/W) were significantly upregulated by dietary SeMet supplementation in the liver of DQ-challenged piglets. Proteomic analysis revealed that a total of 3614 proteins were identified in the liver of piglets. Among them, 85 differentially expressed proteins (DEPs) were identified between the CON and DQ groups, 58 DEPs were observed between the DQ and SeMet groups, and 113 DEPs were identified between the CON and SeMet groups. KEGG analysis indicated that most of the DEPs observed among the three groups were involved in fatty acid metabolism, glycolysis/gluconeogenesis, and the PPAR signaling pathway. Together, these results indicate that dietary supplementation with supernutritional SeMet alleviates the negative effects of the DQ challenge on growth performance and liver injury in piglets. This effect is associated with increased antioxidant capacity, enhanced expression of certain selenoprotein genes, and the regulation of fatty acid metabolism. Full article
(This article belongs to the Section Pigs)
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21 pages, 6314 KiB  
Article
Metagenomic and Metabolomic Perspectives on the Drought Tolerance of Broomcorn Millet (Panicum miliaceum L.)
by Yuhan Liu, Jiangling Ren, Binhong Yu, Sichen Liu and Xiaoning Cao
Microorganisms 2025, 13(7), 1593; https://doi.org/10.3390/microorganisms13071593 - 6 Jul 2025
Viewed by 452
Abstract
Drought stress is an important abiotic stress factor restricting crop production. Broomcorn millet (Panicum miliaceum L.) has become an ideal material for analyzing the stress adaptation mechanisms of crops due to its strong stress resistance. However, the functional characteristics of its rhizosphere [...] Read more.
Drought stress is an important abiotic stress factor restricting crop production. Broomcorn millet (Panicum miliaceum L.) has become an ideal material for analyzing the stress adaptation mechanisms of crops due to its strong stress resistance. However, the functional characteristics of its rhizosphere microorganisms in response to drought remain unclear. In this study, metagenomics and metabolomics techniques were employed to systematically analyze the compositional characteristics of the microbial community, functional properties, and changes in metabolites in the rhizosphere soil of broomcorn millet under drought stress. On this basis, an analysis was conducted in combination with the differences in functional pathways. The results showed that the drought treatment during the flowering stage significantly altered the species composition of the rhizosphere microorganisms of broomcorn millet. Among them, the relative abundances of beneficial microorganisms such as Nitrosospira, Coniochaeta, Diversispora, Gigaspora, Glomus, and Rhizophagus increased significantly. Drought stress significantly affects the metabolic pathways of rhizosphere microorganisms. The relative abundances of genes associated with prokaryotes, glycolysis/gluconeogenesis, and other metabolic process (e.g., ribosome biosynthesis, amino sugar and nucleotide sugar metabolism, and fructose and mannose metabolism) increased significantly. Additionally, the expression levels of functional genes involved in the phosphorus cycle were markedly upregulated. Drought stress also significantly alters the content of specific rhizosphere soil metabolites (e.g., trehalose, proline). Under drought conditions, broomcorn millet may stabilize the rhizosphere microbial community by inducing its restructuring and recruiting beneficial fungal groups. These community-level changes can enhance element cycling efficiency, optimize symbiotic interactions between broomcorn millet and rhizosphere microorganisms, and ultimately improve the crop’s drought adaptability. Furthermore, the soil metabolome (e.g., trehalose and proline) functions as a pivotal interfacial mediator, orchestrating the interaction network between broomcorn millet and rhizosphere microorganisms, thereby enhancing plant stress tolerance. This study sheds new light on the functional traits of rhizosphere microbiota under drought stress and their mechanistic interactions with host plants. Full article
(This article belongs to the Section Microbiomes)
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24 pages, 3627 KiB  
Article
Andrographolide Mitigates Inflammation and Reverses UVB-Induced Metabolic Reprogramming in HaCaT Cells
by Carolina Manosalva, Pablo Alarcón, Lucas Grassau, Carmen Cortés, Juan L. Hancke and Rafael A. Burgos
Int. J. Mol. Sci. 2025, 26(13), 6508; https://doi.org/10.3390/ijms26136508 - 6 Jul 2025
Viewed by 516
Abstract
Andrographolide (AP), a bioactive compound from Andrographis paniculata, is known for its anti-inflammatory and antioxidant properties, both essential for wound healing. However, its effects on energy metabolism during tissue repair and its role in UVB-induced photoaging remain poorly understood. This study explored [...] Read more.
Andrographolide (AP), a bioactive compound from Andrographis paniculata, is known for its anti-inflammatory and antioxidant properties, both essential for wound healing. However, its effects on energy metabolism during tissue repair and its role in UVB-induced photoaging remain poorly understood. This study explored AP’s multitarget therapeutic effects on wound healing under photoaging conditions (PhA/WH) using network pharmacology and experimental validation. Scratch wound assays showed that AP promoted keratinocyte migration in UVB-exposed HaCaT cells. Bioinformatic analysis identified 10 key targets in PhA/WH, including TNF-α, IL-1β, JUN, PPARγ, MAPK3, TP53, TGFB1, HIF-1α, PTGS2, and CTNNB1. AP suppressed UVB-induced pro-inflammatory gene expression (IL-1β, IL-6, IL-8, and COX-2) and inhibited the phosphorylation of ERK1/2 and P38, while enhancing Hypoxia-Inducible Factor-1alpha (HIF-1α) and peroxisome proliferator-activated receptors (PPARγ) expression. GC/MS-based metabolomics revealed that AP reversed UVB-induced disruptions in fatty acid metabolism, glycolysis/gluconeogenesis, and tricarboxylic acid (TCA) cycle, indicating its role in restoring the metabolic balance necessary for tissue regeneration. In conclusion, andrographolide modulates key inflammatory and metabolic pathways involved in wound repair and photoaging. These mechanistic insights contribute to a better understanding of the molecular processes underlying skin regeneration under photodamage and may inform future therapeutic strategies. Full article
(This article belongs to the Section Molecular Pharmacology)
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19 pages, 8300 KiB  
Article
Genome-Wide Association Study and RNA-Seq Analysis Uncover Candidate Genes Controlling Growth Traits in Red Tilapia (Oreochromis spp.) Under Hyperosmotic Stress
by Bingjie Jiang, Yifan Tao, Wenjing Tao, Siqi Lu, Mohamed Fekri Badran, Moustafa Hassan Lotfy Saleh, Rahma Halim Mahmoud Aboueleila, Pao Xu, Jun Qiang and Kai Liu
Int. J. Mol. Sci. 2025, 26(13), 6492; https://doi.org/10.3390/ijms26136492 - 5 Jul 2025
Viewed by 371
Abstract
Growth traits are the most important economic traits in red tilapia (Oreochromis spp.) production, and are the main targets for its genetic improvement. Increasing salinity levels in the environment are affecting the growth, development, and molecular processes of aquatic animals. Red tilapia [...] Read more.
Growth traits are the most important economic traits in red tilapia (Oreochromis spp.) production, and are the main targets for its genetic improvement. Increasing salinity levels in the environment are affecting the growth, development, and molecular processes of aquatic animals. Red tilapia tolerates saline water to some degree. However, few credible genetic markers or potential genes are available for choosing fast-growth traits in salt-tolerant red tilapia. This work used genome-wide association study (GWAS) and RNA-sequencing (RNA-seq) to discover genes related to four growth traits in red tilapia cultured in saline water. Through genotyping, it was determined that 22 chromosomes have 12,776,921 high-quality single-nucleotide polymorphisms (SNPs). One significant SNP and eight suggestive SNPs were obtained, explaining 0.0019% to 0.3873% of phenotypic variance. A significant SNP peak associated with red tilapia growth traits was located on chr7 (chr7-47464467), and plxnb2 was identified as the candidate gene in this region. A total of 501 differentially expressed genes (DEGs) were found in the muscle of fast-growing individuals compared to those of slow-growing ones, according to a transcriptome analysis. Combining the findings of the GWAS and RNA-seq analysis, 11 candidate genes were identified, namely galnt9, esrrg, map7, mtfr2, kcnj8, fhit, dnm1, cald1, plxnb2, nuak1, and bpgm. These genes were involved in ‘other types of O-glycan biosynthesis’, ‘glycine, serine and threonine metabolism’, ‘glycolysis/gluconeogenesis’, ‘mucin-type O-glycan biosynthesis’ and ‘purine metabolism signaling’ pathways. We have developed molecular markers to genetically breed red tilapia that grow quickly in salty water. Our study lays the foundation for the future marker-assisted selection of growth traits in salt-tolerant red tilapia. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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18 pages, 3016 KiB  
Article
Effects of Gallic Acid on In Vitro Ruminal Fermentation, Methane Emission, Microbial Composition, and Metabolic Functions
by Wei Zhu, Jianjun Guo, Xin Li, Yan Li, Lianjie Song, Yunfei Li, Baoshan Feng, Xingnan Bao, Jianguo Li, Yanxia Gao and Hongjian Xu
Animals 2025, 15(13), 1959; https://doi.org/10.3390/ani15131959 - 3 Jul 2025
Viewed by 359
Abstract
The objective of this study was to assess the effects of gallic acid (GA) on nutrient degradability, gas production, rumen fermentation, and the microbial community and its functions using in vitro fermentation methods. An in vitro experiment was conducted to test GA dose [...] Read more.
The objective of this study was to assess the effects of gallic acid (GA) on nutrient degradability, gas production, rumen fermentation, and the microbial community and its functions using in vitro fermentation methods. An in vitro experiment was conducted to test GA dose levels (0, 5, 10, 20, and 40 mg/g DM) in the cow’s diet. Based on the results of nutrient degradability, gas production, and rumen fermentation, the control group (0 mg/g DM, CON) and the GA group (10 mg/g DM, GA) were selected for metagenomic analysis to further explore the microbial community and its functions. The degradability of dry matter and crude protein, as well as total gas production, CH4 production, CH4/total gas, CO2 production, and CO2/total gas, decreased quadratically (p < 0.05) with increasing GA doses, reaching their lowest levels at the 10 mg/g DM dose. Total volatile fatty acid (VFA) (p = 0.004), acetate (p = 0.03), and valerate (p = 0.03) exhibited quadratic decreases, while butyrate (p = 0.0006) showed a quadratic increase with increasing GA doses. The 10 mg/g DM dose group had the lowest levels of total VFA, acetate, and valerate, and the highest butyrate level compared to the other groups. The propionate (p = 0.03) and acetate-to-propionate ratio (p = 0.03) linearly decreased with increasing gallic acid inclusion. At the bacterial species level, GA supplementation significantly affected (p < 0.05) a total of 38 bacterial species. Among these, 29 species, such as Prevotellasp.E15-22, bacteriumP3, and Alistipessp.CAG:435, were less abundant in the GA group, while 9 species, including Aristaeella_lactis and Aristaeella_hokkaidonensis, were significantly more abundant in the GA group. At the archaeal species level, the relative abundances of Methanobrevibacter_thaueri, Methanobrevibacter_boviskoreani, and Methanobrevibactersp.AbM4 were significantly reduced (p < 0.05) by GA supplementation. Amino sugar and nucleotide sugar metabolism, Starch and sucrose metabolism, Glycolysis/Gluconeogenesis, and Pyruvate metabolismwere significantly enriched in the GA group (p < 0.05). Additionally, Alanine, aspartate and glutamate metabolism was also significantly enriched in the GA group (p < 0.05). GA use could potentially be an effective strategy for methane mitigation; however, further research is needed to assess its in vivo effects in dairy cows over a longer period. Full article
(This article belongs to the Section Animal Nutrition)
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32 pages, 6041 KiB  
Article
Glucagon and Glucose Availability Influence Metabolic Heterogeneity and Malignancy in Pancreatic Neuroendocrine Tumour (pNET) Cells: Novel Routes for Therapeutic Targeting
by Bárbara Ferreira, Isabel Lemos, Cindy Mendes, Beatriz Chumbinho, Fernanda Silva, Daniela Pereira, Emanuel Vigia, Luís G. Gonçalves, António Figueiredo, Daniela Cavaco and Jacinta Serpa
Molecules 2025, 30(13), 2736; https://doi.org/10.3390/molecules30132736 - 25 Jun 2025
Viewed by 1453
Abstract
Cancer metabolism is a hallmark of cancer. However, the impact of systemic metabolism and diet on tumour evolution is less understood. This study delves into the role of glucagon, as a component of the pancreatic microenvironment, in regulating features of pancreatic neuroendocrine tumour [...] Read more.
Cancer metabolism is a hallmark of cancer. However, the impact of systemic metabolism and diet on tumour evolution is less understood. This study delves into the role of glucagon, as a component of the pancreatic microenvironment, in regulating features of pancreatic neuroendocrine tumour (pNET) cells and the metabolic remodelling occurring in the presence and absence of glucose. pNET cell lines (BON-1 and QGP-1) and the non-malignant pancreatic α-TC1 cell line were used as models. Results showed that pNET cells responded differently to glucose deprivation than α-TC1 cells. Specifically, pNET cells upregulated the GCGR in the absence of glucose, while α-TC1 cells did so in high-glucose conditions, allowing the glucagon-related pERK1/2 activation under these conditions in pNET cells. Glucagon enhanced cancerous features in pNET BON-1 cells under glucose-deprived and hyperglucagonemia-compatible concentrations. In the α-TC1 cell line, glucagon modulated cell features under high-glucose and physiological glucagon levels. NMR exometabolome analysis revealed differences in metabolic processes based on glucose availability and glucagon stimulation across cell lines, highlighting amino acid metabolism, glycolysis, and gluconeogenesis. The expression of metabolic genes was consistent with these findings. Interestingly, QGP-1 and α-TC1 cells produced glucose in no-glucose conditions, and glucagon upregulated glucose production in α-TC1 cells. This suggests that gluconeogenesis may be beneficial for some pNET subsets, pointing out novel metabolism-based strategies to manage pNETs, as well as a step forward in endocrinology and systemic metabolism. The association between GCGR expression and malignancy and a negative correlation between glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R) expression was observed, indicating a biological role of glucagon in pNETs that deserves to be explored. Full article
(This article belongs to the Special Issue Novel Metabolism-Related Biomarkers in Cancer)
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27 pages, 5470 KiB  
Article
Age-Associated Proteomic Changes in Human Spermatozoa
by Mohd Amin Beg, Abrar Osama Ismail, Ayodele Alaiya, Firdous Ahmad Khan, Taha Abo-Almagd Abdel-Meguid Hamoda, Ishfaq Ahmad Sheikh, Priyanka Sharma, Omar Mohammed Baothman, Ali Hasan Alkhzaim, Zakia Shinwari, Rinad Fahad Abuzinadah, Arif Mohammed, Abdullah Mohammed Assiri, Adel Mohammad Abuzenadah, Erdogan Memili and Jean Magloire Feugang
Int. J. Mol. Sci. 2025, 26(13), 6099; https://doi.org/10.3390/ijms26136099 - 25 Jun 2025
Viewed by 1340
Abstract
Advancing age in men significantly contributes to declining sperm fertility. Information on age-related proteomic changes in spermatozoa is limited. This study involved normal fertile Arab men in three age groups: young adult (21–30 years; n = 6), late adult (31–40 years; n = [...] Read more.
Advancing age in men significantly contributes to declining sperm fertility. Information on age-related proteomic changes in spermatozoa is limited. This study involved normal fertile Arab men in three age groups: young adult (21–30 years; n = 6), late adult (31–40 years; n = 7), and advanced age (40–51 years; n = 5). Gradient-purified spermatozoa were analyzed using LC-MS/MS and proteomic data were processed using Progenesis QI (QIfp) v3.0 and UniProt/SwissProt. Significantly enriched annotations and clustering of proteins in the proteomic datasets were identified (2-fold change; p < 0.05). A total of 588 proteins were identified, with 93% shared across the three groups. Unique proteins were MYLK4 for the young adult group, PRSS57 for the late adult group, and HMGB4, KRT4, LPGAT1, OXCT2, and MGRN1 for the advanced age group. Furthermore, 261 (44%) proteins were differentially expressed (p < 0.05) across the three groups. Functional enrichment analysis suggested an aging-related significant increase in pathways associated with neurodegenerative diseases and protein folding, alongside decreases in glycolysis/gluconeogenesis, flagellated sperm motility, acetylation, phosphoprotein modifications, oxidation processes, and Ubl conjugation. Cluster analysis highlighted significantly upregulated proteins in young adults (e.g., H2BC1, LAP3, SQLE, LTF, PDIA4, DYNLT2) and late adults (e.g., ATP5F1B, ODF2, TUBA3C, ENO1, SPO11, TEX45, TEKT3), whereas most proteins in the advanced age group exhibited downregulation (e.g., SPESP1, RAB10, SEPTIN4, RAB15, PTPN7, USP5, ANXA1, PRDX1). In conclusion, this study revealed aging-associated proteomic changes in spermatozoa that impact critical processes, including spermatogenesis, motility, metabolism, and fertilization, potentially contributing to fertility decline. These changes provide a molecular framework for developing therapies to preserve sperm proteostasis and enhance fertility in older men. Full article
(This article belongs to the Special Issue Advances in Spermatogenesis and Male Infertility)
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18 pages, 2128 KiB  
Article
Deciphering the Molecular Adapting Mechanism of Lactic Acid-Tolerant Saccharomyces cerevisiae Through Genomic and Transcriptomic Analysis
by Haowei Fan, Yin Wan, Wenqin Cai, Feng Li, Jiahui Fan, Juan Du, Mingjing Yi, Jiayi Yuan and Guiming Fu
Foods 2025, 14(12), 2027; https://doi.org/10.3390/foods14122027 - 8 Jun 2025
Viewed by 537
Abstract
During the solid-state brewing process of traditional Chinese Baijiu, lactic acid is the most abundant organic acid, which inhibits the growth and metabolism of Saccharomyces cerevisiae. To reveal the lactic acid tolerance mechanism of S. cerevisiae, the growth, metabolic performance, and [...] Read more.
During the solid-state brewing process of traditional Chinese Baijiu, lactic acid is the most abundant organic acid, which inhibits the growth and metabolism of Saccharomyces cerevisiae. To reveal the lactic acid tolerance mechanism of S. cerevisiae, the growth, metabolic performance, and antioxidant enzyme activity of S. cerevisiae NCUF309.5-44 and S. cerevisiae NCUF309.5 were measured under 4% (v/v) lactic acid stress. Additionally, whole-genome re-sequencing and transcriptomic analyses were performed to identify genetic variations and differentially expressed genes between the two strains under lactic acid stress. The results showed that, compared to the original strain, S. cerevisiae NCUF309.5-44 could adapt to the lactic acid stress faster, with a superior utilization rate of reducing sugar and a 6.43-fold higher ethanol production at 16 h. The strain primarily activated the GSH/GPx system, resulting in a 37.29% lower intracellular ROS content. A total of 1087 SNPs and 698 InDels were found between the strains, with 384 genes significantly upregulated and 254 genes downregulated in the S. cerevisiae NCUF309.5-44 under lactic acid stress. S. cerevisiae NCUF309.5-44 responded to lactic acid stress by activating the pheromone response pathway and the cell wall integrity pathway. Meanwhile, the capacity of strains to maintain the cell membrane and proton extrusion was strengthened. Additionally, its glycolysis/gluconeogenesis metabolism was also enhanced. All these mechanisms collectively contributed to improving the lactic acid tolerance of S. cerevisiae NCUF309.5-44. These findings not only enhanced our understanding of lactic acid tolerance mechanisms of S. cerevisiae NCUF309.5-44 but also paved the way for the application of this strain in optimizing Baijiu production. Full article
(This article belongs to the Section Food Microbiology)
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19 pages, 10694 KiB  
Article
Loss of Myostatin Alters Gut Microbiota and Carbohydrate Metabolism to Influence the Gut–Muscle Axis in Cattle
by Chao Hai, Hongyu Gong, Yanan Xu, Xuefei Liu, Chunling Bai, Guanghua Su, Lei Yang and Guangpeng Li
Vet. Sci. 2025, 12(6), 560; https://doi.org/10.3390/vetsci12060560 - 7 Jun 2025
Viewed by 899
Abstract
The gut–muscle axis plays a vital role in host metabolism and health. Although the MSTN gene is a well-known negative regulator of muscle growth, its role in intestinal function and metabolism remains unclear. Understanding this connection is crucial for revealing the systemic impact [...] Read more.
The gut–muscle axis plays a vital role in host metabolism and health. Although the MSTN gene is a well-known negative regulator of muscle growth, its role in intestinal function and metabolism remains unclear. Understanding this connection is crucial for revealing the systemic impact of MSTN gene editing and its potential to improve metabolic efficiency in livestock. In this study, we investigated the influence of MSTN deletion on gut microbiota composition and carbohydrate metabolism in the cecum and colon of cattle. Using integrated metagenomic, metabolomic, serum biochemical, and muscle transcriptomic analyses, we found significant alterations in microbial communities and key metabolic pathways. Hallella and Escherichia in the colon, as well as Alishewanella in the cecum, were closely linked to carbohydrate metabolism. Differential microbes and metabolites influenced key metabolic pathways, including glycolysis/gluconeogenesis and lipopolysaccharide biosynthesis. Functional gene analysis identified Bacteroides as the most critical bacterium affecting glycolysis/gluconeogenesis. Additionally, genes related to carbohydrate esterases were upregulated. These changes correlated with reduced serum glucose and insulin levels while increasing muscle gene expression related to glucose-to-lactose conversion. Overall, MSTN gene editing alters gut microbiota composition and carbohydrate metabolism in the cecum and colon, thereby influencing host glucose metabolism and energy homeostasis. Full article
(This article belongs to the Section Veterinary Microbiology, Parasitology and Immunology)
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