İrem Mutlu Durğut, Hayrunnisa Yeşil Sarsmaz, Seren Gülşen Gürgen
This study aimed to investigate the effects of maternal supplementation with fish oil, flaxseed oil, and walnut oil rich in omega-3 fatty acids during lactation on mammary tissue structure and milk quality. Rats were randomly assigned to negative control, control, fish oil, walnut oil, and flaxseed oil groups. The supplements were administered by oral gavage from parturition (Day 0) to the end of lactation (Day 21). Mammary tissues were evaluated immunohistochemically, and blood samples were analyzed biochemically. The docosahexaenoic acid (DHA) level in the fish oil group was significantly higher than in other groups (p < 0.05). Fatty Acid Desaturase-2 (FADS2) levels also differed significantly between the negative control and all other groups (p < 0.05), while no significant change was observed in the walnut oil group (p > 0.05). Immunostaining intensities for insulin-like growth factor 1 (IGF-1), transforming growth factor beta 1 (TGF-β1), and vascular endothelial growth factor (VEGF) varied significantly among all groups (p < 0.05). These findings suggest that maternal fish oil supplementation during lactation more effectively enhances milk quality and mammary tissue function than flaxseed or walnut oil, indicating its potential as a dietary strategy to improve milk composition and support offspring nutrition.
Trial Registration: Registered on the Clinical Trial Registry (www.clinicaltrials.gov; Clinical Trials identifier: NCT06111378 (26/10/2023)
{"title":"A Comparative Study on the Effect of Omega-3 Fatty Acids on Lactation","authors":"İrem Mutlu Durğut, Hayrunnisa Yeşil Sarsmaz, Seren Gülşen Gürgen","doi":"10.1002/mnfr.70393","DOIUrl":"10.1002/mnfr.70393","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aimed to investigate the effects of maternal supplementation with fish oil, flaxseed oil, and walnut oil rich in omega-3 fatty acids during lactation on mammary tissue structure and milk quality. Rats were randomly assigned to negative control, control, fish oil, walnut oil, and flaxseed oil groups. The supplements were administered by oral gavage from parturition (Day 0) to the end of lactation (Day 21). Mammary tissues were evaluated immunohistochemically, and blood samples were analyzed biochemically. The docosahexaenoic acid (DHA) level in the fish oil group was significantly higher than in other groups (<i>p</i> < 0.05). Fatty Acid Desaturase-2 (FADS2) levels also differed significantly between the negative control and all other groups (<i>p</i> < 0.05), while no significant change was observed in the walnut oil group (<i>p</i> > 0.05). Immunostaining intensities for insulin-like growth factor 1 (IGF-1), transforming growth factor beta 1 (TGF-β1), and vascular endothelial growth factor (VEGF) varied significantly among all groups (<i>p</i> < 0.05). These findings suggest that maternal fish oil supplementation during lactation more effectively enhances milk quality and mammary tissue function than flaxseed or walnut oil, indicating its potential as a dietary strategy to improve milk composition and support offspring nutrition.</p>\u0000 <p><b>Trial Registration</b>: Registered on the Clinical Trial Registry (www.clinicaltrials.gov; Clinical Trials identifier: NCT06111378 (26/10/2023)</p>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemotherapy-induced senescence-associated tumor microenvironment (S-TME) facilitates colorectal cancer (CRC) progression. This study elucidates the mechanism by which Tianma granule (TMG), a traditional Chinese medicine formula, remodels the S-TME and inhibits CRC, specifically investigating the role of the miR-29a-5p/P53 axis. Liquid chromatography–tandem mass spectrometry (LC–MS/MS) identified 18 bioactive components in TMG, and network pharmacology highlighted P53 as a core target. Functional assays, including Cell Counting Kit-8 (CCK-8), β-galactosidase staining, flow cytometry, wound-healing, and Transwell migration tests, were conducted using doxorubicin (DOX)–induced senescent human umbilical vein endothelial cells (HUVECs) and CRC lines. TMG suppressed CRC cell proliferation, motility, and invasiveness while promoting apoptosis. TMG reduced P53/cyclin-dependent kinase inhibitor 1A (P21) and senescence-associated secretory phenotype (SASP) factors (IL-6, IL-8, CCL20), while upregulating miR-29a-5p in senescent HUVECs. miR-29a-5p inhibition enhanced senescence and increased P53/P21/SASP, whereas P53 silencing lowered P21 and decreased miR-29a-5p, indicating mutual regulation. In azoxymethane/dextran sulfate sodium (AOM/DSS)-CRC mice, TMG reduced tumor burden and improved survival, accompanied by lower P53/P21 and restored miR-29a-5p in tissues. TMG remodels the chemotherapy-induced S-TME and suppresses CRC progression by modulating the miR-29a-5p/P53 axis, enhancing apoptosis in senescent cells, and counteracting S-TME-mediated tumor growth and metastasis. This highlights TMG's therapeutic potential.
{"title":"Targeting Senescence: Tianma Granule Inhibits Colorectal Cancer Progression by Modulating miR-29a-5p/P53 Signaling in the Tumor Microenvironment","authors":"Xiaojuan Tang, Yuan Ren, Yongmin Li, Yuan Lv, Liang Zhao, Yongheng He","doi":"10.1002/mnfr.70338","DOIUrl":"10.1002/mnfr.70338","url":null,"abstract":"<p>Chemotherapy-induced senescence-associated tumor microenvironment (S-TME) facilitates colorectal cancer (CRC) progression. This study elucidates the mechanism by which Tianma granule (TMG), a traditional Chinese medicine formula, remodels the S-TME and inhibits CRC, specifically investigating the role of the miR-29a-5p/P53 axis. Liquid chromatography–tandem mass spectrometry (LC–MS/MS) identified 18 bioactive components in TMG, and network pharmacology highlighted P53 as a core target. Functional assays, including Cell Counting Kit-8 (CCK-8), β-galactosidase staining, flow cytometry, wound-healing, and Transwell migration tests, were conducted using doxorubicin (DOX)–induced senescent human umbilical vein endothelial cells (HUVECs) and CRC lines. TMG suppressed CRC cell proliferation, motility, and invasiveness while promoting apoptosis. TMG reduced P53/cyclin-dependent kinase inhibitor 1A (P21) and senescence-associated secretory phenotype (SASP) factors (IL-6, IL-8, CCL20), while upregulating miR-29a-5p in senescent HUVECs. miR-29a-5p inhibition enhanced senescence and increased P53/P21/SASP, whereas P53 silencing lowered P21 and decreased miR-29a-5p, indicating mutual regulation. In azoxymethane/dextran sulfate sodium (AOM/DSS)-CRC mice, TMG reduced tumor burden and improved survival, accompanied by lower P53/P21 and restored miR-29a-5p in tissues. TMG remodels the chemotherapy-induced S-TME and suppresses CRC progression by modulating the miR-29a-5p/P53 axis, enhancing apoptosis in senescent cells, and counteracting S-TME-mediated tumor growth and metastasis. This highlights TMG's therapeutic potential.</p>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mnfr.70338","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Based on Traditional Chinese Medicine (TCM) theory, the efficacy and mechanism of Ginger juice processed Ziziphi Spinosae Semen (GJPZSS) for treating insomnia, particularly stress-related types, were investigated to provide empirical evidence. An insomnia model was induced in mice by DL-4-chlorophenylalanine (PCPA) and chronic tail clamping. The sedative effect was evaluated by behavioral tests. Serum components from GJPZSS were analyzed by UHPLC-Q-TOF-MS/MS, and 64 potential targets were identified. The cAMP signaling pathway was enriched as the core pathway by Kyoto Encyclopedia of genes and genomes (KEGG) analysis and was validated by molecular docking. GJPZSS was demonstrated to prolong sleep time, reduce immobility time, increase 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA) levels, decrease hypothalamic-pituitary-adrenal (HPA) axis levels, and suppress neuronal death. The reduction of the cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the brain was also significantly inhibited. It was concluded that the sleep-improving effect of GJPZSS was mediated through the regulation of the HPA axis and the cAMP/PKA/CREB/BDNF signaling pathway.
{"title":"Discovery of the Underlying Mechanism of Ginger Juice Processed Ziziphi Spinosae Semen for Its Sedative-Hypnotic Effect on Insomnia Mice via Regulation of HPA Axis and cAMP/PKA Signaling Pathway","authors":"Lintong Xie, Xia Zhang, Fangfang Xue, Yifei Gao, Jizhen Guo, Hui Zhu, Xiao Liu","doi":"10.1002/mnfr.70327","DOIUrl":"10.1002/mnfr.70327","url":null,"abstract":"<div>\u0000 \u0000 <p>Based on Traditional Chinese Medicine (TCM) theory, the efficacy and mechanism of Ginger juice processed Ziziphi Spinosae Semen (GJPZSS) for treating insomnia, particularly stress-related types, were investigated to provide empirical evidence. An insomnia model was induced in mice by DL-4-chlorophenylalanine (PCPA) and chronic tail clamping. The sedative effect was evaluated by behavioral tests. Serum components from GJPZSS were analyzed by UHPLC-Q-TOF-MS/MS, and 64 potential targets were identified. The cAMP signaling pathway was enriched as the core pathway by Kyoto Encyclopedia of genes and genomes (KEGG) analysis and was validated by molecular docking. GJPZSS was demonstrated to prolong sleep time, reduce immobility time, increase 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA) levels, decrease hypothalamic-pituitary-adrenal (HPA) axis levels, and suppress neuronal death. The reduction of the cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the brain was also significantly inhibited. It was concluded that the sleep-improving effect of GJPZSS was mediated through the regulation of the HPA axis and the cAMP/PKA/CREB/BDNF signaling pathway.</p>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146016638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ana Paula Ribeiro Gaspar, Cíntia Tomaz Sant' Ana, Mariana Grancieri, Ana Paula Carvalho de Moura Cruz, Leone Soromenho Viana, Eduardo Lorencetti Fornazier, Marisa da Silva Corrêa, Henrique Jordem Venial, Jankerle Neves Boeloni, Neuza Maria Brunoro Costa
Iron deficiency anemia may affect carbohydrates and lipid metabolism. This study aimed to evaluate the iron bioavailability from biofortified cowpeas in the context of a high-fat/high-sugar diet and its relationship with carbohydrate and lipid metabolism. Forty-eight Wistar rats were induced to anemia for 21 days, and during the repletion phase (35 days), the animals received diets containing 12 ppm of iron from ferrous sulfate or biofortified (BRS Aracê and BRS Tumucumaque) and a conventional (BRS Pajeú) cowpeas. The biofortified cowpea Aracê showed a hemoglobin gain similar to ferrous sulfate, improved crypt size in the colon, lowered insulin levels and area under the curve in the glucose tolerance test compared to ferrous sulfate (p < 0.05). Hepcidin levels were similar between the groups. The biofortified cowpeas increased the production of short-chain fatty acids compared to ferrous sulfate (p < 0.05). Both biofortified and conventional cowpeas increased HDL-c concentrations, reduced the total cholesterol/HDL-c ratio, and decreased fecal triglyceride excretion (p < 0.05). The biofortification process favors beneficial metabolic changes in the iron, glucose, and lipid metabolism.
{"title":"The Effects of Biofortified Cowpeas on Iron, Glucose, and Lipid Metabolism in Rats Fed a High-Fat/High-Sugar Diet","authors":"Ana Paula Ribeiro Gaspar, Cíntia Tomaz Sant' Ana, Mariana Grancieri, Ana Paula Carvalho de Moura Cruz, Leone Soromenho Viana, Eduardo Lorencetti Fornazier, Marisa da Silva Corrêa, Henrique Jordem Venial, Jankerle Neves Boeloni, Neuza Maria Brunoro Costa","doi":"10.1002/mnfr.70392","DOIUrl":"10.1002/mnfr.70392","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Iron deficiency anemia may affect carbohydrates and lipid metabolism. This study aimed to evaluate the iron bioavailability from biofortified cowpeas in the context of a high-fat/high-sugar diet and its relationship with carbohydrate and lipid metabolism. Forty-eight Wistar rats were induced to anemia for 21 days, and during the repletion phase (35 days), the animals received diets containing 12 ppm of iron from ferrous sulfate or biofortified (BRS Aracê and BRS Tumucumaque) and a conventional (BRS Pajeú) cowpeas. The biofortified cowpea Aracê showed a hemoglobin gain similar to ferrous sulfate, improved crypt size in the colon, lowered insulin levels and area under the curve in the glucose tolerance test compared to ferrous sulfate (<i>p</i> < 0.05). Hepcidin levels were similar between the groups. The biofortified cowpeas increased the production of short-chain fatty acids compared to ferrous sulfate (<i>p</i> < 0.05). Both biofortified and conventional cowpeas increased HDL-c concentrations, reduced the total cholesterol/HDL-c ratio, and decreased fecal triglyceride excretion (<i>p</i> < 0.05). The biofortification process favors beneficial metabolic changes in the iron, glucose, and lipid metabolism.</p>\u0000 </section>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12824469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146016681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Armando Navarro, Gerardo E. Rodea, Aldo Hugo de la Cruz-Montoya, Clara Estela Díaz-Velásquez, Felipe Vaca-Paniagua, Armando Navarro-Cid del Prado, Laura L. Tirado-Gómez, Ariel Vilchis-Reyes, Guadalupe García de la Torre, Verónica Cruz-Licea, Carlos Eslava-Campos, Hugo G. Castelán-Sánchez
The gut microbiota is a key determinant of metabolic health in adolescence, a critical period for the onset of obesity. Understanding its associations with body mass index (BMI), diet, and socioeconomic status (SES) helps identify early determinants of metabolic risk. We analyzed stool samples from 95 Mexican adolescents (11–15 years) using 16S rRNA V3–V4 sequencing. The main phyla were Bacteroidetes, Firmicutes, and Proteobacteria, with. At the genus level Azobacteroides Candidatus, Parabacteroides, Bacteroides, and Prevotella being the most abundant. Overweight and obese adolescents showed lower diversity and more Bacteroidetes, while normal-weight peers had more Firmicutes and beneficial taxa. Lactobacillus was enriched in normal-weight individuals, while Parabacteroides and Prevotella were more abundant in adolescents with low SES. A diet high in sugar-sweetened beverages and low in whole grains was associated with a predominance of Bacteroides and lower diversity. Low SES was also associated with potential pathogens, including Escherichia and Salmonella, and gastrointestinal symptoms. In particular, Vibrio and Salmonella were inversely associated with cholesterol and triglycerides, while Clostridiodes was positively correlated with triglycerides. Diet and SES influenced the adolescent gut microbiome, by shaping diversity, potentially pathogenic taxa, and their associations with metabolic health indicators.
{"title":"Gut Microbiota Composition in Adolescents From Mexico City, Associations With Nutritional and Socioeconomic Factors: Results From a Pilot Study","authors":"Armando Navarro, Gerardo E. Rodea, Aldo Hugo de la Cruz-Montoya, Clara Estela Díaz-Velásquez, Felipe Vaca-Paniagua, Armando Navarro-Cid del Prado, Laura L. Tirado-Gómez, Ariel Vilchis-Reyes, Guadalupe García de la Torre, Verónica Cruz-Licea, Carlos Eslava-Campos, Hugo G. Castelán-Sánchez","doi":"10.1002/mnfr.70386","DOIUrl":"10.1002/mnfr.70386","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>The gut microbiota is a key determinant of metabolic health in adolescence, a critical period for the onset of obesity. Understanding its associations with body mass index (BMI), diet, and socioeconomic status (SES) helps identify early determinants of metabolic risk. We analyzed stool samples from 95 Mexican adolescents (11–15 years) using 16S rRNA V3–V4 sequencing. The main phyla were <i>Bacteroidetes, Firmicutes</i>, and <i>Proteobacteria</i>, with. At the genus level <i>Azobacteroides Candidatus</i>, <i>Parabacteroides</i>, <i>Bacteroides</i>, and <i>Prevotella</i> being the most abundant. Overweight and obese adolescents showed lower diversity and more <i>Bacteroidetes</i>, while normal-weight peers had more <i>Firmicutes</i> and beneficial taxa. <i>Lactobacillus</i> was enriched in normal-weight individuals, while <i>Parabacteroides and Prevotella</i> were more abundant in adolescents with low SES. A diet high in sugar-sweetened beverages and low in whole grains was associated with a predominance of <i>Bacteroides</i> and lower diversity. Low SES was also associated with potential pathogens, including <i>Escherichia</i> and <i>Salmonella</i>, and gastrointestinal symptoms. In particular, <i>Vibrio</i> and <i>Salmonella</i> were inversely associated with cholesterol and triglycerides, while <i>Clostridiodes</i> was positively correlated with triglycerides. Diet and SES influenced the adolescent gut microbiome, by shaping diversity, potentially pathogenic taxa, and their associations with metabolic health indicators.</p>\u0000 </section>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12824470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146016650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ren Wang, Susan Goruk, Catherine B. Chan, Catherine J. Field
To investigate whether early-life docosahexaenoic acid (DHA) consumption mitigated the effects of a high-fat diet (HFD) on body composition, endocrine hormones, immune function, inflammatory biomarkers, and identify sex differences.
Wistar rats were fed (PND 0–70) diets differing only in fat composition: control low-fat (10% fat, 0% arachidonic acid [ARA], 0% DHA), control high-fat (HF, 20% fat, 0% ARA, 0% DHA), or DHA HF (20% fat, 1% ARA, 2% DHA) (n = 16/group, males/females = 8/8). Plasma hormones (ELISA), inflammatory biomarkers (electrochemiluminescence), splenocytes phenotype (immunofluorescence), and ex vivo cytokine production (ELISA) after mitogen stimulation were measured. HFD did not alter body weight/composition or inflammatory profile but increased plasma glucagon-like peptide 1 (GLP-1, males, p = 0.02). In the spleen, HFD lowered transforming growth factor-beta (TGF-β) and increased interleukin (IL)-10 (females) and IL-2 production (p < 0.03). It also lowered % of regulatory T cells (Treg), B cells (males), conventional type 1dendritic cells (cDC1), and MHC-II and CD86 expression (males) (p < 0.03). DHA mitigated HFD-related changes in plasma GLP-1 (males) andTGF-β, IL-10 (females), and IL-2 production (p ≤ 0.03) and increased % of B cells (males), cDC1, MHC-II, and CD86 expression (males) (p < 0.03).
DHA mitigated HFD-induced impaired Treg response and compromised adaptive immunity and antigen-presenting function in a sex-specific manner.
{"title":"Docosahexaenoic Acid Consumption Early in Life Improves Immune Dysfunction in High-Fat Diet-Fed Wistar Rats in a Sex-Specific Manner","authors":"Ren Wang, Susan Goruk, Catherine B. Chan, Catherine J. Field","doi":"10.1002/mnfr.70391","DOIUrl":"10.1002/mnfr.70391","url":null,"abstract":"<p>To investigate whether early-life docosahexaenoic acid (DHA) consumption mitigated the effects of a high-fat diet (HFD) on body composition, endocrine hormones, immune function, inflammatory biomarkers, and identify sex differences.</p><p>Wistar rats were fed (PND 0–70) diets differing only in fat composition: control low-fat (10% fat, 0% arachidonic acid [ARA], 0% DHA), control high-fat (HF, 20% fat, 0% ARA, 0% DHA), or DHA HF (20% fat, 1% ARA, 2% DHA) (<i>n</i> = 16/group, males/females = 8/8). Plasma hormones (ELISA), inflammatory biomarkers (electrochemiluminescence), splenocytes phenotype (immunofluorescence), and <i>ex vivo</i> cytokine production (ELISA) after mitogen stimulation were measured. HFD did not alter body weight/composition or inflammatory profile but increased plasma glucagon-like peptide 1 (GLP-1, males, <i>p</i> = 0.02). In the spleen, HFD lowered transforming growth factor-beta (TGF-β) and increased interleukin (IL)-10 (females) and IL-2 production (<i>p</i> < 0.03). It also lowered % of regulatory T cells (Treg), B cells (males), conventional type 1dendritic cells (cDC1), and MHC-II and CD86 expression (males) (<i>p</i> < 0.03). DHA mitigated HFD-related changes in plasma GLP-1 (males) andTGF-β, IL-10 (females), and IL-2 production (<i>p</i> ≤ 0.03) and increased % of B cells (males), cDC1, MHC-II, and CD86 expression (males) (<i>p</i> < 0.03).</p><p>DHA mitigated HFD-induced impaired Treg response and compromised adaptive immunity and antigen-presenting function in a sex-specific manner.</p>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12824472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146016678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Annemarie J. F. Westheim, Ludwig J. Dubois, Elia Prades-Sagarra, Jiyang Chan, Alexander M. A. van der Wiel, Natasja G. Lieuwes, Rianne Biemans, Ying Cong, Tom Houben, Dennis M. Meesters, Ala Yaromina, Miriam van Dijk, Jeroen van Bergenhenegouwen, Ardy van Helvoort, Ramon C. J. Langen, John Penders, Ronit Shiri-Sverdlov, Jan Theys
Several studies demonstrated curative responses of combined radio-immunotherapy, although not standard-of-care for most cancers. Increased fiber intake has been associated with improved radiotherapy and immunotherapy outcomes, but fiber compositions’ impact remains unclear. This study aimed to explore whether dietary fiber composition influences the therapeutic outcome of combined radio-immunotherapy in a preclinical cancer model. A syngeneic mouse model of colon cancer (CT26) (female BALB/cOla Hsd) was used. Mice were randomized into three groups (n = 12) of iso-caloric diets with different fiber compositions. Five instances of local radiotherapy on tumors, combined with injections of anti-PD-L1, were administered over 5 and 10 days. Diets’ impact was assessed on progression-free survival, SCFA levels in fecal and cecal samples, gut microbiome composition, and immunological profile. Progression-free survival was different between compositions, as well as their gut microbiota community structure, at all measured time-points. Therapeutic outcome (cure) was negatively associated with the relative abundance of Bacteroides and positively with Atopobiaceae Family. There was no association with SCFA levels. Cured mice displayed smaller spleens containing increased proportions of CD8+ T-cells and decreased proportions of myeloid-derived suppressor cells. Our data suggest that fiber composition may influence therapeutic outcome of combined radio-immunotherapy treatment in vivo.
{"title":"The Effect of Dietary Fiber Compositions on the Therapeutic Outcome of Combined Radio- and Immunotherapy in a Preclinical Cancer Model","authors":"Annemarie J. F. Westheim, Ludwig J. Dubois, Elia Prades-Sagarra, Jiyang Chan, Alexander M. A. van der Wiel, Natasja G. Lieuwes, Rianne Biemans, Ying Cong, Tom Houben, Dennis M. Meesters, Ala Yaromina, Miriam van Dijk, Jeroen van Bergenhenegouwen, Ardy van Helvoort, Ramon C. J. Langen, John Penders, Ronit Shiri-Sverdlov, Jan Theys","doi":"10.1002/mnfr.70370","DOIUrl":"10.1002/mnfr.70370","url":null,"abstract":"<p>Several studies demonstrated curative responses of combined radio-immunotherapy, although not standard-of-care for most cancers. Increased fiber intake has been associated with improved radiotherapy and immunotherapy outcomes, but fiber compositions’ impact remains unclear. This study aimed to explore whether dietary fiber composition influences the therapeutic outcome of combined radio-immunotherapy in a preclinical cancer model. A syngeneic mouse model of colon cancer (CT26) (female BALB/cOla Hsd) was used. Mice were randomized into three groups (<i>n</i> = 12) of iso-caloric diets with different fiber compositions. Five instances of local radiotherapy on tumors, combined with injections of anti-PD-L1, were administered over 5 and 10 days. Diets’ impact was assessed on progression-free survival, SCFA levels in fecal and cecal samples, gut microbiome composition, and immunological profile. Progression-free survival was different between compositions, as well as their gut microbiota community structure, at all measured time-points. Therapeutic outcome (cure) was negatively associated with the relative abundance of <i>Bacteroides</i> and positively with <i>Atopobiaceae Family</i>. There was no association with SCFA levels. Cured mice displayed smaller spleens containing increased proportions of CD8+ T-cells and decreased proportions of myeloid-derived suppressor cells. Our data suggest that fiber composition may influence therapeutic outcome of combined radio-immunotherapy treatment in vivo.</p>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mnfr.70370","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jack Feehan, Barry Kitchen, Sarah Fraser, Nicholas Tripodi, Narges Dargahi, Vasso Apostolopoulos
Pancreatic cancer treatment typically involves surgery, chemotherapy, and radiotherapy. However, recent studies are investigating alternative therapeutic strategies, including targeted therapies, immunotherapy, and the adjunctive use of compounds like vitamin B6. PLP functions as a cofactor in over 100 enzymatic reactions crucial for amino acid metabolism, neurotransmitter production, and heme synthesis. Previous studies demonstrated PLP's anti-cancer properties in human lymphoma cells, demonstrating its anti-proliferative and anti-migratory effects, as well as its influence on cytokine levels and checkpoint marker expression. Herein, we further investigated PLP's anti-cancer effects on human pancreatic cancer cells, showing a reduction in cell growth, disruption of the mitochondrial membranes, increased superoxide production, and the induction of apoptosis. In addition, PLP treatment in BxPC3 cells affects transcripts related to key pathways like E2F, G2M Checkpoint, mTOR, and KRAS, enhancing functional protein networks that may improve anti-cancer effects. In PANC1 cells, PLP reduces KRAS-related transcripts and increases those involved in Tumor Necrosis Factor signaling and the unfolded protein response, suggesting a regulatory role that may enhance cellular stress responses. Overall, the findings from this study indicate that PLP may pave the way for more effective therapeutic adjunctive options in the management of pancreatic cancer.
{"title":"Pyridoxal 5′-Phosphate Suppresses Growth of Pancreatic Adenocarcinoma Cells In Vitro via Regulation of Oncogenic RAS","authors":"Jack Feehan, Barry Kitchen, Sarah Fraser, Nicholas Tripodi, Narges Dargahi, Vasso Apostolopoulos","doi":"10.1002/mnfr.70333","DOIUrl":"10.1002/mnfr.70333","url":null,"abstract":"<div>\u0000 \u0000 <p>Pancreatic cancer treatment typically involves surgery, chemotherapy, and radiotherapy. However, recent studies are investigating alternative therapeutic strategies, including targeted therapies, immunotherapy, and the adjunctive use of compounds like vitamin B6. PLP functions as a cofactor in over 100 enzymatic reactions crucial for amino acid metabolism, neurotransmitter production, and heme synthesis. Previous studies demonstrated PLP's anti-cancer properties in human lymphoma cells, demonstrating its anti-proliferative and anti-migratory effects, as well as its influence on cytokine levels and checkpoint marker expression. Herein, we further investigated PLP's anti-cancer effects on human pancreatic cancer cells, showing a reduction in cell growth, disruption of the mitochondrial membranes, increased superoxide production, and the induction of apoptosis. In addition, PLP treatment in BxPC3 cells affects transcripts related to key pathways like E2F, G2M Checkpoint, mTOR, and KRAS, enhancing functional protein networks that may improve anti-cancer effects. In PANC1 cells, PLP reduces KRAS-related transcripts and increases those involved in Tumor Necrosis Factor signaling and the unfolded protein response, suggesting a regulatory role that may enhance cellular stress responses. Overall, the findings from this study indicate that PLP may pave the way for more effective therapeutic adjunctive options in the management of pancreatic cancer.</p>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fanette Fontaine, Sondra Turjeman, Meriam Haib, Maria Carmen Collado, Karel Callens, Omry Koren
Childhood malnutrition, including undernutrition, obesity, and micronutrient deficiencies, remains a major global health burden. Emerging evidence points to the gut microbiome as a critical mediator linking maternal, prenatal, and early-life nutrition to long-term offspring health outcomes. From conception and through the first years of life, maternal diet, metabolic state, and environmental exposures shape offspring microbial colonization and maturation. Breastfeeding and consumption of fiber-rich and fermented foods (maternal and post-weaning) support beneficial microbiota, while high-fat, high-sugar diets, xenobiotics, and artificial additives may promote dysbiosis. The composition and diversity of the infant microbiome influence immune, metabolic, and neurodevelopmental processes and may also contribute to the intergenerational transmission of malnutrition. While commercial formulas increasingly include “biotics” to mimic human milk, exclusive breastfeeding remains the gold standard. Complementary feeding practices, including timing and diet quality, are known to modulate microbial maturation. Diet-based interventions in pregnancy show promise in improving microbiome function and preventing disease in offspring. Because the microbiome is highly plastic in the first years of life, this window offers unique opportunities for preventive strategies targeting maternal and child nutrition. Integrating microbiome science into public health and dietary guidelines could enhance current approaches to breaking the cycle of malnutrition and promoting lifelong health.
{"title":"Programming the Infant Gut: How Maternal and Early Life Nutrition Shape the Infant Microbiome and Long-term Health—A Narrative Review","authors":"Fanette Fontaine, Sondra Turjeman, Meriam Haib, Maria Carmen Collado, Karel Callens, Omry Koren","doi":"10.1002/mnfr.70385","DOIUrl":"10.1002/mnfr.70385","url":null,"abstract":"<p>Childhood malnutrition, including undernutrition, obesity, and micronutrient deficiencies, remains a major global health burden. Emerging evidence points to the gut microbiome as a critical mediator linking maternal, prenatal, and early-life nutrition to long-term offspring health outcomes. From conception and through the first years of life, maternal diet, metabolic state, and environmental exposures shape offspring microbial colonization and maturation. Breastfeeding and consumption of fiber-rich and fermented foods (maternal and post-weaning) support beneficial microbiota, while high-fat, high-sugar diets, xenobiotics, and artificial additives may promote dysbiosis. The composition and diversity of the infant microbiome influence immune, metabolic, and neurodevelopmental processes and may also contribute to the intergenerational transmission of malnutrition. While commercial formulas increasingly include “biotics” to mimic human milk, exclusive breastfeeding remains the gold standard. Complementary feeding practices, including timing and diet quality, are known to modulate microbial maturation. Diet-based interventions in pregnancy show promise in improving microbiome function and preventing disease in offspring. Because the microbiome is highly plastic in the first years of life, this window offers unique opportunities for preventive strategies targeting maternal and child nutrition. Integrating microbiome science into public health and dietary guidelines could enhance current approaches to breaking the cycle of malnutrition and promoting lifelong health.</p>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mnfr.70385","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146002811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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