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BACKGROUND: Epilepsy is a widespread central nervous system disorder with an estimated 50 million people affected globally. It is characterized by a bimodal incidence peak among infants and the elderly and is influenced by a variety of risk factors, including a significant genetic component. Despite the use of anti-epileptic drugs (AEDs), drug-refractory epilepsy develops in about one-third of patients, highlighting the need for alternative therapeutic approaches. AIMS: The primary aim of this study was to evaluate the neuroprotective effects of troglitazone (TGZ) in epilepsy and to explore the potential mechanisms underlying its action. METHODS: We employed both in vitro and in vivo models to assess TGZ's effects. The in vitro model involved glutamate-induced toxicity in HT22 mouse hippocampal neurons, while the in vivo model used kainic acid (KA) to induce epilepsy in mice. A range of methods, including Hoechst/PI staining, CCK-8 assay, flow cytometry, RT-PCR analysis, Nissl staining, scanning electron microscopy, and RNA sequencing, were utilized to assess various parameters such as cellular damage, viability, lipid-ROS levels, mitochondrial membrane potential, mRNA expression, seizure grade, and mitochondrial morphology. RESULTS: Our results indicate that TGZ, at doses of 5 or 20 mg/kg/day, significantly reduces KA-induced seizures and neuronal damage in mice by inhibiting the process of ferroptosis. Furthermore, TGZ was found to prevent changes in mitochondrial morphology. In the glutamate-induced HT22 cell damage model, 2.5 µM TGZ effectively suppressed neuronal ferroptosis, as shown by a reduction in lipid-ROS accumulation, a decrease in mitochondrial membrane potential, and an increase in PTGS2 expression. The anti-ferroptotic effect of TGZ was confirmed in an erastin-induced HT22 cell damage model as well. Additionally, TGZ reversed the upregulation of Plaur expression in HT22 cells treated with glutamate or erastin. The downregulation of Plaur expression was found to alleviate seizures and reduce neuronal damage in the mouse hippocampus. CONCLUSION: This study demonstrates that troglitazone has significant therapeutic potential in the treatment of epilepsy by reducing epileptic seizures and the associated brain damage through the inhibition of neuronal ferroptosis. The downregulation of Plaur expression plays a crucial role in TGZ's anti-ferroptotic effect, offering a promising avenue for the development of new epilepsy treatments.
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Epilepsia , Ferroptose , Fármacos Neuroprotetores , Troglitazona , Animais , Camundongos , Epilepsia/tratamento farmacológico , Epilepsia/induzido quimicamente , Ferroptose/efeitos dos fármacos , Ferroptose/fisiologia , Fármacos Neuroprotetores/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Hipocampo/metabolismo , Ácido Glutâmico/metabolismo , Masculino , Ácido Caínico/toxicidade , Camundongos Endogâmicos C57BL , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêuticoRESUMO
Introduction: Human milk is widely acknowledged as the optimal food for infant aged 0 ~ 6 months. While there has been extensive documentation on the mineral and trace element composition of human milk, results on the relationship between mineral content and infant growth remain mixed. This cross-sectional study aims to explore human milk mineral patterns and to investigate associations between human milk mineral patterns, human milk metabolomic profile and infant growth. Methods: A total of 200 breast milk samples from seven cities in China was included. Human milk mineral and trace elements was detected by inductively coupled plasma mass spectrometer (ICP-MS). K-means cluster analysis was utilized to derived human milk mineral patterns. Untargeted human milk metabolomic profiles was determined using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Differences of infant growth rate and metabolomic profiles were then compared across patterns identified. Results: Three human milk mineral patterns were identified. Cluster I was characterized as the highest levels of potassium, magnesium and calcium, while the lowest levels of copper, zinc, manganese and selenium. Cluster II showed the most abundant sodium, iron, zinc, manganese and selenium. Cluster III had the lowest levels of sodium, potassium, magnesium, iron and calcium. Infants of cluster I showed significantly higher length-for-age z score (0.60 ± 2.03, p = 0.03). Compared with other clusters, samples of cluster I showed lower expression of metabolites of arachidonic acid (ARA) and nicotinate and nicotinamide metabolism pathway. Discussion: A human milk mineral pattern was identified which is related to increased infant growth rate and altered metabolic signature. Future work is needed to understand these human milk patterns in terms of biologic mechanisms and generalization to other populations.
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Objectives: Bifidobacterium longum subsp. infantis is a dominant bacterium in infant gut, which plays a critical role in maintaining the health and development of infants. This study investigated the abilities of eight different strains of B. longum subsp. infantis to regulate the T helper (Th)1/Th2 balance. Methods: Eight B. longum subsp. infantis strains, including I2MI (FJSWXI2MIM1), I4MI [FJSWXI4MI (CCFM1270)], I4MNI (FJSWXI4MNIM1), I5TI (FJSWXI5TIM1), I6TI (FJSWXI6TIM1), I8TI [FJSWXI8TI (CCFM1271)], I10TI [FJSWXI10TI (CCFM1272)], and B6MNI [BJSWXB6MNIM1 (CCFM1269)], were gavaged to BALB/C pups in both female (n = 8) and male (n = 8) mice starting from 1 to 3 weeks old (1 × 109 CFU/day/mice). Selected immune cells were assessed by immunofluorescence and flow cytometry. Cytokines and immunoglobulins were determined by ELISA. Bacterial and bifidobacterial communities were determined by 16S rRNA gene sequencing and bifidobacterial groEL sequencing. Results: B. longum subsp. infantis I4MI and I8TI were shown to increase the ration of colonic IgG2a/IgE in male mice (P < 0.05). B6MNI was demonstrated to significantly increase the levels of colonic IFN-γ and IgG2a, as well as the ratio of IgG2a/IgE in female mice (P < 0.05). It was also shown to significantly increase the ratio of colonic IgG2a/IgE (P < 0.05) and reduce the level of colonic IL-4 in male mice (P < 0.05). Furthermore, B6MNI was demonstrated to regulate colonic JAK/STAT pathway in both male and female mice. I4MI, I5TI, and B6MNI were shown to increase the relative abundance of Bifidobacterium and B. longum subsp. infantis in both male and female mice, whereas I8TI was only shown to increase the relative abundance of Bifidobacterium and B. longum subsp. infantis in male mice (P < 0.05). Conclusion: These results indicated supplementation with B. longum subsp. infantis in early infancy may regulate the Th1/Th2 immune balance, which may prevent the development of related diseases.
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The composition of milk lipids varies across different ethnic sources. The lipidome profiles of Chinese Han human milk (HHM) and Chinese Korean human milk (KHM) were investigated in this study. A total of 741 lipids were identified in HHM and KHM. Twenty-eight differentially expressed lipids (DEL) were screened between the 2 milk groups; among these, 6 triacylglycerols (TG), 13 diacylglycerols (DG), 7 free fatty acids (FFA), and 1 monoglyceride (MG) were upregulated in KHM. Carnitine (CAR) was upregulated in HHM. Most DEL showed a single peak distribution in both groups. The correlations, related pathways and diseases of these DEL were further analyzed. The results demonstrated that DG, MG, and FFA showed highly positive correlations with each other (r > 0.8). The most enriched Kyoto Encyclopedia of Genes and Genomes (https://www.kegg.jp/kegg/) and Human Metabolome Database (http://www.hmdb.ca) pathways were inositol phosphate metabolism, and α-linolenic acid and linolenic acid metabolism, respectively. Major depressive disorder-related FFA (20:5) and FFA (22:6) were more abundant in KHM, whereas HHM showed more obesity-related CAR. These data potentially provide lipidome information regarding human milk from different ethnicities in China.
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Lipidômica , Leite Humano , Humanos , Leite Humano/química , Feminino , Lipídeos , Etnicidade/genética , Triglicerídeos/metabolismo , China , República da Coreia , População do Leste AsiáticoRESUMO
Fermented dairy foods such as yogurt exhibit some beneficial effects on consumers, including relieving the symptoms of hypertension. This study aims to obtain fermented dairy products from a co-starter that have a great flavor and the auxiliary function of reducing blood pressure after longtime consumption. Commercial starter cultures composed of Lactobacillus delbrueckii subsp. bulgaricus CICC 6047 and Streptococcus thermophilus CICC 6038 were combined with Lactobacillus plantarum strains Y44, Y12, and Y16, respectively, as a combined starter culture to ferment the mixed milk of skim milk and soybean milk. The fermented milk produced using the combined starter culture mixed with L. plantarum Y44 showed an angiotensin-converting-enzyme (ACE) inhibitory activity (53.56 ± 0.69%). Some peptides that regulate blood pressure were released in the fermented milk, such as AMKPWIQPK, GPVRGPFPII, LNVPGEIVE, NIPPLTQTPV, and YQEPVL. In spontaneously hypertensive rat (SHR) oral-administration experiments compared with the gavage unfermented milk group, the gavage feeding of SHRs with the fermented milk produced using the combined starter culture mixed with L. plantarum Y44 significantly reduced the blood pressure of the SHRs after long-term intragastric administration, shown with the systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreasing by 23.67 ± 2.49 mmHg and 15.22 ± 2.62 mmHg, respectively. Moreover, the abundance of short-chain fatty acids (SCFA), bacterial diversity in the gut microbiota, and SCFA levels including acetic acid, propionic acid, and butyric acid in the feces of the SHRs were increased via oral administration of the fermented milk produced using the combined starter culture containing L. plantarum Y44. Furthermore, the ACE-angiotensin II (Ang II)-angiotensin type 1 (AT 1) axis was downregulated, the angiotensin-converting-enzyme 2 (ACE 2)-angiotensin(1-7) (Ang1-7)-Mas receptor axis of the SHRs was upregulated, and then the RAS signal was rebalanced. The fermented milk obtained from the combined starter culture shows the potential to be a functional food with antihypertension properties.
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In this study, Senescence Accelerated Mice (SAMP8) were supplemented with exogenous DHA milk, endogenous DHA milk, normal milk, or 0.9 % saline solution. Enzyme-linked immunosorbent assay (ELISA), gas chromatography (GC), ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI MS/MS), and Morris water maze were used to characterize the effects of diet on oxidative stress and cognition in SAMP8 mice. Supplementation endogenous DHA milk or exogenous DHA milk can enhance the antioxidant capacity of mice organs. Endogenous DHA milk increased the superoxide dismutase (SOD) activity of mice brain and serum than normal milk and 0.9 % saline solution (P ≤ 0.05), as well as increased SOD activity of mice liver and glutathione peroxidase (GSH-Px) activity of mice brain than normal milk (P ≤ 0.05). Exogenous DHA milk increased SOD activity of mice brain than normal milk and 0.9 % saline solution, as well as increased SOD activity of mice serum than 0.9 % saline solution (P ≤ 0.05). Several polar lipid relative content, such as 18:0/18:2 PS, 17:0 Ceramide, and 20:4 LPC in mice brain was affected by dietary supplementation with DHA-containing milk. Lipid oxidation metabolites in mice brain were not affected by DHA-containing milk. Endogenous DHA milk increased the number of platform location crossing times of mice in the Morris water maze test, compared with Exogenous DHA milk, normal milk, and 0.9 % saline solution (P ≤ 0.05).
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Antioxidantes , Cognição , Ácidos Docosa-Hexaenoicos , Leite , Estresse Oxidativo , Superóxido Dismutase , Animais , Estresse Oxidativo/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/farmacologia , Cognição/efeitos dos fármacos , Leite/química , Camundongos , Superóxido Dismutase/metabolismo , Masculino , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Suplementos Nutricionais , Aprendizagem em Labirinto/efeitos dos fármacos , Fígado/metabolismo , Fígado/efeitos dos fármacosRESUMO
This research aimed to investigate the characteristics of casein phosphopeptides in Chinese human milk, and their potential relationship to infant growth. Using the liquid chromatography-Orbitrap-mass spectrometry technique, a total of 15 casein phosphopeptides were identified from 200 human milk samples. Also, our results indicate that casein phosphopeptides were phosphorylated with only one phosphate. The relative concentrations of casein phosphopeptides at 6 months postpartum were increased compared with milk at 2 months (FDR < 0.05). Significantly positive correlations were observed between casein phosphopeptides and infant growth, as shown by four casein phosphopeptides were positively correlated with the infants' weight-for-age Z-scores (rs range from 0.20 to 0.29), and three casein phosphopeptides were positively correlated with the infants' length-for-age Z-scores (rs range from 0.19 to 0.27). This study is the first to reveal the phosphorylated level and composition of casein phosphopeptides in Chinese human milk, and their potential relationship with infant growth.
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Leite Humano , Fosfopeptídeos , Lactente , Feminino , Humanos , Animais , Leite Humano/química , Fosfopeptídeos/química , Caseínas/química , Estudos Transversais , Leite/química , ChinaRESUMO
Dysregulated eEF2K expression is implicated in the pathogenesis of many human cancers, including triple-negative breast cancer (TNBC), making it a plausible therapeutic target. However, specific eEF2K inhibitors with potent anti-cancer activity have not been available so far. Targeted protein degradation has emerged as a new strategy for drug discovery. In this study, a novel small molecule chemical is designed and synthesized, named as compound C1, which shows potent activity in degrading eEF2K. C1 selectively binds to F8, L10, R144, C146, E229, and Y236 of the eEF2K protein and promotes its proteasomal degradation by increasing the interaction between eEF2K and the ubiquitin E3 ligase ßTRCP in the form of molecular glue. C1 significantly inhibits the proliferation and metastasis of TNBC cells both in vitro and in vivo and in TNBC patient-derived organoids, and these antitumor effects are attributed to the degradation of eEF2K by C1. Additionally, combination treatment of C1 with paclitaxel, a commonly used chemotherapeutic drug, exhibits synergistic anti-tumor effects against TNBC. This study not only generates a powerful research tool to investigate the therapeutic potential of targeting eEF2K, but also provides a promising lead compound for developing novel drugs for the treatment of TNBC and other cancers.
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Quinase do Fator 2 de Elongação , Neoplasias de Mama Triplo Negativas , Humanos , Linhagem Celular Tumoral , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Fosforilação , Transdução de Sinais , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Quinase do Fator 2 de Elongação/antagonistas & inibidoresRESUMO
Odor analysis of human milk (HM) is often challenging. Here, a new strategy for the analysis of odorants in HM using dynamic headspace sampling combined with comprehensive two-dimensional gas chromatography-olfactometry-mass spectrometry (DHS/GC × GC-O-MS) was established based on the comparison of different extraction methods and instrument modes. Overall, DHS/GC × GC-O-MS was proved to be able to provide higher extraction efficiency and better analytical results of the odor-active compounds (OACs) in HM, meanwhile, the salt addition during the extraction further promoted the release of the odorants. Twenty key OACs in HM were identified by flavor dilution analysis and odor activity calculation, of which 1-octen-3-one, 2,3-butanedione, (E)-2-nonenal, and nonanal contributed significantly to the odor of HM. In addition, 2,3-pentanedione was detected as a key OAC in HM for the first time. This study provided a powerful analytical strategy for the comprehensive odor analysis of HM.
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Leite Humano , Odorantes , Humanos , Odorantes/análise , Olfatometria/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodosRESUMO
Osteopontin is a crucial protein ingredient that has been applied in fortified dairy products and infant formula. It has great significance to infant gut health and brain development. However, current techniques including enzyme-linked immunosorbent assay and liquid chromatography coupled with mass spectrometry are still facing the bottleneck of low sensitivity and indirect quantification. Moreover, the unavailable certified commercial OPN standard hinders its accurate quantification. Herein, a novel method of anion-exchange chromatography was established to determine OPN concentration in several dairy matrices. The polarity-reversed capillary isoelectric focusing was utilized to measure the exact isoelectric point (pI) to support method development for OPN separation. Analytical ultracentrifugation was used to calibrate the purity of intact OPN to develop an in-house reference standard. The method showed the merits of limits of detection to 0.04 mg/100 g, relative standard deviation of reproducibility <5% for 13 out of 14 tested matrices, and an average recovery rate of 101.3%. This method has shown the potential to be adopted as an international standard method for the quantification of intact OPN in infant formula and dairy products.
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Fórmulas Infantis , Osteopontina , Lactente , Humanos , Reprodutibilidade dos Testes , Cromatografia Líquida , Ânions , Laticínios , UltracentrifugaçãoRESUMO
Milk fat globule membrane (MFGM) protein profiles of breast milk collected from women in northeast China with male or female babies were investigated using a four-dimensional (4D) label-free proteomic technique. Altogether, 2538 proteins were detected and quantified and 249 were differentially expressed, with 198 decreased proteins compared to the samples of mothers with female babies. Different proteins associated with infant's gender were principally located in nuclear. The differentially expressed proteins were mainly involved in gene ontology (GO) functions of the cellular process, binding, and cell and found to be distributed in lipid-related biological processes and molecular functions to a large extent. The pathway of neurodegeneration-multiple disease ranked top for the altered proteins. The screened proteins were observed to contain some proteins related to typical functions of immunity, lipid metabolism, digestion, and growth and development. 114 proteins formed a relatively compact network (269 interactions) and dolichyl-diphospho-oligosaccharide-protein glycosyltransferase subunit 2 interacted the most with other proteins as the hub protein. MFGM proteins of breast milk were affected by the sex of offspring, and these findings may provide useful information for reasonable adjustments of infant formula powder specifically for boys or girls in the market.
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Proteínas do Leite , Leite Humano , Feminino , Lactente , Masculino , Humanos , Leite Humano/química , Proteínas do Leite/química , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteômica/métodos , Glicolipídeos/química , Gotículas Lipídicas/químicaRESUMO
Human milk is an ideal natural food for infants, and the infant's gender may have impact on protein composition of breast milk. In this study, we used 4D label-free quantitative proteomics techniques to identify and quantitatively analyze casein fraction in breast milk secreted for male and female infants. The results showed that a total of 2064 proteins were identified in human milk, and 95 of them were differentially abundant proteins. Compared to breast milk secreted by mothers of female infants, 21 proteins were up-regulated, and 59 proteins were down-regulated in breast milk secreted by mothers of male infants. The most abundant domain among the differentially abundant proteins was the immunoglobulin V-set domain, which may be involved in immune regulation. Gene Ontology functional analysis revealed that, the main biological processes, molecular functions, and cellular components corresponded to cellular process, binding, and cell part, respectively. The Kyoto Encyclopedia of Genes and Genomes pathways were mainly associated with human diseases and metabolism, with biosynthesis of cofactors being the most involved pathway. The results contribute to our understanding of the composition of casein in breast milk, and may provide information about the nutritional differences in breast milk from mothers of newborns of different genders.
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Caseínas , Leite Humano , Humanos , Lactente , Feminino , Masculino , Recém-Nascido , Leite Humano/química , ProteômicaRESUMO
Breast cancer is the most common deadly malignancy in women worldwide. In particular, triple-negative breast cancer (TNBC) exhibits the worst prognosis among four subtypes of breast cancer due to limited treatment options. Exploring novel therapeutic targets holds promise for developing effective treatments for TNBC. Here, we demonstrated for the first time that LEMD1 (LEM domain containing 1) is highly expressed in TNBC and contributes to reduced survival in TNBC patients, through analysis of both bioinformatic databases and collected patient samples. Furthermore, LEMD1 silencing not only inhibited the proliferation and migration of TNBC cells in vitro, but also abolished tumor formation of TNBC cells in vivo. Knockdown of LEMD1 enhanced the sensitivity of TNBC cells to paclitaxel. Mechanistically, LEMD1 promoted the progress of TNBC by activating the ERK signaling pathway. In summary, our study revealed that LEMD1 may act as a novel oncogene in TNBC, and targeting LEMD1 may be exploited as a promising therapeutic approach to enhance the efficacy of chemotherapy against TNBC.
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Triple-negative breast cancer (TNBC) is a particularly invasive subtype of breast cancer and usually has a poor prognosis due to the lack of effective therapeutic targets. Approximately 25% of TNBC patients carry a breast cancer susceptibility gene1/2 (BRCA1/2) mutation. Clinically, PARP1 inhibitors have been approved for the treatment of patients with BRCA1/2-mutated breast cancer through the mechanism of synthetic lethality. In this study, we identified compound 6 {systematic name: 2-[2-(4-Hydroxy-phenyl)-vinyl]-3H-quinazolin-4-one} as a novel PARP1 inhibitor from established virtual screening methods. Compound 6 exerted stronger PARP1 inhibitory activity and anti-cancer activity as compared to olaparib in BRCA1-mutated TNBC cells and TNBC patient-derived organoids. Unexpectedly, we found that compound 6 also significantly inhibited cell viability, proliferation, and induced cell apoptosis in BRCA wild-type TNBC cells. To further elucidate the underlying molecular mechanism, we found that tankyrase (TNKS), a vital promoter of homologous-recombination repair, was a potential target of compound 6 by cheminformatics analysis. Compound 6 not only decreased the expression of PAR, but also down-regulated the expression of TNKS, thus resulting in significant DNA single-strand and double-strand breaks in BRCA wild-type TNBC cells. In addition, we demonstrated that compound 6 enhanced the sensitivity of BRCA1-mutated and wild-type TNBC cells to chemotherapy including paclitaxel and cisplatin. Collectively, our study identified a novel PARP1 inhibitor, providing a therapeutic candidate for the treatment of TNBC.
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Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Proteína BRCA1/genética , Linhagem Celular Tumoral , Proteína BRCA2 , Poli(ADP-Ribose) Polimerase-1RESUMO
Eukaryotic translation initiation factor 3 subunit A (eIF3a) is the largest subunit of the eukaryotic translation initiation factor 3 (eIF3). eIF3a plays an integral role in protein biosynthesis, hence impacting the onset, development, and treatment of tumors. The proteins regulated by eIF3a are still being explored in vivo. In this study, a Cre-loxP system was used to generate eIF3a conditional knockout mice. Tandem mass tag (TMT) labeling with LC-MS/MS analysis was used to identify differentially expressed proteins (DEPs) in fat, lungs, skin, and spleen tissue of the eIF3a knockout mice and controls. Bioinformatics analysis was then used to explore the functions and molecular signaling pathways of these protein landscapes. It was observed that eIF3a is essential for life sustenance. Abnormal tissue pathology was found in the lungs, fat, skin, spleen, and thymus. In total, 588, 210, 324, and 944 DEPs were quantified in the lungs, fat, skin, and spleen, respectively, of the eIF3a knockout mice as compared to the control. The quantified differentially expressed proteins were tissue-specific, except for eight proteins shared by the four tissues. A broad range of functions for eIF3a, including cellular signaling pathway, immune response, metabolism, defense response, phagocytes, and DNA replication, has been revealed using bioinformatics analysis. Herein, several pathways related to oxidative stress in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, including nitrogen metabolism, peroxisome, cytochrome P450 drug metabolism, pyruvate metabolism, PPAR signaling pathway, phospholipase D signaling pathway, B-cell receptor signaling pathway, ferroptosis, and focal adhesion, have been identified. Collectively, this study shows that eIF3a is an essential gene for sustaining life, and its downstream proteins are involved in diverse novel functions beyond mRNA translational regulation.
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Fermented dairy food, such as yogurt, exhibits some beneficial effects on consumers, including alleviating constipation. In this study, Lactobacillus delbrueckii subsp. bulgaricus DPUL-36, Lactobacillus paracasei DPUL-40 and Lactobacillus paracasei DPUL-44 were used as combined starter cultures at a bacterial cell ratio of 1 : 1 : 1 for reconstituted skim milk fermentation. The milk fermented with the combined starter culture showed good sensory properties. During the storage period, the yogurt showed high lactic acid bacteria vitality and quality stability. Constipated BALB/c mice induced by loperamide (Lop) were orally administered with the combined starter culture fermented milk for 14 days. The results clearly showed that oral administration of the fermented milk relieved Lop-induced constipation in the mice, as evidenced by the significantly increased fecal water content, reduced first black stool time, improved gastrointestinal transmission rate, recovered colon tissue damage, increased level of excitatory neurotransmitters (motilin, gastrin, and substance P) and reduced level of inhibitory neurotransmitters (vasoactive intestinal peptide, somatostatin and endothelin-1) of the mice. Compared with the mice in the Lop group, oral administration of the fermented milk significantly increased the concentrations of acetic acid, propionic acid, butyric acid, isovaleric acid and valeric acid in the feces of the mice, and furthermore, exerted a regulatory effect on the gut microbiota of the mice by up-regulating the abundance of Lactobacillus and Bacteroides, and decreasing the abundance of Helicobacter, Pseudomonas and Porphyromonas. Our results indicated that the combined starter culture fermented milk can effectively alleviate Lop-induced-constipation in BALB/c mice. The relationship between the nutrient profiles and the health promoting function of the yogurt should be further illustrated.
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Constipação Intestinal , Lactobacillus , Iogurte , Animais , Camundongos , Masculino , Camundongos Endogâmicos BALB C , Fermentação , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/dietoterapia , Loperamida/toxicidade , Iogurte/microbiologia , Microbioma GastrointestinalRESUMO
In this study, it is found that the lncRNA, DNA damage inducible transcript 4 antisense RNA1 (DDIT4-AS1), is highly expressed in triple-negative breast cancer (TNBC) cell lines and tissues due to H3K27 acetylation in the promoter region, and promotes the proliferation, migration, and invasion of TNBC cells via activating autophagy. Mechanistically, it is shown that DDIT4-AS1 induces autophagy by stabilizing DDIT4 mRNA via recruiting the RNA binding protein AUF1 and promoting the interaction between DDIT4 mRNA and AUF1, thereby inhibiting mTOR signaling pathway. Furthermore, silencing of DDIT4-AS1 enhances the sensitivity of TNBC cells to chemotherapeutic agents such as paclitaxel both in vitro and in vivo. Using a self-activatable siRNA/drug core-shell nanoparticle system, which effectively deliver both DDIT4-AS1 siRNA and paclitaxel to the tumor-bearing mice, a significantly enhanced antitumor activity is achieved. Importantly, the codelivery nanoparticles exert a stronger antitumor effect on breast cancer patient-derived organoids. These findings indicate that lncRNA DDIT4-AS1-mediated activation of autophagy promotes progression and chemoresistance of TNBC, and targeting of DDIT4-AS1 may be exploited as a new therapeutic approach to enhancing the efficacy of chemotherapy against TNBC.
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RNA Longo não Codificante , Neoplasias de Mama Triplo Negativas , Humanos , Camundongos , Animais , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Linhagem Celular Tumoral , RNA Interferente Pequeno , Autofagia/genética , Paclitaxel/farmacologia , RNA Mensageiro , Fatores de TranscriçãoRESUMO
Calcium deficiency can lead to osteoporosis. Adequate calcium intake can improve calcium deficiency and prevent osteoporosis. Milk powder is the best source of dietary calcium supplements. Probiotics and prebiotics are considered to be beneficial substances for promoting calcium absorption. In this study, synbiotic milk powder (SMP) was prepared by combining the three, and its calcium supplementation effect and osteogenic activity were evaluated in calcium deficient mice. Through prebiotic screening experiments in vitro, after adding 1.2% iso-malto-oligosaccharide, the number of viable bacteria and the calcium enrichment of Lactobacillus plantarum JJBYG12 increased by 8.15% and 94.53% compared with those of the control group. Long-term calcium deficiency led to a significant reduction in calcium absorption and bone calcium content in mice, accompanied by structural deterioration of bone trabeculae. SMP significantly improved apparent calcium absorption, increased serum calcium and phosphorus levels, and decreased ALP activity and CTX-1 levels. In the meantime, the bone mineral density increased significantly, and the number of bone trabeculae and the proliferation and differentiation of osteoblasts also increased. SMP has good dietary calcium supplementation capacity and bone remodeling ability without significant side effects on major organs. These findings provide insights into using SMP as a dietary calcium source to improve bone health.
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Osteoporose , Simbióticos , Camundongos , Animais , Cálcio da Dieta , Cálcio/análise , Pós/análise , Leite/química , Osteoporose/prevenção & controle , Densidade Óssea , Prebióticos/análiseRESUMO
The postharvest shelf life of fresh corn largely depends on the packaging method and storage temperature. This study investigated the effect of vacuum packaging (VP) with high-barrier (HB) or ordinary (OR) nylon/nylon/polypropylene (PP) composite films and the impact of storage temperature (4, 25, and 38 °C) on the shelf life of fresh corn. The sensory quality and color changes of the corn were evaluated, indicating a significant improvement in the glossiness (GL), sourness (SO), and color changes compared to corn packaged using OR films. The results showed that the HB films preserved corn freshness under refrigerated and normal temperature storage conditions, delaying color changes and SO development. A shelf-life model was established based on the Arrhenius equation. The predicted values of the corn at different temperatures were compared with the experimental data, indicating that the model could accurately predict the shelf life. The shelf life observed via sensory evaluation was more than 50% shorter than the results obtained by instrumental measurements. Therefore, sensory evaluation could be applied to determine shelf life and avoid food waste.
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The current study aims to investigate differences in whey protein of breastmilk of volunteered mother collected from two ethnic groups (Korean and Han) in China using data-independent acquisition (DIA) based proteomics technique. The total detected 624 proteins were principally allocated to cellular process of biological process (BP), cell and cell part of cell component (CC) and binding of molecular function (MF) according to Gene Ontology (GO) annotation; and carbohydrate metabolism of Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Among the 54 differently expressed proteins, 8 were related with immunity. Enrichment data showed that intracellular of GO functions and viral myocarditis of KEGG pathways were most significantly enriched (p < 0.05). Protein-protein interaction (PPI) network suggested that 40S ribosomal protein S27a and 60S ribosomal protein L10a which interacted most with other proteins ranked the top two hub proteins by MCC (Maximal Clique Centrality) method. This study may have guiding role for development of infant formula powder for specific infants of Han or Korean groups according to responding breastmilk composition.