BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Yuan Liang,Yu Yang,Ruiyan Huang,Jiangyue Ning,Xingyan Bao,Zelong Yan,Haotian Chen,Li Ding,Chang Shu
Depression ranks as the fourth most prevalent global disease, with suicide incidents occurring at a younger age. Sulpiride (SUL), an atypical antidepressant drug acting as a dopamine D2 receptor antagonist and possessing anti-inflammatory properties, exhibits limited ability to penetrate the blood brain barrier (BBB). This weak penetration hampers its inhibitory effect on prolactin release in the pituitary gland, consequently leading to hyperprolactinemia. In order to enhance the central nervous system efficacy of sulpiride and reduce serum prolactin levels, we covalently linked sulpiride to VPALR derived from the nuclear DNA repair protein ku70. In vivo study on depressive mice using intraperitoneal injection of VPALR-SUL demonstrated a significant increase in struggle time and total distance compared to those treated with only sulpiride while also reducing serum prolactin concentration. The pharmacokinetic study results showed that VPALR-SUL prolonged half-life and increased bioavailability. In conclusion, VPALR-SUL exhibited potential for enhancing sulpiride transport across the BBB, augmenting its antidepressant effects, and reducing serum prolactin levels. This study laid a foundation for improving sulpiride delivery and developing novel antidepressants.
研究领域:
药理学
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神经科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Animal Nutrition
·
2025
·
IF 7.5
Qingyan Yin,Xingwei Jiang,Huifeng Liu,Peiyue Wang,Xiaodong Su,Jun Zhang,Xinjian Lei,Junhu Yao
An essential function carried out by bile acids (BA) is to aid in lipid absorption, as they emulsify lipids and combine with them to form chylomicrons. While BA have been utilized as lipid emulsifiers in monogastric and aquatic animals, their impact on ruminants remains relatively unexplored. Two experiments were conducted to investigate the effects of BA on the lipid absorption of lactating dairy goats. In experiment 1, twelve lactating goats with similar days in milk (42 ± 2 d), body weight (46.2 ± 5.1 kg), and milk yield (1.62 ± 0.33 kg) were administered four BA doses (0, 1, 2, or 4 g/d) to explore the effects of BA supplementation. The results observed a positive correlation between the BA dose and plasma total bile acid concentration ( P < 0.001). Notably, when goats received BA, there was a trend of increase in the proportion of preformed fatty acids in milk ( P = 0.079). In experiment 2, eighteen lactating goats with similar days in milk (100 ± 6 d), body weight (45.0 ± 3.7 kg), and milk yield (1.60 ± 0.31 kg) were divided into two groups (HF and HFB): HF group received no BA, while HFB group received BA (4 g/d). Both the groups were fed diets with fat powder supplementation (1% of dry material) for 5 weeks. BA supplementation led to a significant increase in milk yield ( P = 0.024) and fat concentration ( P = 0.045). Meanwhile, there was a significant rise of total bile acid concentration in plasma ( P < 0.001), rumen ( P < 0.001) and feces ( P < 0.001). Additionally, BA supplementation had a significant impact on blood metabolism, up-regulating 241 metabolites and down-regulating 208 metabolites ( P < 0.05). BA supplementation also altered the correlations among various plasma lipid components ( P < 0.05). In fatty acid (FA) analysis, 26 different FA were detected, out of which 16 showed significant down-regulation upon BA supplementation ( P < 0.05). In conclusion, BA supplementation positively influenced lactating dairy goats, particularly when fed diets with fat powder supplementation. BA supplementation enhanced milk yield, improved milk fat concentration, and significantly altered lipid-related blood metabolism. These findings suggest that BA supplementation could be a valuable strategy for enhancing dairy production and lipid metabolism in dairy goats, offering potential benefits for the dairy industry.
研究领域:
动物营养学
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生物化学
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乳品科学
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产品关联
DOI
PubMed
高影响因子
MEDICAL SCIENCE MONITOR
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2016
·
IF 1.405
De-jing Wang,Chen-meiyi Wang,Yi-ting Wang,Hai Qiao,Liao-qiong Fang,Zhi-biao Wang
Background The complex process by which lactation is initiated upon neonate delivery remains incompletely understood. Microvesicles (MVs) can transmit microRNAs (miRNAs) into recipient cells to influence cell function, and recent studies have identified miRNAs essential for mammary gland development and lactation. This study aimed to investigate the expression of lactation-related miRNAs in MVs isolated from human umbilical cord blood immediately after delivery. Material/Methods Umbilical cord blood samples were collected from 70 healthy pregnant women, and MVs were isolated through differential centrifugation and characterized by transmission electron microscopy, Western blotting, and nanoparticle tracking analysis. Lactation-related miRNAs were screened using bioinformatics tools for miRNA target prediction, gene ontology, and signaling pathway analyses. miRNA PCR arrays were used for miRNA expression analysis, and the results were validated by real-time PCR. Upon exposure of HBL-100 human mammary epithelial cells to MVs, MV uptake was examined by fluorescence confocal microscopy and β-casein secretion was detected by ELISA. Results Spherical MVs extracted from umbilical cord blood expressed CD63 and had an average diameter of 167.0±77.1 nm. We profiled 337 miRNAs in human umbilical cord blood MVs and found that 85 were related to lactation by bioinformatics analysis. The 25 most differentially expressed lactation-related miRNAs were validated by real-time PCR. MV uptake by HBL-100 cells was after 4 h in culture, and significantly increased secretion of β-casein was observed after 96 h from cells exposed to MVs (P<0.05). Conclusions Umbilical cord blood MVs contain many lactation-related miRNAs and can induce β-casein production by HBL-100 cells in vitro . Thus, umbilical cord blood MVs may mediate secretion of β-casein through miRNAs, thereby playing an important role in fetal-maternal crosstalk.
研究领域:
妇产科学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Animals
·
2019
·Vol. 9
·期 12
·1019
·
IF 1.832
Keyuan Liu,Yang Li,Guobin Luo,Hangshu Xin,Yonggen Zhang,Guangyu Li
Simple SummaryThe objective of this study was to determine the relationships between milk odd- and branched-chain fatty acids (OBCFAs) and ruminal fermentation parameters, microbial populations, and base contents. Significant relationships existed between the concentrations of C11:0,iso-C15:0,anteiso-C15:0, C15:0, andanteiso-C17:0 in rumen and milk. The total OBCFA content in milk was positively related to the acetate molar proportion but negatively correlated with isoacid levels. The adenine/N ratio was negatively related to milk OBCFA content but positively associated with theiso-C15:0/iso-C17:0 ratio.AbstractThe purpose of this research was to evaluate whether relationships exist between odd- and branched-chain fatty acids (OBCFAs) originating from milk fat and the corresponding data of ruminal fermentation parameters, microbial populations, and base contents that were used to mark microbial protein in rumen. Nine lactating Holstein dairy cows with similar body weights and parity were selected in this study, and the samples of rumen and milk were collected at the early, middle, and late stages, respectively. The rumen and milk samples were collected over three consecutive days from each cow, and the ruminal and milk OBCFA profiles, ruminal fermentation parameters, bacterial populations, and base contents were measured. The results showed that the concentrations of OBCFAs, with the exception of C11:0 and C15:0, were significantly different between milk and rumen (p< 0.05). The concentrations ofanteiso-fatty acids in milk were higher than those in rumen, and the contents of linear odd-chain fatty acids were higher than those of branched-chain fatty acids in both milk and rumen. Significant relationships that existed between the concentrations of C11:0,iso-C15:0,anteiso-C15:0, C15:0, andanteiso-C17:0 in rumen and milk (p< 0.05). The total OBCFA content in milk was positively related to the acetate molar proportion but negatively correlated with isoacid contents (p< 0.05). The populations ofRuminococcus albus,R. flavefacients, andEubacterium ruminantiumwere significantly related to milk C13:0 contents (p< 0.05). The adenine/N ratio was negatively related to milk OBCFA content (p< 0.05) but positively associated with theiso-C15:0/iso-C17:0 ratio (p< 0.05). Milk OBCFAs were significantly correlated with ruminal fermentation parameters, ruminal bacterial populations, and base contents. Milk OBCFAs had the potential to predict microbial nitrogen flow, and the prediction equations for ruminal microbial nitrogen flow were established for OBCFAs in dairy milk.Keywords:fermentation parameters;microbial populations;microbial bases;odd- and branched-chain fatty acids;lactation stages
研究领域:
动物营养学
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微生物学
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产品关联
DOI
PubMed
高影响因子
Food Science & Nutrition
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2024
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IF 3.5
Jia Hao,Shaohui Beng,Zifeng Ma,Hongmei Xu,Ting Yang,Qiman Yang,Yunduan Wang,Wenhui Zheng,Yisha Ma,Shuo Zhang,Liangde Kuang,Wei Fu
This study aimed to investigate the effects of short-term exposure of Bisphenol A (BPA) on the growth and lactation performance, blood parameters, and milk composition of lactating rabbits and explore its potential molecular mechanisms. Eight lactating rabbits with similar body weight were selected and randomly divided into the experimental group (BPA) and the control group (Ctrl). The group BPA was orally administered 80 mg/kg/day BPA on the 15th day postpartum, while the group Ctrl received a corresponding volume of vehicle. Blood and milk samples were collected after 7 days treatment. The results showed that short-term ingestion of BPA did not obviously alter the body weight, feed intake, or milk yield of the lactating rabbits. ELISA assays indicated that BPA did not significantly affect the plasma levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), creatinine (CRE), alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid (UA), and urea. Utilizing untargeted metabolomics, we first depicted the metabolomic profile of rabbit milk, and identified 277 differential metabolites (DMs), with 141 DMs upregulated (e.g., BPA, and its metabolites including Cetirizine N-oxide) and 136 DMs downregulated (e.g., Oleamide, Tiglic acid, PC O-38:4) in the group BPA. KEGG analysis revealed that the DMs were mainly enriched in pathways comprising fatty acid metabolism, fatty acid degradation, and phosphatidylinositol signaling system, emphasizing the effect of BPA on milk fat metabolism. Hence, we established the BPA-induced MAC-T model, and the results showed that BPA significantly reduced cell viability and impacted lipid synthesis, as evidenced by reduced lipid droplets (BODIPY and Oil Red O staining) and decreased expression of genes related to lipid synthesis (e.g., PPARγ , ACACA , LPL ). In summary, we first drew the metabolomic profile of rabbit milk and confirmed that short-term BPA exposure impacted mammary lipid synthesis, thereby reducing the milk quality of lactating rabbits and providing fundamental data for resolving the toxicological mechanisms of BPA on mammal lactation.
研究领域:
毒理学
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动物科学
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代谢组学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
FASEB JOURNAL
·
2020
·Vol. 34
·期 6
·8671-8685
·
IF 4.966
Jie Cai,Diming Wang,Shulin Liang,Jinrong Peng,Fengqi Zhao,Jianxin Liu
During lactation, an improper glucose supply often threatens mammary gland (MG) health. However, information is limited on the metabolic trajectories and molecules that regulate lactating MGs with an excessive glucose supply. Based on the network analysis of transcriptome and microRNAs, we found that the oversupply of glucose-induced severe glucose metabolic disorders in MGs of lactating goats, shifting lactose synthesis to acute fermentative glycolysis which caused increased flux of glucose metabolism into lactate. Moreover, NF-κB2 played a key role in regulating glycolysis, exhibiting a metabolic shift when MGs had an excessive supply of glucose. In primary mammary epithelial cells, fermentative glycolysis, and intracellular concentration of reactive oxygen species (ROS) were reduced by ganoderic acid A through blocking NF-κB2, while activation of NF-κB2 with phorbol myristate acetate (PMA) upregulated fermentative glycolysis and increased cellular ROS accumulation under excessive glucose. Thus, we established an NF-κB2-targeting method to reform the metabolic shift toward glycolysis caused by glucose oversupply by integrating NF-κB2 blockade and intracellular ROS scavenging.
研究领域:
动物生理学
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分子生物学
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营养学
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DOI
PubMed
高影响因子
Current Research in Food Science
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2024
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IF 6.2
Weidong Xu,Shasha Tian,Guanqun Mao,Yu Li,Hua Qian,Wenhua Tao
Sini San (SNS) is used to treat liver depression and is applied in both food and herbal medicine. Hyperprolactinemia (HPRL) is a common endocrine disorder, and patients with HPRL are usually associated with depressive symptoms. However, whether SNS is effective in treating HPRL combined with liver depression and its underlying mechanisms are unknown. We applied network pharmacology and molecular docking to predict the mechanism of SNS for the treatment of liver-depressed HPRL. Therapeutic effects were validated in animal models and cells. Metabolomics was also used to evaluate the effect of SNS on liver-depressed HPRL. Network pharmacology and molecular docking analysis showed that AKT1, TNF and IL6 were the key targets, and SNS improved depressive behaviors, regulated sex hormone levels, and improved ovarian morphology. Combined network pharmacology and metabolomics analyses showed that SNS could act by regulating lipid metabolism. In addition, SNS significantly reduced the release of prolactin (PRL) in rat pituitary tumor MMQ cells. Overall, SNS can significantly treat HPRL liver depression at both animal and cellular levels, and effectively alleviate the related symptoms by regulating lipid metabolism. AKT1, TNF and IL6 may be key targets.
研究领域:
药理学
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内分泌学
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神经科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Animal Nutrition
·
2025
·
IF 7.5
Zhanbo Xiong,Xiaoyin Zhang,Shiqi Zhang,Kexin Li,Yuan Gao,Ying Bu,Nan Zheng,Shengguo Zhao,Jiaqi Wang
Reducing nitrogen loss and improving nitrogen utilization efficiency in dairy cows can reduce economic costs and mitigate the environmental impact of nitrogen emissions. Red clover isoflavone, a natural compound derived from plant extract, has the advantage of biological safety. This study aimed to investigate the effects of red clover isoflavone on lactation performance and nitrogen metabolism in dairy cows. Sixty-eight Holstein cows (165 ± 21 d in milk, 710 ± 75 kg initial body weight, 2.30 ± 1.21 parities, 33.93 ± 3.81 kg/d milk yield) were chosen in a randomized complete block design. Cows were divided into 5 blocks by milk yield and randomly assigned to 4 treatments (17 cows per treatment). The experimental period lasted 84 d, during which cows were fed a basal diet supplemented with red clover extract (RCE) at 0, 2, 4, or 8 g/kg of total mixed rations (TMR) on a dry matter (DM) basis. These levels corresponded to red clover isoflavones of 0, 0.46 (0.31 g/kg formononetin and 0.15 g/kg biochanin A), 0.93 (0.67 g/kg formononetin and 0.26 g/kg biochanin A), and 1.83 g/kg (1.32 g/kg formononetin and 0.52 g/kg biochanin A), respectively. With increasing supplementation of RCE in TMR, milk yield increased quadratically by 4.65% to 9.64% ( P = 0.020) and feed efficiency improved by 6.58% to 10.53% ( P = 0.005), with the optimal dose identified as 2 g/kg. Additionally, RCE supplementation significantly increased the yield of milk components, including fat, protein, lactose, non-fat milk solid, and total milk solid ( P < 0.05), with the highest in the 2 g/kg group. Regarding nitrogen metabolism, RCE supplementation linearly increased microbial nitrogen (MN) from 782.61 to 956.41 g/d ( P = 0.003), which was accompanied by a linear increase in nitrogen utilization efficiency from 26.32% to 30.31% ( P < 0.001). In contrast, urinary total nitrogen ( P = 0.027) and milk urea nitrogen ( P < 0.001) decreased quadratically with increasing doses of RCE, reaching their minimum at 4 g/kg. Following RCE supplementation, the apparent digestibility of DM, organic matter (OM), and neutral detergent fiber (NDF) exhibited a quadratic effect ( P < 0.05), with significantly higher digestibility observed in the 2 g/kg group. Metabonomics results revealed that RCE supplementation significantly upregulated the top 12 differential metabolites. These findings suggest that RCE supplementation at levels ranging from 2 to 4 g/kg DM enhances lactation performance, milk quality, and nitrogen metabolism in dairy cows.
研究领域:
动物营养学
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乳品科学
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代谢学
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植物化学
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环境生理学
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产品关联
DOI
PubMed
高影响因子
Animal Nutrition
·
2025
·
IF 7.5
Jing Zhang,Jiaojiao Lang,Changjian Xue,Qiang Liu,Caixia Pei
Cobalamin (vitamin B 12 , VB 12 ) has the potential to enhance the digestion of dietary nutrients, optimize energy distribution, and stimulate the proliferation of mammary epithelial cells (MECs), which in turn can promote milk production performance. The influence of VB 12 on nutrient digestion and energy distribution has been studied; however, its effects on MEC proliferation and the underlying mechanism remain unclear. This study investigated the influence of coated VB 12 (CVB 12 ) on milk production, nutrient digestion, MECs proliferation and milk fatty acid synthesis in dairy cows. This in vivo study involved 88 multiparous Holstein cows with similar body weight (BW; 633 ± 16.2 kg), previous 305-d milk production (9035 ± 186.2 kg), parity (3.1 ± 0.28), and age (5.6 ± 0.31 years). These cows were selected from 6 weeks preparturition to 9 weeks postparturition. They were blocked by parity, previous milk yield, and expected calving date and divided into four treatment groups of 22 cows per group: control, low CVB 12 (LCVB 12 ), medium CVB 12 (MCVB 12 ), and high CVB 12 (HCVB 12 ), receiving 0, 6, 12, and 18 mg of VB 12 per cow per day, respectively. Although dry matter intake was unaffected, yields of actual milk, 4% fat-corrected milk, energy-corrected milk, and milk components (fat, true protein, and lactose) increased quadratically ( P < 0.05). Milk fat content increased linearly ( P = 0.021) with no significant changes in milk true protein and lactose contents after CVB12 supplementation. The apparent nutrient digestibility of dry matter, organic matter, crude protein, ether extract, neutral detergent fiber, and acid detergent fiber increased linearly ( P < 0.05) following the provision of CVB 12 . Serum contents of VB 12 , glucose, and total protein linearly increased ( P < 0.05), while those of methylmalonic acid, nonesterified fatty acid, and β-hydroxybutyric acid linearly decreased ( P < 0.05) following CVB 12 provision. Supplementing 12 mg/d of CVB 12 promoted MECs proliferation and fatty acid synthesis, as indicated by the upregulated expression of proliferation-related proteins, the suppression of apoptosis-related proteins, the phosphorylation of protein kinase B (Akt) and rapamycin target protein (mTOR), and the increased expression of fatty acid synthesis-related proteins. The in vitro study verified the promoting effect of VB 12 on MECs proliferation and further elucidated that VB 12 regulates MECs proliferation in dairy cows through the AKT/mTOR signalling pathway. In conclusion, CVB 12 increases milk and milk component production by promoting nutrient digestion, energy distribution, and MECs proliferation through the AKT/mTOR signalling pathway, and fatty acid synthesis-related proteins expression. These findings offer a robust theoretical foundation for future strategies aimed at enhancing milk performance in dairy cows through CVB 12 nutrition.
研究领域:
动物营养
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乳品科学
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分子生物学
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生物化学
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动物生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2020
·Vol. 11
·期 2
·1869-1880
·
IF 4.171
Xinyue Dai,Tinglan Yuan,Xinghe Zhang,Qin Zhou,Huiya Bi,Renqiang Yu,Wei Wei,Xingguo Wang
This study aimed to quantify the short-chain fatty acids (SCFAs) and medium-chain fatty acids (MCFAs) in human milk triacylglycerols (TAGs) and investigate their concentrations in human milk consumed during lactation by infants born at different gestational ages. One hundred and eighty milk samples from the mothers of 30 full-term, 10 early-preterm (≤32 weeks), 10 mild-preterm (32–34 weeks), and 10 near-term (34–37 weeks) infants were collected from the colostrum, transitional, and mature milk. The human milk TAGs were transferred into fatty-acid methyl esters via potassium methoxide in methanol and determined using gas chromatography (GC). The total SCFA (4:0) and MCFA concentrations (6:0 and 8:0) were highest in the mature milk (1.47 ± 0.66 mg g−1 fat from full-term infant milk), approximately 42.18% higher than those in transitional milk. Significantly higher SCFA and MCFA concentrations were found in full-term milk than in preterm milk (p = 0.001). The milk TAGs were analyzed using ultra-high-performance supercritical fluid chromatography with quadrupole-time-of-flight mass spectrometry (UHPSFC-Q-TOF-MS), which showed that the SCFAs and MCFAs were mainly esterified with long-chain fatty-acid groups (16:0, 18:1 n-9, and 18:2 n-6) at the glycerol backbone. The infants’ daily SCFA intake from human milk was estimated; this was highest from mature milk for full-term infants (∼14 mg d−1) which was significantly different from that of preterm infants from colostrum and transitional milk (p < 0.001). The correlation between dietary SCFAs and MCFAs in human milk and nutrition in newborns, especially in the gut microbiotas of preterm infants, requires further study.
研究领域:
营养学
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儿科
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分析化学
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婴儿健康
✓ 已验证
DOI
PubMed
高影响因子
Food Bioscience
·
2022
·
IF 5.318
Cuirong Ren,Jun Jin,Shiwei Zhao,Yanbing Zhang,Qingzhe Jin,Xingguo Wang
Effects of five different breeds (Landrace × Large White, Landrace , Large White, Duroc and Pietrain) and two lactation stages (colostrum and milk) on phospholipids and their fatty acids compositions , cholesterol, and tocopherols in sow milks (n = 100) were investigated in the present study. Six classes of phospholipids were identified using 31 P NMR spectroscopy, with the total phospholipid levels ranging from 56.84 to 151.02 μmol/100 mL. Sphingomyelin (SM) was the most abundant phospholipids (33.57%–48.00%) in both colostrum and milk. Colostrum contained higher percentages of SM, phosphatidylserine (PS), phosphatidylinositol (PI), and ethanolamine plasmalogen (EPLAS) than those in milk, while milk contained higher percentages of phosphatidylcholine (PC), and phosphatidylethanolamine (PE). C16:0 and C18:0, accounting for more than 80% of the saturated fatty acids of phospholipids in both colostrum and milk, decreased throughout the lactation. The average cholesterol concentration in colostrum was 430.60 mg/100 g fat, which was significantly lower than that in milk (646.44 mg/100 g fat). α-Tocopherol levels in Landrace × Large White breed were 38.35 and 15.91 mg/100 g fat in colostrum and milk, respectively, which were significantly higher than other breeds; while no significant variations in β-, γ-, and δ-tocopherols were noted among different breeds. The results demonstrated that lactation stages and breeds were mainly responsible for the significant differences of phospholipids, cholesterol, and tocopherols, providing a theoretical guidance for the manufacture of commercial formula of piglets.
研究领域:
动物科学
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营养学
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生物化学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）