BackgroundMelatonin is mainly secreted by the pineal gland during darkness and regulates biological rhythms through its receptors in the suprachiasmatic nucleus of the hypothalamus. In addition, it also plays a role in the reproductive system by affecting the function of the hypothalamic-pituitary-gonadal axis, and by acting as a free radical scavenger thus contributing to the maintenance of the optimal physiological state of the gonads. Besides, melatonin can freely cross the placenta to influence fetal development. However, there is still a lack of overall understanding of the role of melatonin in the reproductive cycle of female mammals.Aim of reviewHere we focus the role of melatonin in female reproduction from follicular development to delivery as well as the relationship between melatonin and lactation. We further summarize the potential role of melatonin in the treatment of preeclampsia, polycystic ovary syndrome, endometriosis, and ovarian aging.Key scientific concepts of reviewUnderstanding the physiological role of melatonin in female reproductive processes will contribute to the advancement of human fertility and reproductive medicine research.

Inflammatory bowel disease (IBD), characterized by an abnormal immune response, includes two distinct types: Crohn's disease (CD) and ulcerative colitis (UC). Extensive research has revealed that the pathogeny of IBD encompasses genetic factors, environmental factors, immune dysfunction, dysbiosis, and lifestyle choices. Furthermore, patients with IBD exhibit both local and systemic oxidative damage caused by the excessive presence of reactive oxygen species. This oxidative damage exacerbates immune response imbalances, intestinal mucosal damage, and dysbiosis in IBD patients. Meanwhile, the weaning period represents a crucial phase for pigs, during which they experience pronounced intestinal immune and inflammatory responses, leading to severe diarrhea and increased mortality rates. Pigs are highly similar to humans in terms of physiology and anatomy, making them a potential choice for simulating human IBD. Although the exact mechanism behind IBD and post-weaning diarrhea remains unclear, the oxidative damage, in its progression and pathogenesis, is well acknowledged. Besides conventional anti-inflammatory drugs, certain probiotics, particularly Lactobacillus and Bifidobacteria strains, have been found to possess antioxidant properties. These include the scavenging of reactive oxygen species, chelating metal ions to inhibit the Fenton reaction, and the regulation of host antioxidant enzymes. Consequently, numerous studies in the last two decades have committed to exploring the role of probiotics in alleviating IBD. Here, we sequentially discuss the oxidative damage in IBD and post-weaning diarrhea pathogenesis, the negative consequences of oxidative stress on IBD, the effectiveness of probiotics in IBD treatment, the application of probiotics in weaned piglets, and the potential antioxidant mechanisms of probiotics.

BACKGROUND AND AIMS:Amino acids (AAs) not only constitute milk protein but also stimulate milk synthesis through the activation of mTORC1 signaling, but which amino acids that have the greatest impact on milk fat and protein synthesis is still very limited. In this study, we aimed to identify the most critical AAs involved in the regulation of milk synthesis and clarify how these AAs regulate milk synthesis through the G-protein-coupled receptors (GPCRs) signaling pathway.METHODS:In this study, a mouse mammary epithelial cell line (HC11) and porcine mammary epithelial cells (PMECs) were selected as study subjects. After treatment with different AAs, the amount of milk protein and milk fat synthesis were detected. Activation of mTORC1 and GPCRs signaling induced by AAs was also investigated.RESULTS:In this study, we demonstrate that essential amino acids (EAAs) are crucial to promote lactation by increasing the expression of genes and proteins related to milk synthesis, such as ACACA, FABP4, DGAT1, SREBP1, α-casein, β-casein, and WAP in HC11 cells and PMECs. In addition to activating mTORC1, EAAs uniquely regulate the expression of calcium-sensing receptor (CaSR) among all amino-acid-responsive GPCRs, which indicates a potential link between CaSR and the mTORC1 pathway in mammary gland epithelial cells. Compared with other EAAs, leucine and arginine had the greatest capacity to trigger GPCRs (p-ERK) and mTORC1 (p-S6K1) signaling in HC11 cells. In addition, CaSR and its downstream G proteins Gi, Gq, and Gβγ are involved in the regulation of leucine- and arginine-induced milk synthesis and mTORC1 activation. Taken together, our data suggest that leucine and arginine can efficiently trigger milk synthesis through the CaSR/Gi/mTORC1 and CaSR/Gq/mTORC1 pathways.CONCLUSION:We found that the G-protein-coupled receptor CaSR is an important amino acid sensor in mammary epithelial cells. Leucine and arginine promote milk synthesis partially through the CaSR/Gi/mTORC1 and CaSR/Gq/mTORC1 signaling systems in mammary gland epithelial cells. Although this mechanism needs further verification, it is foreseeable that this mechanism may provide new insights into the regulation of milk synthesis.

As a crucial receptor of BHBA and niacin, GPR109A is largely expressed in the mammary gland. However, the role of GPR109A in milk synthesis and its underlying mechanism is still largely unknown. In this study, we first investigated the effect of GPR109A agonists (niacin/BHBA) on milk fat and milk protein synthesis in a mouse mammary epithelial cell line (HC11) and PMECs (porcine mammary epithelial cells). The results showed that both niacin and BHBA promote milk fat and milk protein synthesis with the activation of mTORC1 signaling. Importantly, knockdown GPR109A attenuated the niacin-induced increase of milk fat and protein synthesis and the niacin-induced activation of mTORC1 signaling. Furthermore, we found that GPR109A downstream G protein-Gαi and -Gβγ participated in the regulation of milk synthesis and the activation of mTORC1 signaling. Consistent with the finding in vitro, dietary supplementation with niacin increases milk fat and protein synthesis in mice with the activation of GPR109A-mTORC1 signaling. Collectively, GPR109A agonists promote the synthesis of milk fat and milk protein through the GPR109A/Gi/mTORC1 signaling pathway.

This study aims to evaluate the efficacy of lysozyme-cinnamaldehyde conjugates (LC) as a potential alternative to antibiotics in treating piglets infected with enterotoxigenic Escherichia coli (ETEC). The results demonstrated that piglets fed with the LC diet exhibited lower rectal temperature and fecal scores at 9 h, 24 h, and 48 h post-ETEC challenge. Furthermore, LC supplementation led to significant improvements in the mechanical and immune barriers of the jejunum and ileum, as indicated by an increased villi-height-to-crypt-depth ratio (VCR) and the expression of tight junction proteins, mucin, and β-defensins. Furthermore, the LC diet lowered the levels of pro-inflammatory cytokines TNF-α and IL-1β in the plasma. Further analyses showed that the LC diet downregulated genes (specifically TLR4 and MyD88) linked to the TLRs/MyD88/NF-κB signaling pathway in the small intestine. Additionally, 16SrDNA sequencing data revealed that LC supplementation increased the α diversity of intestinal microorganisms and the relative abundance of Lactobacillus. In summary, the LC-supplemented diet effectively mitigated the adverse effects of E. coli K88, including intestinal barrier damage and inflammation. Furthermore, it improved the structure of the intestinal flora, ultimately contributing to better growth performance in piglets.

This study investigated the effects of Saccharomyces cerevisiae fermentation product (SCFP) on nutrient digestibility and ileal digesta characteristics of cannulated growing pigs fed corn-or barley-sorghum-based diets. Eight ileal-cannulated barrows randomized in a double 4 x 4 Latin square design were fed four diets in a 2 x 2 factorial arrangement, in which the first factor was diet type (corn-or barley-sorghum-based diet), and the second factor was dietary SCPF treatment (supplemented with or without 5 g/kg SCFP). The cannulated barrows (35.63 +/- 0.76 kg) fitted with a T-cannula in the terminal ileum were housed in metabolism cages in an environmentally controlled room. The results show that compared with the corn-based diet, the barley-sorghum-based diet reduced the apparent total tract digestibility (ATTD) and apparent ileal digestibility (AID) of crude protein (CP), the AID of all amino acids, amylase activity, trypsin activity, and pH in the ileal digesta of growing pigs (P < 0.05). Dietary 5 g/kg SCFP supplementation increased the digestible energy (DE)/gross energy (GE) ratio (P < 0.05), and the metabolizable energy (ME)/GE ratio (P < 0.10) of growing pigs in comparison to the nonSCFP-supplemented diet. Additionally, dietary 5 g/kg SCFP supplementation tended to enhance the ATTD of acid detergent fiber (ADF) and the AID of lysine (P < 0.10) and elevated the AID of tryptophan in growing pigs (P < 0.05). However, the nutrient digestibility and ileal digesta characteristics were unaffected by diet type & times; SCFP interaction (P > 0.05). In conclusion, compared with the corn-based diet, the barley-sorghum-based diet reduced the activities of digestive enzymes and the digestive absorption of CP and amino acids in growing pigs. Dietary 5 k/kg SCPF supplementation had beneficial effects on the energy and ADF digestibility of growing pigs. However, the nutrient digestibility and ileal digesta characteristics of the pigs were unaffected by diet type x SCFP interaction.

Artemisinin performs a variety of biological functions, such as anti-cancer, anti-inflammatory, anti-viral, and anti-oxidant effects. However, the effects of artemisinin on sow mastitis have not been studied. The results of the current study showed that mRNA expression abundance and content of the inflammatory factors interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) were significantly increased when using 50 μg/mL LPS to stimulate pMECs for 24 h (p < 0.05). Pretreatment with 20 μM artemisinin weakened LPS-induced inflammatory damage in pMECs and decreased mRNA expression abundance and the content of inflammatory factors (IL-1β, IL-6, and TNF-α) in pMECs (p < 0.05). Mechanistically, artemisinin inhibited LPS-induced activation of the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. In summary, the pretreatment of pMECs with artemisinin showed enhanced anti-inflammatory activity against LPS-induced inflammation.

The present study was conducted to evaluate the impact of dietary fully oxidised β-carotene (OxBC, C40H60O15) supplementation during the perinatal period on immune status and productivity in a sow model. At day 85 of pregnancy, 150 sows were allocated to one of three dietary treatments with fifty sows per treatment. The three experimental diets were supplemented with 0, 4 or 8 mg/kg OxBC in the basal diet. The feeding trial was conducted from gestation day 85 until day 21 of lactation. Dietary OxBC supplementation greatly enhanced colostrum IgM, IgA and IgG levels, and the IgM and IgG content of 14-d milk. Dietary OxBC supplementation decreased the TNF-α and IL-8 levels in colostrum, as well as the TNF-α and IL-18 levels in 14-d milk. There was also a tendency towards an increase in the soluble CD14 level in 14-d milk. Although dietary treatments did not affect average daily feed intake nor backfat thickness loss during lactation, dietary OxBC supplementation tended to enhance litter weight and individual piglet weight at weaning. There was a trend towards increased lactose concentration in 14-d milk with increasing dietary OxBC. It is concluded that dietary supplementation with OxBC during the perinatal period enhances the lactose concentration of sow milk and the immune status of sows, which is reflected by improved cytokine status and immunoglobulin concentrations in colostrum and milk, and thus tending to increase litter weight and individual piglet weight at weaning. The results also provide a scientific nutritional reference for perinatal mothers due to the biological similarity between pigs and humans.

Abstract Early embryo implantation and development is primarily determined by the homeostasis between cellular apoptosis and proliferation as well as placental nutrient transporters. Recent studies showed that L‐carnitine enhances female reproductive performance. However, the potential function of L‐carnitine on placenta is largely unknown. In our study, primary rat trophoblast cells were separated and cultured for 12 hr in medium containing various concentrations of L‐carnitine (0, 1, 10, and 50 mM). Placenta trophoblast cells treated with 50 mM L‐carnitine increased the proportion of cells in S phase of the cell cycle (p < .05). In addition, live cell percentage was increased when treated with either 10 mM or 50 mM L‐carnitine, which was accompanied with decreased necrotic cells, late apoptotic cells, and early apoptotic cells (p < .05). Compared with the control treatment, the mRNA expression of insulin‐like growth factor I (IGF‐1) and insulin‐like growth factor I receptor (IGF‐1R) was higher in rat placenta trophoblasts treated with either 10 mM or 50 mM L‐carnitine (p < .05). Similarly, sodium‐dependent neutral amino acid transporter (SNAT)‐1 and SNAT2 were up‐regulated in both mRNA and protein levels when trophoblast cells were treated with 50 mM L‐carnitine (p < .05). Inhibiting downstream targets (Akt or ERK signaling pathways) of IGF‐1 signaling pathway partially blocked the effect the L‐carnitine‐induced increase in protein abundances of SNAT1 and SNAT2. Collectively, our data showed protective role of L‐carnitine on placenta trophoblast cells through the involvement of IGF‐1 signaling pathway.

Abstract Background Fat percentage and distribution in pigs are associated with their productive efficiency and meat quality. Dietary branched-chain amino acids (BCAA) regulate fat metabolism in weanling piglets with unknown mechanism. It is reported that N6-methyl-adenosine (m6A) is involved in fat metabolism in mice. The current study was designed to investigate the relationship between dietary branched-chain amino acids and fat metabolism through N6-methyl-adenosine (m6A) in weanling piglets. Methods A total of 18 healthy crossbred weaned piglets (Duroc × Landrace × Large White, 10.45 ± 0.41 kg) were divided into 3 treatments and were fed the low BCAA dose diet (L-BCAA), the normal dose BCAA diet (N-BCAA), or the high dose BCAA (H-BCAA) diet for 3 weeks. Results Our results show that compared with the N-BCAA group, the L-BCAA group had higher concentration of serum leptin (P < 0.05), while the H-BCAA group had lower concentration of serum adiponectin (P < 0.05). Fatty acid synthesis in pigs from the H-BCAA group was lower than those from the N-BCAA group with the down-regulation of lipogenic genes (ACACA, FASN, PPAR-r, SREBP-1c in ventral and dorsal fat, SREBP-1c in liver) and up-regulation of lipolysis genes (HSL, ATGL, CPT-1A, FABP4 in ventral fat, HSL in liver) (P < 0.05). Similarly, fatty acid synthesis in pigs from the L-BCAA group was also lower than those from the N-BCAA group with the decrease of lipogenic genes (ACACA in ventral, ACACA and FASN in dorsal fat, ACACA, FASN, SREBP-1c in liver) and the increase of lipolysis genes (ATGL, CPT-1A CD36, FABP4 in ventral fat and HSL, ATGL, CPT-1A in dorsal fat, CPT-1A) (P < 0.05). Feeding H-BCAA diet significantly reduced total m6A levels in ventral and dorsal fat and liver tissues (P < 0.05). The decrease of total m6A is associated with down-regulation of METTL3, METTL14 and FTO in dorsal fat and METTL3 and FTO in liver (P < 0.05). Decreased m6A modification of ACACA and FASN in ventral and dorsal adipose tissues was observed in pig fed with excessive BCAA. Conclusion These results suggest that insufficient or excessive BCAA decreased the fat deposition by increasing lipolysis and deceasing lipogenesis in adipose and liver tissues. Dietary excessive BCAA might regulate the process of lipid metabolism partly through the m6A RNA methylation.

Dietary fiber is a critical nutrient in sow diet and has attracted interest of animal nutritionists for many years. In addition to increase sows' satiety, dietary fiber has been found to involve in the regulation of multiple biological functions in the sow production. The interaction of dietary fiber and gut microbes can produce bioactive metabolites, which are of great significance to sows' metabolism and reproductive performance. This article reviewed the interaction between dietary fiber and gut microbes in regulating sows' gut microbial diversity, intestinal immune system, lactation, and production performance, with the aim to provide a new strategy for the use of dietary fiber in sow diets.

Activated protein kinase (AMP)-activated protein kinase (AMPK) senses the cellular energy status and coordinates catabolic and anabolic processes. Extensive studies have proposed that AMPK regulates energy homeostasis, cell growth, autophagy, mitochondrial biology and inflammation. The biological functions of AMPK vary in different tissues or organs. As a unique organ that produces milk, the mammary gland has recently attracted substantial research attention. This review discusses how AMPK in the mammary gland is activated by energy deprivation and heat stress via the activation of canonical and non-canonical pathways. In addition, the important downstream targets of AMPK and their functions in the mammary gland, especially during milk synthesis, are summarized in the review.

Janus kinase 2 (JAK2) and signal transducers and activators of transcription 5 (STAT5) are involved in the proliferation, differentiation, and survival of mammary gland epithelial cells. Dysregulation of JAK2-STAT5 activity invariably leads to mammary gland developmental defects and/or diseases, including breast cancer. Proper functioning of the JAK2-STAT5 signaling pathway relies on crosstalk with other signaling pathways (synergistically or antagonistically), which leads to normal biological performance. This review highlights recent progress regarding the critical components of the JAK2-STAT5 pathway and its crosstalk with G-protein coupled receptor (GPCR) signaling, PI3K-Akt signaling, growth factors, inflammatory cytokines, hormone receptors, and cell adhesion.

Activated protein kinase (AMP)-activated protein kinase (AMPK) senses the cellular energy status and coordinates catabolic and anabolic processes. Extensive studies have proposed that AMPK regulates energy homeostasis, cell growth, autophagy, mitochondrial biology and inflammation. The biological functions of AMPK vary in different tissues or organs. As a unique organ that produces milk, the mammary gland has recently attracted substantial research attention. This review discusses how AMPK in the mammary gland is activated by energy deprivation and heat stress via the activation of canonical and non-canonical pathways. In addition, the important downstream targets of AMPK and their functions in the mammary gland, especially during milk synthesis, are summarized in the review.

(1) Background: Nutritional strategies to enhance gut function and reduce the piglet diarrhea rate are critical to increase the growth performance of piglets. The purpose of this study was to investigate whether dietary fat types and/or fat microencapsulation techniques are involved in regulating the fatty acid transport system and the mechanical and immunological barriers of the small intestine. (2) Methods: Three hundred twenty-four weaning piglets were randomly divided into three groups fed a soybean oil diet (SBO, control group, 6.0% soybean oil), palm oil diet (PO, 6.0% palm oil), or encapsulated palm oil diet (EPO, 7.5% encapsulated palm oil). (3) Results: A significantly lower mRNA expression of the claudin was observed in the duodenum and jejunum of the PO group than in the SBO group (p < 0.05). However, the mRNA expression and protein abundance of claudin and ZO-1 in the jejunum of the EPO group were higher (p < 0.05) than in the PO group. Porcine β-defensin (pBD) secretion was not significantly different between the SBO and PO groups (p > 0.05), while the pBD-2 levels were significantly different (p < 0.05). Compared with the PO group, the EPO group exhibited a significantly increased secretion of pBD-2 and pBD-129 in the small intestine (p < 0.05) and pBD-1 in the jejunum and ileum (p < 0.05). The protein abundances of apolipoprotein AIV (Apo AIV) and intestinal fatty acid binding protein (I-FABP) were significantly lower in the PO group than in the SBO group (p < 0.05). Simultaneously, the protein abundances of fatty acid transport protein 4 (FATP4), fatty acid translocase (CD36), and I-FABP were higher in the EPO group than in the PO group. Furthermore, the low digestibility of palm oil (PO group) might negatively regulate intestinal tight junctions, fatty acid transporters, lipoproteins, and β-defensin through the activation of the AMPK/mTORC1 and AMPK/Sirt1/NF-κB pathways. (4) Conclusions: In summary, microencapsulation techniques might alleviate the negative effects of palm oil and help to improve the intestinal fatty acid transport system and barrier function.