A retrospective study of ovarian tissue cryopreservation in female patients with hematological diseases for fertility preservation.

PURPOSES: To investigate the effect and safety of ovarian tissue cryopreservation (OTC) for fertility preservation in female patients with hematological diseases. METHODS: We designed a retrospective study. The clinical data of patients with hematological diseases undergoing OTC admitted to Peking University People's Hospital from April 2017 to January 2023 were analyzed and summarized. RESULTS: A total of 24 patients were included in the study, including 19 patients with malignant hematological diseases and 5 patients with non-malignant hematological diseases. The former included 14 patients with acute leukemia, 1 patient with chronic leukemia, and 4 patients with myelodysplastic syndrome, while the latter 5 patients were aplastic anemia (AA). 16 patients had received chemotherapy before OTC. The average age of 24 patients was 22.80 ± 6.81 years. The average anti-Mullerian hormone (AMH) was 1.97 ± 2.12 ng/mL, and the average follicle-stimulating hormone (FSH) was 7.01 ± 4.24 IU/L in examination before OTC. FSH was greater than 10.0 IU/L in 4 cases. The pre-OTC laboratory tests showed that the average white blood cell (WBC) count was (3.33 ± 1.35) × 109/L, the average hemoglobin was 91.42 ± 22.84 g/L, and the average platelet was (147.38 ± 114.46) × 109/L. After injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF), blood transfusion, and iron supplementation in pre-OTC treatment, the average WBC count was (4.91 ± 3.07) × 109/L, the average hemoglobin was 98.67 ± 15.43 g/L, and the average platelet was (156.38 ± 103.22) × 109/L. Of the 24 patients, 22 underwent laparoscopic bilateral partial oophorectomy and oophoroplasty, and 2 underwent laparoscopic unilateral oophorectomy. The average duration of OTC was 59.54 ± 17.58 min, and the average blood loss was 32.1 ± 41.6 mL. The maximum blood loss was 200 mL. There was no significant difference in WBC count and hemoglobin concentration after OTC compared to pre-OTC period. Only the platelet count after OTC surgery was significantly different from that before surgery ([134.54 ± 80.84 vs. 156.38 ± 103.22] × 109/L, p < 0.05). None of the 24 patients had serious complications after OTC. 2 patients had mild infection symptoms, but both recovered well. 23 patients underwent hematopoietic stem cell transplantation (HSCT) after OTC. The median and interquartile range from OTC to the pretreatment of HSCT was 33 (57) days, and the median and interquartile range from OTC to HSCT was 41 (57) days. Seven of them began pretreatment of HSCT within 20 days and began HSCT within 30 days after OTC. All patients were followed up. Of the 23 patients who underwent HSCT after surgery, 22 presented with amenorrhea and 1 with scanty menstrual episodes. Seven patients underwent hormone replacement therapy (HRT) after HSCT. A patient with AA underwent ovarian tissue transplantation (OTT) 3 years after HSCT and resumed regular menstruation 6 months after OTT. CONCLUSIONS: Ovarian tissue cryopreservation has a promising future in fertility protection in patients with hematological diseases. However, patients with hematological malignancies often have received gonadotoxic therapy before OTC, which may be accompanied by myelosuppression while patients with non-malignant hematological diseases often present with severe hemocytopenia. So perioperative complete blood count of patients should be paid attention to. There was no significant difference in the WBC count and hemoglobin concentration in patients with hematological diseases before and after OTC surgery, and the platelet count decreased slightly within the normal range. Infection is the most common post-OTC complication, and HSCT pretreatment can be accepted as early as the 10th day after OTC. OTC has no adverse effects on patients with hematological diseases and does not delay HSCT treatment. For young patients with hematological diseases, OTC is an effective method of fertility preservation.

Assessing the health risks of heavy metals and seasonal minerals fluctuations in Camellia sinensis cultivars during their growth seasons.

The risk assessment of heavy metals in tea is extremely imperative for the health of tea consumers. However, the effects of varietal variations and seasonal fluctuations on heavy metals and minerals in tea plants remain unclear. Inductively coupled plasma optical emission spectrometry (ICP-OES) was used to evaluate the contents of aluminum (Al), manganese (Mn), magnesium (Mg), boron (B), calcium (Ca), copper (Cu), cobalt (Co), iron (Fe), sodium (Na), zinc (Zn), arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), and antimony (Sb) in the two categories of young leaves (YL) and mature leaves (ML) of tea (Camellia sinensis) cultivars throughout the growing seasons. The results showed significant variations in the contents of the investigated nutrients both among the different cultivars and growing seasons as well. Furthermore, the average concentrations of Al, Mn, Mg, B, Ca, Cu, Co, Fe, Na, Zn, As, Cd, Cr, Ni, and Sb in YL ranged, from 671.58-2209.12, 1260.58-1902.21, 2290.56-2995.36, 91.18-164.68, 821.95-5708.20, 2.55-3.80, 3.96-25.22, 37.95-202.84, 81.79-205.05, 27.10-69.67, 0.028-0.053, 0.065-0.127, 2.40-3.73, 10.57-12.64, 0.11-0.14 mg kg-1, respectively. In ML, the concentrations were 2626.41-7834.60, 3980.82-6473.64, 3335.38-4537.48, 327.33-501.70, 9619.89-13153.68, 4.23-8.18, 17.23-34.20, 329.39-567.19, 145.36-248.69, 40.50-81.42, 0.089-0.169, 0.23-0.27, 5.24-7.89, 18.51-23.97, 0.15-0.19 mg kg-1, respectively. The contents of all analyzed nutrients were found to be higher in ML than in YL. Target hazard quotients (THQ) of As, Cd, Cr, Ni, and Sb, as well as the hazard index (HI), were all less than one, suggesting no risk to human health via tea consumption. This research might provide the groundwork for essential minerals recommendations, as well as a better understanding and management of heavy metal risks in tea.

Dietary ethylenediamine dihydroiodide mitigated Escherichia coli O78-induced immune and intestinal damage of ducks via suppression of NF-κB signal.

This study investigated the effect of Ethylenediamine dihydroiodide (EDDI) on growth performance, immune function and intestinal health of meat ducks challenged with Avian pathogenic Escherichia coli (APEC). A total of 360 one-day-old Cherry Valley ducks with similar body weight were randomly allocated to 6 treatments (6 floor cages, 10 birds/cage). A 3 × 2 factor design was used with 3 dietary iodine levels (0, 8, 16 mg/kg in the form EDDI and whether APEC was challenged or not at 7-day-old ducks. The feeding period lasted for 20 d. The results showed that the addition of EDDI reduced APEC-induced decrease of the 20-d weight loss of meat ducks (P < 0.05), and alleviated the inflammatory response of liver tissue induced by APEC challenge in meat ducks. In terms of immune function, EDDI supplementation reduced the immune organ index and increased the immune cell count of meat ducks, reduced the level of endotoxins in the serum of meat ducks (P < 0.05), as well as inhibited the expression levels of liver and spleen inflammatory factors and TLR signaling pathway related genes induced by APEC (P < 0.05). In terms of intestinal health, EDDI inhibited APEC-induced decreases in ZO-3 genes expression and increases in IL-1ß and TNF-α expression, increased relative abundance of beneficial bacteria in the cecum and content of metabolites. Pearson correlation analysis showed that there was a significant correlation between liver inflammatory factors and TLR4 signaling pathway genes, and there might be a significant correlation between intestinal microbial flora and other physiological indexes of meat ducks, which indicated that EDDI could reduce the damage to immune function and intestinal health caused by APEC challenge through regulating the structure of intestinal flora. Collectively, our findings suggest that the EDDI can promote growth performance, improve immune function and the intestinal barrier in APEC-challenged meat ducks, which may be related to the suppression of NF-κB signal.

Effects of maternal methyl donor intake during pregnancy on ileum methylation and function in an intrauterine growth restriction pig model.

BACKGROUND: Intrauterine growth retardation (IUGR) affects intestinal growth, morphology, and function, which leads to poor growth performance and high mortality. The present study explored whether maternal dietary methyl donor (MET) supplementation alleviates IUGR and enhances offspring's growth performance by improving intestinal growth, function, and DNA methylation of the ileum in a porcine IUGR model. METHODS: Forty multiparous sows were allocated to the control or MET diet groups from mating until delivery. After farrowing, 8 pairs of IUGR and normal birth weight piglets from 8 litters were selected for sampling before suckling colostrum. RESULTS: The results showed that maternal MET supplementation tended to decrease the IUGR incidence and increased the average weaning weight of piglets. Moreover, maternal MET supplementation significantly reduced the plasma concentrations of isoleucine, cysteine, urea, and total amino acids in sows and newborn piglets. It also increased lactase and sucrase activity in the jejunum of newborn piglets. MET addition resulted in lower ileal methionine synthase activity and increased betaine homocysteine S-methyltransferase activity in the ileum of newborn piglets. DNA methylation analysis of the ileum showed that MET supplementation increased the methylation level of DNA CpG sites in the ileum of newborn piglets. Down-regulated differentially methylated genes were enriched in folic acid binding, insulin receptor signaling pathway, and endothelial cell proliferation. In contrast, up-regulated methylated genes were enriched in growth hormone receptor signaling pathway and nitric oxide biosynthetic process. CONCLUSIONS: Maternal MET supplementation can reduce the incidence of IUGR and increase the weaning litter weight of piglets, which may be associated with better intestinal function and methylation status.

Effects of Dietary Glutamine Supplementation on the Modulation of Microbiota and Th17/Treg Immune Response Signaling Pathway in Piglets after Lipopolysaccharide Challenge.

BACKGROUND: Glutamine (Gln) has an important effect on the growth performance and immune function of piglets. However, the effect of Gln on intestinal immunity in piglets through modulating the signaling pathways of the helper T cells 17 (Th17)/regulatory T cells (Treg) immune response has not been reported. OBJECTIVE: This study aimed to determine the effect of Gln on piglet growth performance and immune stress response and its mechanism in piglets. METHODS: Twenty-four weaned piglets were randomly assigned to 4 treatments with 6 replicates each, using a 2 × 2 factorial arrangement: diet (basal diet or 1% Gln diet) and immunological challenge [saline or lipopolysaccharide (LPS)]. After 21 d, half of the piglets on the basal diet and 1% Gln diet received the intraperitoneal injection of LPS and the other half received the same volume of normal saline. RESULTS: The results showed that Gln increased average daily feed intake and average daily weight gain in comparison with the control group (P < 0.05). Dietary Gln increased the villus height, villus height-to-crypt depth ratio, and the abundance of Bacteroidetes, Lactobacillus sp., and Ruminococcus sp. while reducing the abundance of Firmicutes, Clostridium sensu stricto 1 sp., and Terrisporobacter sp. (P < 0.05). Furthermore, Gln increased the concentration of short-chain fatty acids in the colon and the expression of genes of interleukin (IL)-10, transforming growth factor-beta-1, forkhead box P3 while downregulating the expression of genes of IL-6, IL-8, IL-1ß, tumor necrosis factor-α, IL-17A, IL-21, signal transducer and activator of transcription 3, and rar-related orphan receptor c in ileum (P < 0.05). Correlation analysis demonstrated a strong association between colonic microbiota, short-chain fatty acids, and ileal inflammatory cytokines. CONCLUSIONS: These results suggest that dietary Gln could improve growth performance and attenuate LPS-challenged intestinal inflammation by modulating microbiota and the Th17/Treg immune response signaling pathway in piglets.

Alpha-ketoglutaric acid attenuates oxidative stress and modulates mitochondrial dynamics and autophagy of spleen in a piglet model of lipopolysaccharide-induced sepsis.

Alpha-ketoglutaric acid (2-ketoglutaric acid or 2-oxoglutaric acid, AKG), a crucial intermediate in the tricarboxylic acid cycle, is pivotal in animal antioxidative process. The purpose of this study was to investigate whether AKG has the efficacy to mitigate spleen oxidative stress in lipopolysaccharide (LPS)-induced sepsis piglets through the modulation of mitochondrial dynamics and autophagy. Utilizing a 2 × 2 factorial design, the study encompassed 24 piglets subjected to varying diets (basal or 1% AKG) and immune stimulations (saline or LPS) over 21 days. Subsequently, they were injected intraperitoneally with either LPS or saline solution. The results showed that LPS decreased antioxidant capacity, whereas AKG supplementation increased antioxidant activities compared to control group. LPS elevated mitochondrial fission factor, mitochondrial elongation factor 1, mitochondrial elongation factor 2, dynamin-related protein 1, voltage-dependent anion channel 1, and fission 1 mRNA abundance, but reduced mRNA abundance of mitofusin 1, mitofusin 2, and optic atrophy 1 compared to controls. LPS elevated mRNA abundance of autophagy related protein 5, autophagy related protein 7, P62, Beclin1, and interleukin-1ß mRNA abundance compared to controls. However, AKG supplementation mitigated these effects induced by LPS. Additionally, AKG intake was associated with lower protein expressions of microtubule-associated protein light chain 3, Parkin, and PTEN-induced putative kinase 1 compared to LPS-challenged piglets. These results suggested that AKG could alleviate spleen oxidative stress caused by LPS by regulating mitochondrial dynamics and autophagy.

Selenomethionine alleviates chronic heat stress-induced breast muscle injury and poor meat quality in broilers via relieving mitochondrial dysfunction and endoplasmic reticulum stress.

In the present study, the chronic heat stress (CHS) broiler model was developed to investigate the potential protection mechanism of organic selenium (selenomethionine, SeMet) on CHS-induced skeletal muscle growth retardation and poor meat quality. Four hundred Arbor Acres male broilers (680 ± 70 g, 21 d old) were grouped into 5 treatments with 8 replicates of 10 broilers per replicate. Broilers in the control group were raised in a thermoneutral environment (22 ± 2 °C) and fed with a basal diet. The other four treatments were exposed to hyperthermic conditions (33 ± 2 °C, 24 h in each day) and fed on the basal diet supplied with SeMet at 0.0, 0.2, 0.4, and 0.6 mg Se/kg, respectively, for 21 d. Results showed that CHS reduced (P < 0.05) the growth performance, decreased (P < 0.05) the breast muscle weight and impaired the meat quality of breast muscle in broilers. CHS induced protein metabolic disorder in breast muscle, which increased (P < 0.05) the expression of caspase 3, caspase 8, caspase 9 and ubiquitin proteasome system related genes, while decreased the protein expression of P-4EBP1. CHS also decreased the antioxidant capacity and induced mitochondrial stress and endoplasmic reticulum (ER) stress in breast muscle, which increased (P < 0.05) the ROS levels, decreased the concentration of ATP, increased the protein expression of HSP60 and CLPX, and increased (P < 0.05) the expression of ER stress biomarkers. Dietary SeMet supplementation linearly increased (P < 0.05) breast muscle Se concentration and exhibited protective effects via up-regulating the expression of the selenotranscriptome and several key selenoproteins, which increased (P < 0.05) body weight, improved meat quality, enhanced antioxidant capacity and mitigated mitochondrial stress and ER stress. What's more, SeMet suppressed protein degradation and improved protein biosynthesis though inhibiting the caspase and ubiquitin proteasome system and promoting the mTOR-4EBP1 pathway. In conclusion, dietary SeMet supplementation increases the expression of several key selenoproteins, alleviates mitochondrial dysfunction and ER stress, improves protein biosynthesis, suppresses protein degradation, thus increases the body weight and improves meat quality of broilers exposed to CHS.

Cowberry extract loaded chitosan hydrogel with photothermal and antioxidant properties promotes infected wound healing.

Bacterial infection and oxidative stress impede clinical wound healing. Herein, the plant-derived cowberry extract (CE) was first explored as a natural photothermal agent and antioxidant to deal with bacterial infection and oxidative stress. After loading in the carboxymethyl chitosan (CMCs)/oxidized dextran (Odex) hydrogel, the photothermal effect of CE was highly enhanced by CMCs. The controlled temperature induced by CE-containing hydrogel under NIR laser irradiation could rapidly (10 min) and effectively kill Staphylococcus aureus (S. aureus, 99.3 %) and Escherichia coli (E. coli, 94.6 %). Besides, this hydrogel exhibited a fast gelation and hemostasis abilities, high stability, adhesion and ROS scavenging capabilities, as well as good injectability and biocompatibility. Above superior properties make this hydrogel to accelerate the wound healing in S. aureus-infected mice, and it is expected to be a potential clinical wound dressing.

Anti-hepatocellular carcinoma activity of Sorbaria sorbifolia by regulating VEGFR and c-Met/apoptotic pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Sorbaria sorbifolia (SS) is a traditional Chinese medicine (TCM) that has been employed anti-hepatocellular carcinoma (HCC) for over 2000 years; yet, its underlying mechanism is still not fully understood. AIM OF THE STUDY: In this study, we evaluated the anti-HCC effect on the freeze-dried powder of the water extract of SS (FDSS) by inhibiting tumor-induced neovascularization, and promoting apoptosis, and elucidated the underlying mechanisms. MATERIALS AND METHODS: HCC cell lines (HepG2 and Huh7 cells) and HepG2 xenograft tumors in zebrafish were employed as in vivo and in vitro models, respectively, to evaluate the anti- HCC-indued neovascularization and apoptosis. In HCC cell lines, CCK-8 assay, wound-healing assay, transwell assay, cell circle assay, apoptosis assay, transmission electron microscopy, and co-culture assay were performed in vitro; in HepG2 xenograft tumor-zebrafish, tumor growth inhibition assay, hematoxylin and eosin (HE) staining, xenograft tumor-zebrafish apoptosis assay, and HCC-indued neovascularization assay were performed to evaluate the effect of FDSS on biological behavior of tumor, HCC-indued neovascularization, and apoptosis. The expression of VEGFR and c-Met/apoptotic pathway-related proteins was detected by western blotting analysis. Assays for c-Met and VEGFR activation were conducted to assess the impact of FDSS in either agonistic or inhibitory roles on these receptor proteins. RESULTS: The findings from our study revealed that FDSS effectively suppresses the proliferation, migration, and invasion of HepG2 and Huh7 cells, as well as inhibiting tumor growth in the HepG2 xenograft zebrafish model by downregulating the expression of p-Met and p-AKT proteins. FDSS decreased the tumor growth associated with promoting apoptosis, including arresting HepG2 and Huh7 cells cycle at G0/G1phase, increasing apoptotic cell numbers and apoptotic bodies in cancer cells, and increasing the apoptotic fluorescence of xenograft tumor zebrafish by downregulating Bcl-2 proteins and upregulating Bax, caspase-9, and caspase-3 levels. We also found that FDSS can inhibit HCC-induced neovascularization and regulate VEGFR. Using an agonist or inhibitor of c-Met and VEGFR in HepG2 cells, we discovered that FDSS can downregulate c-Met and VEGFR protein expression. CONCLUSION: FDSS exerts an anti-HCC effect by inhibiting HCC-indued neovascularization and pro-apoptosis through the inhibition of the action of VEGFR and c-Met/apoptotic pathway.

Zinc glycine chelate ameliorates DSS-induced intestinal barrier dysfunction via attenuating TLR4/NF-κB pathway in meat ducks.

BACKGROUND: Zinc glycine chelate (Zn-Gly) has anti-inflammation and growth-promoting properties; however, the mechanism of Zn-Gly contribution to gut barrier function in Cherry Valley ducks during intestinal inflammation is unknown. Three-hundred 1-day-old ducks were divided into 5 groups (6 replicates and 10 ducks per replicate) in a completely randomized design: the control and dextran sulfate sodium (DSS) groups were fed a corn-soybean meal basal diet, and experimental groups received supplements of 70, 120 or 170 mg/kg Zn in form of Zn-Gly. The DSS and treatment groups were given 2 mL of 0.45 g/mL DSS daily during d 15-21, and the control group received normal saline. The experiment lasted 21 d. RESULTS: Compared with DSS group, 70, 120 and 170 mg/kg Zn significantly increased body weight (BW), villus height and the ratio of villus to crypt, and significantly decreased the crypt depth of jejunum at 21 d. The number of goblet cells in jejunal villi in the Zn-Gly group was significantly increased by periodic acid-Schiff staining. Compared with control, the content of intestinal permeability marker D-lactic acid (D-LA) and fluxes of fluorescein isothiocyanate (FITC-D) in plasma of DSS group significantly increased, and 170 mg/kg Zn supplementation significantly decreased the D-LA content and FITC-D fluxes. Compared with control, contents of plasma, jejunum endotoxin and jejunum pro-inflammatory factors IL-1ß, IL-6 and TNF-α were significantly increased in DSS group, and were significantly decreased by 170 mg/kg Zn supplementation. Dietary Zn significantly increased the contents of anti-inflammatory factors IL-10, IL-22 and sIgA and IgG in jejunum. Real-time PCR and Western blot results showed that 170 mg/kg Zn supplementation significantly increased mRNA expression levels of CLDN-1 and expression of OCLN protein in jejunum, and decreased gene and protein expression of CLDN-2 compared with DSS group. The 120 mg/kg Zn significantly promoted the expressions of IL-22 and IgA. Dietary Zn-Gly supplementation significantly decreased pro-inflammatory genes IL-8 and TNF-α expression levels and TNF-α protein expression in jejunum. Additionally, Zn significantly reduced the gene and protein expression of TLR4, MYD88 and NF-κB p65. CONCLUSIONS: Zn-Gly improved duck BW and alleviated intestinal injury by regulating intestinal morphology, barrier function and gut inflammation-related signal pathways TLR4/MYD88/NF-κB p65.

Mild hyperthermia-assisted chitosan hydrogel with photothermal antibacterial property and CAT-like activity for infected wound healing.

Infected wounds pose a serious threat to public health and pose a significant challenge and financial burden worldwide. The treatment of infected wounds is now an urgent problem to be solved. Herein, mild hyperthermia-assisted hydrogels composed of carboxymethyl chitosan (CMCs), oxidized dextran (Odex), epigallocatechin gallate (EGCG) and PtNPs@PVP (CAT-like nanoenzymes) were proposed for the repair of infected wounds. The incorporation of PtNPs@PVP nanoenzymes give the hydrogels excellent photothermal property and CAT-like activity. When the temperature is maintained at 42-45 °C under 808 nm near infrared (NIR) exposure, the CMCs/Odex/EGCG/Nanoenzymes (COEN2) hydrogel demonstrated highly enhanced antibacterial ability (95.9 % in vivo), hydrogen peroxide (H2O2) scavenging ratio (85.1 % in vitro) and oxygen supply (20.7 mg/L in vitro). Furthermore, this mild-heat stimulation also promoted angiogenesis in the damaged skin area. Overall, this multifunctional hydrogel with antibacterial, antioxidant, oxygen supply, hemostasis, and angiogenesis capabilities has shown great promise in the repair of infected wounds. This study establishes the paradigm of enhanced infected wound healing by mild hyperthermia-assisted H2O2 scavenging, oxygen supplemental, and photothermal antibacterial hydrogels.

Effects of dietary N-carbamylglutamate supplementation on the modulation of microbiota and Th17/Treg balance-related immune signaling after lipopolysaccharide challenge.

BACKGROUND: This study aimed to evaluate the effects of N-carbamylglutamate (NCG) on piglets' growth performance and immune response, and to unravel the mechanisms of such effects. In a 2 × 2 factorial design including diet (with or without NCG) and immunological challenge (saline or lipopolysaccharide (LPS)), 24 piglets were randomly distributed into four groups. After being fed a basic diet or a NCG-supplemented diet for 21 days, piglets were administered LPS or saline intraperitoneally. RESULTS: The results showed that NCG increased the average daily gain and average daily feed intake, and the feed conversion ratio of piglets, and alleviated the adverse effects of LPS stimulation on intestinal morphology. At the phylum level, NCG reversed the increase in the abundance of Firmicutes and the reduction in that of Actinomycete caused by LPS stimulation. At the genus level, NCG increased the abundance of Lactobacillus, Blautia, norank_Butyricicoccaceae, Subdoligranulum, and Ruminococcus_gauvreauii_group, and LPS decreased the abundance of Escherichia-Shigella and Ruminococcus_gauvreauii_group. The short-chain fatty acid content was increased by NCG, but LPS reduced its content. N-Carbamylglutamate also inhibited significantly the LPS-induced increase in the relative expression of signal transducer and activator of transcription (STAT) 3, related orphan receptor (RAR) c, and pro-inflammatory cytokines, and the decrease in the relative expression of STAT5, forkhead box P3, IL-10 and transforming growth factor beta 1 mRNA. A significant correlation was found between intestinal microbiota and inflammatory cytokines and short-chain fatty acids. CONCLUSION: N-Carbamylglutamate can improve piglets' growth performance. It can also attenuate LPS-induced intestinal inflammation by modulating microbiota and Th17/Treg balance-related immune signaling pathways. © 2023 Society of Chemical Industry.

Hydroxy Selenomethionine Exert Different Protective Effects Against Dietary Oxidative Stress-Induced Inflammatory Responses in Spleen and Thymus of Pigs.

Oxidative stress (OS) is widespread in animal husbandry, which causes edema in immune organs and suppresses immune function of animals. Selenium (Se) is an essential trace element involved in immune regulation and improves animals' immunity. In present study, growing and finishing pigs were used to determine the protective effects of the new organic Se (hydroxy selenomethionine, OH-SeMet) on dietary oxidative stress (DOS) induced inflammatory responses, and the corresponding response of selenotranscriptome in spleen and thymus. Forty castrated male pigs (25.0 ± 3.0 kg) were randomly grouped into 5 dietary treatments (n = 8) and fed on basal diet (formulated with normal corn and normal oils) or oxidized diet (formulated with aged corn and oxidized oils) supplied with 0.0, 0.3, 0.6, or 0.9 mg Se/kg OH-SeMet, after 16 weeks, the corresponding indicators were determined. Results showed that DOS moderately increased the spleen and thymus index, decreased the antioxidant capacity of serum, spleen and thymus, and increased the concentration of serum inflammatory cytokines (IL-6 and TNF-α). The inflammatory response in spleen and thymus under DOS were discrepancies, DOS increased the expression of inflammation-related gene (IFN-ß and TNF-α) in thymus, while exhibited no impact on that of the spleen. Dietary OH-SeMet supplementation exhibited protective effects, which decreased the spleen and thymus index, improved the antioxidant capacity of serum, spleen and thymus, and decreased the serum IL-1ß and IL-6 levels. Se supplementation exhibited limited impact on the inflammation-related genes in spleen, except decreased the mRNA expression of IL-8. On the contrary, Se supplementation showed more impact on that of the thymus, which decreased the mRNA expression of IL-8 and TNF-α, increased the expression of IFN-ß, IL-6, IL-10, and MCP1. In addition, selenotranscriptome responsive to dietary Se levels in spleen and thymus were discrepancies. Se supplementation increased the mRNA expression of  the selenotranscriptome in thymus, while exhibited limited impact on that of in spleen. In conclusion, dietary OH-SeMet supplementation mitigates the DOS-induced immunological stress by increasing the antioxidant capacity and altering the expression of inflammation-related genes and selenotranscriptome in immune organs, and these response in spleen and thymus were discrepancies.

Compound bioengineering protein improves growth performance and intestinal health in broiler chickens under high-temperature conditions.

In recent years, more frequent and prolonged periods of high ambient temperature in summer compromised poultry production worldwide. This study was conducted to investigate the effects of compound bioengineering protein (CBP) on the growth performance and intestinal health of broilers under high ambient temperatures. A total of 400 one-day-old Arbor Acres birds were randomly distributed into five treatment groups: control group (CON) with basal diet, or a basal diet supplemented with CBP 250, 500, 750, and 1,000 mg/kg, respectively. The trial lasted 42 d, all birds were raised at normal ambient temperature for the first 21 d and then subjected to the artificial hyperthermal condition with the temperature at 32 ±â€…2 °C and relative humidity at 60 ±â€…5% during 22 to 42 d. Dietary CBP supplementation improved the growth performance and serum antioxidant capacity (total antioxidant capacity and total superoxide dismutase), and decreased serum cortisol, aminotransferase, and alkaline phosphatase of broilers. Dietary CBP inclusion enhanced intestinal barrier function by promoting intestinal morphology and reducing intestinal permeability (diamine oxidase), increased the intestinal antioxidant capacity by elevating glutathione peroxidase activity in the duodenum, reducing malondialdehyde content in the jejunum. Dietary CBP supplementation also alleviated intestinal inflammation by decreasing interleukin (IL)-6 content in the jejunum and ileum, promoting IL-10 levels in the ileum, down-regulating the mRNA abundance of intestinal inflammatory-related genes interferon-gamma (IFN-γ) in the duodenum and up-regulating IL-10 in the jejunum. Additionally, CBP increased the population of total bacteria and Lactobacillus in cecal chyme. Collectively, dietary CBP inclusion exerts beneficial effects on the broilers, which are reflected by enhancing antioxidant capacity, promoting intestinal barrier function, ameliorating intestinal immune response, and regulating intestinal bacteria, thus improving the growth performance of broilers under high-temperature conditions. In general, 750 mg/kg CBP supplementation is more effective.

Extreme high ambient temperature in summer occurs frequently around the world, which causes severe economic losses in the broiler industry, and impairs food safety. Improving the high-temperature resistance of broilers is beneficial to the sustainable development of the broiler industry. Dietary supplementation of anti-stress additives is an effective way to prevent high-temperature stress in broilers. Antimicrobial peptides are excellent anti-stress additives that exhibit multiple biological functions, such as against microbial infection, improving antioxidant capacity and immune function, and perfecting the intestinal health of broilers. In the present study, we added the compound bioengineering protein (CBP) (two bioengineering proteins containing functional fragments of antimicrobial peptides) in diets to investigate the potential protective effects of CBP for broilers under high temperatures. Our present results indicate that dietary CBP supplementation enhances the growth performance of broilers exposed to high temperatures. This improvement is attributed to the increased antioxidant capacity, improved intestinal barrier function, ameliorated intestinal immune function, and improved intestinal bacteria. These results provide a theoretical foundation for CBP utilization in diets to ameliorate growth performance and intestinal health of broilers under high temperatures.

Selenomethionine alleviates environmental heat stress induced hepatic lipid accumulation and glycogen infiltration of broilers via maintaining mitochondrial and endoplasmic reticulum homeostasis.

With the increasing of global mean surface air temperature, heat stress (HS) induced by extreme high temperature has become a key factor restricting the poultry industry. Liver is the main metabolic organ of broilers, HS induces liver damage and metabolic disorders, which impairs the health of broilers and affects food safety. As an essential trace element for animals, selenium (Se) involves in the formation of antioxidant system, and its biological functions are generally mediated by selenoproteins. However, the mechanism of Se against HS induced liver damage and metabolic disorders in broilers is inadequate. Therefore, we developed the chronic heat stress (CHS) broiler model and investigated the potential protection mechanism of organic Se (selenomethionine, SeMet) on CHS induced liver damage and metabolic disorders. In present study, CHS caused liver oxidative damage, and induced hepatic lipid accumulation and glycogen infiltration of broilers, which are accompanied by mitochondrial dysfunction, abnormal mitochondrial tricarboxylic acid (TCA) cycle and endoplasmic reticulum (ER) stress. Dietary SeMet supplementation increased the hepatic Se concentration and exhibited protective effects via promoting the expression of selenotranscriptome and several key selenoproteins (GPX4, TXNRD2, SELENOK, SELENOM, SELENOS, SELENOT, GPX1, DIO1, SELENOH, SELENOU and SELENOW). These key selenoproteins synergistically improved the antioxidant capacity, and mitigated the mitochondrial dysfunction, abnormal mitochondrial TCA cycle and ER stress, thus recovered the hepatic triglyceride and glycogen concentration. What's more, SeMet supplementation suppressed lipid and glycogen biosynthesis and promoted lipid and glycogen breakdown in liver of broilers exposed to CHS though regulating the AMPK signals. Overall, our present study reveals a potential mechanism that Se alleviates environment HS induced liver damage and glycogen and lipid metabolism disorders in broilers, which provides a preventive and/or treatment measure for environment HS-dependent hepatic metabolic disorders in poultry industry.

Different Dietary Sources of Selenium Alleviate Hepatic Lipid Metabolism Disorder of Heat-Stressed Broilers by Relieving Endoplasmic Reticulum Stress.

As global warming continues, the phenomenon of heat stress (HS) in broilers occurs frequently. The alleviating effect of different selenium (Se) sources on HS-induced hepatic lipid metabolism disorders in broilers remains unclear. This study compared the protective effects of four Se sources (sodium selenite; selenium yeast; selenomethionine; nano-Se) on HS-induced hepatic lipid metabolism disorder and the corresponding response of selenotranscriptome in the liver of broilers. The results showed that HS-induced liver injury and hepatic lipid metabolism disorder, which were reflected in the increased activity of serum alanine aminotransferase (ALT), the increased concentration of triacylglycerol (TG) and total cholesterol (TC), the increased activity of acetyl-CoA carboxylase (ACC), diacylglycerol O-acyltransferase (DGAT) and fatty acid synthase (FAS), and the decreased activity of hepatic lipase (HL) in the liver. The hepatic lipid metabolism disorder was accompanied by the increased mRNA expression of lipid synthesis related-genes, the decreased expression of lipidolysis-related genes, and the increased expression of endoplasmic reticulum (ER) stress biomarkers (PERK, IRE1, ATF6, GRP78). The dietary supplementation of four Se sources exhibited similar protective effects. Four Se sources increased liver Se concentration and promoted the expression of selenotranscriptome and several key selenoproteins, enhanced liver antioxidant capacity and alleviated HS-induced ER stress, and thus resisted the hepatic lipid metabolism disorders of broilers exposed to HS. In conclusion, dietary supplementation of four Se sources (0.3 mg/kg) exhibited similar protective effects on HS-induced hepatic lipid metabolism disorders of broilers, and the protective effect is connected to the relieving of ER stress.

Dietary Betaine improves the intestinal health and growth performance of heat-stressed growing rabbits in summer.

The main objective of this study is to explore how various amounts of Bet affect growth performance, nutritional digestibility, and intestinal health of growing rabbits under high-temperature environment in summer. A total of 150 healthy 35-d-old weaned QiXing meat rabbits (Germany White rabbit × Sichuan White rabbit) were individually assigned to five treatments, each with 30 replicates and one rabbit per replicate. The control group was fed with basal diet, while the experimental group received a basal diet supplemented with 0.75, 1.0, 1.5, and 2.0 g Bet/kg diet, respectively. During the whole experimental stage, all animals can eat and drink freely, and they were kept in the rabbit house with an average daily temperature of 30.11 ±â€…0.5 ℃ and a relative humidity of 71.02 ±â€…5.07%. The results showed that dietary supplementation with 1.5 g/kg Bet increased average daily gain and decreased feed to gain ratio from days 1 to 42 as compared to the control group (P < 0.05), adding 0.75, 1.0, 1.5, and 2.0 g/kg Bet increased average daily gain and average daily feed intake from days 22 to 42 (P < 0.05), and increased the nutritional digestibility of acid detergent fiber (P < 0.05). Furthermore, dietary supplementation with 1.0, 1.5, and 2.0 g/kg Bet reduced d-lactate content and diamine oxidase activity in the serum (P < 0.05). Compared to the control group, supplementation of 0.75 and 1.5 g/kg Bet improved glutathione peroxidase activities in the duodenum and ileum, adding 0.75, 1.0, 1.5, and 2.0 g/kg Bet decreased malonaldehyde content in the duodenum and jejunum (P < 0.05). Moreover, the supplement of 1.5 and 2.0 g/kg Bet upregulated JAM-2 and IL-10 levels in the jejunum (P < 0.05). In conclusion, supplementation with Bet in the diet improves the growth performance, nutrient digestibility, and intestinal health of growing rabbits under high-temperature environments, and the 1.5 g Bet/kg diet group has the best effect.

Due to the lack of functional sweat glands, rabbits find it difficult to release excess heat under high-temperature conditions, resulting in heat stress. This high-level temperature condition leads to substantial damage to growth performance and intestinal health resulting in significant financial losses for the meat rabbit industry. This study found that adding betaine (Bet) to the diet can improve the growth performance and intestinal barrier integrity of heat-stressed growing rabbits, which may be related to improving intestinal antioxidant capacity and immune status. 1.5 g Bet/kg diet group showed better effects than 0, 0.75, 1.0, and 2.0 g Bet/kg diet groups in improving growth performance and intestinal health of heat-stressed growing rabbits.

Dietary Taurine Supplementation Improves the Meat Quality, Muscle Fiber Type, and Mitochondrial Function of Finishing Pigs.

This study investigated the effects of dietary supplementation with taurine (TAU) on the meat quality, muscle fiber type, and mitochondrial function of finishing pigs. The results demonstrated that TAU significantly increased the a* value while decreasing b*45 min, L*24 h, and drip loss24 h and drip loss48 h in the longissimus dorsi (LD) muscle. Dietary supplemented with TAU reduced the content of lactate and the glycolytic potential (GP) in the LD muscle. Dietary supplemented with TAU enhanced the oxidative fiber-related gene expression as well as increased succinic dehydrogenase and malate dehydrogenase activities while reducing lactate dehydrogenase activity. Furthermore, dietary supplementation with TAU increased the contents of mtDNA and ATP and mitochondrial function-related gene expression. Moreover, TAU enhanced the mRNA expressions of calcineurin (CaN) and nuclear factor of activated T cells c1 (NFATc1) and protein expressions of CNA and NFATc1. The results indicate that dietary TAU supplementation improves meat quality and mitochondrial biogenesis and function and promotes muscle fiber-type conversion from the glycolytic fiber to the oxidative fiber via the CaN/NFATc1 pathway.

Dietary lysolecithin supplementation improves growth performance of weaned piglets via improving nutrients absorption, lipid metabolism, and redox status.

Lysolecithin is widely used as emulsifier to improve the digestibility and retention of fat. The current study aimed to investigate the effects of dietary lysolecithin supplementation on growth performance, nutrients absorption, lipid metabolism, and redox status of weaned pigs. A total of 60 weaned piglets were assigned into 2 dietary treatments in a randomized complete block design, receiving basal diet with 0 or 1,000 mg/kg lysolecithin for a period of 28 d. Each dietary treatment had 10 replicates with 3 piglets per replicate. Growth performance and fecal score were monitored during trial. Samples of blood, ileum, and liver tissues were collected and analyzed for serology, intestinal histomorphology, and lipid metabolism-related gene and protein expressions. Dietary lysolecithin supplementation increased average daily gain (+15%, P < 0.05) and tended to increase average daily feed intake (+14%, P = 0.08) in overall experimental period. At final, the average body weight of piglets in lysolecithin group was 10% greater than that of control group (P = 0.09). In addition, dietary lysolecithin supplementation improved the ability of nutrients absorption as indicated by the higher d-xylose level in plasma (P < 0.05). Moreover, piglets from lysolecithin group had higher concentration of high-density lipoprotein (P < 0.05), but lower triglyceride (P < 0.05) in plasma. The inclusion of lysolecithin in diet increased the level of reduced glutathione (GSH) and GSH to oxidized glutathione (GSSG) ratio in plasma and liver (P < 0.05), but attenuated the levels of malondialdehyde and GSSG in ileum (P < 0.05). The upregulation of lipogenesis-related genes (FAS and ACC), downregulation of lipolysis (PNPLA2 and PABP1), and lipid mobilization (PGC-1α and SRIT1) genes were observed in lysolecithin relative to control piglets. Compared with control group, dietary lysolecithin supplementation upregulated protein expressions of GPX4, SREBP1, and LPL in liver and LPL in ileum (P < 0.05). Collectively, our study indicates that dietary lysolecithin supplementation improved growth performance of weaned piglets, which may be associated with the improved nutrients absorption, redox status, and lipid metabolism.

Early weaning has been widely adopted to maximize productivity for swine production. However, the weaned piglets suffer from insufficient energy intake due to the reduced feed intake caused by weaning stress, which compromises the growth rate of piglets. In the present study, dietary lysolecithin supplementation increased average daily gain and average daily feed intake in overall experimental period, thereby showed positive effect on final body weight of weaned piglets. In addition, lysolecithin supplementation improved adipogenesis and anti-oxidant capacity, but suppressed lipolysis and pro-oxidant factors.

Tryptophan alleviates lipopolysaccharide-induced liver injury and inflammation by modulating necroptosis and pyroptosis signaling pathways in piglets.

The liver plays crucial roles in material metabolism and immune response. Bacterial endotoxin can cause various liver diseases, thereby causing significant economic losses to pig industry. Tryptophan is an essential amino acid in piglets. However, whether tryptophan can alleviate liver injury and inflammation by regulating necroptosis and pyroptosis has not been clarified. This study aimed to investigate whether dietary tryptophan can alleviate lipopolysaccharide (LPS)-induced liver injury in weaned piglets. 18 weaned piglets were randomly distributed to three treatments, each with 6 replicates: (1) control; (2) LPS-challenged control; (3) LPS + 0.2% tryptophan. After feeding with control or 0.2% tryptophan-supplemented diets for 35 d, pigs were intraperitoneally injected with saline or LPS (100 mg/kg body weight). At 4 h post-injection, blood samples and liver were collected. Results indicated that tryptophan reduced alanine aminotransferase, aspartate aminotransferase, decreased the mRNA expression and protein expression of 70-kDa heat shock proteins. Moreover, tryptophan increased the mRNA expression and protein expression of claudin-1, occludin and zonula occludens and decreased hydrogen peroxide and malondialdehyde contents, and increased catalase, glutathione peroxidase and total superoxide dismutase activities and proinflammatory cytokine levels in the liver. Meanwhile, tryptophan inhibited pyroptosis-related and necroptosis-related protein expression in liver. Collectively, tryptophan could relieve liver damage, increased the antioxidant capacity and reduced inflammation by inhibiting pyroptosis and necroptosis signaling pathways.