Recent advances in the exploration and discovery of SARS-CoV-2 inhibitory peptides from edible animal proteins.

The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19), is spreading worldwide. Although the COVID-19 epidemic has passed its peak of transmission, the harm it has caused deserves our attention. Scientists are striving to develop medications that can effectively treat COVID-19 symptoms without causing any adverse reactions. SARS-CoV-2 inhibitory peptides derived from animal proteins have a wide range of functional activities in addition to safety. Identifying animal protein sources is crucial to obtaining SARS-CoV-2 inhibitory peptides from animal sources. This review aims to reveal the mechanisms of action of these peptides on SARS-CoV-2 and the possibility of animal proteins as a material source of SARS-CoV-2 inhibitory peptides. Also, it introduces the utilization of computer-aided design methods, phage display, and drug delivery strategies in the research on SARS-CoV-2 inhibitor peptides from animal proteins. In order to identify new antiviral peptides and boost their efficiency, we recommend investigating the interaction between SARS-CoV-2 inhibitory peptides from animal protein sources and non-structural proteins (Nsps) using a variety of technologies, including computer-aided drug approaches, phage display techniques, and drug delivery techniques. This article provides useful information for the development of novel anti-COVID-19 drugs.

Recent Progress on Green New Phase Extraction and Preparation of Polyphenols in Edible Oil.

With the proposal of replacing toxic solvents with non-toxic solvents in the concept of green chemistry, the development and utilization of new green extraction techniques have become a research hotspot. Phenolic compounds in edible oils have good antioxidant activity, but due to their low content and complex matrix, it is difficult to achieve a high extraction rate in a green and efficient way. This paper reviews the current research status of novel extraction materials in solid-phase extraction, including carbon nanotubes, graphene and metal-organic frameworks, as well as the application of green chemical materials in liquid-phase extraction, including deep eutectic solvents, ionic liquids, supercritical fluids and supramolecular solvents. The aim is to provide a more specific reference for realizing the green and efficient extraction of polyphenolic compounds from edible oils, as well as another possibility for the future research trend of green extraction technology.

Maternal nucleotide supplementation improves the intestinal morphology and immune function in lipopolysaccharide-challenged newborn piglets.

This study aimed to evaluate the effects of maternal nucleotide (NT) supplementation on intestinal morphology and immune function in lipopolysaccharide-challenged newborn piglets. At 85 d gestation, 12 sows were selected and assigned to two groups: the CON group (basal diet, n = 6) and the NT group (basal diet with 1 g/kg NT mixture, n = 6). After parturition, newborn piglets were collected without suckling. Piglets from the CON group were intraperitoneally injected with sterile saline or lipopolysaccharide (LPS, 10 mg/kg body weight), and divided into the C-CON (n = 6) and C-LPS groups (n = 6). Piglets from the NT group received the same treatment and were divided into the N-CON (n = 6) and N-LPS groups (n = 6). The blood and small intestinal samples of piglets were collected 1 h after injection. The results showed that: (1) maternal NT supplementation increased the concentrations of serum complement C3 and C4 (P < 0.05), and suppressed the increase in serum hypersensitive C-reactive protein in LPS-challenged newborn piglets (P < 0.05); (2) maternal NT supplementation increased the villus height and the ratio of villus height to crypt depth in the duodenum of newborn piglets (P < 0.05) and inhibited the LPS-induced decrease in the villus height in the jejunum and ileum (P < 0.05). (3) The LPS-induced increased levels of interleukin-6 in the jejunum and tumor necrosis factor-α in the ileum of newborn piglets were suppressed by maternal NT supplementation (P < 0.05). (4) In the jejunum of newborn piglets, maternal NT supplementation inhibited the LPS-induced increase in toll-like receptor 4 (TLR4) mRNA and protein expression (P < 0.05) and the decrease of nuclear factor-κB inhibitor α (IκBα) protein expression (P < 0.05). In the ileum, piglets had a lower nuclear factor-κB (NFκB) mRNA expression in the NT groups than the CON groups (P < 0.05), and maternal NT supplementation suppressed the decrease of IκBα mRNA in LPS-treated piglets (P < 0.05). In conclusion, maternal NT supplementation could promote the intestinal development and immune function of newborn piglets, and may improve LPS-induced intestinal inflammatory responses via the TLR4/IκBα/NFκB pathway.

Treatment of immune dysfunction in intrauterine growth restriction piglets via supplementation with dimethylglycine sodium salt during the suckling period.

This study aimed to investigate the mechanism of small intestinal immune dysfunction in intrauterine growth restriction (IUGR) newborn piglets and relieve this dysfunction via dimethylglycine sodium salt (DMG-Na) supplementation during the suckling period. Thirty sows (Duroc × [Landrace × Yorkshire]) were selected, and 1 male newborn piglet with normal birth weight (NBW) and 1 male newborn piglet with IUGR were obtained from each sow. Among them, 10 NBW and 10 IUGR newborns were euthanized without suckling. The other 20 NBW newborns were allocated to the group named NCON, which means NBW newborns fed a basic milk diet (BMD) (n = 10), and the group named ND, which means NBW newborns fed BMD supplemented with 0.1% DMG-Na (n = 10); the other 20 IUGR newborns were assigned to the group named ICON, which means IUGR newborns fed BMD (n = 10), and the group named ID, which means IUGR newborns fed BMD supplemented with 0.1% DMG-Na (n = 10). The newborns were fed BMD from 7 to 21 d of age and euthanized at 21 d of age to collect serum and small intestinal samples. The growth performance, small intestinal histological morphology and sub-organelle ultrastructure, serum immunoglobulin, small intestinal digestive enzyme activity, inflammatory cytokine level, and jejunum mRNA and protein expression of the toll-like receptor 4 (TLR4)/nucleotide-binding oligomerization domain protein (NOD)/nuclear factor-κB (NF-κB) network deteriorated in the ICON group compared to that in the NCON group. The small intestinal histological morphology and sub-organelle ultrastructure, serum immunoglobulin, small intestinal digestive enzyme activity, and inflammatory cytokine level improved (P < 0.05) in the ID group compared to those in the ICON group. The jejunum mRNA and protein expression of the TLR4/NOD/NF-κB network improved (P < 0.05) in the ID group compared to that in the ICON group. In conclusion, the activity of the TLR4/NOD/NF-κB pathway was inhibited in the IUGR newborns, which in turn led to their jejunum immune dysfunction and reduced their performance. By ingesting DMG-Na, the IUGR newborns activated the TLR4/NOD/NF-κB pathway, thereby improving their unfavorable body state during the suckling period.

Supplementation of Dimethylglycine Sodium Salt in Sow Milk Reverses Skeletal Muscle Redox Status Imbalance and Mitochondrial Dysfunction of Intrauterine Growth Restriction Newborns.

The current study sought to understand the mechanism underlying skeletal muscle dysfunction brought on by intrauterine growth restriction (IUGR) and to explore the treatment benefits of applying dimethylglycine sodium salt (DMG-Na) in sow milk to newborns during the suckling period. Each of the 10 sows delivered one newborn with a normal birth weight (NBW) and one with an IUGR. Additionally, two NBW and two IUGR newborns were collected per litter of another 10 sows. The 20 NBW newborns were divided between the N (sow milk) and ND (sow milk + 0.1% DMG-Na) groups, while 20 IUGR newborns were divided between the I (sow milk) and ID (sow milk + 0.1% DMG-Na) groups. The skeletal muscle histomorphology, redox status, and levels of gene and protein expression were worse (p < 0.05) in the I group than in the N group. In addition, supplementation with DMG-Na (ND and ID groups) improved (p < 0.05) those parameters compared to the unsupplemented groups (N and I groups). Inhibited nuclear factor erythroid 2-related factor 2 (Nrf2)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptorγcoactivator-1α (PGC-1α) activity resulted in decreased redox status, skeletal muscle structural damage, skeletal muscle mitochondrial function impairment, and decreased performance in IUGR newborns. Supplementation of DMG-Na in sow milk activated the Nrf2/SIRT1/PGC-1α in IUGR newborns, thereby improving their skeletal muscle performance.

Dietary dimethylglycine sodium salt supplementation alleviates redox status imbalance and intestinal dysfunction in weaned piglets with intrauterine growth restriction.

There are few studies on the mechanism of redox status imbalance and intestinal dysfunction in intrauterine growth restricted (IUGR) newborn piglets. Here, we investigated the mechanism of jejunum dysfunction in weaned piglets with IUGR and the mechanism through which dimethylglycine sodium salt (DMG-Na) supplementation improving the imbalance of their redox status. In this work, a total of 10 normal birth weight (NBW) newborn piglets and 20 IUGR newborn piglets were obtained. After weaning at 21 d, they were assigned to 3 groups (n = 10/group): NBW weaned piglets fed standard basal diets (NBWC); one IUGR weaned piglets fed standard basal diets (IUGRC); another IUGR weaned piglets from the same litter fed standard basal diets plus 0.1% DMG-Na (IUGRD). The piglets in these 3 groups were sacrificed at 49 d of age, and the blood and jejunum samples were collected immediately. The growth performance values in the IUGRC group were lower (P < 0.05) than those in the NBWC group. Jejunum histomorphological parameters, inflammatory cytokines, and digestive enzyme activity as well as serum immunoglobulin were lower (P < 0.05) in the IUGRC group than those in the NBWC group. Compared with these in the NBWC group, the redox status of serum, jejunum, and mitochondria and the expression levels of jejunum redox status-related, cell adhesion-related, and mitochondrial function-related genes and proteins were suppressed in the IUGRC group (P < 0.05). However, compared with those in the IUGRC group, the growth performance values, jejunum histomorphological parameters, inflammatory cytokines, digestive enzyme activity, serum immunoglobulin, redox status of serum, jejunum, and mitochondria, and the expression levels of jejunum redox status-related, cell adhesion-related, and mitochondrial function-related genes and proteins were improved (P < 0.05) in the IUGRD group. In conclusion, dietary DMG-Na supplementation alleviates redox status imbalance and intestinal dysfunction in IUGR weaned piglets mainly by activating the sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptorγcoactivator-1α (PGC1α) pathway, thereby improving their unfavorable body state.

Dimethylglycine Sodium Salt Alleviates Intrauterine Growth Restriction-Induced Low Growth Performance, Redox Status Imbalance, and Hepatic Mitochondrial Dysfunction in Suckling Piglets.

This study aimed to investigate the mechanism of redox status imbalance and hepatic mitochondrial dysfunction induced by intrauterine growth restriction (IUGR) and relieve this condition through dimethylglycine sodium salt (DMG-Na) supplementation during the suckling period. Thirty normal birth weight (NBW) and 30 IUGR newborns were selected from 20 sows. Briefly, 1 NBW and 1 IUGR newborn were obtained from each litter of 10 sows, and 10 NBW and 10 IUGR newborns were obtained. Additionally, 2 NBW and 2 IUGR newborns were obtained from each litter of another 10 sows, and 20 NBW newborns were allocated to the N [basic milk diets (BMDs)] and ND (BMDs+0.1% DMG-Na) groups. Furthermore, 20 IUGR newborns were assigned to the I (BMDs) and ID (BMDs+0.1% DMG-Na) groups. The results revealed that the growth performance, serum and hepatic redox status, and hepatic gene and protein expression levels were lower (P < 0.05) in the I group compared to the N group. Additionally, supplementation with DMG-Na (ND and ID groups) improved (P < 0.05) these parameters compared to the non-supplemented groups (N and I groups). In conclusion, the activity of Nrf2/SIRT1/PGC1α was inhibited in IUGR newborns, and this led to their hepatic dysfunctions. Supplementation with DMG-Na activated Nrf2/SIRT1/PGC1α in IUGR newborns, thereby improving their performance.

Dimethylglycine sodium salt activates Nrf2/SIRT1/PGC1α leading to the recovery of muscle stem cell dysfunction in newborns with intrauterine growth restriction.

The objectives of this study were focused on the mechanism of mitochondrial dysfunction in skeletal muscle stem cells (MuSCs) from intrauterine growth restriction (IUGR) newborn piglets, and the relief of dimethylglycine sodium salt (DMG-Na) on MuSCs mitochondrial dysfunction by Nrf2/SIRT1/PGC1α network. In this study, six newborn piglets with normal birth weight (NBW) and six IUGR newborn piglets were slaughtered immediately after birth to obtain longissimus dorsi muscle (LM) samples. MuSCs were collected and divided into three groups: MuSCs from NBW newborn piglets (N), MuSCs from IUGR newborn piglets (I), and MuSCs from IUGR newborn piglets with 32 µmol DMG-Na (ID). Compared with the NBW group, the IUGR group showed decreased (P < 0.05) serum and LM antioxidant defense capacity, and increased (P < 0.05) serum and LM damage. Compared with the N group, the I group showed decreased (P < 0.05) MuSCs antioxidant defense capacity, mitochondrial ETC complexes, energy metabolites, and antioxidant defense-related and mitochondrial function-related gene and protein expression levels. The antioxidant defense capacity, mitochondrial ETC complexes, energy metabolites, and antioxidant defense-related and mitochondrial function-related gene and protein expression levels of MuSCs were improved (P < 0.05) in the ID group compared to those in the I group. The MuSCs of IUGR newborns activate the Nrf2/SIRT1/PGC1α network by taking in DMG-Na, thereby neutralizing excessive generated O2•- that may help to improve their unfavorable mitochondrial dysfunction in skeletal muscle.

"Drug-Carrier" Synergy Therapy for Amyloid-ß Clearance and Inhibition of Tau Phosphorylation via Biomimetic Lipid Nanocomposite Assembly.

Amyloid-ß (Aß) toxicity is considered to be companioned by Tau phosphorylation in Alzheimer's disease (AD). The clinical AD therapy is usually subjected to low blood-brain barrier (BBB) penetration and complex interaction mechanisms between Aß and phosphorylated Tau. A "Drug-Carrier" synergy therapy is herein designed to simultaneously target Aß and Tau-associated pathways for AD treatment. To imitate natural nanoparticle configuration, the endogenous apolipoprotein A-I and its mimicking peptide 4F fused angiopep-2 (Ang) are sequentially grafted onto lipid nanocomposite (APLN), providing liberty of BBB crossing and microglia targeted Aß clearance. For synergy treatment, methylene blue (MB) is further assembled into APLN (APLN/MB) for Tau aggregation inhibition. After intravenous administration, the optimized density (5 wt%) of Ang ligands dramatically enhances APLN/MB intracerebral shuttling and accumulation, which is 2.15-fold higher than that Ang absent-modification. The site-specific release of MB collaborates APLN to promote Aß capture for microglia endocytosis clearance and reduce p-Tau level by 25.31% in AD pathogenesis. In AD-Aß-Tau bearing mouse models, APLN/MB can relieve AD symptoms, rescue neuron viability and cognitive functions. Collectively, it is confirmed that "Drug-Carrier" synergy therapy of APLN/MB is a promising approach in the development of AD treatments.

Lipoprotein-Inspired Nanoscavenger for the Three-Pronged Modulation of Microglia-Derived Neuroinflammation in Alzheimer's Disease Therapy.

The inflammatory dysfunction of microglia from excess amyloid-ß peptide (Aß) disposal is an overlooked but pathogenic event in Alzheimer's disease (AD). Here, we exploit a native high-density lipoprotein (HDL)-inspired nanoscavenger (pHDL/Cur-siBACE1) that combines the trinity of phosphatidic acid-functionalized HDL (pHDL), curcumin (Cur), and ß-site APP cleavage enzyme 1 targeted siRNA (siBACE1) to modulate microglial dysfunction. By mimicking the natural lipoprotein transport route, pHDL can penetrate the blood-brain barrier and sequentially target Aß plaque, where Aß catabolism is accelerated without microglial dysfunction. The benefit results are from a three-pronged modulation strategy, including promoted Aß clearance with an antibody-like Aß binding affinity, normalized microglial dysfunction by blocking the NF-κB pathway, and reduced Aß production by gene silence (44%). After treatment, the memory deficit and neuroinflammation of APPswe/PSEN 1dE9 mice are reversed. Collectively, this study highlights the double-edged sword role of microglia and provides a promising tactic for modulating microglial dysfunction in AD treatment.

Preparation and activity evaluation of angiotensin-I converting enzyme inhibitory peptides from protein hydrolysate of mulberry leaf.

Angiotensin-I converting enzyme (ACE) inhibitory peptides drew wide attention in the food industry because of their natural reliability, non-toxicity, and safety. However, the characteristics of ACE inhibitory peptides obtained from protein hydrolysate of mulberry leaf prepared by Flavourzyme were still unclear. Based on the single-factor test, the Plackett-Burman test and response surface test were used to determine the key factors affecting the ACE inhibition rate in mulberry leaf protein hydrolysate and the optimum conditions of enzymatic hydrolysis. The results showed that the optimum technical parameters were as follows: the ratio of material to liquid is 1: 25 (w / v, g/mL), the Flavourzyme to substrate ratio was 3,000 U/g, the temperature of enzymatic hydrolysis was 50°C, pH was 6.3, and the time of enzymatic hydrolysis was 2.9 h. The ACE inhibitory peptides in the mulberry leaf protein hydrolysates were purified by ultrafiltration and gel filtration, aiming to obtain the highest active component. The 12 peptide sequences were identified by reverse liquid chromatography-mass spectrometry, and then, they were docked to the crystal structure of human angiotensin-I converting enzyme (1O8A), and the interaction mechanisms of 12 peptide sequences and 1O8A were analyzed. The docking results showed that among the 12 peptide sequences, ERFNVE (792.37 Da), TELVLK (351.72 Da), MELVLK (366.72 Da), and FDDKLD (376.67 Da), all had the lowest docking energy, and inhibition constant. The chemosynthetic ERFNVE (IC50: 2.65 mg/mL), TELVLK (IC50: 0.98 mg/mL), MELVLK (IC50:1.90 mg/mL) and FDDKLD (IC50:0.70 mg/mL) demonstrated high ACE-inhibitory activity with competitive inhibition mode. These results indicated that the ACE-inhibiting peptides from mulberry leaf protein hydrolyzed (FHMP) had the potential activities to inhibit ACE and could be used as functional food or drugs to inhibit ACE. This work provides positive support for mining the biological activity of mulberry leaves in the treatment of hypertension.

Dietary dimethylglycine sodium salt supplementation improves growth performance, redox status, and skeletal muscle function of intrauterine growth-restricted weaned piglets.

Few studies have focused on the role of dimethylglycine sodium (DMG-Na) salt in protecting the redox status of skeletal muscle, although it is reported to be beneficial in animal husbandry. This study investigated the beneficial effects of DMG-Na salt on the growth performance, longissimus dorsi muscle (LM) redox status, and mitochondrial function in weaning piglets that were intrauterine growth restricted (IUGR). Ten normal birth weight (NBW) newborn piglets (1.53 ± 0.04 kg) and 20 IUGR newborn piglets (0.76 ± 0.06 kg) from 10 sows were obtained. All piglets were weaned at 21 d of age and allocated to the three groups with 10 replicates per group: NBW weaned piglets fed a common basal diet (N); IUGR weaned piglets fed a common basal diet (I); IUGR weaned piglets fed a common basal diet supplemented with 0.1% DMG-Na (ID). They were slaughtered at 49 d of age to collect the serum and LM samples. Compared with the N group, the growth performance, LM structure, serum, and, within the LM, mitochondrial redox status, mitochondrial respiratory chain complex activity, energy metabolites, redox status-related, cell adhesion-related, and mitochondrial function-related gene expression, and protein expression deteriorated in group I (P < 0.05). The ID group showed improved growth performance, LM structure, serum, and, within the LM, mitochondrial redox status, mitochondrial respiratory chain complex activity, energy metabolites, redox status-related, cell adhesion-related, and mitochondrial function-related gene expression, and protein expression compared with those in the I group (P < 0.05). The above results indicated that the DMG-Na salt treatment could improve the LM redox status and mitochondrial function in IUGR weaned piglets via the nuclear factor erythroid 2-related factor 2/sirtuin 1/peroxisome proliferator-activated receptorγcoactivator-1α network, thus improving their growth performance.

Dimethylglycine sodium salt protects against oxidative damage and mitochondrial dysfunction in the small intestines of mice.

Few studies have investigated the use of dimethylglycine sodium salt (DMG­Na) to protect against small intestinal damage, despite its prevalence in the treatment of human diseases. The present study aimed to evaluate the protective effects of DMG­Na against oxidative damage and mitochondrial dysfunction in the small intestines of mice. A total of 100 male Kunming mice were randomly assigned to five groups (n=20 per group): i) Mice gastric intubation with 0.3 ml sterile saline solution (once), then subcutaneously injected with sterile saline solution (0.5 ml) after 1 h (CON); ii) mice gastric intubation with 12 mg DMG­Na/0.3 ml of sterile saline solution once, then subcutaneously injected with sterile saline solution (0.5 ml) 1 h later (D); iii) mice gastric intubation with 0.3 ml sterile saline solution once, then subcutaneously injected with indomethacin (10 mg/kg BW) 1 h later (IN); iv) mice gastric intubation with 12 mg DMG­Na/0.3 ml sterile saline solution once, then subcutaneously injected with indomethacin (10 mg/kg BW) 1 h later (DIN); and v) mice subcutaneously injected with indomethacin (10 mg/kg BW), then gastrically intubated with 12 mg DMG­Na/0.3 ml sterile saline solution once after 1 h (IND). The present study was evaluated the effects of DMG­Na on mice intestinal damage induced by indomethacin injection. The histological morphology of the small intestine improved (P<0.05) in the DIN and IND groups, compared with the IN group. The antioxidant system was enhanced, oxidative damage was reduced, and the expression of antioxidant­associated genes was increased in the small intestine and its mitochondria in the DIN and IND groups, compared with the IN group. The above results suggested that pretreatment and treatment with DMG­Na reduced oxidative damage by enhancing antioxidant capacity, increasing the expression of antioxidant­associated genes, ameliorating mitochondrial dysfunction and suppressing apoptosis. Further study is required to determine the specific mechanism by which pretreatment and treatment with DMG­Na reduced small intestinal damage.

In vitro free radical scavenging capacity of dimethylglycine sodium salt and its protective ability against oleic acid hydroperoxide-induced oxidative damage in IPEC-J2 cells.

The aim of the present study was to evaluate the in vitro free radical scavenging capacity of dimethylglycine sodium (DMG­Na) and its protective ability against oleic acid hydroperoxide (OAHPx)­induced oxidative damage in IPEC­J2 cells. Initially, the free radical scavenging activities of water­soluble pigments (DMG­Na, betalain, capsanthin and cyanidin­3­rutinoside) were measured and compared with those of Trolox. Subsequently, freshly collected swine blood was mixed with heparin and centrifuged to obtain erythrocytes. In order to induce the free radical chain oxidation in erythrocytes, the aqueous peroxyl radicals were generated by thermal decomposition of 2,2'­azobis(2­amidinopropane) dihydrochloride (AAPH) in oxygen. A 2% suspension of porcine erythrocytes in PBS buffer were pre­incubated for 30 min at 37˚C with DMG­Na (32 µM), followed by incubation with or without AAPH (75 mM) for 5 h with gentle shaking. Additionally, IPEC­J2 cells were randomly assigned to four groups (n=6 per group): Cells treated with phosphate buffered saline (PBS); cells treated with DMG­Na (32 µM); cells treated with oleic acid hydroperoxides (OAHPx, 20 µM; TO group); cells treated with DMG­Na (32 µM) followed by OAHPx (20 µM; DTO group). The cells were cultured in Dulbecco's modified Eagle's medium, Ham's F­12 mixture, 1.5 mM HEPES, 5% (v/v) fetal bovine serum, 1% (v/v) insulin­transferrin­selenium mixture, 1% (v/v) penicillin­streptomycin mixture and 2.5 µg/ml fungizone (37˚C, 5% CO2). The results showed that DMG­Na exerted the strongest free radical scavenging capacity at 0.32 M from 0.08­0.64 M, and that it could prevent AAPH­induced porcine erythrocyte hemolysis by increasing its antioxidant capacity (P<0.05). The results also demonstrated that antioxidant capacity and antioxidant­associated gene expression increased in the DTO group relative to the TO group (P<0.05), indicating that DMG­Na prevented the OAHPx­induced oxidative damage in IPEC­J2 cells by improving the antioxidant capacity and antioxidant­associated gene expression.

Dietary curcumin supplementation attenuates inflammation, hepatic injury and oxidative damage in a rat model of intra-uterine growth retardation.

Rats with a normal birth weight (NBW) or intra-uterine growth retardation (IUGR) were fed basic diets (NBW and IUGR groups) or basic diets supplemented with curcumin (NC and IC groups) from 6 to 12 weeks. The body weight of IUGR rats was lower (P<0·05) than that of the controls. Rats with IUGR showed higher (P<0·05) concentrations of TNF-α, IL-1ß and IL-6; higher (P<0·05) activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in their serum; and increased (P<0·05) concentrations of malondialdehyde (MDA), protein carbonyl (PC) and 8-hydroxy-2'-deoxyguanosine (8-OHDG) in the liver compared with the NBW rats. The livers of IUGR rats exhibited a lower (P<0·05) superoxide dismutase activity and decreased (P<0·05) metabolic efficiency of the hepatic glutathione redox cycle compared with those of the NBW rats. In response to dietary curcumin supplementation, concentrations of inflammatory cytokines and activities of AST and ALT in the serum and MDA, PC and 8-OHDG in the liver were lower (P<0·05), and the hepatic glutathione redox cycle in the liver was improved (P<0·05) in the IC group than in the IUGR group. These results were associated with lower (P<0·05) phosphorylated levels of the NF-κB pathway and Janus kinase 2 (JAK2) and higher (P<0·05) mRNA expression of genes involved in the nuclear factor, erythroid 2-like 2 (Nfe2l2)/antioxidant response element (ARE) pathway in the liver of the IC rats than that of the IUGR rats. Maternal undernutrition decreased birth weight and led to inflammation, oxidative damage and injury in rats. Curcumin appeared to be beneficial in preventing IUGR-induced inflammation, oxidative damage and injury by activating the expression of the NF-κB, JAK/STAT and Nfe2l2/ARE pathways in the liver.

Effects of dimethylglycine sodium salt supplementation on growth performance, hepatic antioxidant capacity, and mitochondria-related gene expression in weanling piglets born with low birth weight1.

Dimethylglycine sodium salt (DMG-Na) has exhibited excellent advantages in animal experiments and human health. The present study aimed to investigate the effects of dietary supplementation with 0.1% DMG-Na on the growth performance, hepatic antioxidant capacity, and mRNA expression of mitochondria-related genes in low birth weight (LBW) piglets during weaning period. Sixteen piglets with normal birth weight (NBW) and 16 LBW piglets were fed either a basal diet or a 0.1% DMG-Na supplemented diet from age of 21 to 49 d. Blood and liver samples were collected at the end of the study. The results showed that compared with NBW piglets, LBW piglets exhibited greater (P < 0.05) alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase activities in the serum. LBW decreased (P < 0.05) the activity of glutathione peroxidase and increased (P < 0.05) the contents of malondialdehyde and H2O2 in liver. DMG-Na supplementation increased (P < 0.05) body weight gain, feed intake, and feed efficiency, decreased (P < 0.05) ALT and AST activities, and reduced the content of H2O2 in LBW piglets. LBW piglets had downregulated (P < 0.05) mRNA expression of thioredoxin 2, thioredoxin reductases 2, and nuclear respiratory factor-1 (Nrf1) in the liver. However, DMG-Na supplementation increased (P < 0.05) mRNA expression of Nrf1 in the liver. In conclusion, DMG-Na supplementation has beneficial effects in alleviating LBW-induced hepatic oxidative damage and changed mitochondrial genes expression levels, which is associated with increased antioxidant enzyme activities and up-regulating mRNA gene abundance.

Dietary effects of Bacillus subtilis fmbj on growth performance, small intestinal morphology, and its antioxidant capacity of broilers.

This paper aimed to study the dietary effects of Bacillus subtilis fmbj (BS fmbj) on growth performance, small intestinal histomorphology, and its antioxidant capacity of broilers at 21 d of raising. A total of 300 1-d old male Arbor Acres broilers were randomly assigned to 5 groups: broilers fed the basal diets with 0 g/kg BS fmbj (CON), 0.2 g/kg BS fmbj (BS-1), 0.3 g/kg BS fmbj (BS-2), 0.4 g/kg BS fmbj (BS-3), and 0.5 g/kg BS fmbj (BS-4). The results showed that there were no differences in the growth performance among treatments during the trail. Dietary BS fmbj in broiler diets increased (P < 0.05) the serum immunoglobulin A (IgA) and immunoglobulin G (IgG) concentration, and enhanced the secretory immunoglobulin A (sIgA) level of small intestine (jejunum and ileum) compared with those in the CON group. The BS groups could improve (P < 0.05) the values of villus length, villus width, crypt depth, and villus area of small intestine compared with that in the CON group. Compared with the CON group, the BS group increased (P < 0.05) small intestinal antioxidant capacity and its mitochondrial antioxidant capacity, and also improved the antioxidant related-gene expression. The BS group exerted a lower (P < 0.05) level of oxidative damages in small intestine than that of the CON group. In conclusion, dietary BS fmbj in broiler diets was potential to improve the small intestinal histomorphology, small intestinal antioxidant capacity, and its mitochondrial antioxidant capacity. Thus this BS fmbj might be considered to be an important additive for the poultry industry.

Dietary effects of Bacillus subtilis fmbj on the antioxidant capacity of broilers at an early age.

This study was designed to evaluate the usage of Bacillus subtilis fmbj (BS fmbj) in broiler diets, and its effects on the antioxidant capacity of broilers at an early age. A total of 240 day-old male Arbor Acres (AA) broilers were randomly assigned to 4 groups, namely the control (CON) group (fed basal diets with 0 cfu/kg BS fmbj), the BS-1 group (fed basal diet with 0.2 × 1011 cfu/kg BS fmbj), BS-2 group (fed basal diet with 0.3 × 1011 cfu/kg BS fmbj), and BS-3 group (fed basal diet with 0.4 × 1011 cfu/kg BS fmbj). No differences were found in the average daily gain (ADG), average daily feed intake (ADFI), and feed conversion ratio (FCR) among the different treatments at 21 d. The BS groups showed lower (P < 0.05) levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) than that in the CON group at 21 d of growth. The dietary BS fmbj increased (P < 0.05) the antioxidant activity in the serum, liver, and hepatic mitochondria, but decreased (P < 0.05) the serum and hepatic malondialdehyde (MDA) levels compared to those in the CON group at 21 d of feeding. The BS groups showed lower (P < 0.05) level of hepatic mitochondrial reactive oxygen species (ROS), protein carbonyls (PC), and 8-hydroxy-2-deoxyguanosine (8-OHdG); however, in this group, higher (P < 0.05) levels of mitochondrial membrane potential (MMP), adenosine triphosphate (ATP), and mitochondria DNA (mtDNA) were determined compared to those in the birds of the CON group at 21 d. The BS group showed increased (P < 0.05) levels of antioxidant related-gene expression in the liver and hepatic mitochondria compared to that in the CON group. In conclusion, BS fmbj (0.3 g/kg in broiler diets) has the potential to improve the antioxidant status of the body as well as the hepatic mitochondrial function and thus, appears to be an important additive for both the consumer and the industry.

Dietary enzymatically treated Artemisia annua L. supplementation alleviates liver oxidative injury of broilers reared under high ambient temperature.

Heat stress induced by high ambient temperature is a major concern in commercial broiler production. To evaluate the effects of dietary enzymatically treated Artemisia annua L. (EA) supplementation on growth performance and liver oxidative injury of broilers reared under heat stress, a total of 320 22-day-old male broilers were randomly allotted into five groups with eight replicates of eight birds each. Broilers in the control group were housed at 22 ± 1 °C and fed the basal diet. Broilers in the HS, HS-EA1, HS-EA2, and HS-EA3 groups were fed basal diet supplemented with 0, 0.75, 1.00, and 1.25 g/kg EA, respectively, and reared under cyclic high temperature (34 ± 1 °C for 8 h/day and 22 ± 1 °C for 16 h/day). Broilers fed EA diets had higher final body weight, average daily body weight gain, and average daily feed intake, as well as liver concentration of reduced glutathione, activities of antioxidant enzymes, abilities to inhibit hydroxyl radical and superoxide radical (HS-EA2 and HS-EA3), and lower liver concentrations of reactive oxygen metabolites, malondialdehyde, and protein carbonyl (HS-EA1, HS-EA2, and HS-EA3) than HS group (P < 0.05). EA treatment downregulated the mRNA levels of heat shock proteins 70 and 90, upregulated the mRNA levels of nuclear factor erythroid 2-related factor 2 (HS-EA1, HS-EA2, and HS-EA3) and heme oxygenase 1 (HS-EA2 and HS-EA3) in liver of heat-treated broilers (P < 0.05). In conclusion, EA alleviated heat stress-induced growth depression and liver oxidative injury in broilers, possibly through improving the antioxidant capacity and regulating the pertinent mRNA expression. The appropriate inclusion level of EA in broiler diet is 1.00-1.25 g/kg.

Protective effects of leucine on redox status and mitochondrial-related gene abundance in the jejunum of intrauterine growth-retarded piglets during early weaning period.

The aim of this study was to investigate the effects of dietary supplementation with 0.35% l-leucine on redox status and gene abundance relating to mitochondrial biogenesis and function in the jejunum of intrauterine growth-retarded (IUGR) piglets during early weaning period. According to a 2 × 2 factorial arrangement, 16 IUGR and 16 normal body weight (NBW) piglets were fed a basal diet without l-leucine supplementation or a basal diet plus 0.35% l-leucine supplementation from the age of 14 to 35 d. The results showed that compared with NBW piglets, IUGR piglets had a lower (p < 0.05) jejunal DNA concentration, a reduced (p < 0.05) manganese superoxide dismutase (MnSOD) and total antioxidant capability (T-AOC) activities and mitochondrial DNA content in the jejunum. Leucine supplementation increased (p < 0.05) MnSOD and T-AOC activities and decreased (p < 0.05) the malondialdehyde content in the jejunum of IUGR piglets. The mRNA gene abundance of nuclear respiratory factor-1 (NRF1), mitochondrial transcription factor A (TFAM), ATP synthase (ATPs), cytochrome c oxidase V (CcOX V), cytochrome c and glucokinase in the jejunum of IUGR piglets was reduced (p < 0.05) compared with NBW piglets. However, NRF1, peroxisome proliferation-activated receptor gamma coactivator-1 alpha, TFAM, ATPs and CcOX I mRNA gene abundance in the jejunum of IUGR piglets were increased (p < 0.05) by diets supplemented with leucine. These data indicate that leucine supplementation has therapeutic potential for attenuating intestinal oxidative stress and mitochondrial dysfunction in IUGR piglets during the early period of life via increasing enzyme activities and up-regulating mRNA gene abundance.