Efficacy of a novel multi-enzyme feed additive on growth performance, nutrient digestibility, and gut microbiome of weanling pigs fed corn-wheat or wheat-barley-based diet.

One-hundred-and-ninety-two weanling pigs (6.7 kg body weight) were used to evaluate the impact of a carbohydrases-protease enzyme complex (CPEC) on growth performance, nutrient digestibility, and gut microbiome. Pigs were assigned to one of the four dietary treatments for 42 d according to a 2 × 2 factorial arrangement of diet type (low fiber [LF] or high fiber [HF]) and CPEC supplementation (0 or 170 mg/kg diet). The LF diet was prepared as corn-wheat-based diet while the HF diet was wheat-barley-based and contained wheat middlings and canola meal. Each dietary treatment consisted of 12 replicate pens (six replicates per gender) and four pigs per replicate pen. Over the 42-d period, there was no interaction between diet type and CPEC supplementation on growth performance indices of pigs. Dietary addition of CPEC improved (P < 0.05) the body weight of pigs at days 28 and 42 and the gain-to-feed ratio of pigs from days 0 to 14. During the entire experimental period, dietary CPEC supplementation improved (P < 0.05) the average daily gain and gain-to-feed ratio of pigs. There were interactions between diet type and CPEC supplementation on apparent total tract digestibility (ATTD) of dry matter (DM; P < 0.01), gross energy (GE; P < 0.01), and neutral detergent fiber (NDF; P < 0.05) at d 42. Dietary CPEC addition improved (P < 0.05) ATTD of DM, GE, and NDF in the HF diets. At day 43, dietary CPEC addition resulted in improved (P < 0.05) apparent ileal digestibility (AID) of NDF and interactions (P < 0.05) between diet type and CPEC supplementation on AID of DM and crude fiber. Alpha diversity indices including phylogenetic diversity and observed amplicon sequence variants of fecal microbiome increased (P < 0.05) by the addition of CPEC to the HF diets on day 42. An interaction (P < 0.05) between diet type and CPEC addition on Bray-Curtis dissimilarity index and Unweighted UniFrac distances was observed on day 42. In conclusion, CPEC improved weanling pig performance and feed efficiency, especially in wheat-barley diets, while dietary fiber composition had a more significant impact on fecal microbial communities than CPEC administration. The results of this study underscores carbohydrase's potential to boost pig performance without major microbiome changes.

There is a pressing need to enhance livestock production efficiency to meet the growing global demand for meat. Carbohydrases and proteases are enzymes typically added to swine diets to improve nutrient utilization, leading to better growth rates and feed efficiency. This ultimately contributes to sustainable and economically viable pig farming. However, more research is required to better understand how carbohydrases and proteases interact with different diet types to optimize dietary formulations, and how this may influence gut microbiome composition. In this study, 192 weaner pigs (~7 kg) were assigned to a low-fiber diet or a high-fiber diet. Each diet type was with or without a carbohydrases and protease multi-enzyme supplementation. The results showed that adding a multi-enzyme combination to the pigs' diet significantly improved the pig's performance, regardless of diet type. Improvement in nutrient digestibility was more pronounced in pigs fed the high-fiber diet and that dietary fiber had a greater influence on the composition of fecal microbes. In essence, the study demonstrates that the multi-enzyme can boost pig growth and feed efficiency in diets with varying fiber complexity without causing significant changes in their gut microbiome.

TRPM7 Mediates Neuropathic Pain by Activating mTOR Signaling in Astrocytes after Spinal Cord Injury in Rats.

In this study, we investigated whether transient receptor melastatin 7 (TRPM7), known as a non-selective cation channel, inhibits neuropathic pain after spinal cord injury (SCI) and how TRPM7 regulates neuropathic pain. Neuropathic pain was developed 4 weeks after moderate contusive SCI and TRPM7 was markedly upregulated in astrocytes in the lamina I and II of L4-L5 dorsal horn. In addition, both mechanical allodynia and thermal hyperalgesia were significantly alleviated by a TRPM7 inhibitor, carvacrol. In particular, carvacrol treatment inhibited mechanistic target of rapamycin (mTOR) signaling, which was activated in astrocytes. When rats were treated with rapamycin, an inhibitor of mTOR signaling, neuropathic pain was significantly inhibited. Furthermore, blocking TRPM7 and mTOR signaling by carvacrol and rapamycin inhibited astrocyte activation in lamina I and II of dorsal spinal cord and reduced the level of p-JNK and p-c-Jun, which are known to be activated in astrocytes. Finally, inhibiting TRPM7/mTOR signaling also downregulated the production of pain-related factors such as tumor necrosis factor-α, interleukin-6, interleukin-1ß, chemokine (C-C motif) ligand (CCL) 2, CCL-3, CCL-4, CCL-20, chemokine C-X-C motif ligand 1, and matrix metalloproteinase 9 which are known to be involved in the induction and/or maintenance of neuropathic pain after SCI. These results suggest an important role of TRPM7-mediated mTOR signaling in astrocyte activation and thereby induction and/or maintenance of neuropathic pain after SCI.

Autoclaving time-related reduction in amino acid digestibility of poultry meal in broiler chickens and growing pigs.

Poultry meal, a rendered byproduct of poultry slaughter, is a valuable protein source in swine and poultry diets because of its highly digestible protein content and balanced amino acid (AA) profile. Rendering of poultry meal may reduce its AA digestibility because of heat damage to the byproduct. The effect of heat damage on AA digestibility of poultry meal may be different between broiler chickens and growing pigs. For this reason, the objective of this study was to determine the effect of autoclaving time on standardized ileal digestibility (SID) of AA in poultry meal fed to broiler chickens and growing pigs. Poultry meal from the same batch was autoclaved at 134 °C for 0, 30, 60, 90, 120, 150, or 180 min to produce seven heat-treated samples. Eight experimental diets were formulated. Poultry meal served as the sole source of nitrogen in seven diets that each contained one of the heat-treated byproducts and a nitrogen-free diet was formulated to assess basal ileal endogenous losses of AA. In experiment 1, 656 male broiler chickens (initial body weight = 719 ±â€…97 g) at day 18 post hatching were assigned to the eight diets in a randomized complete block design with body weight as a blocking factor. On day 23, birds were euthanized by CO2 asphyxiation and dissected for the collection of ileal digesta. In experiment 2, 16 barrows (initial body weight = 23.3 ±â€…0.7 kg) were surgically fitted with T-cannulas at the distal ileum and allotted to a duplicate 8 × 4 incomplete Latin square design with the eight diets and four periods. Each experimental period consisted of 5-day adaptation and 2-day ileal digesta collection periods. Data for experiments 1 and 2 were pooled and analyzed as a 2 × 7 factorial treatment arrangement with the effects of species (i.e., pigs and broiler chickens) and autoclaving time (i.e., 0 to 180 min) as the two factors. Increasing autoclaving time decreased SID of nitrogen and all AA in both species, but the decrease in SID values except for leucine was greater (interaction, P < 0.05) or tended to be greater in pigs compared with broiler chickens. Given the species differences in AA utilization response to the severity of heat damage, target species should be considered when using SID of AA values of poultry meal in diet formulation.

Poultry meal, a rendered byproduct of poultry slaughter, is a valuable protein source in swine and poultry diets. Rendering is required during the processing of poultry meal to inactivate potential harmful bacteria and to reduce moisture content in the raw byproduct. However, rendering can induce heat damage to poultry meal, which may reduce amino acid (AA) digestibility. To mimic heat damage to poultry meal, the byproduct was autoclaved at 134 °C for 0, 30, 60, 90, 120, 150, or 180 min in the current study. These seven heat-treated poultry meal samples were then fed to broiler chickens and growing pigs. AA digestibility in poultry meal decreased with increasing autoclaving time, but the decrease in digestibility of most AAs by autoclaving was larger in growing pigs compared with broiler chickens.

TRPM7 Mediates BSCB Disruption After Spinal Cord Injury by Regulating the mTOR/JMJD3 Axis in Rats.

After spinal cord injury (SCI), secondary injuries including blood cells infiltration followed by the production of inflammatory mediators are led by blood-spinal cord barrier (BSCB) breakdown. Therefore, preventing BSCB damage could alleviate the secondary injury progresses after SCI. Recently, we reported that transient receptor potential melastatin 7 channel (TRPM7) expression is increased in vascular endothelial cells after injury and thereby mediates BSCB disruption. However, the mechanism by which TRPM7 regulates BSCB disruption has not been examined yet. In current research, we show that TRPM7 mediates BSCB disruption via mammalian target of rapamycin (mTOR) pathway after SCI in rats. After contusion injury at T9 level of spinal cord, mTOR pathway was activated in the endothelial cells of blood vessels and TRPM7 was involved in the activation of mTOR pathway. BSCB disruption, MMP-2/9 activation, and blood cell infiltration after injury were alleviated by rapamycin, a mTOR signaling inhibitor. Rapamycin also conserved the level of tight junction proteins, which were decreased after SCI. Furthermore, mTOR pathway regulated the expression and activation of histone H3K27 demethylase JMJD3, known as a key epigenetic regulator mediating BSCB damage after SCI. In addition, rapamycin inhibited JMJD3 expression, the loss of tight junction molecules, and MMP-2/9 expression in bEnd.3, a brain endothelial cell line, after oxygen-glucose deprivation/reoxygenation. Thus, our results suggest that TRPM7 contributes to the BSCB disruption by regulating JMJD3 expression through the mTOR pathway after SCI.

IL-6/JAK2/STAT3 axis mediates neuropathic pain by regulating astrocyte and microglia activation after spinal cord injury.

After spinal cord injury (SCI), the control of activated glial cells such as microglia and astrocytes has emerged as a promising strategy for neuropathic pain management. However, signaling mechanism involved in glial activation in the process of neuropathic pain development and maintenance after SCI is not well elucidated. In this study, we investigated the potential role and mechanism of the JAK2/STAT3 pathway associated with glial cell activation in chronic neuropathic pain development and maintenance after SCI. One month after contusive SCI, the activation of JAK2/STAT3 pathway was markedly upregulated in both microglia and astrocyte in nociceptive processing regions of the lumbar spinal cord. In addition, both mechanical allodynia and thermal hyperalgesia was significantly inhibited by a JAK2 inhibitor, AG490. In particular, AG490 treatment inhibited both microglial and astrocyte activation in the lumbar (L) 4-5 dorsal horn and significantly decreased levels of p-p38MAPK, p-ERK and p-JNK, which are known to be activated in microglia (p-p38MAPK and p-ERK) and astrocyte (p-JNK). Experiments using primary cell cultures also revealed that the JAK2/STAT3 pathway promoted microglia and astrocyte activation after lipopolysaccharide stimulation. Furthermore, JAK2/STAT3 signaling and pain behaviors were significantly attenuated when the rats were treated with anti-IL-6 antibody. Finally, minocycline, a tetracycline antibiotic, inhibited IL-6/JAK2/STAT3 signaling pathway in activated glial cells and restored nociceptive thresholds and the hyperresponsiveness of dorsal neurons. These results suggest an important role of the IL-6/JAK2/STAT3 pathway in the activation of microglia and astrocytes and in the maintenance of chronic below-level pain after SCI.

Acute Distal Vertebral Artery Occlusion in Patients with Asymmetrical Vertebral Artery Geometry: Role of Black-Blood-Enhanced MR Imaging.

Background: The purpose of this study was to evaluate the diagnostic value of contrast enhancement in a unilateral distal vertebral artery (VA) using black blood (BB)-enhanced magnetic resonance (MR) imaging in patients with acute neurological symptoms and asymmetrical VA geometry. Methods: From January 2020 to August 2021, we retrospectively analyzed BB-contrast-enhanced MR imaging and MR angiography (MRA) findings in stroke patients visiting the emergency room for an evaluation of acute neurological symptoms. We classified four patterns according to asymmetrical VA geometry using MRA and contrast enhancement using BB-enhanced MR imaging: type 1 = enhanced VA + no visualization of VA, type 2 = enhanced VA + hypoplastic VA, type 3 = non-enhanced VA + hypoplastic VA, or type 4 = non-enhanced VA + no visualization of VA. Results: In total, 288 patients (type 1 = 65, type 2 = 17, type 3 = 130, type 4 = 76) were enrolled in this study. Of these patients, 82 (28.5%) showed contrast enhancement of a unilateral distal VA on BB-enhanced MR imaging, and 51 (17.8%) had positive findings on diffusion-weighted imaging (DWI) in the ipsilateral medulla, pons, or posterior inferior cerebellar artery (PICA) territory. The contrast enhancement of a unilateral distal VA using BB-enhanced MR imaging demonstrated a significantly higher prevalence in patients with acute infarction on DWI (50.0% vs. 4.9%, p < 0.001). Conclusions: The contrast enhancement of a unilateral distal VA on BB-enhanced MR imaging is associated with acute infarction of the medulla, pons, or PICA territory and suggests acute occlusion of a distal VA.

Suppression of Transient Receptor Potential Melastatin 7 by Carvacrol Protects against Injured Spinal Cord by Inhibiting Blood-Spinal Cord Barrier Disruption.

When the blood-spinal cord barrier (BSCB) is disrupted after a spinal cord injury (SCI), several pathophysiological cascades occur, including inflammation and apoptotic cell death of neurons and oligodendrocytes, resulting in permanent neurological deficits. Transient receptor potential melastatin 7 (TRPM7) is involved in the pathological processes in many neuronal diseases, including traumatic brain injury, amyotrophic lateral sclerosis, parkinsonism dementia, and Alzheimer's disease. Further, carvacrol (CAR), a TRPM7 inhibitor, is known to protect against SCI by reducing oxidative stress and inhibiting the endothelial nitric oxide synthase pathway. However, the functions of TRPM7 in the regulation of BSCB homeostasis after SCI have not been examined. Here, we demonstrated that TRPM7, a calcium-mediated non-selective divalent cation channel, plays a critical role after SCI in rats. Rats were contused at T9 and given CAR (50 mg/kg) intraperitoneally immediately and 12 h after SCI, and then given the same dose once a day for 7 days. TRPM7 was found to be up-regulated after SCI in both in vitro and in vivo studies, and it was expressed in blood vessels alongside neurons and oligodendrocytes. Additionally, CAR treatment suppressed BSCB disruption by inhibiting the loss of tight junction (TJ) proteins and preserved TJ integrity. CAR also reduced apoptotic cell death and improved functional recovery after SCI by preventing BSCB disruption caused by blood infiltration and inflammatory responses. Based on these findings, we propose that blocking the TRPM7 channel can inhibit the destruction of the BSCB and it is a potential target in therapeutic drug development for use in SCI.

Digestibility of amino acids in fish meal and blood-derived protein sources fed to pigs.

OBJECTIVE: An experiment was conducted to determine the standardized ileal digestibility (SID) of amino acids (AA) in fish meal (FM) and blood-derived protein sources including spray-dried porcine plasma (SDPP), porcine red blood cells (PRBC), and blood meal (BM) fed to growing pigs. METHODS: Ten barrows (mean initial body weight of 22.1±1.54 kg) surgically fitted with T-cannulas at the distal ileum were allotted to a duplicated 5×4 incomplete Latin square design with 5 experimental diets and 4 periods. Four experimental diets were prepared to contain FM, SDPP, PRBC, or BM as the sole source of nitrogen. A nitrogen-free diet was prepared and included to estimate the basal ileal endogenous losses of AA. For the 7-day experimental period, pigs were fed for 5 days as adaptation, and ileal digesta samples were collected for 9 hours on days 6 and 7. RESULTS: The SID of crude protein in BM (48.0%) was less (p<0.05) than in FM, SDPP, and PRBC (83.4%, 83.9%, and 87.3%, respectively). Pigs fed the diet containing BM had less (p<0.05) SID of AA, except isoleucine and proline, than those fed the diet containing FM, SDPP, or PRBC. Among FM, SDPP, and PRBC, there was no difference in the SID of crude protein and all AA, except isoleucine. The SID of isoleucine in PRBC and BM (62.7% and 48.3%, respectively) was less (p<0.05) than in FM and SDPP (88.0% and 84.9%, respectively). The SID of lysine in FM, SDPP, PRBC, and BM was 85.4%, 84.9%, 89.7%, and 51.9%, respectively. CONCLUSION: The SID of most AA was not different among FM, SDPP, and PRBC, but BM had lower SID of most AA than FM, SDPP, and PRBC.

Erratum: Lee et al. Ginseng Extracts, GS-KG9 and GS-E3D, Prevent Blood-Brain Barrier Disruption and Thereby Inhibit Apoptotic Cell Death of Hippocampal Neurons in Streptozotocin-Induced Diabetic Rats. Nutrients 2020, 12, 2383.

The authors have requested that the following changes be made to their paper [...].

Energy and phosphorus evaluation of poultry meal fed to broiler chickens using a regression method.

Two experiments were conducted to determine energy (Exp. 1) and P (Exp. 2) utilization in poultry meal (PM) for broiler chickens. A total of 192 birds were allotted to 3 experimental diets in a randomized complete block design with BW as a blocking factor on d 15 and 16 post hatching in Exp. 1 and 2, respectively. Each diet was fed to 8 replicate cages with 8 birds per cage in both experiments. Initial BW of birds in Exp. 1 and 2 were 438 ± 76.9 g and 543 ± 50.2 g, respectively. Three corn-soybean meal-based diets were prepared to contain 0, 80, or 160 g/kg in Exp. 1 and 0, 50, or 100 g/kg in Exp. 2. In Exp. 1, the addition of PM to the reference diet linearly decreased (P < 0.01) the apparent ileal digestibility of DM and gross energy (GE), as well as the apparent total tract utilization (ATTU) of DM, GE, and N in diets; but did not affect the ileal digestible energy, ME, and MEn of diets. The ileal digestible energy, ME, and MEn of PM estimated by the regression method were 4,002, 3,756, and 3,430 kcal/kg DM, respectively, representing 58 to 68% of the GE in PM. In Exp. 2, graded concentration of PM in the reference diet linearly decreased (P < 0.05) ATTU of DM but linearly increased (P < 0.01) ATTU of P and quadratically increased ATTU of Ca in diets. The true ileal digestibility and true total tract utilization of P in PM estimated by the regression method were 77.5 and 79.0%, respectively. In conclusion, these results showed that inclusion of poultry meal in the diets of broiler chickens reduced the digestibility of GE but increased the utilization of P. The regression-estimated energy values and P digestibility of PM in the current studies may be used in diet formulation.

Nutritional Potentials of Atypical Feed Ingredients for Broiler Chickens and Pigs.

Diets play an important part in monogastric nutrition. This is because diets are comprised of various feed ingredients that supply energy and nutrients required by broiler chickens or pigs for normal growth and development. The main feed ingredients used for formulating diets for pigs and chickens are comprised of cereals and oilseed meals. Corn and soybean meal (SBM) are mostly used in North America for animal feeds. However, due to geographical locations, availability, and cost, ingredients such as wheat, barley, and canola meal are often used for feeding pigs and chickens. Overdependence on common ingredients such as corn and SBM for decades has resulted in rising costs of animal production. Therefore, the need has risen to examine the potentials of alternative feed ingredients capable of supplying the required energy and nutrients for monogastric animals. Research has been carried out to identify and evaluate several uncommon feed ingredients and their utilization by broiler chickens and pigs. Thus, this review enumerates the nutritional potentials of feed ingredients in 4 main nutritional classes using information from articles in peer-reviewed journals. Feeding practices, advantages, and limitations of using certain uncommon feed ingredients are discussed. In addition, species-specific factors in terms of practical applications are explored.

Energy values of copra meal and cornstarch for broiler chickens.

Two studies were conducted with broiler chickens to determine the ileal digestible energy (IDE), ME, and MEn in copra meal (CM) and cornstarch using the regression method. On day 15 and 16 for experiments 1 and 2, respectively, 192 male birds were individually weighed and allotted into 3 dietary treatments with 8 replicate cages and 8 birds per cage in a randomized complete block design with the BW as a blocking factor in each experiment. Dietary treatments consisted of 3 inclusion levels of test ingredients (i.e., 0, 100, or 200 g/kg) in corn-soybean meal-based diets using CM or cornstarch as test ingredients for experiment 1 or 2, respectively. Titanium dioxide was added as an indigestible marker to determine the ileal digestibility and utilization of energy by the index method. Experiments lasted 5 d, and excreta collection was conducted during the last 3 d of each experiment. At the end of experiments, birds were euthanized by CO2 asphyxiation, and ileal digesta samples were collected. Data were analyzed by the ANOVA using the GLM procedure. In experiment 1, the apparent ileal digestibility (AID) of DM and gross energy (GE) and IDE in test diets linearly decreased (P < 0.05) with substitution of CM in test diets. In experiment 2, there were quadratic increases (P < 0.01) in the AID of DM and GE and IDE in diets as the concentration of cornstarch in test diets increased. In addition, linear increases (P < 0.05) in the apparent total tract utilization of DM, N, and GE and ME and MEn in test diets were observed. The estimates of IDE, ME, and MEn in CM were 2,493, 3,727, and 3,546 kcal/kg DM, respectively, whereas respective values of cornstarch were estimated at 4,181, 3,992, and 3,946 kcal/kg DM, respectively. In conclusion, inclusion of CM in diets may reduce the digestibility of GE, whereas the digestibility and utilization of GE may increase when adding cornstarch into diets for broiler chickens.

Digestible and metabolizable energy concentrations and amino acid digestibility of dried yeast and soybean meal for growing pigs.

Energy values and amino acid (AA) digestibility of dried yeast (DY) and soybean meal (SBM) were determined in 2 experiments with growing pigs. Experiment 1 was conducted to determine the digestible energy (DE) and metabolizable energy (ME) in DY and SBM. Thirty barrows with a mean initial body weight (BW) of 20.6 kg (SD = 1.04) were assigned to 5 dietary treatments in a randomized complete block design with period and BW as blocking factors. A reference diet was prepared with corn, canola meal, and soybean oil as energy-contributing ingredients. Four additional diets were prepared by adding 5% and 10% DY or SBM at the expense of energy-contributing ingredients in the reference diet. The ratio of corn, canola meal, and soybean oil was kept consistent across the experimental diets. Each experimental period consisted of 5-d adaptation and 5-d quantitative collection of feces and urine. Test ingredient-associated DE or ME intake (kcal/d) was regressed against test ingredient intake [kg dry matter (DM)/d] to estimate the DE or ME in test ingredients as the slope of linear regression model. The DE in DY was estimated at 3,933 kcal/kg DM, which was not different from the estimated DE in SBM at 4,020 kcal/kg DM. Similarly, there was no difference between DY and SBM in the estimated ME (3,431 and 3,756 kcal/kg DM, respectively). Experiment 2 was conducted to determine the standardized ileal digestibility (SID) of AA in DY and SBM. Twenty-one barrows with a mean initial BW of 20.0 kg (SD = 1.31) were surgically fitted with T-cannulas at the distal ileum and assigned to 3 dietary treatments in a randomized complete block design with BW as a blocking factor. Two semi-purified diets containing DY or SBM as the sole nitrogen source and one nitrogen-free diet (NFD) were prepared. The NFD was used to estimate the basal ileal endogenous losses of CP and AA. Pigs were fed the 3 diets for 5 d as adaptation, followed by 2 d of feeding with ileal digesta collection. The SID of AA, except Gly and Pro, in DY was less (P < 0.05) than in SBM. The SID of indispensable AA in DY ranged from 64.1% for Thr to 85.2% for Arg, and those in SBM ranged from 83.9% for Thr to 91.8% for Arg. In conclusion, energy values of DY are not different from those of SBM, whereas AA in DY is less digestible than in SBM. The estimated DE and ME as well as the SID of AA in DY and SBM can be used in diet formulation for growing pigs using these ingredients.

Total saponin extract, ginsenoside Rb1, and compound K alleviate peripheral and central neuropathic pain through estrogen receptors on rats.

In this study, we investigated whether total saponin extract (TSE), ginsenoside Rb1, and Rb1 metabolite compound K, which are isolated from red ginseng, have antinociceptive effects on peripheral and central neuropathic pain (PNP and CNP, respectively). PNP and CNP were induced by tail nerve injury (TNI) at S1 and by contusive spinal cord injury (SCI) at T9 in male Sprague-Dawley rats, respectively. Two weeks after TNI or 4 weeks after SCI, pain-induced rats were orally administered vehicle, TSE (50 mg/kg), Rb1 (12.5 mg/kg), compound K (7 mg/kg), or gabapentin (GBP, 60 mg/kg), and the antinociceptive effects were examined by von Frey filament, cold/warm water, and hot plate analyses. Allodynia and hyperalgesia were significantly alleviated by TSE, Rb1, and GBP 1 hr after drug administration. The immunohistochemistry and real-time RT-PCR results showed that the activation of microglia/astrocytes and the expression of inflammatory mediators such as Il-1ß, Il-6, iNOS, and Cox-2 were also significantly inhibited in L4-L5 spinal cord of CNP-induced rats 1 hr after drug administration. Furthermore, the antinociceptive effects of TSE and Rb1 were reversed by treatment with the estrogen receptor (ER) antagonist ICI182780. In particular, compound K also significantly alleviated both PNP and CNP. Therefore, our results indicate that TSE, Rb1, and compound K have potential antinociceptive effects against neuropathic pain that might be mediated through the ER.

Digestibility of Amino Acids in Protein-Rich Feed Ingredients Originating from Animals, Peanut Flour, and Full-Fat Soybeans Fed to Pigs.

Standardized ileal digestibility (SID) of amino acids (AA) in alternative protein sources for growing pigs was determined in this study. Diets containing egg albumen (EA), casein, blood meal (BM), and blood plasma meal (BPM) and a nitrogen-free diet (NFD) were fed to 20 barrows in a quadruplicate 5 × 2 incomplete Latin square design with two periods in experiment 1. The SID of AA was greater in casein than other ingredients (p < 0.05), except Pro. The SID of Arg, Ile, and Met was lower (p < 0.05) in EA than BM and BPM. The SID of Trp in BM was greater (p < 0.05) than EA but not different from BPM. In experiment 2, 20 pigs were fed diets containing peanut flour (PF) or full-fat soybeans (FFSB) or NFD in a randomized complete block design with body weight as a blocking factor but providing six observations for NFD. The SID of Arg, Ileu, Leu, Met, Phe, and Val was greater (p < 0.05) in PF than FFSB. The SID of Lys was greater (p < 0.05) in FFSB than PF. In summary, the test ingredients contain readily digestible AA and could serve as alternative protein sources for growing pigs.

Gallic acid attenuates blood-spinal cord barrier disruption by inhibiting Jmjd3 expression and activation after spinal cord injury.

After spinal cord injury (SCI), blood-spinal cord barrier (BSCB) disruption results in secondary injury including apoptotic cell death of neurons and oligodendrocytes, thereby leads to permanent neurological deficits. Recently, we reported that the histone H3K27me3 demethylase Jmjd3 plays a role in regulating BSCB integrity after SCI. Here, we investigated whether gallic acid (GA), a natural phenolic compound that is known to be anti-inflammatory, regulates Jmjd3 expression and activation, thereby attenuates BSCB disruption following the inflammatory response and improves functional recovery after SCI. Rats were contused at T9 and treated with GA (50 mg/kg) via intraperitoneal injection immediately, 6 h and 12 h after SCI, and further treated for 7 d with the same dose once a day. To elucidate the underlying mechanism, we evaluated Jmjd3 activity and expression, and assessed BSCB permeability by Evans blue assay after SCI. GA significantly inhibited Jmjd3 expression and activation after injury both in vitro and in vivo. GA also attenuated the expression and activation of matrix metalloprotease-9, which is well known to disrupt the BSCB after SCI. Consistent with these findings, GA attenuated BSCB disruption and reduced the infiltration of neutrophils and macrophages compared with the vehicle control. Finally, GA significantly alleviated apoptotic cell death of neurons and oligodendrocytes and improved behavior functions. Based on these data, we propose that GA can exert a neuroprotective effect by inhibiting Jmjd3 activity and expression followed the downregulation of matrix metalloprotease-9, eventually attenuating BSCB disruption after SCI.

Ginseng Extracts, GS-KG9 and GS-E3D, Prevent Blood-Brain Barrier Disruption and Thereby Inhibit Apoptotic Cell Death of Hippocampal Neurons in Streptozotocin-Induced Diabetic Rats.

Type 1 diabetes mellitus is known to be linked to the impairment of blood-brain barrier (BBB) integrity following neuronal cell death. Here, we investigated whether GS-KG9 and GS-E3D, bioactive ginseng extracts from Korean ginseng (Panax ginseng Meyer), inhibit BBB disruption following neuronal death in the hippocampus in streptozotocin-induced diabetic rats showing type 1-like diabetes mellitus. GS-KG9 and GS-E3D (50, 150, or 300 mg/kg, twice a day for 4 weeks) administered orally showed antihyperglycemic activity in a dose-dependent manner and significantly attenuated the increase in BBB permeability and loss of tight junction proteins. GS-KG9 and GS-E3D also inhibited the expression and activation of matrix metalloproteinase-9 and the infiltration of macrophages into the brain parenchyma, especially into the hippocampal region. In addition, microglia and astrocyte activation in the hippocampus and the expression of proinflammatory mediators such as tnf-α, Il-1ß, IL-6, cox-2, and inos were markedly alleviated in GS-KG9 and GS-E3D-treated group. Furthermore, apoptotic cell death of hippocampal neurons, especially in CA1 region, was significantly reduced in GS-KG9 and GS-E3D-treated groups as compared to vehicle control. These results suggest that GS-KG9 and GS-E3D effectively prevent apoptotic cell death of hippocampal neurons by inhibiting BBB disruption and may be a potential therapy for the treatment of diabetic patients.

Comparative amino acid digestibility between broiler chickens and pigs fed different poultry by-products and meat and bone meal.

The objective of this study was to compare the standardized ileal digestibility (SID) of amino acids (AA) in 3 poultry by-products including hydrolyzed feather meal (HFM), flash dried poultry protein (FDPP), and poultry meal (PM) and also a meat and bone meal (MBM) between broiler chickens and pigs. Experimental diets consisted of 4 diets containing each test ingredient as a sole source of nitrogen and a nitrogen-free diet. In experiment 1, 416 male broiler chickens with a mean initial body weight (BW) of 705 ± 100 g were allotted to 5 diets with 8 replicate cages per diet in a randomized complete block design with BW as a blocking factor at day 18 posthatching. After 5 d of feeding experimental diets, birds were euthanized by CO2 asphyxiation, and ileal digesta samples were collected from distal two-thirds of the ileum. In experiment 2, 10 barrows with a mean initial BW of 22.1 ± 1.59 kg were surgically fitted with T-cannulas at the distal ileum and allotted to a duplicate 5 × 4 incomplete Latin Square design with 5 diets and 4 periods. Each period lasted for 7 d including 5 d of adaptation and 2 d of ileal digesta collection. Data from experiments 1 and 2 were pooled together and analyzed as a 2 × 4 factorial arrangement with the effects of species (broiler chickens or pigs) and 4 experimental diets (HFM, FDPP, PM, or MBM). There were interactions (P < 0.05) between experimental diets and species in the SID of His, Lys, Thr, Trp, Val, and all dispensable AA except Tyr. In broiler chickens, the SID of Lys in FDPP (73.3%) was greater (P < 0.05) than in HFM (55.7%) but was lower (P < 0.05) than in MBM (86.5%), which was not different from PM (78.7%). In pigs, however, the SID of Lys in FDPP and PM (70.0 and 70.1%, respectively) were greater (P < 0.05) than in HFM (39.0%) but were lower (P < 0.05) than in MBM (79.2%). Broiler chickens fed FDPP and PM had lower (P < 0.05) SID of His, Thr, and Trp than those fed MBM; however, there was no difference in the SID of His, Thr, or Trp among pigs fed FDPP, PM, or MBM. The SID of Val in MBM was greater (P < 0.05) than in the other test ingredients for broiler chickens, but there was no difference in the SID of Val among test ingredients for pigs. Pigs had greater (P < 0.05) SID of Ile and Met than broiler chickens. In conclusion, the pattern of differences in the SID of His, Lys, Thr, Trp, and Val, but not the other indispensable AA, among poultry by-products and MBM were different between broiler chickens and pigs.

Inhibition of COX-2 alleviates lumbar spinal stenosis-induced chronic mechanical allodynia in rats.

Chronic low back pain due to lumbar spinal stenosis (LSS) is common, costly, mechanistically complex, and clinically challenging. However, the factors and mechanisms causing and mediating chronic pain induced by cauda equina compression remain unclear. Here, we examined the role of cyclooxygenase (COX)-2 in infiltrated macrophages, a key mediator of inflammation, in chronic neuropathic pain by LSS using an animal model. LSS was induced in adult male rats by cauda equina compression procedure using a silicone block within the epidural spaces of L5-L6 vertebrae. Locomotor deficit was observed after compression and mechanical allodynia was developed progressively for 4 weeks after injury. A number of macrophage were also infiltrated into the spinal parenchyma and cauda equina and COX-2 was expressed in infiltrated macrophages at 28 days after cauda equina compression. The administration of COX-2 inhibitors, celecoxib and MPO-0029, significantly alleviated LSS-induced chronic mechanical allodynia and inhibited the mRNA expression of inflammatory mediators such as tnf-α, Il-1ß, il-6, and inos. Furthermore, COX-2 inhibitors significantly reduced prostaglandin E2 production. These results demonstrated the role of COX-2 in LSS-induced chronic neuropathic pain and suggest that the regulation of COX-2 can be considered as a therapeutic target to relive neuropathic pain.

Amino acid digestibility in plant protein sources fed to growing pigs.

OBJECTIVE: The objective was to determine standardized ileal digestibility (SID) of amino acids (AA) in 11 plant protein sources fed to growing pigs. METHODS: Eleven feed ingredients used were sesame meal, two sources of soybean meal (SBM) produced in the Republic of Korea, a source of SBM produced in India, high-protein distillers dried grains (HPDDG), perilla meal, canola meal, copra meal, corn germ meal, palm kernel expeller, and tapioca distillers dried grains (TDDG). Experimental diets were prepared to contain each test ingredient as a sole source of AA, and a nitrogen-free diet was also prepared to estimate the basal ileal endogenous losses of AA. Twelve barrows surgically fitted with T-cannulas the distal ileum with an initial body weight of 29.0 kg (standard deviation = 3.0) were individually housed in metabolism crates equipped with a feeder and a nipple drinker. A 12 × 9 incomplete Latin square design was employed with 12 experimental diets, 12 animals, and 9 periods. After a 5-d adaptation period, ileal digesta were collected on d 6 and 7 in each experimental period. RESULTS: Values for apparent ileal digestibility of most indispensable AA in three sources of SBM were greater compared with other test ingredients except HPDDG and canola meal (p&lt;0.05). Pigs fed diets containing SBM sources had also greater SID of most indispensable AA compared with those fed diets containing other test ingredients (p&lt;0.05) except for HPDDG and canola meal. There was no difference in the apparent ileal digestibility and SID of AA among sources of SBM. The TDDG had the least value for the SID of methionine among test ingredients (p&lt;0.05). CONCLUSION: Standardized ileal digestibility of most amino acids in soybean meal, high-protein distillers dried grains, and canola meal were greater than those in sesame meal, perilla meal, copra meal, and tapioca distillers dried grains.