Publications by authors named "Zhiqing Huang"

239 Publications

Effect of dietary L-theanine supplementation on skeletal muscle fiber type transformation in vivo.

J Nutr Biochem 2021 Sep 10:108859. Epub 2021 Sep 10.

Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China; Key Laboratory of Animal Disease-Resistant Nutrition, Sichuan Province, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, People's Republic of China. Electronic address:

The aim of this study was to investigate the effect of dietary L-theanine supplementation on skeletal muscle fiber type transition in mice. Our data indicated that dietary 0.15% L-theanine supplementation significantly increased the mRNA expression levels of muscle fiber type related genes (MyHC I, MyHC IIa, PGC-1α, Sirt1, Tnnt1, Tnnc1, Tnni1, MEF2C) and the protein expression levels of MyHC IIa, myoglobin, PGC-1α, Sirt1 and Troponin I-SS, but significantly decreased the mRNA and protein expression levels of MyHC IIb. Dietary 0.15% L-theanine supplementation significantly increased the activities of SDH and MDH and decreased the activity of LDH. Furthermore, immunofluorescence demonstrated that dietary 0.15% L-theanine supplementation significantly increased the percentage of type I fibers, and significantly decreased the percentage of type II fibers. In addition, we found that dietary 0.15% L-theanine supplementation increased the fatigue-resistant, antioxidant capacity, mitochondrial biogenesis and function in skeletal muscle of mice. Furthermore, dietary 0.15% L-theanine supplementation significantly increased the mRNA levels of prox1, CaN and NFATc1, the protein levels of prox1, CNA and NFATc1 and the activity of CaN in GAS muscle when compared with the control group. These results indicated that dietary L-theanine supplementation promoted skeletal muscle fiber transition from type II to type I, which might be via activation of CaN/NFATc1 signaling pathway.
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http://dx.doi.org/10.1016/j.jnutbio.2021.108859DOI Listing
September 2021

Apoptotic Extracellular Vesicles Ameliorate Multiple Myeloma by Restoring Fas-Mediated Apoptosis.

ACS Nano 2021 Sep 10. Epub 2021 Sep 10.

South China Center of Craniofacial Stem Cell Research, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510080, China.

Apoptosis is critical for maintaining bodily homeostasis and produces a large number of apoptotic extracellular vesicles (apoEVs). Several types of cancer cells display reduced expression of Fas on the cell surface and are thus capable of escaping Fas ligand-induced apoptosis. However, it is unknown whether normal cell-derived apoEVs can regulate tumor growth. In this study, we show that apoEVs can induce multiple myeloma (MM) cell apoptosis and inhibit MM cell growth. Systemic infusion of mesenchymal stem cell (MSC)-derived apoEVs significantly prolongs the lifespan of MM mice. Mechanistically, apoEVs directly contact MM cells to facilitate Fas trafficking from the cytoplasm to the cell membrane by evoking Ca influx and elevation of cytosolic Ca. Subsequently, apoEVs use their Fas ligand to activate the Fas pathway in MM cells, leading to the initiation of apoptosis. This study identifies the role of apoEVs in inducing MM apoptosis and suggests a potential for apoEVs to treat MM.
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http://dx.doi.org/10.1021/acsnano.1c03517DOI Listing
September 2021

CD146 controls the quality of clinical grade mesenchymal stem cells from human dental pulp.

Stem Cell Res Ther 2021 Aug 30;12(1):488. Epub 2021 Aug 30.

South China Center of Craniofacial Stem Cell Research and Guangdong Province Key Laboratory of Stomatology, Guanghua School and Hospital of Stomatology, Sun Yat-Sen University, Guangzhou, 510055, Guangdong, People's Republic of China.

Background: Human mesenchymal stem cells from dental pulp (hMSC-DP), including dental pulp stem cells from permanent teeth and exfoliated deciduous teeth, possess unique MSC characteristics such as expression of specific surface molecules and a high proliferation rate. Since hMSC-DP have been applied in numerous clinical studies, it is necessary to establish criteria to evaluate their potency for cell-based therapies.

Methods: We compared stem cell properties of hMSC-DP at passages 5, 10 and 20 under serum (SE) and serum-free (SF) culture conditions. Cell morphology, proliferation capacity, chromosomal stability, surface phenotypic profiles, differentiation and immunoregulation ability were evaluated. In addition, we assessed surface molecule that regulates hMSC-DP proliferation and immunomodulation.

Results: hMSC-DP exhibited a decrease in proliferation rate and differentiation potential, as well as a reduced expression of CD146 when cultured under continuous passage conditions. SF culture conditions failed to alter surface marker expression, chromosome stability or proliferation rate when compared to SE culture. SF-cultured hMSC-DP were able to differentiate into osteogenic, adipogenic and neural cells, and displayed the capacity to regulate immune responses. Notably, the expression level of CD146 showed a positive correlation with proliferation, differentiation, and immunomodulation, suggesting that CD146 can serve as a surface molecule to evaluate the potency of hMSC-DP. Mechanistically, we found that CD146 regulates proliferation and immunomodulation of hMSC-DP through the ERK/p-ERK pathway.

Conclusion: This study indicates that SF-cultured hMSC-DP are appropriate for producing clinical-grade cells. CD146 is a functional surface molecule to assess the potency of hMSC-DP.
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http://dx.doi.org/10.1186/s13287-021-02559-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404346PMC
August 2021

Effects of dietary grape seed proanthocyanidin extract supplementation on meat quality, muscle fiber characteristics and antioxidant capacity of finishing pigs.

Food Chem 2022 Jan 6;367:130781. Epub 2021 Aug 6.

Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China.

The aim of this study was to investigate effects of dietary grape seed proanthocyanidin extract (GSPE) supplementation on meat quality, muscle fiber characteristics and antioxidant capacity of finishing pigs. The data showed GSPE increased pH, redness, crude protein content and decreased shear force, drip loss, lactate content and glycolytic potential in longissimus dorsi (LD) muscle, accompanied by increased contents of total polyunsaturated fatty acid (PUFA), n-3 PUFA, and the ratio of PUFA to saturated fatty acid. GSPE promoted MyHC I mRNA and slow MyHC protein expression, and increased slow-twitch fiber percentage. The activities of total antioxidant capacity, total superoxide dismutase, catalase and glutathione peroxidase in LD muscle were increased by GSPE while malondialdehyde content was decreased. Together, this study demonstrated that dietary GSPE supplementation can effectively improve the color, water-holding capacity, tenderness and nutritional value of pork, and increase slow-twitch fiber percentage and antioxidant capacity of finishing pigs.
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http://dx.doi.org/10.1016/j.foodchem.2021.130781DOI Listing
January 2022

Effects of Cold Exposure on Performance and Skeletal Muscle Fiber in Weaned Piglets.

Animals (Basel) 2021 Jul 20;11(7). Epub 2021 Jul 20.

Key Laboratory for Animal Disease-Resistance Nutrition of Sichuan Province, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China.

Low-temperature is one of the most significant risks for the animal industry. In light of this, the present study aimed to explore the effects of low-temperature on growth performance, nutrient digestibility, myofiber types and mitochondrial function in weaned piglets. A total of sixteen 21-day-old male Duroc × Landrace × Yorkshire (DLY) piglets were randomly divided into a control group (CON, 26 ± 1 °C) and a low-temperature group (LT, 15 ± 1 °C), with eight duplicate piglets in each group. The trial period lasted for 21 days. We showed that LT not only increased the ADFI ( < 0.05), as well as increasing the diarrhea incidence and diarrhea index of weaned piglets in the early stage of the experiment ( < 0.01), but it also decreased the apparent digestibility of crude protein (CP), organic matter (OM) and dry matter (DM) ( < 0.05). Meanwhile, in the LT group, the mRNA expression of ( < 0.05) in longissimus dorsi muscle (LM) and ( < 0.01) in psoas muscle (PM) were increased, while the mRNA expression of in PM was decreased ( < 0.05). In addition, LT increased the mRNA expression of mitochondrial function-related genes citrate synthase (CS) and succinate dehydrogenase-b (SDHB) in LM, as well as increased the mRNA expression of CS ( < 0.05) and carnitine palmitoyl transferase-1b (CPT-1b) ( < 0.01) in PM. Furthermore, LT increased the T-AOC activity in serum and LM ( < 0.01), as well as increased the T-SOD activity in PM ( < 0.05). Taken together, these findings showed that low-temperature could negatively affect the growth performance and nutrient digestibility, but resulted in a shift toward oxidative muscle fibers, which may occur through mitochondrial function regulation.
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http://dx.doi.org/10.3390/ani11072148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300759PMC
July 2021

The immunomodulatory function of the porcine β-defensin 129: Alleviate inflammatory response induced by LPS in IPEC-J2 cells.

Int J Biol Macromol 2021 Oct 3;188:473-481. Epub 2021 Aug 3.

Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China; Key Laboratory of Animal Disease-resistant Nutrition, Sichuan Province, Chengdu 611130, PR China. Electronic address:

β-defensin family plays a critical role in host defense against infections. In this study, we found that pBD129 are widely expressed in porcine tissues such as the intestine, liver, and spleen. Interestingly, the expression level of pBD129 in most tissues was higher in Tibetan pigs than in DLY (Duroc × Landrace × Yorkshire) pigs (P < 0.05), and was significantly upregulated upon E. coli K88 infection (P < 0.05). The pBD129 protein was successfully expressed in E. coli and the molecule weight was estimated by SDS-PAGE to be 37.2 kDa. Mass spectrometry verified the protein as a pBD129. The protein showed antibacterial activities against Streptococcus and E. coli DH5α with a minimal inhibitory concentration (MIC) of 32 μg/mL. Hemolytic and cytotoxicity assays indicated that pBD129 had no detrimental effect on cell viability. Importantly, pBD129 significantly reduced the apoptosis of porcine intestinal epithelial cells exposure to bacterial endotoxins, which was associated with down-regulation of inflammatory cytokines such as the IL-1β, IL-6 and TNFα (P < 0.05), and down-regulation of apoptosis-related genes such as the caspase-3, caspase-8, and caspase-9 (P < 0.05). These results suggested that pBD129 is a novel modulator of innate immunity involved in mammalian inflammatory responses.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.07.194DOI Listing
October 2021

Chitosan oligosaccharide attenuates endoplasmic reticulum stress-associated intestinal apoptosis the Akt/mTOR pathway.

Food Funct 2021 Aug 4. Epub 2021 Aug 4.

Key Laboratory of Animal Disease-Resistance Nutrition, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.

Endoplasmic reticulum stress (ERS) and apoptosis are widely considered as essential factors associated with intestinal disorders, whereas nutritional therapeutic approaches targeting ERS may control disease activity. Thus, we focus on the potential benefit of chitosan oligosaccharide (COS) on repressing ERS and ERS-induced apoptosis. In this study, we used the ERS model with tunicamycin (TM)-induced IPEC-J2 cells in vitro and nutrient deprivation-induced ERS in piglets to evaluate the protective mechanism of COS against ERS and ERS-induced apoptosis. The results showed that cells were characterized by activation of the unfolded protein response (UPR) and increased epithelial apoptosis upon exposure to TM. However, these changes were significantly attenuated by COS and the expressions of Akt and mTORC1 were inhibited. Furthermore, a specific inhibitor of mTOR confirmed the suppression of Akt and reduced the activation of the UPR and apoptosis. In vivo, COS protected against nutrient deprivation-induced ERS in the jejunum of piglets, in which the overexpression of the UPR and apoptosis was rescued. Consistently, COS attenuated nutrient deprivation-induced disruption of intestinal barrier integrity and functional capacity. Together, we provided the first evidence that COS could protect against intestinal apoptosis through alleviating severe ERS, which may be related to the inhibition of the Akt/mTOR signaling pathway.
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http://dx.doi.org/10.1039/d1fo01234gDOI Listing
August 2021

Comparisons of the micronization, steam explosion, and gamma irradiation treatment on chemical composition, structure, physicochemical properties, and in vitro digestibility of dietary fiber from soybean hulls.

Food Chem 2022 Jan 17;366:130618. Epub 2021 Jul 17.

Key Laboratory of Animal Disease-Resistance Nutrition, Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China. Electronic address:

The objective of this study was to compare the effects of the micronization (MT), steam explosion (SE), and gamma irradiation (GI) treatment on the chemical composition, structure, physicochemical properties, and in vitro digestibility of dietary fiber from soybean hulls. GI (1200 kGy) treatment exerted the optimum effects on improving soluble dietary fiber content, in vitro gross energy digestibility (IVGED), and reducing sugar yield (RS) in the three modification methods, increased by 342.88%, 55.24%, and 117.02%, respectively. Compared with GI treatment, MT-GI combined treatment could further enhance the degradation effect of irradiation and improve the physicochemical properties (p<0.05) in soybean fibers. From the results of correlation analysis, RS was a significant positive correlation (p<0.05) with IVGED, and RS = -112.24 + 4.90 × IVGED (r = 0.82, p<0.01). In summary, MT-GI combined treatment could be considered the ideal modification method to improve the quality of soybean fiber.
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http://dx.doi.org/10.1016/j.foodchem.2021.130618DOI Listing
January 2022

Functional Characterization of Porcine NK-Lysin: A Novel Immunomodulator That Regulates Intestinal Inflammatory Response.

Molecules 2021 Jul 13;26(14). Epub 2021 Jul 13.

Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China.

Porcine NK-Lysine (PNKL) is a new antimicrobial peptide (AMP) identified in the small intestine. In this study, PNKL protein was obtained through heterologous expression in and was estimated by SDS-PAGE at 33 kDa. The antibacterial activities of PNKL were determined using various bacterial strains and showed broad-spectrum antimicrobial activity against Gram-negative and Gram-positive bacteria. Furthermore, K88-challenged IPEC-J2 cells were used to determine PNKL influences on inflammatory responses. Hemolytic assays showed that PNKL had no detrimental impact on cell viability. Interestingly, PNKL elevated the viability of IPEC-J2 cells exposure to K88. PNKL significantly decreased the cell apoptosis rate, and improved the distribution and abundance of tight junction protein ZO-1 in IPEC-J2 cells upon K88-challenge. Importantly, PNKL not only down regulated the expressions of inflammatory cytokines such as the IL-6 and TNF-α, but also down regulated the expressions of NF-κB, Caspase3, and Caspase9 in the K88-challenged cells. These results suggest a novel function of natural killer (NK)-lysin, and the anti-bacterial and anti-inflammatory properties of PNKL may allow it a potential substitute for conventionally used antibiotics or drugs.
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http://dx.doi.org/10.3390/molecules26144242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307250PMC
July 2021

Prebiotic inulin as a treatment of obesity related nonalcoholic fatty liver disease through gut microbiota: a critical review.

Crit Rev Food Sci Nutr 2021 Jul 22:1-11. Epub 2021 Jul 22.

Key laboratory of Animal Disease-resistant Nutrition, Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, People's Republic of China.

The microbial-derived products, including short chain fatty acids, lipopolysaccharide and secondary bile acids, have been shown to participate in the regulation of hepatic lipid metabolism. Previous studies have demonstrated that prebiotics, such as oligosaccharide and inulin, have abilities to change the concentration of microbial-derived products through modulating the microbial community structure, thus controlling body weight and alleviating hepatic fat accumulation. However, recent evidence indicates that there are individual differences in host response upon inulin treatment due to the differences in host microbial composition before dietary intervention. Probably it is because of the multiple relationships among bacterial species (e.g., competition and mutualism), which play key roles in the degradation of inulin and the regulation of microbial structure. Thereby, analyzing the composition and function of initial gut microbiota is essential for improving the efficacy of prebiotics supplementation. Furthermore, considering that different structures of polysaccharides can be used by different microorganisms, the chemical structure of processed inulin should be tested before using prebiotic inulin to treat obesity related nonalcoholic fatty liver disease.
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http://dx.doi.org/10.1080/10408398.2021.1955654DOI Listing
July 2021

Naringin induces skeletal muscle fiber type transformation via AMPK/PGC-1α signaling pathway in mice and C2C12 myotubes.

Nutr Res 2021 08 24;92:99-108. Epub 2021 Jun 24.

Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China.

A large number of studies have shown that polyphenols can regulate skeletal muscle fiber type transformation through AMPK signal. However, the effects and mechanism of naringin (a natural polyphenol) on muscle fiber type transformation still remains unclear. Thus, we hypothesized that naringin would induce the transformation of skeletal muscle fibers from type II to type I by AMPK signaling. C2C12 myotubes and BALB/c mice models were used to test this hypothesis. We found that naringin significantly increased the protein expression of slow myosin heavy chain (MyHC), myoglobin and troponin I type I slow skeletal (Troponin I-SS) and the activities of succinate dehydrogenase (SDH) and malate dehydrogenase (MDH), and significantly decreased fast MyHC protein expression and lactate dehydrogenase (LDH) activity, accompanied by the activation of AMPK and the activity of peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α) in mice and C2C12 myotubes. Further inhibition of AMPK activity by compound C showed that the above effects were significantly inhibited in C2C12 myotubes. In conclusion, naringin promotes the transformation of skeletal muscle fibers from type II to type I through AMPK/PGC-1α signaling pathway, which not only enriches the nutritional and physiological functions of naringin, but also provides a theoretical basis for the regulation of muscle fiber type transformation by nutritional approaches.
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http://dx.doi.org/10.1016/j.nutres.2021.06.003DOI Listing
August 2021

rich enterotype may benefit gut health in finishing pigs fed diet with a high amylose-to-amylopectin ratio.

Anim Nutr 2021 Jun 25;7(2):400-411. Epub 2021 Feb 25.

Key Laboratory for Animal Disease-Resistance Nutrition of Ministry of Education of China, Key Laboratory for Animal Disease-Resistance Nutrition and Feed of Ministry of Agriculture of China, Key Laboratory of Animal Disease-resistant Nutrition of Sichuan Province, And Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China.

To investigate the influence of baseline enterotypes and dietary starch type on the concentration of short-chain fatty acids (SCFA), numbers of butyrate producing bacteria and the expression of genes related to intestinal barrier and inflammatory response in the colon of finishing pigs, a 60-d in vivo trial was conducted. A 2-wk pre-trial with 102 crossbred (Duroc × [Landrace × Yorkshire]) finishing barrows (90 d old) was conducted to screen enterotypes. Then, a total of 32 pigs (87.40 ± 2.76 kg) with high (HPBR, ≥ 14) and low (LPBR, ≤ 2) -to- ratios (PBR) in equal measure were selected and randomly divided into 4 groups with 8 replicates per group and 1 pig per replicate. The trial was designed following a 2 (PBR) × 2 (amylose-to-amylopectin ratio, AMR) factorial arrangement. Pigs with different PBR were fed diets based on corn-soybean meal with high AMR (HAMR, 1.24) or low AMR (LAMR, 0.23), respectively. Results showed that neither PBR nor AMR influenced the growth performance of pigs. HPBR pigs fed HAMR diet had a higher number of colonic cluster XIVa and higher gene expression of butyrate kinase compared to the LPBR pigs ( < 0.05). The HPBR pigs fed HAMR diets also had increased colonic concentrations of total SCFA and propionate compared to the LPBR pigs ( < 0.05). Comparing with other pigs, HPBR pigs fed HAMR diets showed a lower ( < 0.05) expression of histone deacetylases () gene and higher ( < 0.05) expression of G protein-coupled receptor 43 gene () in the colonic mucosa. The interaction ( < 0.05) of HPBR and HAMR was also found to decrease the gene expression of interleukin ()-6, , and tumor necrosis factor-α () in colonic mucosa. These findings show that HAMR diet increased the abundance and activity of butyrate-producing bacteria and the concentration and absorption of SCFA, which may be associated with the decreased gene expression of inflammatory cytokines in the colonic mucosa of pigs with -rich enterotype. All these alterations are likely to have a positive effect on the intestinal health of finishing pigs.
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http://dx.doi.org/10.1016/j.aninu.2020.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245826PMC
June 2021

Effects of soybean raffinose on growth performance, digestibility, humoral immunity and intestinal morphology of growing pigs.

Anim Nutr 2021 Jun 6;7(2):393-399. Epub 2021 Mar 6.

Animal Nutrition Institute, Sichuan Agricultural University, Ya'an, 625014, Sichuan, China.

There are appreciable does of raffinose in soybean, but the impacts of raffinose on pigs are poorly investigated. We used 2 experiments to investigate the influence of soybean raffinose on growth performance, digestibility, humoral immunity and intestinal morphology of growing pigs. In Exp. 1, a total of 30 crossbred (Duroc × Landrace × Yorkshire) barrows (21.93 ± 0.43 kg) were randomly divided into 3 groups, and were fed with the control diet, the control diets supplemented with 0.2% and 0.5% raffinose, respectively, for 21 d. Results showed that the addition of 0.2% or 0.5% raffinose reduced ( < 0.05) average daily feed intake (ADFI), average daily gain (ADG) and nutrient digestibility, and dietary 0.5% raffinose increased the ratio of feed to gain ( < 0.05). For serum indexes, dietary 0.5% raffinose decreased growth hormone and increased glucagon-like peptide-2, immunoglobulin G, tumor necrosis factor-α (TNF-α) and interleukin-6 concentration ( < 0.05). In Exp. 2, a total of 24 crossbred barrows (38.41 ± 0.45 kg) were randomly divided into 3 groups, and were fed with the control diet (ad libitum), the raffinose diet (0.5% raffinose, ad libitum), and the control diet in the same amount as the raffinose group (feed-pair group) for 14 d, respectively. Compared with the control diet, dietary 0.5% raffinose decreased ADFI ( < 0.05). Intriguingly, the raffinose group had lower ADG than the feed-pair group, lower nutrient digestibility, lower amylase activity in duodenum, lower amylase, lipase and trypsin activities in jejunum and higher TNF-α concentration in serum compared with the other 2 groups, and a higher ratio of villus height to crypt depth compared with the control group ( < 0.05). These results showed that soybean raffinose could reduce feed voluntary intake and body gain while improving intestinal morphology without a significant negative influence on immunity. Taken together, dietary raffinose could decrease growth performance by reducing both feed intake and nutrient digestibility while inducing humoral immune response of growing pigs.
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http://dx.doi.org/10.1016/j.aninu.2020.06.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245804PMC
June 2021

Effects of essential oil on growth performance, digestibility, immunity, and intestinal health in broilers.

Poult Sci 2021 Aug 13;100(8):101242. Epub 2021 May 13.

Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, People's Republic of China. Electronic address:

Essential oils (EO) are concentrated hydrophobic liquids containing volatile aromatic compounds obtained from plants, which have properties as withdrawn antibiotic growth promoters. The objective of this study was to explore the effects of EO on growth performance, digestibility, immunity and intestinal health in broilers. A total of 500 1-day-old Arbor Acre broilers were randomly put into five groups with 10 replicate cages containing 10 birds each. Birds in the 5 groups were fed a basal diet (CON), and basal diet with 50, 100, 200 or 400 mg/kg EO (EO0.5, EO1, EO2 and EO4) for 42 d respectively. Birds were euthanized at 21d and 42 d, blood and tissue samples were collected. In the study, the digestibility of DM, GE and EE in groups with EO supplementation were significantly increased compared with CON group (P < 0.05). However, only EO2 and EO4 significantly increased the digestibility of CP compared with CON group (P < 0.05). In contrast to CON group, EO0.5 and EO1 in jejunum at 21 d, and EO1 in jejunum at 42 d markedly increased the activity of sucrase (P < 0.05). In addition, the level of SOD of EO2 and EO4 in serum at 21 d was significantly increased compared with CON group (P < 0.05). What's more, the concentration of intestinal mucosa SIgA in jejunum and ileum at 21 d of groups with EO supplementation was significantly increased compared with CON group (P < 0.05). Moreover, V/C in jejunum at 21 d of groups with EO supplementation, CD in jejunum at 42 d was also significantly increased to compare with CON group (P < 0.05). Furthermore, the expression levels of critical genes associated with nutrient transportation (i.e., GLUT2, SGLT1, SLC38A, SLC79A and SLC27A4) and barrier function (TJP1) were quadratically and linearly up-regulated in jejunum and ileum with EO supplementation (P < 0.05). These results suggest that EO has a positive impact on growth, immunity and intestinal health in broilers, and 200 mg/kg of EO was recommended in broiler diet.
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http://dx.doi.org/10.1016/j.psj.2021.101242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242051PMC
August 2021

Protective effect of Bombyx mori gloverin on intestinal epithelial cells exposure to enterotoxigenic E. coli.

Braz J Microbiol 2021 Sep 21;52(3):1235-1245. Epub 2021 Jun 21.

Institute of Animal Nutrition, Sichuan Agricultural University, Sichuan Province, Chengdu, 611130, People's Republic of China.

Bombyx mori gloverin A2 (BMGlvA2) is an induced antimicrobial insect protein isolated from Bombyx mori. This study was conducted to explore the effect and potential mechanisms of BMGlvA2 on inflammatory responses and cellular functions in intestinal epithelial cells (IPEC-J2) exposure to enterotoxigenic E. coli (ETEC). IPEC-J2 cells pretreated with or without BMGlvA2 (12.5 μg/mL) were challenged by ETEC K88 (1×10 CFU/well) or culture medium. We show that BMGlvA2 pretreatment increased the cell viability and improved the distribution and abundance of tight junction protein ZO-1 in IPEC-J2 cells exposure to ETEC (P < 0.05). Interestingly, BMGlvA2 not only decreased the expression levels of inflammatory cytokines such as the tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), but also decreased the expression level of Caspase3 and the apoptosis rate in the ETEC-challenged cells (P < 0.05). Importantly, BMGlvA2 decreased the protein abundances of two critical inflammation-associated signaling proteins, phosphorylated nuclear factor-kappa-B inhibitor alpha (p-IκBα) and phosphorylated nuclear factor-kappa B (p-NF-κB), in the ETEC-challenged cells. These results indicate that BMGlvA2 attenuates ETEC-induced inflammation in the IPEC-J2 cells by regulating the NF-κB signaling pathway, resulting in decreased secretion of inflammatory cytokine and reduced cell apoptosis.
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http://dx.doi.org/10.1007/s42770-021-00532-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324673PMC
September 2021

A pig BodyMap transcriptome reveals diverse tissue physiologies and evolutionary dynamics of transcription.

Nat Commun 2021 06 17;12(1):3715. Epub 2021 Jun 17.

Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, China.

A comprehensive transcriptomic survey of pigs can provide a mechanistic understanding of tissue specialization processes underlying economically valuable traits and accelerate their use as a biomedical model. Here we characterize four transcript types (lncRNAs, TUCPs, miRNAs, and circRNAs) and protein-coding genes in 31 adult pig tissues and two cell lines. We uncover the transcriptomic variability among 47 skeletal muscles, and six adipose depots linked to their different origins, metabolism, cell composition, physical activity, and mitochondrial pathways. We perform comparative analysis of the transcriptomes of seven tissues from pigs and nine other vertebrates to reveal that evolutionary divergence in transcription potentially contributes to lineage-specific biology. Long-range promoter-enhancer interaction analysis in subcutaneous adipose tissues across species suggests evolutionarily stable transcription patterns likely attributable to redundant enhancers buffering gene expression patterns against perturbations, thereby conferring robustness during speciation. This study can facilitate adoption of the pig as a biomedical model for human biology and disease and uncovers the molecular bases of valuable traits.
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http://dx.doi.org/10.1038/s41467-021-23560-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211698PMC
June 2021

Dietary dihydromyricetin supplementation enhances antioxidant capacity and improves lipid metabolism in finishing pigs.

Food Funct 2021 Aug;12(15):6925-6935

Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, P. R. China.

Nowadays, chronic diseases have become a potential danger to human health and are highly concerning. Given that pigs are a suitable animal model for human nutrition and metabolism for its similar anatomical and physiological properties to those of humans, this study has used 24 castrated male Duroc × Landrace × Yorkshire (DLY) pigs as experimental subjects to explore the effects of dietary dihydromyricetin (DHM) supplementation on the antioxidant capacity and lipid metabolism. Results showed that dietary 300 and 500 mg DHM kg-1 diet supplementation increased the serum total superoxide dismutase (T-SOD) level, serum and liver reduced glutathione (GSH), muscle catalase (CAT) level and serum high-density lipoprotein cholesterol (HDL-C) level, and reduced the liver malondialdehyde (MDA) level and muscle triglyceride (TG) level in finishing pigs. Western blot analysis showed that dietary DHM supplementation activated the nuclear-related factor 2 (Nrf2) and AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signals. Real-time quantitative PCR analysis showed that dietary DHM supplementation upregulated the mRNA levels of lipolysis and fatty acid oxidation-related genes, and down-regulated the mRNA expression of lipogenesis-related genes in finishing pigs. Together, we provide evidence that dietary DHM supplementation improved the antioxidant capacity and lipid metabolism in finishing pigs.
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http://dx.doi.org/10.1039/d0fo03094eDOI Listing
August 2021

Association between PEG3 DNA methylation and high-grade cervical intraepithelial neoplasia.

Infect Agent Cancer 2021 Jun 13;16(1):42. Epub 2021 Jun 13.

Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, USA.

Background: Epigenetic mechanisms are hypothesized to contribute substantially to the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer, although empirical data are limited.

Methods: Women (n = 419) were enrolled at colposcopic evaluation at Duke Medical Center in Durham, North Carolina. Human papillomavirus (HPV) was genotyped by HPV linear array and CIN grade was ascertained by biopsy pathologic review. DNA methylation was measured at differentially methylated regions (DMRs) regulating genomic imprinting of the IGF2/H19, IGF2AS, MESTIT1/MEST, MEG3, PLAGL1/HYMAI, KvDMR and PEG10, PEG3 imprinted domains, using Sequenom-EpiTYPER assays. Logistic regression models were used to evaluate the associations between HPV infection, DMR methylation and CIN risk overall and by race.

Results: Of the 419 participants, 20 had CIN3+, 52 had CIN2, and 347 had ≤ CIN1 (CIN1 and negative histology). The median participant age was 28.6 (IQR:11.6) and 40% were African American. Overall, we found no statistically significant association between altered methylation in selected DMRs and CIN2+ compared to ≤CIN1. Similarly, there was no significant association between DMR methylation and CIN3+ compared to ≤CIN2. Restricting the outcome to CIN2+ cases that were HR-HPV positive and p16 staining positive, we found a significant association with PEG3 DMR methylation (OR: 1.56 95% CI: 1.03-2.36).

Conclusions: While the small number of high-grade CIN cases limit inferences, our findings suggest an association between altered DNA methylation at regulatory regions of PEG3 and high grade CIN in high-risk HPV positive cases.
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http://dx.doi.org/10.1186/s13027-021-00382-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201933PMC
June 2021

1,25-Dihydroxyvitamin D inhibits porcine epidemic diarrhea virus replication by regulating cell cycle resumption in IPEC-J2 porcine epithelial cells.

Microb Pathog 2021 Sep 7;158:105017. Epub 2021 Jun 7.

Institute of Animal Nutrition, Sichuan Agricultural University, NO. 46 Xinkang Road, Yucheng District, Yaan, Sichuan, 625014, People's Republic of China. Electronic address:

Porcine epidemic diarrhea virus (PEDV) infection causes heavy economic losses in the pig industry. Currently, the lack of effective treatments prompts new antiviral researches. We have shown that 25-hydroxyvitamin D supplementation alleviated PEDV infection in weaned pigs before. However, it is not clear whether vitamin D inhibits PEDV replication. In this study, 1,25-dihydroxyvitamin D (1,25(OH)D) inhibited PEDV induced mitochondria damage and cell apoptosis. In addition, 1,25(OH)D treatment decreased PEDV nucleocapsid gene and protein levels in IPEC-J2 cells. Transcriptomic data showed that PEDV infection altered the expression of 5316 genes (2498 up, 2818 down) in IPEC-J2 cells. The differentially expressed genes were mainly involved in cell cycle process, ribonucleoprotein complex biogenesis, mitotic nuclear division, and other biological processes. Then we examined the effects of PEDV infection on cell cycle progression in IPEC-J2 cells, and the results showed that PEDV induced G0/G1 phase arrest. G0/G1-phase arrest was also conducive to PEDV replication. However, 1,25(OH)D treatment decreased G0/G1 phase percentage induced by PEDV. Cyclin D and cyclin E mRNA expression were also increased by 1,25(OH)D supplementation upon PEDV infection. Moreover, the regulation of 1,25(OH)D on cell cycle progression was abrogated by ERK1/2 inhibitor, as well as the mRNA expression of cyclin D. The inhibition of 1,25(OH)D on PEDV replication was also eliminated by ERK1/2 inhibitor. Taken together, these results demonstrated that 1,25(OH)D supplementation inhibited PEDV replication, and the anti-virus effect of 1,25(OH)D was mediated in part by regulating cell cycle progression through ERK1/2 signaling pathway.
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http://dx.doi.org/10.1016/j.micpath.2021.105017DOI Listing
September 2021

Fermented Diet Liquid Feeding Improves Growth Performance and Intestinal Function of Pigs.

Animals (Basel) 2021 May 19;11(5). Epub 2021 May 19.

Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China.

Accumulating evidences demonstrate that fermented feed and liquid feeding exerted a great beneficial influence on growth performance and health in the pig industry. This experiment was conducted to evaluate the effects of fermented liquid feeding on the growth performance and intestinal function of pigs. Two hundred and eighty-eight 27-day-old weaned piglets (8.21 ± 0.27 kg) were randomly allocated to a control group (basal diet (CON)), an antibiotic group (basal diet supplemented with antibiotics (AB)) and a fermented liquid feeding group (basal diet with fermented liquid feeding (FLF)), with 6 replicates per treatment and 16 weaned piglets per replicate. The experiment lasted for 160 days. Fresh fecal samples were collected to evaluate the apparent total tract digestibility (ATTD) of nutrients from the last 4 days of each stage. The results are shown as follows: (1) Compared with the CON group, in the whole stage, the FLF diet significantly increased the final body weight (BW) and ADG of pigs ( < 0.05), and had a tendency to increase ADFI ( = 0.086), but had no effect on F/G. (2) The ATTD of dry matter (DM), crude protein (CP), ether extract (EE), crude ash (CA), crude fiber (CF), gross energy (GE), calcium (Ca) and total phosphorus (TP) in the FLF group was significantly elevated compared with those of the CON group at 8-20 kg stage ( < 0.05). Meanwhile, the ATTD of EE in the FLF group was significantly increased compared with that of the CON group at the 50-75 kg and 100-125 kg stages ( < 0.05), and the ATTD of Ca was higher than that of CON group at the 100-125 kg stage ( < 0.05). (3) Compared with that of the CON group, the level of serum leptin in the FLF group had a tendency to decrease ( = 0.054), the level of serum ghrelin in the FLF group was significantly elevated ( < 0.05) and the level of serum peptide YY in the FLF group was significantly decreased ( < 0.05). (4) The abundance of in cecal and colonic digesta was observably enhanced in FLF group. Meanwhile, the abundance of in cecal and colonic digesta were dramatically reduced in the FLF group compared with that in the CON and AB groups ( < 0.05). (5) The levels of acetic acid in colonic digesta were significantly increased in the FLF group ( < 0.05), and an increasing trend was observed in total VFA in colonic digesta compared with CON ( < 0.1). The levels of acetic acid in colonic digesta were significantly promoted in the FLF group compared with that of the AB group ( < 0.05). In conclusion, these results indicate that fermented liquid feeding improved the growth performance of pigs, which might be associated with gastrointestinal hormone and intestinal functions.
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http://dx.doi.org/10.3390/ani11051452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158733PMC
May 2021

Procyanidin B2 induces porcine skeletal slow-twitch myofiber gene expression by AMP-activated protein kinase signaling pathway.

Anim Biotechnol 2021 Jun 1:1-10. Epub 2021 Jun 1.

Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China.

In this study, our aim is to investigate the effect of dimer procyanidin B2 [epicatechin-(4β-8)-epicatechin] (PB2) on porcine skeletal myofiber gene expression . Our data showed PB2 promoted the protein expression of slow myosin heavy chain (MyHC) in porcine myotubes, concomitant with the increases in mRNA levels of , and . We also found PB2 activated AMPK signaling in porcine myotubes. NRF1 and CaMKKβ that are two important upstream factors of AMPK, and Sirt1 and PGC-1α that are two major downstream factors of AMPK, were also up-regulated by PB2. The mechanism study showed the effect of PB2 on slow-twitch myofiber gene expression was abolished by AMPK inhibitor compound C or by AMPKα1 siRNA. Together, we found PB2 induced porcine skeletal slow-twitch myofiber gene expression by AMPK signaling pathway.
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http://dx.doi.org/10.1080/10495398.2021.1927065DOI Listing
June 2021

DNA Methylation in Babies Born to Nonsmoking Mothers Exposed to Secondhand Smoke during Pregnancy: An Epigenome-Wide Association Study.

Environ Health Perspect 2021 May 19;129(5):57010. Epub 2021 May 19.

Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina, USA.

Background: Maternal smoking during pregnancy is related to altered DNA methylation in infant umbilical cord blood. The extent to which low levels of smoke exposure among nonsmoking pregnant women relates to offspring DNA methylation is unknown.

Objective: This study sought to evaluate relationships between maternal prenatal plasma cotinine levels and DNA methylation in umbilical cord blood in newborns using the Infinium HumanMethylation 450K BeadChip.

Methods: Participants from the Newborn Epigenetics Study cohort who reported not smoking during pregnancy had verified low levels of cotinine from maternal prenatal plasma (0 to ), and offspring epigenetic data from umbilical cord blood were included in this study (). Multivariable linear regression models were fit to the data, controlling for cell proportions, age, race, education, and parity. Estimates represent changes in response to any unit increase in exposure.

Results: Multivariable linear regression models yielded 29,049 CpGs that were differentially methylated in relation to increases in cotinine at a 5% false discovery rate. Top CpGs were within or near genes involved in neuronal functioning (, , ), carcinogenesis (, ) and inflammation (). Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggest cotinine was related to methylation of gene pathways controlling neuronal signaling, metabolic regulation, cell signaling and regulation, and cancer. Further, enhancers associated with transcription start sites were enriched in altered CpGs. Using an independent sample from the same study population (), bisulfite pyrosequencing was performed with infant cord blood DNA for two genes within our top 20 hits ( and ). Results from pyrosequencing replicated epigenome results for (cg17079497, , , ) but not for AGER (cg09199225; , , ).

Discussion: Secondhand smoke exposure among nonsmoking women may alter DNA methylation in regions involved in development, carcinogenesis, and neuronal functioning. These novel findings suggest that even low levels of smoke exposure during pregnancy may be sufficient to alter DNA methylation in distinct sites of mixed umbilical cord blood leukocytes in pathways that are known to be altered in cord blood from pregnant active smokers. https://doi.org/10.1289/EHP8099.
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http://dx.doi.org/10.1289/EHP8099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132610PMC
May 2021

Lycopene increases the proportion of slow-twitch muscle fiber by AMPK signaling to improve muscle anti-fatigue ability.

J Nutr Biochem 2021 08 29;94:108750. Epub 2021 Apr 29.

Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, China.

Lycopene has a wide range of biological functions, especially its antioxidant capacity. However, effects of lycopene on muscle fatigue resistant and muscle fiber type conversion are unknown. In this study, we found that lycopene significantly prolonged the swimming time to exhaustion in mice. We also showed that lycopene increased the proportion of slow-twitch muscle fiber by promoting muscle fiber type conversion from fast-twitch to slow-twitch in mice and in C2C12 myotubes. The AMP-activated protein kinase (AMPK) signaling was activated by lycopene. AMPK upstream and downstream regulators including nuclear respiratory factor 1, calcium calmodulin-dependent protein kinase kinase-β, sirtuin 1 and peroxisome proliferator activated receptor-γ coactivator-1ɑ were also increased by lycopene. AMPK inhibitor compound C markedly attenuated the lycopene-induced skeletal muscle fiber type conversion in C2C12 myotubes. Taken together, we provided the first evidence that lycopene increases the proportion of slow-twitch muscle fiber through AMPK signaling pathway to improve fatigue resistant of skeletal muscle.
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http://dx.doi.org/10.1016/j.jnutbio.2021.108750DOI Listing
August 2021

Effects of slaughter age on carcass traits and meat quality of crossbred (Duroc × Landrace × Yorkshire) finishing pigs.

Anim Biotechnol 2021 Apr 30:1-7. Epub 2021 Apr 30.

Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, P. R. China.

Thirty castrated Duroc × Landrace × Yorkshire (DLY) pigs were randomly divided into three groups and slaughtered at 180, 210, and 240 days of age, respectively. Here, we found that the live weight, carcass weight, carcass length, dressing percentage, eye muscle area, backfat deposit, muscle yellowness b* value, drip loss, and cooking loss increased significantly, and the muscle pH 45 min value decreased dramatically as the slaughter age of DLY pigs extended. Moreover, increasing the slaughter age of DLY pigs could obtain higher n-3 polyunsaturated fatty acid (PUFA) percentage, crude protein, essential amino acids (EAA) contents and EAA/NEAA level, and lower n-6/n-3 PUFA level and antioxidant capacity. Together, this study suggests that the older slaughter age improves the carcass traits and nutritional value of pork, but leads to a significant decrease in pork sensory quality in DLY finishing pigs.
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http://dx.doi.org/10.1080/10495398.2021.1916512DOI Listing
April 2021

Influences of Selenium-Enriched Yeast on Growth Performance, Immune Function, and Antioxidant Capacity in Weaned Pigs Exposure to Oxidative Stress.

Biomed Res Int 2021 27;2021:5533210. Epub 2021 Mar 27.

Institute of Animal Nutrition, Sichuan Agricultural University, Sichuan Province, Chengdu 611130, China.

This study elucidated the function role of dietary selenium-enriched yeast (SeY) supplementation on growth performance, immune function, and antioxidant capacity in weaned pigs exposure to oxidative stress. Thirty-two similarity weight pigs were randomly divided into four treatments: (1) nonchallenged control, (2) control+SeY, (3) control+diquat, and (4) control+SeY+diquat. The period of experiment was 21 days; on day 16, pigs were injected with diquat or sterile saline. Results revealed that oxidative stress was notably detrimental to the growth performance of piglets, but SeY supplementation ameliorated this phenomenon, which might be regarding the increasing of body antioxidant capacity and immune functions. In details, SeY supplementation improved the digestibility of crude protein (CP), ash, and gross energy (GE). Moreover, the serum concentrations of proinflammatory cytokines (TNF-, IL-1, and IL-6), glutamic-pyruvic transaminase(GPT), and glutamic-oxaloacetic transaminase (GOT) were reduced via SeY supplemented, and serum concentrations of immunoglobulins A (IgA), IgG, and activities of antioxidant enzymes such as the superoxide dismutase (SOD), catalase (CAT) ,and glutathione peroxidase (GSH-Px) were improved in the diquat-challenged pigs ( < 0.05). In addition, SeY supplementation acutely enhanced the activities of these antioxidant enzymes in the liver and thymus upon diquat challenge, which involved with the upregulation of the critical genes related antioxidant signaling such as the nuclear factor erythroid-derived 2-related factor 2 (Nrf-2) and heme oxygenase-1 (HO-1) ( < 0.05). Importantly, we also found that SeY supplementation apparently reduced the malondialdehyde (MDA) concentrations in the liver, thymus, and serum ( < 0.05). Specifically, the expression levels of TNF-, IL-6, IL-1, Toll-like receptor 4 (TLR-4), and nuclear factor-B (NF-B) in the liver and thymus were downregulated by SeY upon diquat challenge. These results suggested that SeY can attenuate oxidative stress-induced growth retardation, which was associated with elevating body antioxidant capacity, immune functions, and suppressed inflammatory response.
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http://dx.doi.org/10.1155/2021/5533210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019624PMC
May 2021

Epigenetic Regulation of Claudin-1 in the Development of Ovarian Cancer Recurrence and Drug Resistance.

Front Oncol 2021 22;11:620873. Epub 2021 Mar 22.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, United States.

Over 21,000 women are diagnosed with ovarian cancer (OC) in the United States each year and over half that number succumb to this disease annually, often due to recurrent disease. A deeper understanding of the molecular events associated with recurrent disease is needed to identify potential targets. Using genome-scale DNA methylation and gene expression data for 16 matched primary-recurrent advanced stage serous epithelial OCs, we discovered that Claudin-1 (1), a tight junction protein, shows a stronger correlation between expression and methylation in recurrent versus primary OC at multiple CpG sites (R= -0.47 to -0.64 versus R= -0.32 to -0.57, respectively). An independent dataset showed that this correlation is stronger in tumors from short-term (<3y) survivors than in tumors from long-term (>7y) survivors (R= -0.41 to -0.46 versus R= 0.06 to -0.19, respectively). The presence of this inverse correlation in short-term survivors and recurrent tumors suggests an important role for this relationship and potential predictive value for disease prognosis. expression increased following pharmacologic inhibition of DNA methyltransferase activity (p< 0.001), thus validating the role of methylation in gene inhibition. knockdown enhanced chemosensitivity and suppressed cell proliferation, migration, and wound healing (p< 0.05). Stable knockdown resulted in reduced xenograft tumor growth but did not reach significance. Our results indicate that the relationship between methylation and expression plays an important role in OC aggressiveness and recurrence.
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http://dx.doi.org/10.3389/fonc.2021.620873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019902PMC
March 2021

HO-Driven Anticancer Activity of Mn Porphyrins and the Underlying Molecular Pathways.

Oxid Med Cell Longev 2021 15;2021:6653790. Epub 2021 Mar 15.

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710, USA.

Mn(III) --alkyl- and -alkoxyalkyl porphyrins (MnPs) were initially developed as superoxide dismutase (SOD) mimics. These compounds were later shown to react with numerous reactive species (such as ONOO, HO, HS, CO , ascorbate, and GSH). Moreover, the ability of MnPs to oxidatively modify activities of numerous proteins has emerged as their major mechanism of action both in normal and in cancer cells. Among those proteins are transcription factors (NF-B and Nrf2), mitogen-activated protein kinases, MAPKs, antiapoptotic bcl-2, and endogenous antioxidative defenses. The lead Mn porphyrins, namely, MnTE-2-PyP (BMX-010, AEOL10113), MnTnBuOE-2-PyP (BMX-001), and MnTnHex-2-PyP, were tested in numerous injuries of normal tissue and cellular and animal cancer models. The wealth of the data led to the progression of MnTnBuOE-2-PyP into four Phase II clinical trials on glioma, head and neck cancer, anal cancer, and multiple brain metastases, while MnTE-2-PyP is in Phase II clinical trial on atopic dermatitis and itch.
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http://dx.doi.org/10.1155/2021/6653790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987459PMC
May 2021

Effects of dietary Bacillus coagulans and yeast hydrolysate supplementation on growth performance, immune response and intestinal barrier function in weaned piglets.

J Anim Physiol Anim Nutr (Berl) 2021 Sep 14;105(5):898-907. Epub 2021 Mar 14.

Key Laboratory for Animal Disease-Resistance Nutrition of Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, China.

The present study investigated the effects of Bacillus coagulans and yeast hydrolysate supplementation on growth performance, immune response and intestinal barrier function of weaned piglets. Twenty-four weaned piglets with an average body weight (BW) of 6.89 ± 0.15 kg were divided into four diets for 28 days. The treatments were basal diet (control), basal diet supplemented with antibiotic (20 mg/kg colistin sulphate and 40 mg/kg bacitracin zinc, AT), probiotics (400 mg/kg Bacillus coagulans ≥5 × 109 CFU/g, BC) or yeast hydrolysate (5000 mg/kg yeast hydrolysate, YH). Average daily gain (ADG) and average daily feed intake (ADFI) were improved by AT and YH diets (p < 0.05), while BC diet only increased ADG (p < 0.05). The complement 3 (C3), lysozyme (LZM) and tumour necrosis factor-α (TNF-α) concentrations in serum were increased in BC diet (p < 0.05). Feeding AT and YH caused the increase of jejunal villus height (p < 0.05), and a higher ratio of villus height/crypt depth was observed in AT, BC and YH groups (p < 0.05). The mRNA expression of zonula occludens-1 (ZO-1) in jejunal mucosa was up-regulated by AT, BC and YH diets (p < 0.05). Dietary AT, BC or YH inclusion decreased the interleukin-1β (IL-1β) concentration and TNF-α mRNA expression (p < 0.05), and YH supplementation even down-regulated toll-like receptor 4 (TLR4) and CD14 expressions (p < 0.05). In summary, the dietary administration of BC or YH both improves growth performance through promoting the intestinal barrier function, indicating both of them can serve as potential alternatives to antibiotics growth promoters for the piglet production.
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http://dx.doi.org/10.1111/jpn.13529DOI Listing
September 2021

The Nutritional Significance of Intestinal Fungi: Alteration of Dietary Carbohydrate Composition Triggers Colonic Fungal Community Shifts in a Pig Model.

Appl Environ Microbiol 2021 04 27;87(10). Epub 2021 Apr 27.

Key Laboratory for Animal Disease-Resistance Nutrition of the Ministry of Education of China, Key Laboratory for Animal Disease-Resistance Nutrition and Feed of the Ministry of Agriculture of China, Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, China

Carbohydrates represent the most important energy source in the diet of humans and animals. A large number of studies have shown that dietary carbohydrates (DCHO) are related to the bacterial community in the gut, but their relationship with the composition of intestinal fungi is still unknown. Here, we report the response of the colonic fungal community to different compositions of DCHO in a pig model. Three factors, ratio (2:1, 1:1, and 1:2) of amylose to amylopectin (AM/AP), level of nonstarch polysaccharides (NSP; 1%, 2%, and 3%), and mannan-oligosaccharide (MOS; 400, 800, and 1,200 mg/kg body weight), were considered according to an L9 (3) orthogonal design to form nine diets with different carbohydrate compositions. Sequencing based on an Illumina HiSeq 2500 platform targeting the internal transcribed spacer 1 region showed that the fungal community in the colon of the pigs responded to DCHO in the order of MOS, AM/AP, and NSP. A large part of some low-abundance fungal genera correlated with the composition of DCHO, represented by , , , , , , and , were also associated with the concentration of glucose and fructose, as well as the activity of β-d-glucosidase in the colonic digesta, suggesting a role of these fungi in the degradation of DCHO in the colon of pigs. Our study provides direct evidence for the relationship between the composition of DCHO and the fungal community in the colon of pigs, which is helpful to understand the function of gut microorganisms in pigs. Although fungi are a large group of microorganisms along with bacteria and archaea in the gut of monogastric animals, the nutritional significance of fungi has been ignored for a long time. Our previous studies revealed a distinct fungal community in the gut of grazing Tibetan pigs (J. Li, D. Chen, B. Yu, J. He, et al., Microb Biotechnol 13:509-521, 2020, https://doi.org/10.1111/1751-7915.13507) and a close correlation between fungal species and short-chain fatty acids, the main microbial metabolites of carbohydrates in the hindgut of pigs (J. Li, Y. Luo, D. Chen, B. Yu, et al., J Anim Physiol Anim Nutr 104:616-628, 2020, https://doi.org/10.1111/jpn.13300). These groundbreaking findings indicate a potential relationship between intestinal fungi and the utilization of DCHO. However, no evidence directly proves the response of intestinal fungi to changes in DCHO. Here, we show a clear alteration of the colonic fungal community in pigs triggered by different compositions of DCHO simulated by varied concentrations of starch, nonstarch polysaccharides (NSP), and oligosaccharides. Our results highlight the potential involvement of intestinal fungi in the utilization of nutrients in monogastric animals.
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http://dx.doi.org/10.1128/AEM.00038-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117771PMC
April 2021

Additive value of texture analysis based on breast MRI for distinguishing between benign and malignant non-mass enhancement in premenopausal women.

BMC Med Imaging 2021 Mar 12;21(1):48. Epub 2021 Mar 12.

Department of Radiology, Guangdong Women and Children Hospital, No.521, Xingnan Road, Panyu District, Guangzhou, 511400, China.

Background: Non-mass enhancement (NME) is a diagnostic dilemma and highly reliant on the experience of the radiologists. Texture analysis (TA) could serve as an objective method to quantify lesion characteristics. However, it remains unclear what role TA plays in a predictive model based on routine MRI characteristics. The purpose of this study was to explore the value of TA in distinguishing between benign and malignant NME in premenopausal women.

Methods: Women in whom NME was histologically proven (n = 147) were enrolled (benign: 58; malignant: 89) was retrospective. Then, 102 and 45 patients were classified as the training and validation groups, respectively. Scanning sequences included Fat-suppressed T2-weighted and fat-suppressed contrast-enhanced T1-weighted which were acquired on a 1.5T MRI system. Clinical and routine MR characteristics (CRMC) were evaluated by two radiologists according to the Breast Imaging and Reporting and Data system (2013). Texture features were extracted from all post-contrast sequences in the training group. The combination model was built and then assessed in the validation group. Pearson's chi-square test and Mann-Whitney U test were used to compare categorical variables and continuous variables, respectively. Logistic regression analysis and receiver operating characteristic curve were employed to assess the diagnostic performance of CRMC, TA, and their combination model in NME diagnosis.

Results: The combination model showed superior diagnostic performance in differentiating between benign and malignant NME compared to that of CRMC or TA alone (AUC, 0.887 vs 0.832 vs 0.74). Moreover, compared to CRMC, the model showed high specificity (72.5% vs 80%). The results obtained in the validation group confirmed the model was promising.

Conclusions: With the combined use of TA and CRMC could afford an improved diagnostic performance in differentiating between benign and malignant NME.
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http://dx.doi.org/10.1186/s12880-021-00571-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953679PMC
March 2021
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