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Background: Endothelial mesenchymal transition (EndMT) is a key pathological event for vasculopathy which is one of the early features and hallmarks of systemic scleroderma (SSc). It is well established that hypoxia contributes to EndMT, however, little is known about the effects of EndMT induced by hypoxia on skin microvascular remodeling of SSc,as well as the underlying mechanism.Methods: Skin biopsy was down for SSc patients and healthy controls and skin tissues were collected for iTRAQ-based proteomics and Immunohistochemical test. Human microvascular endothelial cell line (HMEC-1) cultured with hypoxic or normal conditions, treated by either tamoxifen or bevacizumab. The expression of Hypoxia inducible factor-1α (HIF-1α) ,vascular endothelial growth factor (VEGF)-a, CD31, α-smooth muscle actin (α-SMA), VE-cadherin, fibronectin were detected at both protein and mRNA level.Results : The iTRAQ-based proteomics indicated significantly up-regulated HIF-1 sigaling in the skin tissues of SSc patients. Immunohistochemical results demonstrated a significant downregulation of the endothelial cell (EC) marker CD31 and a distinct positive staining of the interstitial cell (IC) marker α-SMA at sites lining the vessel lumens in the skin tissues of SSc. Meanwhile the positive staining of HIF-1α, a key transcription factor in response to chronic hypoxia, and VEGF-a were found to be diffusely distributed in SSc skin tissue. Consistent with these observations, HMEC-1 cells cultured under hypoxic conditions exhibited a significant decrease in CD31 and VE-cadherin expression, alongside a marked increase in the expression of α-SMA and fibronectin, as well as a distinct up-regulation of HIF-1α and VEGF-a, while comparing with them under normal condition. Of note, the inhibition of HIF-1α by tamoxifen effectively down-regulated the hypoxic induction VEGF-a, α-SMA, while rescuing hypoxic suppression of CD31. In addition, a VEGF-a inhibitor bevacizumab treatment had the same effect on the hypoxic expression of α-SMA and CD31 as tamoxifen intervention, but did not reduce HIF-1α.Conclusion: These results suggest that the HIF-1α/VEGF signaling pathway has a critical role in mediating the effect of hypoxia-induced EndMT on skin microvascular remodeling of SSc.

Because cutaneous melanoma (CM) is one of the most lethal human tumors, major treatment advances are vital. miR-140-3p has been suggested to act as a suppressor in a range of malignant tumors, implying its possible use as a biomarker for effective antineoplastic treatment. However, the potential role of miR-140-3p in CM and the underlying mechanism remain unclear. In the present study, we identified lower levels of miR-140-3p in both CM tissues and cell lines; this downregulation was strongly associated with worse CM survival. Additionally, overexpression of miR-140-3p significantly inhibited cell proliferation, migration, and invasion in CM cells with different cell line origins. Importantly, by means of both bioinformatics analysis and luciferase reporter assay, we revealed abhydrolase domain containing 2 (ABHD2) to be a target of miR-140-3p in CM cells. Upregulation of ABHD2 reversed the tumor-suppressive effects of miR-140-3p in CM cells. Furthermore, miR-140-3p-targeted ABHD2 played a role in both activation of JNK signaling and inhibition of the AKT/p70S6K pathway in CM cells. Finally, in vivo results strongly suggested the suppressive effects of miR-140-3p on CM growth and metastasis. Collectively, our findings highlight a novel antineoplastic function for miR-140-3p in CM through ABHD2., Graphical Abstract, Cutaneous melanoma (CM) is one of the most lethal human tumors; major treatment advances are vital. miR-140-3p has been suggested as a suppressor in a range of malignant tumors, implying its possible use as a biomarker for effective antineoplastic treatment. He et al. highlight a novel antineoplastic function for miR-140-3p in CM through ABHD2 in both in vitro and in vivo models.

Lung cancer is one of the most malignant cancers around the world, with high morbidity and mortality. Metastasis is the leading cause of lung cancer deaths and treatment failure. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs), two groups of small non-coding RNAs (nc-RNAs), are confirmed to be lung cancer oncogenes or suppressors. Transforming growth factor-β (TGF-β) critically regulates lung cancer metastasis. In this review, we summarize the dual roles of miRNAs and lncRNAs in TGF-β signaling-regulated lung cancer epithelial-mesenchymal transition (EMT), invasion, migration, stemness, and metastasis. In addition, lncRNAs, competing endogenous RNAs (ceRNAs), and circular RNAs (circRNAs) can act as miRNA sponges to suppress miRNAs, thereby mediating TGF-β signaling-regulated lung cancer invasion, migration, and metastasis. Through this review, we hope to cast light on the regulatory mechanisms of miRNAs and lncRNAs in TGF-β signaling-regulated lung cancer metastasis and provide new insights for lung cancer treatment.

The mammalian intestine is not only an organ for food digestion and nutrient absorption but also an integral part of the immune and endocrine systems. The intestinal epithelium under stressful environments requires epithelial cells to rapidly elicit changes in gene expression patterns to regulate their survival, adapt to stress, and maintain epithelial homeostasis. Recently, miRNAs have emerged as a novel class of posttranscriptional gene regulators that are fundamentally involved in many aspects of intestinal epithelial differentiation, architecture, and barrier function. In this review, we highlight the critical roles of miRNAs in both the crypt-villus axis of cellular self-renewal and inflammation in the mammalian intestinal mucosa and their impact on the microbiota. We also discuss the functions of specific miRNAs within the intestine to better understand the cellular mechanisms that promote intestinal homeostasis, and the influence of dietary components in the regulation of endogenous miRNA in the study of nutrition and gene regulation in intestinal health.

Fish gelatin is a class of biopolymers acquired from the hydrolysis of fish collagen, and it contains abundant amino acids for nutritive uses as dietary products. The natural characteristics of fish gelatin mean that fish gelatin products are relatively harmless to the body compared with clinical therapies and drugs. Thus, the dietary use of fish gelatin can potentially have excellent benefits for people with chronic diseases such as hypertension, osteoporosis, and diabetes. Moreover, researchers have found multiple routes for the administration of fish gelatin products such as external use or injection. In this review, we summarize the new usage of fish gelatin products and provide an update on the latest research on other properties and applications of fish gelatin. These new applications will provide multiple uses for fish gelatin products in the future, though further research is still needed.

Cancer ranks as the second leading cause of death worldwide, causing a large social and economic burden. However, most anti-cancer treatments face the problems of tumor recurrence and metastasis. Therefore, finding an effective cure for cancer needs to be solved urgently. Recently, the discovery of cancer stem cells (CSCs) provides a new orientation for cancer research and therapy. CSCs share main characteristics with stem cells and are able to generate an entire tumor. Besides, CSCs usually escape from current anti-cancer therapies, which is partly responsible for tumor recurrence and poor prognosis. microRNAs (miRNAs) belong to small noncoding RNA and regulate gene post-transcriptional expression. The dysregulation of miRNAs leads to plenty of diseases, including cancer. The aberrant miRNA expression in CSCs enhances stemness maintenance. In this review, we summarize the role of miRNAs on CSCs in the eight most common cancers, hoping to bridge the research of miRNAs and CSCs with clinical applications. We found that miRNAs can act as tumor promoter or suppressor. The dysregulation of miRNAs enhances cell stemness and contributes to tumor metastasis and therapeutic resistance via the formation of feedback loops and constitutive activation of carcinogenic signaling pathways. More importantly, some miRNAs may be potential targets for diagnosis, prognosis, and cancer treatments.

Glucan has been studied as a potential alternative to antibiotics for animals in recent years. The aim of this study was to evaluate the effect of dietary glucan on growth performance and gut health of weaning piglets, which is a water-soluble extracellular ꞵ-glucan produced by Agrobacterium sp. ZX09. A total of 108 weaned piglets (21 d of age; 6.05 ± 0.36 kg) were randomly assigned (6 pens/diet; 18 piglets/pen) to 3 dietary treatments consisting of a basal diet (control group) or the basal diet supplemented with 20 ppm olaquindox or 200 ppm glucan for 14 days, respectively. The results showed that piglets fed with glucan had greater (P < 0.05) body weight and average daily gain than piglets in control group. Piglets fed with glucan or antibiotic had greater villus height to crypt depth ratio on duodenum compared with control group (P < 0.05). The mRNA expression of Claudin-1 on duodenum or ileum was higher (P < 0.05) in glucan group than that on the other groups. The mRNA expression of TLR4, MYD88 and NFκB on jejunum were lower (P < 0.05) in glucan or antibiotic group than those in control group. Dietary supplementation with glucan tended to increase the IL-10 and SIgA concentration on ileum (0.05 < P < 0.1). Dietary supplementation with glucan tended to increase the total antioxidant capacity on jejunum (P = 0.093). In conclusion, 200 ppm glucan or 20 ppm olaquindox can improve the growth performance of weaning piglets. The glucan may can accelerate the growth of weaned piglets by improving gut health. This research will provide guidance for the olaquindox alternative on growing piglets.

Artificial abnormal microenvironment caused by microperfusion of l-glutamate (Glu) and Ca2+in the hippocampus results in neuron damage, which is closely related to cerebral ischemia. Ginsenoside Rb1, a compound from Panax notoginseng, was previously used to counter the artificial abnormal hippocampal environment in a microperfusion model. In addition, while the Akt/mTOR/PTEN signaling pathway has been shown to mediate neuronprotection in cerebral ischemia, whether this pathway is involved in the neuroprotection of ginsenoside Rb1 is unknown. Here SH-SY5Y cells exposed to OGD/R injury in treated with LY294002, ginsenoside Rb1, ginsenoside Rb1+ LY294002. Expressions of phosphorylation (P-)Akt/P-mTOR/P-PTEN (24 h after OGD/R) were detected by Western blotting. Effects were examined via the memory function of rats (by Morris water maze test), morphological changes in pyramidal cell (by histology), and mRNA expression (by qRT-PCR) and phosphorylation (P-) (by Western blotting and immunohistochemical staining) of Akt, P-mTOR, and P-PTEN in the hippocampus. The memory deficit of rats and pyramidal cellular necrosis and apoptosis in the CA1 region of hippocampus after microperfusion of Glu and Ca2+were dose dependently alleviated by ginsenoside Rb1.Moreover,Western blot showed that ginsenoside Rb1 increased the expressions of P-Akt, P-mTOR and reduced P-PTEN in vivo and vitro. Thus, the potent neuroprotection of ginsenoside Rb1 in artificial abnormal microenvironment is, at least partially, related to the activation of P-AKT/P-mTOR signaling pathway and inhibition of P-PTEN protein. Refereed/Peer-reviewed

Background/Aims: Intestinal morphology and the types of enterocytes are changed in piglets during the suckling period, but it is unclear whether these changes are associated with metabolic changes in epithelium. The present study was conducted to test the hypothesis that glucose, fatty acids, and amino acid metabolism in differentiated piglet enterocytes changed during suckling. Methods: Twenty-four piglets (Duroc × [Landrace × Yorkshire]) from 8 litters (3 piglets/litter) were selected. A single piglet from each litter was randomly selected and euthanized at days 7, 14, and 21. Differentiated enterocytes (DE) were isolated from their mid-jejunum. Isobaric tags for relative and absolute quantification and subsequent liquid chromatography-tandem mass spectrometry were used to identify and measure protein synthesis. Results: The results showed that various activities, including: cellular processes; metabolic processes; biological regulation; pigmentation; and, localization, in DEs changed during suckling. Metabolic process analyses revealed that protein expression related to glycolysis and citrate cycle was decreased from day 7 to day 14. The number of differentiated enterocytes of 21 d piglets increased compared to 7 d piglets. Most of the proteins involved in fatty acid and amino acids metabolism had decreased DE expression between day 7 and day 14. Some, but not all, detected proteins down-regulated in DEs of 21 day piglets compared to 7 day piglets. Conclusion: These results indicate that glucose, fatty acids, and amino acids metabolism changed during suckling. This may provide useful information for designing feed formulas and regulating piglet intestinal growth and development.

As a highly heterogeneous malignancy, breast cancer (BC) has become the most significant threat to female health. Distant metastasis and therapy resistance of BC are responsible for most of the cases of mortality and recurrence. Distant metastasis relies on an array of processes, such as cell proliferation, epithelial-to-mesenchymal transition (EMT), mesenchymal-to-epithelial transition (MET), and angiogenesis. Long non-coding RNA (lncRNA) refers to a class of non-coding RNA with a length of over 200 nucleotides. Currently, a rising number of studies have managed to investigate the association between BC and lncRNA. In this study, we summarized how lncRNA has dual effects in BC metastasis by regulating invasion, migration, and distant metastasis of BC cells. We also emphasize that lncRNA has crucial regulatory effects in the stemness and angiogenesis of BC. Clinically, some lncRNAs can regulate chemotherapy sensitivity in BC patients and may function as novel biomarkers to diagnose or predict prognosis for BC patients. The exact impact on clinical relevance deserves further study. This review can be an approach to understanding the dual effects of lncRNAs in BC, thereby linking lncRNAs to quasi-personalized treatment in the future.

Ethanolamine (Etn) contained in milk is the base constituent of phosphatidylethanolamine and is required for the proliferation of intestinal epithelial cells and bacteria, which is important for maintenance of the gut microbiome and intestinal development. The present study investigated the effect of Etn on intestinal function and microbiome using 21-d-old Sprague–Dawley rats treated with 0, 250, 500 and 1000 μmEtn in drinking water for 2 weeks immediately after weaning. Growth performance, intestinal morphology, antioxidant capacity and mucosal immunity, as well as gut microbiota community composition, were evaluated. Metagenomic prediction and metabolic phenotype analysis based on 16S RNA sequencing were also carried out to assess changes in metabolic functions. We found that weaned rats administered 500 μmEtn enhanced mucosal antioxidant capacity, as evidenced by higher superoxide dismutase and glutathione peroxidase levels in the jejunum (Pmshifted colonic microbial metabolic functions that are in favour of lipid- and sugar-related metabolism and biosynthesis. Etn also altered the metabolic phenotypes such as anaerobic microbial counts, and oxidative stress tolerance at over 250 µm. This is the first report for a role of Etn in modifying gut microbiota and intestinal functions. Our findings highlighted the important role of Etn in shaping gut microbial community and promotes intestinal functions, which may provide a better insight of breast-feeding to infant’s gut health.

Weaning stress results in gastrointestinal dysfunction and depressed performance in pigs. This study aimed to investigate the effect of soy oil, glucose, and glutamine on the growth and health of weaned piglets. Compared with those in the glutamine group, piglets in the glucose and soy oil groups had greater average daily gain, average daily feed intake, and gain: feed ratio from day 0 to 14, and gain: feed ratio for the overall period. There were no differences with regard to serum amino acids among the three groups on day 14, except glycine and threonine. The serum concentration of histidine, serine, threonine, proline, and cysteine was the highest in the glutamine group, while the content of glycine and lysine in the soy oil group on day 28 was the highest among all groups. Piglets fed with glutamine had greater serum glucose and creatinine on day 14, high-density lipoprotein on day 28, and serum IgG and IgM on day 28. Piglets in the glutamine group demonstrated lower serum total superoxide dismutase on day 14 and 28; however, they demonstrated higher total superoxide dismutase and total antioxidant capacity in the duodenum and ileum on day 14. Weaned pigs supplemented with glucose or soy oil demonstrate better growth performance possibly due to their enhanced feed intake, whereas those supplemented with glutamine may have improved immunity and intestinal oxidative capacity.

Cocaine- and amphetamine-regulated transcript (CART) peptide is a widely distributed neurotransmitter that attenuates cocaine-induced locomotor activity when injected into the nucleus accumbens (NAc). Our previous work first confirmed that the inhibitory mechanism of the CART peptide on cocaine-induced locomotor activity is related to a reduction in cocaine-enhanced phosphorylated Ca2+ /calmodulin-dependent protein kinaseIIα (pCaMKIIα) and the enhancement of cocaine-induced D3R function. This study investigated whether CART peptide inhibited cocaine-induced locomotor activity via inhibition of interactions between pCaMKIIα and the D3 dopamine receptor (D3R). We demonstrated that lentivirus-mediated gene transfer transiently increased pCaMKIIα expression, which peaked at 10 days after microinjection into the rat NAc shell, and induced a significant increase in Ca2+ influx along with greater behavioral sensitivity in the open field test after intraperitoneal injections of cocaine (15 mg/kg). However, western blot analysis and coimmunoprecipitation demonstrated that CART peptide treatment in lentivirus-transfected CaMKIIα-over-expressing NAc rat tissues or cells prior to cocaine administration inhibited the cocaine-induced Ca2+ influx and attenuated the cocaine-increased pCaMKIIα expression in lentivirus-transfected CaMKIIα-over-expressing cells. CART peptide decreased the cocaine-enhanced phosphorylated cAMP response element binding protein (pCREB) expression via inhibition of the pCaMKIIα-D3R interaction, which may account for the prolonged locomotor sensitization induced by repeated cocaine treatment in lentivirus-transfected CaMKIIα-over-expressing cells. These results provide strong evidence for the inhibitory modulation of CART peptide in cocaine-induced locomotor sensitization. Cover Image for this issue: doi: 10.1111/jnc.14187.

Psoriasis is a common, chronic, inflammatory skin disease that affects 2%–4% of the global population. Recent studies have shown that increased oxidative stress (OS) and T-cell abnormalities are central to the pathogenesis of this disease. The resulting reactive oxygen species (ROS) induces proliferation and differentiation of Th17/Th1/Th22 cells and inhibits the anti-inflammatory activities of regulatory T lymphocytes (Treg). Subsequent secretions of inflammatory cytokines, such as interleukin (IL)-17, IL-22, tumor necrosis factor alpha (TNF-α), and interferon-gamma (IFN-γ), and vascular endothelial growth factor (VEGF), stimulate keratinocyte proliferation and angiogenesis. Proanthocyanidins are a class of flavonoids from plants and fruits, and have various antioxidant, anti-inflammatory, and anti-angiogenic properties. Numerous reports have demonstrated therapeutic effects of proanthocyanidins for various diseases. Among clinical activities, proanthocyanidins suppress cell proliferation, prevent OS, and regulate Th17/Treg cells. Because the pathogenesis of psoriasis involves OS and T cells dysregulation, we reviewed the effects of proanthocyanidins on OS, Th17 and Treg cell activities, and keratinocyte proliferation and angiogenesis. Data from multiple previous studies warrant consideration of proanthocyanidins as a promising strategy for the treatment of psoriasis.

Early weaning results in intestinal dysfunction in piglets, while sulfur amino acids (SAA) are involved in improving intestinal functions. We tested a hypothesis that dietary supplementation with SAA can improve intestinal functions of weaning piglets and analyzed the effects of different dietary SAA levels on intestinal functions. A total of 80 piglets (Duroc × Landrace × Yorkshire) were weaned at 21 d of age and randomly assigned to one of the five diets that contained 0.53%, 0.63%, 0.74%, 0.85%, or 0.96% SAA, which corresponded to 70%, 85%, 100%, 115%, or 130% of the SAA:Lys ratio recommended by the National Research Council (2012). The 14 d feeding experiment involved 16 pens per diet and one piglet per pen. Eight randomly selected piglets from each treatment were euthanized for tissue sampling on day 7 and 14 post weaning. Supplementation with SAA led to a rise over time in G:F (linear, P = 0.001; quadratic, P = 0.001). Between day 0 and 14 of treatment, the jejunal crypt depth decreased (linear, P = 0.018; quadratic, P = 0.015), while that of the duodenal villus (linear, P = 0.049) and ileal villus width (linear, P = 0.029; quadratic, P = 0.034) increased. The activities of jejunal alkaline phosphatase (ALP) were quadratically increased (P = 0.040) from day 0 to 14 due to dietary SAA. Dietary SAA also elevated the activities of jejunal lactase (linear, P = 0.003; quadratic, P = 0.004), jejunal sucrase (linear, P = 0.032; quadratic, P = 0.027), and jejunal contents of glutathione (GSH) from day 0 to 7, as well as the activity of jejunal maltase (linear, P = 0.014; quadratic, P = 0.001) between day 0 and 14. During the first wk, dietary SAA linearly increased the amounts of intestinal-type fatty acid-binding protein (I-FABP) (P = 0.048) and SGLT-1 (P = 0.021) and linearly decreased the amount of GLUT2 (P = 0.029) proteins in the jejunum. The abundance of jejunal I-FABP (P = 0.044) and PEPT1 (P = 0.049) protein linearly increased from day 0 to 14 in response to this supplementation. These findings indicate that there is a dose-dependent response to dietary SAA on feed efficiency and intestinal parameters of weanling pigs.

Acne vulgaris has been postulated to have a gastrointestinal mechanism; however, little is known about gut microbiota dysfunction in this condition. The aim of this cross-sectional study was to investigate whether the gut microbiota is altered in acne. Faecal bacterial diversity was analysed in 43 patients with acne and 43 controls, using hypervariable tag sequencing of the V3–V4 region of the 16S rDNA gene. Distinct differences were found in microbial diversity between patients with acne and controls (Shannon diversity index (p = 0.009) and Simpson diversity index (p = 0.01)). At the phylum level, the abundance of Firmicutes was lower in the patient group, but that of Bacteroidiain was higher. The most significantly depleted taxa in acne were Clostridia, Clostridiales, Lachnospiraceae and Ruminococcaceae genera, which are potentially beneficial. In conclusion, patients with acne vulgaris have gut microbial dysbiosis; further study is needed to understand its role in the pathogenesis of acne.

This study aimed to assess oxidative stress and microbiota in pigs at different stocking densities. Markers for oxidative stress were investigated and gut bacteria identified. The pigs were randomly assigned to high-, medium- or low-density groups. The results showed that the superoxide dismutase (SOD) levels in the high- and low-density groups were lower than in the medium-density group. Glutathione peroxidase (GSH-Px) activity was significantly lower in the low-density group and highest in the medium-density group. We found no discrepancies between estimators of bacterial richness across the three groups. The jejunum and ileum were mainly occupied by Firmicutes and Proteobacteria of the classes Bacilli, Clostridia, Erysipelotrichia and Gammaproteobacteria. The ceacum was mainly occupied by Bacteroidetes and Firmicutes of the classes Bacteroidetes, Clostridia and Negativicutes. The results revealed that gut flora was not affected by stocking density. However, stocking density may influence oxidative stress.

Ferritin H can participate in the regulation of fish immunity. Tissue-specific analysis revealed that the highest expressions of Ferritin H in parental species were observed in spleen, while peaked level of Ferritin H mRNA in hybrid fish was observed in liver. In addition, A. hydrophila challenge could sharply enhance their Ferritin H mRNA expression in liver, kidney and spleen. To further investigate their roles in immune regulation, their Ferritin H fusion proteins were produced in vitro. Ferritin H fusion proteins could exhibit a direct binding activity to A. hydrophila and endotoxin in a dose-dependent manner, restrict dissemination of A. hydrophila to tissues and abrogate inflammatory cascades. Moreover, treatment with Ferritin H fusion proteins could reduce A. hydrophila-induced lipid peroxidation. These results indicated that Ferritin H in hybrid fish elicited a similar immune regulation of A. hydrophila-induced inflammatory signals in comparison with those of its parents.

Nitric oxide (NO), a ubiquitous intracellular and intercellular messenger molecule, plays vital roles in many physiological processes and is closely related to many diseases. Although a lot of fluorescent probes have been developed for real-time detection of NO successfully, the probes still suffer from poor tissue permeability and limited selectivity. In this study, a novel far-red fluorescent probe ZJL-3 based on rhodamine fluorescent dye was designed, synthesized, and used for NO determination. The probe contains a rhodamine as fluorophore and o-phenylenediamino as recognition unit. Upon addition of NO, the probe ZJL-3 showed an obvious far-red emission at 637 nm. The results of fluorescence spectrum experiments indicated that probe ZJL-3 exhibited desirable selectivity to NO. Furthermore, probe ZJL-3 has low cytotoxicity and was applied for the detection of exogenous and endogenous NO in RAW264.7 cells and C. elegans with satisfactory results.

Simultaneous nitrification/denitrification (SND) can efficiently deplete NH4+ by using air-exposed biocathode (AEB) in bioelectrochemical reactors. However, the fluctuation of wastewater adversely affects the functional biofilms and therefore the performance. In this work, four up-flow bioelectrochemical reactors (UBERs) with some novel inocula were investigated to improve domestic wastewater treatment. The UBERs exhibited favorable removal of chemical oxygen demand (COD, 95%), NH4+-N (99%), and total nitrogen (TN, 99%). The maximum of current (2.7 A/m3), power density (136 mW/m3) and coulombic efficiency (20.5%) were obtained. Cyclic voltammetry analysis showed all the electrodes were of diversified catalytic reactions. Illumina pyrosequencing showed the predominant Ignavibacterium, Thauera, Nitrosomonas, Geminicoccus and Nitrospira were in all electrodes, contributing functional biofilms performing SND, comammox, and bioelectrochemical reactions. FAPROTAX analysis confirmed twenty-one functional groups with obvious changes related to chemoheterotrophy, respiration/oxidation/denitrification of nitrite and nitrate. Comfortingly, such novel diversified consortia in UBERs enhance the microbial metabolisms to treat domestic wastewater.

Bacterial LPS is a heat-stable endotoxin and wall components of gram negative bacteria, which can exhibit a toxicological effect on physiology and biochemical activities of fish. In this study, we investigated the effect of LPS exposure on cell viability, oxidative stress, caspase activity and immune-related gene expressions in cultured fin cell lines of red crucian carp, white crucian carp and their hybrid offspring. LPS stimulation could reduce fish cell viability, whereas gene expression levels and promoter activities in inflammatory signals increased dramatically. Moreover, enhanced levels of intracellular oxidative stress and decreased levels of mitochondrial membrane potential (MMP) were observed in LPS-induced fish cells. N-Acetyl-L-cysteine (NAC) could alleviate LPS-stimulated reactive oxygen species (ROS) generation and caspase-3 activity in fish cells. These results suggested that ROS-mediated cytotoxic stress was involved in LPS-induced inflammation and mitochondrial damage in cultured fish cells.

Epithelial–mesenchymal transition (EMT) is a biological process of phenotypic transition of epithelial cells that can promote physiological development as well as tissue healing and repair. In recent years, cancer researchers have noted that EMT is closely related to the occurrence and development of tumors. When tumor cells undergo EMT, they can develop enhanced migration and local tissue invasion abilities, which can lead to metastatic growth. Nevertheless, two researches in NATURE deny its necessity in specific tumors and that is discussed in this review. The degree of EMT and the detection of EMT-associated marker molecules can also be used to judge the risk of metastasis and to evaluate patients’ prognosis. MicroRNAs (miRNAs) are noncoding small RNAs, which can inhibit gene expression and protein translation through specific binding with the 3′ untranslated region of mRNA. In this review, we summarize the miRNAs that are reported to influence EMT through transcription factors such as ZEB, SNAIL, and TWIST, as well as some natural products that regulate EMT in tumors. Moreover, mutual inhibition occurs between some transcription factors and miRNAs, and these effects appear to occur in a complex regulatory network. Thus, understanding the role of miRNAs in EMT and tumor growth may lead to new treatments for malignancies. Natural products can also be combined with conventional chemotherapy to enhance curative effects.

The small intestine is not only an organ for food digestion and nutrient absorption but also an integral part of the immune and endocrine systems. Differentiation of enterocytes plays an important role in the damage repair mechanism after immune response elicitation by the intestine, for restoring the intestinal barrier function and homeostasis. Recently, research related to self-renewal, differentiation, and regulation of the intestinal epithelial crypt stem cells has been developing rapidly. In this review, we attempt to sum up recent studies related to the expression pattern of genes and proteins along the crypt-villus axis, and the effect of signaling pathways, transcription factors, and epigenetic modifications on the differentiation of crypt stem cells. We also examine the mechanisms by which nutritional factors influence the differentiation and damage repair processes of the intestinal epithelial cells. This review could provide valuable theoretical framework in nutritional and pharmacological aspects and guidance for intervention and treatment of intestinal damage and related diseases.

Weaning affects intestinal development in mammals, and pigs are often used as an animal model for analyzing the metabolism and physiology of differentiating middle villus intestinal epithelial cells (DIECs). To assess the impact of weaning on the proteomes of DIECs, we weaned piglets on day 14 and collected their jejunum on days 0, 1, 3, 5, and 7 after weaning. Levels of proteins associated with (a) Golgi vesicle transport and protein glycosylation; (b) monosaccharide, lipid, phospholipid, and nucleotide metabolism; and (c) Krebs cycle and respiratory electron transport chain were decreased in DIECs after weaning. These results indicate that weaning decreases nutrient metabolism in DIECs. Moreover, these results suggest that dietary interventions (e.g., supplementation with functional amino acids) are required to counter these changes.

// Jie Yin 1, 2, * , Miaomiao Wu 1, * , Yuying Li 1, 2, * , Wenkai Ren 1, 2 , Hao Xiao 1 , Shuai Chen 1, 2 , Chunyong Li 1 , Bie Tan 1 , Hengjia Ni 1 , Xia Xiong 1 , Yuzhe Zhang 1 , Xingguo Huang 3, 4 , Rejun Fang 3 , Tiejun Li 1, 4 , Yulong Yin 1, 4, 5 1 Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Hunan Provincial Engineering Research Center of Healthy Livestock, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan 410125, China 2 University of Chinese Academy of Sciences, Beijing 100039, China 3 Department of Animal Science, Hunan Agriculture University, Changsha, Hunan 410125, China 4 Hunan Co-Innovation Center of Animal Production Safety, Changsha, Hunan 410128, China 5 College of Animal Science of South China Agricultural University, Guangzhou 510642, China * These authors contributed equally to this work Correspondence to: Tiejun Li, email: tjli@isa.ac.cn Yulong Yin, email: yinyulong@isa.ac.cn Keywords: H 2 O 2 , TLRs, apoptosis, mitochondrial respiration, piglet Received: September 28, 2016 Accepted: November 24, 2016 Published: December 09, 2016 ABSTRACT In this study, expressions of toll-like receptors (TLRs) and apoptosis-related genes in piglets and mitochondrial respiration in intestinal porcine epithelial cells were investigated after hydrogen peroxide (H 2 O 2 ) exposure. The in vivo results showed that H 2 O 2 influenced intestinal expressions of TLRs and apoptosis related genes. H 2 O 2 treatment (5% and 10%) downregulated uncoupling protein 2 (UCP2) expression in the duodenum ( P < 0.05), while low dosage of H2O2 significantly increased UCP2 expression in the jejunum ( P < 0.05). In IPEC-J2 cells, H 2 O 2 inhibited cell proliferation ( P < 0.05) and caused mitochondrial dysfunction via reducing maximal respiration, spare respiratory, non-mitochondrial respiratory, and ATP production ( P < 0.05). However, 50 uM H 2 O 2 significantly enhanced mitochondrial proton leak ( P < 0.05). In conclusion, H 2 O 2 affected intestinal TLRs system, apoptosis related genes, and mitochondrial dysfunction in vivo and in vitro models. Meanwhile, low dosage of H 2 O 2 might exhibit a feedback regulatory mechanism against oxidative injury via increasing UCP2 expression and mitochondrial proton leak.

The present study was conducted to evaluate the effects of glucose, soya oil or glutamine on jejunal morphology, protein metabolism and protein expression of the mammalian target of rapamycin complex 1 (mTORC1) signalling pathway in jejunal villus or crypt compartment of piglets. Forty-two 21 d-weaned piglets were randomly allotted to one of the three isoenergetic diets formulated with glucose, soya oil or glutamine for 28 d. On day 14 or 28, the proteins in crypt enterocytes were analysed with isobaric tags for relative and absolute quantification and proteins involved in mTORC1 signalling pathway in villus or crypt compartment cells were determined by Western blotting. Our results showed no significant differences (P > 0·05) in jejunal morphology among the three treatments on day 14 or 28. The differentially expressed proteins mainly took part in a few network pathways, including antimicrobial or inflammatory response, cell death and survival, digestive system development and function and carbohydrate metabolism. On day 14 or 28, there were higher protein expression of eukaryotic initiation factor-4E binding protein-1 in jejunal crypt compartment of piglets supplemented with glucose or glutamine compared with soya oil. On day 28, higher protein expression of phosphor-mTOR in crypt compartment was observed in piglets supplemented with glucose compared with the soya oil. In conclusion, the isoenergetic glucose, soya oil or glutamine did not affect the jejunal morphology of piglets; however, they had different effects on the protein metabolism in crypt compartment. Compared with soya oil, glucose or glutamine may be better energy supplies for enterocytes in jejunal crypt compartment.

Diffuse large B-cell lymphoma (DLBCL) is a clinically aggressive B-cell non-Hodgkin’s lymphoma (NHL) with high treatment difficulty and high relapse rate. The bromodomain and extra-terminal (BET) proteins play significant roles in supporting the transcription of known DLBCL oncogene MYC, which provides a way for the development of targeted therapeutic agents to address this kind of malignant tumor. Here, we reported a novel benzoxazinone derivative YLT-LL-11 as potential BRD4 inhibitor and further investigated the biological activities against DLBCL. The results suggested that YLT-LL-11 inhibited cell growth against a panel of human hematopoietic malignancies cell lines in a dose- and time-dependent manner. In addition, flow cytometry and Western blotting assays showed that YLT-LL-11 inhibited the proliferation of a DLBCL cell line OCI-LY10 via inducing G0/G1 cell cycle arrest with regulation of the cyclin-dependent kinases (CDKs) expression. Furthermore, YLT-LL-11 facilitated OCI-LY10 cell apoptosis by up-regulation of pro-apoptotic protein BAX and down-regulation of anti-apoptotic protein Bcl-2. Taken together, these results revealed that BRD4 inhibitor YLT-LL-11 can down-regulate growth-associated transcription factors MYC in DLBCL thus resulted in cell growth inhibition and apoptosis.

Purpose Type 1 diabetes mellitus (T1DM) is characterized by irreversible islet β cell destruction. Accumulative evidence indicated that Cdc42 and Wnt/β-catenin signaling both play a critical role in the pathogenesis and development of T1DM. Further, bio-molecular mechanisms in adipose-derived mesenchymal stem cells (ADSCs)-derived insulin-producing cells (IPCs) remain largely unknown. Our aim was to investigate the underlying mechanism of Cdc42/Wnt/β-catenin pathway in ADSC-derived IPCs, which may provide new insights into the therapeutic strategy for T1DM patients. Methods ADSC induction was accomplished with DMSO under high-glucose condition. ML141 (Cdc42 inhibitor) and Wnt-3a (Wnt signaling activator) were administered to ADSCs from day 2 until the induction finished. Morphological changes were determined by an inverted microscope. Dithizone staining was employed to evaluate the induction of ADSC-derived IPCs. qPCR and Western blotting were employed to measure the mRNA and protein expression level of islet cell development-related genes and Wnt signaling-related genes. The proliferation ability of ADSC-derived IPCs was also detected with a cell counting kit (CCK) assay. The expression and secretion of Insulin were detected with immunofluorescence test and enzyme-linked immunosorbent assay (ELISA) respectively. Results During induction, morphological characters of ADSCs changed into spindle and round shape, and formed islet-line cell clusters, with brown dithizone–stained cytoplasm. Expression levels of islet cell development-related genes were up-regulated in ADSC-derived IPCs. Wnt-3a promoted Wnt signaling markers and islet cell development-related gene expression at mRNA and protein levels, while ML141 played a negative effect. Wnt-3a promoted ADSC-derived IPC proliferation and glucose-stimulated insulin secretion (GSIS), while ML141 played a negative effect. Conclusion Our research demonstrated that DMSO and high-glucose condition can induce ADSCs into IPCs, and Wnt signaling promotes the induction. Cdc42 may promote IPC induction, IPC proliferation and insulin secretion via Wnt/β-catenin pathway, meaning that Cdc42 may be regarded as a potential target in the treatment of T1DM.

Breast cancer is the most common type of invasive cancer in females and metastasis is one of the major causes of breast cancer-associated mortality. Following detachment from the primary site, disseminated tumor cells (DTCs) enter the bloodstream and establish secondary colonies during the metastatic process. An increasing amount of studies have elucidated the importance of Notch signaling in breast cancer metastasis; therefore, the present review focuses on the mechanisms by which Notch contributes to the occurrence of breast cancer DTCs, increases their motility, establishes interactions with the tumor microenvironment, protects DTCs from host surveillance and finally facilitates secondary colonization. Identification of the underlying mechanisms of Notch-associated breast cancer metastasis will provide additional insights that may contribute towards the development of novel Notch-targeted therapeutic strategies, which may aid in reducing metastasis, culminating in an improved patient prognosis.

Pemphigus vulgaris (PV) is an autoimmune disease characterized by the production of IgG autoantibodies owing to an imbalance in the Th1/Th2 and Th17/Tregs cell pathways. The role of gut microbiota in the development of immune system and autoimmune diseases has been unraveled in the last two decades. However, data pertaining to gut microbiota of PV patients is largely lacking. We aimed to compare the gut microbiota of PV patients and healthy controls and assessed potential correlation with circulating cytokines of Th1/Th2/Th17 cell. Faecal bacterial diversity was analysed in 18 PV patients and 14 age- and gender-matched healthy individuals using hypervariable tag sequencing of the V3-V4 region of the 16S rRNA gene. Plasma levels of 20 inflammatory cytokines were assessed using the Luminex screening system. As a result, we identified 10 differentially abundant taxa between patients and controls. At the genera level, Lachnospiracea_incertae_sedis and Coprococcus decreased, while Granulicatella, Flavonifractor enriched in PV. Plasma levels of C5a, interleukin (IL)-2R, IL-6, IL-8, IL-7, IL-1β, IL17A, IL-5 and IL-21 were significantly increased in PV Flavonifractor exhibited a positive correlation with C5a, IL-6, IL-8, IL-7, IL-1β, IL17A and IL-21. Lachnospiracea_incertae_sedis and Coprococcus showed a negative correlation with IL-17A. Our results are consistent with the hypothesis that PV patients have gut microbial dysbiosis which might contribute to the immune disorder and the development of PV.

Background Brain-derived neurotrophic factor (BDNF) is one of the proteins that contributes to the survival, growth, maintenance of neurons, and plays important roles in the pathophysiology of depression. It has been reported that depression is closely associated with the pathogenesis of acne vulgaris disease. But, there is no report of serum BDNF levels in patients with acne vulgaris. The study aimed to determine the potential association between BDNF and depressive symptoms in young adults with acne vulgaris. Methods In this analytical cross-sectional study, the serum BDNF levels were measured in peripheral blood samples of 20 consecutive acne vulgaris patients with depression and 98 consecutive acne vulgaris patients without depression and also compared it with a 59 healthy control group by using a ELISA. The potential correlation between the BDNF levels, interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), and depressive symptoms such as nine-item patient health questionnaire (PHQ-9) and Athens insomnia scale (AIS) were evaluated with multivariate logistic regression analysis. Results Our results showed that levels of BDNF expression were lower in consecutive acne vulgaris patients when compared with healthy control (P 0.05). Similarly, the overall area under the curve of receiver operating characteristic was 0.82, indicating the highly conserving of serum BDNF levels as an biomarker for screening of depression in young adults with acne vulgaris (72% sensitivity and 85% specificity). Conclusion Serum BDNF levels were decreased and negatively associated with depressive symptoms in young Chinese adults with acne vulgaris. Electronic supplementary material The online version of this article (10.1186/s12888-019-2182-8) contains supplementary material, which is available to authorized users.

Human breast cancer is one of the most frequent cancer diseases and causes of death among female population worldwide. It appears at a high incidence and has a high malignancy, mortality, recurrence rate and poor prognosis. Caveolin-1 (Cav1) is the main component of caveolae and participates in various biological events. More and more experimental studies have shown that Cav1 plays a critical role in the progression of breast cancer including cell proliferation, apoptosis, autophagy, invasion, migration and breast cancer metastasis. Besides, Cav1 has been found to be involved in chemotherapeutics and radiotherapy resistance, which are still the principal problems encountered in clinical breast cancer treatment. In addition, stromal Cav1 may be a potential indicator for breast cancer patients’ prognosis. In the current review, we cover the state-of-the-art study, development and progress on Cav1 and breast cancer, altogether describing the role of Cav1 in breast cancer progression and application in clinical treatment, in the hope of providing a basis for further research and promoting CAV1 gene as a potential target to diagnose and treat aggressive breast cancers.

Mature brain-derived neurotrophic factor (mBDNF) has neuroprotection in cerebral ischemia. Conversely, the precursor of brain derived neurotrophic factor (proBDNF) has the opposite function to its mature form, inducing apoptosis. However, whether the neuroprotection of Panax notoginsenoside Rb1 (PNS-Rb1) on ischemic stroke is due to, at least partially, its modulation of suppressing proBDNF/P75NTR/sortilin or upregulation of mBDNF is not clear. To test this hypothesis, rats induced by photothrombotic stroke were treated with PNS-Rb1 100 mg/kg or nimodipine 1 mg/kg twice a day until 3, 7, and 14 days.Our data indicate that PNS-Rb1 significantly reduced cerebral infarction rate, proBDNF/P75NTR/sortilin, and plasminogen activator inhibitor-1 (PAI-1) protein levels, and improved sensorimotor dysfunctions induced by ischemic stroke, upregulation of BDNF/TrkB levels, and its processing enzymes (tissue plasminogen activator, tPA) in a time-dependent manner. Taken together, our findings indicate that the improvement of sensorimotor dysfunctions by PNS-Rb1 following ischemic stroke is made, at least partially, by activating the BDNF/TrkB and inhibiting proBDNF/sortilin/P75NTR. Refereed/Peer-reviewed

Strategies to battle malignant tumors have always been a dynamic research endeavour. Although various vehicles (e.g., chemotherapeutic therapy, radiotherapy, surgical resection, etc.) are used for skin cancer management, they mostly remain unsatisfactory due to the complex mechanism of carcinogenesis. Increasing evidence indicates that redox imbalance and aberrant reactive oxygen species (ROS) are closely implicated in the oncogenesis of skin cancer. When ROS production goes beyond their clearance, excessive or accumulated ROS could disrupt redox balance, induce oxidative stress, and activate the altered ROS signals. These would damage cellular DNA, proteins, and lipids, further leading to gene mutation, cell hyperproliferation, and fatal lesions in cells that contribute to carcinogenesis in the skin. It has been known that ROS-mediated skin carcinogenesis involves multiple ways, including modulating related signaling pathways, changing cell metabolism, and causing the instability of the genome and epigenome. Nevertheless, the exact role of ROS in skin cancer has not been thoroughly elucidated. In spite of ROS inducing skin carcinogenesis, toxic-dose ROS could trigger cell death/apoptosis and, therefore, may be an efficient therapeutic tool to battle skin cancer. Considering the dual role of ROS in the carcinogenesis and treatment of skin cancer, it would be essential to clarify the relationship between ROS and skin cancer. Thus, in this review, we get the related data together to seek the connection between ROS and skin carcinogenesis. Besides, strategies basing on ROS to fight skin cancer are discussed.

Background. Diabetes is a progressive metabolic disease characterized by hyperglycemia. Functional impairment of islet β cells can occur to varying degrees. This impairment can initially be compensated for by proliferation and metabolic changes of β cells. Cell division control protein 42 (Cdc42) and the microRNA (miRNA) miR-29 have important roles in β-cell proliferation and glucose-stimulated insulin secretion (GSIS), which we further explored using the mouse insulinoma cell line MIN6. Methods. Upregulation and downregulation of miR-29a and Cdc42 were accomplished using transient transfection. miR-29a and Cdc42 expression was detected by real-time PCR and western blotting. MIN6 proliferation was detected using a cell counting kit assay. GSIS under high-glucose (20.0 mM) or basal-glucose (5.0 mM) stimulation was detected by enzyme-linked immunosorbent assay. The miR-29a binding site in the Cdc42 mRNA 3′-untranslated region (UTR) was determined using bioinformatics and luciferase reporter assays. Results. miR-29a overexpression inhibited proliferation (P<0.01) and GSIS under high-glucose stimulation (P<0.01). Cdc42 overexpression promoted proliferation (P<0.05) and GSIS under high-glucose stimulation (P<0.05). miR-29a overexpression decreased Cdc42 expression (P<0.01), whereas miR-29a downregulation increased Cdc42 expression (P<0.01). The results showed that the Cdc42 mRNA 3′-UTR is a direct target of miR-29a in vitro. Additionally, Cdc42 reversed miR-29a-mediated inhibition of proliferation and GSIS (P<0.01). Furthermore, miR-29a inhibited β-catenin expression (P<0.01), whereas Cdc42 promoted β-catenin expression (P<0.01). Conclusion. By negatively regulating Cdc42 and the downstream molecule β-catenin, miR-29a inhibits MIN6 proliferation and insulin secretion.

Cdc42, a member of the Rho GTPases family, is involved in the regulation of several cellular functions including cell cycle progression, survival, transcription, actin cytoskeleton organization and membrane trafficking. Diabetes is a chronic and metabolic disease, characterized as glycometabolism disorder induced by insulin deficiency related to β cell dysfunction and peripheral insulin resistance (IR). Diabetes could cause many complications including diabetic nephropathy (DN), diabetic retinopathy and diabetic foot. Furthermore, hyperglycemia can promote tumor progression and increase the risk of malignant cancers. In this review, we summarized the regulation of Cdc42 in insulin secretion and diabetes-associated diseases. Organized researches indicate that Cdc42 is a crucial member during the progression of diabetes, and Cdc42 not only participates in the process of insulin synthesis but also regulates the insulin granule mobilization and cell membrane exocytosis via activating a series of downstream factors. Besides, several studies have demonstrated Cdc42 as participating in the pathogenesis of IR and DN and even contributing to promote cancer cell proliferation, survival, invasion, migration, and metastasis under hyperglycemia. Through the current review, we hope to cast light on the mechanism of Cdc42 in diabetes and associated diseases and provide new ideas for clinical diagnosis, treatment, and prevention.

In the published article, the images for Actin in Figs. 4a, 5a, 6a, and 6c were incorrectly presented.

Background: Acute myeloid leukemia (AML) and myelodysplasia (MDS) are usually associated with poor outcomes, especially in high-risk AML/MDS. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable option for patients suffering from high-risk AML/MDS. However, there were still many patients relapsed after allo-HSCT, especially for some patients are MRD positive before transplantation. Novel therapy to prevent replase is urgently needed. Both BCL-2 inhibitor, venetoclax (VEN) and hypomethylating agent, decitabine (DEC) possess significant antitumor activity effects against AML/MDS. Administration DEC has been shown to ameliorate GVHD and boost GVL post-transplantation. Several clinical trials have also shown that venetoclax plus decitabine can be a safety and effective salvage treatment for patients with AML/MDS relapsing after allo-HSCT. We therefore conducted a prospective study (ChiCTR1900025374) to exam the tolerability and efficacy of a maintenance therapy low-dose decitabine (LDEC) plus VEN to prevent relapse after allo-HSCT for MRD positive high-risk AML/MDS patients. To our knowledge, this is the first report of venetoclax combined decitabine in this setting. Methods: Six patients with MRD positive high-risk AML (n=5) /MDS(n=1) post transplantation were recruited. Around day 100 post transplantation, all patients received LDEC (15mg/m2 for 3 days) followed by VEN (200mg) on day 1 to 21. Two months is a cycle. The primary end points of this study were rates of Overall survival (OS) and event-free survival (EFS). The secondary endpoints included adverse events (AEs), incidence of cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), incidences of acute GVHD (aGVHD) and chronic GVHD (cGVHD) and incidences of viral infection after allo-HSCT. Survival outcomes were analyzed using Kaplan-Meier analysis Results: Two of the six patients were partial remission (PR) before transplantation, and the remaining 4 patients were MRD+ before transplantation. The median follow-up was 16 (11-26.5) months. Both 2-year OS and 2-year EFS were 83%. The median 2-year EFS time was 16(9-26.5) months, and five patients still EFS alive at the time of this writing. The 2-year cumulative incidence of relapse after LDEC+VEN was 17% and 2-year non-relapse mortality was 0%. No tumor lysis syndrome (TLS) was observed. The most common AEs were neutropenia, anemia, thrombocytopenia, neutropenic fever, and fatigue. Grade 2 or 3 adverse events were observed in 33% (2/6). No grade>3 AEs were observed. Acute (any grade) and chronic (limited or extensive) graft-versus-host disease occurred in 67% and 17% of patients, respectively. The 2-year cumulative incidence of CMV viremia and EBV viremia were 33.3% and 16.7%, respectively. Conclusion: We conclude LDEC+VEN can be administered safely after allo-HSCT, without evidence for increased incidence of GVHD, and this combination demonstrates decreased relapse for MRD positive high-risk AML/MDS patients. This novel maintenance therapy may be a promising way to prevent replase for MRD positive high-risk AML/MDS patients, and the clinical benefits need to be assessed in a comparative prospective trial. Figure Disclosures No relevant conflicts of interest to declare.

The present experiment was conducted to determine the effects of chito-oligosaccharide (COS) on intestinal mucosal amino acid profiles and alkaline phosphatase (ALP) activities, and serum biochemical variables in weaned piglets. A total of 24 piglets (BW=7.82±0.21 kg) were weaned at 25 d of age and were blocked by body weight, sex, and litter and randomly assigned to one of two treatments consisting of a basal diet (CON) or the basal diet supplemented with 30 mg/kg COS for a 14-d period. Each treatment was assigned to 6 pens (2 piglets/pen) and 6 piglets (3 males and 3 females) were randomly selected from each treatment (1 pigs/pen) for blood and tissue sampling. Dietary supplementation with COS increased ( P P P P P P P