Alleviating effect of methionine on intestinal mucosal injury induced by heat stress.

Climate change is an increasing concern of stakeholders worldwide. The intestine is severely impacted by the heat stress. This study aimed to investigate the alleviating effects of methionine on the intestinal damage induced by heat stress in mice. The mice were divided into four groups: control group (C), methionine deficiency group (MD), methionine + heat stress group (MH), and methionine deficiency + heat stress group (MDH). Histopathological techniques, PAS-Alcian blue staining, immunohistochemistry method, biochemical quantification method, ELISA, and micro method were used to study the changes in the intestinal mucosal morphology, the number of goblet cells, the expression of tight junction proteins, the peroxide product contents and antioxidant enzyme activities, the intestinal mucosal damage, the content of immunoglobulins and HSP70, the activity of Na+/K+-ATPase. The results showed that methionine can improve intestinal mucosal morphology (increase the villi height, V/C value, and muscle layer thickness, decrease crypt depth), increase the expression of tight junction proteins (Claudin-1, Occludin, ZO-1) and the content of DAO, decrease the content of intestinal mucosa damage markers (ET, FABP2) and peroxidation products (MDA), increase the activity of antioxidant enzymes (GR, GSH-Px, SOD), the number of goblet cells, the contents of immunoglobulins (sIgA, IgA, IgG, IgM) and stress protein (HSP70), and the activity of Na+/K+-ATPase. It is suggested that methionine can alleviate intestinal damage in heat-stressed mice.

Protective effect of methionine on the intestinal oxidative stress and microbiota change induced by nickel.

Nickel is a common heavy metal pollutant in industrial areas and can cause oxidative damage to human and animal organs. As an essential amino acid with antioxidant function, methionine (Met) may protect the body from the oxidative stress induce by nickel, however, there is not enough research to study in this aspect. The study aims at investigating the effect of Met on the nickel-induced intestinal oxidative stress and further detected the gut microbiota changes. Mice were gavaged with quantitative NiCl2 (1.6 mg/ml, 0.25 ml) and fed with different doses of methionine in each group. The contents of intestinal oxidation product and antioxidant enzymes were determined by different biochemical quantitative methods, and the data showed that NiCl2 increased the content of intestinal oxidation product (MDA), and the antioxidant enzymes (GSH-Px, GR, SOD and CAT) were decreased. But this situation was alleviated in the group fed with additional methionine solution (0.5 mg/ml). In addition, we detected changes in the gut microbiota using high-throughput sequencing, the results showed that the structure of intestinal flora was disturbed by NiCl2, but methionine restored the germs with antioxidant capacity. Based on the results, we speculate that methionine can alleviate the impact of NiCl2 on the intestinal by enhancing the activity of antioxidant enzymes and the number of gut bacteria with anti-oxidation, suggesting that methionine as a nutritional additive may have the potential to treat nickel poisoning.

Preventive effects of Lactobacillus johnsonii on the renal injury of mice induced by high fluoride exposure: Insights from colonic microbiota and co-occurrence network analysis.

Fluoride (F) exposure was widely reported to be associated with renal diseases. Since absorbed F enters the organism from drinking water mostly through the gastrointestinal tract, investigating changes of gut microbes may have profound implications for the prevention of chronic F exposure because increasing evidence supported the existence of the gut-kidney axis. In the present study, we aimed to explore the potential positive effects of probiotics on high F exposure-induced renal lesions and dysfunction in mice by the modulation of the colonic microbiota. Mice were fed with normal (Ctrl group) or sodium-fluoride (F and Prob groups; 100 mg/L sodium fluoride (NaF)) drinking water with or without Lactobaillus johnsonii BS15, a probiotic strain proven to be preventive for F exposure. Mice fed with sodium-fluoride drinking water alone exhibited renal tissue damages, decreased the renal antioxidant capability and dysfunction. In contrast, L. johnsonii BS15 reversed these F-induced renal changes. 16S rRNA gene sequencing shows that L. johnsonii BS15 alleviated the increased community diversity (Shannon diversity) and richness index (number of observed features) as well as the distured structure of colon microbiota in F-exposed mice. A total of 13 OTUs with increased relative abundance were identified as the keystone OTUs in F-exposed mice based on the analysis of degree of co-occurrence and abundance of OTUs. Moreover, Spearman's rank correlation shows that the 13 keystone OTUs had negative effect on renal health and intestinal integrity. L. johnsonii BS15 reversed four of keystone OTUs (OTU 5, OTU 794, OTU 1035, and OTU 868) changes which might be related to the underlying protected mechanism of L. johnsonii BS15 against F-induced renal damages.

Effect of dietary NiCl2 on the cell cycle of cecal tonsil in the chicken broiler.

Although the effects of nickel chloride (NiCl2) on the immune system have long been recognized, little is known about the effects of nickel (II) on the cell cycle and related signaling events in immune organs, such as cecal tonsil, a key immune organ of chicken. In the present study, we investigated the effect of NiCl2 on the cell cycle of cecal tonsil. The cell cycle was detected by the methods of flow cytometry (FCM), quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). The results showed that dietary NiCl2 in excess of 300 mg/kg caused the G2/M cell cycle arrest and the reduction of cell proportion at S phase of the cecal tonsil. The G2/M cell cycle arrest was accompanied by the up-regulation of p53, p21 protein expression and mRNA expression, and down-regulation of cyclinB and proliferating cell nuclear antigen (PCNA) protein expression and mRNA expression. The data suggested that the cells' (mainly the T lymphocytes) proliferation in the cecal tonsil was inhibited by the high dietary NiCl2.

Effect of methionine deficiency on oxidative stress and apoptosis in the small intestine of broilers.

The aim of this study was to investigate the effects of methionine (Met) deficiency on antioxidant functions (in the duodenal, jejunal and ileal mucosa) and apoptosis in the duodenum, jejunum and ileum of broiler chickens. A total of 120 one-day-old Cobb broilers were divided into two groups and fed a Metdeficient diet and a control diet, respectively, for six weeks. The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), the ability to inhibit hydroxyl radicals, and glutathione (GSH) content were significantly decreased in the Met-deficient group compared to the control. In contrast, malondialdehyde (MDA) content was significantly higher in the Met-deficient group. As measured by terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'- triphosphate dUTP nick end-labelling (TUNEL) and flow cytometry (FCM), the percentages of apoptotic cells were significantly increased. In conclusion, dietary Met deficiency can cause oxidative stress and then induce increased apoptosis in the intestine. Oxidative stress contributes to intestinal apoptosis. This results in the impairment of local intestinal mucosal immunity due to oxidative stress and apoptosis in the small intestine. The results of this study provide new experimental evidence for understanding the negative effects of Met deficiency on mucosal immunity or the functions of other immune tissues.

Toxicological effects of nickel chloride on the cytokine mRNA expression and protein levels in intestinal mucosal immunity of broilers.

The purpose of this study was to examine the toxicological effects of nickel chloride (NiCl2 ; 300, 600, and 900 mg kg(-1) diet) on the cytokine mRNA expression and protein levels in the intestinal mucosa and cecal tonsil, and on the ileac and cecal tonsil T cells in broilers by the methods of qRT-PCR, flow cytometry and ELISA for 42 days. Results showed that the IL-2, IL-6, IL-10, IL-17, IFN-γ, and TNF-α (LITAF) cytokine mRNA expression and protein levels were lower (P < 0.05 or P < 0.01) and the percentages of T-cell subsets were also lower in the 300, 600, and 900 mg kg(-1) groups than in the control group. It was concluded that dietary NiCl2 in excess of 300 mg kg(-1) could reduce cytokine mRNA expression and protein levels in the intestinal mucosa and cecal tonsil, and the percentages of ileac and cecal tonsil T-cell subsets. Decreasing in cytokine mRNA expression and protein levels of intestinal mucosa and cecal tonsil induced by NiCl2 was closely related to the reduction of T-cell population. Thus, the abnormal expression of these cytokines impacts the intestinal mucosal immune function by the pathways of reducing of lymphocyte population and activation. Also, this study first proved that NiCl2 at higher levels has the toxicological effects on intestinal mucosal immunity.

Research Advances on Pathways of Nickel-Induced Apoptosis.

High concentrations of nickel (Ni) are harmful to humans and animals. Ni targets a number of organs and produces multiple toxic effects. Apoptosis is important in Ni-induced toxicity of the kidneys, liver, nerves, and immune system. Apoptotic pathways mediated by reactive oxygen species (ROS), mitochondria, endoplasmic reticulum (ER), Fas, and c-Myc participate in Ni-induced cell apoptosis. However, the exact mechanism of apoptosis caused by Ni is still unclear. Understanding the mechanism of Ni-induced apoptosis may help in designing measures to prevent Ni toxicity.

Modulation of the PI3K/Akt Pathway and Bcl-2 Family Proteins Involved in Chicken's Tubular Apoptosis Induced by Nickel Chloride (NiCl2).

Exposure of people and animals to environments highly polluted with nickel (Ni) can cause pathologic effects. Ni compounds can induce apoptosis, but the mechanism and the pathway of Ni compounds-induced apoptosis are unclear. We evaluated the alterations of apoptosis, mitochondrial membrane potential (MMP), phosphoinositide-3-kinase (PI3K)/serine-threonine kinase (Akt) pathway, and Bcl-2 family proteins induced by nickel chloride (NiCl2) in the kidneys of broiler chickens, using flow cytometry, terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate dUTP nick end-labeling (TUNEL), immunohistochemstry and quantitative real-time polymerase chain reaction (qRT-PCR). We found that dietary NiCl2 in excess of 300 mg/kg resulted in a significant increase in apoptosis, which was associated with decrease in MMP, and increase in apoptosis inducing factor (AIF) and endonuclease G (EndoG) protein and mRNA expression. Concurrently, NiCl2 inhibited the PI3K/Akt pathway, which was characterized by decreasing PI3K, Akt1 and Akt2 mRNA expression levels. NiCl2 also reduced the protein and mRNA expression of anti-apoptotic Bcl-2 and Bcl-xL and increased the protein and mRNA expression of pro-apoptotic Bax and Bak. These results show that NiCl2 causes mitochondrial-mediated apoptosis by disruption of MMP and increased expression of AIF and EndoG mRNA and protein, and that the underlying mechanism of MMP loss involves the Bcl-2 family proteins modulation and PI3K/Akt pathway inhibition.

Toxicological effects of dietary nickel chloride on intestinal microbiota.

This study was designed to evaluate the toxicological effect of dietary nickel chloride (NiCl2) on the counts of intestinal bacteria and diversity of microorganisms in broilers. Plate counting and polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) assays were used. A total of 240 one-day-old avian broilers chicks were divided into four equal groups and kept on corn-soybean basal diet along with supplementation of 0, 300, 600 and 900 mg/kg NiCl2 for 42 days. Samples were taken at 21 and 42 days of age during the experiment. The bacterial count results showed that dietary NiCl2 in the range of 300 to 900 mg/kg decreased the counts of Bifidobacterium spp. and Lactobacillus, increased Escherichia coli (E. coli) and Enterococcus spp. in the ileum and cecum. PCR-DGGE analysis showed that bacterial band numbers, profile similarity, and the Shannon index of the ileum and cecum were all decreased in the 300, 600, and 900 mg/kg groups at 21 and 42 days of age. In conclusion, dietary NiCl2 affected the amount and diversity of intestinal microbiota in the ileum and cecum of broilers. This finding implies that NiCl2 has toxicological effect on the intestinal ecosystem and, possibly functions.

The Protective Effects of Methionine on Nickel-Induced Oxidative Stress via NF-κB Pathway in the Kidneys of Mice.

Nickel (Ni) is a human carcinogen that causes oxidative damage to many organs, and methionine has been studied to protect mammals from similar toxic effects by other heavy metals possibly through sulfur metabolism. This study aimed to investigate the protective effects of methionine on Ni-induced injuries to the kidneys. In this study, the mice were randomly divided into BC (normal diet), MD (methionine deficiency diet), MN (methionine plus nickel diet), and MDN (methionine deficiency plus nickel diet) treatment groups. Their renal function, histological changes, cell cycle, apoptosis, oxidative damage, and NF-κB inflammatory cytokines were detected after 21 days by HE, immunohistochemistry, TUNEL staining, and biochemical and ELISA methods. The results showed that serum Cr, BUN, and the NAG content increased in MDN (P < 0.01), MN (P < 0.05), and MD (P < 0.05) group mice compared to BC group mice. Glomerulus atrophy and renal tubular atrophy were observed in the MDN, MN, and MD groups but less severe in MN group mice. The PCNA protein content was the highest in BC group mice followed by MD, MN, and MDN. The activities of antioxidant enzymes (SOD, CAT, GSH, GSH-Px, and GSH-ST) were lower significantly in MD, MN, and MDN group mice, and the oxidant products content (MDA, LPO, and ROS) in the BC group were higher than those in other groups with a similar trend. The contents of NF-κB, TNF-α, IFN-γ, IL-1a, and IL-6 in the BC group were found to increase significantly in MD, MN, and MDN groups. In conclusion, Ni-induced kidney injury was indicated by renal tissue and cell damage, increased kidney metabolism products release in the serum, and renal oxidative stress while methionine addition helped alleviate the injury. In addition, the NF-κB signal pathway was involved in the renal inflammatory reaction induced by Ni where methionine helped mitigate it.

Effects of hesperidin on the histological structure, oxidative stress, and apoptosis in the liver and kidney induced by NiCl2.

The aim of this study was to investigate the effect of hesperidin on the liver and kidney dysfunctions induced by nickel. The mice were divided into six groups: nickel treatment with 80 mg/kg, 160 mg/kg, 320 mg/kg hesperidin groups, 0.5% CMC-Na group, nickel group, and blank control group. Histopathological techniques, biochemistry, immunohistochemistry, and the TUNEL method were used to study the changes in structure, functions, oxidative injuries, and apoptosis of the liver and kidney. The results showed that hesperidin could alleviate the weight loss and histological injuries of the liver and kidney induced by nickel, and increase the levels of lactate dehydrogenase (LDH), alanine aminotransferase (GPT), glutamic oxaloacetic transaminase (GOT) in liver and blood urea nitrogen (BUN), creatinine (Cr) and N-acetylglucosidase (NAG) in kidney. In addition, hesperidin could increase the activities of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px) in the liver and kidney, decrease the content of malondialdehyde (MDA) and inhibit cell apoptosis. It is suggested that hesperidin could help inhibit the toxic effect of nickel on the liver and kidney.

Transcriptional profiling of hilar nodes from pigs after experimental infection with Actinobacillus pleuropneumoniae.

The gram-negative bacterium Actinobacillus pleuropneumoniae (APP) is an inhabitant of the porcine upper respiratory tract and the causative agent of porcine pleuropneumonia (PP). In recent years, knowledge about the proinflammatory cytokine and chemokine gene expression that occurs in lung and lymph node of the APP-infected swine has been advanced. However, systematic gene expression profiles on hilar nodes from pigs after infection with Actinobacillus pleuropneumoniae have not yet been reported. The transcriptional responses were studied in hilar nodes (HN) from swine experimentally infected with APP and the control groupusing Agilent Porcine Genechip, including 43,603 probe sets. 9,517 transcripts were identified as differentially expressed (DE) at the p ≤ 0.01 level by comparing the log2 (normalized signal) of the two groups named treatment group (TG) and controls (CG). Eight hundred and fifteen of these DE transcripts were annotated as pig genes in the GenBank database (DB). Two hundred and seventy-two biological process categories (BP), 75 cellular components and 171 molecular functions were substantially altered in the TG compared to CG. Many BP were involved in host immune responses (i.e., signaling, signal transmission, signal transduction, response to stimulus, oxidation reduction, response to stress, immune system process, signaling pathway, immune response, cell surface receptor linked signaling pathway). Seven DE gene pathways (VEGF signaling pathway, Long-term potentiation, Ribosome, Asthma, Allograft rejection, Type I diabetes mellitus and Cardiac muscle contraction) and statistically significant associations with host responses were affected. Many cytokines (including NRAS, PI3K, MAPK14, CaM, HSP27, protein phosphatase 3, catalytic subunit and alpha isoform), mediating the proliferation and migration of endothelial cells and promoting survival and vascular permeability, were activated in TG, whilst many immunomodulatory cytokines were suppressed. The significant changes in the expression patterns of the genes, GO terms, and pathways, led to a decrease of antigenic peptides with antigen presenting cells presented to T lymphocytes via the major histocompatibility complex, and alleviated immune response induced APP of HN. The immune response ability of HN in the APP-infected pigs was weakened; however, cell proliferation and migration ability was enhanced.

Comparative Research on Intestinal Functions of Wild and Cultured Hemibarbus maculatus in Jialing River.

Hemibarbus maculatus is a common economic fish in the midstream and downstream of the Jialing River. In order to resolve the difficulties in aquacultural cultivation, we tested the intestinal and liver digestive function of wild and cultured Hemibarbus maculatus. Histological methods and special biochemical staining methods were used to compare the differences of morphological structure, goblet cells, argyrophil cells, lymphocytes and Na+/K+ATPase in the intestine, and the morphological structure, glycogen and lipid in the liver between the two kinds of Hemibarbus maculatus. The results showed that higher amount of fat was found to attached to the gut, lower Na+/K+ATPase vitality in the foregut and hidgut (p < 0.01) and lower number of goblet cells in the hindgut (p < 0.01) of the cultured Hemibarbus maculatus when compared to the wild ones. The number of the argyrophilic cells did not show significant differences between the two kinds, but the number of lymphocytes was significantly lower in the segments of gut in cultured. This suggests the absorptive function and intestinal immunity are weaker in the cultured Hemibarbus maculatus. In addition, more glycogen and lipid were found in the liver of cultured fishes, which indicates the decreased digestive function of the cultured Hemibarbus maculatus. In conclusion, the intestinal digestion, absorption and lymphocytes level of the wild are generally better than those of the cultured, and more hepatic lipopexia and glycogen are present in the cultured ones. Future aquacultural activities should consider these changes when facing pragmatic problems.

Effects of prolonged fluoride exposure on innate immunity, intestinal mechanical, and immune barriers in mice.

The aim of this study is to explore the effects of fluoride on the innate immunity, intestinal mechanical barrier, and immune barrier of C57BL/6 mice, as well as to analyze the degree of structural and tissue damage, providing reference data for related research. Mice were randomly divided into four groups and then treated with 0 mg/L (control), 50 mg/L, 100 mg/L, 125 mg/L sodium fluoride solution, respectively, for 120 days. Histological technique, ELISA, MTT colorimetry methods were used to detect and analyze the effects of different concentrations of fluoride on the intestinal morphology, mechanical barrier and the immune functions and innate immunity of mice. The results showed that compared with the control group, the villi were injured in different degrees of the three fluoride groups, the number of goblet cells, the protein expression levels of connexin ZO-1, Claudin-1 and Occludin, the content of Diamine Oxidase (DAO), endotoxin (ET) and D-lactic acid (D-LA), the activity of natural killer cell (NK cells), the number and percentage of neutrophils and erythrocytes, the phagocytic rate of neutrophils, and the rate of C3bR rosette (which is formed by the adhesion of C3b receptors on the red blood cell membrane to complement sensitized yeast) and IC rosette (which is formed by the adhesion of C3b molecules in the immunecomplex adhered to the red blood cell membrane to non sensitized yeast) of red blood cells, the content of interlenkin 1 beta (IL-1ß) and interlenkin 8 (IL-8), the number and percentage of lymphocytes decreased with the increasing of fluoride concentration. In addition, the content of the Immunoglobulin A (sIgA) showed a trend of increase at first and then decrease in salivary gland and jejunum. It is concluded that excessive intake of fluoride for a long time has a certain damage effect on the intestinal tract, leading to an increase in the permeability of the intestinal tract, thereby destroying the mechanical and immune barrier function of the intestinal tract.

Compound Probiotics Improve Body Growth Performance by Enhancing Intestinal Development of Broilers with Subclinical Necrotic Enteritis.

The aim of this study is to explore whether or not the combined application of BS15 and H2 is capable to have a more effective control effect on SNE in broilers. A total of 240 1-day-old female chickens were randomly divided into 5 groups: (a) basal diet in negative control group (NC group); (b) basal diet + SNE infection (coccidiosis vaccine + CP) (PC group); (c) basal diet + SNE infection + H2 pre-treatment (BT group); (d) basal diet + SNE infection + BS15 pre-treatment (LT group); and (e) basal diet + SNE infection + H2 pre-treatment + BS15 pre-treatment (MT group). The results showed the MT group had the most positive effect on inhibiting the negative effect of growth performance at 42 days of age. In the detection of the NC, PC, and MT group indicators at 28 days of age, we found that MT group significantly promoted ileum tissue development of broilers, and the ileum of broilers in the MT group formed a flora structure different from NC and PC, although it was found that the MT group had no effect on the butyrate level in the cecum, but it could affect the serum immune level, such as significantly reducing the level of pro-inflammatory cytokine IL-8 and increasing the content of immunoglobulin IgM and IgG. In conclusion, the composite preparation of Lactobacillus johnsonii BS15 and Bacillus licheniformis H2 could effectively improve the growth performance against SNE broilers, which is possibly caused by the improvement of the immune levels, the reduction of inflammation levels, and the promotion of the intestinal development.

Mechanism of effects of nickel or nickel compounds on intestinal mucosal barrier.

As an important metal in industry, national defense, and production, nickel widely exists in nature and is also a necessary trace element for human beings and animals. Nickel deficiency will affect the growth and development of animals, the contents of related active substances, enzymes and other essential elements in vivo. However, excessive nickel or longer nickel exposure can induce excessive free radicals (reactive oxygen species and reactive nitrogen) in the body, which can lead to a variety of cell damage, apoptosis and canceration, and ultimately pose negative effects on the health of the body. Among them, the intestinal tract, as the largest interface between the body and the external environment, greatly increases the contact probability between nickel or nickel compounds and the intestinal mucosal barrier, thus, the intestinal structure and function are also more vulnerable to nickel damage, leading to a series of related diseases such as enteritis. Therefore, this paper briefly analyzed the damage mechanism of nickel or its compounds to the intestinal tract from the perspective of four intestinal mucosal barriers: mechanical barrier, immune barrier, microbial barrier and chemical barrier, we hope to make a certain theoretical contribution to the further research and the prevention and treatment of nickel related diseases.

Alleviating Effect of Methionine on Intestinal Development and Intercellular Junction Induced by Nickel.

The aim of this study was to investigate the alleviating effect of methionine (Met) on intestinal injury induced by nickel. The mice were divided into six groups: Met-deficient + nickel group (MDN), Met-deficient group (MD), Met + nickel group (MN), high-dose Met + nickel group (HMN), high-dose Met group (HM), and blank control group (BC). Histopathological techniques, Alcian blue-periodic acid Schiff (AB-PAS) staining, enzyme-linked immunosorbent assay (ELISA), and real-time PCR were used to study the changes of intestinal development, the number of goblet cells, and the intercellular junction. The results showed that Met can inhibit the intestinal villus length and crypt depth decreases induced by nickel and increase the index villus length and crypt depth (V/C), the number of goblet cells, and the content of diamine oxidase (DAO) and decrease the content of fatty acid binding protein2 (FABP2) and endotoxin (ET) of the intestinal mucosa damage parameters, and the mRNA expression of intercellular junction (occludin, ZO-1, claudin-1) was damaged. It is suggested that Met could help inhibit the toxic effect of nickel on the intestinal development and intercellular connection.

Effect of methionine deficiency on the apoptosis and cell cycle of kidney in broilers.

Abundant evidence now supports the idea that methionine deficiency has negative effects on chicken healthy especially in the aspect of cell cycle regulation and apoptosis. But, lacking of knowledge is the evaluation on metabolic organs. To test the effect of methionine deficiency on the kidney, we assessed the apoptosis and the cell cycle of kidney induced by methionine deficiency by the methods of TdT-mediated dUTP Nick-End Labeling (TUNEL), flow cytometry (FCM), quantitative real-time PCR (qRT-PCR) and Enzyme-Linked ImmunoSorbent Assay (ELISA) of chickens for 42 days of age. Our results showed that the number of the apoptotic cells was increased (p < .05 or p < .01), while bcl-2 mRNA expression levels were decreased (p < .05 or p < .01) and bax and caspase-3 mRNA expression levels were higher (p < .01) in methionine deficiency group. Furthermore, the cell cycle results showed a time-dependent increase in G2M phase cells and a corresponding decrease in cells at G2M and S stages, the mRNA expression of p53 and p21 was increased (P < .05 or P < .01) and cyclin B and PCNA was significantly lower (P < .05 or P < .01) in the methionine deficiency group than that of the control group. These findings suggested that methionine deficiency could induce renal apoptosis and cell cycle arrest.

Methionine Deficiency Affects Liver and Kidney Health, Oxidative Stress, and Ileum Mucosal Immunity in Broilers.

Methionine (Met) is the first limiting amino acid in broiler diets, but its unclear physiological effects hamper its effective use in the poultry production industry. This study assessed the effect of a Met-deficient (MD) diet on chicken liver and kidney health, exploring the associated mechanisms of antioxidant capacity and ileum mucosal immunity. Seventy-two broilers were administered either the control diet (0.46% Met in starter diet, 0.36% Met in grower diet) or the MD diet (0.22% Met in starter diet, 0.24% Met in grower diet). Liver and kidney samples were collected every 14 days for anatomical, histological, and ultrastructural analyses, accompanied by oxidative stress assessment. Meanwhile, T- and B-lymphocyte abundance and essential cytokine gene expression were measured in the ileum, the center of the gut-liver-kidney axis. Signs of kidney and liver injury were observed morphologically in the MD group at 42 days of age. Furthermore, aspartate aminotransferase, alanine aminotransferase, creatinine, and uric acid levels were decreased in the MD group compared with the control group, accompanied by decreased superoxide dismutase activity, increased malondialdehyde content, decreased numbers of T and B lymphocytes, and decreased cytokine expression in the ileum, such as IL-2, IL-6, LITAF, and IFN-γ. These results suggest that MD can induce kidney and liver injury, and the injury pathway might be related to oxidative stress and intestinal immunosuppression.

DUSP16 promotes cancer chemoresistance through regulation of mitochondria-mediated cell death.

Drug resistance is a major obstacle to the treatment of most human tumors. In this study, we find that dual-specificity phosphatase 16 (DUSP16) regulates resistance to chemotherapy in nasopharyngeal carcinoma, colorectal cancer, gastric and breast cancer. Cancer cells expressing higher DUSP16 are intrinsically more resistant to chemotherapy-induced cell death than cells with lower DUSP16 expression. Overexpression of DUSP16 in cancer cells leads to increased resistance to cell death upon chemotherapy treatment. In contrast, knockdown of DUSP16 in cancer cells increases their sensitivity to treatment. Mechanistically, DUSP16 inhibits JNK and p38 activation, thereby reducing BAX accumulation in mitochondria to reduce apoptosis. Analysis of patient survival in head & neck cancer and breast cancer patient cohorts supports DUSP16 as a marker for sensitivity to chemotherapy and therapeutic outcome. This study therefore identifies DUSP16 as a prognostic marker for the efficacy of chemotherapy, and as a therapeutic target for overcoming chemoresistance in cancer.