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1.
Theranostics ; 10(7): 3308-3324, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32194870

RESUMO

Rationale: Busulfan is currently an indispensable anti-cancer drug, particularly for children, but the side effects on male reproduction are so serious that critical drug management is needed to minimize any negative impact. Meanwhile, alginate oligosaccharides (AOS) are natural products with many consequent advantages, that have attracted a great deal of pharmaceutical attention. In the current investigation, we performed single-cell RNA sequencing on murine testes treated with busulfan and/or AOS to define the mitigating effects of AOS on spermatogenesis at the single cell level. Methods: Testicular cells (in vivo) were examined by single cell RNA sequencing analysis, histopathological analysis, immunofluorescence staining, and Western blotting. Testes samples (ex vivo) underwent RNA sequencing analysis. Blood and testicular metabolomes were determined by liquid chromatography-mass spectrometry (LC/MS). Results: We found that AOS increased murine sperm concentration and motility, and rescued busulfan disrupted spermatogenesis through improving (i) the proportion of germ cells, (ii) gene expression important for spermatogenesis, and (iii) transcriptional factors in vivo. Furthermore, AOS promoted the ex vivo expression of genes important for spermatogenesis. Finally, our results showed that AOS improved blood and testis metabolomes as well as the gut microbiota to support the recovery of spermatogenesis. Conclusions: AOS could be used to improve fertility in patients undergoing chemotherapy and to combat other factors that induce infertility in humans.

2.
Ecotoxicol Environ Saf ; 194: 110412, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32155482

RESUMO

Hydrogen sulfide (H2S) is a toxic air pollutant that causes immune damage. Recent studies have found that neutrophil extracellular trap (NET) formation is one way in which neutrophils exert immune functions. In addition, the formation of NETs is also related to thrombosis and autoimmune diseases. Recent studies have shown that miRNAs are involved in the regulation of a variety of pathophysiological processes. Here, we investigated the role of H2S in regulating the formation of NETs by affecting miR-16-5p. Our study established an in vitro H2S exposure model for neutrophils using phorbol-myristate-acetate (PMA) to induce NET formation. We observed the morphological changes of cells with scanning electron microscopy and fluorescence microscopy. Then, the content of extracellular DNA and the expression of MPO and NE in each group were detected. The results showed that H2S inhibited the formation of NETs. The expression of miR-16-5p and its target genes PiK3R1 and RAF1 was then measured by qRT-PCR. H2S upregulated miR-16-5p and inhibited expression of the target genes PiK3R1 and RAF1, and it subsequently inhibited the Pi3K/AKT and ERK pathways and decreased respiratory burst levels. Furthermore, H2S attenuated inositol 1,4,5-trisphosphate receptor (IP3R)-mediated endoplasmic reticulum calcium outflow as well as autophagy caused by PMA. This study enriches H2S immunotoxicity research and provides a possible solution for the treatment of NET-related diseases.

3.
Animals (Basel) ; 10(2)2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32085517

RESUMO

This study aimed to investigate the effects of maternal lipopolysaccharide (LPS) challenge and dietary fat sources on colostrum quality and inflammatory response in sows. Sixty Landrace × Yorkshire sows were randomly assigned to three dietary treatments supplemented with 3% soybean oil (SO), 3% coconut oil (CO) or 3% fish oil (FO), respectively, from Day 90 of gestation until parturition. On Day 112 of gestation, half the sows from each dietary treatment were challenged with LPS (10 µg/kg BW) or saline. The results showed that maternal LPS challenge decreased colostrum yield and dry matter content. A similar pattern of changes was observed for body weight gain and colostrum intake in piglets from LPS-challenged sows. Maternal LPS challenge increased the levels of tumor necrosis factor α (TNFα), interleukin 1ß (IL1ß) and IL6 in colostum, and the mRNA abundance of IL6, IL1ß and TNFα and the phosphorylation level of p65 in mammary glands. However, the responses of these variables to LPS treatment were lower in sows fed a FO diet. In conclusion, maternal immune challenge reduced the growth performance of piglets by decreasing colostrum yield and intake by piglets, and dietary supplementation with FO in sows attenuates the LPS-induced inflammatory response in mammary glands.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32072901

RESUMO

Amino acids (AAs) and their metabolites regulate key metabolic pathways that are necessary for growth, reproduction, and immunity, metabolism of the body. It has been convinced that metabolic diseases are closely related to disorders of glycolipid metabolism. A growing number of studies have shown that AAs are closely related to energy metabolism. This review focuses on the effects of amino acids (arginine, branched-chain amino acids, glutamine) and their metabolites (short chain fatty acids) on glycolipid metabolism by regulating PI3K/AKT/mTOR and AMPK signaling pathways and GPCRs receptors, reducing intestinal Firmicutes/Bacteroidetes ratio associated with obesity.

5.
Mucosal Immunol ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900405

RESUMO

Worldwide the incidence of cancer has been continuing increasing. Mucositis of the gastrointestinal tract is a common side effect in patients under chemotherapy. Anticancer drug busulfan, used for treating chronic myeloid leukemia especially in pediatric patients, causes mucositis of the gastrointestinal tract. Alginate oligosaccharides (AOS) are natural products with attractive pharmaceutical potentials. We aimed to investigate, at the single-cell level, AOS preventing small intestine mucositis induced by busulfan. We found that busulfan disturbed the endoplasmic reticulum and mitochondria of cells in the small intestine, damaged cell membranes especially cell junctions, and disrupted microvilli; all of which were rescued by AOS. Single-cell RNA sequencing analysis and functional enrichment analysis showed that AOS could recover small intestinal function. Deep analysis found that AOS improved the expression of transcriptional factors which explained AOS regulating gene expression to improve small intestine function. Further investigation in IPEC-J2 cells found that AOS acts its function through mannose receptor signaling pathway. Moreover, the improved blood metabolome confirmed small intestinal function was recovered by AOS. As a natural product with many advantages, AOS could be developed to assist in the recovery of intestinal functions in patients undergoing anticancer chemotherapy or other treatments.

6.
J Agric Food Chem ; 68(2): 530-540, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31891490

RESUMO

The influence of ß-hydroxy-ß-methylbutyrate (HMB) on proliferation and differentiation of myogenic cells has been well-studied. However, the role of HMB in myofiber specification and potential mechanisms is largely unknown. Thus, the objective of this research was to explore the role of HMB supplementation in myofiber specification. Results showed that HMB treatment significantly increased the fast MyHC protein level (mice: 1.59 ± 0.08, P < 0.01; C2C12: 2.26 ± 0.11, P < 0.001), decreased the slow MyHC protein level (mice: 0.76 ± 0.05, P < 0.05; C2C12: 0.52 ± 0.02, P < 0.001), and increased the miR-199a-3p level (mice: 4.93 ± 0.37, P < 0.001; C2C12: 11.25 ± 0.57, P < 0.001). Besides, we also observed that HMB promoted the activity of glycolysis-related enzymes and reduced the activities of oxidation-related enzymes in mice and C2C12 cells. Overexpression of miR-199a-3p downregulated the slow MyHC protein level (0.71 ± 0.02, P < 0.01) and upregulated the fast MyHC protein level (2.13 ± 0.09, P < 0.001), while repression of miR-199a-3p exhibited the opposite effect. Target identification results verified that miR-199a-3p targets the 3'UTR of the TEA domain family member 1 (TEAD1) to cause its post-transcriptional inhibition (0.41 ± 0.07, P < 0.01). Knockdown of TEAD1 exhibited a similar effect with miR-199a-3p on myofiber specification. Moreover, suppression of miR-199a-3p blocked slow-to-fast myofiber type transition induced by HMB. Together, our finding revealed that miR-199-3p is induced by HMB and contributes to the action of HMB on slow-to-fast myofiber type conversion via targeting TEAD1.


Assuntos
MicroRNAs/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos , Mioblastos Esqueléticos/efeitos dos fármacos , Valeratos/farmacologia , Regiões 3' não Traduzidas , Animais , Diferenciação Celular/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Camundongos , MicroRNAs/genética , Fibras Musculares Esqueléticas/citologia , Fibras Musculares Esqueléticas/metabolismo , Mioblastos Esqueléticos/citologia , Mioblastos Esqueléticos/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação para Cima/efeitos dos fármacos
7.
J Hazard Mater ; 386: 121626, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31791863

RESUMO

Ammonia (NH3) is a known harmful gas that causes injury to the respiratory system. Ammonia also exists in haze, forming secondary organic aerosols. However, the specific damage caused by NH3 in chicken trachea has not been determined. The regulatory mechanism of ceRNA and its multiple roles have been proposed in many pathomechanisms; therefore, we investigated the functional role of ceRNA in chicken trachea after NH3 inhalation. Broiler chicken trachea exposed to NH3 was selected as the research object. The pathological ultrastructure was observed by transmission electron microscopy. Transcriptome analyses were applied and referenced, and lncRNA-107053293 and miR-148a-3p and FAF1 were selected. A dual-luciferase reporter assay verified the target relationship. Real-time quantitative PCR (RT-PCR) and western blotting were performed to examine the expression levels of necroptosis genes, such as RIPK1, RIPK3, MLKL, caspase 8, and FADD. Our results indicated that lncRNA-107053293 regulated necroptosis by acting as a competing endogenous RNA of miR-148a-3p. FAF1, as a gene target of miR-148a-3p, also affects necroptosis.

8.
Ecotoxicol Environ Saf ; 188: 109908, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31706243

RESUMO

Pesticides have been extensively produced and used to help the agricultural production which leads to the contamination of the environment, soil, groundwater sources, and even foodstuffs. Fungicides carbendazim (CBZ) and chlorothalonil (Chl) are widely applied in agriculture and other aspects. CBZ or Chl have been reported to disrupt spermatogenesis and decrease semen quality. However, it is not understood the effects of pubertal exposure to low doses of CBZ and Chl together, and the underlying mechanisms. Therefore, the aim of current investigation was to explore the negative impacts of pubertal exposure to low doses of CBZ and Chl together on spermatogenesis and the role of epigenetic modifications in the process. We demonstrated that CBZ and Chl together synergize to decrease sperm motility in vitro (CBZ 1.0 + Chl 0.1, CBZ 10.0 + CHl 1.0, CBZ 100.0 + Chl 10 µM in incubation medium for 24 h) and sperm concentration and motility in vivo with ICR mice (CBZ 0.1 + Chl 0.1, CBZ 1.0 + CHl 1.0, CBZ 10.0 + Chl 10 mg/kg body weight; oral gavage for five weeks). CBZ + Chl significantly increase reactive oxygen species (ROS) and apoptosis by the increase in the protein level of caspase 8 in vitro. Moreover, CBZ + Chl synergized to disrupt mouse spermatogenesis with the disturbance in sperm production proteins and sperm proteins (VASA, A-Myb, STK31, AR, Acrosin). CBZ + Chl synergized to decrease the protein level of estrogen receptor alpha and the protein level of DNA methylation marker 5 mC in Leydig cells, and to increase the protein levels of histone methylation marker H3K9 and the methylation enzyme G9a in germ cells. Therefore, greater attention should be paid to the use of CBZ and Chl as pesticides to minimise their adverse impacts on spermatogenesis.


Assuntos
Benzimidazóis/toxicidade , Carbamatos/toxicidade , Epigênese Genética/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Nitrilos/toxicidade , Espermatogênese/efeitos dos fármacos , Animais , Sinergismo Farmacológico , Receptor alfa de Estrogênio/metabolismo , Masculino , Metilação/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Transdução de Sinais/efeitos dos fármacos , Espermatogênese/genética , Espermatozoides/efeitos dos fármacos
9.
Sci Total Environ ; 699: 134296, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31683218

RESUMO

Hydrogen sulfide (H2S) is an air pollutant, has toxic effects on respiratory tract. However, the underlying mechanisms of H2S induced respiratory toxicity and the roles of long non-coding RNAs (lncRNA) and microRNA (miRNA) in this process remain poorly understood. To clear this, we investigated the change of tracheal tissue ultrastructure and the expression profiles of lncRNAs and miRNAs of chicken trachea exposed to H2S for 42 days. Results showed that H2S exposure triggered apoptosis, necroptosis, and differential expression of 16 lncRNAs and 18 miRNAs in broiler tracheas. The results of LMH cells stimulated by NaHS in vitro also showed the occurrence of apoptosis and necroptosis. LncRNA3037 is down-regulated and miR-15a is up-regulated in tracheal tissue and LMH cells under H2S exposure. Bioinformatics analysis and dual luciferase reporter system showed lncRNA3037 bound directly to miR-15a and negatively regulates each other. A20 and BCL2 are the target genes of miR-15a and negatively regulated by it. Overexpression of miR-15a caused apoptosis and necroptosis and its inhibition partially reversed apoptosis and necroptosis of LMH cells caused by NaHS stimulation and lncRNA3037 knockdown. Taken together, we concluded that H2S exposure mediates apoptosis and necroptosis through lncRNA3037/miR-15/A20-BCL2. These results provide new insights for unveiling the biological effects of H2S in vivo and in vitro.


Assuntos
Poluentes Atmosféricos/toxicidade , Sulfeto de Hidrogênio/toxicidade , Animais , Apoptose , Galinhas , Proteínas Proto-Oncogênicas c-bcl-2 , Transdução de Sinais , Testes de Toxicidade , Traqueia
10.
Toxicol Appl Pharmacol ; 388: 114869, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31863799

RESUMO

Ammonia (NH3), a toxic gas, is an important cause of atmospheric haze and one of the main pollutants in air environment of poultry houses, threatening the health of human beings and poultry. However, little is known about the effect of NH3 on liver apoptotic damage. This study aimed to investigate the mechanism of oxidative stress-mediated apoptosis caused by NH3 in chicken livers and whether miR-187-5p/apaf-1 axis was involved in this mechanism. Here we duplicated NH3 poisoning model of chickens for fattening to study the ultrastructure of chicken livers, apoptosis rate, oxidative stress indexes, miR-187-5p, and apoptosis-related genes. Obvious apoptotic characteristics of liver tissues exposed to excess NH3 were observed, and the apoptosis rate increased. Excess NH3 decreased the activities of catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px), and increased the content of malondialdehyde (MDA), suggesting that oxidative stress occurred. miR-187-5p decreased, and apoptotic protease activating factor-1 (apaf-1) increased, indicating that excess NH3 dysregulated miR-187-5p/apaf-1 axis. The expression of tumor protein p53 (p53), Bcl-2 associated X protein (Bax), Bcl-2 homologous antagonist/killer (Bak), Cytochrome-c (Cyt-c), Caspase-9, Caspase-8, and Caspase-3 was promoted, and the expression of B-cell lymphoma-2 (Bcl-2) was inhibited, resulting in apoptosis. Moreover, oxidative stress indexes, miR-187-5p, and apoptosis-related genes changed in dose- and time-dependent manner. Altogether, miR-187-5p/apaf-1 axis participated in oxidative stress-mediated apoptosis caused by NH3 via mitochondrial pathway in the livers of chickens for fattening. This study may provide new ideas to study the mechanism of liver apoptotic damage induced by NH3 exposure.

11.
Microbiome ; 7(1): 151, 2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-31779704

RESUMO

BACKGROUND: Ochratoxin A (OTA) is a widespread mycotoxin and induces liver inflammation to human and various species of animals. The intestinal microbiota has critical importance in liver inflammation; however, it remains to know whether intestinal microbiota mediates the liver inflammation induced by OTA. Here, we treated ducklings with oral gavage of OTA (235 µg/kg body weight) for 2 weeks. Then, the microbiota in the cecum and liver were analyzed with 16S rRNA sequencing, and the inflammation in the liver was analyzed. To explore the role of intestinal microbiota in OTA-induced liver inflammation, intestinal microbiota was cleared with antibiotics and fecal microbiota transplantation was conducted. RESULTS: Here, we find that OTA treatment in ducks altered the intestinal microbiota composition and structure [e.g., increasing the relative abundance of lipopolysaccharides (LPS)-producing Bacteroides], and induced the accumulation of LPS and inflammation in the liver. Intriguingly, in antibiotic-treated ducks, OTA failed to induce these alterations in the liver. Notably, with the fecal microbiota transplantation (FMT) program, in which ducks were colonized with intestinal microbiota from control or OTA-treated ducks, we elucidated the involvement of intestinal microbiota, especially Bacteroides, in liver inflammation induced by OTA. CONCLUSIONS: These results highlight the role of gut microbiota in OTA-induced liver inflammation and open a new window for novel preventative or therapeutic intervention for mycotoxicosis.

12.
Front Pharmacol ; 10: 1012, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31572187

RESUMO

Air pollution is a global threat to human health especially spermatogenesis. Animal and epidemiological studies suggest that epigenetic factors can transmit the pathologies transgenerationally. Paternal epigenetic effects can greatly impact offspring health. In this study and together with our previous report, we found that H2S donor Na2S and/or NH3 donor NH4Cl diminished mouse fertility, decreased spermatozoa concentration and motility, and impaired spermatogenesis in three consequent generations (F0, F1, and F2). In the current study, we found that DNA methylation, histone methylation, and estrogen receptor alpha (ERα) were impaired by NH4Cl and/or Na2S in F0, F1, and F2 mouse testes. Moreover, NH4Cl and/or Na2S might act as environmental endocrine-disrupting chemicals to decrease estrogen and testosterone in mouse blood. It has been reported that ERα signaling is intertwined together with DNA methylation and histone methylation, which plays very important roles in spermatogenesis. These data together indicate that the transgenerational disruption in spermatogenesis by NH4Cl and/or Na2S may be through ERα-related DNA methylation and histone methylation pathways. Therefore, we strongly recommend that greater attention should be paid to NH3 and/or H2S contamination to minimize their impact on human health especially spermatogenesis.

13.
Animals (Basel) ; 9(9)2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31509946

RESUMO

The differences of pork quality characteristics among different pig breeds mainly came from the differences in myofiber type compositions. Growing evidence indicated the key role of miRNAs in myofiber specification. In the present study, we found that miR-152 is more abundant in the slow-twitch myofiber-enriched muscles. However, its role in myofiber type transformation and myogenesis is largely unknown. Overexpression of miR-152 in porcine myotubes promoted the formation of slow-twitch myofibers and myogenesis. While, inhibition of miR-152 expression showed the opposite effect to miR-152 mimics transfection. The luciferase reporter analysis confirmed that miR-152 straightly targets the 3'-untranslated region (3'-UTR) of uncoupling protein 3 (UCP3) to cause its post-transcriptional inhibition in the protein level. The knockdown of UCP3 by siRNA showed the similar effect of miR-152 on myofiber type transition. Furthermore, the rescue experiment in the porcine myotube transfected with miR-152 mimics or/and UCP3 overexpression plasmid with or without the 3'UTR revealed that UCP3 mediates the action of miR-152 in slow-twitch myofiber formation. Taken together, our findings proposed a novel molecular mechanism through which miR-152 epigenetically regulates meat quality via promoting slow-twitch myofiber formation and skeletal myogenesis.

14.
Sci Rep ; 9(1): 11022, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31363155

RESUMO

Temperature, which is an important environmental factor in broiler farming, can significantly influence the deposition of fatty acids in muscle. 300 one-day-old broiler chicks were randomly divided into three groups and reared at high, medium and low temperatures (HJ, MJ and LJ), respectively. Breast muscle and jejunal chyme samples were collected and subjected to analyses of fatty acid composition and 16S rRNA gene sequencing. Through spearman's rank correlation coefficient, the data were used to characterize the correlation between jejunal microbial diversity and muscle fatty acid deposition in the broilers. The results showed that Achromobacter, Stenotrophomonas, Pandoraea, Brevundimonas, Petrobacter and Variovorax were significantly enriched in the MJ group, and all of them were positively correlated with the fatty acid profiling of muscle and multiple lipid metabolism signaling pathways. Lactobacillus was significantly enriched in the HJ group and exhibited a positive correlation with fatty acid deposition. Pyramidobacter, Dialister, Bacteroides and Selenomonas were significantly enriched in the LJ group and displayed negative correlation with fatty acid deposition. Taken together, this study demonstrated that the jejunal microflora manifested considerable changes at high and low ambient temperatures and that jejunal microbiota changes were correlated with fatty acid deposition of muscle in broilers.

15.
J Therm Biol ; 84: 375-383, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31466777

RESUMO

Bile acids (BAs) are critical for cholesterol homeostasis and new roles in metabolism and endocrinology have been demonstrated recently. It remains unknown whether BA metabolism can be affected by heat stress (HS). The objective of this study was to describe the shifts in serum, hepatic and intestinal BA profiles induced by chronic HS. Twenty-seven Large White pigs weighing 40.8 ±â€¯2.7 kg were assigned to one of the three treatments: a control group (CON, 23 °C), a HS group (33 °C), or a pair-fed group (PF, 23 °C and fed the same amount as HS group) for 21 d. The concentrations of taurine-conjugated BAs (TUDCA and THDCA in serum and TCDCA, TUDCA, THDCA and THCA in liver) were decreased in HS and PF pigs. However, in HS pigs, a reduction in taurine-conjugated BAs (TCBA) correlated with decreased liver genes expression of BA synthesis, conjugation and uptake transport. BA regulated-genes (FXR, TGR5 and FGFR4) in HS pigs and TGR5, FGFR4 and KLß in PF pigs were down-regulated in liver. In ileum, total BAs and glycoursodeoxycholic acid concentrations were higher in HS pigs than other groups and PF group, respectively (P < 0.05). TCBA (P = 0.01) and tauroursodeoxycholic acid (P < 0.01) were decreased in PF group. BA transporters (OSTα and MRP3) were up-regulated in HS pigs compared with CON and PF pigs, respectively (P < 0.01). In cecum, ursodeoxycholic acid was higher in HS (P = 0.02) group than CON group. The expression of apical sodium-coupled bile acid transporter (P = 0.04) was lower in HS pigs than CON pigs, while OSTß (P < 0.01) was greater in HS group than PF group. These results suggest that chronic HS suppressed liver activity of synthesis and uptake of TCBA, at least in part, which was independent of reduced feed intake.


Assuntos
Ácidos e Sais Biliares/metabolismo , Transtornos de Estresse por Calor/metabolismo , Doenças dos Suínos/metabolismo , Suínos/metabolismo , Animais , Ácidos e Sais Biliares/sangue , Conteúdo Gastrointestinal/química , Conteúdo Gastrointestinal/microbiologia , Transtornos de Estresse por Calor/veterinária , Resposta ao Choque Térmico , Temperatura Alta , Fígado/metabolismo , Masculino
16.
Sci Total Environ ; 696: 134035, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31470328

RESUMO

Ammonia (NH3), an inhaled harmful gas, is not only an important volatile in fertilizer production and ranching, but also the main basic component of haze. However, the effect and mechanism of NH3 on the intestines are still unclear. To investigate the intestinal toxicity of NH3 inhalation, morphological changes, transcriptome profiles and oxidative stress indicators of jejunum in broiler chicken exposed to NH3 for 42 days were examined. Results of morphological observation showed that NH3 exposure caused deficiency of jejunal microvilli and neutrophil infiltration. Transcriptomics sequencing identified 677 differential expressed genes (DEGs) including 358 up-regulated genes and 319 down-regulated genes. Enrichment analysis of obtained DEGs by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) found that biological functions and pathways affected by NH3 included antioxidant function, inflammation, microtubule and nutrition transport. Relative genes validation and chemical detection confirmed that NH3-induced oxidative stress by activating CYPs and inhibiting antioxidant enzymes promoted inflammatory response and decreased microtubule activity, thus destroying the balance of nutritional transporters. Our study perfects the injurious mechanism of NH3 exposure and provides a new insight and method for environmental risk assessment.


Assuntos
Poluentes Atmosféricos/toxicidade , Amônia/toxicidade , Microtúbulos/fisiologia , Microvilosidades/fisiologia , Estresse Oxidativo/fisiologia , Transcriptoma , Animais , Antioxidantes , Galinhas , Regulação para Baixo , Perfilação da Expressão Gênica , Inflamação , Transdução de Sinais , Regulação para Cima
17.
Toxicol Lett ; 315: 31-38, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31419471

RESUMO

Endocrine disruptor zearalenone (ZEA) has been found to damage the reproductive system especially spermatogenesis. In our previous report, we have found that low dose (lower than No-Observed Effect Level, NOEL) ZEA exposure disturbed mouse spermatogenesis and diminished mouse semen quality. The purpose of current investigation was to explore the underlying mechanisms of pubertal low dose ZEA exposure upsetting spermatogenesis. And it was demonstrated that pubertal low dose ZEA exposure disrupted the meiosis process and the important genetic pathways to inhibit the spermatogenesis and even to diminish the semen quality with the decrease in spermatozoa motility and concentration. The DNA methylation markers 5mC and 5hmC were decreased, the histone methylation marker H3K27 was increased, at the same time estrogen receptor alpha was diminished in mouse testis after pubertal low dose ZEA exposure. The data indicate that the disruption in spermatogenesis by pubertal low dose ZEA exposure may be through the alterations in genetic and epigenetic pathways, and the interactions with estrogen receptor signaling pathway. Therefore, we should pay great attention on ZEA exposure to reduce its adverse impacts on male reproductive health.


Assuntos
Divisão Celular/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Receptor alfa de Estrogênio/efeitos dos fármacos , Motilidade Espermática/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatogênese/genética , Zearalenona/toxicidade , Adolescente , Animais , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Transdução de Sinais/efeitos dos fármacos
18.
Chemosphere ; 235: 858-866, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31284134

RESUMO

Ammonia is a known environmental pollutant around the world. It leads to the deterioration of air quality and has adverse effects on human health. Although previous studies have demonstrated that ammonia caused some health problems to chickens, it is still unclear whether ammonia causes cardiac toxicity. The functional autophagy is very important for cardiac homeostasis. Therefore, the role of autophagy was investigated in the mechanism of chicken heart damage induced by environmental contaminant ammonia in our present study. The results from the oxidative stress index (SOD, GPx, H2O2, and MDA), NO content, iNOS activity, and transmission electron microscopy indicated that excess ammonia induced oxidative stress and autophagy in the chicken heart. The expression results from miR-202-5p and PTEN/AKT/mTOR (PTEN, LC3-I, LC3-II, p-AKT, AKT, Beclin1, Dynein, ATG5, p-mTOR and mTOR) signaling pathway-related genes further confirmed that excess ammonia induced cardiac autophagy. In conclusion, these results demonstrated that excess ammonia can cause cardiac damage and mediate mir-202-5p to regulate autophagy through PTEN/AKT/mTOR pathway in the chicken heart injury. Our findings will provide a new insight for better assessing the toxicity mechanism of environmental pollutants ammonia on the heart.


Assuntos
Poluentes Atmosféricos/toxicidade , Amônia/toxicidade , Autofagia/genética , Traumatismos Cardíacos/induzido quimicamente , MicroRNAs/genética , Miocárdio/patologia , Animais , Cardiotoxicidade , Galinhas/metabolismo , Coração/fisiopatologia , Peróxido de Hidrogênio/farmacologia , Miocárdio/química , Estresse Oxidativo/efeitos dos fármacos , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
19.
In Vitro Cell Dev Biol Anim ; 55(7): 548-558, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31313007

RESUMO

Recently, the mean maternal age at first birth has been continuing to increase. The decline in the age-related fertility is due to the reduction in the number and the quality of the oocyte. An elevation in intra-ovarian reactive oxygen species (ROS) is correlated with the increase in maternal age, and the oxidative stress is involved in the decline in oocyte quality. Although ß-carotene, a very effective quencher of ROS, has been found to have the beneficial contribution to the ovarian development and steroidogenesis, it is unknown the effect of ß-carotene on the oocyte development especially oocyte maturation. This investigation aimed to explore the beneficial contribution of ß-carotene on oocyte maturation under oxidative stress and the underlying mechanism. We found that the oxidative stress induced by ROS reagent Rosup inhibited oocyte development/maturation and parthenogenetic activation which could be dramatically rescued by ß-carotene (57.1 ± 4.7% vs 78.9 ± 3.8%; p < 0.05) in vitro. The underlying mechanisms include that ß-carotene not only reduces ROS formation and cell apoptosis, but also it can restore actin expression, cortical granule-free domain (CGFD) formation, mitochondria homogeneous distribution, and nuclear maturation. The data suggest that ß-carotene acts as a potential antioxidant in the oocyte. Therefore, the findings from this investigation provide the fundamental 7knowledge for using ß-carotene as an antioxidant to improve the oocyte quality and even the ovarian function.


Assuntos
Antioxidantes/farmacologia , Oócitos/citologia , Oogênese/fisiologia , Estresse Oxidativo/efeitos dos fármacos , beta Caroteno/farmacologia , Actinas/biossíntese , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Feminino , Idade Materna , Camundongos , Mitocôndrias/fisiologia , Espécies Reativas de Oxigênio/metabolismo
20.
J Anim Physiol Anim Nutr (Berl) ; 103(4): 1125-1134, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31155767

RESUMO

Our previous study has shown that high levels of l-arginine (ARG) have reduced serum and mucosal antibody concentrations. In order to provide a better understanding in the application of ARG supplementation in the poultry industry, the study was conducted to investigate the effect of high levels of ARG on performance and B-cell secretion of immunoglobulin M (IgM) and IgG development in broiler chickens. A total of 192 1-day-old male Arbor Acres Plus broilers were randomly allocated into 4 groups (8 replicates per group, 6 birds per replicate) fed diets containing one of four ARG concentrations (analysed): 9.8, 14.7, 19.1 and 23.4 g/kg respectively. Growth performance was measured based on body weight gain (BWG), feed intake (FI) and feed conversion ratio (FCR). Increasing ARG quadratically increased (p < 0.05) BWG and FI with reaching plateau at 14.7 g/kg, while linearly decreased (p < 0.05) FCR, indicating that maximal performance required ARG no more than 14.7 g/kg in diets. Serum IgG and IgM concentrations were linearly reduced (p < 0.05) with increasing ARG. Chickens fed 19.1 g/kg or 23.4 g/kg ARG had lower (p < 0.05) serum IgG or IgM than chickens fed 9.8 g/kg ARG. As for the mRNA expression of bursal IgG and IgM, they were significantly downregulated with increasing ARG (p < 0.05). Chickens on ARG (>19.1 g/kg) had a lower (p < 0.05) IgG and IgM mRNA expression than chickens fed 9.8 g/kg. Activator of transcription 3 (STAT3) mRNA expression was linearly reduced with increasing ARG (p < 0.05), the transcriptional repressor B-cell lymphoma 6 (BCL6) mRNA expression was quadratically (p < 0.05) responded, and these cytokines had the lowest expression at 19.1 g/kg. ARG supplementation (>14.7 g/kg) did not significantly improve the growth performance, while it may have a potential negative regulatory effect on B-cell-mediated humoral immunity in chickens associated with suppression of the STAT3 expression associated with the JAK/STAT3 pathway.


Assuntos
Arginina/administração & dosagem , Linfócitos B/metabolismo , Galinhas/crescimento & desenvolvimento , Dieta/veterinária , Imunoglobulinas/metabolismo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Apoptose , Ciclo Celular , Suplementos Nutricionais , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino
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