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1.
Chemosphere ; 286(Pt 1): 131683, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34351278

RESUMO

Butachlor being an important member of chloroacetanilide herbicides, is frequently used in agriculture to control unwanted weeds. Exposure to butachlor can induce cancer, human lymphocyte aberration, and immunotoxic effects in animals. The current experimental trial was executed to determine the potential risks of herbicide butachlor to immunotoxicity and its mechanism of adverse effects on the spleen. For this purpose, mice were exposed to 8 mg/kg butachlor for 28 days, and the toxicity of butachlor on the spleen of mice was evaluated. We found that butachlor exposure led to an increase in serum ALB, GLU, TC, TG, and TP and changes in the morphological structure of the spleen of mice. More importantly, results showed that butachlor significantly increased the expression level of ATG-5, decreased the protein expression of LC3B and M-TOR, and significantly decreased the mRNA content of M-TOR and p62. Results revealed that the mRNA contents of APAF-1, CYTC, and CASP-9 related genes were significantly decreased after butachlor treatment. Subsequently, the mRNA levels of inflammatory cytokines (IL-1ß, TNF-α, IL-10) were reduced in the spleen of treated mice. This study suggested that butachlor induce spleen toxicity and activate the immune response of spleen tissue by targeting the CYTC/BCL2/M-TOR pathway and caspase cascading activation of spleen autophagy and apoptosis pathways which may ultimately lead to immune system disorders.


Assuntos
Herbicidas , Acetanilidas , Animais , Apoptose , Autofagia , Herbicidas/toxicidade , Camundongos , Baço
2.
Toxicology ; 462: 152957, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34537261

RESUMO

Zearalenone (ZEN), a mycotoxin is frequently detected in different food products and has been widely studied for its toxicity. However, the underlying mechanisms of hepatotoxic effects, relationship between gut microbiome and liver metabolite mediated hepatotoxicity mechanisms induced by ZEN are still not clear. Here, we reported that the different microscopic changes like swelling of hepatocyte, disorganization of hepatocytes and extensive vacuolar degeneration were observed, and the mitochondrial functions decreased in exposed mice. Results exhibited up-regulation in expression of signals of apoptosis and autophagy in liver of treated mice via mitochondrial apoptotic and autophagy pathway (Beclin1/p62). The diversity of gut microbiome decreased and the values of various microbiome altered in treated mice, including 5 phyla (Chloroflexi, Sva0485, Methylomirabilota, MBNT15 and Kryptonia) and genera (Frankia, Lactococcus, Anaerolinea, Halomonas and Sh765B-TzT-35) significantly changed. Liver metabolism showed that the concentrations of 91 metabolite including lipids and lipid like molecules were significantly changed. The values of phosphatidylcholine, 2-Lysophosphatidylcholine and phosphatidate concentrations suggestive of abnormal glycerophosphate metabolism pathway were significantly increased in mice due to exposure to ZEN. In conclusion, the findings suggest that the disorders in gut microbiome and liver metabolites due to exposure to ZEN in mice may affect the liver.

3.
Toxicology ; 461: 152906, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34450209

RESUMO

Fluoride is one of the most widely distributed elements in nature, while some fluorine-containing compounds are toxic to several vertebrates at certain levels. The current study was performed to evaluate the nephrotoxic effects of fluoride exposure in ducks. The results showed that the renal index was decreased in NaF group, and fluoride exposure significantly decreased the levels of serum Albumin, Glucose, Total cholesterol, Urea, protein and Triglycerides, confirming that NaF exhibited adverse effects on the kidney. The overall structure of renal cells showed damage with the signs of nuclelytic, vacuolar degeneration, atrophy, renal cystic cavity widening after fluoride induction. Renal vascular growth was impaired as the expression of VEGF and HIF-1α decreased (p > 0.05). More importantly, autophagy and apoptosis levels of CYT C, LC3, p62, Beclin, M-TOR, Bax and Caspase-3 were increased (p < 0.05) in the NaF treated group. Interestingly, our results showed that Phosphatidylethanolamine (PE) and Phosphatidylcholine (PC) activated the M-TOR autophagy pathway. Meanwhile, the PE acted on Atg5/ LC3 autophagy factor, followed by the auto-phagosome generation and activation of cell autophagy. These results indicate that NaF exposure to duck induced nephron-toxicity by activating autophagy, apoptosis and glucolipid metabolism pathways, which suggest that fluorine exposure poses a risk of poisoning.

4.
Ecotoxicol Environ Saf ; 224: 112662, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34411823

RESUMO

Fluorine being a well-known and essential element for normal physiological functions of tissues of different organisms is frequently used for growth and development of body. The mechanisms of adverse and injurious impacts of fluoride are not clear and still are under debate. Therefore, this study was executed to ascertain the potential mechanisms of sodium fluoride in liver tissues of ducks. For this purpose, a total of 14 ducks were randomly divided and kept in two groups including control group and sodium fluoride treated group. The ducks in control group were fed with normal diet while the ducks in other group were exposed to sodium fluoride (750 mg/kg) for 28 days. The results showed that exposure to sodium fluoride induced deleterious effects in different liver tissues of ducks. The results indicated that mRNA levels of Cas-3, Cas-9, p53, Apaf-1, Bax and Cyt-c were increased in treated ducks with significantly higher mRNA level of Cas-9 and lower levels of the mRNA level of Bcl-2 as compared to untreated control group (P < 0.01). The results showed that protein expression levels of Bax and p53 were increased while protein expression level of Bcl-2 was reduced in treated ducks. No difference was observed in protein expression level of Cas-3 between treated and untreated ducks. The results of this study suggest that sodium fluoride damages the normal structure of liver and induces abnormal process of apoptosis in hepatocyte, which provide a new idea for elucidating the mechanisms of sodium fluoride induced hepatotoxicity in ducks.

5.
Chemosphere ; 283: 131226, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34146870

RESUMO

Butachlor is a systemic herbicide widely applied on wheat, rice, beans, and different other crops, and is frequently detected in groundwater, surface water, and soil. Therefore, it is necessary to investigate the potential adverse health risks and the underlying mechanisms of hepatotoxicity caused by exposure to butachlor in invertebrates, other nontarget animals, and public health. For this reason, a total of 20 mice were obtained and randomly divided into two groups. The experimental mice in one group were exposed to butachlor (8 mg/kg) and the mice in control group received normal saline. The liver tissues were obtained from each mice at day 21 of the trial. Results indicated that exposure to butachlor induced hepatotoxicity in terms of swelling of hepatocyte, disorders in the arrangement of hepatic cells, increased concentrations of different serum enzymes such as alkaline phosphate (ALP) and aspartate aminotransferase (AST). The results on the mechanisms of liver toxicity indicated that butachlor induced overexpression of Apaf-1, Bax, Caspase-3, Caspase-9, Cyt-c, p53, Beclin-1, ATG-5, and LC3, whereas decreases the expression of Bcl-2 and p62 suggesting abnormal processes of apoptosis and autophagy. Results on different metabolites (61 differential metabolites) revealed upregulation of PE and LysoPC, whereas downregulation of SM caused by butachlor exposure in mice led to the disruption of glycerophospholipids and lipid metabolism in the liver. The results of our experimental research indicated that butachlor induces hepatotoxic effects through disruption of lipid metabolism, abnormal mechanisms of autophagy, and apoptosis that provides new insights into the elucidation of the mechanisms of hepatotoxicity in mice induced by butachlor.


Assuntos
Herbicidas , Acetanilidas/toxicidade , Animais , Herbicidas/toxicidade , Metabolismo dos Lipídeos , Fígado , Camundongos
6.
Front Zool ; 17: 9, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32256671

RESUMO

Background: Severe hypoxia induces a series of stress responses in mammals; however, subterranean rodents have evolved several adaptation mechanisms of energy metabolisms and O2 utilization for hypoxia. Mammalian brains show extreme aerobic metabolism. Following hypoxia exposure, mammals usually experience irreversible brain damage and can even develop serious diseases, such as hypoxic ischemic encephalopathy and brain edema. To investigate mechanisms underlying the responses of subterranean rodents to severe hypoxia, we performed a cross-species brain transcriptomic analysis using RNA sequencing and identified differentially expressed genes (DEGs) between the subterranean rodent Lasiopodomys mandarinus and its closely related aboveground species L. brandtii under severe hypoxia (5.0% O2, 6 h) and normoxia (20.9% O2, 6 h). Results: We obtained 361 million clean reads, including 69,611 unigenes in L. mandarinus and 69,360 in L. brandtii. We identified 359 and 515 DEGs by comparing the hypoxic and normoxia groups of L. mandarinus and L. brandtii, respectively. Gene Ontology (GO) analysis showed that upregulated DEGs in both species displayed similar terms in response to severe hypoxia; the main difference is that GO terms of L. brandtii were enriched in the immune system. However, in the downregulated DEGs, GO terms of L. mandarinus were enriched in cell proliferation and protein transport and those of L. brandtii were enriched in nuclease and hydrolase activities, particularly in terms of developmental functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that upregulated DEGs in L. mandarinus were associated with DNA repair and damage prevention as well as angiogenesis and metastasis inhibition, whereas downregulated DEGs were associated with neuronal synaptic transmission and tumor-associated metabolic pathways. In L. brandtii, upregulated KEGG pathways were enriched in the immune, endocrine, and cardiovascular systems and particularly in cancer-related pathways, whereas downregulated DEGs were associated with environmental information processing and misregulation in cancers. Conclusions: L. mandarinus has evolved hypoxia adaptation by enhancing DNA repair, damage prevention, and augmenting sensing, whereas L. brandtii showed a higher risk of tumorigenesis and promoted innate immunity toward severe hypoxia. These results reveal the hypoxic mechanisms of L. mandarinus to severe hypoxia, which may provide research clues for hypoxic diseases.

7.
BMC Genomics ; 19(1): 901, 2018 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-30537924

RESUMO

BACKGROUND: Subterranean rodents have evolved many features to adapt to their hypoxic environment. The brain is an organ that is particularly vulnerable to damage caused by exposure to hypoxic conditions. To investigate the mechanisms of adaption to a hypoxic underground environment, we carried out a cross-species brain transcriptome analysis by RNA sequencing and identified genes that are differentially expressed between the subterranean vole Lasiopodomys mandarinus and the closely related above-ground species Lasiopodomys brandtii under chronic hypoxia [10.0% oxygen (O2)] and normoxia (20.9% O2). RESULTS: A total of 355 million clean reads were obtained, including 69,611 unigenes in L. mandarinus and 69,360 in L. brandtii. A total of 235 and 92 differentially expressed genes (DEGs) were identified by comparing the hypoxic and control groups of L. mandarinus and L. brandtii, respectively. A Gene Ontology (GO) analysis showed that upregulated DEGs in both species had similar functions in response to hypoxia, whereas downregulated DEGs in L. mandarinus were enriched GO terms related to enzymes involved in aerobic reactions. In the Kyoto Encyclopedia of Genes and Genomes pathway analysis, upregulated DEGs in L. mandarinus were associated with angiogenesis and the increased O2 transport capacity of red blood cells, whereas downregulated DEGs were associated with immune responses. On the other hand, upregulated DEGs in L. brandtii were associated with cell survival, vascular endothelial cell proliferation, and neuroprotection, while downregulated genes were related to the synaptic transmission by neurons. CONCLUSIONS: L. mandarinus actively adapts its physiological functions to hypoxic conditions, for instance by increasing O2 transport capacity and modulating O2 consumption. In contrast, L. brandtii reacts passively to hypoxia by decreasing overall activity in order to reduce O2 consumption. These results provide insight into hypoxia adaptation mechanisms in subterranean rodents that may be applicable to humans living at high altitudes or operating in other O2-poor environments.


Assuntos
Arvicolinae/genética , Encéfalo/metabolismo , Perfilação da Expressão Gênica , Hipóxia/genética , Animais , Doença Crônica , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Anotação de Sequência Molecular , Reprodutibilidade dos Testes , Especificidade da Espécie , Transcriptoma/genética
8.
BMC Med Genet ; 19(1): 60, 2018 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-29649976

RESUMO

BACKGROUND: X-linked lymphoproliferative syndrome type 1 (XLP1) is an X-linked recessive genetic disorder with a strong resemblance to hemophagocytic lymphohistiocytosis (HLH). Causative mutations for XLP1 have been identified in SH2D1A, located on chromosome Xq25. CASE PRESENTATION: We report a case of an 18-month-old male with a novel nonsense mutation in SH2D1A. The patient presented the typical phenotype of HLH, including splenomegaly and hemophagocytosis in the bone marrow. Thus, he was initially diagnosed with HLH based on HLH-2004 guidelines. High-throughput amplicon sequencing was performed to detect mutations in the most commonly reported causative genes of HLH, i.e., PRF1, UNC13D, STX11, STXBP2, SH2D1A, and XIAP. A likely pathogenic nonsense mutation was detected in SH2D1A (NM_002351.4:c.300T>A). The mutation was inherited from the patient's mother, and an X-linked recessive mode of inheritance was confirmed by a two-generation pedigree analysis based on Sanger sequencing results. CONCLUSIONS: The nonsense mutation in SH2D1A (NM_002351.4:c.300T>A) was reported for the first time in a case of XLP1 and was considered to be likely pathogenic based on the truncation of the mRNA sequence. This finding expands the spectrum of known XLP-related mutations in Chinese patients and indicates the utility of amplicon sequencing for XLP and HLH diagnosis.


Assuntos
Códon sem Sentido , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Transtornos Linfoproliferativos/genética , Proteína Associada à Molécula de Sinalização da Ativação Linfocitária/genética , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Masculino , Herança Materna , Linhagem , RNA Mensageiro/genética , Análise de Sequência de DNA
9.
Mol Med Rep ; 17(3): 4645-4650, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29328474

RESUMO

Despite recent medical advances, atherosclerosis is a global burden accounting for numerous mortalities and hospital admissions. MicroRNAs (miRNAs/miRs) regulate cardiovascular biology and disease, but the role of microRNA­34a in atherosclerosis remains unclear. In the present study, it was demonstrated that miR­34a was highly expressed in atherosclerotic lesions and oxidized low­density lipoprotein (Ox­LDL)­treated human aortic endothelial cells (HAECs) (atherosclerotic cell model) using reverse transcription­quantitative polymerase chain reaction. The expression of histone deacetylase (HDAC) 1 was reduced in atherosclerotic lesions and Ox­LDL treated HAECs. TargetScan predicted that HDAC1 is the potential target of miR­34a and the double­luciferase reporter assay confirmed that HDAC1 was directly targeted by miR­34a. Furthermore, miR­34a inhibitor significantly enhanced the cell viability of HAECs and the cell apoptosis was suppressed. In addition, the expression of apoptotic­related proteins was detected by western blotting. The results showed that miR­34a inhibitor significantly upregulated B­cell lymphoma 2, procaspase­3, procaspase­9 and proto­oncogene c­Myc protein expression, and downregulated the expression of p21. In contrast, co­transfection of HDAC1­small interfering RNA and miR­34a inhibitor eliminated the effects of miR­34a on HAECs. This indicated that miR­34a inhibitor promoted cell viability and prevented cell apoptosis of HAECs through regulating HDAC1. In conclusion, it was demonstrated that miR­34a promoted atherosclerotic formation by modulating the proliferation and apoptosis of HAECs, and regulating the expression of apoptosis­related proteins by targeting HDAC1.


Assuntos
Apoptose , Aterosclerose/patologia , Histona Desacetilase 1/metabolismo , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Antagomirs/metabolismo , Aorta/citologia , Aterosclerose/genética , Aterosclerose/metabolismo , Sequência de Bases , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Histona Desacetilase 1/antagonistas & inibidores , Histona Desacetilase 1/genética , Humanos , Lipoproteínas LDL/toxicidade , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Alinhamento de Sequência
10.
Int J Biol Macromol ; 109: 932-940, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29141193

RESUMO

Lasiopodomys mandarinus, a subterranean rodent, spends its entire life underground. To test whether the CLOCK and BMAL1 genes of L. mandarinus have undergone adaptive evolution to underground darkness, we cloned and analyzed their complete cDNA sequences, using Lasiopodomys brandtii as a control. The phylogenetic trees of the CLOCK and BMAL1 genes were similar to the trees of the conserved Cyt b gene,further, L. mandarinus clustered with L. brandtii and Microtus ochrogaster in the phylogenetic tree. The Q-rich region of the CLOCK gene in L. mandarinus was different from that of other subterranean rodents. Using phylogenetic analysis maximum likelihood (PAML), the ω value (ω<1) in different lineages showed that both genes have undergone purifying selection. The M8 model identified some positive selection sites in the CLOCK gene, most of which were located in the trans-transcription activation domain (TAD). In conclusion, CLOCK and BMAL1 genes did not exhibit convergent molecular evolution in subterranean rodents. Moreover, our study highlights the important functionality of the TAD, which is putatively of functional relevance to CLOCK protein activity. The present findings provide novel insights into adaptation to underground darkness, at the gene level, in subterranean rodents.


Assuntos
Fatores de Transcrição ARNTL/genética , Proteínas CLOCK/genética , Evolução Molecular , Roedores/genética , Sequência de Aminoácidos , Animais , Clonagem Molecular , DNA Complementar/química , DNA Complementar/genética , Variação Genética , Filogenia , Roedores/classificação , Seleção Genética , Análise de Sequência de DNA
11.
Gene ; 593(2): 302-7, 2016 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-27562081

RESUMO

Mandarin vole (Lasiopodomys mandarinus) is a subterranean rodent that is often used as a model for studying subterranean hypoxic stress in mammals. However the taxonomy of this species is still in dispute. Mitochondrial DNA (mtDNA) has long been used for phylogenetic reconstruction and, in this study, the complete mitochondrial genome of L. mandarinus mandarinus was sequenced. Our results showed that the mitochondrial genome of L. m. mandarinus is a circular molecule of 16,367bp, which contains 13 protein-coding genes, 22 tRNA and 2 rRNA genes. Except for the 8 tRNA and ND6 genes, all other mitochondrial genes are encoded on the heavy strand. We also analyzed the phylogenetic position of L. mandarinus in respect to the tribe Arvicolini using the sequence of complete Cytb gene, 2rRNA genes and 12 protein-coding genes, and maximum likelihood and Bayesian methods. Our results gave further support to the species status of L. mandarinus and the generic status of Lasiopodomys.


Assuntos
Arvicolinae/genética , Genoma Mitocondrial , Filogenia , Animais , Arvicolinae/classificação , Anotação de Sequência Molecular , Fases de Leitura Aberta , RNA Ribossômico/genética , RNA de Transferência/genética
12.
Artigo em Inglês | MEDLINE | ID: mdl-26258511

RESUMO

Mandarin voles (Lasiopodomys mandarinus) is a subterranean rodent species that are often used as a model for studying subterranean hypoxic stress in mammals. Its subspecies L. m. mandarinus span in cropland in most area of north China and is regarded as an agricultural pest. In this paper, the complete mitochondrial genome of L. m. mandarinus has been determined. Our results showed that the mitochondrial genome of L. m. mandarinus is a circular molecule of 16,367 bp, which contents 13 protein-coding, 22 tRNAs and 2 rRNAs genes. The overall base composition of the heavy strand is 32.47% A, 27.04% T, 27.01% C, and 13.47% G. with an AT content of 59.51%.


Assuntos
Arvicolinae/genética , Genoma Mitocondrial , Mitocôndrias/genética , Animais , Composição de Bases , Tamanho do Genoma , Filogenia , Análise de Sequência de DNA/métodos
13.
Artigo em Inglês | MEDLINE | ID: mdl-26258515

RESUMO

Manchurian Zokor (Myospalax psilurus) is a common subterranean rodents which have a wide distribution in Transbaikalia, east Mongolia, east and central China, and Far East of Russian. The complete mitochondrial (MT) genome of M. psilurus has been determined in this study. It is a 16,360 bp circular molecule containing 13 protein-coding, 22 tRNAs and 2 rRNAs genes. Except for the seven tRNA and Nd6 genes, all other mitogenes are encoded on the heavy strand. The overall nucleotide composition of the H-strand is 33.68% A, 28.77% T, 25.35% C, and 12.17% G. Total A + T content is 54.12%.


Assuntos
Genoma Mitocondrial , Mitocôndrias/genética , Roedores/genética , Animais , Composição de Bases , Tamanho do Genoma , Análise de Sequência de DNA/métodos
14.
Mitochondrial DNA ; 22(5-6): 174-5, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22165832

RESUMO

Plateau zokors Myospalax baileyi are subterranean rodents and endemic to the cold and hypoxic (2800-4300 m above sea level) climate of the farm, prairie, alpine prairie, and meadow habitats across the Tibetan plateau. The complete mitochondrial (mt) genome of M. baileyi has been determined. Our results showed that the total length of the mitogenome was 16,351 bp, and had a gene content of 13 protein coding, 22 tRNAs and 2 rRNAs. Except for the seven tRNA and Nd6 genes, all other mt genes are encoded on the heavy strand. The overall base composition of the heavy strand is 33.65% A, 29.65% T, 24.42% C, and 12.28% G, with an AT content of 63.3%.


Assuntos
DNA Mitocondrial/genética , Genoma Mitocondrial , Roedores/genética , Animais , RNA Ribossômico/genética , RNA de Transferência/genética , Análise de Sequência de DNA , Especificidade da Espécie
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