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1.
Food Chem Toxicol ; 137: 111179, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32035215

RESUMO

Methamphetamine (METH) is a highly addictive stimulant that results in serious and persistent neurotoxic effects. Studies have indicated that luteolin, a flavonoid, may confer neuroprotection against neurotoxicity. Nevertheless, the effects of luteolin on METH-induced neurotoxicity have not been sufficiently verified. In the present study, Sprague Dawley rats were pretreated with luteolin (100 mg/kg) or sodium dodecyl sulfate water, followed by administration of METH (15 mg/kg) or saline. Rat striata were then collected for RNA-sequencing and subsequent analyses. A total of 347 differentially expressed genes (DEGs) were identified in the METH group with 20 pathways, including the phosphoinositol 3 kinase (PI3K)/protein kinase B (Akt), found to be enriched by the KEGG analysis. Seventy-five of the 347 DEGs were modulated in luteolin-pretreated rats, which were enriched into 12 pathways, containing the PI3K/Akt. Results further showed that luteolin pretreatment significantly repressed the METH-induced increases of PI3K, Akt, p-Akt, p53, Bax, caspase 3, normalized the ratio of p-Akt/Akt, and autophagy-related proteins (Beclin1, Atg5 and LC3-II) expression. Taken together, these findings indicate that luteolin attenuates METH-induced apoptosis and autophagy by suppressing the PI3K/Akt pathway. In this case, it exerts protection against METH-induced neurotoxicity. This provides a platform for development of potential therapies for METH treatment.

2.
Exp Cell Res ; 389(2): 111855, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31978385

RESUMO

Takeda-G-protein-receptor-5 (TGR5) is a G-protein-coupled receptor (GPCR) activated by bile acids, and mortalin is a multipotent chaperone of the HSP70 family. In the present study, TGR5 was detected by immunohistochemistry (IHC) in extrahepatic cholangiocarcinoma (ECC) specimens, and TGR5 expression in ECC tissues and adjacent tissues was compared. In vitro TGR5 was overexpressed and knocked down in human intrahepatic cholangiocarcinoma (ICC) cell line RBE and human extrahepatic cholangiocarcinoma (ECC) cell line QBC-939 to observe its effects on the biological behavior of cholangiocarcinoma (CC) cells, including proliferation, apoptosis and migration. In vivo xenograft model was constructed to explore the role of TGR5 in CC growth. Proteins that interacted with TGR5 were screened using an immunoprecipitation spectrometry approach, and the identified protein was down-regulated to investigate its contribution to CC growth. The present study demonstrated that TGR5 is highly expressed in CC tissues, and strong TGR5 expression may indicate high malignancy in CC. Furthermore, TGR5 promotes CC cell proliferation, migration, and apoptosis resistance. TGR5 boosts CC growth in vivo. In addition, TGR5 combines with mortalin and regulates mortalin expression in the CC cell line. Mortalin participates in the TGR5-induced increase in CC cell proliferation. In conclusion, TGR5 is of clinical significance based on its implications for the degree of malignancy in patients with CC. Mortalin may be a downstream component regulated by TGR5, and TGR5 promotes cholangiocarcinoma at least partially by interacting with mortalin and upregulating its expression. Both TGR5 and mortalin are positive regulators, and may serve as potential therapeutic targets for CC.

3.
Oncol Rep ; 42(1): 263-272, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115555

RESUMO

Piwi­interacting RNAs (piRNAs), a novel class of non­coding RNAs, are enriched in germ cells and implicated in spermatogenesis. Emerging evidence demonstrated deregulated expression of piRNAs in numerous tumor types. However, changes in piRNA expression profiles in colorectal cancer (CRC) have not yet been investigated. In the present study, small RNA sequencing was used to evaluate the differences in piRNA expression profiles between CRC and adjacent non­tumor tissues, as well as to screen for differentially expressed piRNAs. The present results demonstrated that the percentage of unique piRNA reads had no notable difference between the paired CRC and adjacent non­tumor samples (0.12% vs. 0.13%); however, the counts of total piRNA reads in CRC samples were increased, compared with those in adjacent non­tumor samples (0.15% vs. 0.07%). Differential expression analysis identified 33 upregulated piRNAs and 2 downregulated piRNAs in CRC samples, among which piR­18849, piR­19521 and piR­17724 were the top three upregulated piRNAs. Reverse transcription­quantitative polymerase chain reaction further confirmed that the expression levels of piR­18849, piR­19521 and piR­17724 were increased in 80 CRC tissues, compared with paired adjacent non­tumor tissues. Furthermore, the high expression of piR­18849 and piR­19521 was associated with a poor degree of differentiation. The increased expression of piR­18849 was also associated with high lymph node metastasis. However, no associations were determined between piR­17724 expression and clinicopathological characteristics of patients. In summary, the present study is the first to provide an overview of the changes in piRNA expression patterns in CRC, shedding new light on the regulatory roles of piRNAs in colorectal carcinogenesis. piR­18849 and piR­19521 may be prognostic biomarkers for patients with CRC.


Assuntos
Neoplasias Colorretais/genética , Perfilação da Expressão Gênica/métodos , RNA Interferente Pequeno/genética , Idoso , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sequência de RNA/métodos
4.
Onco Targets Ther ; 12: 2661-2675, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31040704

RESUMO

Purpose: Gastric cancer (GC) patients display aberrant miRNA expression and defective dendritic cell function. However, the role of cancer cell-derived oncomiR in GC detection and dendritic cell (DC) maturation remains largely elusive. Methods: Candidate miRNAs were selected by deep sequencing (8 GC plasma samples vs 8 control plasma samples; 8 GC tissues vs 8 adjacent normal gastric tissues) and confirmed by PCR with 164 plasma samples and 72 formalin-fixed paraffin-embedded GC tissue samples. Their diagnostic performance was evaluated by receiver operating characteristic curve. Cy3 fluorescence signals in DCs, exposed to conditioned medium obtained from BGC-823 cells pre-transfected with Cy3-miR-17-5p, were determined by flow cytometry and visualized by confocal microscopy. Functional and phenotypical alterations of DCs were assayed when DCs were transfected with miR-17-5p in vitro. Results: Deep sequencing and RT-PCR confirmed that five shared miRNAs were upregulated in plasma and tissue samples of GC patients. Cell-free miR-17-5p was superior to others in GC detection with an area under the curve of 0.82, and correlated with lymphatic metastasis and poor overall survival. GC cell-shuttled miR-17-5p can be delivered to immature DCs, and they significantly inhibited LPS-stimulated phenotypic maturation by diminishing the expression of maturation markers (MHC II, CD80 and CD86 molecules). In line with those alterations in the phenotypic markers, functional experiments demonstrated that miR-17-5p triggered an inhibitory effect on DCs endocytic activity and decreased tumor necrosis factor-α and IL-12 secretion, while enhancing IL-10 production. Mixed lymphocyte reaction showed that miR-17-5p inhibited the T cell stimulating effect of DCs and favored regulatory T cells expansion. Conclusion: GC cell-derived miR-17-5p is a potential biomarker for GC detection. Taken up by DCs, miR-17-5p weakened antitumor immune responses via inhibiting the maturation of dendritic cells.

5.
Chemosphere ; 227: 389-400, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31003123

RESUMO

Polychlorinated biphenyls (PCBs), a kind of persistent organic pollutant, can induce hepatotoxicity in mammals. However, PCB-induced hepatotoxicity in offspring and the underlying mechanisms have been rarely studied. In the present study, Wistar rats were administered with corn oil or PCB52 (1 mg/kg body weight/day, by gavage) from gestational day 7 to postnatal day 21. In the PCB52-treated group, birth body lengths and weights were significantly decreased compared with the control group, suggesting developmental toxicity. Cytoplasmic injury in hepatocytes was observed in PCB52-treated male offspring, while no pathologic change was observed in female offspring, suggesting sex-biased hepatotoxicity. Furthermore, using an RNA-Seq method, coincided with the sexual bias, 454 differential expression genes (DEGs) were screened out in liver tissues of PCB52-treated male offspring, while 10 DEGs were screened out in female offspring. By KEGG annotation analysis, 4 in 12 significant pathways in male offspring were metabolism-related. In the present study, together with cytoplasmic injury of hepatocytes, decreased metabolic enzymes both at RNA and protein levels might aggravate loss of clearance capacity of hepatocytes and induce hepatotoxicity. Moreover, over-expressed peroxisome proliferator-activated receptor delta and mitogen-activated protein kinase 9 might activate apoptosis, which was verified by the augments of cleaved poly ADP-ribose polymerase 1 and caspase 3 in PCB52-treated male offspring. Taken together, PCB52 had developmental toxicity and induced sex-biased hepatotoxicity. The hepatotoxicity in male offspring might be attributed to the aggravated loss of clearance capacity and activation of apoptosis.


Assuntos
Poluentes Ambientais/toxicidade , Bifenilos Policlorados/toxicidade , Animais , Apoptose/efeitos dos fármacos , Caspase 3 , Doença Hepática Induzida por Substâncias e Drogas , Feminino , Hepatócitos/efeitos dos fármacos , Cinética , Masculino , Poli(ADP-Ribose) Polimerase-1 , Ratos , Ratos Wistar , Fatores Sexuais , Testes de Toxicidade
6.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(2): 168-171, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30782281

RESUMO

OBJECTIVE: To study the clinical effect of alanyl-glutamine-enriched nutritional support in the treatment of children with abdominal Henoch-Schönlein purpura. METHODS: Children with abdominal Henoch-Schönlein purpura who needed nutritional support were enrolled and stratified according to age, sex and the severity of disease, and were randomly divided into a control group (n=118) and an enriched nutritional support group (n=107). The control group was given nutritional support without using alanyl-glutamine, while the enriched nutritional support group was given alanyl-glutamine-enriched nutritional support. Intravenous steroids were used according to the severity of disease in both groups. Other therapies were the same in the two groups. The two groups were compared in terms of the length of hospital stay, the rate and duration of use of intravenous steroids, the recurrence rate of symptoms during hospitalization, the rate of total parenteral nutrition (TPN), the rate of weight loss and the rate of fasting for more than 5 days. All patients were followed up for 3 months after discharge to monitor the recurrence of symptoms. RESULTS: There were no significant differences in the length of hospital stay, the rate of TPN and the rate of fasting for more than 5 days between the two groups (P>0.05). Compared with the enriched nutritional support group, the control group showed significant increases in the rate and duration of use of intravenous steroids, the recurrence rate of symptoms and the rate of weight loss (P<0.05). After the 3-month follow-up, all the children resumed normal diet, and the recurrence rate of digestive symptoms was less than 20% in each group. Abdominal pain was the most common symptom (83.33%, 30/36), followed by vomiting and abdominal distention. No digestive hemorrhage was observed. All the symptoms were relieved after symptomatic treatment. No significant difference was found between the two groups in the recurrence rate of digestive symptoms (P=0.693). CONCLUSIONS: Alanyl-glutamine-enriched nutritional support in the treatment of children with abdominal Henoch-Schönlein purpura can reduce the use of intravenous steroids and weight loss, but without impact on the length of hospital stay and post-discharge recurrence.


Assuntos
Púrpura de Schoenlein-Henoch , Criança , Dipeptídeos , Humanos , Nutrição Parenteral Total , Recidiva
7.
Exp Mol Med ; 51(1): 6, 2019 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-30635551

RESUMO

The clearance of activated hepatic stellate cells (HSCs) by apoptosis is critical for the reversibility of hepatic fibrosis. Mitochondrial homeostasis is regulated by mitophagy, which is an efficient way of clearing injured mitochondria that plays an important role in apoptosis. However, the role of mitophagy in apoptosis in HSCs and hepatic fibrosis is still unclear. Here, we show that mitophagy is enhanced in parallel with increased apoptosis in hepatic stellate cells during the reversal of hepatic fibrosis. The inhibition of mitophagy suppressed apoptosis in HSCs and aggravated hepatic fibrosis in mice. In contrast, the activation of mitophagy induced apoptosis in HSCs. Furthermore, we confirmed that BCL-B, which is a member of the BCL-2 family, is a regulator mediating mitophagy-related apoptosis. The knockdown of BCL-B resulted in increased apoptosis and mitophagy in HSCs, while the overexpression of BCL-B caused the opposite effects. BCL-B inhibited the phosphorylation of Parkin (a key regulator of mitophagy) and directly bound phospho-Parkin. Altogether, enhanced mitophagy promotes apoptosis in HSCs during the reversal of hepatic fibrosis. BCL-B suppresses mitophagy in HSCs by binding and suppressing phospho-Parkin, thereby inhibiting apoptosis. BCL-B-dependent mitophagy is a new pathway for the regulation of apoptosis in HSCs during the regression of hepatic fibrosis.


Assuntos
Apoptose , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Animais , Linhagem Celular , Células Cultivadas , Cirrose Hepática/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
8.
Biochem Biophys Res Commun ; 509(2): 395-401, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30594393

RESUMO

Methamphetamine (METH) is a psychostimulant with severe neurotoxicity, which is related to an increase of blood-brain barrier (BBB) permeability. However, the exact mechanisms have not been fully illuminated. In the present study, male Sprague Dawley rats were treated with METH or saline with 8 injections (i.p.) at 12-h intervals and sacrificed 24 h after the last METH injection. To evaluate BBB permeability, 6 rats were administered with Evans blue (EB) by tail vein injection 1 h prior to sacrifice. EB levels significantly increased in both left and right frontal lobes in METH-treated rats, suggesting increase of BBB permeability, which was proved by the rearrangement of F-actin cytoskeleton and decreased expressions of tight junction (TJ) proteins in hippocampus. Over-expressions of RhoA, ROCK, myosin light chain (MLC), cofilin, phosphorylation (p)-MLC, p-cofilin and matrix metalloproteinase (MMP)-9 were observed, indicating activated RhoA/ROCK pathway. Rat brain microvascular endothelial cells (RBMECs) were isolated and treated with inhibitors of RhoA and ROCK followed by METH. Pretreatments of the inhibitors significantly decreased expressions of RhoA, ROCK, MLC, cofilin, p-MLC and p-cofilin, increased expressions of TJ proteins, suppressed F-actin cytoskeleton rearrangement and reduced the permeability of RBMECs. These results suggested that METH increased BBB permeability through activating the RhoA/ROCK pathway, which resulted in F-actin cytoskeleton rearrangement and down-regulation of TJ proteins.


Assuntos
Citoesqueleto de Actina/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Hipocampo/efeitos dos fármacos , Metanfetamina/farmacologia , Junções Íntimas/efeitos dos fármacos , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/ultraestrutura , Actinas/genética , Actinas/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Cofilina 1/genética , Cofilina 1/metabolismo , Corantes/farmacocinética , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Azul Evans/farmacocinética , Regulação da Expressão Gênica , Hipocampo/citologia , Hipocampo/metabolismo , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Cadeias Leves de Miosina/genética , Cadeias Leves de Miosina/metabolismo , Permeabilidade/efeitos dos fármacos , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas/metabolismo , Junções Íntimas/ultraestrutura , Proteínas rho de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/metabolismo , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismo
9.
Front Neurosci ; 12: 802, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30450033

RESUMO

Abuse of methamphetamine (METH) results in neurological and psychiatric abnormalities. Lactulose is a poorly absorbed derivative of lactose and can effectively alleviate METH-induced neurotoxicity in rats. The present study was designed to investigate the effects of lactulose on METH-induced neurotoxicity. Rats received METH (15 mg/kg, 8 intraperitoneal injections, 12-h interval) or saline and received lactulose (5.3 g/kg, oral gavage, 12-h interval) or vehicle 2 days prior to the METH administration. Reactive oxygen species (ROS) and malondialdehyde (MDA) were measured. Protein levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor associated factor 6 (TRAF6), nuclear factor κB (NFκB), interleukin (IL)-1ß, IL-6, TNF-α, cleaved caspase 3, and poly(ADP-ribose) polymerase-1 (PARP-1) were determined by western blotting. mRNA expressions of nuclear factor erythroid 2-relatted factor-2 (Nrf2), p62, and heme oxygenase-1 (HO-1) were assessed by RT-qPCR. The lactulose pretreatment decreased METH-induced cytoplasmic damage in rat livers according to histopathological observation. Compared to the control group, overproduction of ROS and MDA were observed in rat striatums in the METH alone-treated group, while the lactulose pretreatment significantly attenuated the METH-induced up-regulation of oxidative stress. The lactulose pretreatment significantly repressed over-expressions of proteins of TLR4, MyD88, TRAF6, NFκB, IL-1ß, IL-6, TNF-α, cleaved caspase 3, PARP-1. The lactulose pretreatment increased mRNA expressions of Nrf2, p62, and HO-1. These findings suggest that lactulose pretreatment can alleviate METH-induced neurotoxicity through suppressing neuroinflammation and oxidative stress, which might be attributed to the activation of the Nrf2/HO-1 axis.

10.
J Forensic Leg Med ; 59: 8-12, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30059828

RESUMO

The detection of vitality of wounds is very important in forensic practice. This study is performed using quantitative real-time reverse transcriptase polymerase chain reaction (RT-qPCR) in both mouse and human skin wounds for the application of IL-6 and IL-20 in order to differentiate intravital wounds from postmortem wounds. RT-qPCR analysis of contused mouse skin showed that increased IL-6 and IL-20 mRNA levels were found in comparison to intact skin tissues. The increased mRNA expressions of IL-6 and IL-20 were observed until 72 h after death in contused mouse skin, whereas there were no marked changes in these two cytokines in the postmortem contusion group. The alterations of IL-6 and IL-20 can also be detected in human skin wound samples. These finding suggest that mRNA levels of IL-6 and IL-20 might be used as potential markers for vital reaction.


Assuntos
Contusões/metabolismo , Interleucina-6/metabolismo , Interleucinas/metabolismo , Mudanças Depois da Morte , Pele/metabolismo , Adolescente , Adulto , Animais , Biomarcadores/metabolismo , Feminino , Patologia Legal , Humanos , Interleucina-6/genética , Interleucinas/genética , Masculino , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Pele/lesões , Adulto Jovem
11.
Forensic Sci Med Pathol ; 14(2): 174-179, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29607464

RESUMO

Detection of the vitality of wounds is one of the most important issues in forensic practice. This study investigated mRNA and protein levels of CXCL1 and CXCR2 in skin wounds in mice and humans. Western blot analysis of CXCL1 and CXCR2 protein levels showed no difference between wounded and intact skin. However, mRNA levels demonstrated higher expression of CXCL1 and CXCR2 in contused mouse and human skin, compared with intact skin. At postmortem there were no remarkable changes in CXCL1 and CXCR2 mRNA levels in contused mouse skin. Increased mRNA expression was observed in contused mouse skin up to 96 h and 72 h after death for CXCL1 and CXCR2 respectively. In human samples of wounded skin, increased CXCL1 mRNA levels were detected up to 48 h after autopsy in all 5 cases, while increased CXCR2 mRNA levels were observed 48 h after autopsy in 4 of 5 cases. These findings suggest that the levels of CXCL1 and CXCR2 mRNA present in contused skin can be used as potential markers for a vital reaction in forensic practice.


Assuntos
Quimiocina CXCL1/metabolismo , Contusões/metabolismo , Patologia Legal , Receptores de Interleucina-8B/metabolismo , Animais , Biomarcadores/metabolismo , Quimiocina CXCL1/genética , Contusões/patologia , Humanos , Camundongos , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Interleucina-8B/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
12.
Forensic Sci Med Pathol ; 14(2): 209-215, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29679215

RESUMO

Postmortem diagnosis of sudden death due to anaphylaxis can be very difficult due to the non-specific pathological findings in forensic practice. Postmortem serum tryptase has been used as an indicator of possible ante-mortem anaphylaxis. Though many previous studies have been conducted to explore the diagnostic significance of serum tryptase for lethal anaphylaxis, inconsistent results were documented. In this study, we made a retrospective study and presented a systematic review and meta-analysis that aims to summarize the diagnostic significance of postmortem serum tryptase in the deceased with and without anaphylactic shock and to calculate a cutoff value for future reference in the identification of deaths due to anaphylactic shock. A complete literature search in the PubMed, Cochrane Library, CNKI and Embase databases (published prior to March 1st, 2017) was performed. The quality of the eligible literature was evaluated according to the Newcastle-Ottawa Quality Assessment Scale (NOS), and the relevant data was extracted. The procedure of meta-analysis was performed by RevMan 5.3 software. Subgroup analysis was performed according to different causes of death. A total of nine studies with 296 patients were identified. The NOS of each included study was equal to 7. The results indicated that high concentrations of tryptase were significantly associated with anaphylactic shock when compared to the other causes of death. The weighted mean difference (WMD) was 29.53 (95% CI = 7.58-51.47, p = 0.008). Similar results were detected in the subgroup analysis when compared to deaths due to cardiovascular disease (CVD). However, no obvious elevation of tryptase in decedents with CVD compared to the other cause of death was observed (WMD = 4.42, 95% CI = -0.94-9.79). We concluded that high serum tryptase is a promising diagnostic biomarker for deaths due to anaphylactic shock, especially when it is higher than 30.4 µg/L.


Assuntos
Anafilaxia/diagnóstico , Triptases/sangue , Biomarcadores/sangue , Medicina Legal , Humanos
13.
Toxicol Lett ; 289: 28-41, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29518472

RESUMO

Hepatotoxicity is one of the adverse health effects induced by polychlorinated biphenyls (PCBs). Recently, autophagy was revealed to play an important role in PCBs-induced toxicology, however, its precise role in PCBs-induced hepatotoxicity is as yet unknown. In this study, treatment of PCB28/PCB52 for 48 h dose-dependently induced hepatotoxicity at doses of 10, 20, 40 and 80 µM in homo and rattus hepatocytes. Expressions of proteins of BECN1, LC3-II and ULK1 significantly increased in PCB28/PCB52-treated cells at a dose of 40 µM, implying initiation of autophagy. Over-expression of p62 suggested deficient clearance of autophagosome. Consistently, accumulation of autophagosome was observed by transmission-electron microscopy and confocal fluorescence microscopy using adenovirus expressing mRFP-GFP-LC3, which may initiate apoptosis. Furthermore, increased reactive oxygen species levels might also induce autophagy and apoptosis. Consistently, cell apoptosis was evoked by the treatment of PCB28/PCB52 compared to the respective controls, which coincided with obvious hepatotoxicity. Subsequently, an inhibitor (3-methlyadenine) and an initiator (rapamycin) of autophagy were used. Compared to PCB28/PCB52 alone-treated cells, initiation of autophagy, blocked autophagic flux, cell apoptosis and hepatotoxicity were alleviated by 3-methlyadenine and aggravated by rapamycin, respectively. Taken together, PCB28 and PCB52 induced hepatotoxicity by impairing autophagic flux and stimulating cell apoptosis in vitro.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Bifenilos Policlorados/toxicidade , Animais , Autofagossomos/efeitos dos fármacos , Autofagossomos/metabolismo , Autofagossomos/ultraestrutura , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Hepatócitos/metabolismo , Hepatócitos/ultraestrutura , Humanos , Cinética , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Estresse Oxidativo/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Proteínas Recombinantes de Fusão/metabolismo
14.
Toxicol Lett ; 289: 107-113, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29550550

RESUMO

Methamphetamine (METH) is a widely abused psychostimulant. Lactulose is a non-absorbable sugar, which effectively decreases METH-induced neurotoxicity in rat. However, the exact mechanisms need further investigation. In this study, 5-week-old male Sprague Dawley rats received METH (15 mg/kg, 8 intraperitoneal injections, 12-h interval) or saline and received lactulose (5.3 g/kg, oral gavage, 12-h interval) or vehicle 2 days prior to the METH administration. Compared to the control group, in the METH alone group, cytoplasmic vacuolar degeneration in hepatocytes, higher levels of alanine transaminase, aspartate transaminase and ammonia, overproduction of reactive oxygen species (ROS) and increase of superoxide dismutase activity in the blood were observed. Moreover, in rat striatum, expressions of nuclear factor erythroid 2-relatted factor-2 (Nrf2) and heme oxygenase-1 were suppressed in the nucleus, although over-expression of Nrf2 were observed in cytoplasm. Over-expressions of BECN1 and LC3-II indicated initiation of autophagy, while overproduction of p62 might suggest deficient autophagic vesicle turnover and impaired autophagy. Furthermore, accumulation of p62 cloud interact with Keap1 and then aggravate cytoplasmic accumulation of Nrf2. Consistently, over-expressions of cleaved caspase 3 and poly(ADP-ribose) polymerase-1 suggested the activation of apoptosis. The pretreatment with lactulose significantly decreased rat hepatic injury, suppressed hyperammonemia and ROS generation, alleviated the impaired autophagy in striatum, rescued the antioxidant system and repressed apoptosis. Taken together, with decreased blood ammonia, lactulose pretreatment reduced METH-induced neurotoxicity through alleviating the impaired autophagy, stabilizing the perturbed antioxidant system and suppressing apoptosis in rat striatum.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Lactulose/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Síndromes Neurotóxicas/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/uso terapêutico , Biomarcadores/metabolismo , Estimulantes do Sistema Nervoso Central/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Metanfetamina/toxicidade , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Distribuição Aleatória , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
15.
Shanghai Kou Qiang Yi Xue ; 27(5): 467-471, 2018 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-30680387

RESUMO

PURPOSE: To study the effect of root canal wall moisture and filling techniques on the sealability of iRoot sp. METHODS: Sixty-two undamaged extracted human single-rooted teeth with fully developed apex were selected and prepared by crown-down technique. Two teeth were selected randomly to observe dentin tubules, opening, the residual teeth were randomly assigned to 3 groups: group A (wet), group B (slightly moist),group C(dry).The roots were further divided into 4 subgroups, group a: iRoot sp sealer without a core material (bulk-fill); group b: iRoot sp sealer with single cone obturation techniques; group c: iRoot sp sealer with heated gutta-purcha vertical pressure; group d: iRoot sp sealer with cold gutta-percha lateral compression technique. Glucose microleakage were measured in each group by glucose oxidase method. The differences in distribution of each group were analyzed with SPSS 19.0 software package. RESULTS: Group A and group B always showed the maximum and minimum amount of glucose penetration in the whole experimental process, and the difference was statistically significant at 28d (P<0.05). Under the same degree of moisture of root canal wall, glucose leakage of subgroup Aa was significantly higher than that of subgroup Ab and Ac at 15 d; and significantly higher than Ab, Ac, Ad at 21 d and 28 d(P<0.05). In group B and C, the subgroups a, b, c, d had no significant difference from each other during the experimental process(P>0.05). CONCLUSIONS: iRoot sp sealer has the best sealing effect when root canals were slightly moist. When the root canal wall is completely dry or slightly moist, the sealability of iRoot sp bulk-fill is similar to that of iRoot sp sealer with gutta-percha filling technique.


Assuntos
Cavidade Pulpar , Materiais Restauradores do Canal Radicular , Preparo de Canal Radicular , Silicatos , Infiltração Dentária , Guta-Percha , Humanos , Obturação do Canal Radicular
16.
Environ Sci Pollut Res Int ; 25(7): 6407-6413, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29249028

RESUMO

In the hilly areas of southern China, uplands and paddies are located adjacent to each other. Using rice straw as mulch for upland soil may improve crop production and partially replace chemical fertilizers, which may mitigate N2O emissions. A field experiment was conducted to investigate the potential of rice straw mulching for mitigating N2O emissions and increasing crop production. The treatments included no mulching (CK), 5000 kg ha-1 of straw mulching (SM5), and 10,000 kg ha-1 of straw mulching (SM10). Moreover, all the treatments received equivalent amounts of nitrogen, phosphorus, and potassium from chemical fertilizers plus rice straw. Relative to CK, cumulative N2O emissions decreased by 23.1 and 33.5% with SM5 and SM10, respectively. Significant positive correlations were observed between N2O fluxes and soil water-filled pore space (WPFS) (r 2 = 0.495, P < 0.05) and between seasonal cumulative N2O fluxes and the chemical N fertilization rate (r 2 = 0.814, P < 0.05). These findings indicate that soil WPFS was the key environmental factor in N2O emissions and that the substitution of chemical nitrogen fertilizer with rice straw was the main driver of N2O mitigation. Relative to CK, the maize yield increased by 16.5 and 29.6% with SM5 and SM10, respectively, which can be attributed primarily to the increases in soil moisture. The chemical fertilizer input could be decreased and N2O emissions could be mitigated through straw mulching, while achieving improved crop yield. This management strategy has great potential, and this study provides an important reference for low-carbon agriculture.


Assuntos
Poluentes Atmosféricos/análise , Fertilizantes/análise , Óxido Nitroso/análise , Oryza/química , Chuva , Zea mays/crescimento & desenvolvimento , Agricultura , China , Solo/química
17.
PLoS One ; 12(12): e0189280, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29216292

RESUMO

Rice cultivation has been challenged by increasing food demand and water scarcity. We examined the responses of water use, grain yield, and water productivity to various modes of field water managements in Chinese double rice systems. Four treatments were studied in a long-term field experiment (1998-2015): continuous flooding (CF), flooding-midseason drying-flooding (F-D-F), flooding-midseason drying-intermittent irrigation without obvious standing water (F-D-S), and flooding-rain-fed (F-RF). The average precipitation was 483 mm in early-rice season and 397 mm in late-rice season. The irrigated water for CF, F-D-F, F-D-S, and F-RF, respectively, was 263, 340, 279, and 170 mm in early-rice season, and 484, 528, 422, and 206 mm in late-rice season. Grain yield for CF, F-D-F, F-D-S, and F-RF, respectively, was 4,722, 4,597, 4,479, and 4,232 kgha-1 in early-rice season, and 5,420, 5,402, 5,366, and 4,498 kgha-1 in late-rice season. Compared with CF, F-D-F consumed more irrigated water, which still decreased grain yield, leading to a decrease in water productivity by 25% in early-rice season and by 8% in late-rice season. Compared with F-D-F, F-D-S saved much irrigated water with a small yield reduction, leading to an increase in water productivity by 22% in early-rice season and by 26% in late-rice season. The results indicate that CF is best for early-rice and FDS is best for late-rice in terms of grain yield and water productivity.


Assuntos
Irrigação Agrícola/métodos , Produtos Agrícolas , Oryza , Água , China , Estações do Ano
18.
Sci Rep ; 7(1): 14549, 2017 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-29109431

RESUMO

Paddy soils have been widely recognized as important carbon sinks. However, paddy field abandonment is increasing in the hilly area in subtropical China. Soil waterlogging and weed burning are common practices in abandoned paddy fields, which could affect vegetation cover and carbon sequestration. An rice cultivation experiment was ceased in 2006, and four new treatments were applied as waterlogging (W), drainage (D), waterlogging combined with burning (WB), and drainage combined with burning (DB). Waterlogging altered the vegetation cover and caused an associated change in biomass. Paspalum paspaloides, Murdannia triquetra, and Bidens frondosa dominated W and WB plots, and Microstegium vimineum and Bidens frondosa dominated D and DB plots. Abandonment of paddy fields led to a rapid decrease in soil organic carbon (SOC), and waterlogging accelerates SOC loss which should be attributed mainly to alteration of the vegetation cover. Six years' rice cultivation increased SOC content by 13.5% (2.4 g kg-1) on average. In contrast, six years' abandonment reduced SOC content by 14.5% (3.0 g kg-1) on average. Decline rate of SOC was 0.38, 0.64, 0.30, and 0.65 g kg-1 a-1 for D, W, DB, and WB, respectively. Such results indicate a significant risk of SOC loss from abandoned paddy fields.

19.
Oncotarget ; 8(35): 59359-59375, 2017 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-28938642

RESUMO

Lysicamine is a natural oxoaporphine alkaloid, which isolated from traditional Chinese medicine (TCM) herbs and has been shown to possess cytotoxicity to hepatocarcinoma cell lines. Reports on its antitumor activity are scarce because lysicamine occurs in plants at a low content. In this work, we demonstrate a facile concise total synthesis of lysicamine from simple raw materials under mild reaction conditions, and the preparation of the Ru(II), Rh(III), Mn(II) and Zn(II) complexes 1-4 of lysicamine (LY). All the compounds were fully characterized by elemental analysis, IR, ESI-MS, 1H and 13C NMR, as well as single-crystal X-ray diffraction analysis. Compared with the free ligand LY, complexes 2 and 3 exhibited superior in vitro cytotoxicity against HepG2 and NCI-H460. Mechanistic studies indicated that 2 and 3 blocked the cell cycle in the S phase by decreasing of cyclins A2/B1/D1/E1, CDK 2/6, and PCNA levels and increasing levels of p21, p27, p53 and CDC25A proteins. In addition, 2 and 3 induced cell apoptosis via both the caspase-dependent mitochondrial pathway and the death receptor pathway. in vivo study showed that 2 inhibited HepG2 tumor growth at 1/3 maximum tolerated dose (MTD) and had a better safety profile than cisplatin.

20.
Arterioscler Thromb Vasc Biol ; 37(10): 1849-1859, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28798142

RESUMO

OBJECTIVE: Smooth muscle (SM) 22α, an actin-binding protein, displays an upregulated expression as a marker during cellular senescence. However, the causal relationship between SM22α and senescence is poorly understood. This study aimed to investigate the role of SM22α in angiotensin II (Ang II)-induced senescence of vascular smooth muscle cells (VSMCs). APPROACH AND RESULTS: We prepared a model of VSMC senescence induced by Ang II and found that the expression of SM22α in VSMCs was increased in response to chronic Ang II treatment. Overexpression of SM22α promoted Ang II-induced VSMC senescence, whereas knockdown of SM22α suppressed this process. Moreover, this effect of SM22α was p53 dependent. Increased SM22α protein obstructed ubiquitination and degradation of p53 and subsequently improved its stability. Furthermore, SM22α inhibited phosphorylation of Mdm2 (mouse double minute 2 homolog), an E3 ubiquitin-protein ligase, accompanied by a decreased interaction between Mdm2 and p53. Using LY294002, a PI3K/Akt inhibitor, we found that PI3K/Akt-mediated Mdm2 phosphorylation and activation was inhibited in senescent or SM22α-overexpressed VSMCs, in parallel with decreased p53 ubiquitination. We further found that SM22α inhibited activation of PI3K/Akt/Mdm2 pathway via strengthening actin cytoskeleton. In the in vivo study, we showed that the disruption of SM22α reduced the increase of blood pressure induced by Ang II, associated with decreased VSMC senescence through a mechanism similar to that in VSMCs in vitro. CONCLUSIONS: In conclusion, these findings suggest that the accumulation of SM22α promotes Ang II-induced senescence via the suppression of Mdm2-mediated ubiquitination and degradation of p53 in VSMCs in vitro and in vivo.


Assuntos
Senescência Celular , Proteínas dos Microfilamentos/metabolismo , Proteínas Musculares/metabolismo , Músculo Liso Vascular/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Citoesqueleto de Actina/metabolismo , Angiotensina II/farmacologia , Animais , Aorta/metabolismo , Senescência Celular/efeitos dos fármacos , Hipertensão/fisiopatologia , Camundongos , Modelos Animais , Músculo Liso Vascular/citologia , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Ubiquitinação , Regulação para Cima
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