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1.
Sci Transl Med ; 12(530)2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32051225

RESUMO

Neonatal hyperbilirubinemia is a common clinical condition that can lead to brain encephalopathy, particularly when concurrent with acidosis due to infection, ischemia, and hypoxia. The prevailing view is that acidosis increases the permeability of the blood-brain barrier to bilirubin and exacerbates its neurotoxicity. In this study, we found that the concentration of the cell death marker, lactate dehydrogenase (LDH) in cerebrospinal fluid (CSF), is elevated in infants with both hyperbilirubinemia and acidosis and showed stronger correlation with the severity of acidosis rather than increased bilirubin concentration. In mouse neonatal neurons, bilirubin exhibits limited toxicity but robustly potentiates the activity of acid-sensing ion channels (ASICs), resulting in increases in intracellular Ca2+ concentration, spike firings, and cell death. Furthermore, neonatal conditioning with concurrent hyperbilirubinemia and hypoxia-induced acidosis promoted long-term impairments in learning and memory and complex sensorimotor functions in vivo, which are largely attenuated in ASIC1a null mice. These findings suggest that targeting acidosis and ASICs may attenuate neonatal hyperbilirubinemia complications.

2.
Anal Chem ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32066231

RESUMO

Liver fibrosis is a major stage in the development of liver diseases and it is important to investigate its pathogenesis for early intervene or even reversing. Recent studies have found that intestinal disease can aggravate liver fibrosis through the role of the "gut-liver axis". Hypoxia is considered to be a typical characteristic of many diseases including ulcerative colitis and liver fibrosis. However, there is no fluorescent probe for hypoxia detection to investigate "gut-liver axis". Herein, we design and synthesize a turn-on fluorescent probe termed Cy-AP, which displays high sensitivity and selectivity to hypoxia given by sodium dithionite (Na2S2O4) in vitro with near-infrared (NIR) emission (735 nm). And the possible response mechanism of Cy-AP towards hypoxia is given and proved by HPLC, MS and theory calculation. Moreover, on the basis of low cell cytotoxicity, the probe is successfully applied in visualizing hypoxia in four cell lines (HepG2, HCT116, HeLa and MCF-7 cells) by fluorescence imaging, flow cytometry and 3D imaging. Furthermore, due to its NIR emission, Cy-AP can monitor the hypoxia condition in vivo such as liver fibrosis mice and ulcerative colitis mice model. In particular, the probe can validate the existence and mechanism of "gut-liver axis" in vivo by monitoring hypoxia. To the best of our knowledge, this is the first report to describe a strategy for study "gut-liver axis" by a NIR hypoxia-sensitive fluorescent probe, which will provide some powerful support for delaying the progression of liver fibrosis and thus promoting the treatment of liver disease.

3.
Int J Neurosci ; : 1-5, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31944864

RESUMO

Purpose: Sjögren-Larsson syndrome is a rare, autosomal, recessive neurocutaneous disorder caused by mutations in the ALDH3A2 gene, which encodes the fatty aldehyde dehydrogenase enzyme. Deficiency in fatty aldehyde dehydrogenase results in an abnormal accumulation of toxic fatty aldehydes in the brain and skin, which cause spasticity, intellectual disability, ichthyosis, and other clinical manifestations. We present the clinical features and mutation analyses of a case of SLS.Materials and Methods: The family history and clinical data of the patient were collected. Genomic DNA was extracted from peripheral blood samples of the patient and her parents, and next-generation sequencing was performed. The candidate mutation sites that required further validation were then sequenced by Sanger sequencing. Bioinformatics software PSIPRED and RaptorX were used to predict the secondary and tertiary structures of proteins.Results: The patient, a five-year-old girl with complaints of cough for three days and intermittent convulsions for seven hours, was admitted to the hospital. Other clinical manifestations included spastic paraplegia, mental retardation, tooth defects, and ichthyosis. Brain magnetic resonance imaging showed periventricular leukomalacia. Genetic screening revealed compound heterozygous mutations in the ALDH3A2 gene: a frameshift mutation c.779delA (p.K260Rfs*6) and a missense mutation c.1157A > G (p.N386S). Neither of the ALDH3A2 alleles in the compound heterozygote patient were able to generate normal fatty aldehyde dehydrogenase, which were likely responsible for her phenotype of Sjögren-Larsson syndrome.Conclusion: The compound heterozygous mutations found in the ALDH3A2 gene support the diagnosis of Sjögren-Larsson syndrome in the patient and expand the genotype spectrum of the gene.

4.
Fitoterapia ; 140: 104415, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31704260

RESUMO

Four new sesquiterpenoids, phellinignins A-D (1-4), together with four known ones (5-8), were isolated from cultures of the fungus Phellinus igniarius. The structures were established by extensive spectroscopic methods including MS, NMR, and the single crystal X-ray diffraction. Compounds 1-3 and 5-8 are tremulane sesquiterpenoids, while compound 4 possesses a new carbon skeleton that might derive from an illudane framework. Compounds 1, 2, 4, and 5 showed certain cytotoxicities to three human cancer cell lines.


Assuntos
Antineoplásicos/farmacologia , Basidiomycota/química , Sesquiterpenos/farmacologia , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , China , Humanos , Estrutura Molecular , Sesquiterpenos/isolamento & purificação
5.
CNS Neurol Disord Drug Targets ; 18(10): 791-797, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31686636

RESUMO

BACKGROUND: Our previous study has indicated that somatostatin potently inhibits neuropathic pain through the activation of its type 2 receptor (SSTR2) in mouse dorsal root ganglion and spinal cord. However, the underlying mechanism of this activation has not been elucidated clearly. OBJECTIVE: The aim of this study is to perform the pharmacological studies on the basis of sciatic nerve-pinch mice model and explore the underlying mechanism involving SSTR2. METHODS: On the basis of a sciatic nerve-pinch injury model, we aimed at comparing the painful behavior and dorsal root ganglion neurons neurochemical changes after the SSTR2 antibody (anti- SSTR2;5µl,1µg/ml) administration in the mouse. RESULTS: After pinch nerve injury, we found that the mechanical hyperalgesia and severely painful behavior (autotomy) were detected after the application of SSTR2 antibody (anti-SSTR2; 5µl, 1µg/ml) on the pinch-injured nerve. The up-regulated phosphorylated ERK (p-ERK) expression and the apoptotic marker (i.e., Bax) were significantly decreased in DRGs after anti-SSTR2 treatment. CONCLUSION: The current data suggested that inhibitory changes in proteins from the apoptotic pathway in anti-SSTR2-treated groups might be taking place to overcome the protein deficits caused by SSTR2 antibody and supported the new therapeutic intervention with SSTR2 antagonist for neuronal degeneration following nerve injury.

6.
Chem Commun (Camb) ; 55(95): 14307-14310, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31713549

RESUMO

A novel hepatocyte-targeting near-infrared fluorescent probe named Gal-NIR is developed. Gal-NIR shows ratiometric response to ONOO- with high sensitivity and selectivity. Moreover, the probe can accurately target the hepatocyte, and thus is used for assessing drug-induced hepatotoxicity and its remediation by using hepatoprotective medicines in living cells and mice.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/patologia , Corantes Fluorescentes/análise , Hepatócitos/efeitos dos fármacos , Imagem Óptica , Ácido Peroxinitroso/análise , Acetaminofen/administração & dosagem , Acetaminofen/farmacologia , Animais , Linhagem Celular Tumoral , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/química , Humanos , Raios Infravermelhos , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular
7.
Polymers (Basel) ; 11(9)2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31450656

RESUMO

The herbicide diuron is hardly soluble in water and most organic solvents and is usually made into a wettable powder or mixed with soil when used, which causes environmental risk and a reduction in herbicidal efficacy. In this study, the physicochemical properties were changed by using ß-cyclodextrin (ß-CD) to encapsulate diuron to form an inclusion complex. Some key technologies, including X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and nuclear magnetic resonance (1H NMR), were used to characterize the inclusion complex. The stoichiometry of the inclusion complex was determined by recording the 1H NMR spectrum or by using a diagram of inclusion ratios. A phase solubility study proved that the formed inclusion complex exhibited higher water solubility. Thermogravimetric analysis (TGA) demonstrated that the formed inclusion complex exhibited better thermal stability. Biological activity studies indicated that the herbicidal activity, in terms of herbicide removal, of the formed inclusion complex was higher than that of the original diuron. In general, the formation of the inclusion complex could reduce the environmental damage caused by diuron and enhance its herbicidal activity, providing an environmentally friendly method for using diuron.

8.
Molecules ; 24(17)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443550

RESUMO

Herbicide safeners selectively protect crops from herbicide injury while maintaining the herbicidal effect on the target weed. To some extent, the detoxification of herbicides is related to the effect of herbicide safeners on the level and activity of herbicide target enzymes. In this work, the expression of the detoxifying enzyme glutathione S-transferase (GST) and antioxidant enzyme activities in maize seedlings were studied in the presence of three potential herbicide safeners: 3-dichloroacetyl oxazolidine and its two optical isomers. Further, the protective effect of chiral herbicide safeners on detoxifying chlorsulfuron in maize was evaluated. All safeners increased the expression levels of herbicide detoxifying enzymes, including GST, catalase (CAT), and peroxidase (POD) to reduce sulfonylurea herbicide phytotoxicity in maize seedlings. Our results indicate that the R-isomer of 3-(dichloroacetyl)-2,2,5-trimethyl-1,3-oxazolidine can induce glutathione (GSH) production, GST activity, and the ability of GST to react with the substrate 1-chloro-2,4-dinitrobenzene (CDNB) in maize, meaning that the R-isomer can protect maize from damage by chlorsulfuron. Information about antioxidative enzyme activity was obtained to determine the role of chiral safeners in overcoming the oxidative stress in maize attributed to herbicides. The interaction of safeners and active target sites of acetolactate synthase (ALS) was demonstrated by molecular docking modeling, which indicated that both isomers could form a good interaction with ALS. Our findings suggest that the detoxification mechanism of chiral safeners might involve the induction of the activity of herbicide detoxifying enzymes as well as the completion of the target active site between the safener and chlorsulfuron.


Assuntos
Inativação Metabólica/efeitos dos fármacos , Oxazóis/química , Oxazóis/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Zea mays/efeitos dos fármacos , Zea mays/metabolismo , Acetolactato Sintase/química , Acetolactato Sintase/metabolismo , Sítios de Ligação , Catalase/metabolismo , Domínio Catalítico , Glutationa/metabolismo , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Peroxidase/metabolismo , Ligação Proteica , Relação Estrutura-Atividade , Zea mays/química
9.
Anal Chem ; 91(16): 10901-10907, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31362489

RESUMO

Azoreductase (AzoR) is an essential reductive enzyme which is closely associated with the intestinal disease such as ulcerative colitis (UC). To date, only a few fluorescent probes for detecting AzoR activity in bacteria or cells have been constructed successfully. It is still challenging to design fluorescent probes for in situ monitoring AzoR in vivo. In this paper, a near-infrared (NIR) fluorescent probe (Cy-Azo) based on hemicyanine is designed and synthesized. The emission of the probe is located at 735 nm in the NIR region, which is favorable for its application in vivo. In addition, Cy-Azo shows high sensitivity to AzoR activity with 17-fold fluorescence enhancement and is particularly selective to AzoR over other enzymes, ions, and amino acids. Meanwhile, a possible response mechanism (the azo group in Cy-Azo is reduced by AzoR and cleaved resulting in the production of Cy-NH2) was proposed and verified by HPLC, MS, and theory calculation. In addition, based on low cell cytotoxicity, Cy-Azo is successfully applied in visualizing the activity of AzoR in two cell lines (HCT116 and HepG2 cells) and three types of bacteria (E. coli, S. aureus, and P. aeruginosa). In particular, due to its NIR emission, the probe can monitor AzoR activity in acute and chronic UC mice models. To our knowledge this is the first fluorescent probe for detecting AzoR activity in vivo, which can provide much important information for the diagnosis and treatment of UC.

10.
Opt Express ; 27(9): 13172-13181, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31052846

RESUMO

We propose two hyperentanglement concentration protocols (hyper-ECPs) for two-photon entangled states in the polarization and orbital angular momentum degrees of freedom. The two cases distilling a maximally hyperentangled state from partially entangled pure state with unknown parameters and known parameters are dissected respectively. Both of the protocols require only linear optical elements which make our protocols more feasible for current technologies. In our protocols, the remote parties perform different local operations, which will reduce everyone's operation and improve the total efficiency. Each of them has the theoretical maximum success probability in the corresponding situation. The hyper-ECPs can be exploited simply to hyperentangled Greenberger-Horne-Zeilinger states.

11.
Talanta ; 197: 436-443, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30771959

RESUMO

Nitric oxide (NO) plays vital roles in many physiological process and is closely related to many diseases. So far, a number of fluorescent probes have been constructed for the detection of NO successfully. However, the probes still suffer from long-time reaction and limited selectivity. Herein, a fluorescent probe named dRB-OPD is synthesized and used to recognize NO. The probe contains a deoxy-rhodamine B as fluorophore and o-phenylenediamino as reaction site. dRB-OPD shows fast response to NO within 40 s with 170-fold fluorescence enhancement. Moreover, the probe shows high selectivity towards NO over dehydroascorbic acid (DHA), ascorbic acid (AA), and methylglyoxal (MGO). Particularly, the probe can avoid the serious interference from cysteine (Cys) found in the rhodamine lactam-based fluorescent NO probes (RB-OPD). In addition, the probe is applied for the detection of exogenous and endogenous NO in the HepG2 and RAW 264.7 cells with satisfactory results.


Assuntos
Corantes Fluorescentes/química , Óxido Nítrico/análise , Rodaminas/química , Animais , Corantes Fluorescentes/síntese química , Células Hep G2 , Humanos , Camundongos , Estrutura Molecular , Células RAW 264.7
12.
Chemistry ; 25(17): 4358-4366, 2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30681743

RESUMO

The potential application of the jellium model as guidance in the rational design of bimetallic superalkali cations is examined under gradient-corrected density functional theory for the first time. By using Li, Mg, and Al as atomic building blocks, a series of bimetallic cationic clusters with 2, 8, 20, and 40 valence electrons are obtained and investigated. As the corresponding neutral clusters tend to lose one valence electron to achieve closed-shell states in the jellium model, these studied cations exhibit much lower vertical electron affinities (EAvert , 3.42-4.95 eV) than the ionization energies (IEs) of alkali metal atoms, indicating their superalkali identities. The high stability of these cationic clusters is guaranteed by their considerable HOMO-LUMO gaps and binding energies per atom. Moreover, the feasibility of using the designed superalkalis as efficient reductants to activate CO2 and N2 molecules and as stable building blocks to assemble ionic superatom compounds is explored. Therefore, this study may provide an effective method for obtaining various metallic superatoms with extensive applications on the basis of the simple jellium rule.

13.
J Mol Graph Model ; 87: 56-67, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30503995

RESUMO

Numerous isomeric equilibrium structures have been identified for the Al10-xBex (x = 1-9) nanoalloy clusters by using the stochastic search procedure in combination with density functional theory calculations. The relative stability and various electronic properties of the lowest-energy Al10-xBex (x = 0-10) clusters have been systematically studied by using the B3LYP and CCSD(T) methods with the aug-cc-pVDZ basis set. The evolution of the binding energies, the second difference in energy, HOMO-LUMO gaps, vertical detachment energies, vertical ionization potentials, vertical electron affinities, and hardness with the increasing number of Be atoms in the most stable Al10-xBex (x = 0-10) clusters demonstrates that the global minimum of Al8Be2 cluster possesses a special stability. Thus, the electronic structure of the lowest-energy Al8Be2 cluster has been also detected in detail. In addition, it is found that the polarizabilities gradually decrease with increasing number of Be atoms, and the charges always transfer from Al to Be atoms in these nanoalloy clusters. We hope this work could provide helpful insight into the composition-dependent electronic properties of BeAl alloy at the nanoscale, serving as powerful guidelines for future experimental research.

14.
Leuk Lymphoma ; 60(4): 934-939, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30277105

RESUMO

Diffuse large B cell lymphoma is one of the predominant histological subtypes of primary gastric lymphomas. Factors that contribute to precise stratification and guide the treatment of this disease are still not well understood. We analyzed 73 primary gastric diffuse large B cell lymphoma patients retrospectively, and found that patients characterized by late stage, multiple localization, B symptoms, lower serum albumin level and elevated LDH level had a shorter overall survival through Univariate Cox regression analysis. Multivariate Cox regression analysis demonstrated that ALB ≤ 35g/L, staging ≥ IIE and multiple sites localization were independent adverse prognostic factors. Significantly, in 35 patients who received endoscopy at diagnosis, Kaplan-Meier analyses indicated that patients with large (≥3 cm) and deep lesions (≥11 mm) had an inferior OS (p = .01 and .039). These findings implicated that tumor size and depth are two indicators of prognosis under ultrasonography. Further randomized studies with large number of cases are needed.

15.
Anal Chem ; 91(1): 1056-1063, 2019 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-30539637

RESUMO

The ability to detect cancer early in an accurate and rapid fashion is of critical importance for cancer diagnosis and accurate resection in surgery. γ-Glutamyltranspeptidase (GGT) is overexpressed in several human cancers, while maintaining a low expression in normal microenvironments, and thus is recognized as an important cancer biomarker. To date, rational design of a zero cross-talk ratiometric near-infrared (NIR) GGT fluorescent probe for efficient cancer diagnosis in various biological samples is still a big challenge. In this work, a zero cross-talk ratiometric NIR GGT fluorescent probe named Cy-GSH is developed. Cy-GSH shows high sensitivity to GGT, which is desired for early cancer diagnosis. Upon additional GGT, a large emission shift from 805 to 640 nm is observed, which is suitable for visualizing deeply located cancer in vivo. In addition, successful monitoring of GGT activity in blood, cells, tissues, and in vivo makes Cy-GSH possess great potential for the clinical cancer early diagnosis. Furthermore, accurately visualizing tumors and metastases in mouse models illuminates that the probe may be a convenient tool for fluorescence-guided cancer surgery. To our knowledge, this is the first report to describe the strategy of a zero cross-talk ratiometric NIR GGT fluorescent probe for early cancer diagnosis and fluorescence-guided surgery.

16.
Chem Commun (Camb) ; 54(93): 13159, 2018 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-30406232

RESUMO

Correction for 'A ratiometric fluorescent probe for peroxynitrite prepared by de novo synthesis and its application in assessing the mitochondrial oxidative stress status in cells and in vivo' by Dong-Ye Zhou et al., Chem. Commun., 2018, 54, 11590-11593.

17.
ACS Sens ; 3(11): 2311-2319, 2018 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-30375854

RESUMO

Nitric oxide (NO) is a vital gaseous signal molecule and plays an important role in diverse physiological and pathological processes including regulation of vascular functions. Endoplasmic reticulum (ER) stress is caused by the accumulation of misfolded or unfolded protein in the ER. Besides, ER stress induced by NO can be involved in the pathogenesis of various vascular diseases. Unfortunately, to the best of our knowledge, no ER-targeting probe for NO is reported to study the relationship between ER stress and the level of NO in a biological system. Herein, an ER-targeted fluorescent probe named ER-Nap-NO for imaging of NO is designed and synthesized. ER-Nap-NO consists of three main parts: naphthalimide (two-photon fluorophore), o-phenylenediamino (NO recognition group), and methyl sulfonamide (ER-targetable group). The probe itself is nonfluorescent because a photoinduced electron transfer (PET) process exists. After the addition of NO, the PET process is inhibited and thus strong fluorescence is released. Moreover, the response mechanism is confirmed by 1H NMR and mass spectra and DFT calculation in detail. In addition, from the experimental results, we can conclude that the probe displays several obvious advantages including high sensitivity, selectivity, and ER-targetable ability. Based on these excellent properties, the probe is used for the two-photon imaging of exogenous and endogenous NO in ER of living cells. Most importantly, the ER-targetable probe has potential capability as a tool for investigating the level of NO during tunicamycin-induced ER stress in cells and tissues, which is beneficial for revealing the role of NO in ER-associated vascular diseases.


Assuntos
Estresse do Retículo Endoplasmático/fisiologia , Retículo Endoplasmático/metabolismo , Corantes Fluorescentes/química , Naftalimidas/química , Óxido Nítrico/análise , Animais , Teoria da Densidade Funcional , Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Limite de Detecção , Camundongos , Microscopia de Fluorescência/métodos , Modelos Químicos , Naftalimidas/síntese química , Naftalimidas/efeitos da radiação , Naftalimidas/toxicidade , Fenilenodiaminas/síntese química , Fenilenodiaminas/química , Fenilenodiaminas/toxicidade , Fótons , Espectrometria de Fluorescência/métodos , Sulfonamidas/síntese química , Sulfonamidas/química , Sulfonamidas/toxicidade , Tunicamicina/farmacologia
18.
Chem Commun (Camb) ; 54(82): 11590-11593, 2018 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-30264083

RESUMO

A ratiometric fluorescent probe Cy-NEt2 for detecting ONOO- is designed and prepared by de novo synthesis, which is a reliable, cheap and flexible route. The probe is applied for monitoring the level of mitochondrial ONOO- and assessing the lipopolysaccharide (LPS)-induced mitochondrial oxidative stress status in living cells and in vivo successfully.


Assuntos
Corantes Fluorescentes/química , Mitocôndrias/química , Imagem Óptica/métodos , Estresse Oxidativo , Ácido Peroxinitroso/análise , Animais , Corantes Fluorescentes/síntese química , Células Hep G2 , Humanos , Lipopolissacarídeos/metabolismo , Camundongos , Mitocôndrias/metabolismo , Ácido Peroxinitroso/metabolismo , Espectrometria de Fluorescência/métodos
19.
Mol Ther Nucleic Acids ; 12: 578-590, 2018 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-30195794

RESUMO

Doxorubicin is a widely used anthracycline-based anti-tumor agent for both solid and liquid tumors. Mounting evidence has demonstrated that microRNAs (miRNAs) are involved in chemoresistance and tumorigenesis. However, the roles of microRNA-501-5p (miR-501) in doxorubicin resistance and gastric cancer cell proliferation and invasion are still not fully understood. In this study, we identified that BLID (BH3-like motif-containing protein, cell death inducer) was directly regulated by miR-501 at the post-transcriptional level in multiple gastric cancer cell lines. Endogenous miR-501 was higher, whereas BLID was lower, in doxorubicin-resistant gastric cancer SGC7901/ADR cells compared with their parental SGC7901 cells. miR-501 suppressed gastric cancer cell apoptosis, induced resistance to doxorubicin, and enhanced cell proliferation, migration, and invasion. Subcutaneous injection of miR-501 lentivirus-infected SGC7901 cells resulted in rapid growth of xenograft tumors and resistance to doxorubicin treatment, unlike injection of negative miRNA lentivirus-infected SGC7901 cells. This is achieved at least partially by directly targeting BLID and subsequent inactivation of caspase-9 and caspase-3 and phosphorylation of Akt. Taken together, miR-501 induces doxorubicin resistance and enhances the tumorigenesis of gastric cancer cells by suppressing BLID. miR-501 might be a potential target for doxorubicin resistance and gastric cancer therapy.

20.
Exp Appl Acarol ; 76(1): 53-70, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30238307

RESUMO

Infestation by the ectoparasitic mite Sarcoptes scabiei (Acari: Sarcoptidae) has important implications for global wildlife conservation and both animal and human health. Ribosomal and mitochondrial DNA sequences of parasites are useful to determine genetic diversity and to describe their likely dynamic evolution. In this study, we described the genetic diversity of S. scabiei individuals collected from wild animals in China by sequencing the ribosomal ITS-2 and mitochondrial 16S rRNA genes. A total of 13 Sarcoptes isolates of wildlife, coupled with one of rabbit origin, were subjected to genetic characteristics. After cloning and sequencing, 14 ITS-2 sequences and 12 16S rRNA sequences were obtained and analyzed. Further analysis of haplotype network and population genetic structure revealed that there were 79 haplotypes in ITS-2 (main haplotype H2) and 31 haplotypes in 16S rRNA (main haplotype C10). The phylogenetic trees showed some partial clustering by location and host, and the analysis of gene polymorphism may prompt that all isolates of S. scabiei have a similar origin. We speculate that the genetic evolution of S. scabiei may be related with that of the hosts, but more research is necessary to better understand the host-parasite co-evolutionary relationship in S. scabiei. These results provide new insights into understanding the population genetics and evolutionary biology of S. scabiei and therefore a better understanding of controlling its infestation pathways worldwide.


Assuntos
Variação Genética , Ruminantes , Sarcoptes scabiei/genética , Animais , Animais Selvagens , DNA Intergênico/análise , DNA Espaçador Ribossômico/análise , Genes Mitocondriais , Cabras , RNA Ribossômico 16S/análise , Sarcoptes scabiei/fisiologia
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