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1.
Int Immunopharmacol ; : 105947, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31796384

RESUMO

Our previous study has found that zileuton, a selective 5-lipoxygenase (5LO) inhibitor, abrogated lipopolysaccharide-induced depressive-like behaviors and hippocampal neuroinflammation. Herein, we further extended our curiosity to investigate effects of zileuton on stress-induced depressive-like behaviors. Our data indicated that zileuton significantly ameliorated depressive-like behaviors in mice subjected to chronic mild stress (CMS), as shown in the tail suspension test, forced swimming test and novelty-suppressed feeding test. The further studies indicated that zileuton suppressed hippocampal neuroinflammation, evidenced by lower levels of TNF-α, IL-1ß and nuclear NF-κB p65 as well as decreased number of Iba1-positive cells. It also significantly ameliorated hippocampal apoptosis, indicated by deceased number of TUNEL-positive cells, deceased ratio of cleaved caspase-3/procaspase-3 and increased ratio of Bcl-2/Bax. More importantly, zileuton increased the level of synaptic proteins PSD-95 and SYN and the number of NeuN+/BrdU+ cells in the hippocampus. Over all, zileuton alleviated CMS-induced depressive-like behaviors, neuroinflammatory and apoptotic responses, abnormalities of synapse and neurogenesis in the hippocampus, suggesting that it might has beneficial effects on depression.

2.
Front Genet ; 10: 1171, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31803241

RESUMO

Long noncoding RNAs (lncRNAs) have emerged as essential regulators of skeletal myogenesis, but few myogenesis-associated lncRNAs have been identified and our understanding of their regulatory mechanisms remains limited, particularly in goat. Here, we identified a novel lncRNA, TCONS_00006810 (named lncR-125b), from our previous lncRNA sequencing data on fetal (45, 60, and 105 days of gestation, three biological replicates for each point) and postnatal (3 days after birth, n = 3) goat skeletal muscle, and found that it is highly expressed in skeletal muscle and gradually upregulated during skeletal muscle satellite cell (SMSC) differentiation in goat. Notably, overexpression of lncR-125b accelerated the expression of myogenic differentiation 1 (MyoD 1) and myogenin (MyoG), and the formation of myotubes, and knockdown of lncR-125b showed opposite effects in SMSCs. Results of dual-luciferase assay and quantitative real-time polymerase chain reaction revealed that lncR-125b acts as a molecular sponge for miR-125b and that insulin-like growth factor 2 (IGF2), a critical regulator of skeletal myogenesis, is a direct target gene of miR-125b. Further analyses showed that lncR-125b negatively regulates miR-125b expression and positively regulates IGF2 expression in SMSCs. Mechanistically, lncR-125b promotes SMSC differentiation by functioning as a competing endogenous RNA (ceRNA) for miR-125b to control IGF2 expression. These findings identify lncR-125b as a novel noncoding regulator of muscle cell differentiation and skeletal muscle development in goat.

3.
Malar J ; 18(1): 429, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852503

RESUMO

BACKGROUND: Imported malaria has been an important challenge for China. Fatality rates from malaria increased in China, particularly in Henan Province, primarily due to malpractice and misdiagnoses in healthcare institutions, and the level of imported malaria. This study aims to investigate the relationship between the state of diagnosis and subsequent complications among imported malaria cases at healthcare institutions, based on malaria surveillance data in Henan Province from 2012 to 2017. METHODS: A retrospective descriptive analysis was performed using data from the Centre for Disease Control and Prevention, Zhengzhou City, the capital of Henan Province. A decision tree method was exploited to provide valuable insight into the correlation between imported malaria cases and healthcare institutions. RESULTS: From 2012 to 2017, there were 371 imported malaria cases, mostly in males aged between 20 and 50 years, including 319 Plasmodium falciparum cases. First visits of 32.3%, 19.9% and 15.9% malaria cases for treatment were to provincial, municipal and county healthcare institutions, respectively. The time interval between onset and initial diagnosis of 284 cases (76.5%) and the time interval between initial diagnosis and final diagnosis of 197 cases (53.1%) was no more than 72 h. An apparent trend was found that there were notably fewer patients misdiagnosed at first visit to healthcare institutions of a higher administrative level; 12.5% of cases were misdiagnosed in provincial healthcare institutions compared to 98.2% in private clinics, leading to fewer complications at healthcare institutions of higher administrative level due to correct initial diagnosis. In the tree model, the rank of healthcare facilities for initial diagnosis, and number of days between onset and initial diagnosis, made a major contribution to the classification of initial diagnosis, which subsequently became the most significant factor influencing complications developed in the second tree model. The classification accuracy were 82.2 and 74.1%, respectively for the tree models of initial diagnosis and complications developed. CONCLUSION: Inadequate seeking medical care by imported malaria patients, and insufficient capacity to diagnose malaria by healthcare institutions of lower administrative level were identified as major factors influencing complications of imported malaria cases in Henan Province. The lack of connection between uncommon imported malaria cases and superior medical resources was found to be the crucial challenge. A web-based system combined with WeChat to target imported malaria cases was proposed to cope with the challenge.

4.
Crit Rev Eukaryot Gene Expr ; 29(2): 113-121, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679266

RESUMO

Endometriosis is a common debilitating gynecologic disease. Almost 10% of reproductive-age women are affected by this disease; they commonly suffer pelvic pain and/or infertility. Early diagnosis of this multifactorial disease remains difficult because its etiology is not clear and the early symptoms are nonspecific. In addition, many reproductive-age women are unwilling to undergo invasive laparoscopic surgery because of the possibility of decreasing fertility. Thus, identifying biomarkers for the early diagnosis of endometriosis a key focus of current research. Long noncoding RNAs (lncRNAs) are a class of noncoding transcripts that have length of > 200 nucleotides and lack protein-coding ability but still influence gene expression in various ways. With advances in genome-wide analysis, researchers have determined that lncRNAs play an important role in many human diseases, particularly tumors. Moreover, the role of lncRNAs in the pathogenesis of endometriosis has been continually recognized. In this review, we discuss the status of current research on dysregulated lncRNAs and their roles in the pathogenesis of endometriosis. We aim to stimulate new investigations toward the identification of lncRNAs as biomarkers for the early diagnosis and therapy of this long-term gynecological disease.

5.
Front Oncol ; 9: 857, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31552181

RESUMO

Immune checkpoint blockade of programmed cell death protein 1 (PD-1) had an impressive long-lasting effect in a portion of advanced-stage melanoma patients, however, this therapy failed to induce responses in several patients; how to increase the objective response rate is very important. Cellular FLICE-inhibitory protein (c-FLIP) could inhibit apoptosis directly at the death-inducing signaling complex of death receptors and is also considered to be the main cause of immune escape. The overexpression of c-FLIPL occurs frequently in melanoma and its expression is associated with the prognosis. We found that the level of c-FLIPL expression was associated with the PD-1 blockade response rate in melanoma patients. Thus, we performed this research to investigate how c-FLIPL regulates immunotherapy in melanoma. We demonstrate that down regulation of c-FLIPL enhances the PD-1 blockade efficacy in B16 melanoma tumor model. Down regulation of c-FLIPL could increase the tumor apoptosis and enhance the antitumor response of T cells in the lymphocyte tumor cells co-culture system. Moreover, knockdown of c-FLIPL could decrease the expression of PD-L1 and recruit more effector T cells in the tumor microenvironment. Our results may provide a new combined therapeutic target for further improving the efficacy of PD-1 blockade in melanoma.

6.
Int J Ophthalmol ; 12(8): 1262-1271, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456915

RESUMO

AIM: To evaluate the protective effects of lipoic acid-niacin (N2L) dimers against blue light (BL)-induced oxidative damage to human retinal pigment epithelium (hRPE) cells in vitro. METHODS: hRPE cells were divided into a control group (CG), a BL group, an N2L plus BL irradiation group, an α-lipoic acid (ALA) plus BL group, an ALA-only group, and an N2L-only group. hRPE cellular viability was detected by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) bromide assays, and apoptosis was evaluated by annexin-V-PE/7-AAD staining followed by flow cytometry. Ultrastructural changes in subcellular organelles were observed by transmission electron microscopy. Reactive oxygen species formation was assayed by flow cytometry. The expression levels of the apoptosis-related proteins BCL-2 associated X protein (BAX), B-cell leukmia/lymphoma 2 (BCL-2), and caspase-3 were quantified by Western blot analysis. RESULTS: BL exposure with a light density of 4±0.5 mW/cm2 exceeding 6h caused hRPE toxicity, whereas treatment with a high dose of N2L (100 mol/L) or ALA (150 mol/L) maintained cell viability at control levels. BL exposure caused vacuole-like degeneration, mitochondrial swelling, and reduced microvillus formation; however, a high dose of N2L or ALA maintained the ultrastructure of hRPE cells and their organelles. High doses of N2L and ALA also protected hRPE cells from BL-induced apoptosis, which was confirmed by Western blot analysis: BCL-2 expression significantly increased, while BAX and caspase-3 expression slightly decreased compared to the CG. CONCLUSION: High-dose N2L treatment (>100 mol/L) can reduce oxidative damage in degenerating hRPE cells exposed to BL with an efficacy similar to ALA.

7.
Front Physiol ; 10: 921, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31427980

RESUMO

The hypothesis of the present study is that apoptosis through an intrinsic mitochondrial pathway may mediate high fat diet (HFD)-induced changes in the metabolism of Pelteobagrus fulvidraco. To this end, we cloned the full-length cDNA sequences of Cycs, Apaf1, Casp9, Casp3a, and Casp3b involved in the mitochondria apoptotic pathway, and explored their mRNA tissue expressions and transcriptional responses to HFD. All of these members shared similar domains to their orthologous vertebrate genes. They were constitutively expressed in all analyzed tissues but varied from tissue to tissue. Compared to the control, HFD up-regulated the mRNA expression of partial genes among these five key genes (Cycs, Apaf1, Casp9, Casp3a, and Casp3b) in mesenteric fat, intestine, ovary and the kidney, indicating the induction of apoptosis in these tissues; in contrast, HFD down-regulated mRNA levels of partial genes among the five key genes (Cycs, Apaf1, Casp9, Casp3a, and Casp3b) in the heart, spleen and gill tissues, indicating the inhibition of apoptosis in these tissues. The present study will facilitate further exploration into the functions of these genes at the molecular level and disclose the critical involvement of these genes against nutrient changes, indicating that processes of apoptosis in various tissues may differentially be modified by HFD.

8.
Front Pharmacol ; 10: 646, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31333446

RESUMO

Objective: To observe the protective role of hapatopoietin Cn (HPPcn) on acute liver injury. Methods: Six hours after 10 mmol/L CCl4, 150 mmol/L ethanol, or 0.6 mmol/L H2O2 treatment, SMMC7721 human hepatoma cells were incubated with 10, 100, or 200 ng/ml recombinant human HPPCn protein (rhHPPCn) for an additional 24 h. The cell survival rate was analyzed using the CCK-8 assay. The CCl4-induced apoptosis of SMMC7721 cells was detected by flow cytometry. Then, the levels of glutamic oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), malondialdehyde (MDA), lactate dehydrogenase (LDH), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD) in SMMC7721 cell lysates and cell culture supernatant were detected. SMMC7721 cells were treated with different concentrations of rhHPPCn (0, 10, and 100 ng/ml). The cell proliferation indexes (BrdU incorporation and PCNA expression) were detected by immunohistochemistry (IHC). An acute liver injury mouse model was established by a one-time intraperitoneal injection of 20% CCl4 at a volume of 5 ml/kg body weight. One hour after CCl4 injection, 1.25 or 2.5 mg rhHPPCn/12 h/kg body weight was injected via the tail vein. The serum levels of GOT and GPT were detected at different time points. Pathological changes in the liver were evaluated. PCNA expression levels were observed by IHC. Results: rhHPPCn increased the survival rate of SMMC7721 cells and inhibited chemical toxicity-induced cell apoptosis. The levels of GOT, GPT, MDA, and LDH in the cell supernatant were significantly reduced, while GSH-PX and SOD were significantly increased after rhHPPCn treatment in the CCl4-treated SMMC7721 cells. BrdU incorporation and PCNA expression increased in a concentration-dependent manner, indicating that rhHPPCn promotes cell proliferation. The results showed that rhHPPCn significantly reduced the serum levels of GOT and GPT in CCl4-induced acute liver injury mice. rhHPPCn alleviated the tissue damage and increased PCNA expression, indicating the promotion of proliferation after acute injury. Conclusion: rhHPPCn protects hepatocytes from chemical toxins by promoting proliferation and inhibiting apoptosis in vivo and in vitro. Our study provides new insights for the clinical treatment of acute liver injury.

9.
J Cell Mol Med ; 23(8): 5403-5414, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31148354

RESUMO

Cytochrome P450 26A1 (CYP26A1) plays important roles in the mice peri-implantation period. Inhibiting its expression or function leads to pregnancy failure. However, little is known about the underlying mechanisms involved, especially the relationship between CYP26A1 and immune cells. In this study, using Cyp26a1-specific antisense morpholigos (Cyp26a1-MO) knockdown mice model and pCR3.1-Cyp26a1 vaccine mice model, we found that the number of uterine CD45+ CD11c+ MHCIIlo-hi F4/80- dendritic cells (DCs) was significantly decreased in the treated mice. The percentage of mature DCs (CD86hi ) was obviously lower and the percentage of immature DCs (CD86lo ) was remarkably higher in uterine DCs in the treatment group than that of the control group. Further experiments found that ID2, a transcription factor associated with DCs development, and CD86, a DC mature marker molecule, were both significantly reduced in mice uteri in the treated group. In vitro, ID2 and CD86 also decreased in bone marrow-derived DCs under Cyp26a1-MO treatment. These findings provide novel information that CYP26A1 might affect the embryo implantation via modulating the differentiation and maturation of uterine DCs.

10.
Front Neurosci ; 13: 472, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31156366

RESUMO

To study the impact of donepezil, rivastigmine, galantamine, and memantine on cognitive, functional, behavioral, global changes and adverse effects in patients with mild, moderate and severe Alzheimer's disease (AD), we screened the literature published before September 2017 in the Pubmed, Embase, Cochrane library and Web of Science Electronic databases according to the inclusion criteria. Thirty-six studies were finally determined from 1560 preliminary screened articles. The AD Assessment Scale-cognitive Subscale (ADAS-cog), AD Cooperative Study-Activities of Daily Living (ADCS-ADL), Neuropsychiatric Inventory (NPI), and Clinician's Interview-Based Impression of Change Plus Caregiver Input scale (CIBIC+) were used as valid endpoints. Of the 36 trials included, meta-analyses of these placebo-control trials showed that there were significant differences between the donepezil, rivastigmine and placebo groups using ADAS-cog, ADCS-ADL, and CIBIC+. Meta-analyses of these placebo-controlled trials showed that there were significant differences between the galantamine and placebo groups using ADAS-cog, ADCS-ADL, NPI, and CIBIC+. These observations suggest that memantine is beneficial for stabilizing or slowing the decline in ADAS-cog and ADCS-ADL19 changes in AD patients. However, there was no significant effect according to the ADCS-ADL23, NPI, and CIBIC+ tests, which indicated that memantine treatment has no significant effect on these cognitive aspects of AD patients. Different effects of donepezil, rivastigmine, galantamine, or memantine on AD were found in this study. According to the results, we conclude that galantamine is effective in treating all aspects of AD and is the first choice for the treatment of AD. However, due to limited data, we should consider additional data to obtain more stable results.

11.
Planta ; 250(2): 535-548, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31111205

RESUMO

MAIN CONCLUSION: ACOS5, OsACOS12 and PpACOS6 are all capable of fatty acyl-CoA synthetase activity but exhibit different substrate preferences. The transcriptional regulation of ACOS for sporopollenin synthesis appears to have been conserved in Physcomitrella, rice and Arabidopsis during evolution. Sporopollenin is the major constituent of spore and pollen exines. In Arabidopsis, acyl-CoA synthetase 5 (ACOS5) is an essential enzyme for sporopollenin synthesis, and its orthologues are PpACOS6 from the moss Physcomitrella and OsACOS12 from monocot rice. However, knowledge regarding the evolutionary conservation and divergence of the ACOS gene in sporopollenin synthesis remains limited. In this study, we analysed the function and regulation of PpACOS6 and OsACOS12. A complementation test showed that OsACOS12 driven by the ACOS5 promoter could partially restore the male fertility of the acos5 mutant in Arabidopsis, while PpACOS6 did not rescue the acos5 phenotype. ACOS5, PpACOS6 and OsACOS12 all complemented the acyl-CoA synthetase-deficient yeast strain (YB525) phenotype, although they exhibited different substrate preferences. To understand the conservation of sporopollenin synthesis regulation, we constructed two constructs with ACOS5 driven by the OsACOS12 or PpACOS6 promoter. Both constructs could restore the fertility of acos5 plants. The MYB transcription factor MS188 from Arabidopsis directly regulates ACOS5. We found that MS188 could also bind the promoters of OsACOS12 and PpACOS6 and activate the genes driven by the promoters, suggesting that the transcriptional regulation of these genes was similar to that of ACOS5. These results show that the ACOS gene promoter region from Physcomitrella, rice and Arabidopsis has been functionally conserved during evolution, while the chain lengths of fatty acid-derived monomers of sporopollenin vary in different plant species.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Bryopsida/enzimologia , Coenzima A Ligases/metabolismo , Oryza/enzimologia , Proteínas de Plantas/metabolismo , Sequência de Aminoácidos , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/ultraestrutura , Proteínas de Arabidopsis/genética , Biopolímeros/biossíntese , Bryopsida/genética , Bryopsida/crescimento & desenvolvimento , Bryopsida/ultraestrutura , Carotenoides/biossíntese , Coenzima A Ligases/genética , Genes Reporter , Mutação , Oryza/genética , Oryza/crescimento & desenvolvimento , Oryza/ultraestrutura , Filogenia , Infertilidade das Plantas , Proteínas de Plantas/genética , Pólen/enzimologia , Pólen/genética , Pólen/crescimento & desenvolvimento , Pólen/ultraestrutura , Alinhamento de Sequência , Especificidade por Substrato , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
12.
Int J Mol Sci ; 20(9)2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31067654

RESUMO

As a gaseous biological signaling molecule, nitric oxide (NO) regulates many physiological processes in plants. Over the last decades, this low molecular weight compound has been identified as a key signaling molecule to regulate plant stress responses, and also plays an important role in plant development. However, elucidation of the molecular mechanisms for NO in leaf development has so far been limited due to a lack of mutant resources. Here, we employed the NO-deficient mutant nia1nia2 to examine the role of NO in leaf development. We have found that nia1nia2 mutant plants displayed very different leaf phenotypes as compared to wild type Col-0. Further studies have shown that reactive oxygen species (ROS) levels are higher in nia1nia2 mutant plants. Interestingly, ROS-related enzymes ascorbate peroxidase (APX), catalases (CAT), and peroxidases (POD) have shown decreases in their activities. Our transcriptome data have revealed that the ROS synthesis gene RBOHD was enhanced in nia1nia2 mutants and the photosynthesis-related pathway was impaired, which suggests that NO is required for chloroplast development and leaf development. Together, these results imply that NO plays a significant role in plant leaf development by regulating ROS homeostasis.


Assuntos
Arabidopsis/metabolismo , Homeostase , Óxido Nítrico/metabolismo , Folhas de Planta/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Nitrato Redutase/genética , Nitrato Redutase/metabolismo , Fotossíntese , Folhas de Planta/crescimento & desenvolvimento
13.
ACS Appl Mater Interfaces ; 11(22): 20167-20173, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31081318

RESUMO

Barium strontium zirconate titanate ceramics ((BaSr)(ZrTi)O3-BSZT) with Zr4+ ionic contents of 15 and 20 mol % and Sr2+ ionic contents of 15, 20, 25, and 30 mol % were prepared using a solid-state reaction approach. X-ray diffraction and scanning electron microscopy were used to characterize the lattice structure and morphologies of the ceramics. Permittivity and polarization as a function of temperature were characterized using an impedance analyzer and a Tower-Sawyer circuit. The electrocaloric effect was measured directly and calculated using the Maxwell relation (indirectly). The results indicated that the BSZT ceramics change from a normal ferroelectric to a relaxor ferroelectric with increasing Zr4+ ionic content, which can be further modified by the addition of Sr2+ ionic content. The optimized adiabatic temperature change Δ T obtained is 2.43 K in (Ba0.85Sr0.15)(Zr0.15Ti0.75)O3 ceramics, and Δ T >1.6 K over a wide temperature span of 120 °C was obtained.

14.
Oxid Med Cell Longev ; 2019: 5647219, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31093316

RESUMO

Hyperglycemia fluctuation is associated with diabetes mellitus (DM) complications when compared to persistent hyperglycemia. Previous studies have shown that paeoniflorin (PF), through its antiapoptosis, anti-inflammation, and antithrombotic properties, effectively protects against cardiovascular and cerebrovascular disease. However, the mechanism underlying the protection from PF against vascular injuries induced by hyperglycemia fluctuations remains poorly understood. Herein, we investigated the potential protective role of PF on human umbilical vein endothelial cells (HUVECs) subjected to intermittent glucose levels in vitro and in DM rats with fluctuating hyperglycemia in vivo. A remarkable increased apoptosis associated with elevated inflammation, increased oxidative stress, and high protein level of PKCß1 was induced in HUVECs by intermittently changing glucose for 8 days, and PF recovered those detrimental changes. LY333531, a potent PKCß1 inhibitor, and metformin manifested similar effects. Additionally, in DM rats with fluctuating hyperglycemia, PF protected against vascular damage as what has been observed in vitro. Taken together, PF attenuates the vascular injury induced by fluctuant hyperglycemia through oxidative stress inhibition, inflammatory reaction reduction, and PKCß1 protein level repression, suggesting its perspective clinical usage.

15.
Biomater Sci ; 7(5): 1962-1972, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30810135

RESUMO

Functional polymeric drug delivery systems have generated enormous interest due to their excellent features. This paper reports the development of a novel pH and redox dual-sensitive polymer for anticancer paclitaxel (PTX) delivery applications. The polymer was prepared by polycondensation of disulfide bond-containing dimethyl l-cystinate (Cys) and polycaprolactone (PCL) oligomer via a pH-responsive imine bond. Using the nanoprecipitation method, the polymer can be formulated as nanoparticles (poly(Cys-PCL)/PTX NPs) with a diameter less than 100 nm, as measured by TEM and DLS. The NPs release PTX significantly faster at mildly acidic pH and high concentrations of GSH, exhibiting almost no burst release under the physiological conditions of plasma. Notably, the NPs efficiently deliver PTX to the tumor cells, which was more cytotoxic to 4T1 cancer cells than the pure PTX alone. In vivo results reveal an excellent tumor inhibiting ability, good drug tolerability and biosafety of poly(Cys-PCL)/PTX NPs. Overall, the poly(Cys-PCL)/PTX NPs platform may have greater potential in enhancing cancer therapy.


Assuntos
Antineoplásicos/química , Portadores de Fármacos/química , Nanopartículas/química , Paclitaxel/química , Polímeros/química , Animais , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Transporte Biológico , Linhagem Celular Tumoral , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Espaço Intracelular/metabolismo , Masculino , Camundongos , Paclitaxel/metabolismo , Paclitaxel/farmacologia , Tamanho da Partícula , Polímeros/farmacocinética , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
16.
Eur J Pharmacol ; 851: 1-12, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30768982

RESUMO

Cisplatin is a widely used chemotherapeutic drug that often causes acute kidney injury (AKI) in cancer patients. The contribution of miRNAs to the cisplatin-induced renal tubular epithelial cell injury remains largely unknown. Here we performed an integrative network analysis of miRNA and mRNA expression profiles to shed light into the underlying mechanism of cisplatin-induced renal tubular epithelial cell injury. Microarray analysis identified 47 differentially expressed miRNAs, among them 26 were upregulated and 21 were downregulated. Moreover, integrating dysregulated miRNAs target prediction and altered mRNA expression enabled us to identify 1181 putative target genes for further bioinformatics analysis. Gene ontology (GO) analysis revealed that the putative target genes were involved in apoptosis process and regulation of transcription. Pathway analysis indicated that the top upregulated pathways included MAPK and p53 signaling pathway, while the top downregulated pathways were PI3K-Akt and Wnt signaling pathway. Further network analysis showed that MAPK signaling pathway and apoptosis with the highest degree were identified as core pathways, hsa-miR-9-3p and hsa-miR-371b-5p as the most critical miRNAs, and CASK, ASH1L, CDK6 etc. as hub target genes. In addition, the expression level change of selected five microRNAs (hsa-miR-4299, hsa-miR-297, hsa-miR-3135b, hsa-miR-9-3p, and hsa-miR-371b-5p) and two mRNAs( CASK and CDK6) were validated in cisplatin-induced HK-2 cells. Furthermore, a similar trend of expression level change was observed in NRK-52E cells by cisplatin treatment. Overall, our results provide the molecular basis and potential targets for the treatment of cisplatin-induced renal tubular cell injury.


Assuntos
Cisplatino/farmacologia , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Túbulos Renais/citologia , MicroRNAs/genética , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , RNA Mensageiro/genética , Transcriptoma/efeitos dos fármacos
18.
Clin Hemorheol Microcirc ; 72(2): 151-160, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30689559

RESUMO

OBJECTIVE: To investigate the stiffness distribution in the ablated zone after radiofrequency ablation (RFA), we used a device called tissue elastometer based on gross liver samples. MATERIALS: AND METHODS: Twelve freshly excised porcine livers were subject to RFA under a same setup to form elliptic ablated samples. Each sample was cut open for gross examination, and then the surface of the section plane was sliced into one piece for Young's modulus test using the tissue elastometer. Five test points along the long- and short-axis on each piece were selected to evaluate stiffness distribution respectively. Among them, four points distributed equidistantly from center to boundary in the ablated zone and one was in the unablated zone. RESULTS: In the ablated zone, we found the Young's moduli were significantly different among the four test points both in long- (F = 99.04, p <0.001) and short-axis (F = 79.47, p <0.001) directions. The Young's modulus showed a downtrend in each direction, and was linearly related to the distance from the center to the test point (for long axis, R2 = 0.968; for short axis, R2 = 0.984, both p <0.001). A more significant downtrend was observed in short-axis direction. The Young's moduli gained from the inner edge of ablated zone were comparable and significantly higher than those from the outer edge for both directions. The maximum value of 24.71kPa for Young's modulus was the appropriate threshold to ensure the tissues were necrotic completely. CONCLUSION: The stiffness inside the ablated zone represented a radial distribution with downtrend, following a linear law. The stiffness at the inner edge of ablated zone is stable and significantly higher than that at the outer edge. The maximum value of 24.71 kPa close to the inner edge of Wz may be used as the standard of complete ablation.


Assuntos
Ablação por Cateter/métodos , Fígado/efeitos da radiação , Ablação por Radiofrequência/métodos , Animais , Módulo de Elasticidade , Humanos , Suínos
19.
Future Oncol ; 15(5): 473-483, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30628844

RESUMO

AIM: To study the expression and prognostic significance of CD80 in patients with gastric adenocarcinoma. Materials & methods: Real-time quantitative PCR, western blot and immunohistochemistry were performed to detect the expression of CD80 in gastric cancer tissues and matched adjacent normal tissues. Double immunohistochemical staining was performed to preliminary examine the relationship between CD80+ cells and CD8+ cytotoxic T lymphocytes. RESULTS: The expression of CD80 was downregulated in tumor tissues compared with normal tissues (p = 0.002). Immunohistochemistry analysis showed that 49 (39.8%) of 123 patients with gastric cancer demonstrated reduced CD80 expression, which was correlated with the tumor differentiation grade. CONCLUSION: Our data suggest that reduced CD80 expression independently predicts a poor prognosis in patients with gastric adenocarcinoma.


Assuntos
Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Antígeno B7-1/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Antígeno B7-1/genética , Biomarcadores Tumorais , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Gástricas/patologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
20.
Environ Toxicol Pharmacol ; 66: 109-115, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30641414

RESUMO

Non-small cell lung cancer (NSCLC) is one of the most common malignancies, and Taxol is a cornerstone in the treatment. However, taxol-resistance eventually limits the clinical effects and applications. Daurinoline could restore the sensitivity of resistant MCF-7/adr and KBv200 cells. Whereas, the effect of daurinoline on the chemo-resistant NSCLC cells and the mechanism has not been elucidated. In this study, daurinoline was firstly demonstrated that inhibited the proliferation, migration, invasion and EMT phenotype of chemo-resistant NSCLC cells. And these effects were associated with EMT and Notch-1 reversal. Moreover, daurinoline could significantly enhance the anti-tumor effect of Taxol rather than epirubicin, adriamycin and cisplatin. And the reverse fold (RF) value of daurinoline was greater than terfenadine reported before. There are little cytotoxic effects of daurinoline and its derivatives reported by L.W. Fu, et al. (2001). Therefore, daurinoline may be a potential anti-tumor agent or chemosensitizer for chemo-resistant NSCLC patients.


Assuntos
Alcaloides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Paclitaxel/farmacologia , Receptor Notch1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Cicatrização
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