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1.
Int J Med Sci ; 16(6): 902-908, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31337964

RESUMO

Diabetes mellitus (DM) is a principal health problem with increasing incidence worldwide. It can be associated with various systemic diseases. Long non-coding RNA (lncRNA), a member of non-coding RNA has been newly linked with various human diseases. Recent evidence from animal experiments has shown that the incidence and development of type 2 diabetes are contributed by the atypical expression of lncRNA in which the biomarker with capable clinical potential was lncRNA NONRATT021972. In this review, we demonstrated the numerous functions of NONRATT021972 in different diabetes-related diseases including diabetic neuropathy, diabetic cardiac autonomic neuropathy, myocardial ischemia, and hepatic glucokinase dysfunction. The emerging evidence shows that the role of NONRATT021972 in diabetic-related disease is novel and therapeutic. These results direct us to conclude that NONRATT021972 is a potential diagnostic and future targeted therapy for diabetes-associated diseases.

2.
Int J Med Sci ; 16(4): 513-518, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31171902

RESUMO

Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNAs produced by back-splicing. They are found to be expressed in eukaryotic cells and play certain roles in various cellular functions, including fibrosis, cell proliferation, differentiation, apoptosis and angiogenesis. Dysregulated circRNAs are found in several human disorders including, malignancy, vascular, inflammatory as well as nervous diseases. Although, increasing evidence suggests that circRNAs may also contribute in different ocular diseases, the outline of circRNAs in ocular diseases remains obscure. In this review we consider the current state of knowledge regarding the potential role and underlying mechanism of circRNAs in ocular diseases including pterygium, age-related cataract, glaucoma, diabetic retinopathy, retinoblastoma, retinal vascular dysfunction and hyperhomocysteinemia induced ocular diseases, emphasizing that circRNAs could be promising biomarkers for the diagnosis and prognosis evaluation. Future circRNAs-targeted intervention may become a novel therapeutic tool for the treatment of ocular diseases.

3.
Int J Med Sci ; 16(4): 548-555, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31171906

RESUMO

Diabetes mellitus is a global issue with increasing incidence rate worldwide. In an uncontrolled case, it can advance to various organ-related complications leading to an increase in morbidity and mortality. Long non-coding RNA (lncRNA) Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) appears to be a fairly novel lncRNA that is relevant to diabetes and its role in diabetic-related diseases initiation and progression have long been a subject of attention to many scholars. The expression of MALAT1 is elevated in different diabetic-related diseases. In this review, we demonstrate the various functions of MALAT1 in the different diabetes-related complications including ischemic reperfusion injury, retinopathy, cataract, atherosclerosis, cardiomyopathy, non-alcoholic steatohepatitis, gastroparesis, kidney disease, and gestational diabetes. The emerging evidence showed that the role of MALAT1 in diabetic-related complications is both pro-inflammatory and apoptosis in different cell types. These results concluded that MALAT1 is a potential diagnostic and future targeted therapy for diabetes-associated complications.

4.
Pharmacology ; 104(1-2): 36-42, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31055581

RESUMO

BACKGROUND: Endothelium-dependent dilatation is a predictor for vascular function. NADPH oxidase-derived O2- can inactivate nitric oxide and induce vascular injury. METHOD: The crude ethanolic extract of Lysimachia christinae Hance were separated out 4 fractions of different olarities by petroleum ether, ethyl acetate, n-butanol (NB), and aqueous. The endothelial integrity was appraised by vascular tension measurement. Dihydroethidium was utilized to observe the vascular reactive oxygen species (ROS) production. Western-blot was adopted to detect protein expression. RESULTS: Among the 4 fractions of L. christinae Hance, the NB fraction showed the most potent capacity of promoting endothelium-dependent vascular relaxation and inhibiting ROS formation in aortic rings, which were likely attributed by suppressing the expression of NAD(P)H oxidase subunit (gp91phox, p47phox, and p67phox) and enhancing the phosphorylation of endothelial NOS in vascular tone. CONCLUSIONS: These results suggest that the NB fraction possess the strongest vascular pharmacological activities among the crude ethanolic extract of L. christinae Hance, which may help us for purifying bioactive constituents and discovering new drugs from this herb in future.

5.
Proc Natl Acad Sci U S A ; 116(10): 4592-4598, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30782819

RESUMO

Multiple myeloma (MM) is a B cell malignancy for which new treatments are urgently needed. The B cell maturation antigen (BCMA) is a lineage-restricted differentiation protein highly expressed on myeloma. Recombinant immunotoxins (RITs) are proteins composed of the Fv or Fab portion of an antibody fused to a bacterial toxin. We previously treated H929 myeloma s.c. tumors with anti-BCMA immunotoxins, very active on killing cultured cells, and observed tumor growth inhibition but not complete tumor responses. To determine if immunotoxins were more active against cells growing in the bone marrow (BM), the normal location of myeloma cells, we developed a BM mouse model that is more relevant to human disease. H929 cells were transfected with luciferase and GFP, enriched by flow, recycled through the BM of a mouse, and injected IV into nonobese diabetic scid γ mice (NSG) mice. A second myeloma mouse model used the MM.1S-GFP-luc cell line. Mice were treated IV with immunotoxins, and the tumor burden was assessed using bioluminescence imaging. We achieved complete durable remissions when treating mice with H929-GFP-luc cells with anti-BCMA RITs both leptomycin B-75 (LMB-75) [anti-BCMA-disulfide-stabilized (ds)-Fv-PE24] (where PE represents Pseudomonas exotoxin A) or LMB-70 (anti-BCMA-Fab-PE24) given every other day for 5-d (QOD×5) doses beginning on day 4 or day 8. Mice were disease free at 3 months; untreated mice became moribund around day 40. We also achieved long-term responses using the MM.1S-GFP-luc myeloma cell line. Treatment with an 1.5 mg/kg LMB-75 QOD×5 anti-BCMA RIT beginning on day 4 caused the complete disappearance of tumors for 80 days. To summarize, LMB-75 and LMB-70, our anti-BCMA RITs, induced complete durable responses in two myeloma models.

6.
J Mol Cell Cardiol ; 124: 26-34, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30292723

RESUMO

The effects of curcumin on regulating cardiac apoptosis and autophagy were analyzed in diabetic models both in vivo and in vitro. In vivo, experimental diabetes was induced in mice by low-dose STZ injection combined with a high-fat diet. In vitro, cultured H9c2 cardiomyoblasts were exposed to high d-glucose concentrations combined with palmitate. Our results showed that apoptosis was increased and autophagy was suppressed in the hearts of diabetic mice, which was ameliorated by curcumin treatment, ultimately improving cardiac function. Moreover, the inhibition of autophagy exacerbated apoptotic death in cardiac cells under diabetic condition. Curcumin activated AMPK and JNK1, which phosphorylated Bcl-2 and Bim and subsequently disrupted their interactions with Beclin1, thereby promoting autophagy and alleviating apoptosis respectively. In addition, AMPK-mediated inhibition of mTORC1 pathway likely played a role in regulating autophagy by curcumin under diabetic condition. Our study suggests that curcumin protects against diabetic cardiomyopathy by modulating the crosstalk between autophagic and apoptotic machinery. Modulation of autophagy may be an effective strategy for the treatment of cardiovascular diseases associated with diabetes.

7.
Biol Chem ; 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30218597

RESUMO

The functionality of eukaryotic translation elongation factor 2 (eEF2) is modulated by phosphorylation, eEF2 is simultaneously the molecular target of ADP-ribosylating toxins. We analyzed the interplay between phosphorylation and diphthamide-dependent ADPribosylation. Phosphorylation does not require diphthamide, eEF2 without it still becomes phosphorylated. ADP-ribosylation not only modifies the H715 diphthamide but also inhibits phosphorylation of S595 located in proximity to H715, and stimulates phosphorylation of T56. S595 can be phosphorylated by CDK2 and CDK1 which affects EEF2K-mediated T56- phosphorylation. Thus, ADP-ribosylation and S595-phosphorylation by kinases occur within the same vicinity and both trigger T56-phosphorylation. Diphthamide is surface-accessible permitting access to ADP-ribosylating enzymes, the adjacent S595 side chain extends into the interior. This orientation is incompatible with phosphorylation, neither allowing kinase access nor phosphate attachment. S595 phosphorylation must therefore be accompanied by structural alterations affecting the interface to ADP-ribosylating toxins. In agreement with that, replacement of S595 with Ala, Glu or Asp prevents ADP-ribosylation. Phosphorylation (starvation) as well as ADP-ribosylation (toxins) inhibit protein synthesis, both affect the S595/H715 region of eEF2, both trigger T57-phosphorylation eliciting similar transcriptional responses. Phosphorylation is short lived while ADP-ribosylation is stable. Thus, phosphorylation of the S595/H715 'modifier region' triggers transient interruption of translation while ADP-ribosylation arrests irreversibly.

8.
Cancer Med ; 7(8): 3792-3799, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29992790

RESUMO

The cancers are the leading cause of disease-related deaths worldwide with a high risk of morbidity and mortality. Long noncoding RNAs (lncRNAs) play a critical role in a wide range of biological processes, including tumorigenesis. HOXA11-AS (NCRNA00076), the antisense strands of HOXA11 gene, was initially revealed in a mouse embryonic cDNA library in 2009 and it was a fairly novel lncRNA. This review summarized the advanced research progression concerning the expression and role of HOXA11-AS in different human malignancies. The expression of HOXA11-AS is aberrantly altered in many cancers, either as a tumor suppressor or as a tumor accelerator. The different underlying mechanism of HOXA11-AS in different cancers (including, nonsmall cell lung cancers, osteosarcoma, uveal melanoma, glioma, hepatocellular carcinoma, gastric cancer, breast cancer, cervical cancer, ovarian cancer, colorectal cancer, ovarian cancer, and glioblastoma) was also detailed. These findings lead us to conclude that HOXA11-AS participate in the complex network of cancers and plays an important role in the tumorigenesis and progression. Functional HOXA11-AS could be a promising biomarker for early detection as well as prognosis evaluation in cancer patients. Future HOXA11-AS-targeted intervention may become a valuable novel therapeutic tool, improving the clinical management of cancers.

9.
Int J Biol Sci ; 14(9): 1090-1098, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29989056

RESUMO

Retinal ganglion cells (RGCs) are one of the important cell types affected in many ocular neurodegenerative diseases. Oxidative stress is considered to be involved in retinal RGCs death in ocular neurodegenerative diseases. More and more attention has been focused on studying the agents that may have neuroprotective effects. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key nuclear transcription factor for the systemic antioxidant defense system. This review elucidates the underlying mechanism of the Nrf2-mediated neuroprotective effects on RGCs in ocular neurodegenerative diseases, such as diabetic retinopathy and retinal ischemia-reperfusion injury. Several Nrf2 inducers that shield RGCs from oxidative stress-induced neurodegeneration via regulating Nrf2 signaling are discussed.

10.
Cell Physiol Biochem ; 46(5): 2031-2040, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29723857

RESUMO

BACKGROUND/AIMS: Diabetic cardiomyopathy is associated with increased apoptosis and suppressed autophagy in cardiac cells. The polyphenol resveratrol has shown beneficial effects in various cardiovascular diseases. This study investigated if resveratrol protected cardiac cells by modulating apoptosis and autophagy in the context of diabetes. METHODS: H9c2 cardiac myoblast cells were exposed to high glucose combined with palmitate. Autophagy was evaluated by estimating LC3-II/I ratio, P62 protein levels, and LC3 fluorescent puncta. Apoptosis was assessed by using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), flow cytometry, and analysis of the protein expression of apoptotic markers (cleavage of caspase-3 and PARP). RESULTS: High glucose and palmitate suppressed autophagic activity and exacerbated apoptotic cell death in cardiac myoblast cells. Resveratrol restored autophagy and attenuated apoptosis in cells upon diabetic stimuli. Moreover, resveratrol activated AMPK and JNK1, thereby suppressing mTOR and its downstream effectors p70S6K1 and 4EBP1, as well as disrupting the Beclin1-Bcl-2 complex. CONCLUSION: Resveratrol protects cardiac cells by regulating the switch between autophagy and apoptotic machinery under diabetic conditions, which is attributed by AMPK-mediated phosphorylation of mTORC1/p70S6K1/4EBP1 and JNK-mediated dissociation of Beclin1-Bcl-2. Our study suggests that autophagy may be an important target for resveratrol in the treatment of diabetic cardiomyopathy.


Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Glucose/metabolismo , Mioblastos Cardíacos/efeitos dos fármacos , Palmitatos/metabolismo , Estilbenos/farmacologia , Animais , Linhagem Celular , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/metabolismo , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , Mioblastos Cardíacos/citologia , Mioblastos Cardíacos/metabolismo , Ratos , Resveratrol
11.
Proc Natl Acad Sci U S A ; 115(15): E3501-E3508, 2018 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-29581296

RESUMO

Recombinant immunotoxins (RITs) are chimeric proteins consisting of a Fv that binds to a cancer cell and a portion of a protein toxin. One of these, Moxetumomab pasudotox, was shown to be effective in treating patients with some leukemias, where the cells are readily accessible to the RIT. However, their short half-life limits their efficacy in solid tumors, because penetration into the tumors is slow. Albumin and agents bound to albumin have a long half-life in the circulation. To increase the time tumor cells are exposed to RITs, we have produced and evaluated variants that contain either an albumin-binding domain (ABD) from Streptococcus or single-domain antibodies from Llama. We have inserted these ABDs into RITs targeting mesothelin, between the Fv and the furin cleavage site. We find that these proteins can be produced in large amounts, are very cytotoxic to mesothelin-expressing cancer cell lines, and have a high affinity for human or mouse serum albumin. In mice, the RIT containing an ABD from Streptococcus has a longer half-life and higher antitumor activity than the other two. Its half-life in the circulation of mice ranges from 113 to 194 min compared with 13 min for an RIT with no ABD. Cell uptake studies show the RIT enters the target cell bound to serum albumin. We conclude that RITs with improved half-lives and antitumor activity should be evaluated for the treatment of cancer in humans.


Assuntos
Imunotoxinas/farmacocinética , Animais , Toxinas Bacterianas/farmacocinética , Toxinas Bacterianas/farmacologia , Linhagem Celular Tumoral/efeitos dos fármacos , Modelos Animais de Doenças , Exotoxinas/farmacocinética , Exotoxinas/farmacologia , Feminino , Proteínas Ligadas por GPI/efeitos dos fármacos , Meia-Vida , Humanos , Imunotoxinas/imunologia , Leucemia/tratamento farmacológico , Camundongos , Camundongos Nus , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes/metabolismo , Albumina Sérica/metabolismo , Albumina Sérica/uso terapêutico
12.
Cell Prolif ; 51(4): e12449, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29484737

RESUMO

Long non-coding RNAs (lncRNAs) participate in the complex network of cancer and play an important role in tumourigenesis and progression. BRAF activated non-coding RNA (BANCR), a 4-exon transcript of 693-bp, was first discovered as an oncogenic long non-coding RNA in BRAFV600E melanomas cells in 2012 and was related to melanoma cell migration. Besides melanoma, increasing evidence has explored the potential role of BANCR in the development and progression of multiple other human malignancies, such as retinoblastoma, lung cancer, gastric cancer etc. since its discovery. The expression pattern of BANCR varies in different types of cancers, either as a tumour suppressor or as an accelerator. Functional BANCR may serve as a promising biomarker for cancer diagnosis as well as prognosis evaluation. BANCR-targeted intervention may also become a valuable novel therapeutic tool against human malignancies. This review summarized the advanced research progresses concerning the expression and role of BANCR in different human malignancies.


Assuntos
Neoplasias/patologia , RNA Longo não Codificante/metabolismo , Animais , Biomarcadores Tumorais/genética , Caderinas/metabolismo , Humanos , Melanoma/genética , Melanoma/metabolismo , Melanoma/patologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , Transdução de Sinais
13.
Proc Natl Acad Sci U S A ; 115(4): E733-E742, 2018 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-29311317

RESUMO

Protein-based drugs are very active in treating cancer, but their efficacy can be limited by the formation of neutralizing antidrug antibodies (ADAs). Recombinant immunotoxins are proteins that are very effective in patients with leukemia, where immunity is suppressed, but induce ADAs, which compromise their activity, in patients with intact immunity. Here we induced a specific, durable, and transferable immune tolerance to recombinant immunotoxins by combining them with nanoparticles containing rapamycin (SVP-R). SVP-R mitigated the formation of inhibitory ADAs in naïve and sensitized mice, resulting in restoration of antitumor activity. The immune tolerance is mediated by colocalization of the SVP-R and immunotoxin to dendritic cells and macrophages in the spleen and is abrogated by depletion of regulatory T cells. Tolerance induced by SVPs was not blocked by checkpoint inhibitors or costimulatory agonist monoclonal antibodies that by themselves enhance ADA formation.


Assuntos
Imunomodulação , Imunossupressores/administração & dosagem , Imunotoxinas/administração & dosagem , Leucemia/terapia , Sirolimo/administração & dosagem , Animais , Anticorpos Neutralizantes , Proteínas Ligadas por GPI/imunologia , Humanos , Imunotoxinas/imunologia , Nanopartículas , Fatores de Tempo
14.
Acta Pharmacol Sin ; 39(2): 195-204, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28905939

RESUMO

Cardiac fibrosis is considered the initial change of diabetic cardiomyopathy (DCM). We have shown that curcumin alleviates collagen deposition in DCM, but the mechanism remains unknown. In this study we sought to investigate the effects of curcumin on cardiac fibrosis in vivo and in vitro and to elucidate the underlying mechanisms. Experimental diabetes was induced in rats by injection of low-dose streptozotocin (STZ) combined with high energy diet. The rats were orally treated with curcumin (300 mg·kg-1·d-1) for 16 weeks. Curcumin administration significantly suppressed the deposition of type I and type III collagens in the heart tissues of diabetic rats, accompanied by markedly reduced TGF-ß1 production, suppressed TßR II levels and Smad2/3 phosphorylation, and increased Smad7 expression. Similar effects were observed in human cardiac fibroblasts exposed to high glucose (HG, 30 mmol/L) or exogenous TGF-ß1 (5 ng/mL). Furthermore, TGF-ß1 or HG treatment significantly increased the phosphorylation levels of AMPK and p38 MAPK in the fibroblasts. Application of curcumin (25 µmol/L) inhibited TGF-ß1- or HG-induced AMPK/p38 MAPK activation and suppressed collagen synthesis in the fibroblasts. These effects were similar to those of the AMPK inhibitor compound C (10 µmol/L) but opposite to the effects of the AMPK activator metformin (2 mmol/L) in the fibroblasts. Our results demonstrate that curcumin suppresses diabetes-associated collagen synthesis in rat myocardium not only by inhibiting TGF-ß1 production and canonical Smad signaling but also by blocking the non-canonical AMPK/p38 MAPK pathway.


Assuntos
Colágeno Tipo III/antagonistas & inibidores , Colágeno Tipo I/antagonistas & inibidores , Curcumina/farmacologia , Diabetes Mellitus Experimental/metabolismo , Miocárdio/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Cardiomiopatias Diabéticas/metabolismo , Modelos Animais de Doenças , Fibroblastos/efeitos dos fármacos , Fibrose/prevenção & controle , Glucose/metabolismo , Humanos , Masculino , Proteínas Serina-Treonina Quinases/metabolismo , Ratos Sprague-Dawley , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
15.
Oxid Med Cell Longev ; 2017: 2326178, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29209447

RESUMO

Corneal diseases are one of the major causes of blindness worldwide. Conservative medical agents, which may prevent sight-threatening corneal disease progression, are urgently desired. Numerous evidences have revealed the involvement of oxidative stress in various corneal diseases, such as corneal wound healing and Fuchs endothelial corneal dystrophy (FECD). Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Kelch-like erythroid-cell-derived protein with CNC homology- (ECH-) associated protein 1 (Keap1)/antioxidant response element (ARE) signaling is well known as one of the main antioxidative defense systems. To the best of our knowledge, this is the first review to elucidate the different expression profiles of Nrf2 signaling as well as the underlying mechanisms in corneal diseases, implicating that Nrf2 may serve as a potentially promising therapeutic target for corneal diseases.


Assuntos
Doenças da Córnea/patologia , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo , Aldeídos/metabolismo , Animais , Proteínas de Transporte de Ânions/metabolismo , Elementos de Resposta Antioxidante , Doenças da Córnea/metabolismo , Doenças da Córnea/veterinária , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Camundongos , Camundongos Knockout , Fator 2 Relacionado a NF-E2/deficiência , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Simportadores/metabolismo , Raios Ultravioleta
16.
Oncotarget ; 8(50): 87307-87316, 2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-29152082

RESUMO

LMB-100 (RG7787) is a recombinant immunotoxin, which kills mesothelin-expressing cancer cells and now being evaluated in phase 1 trials. To enhance the anti-tumor activity of LMB-100, we have searched for agents, already approved for cancer therapy, that can be combined with LMB-100 to increase its efficacy. Panbinostat is a pan-histone deacetylase inhibitor that is used to treat multiple myeloma. We incubated different types of cancer cells with panbinostat and LMB-100 and found that they interacted synergistically to cause cell death. We found that panbinostat and the combination increased levels of mRNAs encoding TNF/TNFR family members, as well as BNIP3L and CASP-9, and markedly decreased mRNA levels for c-FLIP and BID. Western blots confirmed a fall in levels of cFLIP protein and a rise in BNIP3L and caspase-9. The combination also increased levels of cleaved BID (t-BID), cleaved-capsase-3 and -8 and PARP. To assess the importance of the fall in cFLIP levels, we treated cells with the cFLIP inhibitor, Rocaglamide, and found it also enhanced killing of tumor cells by LMB-100. LMB-100, which activates the intrinsic pathway of apoptosis, and panbinostat, which activates the extrinsic pathway, work in a synergistic manner to kill cancer cell lines.

17.
Cell Prolif ; 50(6)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29027279

RESUMO

The digestive system cancers are leading cause of cancer-related death worldwide, and have high risks of morbidity and mortality. More and more long non-coding RNAs (lncRNAs) have been studied to be abnormally expressed in cancers and play a key role in the process of digestive system tumour progression. Plasmacytoma variant translocation 1 (PVT1) seems fairly novel. Since 1984, PVT1 was identified to be an activator of MYC in mice. Its role in human tumour initiation and progression has long been a subject of interest. The expression of PVT1 is elevated in digestive system cancers and correlates with poor prognosis. In this review, we illustrate the various functions of PVT1 during the different stages in the complex process of digestive system tumours (including oesophageal cancer, gastric cancer, colorectal cancer, hepatocellular carcinoma and pancreatic cancer). The growing evidence shows the involvement of PVT1 in both proliferation and differentiation process in addition to its involvement in epithelial to mesenchymal transition (EMT). These findings lead us to conclude that PVT1 promotes proliferation, survival, invasion, metastasis and drug resistance in digestive system cancer cells. We will also discuss PVT1's potential in diagnosis and treatment target of digestive system cancer. There was a great probability PVT1 could be a novel biomarker in screening tumours, prognosis biomarkers and future targeted therapy to improve the survival rate in cancer patients.


Assuntos
Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Animais , Proliferação de Células/genética , Humanos
18.
Exp Ther Med ; 14(2): 1109-1113, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28810564

RESUMO

The aim of the present study was to investigate the use and effectiveness of a selective, partial, pedunculated (tongue-shaped) conjunctival flap (CF) for the treatment of refractory fungal keratitis (FK) with or without perforation. A total of 31 cases of corneal diseases treated by CF surgery between April 2014 and October 2015 were evaluated. Among the 31 cases, 16 cases (male:female, 11:5) with FK were selected. Logistic regression analysis was used to investigate factors associated with complications of CF surgery. A higher prevalence of FK was identified among male farmers compared with female farmers, in which plant trauma was the most prevalent cause of the disease. Only 4 patients had experienced corneal perforation prior to CF surgery. Patients aged 61-80 years had a higher prevalence of FK (50%) compared with other age groups; however, there was no statistically significant correlation between the prevalence of FK and sex or age. It was also demonstrated that age, sex, combined surgery and surgery duration were not significantly associated with post-surgical complications. All CF surgeries were performed following corneal ulcer scraping; however, 4 patients (12.5%) required additional surgery. The visual acuity of participants post-surgery decreased in 4 cases and remained unchanged in 12 cases. A total of 3 study patients experienced post-surgical complications of corneal perforation (1 patient) and purulent exudate spreading (2 patients). The post-surgical outcome was good for all study participants as the surgeries were able to control infection and preserve the eyeball, with the potential of future corneal transplant. These results suggest that CF surgery may be a useful alternative treatment for refractory FK in countries such as China where there is lack of cornea donors.

19.
Aging Cell ; 16(5): 934-942, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28722304

RESUMO

Cataract is one of the most important causes of blindness worldwide, with age-related cataract being the most common one. Agents preventing cataract formation are urgently required. Substantial evidences point out aggravated oxidative stress as a vital factor for cataract formation. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Kelch-like erythroid-cell-derived protein with CNC homology (ECH)-associated protein 1 (Keap1) system is considered as one of the main cellular defense mechanisms against oxidative stresses. This review discusses the role of Nrf2 pathway in the prevention of cataracts and highlights that Nrf2 suppressors may augment oxidative stress of the lens, and Nrf2 inducers may decrease the oxidative stress and prevent the cataract formation. Thus, Nrf2 may serve as a promising therapeutic target for cataract treatment.


Assuntos
Envelhecimento/genética , Antioxidantes/uso terapêutico , Cegueira/prevenção & controle , Catarata/prevenção & controle , Fator 2 Relacionado a NF-E2/agonistas , Envelhecimento/metabolismo , Benzofuranos/uso terapêutico , Cegueira/genética , Cegueira/metabolismo , Cegueira/patologia , Catarata/genética , Catarata/metabolismo , Catarata/patologia , Flavonoides/uso terapêutico , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Cristalino , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Quercetina/análogos & derivados , Quercetina/uso terapêutico , Transdução de Sinais , Transcrição Genética
20.
Exp Ther Med ; 14(1): 283-285, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28672926

RESUMO

Diffuse lamellar keratitis (DLK) is a sterile inflammation of the cornea, which may occur after laser-assisted in situ keratomileusis (LASIK) surgery. Little is known about the association of DLK with permanent eyeliner tattoo. The present case report describes the case of a 37-year-old Chinese woman who developed severe foreign body sensation in both eyes 1 week after receiving bilateral permanent eyeliner tattoo treatment. The patient had received bilateral LASIK surgery 10 years previously. Slit-lamp biomicroscopy revealed diffused granular infiltrates precipitated around the edge of the corneal flaps in both eyes. After topical treatment, DLK persisted. Therefore, the patient underwent surgery to remove the corneal epithelium around the DLK lesion. There was no recurrence of the disease during the 3-month observation period. To our knowledge, this is the first case report describing a case of late-onset of DLK that was triggered by permanent eyeliner tattoo. Doctors should be aware of the diagnosis and treatment of this complication associated with the application of permanent eyeliner tattoo as the popularity of this cosmetic procedure increases.

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