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1.
Int J Lab Hematol ; 2020 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-32359033

RESUMO

INTRODUCTION: The development of drug resistance is the main obstacle for successful treatment in acute myeloid leukemia (AML). Noncoding RNAs have been implicated in biological function in AML drug resistance. Aberrant protein glycosylation is associated with AML progression. The aim of the study was to explore the potential regulatory mechanism of lncRNA MEG3/miR-155/ALG9 axis in drug resistance of AML. METHODS: QRT-PCR and Western blot were used for comparison analyses of ALG9, MEG3, and miR-155 levels. CCK-8 and colony formation assays were determined for drug sensitivity and proliferative capability of AML cells. Luciferase reporter assay was used to confirm the targets of miR-155. RESULTS: The mannosyltransferase ALG9 and MEG3 was downregulated in peripheral blood mononuclear cells (PBMCs) of M5/multidrug resistance (MDR) AML patients and adriamycin (ADR)-resistant AML cell lines, which determined a positive correlation in AML patients. Low expression of ALG9 and MEG3 predicted poor prognosis of AML patients. The altered level of ALG9 was found corresponding to the drug-resistant phenotype and sphere formation of AML cells. MiR-155 was overexpressed in M5/MDR patients and ADR-resistant AML cells, as well as inversely correlated to ALG9 expression. MEG3 was a direct target of miR-155 and could sponge miR-155 in AML cells. MEG3 interacted with miR-155 to regulate ALG9 expression, which reversed the effects of ALG9 regulation on proliferation and drug resistance in AML cells. CONCLUSION: MEG3 sponged miR-155 by competing endogenous RNA (ceRNA) mechanism, which further modulated ALG9 expression and AML procession, providing a novel therapeutic target for AML chemoresistance.

2.
Inorg Chem ; 2020 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-32363865

RESUMO

p-tert-Butylthiacalix[4]arene (H4TC4A)-decorated tetranuclear (Ti4) and hexanuclear (Ti6) polyoxo-titanium clusters (PTCs) were synthesized in isopropyl alcohol by a low-temperature solvothermal method. The structures were determined by single-crystal X-ray diffraction, in which the ligands adopt 1,2-alternative and cone-shaped conformations, respectively. Both PTCs show UV-vis absorptions up to 600 nm with band gaps at 2.19 eV (Ti4) and 2.24 eV (Ti6), respectively. Visible-light photocatalytic H2 production for Ti4 was measured to be 73.56 µmol/(g h), which is almost 5 times of that of Ti6 (15.16 µmol/(g h)). Results of density functional theory (DFT) calculations suggested that the different Ti-S coordination modes originating from the conformational disparity of the ligands are primarily responsible for the observed different photocatalytic activities. Not only does this work provides a better understanding of the structure-property relationships in using titanium-oxo clusters for photocatalytic H2 production but it also offers a means of tuning the band gap of the catalysts by varying the conformations of the ligands.

3.
Anal Chim Acta ; 1110: 141-150, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32278389

RESUMO

Bioselenols are important substances for the maintenance of physiological balance and offer anticancer properties; however, their causal mechanisms and effectiveness have not been assessed. One way to explore their physiological functions is the in vivo detection of bioselenols at the molecular level, and one of the most efficient ways to do so is to use fluorescent probes. Various types of bioselenol-specific fluorescent probes have been synthesized and optimized using chemical simulations and by improving biothiol fluorescent probes. Here, we review recent advances in bioselenol-specific fluorescent probes for selenocysteine (Sec), thioredoxin reductase (TrxR), and hydrogen selenide (H2Se). In particular, the molecular design principles of different types of bioselenols, their corresponding sensing mechanisms, and imaging applications are summarized.

4.
Biochem Biophys Res Commun ; 526(1): 70-77, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32192769

RESUMO

Genetic alterations can drive carcinogenesis. Numerous studies have shown that gene fusion is associated with cancer progression and could provide valuable biomarkers for clinical diagnosis or targets for cancer therapy. Adenoid cystic carcinoma (ACC) is a rare form of adenocarcinoma, characterized by frequent local recurrence and high rates of distant metastasis, ultimately resulting in low survival rates. Owing to the lack of effective therapeutic targets and limited biomarkers for diagnosis, a deeper understanding of the molecular basis of ACC is urgently needed. Here, we show that gene fusion is associated with ACC metastasis. We identified a metastasis suppressor KISS1 fused with a close-by gene, GOLT1A, in highly metastatic ACC cell lines and human specimens. Such fusion blocks KISS1 translation, but not transcription, by introducing 5' upstream open reading frames (uORFs) in the GOLT1A-KISS1 fusion transcript. Deletion of these uORFs rescued KISS1 expression and reduced invasion and migration of metastatic ACC cells. We also detected GOLT1A-KISS1 fusion transcripts in other types of highly metastatic cancer cell lines. Taken together, our results highlight the significance of this novel GOLT1A-KISS1 gene fusion in tumor metastasis and provide a valuable biomarker for clinical diagnosis and future therapeutic targeting of ACC.

5.
J Am Chem Soc ; 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32202784

RESUMO

As an alternative for depleting fossil fuel energy, hydrogen economy desires low-cost and efficient hydrogen production from water splitting. In order to explore a cheap, abundant, active, and durable catalyst for the electrocatalytic hydrogen evolution reaction (HER), two-dimensional (2D) ceria nanosheets are produced through a thermal decomposition exfoliation method from CeCO3OH with a layer-stacked structure. The additional cobalt dopant promotes formation of oxygen vacancies in ceria nanosheets and, in turn, optimizes hydrogen binding/water dissociation and increases the active sites. As a result, the 2D Co-doped CeO2 nanosheets exhibit an excellent catalytic performance in alkaline HER such that the overpotential is as low as 132 and 215 mV to deliver a high current density of 100 and 500 mA cm-2, respectively, outperforming Pt. Such 2D Co-doped CeO2 nanosheets are also durable HER electrocatalysts, as the activity loss during an extended period of operation is nearly negligible.

6.
Acta Pharmacol Sin ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32051552

RESUMO

Traditional Chinese medicine (TCM) has evolved over several thousands of years, which has been shown to be efficacious in the treatment of ischemic heart disease. Three classical TCM prescriptions, namely Xuefu Zhuyu Decoction, Zhishi Xiebai Guizhi Decoction, and Gualou Xiebai Banxia Decoction, have been extensively used in the treatment of coronary heart disease (CHD). Based on molecular network modeling, we performed a comparative pharmacogenomic analysis to systematically determine the drug-targeting spectrum of the three prescriptions at molecular level. Wide-area target molecules of CHD were covered, which was a common feature of the three decoctions, demonstrating their therapeutic functions. Meanwhile, collective signaling involved metabolic/pro-metabolic pathways, driving and transferring pathways, neuropsychiatric pathways, and exocrine or endocrine pathways. These organized pharmacological disturbance was mainly focused on almost all stages of CHD intervention, such as anti-atherosclerosis, lipid metabolism, inflammation, vascular wall function, foam cells formation, platelets aggregation, thrombosis, arrhythmia, and ischemia-reperfusion injury. In addition, heterogeneity analysis of the global pharmacological molecular spectrum revealed that signaling crosstalk, cascade convergence, and key targets were tendentious among the three decoctions. After all, it is unadvisable to rank the findings on targeting advantages of the three decoctions. Comparative pharmacological evidence may provide an appropriate decoction scheme for individualized intervention of CHD.

7.
J Med Chem ; 63(6): 3028-3046, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32069401

RESUMO

PI3K-Akt-mTOR signaling pathway has been validated as an effective targeting pathway for cancer therapy. However, no PI3K/mTOR dual inhibitor has been approved by the FDA yet. Therefore, it is still essential to discover a candidate with good efficacy and low toxicity. In our design, a series of imidazo[1,2-a]pyridine derivatives had been synthesized and subjected to activity assessment in vitro and in vivo. 15a was proved to be a potent PI3K/mTOR dual inhibitor with excellent kinase selectivity, modest plasma clearance, and acceptable oral bioavailability. Besides, 15a displayed significant inhibition of tumor growth in HCT116 and HT-29 xenografts without obvious effect on body weight.

8.
Acta Neuropathol ; 139(1): 157-174, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31664505

RESUMO

In Neurofibromatosis type 1, NF1 gene mutations in Schwann cells (SC) drive benign plexiform neurofibroma (PNF), and no additional SC changes explain patient-to-patient variability in tumor number. Evidence from twin studies suggests that variable expressivity might be caused by unidentified modifier genes. Whole exome sequencing of SC and fibroblast DNA from the same resected PNFs confirmed biallelic SC NF1 mutations; non-NF1 somatic SC variants were variable and present at low read number. We identified frequent germline variants as possible neurofibroma modifier genes. Genes harboring variants were validated in two additional cohorts of NF1 patients and by variant burden test. Genes including CUBN, CELSR2, COL14A1, ATR and ATM also showed decreased gene expression in some neurofibromas. ATM-relevant DNA repair defects were also present in a subset of neurofibromas with ATM variants, and in some neurofibroma SC. Heterozygous ATM G2023R or homozygous S707P variants reduced ATM protein expression in heterologous cells. In mice, genetic Atm heterozygosity promoted Schwann cell precursor self-renewal and increased tumor formation in vivo, suggesting that ATM variants contribute to neurofibroma initiation. We identify germline variants, rare in the general population, overrepresented in NF1 patients with neurofibromas. ATM and other identified genes are candidate modifiers of PNF pathogenesis.

9.
BMC Med Genomics ; 12(Suppl 12): 177, 2019 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-31829182

RESUMO

BACKGROUND: Disease comorbidity is popular and has significant indications for disease progress and management. We aim to detect the general disease comorbidity patterns in Chinese populations using a large-scale clinical data set. METHODS: We extracted the diseases from a large-scale anonymized data set derived from 8,572,137 inpatients in 453 hospitals across China. We built a Disease Comorbidity Network (DCN) using correlation analysis and detected the topological patterns of disease comorbidity using both complex network and data mining methods. The comorbidity patterns were further validated by shared molecular mechanisms using disease-gene associations and pathways. To predict the disease occurrence during the whole disease progressions, we applied four machine learning methods to model the disease trajectories of patients. RESULTS: We obtained the DCN with 5702 nodes and 258,535 edges, which shows a power law distribution of the degree and weight. It further indicated that there exists high heterogeneity of comorbidities for different diseases and we found that the DCN is a hierarchical modular network with community structures, which have both homogeneous and heterogeneous disease categories. Furthermore, adhering to the previous work from US and Europe populations, we found that the disease comorbidities have their shared underlying molecular mechanisms. Furthermore, take hypertension and psychiatric disease as instance, we used four classification methods to predicte the disease occurrence using the comorbid disease trajectories and obtained acceptable performance, in which in particular, random forest obtained an overall best performance (with F1-score 0.6689 for hypertension and 0.6802 for psychiatric disease). CONCLUSIONS: Our study indicates that disease comorbidity is significant and valuable to understand the disease incidences and their interactions in real-world populations, which will provide important insights for detection of the patterns of disease classification, diagnosis and prognosis.

10.
Viruses ; 11(11)2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31717393

RESUMO

The prevalence and variation of the H9N2 avian influenza virus (AIV) pose a threat to public health. A total of eight viruses isolated from farmed poultry in South China during 2017-2018 were selected as representative strains for further systematic study. Phylogenetic analyses indicated that these prevalent viruses belong to the Y280-like lineage and that the internal genes are highly similar to those of recently circulating human H7N9 viruses. The receptor-binding assay showed that most of the H9N2 isolates preferentially bound to the human-like receptor, increasing the risk of them crossing the species barrier and causing human infection. Our in vitro, multi-step growth curve results indicate these viruses can effectively replicate in mammalian cells. Infection in mice showed that three viruses effectively replicated in the lung of mice. Infection in swine revealed that the viruses readily replicated in the upper respiratory tract of pig and effectively induced viral shedding. Our findings suggested that the H9N2 AIVs circulating in poultry recently acquired an enhanced ability to transmit from avian to mammalians, including humans. Based on our findings, we propose that it is essential to strengthen the efforts to surveil and test the pathogenicity of H9N2 AIVs.

11.
World J Gastroenterol ; 25(35): 5344-5355, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31558878

RESUMO

BACKGROUND: Endoscopic submucosal dissection (ESD) has been routinely performed in applicable early gastric cancer (EGC) patients as an alternative to conventional surgical operations that involve lymph node dissection. The indications for ESD have been recently expanded to include larger, ulcerated, and undifferentiated mucosal lesions, and differentiated lesions with slight submucosal invasion. The risk of lymph node metastasis (LNM) is the most important consideration when deciding on a treatment strategy for EGC. Despite the advantages over surgical procedures, lymph nodes cannot be removed by ESD. In addition, whether patients who meet the expanded indications for ESD can be managed safely remains controversial. AIM: To determine whether the ESD indications are applicable to Chinese patients and to investigate the predictors of LNM in EGC. METHODS: We retrospectively analyzed 12552 patients who underwent surgery for gastric cancer between June 2007 and December 2018 at the Affiliated Hospital of Qingdao University. A total of 1262 (10.1%) EGC patients were eligible for inclusion in this study. Data on the patients' clinical, endoscopic, and histopathological characteristics were collected. The absolute and expanded indications for ESD were validated by regrouping the enrolled patients and determining the positive LNM results in each subgroup. Predictors of LNM in patients were evaluated by univariate and multivariate analyses. RESULTS: LNM was observed in 182 (14.4%) patients. No LNM was detected in the patients who met the absolute indications (0/90). LNM occurred in 4/311 (1.3%) patients who met the expanded indications. According to univariate analysis, LNM was significantly associated with positive tumor marker status, medium (20-30 mm) and large (>30 mm) lesion sizes, excavated macroscopic-type tumors, ulcer presence, submucosal invasion (SM1 and SM2), poor differentiation, lymphovascular invasion (LVI), perineural invasion, and diffuse and mixed Lauren's types. Multivariate analysis demonstrated SM1 invasion (odds ration [OR] = 2.285, P = 0.03), SM2 invasion (OR = 3.230, P < 0.001), LVI (OR = 15.702, P < 0.001), mucinous adenocarcinoma (OR = 2.823, P = 0.015), and large lesion size (OR = 1.900, P = 0.006) to be independent risk factors. CONCLUSION: The absolute indications for ESD are reasonable, and the feasibility of expanding the indications for ESD requires further investigation. The predictors of LNM include invasion depth, LVI, mucinous adenocarcinoma, and lesion size.


Assuntos
Adenocarcinoma Mucinoso/cirurgia , Ressecção Endoscópica de Mucosa/normas , Gastroscopia/normas , Metástase Linfática/diagnóstico , Seleção de Pacientes , Neoplasias Gástricas/cirurgia , Adenocarcinoma Mucinoso/patologia , Biomarcadores Tumorais/análise , Ressecção Endoscópica de Mucosa/métodos , Estudos de Viabilidade , Feminino , Gastrectomia/estatística & dados numéricos , Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , Gastroscopia/métodos , Humanos , Excisão de Linfonodo/estatística & dados numéricos , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Guias de Prática Clínica como Assunto , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/patologia , Carga Tumoral
12.
World J Clin Cases ; 7(13): 1696-1702, 2019 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-31367629

RESUMO

BACKGROUND: Gastric adenocarcinoma of fundic gland type (GA-FG) has recently been proposed as a novel histological type of gastric cancer. CASE SUMMARY: We report a case of GA-FG in a 77-year-old Chinese woman with epigastric distention who was referred to endoscopy for the management of an incidentally found submucosal tumor-like elevated lesion in the lower part of the gastric body. The tumor occurred after Helicobacter pylori (H. pylori) eradication therapy without long-term use of proton pump inhibitors. Complete and curable removal of the tumor was performed by endoscopic submucosal dissection. Histopathological findings showed numerous cells with basophilic cytoplasm and mildly atypical nuclei-like chief cells of the fundic gland. The tumor was observed to have the so-called "endless glands" pattern of the well-differentiated mixed phenotype. A safe resection margin without lymphatic and venous invasion was observed. As the tumor occurred after H. pylori eradication therapy, it is unknown whether there was a relationship with H. pylori eradication. The patient will be followed up by periodic gastroscopic observation. CONCLUSION: In conclusion, we report a case of GA-FG after H. pylori eradication therapy without long-term proton pump inhibitors use. Further analysis of similar cases will reveal the clinical behavior of GA-FG.

13.
Chin J Integr Med ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31418133

RESUMO

OBJECTIVE: To investigate a Met-controlled allosteric module (AM) of neural generation as a potential therapeutic target for brain ischemia. METHODS: We selected Markov clustering algorithm (MCL) to mine functional modules in the related target networks. According to the topological similarity, one functional module was predicted in the modules of baicalin (BA), jasminoidin (JA), cholic acid (CA), compared with I/R model modules. This functional module included three genes: Inppl1, Met and Dapk3 (IMD). By gene ontology enrichment analysis, biological process related to this functional module was obtained. This functional module participated in generation of neurons. Western blotting was applied to present the compound-dependent regulation of IMD. Co-immunoprecipitation was used to reveal the relationship among the three members. We used IF to determine the number of newborn neurons between compound treatment group and ischemia/reperfusion group. The expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) were supposed to show the changing circumstances for neural generation under cerebral ischemia. RESULTS: Significant reduction in infarction volume and pathological changes were shown in the compound treatment groups compared with the I/R model group (P<0.05). Three nodes in one novel module of IMD were found to exert diverse compound-dependent ischemic-specific excitatory regulatory activities. An anti-ischemic excitatory allosteric module (AME) of generation of neurons (AME-GN) was validated successfully in vivo. Newborn neurons increased in BJC treatment group (P<0.05). The expression of VEGF and MMP-9 decreased in the compound treatment groups compared with the I/R model group (P<0.05). CONCLUSIONS: AME demonstrates effectiveness of our pioneering approach to the discovery of therapeutic target. The novel approach for AM discovery in an effort to identify therapeutic targets holds the promise of accelerating elucidation of underlying pharmacological mechanisms in cerebral ischemia.

14.
Artif Cells Nanomed Biotechnol ; 47(1): 3500-3510, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31432697

RESUMO

Salidroside is an active ingredient extracted from Rhodiola rosea that has anti-tumor activities. The current paper attempted to assess the impact of Salidroside on gastric cancer (GC) and explore the potential mechanism. GC cell lines (SNU-216 and MGC803) and gastric epithelial cell line GES-1 were treated with Salidroside. CCK-8 assay, colony formation assay, flow cytometry and Transwell assay were respectively performed to evaluate GC cells phenotype. qRT-PCR and western blot were conducted to reveal the downstream genes and signaling of Salidroside. We found that 800 µM Salidroside was capable of reducing GC cells viability, while has no such impacts on GES-1 cells. Salidroside inhibited GC cells proliferation, migration, invasion and promoted apoptosis, which coupled with the down-regulation of p21, Bcl-2, MMP2, RhoA, p-ROCK1, Vimentin and the up-regulations of CyclinD1, Bax, cleaved caspases. miR-99a was found to be highly expressed in response to Salidroside treatment. Besides, the inhibition of MAPK/ERK and PI3K/AKT signaling induced by Salidroside was attenuated by miR-99a silence and in this process, IGF1R worked as a target of miR-99a. The anti-GC effect of Salidroside was also confirmed in a mouse model of GC. The promoting effect of Salidroside on miR-99a expression was also verified in vivo. Furthermore, Salidroside promoted the cisplatin-sensitivity of SGC7901/DDP cells. In conclusion, this study demonstrated that Salidroside possessed anti-GC effects through regulating miR-99a/IGF1R axis and inhibiting MAPK/ERK and PI3K/AKT pathways.


Assuntos
Antineoplásicos/farmacologia , Glucosídeos/farmacologia , MicroRNAs/genética , Fenóis/farmacologia , Neoplasias Gástricas/patologia , Regulação para Cima/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Receptor IGF Tipo 1/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Mol Med Rep ; 20(4): 3292-3300, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432190

RESUMO

Previous studies have demonstrated the effects of hyperuricemia on the damage to target organs, including the kidneys, joints and the heart. However, it is unclear whether hyperuricemia results in damage to the intestines. The aim of the present study was to investigate intestinal barrier dysfunction in a mouse model of hyperuricemia constructed by knocking out the urate oxidase (Uox) gene. The morphology of the intestine was assessed via hematoxylin and eosin, and alcian blue staining. The serum and intestinal tissue levels of uric acid, tumor necrosis factor (TNF)­α and interleukin (IL)­6, in addition to the presence of uremic toxins in the serum, were assessed. The levels of diamine oxidase (DAO), D­lactate (D­LAC) and endotoxins in the serum, which are markers of the intestinal permeability, were measured using ELISA. The expression of the intestinal tight junction proteins zona occludens­1 (ZO­1) and occludin were detected by reverse transcription­quantitative polymerase chain reaction, western blotting and immunohistochemical analysis. The Uox­knockout mice spontaneously developed hyperuricemia. Histopathological analysis indicated notable intestinal defects including sparse villi, mucosal edema and a declining mucus layer in hyperuricemic mice. The expression levels of ZO­1 and occludin in the intestines were downregulated, and the serum levels of DAO, D­LAC and endotoxins were higher in the hyperuricemic mice, compared with control mice. The serum and intestinal tissue levels of IL­6 and TNF­α were significantly increased. Additionally, the expression levels of the serum uremic toxins, serum creatinine, blood urea nitrogen were significantly increased in hyperuricemic mice compared with the control mice, while only a marked increase in indoxyl sulfate (IS) and p­cresol sulfate was reported. Collectively, the results of the present study suggested that intestinal barrier dysfunction and subsequent enhanced intestinal permeability may occur as a result of hyperuricemia in mice. Furthermore, we proposed that the loss of intestinal epithelium barrier function may be associated with uric acid­induced inflammatory responses; however, further investigation is required.


Assuntos
Hiperuricemia , Mucosa Intestinal/metabolismo , Urato Oxidase/deficiência , Ácido Úrico/metabolismo , Animais , Modelos Animais de Doenças , Hiperuricemia/genética , Hiperuricemia/metabolismo , Hiperuricemia/patologia , Interleucina-6/genética , Interleucina-6/metabolismo , Mucosa Intestinal/patologia , Camundongos , Camundongos Knockout , Ocludina/genética , Ocludina/metabolismo , Permeabilidade , Junções Íntimas/genética , Junções Íntimas/metabolismo , Junções Íntimas/patologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismo
16.
Sci Total Environ ; 687: 601-609, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31220714

RESUMO

Coastal saline soil is an important reserve land resource that has high potential for agricultural utilization. The present study adopted a high-throughput absolute quantification 16S rRNA sequencing method to investigate the effect of four different fertilization regimes (namely 100% of bio-organic fertilizer, 70% of bio-organic fertilizer +30% of chemical fertilizer, 30% of bio-organic fertilizer +70% of chemical fertilizer, and 100% of chemical fertilizer) on bacterial community assembly in a tomato cultivated saline soil. The results from the field experiment showed that a combination of 70% bio-organic fertilizer plus 30% of chemical fertilizer was the optimal dose to develop tomato cultivation (for improving yield and fruit quality) in this coastal tidal zone. The pot experiment gave the similar results on tomato growth and indicated the application of 70% bio-organic fertilizer plus 30% of chemical fertilizer as the best treatment to active the soil microbiome. The input of nutrients by fertilizers increased the total abundance of bacteria (to >3 fold compared to the initial soil) and simultaneously led to a significant loss of bacterial diversity in soil. The predominant phyla including Proteobacteria, Bacteroidetes and Firmicutes were the main contributors in the microbiome shift especially shown by their remarkable enrichment in the soil that treated by 70% of bio-organic fertilizer and those by the 100% chemical fertilizer. The RDA and Pearson correlation analyses indicated that the soil nutrient availability, especially available P and K, and soil salinity were the key environmental factors that shaped the bacterial community in this ecosystem, though the organic matter content and soil pH also played important roles in microbiome assembly.


Assuntos
Fertilizantes , Lycopersicon esculentum/fisiologia , Microbiologia do Solo , Agricultura , Monitoramento Ambiental , Salinidade , Solo/química
17.
Sci Adv ; 5(4): eaau8389, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31032403

RESUMO

Patients with neurofibromatosis type 1 (NF1) are predisposed to develop neurofibromas, but the underlying molecular mechanisms of neurofibromagenesis are not fully understood. We showed dual genetic deletion of Runx1 and Runx3 in Schwann cells (SCs) and SC precursors delayed neurofibromagenesis and prolonged mouse survival. We identified peripheral myelin protein 22 (Pmp22/Gas3) related to neurofibroma initiation. Knockdown of Pmp22 with short hairpin RNAs increased Runx1fl/fl;Runx3fl/fl;Nf1fl/fl;DhhCre tumor-derived sphere numbers and enabled significantly more neurofibroma-like microlesions on transplantation. Conversely, overexpression of Pmp22 in mouse neurofibroma SCs decreased cell proliferation. Mechanistically, RUNX1/3 regulated alternative promoter usage and induced levels of protein expression of Pmp22 to control SC growth. Last, pharmacological inhibition of RUNX/core-binding factor ß (CBFB) activity significantly reduced neurofibroma volume in vivo. Thus, we identified a signaling pathway involving RUNX1/3 suppression of Pmp22 in neurofibroma initiation and/or maintenance. Targeting disruption of RUNX/CBFB interaction might provide a novel therapy for patients with neurofibroma.

18.
Cancer Med ; 8(5): 2268-2277, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30938105

RESUMO

The potential biological relationship between type-2 diabetes mellitus (T2DM) has been focused in numerous studies. To investigate the molecular associations among T2DM, prostate cancer (PCa), and chronic myeloid leukemia (CML), using a biomolecular network enrichment analysis. We obtained a list of disease-related genes and constructed disease networks. Then, GO enrichment analysis was performed to identify the significant functions and pathways of overlapping modules in the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. More than 75% of these overlapping genes were found to be consistent with the findings of previous studies. In the three diseases, we found that Sarcoglycan delta (SGCD) and Rho family GTPase 3 (RND3) were the overlapping genes and identified negative regulation of apoptotic process and negative regulation of transcription from RNA polymerase II promoter RNA as the two overlapping biological functions. CML and PCa were the most closely related, with 34 overlapping genes, five overlapping modules, 27 overlapping biological functions, and nine overlapping pathways. There were 13 overlapping genes, one overlapping modules, four overlapping biological functions and one overlapping pathway (FoxO signaling pathway) were found in T2DM and CML.And T2DM and PCa were the least related pair in our study, with only six overlapping genes, five overlapping modules, and one overlapping biological function. SGCD and RND3 were the main gene-to-gene relationship among T2DM, CML, and PCa; apoptosis, development, and transcription from RNA polymerase II promote processes were the main functional connections among T2DM, CML, and PCa by network enrichment analysis. There is a "scalene" relationship among T2DM, CML, and PCa at gene, pathway, biological process, and module levels: CML and PCa were the most closely related, the second were T2DM and PCa, and T2DM and PCa were the least related pair in our study. Our study provides a new avenue for further studies on T2DM and cancers, which may promote the discovery and development of novel therapeutic and can be used to treat multiple diseases.

19.
Sci Rep ; 9(1): 6400, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30996288

RESUMO

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

20.
Phytother Res ; 33(6): 1706-1716, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30989726

RESUMO

Celastrol could inhibit cancer cell growth in vitro. However, effect(s) of celastrol on gastric cancer is not well studied. Therefore, we investigated the effects of celastrol on human gastric cancer cell line MKN45 and the underlying mechanisms. We found that celastrol inhibited cell proliferation, migration, and invasion and induced cell apoptosis and G2/M cell cycle arrest (p < .05, p < .01, or p < .001). Under celastrol treatment, overexpression of microRNA-21 (miR-21) increased cell viability, migration, and invasion and inhibited cell apoptosis compared with negative control (p < .05, p < .01, or p < .001). In addition, the phosphorylation of PTEN was significantly up-regulated, whereas PI3K, AKT, p65, and IκBα phosphorylation was statistically decreased by celastrol (p < .05 or p < .01) and then further reversed by miR-21 overexpression (p < .05 or p < .01). On the other side, miR-21 silence showed contrary results (p < .05) as relative to miR-21 overexpression. In conclusion, celastrol inhibits proliferation, migration, and invasion and inactivates PTEN/PI3K/AKT and nuclear factor κB signaling pathways in MKN45 cells by down-regulating miR-21.


Assuntos
Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , MicroRNAs/genética , Neoplasias Gástricas/patologia , Triterpenos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Metástase Neoplásica , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Neoplasias Gástricas/genética
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