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1.
J Cell Mol Med ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32039564

RESUMO

Numerous studies have demonstrated that thioredoxin-interacting protein (TXNIP) expression of peripheral blood leucocytes is increased in coronary artery disease (CAD). However, the molecular mechanism of this phenomenon remained unclear. DNA methylation plays important roles in the regulation of gene expression. Therefore, we speculated there might be a close association between the expression of TXNIP and methylation. In this study, we found that compared with controls, DNA methylation at cg19693031 was decreased in CAD, while mRNA expressions of TXNIP and inflammatory factors, NLRP3, IL-1ß, IL-18, were increased. Methylation at cg19693031 was negatively associated with TXNIP expression in the cohort, THP-1 and macrophages/foam cells. Furthermore, Transwell assay and co-cultured adhesion assay were performed to investigate functions of TXNIP on the migration of THP-1 or the adhesion of THP-1 on the surface of endothelial cells, respectively. Notably, overexpressed TXNIP promoted the migration and adhesion of THP-1 cells and expressions of NLRP3, IL-18 and IL-1ß. Oppositely, knock-down TXNIP inhibited the migration and adhesion of THP-1 and expressions of NLRP3, IL-18. In conclusion, increased TXNIP expression, related to cg19693031 demethylation orientates monocytes towards an inflammatory status through the NLRP3 inflammasome pathway involved in the development of CAD.

2.
Eur J Med Chem ; 190: 112074, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32045788

RESUMO

A series of thiochromeno[2,3-c]quinolin-12-one derivatives with various substitutions were synthesized and evaluated as topoisomerase (Topo) inhibitors. Six (8, 10, 12, 14, 19, and 26) of 23 compounds showed strong inhibitory activities against Topo-mediated DNA relaxation and proliferation of five human cell lines including breast (MDA-MB-231, MDA-MB-468 and MCF7), colorectal (HCT116) and non-small cell lung (H1299) cancers. Among these, compounds 14 and 26 exhibited full inhibitory activities against Topo I at 3 µM and Topo IIα at 1 µM. Cancer cells treated with 26 accumulated DNA damage and were arrested at the G2/M phase. With time, cells proceeded to apoptosis, as revealed by increased amounts of cells with fragmented DNA and cleavage of caspase-8 and -9. In contrast, normal breast epithelial cells showed low sensitivity to 26. Taken together, our study identifies 26 as a potent Topo dual-inhibitor with low toxicity to normal cells, and elucidates that the terminal amino group of N-2-aminoethylamino or N-3-aminopropylamino at the 6th position and 8,10-di-halogen substituents on thiochromeno[2,3-c]quinolin-12-one are critical for the Topo-inhibiting and cancer-killing activities.

3.
Cereb Cortex ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32080705

RESUMO

Neuronal activity initiates transcriptional programs that shape long-term changes in plasticity. Although neuron subtypes differ in their plasticity response, most activity-dependent transcription factors (TFs) are broadly expressed across neuron subtypes and brain regions. Thus, how region- and neuronal subtype-specific plasticity are established on the transcriptional level remains poorly understood. We report that in young adult (i.e., 6-8 weeks old) mice, the developmental TF SOX11 is induced in neurons within 6 h either by electroconvulsive stimulation or by exploration of a novel environment. Strikingly, SOX11 induction was restricted to the dentate gyrus (DG) of the hippocampus. In the novel environment paradigm, SOX11 was observed in a subset of c-FOS expressing neurons (ca. 15%); whereas around 75% of SOX11+ DG granule neurons were c-FOS+, indicating that SOX11 was induced in an activity-dependent fashion in a subset of neurons. Environmental enrichment or virus-mediated overexpression of SOX11 enhanced the excitability of DG granule cells and downregulated the expression of different potassium channel subunits, whereas conditional Sox11/4 knock-out mice presented the opposite phenotype. We propose that Sox11 is regulated in an activity-dependent fashion, which is specific to the DG, and speculate that activity-dependent Sox11 expression may participate in the modulation of DG neuron plasticity.

4.
Zygote ; : 1-8, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31965957

RESUMO

Stem cells are an immortal cell population capable of self-renewal; they are essential for human development and ageing and are a major focus of research in regenerative medicine. Despite considerable progress in differentiation of stem cells in vitro, culture conditions require further optimization to maximize the potential for multicellular differentiation during expansion. The aim of this study was to develop a feeder-free, serum-free culture method for human embryonic stem cells (hESCs), to establish optimal conditions for hESC proliferation, and to determine the biological characteristics of the resulting hESCs. The H9 hESC line was cultured using a homemade serum-free, feeder-free culture system, and growth was observed. The expression of pluripotency proteins (OCT4, NANOG, SOX2, LIN28, SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81) in hESCs was determined by immunofluorescence and western blotting. The mRNA expression levels of genes encoding nestin, brachyury and α-fetoprotein in differentiated H9 cells were determined by RT-PCR. The newly developed culture system resulted in classical hESC colonies that were round or elliptical in shape, with clear and neat boundaries. The expression of pluripotency proteins was increased, and the genes encoding nestin, brachyury, and α-fetoprotein were expressed in H9 cells, suggesting that the cells maintained in vitro differentiation capacity. Our culture system containing a unique set of components, with animal-derived substances, maintained the self-renewal potential and pluripotency of H9 cells for eight passages. Further optimization of this system may expand the clinical application of hESCs.

5.
J Neurochem ; : e14959, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31943210

RESUMO

Psychostimulants are widely abused drugs that may cause addiction in vulnerable individuals. While the reward circuitry of the brain is involved in addiction establishment, various pathways in the brain may provide protection at the molecular level that limits the acute and chronic effects of drugs. These targets may be used for strategies designed to prevent and treat addiction. Swiprosin-1/EF hand domain 2 (EFhd2) is a Ca2+ -binding cytoskeletal adaptor protein involved in sensation-seeking behaviour, anxiety and alcohol addiction. Here, we tested how EFhd2 contributes to the physiological and behavioural effects of the psychostimulant drugs methamphetamine (METH) and cocaine. An in vivo microdialysis study in EFhd2 knockout mice revealed that EFhd2 controls METH- and cocaine-induced changes in extracellular dopamine, serotonin and noradrenaline levels through different mechanisms in the nucleus accumbens and prefrontal cortex. Electrophysiological recordings in a slice preparation showed that a lack of EFhd2 increases dopaminergic neuronal activity in the ventral tegmental area and increases the sensitivity of neurons to stimulation. We report a role of EFhd2 in METH-induced locomotor activation and in the conditioned locomotor effects. No role, however, was observed in the establishment of METH- or cocaine-induced conditioned place preference. These findings may suggest that EFhd2 modulates the activity of the dopaminergic system and the neurochemical effects of METH and cocaine, which translate into a modulation of the behavioural effects of these drugs at the level of the acute and conditioned locomotor activity.

6.
Sci Rep ; 10(1): 812, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964991

RESUMO

Human status epilepticus (SE) is associated with a pathological reduction in cerebral blood flow termed the inverse hemodynamic response (IHR). Canonical transient receptor potential 3 (TRPC3) channels are integral to the propagation of seizures in SE, and vascular smooth muscle cell (VSMC) TRPC3 channels participate in vasoconstriction. Therefore, we hypothesize that cerebrovascular TRPC3 channels may contribute to seizure-induced IHR. To examine this possibility, we developed a smooth muscle-specific TRPC3 knockout (TRPC3smcKO) mouse. To quantify changes in neurovascular coupling, we combined laser speckle contrast imaging with simultaneous electroencephalogram recordings. Control mice exhibited multiple IHRs, and a limited increase in cerebral blood flow during SE with a high degree of moment-to-moment variability in which blood flow was not correlated with neuronal activity. In contrast, TRPC3smcKO mice showed a greater increase in blood flow that was less variable and was positively correlated with neuronal activity. Genetic ablation of smooth muscle TRPC3 channels shortened the duration of SE by eliminating a secondary phase of intense seizures, which was evident in littermate controls. Our results are consistent with the idea that TRPC3 channels expressed by cerebral VSMCs contribute to the IHR during SE, which is a critical factor in the progression of SE.

7.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(1): 47-52, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31948524

RESUMO

OBJECTIVE: To study the influence of dasatinib treatment on body height in children with acute myeloid leukemia (AML). METHODS: A retrospective analysis was performed for the clinical data of 86 AML children aged <17 years. According to the treatment regimen, these children were divided into a conventional chemotherapy group and a dasatinib chemotherapy group. The 57 children in the conventional chemotherapy group were given conventional chemotherapy drugs without tyrosine kinase inhibitor, and the 29 children in the dasatinib chemotherapy group were given conventional chemotherapy drugs and dasatinib. The two groups were compared in terms of height standard deviation score (HtSDS) at the beginning of treatment and after treatment, as well as the change in HtSDS after 1 and 2 years of treatment. RESULTS: There was no significant difference in HtSDS between the conventional and dasatinib chemotherapy groups before treatment. Within the first two years of treatment, the dasatinib chemotherapy group had a similar change trend of HtSDS as the conventional chemotherapy group. Four children in the dasatinib chemotherapy group reached the final adult height during follow-up, which was significantly lower than the target height (P=0.044). In the conventional chemotherapy group, there was no significant difference between final adult height and target height. In the dasatinib chemotherapy group, the children in adolescence had a significant change in HtSDS after treatment (P=0.032). CONCLUSIONS: Dasatinib treatment may affect the final height of children with AML, and the use of dasatinib after the beginning of adolescence may lead to growth disorder, but dasatinib treatment has little effect on body height in the short-term treatment.


Assuntos
Estatura , Dasatinibe/uso terapêutico , Leucemia Mieloide Aguda , Adolescente , Criança , Transtornos do Crescimento , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Estudos Retrospectivos
8.
Carbohydr Polym ; 230: 115637, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887887

RESUMO

Some carbohydrate polymers, usually oligosaccharides or polysaccharides, have great potential as an elicitor of plant defense. However, due to the complexity and diversity of poly- and oligosaccharide structure, the molecular mechanisms and structure-activity relationships of carbohydrate elicitors are still not well understood, which hinders the application of carbohydrate elicitors in agriculture. This review introduces the mechanisms of carbohydrate elicitor perception and signaling in plants. The structure and activity relationships of main poly- and oligosaccharides studied for the control of plant diseases are discussed and summarized. Additionally, the effects of carbohydrate elicitors on the secondary metabolite production are also summarized.

9.
Nat Prod Res ; 34(4): 489-493, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30369253

RESUMO

(±)-Quassidine K (1), a pair of new bis-ß-carboline alkaloid enantiomers, were isolated from Picrasma quassioides. Their structures were determined on the basis of detailed spectroscopic data analysis. The absolute configurations of (+)-S-quassidine K (1a) and (-)-R-quassidine K (1b) were determined by comparing with the reported experimental ECD spectra after chiral separation. The cytotoxicity assay showed activity against HeLa cells with IC50 values of 15.8 and 20.1 µM, respectively.

10.
J Ethnopharmacol ; 249: 112408, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31751653

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The Herb Ephedra (Ma Huang in Chinese)-Ramulus Cinnamomi (Gui Zhi in Chinese) herb pair is a classic traditional Chinese herb pair used to treat asthma, nose and lung congestion, and fever with anhidrosis. In previous study, we found that chronic administration of ma huang induced obvious neurodegeneration in rat brains, with the prefrontal cortex showing the greatest effect. Gui zhi decreased hyperactivity produced by repeated ma huang administration, and attenuated oxidative stress in rat prefrontal cortex induced by ma huang. AIM OF THE STUDY: The study was aimed to investigate the protective effect of gui zhi on ma huang-induced abnormal levels of four amino acid neurotransmitters in rat prefrontal cortex. MATERIALS AND METHODS: All ma huang and ma huang-gui zhi herb pair extracts were prepared using methods of traditional Chinese medicine and were normalized based on the ephedrine content. Two-month-old male Sprague-Dawley rats (6 rats/group) were administered ma huang or ma huang-gui zhi herb pair extracts for 1, 3, 5 or 7 days (ephedrine = 48 mg/kg). The contents of ephedrine, glutamate (Glu), aspartic acid (Asp), glycine (Gly), and gamma-aminobutyric acid (GABA) in the prefrontal cortex were determined using ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) at 0.5, 1.0, 5.0 h after administration. RESULTS: Ma huang significantly enhanced the levels of GABA, Gly, Glu and Asp in the prefrontal cortex, while gui zhi partially abolished the effects. CONCLUSIONS: Ma huang-induced neurotoxicity may be associated with its effects on amino acid neurotransmitters. Gui zhi is a promising neuroprotective agent against for ma huang-induced neurotoxicity. The information presented in this study will help supplement the available data for future ma huang-gui zhi herb pair compatibility studies.

11.
FEBS Lett ; 594(1): 189-198, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31369681

RESUMO

The C-type lectin receptor Clec4f has been identified as a specific surface marker for Kupffer cells, although its ortholog is absent in humans and its biological function remains elusive. Here, we report the crystal structure of a truncated mouse trimeric Clec4f. The orientation between the carbohydrate-recognition domain of Clec4f and its neck region differs from other C-type lectins, resulting in an observed distance of 45 Å between the glycan-binding sites within the Clec4f trimer. Interestingly, the trimeric coiled-coil interface within its heptad neck region contains multiple polyglutamine interactions instead of the predominantly hydrophobic leucine zipper found in other C-type lectin receptors. The Clec4f trimeric structure displays unique features regarding its assembly and ligand recognition, shedding light on the evolution and diversity of the C-type lectin family.

12.
Redox Biol ; 28: 101355, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31677554

RESUMO

Nuclear prelamin A recognition factor-like (NARFL) is a human protein that participates in cytosolic iron-sulfur (Fe-S) protein biogenesis and cellular defense against oxidative stress. Previous studies of Narfl knockout mice did not reveal well the regulatory mechanisms of embryonic development mediated by Narfl because the homozygous mice die in utero. Here, we investigated the function of narfl in an established zebrafish knockout model by taking advantage of zebrafish external fertilization and ease of embryonic development examination. Our experiments showed that narfl deletion resulted in larvae lethality, subintestinal vessel (SIV) malformation and digestive organ defects in the early stages of embryonic development. Biochemical analyses and western blot revealed increased oxidative stress and upregulated hypoxia-inducible factor-1α (HIF-1α) expression in narfl-/- fish. The use of HIF-1α inhibitor 2-methoxyestradiol (2ME2) for the treatment of mutants partially rescued the SIV sprouting. These results suggest that narfl deletion causes increased oxidative stress and subintestinal vessel malformation, which further influence the development of digestive organs and might contribute to the lethality of the narfl knockout fish.

13.
J Plant Physiol ; 245: 153107, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31881440

RESUMO

Plant-derived elicitor is a new type of plant vaccine developed in the contemporary era, and it has safe and broad application prospects in organic agriculture. Research on defense mechanisms triggered by elicitor has become a hot topic in recent years. The Chrysanthemum indicum polysaccharide (CIP) obtained by separation and purification from Chrysanthemum indicum was used as an elicitor in this work. This elicitor has been shown to be effective in Atractylodes macrocephala Koidz (A. macrocephala) against Sclerotium rolfsii sacc (S. rolfsii) infection and soil-borne diseases. However, the mechanism of induced disease resistance has not been elucidated. In this research, we study the CIP-induced A. macrocephala defense response from the level of signal molecules and the defensive enzyme gene expression. Several defense responses to CIP treatment have been found in A. macrocephala, including early hydrogen peroxide (H2O2) production, accumulation of salicylic acid (SA) and increased phytoalexin (PA) content. In addition, CIP significantly increased the activity of related defense enzymes in A. macrocephala. RT-qPCR analysis showed that defense-related genes such as polyphenol oxidase (PPO) and phenylalanine ammonia lyase (PAL) were up-regulated after CIP treatment. To obtain the sequence of the defense enzyme gene, we are the first to provide a public and comprehensive A. macrocephala database by transcriptome sequencing. These results together demonstrate that CIP triggers defense responses in A. macrocephala. Our research not only provides further research on immune mechanism between plant and elicitor, but also sheds new light on strategy for biocontrol in the future.

14.
Am J Ophthalmol ; 209: 18-26, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31562858

RESUMO

PURPOSE: Choriocapillaris (CC) imaging of normal eyes with swept-source optical coherence tomographic angiography (SS-OCTA) was performed, and the percentage of CC flow deficits (FD%) and the average area of CC flow deficits (FDa) were compared within the given macular regions. DESIGN: A prospective, cross-sectional study. METHODS: Subjects with normal eyes ranging in age from their 20s through their 80s were imaged with SS-OCTA (PLEX Elite 9000; Carl Zeiss Meditec, Dublin, California, USA) using both 3×3-mm and 6×6-mm macular scan patterns. The CC images were generated using a previously published and validated algorithm. In both 3×3-mm and 6×6-mm scans, the CC FD% and FDa were measured in circular regions centered on the fovea with diameters as 1 mm and 2.5 mm (C1 and C2.5). In 6×6-mm scans, the FD% and FDa were measured within an additional circular region with diameter as 5 mm (C5). The correlations between FD% and FDa from each region were analyzed with Pearson correlation coefficients. RESULTS: A total of 164 eyes were analyzed. There was excellent correlation between CC FDa and FD% measurements from each region. In the 3×3-mm scans, the correlations in the C1 and C2.5 regions were 0.83 and 0.90, respectively. In the 6×6-mm scans, the correlations in C1, C2.5, and C5 regions were 0.90, 0.89, and 0.89, respectively. CONCLUSIONS: When measuring CC FDs, we found excellent correlations between FDa and FD% in regions from 3×3-mm and 6×6-mm scans. Further studies are needed to determine if one parameter is more useful when studying diseased eyes.

15.
Micromachines (Basel) ; 10(12)2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31835793

RESUMO

The clinical characteristics of excreted tumor cells can be found in the urine of bladder cancer patients, meaning the identification of tumor cells in urine can assist in bladder cancer diagnosis. The presence of white blood cells and epithelial cells in the urine interferes with the recognition of tumor cells. In this paper, a technique for detecting cancer cells in urine based on microfluidics provides a novel approach to bladder cancer diagnosis. The bladder cancer cell line (T24) and MeT-5A were used as positive bladder tumor cells and non-tumor cells, respectively. The practicality of the tumor cell detection system based on microfluidic cell chip detection technology is discussed. The tumor cell (T24) concentration was around 1 × 104 to 300 × 104 cells/mL. When phosphate buffer saline (PBS) was the diluted solution, the tumor cell detected rate was 63-71% and the detection of tumor cell number stability (coefficient of variation, CV%) was 6.7-4.1%, while when urine was the diluted solution, the tumor cell detected rate was 64-72% and the detection of tumor cell number stability (CV%) was 6.3-3.9%. In addition, both PBS and urine are tumor cell dilution fluid solutions. The sample was analyzed at a speed of 750 microns per hour. Based on the above experiments, a system for detecting bladder cancer cells in urine by microfluidic analysis chip technology was reported. The rate of recognizing bladder cancer cells reached 68.4%, and the speed reached 2 mL/h.

16.
Onco Targets Ther ; 12: 10115-10127, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819506

RESUMO

Background: Lung cancer is a leading cause of cancer-related death worldwide. Previously we demonstrated that polyphyllin I (PPI), a bioactive component extracted from Paris polyphylla, inhibited the growth of non-small cell lung cancer (NSCLC) cells through the SAPK/JNK-mediated suppressing p65, DNMT1 and EZH2 expressions. However, the molecular mechanism underlying anti-lung cancer effect by PPI still remain elusive. Purpose: In this current study, we further explored the molecular mechanism underlying the anti-lung cancer effect of PPI. Methods: MTT, Cell-LightTM EdU DNA cell proliferation and colony formation assays were used to measure cell growth. Western blot were used to examine protein levels of c-Jun and p21. The expression level of long non-codingth RNA HOX transcript antisense RNA (HOTAIR) was measured by qRT-PCR. The p21 promoter activity was measured by Dual-Luciferase Reporter Assay System. The transient transfection experiments were used to silence and overexpression of c-Jun, p21 and HOTAIR. Tumor xenograft and bioluminescent imaging experiments were carried out to confirm the in vitro findings. Results:  We showed that PPI suppressed growth of NSCLC cells. Mechanistically, we observed that PPI reduced expression of HOTAIR, while increased transcription factor c-Jun protein levels. Additionally, PPI also induced protein expression and promoter activity of p21, a cyclin-dependent kinase inhibitor. While exogenously expressed HOTAIR showed no effect on c-Jun levels, silencing of c-Jun significantly reversed the PPI-inhibited HOTAIR expression. Moreover, excessive expressed c-Jun further enhanced PPI-inhibited HOTAIR expression and PPI-induced p21 protein levels. Intriguingly, overexpression of HOTAIR and silencing of c-Jun overcame the PPI-induced p21 protein and promoter activity. Finally, silencing of p21 neutralized the PPI-inhibited cell proliferation. Similar results were also found in one xenograft mouse model. Conclusion:  Our results demonstrate that PPI inhibits growth of NSCLC cells through regulation of HOTAIR and c-Jun expressions, which lead to induction of p21 gene. The interactions among HOTAIR, c-Jun and p21 regulatory axis converge in the overall anti-lung cancer effect of PPI. This study unveils an additional new mechanism for the anti-lung cancer role of PPI.

17.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(6): 925-929, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31880126

RESUMO

OBJECTIVE: To compare the difference of health-related quality of life after oncologic esophagectomy between the patients using Jiang's gastroesophageal anastomosis and traditional end-to-end gastroesophageal anastomosis. METHODS: A total of 419 patients (223 in Jiang's anastomosis group, and 196 in end-to-end anastomosis group) underwent minimal invasive esophagectomy with cervical anastomosis from October 2012 to August 2016. All patients received radical esophageal cancer resection and cervical anastomosis. EORTC-QLQ-C30 and QLQ-OES18 were used to assess the health-related quality of life at the 1st, 3rd, 6th, 12th, 24th month after esophagectomy. RESULTS: There were 25 dimensions and items in EORTC-QLQ-C30 and QLQ-OES18. The postoperative quality of life decreased obviously at the 1st month and then recovered obviously at the 6th month after the surgery, and it ranged small at the 12th and 24th month. Compared with end-to-end anastomosis group, Jiang's anastomosis group had less reflux and less cough at the 1st month (P=0.023, P=0.010) and the 3rd month (P=0.004, P=0.013), then had better emotional function, less reflux and less cough at the 6th month (P=0.013, P=0.014, P=0.043), better emotional function, less nausea, and less reflux at the 12th month(P=0.004, P=0.023, P=0.021), as well as less reflux at the 24th month (P=0.020). There was no significant difference in other dimensions and items between the two groups during the follow-up period. CONCLUSION: Jiang's anastomosis is safe and feasible, and could improve the postoperative quality of life of the patients with esophagectomy. It is worth to further application in clinical practice.


Assuntos
Neoplasias Esofágicas , Refluxo Gastroesofágico , Anastomose Cirúrgica , Esofagectomia , Humanos , Qualidade de Vida
18.
Front Oncol ; 9: 1081, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681610

RESUMO

Solasonine (SS), a natural glycoalkaloid component, has been shown to have potent inhibitory activity and cytotoxicity against many cancer types. However, the precise mechanisms underlying this, particularly in hepatocellular carcinoma (HCC) are poorly understood. In this study, we showed that SS inhibited growth of HCC cells. Mechanistically, we observed that SS increased the expression of miR-375-3p, whereas reducing levels of long non-coding RNAs (lncRNAs) CCAT1 was noticed in HepG2 HCC and other cells. In addition, we found that SS repressed transcription factors, SP1 and interferon regulatory factor 5 (IRF5), protein expressions. There was a reciprocal interaction among miR-375-3p, CCAT1, and SP1. Moreover, SS inhibited IRF5 promoter activity, which was not observed in cells transfected with excessive expressed SP1 vectors. Interestingly, exogenously expressed IRF5 was shown to reverse expressions of SS-inhibited CCAT1 and induced-miR-375-3p; and neutralized SS-inhibited growth of HCC cells. Similar results were also found in vivo mouse model. Collectively, our results show that SS inhibits HepG2 HCC growth through the reciprocal regulation between the miR-375-3p and lncRNA CCAT1, and this results in transcription factor SP1-mediated reduction of IRF5 expression. The regulations and interactions among miR-375-3p, CCAT1, SP1, and IRF5 axis unveil a novel molecular mechanism underlying the anti-HCC growth by SS. IRF5 may be a potential target for treatment of HCC.

20.
BMC Public Health ; 19(1): 1482, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703659

RESUMO

BACKGROUND: The incidence of hand, foot and mouth disease (HFMD) varies over space and time and this variability is related to climate and social-economic factors. Majority of studies on HFMD were carried out in humid regions while few have focused on the disease in arid/semi-arid regions, more research in such climates would potentially make the mechanism of HFMD transmission clearer under different climate conditions. METHODS: In this paper, we explore spatial-temporal distribution of HFMD in Ningxia province, which has an arid/semi-arid climate in northwest China. We first employed a Bayesian space-time hierarchy model (BSTHM) to assess the spatial-temporal heterogeneity of the HFMD cases and its relationship with meteorological factors in Ningxia from 2009 to 2013, then used a novel spatial statistical software package GeoDetector to test the spatial-temporal heterogeneity of HFMD risk. RESULTS: The results showed that the spatial relative risks in northern part of Ningxia were higher than those in the south. The highest temporal risk of HFMD incidence was in fall season, with a secondary peak in spring. Meteorological factors, such as average temperature, relative humidity, and wind speed played significant roles in the spatial-temporal distribution of HFMD risk. CONCLUSIONS: The study provide valuable information on HFMD distribution in arid/semi-arid areas in northwest China and facilitate understanding of the concentration of HFMD.


Assuntos
Doença de Mão, Pé e Boca/epidemiologia , Conceitos Meteorológicos , Teorema de Bayes , China/epidemiologia , Clima , Mudança Climática , Feminino , Doença de Mão, Pé e Boca/etiologia , Humanos , Incidência , Masculino , Risco , Estações do Ano , Análise Espaço-Temporal , Temperatura Ambiente , Vento
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