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1.
Chin J Nat Med ; 17(8): 585-590, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31472895

RESUMO

The aim is to select a universal DNA barcode for identifying all poisonous medicinal plants in Chinese pharmacopoeia and their poisonous related species or adulterants. We chose 4 commonly used regions as candidate DNA barcodes (ITS2, psbA-trnH, matK and rbcL) and compared their identification efficiency in 106 species from 27 families and 65 genera totally. Data analysis was performed including the information of sequence alignment, inter/intra-specific genetic distance and data distribution, identification efficiency and the situation of Neighbor-Joining (NJ) phylogenetic trees. We found ITS2 sequence region had high variation, stable genetic distance and identification efficiency relatively. The topological structure of NJ phylogenetic tree showed monophyletic. Our findings show that ITS2 can be applied as a universal barcode for identifying poisonous medicinal plants in Chinese pharmacopoeia and their poisonous related species or adulterants.

2.
Circ Cardiovasc Qual Outcomes ; 12(9): e005805, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31474119

RESUMO

BACKGROUND: Mobile health interventions may support risk factor management and are readily scalable in healthcare systems. We aim to evaluate the efficacy of a text messaging-based intervention to improve glycemic control in patients with coronary heart disease and diabetes mellitus in China. METHODS AND RESULTS: The CHAT-DM study (Cardiovascular Health and Texting-Diabetes Mellitus) was a parallel-group, single-blind, randomized clinical trial that included 502 patients with both coronary heart disease and diabetes mellitus from 34 hospitals in China. The intervention group (n=251) received 6 text messages per week for 6 months in addition to usual care. Messages were theory driven and culturally tailored to provide educational and motivational information on glucose monitoring, blood pressure control, medication adherence, physical activity, and lifestyle. The control group (n=251) received usual care and 2 thank you messages per month. The primary outcome was change in glycated hemoglobin (HbA1C [hemoglobin A1C]) from baseline to 6 months. Secondary outcomes were change in proportion of patients achieving HbA1C <7%, fasting blood glucose, systolic blood pressure, LDL (low-density lipoprotein) cholesterol, body mass index, and physical activity from baseline to 6 months. The end points were assessed using analyses of covariance. The follow-up rate was 99%. When compared with control group at 6 months, the intervention group had a greater reduction in HbA1C (-0.2% versus 0.1%; P=0.003) and a greater proportion of participants who achieved HbA1C <7% (69.3% versus 52.6%; P=0.004). Change in fasting blood glucose was larger in the intervention group (between-group difference: -0.6 mmol/L; 95% CI, -1.1 to -0.2; P=0.011), but no other outcome differences were observed. Nearly all participants reported that messages were easy to understand (97.1%) and useful (94.1%). CONCLUSIONS: A text message intervention resulted in better glycemic control in patients with diabetes mellitus and coronary heart disease. While the mechanism of this benefit remains to be determined, the results suggest that a simple, culturally sensitive mobile text messaging program may provide an effective and feasible way to improve disease self-management. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02883842.

3.
Food Funct ; 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31482900

RESUMO

The major bioactive ingredient THSG of Polygonum multiflorum is well established for its anti-oxidation, anti-aging and anti-inflammation properties. Increasing evidence supports the capacity of THSG to ameliorate the biochemistry of neurotrophins and their downstream signaling axis in mouse models to attenuate neurodegenerative diseases such as Alzheimer's and Parkinson's disease. In this study, the neuroprotective effects of THSG were studied in vitro and in vivo. In cultured mesencephalic dopamine neurons and SH-SY5Y cell line, it was found that THSG protected the integrity of the cell body and neurite branching from MPP+-induced toxicity by restoring the expression of FGF2 and BDNF and their downstream signaling pathways to inhibit apoptosis and promote cell survival. The inhibition of Akt signaling by LY294002 or TrkB activity by K252a eliminated the neuroprotective effects of THSG. In the MPTP-induced mouse models of Parkinson's disease, THSG ameliorated the animal behaviors against MPTP-induced neurotoxicity, which was demonstrated by the pole test and the tail suspension test. Biochemical and immunohistochemical analysis verified the THSG-mediated restoration of the FGF2-Akt and BDNF-TrkB signaling axis in the substantia nigra and corpus striatum and the recovery of dopaminergic neurons. These results establish the neuroprotective effects of THSG in vitro and in vivo and unravel the underlying mechanism against toxin-induced neural atrophy, providing a new avenue for the use and pharmacological research of edible medicine for anti-neurodegenerative diseases.

4.
J Colloid Interface Sci ; 556: 726-733, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31499443

RESUMO

A 3D flower-like mesoporous Ce doped ZnO composite composed of nanosheets was prepared by a facile, one-step wet chemical method at room temperature. It was found that the moderate Ce doping can improve the light absorption of ZnO. The photocatalytic activities of the samples were studied by the degradation of Rhodamine B (RhB) and phenol under stimulated sunlight. The 1% mole ratio of Ce doped ZnO composites (denoted as CZ1) showed higher photocatalytic performance than other samples, where 85.1% of RhB and 69.6% of phenol can be removed within 125 min and 120 min, respectively. The Ce4+ doped in the lattice of ZnO can act as the electron trapping sites, which effectively improve the electron-hole separation. In addition, it was also found the annealing temperature had effect on the morphology and structure of Ce doped ZnO. The photocatalytic performance can be further enhanced at proper annealing temperature (500 °C) due to the increase of ZnO crystallinity with maintained flower-like structure and the formation of CeO2-ZnO heterojunction at their tight interface promoting the separation of photogenerated electron-hole pairs.

5.
Chin J Nat Med ; 17(7): 481-489, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31514979

RESUMO

American ginseng (Panax quinquefolius L.) is a well-known Asian traditional herbal medicine with a large market demand. The plant is native to eastern North America, and its main producing areas worldwide are decreasing due to continuous cropping obstacles and environmental changes. Therefore, the identification of maximum similarities of new ecological distribution of P. quinquefolius, and prediction of its response to climate change in the future are necessary for plant introduction and cultivation. In this study, the areas with potential ecological suitability for P. quinquefolius were predicted using the geographic information system for global medicinal plants (GMPGIS) based on 476 occurrence points and 19 bioclimatic variables. The results indicate that the new ecologically suitable areas for P. quinquefolius are East Asia and the mid-eastern Europe, which are mainly distributed in China, Russia, Japan, Ukraine, Belarus, North Korean, South Korea, andRomania. Under global climate change scenarios, the suitable planting areas for P. quinquefolius would be increased by 9.16%-30.97%, and expandingnorth and west over the current ecologically suitable areas by 2070. The potential increased areas that are ecologically suitable include northern Canada, Eastern Europe, and the Lesser Khingan Mountains of China, and reduced regions are mainly in central China, the southern U.S., and southern Europe. Jackknife tests indicate that the precipitation of the warmest quarter was the important climatic factor controlling the distribution of P. quinquefolius. Our findings can be used as auseful guide for P. quinquefolius introduction and cultivation in ecologically suitable areas.

6.
Chin J Nat Med ; 17(7): 506-516, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31514982

RESUMO

MSC transplantation has been explored as a new clinical approach to stem cell-based therapies for bone diseases in regenerative medicine due to their osteogenic capability. However, only a small population of implanted MSC could successfully reach the injured areas. Therefore, enhancing MSC migration could be a beneficial strategy to improve the therapeutic potential of cell transplantation. Catharmus tinctorius volatile oil (CTVO) was found to facilitate MSC migration. Further exploration of the underlying molecular mechanism participating in the pro-migratory ability may provide a novel strategy to improve MSC transplantation efficacy. This study indicated that CTVO promotes MSC migration through enhancing ROCK2 mRNA and protein expressions. MSC migration induced by CTVO was blunted by ROCK2 inhibitor, which also decreased myosin light chain (MLC) phosphorylation. Meanwhile, the siRNA for ROCK2 inhibited the effect of CTVO on MSC migration ability and attenuated MLC phosphorylation, suggesting that CTVO may promote BMSC migration via the ROCK2/MLC signaling. Taken together, this study indicates that C. tinctorius volatile oil could enhance MSC migration via ROCK2/MLC signaling in vitro. C. tinctorius volatile oil-targeted therapy could be a beneficial strategy to improve the therapeutic potential of cell transplantation for bone diseases in regenerative medicine.

7.
Microb Ecol ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511911

RESUMO

This data-intensive study investigated the delicate balance of niche and neutrality underlying microbial communities in freshwater ecosystems through comprehensive application of high-throughput sequencing, species abundance distribution (SAD), and the neutral community model (NCM), combined with species diversity and phylogenetic measures, which unite the traditional and microbial ecology. On the genus level, 45.10% and 41.18% of the water samples could be explained by the log-normal and Volkov model respectively, among which 31.37% could fit both models. Meanwhile, 55.56% of the sediment samples could be depicted by the log-normal model, and Volkov-fitted samples comprised only 13.33%. Besides, operational taxonomic units (OTUs) from water samples fit Sloan's neutral model significantly better than those in sediment. Therefore, it was concluded that deterministic processes played a great role in both water and sediment ecosystems, whereas neutrality was much more involved in water assemblages than in non-fluidic sediment ecosystems. Secondly, log-normal fitted samples had lower phylogenetic species variability (PSV) than Volkov-fitted ones, indicating that niche-based communities were more phylogenetically clustered than neutrally assembled counterparts. Additionally, further testing showed that the relative richness of rare species was vital to SAD modeling, either niche-based or neutral, and communities containing fewer rare species were more easily captured by theoretical SAD models.

8.
Math Biosci Eng ; 16(5): 4107-4121, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31499653

RESUMO

This paper focuses on numerical approximation of the basic reproduction number R0, which is the threshold defined by the spectral radius of the next-generation operator in epidemiology. Generally speaking, R0 cannot be explicitly calculated for most age-structured epidemic systems. In this paper, for a deterministic age-structured epidemic system and its stochastic version, we discretize a linear operator produced by the infective population with a theta scheme in a finite horizon, which transforms the abstract problem into the problem of solving the positive dominant eigenvalue of the next-generation matrix. This leads to a corresponding threshold R0,n . Using the spectral approximation theory, we obtain that R0,n → R0 as n → +∞. Some numerical simulations are provided to certify the theoretical results.

9.
J Gastrointestin Liver Dis ; 28(3): 289-296, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31517325

RESUMO

BACKGROUND AND AIMS: Liver fibrosis is stage-dependently associated with non-alcoholic fatty liver disease (NAFLD) progression. The increased awareness of non-invasive diagnosis has led to the establishment of many fibrosis diagnosis models with various accuracies. We aimed to evaluate the diagnostic performance of nine clinical non-invasive fibrosis models in NAFLD and provide an optimal diagnostic method for advanced fibrosis by step layered combination of non-invasive models. METHODS: 453 consecutive patients with biopsy-proven NAFLD were enrolled from three centers and were divided into study cohort and validation cohort randomly. Aspartate aminotransferase-to-platelet ratio index (APRI), BARD, FiB-4, FibroMeter NAFLD, Forns' Index, Hui model, non-invasive Koeln-Essen- index (NIKEI), S Index and NAFLD fibrosis score (NFS) were calculated. The high area under the receiver operating characteristic curve (AUROC) models were stepwise combined for further diagnosing NAFLD advanced fibrosis. RESULTS: All models had good performance with high negative predictive value (NPV) and specificity for diagnosing fibrosis, while positive predictive value (PPV) and sensitivity were low. APRI, BARD, FibroMeter NAFLD and NIKEI had higher AUROCs and their step layered combination for diagnosing advanced fibrosis showed high specificity, sensitivity, NPV and PPV up to 89.13%, 72.50%, 74.36%, and 88.17%, which also performed well in the validation cohort. CONCLUSIONS: APRI, BARD, FibroMeter NAFLD and NIKEI had better diagnostic accuracy, and could be preferred for diagnosing NAFLD fibrosis. The step layered combination of these models performed much better than each single scoring system for diagnosing advanced fibrosis, provides valuable reference for clinical practice and might be a potential substitution of liver biopsy.

10.
Invest New Drugs ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31463638

RESUMO

Renal cell carcinoma (RCC) is one of the most common malignancies worldwide, and metabolic reprogramming has a profound effect on RCC tumorigenesis. mTORC1 inhibitors are widely used in RCC treatment, yet some types of RCC cells are resistant to these compounds. Thus, clarification of the metabolic mechanism of mTORC1 inhibitors and exploration of new therapeutic approaches are urgently needed. In this study, we found that the mTORC1 pathway was hyperactive in RCC. Immunohistochemistry and western blot analysis showed that phosphorylation of the mTORC1 substrate 4EBP1 at threonine 37/46 increased in RCC tissues compared with that in normal renal tissues. It was also found that mTORC1 inhibitor everolimus suppressed glucose consumption, lactate production, and multiple catalytic enzymes involved in glycolysis in 786-O and ACHN cells, but the accumulation of HIF1α induced by CoCl2 blocked the inhibitory effect of everolimus on aerobic glycolysis. Interestingly, western blot and metabolite analysis showed that the tumor suppressor NDRG2 (N-Myc downstream regulated gene 2) was able to inhibit mTORC1 activity and cooperate with an mTOR inhibitor to decrease aerobic glycolysis in 786-O and ACHN cells. These results demonstrate that NDRG2 may potentially synergize with mTORC1 inhibitors to suppress malignant phenotype of RCC. Taken together, these data provided preclinical evidence that the combination of NDRG2 and mTORC1 inhibitors might be a promising strategy for RCC therapy.

11.
J Phys Chem Lett ; : 5428-5433, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31433648

RESUMO

The iron-amino acid interactions Fe-O(Glu/Asp), Fe-N(His), and Fe-S(Cys) are the three major iron-ligand bonds in proteins. To compare their properties in proteins, we used atomic force microscopy (AFM)-based single-molecule force spectroscopy to investigate a superoxide reductase (Fe(III)-SOR) with all three types of bonds forming an Fe(His)4CysGlu center. We first found that Apo-SOR without bound iron showed multiple unfolding pathways only from the ß-barrel core. Then, using Holo-SOR with a ferric ion, we found that a single Fe-O(Glu) bond can tightly connect the flexible N-terminal fragment to the ß-barrel and stabilize the whole protein, showing a complete protein unfolding scenario, while the single Fe-N(His) bond was weak and unable to provide such a stabilization. Moreover, when multiple Fe-N bonds are present, a similar stabilization effect can be achieved. Our results showed that the iron-ligand bond modulates protein structure and stability in different modes at the single-bond level.

12.
Nano Lett ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31466437

RESUMO

Nitric oxide (NO) molecular messenger can reverse the multidrug resistance (MDR) effect of cancer cells through reducing P-glycoprotein (P-gp) expression, beneficial for creating a favorable microenvironment for the treatment of doxorubicin (Dox)-resistant cancer cells. Development of sophisticated nanosystems to programmably release NO and Dox becomes an efficient strategy to overcome the MDR obstacles and achieve promising therapeutic effects in Dox-resistant cancer. Herein, a NO stimulated nanosystem was designed to engineer a significant time gap between NO and Dox release, promoting MDR cancer therapy. A o-phenylenediamine-containing lipid that can hydrolyze in response to NO was embedded in the phospholipid bilayer structure of liposome to form NO-responsive liposome, which could further encapsulate l-arginine (l-Arg)/Dox-loaded gold@copper sulfide yolk-shell nanoparticls (ADAu@CuS YSNPs) to form ADLAu@CuS YSNPs. Under 808 nm laser irradiation, the unique resonant energy transfer (RET) process and reactive oxygen species (ROS) generation in the confined space of ADLAu@CuS YSNPs could effectively convert l-Arg into NO, regionally destabilizing the phospholipid bilayer structure, as a result of NO release. However, at this early stage Dox could not be released from YSNPs due to the molecular scaffold limit. As the NO release progressed, the NO-responsive liposome layer was deteriorated more severely, allowing Dox to escape. This NO and Dox sequential release of ADLAu@CuS YSNPs could significantly inhibit P-gp expression and enhance Dox accumulation in Dox-resistant MCF-7/ADR cells, leading to promising in vitro and in vivo therapeutic effects and presenting their great potential for MDR cancer therapy.

13.
J Microbiol Methods ; 164: 105684, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31394120

RESUMO

RNA-based molecular technique (RT-qPCR) is a promising method for microcystin monitoring in lakes and reservoirs, but great lability of RNA in cyanobacterial samples limits its application. To date, no studies have investigated how to effectively preserve RNA in cyanobacterial samples. In this study, four different treatments (-80 °C freezer, -196 °C liquid nitrogen, 4 °C or 25 °C preservation after adding RNA protective fluid) were employed to preserve RNA in pure culture and field Microcystis samples, and RNA degradation in these treatments were systematically evaluated. Results showed liquid nitrogen was the most effective treatment to preserve RNA in pure culture and field Microcystis samples. RNA preservation using RNA protective fluid was temperature dependent. Low temperature (4 °C) could effectively slow down RNA degradation within a short time (1-7 d), since decay rate of mcyH mRNA (k = 0.00094 d-1) was much lower at 4 °C than that at 25 °C (0.0549 d-1) (P < 0.05). However, for field samples, RNA degradation was much faster than pure culture samples with the same treatment. Therefore, to better preserve RNA in field samples, a practical strategy for RNA preservation combining RNA protective fluid and liquid nitrogen, was proposed. Tests of field experiments showed it was more effective than individual treatment for RNA preservation in Microcystis samples during field sampling. Thus, this strategy could be employed to preserve RNA in cyanobacterial samples during field sampling, which will contribute to the application of RT-qPCR technique for microcystin monitoring in lakes and reservoirs.

14.
J Alzheimers Dis ; 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31403945

RESUMO

Cyclin-dependent kinase 5 (CDK5) in adipose tissue mediates peroxisome proliferator-activated receptor γ (PPARγ) phosphorylation at Ser273 to inhibit its activity, causing PPARγ target gene expression changes. Among these, insulin-degrading enzyme (IDE) degrades amyloid-ß peptide (Aß), the core pathological product of Alzheimer's disease (AD), whereas ß-amyloid cleavage enzyme 1 (BACE1) hydrolyzes amyloid-ß protein precursor (AßPP). Therefore, we speculated that CDK5 activity in the brain might participate in Aß production, thereby functioning as a key molecule in AD pathogenesis. To confirm this hypothesis, we transduced primary rat hippocampal neurons using CDK5-expressing lentiviral vectors. CDK5 overexpression increased PPARγ Ser273 phosphorylation, decreased IDE expression, increased BACE1 and AßPP expression, increased Aß levels, and induced neuronal apoptosis. The CDK5 inhibitor roscovitine effectively reversed these CDK5 overexpression-mediated effects. Moreover, silencing of the Cdk5 gene via CDK5 shRNA-expressing lentiviral vectors in primary hippocampal neurons did not exert any protective effect against normal neuronal apoptosis, nor were significant effects observed on Aß levels, PPARγ phosphorylation, or PPARγ target gene expression in the cells. However, Cdk5 gene silencing exhibited a neuroprotective effect in the Aß-induced AD neuron model by effectively inhibiting the Aß-induced neuronal apoptosis, PPARγ phosphorylation, PPARγ expression downregulation, and PPARγ target gene expression changes, and reducing Aß levels. In conclusion, this study demonstrated that CDK5 played an important role in the pathogenesis of AD. Specifically, CDK5 participated in Aß production by regulating PPARγ phosphorylation. Targeted therapy against CDK5 could effectively reduce and reverse the neurotoxic effects of Aß and may represent a novel approach for AD treatment.

15.
Metabolism ; 100: 153955, 2019 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-31390528

RESUMO

OBJECTIVES: The activation of brown adipose tissue (BAT) is considered as a promising therapeutic target for obesity. APPL1 (Adaptor protein containing the Pleckstrin homology domain, Phosphotyrosine binding domain and Leucine zipper motif) is an intracellular adaptor protein and its genetic variation is correlated with BMI and body fat distribution in diabetic patients. However, little is known about the roles of APPL1 in BAT thermogenesis. MATERIALS/METHODS: In this study, adipose tissue specific knockout (ASKO) mice were generated to evaluate APPL1's role in BAT thermogenesis in vivo, and possible signaling pathways were further explored in cultured brown adipocytes. RESULTS: After high fat diet challenge, APPL1 ASKO mice developed more severe obesity, glucose intolerance and insulin resistance compared with control mice. Metabolic cage study showed that APPL1 deficiency impaired energy expenditure and adaptive thermogenesis in ASKO mice. PET-CT analysis showed decreased standardized uptake value (SUV) in the inter-scapular region which indicated impaired BAT activity in ASKO mice. Further study showed deletion of APPL1 attenuated brown fat specific gene expression, such as UCP1 and PGC1α in both BAT and brown adipocytes. In cultured brown adipocytes, upon cAMP stimulation, APPL1 shuttled from cytosol to nuclei. Co-IP and ChIP study showed that APPL1 could directly interact with histone deacetylase 3 (HDAC3) to mediate chromatin remodeling and UCP1 gene expression. CONCLUSIONS: Our data demonstrated the essential role of APPL1 in regulating brown adipocytes thermogenesis via interaction with HDAC3, which may have potential therapeutic implications for treatment of obesity.

17.
Toxicol Appl Pharmacol ; 380: 114704, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31400413

RESUMO

Cisplatin (CDDP) is the most commonly used chemotherapeutic drug and has an irreplaceable role in cancer treatment. However, CDDP-induced acute kidney injury (AKI) greatly limits its use. Abundant evidence has confirmed that apoptosis contributes to AKI caused by CDDP administration. The nanoparticle form of selenium, also known as Se@SiO2 nanocomposites (NPs), has been proven to be a potential agent to prevent apoptotic cell death. In this article, we established acute kidney injury models in vivo via a single injection of CDDP and used human kidney 2 (HK-2) cells for experiments in vitro. We demonstrated that NPs can improve CDDP-induced renal dysfunction. In addition, therapy with NPs attenuated apoptosis in cells and kidney tissues treated with CDDP. In terms of mechanism, we discovered that Sirt1, a deacetylase with an important role in CDDP-induced acute kidney injury, was remarkedly increased after NPs pretreatment, and the anti-apoptotic effect of the NPs was markedly abrogated after the inhibition of Sirt1. The results linked the protective effect of NPs on nephrotoxicity with Sirt1, suggesting the potential clinical importance of nanomaterials in alleviating the side effects of chemotherapy.

18.
Theranostics ; 9(16): 4717-4729, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31367252

RESUMO

Rationale: Chemoresistance frequently occurs in patients with small cell lung cancer (SCLC) and leads to a dismal prognosis. However, the mechanisms underlying this process remain largely unclear. Methods: The effects of chromodomain Y-like (CDYL) on chemoresistance in SCLC were determined using Western blotting, immunohistochemistry, cell counting kit-8 assays, flow cytometry, and tumorigenicity experiments, and the underlying mechanisms were investigated using mRNA sequencing, chromatin immunoprecipitation-qPCR, electrophoretic mobility shift assays, co-immunoprecipitation, GST pull down assays, bisulfite sequencing PCR, ELISA, and bioinformatics analyses. Results: CDYL is expressed at high levels in chemoresistant SCLC tissues from patients, and elevated CDYL levels correlate with an advanced clinical stage and a poor prognosis. Furthermore, CDYL expression is significantly upregulated in chemoresistant SCLC cells. Using gain- and loss-of-function methods, we show that CDYL promotes chemoresistance in SCLC in vitro and in vivo. Mechanistically, CDYL promotes SCLC chemoresistance by silencing its downstream mediator cyclin-dependent kinase inhibitor 1C (CDKN1C). Further mechanistic investigations showed that CDYL recruits the enhancer of zeste homolog 2 (EZH2) to regulate trimethylation of lysine 27 in histone 3 (H3K27me3) at the CDKN1C promoter region and promotes transcriptional silencing. Accordingly, the EZH2 inhibitor GSK126 de-represses CDKN1C and decreases CDYL-induced chemoresistance in SCLC. Principal conclusions: Based on these results, the CDYL/EZH2/CDKN1C axis promotes chemoresistance in SCLC, and these markers represent promising therapeutic targets for overcoming chemoresistance in patients with SCLC.

19.
J Invest Dermatol ; 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31376385

RESUMO

Venous ulcers (VU) are the most common type of human chronic non-healing wounds and stalled in a constant and excessive inflammatory state. The molecular mechanisms underlying the chronic wound inflammation remains elusive. Moreover, little is known about the role of regulatory RNAs, such as microRNAs (miRNAs), in the pathogenesis of VU. We found that both miR-34a and miR-34c were upregulated in the wound-edge epidermal keratinocytes of VU compared with normal wounds or the skin. In keratinocytes, miR-34a and miR-34c promoted inflammatory chemokine and cytokine production. In wounds of wild-type mice, miR-34a mimic treatment enhanced inflammation and delayed healing. To further explore how miR-34 function, LGR4 was identified as a direct target mediating the pro-inflammatory function of miR-34a and miR-34c. Interestingly, impaired wound closure with enhanced inflammation was also observed in Lgr4 KO mice. Mechanistically, miR-34-LGR4 axis regulated GSK-3ß -induced p65 Ser468 phosphorylation, changing the activity of NF-κB signaling pathway. Collectively, the miR-34-LGR4 axis was shown to regulate keratinocyte inflammatory response, which deregulation may play a pathological role in VU.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31380759

RESUMO

Image semantic segmentation tasks and methods based on weakly supervised conditions have been proposed and achieve better and better performance in resent years. However, the purpose of these tasks is mainly to simplify the labeling work. In this paper, we establish a new and more challenging task condition: weaklier supervision with one image level annotation per category, which only provides prior knowledge that humans need to recognize new objects, and aims to achieve pixel level object semantic understanding. In order to solve this problem, a three stage semantic segmentation framework is put forward, which realizes image level, pixel level and object common features learning from coarse to fine gradually, and finally obtains semantic segmentation results with accurate and complete object regions. Researches on PASCAL VOC 2012 dataset demonstrates effectiveness of the proposed method, which makes an obvious improvement compare to baselines. Based on fewer supervised information, the method also provides satisfactory performance compared to weakly supervised learning based methods with complete image level annotations.

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