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1.
Chin Med J (Engl) ; 2021 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-33950871

RESUMEN

BACKGROUND: There have been few real-life dose-comparing studies on the efficacy and safety of secukinumab in Chinese patients with plaque psoriasis. We conducted a real-life cohort study to investigate the efficacy and safety of secukinumab 150 and 300 mg in Chinese patients with moderate-to-severe plaque psoriasis. METHODS: A total of 106 patients with moderate-to-severe plaque psoriasis were included in this study. Patients received either secukinumab 150 mg or secukinumab 300 mg according to patients' weights and severity of psoriasis. The treatment continued for at least 24 weeks. The efficacy was evaluated by improvement in the psoriasis area and severity index (PASI) scores. The safety was also analyzed. RESULTS: Fifty-nine patients (55.7%) were treated with secukinumab 300 mg and 47 patients (44.3%) were treated with secukinumab 150 mg. After 12-week treatment, PASI75/90/100 responses were achieved in 100%, 97.8%, and 95.7% of patients, respectively, in secukinumab 150 mg group, and the efficacy was maintained to week 24. In secukinumab 300 mg group, PASI75/90/100 responses were achieved in 93.2%, 81.4%, and 76.3% of patients, respectively, at week 12. In this group, PASI75/90/100 responses reached 91.5%, 86.4%, and 79.9%, respectively, at week 24. Biologic-experienced patients had lower responses than biologic-naïve patients. Secukinumab 150 and 300 mg were well tolerated. Five patients discontinued treatment due to poor response, adverse event, or economic reasons. CONCLUSIONS: This real-life study demonstrated that high PASI 90 and PASI 100 responses were achieved in Chinese psoriasis patients receiving secukinumab 150 or 300 mg. Biologic-naïve was associated with better clinical efficacy.

2.
Thorac Cancer ; 2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-33949784

RESUMEN

BACKGROUND: To investigate the survival benefit of concurrent chemoradiotherapy (CCRT) for patients with locally advanced esophageal squamous cell carcinoma (ESCC) during the years of intensity-modulated radiotherapy (IMRT). METHODS: Medical records of 1089 patients with ESCC who received IMRT from January 2005 to December 2017 were retrospectively reviewed. A total of 617 patients received CCRT, 472 patients received radiotherapy (RT) alone. Propensity score matching (PSM) method was used to eliminate baseline differences between the two groups. Survival and toxicity profile were evaluated afterward. RESULTS: After a median follow-up time of 47.9 months (3.2-149.8 months), both overall survival (OS) and progression-free survival (PFS) of the CCRT group were better than those of the RT alone group, either before or after PSM. After PSM, the 1-, 3-, and 5-year OS of RT alone and CCRT groups were 59.0% versus 70.2%, 27.7% versus 40.5% and 20.3% versus 33.1%, respectively (p < 0.001). The 1-, 3-, and 5-year PFS were 39.4% versus 49.0%, 18.3% versus 30.4% and 10.5% versus 25.0%, respectively (p < 0.001). The rates of ≥ grade 3 leukopenia and radiation esophagitis in the CCRT group were higher than that of RT alone group (p < 0.05). There was no significant difference in the probability of radiation pneumonitis between the two groups (p = 0.167). Multivariate Cox analysis indicated that female, EQD2 ≥60 Gy and concurrent chemotherapy were favorable prognostic factors for both OS and PFS. CONCLUSIONS: Concurrent chemotherapy can bring survival benefits to patients with locally advanced ESCC receiving IMRT. For patients who cannot tolerate concurrent chemotherapy, RT alone is an effective alternative with promising results.

3.
IEEE Trans Image Process ; 30: 4855-4866, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33945479

RESUMEN

Inpainting arbitrary missing regions is challenging because learning valid features for various masked regions is nontrivial. Though U-shaped encoder-decoder frameworks have been witnessed to be successful, most of them share a common drawback of mask unawareness in feature extraction because all convolution windows (or regions), including those with various shapes of missing pixels, are treated equally and filtered with fixed learned kernels. To this end, we propose our novel mask-aware inpainting solution. Firstly, a Mask-Aware Dynamic Filtering (MADF) module is designed to effectively learn multi-scale features for missing regions in the encoding phase. Specifically, filters for each convolution window are generated from features of the corresponding region of the mask. The second fold of mask awareness is achieved by adopting Point-wise Normalization (PN) in our decoding phase, considering that statistical natures of features at masked points differentiate from those of unmasked points. The proposed PN can tackle this issue by dynamically assigning point-wise scaling factor and bias. Lastly, our model is designed to be an end-to-end cascaded refinement one. Supervision information such as reconstruction loss, perceptual loss and total variation loss is incrementally leveraged to boost the inpainting results from coarse to fine. Effectiveness of the proposed framework is validated both quantitatively and qualitatively via extensive experiments on three public datasets including Places2, CelebA and Paris StreetView.

4.
Artículo en Inglés | MEDLINE | ID: mdl-33961568

RESUMEN

The neural-network (NN)-based control method is a new emerging promising technique for controller design in a power electronic circuit (PEC). However, the optimization of NN-based controllers (NNCs) has significant challenges in two aspects. The first challenge is that the search space of the NNC optimization problem is such complex that the global optimization ability of the existing algorithms still needs to be improved. The second challenge is that the training process of the NNC parameters is very computationally expensive and requires a long execution time. Thus, in this article, we develop a powerful evolutionary computation-based algorithm to find a high-quality solution and reduce computational time. First, the differential evolution (DE) algorithm is adopted because it is a powerful global optimizer in solving a complex optimization problem. This can help to overcome the premature convergence in local optima to train the NNC parameters well. Second, to reduce the computational time, the DE is extended to distribute DE (DDE) by dispatching all the individuals to different distributed computing resources for parallel computing. Moreover, a resource-aware strategy (RAS) is designed to further efficiently utilize the resources by adaptively dispatching individuals to resources according to the real-time performance of the resources, which can simultaneously concern the computing ability and load state of each resource. Experimental results show that, compared with some other typical evolutionary algorithms, the proposed algorithm can get significantly better solutions within a shorter computational time.

5.
Aging (Albany NY) ; 132021 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-33962394

RESUMEN

The ketogenic diet has been widely used in the treatment of various nervous system and metabolic-related diseases. Our previous research found that a ketogenic diet exerts a protective effect and promotes functional recovery after spinal cord injury. However, the mechanism of action is still unclear. In this study, different dietary feeding methods were used, and myelin expression and gene level changes were detected among different groups. We established 15 RNA-seq cDNA libraries from among 4 different groups. First, KEGG pathway enrichment of upregulated differentially expressed genes and gene set enrichment analysis of the ketogenic diet and normal diet groups indicated that a ketogenic diet significantly improved the steroid anabolic pathway in rats with spinal cord injury. Through cluster analysis, protein-protein interaction analysis and visualization of iPath metabolic pathways, it was determined that Sqle, Sc5d, Cyp51, Dhcr24, Msmo1, Hsd17b7, and Fdft1 expression changed significantly. Second, through weighted gene co-expression network analysis showed that rats fed a ketogenic diet showed a significant reduction in the expression of genes involved in immune-related pathways, including those associated with immunity and infectious diseases. A ketogenic diet may improve the immune microenvironment and myelin growth in rats with spinal cord injury through reprogramming of steroid metabolism.

6.
Ann Clin Lab Sci ; 51(2): 245-254, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33941565

RESUMEN

OBJECTIVE: Ulcerative colitis (UC) is a chronic, relapsing, and non-specific inflammatory bowel disease. To date, the pathogenesis of UC has not been fully understood. This study aimed to identify crucial genes and related transcription factors in UC by bioinformatic methods. METHODS: Datasets GSE75214 and GSE48958 were used to identify the common differentially expressed genes (DEGs). GO and KEGG pathway enrichment analyses were performed using the STRING database. The protein-protein interaction (PPI) network was constructed to screen hub genes using the STRING database and Cytoscape software. The expressions of the identified hub genes were verified using dataset GSE73661, and their correlations with Mayo scores were analyzed using dataset GSE92415. The transcriptional factor (TF) regulatory network of the hubgenes was constructed by Network Analyst. RESULTS: A total of 147 common DEGs, including 114 up-regulated and 33 down-regulated genes, were screened out, among which CXCL9, TIMP1, PTGS2, ICAM1, CXCL1, MMP9, IL1B, CXCL8, and IL6 were identified as hub genes with high degrees in the PPI network. Correlation analysis showed that the expressions of these hub genes were significantly correlated with Mayo scores in UC patients. Finally, RELA, FLI1, and BACH1 were predicted to be the key TFs regulating these nine hub genes. CONCLUSIONS: This study systematically analyzed the differential gene expression pattern and associated key TFs in UC, which may provide new insights into the pathogenesis and offer opportunities for discovering novel biomarkers and therapeutic targets for UC.

8.
Orthop Surg ; 2021 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-33945217

RESUMEN

OBJECTIVE: To evaluate the clinical outcomes of oblique lumbar interbody fusion (OLIF) in conjunction with unilateral pedicle screw fixation (UPSF) via the Wiltse approach in treating degenerative lumbar scoliosis (DLS). METHODS: The article is a retrospective analysis. Twelve patients with DLS who underwent combined OLIF and UPSF between July 2017 and December 2018 were included. The study included 2 male and 10 female patients, with a mean age at the time of the operation of 67.2 ± 9.1 years. The surgical characteristics and complications were evaluated. The clinical and radiological data such as the correction of deformity, coronal and sagittal profile were analyzed. RESULTS: The mean follow-up time of the study was 26.8 ± 1.8 months. At the final follow-up, all patients who underwent combined OLIF and UPSF achieved statistically significant improvements in coronal Cobb angle (from 19.6° ± 4.8° to 6.9° ± 3.8°, P < 0.01), distance between the C7 plumb line and central sacral vertebral line (from 2.5 ± 1.7 cm to 0.9 ± 0.6 cm, P < 0.01), sagittal vertebral axis (from 4.3 ± 4.3 cm to 1.5 ± 1.0 cm, P = 0.03), lumbar lordosis (from 29.4° ± 8.6° to 40.8° ± 5.8°, P < 0.01), pelvic tilt (from 27.6° ± 10.8° to 18.3° ± 7.0°, P < 0.01), pelvic incidence-lumbar lordosis mismatch (from 23.3° ± 10.5° to 11.9° ± 8.4°, P < 0.01), and cross-sectional area of the dural sac (from 87.33 ± 39.41 mm2 to 124.70 ± 39.26 mm2 , P < 0.01). The visual analogue score for back and leg pain and Oswestry Disability Index of all patients significantly improved postoperatively (P < 0.01). One case of lumbar plexus injury was found after surgery. During the follow-up period, one patient had cage subsidence. A fusion rate of 100% and good positioning of the pedicle screws were achieved in all patients at the final follow-up. CONCLUSION: OLIF in conjunction with UPSF is a safe and effective minimally invasive procedure for correcting both coronal and sagittal deformities, as it results in an improved quality of life in patients with DLS.

10.
Phytother Res ; 2021 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-33860590

RESUMEN

Isoliquiritigenin (ISO) is a flavonoid extracted from the root of licorice, which serves various biological and pharmacological functions including antiinflammatory, antioxidation, liver protection, and heart protection. However, the mechanism of its action remains elusive and the direct target proteins of ISO have not been identified so far. Through cell-based screening, we identified ISO as a potent lipid-lowering compound. ISO treatment successfully ameliorated fatty acid-induced cellular lipid accumulation and improved nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) by increasing PPARα-dependent lipid oxidation and decreasing SREBPs-dependent lipid synthesis. Both these signaling required the activation of SIRT1. Knockdown of SIRT1 resulted in the reversal of ISO beneficiary effects suggesting that the lipid-lowering activity of ISO was regulated by SIRT1 expression. To identify the direct target of ISO, limited proteolysis combined with mass spectrometry (LiP-SMap) strategy was applied and IQGAP2 was identified as the direct target for ISO in regulating lipid homeostasis. In the presence of ISO, both mRNA and protein levels of SIRT1 were increased; however, this effect was abolished by blocking IQGAP2 expression using siRNA. To explore how IQGAP2 regulated the expression level of SIRT1, proteome profiler human phospho-kinase array kit was used to reveal possible phosphorylated kinases and signaling nodes that ISO affected. We found that through phosphorylation of CREB, ISO transduced signals from IQGAP2 to upregulate SIRT1 expression. Thus, we not only demonstrated the molecular basis of ISO in regulating lipid metabolism but also exhibited for the first time a novel IQGAP2-CREB-SIRT1 axis in treating NAFLD/NASH.

11.
Lett Appl Microbiol ; 2021 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-33817824

RESUMEN

The microbial degradation of thin stillage for environment-friendly treatment has been studied extensively in recent years, and useful compounds in the treated-thin stillage are expected to be utilized in the subsequent fermentation. In this study, an Aspergillus oryzae H18, suitable for growing in thin stillage, was isolated from soil and served to degrade the organic matter in thin stillage, with the increase in pH (from 3·75 to 4·8) and decrease in chemical oxygen demand (COD, 81·3% removal rate). The effect of thin stillage as backset water after degradation of the strain H18 on alcohol production in syrup liquid was investigated. Compared with zero addition of thin stillage, the alcohol yield in mixed syrup liquid increased by 8·6% when the concentration of treated-thin stillage was 20%. After the addition of nutrients at proper concentration (0·5% urea, 1% molasses, 0·25% NaCl, 0·2% NaH2 PO4 , 0·3% MgSO4 and 0·25% CaCl2 ) in thin stillage, the alcohol yield in yeast fermentation was increased by 32·7% when mixed syrup liquid (with 40% thin stillage treated by H18) was employed, in comparison to control group without thin stillage addition. Meanwhile, the fermentation time was shortened, and alcohol production rate was enhanced.

12.
Neoplasma ; 2021 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-33847133

RESUMEN

Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide. Accumulating researches have highlighted the ability of exosome-encapsulated microRNAs (miRNAs or miRs) as potential circulating biomarkers for lung cancer. The current study aimed to evaluate the significance of mesenchymal stem cells (MSCs)-derived exosomal miR-204 in the invasion, migration, and epithelial-mesenchymal transition (EMT) of NSCLC cells. Initially, the expression of miR-204 in human NSCLC tissues and cells was determined by RT-qPCR, which demonstrated that miR-204 was downregulated in NSCLC tissues and cells. Next, Krüppel-like factor 7 (KLF7) was predicted and validated to be a target of miR-204 using dual-luciferase reporter gene assay. NSCLC A549 cells were treated with MSCs-derived exosomes, after which the migration and invasion of A549 cells were detected and expression of EMT-related proteins (E-cadherin, N-cadherin, and Vimentin), KLF7, p-AKT/AKT, and HIF-1α were measured. The results of gain- and loss-of-function assays revealed that miR-204 overexpression in MSCs-derived exosomes inhibited KLF7 expression and the AKT/HIF-1α pathway activity, resulting in impaired cell migration, invasion, as well as EMT. In conclusion, the key findings of the current study demonstrate that exosomal miR-204 from MSCs possesses anticarcinogenic properties against NSCLC via the KLF7/AKT/HIF-1α axis.

13.
Infect Dis Poverty ; 10(1): 44, 2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33789759

RESUMEN

BACKGROUND: Acute-on-chronic liver failure (ACLF) is characterized by an excessive systemic inflammatory response and organ failure and has high mortality. Bacterial infections (BIs) worsen the clinical course of ACLF and carry a poor prognosis in ACLF patients. The efficacy of third-generation cephalosporins has been challenged in recent years. The aim of this study was to characterize the difference between ACLF patients with and without BIs and to provide a reference for medical intervention. METHODS: A total of 140 patients with hepatitis B virus-related ACLF (HBV-ACLF) hospitalized at the Department of Infectious Diseases, Huashan Hospital, Fudan University (Shanghai, China) between May 2013 and January 2020 were enrolled. Mann-Whitney U test was used to compare the baseline characteristics of HBV-ACLF patients with and without BIs. Univariate and multivariate analyses were performed to find predictors of BIs. The characteristics of BIs and the role of prophylactic antibiotics were profiled. RESULTS: A total of 97 episodes of BIs occurred in patients during the course of HBV-ACLF. Patients with and without BIs differed in clinical characteristics. The incidence of BIs showed a positive correlation with the ACLF grade (P = 0.003) and the clinical course (P = 0.003). The 90-day transplant-free survival of patients with BIs was lower than those without BIs (P < 0.0001). Patients administered prophylactic antibiotics showed a lower incidence of BIs and had a higher transplant-free survival probability than those who did not (P = 0.046). No statistical differences in antibiotic efficacy between third-generation and other antibiotics were observed (P = 0.108). CONCLUSIONS: BIs affected the clinical course and prognosis of patients with HBV-ACLF. Prophylactic antibiotics were of potential clinical importance in the prevention of BIs and improving the clinical course and prognosis in HBV-ACLF patients. Third-generation cephalosporins were qualified for use in antibiotic prophylaxis.

14.
Enzyme Microb Technol ; 146: 109781, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33812562

RESUMEN

L-amino acid ligases (Lals) are promising biocatalysts for the synthesis of dipeptides with special biological properties. However, their poor (or broad) substrate specificity limits their industrial applications. To address this problem, a molecular engineering method for Lals was developed to enhance their catalytic performance. Based on substrate channeling, entrances to the active site for different substrates were identified, and the "gate" located around the active site pocket, which plays an essential role in substrate recognition, was then engineered to facilitate acceptance of L-Gln. Two mutants (L110Y and N108F/L110Y) were discovered to display significantly increased catalytic activity toward L-Ala and L-Gln in the biosynthesis of Ala-Gln. The catalytic efficiency (kcat/ Km) of the L110Y and N108F/L110Y mutants was improved by 2.64-fold and 4.06-fold, respectively, compared with that of the wild type. N108F/L110Y was then further applied for batch production of Ala-Gln, which showed that the released Pi yield was 694.47 µM, which was an increase of approximately 21.4 %, and the yield of Ala-Gln was approximately 2.59 mM-1 L-1 mg-1. Collectively, these findings suggest the potential practical application of this method in the rational design of Lals for increased catalytic performance.

15.
Mycopathologia ; 2021 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-33813690

RESUMEN

Disseminated cryptococcosis primarily affects immunosuppressed patients and has a poor outcome if diagnosis and treatment are delayed. Skin lesions are rarely manifest causing misdiagnosis. We present a case of cryptococcal cellulitis with severe pain in a kidney transplant recipient on long-term immunosuppressive therapy. Multiple organs were involved, and there was cutaneous dissemination of the lesions. Histopathology revealed abundant yeast-like cells with wide capsular halos in subcutaneous tissue, suggesting Cryptococcus spp. infection. Laser capture microdissection (LCM)-PCR on skin biopsies confirmed Cryptococcus neoformans var. grubii. A literature review of 17 cases of disseminated cryptococcosis with cutaneous cellulitis or panniculitis in HIV-negative individuals found that over half the patients (52.9%, 9/17) had a history of glucocorticoid therapy, and that the most common site was the legs (76.5%, 13/17). C. neoformans was the main pathogenic species, accounting for 88.2% (15/17) of cases. Fungal cellulitis should be included in the differential diagnosis of cellulitis that fails to respond to antimicrobial therapy in HIV-negative immunosuppressed individuals. Non-culture-based molecular techniques aid in rapid pathogen identification in histologically positive, unculturable specimens.

16.
Artículo en Inglés | MEDLINE | ID: mdl-33846561

RESUMEN

Diffuse alveolar haemorrhage (DAH) is a life-threatening pulmonary complication occurring after allogeneic haematopoietic stem cell transplantation (allo-HSCT) without an explicit aetiology or a standard treatment. This study aimed to explore the occurrence and prognosis of DAH after allo-HSCT, in addition to comparing discrepancies in the incidence, clinical characteristics and outcomes of DAH between patients undergoing haploidentical HSCT (HID-HSCT) and matched related donor HSCT (MRD-HSCT). We retrospectively evaluated 92 consecutive patients among 3987 patients with a confirmed diagnosis of DAH following allo-HSCT (HID: 71 patients, MRD: 21 patients). The incidence of DAH after allo-HSCT was 2.3%, 2.4% after HID-HSCT and 2.0% after MRD-HSCT (P = 0.501). The prognosis of patients with DAH after transplantation is extremely poor. The duration of DAH was 7.5 days (range, 1-48 days). The probabilities of overall survival (OS) were significantly different between patients with and without DAH within 2 years after transplantation (P < 0.001). According to the Cox regression analysis, a significant independent risk factor for the occurrence of DAH was delayed platelet engraftment (P < 0.001), and a high D-dimer level (>500 ng/ml) was a significant risk factor for the poor prognosis of DAH. HID-HSCT is similar to MRD-HSCT in terms of the outcomes of DAH.

17.
Neurol Sci ; 2021 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-33855621

RESUMEN

OBJECTIVE: The efficacy and safety of deep brain stimulation (DBS) under general anesthesia for the treatment of dystonia have not yet been confirmed with high level of evidence. This meta-analysis with pooled individual patient data aims to assess the clinical outcomes and identify the potential prognostic factors of dystonia patients who underwent general anesthesia DBS. METHODS: We searched PubMed, Web of Science, and Embase for articles describing patients with dystonia who underwent asleep DBS and had individual Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores. The relative improvement in BFMDRS scores was considered the primary outcome. Pearson correlation analyses and multivariate linear regression analysis were conducted to explore the prognostic factors. RESULTS: A total of 34 studies involving 341 patients were included. The mean postoperative improvement in BFMDRS-M (BFMDRS movement subscale) and BFMDRS-D (BFMDRS disability subscale) scores were 58.6±36.2% and 48.5±38.7% at the last follow-up visit, respectively, with a mean follow-up time of 22.4±27.6 months. Age at surgery and disease duration showed a negative correlation with the percent improvement of BFMDRS-M (%) at the last visit (r=-0.134, P=0.013; r=-0.165, P=0.006). In the stepwise multivariate regression, only disease duration remained a relevant factor. Additionally, the adverse events were acceptable. CONCLUSION: General anesthesia DBS is a safe, effective, and feasible option for dystonia patients in the long term. Shorter disease duration predicts better clinical outcomes.

18.
Funct Plant Biol ; 2021 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-33820599

RESUMEN

The responses of plants to recurrent stress may differ from their responses to a single stress event. In this study, we investigated whether clonal plants can remember past environments. Parental ramets of Glechoma longituba (Nakai) Kuprian were exposed to UV-B stress treatments either once or repeatedly (20 and 40 repetitions). Differences in DNA methylation levels and growth parameters among parents, offspring ramets and genets were analysed. Our results showed that UV-B stress reduced the DNA methylation level of parental ramets, and the reduction was enhanced by increasing the number of UV-B treatments. The epigenetic variation exhibited by recurrently stressed parents was maintained for a long time, but that of singly stressed parents was only short-term. Moreover, clonal plants responded to different UV-B stress treatments with different growth strategies. The one-time stress was a eustress that increased genet biomass by increasing offspring leaf allocation and defensive allocation in comparison to the older offspring. In contrast, recurring stress was a distress that reduced genet biomass, increased the biomass of storage stolons, and allocated more defensive substances to the younger ramets. This study demonstrated that the growth of offspring and genets was clearly affected by parental experience, and parental epigenetic memory and the transgenerational effect may play important roles in this effect.

19.
Int J Mol Med ; 47(6)2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33846770

RESUMEN

Following the publication of the above paper, a concerned reader drew to the Editor's attention that several figures contained data that bore striking similarities to data published in other papers; notably, the western blot data shown in Fig. 6 appeared to have been presented in other studies, notably in Fig. 7B of another paper published around the same time and written by different authors based at different research institutions [Li P, Zhang Z, Zhang F, Zhou H and Sun W: Effects of 3­tetrazolyl methyl­3­hydroxy­oxindole hybrid (THOH) on cell proliferation, apoptosis, and G2/M cell cycle arrest occurs by targeting platelet­derived growth factor D (PDGF­D) and the MEK/ERK signaling pathway in human lung cell lines SK­LU­1, A549, and A­427. Med Sci Monit 24: 4547­4554, 2018]. Furthermore, cellular images featured in Fig. 2A and B of the above paper appeared in Fig. 2 of the following paper, albeit the data were presented in a different field of view: Yu L, Zhou G­Q and Li D­C: MiR­136 triggers apoptosis in human gastric cancer cells by targeting AEG­1 and BCL2. Eur Rev Med Pharmacol Sci 22: 7251­7256, 2018. After having conducted an independent investigation in the Editorial Office, the Editor of International Journal of Molecular Medicine has determined that this article should be retracted from the Journal on account of a lack of confidence concerning the originality and the authenticity of the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office never received any reply. The Editor regrets any inconvenience that has been caused to the readership of the Journal. [the original article was published on International Journal of Molecular Medicine 41, 3485-3492, 2018; DOI: 10.3892/ijmm.2018.3531].

20.
Int J Biol Sci ; 17(5): 1234-1249, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33867842

RESUMEN

Dickkopf-1 (DKK1) was recently shown to play an important role in cardiovascular disease. The aim of this work was to assess the role of DKK1 in the regulation of smooth muscle cell function by mechanical stretch and the mechanisms underlying this process. Methods: Wild-type C57BL/6J mice were subjected to sham or abdominal aortic constriction (AAC) surgery. The expression level of DKK1 was examined by immunohistochemical staining and Western blotting. Analyses of DKK1 function in vascular smooth muscle cell (VSMC) proliferation and migration were performed. Transcriptome sequencing analysis was performed to identify the differentially expressed genes and pathways regulated by DKK1. Smooth muscle-specific Dkk1 knockout mice were used to confirm the function of DKK1 in vivo. Chromatin immunoprecipitation (ChIP) was used to confirm DNA-protein interactions. Promoter luciferase analysis was used to detect transcription factor activity. Results: We found that AAC significantly increased DKK1 protein levels in the thoracic aorta and coronary artery in vivo. In vitro, high-level stretch (18%) induced the expression of DKK1 in VSMCs. Knocking down DKK1 inhibited VSMC proliferation and migration under high-level stretch (18%). We identified ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) as a target gene of DKK1. Knockdown of UHRF1 with small interfering RNAs partially reversed the regulatory effect of recombinant DKK1 on VSMCs. Specific deletion of DKK1 in VSMCs was sufficient to attenuate the AAC-induced upregulation of UHRF1, thickening of arterial media and increase in VSMC proliferation. Furthermore, we found that DKK1 regulated UHRF1 expression through the YAP-TEAD pathway. TEAD1 and TEAD4 bound directly to the promoter of UHRF1, and blocking the YAP-TEAD interaction inhibited UHRF1 upregulation due to DKK1. Conclusions: This study reveals that DKK1 mediates the mechanical stretch regulation of smooth muscle cell function by modulating UHRF1 expression through the YAP-TEAD pathway.

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