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1.
J Foot Ankle Surg ; 58(6): 1192-1196, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31679671

RESUMO

This study reviewed the efficacy of a modified Ponseti method (MP) for treating rigid clubfeet insufficiently corrected by the classic Ponseti method. Briefly, the MP consisted of 3 procedures. First, Achilles tenotomy, abductor hallucis tenotomy, and plantar fasciotomy were conducted through 3 small incisions. Second, the talocalcaneal and talonavicular joints were manually reduced. Third, plaster immobilization was introduced to maintain the initial correction. Dimeglio scores, radiographs, and pain evaluations were used to analyze outcomes. All 38 patients with 56 clubfeet enrolled in the present study achieved initial correction after the MP, followed by a mean of 3.68 ± 0.77 (range 3 to 5) cast immobilizations, which were changed each week. The average duration of treatment was 30.63 ± 6.45 days (range 23 to 47), and 6 (10.71%) clubfeet exhibited cast-related pressure injury. After a mean follow-up period of 19.71 ± 4.83 months (range 12.47 to 31.33), no child presented foot pain, and except for 1 patient with relapse, all patients received correction, with Dimeglio scores of 0.55 ± 1.06 points (range 0 to 7). The recurrence rate was 1.79% (1 of 56) at the first year. The anteroposterior talocalcaneal angle was 34.83° ± 10.65°, and the lateral talocalcaneal angle was 31.38° ± 9.86° at the last follow-up period, and both were significantly improved compared with the corresponding preoperative angles (p < .001). The anteroposterior talus-first metatarsal angle was 12.33° ± 10.04°, and the lateral calcaneal tibial angle was 74.15° ± 14.12°, which were significantly decreased compared with the preoperative values (p < .001). In conclusion, the present short-term evaluation of this minimally invasive soft-tissue release method showed promising results for treating rigid clubfoot that was not responsive to the traditional Ponseti method.

2.
Curr Mol Med ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31729291

RESUMO

BACKGROUND: Drug repositioning refers to discovering new indications for the existing drugs, which can improve the efficiency of drug research and development. METHODS: In this work, a novel drug repositioning approach based on integrative multiple similarity measure, called DR_IMSM, is proposed. The process of integrative similarity measure contains three steps. First, a heterogeneous network can be constructed based on known drug-disease association, shared entities information for drug pairwise and diseases pairwise. Second, a deep learning method, DeepWalk, is used to capture the topology similarity for drug and disease. Third, a similarity integration and adjusting process are further conducted to obtain more comprehensive drug and disease similarity measure,respectively. RESULTS: On this basis, an Bi-random walk algorithm is implemented in the constructed heterogeneous network to rank diseases for each drug. Compared with other approaches, the proposed DR_IMSM can achieve superior performance in terms of AUC on the gold standard datasets. Case studies further confirm the practical significance of DR_IMSM.

3.
Dig Liver Dis ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31704308

RESUMO

BACKGROUND AND AIMS: Aberrant long non-coding RNA (lncRNA) expression in cancer can be used as a potential diagnostic biomarker and therapeutic target. In the present study we determined the potential pathogenic mechanism underlying significant aberrant expression of lncRNAs in HepG2-ADR. METHODS: First, we identified different levels of lncRNA expression in liver cancer and adjacent non-tumor tissues obtained from public data (GSE70880) in NCBI. Then, the results were verified in a sensitive liver cancer cell line (HepG2) and a adriamycin-resistant liver cancer cell line (HepG2-ADR). Then, the effects of lncRNAs on the phenotype and some biological characteristics were also determined in HepG2 and HepG2-ADR through overexpression and using siRNA interference methods. RESULTS: We showed that lncRNA ENST00000425005 is highly expressed in a liver cancer-resistant cell line when compared with adjacent non-tumor tissues based on bioinformatics analysis and qPCR verification. Compared with the control group, overexpression of lncRNA ENST00000425005 significantly promoted proliferation and adhesiveness, but inhibited apoptosis in HepG2-ADR cells. In contrast, interference of lncRNA in HepG2-ADR cells suppressed proliferation and adhesiveness, and induced apoptosis. CONCLUSION: In conclusion, lncRNA ENST00000425005 promotes cell proliferation and invasion in drug-resistant liver cancer cells by regulating epithelial-mesenchymal transition-related gene expression and participating in the regulation of EGF and FGF7.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31767769

RESUMO

Intensive agriculture can contribute to pollinator decline, exemplified by alarmingly high annual losses of honey bee colonies in regions dominated by annual crops (e.g., midwestern United States). As more natural or seminatural landscapes are transformed into monocultures, there is growing concern over current and future impacts on pollinators. To forecast how landscape simplification can affect bees, we conducted a replicated, longitudinal assessment of honey bee colony growth and nutritional health in an intensively farmed region where much of the landscape is devoted to production of corn and soybeans. Surprisingly, colonies adjacent to soybean fields surrounded by more cultivated land grew more during midseason than those in areas of lower cultivation. Regardless of the landscape surrounding the colonies, all experienced a precipitous decline in colony weight beginning in August and ended the season with reduced fat stores in individual bees, both predictors of colony overwintering failure. Patterns of forage availability and colony nutritional state suggest that late-season declines were caused by food scarcity during a period of extremely limited forage. To test if habitat enhancements could ameliorate this response, we performed a separate experiment in which colonies provided access to native perennials (i.e., prairie) were rescued from both weight loss and reduced fat stores, suggesting the rapid decline observed in these agricultural landscapes is not inevitable. Overall, these results show that intensively farmed areas can provide a short-term feast that cannot sustain the long-term nutritional health of colonies; reintegration of biodiversity into such landscapes may provide relief from nutritional stress.

5.
J Med Virol ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31769518

RESUMO

BACKGROUND AND AIMS: Recurrent hepatitis activity during chronic hepatitis B virus infection results in fibrosis and even hepatocellular carcinoma. It is still unclear what causes acute exacerbation. As platelets have recently been identified a significant role in inflammation, we here investigated the role of platelets in mediating liver damage in patients with chronic hepatitis B virus infection. METHODS: Platelet aggregation testing and flow cytometry were carried out to evaluate platelet activation status in 121 patients chronically infected with hepatitis B across different phases of the condition. The correlation between platelet aggregation rate and liver inflammation or liver fibrosis index was evaluated. To investigate the genesis of platelet activation, several serum cytokines were also assessed by MILLIPLEX microsphere-based multiplex cytokine assay. RESULTS: Active hepatitis patients showed a higher aggregation rate than others. Levels of CD62p, a marker of platelet activation, were also increased in this group of patients. Positive correlations between platelet aggregation rate and liver inflammation or liver fibrosis were also noted, indicating significant role of platelet in the progression of liver disease. The level of tumor necrosis factor alpha, which is known to trigger platelet activation, was markedly higher in the active hepatitis group (P <0.005). CONCLUSION: Based on the findings in our study, platelet activation plays a vital role in the progression of chronic hepatitis B virus infection. Anti-platelet therapy may provide a new means of hepatitis B infection treatment. This article is protected by copyright. All rights reserved.

6.
Chin J Traumatol ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31761697

RESUMO

PURPOSE: To investigate the characteristics of the onset and treatment of radial head subluxation (RHS) in pediatric clinics and emergency departments. METHODS: A retrospective study was performed on 11, 404 RHS cases in 9827 children who visited pediatric clinics and emergency departments from January 2015 to December 2018. The patients who with history of trauma and fracture of the affected limb were excluded. The following factors were examined: the mechanisms of RHS, the type of manual reduction, the attending physician's clinical background (emergency surgeon, junior pediatric orthopedic surgeon or senior pediatric orthopedic surgeon), and the epidemiological features (gender, age, climate and location) of the injury. RESULTS: The mean age of the patients was 27.93 ± 17.94 months (range 0.93-214.53 months), with a peak incidence of 10.73-44.53 months. Approximately two-thirds of RHS cases occurred in cold weather from January to March and from September to December. Females accounted for 53.81% (n = 6137) of the cases, and left injuries were predominant (56.87%, n = 6485) in all cases. Mechanisms of injury were classified as "pull" (90.57%, n = 10, 339), "fall" (1.56%, n = 178), "hit" (0.75%, n = 86) and "unknown" (7.02%, n = 801). The overall success rate of manual reduction was 99.47%, and the success rate of reduction was higher for senior pediatric orthopedic surgeons than for emergency surgeons and junior pediatric orthopedic surgeons (p < 0.05). However, there was still a recurrence rate of 12.16% in the 9827 patients. CONCLUSION: Younger children are predisposed to RHS, and there is a possibility of recurrence. Trained emergency doctors can handle it well, but it is essential to refer patients to specialists when manual reduction failed.

7.
Cell Commun Signal ; 17(1): 145, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718671

RESUMO

BACKGROUND: Notch1 signalling is a stem-cell-related pathway that is essential for embryonic development, tissue regeneration and organogenesis. However, the role of Notch1 in the formation of myofibroblasts and fibrosis in kidneys following injury remains unknown. METHODS: The activity of Notch1 signalling was evaluated in fibrotic kidneys in CKD patients and in ureteral obstructive models in vivo and in cultured fibroblasts and TECs in vitro. In addition, the crosstalk of Notch1 with TGF-ß1/Smad2/3 signalling was also investigated. RESULTS: Notch1 activity was elevated in fibrotic kidneys of rat models and patients with chronic kidney disease (CKD). Further study revealed that epithelial and interstitial Notch1 activity correlated with an α-SMA-positive myofibroblastic phenotype. In vitro, injury stimulated epithelial Notch1 activation and epithelial-mesenchymal transition (EMT), resulting in matrix deposition in tubular epithelial cells (TECs). Additionally, interstitial Notch1 activation in association with fibroblast-myofibroblast differentiation (FMD) in fibroblasts mediated a myofibroblastic phenotype. These TGF-ß1/Smad2/3-dependent phenotypic transitions were abolished by Notch1 knockdown or a specific antagonist, DAPT, and were exacerbated by Notch1 overexpression or an activator Jagged-1-Fc chimaera protein. Interestingly, as a major driving force behind the EMT and FMD, TGF-ß1, also induced epithelial and interstitial Notch1 activity, indicating that TGF-ß1 may engage in crosstalk with Notch1 signalling to trigger fibrogenesis. CONCLUSION: These findings suggest that epithelial and interstitial Notch1 activation in kidneys following injury contributes to the myofibroblastic phenotype and fibrosis through the EMT in TECs and to the FMD in fibroblasts by targeting downstream TGF-ß1/Smad2/3 signalling.

8.
World J Surg ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31605180

RESUMO

BACKGROUND: The extent to which obesity and genetics determine postoperative complications is incompletely understood. METHODS: We performed a retrospective study using two population cohorts with electronic health record (EHR) data. The first included 736,726 adults with body mass index (BMI) recorded between 1990 and 2017 at Vanderbilt University Medical Center. The second cohort consisted of 65,174 individuals from 12 institutions contributing EHR and genome-wide genotyping data to the Electronic Medical Records and Genomics (eMERGE) Network. Pairwise logistic regression analyses were used to measure the association of BMI categories with postoperative complications derived from International Classification of Disease-9 codes, including postoperative infection, incisional hernia, and intestinal obstruction. A genetic risk score was constructed from 97 obesity-risk single-nucleotide polymorphisms for a Mendelian randomization study to determine the association of genetic risk of obesity on postoperative complications. Logistic regression analyses were adjusted for sex, age, site, and race/principal components. RESULTS: Individuals with overweight or obese BMI (≥25 kg/m2) had increased risk of incisional hernia (odds ratio [OR] 1.7-5.5, p < 3.1 × 10-20), and people with obesity (BMI ≥ 30 kg/m2) had increased risk of postoperative infection (OR 1.2-2.3, p < 2.5 × 10-5). In the eMERGE cohort, genetically predicted BMI was associated with incisional hernia (OR 2.1 [95% CI 1.8-2.5], p = 1.4 × 10-6) and postoperative infection (OR 1.6 [95% CI 1.4-1.9], p = 3.1 × 10-6). Association findings were similar after limitation of the cohorts to those who underwent abdominal procedures. CONCLUSIONS: Clinical and Mendelian randomization studies suggest that obesity, as measured by BMI, is associated with the development of postoperative incisional hernia and infection.

9.
Bull Environ Contam Toxicol ; 103(5): 756-762, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31583424

RESUMO

The current study investigated the efficiency and mechanisms of in situ immobilization of artificially Cd-contaminated soils with ferronickel slag (FNS). The available Cd content of soil was measured and the modified European Community Bureau of Reference (BCR) sequential extraction procedure (SEP) was adopted to quantify the evolutions of Cd chemical speciation after the immobilization by the FNS. The results showed that the addition of FNS (5%‒15%) remarkably reduced the available Cd content and increased the pH and cation exchange capacity of soils. The passivation rate of Cd increased from 58.13% to 73.25% as the spiked Cd content rose from 10 to 120 mg kg‒1. The BCR SEP test revealed that the FNS addition substantially reduced the acid soluble fraction and increased the residual fraction of Cd, indicating the reduction of mobility and bioavailability of Cd in soils. The chemical precipitation, ion exchange and surface complexation might be involved in in situ immobilization of Cd-contaminated soils by the FNS.

10.
Nat Commun ; 10(1): 4579, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31594926

RESUMO

Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by progressive bone erosion. Leflunomide is originally developed to suppress inflammation via its metabolite A77 1726 to attenuate bone erosion. However, distinctive responsiveness to Leflunomide is observed among RA individuals. Here we show that Leflunomide exerts immunosuppression but limited efficacy in RA individuals distinguished by higher serum C-reactive protein (CRPHigher, CRPH), whereas the others with satisfactory responsiveness to Leflunomide show lower CRP (CRPLower, CRPL). CRP inhibition decreases bone erosion in arthritic rats. Besides the immunomodulation via A77 1726, Leflunomide itself induces AHR-ARNT interaction to inhibit hepatic CRP production and attenuate bone erosion in CRPL arthritic rats. Nevertheless, high CRP in CRPH rats upregulates HIF1α, which competes with AHR for ARNT association and interferes Leflunomide-AHR-CRP signaling. Hepatocyte-specific HIF1α deletion or a HIF1α inhibitor Acriflavine re-activates Leflunomide-AHR-CRP signaling to inhibit bone erosion. This study presents a precision medicine-based therapeutic strategy for RA.

11.
Biol Trace Elem Res ; 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31473898

RESUMO

Iron is one of the important trace elements in life activities. Abnormal iron metabolism increases the incidence of many skeletal diseases, especially for osteoporosis. Iron metabolism plays a key role in the bone homeostasis. Disturbance of iron metabolism not only promotes osteoclast differentiation and apoptosis of osteoblasts but also inhibits proliferation and differentiation of osteoblasts, which eventually destroys the balance of bone remodeling. The strength and density of bone can be weakened by the disordered iron metabolism, which increases the incidence of osteoporosis. Clinically, compounds or drugs that regulate iron metabolism are used for the treatment of osteoporosis. The goal of this review summarizes the new progress on the effect of iron overload or deficiency on osteoporosis and the mechanism of disordered iron metabolism on osteoporosis. Explaining the relationship of iron metabolism with osteoporosis may provide ideas for clinical treatment and development of new drugs.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31483238

RESUMO

BACKGROUND: Bone is an important tissue and its normal function requires tight coordination of transcriptional networks and signaling pathways, and many of these networks/ pathways are dysregulated in pathological conditions affecting cartilage and bone. Long non-coding RNA (lncRNA) refers to a class of RNAs with the length of more than 200 nucleotides, lack of protein-coding potential, and exhibiting a wide range of biological functions. Although studies on lcnRNAs are still in their infancy, they have emerged as critical players in bone biology and bone related diseases. The functions and exact mechanism of bone related lncRNAs have not been fully classified yet. OBJECTIVE: To summarize the current literature of lncRNAs on the basis of their role in bone biology and disease, focusing on their emerging molecular mechanism, pathological implications and therapeutic potential. DISCUSSION: A number of lncRNAs have been identified and shown to play important roles in multiple bone cells and bone disease. The function and mechanism of bone related lncRNA remain to be elucidated. CONCLUSION: At present, the major of knowledge is limited to cellular levels and less is known on how lncRNAs could potentially control the development and homeostasis of bone. In the present review, we highlight some lncRNAs in the field of bone biology and bone disease. We also delineate some lncRNAs that might have deep impacts on understanding bone diseases and providing new therapeutic strategies to treat these diseases.

13.
Nat Commun ; 10(1): 3927, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477735

RESUMO

The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P = 3.96 × 10-14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31562080

RESUMO

High frame rate 3-D ultrasound imaging technology combined with super-resolution processing method can visualize 3-D microvascular structures by overcoming the diffraction limited resolution in every spatial direction. However, 3-D superresolution ultrasound imaging using a full 2-D array requires a system with large number of independent channels, the design of which might be impractical due to the high cost, complexity, and volume of data produced. In this study, a 2-D sparse array was designed and fabricated with 512 elements chosen from a density-tapered 2-D spiral layout. High frame rate volumetric imaging was performed using two synchronized ULA-OP 256 research scanners. Volumetric images were constructed by coherently compounding 9-angle plane waves acquired at a pulse repetition frequency of 4500 Hz. Localization-based 3-D super-resolution images of two touching sub-wavelength tubes were generated from 6000 volumes acquired in 12 seconds. In conclusion, this work demonstrates the feasibility of 3-D super-resolution imaging and super-resolved velocity mapping using a customized 2-D sparse array transducer.

15.
Medicine (Baltimore) ; 98(37): e17109, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517844

RESUMO

BACKGROUND: Patients suffering from chemotherapy-induced nausea and vomiting (CINV) might have negative adherence of treatment. Acupoint therapies, including acupuncture, acupressure, acupoints injection, massage, and moxibustion, are safe medical procedures with minimal side effects for CINV, but studies about overall safety and effectiveness of acupoint therapies have not been scientifically and methodically evaluated in recent years. Evaluating the overall safety and effectiveness of acupoint therapies in patients with CINV is the purpose of this review. METHODS AND ANALYSIS: Relevant randomized controlled trials (RCTSs) are being searched in the following electronic databases: PubMed, Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database), Wanfang Data Knowledge Service Platform, and Chinese Biomedical Literature Database (CBM). We will also attempt to obtain the unpublished academic data by contacting the colleague, professor, or Institute of Traditional Chinese Medicine. The RCTs of the acupoint therapies for CINV patients will be searched in the databases from inception to July 2019. The primary outcomes are defined as severity, duration and frequency of nausea or vomiting, or both. The secondary outcomes are defined as any adverse events and quality of life. Performing the meta-analysis by using RevMan version 5 software. Mean difference (MD) or standardized mean difference (SMD) will express the continuous variables, while relative risk (RR) will express the categorical variables. RESULTS: The results of this review will provide a high-quality synthesis to evaluate the effectiveness and safety of acupoint therapies for CINV. CONCLUSION: This review will provide evidence to estimate whether acupoint therapies are effective interventions for CINV. DISSEMINATION: Evidence whether acupoint therapies are effective interventions for CINV will be provided by this systematic review. This knowledge will recommend better acupoint therapies and selections of acupoints which might be helpful in treating CINV. The findings of this systematic review will be disseminated via various forms of presentation and publication of the data in a journal or electronic databases. PROSPERO REGISTRATION NUMBER: CRD42019125538.


Assuntos
Terapia por Acupuntura/normas , Tratamento Farmacológico/métodos , Náusea/etiologia , Vômito/etiologia , Terapia por Acupuntura/métodos , Antineoplásicos/efeitos adversos , Humanos , Náusea/prevenção & controle , Náusea/terapia , Vômito/prevenção & controle , Vômito/terapia
16.
BMC Bioinformatics ; 20(1): 412, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31366320

RESUMO

BACKGROUND: Cartilage damage is a crucial feature involved in several pathological conditions characterized by joint disorders, such as osteoarthritis and rheumatoid arthritis. Accumulated evidences showed that Wnt/ß-catenin pathway plays a role in the pathogenesis of cartilage damage. In addition, it is experimentally documented that lncRNA (long non-coding RNA) HOTAIR plays a key role in the regulation of Wnt/ß-catenin pathway based on directly decreased WIF-1 expression. Further, it is reported that Wnt/ß-catenin pathway is a potent pathway to regulate the expression of MMP-13, which is responsible for degradation of collagen type II in articular cartilage. It is increasingly recognized that systems modeling approach provides an opportunity to understand the complex relationships and direct quantitative analysis of dynamic network in various diseases. RESULTS: A dynamic network of lncRNA HOTAIR-mediated Wnt/ß-catenin pathway regulating MMP-13 is developed to investigate the dynamic mechanism of the network involved in the pathogenesis of cartilage damage. Based on the network modeling, the potential therapeutic intervention point Axin is predicted and confirmed by the experimental validation. CONCLUSIONS: Our study provides a promising strategy for revealing potential dynamic mechanism and assessing potential targets which contribute to the prevention of the pathological conditions related to cartilage damage.


Assuntos
Cartilagem Articular/patologia , Redes Reguladoras de Genes , Terapia de Alvo Molecular , RNA Longo não Codificante/metabolismo , Via de Sinalização Wnt , Proteína Axina/farmacologia , Cartilagem Articular/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , Metaloproteinase 13 da Matriz/metabolismo , Modelos Biológicos , RNA Longo não Codificante/genética , Reprodutibilidade dos Testes , Fatores de Tempo , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/genética
17.
Hum Hered ; 84(1): 34-46, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31466062

RESUMO

In the biomedical field, large amounts of biological and clinical data have been accumulated rapidly, which can be analyzed to emphasize the assessment of at-risk patients and improve diagnosis. However, a major challenge encountered associated with biomedical data analysis is the so-called "curse of dimensionality." For this issue, a novel feature selection method based on an improved binary clonal flower pollination algorithm is proposed to eliminate unnecessary features and ensure a highly accurate classification of disease. The absolute balance group strategy and adaptive Gaussian mutation are adopted, which can increase the diversity of the population and improve the search performance. The KNN classifier is used to evaluate the classification accuracy. Extensive experimental results in six, publicly available, high-dimensional, biomedical datasets show that the proposed method can obtain high classification accuracy and outperforms other state-of-the-art methods.

18.
Biomaterials ; 219: 119395, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31374481

RESUMO

Photothermal therapy, assisted with long-term immunological anti-tumor effect, has great potential in clinical medical practice. Herein, a brand new DNA-template hydrothermal method was developed to prepare novel Co9S8 nanoplatform with outstanding hydrophily and mesoporous internal structure. Based on the mesoporous Co9S8 nanoplatform, MRI-guided enhanced photothermal-immunology "double-hit" synergistic cancer therapy was achieved, through the HSP90 inhibition and immunology activation effect of the loaded epigallocatechin gallate and oxaliplatin. It is noteworthy that the drugs were stepwise released from the nanoplatform under the trigger of pH and heat, respectively. More importantly, the high efficient synergistic cancer therapy and long-term immunological anti-tumor effect were confirmed in vivo. The developed porous nanoplatform, taking accounts of both high efficient tumor ablation and long-term anti-tumor effect, provide a new strategy to the development of next generation nanomedicine for clinical cancer treatment.

19.
Echocardiography ; 36(9): 1675-1681, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31454106

RESUMO

PURPOSE: The primary aim of this study was to evaluate early changes in cardiac function after anthracycline therapy with layer-specific speckle-tracking echocardiography (STE) and mechanical dys-synchrony. METHODS: A total of 78 breast cancer patients (ranging 31~72 years) exposed to anthracycline treatment were recruited in this study. All patients received both conventional two-dimensional speckle-tracking echocardiographs at baseline, as well as after the completion of 2 and 4 cycles of the regimen. Layer-specific longitudinal strain (LS) and circumferential strain (CS) of the 3 myocardial layers (endocardium, mid-myocardium, and epicardium) were automatically measured. Peak systolic dispersion (PSD) was defined as the standard deviation of the time to peak strain of the 18 segments, divided by the RR interval. RESULTS: There were no significant differences in conventional echocardiographic parameters during treatment (all P > .05). Peak endocardium CS at basal level decreased significantly after 2 and 4 cycles compared with baseline (both P = .001), while PSD significantly increased in that same period versus baseline (both P = .000). Endocardium and mid-myocardium LS, peak mid-myocardium and epicardium CS at the basal level, peak CS of all three layers at the papillary level, and peak endocardium and mid-myocardium CS at the apical level all significantly decreased after 4 cycles, compared with baseline and 2 cycles (all P = .000). CONCLUSION: This study showed that myocardial deformation impairment occurred as early as 2 cycles after anthracycline chemotherapy. Endocardium CS at the basal level and left ventricular dys-synchrony index PSD were the initial cardiac abnormalities in anthracycline-treated breast cancer patients.

20.
Mol Immunol ; 114: 260-268, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31398665

RESUMO

Th17 cells are essential for the pathogenesis of inflammatory and autoimmune diseases. In the presence of TGF-ß, the differentiation of Th17 cells can be induced by inflammatory cytokines, especially IL-6, which is mainly produced by antigen presenting cells (APCs); or IL-21, which is derived from T cells. IL-21 is required for IL-6-induced Th17 cell differentiation. However, the key regulators and underlying mechanisms for IL-21-induced Th17 differentiation is still elusive. Here we show that SMAD4 is a key regulator in IL-21-induced Th17 differentiation. SMAD4 deficient naïve T cells can differentiate into Th17 cells in the absence of TGF-ß signaling, and these Th17 cells are pathogenic during EAE. SMAD4 represses Rorc mRNA transcription to constrain IL-21-induced Th17 differentiation in the absence of TGF-ß signaling. While in the presence of TGF-ß, SMAD4 losses its suppressive ability due to the degradation of SKI. Mutation of Y429A or A432E on SMAD4 disrupts the interaction of SKI from SMAD4 and eliminates SMAD4 mediated suppression of Th17 differentiation. SMAD4 is indispensable for SKI binding to Rorc promoter region to regulate Th17 differentiation. Moreover, activin can induce Th17 differentiation in combination with IL-21, and the process is also subjected to the control of SKI and SMAD4. This study therefore elucidates critical mechanism for IL-21-induced Th17 differentiation to indicate SKI and SMAD4 as potential therapeutic targets for treating autoimmune diseases.

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