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1.
Int J Cancer ; 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31472018

RESUMO

Kirsten rat sarcoma (KRAS) mutant cancers, which constitute the vast majority of pancreatic tumors, are characterized by their resistance to established therapies and high mortality rates. Here, we developed a novel and extremely effective combinational therapeutic approach to target KRAS mutant tumors through the generation of a cytotoxic oxidative stress. At high concentrations, Vitamin C (VC) is known to provoke oxidative stress and selectively kill KRAS mutant cancer cells, although its effects are limited when it is given as monotherapy. We found that the combination of VC and the oxidizing drug arsenic trioxide (ATO) is an effective therapeutic treatment modality. Remarkably, its efficiency is dependent on chirality of VC as its enantiomer D-VC is significantly more potent than the natural L-VC. Thus, our results demonstrate that the oxidizing combination of arsenic trioxide and D-VC is a promising approach for the treatment of KRAS mutant human cancers. This article is protected by copyright. All rights reserved.

2.
New Phytol ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31491809

RESUMO

Seed germination is a crucial transition point in plant life and is tightly regulated by environmental conditions through the coordination of two phytohormones, gibberellin and abscisic acid (ABA). To avoid unfavorable conditions, plants have evolved safeguard mechanisms for seed germination. Here, we report a novel function of the Arabidopsis MADS-box transcription factor ARABIDOPSIS NITRATE REGULATED 1 (ANR1) in seed germination. ANR1 knockout mutant is insensitive to ABA, salt, and osmotic stress during the seed germination and early seedling development stages, whereas ANR1-overexpressing lines are hypersensitive. ANR1 is responsive to ABA and abiotic stresses and upregulates the expression of ABI3 to suppress seed germination. ANR1 and ABI3 have similar expression pattern during seed germination. Genetically, ABI3 acts downstream of ANR1. Chromatin immunoprecipitation and yeast-one-hybrid assays showed that ANR1 could bind to the ABI3 promoter to regulate its expression. In addition, ANR1 acts synergistically with AGL21 to suppress seed germination in response to ABA as evidenced by anr1 agl21 double mutant. Taken together, our results demonstrate that the ANR1 plays an important role in regulating seed germination and early post-germination growth. ANR1 and AGL21 together constitutes a safeguard mechanism for seed germination to avoid unfavorable conditions.

3.
PLoS Comput Biol ; 15(9): e1007344, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31504033

RESUMO

Prostate cancer (PCa) is the most commonly diagnosed malignancy and the second leading cause of cancer-related death in American men. Androgen deprivation therapy (ADT) has become a standard treatment strategy for advanced PCa. Although a majority of patients initially respond to ADT well, most of them will eventually develop castration-resistant PCa (CRPC). Previous studies suggest that ADT-induced changes in the immune microenvironment (mE) in PCa might be responsible for the failures of various therapies. However, the role of the immune system in CRPC development remains unclear. To systematically understand the immunity leading to CRPC progression and predict the optimal treatment strategy in silico, we developed a 3D Hybrid Multi-scale Model (HMSM), consisting of an ODE system and an agent-based model (ABM), to manipulate the tumor growth in a defined immune system. Based on our analysis, we revealed that the key factors (e.g. WNT5A, TRAIL, CSF1, etc.) mediated the activation of PC-Treg and PC-TAM interaction pathways, which induced the immunosuppression during CRPC progression. Our HMSM model also provided an optimal therapeutic strategy for improving the outcomes of PCa treatment.

4.
Molecules ; 24(18)2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31500191

RESUMO

Numerous reports have shown that conjugated benzimidazole derivatives possess various kinds of biological activities, including anticancer properties. In this report, we designed and synthesized 24 new molecules comprising a benzimidazole ring, arene, and alkyl chain-bearing cyclic moieties. The results showed that the N-substituted benzimidazole derivatives bearing an alkyl chain and a nitrogen-containing 5- or 6-membered ring enhanced the cytotoxic effects on human breast adenocarcinoma (MCF-7) and human ovarian carcinoma (OVCAR-3) cell lines. Among the 24 synthesized compounds, (2E)-1-(1-(3-morpholinopropyl)-1H-benzimidazol-2 -yl)-3-phenyl-2-propen-1-one) (23a) reduced the proliferation of MCF-7 and OVCAR-3 cell lines demonstrating superior outcomes to those of cisplatin.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31494973

RESUMO

BACKGROUND: Recent evidence suggests melasma to be a photoaging disorder. Triple combination creams (TCC; fluocinolone acetonide 0.01%, hydroquinone 4%, and tretinoin 0.05%) remain the gold standard treatment. Picosecond alexandrite laser treatment using a diffractive lens array (DLA) has been identified to be effective for improving photoaging conditions. OBJECTIVE: We aimed to compare the efficacy and tolerance of the picosecond alexandrite laser with those of DLA and TCC in female Asian patients with melasma. METHODS: Twenty-nine patients were randomly assigned to group A1 (3 laser sessions at 4-week intervals), A2 (5 laser sessions at 4-week intervals), or B (TCC daily for at least 8 weeks and then tapered until the final evaluation). The Melasma Area, Severity Index (MASI) score and VISIA were assessed at baseline, week 12, and week 20. By week 20, the follow-up periods for groups A1 and A2 were 3 months and 1 month, respectively. RESULTS: Nine, 11, and 6 participants in groups A1, A2, and B completed the study, respectively. MASI scores were significantly improved in all 3 groups at weeks 12 and 20. In groups A1, A2, and B, the improvement rates at week 20 were 53%, 38%, and 50%, respectively. VISIA® analysis additionally revealed a significant improvement in spots, porphyria, pores, and brown spots after 3 laser sessions (p<0.05). Group A2 showed greater improvements than group A1 in terms of spots, wrinkles, and pores; however, only red areas were significantly different (p<0.001). All side effects in the 3 groups were transient and gradually subsided after 1 to 3 months. CONCLUSION: Picosecond alexandrite laser treatment using DLA showed comparable efficacy with TCC for the treatment of melasma. Improvements in texture, spots, wrinkles, and pores were observed in the laser groups. Patients with melasma lesions that exhibit telangiectasia may benefit from additional laser treatment sessions. This article is protected by copyright. All rights reserved.

6.
J Mol Cell Cardiol ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31445005

RESUMO

AIMS: Doxorubicin (DOX), a widely used powerful chemotherapeutic component for cancer treatment, can give rise to severe cardiotoxicity that limits its clinical use. Pyroptosis is characterized by proinflammation and has been defined as a new type of programmed cell death in recent years. However, whether the DOX-induced cardiotoxicity is related to pyroptosis, and if so, which genes are involved in this process is largely unknown. In this study, we sought to identify the effect of DOX on cardiomyocyte pyroptosis and further reveal the underlying regulatory mechanism. METHODS AND RESULTS: In vitro and in vivo experiments showed that DOX treatment induced cardiomyocyte pyroptosis as evidenced by increased cell death and upregulated expression levels of NLR family pyrin domain containing 3 (NLRP3), caspase-3, IL-1ß, IL-18 and GMDSD-N. Inhibition of NLRP3 rescued the DOX-induced pyroptosis. qRT-PCR showed that TINCR lncRNA was upregulated by DOX treatment and knockdown of TINCR reversed the DOX-induced pyroptosis both in vitro and in vivo. Mechanistic investigations revealed that TINCR increased NLRP3 level via recruiting IGF2BP1 to enhance NLRP3 mRNA. And the effect of TINCR on cardiomyocyte pyroptosis was attenuated by the inhibition of NLRP3 or IGF2BP1. Finally, TINCR was not involved in DOX-induced pyroptosis in cancer cells. CONCLUSION: TINCR mediates the DOX-induced cardiotoxicity and pyroptosis in an IGF2BP1-dependent manner. Therefore, TINCR may serve as a promising therapeutic target to overcome the cardiotoxicity of chemotherapy for cancer therapy.

7.
Vaccine ; 37(36): 5147-5152, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31377076

RESUMO

The study aimed to investigate the impact of 13-valent pneumococcal conjugate vaccine (PCV13) immunization on the overall pneumococcal disease in children in Taiwan by surveillance of culture-confirmed pneumococcal disease (CCPD). This study was conducted in a medical center from 2012 to 2016. Clinical isolates of Streptococcus pneumoniae were prospectively collected from pediatric patients. Serotyping, multi-locus sequence typing, and antimicrobial susceptibility testing were performed. A total of 473 patients with CCPD, including 58 with invasive pneumococcal disease (IPD), were identified. The incidence of CCPD per 10,000 admissions decreased from 71.7 in 2012 to 27.0 in 2016. The proportion of additional PCV13 serotypes significantly decreased from 52.0% in 2012 to 21.7% in 2015 but increased slightly to 26.7% because of serotype 19A in 2016 (P < 0.0001). The proportion of non-vaccine serotypes (NVTs) increased significantly from 18.4% in 2012 to 66.7% in 2016, but the increase of the incidence of CCPD caused by NVTs was not considered significant (P = 0.0885). Genotyping identified predominant clones, ST6315A, ST8315B, and ST166/33823A, for major NVTs. The penicillin non-susceptibility of PCV13 serotypes was significantly higher than that of NVTs (P < 0.0001). Surveillance of CCPD appears superior to IPD alone for evaluation of the overall impact of pneumococcal immunization. Serotype replacement occurred quickly after the use of PCV13, while the incidence of NVT infection did not show a significant increase in children over the years. The gradual introduction of PCV13 into national immunization program is effective in reducing overall pneumococcal disease in children.

8.
Cell Commun Signal ; 17(1): 100, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429764

RESUMO

BACKGROUND: Androgen receptor (AR) plays important role in the development, progression, and metastasis of prostate cancer (PCa). Caffeic acid phenethyl ester (CAPE) is the main component of honey bee propolis. We determined if CAPE affects the signaling and stability of AR in PCa cells. METHODS: Effects of CAPE on AR transcriptional activity and localization were determined by reporter gene assay and immunofluorescent microscopy. Western blotting, fluorescent polarization, computer simulation, and animal experiment were performed to investigate the molecular mechanism how CAPE reduces the stability of AR. RESULTS: CAPE treatment dose-dependently suppressed the transcriptional activity of AR as well as the protein levels of AR and its target gene PSA. Cyclohexamide treatment revealed that androgen stabilized AR protein, but AR stability was diminished by CAPE. Fluorescence microscopy demonstrated that androgen promoted the nucleus translocation of AR in PCa cells, while treatment with CAPE reduced protein level of AR in both nucleus and cytoplasm. CAPE treatment suppressed the phosphorylation of Ser81 and Ser213 on AR, which regulates the stability of AR. CDK1 and AKT are the kinases phosphorylating Ser81 and Ser213 on AR, respectively. CAPE treatment significantly reduced the protein level and activity of CDK1 and AKT in PCa cells. Overexpression of CDK1 or AKT rescued the AR protein level under CAPE treatment. CONCLUSIONS: Our results suggested that CAPE treatment reduced AR stability and AR transcriptional activity in PCa cells, implying the possibility of using CAPE as a treatment for advanced PCa.

9.
Chem Pharm Bull (Tokyo) ; 67(8): 778-785, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366827

RESUMO

Herbal formulae have a long history in clinical medicine in Asia. While the complexity of the formulae leads to the complex compound-target interactions and the resultant multi-target therapeutic effects, it is difficult to elucidate the molecular/therapeutic mechanism of action for the many formulae. For example, the Hua-Yu-Qiang-Shen-Tong-Bi-Fang (TBF), an herbal formula of Chinese medicine, has been used for treating rheumatoid arthritis. However, the target information of a great number of compounds from the TBF formula is missing. In this study, we predicted the targets of the compounds from the TBF formula via network analysis and in silico computing. Initially, the information of the phytochemicals contained in the plants of the herbal formula was collected, and subsequently computed to their corresponding fingerprints for the sake of structural similarity calculation. Then a compound structural similarity network infused with available target information was constructed. Five local similarity indices were used and compared for their performance on predicting the potential new targets of the compounds. Finally, the Preferential Attachment Index was selected for it having an area under curve (AUC) of 0.886, which outperforms the other four algorithms in predicting the compound-target interactions. This method could provide a promising direction for identifying the compound-target interactions of herbal formulae in silico.


Assuntos
Medicamentos de Ervas Chinesas/química , Algoritmos , Artrite Reumatoide/tratamento farmacológico , Composição de Medicamentos , Interações de Medicamentos , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Medicina Tradicional Chinesa
10.
Mar Pollut Bull ; 146: 215-224, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31426149

RESUMO

Microplastics (MPs) contamination has been recognized as one of major threats to coastal marine environments. Although studies evidenced severe MPs contaminations to the Pacific Ocean, environmental implications of MPs concentrations, distributions, and characteristics have not been evaluated in sufficient detail. Here, we report on the distribution, abundance, and characteristics of MPs at the surface of the Northwestern Pacific Ocean, from which environmental implications are assessed. A manta trawl with a mesh size of ~330 µm and a rectangular net opening of 0.45 × 1 m was used to collect MPs samples on May 11-June 3, 2018. The MPs samples were sequentially isolated, digested, filtered, and characterized using an optical microscope, micro-Raman spectroscopy, and scanning electron microscopy. The results indicate the heterogeneity in abundance, shapes, color, and sizes of MPs. The study provides strong environmental implications such as sources, environmental degradation, residence time, transportation routes, and biological interactions.

11.
Acta Biomater ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31437637

RESUMO

Human amniotic membrane (AM) offers unique advantages as a matrix to support the transplantation of limbal stem cells (LSCs) due to its inherent pro-regenerative and anti-inflammatory properties. However, the widespread use of AM in clinical treatments of ocular surface disorders is limited by its weak mechanical strength and fast degradation, and high cost associated with preserving freshly isolated AM. Here we constructed a composite membrane consisting of an electrospun bioabsorbable poly(ε-caprolactone) (PCL) nanofiber mesh to significantly improve the ultimate tensile strength, toughness, and suture retention strength by 4-10-fold in comparison with decellularized AM sheet. The composite membrane showed extended stability and conferred longer-lasting coverage on wounded cornea surface compared with dAM. The composite membrane maintained the pro-regenerative and immunomodulatory properties of dAM, promoted LSC survival, retention, and organization, improved re-epithelialization of the defect area, and reduced inflammation and neovascularization. This study demonstrates the translational potential of our composite membrane for stem cell-based treatment of ocular surface damage. STATEMENT OF SIGNIFICANCE: Human decellularized amniotic membrane (dAM) has been widely shown as a biodegradable and bioactive matrix for regenerative tissue repair. However, the weak mechanical property has limited its widespread use in the clinic. Here we constructed a composite membrane using a layer of electrospun poly(ε-caprolactone) (PCL) nanofiber mesh to reinforce the dAM sheet through covalent interfacial bonding, while retaining the unique bioactivity of dAM. In a rabbit model of limbal stem cell (LSC) deficiency induced by alkaline burn, we demonstrated the superior property of this PCL-dAM composite membrane for repairing damaged cornea through promoting LSC transplantation, improving re-epithelialization, and reducing inflammation and neovascularization. This new composite membrane offers great translational potential in supporting stem cell-based treatment of ocular surface damage.

12.
Environ Pollut ; 254(Pt B): 113031, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31454569

RESUMO

Myopia is caused by complex genetic and environmental factors. However, information regarding the effect of long-term exposure to air pollutants on the risk of development of myopia is lacking. We collected data from two linked databases: the Taiwan National Health Insurance Research Database (NHIRD) and the Taiwan Air Quality-Monitoring Database (TAQMD). A total of 15,822 children (16.3%) were diagnosed with myopia within the cohort. The incidence rate of myopia increased with exposure to increasing concentrations of particulate matter (PM2.5) and nitrogen oxides (NOx), increasing from 15.8 to 24.5 and from 13.7 to 34.4, per 1000 person-years, respectively. The adjusted hazard ratio for myopia increased with elevated PM2.5 and NOx exposure concentrations in Q4 to 1.57 and 2.60, respectively, compared to those exposed to the corresponding concentrations in Q1. In the animal experiments, PM2.5 induced myopia in hamsters by enhancing inflammation and was inhibited by resveratrol treatment compared to the control group. The change in axial length in the PM2.5 group was 0.386 ± 0.069 mm versus 0.287 ± 0.086 mm in the control group and 0.257 ± 0.059 mm in the PM2.5 + resveratrol group. We provide both clinical and experimental correlations that exposure to ambient air pollutants is associated with the pathogenesis of myopia.

13.
Thorac Cancer ; 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31407523

RESUMO

BACKGROUND: Chest radiography (CXR) is the main tool used to detect pulmonary nodules. Lateral views of CXR are less effective and the aim of our study was to develop a rotation angle recommendation model to obtain the best oblique CXR with significantly increased contrast between lesions and surrounding normal structures in order to enhance the detection rate for potential obscured lesions on traditional posterior and anterior (PA) CXR. METHODS: A total of 140 subjects receiving low-dose lung computed tomography (CT) screening were enrolled from the health check-up database. An additional 14 cases with lung lesions on chest CT were included. Demography was also reviewed. Gross, left and right cardiothoracic ratios (CTR) were measured. All CT images were transformed to CXR to detect the best rotation angles and produce different views of CXR. Contrast ratio was calculated in the transformed CXR from CT with lesions. Comparison of contrast ratio among oblique, posterior-anterior and lateral views was performed. RESULTS: CXR shows smaller gross CTR and left CTR but larger heart width and thoracic width in men than in women. Correlation evaluation displays gross CTR, heart width and left CTR are positively correlated with age only for the women group. The most important factor for the best rotation angle is right CTR for left rotation angle and left CTR for right rotation angle. The contrast ratio of the lesion to surrounding structures is significantly better on the oblique views in the designed angles than that on the traditional views. CONCLUSION: CXR oblique views in the assigned angle from the 10-degree rotation angle recommendation are able to enhance contrast ratio between the possible obscured lesions and surrounding structures on CXR.

15.
Virology ; 536: 16-19, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31394407

RESUMO

Kaposi's sarcoma-associated herpesvirus (KSHV) causes several cancers such as Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). PD-1/PD-Ls immune checkpoint molecules play important roles in cancer cell immune escape. The expression of PD-1/PD-Ls and their regulation by oncogenic viruses, in particular KSHV, remain largely undefined. Here we demonstrate strong PD-1/PD-L1/PD-L2 expression in KS tissues from a cohort of HIV + patients. We found that induction of KSHV lytic reactivation significantly upregulates PD-L1 expression on infected tumor cells, potentially through several major cellular signaling pathways and IL-1ß, which may represent a novel mechanism for virus-associated tumor cell immune escape.

16.
Photobiomodul Photomed Laser Surg ; 37(9): 559-566, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31411549

RESUMO

Objective: To evaluate the efficacy and safety of picosecond (ps) 755-nm alexandrite laser with a diffractive lens array (DLA) generating laser-induced optical breakdown, which may be beneficial for melasma treatment. Background: Melasma is notorious for difficult to treat with any modality setting. Recently, picosecond alexandrite laser with DLA seems promising for dealing with it without intolerable complications. Methods: Twenty (N = 20) Asian female melasma patients with Fitzpatrick skin type IV were recruited for 3 treatment sessions of picosecond 755-nm alexandrite laser with DLA at a 4- to 6-week interval. The pulse duration was 750 ps. An 8-mm spot size and the fluence of 0.4 J/cm2 was used over the target area with 2 passes per treatment area and around 2000-2500 passes in total. The repetition rate was 10 Hz. Melasma Area and Severity Index (MASI) score and VISIA® imaging system analysis were utilized for evaluation before treatment and 4 weeks after the completion of the third treatment session. The clinical improvement and adverse events were assessed by the physicians and patients, respectively. Results: The median age of the patients was 45 years (from 27 to 55 years). In the physicians' evaluation, 40% (n = 8) of patients showed good improvement and 40% (n = 8) of patients showed moderate improvement. The mean MASI score before and after laser therapy showed significant improvement from 9.0 ± 4.8 to 6.5 ± 3.7 (p < 0.001). VISIA analysis of the forehead presented significant improvement in spots (p = 0.007) and porphyrins (p = 0.032). Some patients experienced erythema (25%), pruritus (20%), and scaling (20%) but subsided within few days of using emollients and sunscreen. Only 5% (n = 1) of patients developed mild postinflammatory hyperpigmentation, which also subsided in 3 weeks. Conclusions: Three sessions of picosecond 755-nm alexandrite laser with a DLA were effective for melasma treatment in Asian patients with minimal side effects.

17.
Neuropharmacology ; : 107736, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31398381

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by social interaction impairment, stereotypical/repetitive behaviors and emotional deregulation. The endocannabinoid (eCB) system plays a crucial role in modulating the behavioral traits that are typically core symptoms of ASD. The major molecular mechanisms underlying eCB-dependent long-term depression (eCB-LTD) are mediated by group 1 metabotropic glutamate receptor (mGluR)-induced removal of postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Recently, modulation of anandamide (AEA), one of the main endocannabinoids in the brain, has been reported to alter social behaviors in genetic models of ASD. On this basis, we investigated the effects of treatment and the synaptic mechanism underlying AEA-mediated signaling in prenatal exposure to valproic acid (VPA) in rats. We found that the social deficits, repetitive behaviors and abnormal emotion-related behaviors in VPA-exposed offspring were improved after treatment with an inhibitor of AEA degrading enzyme, URB597. Using an integrative approach combing electrophysiological and cellular mechanisms, the results showed that the impaired eCB-LTD, abnormal mGluR-mediated LTD (mGluR-LTD) and decreased removal of AMPAR subunits GluA1 and GluA2 were reversed by URB597 in the prefrontal cortex (PFC) of VPA-exposed offspring. Taken together, these results provide the first evidence that rescue of the ASD-like phenotype by URB597 is mediated by enhancing the mechanism of removal of AMPAR subunits GluA1/2 underlying AEA signaling in the PFC in a VPA-induced model of ASD.

18.
Mol Med Rep ; 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31432174

RESUMO

Heterotopic ossification (HO) refers to the appearance of osteoblasts in soft tissues under pathological conditions, such as trauma or infection. HO arises in an unpredictable way without any recognizable initiation. Activin receptor­like kinase­2 (ALK2) is a type I cell surface receptor for bone morphogenetic proteins (BMPs). The dysregulation of ALK2 signaling is associated with a variety of diseases, including cancer and HO. At present, the prevention and treatment of HO in the clinic predominantly includes nonsteroidal anti­inflammatory drugs (NSAIDs), bisphosphonates and other drug treatments, low­dose local radiation therapy and surgical resection, rehabilitation treatment and physical therapy. However, most of these therapies have adverse effects. These methods do not prevent the occurrence of HO. The pathogenesis of HO is not being specifically targeted; the current treatment strategies target the symptoms, not the disease. These treatments also cannot solve the fundamental problem of the occurrence of HO. Therefore, scholars have been working to develop targeted therapies based on the pathogenesis of HO. The present review focuses on advances in the understanding of the underlying mechanisms of HO, and possible options for the prevention and treatment of HO. In addition, the role of ALK2 in the process of HO is introduced and the progress made towards the targeted inhibition of ALK2 is discussed. The present study aims to offer a platform for further research on possible targets for the prevention and treatment of HO.

19.
Am J Emerg Med ; 37(8): 1446-1449, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31378298

RESUMO

BACKGROUND: Emergency medical services (EMSs) are used by approximately 383,000 patients with out-of-hospital sudden cardiac arrest (SCA) in the United States. Hence, it is crucial to implement automated external defibrillator (AED) programs to prepare responders for an SCA emergency. Taiwanese pass legislature to enforce AED installation in 8 mandatory areas since 2013. Our study investigated the efficacy of the policy regarding AED installation. MATERIALS AND METHODS: We collected data of patients who had sudden cardiac arrest (SCA) in pre-hospital settings, and received resuscitative efforts, including cardiopulmonary resuscitation or defibrillation with AEDs. The data were from July 11, 2013 to July 31, 2015. In total, 209 adult patients were documented by on-site caregivers of different facilities, and a report was mailed to the central health and welfare unit. RESULTS: Schools, large-scale gathering places, and special institutions used AEDs the most, accounting for 33 (15.3%) cases. From non-mandatory AED areas, long-term care facilities had the maximum cases of AED use (32 cases; 14.9%). With commuting stations as a reference, long-distance transport had the lowest odds ratio (OR) of 0.481 (95% confidence interval [CI], 0.24-0.962). The OR for schools, large-scale gathering places, and special institutions was 4.474 (95% CI: 2.497-8.015). Regarding failure of return of spontaneous circulation (ROSC), the OR for the ≥80-year age group was higher than that for the 20-39-year age group. CONCLUSIONS: The policy regarding the legislation to install AEDs in mandatory areas improved AED accessibility. Elderly patients aged ≥80 years have a higher rate of ROSC failure.

20.
Biosci Rep ; 39(8)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31341010

RESUMO

Heterotopic ossification (HO) is the aberrant formation of mature, lamellar bone in nonosseous tissue. Fibrodysplasia ossificans progressiva (FOP) is a rare and devastating genetic disorder that causes progressive HO in the ligaments, tendons, and muscles throughout the body. FOP is attributed to an autosomal mutation in activin receptor-like kinase 2 (ALK2), a bone morphogenetic protein (BMP) type I receptor. Initial studies show that mutant ALK2 drives HO by constitutively activating the BMP signaling pathway. Recently, mutant ALK2 has been shown to transduce Smad1/5 signaling and enhance chondrogenesis, calcification in response to Activin A, which normally signals through Smad2/3 and inhibits BMP signaling pathway. Furthermore, Activin A induces heterotopic bone formation via mutant ALK2, while inhibition of Activin A blocks spontaneous and trauma-induced HO. In this manuscript, we describe the molecular mechanism of the causative gene ALK2 in FOP, mainly focusing on the prominent role of Activin A in HO. It reveals a potential strategy for prevention and treatment of FOP by inhibition of Activin A. Further studies are needed to explore the cellular and molecular mechanisms of Activin A in FOP in more detail.

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