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1.
In Vivo ; 34(4): 2043-2048, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606180

RESUMO

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a rare type of soft-tissue neoplasm. IMT of the urinary tract is more common in the bladder and kidneys. Prostatic IMT is extremely rare. CASE REPORT: We present a rare case of IMT of the prostate and a literature review on this condition. The patient was a 72-year-old man who presented with urinary symptoms. Transrectal needle biopsy of the prostate revealed prostatic adenocarcinoma with nodular hyperplasia. Radical prostatectomy revealed IMT without residual adenocarcinoma. On immunohistochemical examination, the tumor cells showed positive immunoreactivity for α-smooth muscle actin, CD10, CD34, and desmin but negative immunoreactivities for anaplastic lymphoma kinase (ALK), receptor tyrosine kinase (c-KIT), and S-100 protein. The patient underwent regular follow-up examination. No recurrence was observed 4 months after the diagnosis. CONCLUSION: This was a case of IMT arising in the prostate. Pathologists should be aware of such an entity whenever they see spindle-cell lesions in the transrectal needle biopsy of the prostate.

3.
Cell Death Dis ; 11(7): 497, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32612123

RESUMO

Fusion and apoptosis share a breakdown of the membrane phospholipids asymmetry, modes of which are largely unknown in osteoclastogenesis. Here, we investigated the externalization of phosphatidylserine (PS) and its receptors, and their biological functions in osteoclastogenesis. Strong immunoreactivities in vivo for the PS receptors TIM4, BAI1, and STAB2 were observed in the TRAP-positive multinucleated cells in the alveolar bone that was being remodeled around the developing dental follicles in rats. These receptors were significantly upregulated during M-CSF/RANKL-induced in vitro osteoclastogenesis using mouse bone marrow-derived cells. PS externalization in preosteoclasts was increased by the M-CSF/RANKL treatment. Multinucleation of preosteoclasts was markedly inhibited by antibodies against PS and its receptors. Among the investigated lipid transporter proteins, floppases (Abcb4, Abcc5, and Abcg1) were upregulated, whereas flippases (Atp11c and Atp8a1) downregulated during osteoclastogenesis. Preosteoclast fusion was markedly blocked by the ATPase inhibitor Na3VO4 and siRNAs against Abcc5 and Abcg1, revealing the importance of these lipid transporters in PS externalization. Further, the levels of Cd47 and Cd31, don't-eat-me signal inducers, were increased or sustained in the early phase of osteoclastogenesis, whereas those of AnnexinI and Mfg-e8, eat-me signals inducers, were increased in the late apoptotic phase. In addition, Z-VAD-FMK, a pan caspase inhibitor, had no effect on preosteoclast fusion in the early phase of osteoclastogenesis, whereas Abs against PS, TIM4, and BAI1 decreased osteoclast apoptosis during the late phase. These results suggest that PS externalization is essential for the whole process of osteoclastogenesis and share PS receptors and transporters in the early stage fusion and late stage apoptosis. Therefore, modulation of PS and its receptors could be a useful strategy to develop anti-bone resorptive agents.

4.
Life Sci ; : 118031, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32615186

RESUMO

AIMS: We had previously reported that addition of putrescine to the culture medium was reported to reduce methylmercury toxicity in C17.2 neural stem cells. Here, we have examined the inhibition of methylmercury-induced cytotoxicity by putrescine using ODC1-overexpressing C17.2 cells. MATERIALS AND METHODS: We established stable ODC1-overexpressing C17.2 cells and evaluated methylmercury-induced apoptosis by examining the TUNEL assay and cleaved caspase-3 levels. Mitochondria-mediated apoptosis was also evaluated by reduction of mitochondrial membrane potential and recruitment of Bax and Bak to the mitochondria. KEY FINDINGS: ODC is encoded by ODC1 gene, and putrescine levels in ODC1-overexpressing cells were significantly higher than in control cells. Overexpression of ODC1 and addition of putrescine to the culture medium suppressed DNA fragmentation and caspase-3 activation, which are observed when apoptosis is induced by methylmercury. Moreover, mitochondrial dysfunction and reactive oxygen species (ROS) generation, caused by methylmercury, were also inhibited by the overexpression of ODC1 and putrescine; pretreatment with ODC inhibitor, however, promoted both ROS generation and apoptosis by methylmercury. Finally, we found that Bax and Bak, the apoptosis-promoting factors, to be increased in mitochondria, following methylmercury treatment, and the same was inhibited by overexpression of ODC1. These results suggest that overexpression of ODC1 may prevent mitochondria-mediated apoptosis by methylmercury via increase of putrescine levels. SIGNIFICANCE: Our findings provide important clues to clarify mechanisms involved in the defense against methylmercury toxicity and suggest novel biological functions of putrescine.

6.
Am J Cardiol ; 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32540169

RESUMO

We compared the long-term outcomes and difference in dilatation rates of the ascending aorta after aortic valve (AV) replacement (AVR) between bicuspid and tricuspid AV patients, and evaluated risk factors associated with ascending aorta dilatation and aortic events during the follow-up. Of 1,127 patients who underwent AVR from 1995 to 2015, 259 patients with a dilated ascending aorta (≥40 mm in diameter) were included. The patients were divided into those with bicuspid (group bicuspid aortic valve [BAV], n = 105) and with tricuspid (group tricuspid aortic valve [TAV], n = 154) AV, and a propensity score-matched analysis was performed to match 98 patients in each group. The differences in the dilation rate of the ascending aorta and long-term outcomes were analyzed. Risk factors for ascending aorta dilatation, mortality, and aortic events were identified. Follow-up was completed in 100% of patients with a median follow-up duration of 106.1 [68.8, 163.0] months. The early clinical outcomes and dilation rate of the ascending aorta were similar between the groups. Overall survivals up to 15 years postoperatively were similar between groups BAV and TAV (p = 0.223). Aortic events occurred in 6 patients (groups BAV vs TAV, 2 vs 4;p = 0.678). Preoperative ascending aorta diameter showed a linear relationship with the dilatation rate of ascending aorta (p <0.001) and was related to progressive aortic dilatation and aortic events (odds ratio: 1.25, p <0.001 and hazard ratio = 1.56, p <0.001, respectively). In conclusion, the long-term outcomes and ascending aorta dilatation rate were similar between the BAV and TAV patients up to 15 years after AVR. Bicuspid AV was not a risk factor of mortality or aortic events.

7.
Doc Ophthalmol ; 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32472235

RESUMO

PURPOSE: To report a case of melanoma-associated retinopathy (MAR) with autoantibodies against the transient receptor potential cation channel, subfamily M, member 1 (TRPM1) with asymmetric severe vision loss. METHODS: We evaluated a patient with heel skin melanoma showing progressive vision loss in both eyes confirmed with a baseline ophthalmic examination, fluorescein angiography, spectral domain optical coherence tomography (OCT), visual field test, and full-field electroretinogram (ERG). Immunofluorescence assays and western blot analysis revealed autoantibodies in the patient's serum. RESULTS: The patient's best-corrected visual acuities were 20/50 in the right eye and hand motion in the left eye. Visual field test showed severely depressed visual fields especially in the left eye. Fluorescein angiography and OCT revealed extrafoveal choroidal neovascularization in the left eye. The patient had an electronegative ERG, suggesting MAR, and autoantibodies against TRPM1 and aldolase C were detected in the patient's blood sample. CONCLUSIONS: The clinical features of MAR patients with positive anti-TRPM1 autoantibodies can be manifested as severe vision loss, and the identification of autoantibodies can be helpful for confirming the diagnosis.

8.
Korean J Intern Med ; 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32380800

RESUMO

Background/Aims: This study investigated the prognostic power of corrected QT (QTc) interval in patients with acute heart failure (AHF) according to sex. Methods: We analyzed multicenter Korean Acute Heart Failure registry with patients with AHF admitted from 2011 to 2014. Among them, we analyzed 4,990 patients who were followed up to 5 years. Regarding QTc interval based on 12 lead electrocardiogram, patients were classified into quartiles according to sex. Results: During follow-up with median 43.7 months, 2,243 (44.9%) patients died. The relationship between corrected QT interval and all-cause mortality followed a J-curve relationship. In Kaplan-Meier analysis, both sex had lowest mortality in the second QTc quartile. There were significant prognostic differences between the second and the fourth quartiles in male (log-rank p = 0.002), but not in female (log-rank p = 0.338). After adjusting covariates, the third (hazard ratio [HR], 1.185; 95% confidence interval [CI], 1.001 to 1.404; p = 0.049) and the fourth (HR, 1.404; 95% CI, 1.091 to 1.535; p = 0.003) quartiles demonstrated increased risk of mortality compared to the second quartile in male. In female, however, there was no significant difference across quartiles. QTc interval was associated with 5-year all-cause mortality in J-shape with nadir of 440 to 450 ms in male and 470 to 480 ms in female. Conclusions: QTc interval was an independent predictor of overall death in male, but its significance decreased in female. The relationship between QTc interval and all-cause mortality was J-shaped in both sex.

9.
Reprod Toxicol ; 95: 75-85, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32454085

RESUMO

Maternal smoking during the perinatal period is linked to adverse neonatal outcomes such as low birth weight and birth defects. Numerous studies have shown that cigarette smoke or nicotine exposure has a widespread effect on fetal nerve development. However, there exists a lack of understanding of what specific changes occur at the cellular level on persistent exposure to cigarette smoke during the differentiation of embryonic stem cells (ESCs) into neural cells. We previously investigated the effects of cigarette smoke extract (CSE) and its major component, nicotine, on the neural differentiation of mouse embryonic stem cells (mESCs). Differentiation of mESCs into neural progenitor cells (NPCs) or neural crest cells (NCCs) was induced with chemically defined media, and the cells were continuously exposed to CSE or nicotine during neural differentiation and development. Disturbed balance of the pluripotency state was observed in the NPCs, with consequent inhibition of neurite outgrowth and glial fibrillary acidic protein (Gfap) expression. These inhibitions correlated with the altered expression of proteins involved in the Notch-1 signaling pathways. The migration ability of NCCs was significantly decreased by CSE or nicotine exposure, which was associated with reduced protein expression of migration-related proteins. Taken together, we concluded that CSE and nicotine inhibit differentiation of mESCs into NPCs or NCCs, and may disrupt functional development of neural cells. These results imply that cigarette smoking during the perinatal period potentially inhibits neural differentiation and development of ESCs cells, leading to neonatal abnormal brain development and behavioral abnormalities.

10.
Arch Oral Biol ; 115: 104733, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32408131

RESUMO

OBJECTIVE: This study aimed to determine the expression of chemokine (C-X-C motif) ligand 14 (CXCL14) in pulpal and periodontal cells in vivo and in vitro, and investigate function of CXCL14 and its underlying mechanism in the proliferation and osteogenic differentiation of human periodontal ligament (hPDL) cells. METHODS: To determine the expression level of CXCL14 in adult rat oral tissues and in hPDL cells after application of biophysical forces, RT-PCR, western blot, and histological analyses were performed. The role of CXCL14 in proliferation and osteogenic differentiation of PDL cells was evaluated by measuring dehydrogenase activity and Alizarin red S staining. RESULTS: Strong immunoreactivity against CXCL14 was observed in the PDL tissues and pulpal cells of rat molar, and attenuated apparently by orthodontic biophysical forces. As seen in rat molar, highly expressed CXCL14 was observed in human dental pulp and hPDL cells, and attenuated obviously by biophysical tensile force. CXCL14 expression in hPDL cells was increased in incubation time-dependent manner. Proliferation of hPDL cells was inhibited dramatically by small interfering (si) RNA against CXCL14. Furthermore, dexamethasone-induced osteogenic mineralization was inhibited by recombinant human (rh) CXCL14, and augmented by CXCL14 siRNA. rhCXCL14 increased transforming growth factor-beta1 (TGF- ß1) in hPDL cells. Inhibition of the cell proliferation and osteogenic differentiation of hPDL cells by CXCL14 siRNA and rhCXCL14 were restored by rhTGF-ß1 and SB431542, respectively. CONCLUSION: These results suggest that CXCL14 may play roles as a growth factor and a negative regulator of osteogenic differentiation by increasing TGF-ß1 expression in hPDL cells.

11.
Zootaxa ; 4732(3): zootaxa.4732.3.6, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32230251

RESUMO

The morphologies of the three freshwater stentorid ciliates in Korea, Stentor coeruleus (Pallas, 1766); Stentor muelleri Ehrenberg, 1831, and Stentor tartari Murthy Bai, 1974, were investigated based on live observations and protargol impregnation. The Korean population of S. tartari exhibits the following characteristics: body size 200-355 × 85-135 µm in vivo, 62-106 somatic kineties, 8-13 peristomial kineties, 110-180 adoral membranelles, mostly two macronuclear nodules and 5-18 micronuclei, reddish and colorless cortical granules and the presence of symbiotic algae. We identified S. tartari based on unique characteristics compared to close congeners. Korean populations of S. coeruleus and S. muelleri are congruent with previously described populations in most aspects of their morphologies. Here, for the first time, we report molecular gene sequence information for S. tartari. Small subunit (SSU) rRNA gene sequence-based phylogeny indicates that S. tartari, which has multiple macronuclei, forms a monophyletic group with other Stentor species having a single macronucleus. Our findings based on morphology and SSU rRNA gene sequence information corroborate the hypothesis that the elongated macronucleus evolved from the compact single or multi macronucleus state.


Assuntos
Cilióforos , Animais , China , DNA de Protozoário , Filogenia , República da Coreia
12.
BMC Pulm Med ; 20(1): 71, 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32199453

RESUMO

BACKGROUND: The concurrence of sarcoidosis and primary lung cancer is very rare. We report a very rare case with a delayed diagnosis of primary lung cancer due to its misdiagnosis as worsening of pulmonary sarcoidosis. CASE PRESENTATION: A 68-year-old man presented to the outpatient department for evaluation of a mass in the right hilar area with lymphadenopathies in subcarinal and both interlobar areas on chest computed tomography (CT). Sufficient core samples were obtained from subcarinal and bilateral interlobar lymph nodes using endobronchial ultrasonography (EBUS) guided transbronchial needle aspiration (TBNA). EBUS could not reach the right hilar lymph node due to its high angle. The pathologic findings were consistent with sarcoidosis. After 5 months, chest CT revealed aggravation of the right upper paratracheal lymphadenopathy. Assuming worsening of sarcoidosis, he was prescribed an oral corticosteroid for 5 months. However, follow-up chest CT showed a newly developed right lower paratracheal lymphadenopathy and worsening right hilar lymphadenopathy. Bronchoscopy and EBUS were performed once again. Transbronchial lung biopsy from the right upper lobe and EBUS-TBNA from the right lower paratracheal lymph node revealed adenocarcinoma from the lung. CONCLUSIONS: Although coexistence of sarcoidosis and lung cancer is very rare, the clinician should consider the possibility of accompanying lung cancer in sarcoidosis patients who are not responding to initial corticosteroid therapy.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32096917

RESUMO

BACKGROUND: Muscle wasting, resulting from aging or pathological conditions, leads to reduced quality of life, increased morbidity, and increased mortality. Much research effort has been focused on the development of exercise mimetics to prevent muscle atrophy and weakness. In this study, we identified indoprofen from a screen for peroxisome proliferator-activated receptor γ coactivator α (PGC-1α) inducers and report its potential as a drug for muscle wasting. METHODS: The effects of indoprofen treatment on dexamethasone-induced atrophy in mice and in 3-phosphoinositide-dependent protein kinase-1 (PDK1)-deleted C2C12 myotubes were evaluated by immunoblotting to determine the expression levels of myosin heavy chain and anabolic-related and oxidative metabolism-related proteins. Young, old, and disuse-induced muscle atrophic mice were administered indoprofen (2 mg/kg body weight) by gavage. Body weight, muscle weight, grip strength, isometric force, and muscle histology were assessed. The expression levels of muscle mass-related and function-related proteins were analysed by immunoblotting or immunostaining. RESULTS: In young (3-month-old) and aged (22-month-old) mice, indoprofen treatment activated oxidative metabolism-related enzymes and led to increased muscle mass. Mechanistic analysis using animal models and muscle cells revealed that indoprofen treatment induced the sequential activation of AKT/p70S6 kinase (S6K) and AMP-activated protein kinase (AMPK), which in turn can augment protein synthesis and PGC-1α induction, respectively. Structural prediction analysis identified PDK1 as a target of indoprofen and, indeed, short-term treatment with indoprofen activated the PDK1/AKT/S6K pathway in muscle cells. Consistent with this finding, PDK1 inhibition abrogated indoprofen-induced AKT/S6K activation and hypertrophic response. CONCLUSIONS: Our findings demonstrate the effects of indoprofen in boosting skeletal muscle mass through the sequential activation of PDK1/AKT/S6K and AMPK/PGC-1α. Taken together, our results suggest that indoprofen represents a potential drug to prevent muscle wasting and weakness related to aging or muscle diseases.

14.
Korean J Ophthalmol ; 34(1): 67-75, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32037751

RESUMO

PURPOSE: To investigate prognostic factors related to the surgical outcome of vitrectomy in myopic traction maculopathy (MTM). METHODS: Medical records of patients with MTM who underwent pars plana vitrectomy with internal limiting membrane peeling and follow-up over 12 months were reviewed retrospectively. Best-corrected visual acuity (BCVA), fundoscopic examination and spectral-domain optical coherence tomography findings were evaluated postoperatively. Functional success was defined as visual acuity gain and anatomical success was defined as reduction or resolution of foveoschisis without complications. RESULTS: This study included 40 eyes of 36 patients. BCVA improved from 0.70 ± 0.44 to 0.63 ± 0.57 logarithm of minimum angle of resolution and central macular thickness decreased from 526.6 ± 132.1 to 277.8 ± 92.1 µm at final follow-up. Functional success was achieved in 24 (60.0%) eyes, and 33 (82.5%) eyes reached anatomical success. Presence of foveal detachment (FD) and higher category of myopic maculopathy were associated with both functional (p = 0.014, 0.021, respectively) and anatomical (p = 0.011, 0.022, respectively) failure. Longer preoperative axial length showed an association with functional failure but not with anatomical failure (p = 0.041). In multivariate analysis, FD was the only prognostic factor for both functional and anatomical outcome (p = 0.041, 0.043, respectively). Preoperative BCVA (r² = 0.259, p = 0.001), axial length (r² = 0.172, p = 0.008), and myopic maculopathy category (r² = 0.336, p < 0.001) showed significant correlation with final BCVA. CONCLUSIONS: More severe myopic maculopathy and the presence of FD are associated with poorer functional and anatomical outcomes of pars plana vitrectomy in MTM. Better preoperative BCVA, shorter axial length, and less severe myopic maculopathy are correlated with better final BCVA.

15.
Nat Commun ; 11(1): 328, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949156

RESUMO

Counterfeit medicines are a fundamental security problem. Counterfeiting medication poses a tremendous threat to patient safety, public health, and the economy in developed and less developed countries. Current solutions are often vulnerable due to the limited security levels. We propose that the highest protection against counterfeit medicines would be a combination of a physically unclonable function (PUF) with on-dose authentication. A PUF can provide a digital fingerprint with multiple pairs of input challenges and output responses. On-dose authentication can verify every individual pill without removing the identification tag. Here, we report on-dose PUFs that can be directly attached onto the surface of medicines, be swallowed, and digested. Fluorescent proteins and silk proteins serve as edible photonic biomaterials and the photoluminescent properties provide parametric support of challenge-response pairs. Such edible cryptographic primitives can play an important role in pharmaceutical anti-counterfeiting and other security applications requiring immediate destruction or vanishing features.


Assuntos
Medicamentos Falsificados/administração & dosagem , Medicamentos Falsificados/efeitos adversos , Qualidade de Produtos para o Consumidor , Países em Desenvolvimento , Indústria Farmacêutica , Uso de Medicamentos , Proteínas de Fluorescência Verde , Humanos , Saúde Pública
16.
Am J Ophthalmol ; 213: 125-133, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31987902

RESUMO

PURPOSE: To evaluate and compare the morphologic characteristics of buried optic disc drusen (ODD) and optic disc edema (ODE) by using en face optical coherence tomography (OCT) and OCT angiography (OCTA). DESIGN: Retrospective, cross-sectional study. METHODS: We reviewed the medical records of 61 patients (92 eyes) with buried ODD, 45 patients (62 eyes) with ODE, and 42 normal-appearing fellow eyes examined at 1 referral center between November 1, 2017 and April 30, 2019. Characteristic en face OCT and OCTA findings of buried ODD compared to those of ODE and normal optic discs were investigated. RESULTS: On en face OCT, all buried ODD were visualized as hyperreflective kidney-shaped masses well demarcated from the optic nerve axons, whereas ODE was visualized as ill-defined boundaries confluent with the retinal nerve fibers. On OCTA, 25.0% of the eyes with buried ODD showed a C-shaped vessel density decrease in the nasal radial peripapillary capillary layer, while 40.3% of the eyes with ODE had nonspecific focal vessel density decrease around the optic nerve head. Larger ODD were significantly associated with a vessel density decrease on OCTA (P = .009). The disc diameter positively correlated with the ODD area (r = 0.245; P = .018) and negatively correlated with the ODD height (r = -0.237; P = .023). CONCLUSIONS: En face OCT showed the characteristic features of buried ODD compared to those of ODE or normal optic discs. The demarcation of buried ODD from the optic nerve axons on en face OCT and the poor vascular perfusion of buried ODD on OCTA suggest that buried ODD are materials deposited around the optic disc rather than the herniated optic nerve axon fibers.

17.
Phytother Res ; 34(3): 624-633, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31724257

RESUMO

In this study, we investigated whether 4-hydroxycinnamic acid (HA) has a palliative effect on asthmatic inflammatory responses using a mouse model of ovalbumin (OVA)-induced allergic asthma. The mice were divided into five groups, each consisting of seven females (normal control phosphate-buffered saline); OVA (OVA sensitization/challenge); dexamethasone (DEX, OVA sensitization/challenge + dexamethasone 3 mg/kg); HA-10 and HA-20 OVA sensitization/challenge + HA 10 and 20 mg/kg, respectively). Mice treated with HA showed a reduction in airway hyperresponsiveness and in the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) compared with asthmatic control. HA treatment also reduced the levels of interleukin (IL)-5 and IL-13 in BALF and of OVA-specific immunoglobulin E in the serum compared with asthmatic control. HA treatment relieved airway inflammation and mucus overproduction caused by OVA exposure. Additionally, HA inhibited the increases in levels of nuclear factor kappa B, inducible nitric oxide synthase, and cyclooxygenase-2 that normally occur after OVA exposure. HA treatment also reduced the activity and protein level of matrix metalloproteinase-9. Taken together, HA effectively suppressed asthmatic airway inflammation and mucus production caused by OVA exposure. These findings indicate that HA has the potential to be used as a therapeutic agent for asthma.

18.
J Cell Mol Med ; 24(1): 1151-1156, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31762195

RESUMO

BACKGROUND: Melatonin has various biological activities that improve the health of an individual. We evaluated the effects of melatonin on inflammatory response in chronic obstructive pulmonary disease (COPD), focusing on the regulation of SIRT1 expression. METHODS: To investigate the effect of melatonin, we used cigarette smoke (CS)-induced COPD mouse model and CS condensate (CSC)-stimulated J774 macrophage cells. RESULTS: CSC-stimulated J774 macrophages exhibited increased p65 acetylation with a reduction in SIRT1 expression. However, melatonin induced the enhancement of SIRT1 expression, which eventually decreased p65 acetylation in CSC-stimulated J774 cells. Melatonin-treated mice exhibited an enhancement in SIRT1 expression with the reduction in p65 acetylation, which decreased the level of inflammatory mediators induced by CS. Additionally, SIRT1 inhibitor treatment increased the level of inflammatory mediators, which was accompanied by an increase in p65 acetylation. However, cotreatment with melatonin and an SIRT1 inhibitor reduced the level of inflammatory mediators compared with that by treatment with the SIRT1 inhibitor alone, which was accompanied by elevation in SIRT1 expression and reduction in p65 acetylation. CONCLUSIONS: Overall, the results indicated that melatonin has therapeutic effects against COPD, owing to its property to enhance SIRT1 expression.

19.
Heart ; 106(1): 50-57, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30209124

RESUMO

OBJECTIVE: Myocardial ischaemia is a leading cause of acute heart failure (AHF). However, optimal revascularisation strategies in AHF are unclear. We aimed to compare two revascularisation strategies, coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI), in patients with AHF. METHODS: Among 5625 consecutive patients enrolled prospectively in the Korean Acute Heart Failure registry from March 2011 to February 2014, 717 patients who received CABG or PCI during the index hospitalisation for AHF were included in this analysis. We compared adverse outcomes (death, rehospitalisation for HF aggravation or cardiovascular causes, ischaemic stroke and a composite outcome of death and rehospitalisation for HF aggravation or cardiovascular causes) with the use of propensity score matching. RESULTS: For the propensity score-matched cohort with 190 patients, CABG had a lower risk of all-cause mortality than PCI (83 vs 147 deaths per 1000 patient-years; HR 0.57, 95% CI 0.34 to 0.96, p=0.033) during the median follow-up of 4 years. There was also a trend towards lower rates of rehospitalisation due to cardiovascular events or HF aggravation. Subgroup analysis revealed that the adverse outcomes were significantly lower in the CABG group than in PCI group, especially in patients with old age, three-vessel diseases, significant proximal left anterior descending artery disease and those without left main vessel disease or chronic total occlusion. CONCLUSIONS: Compared with PCI, CABG is associated with significant lower all-cause mortality in patients with AHF. Further studies should evaluate proper revascularisation strategies in AHF. CLINICAL TRIAL REGISTRATION: NCT01389843; Results.

20.
Environ Toxicol ; 35(1): 66-77, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31507073

RESUMO

The heart is the first organ formed in the developing fetus, and abnormal development of the heart is a major cause of fetal death. The adverse effects of cigarette smoke on the heart have been well established, but it is not well understood how cigarette smoke components regulate signaling molecules and cardiac specific functions during the early differentiation stage of the embryonic heart. In this study, we identified changes in the size of mouse embryoid bodies (mEBs) in response to treatment with cigarette smoke extract (CSE) via regulation of HDAC2, p53, p21, and cyclin D1 protein expression, which are cardiac differentiation and cell-cycle markers, respectively. In addition, exposure of mouse embryonic stem cells (mESCs) to cigarette smoke components inhibited myocardial differentiation and development through the expression of HDAC1, HDAC2, GATA4, NKX2-5, TBX5, HAND1, and Troponin I. Long-term exposure studies showed that CSE and nicotine may delay the development of mouse cardiomyocytes from mESCs and inhibit the contractibility, which is a fundamental function of the heart. Taken together, these findings suggest that cigarette smoke components, including nicotine, may affect abnormal myocardial differentiation and development.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Células-Tronco Embrionárias Murinas/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Fumaça/efeitos adversos , Tabaco/toxicidade , Animais , Ciclo Celular/efeitos dos fármacos , Ciclina D1/metabolismo , Histona Desacetilase 2/metabolismo , Camundongos , Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Embrionárias Murinas/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fumar/efeitos adversos
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