Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 623
Filtrar
1.
Am J Otolaryngol ; 42(1): 102767, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33166858

RESUMO

PURPOSE: This prospective randomized case-control study was performed to compare the surgical outcomes of our swing-door overlay tympanoplasty with or without absorbable gelatine sponge (AGS, gelfoam) packing in the middle ear cavity, according to the surgical procedure. METHODS: Fifty-seven patients who underwent swing-door overlay tympanoplasty by a single surgeon were enrolled in the study. The data of 30 patients of the gelfoam-packing group (GPG) and 27 patients of the non-gelfoam-packing group (NGPG) were prospectively collected and compared. RESULTS: Closure of the tympanic membrane was found to be successful in all patients at postoperative 3 months evaluation. NGPG showed a statistically better healing process compared to GPG; earlier epithelialization and less fascia edema in NGPG than in GPG (P < 0.05). The air-bone gap (ABG) measured at postoperative 1 and 2 months was smaller in NGPG than GPG, although there were no statistical differences. CONCLUSION: This study revealed earlier healing process and faster recovery of ABG in NGPG, thereby indicating that the gelfoam in the middle ear may interfere with both hearing recovery and the healing process of neodrum.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33184024

RESUMO

BACKGROUND: Current guidelines for the treatment of asthma and chronic obstructive pulmonary disease overlap (ACO) recommend initial treatment using inhaled corticosteroids (ICSs) plus 1 or more bronchodilators. OBJECTIVE: To clarify which therapeutic effect is better between the ICS + long-acting ß2 agonist (LABA) and ICS + LABA + long-acting muscarinic antagonist (LAMA) treatment in patients with ACO. METHODS: We conducted a multicenter, 48-week, randomized, noninferiority trial. Patients with ACO were enrolled if they were treated with a moderate to high dose of ICS + LABA. In total, 303 patients were involved in the present trial, with 149 receiving ICS + LABA + LAMA. The primary end point was the time to first exacerbation. Secondary outcomes included changes in FEV1, forced vital capacity, FEV1/forced vital capacity ratio, asthma control, blood eosinophil count, and fractional exhaled nitric oxide. RESULTS: In the ICS + LABA treatment group, 29 of 154 patients (18.83%) experienced exacerbation, whereas 28 of 149 patients (18.79%) experienced exacerbation in the ICS + LABA + LAMA treatment group. The results of this noninferiority study were ultimately inconclusive (hazard ratio, 1.1; 95% CI, 0.66-1.84). However, the patients treated with the addition of LAMA showed significant improvements in FEV1 and forced vital capacity (P < .001). Asthma control did not improve in either group. CONCLUSIONS: Although this study was unable to conclude that ICS + LABA treatment is not inferior to ICS + LABA + LAMA in terms of exacerbation, it is obvious that the ICS + LABA + LAMA treatment group had improved lung function in ACO.

3.
Biomolecules ; 10(11)2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33172112

RESUMO

Lung cancer is the major cause of cancer-associated death worldwide, and development of new therapeutic drugs is needed to improve treatment outcomes. Three-dimensional (3D) tumorspheroids offer many advantages over conventional two-dimensional cell cultures due to the similarities to in vivo tumors. We found that isoharringtonine, a natural product purified from Cephalotaxus koreana Nakai, significantly inhibited the growth of tumorspheroids with NCI-H460 cells in a dose-dependent manner and induced apoptotic cell death in our 3D cell culture system. On the other hand, A549 tumorspheroids displayed low sensitivity to isoharringtonine-induced apoptosis. Nuclear receptor subfamily 4 group A member 1 (NR4A1) is an orphan nuclear receptor known to regulate proliferation and apoptosis of cancer cells. We observed that knockdown of NR4A1 dramatically increased isoharringtonine-induced cancer cell death in A549 tumorspheroids by activating the intrinsic apoptosis pathway. Furthermore, treatment with combined isoharringtonine and iNR4A1 significantly inhibited multivulva formation in a Caenorhabditis elegans model and tumor development in a xenograft mouse model. Taken together, our data suggest that isoharringtonine is a potential natural product for treatment of non-small cell lung cancers, and inhibition of NR4A1 sensitizes cancer cells to anti-cancer treatment.

4.
PLoS One ; 15(11): e0242274, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33216792

RESUMO

Various incurable eye diseases in companion animals often result in phthisis bulbi and eye removal surgery. Currently, the evisceration method using silicone balls is useful in animals; however, it is not available to those with impaired cornea or severe ocular atrophy. Moreover, ocular implant and prostheses are not widely used because of the diversity in animal size and eye shape, and high manufacturing cost. Here, we produced low-cost and customized artificial eyes, including implant and prosthesis, using computer-aided design and three-dimensional (3D) printing technique. For 3D modeling, the size of the artificial eyes was optimized using B-mode ultrasonography. The design was exported to STL files, and then printed using polycaprolactone (PCL) for prosthesis and mixture of PCL and hydroxyapatite (HA) for ocular implant. The 3D printed artificial eyes could be produced in less than one and half hour. The prosthesis was painted using oil colors and biocompatible resin. Two types of eye removal surgery, including evisceration and enucleation, were performed using two beagle dogs, as a preliminary study. After the surgery, the dogs were clinically evaluated for 6 months and then histopathological evaluation of the implant was done. Ocular implant was biocompatible and host tissue ingrowth was induced after in vivo application. The custom-made prosthesis was cosmetically excellent. Although long-term clinical follow-up might be required, the use of 3D printed-customized artificial eyes may be beneficial for animals that need personalized artificial eye surgery.

5.
Invest Ophthalmol Vis Sci ; 61(12): 24, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33107903

RESUMO

Purpose: To assess the therapeutic effects of fursultiamine on choroidal neovascularization (CNV) through its modulation of inflammation and metabolic reprogramming in the retinal pigment epithelium (RPE). Methods: The anti-angiogenic effects of fursultiamine were assessed by measuring vascular leakage and CNV lesion size in the laser-induced CNV mouse model. Inflammatory responses were evaluated by quantitative polymerase chain reaction, western blot, and ELISA in both CNV eye tissues and in vitro cell cultures using ARPE-19 cells or primary human RPE (hRPE) cells under lipopolysaccharide (LPS) treatment or hypoxia. Mitochondrial respiration was assessed by measuring oxygen consumption in ARPE-19 cells treated with LPS with or without fursultiamine, and lactate production was measured in ARPE-19 cells subjected to hypoxia with or without fursultiamine. Results: In laser-induced CNV, fursultiamine significantly decreased vascular leakage and lesion size, as well as the numbers of both choroidal and retinal inflammatory cytokines, including IL-1ß, IL-6, IL-8, and TNF-α. In LPS-treated ARPE-19 cells, fursultiamine decreased proinflammatory cytokine secretion and nuclear factor kappa B phosphorylation. Furthermore, fursultiamine suppressed LPS-induced upregulation of IL-6, IL-8, and monocyte chemoattractant protein-1 in a dose-dependent and time-dependent manner in primary hRPE cells. Interestingly, fursultiamine significantly enhanced mitochondrial respiration in the LPS-treated ARPE-19 cells. Additionally, fursultiamine attenuated hypoxia-induced aberrations, including lactate production and inhibitory phosphorylation of pyruvate dehydrogenase. Furthermore, fursultiamine attenuated hypoxia-induced VEGF secretion and mitochondrial fission in primary hRPE cells that were replicated in ARPE-19 cells. Conclusions: Our findings show that fursultiamine is a viable putative therapeutic for neovascular age-related macular degeneration by modulating the inflammatory response and metabolic reprogramming by enhancing mitochondrial respiration in the RPE.

6.
Nutrients ; 12(10)2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33092151

RESUMO

The administration of a combination of probiotics and prebiotics is expected to be a promising strategy for improving irritable bowel syndrome (IBS) symptoms. This study aimed to investigate the efficacy of a synbiotic containing Lactobacillus paracasei and Opuntia humifusa extract for symptomatic improvement of IBS in a murine model and to evaluate the mechanism underlying the beneficial effects of this synbiotic. A total of 20 male Wistar rats aged 8 weeks with IBS induced by restraint stress were assigned into four groups and administered L. paracasei as a probiotic and O. humifusa extract as a prebiotic for 4 weeks. The primary outcome was stool consistency at week 4. To evaluate the mechanism underlying the beneficial effects of the synbiotic, fecal microbial analysis was conducted, and the serum corticosterone levels, tumor necrosis factor-α (TNF-α) levels in the colon tissue, and expression of tight junction proteins were investigated. All three treatment groups showed significantly lower scores for stool consistency than the control group at week 4 (all p < 0.001). When compared with the control group, the synbiotic groups showed a significantly greater abundance of L. paracasei in fecal microbial analysis, lower serum corticosterone levels, lower TNF-α levels in the colon tissue, and higher expression of tight junction proteins. This novel synbiotic containing L. paracasei and O. humifusa extract can improve the stool consistency in a murine model of IBS. It may be a promising treatment option for IBS, and human studies are warranted.

7.
Acupunct Med ; : 964528420959340, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33023300
8.
Yeungnam Univ J Med ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33028055

RESUMO

The global obesity epidemic and the growing elderly population largely contribute to the increasing incidence of type 2 diabetes. Insulin resistance acts as a critical link between the present obesity pandemic and type 2 diabetes. Naturally occurring reactive oxygen species (ROS) regulate intracellular signaling and are kept in balance by the antioxidant system. However, the imbalance between ROS production and antioxidant capacity causes ROS accumulation and induces oxidative stress. Oxidative stress interrupts insulin-mediated intracellular signaling pathways, as supported by studies involving genetic modification of antioxidant enzymes in experimental rodents. In addition, a close association between oxidative stress and insulin resistance has been reported in numerous human studies. However, the controversial results with the use of antioxidants in type 2 diabetes raise the question of whether oxidative stress plays a critical role in insulin resistance. In this review article, we discuss the relevance of oxidative stress to insulin resistance based on genetically modified animal models and human trials.

9.
Endocrinol Metab (Seoul) ; 35(3): 647-655, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32981307

RESUMO

BACKGROUND: Hepatic stellate cells (HSCs) are known to play a fundamental role in the progression of liver fibrosis. Once HSCs are activated, they are involved in proliferation, migration, and contractility which are characteristics of liver fibrogenesis. Recent studies have shown that irisin, a myokine secreted during physical exercise, has a protective effect in various metabolic diseases, especially in renal fibrosis. However, whether irisin is involved in HSC activation and other processes associated with liver fibrosis has not yet been investigated. In this study, we reveal the role of irisin in HSC activation as well as in proliferation, migration, and contractile properties of HSCs in vitro. METHODS: LX-2 cells, immortalized human HSCs, were treated with transforming growth factor beta 1 (TGF-ß1), a core regulator of HSC fibrosis, with or without irisin, and markers of the aforementioned processes were analyzed. Further, an inflammatory response was stimulated with TGF-ß1 and lipopolysaccharide (LPS) in combination with irisin and the expression of cytokines was measured. RESULTS: Recombinant irisin significantly suppressed the expression of TGF-ß1-stimulated fibrosis markers including alpha-smooth muscle actin and collagen type 1 alpha 1 and prevented the TGF-ß1-induced proliferation, migration, and contractility of LX-2 cells. Additionally, irisin ameliorated the production of interleukin-6 (IL-6) and IL-1ß induced by TGF-ß1 and LPS treatments. CONCLUSION: These findings suggested that irisin potently improved the progression of hepatic fibrosis by regulating HSC activation, proliferation, migration, contractility, and HSC-mediated production of inflammatory cytokine.

10.
Korean J Intern Med ; 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32872728

RESUMO

Background/Aims: There are few studies describing contemporary status of mechanical ventilation in Korea. We investigated changes in management and outcome of mechanical ventilation in Korea. Methods: International, prospective observational cohort studies have been conducted every six year since 1998. Korean intensive care units (ICUs) participated in 2010 and 2016 cohorts. We compared 2016 and 2010 Korean data. Results: 226 patients from 18 ICUs and 275 patients from 12 ICUs enrolled in 2016 and 2010, respectively. In 2016 compared to 2010, use of non-invasive ventilation outside ICU increased (10.2 vs. 2.5%, p = 0.001). Pressure-control ventilation was the most common mode in both groups. Initial tidal volume (7.1 vs. 7.4 ml/kg, p = 0.372) and positive end-expiratory pressure (6 vs. 6 cmH2O, p = 0.141) were similar, but peak pressure (22 vs. 24 cmH2O, p = 0.011) was lower in 2016. More patients received sedatives (70.7 vs. 57.0%, p = 0.002) and analgesics (86.5 vs. 51.1%, p < 0.001) in 2016. The awakening (48.4% vs. 31.0%, p = 0.002) was more frequently attempted in 2016. The accidental extubation rate decreased to one tenth of what it was in 2010 (1.1% vs. 10.2%, p < 0.001). The ICU mortality did not change (31.4% vs. 35.6%, p = 0.343) but ICU length of stay showed a decreasing trend (9 days vs 10 days, p = 0.054) in 2016. Conclusions: There were temporal changes in care of patients on mechanical ventilation including better control of pain and agitation, and active attempt of awakening.

11.
Crit Care Med ; 48(10): 1462-1470, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32931189

RESUMO

OBJECTIVES: To investigate the impact of normothermia on compliance with sepsis bundles and in-hospital mortality in patients with sepsis who present to emergency departments. DESIGN: Retrospective multicenter observational study. PATIENTS: Nineteen university-affiliated hospitals of the Korean Sepsis Alliance participated in this study. Data were collected regarding patients who visited emergency departments for sepsis during the 1-month period. The patients were divided into three groups based on their body temperature at the time of triage in the emergency department (i.e., hypothermia [< 36°C] vs normothermia [36-38°C] vs hyperthermia [> 38°C]). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 64,021 patients who visited emergency departments, 689 with community-acquired sepsis were analyzed (182 hyperthermic, 420 normothermic, and 87 hypothermic patients). The rate of compliance with the total hour-1 bundle was lowest in the normothermia group (6.0% vs 9.3% in hyperthermia vs 13.8% in hypothermia group; p = 0.032), the rate for lactate measurement was lowest in the normothermia group (62.1% vs 73.1% vs 75.9%; p = 0.005), and the blood culture rate was significantly lower in the normothermia than in the hyperthermia group (p < 0.001). The in-hospital mortality rates in the hyperthermia, normothermia, and hypothermia groups were 8.5%, 20.6%, and 30.8%, respectively (p < 0.001), but there was no significant association between compliance with sepsis bundles and in-hospital mortality. However, in a multivariate analysis, compared with hyperthermia, normothermia was significantly associated with an increased in-hospital mortality (odds ratio, 2.472; 95% CI, 1.005-6.080). This association remained significant even after stratifying patients by median lactate level. CONCLUSIONS: Normothermia at emergency department triage was significantly associated with an increased risk of in-hospital mortality and a lower rate of compliance with the sepsis bundle. Despite several limitations, our findings suggest a need for new strategies to improve sepsis outcomes in this group of patients.

12.
Int J Mol Sci ; 21(18)2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899599

RESUMO

RNA decay is an important regulatory mechanism for gene expression at the posttranscriptional level. Although the main pathways and major enzymes that facilitate this process are well defined, global analysis of RNA turnover remains under-investigated. Recent advances in the application of next-generation sequencing technology enable its use in order to examine various RNA decay patterns at the genome-wide scale. In this study, we investigated human RNA decay patterns using parallel analysis of RNA end-sequencing (PARE-seq) data from XRN1-knockdown HeLa cell lines, followed by a comparison of steady state and degraded mRNA levels from RNA-seq and PARE-seq data, respectively. The results revealed 1103 and 1347 transcripts classified as stable and unstable candidates, respectively. Of the unstable candidates, we found that a subset of the replication-dependent histone transcripts was polyadenylated and rapidly degraded. Additionally, we identified 380 endonucleolytically cleaved candidates by analyzing the most abundant PARE sequence on a transcript. Of these, 41.4% of genes were classified as unstable genes, which implied that their endonucleolytic cleavage might affect their mRNA stability. Furthermore, we identified 1877 decapped candidates, including HSP90B1 and SWI5, having the most abundant PARE sequences at the 5'-end positions of the transcripts. These results provide a useful resource for further analysis of RNA decay patterns in human cells.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32948417

RESUMO

PURPOSE: To evaluate the combined effect of intense pulsed light (IPL) therapy and meibomian gland expression on extracellular matrix metalloproteinase-9 (MMP-9) levels and clinical outcomes of moderate and severe meibomian gland dysfunction (MGD) treatment. METHODS: This retrospective study was conducted on 45 eyes of 23 patients with moderate and severe MGD. Each eye underwent three IPL sessions and meibomian gland expression at 2-week intervals. In this study the evaluated parameters included tear film break-up time (TBUT), corneal and conjunctival fluorescein staining scores, biomicroscopic examination of lid margins and meibomian glands, ocular surface disease index (OSDI) questionnaire score, and extracellular MMP-9 levels using the immunoassay device before and two weeks after the last treatment session. Linear mixed model and generalized estimating equations model were used to evaluate possible differences. RESULTS: There were significant improvements in TBUT (P < 0.001), SICCA ocular staining score (P = 0.008), Oxford staining score (P = 0.023), lid margin irregularity (P < 0.001 for upper and lower eyelids), lid thickness (P < 0.001 for upper and lower eyelids), meibomian gland plugging (P = 0.010 and P = 0.012 for upper and lower eyelids), meibum color (P = 0.044 and P < 0.001 for upper and lower eyelids), meibum consistency (P < 0.001 for upper and lower eyelids), MGD grade (P < 0.001), and OSDI questionnaire score (P < 0.001). Incidence of positive results for MMP-9 immunoassay significantly decreased from 84.0% to 56.0% (P = 0.031) after treatment. CONCLUSION: In patients with moderate to severe MGD, three sessions of IPL combined with meibomian gland expression improved objective findings, subjective symptoms, meibomian gland function, and MMP-9 immunoassay results. The results support the combination of IPL and meibomian gland expression for treating moderate to severe MGD.

14.
Skeletal Radiol ; 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978678

RESUMO

OBJECTIVE: To identify the morphological characteristics of the acromion and subacromial bursal space after arthroscopic acromioplasty using magnetic resonance imaging (MRI). MATERIALS AND METHODS: One hundred patients who received arthroscopic rotator cuff repair and acromioplasty each received at least three MRI examinations (preoperative, first immediate postoperative, and second follow-up imaging between 8 months and 1 year postoperatively). Changes over time in the thickness and morphology of the postoperative acromion as well as the subacromial bursal space were assessed. Clinical and radiological parameters were also analyzed to identify any association with changes in acromial morphology. RESULTS: Despite minimal acromial thinning observed at the first immediate postoperative state, the acromions showed significant thinning at the second postoperative MRI, with a mean reduction of 32%. Along with acromial thinning, an exaggerated concave contour of the acromial undersurface was observed in some patients. In the subacromial space, a loculated fluid collection developed in 91% of the patients at the second postoperative follow-up. No statistically significant association was noted between postoperative acromial thickness change and clinical or radiological factors (P value > 0.05). CONCLUSION: A significant delayed reduction in acromial thickness within approximately 1 year of arthroscopic acromioplasty is thought to be a normal postoperative feature. The simultaneous collection of a loculated, cyst-like fluid in the subacromial bursal space may be an important associated factor of postoperative acromial thinning.

15.
AMB Express ; 10(1): 140, 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32789704

RESUMO

Miraculin, derived from the miracle fruit (Synsepalum dulcificum), is a taste-regulating protein that interacts with human sweet-taste receptors and transforms sourness into sweet taste. Since miracle fruit is cultivated in West Africa, mass production of miraculin is limited by regional and seasonal constraints. Here, we investigated mass production of recombinant miraculin in carrot (Daucus carota L.) callus cultures using an air-lift bioreactor. To increase miraculin expression, the oxidative stress-inducible SWPA2 promoter was used to drive the expression of miraculin gene under various stress treatments. An 8 h treatment of hydrogen peroxide (H2O2) and salt (NaCl) increased the expression of miraculin gene by fivefold compared with the untreated control. On the other hand, abscisic acid, salicylic acid, and methyl jasmonate treatments showed no significant impact on miraculin gene expression compared with the control. This shows that since H2O2 and NaCl treatments induce oxidative stress, they activate the SWPA2 promoter and consequently up-regulate miraculin gene expression. Thus, the results of this study provide a foundation for industrial-scale production of recombinant miraculin protein using transgenic carrot cells as a heterologous host.

16.
Int J Mol Sci ; 21(16)2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32781560

RESUMO

Molecular testing offers more objective information in the diagnosis and personalized decision making for thyroid nodules. In Korea, as the BRAF V600E mutation is detected in 70-80% of thyroid cancer specimens, its testing in fine-needle aspiration (FNA) cytology specimens alone has been used for the differential diagnosis of thyroid nodules until now. Thus, we aimed to develop a mutation panel to detect not only BRAF V600E, but also other common genetic alterations in thyroid cancer and to evaluate the diagnostic accuracy of the mutation panel for thyroid nodules in Korea. For this prospective study, FNA specimens of 430 nodules were obtained from patients who underwent thyroid surgery for thyroid nodules. A molecular test was devised using real-time PCR to detect common genetic alterations in thyroid cancer, including BRAF, N-, H-, and K-RAS mutations and rearrangements of RET/PTC and PAX8/PPARr. Positive results for the mutation panel were confirmed by sequencing. Among the 430 FNA specimens, genetic alterations were detected in 293 cases (68%). BRAF V600E (240 of 347 cases, 69%) was the most prevalent mutation in thyroid cancer. The RAS mutation was most prevalently detected for indeterminate cytology. Among the 293 mutation-positive cases, 287 (98%) were diagnosed as cancer. The combination of molecular testing and cytology improved sensitivity from 72% (cytology alone) to 89% (combination), with a specificity of 93%. We verified the excellent diagnostic performance of the mutation panel applicable for clinical practice in Korea. A plan has been devised to validate its performance using independent FNA specimens.

17.
Exp Eye Res ; 199: 108192, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32805263

RESUMO

Due to their very poor proliferative capacity, the dysfunction of corneal endothelial cells can sometimes lead to incurable eye diseases that require corneal transplantation. Although many studies have been performed to reconstruct corneal endothelial cells, corneal transplantation is still considered to be the established approach. In this study, we developed bio-engineered Descemet stripping endothelial (DSE) layers, using porcine cornea and induced pluripotent stem cell (iPSC)-derived corneal endothelial cells (iCECs). First, we optimized a protocol to prepare an ultra-thin and decellularized Descemet stripping (DS) scaffold from porcine cornea. Our DS layers show over 90% transparency compared to the control. Porcine-derived cells and xenogenic antigens disappeared, whereas the collagen matrix remained in the graft. Next, corneal endothelial cell lines or iCECs were seeded on the decellularized DS graft and cultured for 7 days. The drying method reduced graft rolling and edema, and increased transparency during culture. The reseeded cells were evenly distributed over the graft, and most of the cells survived. Although future clinical studies are warranted, engineered DSE tissues using xenogenic tissues and stem cells will be useful tools for the treatment of incurable corneal diseases.

18.
Cancers (Basel) ; 12(8)2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32824662

RESUMO

Because of the low mortality rate of well-differentiated thyroid cancer (WDTC), investigation of the clinical course leading to death is limited. We analyzed the cause of death and clinical course from diagnosis to death in patients who died of WDTC. A total of 592 WDTC patients died between 1996 and 2018. After exclusion, 79 patients were enrolled and divided into four groups based on their clinical course; that is, inoperable at the time of diagnosis (inoperable), distant metastasis (DM) detected at the time of diagnosis (initial-DM), DM detected during follow-up (late-DM), and loco-regional disease (L-R). Lung (55.6%) in papillary thyroid carcinoma (PTC) and bone (46.7%) in follicular thyroid carcinoma (FTC) were the most common metastasis locations. The most common causes of death were respiratory failure (32.3%) and airway obstruction (30.6%) in PTC, and complications due to immobilization arising from bone metastasis (35.3%) in FTC. Brain metastasis was found in 13.3% of patients and had the worst prognosis. The overall survival (OS) differed significantly (p = 0.001) according to clinical course; the inoperable had the shortest survival, followed by the initial-DM, L-R, and late-DM. However, OS did not differ significantly between PTC and FTC patients with initial-DM (p = 0.83). Other causes of death were far more common than death resulting from WDTC. In patients dying of WDTC, the major cause of death varied by metastatic site. OS differed according to clinical course, but not histologic type. Timing and DM sites differed between PTC and FTC.

19.
Genes Genomics ; 42(8): 957-969, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32648234

RESUMO

BACKGROUND: Brassinosteroids (BRs) are a class of phytohormones with important roles in regulating physiological and developmental processes. Small RNAs, including small interfering RNAs and microRNAs (miRNAs), are non-protein coding RNAs that regulate gene expression at the transcriptional and post-transcriptional levels. However, the roles of small RNAs in BR response have not been studied well. OBJECTIVE: In this study, we aimed to identify BR-responsive small RNA clusters and miRNAs in Arabidopsis. In addition, the effect of BR-responsive small RNAs on their transcripts and target genes were examined. METHODS: Small RNA libraries were constructed from control and epibrassinolide-treated seedlings expressing wild-type BRI1-Flag protein under its native promoter in the bri1-5 mutant. After sequencing the small RNA libraries, differentially expressed small RNA clusters were identified by examining the expression levels of small RNAs in 100-nt bins of the Arabidopsis genome. To identify the BR-responsive miRNAs, the expression levels of all the annotated mature miRNAs, registered in miRBase, were analyzed. Previously published RNA-seq data were utilized to monitor the BR-responsive expression patterns of differentially expressed small RNA clusters and miRNA target genes. RESULTS: In results, 38 BR-responsive small RNA clusters, including 30 down-regulated and eight up-regulated clusters, were identified. These differentially expressed small RNA clusters were from miRNA loci, transposons, protein-coding genes, pseudogenes and others. Of these, a transgene, BRI1, accumulates small RNAs, which are not found in the wild type. Small RNAs in this transgene are up-regulated by BRs while BRI1 mRNA is down-regulated by BRs. By analyzing the expression patterns of mature miRNAs, we have identified BR-repressed miR398a-5p and BR-induced miR156g. Although miR398a-5p is down-regulated by BRs, its predicted targets were not responsive to BRs. However, SPL3, a target of BR-inducible miR156g, is down-regulated by BRs. CONCLUSION: BR-responsive small RNAs and miRNAs identified in this study will provide an insight into the role of small RNAs in BR responses in plants. Especially, we suggest that miR156g/SPL3 module might play a role in BR-mediated growth and development in Arabidopsis.

20.
Molecules ; 25(14)2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32708887

RESUMO

Diabetes mellitus is a chronic metabolic disease, and its progression leads to serious complications. Although various novel therapeutic approaches for diabetes mellitus have developed in the last three decades, its prevalence has been rising more rapidly worldwide. Silk-related materials have been used as anti-diabetic remedies in Oriental medicine and many studies have shown the effects of silk fibroin (SF) in both in vitro and in vivo models. In our previous works, we reported that hydrolyzed SF improved the survival of HIT-T15 cells under high glucose conditions and ameliorated diabetic dyslipidemia in a mouse model. However, we could not provide a precise molecular mechanism. To further evaluate the functions of hydrolyzed SF on the pancreatic ß-cell, we investigated the effects of hydrolyzed SF on the pancreatic ß-cell proliferation and regeneration in the mouse model. Hydrolyzed SF induced the expression of the proliferating cell nuclear antigen (PCNA) and reduced the apoptotic cell population in the pancreatic islets. Hydrolyzed SF treatment not only induced the expression of transcription factors involved in the pancreatic ß-cell regeneration in RT-PCR results but also increased neurogenin3 and Neuro D protein levels in the pancreas of those in the group treated with hydrolyzed SF. In line with this, hydrolyzed SF treatment generated insulin mRNA expressing small cell colonies in the pancreas. Therefore, our results suggest that the administration of hydrolyzed SF increases the pancreatic ß-cell proliferation and regeneration in C57BL/KsJ-Leprdb/db mice.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA