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1.
J Diabetes Investig ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622572

RESUMO

BACKGROUND: The purpose of this study was to investigate the impact of vision and hearing impairments on the risk of adverse cardiovascular outcomes and mortality in patients with type 2 diabetes using a nationwide longitudinal cohort. METHODS: We enrolled 771,128 patients with type 2 diabetes who underwent the National Health Screening Program in 2009. We performed Cox proportional hazards regression analyses to calculate the hazard ratios(HR) of MI, stroke, and mortality in those with or without vision and hearing impairments. Subgroup analyses of patients stratified by age, gender, and diabetic retinopathy were performed. RESULTS: Diabetic patients with either vision or hearing impairment showed higher risk of MI, stroke, or death compared to those without. Among the combinations of impairments, patients with both vision and hearing impairments had the highest risk for MI(adjusted HR[aHR]=1.362, 95% confidence interval[CI]=1.252-1.481) and mortality(aHR=1.591, 95% CI=1.532-1.651). Those with only vision impairment showed higher risk of MI(aHR=1.324, 95% CI=1.275-1.375 and aHR=1.117, 95% CI=1.066-1.170, respectively), stroke(aHR=1.318, 95% CI=1.276-1.362 and aHR=1.134 95% CI=1.089-1.180, respectively), and mortality(aHR=1.417, 95% CI=1.390-1.446 and aHR=1.163, 95% CI=1.135-1.191, respectively) compared to those with only hearing impairment. CONCLUSIONS: Vision and hearing impairments are independently important risk factors for adverse cardiovascular events and mortality in patients with type 2 diabetes. Vision and hearing impairments synergistically increased the risk of MI and all-cause deaths, but not stroke. In addition, in under 65 years of age, the HR of vision impairment was higher than those with vision and hearing impairments.

2.
Gut Liver ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34593670

RESUMO

Background/Aims: Little is known about the clinical course of hepatitis B virus (HBV)-infected patients undergoing anti-tumor necrosis factor α (TNF-α) therapy for inflammatory bowel disease (IBD). We aimed to investigate the clinical course of HBV infection and IBD and to analyze liver dysfunction risks in patients undergoing anti-TNF-α therapy. Methods: This retrospective multinational study involved multiple centers in Korea, China, Taiwan, and Japan. We enrolled IBD patients with chronic or resolved HBV infection, who received anti-TNF-α therapy. The patients' medical records were reviewed, and data were collected using a web-based case report form. Results: Overall, 191 patients (77 ulcerative colitis and 114 Crohn's disease) were included, 28.3% of whom received prophylactic antivirals. During a median follow-up duration of 32.4 months, 7.3% of patients experienced liver dysfunction due to HBV reactivation. Among patients with chronic HBV infection, the proportion experiencing liver dysfunction was significantly higher in the non-prophylaxis group (26% vs 8%, p=0.02). Liver dysfunction occurred in one patient with resolved HBV infection. Antiviral prophylaxis was independently associated with an 84% reduction in liver dysfunction risk in patients with chronic HBV infection (odds ratio, 0.16; 95% confidence interval, 0.04 to 0.66; p=0.01). The clinical course of IBD was not associated with liver dysfunction or the administration of antiviral prophylaxis. Conclusions: Liver dysfunction due to HBV reactivation can occur in HBV-infected IBD patients treated with anti-TNF-α agents. Careful monitoring is needed in these patients, and antivirals should be administered, especially to those with chronic HBV infection.

3.
J Arrhythm ; 37(5): 1240-1249, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34621422

RESUMO

Background: To compare the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) between non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF), this retrospective study was conducted using the Korean Health Insurance Review & Assessment Service (HIRA) claims database. Methods: Patients with AF who initiated NOACs (apixaban, dabigatran, and rivaroxaban) from July 1, 2015 to November 30, 2016 were included. We applied inverse probability of treatment weighting (IPTW) method using propensity score to make weighted populations having similar characteristics between groups. Hazard ratio (HR) of S/SE and MB were estimated by Cox proportional hazard model. Results: Of the 39 783 patients with AF, 10 564; 11 418; and 17 801 used apixaban, dabigatran, and rivaroxaban, respectively. The mean CHA2DS2-VASc and HAS-BLED scores were 4.59 ~ 4.69 and 3.58 ~ 3.62, respectively, among all patients after applying IPTW. For S/SE, there were no significant differences between NOACs (HR [95% confidence interval (CI)]): apixaban vs dabigatran (0.99 [0.87-1.13]), apixaban vs rivaroxaban (0.95 [0.84-1.07]), and dabigatran vs rivaroxaban (0.96 [0.85-1.08]). For MB (HR [95% CI]), both apixaban (0.77 [0.68-0.86]) and dabigatran (0.88 [0.79-0.98]) had a significantly lower risk compared with rivaroxaban. Apixaban also had a significantly lower risk of MB compared with dabigatran (0.87 [0.76-0.99]). Conclusions: In real-world practice among Korean AF patients with relatively high risk of stroke and bleeding, there were no significant differences in the risk of S/SE between all NOAC comparisons. Apixaban was associated with lower risk of MB than dabigatran and rivaroxaban.

4.
Healthcare (Basel) ; 9(9)2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34574959

RESUMO

We examined antithrombotic treatment patterns with clinical characteristics and therapy changes over time in patients with atrial fibrillation (AF) after percutaneous coronary intervention (PCI). Using the Health Insurance Review and Assessment service claims database (01JAN2007-30NOV2016) in Korea, we included adult patients with AF and PCI: (1) who underwent PCI with stenting between 01JAN2008 and 30NOV2016; (2) with ≥1 claim for AF (ICD code: I48) (3) with antithrombotics 1 day prior to or at the date of PCI; and (4) with CHADS2-VASc of ≥2. In this study, 7749 patients with AF who underwent PCI, triple therapy, dual therapy, dual antiplatelet therapy (DAPT), and single antiplatelet therapy were prescribed to 24.6%, 3.4%, 60.8%, and 11.0%, respectively. In the triple therapy group, 23.1% persisted with triple therapy for 12 months, whereas the remaining patients switched to a different therapy. In the entire cohort and several subgroups, the median treatment duration of triple therapy was 55-87 days. DAPT use for 12 months was the most common treatment pattern (62.6%) in the DAPT group (median treatment duration, 324-345 days). A significant discrepancy exists between the current guidelines and real-world practice regarding antithrombotic treatment with PCI for patients with AF. Appropriate use of anticoagulants should be emphasized.

5.
Exp Mol Med ; 53(9): 1278-1286, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34588606

RESUMO

Retinoic acid receptor-related orphan receptor-α (RORα) is a member of the orphan nuclear receptor family and functions as a transcriptional activator in response to circadian changes. Circadian rhythms are complex cellular mechanisms regulating diverse metabolic, inflammatory, and tumorigenic gene expression pathways that govern cyclic cellular physiology. Disruption of circadian regulators, including RORα, plays a critical role in tumorigenesis and facilitates the development of inflammatory hallmarks. Although RORα contributes to overall fitness among anticancer, anti-inflammatory, lipid homeostasis, and circadian clock mechanisms, the molecular mechanisms underlying the mode of transcriptional regulation by RORα remain unclear. Nonetheless, RORα has important implications for pharmacological prevention of cancer, inflammation, and metabolic diseases, and understanding context-dependent RORα regulation will provide an innovative approach for unraveling the functional link between cancer metabolism and rhythm changes.

6.
Food Sci Biotechnol ; 30(8): 1025-1031, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34471557

RESUMO

This study detected phosphine residues and the qualitative effect of phosphine fumigation on Hwangtae (yellowish-dried Alaska pollock). Four types of Hwangtae products commercially purchased were investigated to assess phosphine residue. Hwangtae was fumigated at both laboratory scale, at an aluminum phosphide rate of 33.6 g/m3, and large scale (1.68 g/m3) to evaluate phosphine residue and dissipation. Further, nutritional composition analyses between pre- and post-fumigated Hwangtae were conducted. The concentration of phosphine residues was lower than the detection limit (0.005 mg/kg) in all Hwangtae products. After fumigation in laboratory scale, phosphine residue was 2.47 mg/kg, and after fumigation in large scale, the residue was 3.25 mg/kg. After 3-d aeration in the open air, there was no residue detected from fumigated Hwangtae. Nutritional composition, including proximate, mineral, and amino acid compositions, did not differ (P > 0.05) between pre- and post-fumigated Hwangtae. Overall, Hwangtae did not demonstrate a phosphine residue problem after the proper aeration process, and phosphine did not alter the nutritional composition, suggesting the use of phosphine as a fumigant to protect Hwangtae from insect pests.

7.
Int J Mol Sci ; 22(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34360584

RESUMO

Trichostatin A (TSA) is a representative histone deacetylase (HDAC) inhibitor that modulates epigenetic gene expression by regulation of chromatin remodeling in cells. To investigate whether the regulation of chromatin de-condensation by TSA can affect the increase in the efficiency of Cas9 protein-gRNA ribonucleoprotein (RNP) indel formation from plant cells, genome editing efficiency using lettuce and tobacco protoplasts was examined after several concentrations of TSA treatments (0, 0.1, 1 and 10 µM). RNP delivery from protoplasts was conducted by conventional polyethylene glycol (PEG) transfection protocols. Interestingly, the indel frequency of the SOC1 gene from TSA treatments was about 3.3 to 3.8 times higher than DMSO treatment in lettuce protoplasts. The TSA-mediated increase of indel frequency of the SOC1 gene in lettuce protoplasts occurred in a concentration-dependent manner, although there was not much difference. Similar to lettuce, TSA also increased the indel frequency by 1.5 to 1.8 times in a concentration-dependent manner during PDS genome editing using tobacco protoplasts. The MNase test clearly showed that chromatin accessibility with TSA treatments was higher than that of DMSO treatment. Additionally, TSA treatment significantly increased the level of histone H3 and H4 acetylation from lettuce protoplasts. The qRT-PCR analysis showed that expression of cell division-related genes (LsCYCD1-1, LsCYCD3-2, LsCYCD6-1, and LsCYCU4-1) was increased by TSA treatment. These findings could contribute to increasing the efficiency of CRISPR/Cas9-mediated genome editing. Furthermore, this could be applied for the development of useful genome-edited crops using the CRISPR/Cas9 system with plant protoplasts.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes/métodos , Ácidos Hidroxâmicos/farmacologia , Alface/metabolismo , Proteínas de Plantas/metabolismo , Protoplastos/metabolismo , Tabaco/metabolismo , Divisão Celular , Genoma de Planta , Alface/efeitos dos fármacos , Alface/genética , Alface/crescimento & desenvolvimento , Células Vegetais , Proteínas de Plantas/antagonistas & inibidores , Proteínas de Plantas/genética , Inibidores da Síntese de Proteínas/farmacologia , Protoplastos/efeitos dos fármacos , Tabaco/efeitos dos fármacos , Tabaco/genética , Tabaco/crescimento & desenvolvimento
8.
Sci Rep ; 11(1): 13947, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34230587

RESUMO

This study evaluated the marginal and internal fit and intaglio surface trueness of interim crowns fabricated from tooth preparation scanned at four finish line locations. The right maxillary first molar tooth preparation model was fabricated using a ceramic material and placed in four finish line locations (supragingival, equigingival, subgingival, and subgingival with a cord). Intraoral scanning was performed. Crowns were designed based on the scanned area. Interim crowns were fabricated using a stereolithography three-dimensional (3D) printer (N = 16 per location). Marginal and internal fit were evaluated with a silicone replica technique. Intaglio surface trueness was evaluated using a 3D inspection software. One-way analysis of variance and Tukey HSD test were performed for comparisons (α = 0.05). The marginal and internal fit showed significant differences according to locations (P < 0.05); the marginal fit showed the best results in the supragingival finish line (P < 0.05). Intaglio surface trueness was significantly different in the marginal region, with the highest value in the subgingival location (P < 0.05). Crowns fabricated on the subgingival finish line caused inaccurate marginal fit due to poor fabrication reproducibility of the marginal region. The use of an intraoral scanner should be decided on the clinical situation and needs.

10.
Front Cell Dev Biol ; 9: 653815, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33996814

RESUMO

Abnormal accumulation of misfolded tau aggregates is a pathological hallmark of various tauopathies including Alzheimer's disease (AD). Although tau is a cytosolic microtubule-associated protein enriched in neurons, it is also found in extracellular milieu, such as interstitial fluid, cerebrospinal fluid, and blood. Accumulating evidence showed that pathological tau spreads along anatomically connected areas in the brain through intercellular transmission and templated misfolding, thereby inducing neurodegeneration and cognitive dysfunction. In line with this, the spatiotemporal spreading of tau pathology is closely correlated with cognitive decline in AD patients. Although the secretion and uptake of tau involve multiple different pathways depending on tau species and cell types, a growing body of evidence suggested that tau is largely secreted in a vesicle-free forms. In this regard, the interaction of vesicle-free tau with membrane is gaining growing attention due to its importance for both of tau secretion and uptake as well as aggregation. Here, we review the recent literature on the mechanisms of the tau-membrane interaction and highlights the roles of lipids and proteins at the membrane in the tau-membrane interaction as well as tau aggregation.

11.
Antioxidants (Basel) ; 10(5)2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33925007

RESUMO

Tendinopathy is a common musculoskeletal condition causing pain and dysfunction. Conventional treatment and surgical procedures for tendinopathy are insufficient; accordingly, recent research has focused on tendon-healing regenerative approaches. Tendon injuries usually occur in the hypoxic critical zone, characterized by increased oxidative stress and mitochondrial dysfunction; thus, exogenous intact mitochondria may be therapeutic. We aimed to assess whether mitochondrial transplantation could induce anti-inflammatory activity and modulate the metabolic state of a tendinopathy model. Exogenous mitochondria were successfully delivered into damaged tenocytes by centrifugation. Levels of Tenomodulin and Collagen I in damaged tenocytes were restored with reductions in nuclear factor-κB and matrix metalloproteinase 1. The dysregulation of oxidative stress and mitochondrial membrane potential was attenuated by mitochondrial transplantation. Activated mitochondrial fission markers, such as fission 1 and dynamin-related protein 1, were dose-dependently downregulated. Apoptosis signaling pathway proteins were restored to the pre-damage levels. Similar changes were observed in a collagenase injection-induced rat model of tendinopathy. Exogenous mitochondria incorporated into the Achilles tendon reduced inflammatory and fission marker levels. Notably, collagen production was restored. Our results demonstrate the therapeutic effects of direct mitochondrial transplantation in tendinopathy. These effects may be explained by alterations in anti-inflammatory and apoptotic processes via changes in mitochondrial dynamics.

12.
J Environ Pathol Toxicol Oncol ; 40(2): 65-79, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33822518

RESUMO

Environmental pollution (EP) is a well-known threat to wild animals, but its toxicological impact is poorly understood. In vitro toxicity evaluation using cells of lower predators could be a promising way to assess and monitor the effects of EPs on whole wildlife populations that are related in the food web. Here, we describe EPs' toxic effect and mechanism in the primary fibroblast derived from the embryo of the striped field mouse, Apodemus agrarius. Characterization of the primary fibroblast was via morphology, genetics, immunocytochemistry, and stable culture conditions for optimal toxicity screening. Cell viability assays-MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and lactate dehydrogenase (LDH)-were performed to observe cytotoxicity, and quantitative PCR was conducted to confirm gene alteration by EP exposure. MTT and LDH assays confirmed the cytotoxicity of transfluthrin (TF), benzyl butyl phthalate (BBP), and 17ß-estradiol (E2) with IC50 values of 10.56 µM, 10.82 µM, and 24.08 µM, respectively, following 48-h exposures. mRNA expression of androgen-binding protein, growth hormone receptor, cytochrome C oxidase, and cytochrome P450-1A1 was induced after exposure to TF, BBP, and E2. We unveiled new EP mechanisms at the mammalian cellular level and discovered potential biomarker genes for monitoring of EPs. Based on our findings, we propose the primary fibroblast of A. agrarius as a valuable model to assess the toxicological effects of EP on wildlife.


Assuntos
Ciclopropanos/toxicidade , Disruptores Endócrinos/toxicidade , Estradiol/toxicidade , Estrogênios/toxicidade , Fibroblastos/efeitos dos fármacos , Fluorbenzenos/toxicidade , Inseticidas/toxicidade , Ácidos Ftálicos/toxicidade , Proteína de Ligação a Androgênios/genética , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ciclo-Oxigenase 1/genética , Citocromo P-450 CYP1A1/genética , Embrião de Mamíferos/citologia , Fibroblastos/metabolismo , Murinae , Receptores da Somatotropina/genética
13.
Semin Cancer Biol ; 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33753223

RESUMO

Methylation is a major post-translational modification (PTM) generated by methyltransferase on target proteins; it is recognized by the epigenetic reader to expand the functional diversity of proteins. Methylation can occur on specific lysine or arginine residues localized within regulatory domains in both histone and nonhistone proteins, thereby allowing distinguished properties of the targeted protein. Methylated residues are recognized by chromodomain, malignant brain tumor (MBT), Tudor, plant homeodomain (PHD), PWWP, WD-40, ADD, and ankyrin repeats by an induced-fit mechanism. Methylation-dependent activities regulate distinct aspects of target protein function and are largely reliant on methyl readers of histone and nonhistone proteins in various diseases. Methylation of nonhistone proteins that are recognized by methyl readers facilitates the degradation of unwanted proteins, as well as the stabilization of necessary proteins. Unlike nonhistone substrates, which are mainly monomethylated by methyltransferase, histones are di- or trimethylated by the same methyltransferases and then connected to other critical regulators by methyl readers. These fine-tuned controls by methyl readers are significant for the progression or inhibition of diseases, including cancers. Here, current knowledge and our perspectives about regulating protein function by methyl readers are summarized. We also propose that expanded research on the strong crosstalk mechanisms between methylation and other PTMs via methyl readers would augment therapeutic research in cancer.

14.
J Chest Surg ; 54(3): 200-205, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-33767013

RESUMO

Background: Various methods have been used to reduce postoperative pain after thoracic surgery. However, these methods may affect the patient's respiratory response and delay recovery from anesthesia. We aimed to evaluate the effects of fentanyl and remifentanil during extubation after video-assisted thoracic surgery (VATS). Methods: This study included 45 randomly-selected male patients who underwent VATS for pneumothorax between July 2011 and August 2012. We divided the participants into 3 groups: the F group, which received a bolus injection of 1.0 µg/kg of fentanyl; the R1 group, which received a 0.04 µg/kg/min remifentanil infusion; and the R2 group, which received a 0.08 µg/kg/min remifentanil infusion. Hemodynamics, pain, cough, consciousness level, and nausea were assessed for each group. Results: The number and severity of coughs were lower in the R1 and R2 groups than in the F group, and there were no differences between the R1 and R2 groups. Respiratory depression and loss of consciousness were not observed in any of the patients, and there were no differences in hemodynamics. Conclusion: In comparison with fentanyl, remifentanil did not result in a wide fluctuation of blood pressure and heart rate upon emergence from general anesthesia. Moreover, remifentanil contributed to cough suppression and postoperative pain control. Remifentanil seems to be a safe and effective analgesic after VATS.

15.
Biochim Biophys Acta Mol Basis Dis ; 1867(5): 166099, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33556486

RESUMO

Endoplasmic reticulum (ER) stress is closely associated with various metabolic diseases, such as obesity and diabetes. Development of beige/brite adipocytes increases thermogenesis and helps to reduce obesity. Although the relationship between ER stress and white adipocytes has been studied considerably, the possible role of ER stress and the unfolded protein response (UPR) induction in beige adipocytes differentiation remain to be investigated. In this study we investigated how ER stress affected beige adipocytes differentiation both in vitro and in vivo. Phosphorylation of eIF2α was transiently decreased in the early phase (day 2), whereas it was induced at the late phase with concomitant induction of C/EBP homologous protein (CHOP) during beige adipocytes differentiation. Forced expression of CHOP inhibited the expression of beige adipocytes markers, including Ucp1, Cox8b, Cidea, Prdm16, and Pgc-1α, following the induction of beige adipocytes differentiation. When ER stress was reduced by the chemical chaperone tauroursodeoxycholic acid (TUDCA), the expression of the beige adipocytes marker uncoupling protein 1 (UCP1) was significantly enhanced in inguinal white adipose tissue (iWAT) and high fat diet (HFD)-induced abnormal metabolic phenotype was improved. In summary, we found that ER stress and the UPR induction were closely involved in beige adipogenesis. These results suggest that modulating ER stress could be a potential therapeutic intervention against metabolic dysfunctions via activation of iWAT browning.


Assuntos
Adipócitos Bege/citologia , Diferenciação Celular , Dieta Hiperlipídica/efeitos adversos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Síndrome Metabólica/prevenção & controle , Obesidade/complicações , Ácido Tauroquenodesoxicólico/farmacologia , Adipócitos Bege/efeitos dos fármacos , Adipogenia , Animais , Masculino , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Camundongos , Camundongos Endogâmicos C57BL , Fenótipo , Transdução de Sinais , Termogênese , Resposta a Proteínas não Dobradas
16.
Gastrointest Endosc ; 94(1): 148-154, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33417897

RESUMO

BACKGROUND AND AIMS: Prophylactic application of a hemoclip has been suggested as an alternative to the use of an endoloop for the prevention of postpolypectomy bleeding (PPB) when resecting large, pedunculated colorectal polyps. Therefore, this multicenter, randomized controlled trial investigated the efficacy of prophylactic hemoclip application to reduce PPB during the resection of large pedunculated polyps. METHODS: Large pedunculated polyps (≥10 mm in head diameter) were eligible for inclusion. Polyps were randomized into a study arm (where clips were applied before resection) and a control arm (without pretreatment). The primary outcome was the rate of PPB in each group. PPB included immediate PPB (IPPB) and delayed PPB (DPPB). IPPB was defined as blood oozing (≥1 minute) or active spurting occurring immediately after polyp resection. DPPB was defined as rectal bleeding, occurring after completion of the colonoscopy. RESULTS: In total, 238 polyps from 204 patients were randomized into the clip arm (119 polyps) or the control arm (119 polyps). Overall bleeding adverse events were observed in 20 cases (IPPB, 16; DPPB, 4). The rate of overall PPB, IPPB, and DPPB was 8.4%, 6.7%, and 1.7%, respectively, for all polyps. The rate of overall PPB (clip 4.2% vs control 12.6%, P = .033) and IPPB (clip 2.5% vs control 10.9%, P = .017) was significantly lower in the clip arm than the control arm. CONCLUSIONS: Prophylactic clipping before resecting large pedunculated polyps can reduce overall PPB and IPPB compared with no prior treatment. Therefore, prophylactic clipping may be considered before resection of large pedunculated polyps. (Clinical trial registration number: NCT02156193.).


Assuntos
Pólipos do Colo , Pólipos do Colo/cirurgia , Colonoscopia , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/prevenção & controle , Humanos , Hemorragia Pós-Operatória/prevenção & controle , Instrumentos Cirúrgicos
17.
J Gastroenterol Hepatol ; 36(2): 397-405, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32542773

RESUMO

BACKGROUND AND AIM: We investigated the relationship of BMI and waist circumference with the risk of colorectal cancer (CRC) using a population-based cohort database and to explore the relationship of CRC with diabetes status. METHODS: Retrospective data (age >20 years) on anthropometric variables, blood parameters of fasting sugar, lipid levels, and blood pressure were collected from the National Health Insurance Corporation database between 2009 and 2012. Cox regression models were used to estimate hazard ratio (HR) and corresponding 95% confidence intervals (95% CI). RESULTS: Of the 23 121 360 people studied, 120 579 were diagnosed with CRC after a median follow-up period of 5.4 years. Both waist circumference and body mass index were positively associated with increased risk of CRC, regardless of age or sex. After mutual adjustment, only waist circumference was significantly associated with increased risk of CRC (HR = 1.275, 95% CI: 1.205-1.349). When the risk of CRC was compared according to diabetes status among people with the same waist circumference range, risk of CRC was higher for those with worse diabetes status. CONCLUSION: When waist circumference and body mass index were mutually adjusted, only waist circumference was associated with CRC risk. In addition, the risk of CRC is gradually higher in those with worsening diabetes, even if their waist circumferences are within the same range.

18.
Korean J Thorac Cardiovasc Surg ; 54(3): 218-220, 2021 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-33115975

RESUMO

The simultaneous incidence of infective endocarditis and cervical spondylitis with an epidural abscess is rare, and quadriplegia as a complication after cardiac surgery is very rare. We recently observed quadriplegia after mitral valve replacement in an infective endocarditis patient with cervical spine spondylitis. With early symptom detection, immediate examination, and prompt surgical treatment, the patient successfully recovered without neurological symptoms.

19.
J Bone Miner Res ; 36(3): 553-566, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33125772

RESUMO

Estrogen deficiency leads to osteoporosis as a result of an imbalance in bone remodeling due to greater bone resorption. Estrogen deficiency increases the osteoclastic resorption of bone, and many of the FDA-approved therapies for osteoporosis are antiresorptive drugs that mainly act by reducing osteoclast activity. The mitochondrial enzyme pyruvate dehydrogenase kinase (PDK) is a critical regulator of aerobic glycolysis that exerts its effects by phosphorylating the pyruvate dehydrogenase complex (PDC), which is responsible for oxidative phosphorylation. In the present study, we found that during osteoclast differentiation, PDK2 expression increased more than that of the other PDK isoenzymes. Bone loss was delayed and the number of osteoclasts was lower in ovariectomized (OVX) Pdk2-/- mice than in OVX wild-type mice. The differentiation of osteoclasts was suppressed in Pdk2-/- bone marrow-derived monocyte/macrophage lineage cells, which was associated with lower phosphorylation of cAMP response element-binding protein (CREB) and c-FOS, and a consequent reduction in NFATc1 transcription. Administration of AZD7545, a specific inhibitor of PDK2, prevented the OVX-induced bone loss and reduced the phosphorylation of CREB and c-FOS, and the protein expression of NFATc1, in osteoclasts. Collectively, these results indicate that the inhibition of PDK2 prevents osteoporosis in estrogen-deficient mice by reducing aberrant osteoclast activation, probably via inhibition of the RANKL-CREB-cFOS-NFATc1 pathway. These findings imply that PDK2 inhibitors might be repurposed for the therapy of estrogen deficiency-induced osteoporosis. © 2020 American Society for Bone and Mineral Research (ASBMR).

20.
Prostate ; 81(3): 182-193, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33368416

RESUMO

BACKGROUND: Recent developments in gene editing, using transcriptional activator-like effector nucleases (TALENs), have greatly helped the generation of genetically engineered animal models. The NK3 homeobox 1 (NKX3.1) protein plays important roles in prostate development and protein production, and functions as a tumor suppressor. Recently, NKX3.1 was shown to be associated with breast cancer in humans. METHODS: Our aim was to create a new rat model to elucidate the functions of NKX3.1. To that end, we generated Nkx3.1 knockout rats using TALENs and analyzed their phenotype. TALEN-mediated Nkx3.1 knockout was confirmed by T7 endonuclease I (T7E1) assay and DNA sequencing. Prostate weight and fertility were evaluated in the knockout rats, besides determining the proportion of epithelial cells and messenger RNA (mRNA) expression of genes associated with carcinogenesis. Breast tumors were examined by histopathology. RESULTS: Results suggested Nkx3.1 knockout rats have reduced fertility, decreased prostate weights, and increased epithelial cell layers. The mRNA expression of genes related to prostate carcinogenesis, namely Ar, Akt, and Pi3k, also increased. Moreover, the Nkx3.1 knockout rats often developed malignant breast tumors. CONCLUSIONS: We, therefore, successfully created the first Nkx3.1 knockout rat model, using TALEN-mediated gene targeting, and used it to identify defects associated with Nkx3.1 deficiency, not previously observed in mice. Loss of Nkx3.1 in rats led to lower reproductive capacity, and decreased prostate weights, apart from the risk of developing breast cancer. We, thus, proposed Nkx3.1 knockout rats as reliable models for studying the role of NKX3.1 in decreased prostate weights, fertility, and breast cancer, as well as in prostate cancer.


Assuntos
Técnicas de Inativação de Genes/métodos , Proteínas de Homeodomínio/fisiologia , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição/genética , Fatores de Transcrição/fisiologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Fertilidade , Genes Supressores de Tumor , Proteínas de Homeodomínio/genética , Masculino , Modelos Animais , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição/genética
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