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1.
Pharmaceutics ; 15(12)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38140111

RESUMO

Hypoxia-inducible factor-1 alpha (HIF-1α) is a regulatory factor of intracellular oxygen supersession. The expression or increased activity of HIF-1α is closely related to various human cancers. Previously, IDF-11774 was demonstrated to inhibit HSP70 chaperone activity and suppress the accumulation of HIF-1α. In this study, we aimed to determine the effects of IDF-11774 on gastric cancer cell lines. Treatment with IDF-11774 was found to markedly decrease the proliferation, migration, and invasion of the gastric cancer cell lines. Furthermore, the phosphorylation levels of extracellular signal-regulated kinase 1/2, p38, and Jun N-terminal kinase in the mitogen-activated protein kinase signaling pathways were markedly increased in a dose-dependent manner, ultimately promoting apoptosis via the induction of cell cycle arrest. Our findings indicate that HIF-1α inhibitors are potent drugs for the treatment of gastric cancer.

2.
Tissue Eng Regen Med ; 20(6): 921-937, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37679590

RESUMO

BACKGROUND: Beating cardiomyocyte regeneration therapies have revealed as alternative therapeutics for heart transplantation. Nonetheless, the importance of nitric oxide (NO) in cardiomyocyte regeneration has been widely suggested, little has been reported concerning endogenous NO during cardiomyocyte differentiation. METHODS: Here, we used P19CL6 cells and a Myocardiac infarction (MI) model to confirm NO-induced protein modification and its role in cardiac beating. Two tyrosine (Tyr) residues of ß2-tubulin (Y106 and Y340) underwent nitrosylation (Tyr-NO) by endogenously generated NO during cardiomyocyte differentiation from pre-cardiomyocyte-like P19CL6 cells. RESULTS: Tyr-NO-ß2-tubulin mediated the interaction with Stathmin, which promotes microtubule disassembly, and was prominently observed in spontaneously beating cell clusters and mouse embryonic heart (E11.5d). In myocardial infarction mice, Tyr-NO-ß2-tubulin in transplanted cells was closely related with cardiac troponin-T expression with their functional recovery, reduced infarct size and thickened left ventricular wall. CONCLUSION: This is the first discovery of a new target molecule of NO, ß2-tubulin, that can promote normal cardiac beating and cardiomyocyte regeneration. Taken together, we suggest therapeutic potential of Tyr-NO-ß2-tubulin, for ischemic cardiomyocyte, which can reduce unexpected side effect of stem cell transplantation, arrhythmogenesis.


Assuntos
Infarto do Miocárdio , Miócitos Cardíacos , Animais , Camundongos , Tubulina (Proteína) , Diferenciação Celular , Recuperação de Função Fisiológica , Infarto do Miocárdio/terapia , Microtúbulos
3.
Polymers (Basel) ; 15(12)2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37376229

RESUMO

As the world is shifting from internal combustion engine vehicles to electric vehicles in response to environmental pollution, the tire industry has been conducting research on tire performance to meet the requirements of electric vehicles. In this experiment, functionalized liquid butadiene rubber (F-LqBR) with triethoxysilyl groups at both ends was introduced into a silica-filled rubber compound as a substitute for treated distillate aromatic extract (TDAE) oil, and comparative evaluation was conducted according to the number of triethoxysilyl groups. The results showed that F-LqBRs improved silica dispersion in the rubber matrix through the formation of chemical bonds between silanol groups and the base rubber, and reduced rolling resistance by limiting chain end mobility and improving filler-rubber interaction. However, when the number of triethoxysilyl groups in F-LqBR was increased from two to four, self-condensation increased, the reactivity of the silanol groups decreased, and the improvement of properties was reduced. As a result, the optimized end functionality of triethoxysilyl groups for F-LqBR in silica-filled rubber compound was two. The 2-Azo-LqBR with the optimized functionality showed an improvement of 10% in rolling resistance, 16% in snow traction, and 17% in abrasion resistance when 10 phr of TDAE oil was substituted.

4.
Polymers (Basel) ; 14(16)2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-36015600

RESUMO

The implementation of vehicle electrification and autonomous driving technologies has recently emphasized the importance of abrasion resistance and fuel efficiency of truck bus radial (TBR) tire treads that undergo high loads and long driving times. In this study, a functionalized liquid butadiene rubber (F-LqBR) was introduced to replace the treated distillate aromatic extracted (TDAE) oil as a way to improve abrasion resistance and fuel efficiency in the TBR tire tread compound and to solve the oil migration. First, radical polymerization was used to synthesize nonfunctionalized LqBR (N-LqBR) and amino-LqBR with an amine group at the chain ends. The synthesized LqBRs were then substituted in place of TDAE oil to manufacture carbon-black-filled natural rubber (NR) compounds and to evaluate their physical properties. The results show that LqBRs improved the migration resistance and enhanced the abrasion resistance by lowering the glass transition temperature (Tg) of the compound. In particular, amino-LqBR improved carbon black dispersion in the rubber matrix through a chemical bond between the functional group of the carbon black surface and the base rubber. In conclusion, amino-LqBR successfully served as a processing aid in a carbon black-filled NR compound while simultaneously enhancing its fuel efficiency and abrasion resistance.

5.
Transl Res ; 249: 88-109, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35788054

RESUMO

During the progression of diabetic kidney disease (DKD), renal lactate metabolism is rewired. The relationship between alterations in renal lactate metabolism and renal fibrosis in patients with diabetes has only been partially established due to a lack of biopsy tissues from patients with DKD and the intricate mechanism of lactate homeostasis. The role of lactate dehydrogenase A (LDHA)-mediated lactate generation in renal fibrosis and dysfunction in human and animal models of DKD was explored in this study. Measures of lactate metabolism (urinary lactate levels and LDHA expression) and measures of DKD progression (estimated glomerular filtration rate and Wilms' tumor-1 expression) were strongly negatively correlated in patients with DKD. Experiments with streptozotocin-induced DKD rat models and the rat renal mesangial cell model confirmed our findings. We found that the pathogenesis of DKD is linked to hypoxia-mediated lactic acidosis, which leads to fibrosis and mitochondrial abnormalities. The pathogenic characteristics of DKD were significantly reduced when aerobic glycolysis or LDHA expression was inhibited. Further studies will aim to investigate whether local acidosis caused by renal LDHA might be exploited as a therapeutic target in patients with DKD.


Assuntos
Acidose , Diabetes Mellitus , Nefropatias Diabéticas , Acidose/complicações , Animais , Nefropatias Diabéticas/metabolismo , Fibrose , Humanos , Lactato Desidrogenase 5 , Lactatos/uso terapêutico , Ratos , Estreptozocina/uso terapêutico , Proteínas WT1/uso terapêutico
6.
J Pers Med ; 11(11)2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34834439

RESUMO

Bone-anchored maxillary protraction (BAMP) is effective for skeletal Class III malocclusion. However, infection, screw and plate loosening, and device failures occur with conventional plates. This pilot prospective study analyzed the feasibility of individualized BAMP using preoperative simulation and 3D titanium printing in patients referred by the orthodontic department for four BAMP miniplates. Preoperative cone beam computed tomography data were analyzed using CAD/CAM software to fabricate the individualized 3D-printed BAMP device. The customized plates were printed using selective laser sintering and inserted onto the bone through an adjunct transfer jig. The accuracy of preoperative simulation and actual placement of the BAMP device were tested by superimposing simulated positioned digital images and postoperative computed tomography data. The growth modification effect depended on superimposition of lateral cephalograms and comparative changes in SNA, SNB, ANB, and Wits. Two male patients were finally included in the study. BAMP decreased the ANB difference (-4.56 to -1.09) and Wits appraisal (-7.52 to -3.26) after 2 years. Normal measurement indices for sagittal and vertical growth indicated successful growth modification. The mean accuracy between preoperative simulation and actual surgery was 0.1081 ± 0.5074 mm. This treatment modality involving preoperative simulation and 3D titanium printing for fabricating and placing customized BAMP devices precisely at planned locations is effective for treating skeletal Class III malocclusion.

7.
Polymers (Basel) ; 13(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34451238

RESUMO

Recently, research conducted on tread compounds with liquid butadiene rubber (LqBR) have been conducted in the tire industry. In particular, the introduction of functional groups into LqBRs is expected to lower hysteresis loss caused by the free chain ends of LqBR. To study this, LqBRs with functional groups at different positions were synthesized. The occurrences of in-chain and chain-end functionalization of functionalized LqBRs (F-LqBRs) were confirmed, the microstructure and functionalization efficiency of F-LqBRs were calculated through the characterizations. This novel functionalization technology was beneficial not only to immobilizing the free chain ends of LqBRs to the surfaces of silica to decrease the number of free chain ends, but also chemically bonding the LqBR chains on the base polymer through a crosslinking reaction to enhance the filler-rubber interaction. The effects of the functional group position and number of the free chain ends on the physical properties and hysteresis of the compounds were investigated by partially replacing the treated distillate aromatic extract (TDAE) oil with LqBR in silica-filled rubber compounds. The results showed that compounds that had applied DF-LqBR with both end functionalization performed better, including improving the silica dispersion, higher extraction resistance, and lower rolling resistance, than other F-LqBRs compounds.

8.
Hepatol Int ; 15(5): 1148-1159, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34081289

RESUMO

BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) is associated with atherosclerotic cardiovascular disease (ASCVD). However, few studies have investigated the association between the histological severity of NAFLD and ASCVD. Therefore, we investigated whether the histological severity of NAFLD is associated with ASCVD risk. METHODS: We performed cross-sectional analysis of prospectively enrolled, biopsy-proven NAFLD patients. The 10-year ASCVD risk was assessed using the Korean Risk Prediction Model. The histological spectrum of NAFLD was classified by the nonalcoholic steatohepatitis (NASH) clinical research network histological scoring system. The association between each histological subgroup and ASCVD risk was analyzed using logistic regression analysis. RESULTS: This study included 398 Korean subjects (mean age, 57.9 years; male, 44.2%) with biopsy-proven NAFLD and 102 no-NALFD controls. Subjects with ASCVD risk ≥ 10% showed more severe grades of hepatocellular ballooning and more advanced stages of fibrosis when compared with subjects with ASCVD risk < 10% (p < 0.05 for each). The presence of NASH (odds ratio [OR] 4.07; 95% confidence interval [CI] 1.40-11.88) or advanced fibrosis (OR 8.11; 95% CI 1.83-35.98) was independently associated with a higher risk of ASCVD even after adjustment for age, sex, body mass index, blood pressure, lipids, liver enzymes, systemic inflammation, and insulin resistance. CONCLUSIONS: Patients with NASH or advanced fibrosis are at an increased risk of developing ASCVD compared with no-NAFLD controls or subjects with NAFL, independent of conventional metabolic risk factors for CVD. Histological information on NAFLD may be helpful to promote our understanding of extrahepatic complications, such as ASCVD, resulting from NAFLD progression.


Assuntos
Doenças Cardiovasculares , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Biópsia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos Transversais , Humanos , Fígado , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/epidemiologia
9.
Polymers (Basel) ; 13(6)2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33801957

RESUMO

Liquid butadiene rubber (LqBR) which used as a processing aid play a vital role in the manufacturing of high-performance tire tread compounds. However, the studies on the effect of molecular weight, microstructure, and functionalization of LqBR on the properties of compounds are still insufficient. In this study, non-functionalized and center-functionalized liquid butadiene rubbers (N-LqBR and C-LqBR modified with ethoxysilyl group, respectively) were synthesized with low vinyl content and different molecular weights using anionic polymerization. In addition, LqBR was added to the silica-filled SSBR compounds as an alternative to treated distillate aromatic extract (TDAE) oil, and the effect of molecular weight and functionalization on the properties of the silica-filled SSBR compound was examined. C-LqBR showed a low Payne effect and Mooney viscosity because of improved silica dispersion due to the ethoxysilyl functional group. Furthermore, C-LqBR showed an increased crosslink density, improved mechanical properties, and reduced organic matter extraction compared to the N-LqBR compound. LqBR reduced the glass transition temperature (Tg) of the compound significantly, thereby improving snow traction and abrasion resistance compared to TDAE oil. Furthermore, the energy loss characteristics revealed that the hysteresis loss attributable to the free chain ends of LqBR was dominant.

10.
EMBO J ; 40(7): e106106, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33709453

RESUMO

A critical question in neurodegeneration is why the accumulation of disease-driving proteins causes selective neuronal loss despite their brain-wide expression. In Spinocerebellar ataxia type 1 (SCA1), accumulation of polyglutamine-expanded Ataxin-1 (ATXN1) causes selective degeneration of cerebellar and brainstem neurons. Previous studies revealed that inhibiting Msk1 reduces phosphorylation of ATXN1 at S776 as well as its levels leading to improved cerebellar function. However, there are no regulators that modulate ATXN1 in the brainstem-the brain region whose pathology is most closely linked to premature death. To identify new regulators of ATXN1, we performed genetic screens and identified a transcription factor-kinase axis (ZBTB7B-RSK3) that regulates ATXN1 levels. Unlike MSK1, RSK3 is highly expressed in the human and mouse brainstems where it regulates Atxn1 by phosphorylating S776. Reducing Rsk3 rescues brainstem-associated pathologies and deficits, and lowering Rsk3 and Msk1 together improves cerebellar and brainstem function in an SCA1 mouse model. Our results demonstrate that selective vulnerability of brain regions in SCA1 is governed by region-specific regulators of ATXN1, and targeting multiple regulators could rescue multiple degenerating brain areas.


Assuntos
Tronco Encefálico/metabolismo , Cerebelo/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Ataxias Espinocerebelares/metabolismo , Fatores de Transcrição/metabolismo , Animais , Ataxina-1/genética , Ataxina-1/metabolismo , Linhagem Celular Tumoral , Células Cultivadas , Proteínas de Ligação a DNA/genética , Drosophila melanogaster , Células HEK293 , Humanos , Camundongos , Fosforilação , Estabilidade Proteica , Proteínas Quinases S6 Ribossômicas 90-kDa/genética , Ataxias Espinocerebelares/genética , Fatores de Transcrição/genética
11.
Maturitas ; 146: 57-62, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33722365

RESUMO

OBJECTIVE: The study aimed to evaluate the degree of menopausal hormonal therapy (MHT) use and the related trends, as well as the characteristics of Korean women who used MHT by type of hormone therapy. METHODS: Women aged ≥40 years were selected using data from the Korea National Insurance Service-National Sample Cohort 2002-2013 database. MHT entailed either estrogen therapy or estrogen plus progestogen therapy, as categorized by the Anatomical Therapeutic Chemical system. The prevalence of MHT use was calculated as the number of women with prescriptions annually and the level of hormone consumption was calculated using the defined daily dose (DDD). RESULTS: The proportion of MHT users among women aged ≥40 years was 7.8 % in 2002, which decreased to 6.3 % in 2013. The overall MHT consumption level in 2002 was 27.5 DDDs/1000 inhabitants/day. There was a sharp decline in the first few years after 2002 and this value decreased to 12.5 DID in 2013; however, the decrease had lessened from 2006 to 2013 and differed by HT type, administration route, age, and income level. During the 11-year follow-up, over 70 % of women were prescribed MHT for less than 1 year, while only 11.8 % had a prescription for 3 years or more, and women who started treatment at age 45-59 years showed longer treatment duration. CONCLUSIONS: Since 2002, MHT use among Korean women, especially overall MHT consumption, has declined remarkably. Regarding the pattern of use among women who took hormone preparations during 2002-2013, MHT was used around menopause, over the short term only, and at low dose.


Assuntos
Estrogênios/uso terapêutico , Terapia de Reposição Hormonal , Progestinas/uso terapêutico , Adulto , Idoso , Estudos de Coortes , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , República da Coreia/epidemiologia
12.
Polymers (Basel) ; 12(12)2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33261042

RESUMO

The vulcanizate structure of filled compounds is affected by filler-rubber interactions (FRI) and the chemical crosslink density (CCD) of the matrix rubber. In particular, in filled compounds using a silica-silane system, FRIs due to silica-rubber coupling are a major influencing factor for the vulcanizate structure and physical properties. In this study, the effect of sulfur variation on the vulcanizate structure of silica-filled solution styrene-butadiene rubber compounds using a sulfide-silane coupling agent was studied. The vulcanizate structure according to sulfur variation was quantitatively analyzed using the swelling test and Flory-Rehner and Kraus equations. As the sulfur content increased, both FRI and the CCD increased, and it was confirmed that sulfur variation influenced the silica-rubber coupling efficiency through increased FRI. In addition, field emission scanning electron microscope images showed that increased FRI contributed to improvements in silica dispersion, abrasion resistance, and energy loss characteristics.

13.
BMC Oral Health ; 20(1): 315, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172437

RESUMO

BACKGROUND: Osseointegrated implants are considered as clinically non-movable. Parathyroid hormone (PTH) is known to play a significant role in the regulation of bone remodeling and in intermittent, low doses, result in osteoanabolic effects. This study aimed to investigate the effects of PTH and corticotomy, both under traction force, on osseointegrated implants. METHODS: Four implants-two in each hemimandible-were placed in each of the three study mongrels. Each mongrels were designated as control, normal dose PTH (PTH-1), and high dose PTH (PTH-2) groups, with each groups further subdivided into non-surgery implant and surgery implant. After osseointegration, mechanical force with NiTi closed coil springs (500 g) was applied around each implants. Corticotomy was performed around one of four implants in each mongrels. Parathyroid hormone was administered locally on a weekly basis for 20 weeks. Clinical movement of the implants were evaluated with the superimposed 3D- scanned data, bone- microarchitectural and histologic examinations. RESULTS: Superimposition analysis showed continuous movement of the non-surgery implant of PTH-1 group. Movement was further justified with lowest bone implant contact (adjusted BIC; 44.77%) in histomorphometric analysis. Upregulation of bone remodeling around the implant was observed in the normal dose PTH group. In the surgery implants, the remarkably higher adjusted BIC compared to the non-surgery implants indicated increased bone formation around the implant surface. CONCLUSION: The results indicate that the catabolic and anabolic balance of osseointegrated implants in terms of bone remodeling can be shifted via various interventions including pharmacological, surgical and mechanical force. CLINICAL RELEVANCE: Upregulated bone remodeling by PTH and corticotomy under continuous mechanical force showed the possible implications for the movement of osseointegrated dental implant.


Assuntos
Implantes Dentários , Remodelação Óssea , Osso e Ossos , Humanos , Osseointegração , Hormônio Paratireóideo
14.
Trends Genet ; 36(7): 490-498, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32418713

RESUMO

Viable cells with reduced fitness are often eliminated by neighboring cells with greater fitness. This phenomenon, called cell competition, is an important mechanism for maintaining a high-quality population of cells in tissues. Foundational studies characterizing cellular competition and its molecular underpinnings were first carried out utilizing Drosophila as a model system. More recently, competitive behavior studies have extended into mammalian cell types. In this review, we highlight recent advances in the field, focusing on new insights into the molecular mechanisms regulating competitive behavior in various cellular contexts and in cancer. Throughout the review, we highlight new avenues to expand our understanding of the molecular underpinnings of cell competition and its role in tissue development and homeostasis.


Assuntos
Comunicação Celular , Competição entre as Células , Drosophila/citologia , Drosophila/fisiologia , Homeostase , Animais , Modelos Biológicos
15.
Polymers (Basel) ; 12(4)2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32316510

RESUMO

Tread is an important component that directly affects the performance of passenger car radial (PCR) tires. Styrene-butadiene rubber (SBR) is mainly used for tire tread and it includes solution styrene-butadiene rubber (SSBR) and emulsion styrene-butadiene rubber (ESBR). Although SSBR is mainly used, the manufacturing process for SSBR is more challenging than ESBR, which is environmentally friendly, but has the disadvantage of a broad molecular weight distribution. To overcome this, a reversible addition-fragmentation radical transfer (RAFT) polymerization technique is used in ESBR polymerization. An environmentally friendly RAFT ESBR with a narrow dispersity can be polymerized. Here, carbon black-filled compounds were manufactured while using RAFT ESBR, and their properties were compared to ESBR. The analysis showed a low crosslink density of RAFT ESBR, due to the high polysulfide crosslink structure. We manufactured a carbon black-filled compound with the same crosslink density and structure as the ESBR carbon black-filled compound, and the effect of the dispersity of the base polymer was investigated. RAFT ESBR showed 9% better abrasion resistance and 29% better fuel efficiency than ESBR, according to the analysis of the data. The narrow dispersity can reduce energy loss and positively influence the abrasion resistance and fuel efficiency.

16.
Sci Rep ; 10(1): 7176, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32346034

RESUMO

Leptin-deficient and leptin-resistant mice manifest obesity, insulin resistance, and left ventricular hypertrophy (LVH); however, LVH's mechanisms are not fully understood. Cardiac iron dysregulation has been recently implicated in cardiomyopathy. Here we investigated the protective effects of caloric restriction on cardiac remodeling in impaired leptin signaling obese mice. RNA-seq analysis was performed to assess the differential gene expressions in the heart of wild-type and ob/ob mice. In particular, to investigate the roles of caloric restriction on iron homeostasis-related gene expressions, 10-week-old ob/ob and db/db mice were assigned to ad libitum or calorie-restricted diets for 12 weeks. Male ob/ob mice exhibited LVH, cardiac inflammation, and oxidative stress. Using RNA-seq analysis, we identified that an iron uptake-associated gene, transferrin receptor, was upregulated in obese ob/ob mice with LVH. Caloric restriction attenuated myocyte hypertrophy, cardiac inflammation, fibrosis, and oxidative stress in ob/ob and db/db mice. Furthermore, we found that caloric restriction reversed iron homeostasis-related lipocalin 2, divalent metal transporter 1, transferrin receptor, ferritin, ferroportin, and hepcidin expressions in the heart of ob/ob and db/db mice. These findings demonstrate that the cardioprotective effects of caloric restriction result from the cellular regulation of iron homeostasis, thereby decreasing oxidative stress, inflammation, and cardiac remodeling. We suggest that decreasing iron-mediated oxidative stress and inflammation offers new therapeutic approaches for obesity-induced cardiomyopathy.


Assuntos
Restrição Calórica , Hipertrofia Ventricular Esquerda , Ferro/metabolismo , Leptina/metabolismo , Estresse Oxidativo , Transdução de Sinais , Animais , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/patologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Obesos
17.
Biochem Biophys Res Commun ; 526(4): 999-1004, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32303335

RESUMO

Coronin 1B is an actin-binding protein that plays important roles in actin-dependent cellular processes. We previously reported that coronin 1B is involved in vascular endothelial cell growth factor-induced migration of human umbilical vein endothelial cells (HUVECs). However, the role of coronin 1B in tumor necrosis factor alpha (TNFα)-induced endothelial cell apoptosis remained unknown. In this study, we investigated whether coronin 1B affects TNFα-induced HUVEC apoptosis and sought to elucidate the mechanism by which coronin 1B regulates this cellular process. Depletion of coronin 1B by siRNA transfection decreased TNFα-induced apoptosis of HUVECs, as determined by MTT, terminal deoxynucleotidyl transferase dUTP nick end labeling and caspase-3 activity assays. Coronin 1B depletion also decreased caspase-8 cleavage via a JNK-independent pathway. Coronin 1B interacted with Fas-associated death domain protein (FADD) in both a plasmid overexpression system in HEK293T cells and at the endogenous protein level in TNFα-stimulated HUVECs. Immunoprecipitation and in situ proximity ligation assays showed that coronin 1B depletion diminished the interaction between TNFα-induced TNF receptor-1-associated death domain protein (TRADD) and FADD, suggesting that coronin 1B is required for the TNFα-induced TRADD and FADD interaction and subsequent caspase-8/caspase-3 cascade activation, ultimately leading to apoptosis.


Assuntos
Apoptose , Proteína de Domínio de Morte Associada a Fas/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteína de Domínio de Morte Associada a Receptor de TNF/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Caspase 8/metabolismo , Células HEK293 , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos
18.
J Biol Chem ; 295(8): 2336-2347, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-31959630

RESUMO

Cell growth is positively controlled by the phosphoinositide 3-kinase (PI3K)-target of rapamycin (TOR) signaling pathway under conditions of abundant growth factors and nutrients. To discover additional mechanisms that regulate cell growth, here we performed RNAi-based mosaic analyses in the Drosophila fat body, the primary metabolic organ in the fly. Unexpectedly, the knockdown of the Drosophila von Hippel-Lindau (VHL) gene markedly decreased cell size and body size. These cell growth phenotypes induced by VHL loss of function were recovered by activation of TOR signaling in Drosophila Consistent with the genetic interactions between VHL and the signaling components of PI3K-TOR pathway in Drosophila, we observed that VHL loss of function in mammalian cells causes decreased phosphorylation of ribosomal protein S6 kinase and Akt, which represent the main activities of this pathway. We further demonstrate that VHL activates TOR signaling by directly interacting with the p110 catalytic subunit of PI3K. On the basis of the evolutionarily conserved regulation of PI3K-TOR signaling by VHL observed here, we propose that VHL plays an important role in the regulation and maintenance of proper cell growth in metazoans.


Assuntos
Proteínas de Transporte/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Transdução de Sinais , Animais , Tamanho Corporal , Tamanho Celular , Drosophila melanogaster/citologia , Células HEK293 , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos , Ligação Proteica
19.
Korean J Intern Med ; 35(2): 351-359, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-30808127

RESUMO

BACKGROUND/AIMS: Pheochromocytoma and paraganglioma (PPGL) are catecholamine-producing tumors that can cause blood pressure (BP) elevation and cardiovascular complications. Clinical presentation of these tumors may be changed through widespread use of imaging studies, which enables detection of PPGLs before onset of symptoms. We investigated clinical profiles of patients with surgically resected PPGLs. METHODS: From 2005 to 2017, 111 consecutive patients with surgically resected PPGLs in two tertiary hospitals in Korea were studied. RESULTS: Mean age was 52 ± 16 years, 57 patients (51.4%) were male and 54 (48.6%) were hypertensive. Twenty-nine PPGLs (26.1%) were extra-adrenal paragangliomas. Sixteen (14.4%) and seven patients (6.3%) (Group 1, n = 23) were diagnosed during work-up of hypertension and transient cardiomyopathy respectively, and the remainder (Group 2, n = 88) were incidentalomas detected during routine abdominal imaging. Patients in the Group 1 were younger and more frequently symptomatic, and had higher BPs, heart rates and levels of urinary catecholamines than those in the Group 2. Paragangliomas were less frequent and secretion of epinephrine and metanephrine was more predominant in the Group 1 than in Group 2. After the surgical resections, 18.2% of patients still needed antihypertensive medications. CONCLUSION: Out of 111 patients with surgically resected PPGLs, 88 (79.3%) were diagnosed as incidentalomas. Seven patients presented with transient cardiomyopathy and 16 with hypertension. Tumor location and secretion of catecholamine may vary depending on the presence of symptoms.


Assuntos
Neoplasias das Glândulas Suprarrenais , Paraganglioma , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/cirurgia , Adulto , Idoso , Humanos , Masculino , Metanefrina , Pessoa de Meia-Idade , Paraganglioma/diagnóstico por imagem , Paraganglioma/cirurgia , Feocromocitoma/diagnóstico por imagem , Feocromocitoma/cirurgia , República da Coreia
20.
Polymers (Basel) ; 11(6)2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31195633

RESUMO

In the tire industry, solution styrene butadiene rubber (SSBR), which can introduce a functional group with good reactivity to silica at chain ends, is used to increase rolling resistance performance by considering fuel economy. However, this is not environmentally friendly because SSBR uses an organic solvent for polymerization, and it is difficult to increase its molecular weight. Functionalized emulsion SBR (ESBR) can solve the problems of SSBR. The molecular weight of ESBR molecules can be easily increased in an eco-friendly solvent, i.e., water. A functionalized ESBR introduces a functional group with good reactivity to silica by introducing a third monomer during polymerization. In this field, glycidyl methacrylate (GMA) has been reported to show the best properties as a third monomer. However, for GMA-ESBR, the viscosity is high and processability is disadvantageous. Therefore, we polymerized GMA-ESBR and manufactured silica compounds to clarify the causes of these problems. In addition, wet masterbatch (WMB) technology, which is a new compound manufacturing method, was applied to manufacture the silica compound, and the physical properties are compared with those of a dry masterbatch. The results clarified the problem of GMA-ESBR, which could be solved by using WMB technology.

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