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1.
Ann Surg Treat Res ; 105(1): 20-30, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37441325

RESUMO

Purpose: B-cell lymphoma 2 (BCL2) has an antiapoptotic role, however, has resulted in it being a powerful favorable prognostic factor in breast cancer. Several studies revealed BCL2 is strongly associated with a lower rate of early recurrence after initial treatment in breast cancer patients, but study of a prolonged effect after 5 years is lacking. We investigated BCL2 as a prognostic factor in breast cancer in comparison to early and late recurrence. Methods: We retrieved data from 2,198 patients with primary breast cancer who underwent surgical treatment and adjuvant treatment at the breast cancer center between 2005 and 2015. Each molecular subtype was classified, and Ki-67 and BCL2 were also assessed by immunohistochemistry. BCL2 and the association between molecular subtypes were assessed in early and late recurrences, respectively. Five-year postrecurrence survival and BCL2 were also assessed. Results: The BCL2-positive group was associated with favorable clinicopathologic characteristics. The time to recurrence was significantly longer in the BCL2-positive group (P = 0.035). Late recurrence after 5 years was higher in the BCL2-positive group (P = 0.029). In multivariate survival analysis, tumor size and BCL2-positive expression were the only independent prognostic factors for late recurrence (P = 0.004). In the patients with recurrence, 5-year postrecurrence survival was significantly higher in the BCL2-positive group (P < 0.001). Conclusion: Our result showed that prognosis was better in BCL2-positive patients compared to BCL2-negative patients at late recurrence. We suggested that BCL2 expression could be used as a marker to help determine additional adjuvant therapy or extended hormone therapy in hormone-dependent breast cancer.

2.
J Biomed Sci ; 29(1): 106, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36536341

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive paralysis due to motor neuron degeneration. It has been proposed that epigenetic modification and transcriptional dysregulation may contribute to motor neuron death. In this study, we investigate the basis for therapeutic approaches to target lysine-specific histone demethylase 1 (LSD1) and elucidate the mechanistic role of LSD1-histone H3K4 signaling pathway in ALS pathogenesis. METHODS: In order to examine the role of spermidine (SD), we administered SD to an animal model of ALS (G93A) and performed neuropathological analysis, body weight, and survival evaluation. RESULTS: Herein, we found that LSD1 activity is increased while levels of H3K4me2, a substrate of LSD1, is decreased in cellular and animal models of ALS. SD administration modulated the LSD1 activity and restored H3K4me2 levels in ChAT-positive motor neurons in the lumbar spinal cord of ALS mice. SD prevented cellular damage by improving the number and size of motor neurons in ALS mice. SD administration also reduced GFAP-positive astrogliogenesis in the white and gray matter of the lumbar spinal cord, improving the neuropathology of ALS mice. Moreover, SD administration improved the rotarod performance and gait analysis of ALS mice. Finally, SD administration delayed disease onset and prolonged the lifespan of ALS (G93A) transgenic mice. CONCLUSION: Together, modulating epigenetic targets such as LSD1 by small compounds may be a useful therapeutic strategy for treating ALS.


Assuntos
Esclerose Lateral Amiotrófica , Camundongos , Animais , Esclerose Lateral Amiotrófica/metabolismo , Espermidina/metabolismo , Espermidina/uso terapêutico , Histonas/metabolismo , Superóxido Dismutase , Neurônios Motores , Medula Espinal/metabolismo , Medula Espinal/patologia , Camundongos Transgênicos , Modelos Animais de Doenças
3.
Ann Surg Treat Res ; 103(3): 129-144, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36128031

RESUMO

Purpose: Young age at diagnosis has been considered a poor prognostic factor. However, considering young age itself as an independent poor prognostic factor for all breast cancers is unwarranted. We analyzed the different prognostic effects of age as a prognostic factor according to molecular subtype. Methods: We retrieved data from 1,819 patients with primary breast cancer at the breast cancer center between 2007 and 2012. We classified each molecular subtype in 3 age cohorts (<40, 40-50, and >50 years). The associations of age and molecular subtypes with relapse-free survival (RFS) and disease-specific survival (DSS) were assessed. Results: Patients aged <40 years showed a poor histologic grade, hormone receptor negative expression than older patients, and had a higher proportion of triple-negative breast cancer (TNBC) (P < 0.001). This was thought to have led to a significantly shorter RFS than that of older patients (P < 0.001). In the subgroup analysis according to molecular subtypes, the poorer RFS was observed only in patients aged <40 years with luminal type breast cancer (P < 0.001). Age was an independent prognostic factor of RFS in luminal-type breast cancer (P = 0.001). However, no difference in RFS between age groups was found for patients with other subtypes (human epidermal growth factor receptor 2 overexpression, TNBC). No significant effect between age groups was found in DSS for patients with all molecular subtypes. Conclusion: Age at diagnosis of breast cancer affected prognosis differently according to molecular subtype. Age itself is not an independent prognostic factor. Age of <40 years showed a limited worse prognostic impact of recurrence in luminal type breast cancer only.

4.
J Korean Med Sci ; 37(26): e207, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35790209

RESUMO

BACKGROUND: There are several medical treatment options for endometrioma. Progestin, especially dienogest, is an effective drug for preventing recurrence of endometrioma after surgery. Additionally, oral contraceptive (OC) use after conservative surgery has been reported to reduce significantly the risk of endometrioma recurrence. The aim of this study was to compare the long-term effects of gonadotropin-releasing hormone (GnRH) agonist followed by OC to those of dienogest alone to prevent recurrence of endometrioma after laparoscopic surgery. METHODS: A retrospective cohort study was performed on patients who underwent conservative laparoscopic surgery for endometrioma between January 2000 and December 2020, in the Endometriosis Clinic, Department of Gynecology, Samsung Medical Center. A total of 624 patients who received medical treatment at least six months after laparoscopic conservative surgery for endometrioma was included. Among them, 372 patients used OC after GnRH agonist therapy, and 252 patients used dienogest. Within the OC group, 148 used a 21/7 regiment and 224 used a 24/4 regimen. A cumulative endometrioma recurrence curve was presented using the Kaplan-Meier method to compare the recurrence of those groups. RESULTS: The cumulative recurrence rate of endometrioma for 60 months was 2.08% (n = 4) in the OC after GnRH agonist group and 0.40% (n = 1) in the dienogest group. There was no statistical difference in cumulative recurrence of endometrioma between the two groups. In subgroup analysis, the cumulative recurrence rate of endometrioma over 60 months was 4.21% (n = 2) in the 21/7 OC group and 1.09% (n = 2) in the 24/4 OC group and showed no significant difference. CONCLUSION: Long-term use of OC after GnRH agonist as well as that of dienogest treatment are effective postoperative medical therapies for preventing endometrioma recurrence. Thus, the choice of regimen can be individualized or used interchangeably depending on patient condition, need for contraception, and compliance with drug therapy.


Assuntos
Endometriose , Anticoncepção , Anticoncepcionais Orais/uso terapêutico , Endometriose/tratamento farmacológico , Endometriose/prevenção & controle , Endometriose/cirurgia , Feminino , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Nandrolona/análogos & derivados , Estudos Retrospectivos , Prevenção Secundária/métodos
5.
Antioxidants (Basel) ; 11(7)2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-35883881

RESUMO

Paeonol is a naturally occurring phenolic agent that attenuates neurotoxicity in neurodegenerative diseases. We aimed to investigate the antioxidant and protective effects of paeonol and determine its transport mechanism in wild-type (WT; NSC-34/hSOD1WT) and mutant-type (MT; NSC-34/hSOD1G93A) motor neuron-like amyotrophic lateral sclerosis (ALS) cell lines. Cytotoxicity induced by glutamate, lipopolysaccharides, and H2O2 reduced viability of cell; however, the addition of paeonol improved cell viability against neurotoxicity. The [3H]paeonol uptake was increased in the presence of H2O2 in both cell lines. Paeonol recovered ALS model cell lines by reducing mitochondrial oxidative stress induced by glutamate. The transport of paeonol was time-, concentration-, and pH-dependent in both NSC-34 cell lines. Kinetic parameters showed two transport sites with altered affinity and capacity in the MT cell line compared to the WT cell line. [3H]Paeonol uptake increased in the MT cell line transfected with organic anion transporter1 (Oat1)/Slc22a6 small interfering RNA compared to that in the control. Plasma membrane monoamine transporter (Pmat) was also involved in the uptake of paeonol by ALS model cell lines. Overall, paeonol exhibits neuroprotective activity via a carrier-mediated transport system and may be a beneficial therapy for preventing motor neuronal damage under ALS-like conditions.

6.
Sci Rep ; 12(1): 5762, 2022 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-35388056

RESUMO

Approximately 58 shorebird species, including endangered and threatened species, use various habitats while traveling on their long-distance migratory routes in the East Asian-Australasian Flyway (EAAF). Coastal rice paddies in midwestern Korea, which are located in the EAAF, serve as inland wetlands and provide important stopover sites for long-distance migratory shorebirds. We studied how shorebird population density is affected across periods, time since habitat formation, and field type, at the rice field scale. The shorebirds most frequently observed in rice paddies were, in order, black-tailed godwits (Limosa limosa), common greenshanks (Tringa nebularia), and wood sandpipers (T. glareola). Black-tailed godwits and wood sandpipers were affected by time since formation, field type, and water level, whereas field type affected common greenshanks. We propose that (1) flooding time, (2) shallow water level, (3) harrowed field type, and (4) 5-7 days of management intervals at paddy fields are important factors influencing shorebird species density, although all the factors did not influence common greenshank density. We propose that environmental characteristics derived from field management in rice paddies influence habitat use by migratory shorebirds. These factors need to be considered to systematically protect and manage shorebirds that use rice paddies as stopovers during their migration events.


Assuntos
Charadriiformes , Oryza , Agricultura , Migração Animal , Animais , Conservação dos Recursos Naturais , Ecossistema , Água
7.
J Biomed Sci ; 29(1): 2, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35012534

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devasting neurodegenerative disorder for which no successful therapeutics are available. Valproic acid (VPA), a monocarboxylate derivative, is a known antiepileptic drug and a histone deacetylase inhibitor. METHODS: To investigate whether monocarboxylate transporter 1 (MCT1) and sodium-coupled MCT1 (SMCT1) are altered in ALS cell and mouse models, a cellular uptake study, quantitative real time polymerase chain reaction and western blot parameters were used. Similarly, whether VPA provides a neuroprotective effect in the wild-type (WT; hSOD1WT) and ALS mutant-type (MT; hSOD1G93A) NSC-34 motor neuron-like cell lines was determined through the cell viability assay. RESULTS: [3H]VPA uptake was dependent on time, pH, sodium and concentration, and the uptake rate was significantly lower in the MT cell line than the WT cell line. Interestingly, two VPA transport systems were expressed, and the VPA uptake was modulated by SMCT substrates/inhibitors in both cell lines. Furthermore, MCT1 and SMCT1 expression was significantly lower in motor neurons of ALS (G93A) model mice than in those of WT mice. Notably, VPA ameliorated glutamate- and hydrogen peroxide-induced neurotoxicity in both the WT and MT ALS cell lines. CONCLUSIONS: Together, the current findings demonstrate that VPA exhibits a neuroprotective effect regardless of the dysfunction of an MCT in ALS, which could help develop useful therapeutic strategies for ALS.


Assuntos
Esclerose Lateral Amiotrófica , Transportadores de Ácidos Monocarboxílicos/metabolismo , Fármacos Neuroprotetores , Simportadores/metabolismo , Ácido Valproico/farmacologia , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/metabolismo , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Transgênicos , Neurônios Motores , Fármacos Neuroprotetores/farmacologia , Superóxido Dismutase
8.
Korean J Clin Oncol ; 18(2): 93-96, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36945243

RESUMO

Breast metastases from extramammary malignancies are rare. Here, we report a case of breast metastasis from hepatocellular carcinoma (HCC) after breast mass excision in a 63-year-old woman. A new breast nodule was noticed after transarterial chemoembolization, transarterial radioembolization, and stereotactic body radiation therapy for HCC. Breast ultrasound and core needle biopsy were performed to differentiate between the breast tumors. The biopsy result was invasive breast carcinoma, and wide excision of the breast was performed. The final pathological diagnosis was HCC breast metastasis based on histological findings and immunohistochemical staining results. After 9 months of follow-up, HCC and breast metastasis recurred. Despite palliative treatment, the patient died due to complications and general health deterioration. Although breast metastasis due to HCC is very rare, HCC breast metastasis should be considered when a new breast mass is discovered in a patient with a history of HCC for effective treatment and management.

9.
Int J Mol Sci ; 22(22)2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34830381

RESUMO

Huntington's disease (HD) is a rare neurodegenerative disorder caused by an expansion of CAG trinucleotide repeat located in the exon 1 of Huntingtin (HTT) gene in human chromosome 4. The HTT protein is ubiquitously expressed in the brain. Specifically, mutant HTT (mHTT) protein-mediated toxicity leads to a dramatic degeneration of the striatum among many regions of the brain. HD symptoms exhibit a major involuntary movement followed by cognitive and psychiatric dysfunctions. In this review, we address the conventional role of wild type HTT (wtHTT) and how mHTT protein disrupts the function of medium spiny neurons (MSNs). We also discuss how mHTT modulates epigenetic modifications and transcriptional pathways in MSNs. In addition, we define how non-cell autonomous pathways lead to damage and death of MSNs under HD pathological conditions. Lastly, we overview therapeutic approaches for HD. Together, understanding of precise neuropathological mechanisms of HD may improve therapeutic approaches to treat the onset and progression of HD.


Assuntos
Epigênese Genética , Proteína Huntingtina/genética , Doença de Huntington/genética , Neurônios/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Modelos Animais de Doenças , Humanos , Doença de Huntington/patologia , Neostriado/metabolismo , Neostriado/patologia , Proteínas do Tecido Nervoso/genética , Neurônios/patologia
10.
Sci Rep ; 11(1): 20633, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34667193

RESUMO

Artificial synaptic devices based on natural organic materials are becoming the most desirable for extending their fields of applications to include wearable and implantable devices due to their biocompatibility, flexibility, lightweight, and scalability. Herein, we proposed a zein material, extracted from natural maize, as an active layer in an artificial synapse. The synaptic device exhibited notable digital-data storage and analog data processing capabilities. Remarkably, the zein-based synaptic device achieved recognition accuracy of up to 87% and exhibited clear digit-classification results on the learning and inference test. Moreover, the recognition accuracy of the zein-based artificial synapse was maintained within a difference of less than 2%, regardless of mechanically stressed conditions. We believe that this work will be an important asset toward the realization of wearable and implantable devices utilizing artificial synapses.

11.
J Clin Biochem Nutr ; 69(2): 158-170, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34616108

RESUMO

Dietary intervention to prevent Helicobacter pylori (H. pylori)-gastric cancer might be ideal by long-term intervention, rejuvenating action, and no risk of bacterial resistance. Stimulated with finding that kimchi prevented H. pylori-gastric cancer, we compared the efficacy of cancer preventive kimchi (cpkimchi) and standard recipe kimchi (skimchi) and the efficacy between fermented kimchi and non-fermented kimchi (kimuchi) in H. pylori-initiated gastric cancer model and explored novel mechanisms hinted from RNAseq transcriptome analysis. Animal models assessing gastric pathology on 24 and 36 weeks after H. pylori initiated, salt diet-promoted gastric mutagenesis model showed fermented cpkimchi afforded the best outcome of either rejuvenating atrophic gastritis or inhibiting tumorigenesis compared to skimchi and kimuchi. Highest inhibition of atrophic gastritis was achieved with cpkimchi, while significantly lower in kimuchi. Transcriptomic analysis showed ameliorated-endoplasmic reticulum (ER) stress, -oxidative stress, and -apoptosis as major rejuvenating action of cpkimchi. Homogenates from animal model showed that elevated expressions of p-PERK, IRE, ATF6, p-elf, and XBP1 in control group, while significantly decreased with dietary intake of only cpkimchi. Significantly increased expressions of HO-1 and γ-GCS were only noted with cpkimchi. Conclusively, long-term dietary intervention of fermented cpkimchi can be potential way preventing H. pylori-associated carcinogenesis via rejuvenation of atrophic gastritis.

12.
J Clin Biochem Nutr ; 69(2): 171-187, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34616109

RESUMO

Dietary intervention to prevent Helicobacter pylori (H. pylori)-gastric cancer might be ideal because of no risk of bacterial resistance, safety, and rejuvenating action of atrophic gastritis. We have published data about the potential of fermented kimchi as nutritional approach for H. pylori. Hence recent advances in RNAseq analysis lead us to investigate the transcriptome analysis to explain these beneficiary actions of kimchi. gastric cells were infected with either H. pylori or H. pylori plus kimchi. 943 genes were identified as significantly increased or decreased genes according to H. pylori infection and 68 genes as significantly changed between H. pylori infection and H. pylori plus kimchi (p<0.05). Gene classification and Medline database showed DLL4, FGF18, PTPRN, SLC7A11, CHAC1, FGF21, ASAN, CTH, and CREBRF were identified as significantly increased after H. pylori, but significantly decreased with kimchi and NEO1, CLDN8, KLRG1, and IGFBP1 were identified as significantly decreased after H. pylori, but increased with kimchi. After KEGG and STRING-GO analysis, oxidative stress, ER stress, cell adhesion, and apoptosis genes were up-regulated with H. pylori infection but down-regulated with kimchi, whereas tissue regeneration, cellular anti-oxidative response, and anti-inflammation genes were reversely regulated with kimchi (p<0.01). Conclusively, transcriptomes of H. pylori plus kimchi showed significant biological actions.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33572436

RESUMO

Women's participation in society has been increasing; however, they often remain overloaded with housework, and this gender role difference can hinder their work-life balance in Korea. Therefore, this study classified latent profiles according to job quality indices for South Korean female employees and examined the characteristics of each profile and how they affect work-life balance. This study was a secondary analysis of data collected through the fifth Korean Working Conditions Survey in South Korea. The Bayesian information criterion, entropy, and the Lo-Mendell-Rubin adjusted likelihood ratio test were used to determine the number of latent profiles. Chi-square tests were conducted to understand the characteristics of each profile. Comparisons between work-life balance and the latent profiles were made using the Bolck-Croon-Hagenaars method. Female employees in South Korea were classified into five profiles: "high-flying," "smooth," "footloose," "strict," and "manual." The "footloose" profile showed the most positive work-life balance, and the "manual" profile had the highest level of work-family conflict. Therefore, policies and social supports should be created with the aim of improving the implementation of current strategies promoting work-life balance to better fit each working condition.


Assuntos
Apoio Social , Equilíbrio Trabalho-Vida , Teorema de Bayes , Feminino , Humanos , Satisfação no Emprego , República da Coreia , Inquéritos e Questionários
14.
Artigo em Inglês | MEDLINE | ID: mdl-33467475

RESUMO

As a result of mass media development, disaster-related information, such as the severity of damage, can be easily shared; thus, the issue of consequent indirect trauma has become as important as that of direct trauma. This study developed a scale to measure the degree of indirect trauma caused by media exposure to social disasters and then verified this scale's reliability and validity. Initial items were developed through a literature review; 39 items were selected by examining their content validity and conducting a pretest. To verify the scale's validity and reliability, exploratory factor analyses were conducted, and Cronbach's alpha coefficients were calculated. The explanatory power of the screening scale developed through this study was 62.2%. The scale was ultimately composed of three factors comprising 24 items. Through exploratory factor analyses, factors were identified as "psychological, physical, and behavioral responses to social disasters" (factor 1), "moral resentment due to social disasters" (factor 2), and "a sense of threat to life due to social disasters" (factor 3). Regarding internal reliability, Cronbach's alpha values ranged between 0.85 and 0.96. Future studies with expanded participant populations are suggested, which could further verify the scale's validity and reliability and complement its shortcomings.


Assuntos
Desastres , Análise Fatorial , Humanos , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
15.
Healthcare (Basel) ; 9(1)2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33466252

RESUMO

The objective of this study was to investigate the factors affecting the quality of dying and death among terminally ill patients in an intensive care unit in Korea using a cross-sectional, online survey. A total of 300 nurses in the intensive care unit who had cared for a terminally ill patient for at least 48 h prior to death in the past six months were chosen to participate. The person-centered critical care nursing (PCCN) score and quality of dying and death (QODD) had a positive correlation. The QODD score increased when the consultation was conducted between the terminally ill patients and their doctors when CPR was not performed within 48 h of death, and when the PCCN score increased. The quality of death of patients is affected by whether they have sufficiently consulted with healthcare providers regarding their death and how much respect they receive. It is important for nurses to practice and improve patient-centered nursing care in order to ensure a good quality of death for terminally ill patients.

16.
Biochem Biophys Res Commun ; 532(2): 315-320, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-32873393

RESUMO

BRAF mutants are categorized into three classes according to dependency on RAS signaling and RAF dimerization-dependency. Class I BRAF V600 mutants (RAS-independent monomer) are sensitive to vemurafenib. In contrast, both class II mutants (RAS-independent dimer) and class III mutants (RAS-dependent heterodimer) are insensitive to vemurafenib. It is not likely that BRAF inhibitors capable of inhibiting all classes of BRAF mutants are currently available. Herein, we report GNF-7 and its novel derivative, SIJ1227 as the first BRAF inhibitors capable of inhibiting all classes of BRAF mutants. Compared with vemurafenib and PLX8394, both GNF-7 and SIJ1227 possess much more strong anti-proliferative activities on melanoma (A375 and C8161) and lung cancer cells (H1755 and H1666) harboring BRAF V600E (class I mutant), BRAF G464E/G469A (class II mutant) and BRAF G466V (class III mutant), respectively. Also, both GNF-7 and SIJ1227 are capable of inhibiting more strongly colony formation than vemurafenib and PLX8394 in 3D soft agar assay using C8161 melanoma cells. In addition, GNF-7 and SIJ1227 suppress more strongly migration/invasion of these cancer cells than vemurafenib and PLX8394. Taken together, both GNF-7 and SIJ1227 are much superior to vemurafenib and PLX8394 in terms of capability to inhibit all classes of BRAF mutants.


Assuntos
Antineoplásicos/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/patologia , Simulação de Acoplamento Molecular , Mutação , Proteínas Proto-Oncogênicas B-raf/química , Pirimidinonas/farmacologia , Vemurafenib/farmacologia
17.
Eur J Med Chem ; 208: 112688, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32906067

RESUMO

Anoctamin1 (ANO1), a calcium-activated chloride ion channel (CaCC), is associated with various physiological functions including cancer progression and metastasis/invasion. ANO1 has been considered as a promising target for cancer therapeutics as ANO1 is over-expressed in a variety of cancers including glioblastoma (GBM) and inhibition of ANO1 has been reported to suppress cell proliferation, migration and invasion in GBM. GBM is one of the most common and aggressive cancers with poor prognosis with median survival for 15 months. Lack of effective treatment options against GBM emphasizes urgent necessity of effective GBM therapeutics. In an effort to discover potent and selective ANO1 inhibitors capable of inhibiting GBM cells, we have designed and synthesized a series of new 2-aminothiophene-3-carboxamide derivatives and performed SAR studies using both fluorescent cellular membrane potential assay and whole-cell patch-clamp recording. We observed that among these substances, 9c and 10q strongly suppress ANO1 channel activities and possess remarkable selectivity over ANO2. Unique structural feature of 10q, a cyclopentane-fused thiophene-3-carboxamide derivative, is the presence of benzoylthiourea functionality which dramatically contributes to activity. Both 9c and 10q suppress more strongly proliferation of GBM cells than four reference compounds including 3, Ani-9 and are also capable of inhibiting much more strongly colony formation than reference compounds in both 2D colony formation assay and 3D soft agar assay using U251 glioma cells. In addition, 9c and 10q suppress far more strongly migration/invasion of GBM cells than reference compounds. We, for the first time, found that the combination of ANO1 inhibitor (9c or 3) and temozolomide (TMZ) brings about remarkable synergistic effects in suppressing proliferation of GBM cells. Our study may provide an insight into designing selective and potent ANO1 inhibitors aiming at GBM treatment.


Assuntos
Anoctamina-1/antagonistas & inibidores , Antineoplásicos/farmacologia , Glioblastoma/tratamento farmacológico , Proteínas de Neoplasias/antagonistas & inibidores , Tiofenos/farmacologia , Animais , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Sinergismo Farmacológico , Células HEK293 , Humanos , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade , Temozolomida/farmacologia , Tiofenos/síntese química
18.
Artigo em Inglês | MEDLINE | ID: mdl-32635500

RESUMO

Maintaining a healthy work-life balance is important for both males and females. Nevertheless, gender segregation still exists in labor markets in South Korea. Therefore, this study aimed to investigate differences in occupational characteristics, job quality indices, and work-life balance between male and female employees. This study was a secondary analysis of the data collected through the fifth Korean Working Conditions Survey in South Korea. Generalized ordinal logistic regression analysis was carried out to investigate the associations between job quality indices and work-life balance of employees by gender. The job quality indices were different according to gender. Male employees were mainly affected by working time quality and work intensity, while female employees were affected by both these factors and by the physical environment. Therefore, strategies differentiated by gender are necessary to improve work-life balance. In particular, more careful attention should be paid to female workers' physical environment.


Assuntos
Emprego/psicologia , Satisfação no Emprego , Ocupações , Apoio Social , Estresse Psicológico , Equilíbrio Trabalho-Vida , Adolescente , Adulto , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Saúde Ocupacional , República da Coreia , Fatores Sexuais , Inquéritos e Questionários , Carga de Trabalho , Adulto Jovem
19.
Zoolog Sci ; 37(3): 255-262, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32549539

RESUMO

Successful refueling at staging sites is essential for the survival and reproduction of migratory birds. Understanding their staging ecology is therefore crucial for the conservation of migrant species. Rice fields in the mid-western region of the Korean Peninsula serve as staging habitats for the black-tailed godwit (Limosa limosa). We examined the behavior of staging black-tailed godwits in rice fields located in the East Asian-Australasian Flyway during their northward migration. Specifically, we tested the effect of flock size and water level on the foraging, vigilance, and resting behaviors of black-tailed godwits. Our observations revealed that as flock size increased, stepping rate, pecking rate, and vigilance duration decreased, while probing rate, preening duration, and foraging efficiency increased. Stepping and pecking rates increased at low water levels, compared with high water levels. We determined that the behavior of black-tailed godwits at the staging site is influenced by flock size and water level. These observations suggest that black-tailed godwits form larger flocks to increase foraging efficiency by lowering individual-level vigilance, and to spend more time on preening, which is critical for flight and survival. It can be also inferred, based on the shift in primary foraging mode between probing and pecking depending on the water level, that they obtain higher foraging efficiency by flexibly adapting their foraging mode to the conditions in rice fields that are subject to agricultural activities. Our results are expected to serve as basic data for establishing efficient management strategies for anthropogenic habitats for the conservation of migratory shorebirds such as black-tailed godwit.


Assuntos
Migração Animal , Charadriiformes/fisiologia , Conservação dos Recursos Naturais , Comportamento Alimentar , Animais , Produção Agrícola , Meio Ambiente , Oryza/crescimento & desenvolvimento , República da Coreia
20.
Chem Commun (Camb) ; 56(25): 3657-3660, 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32108200

RESUMO

We report blue- and green-emitting two-photon probes derived from naphthalene and fluorene derivatives (as fluorophores) and an endoplasmic reticulum (ER) retrieval peptide (KDEL; as an ER-targeting moiety) that can detect the ER in a live cell by both one-photon and two-photon microscopy (TPM) and in a live tissue by TPM.


Assuntos
Retículo Endoplasmático/química , Corantes Fluorescentes/química , Microscopia de Fluorescência por Excitação Multifotônica , Fótons , Fluorenos/química , Células HeLa , Humanos , Estrutura Molecular , Naftalenos/química , Imagem Óptica , Peptídeos/química
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