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Upon glucose restriction, eukaryotic cells upregulate oxidative metabolism to maintain homeostasis. Using genetic screens, we find that the mitochondrial serine hydroxymethyltransferase (SHMT2) is required for robust mitochondrial oxygen consumption and low glucose proliferation. SHMT2 catalyzes the first step in mitochondrial one-carbon metabolism, which, particularly in proliferating cells, produces tetrahydrofolate (THF)-conjugated one-carbon units used in cytoplasmic reactions despite the presence of a parallel cytoplasmic pathway. Impairing cytoplasmic one-carbon metabolism or blocking efflux of one-carbon units from mitochondria does not phenocopy SHMT2 loss, indicating that a mitochondrial THF cofactor is responsible for the observed phenotype. The enzyme MTFMT utilizes one such cofactor, 10-formyl THF, producing formylmethionyl-tRNAs, specialized initiator tRNAs necessary for proper translation of mitochondrially encoded proteins. Accordingly, SHMT2 null cells specifically fail to maintain formylmethionyl-tRNA pools and mitochondrially encoded proteins, phenotypes similar to those observed in MTFMT-deficient patients. These findings provide a rationale for maintaining a compartmentalized one-carbon pathway in mitochondria.
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Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Glicina Hidroximetiltransferase/metabolismo , Mitocôndrias/genética , Iniciação Traducional da Cadeia Peptídica , RNA de Transferência de Metionina/química , Serina/química , Animais , Apoptose , Neoplasias da Mama/metabolismo , Sistemas CRISPR-Cas , Proliferação de Células , Citosol/metabolismo , Feminino , Glicina Hidroximetiltransferase/antagonistas & inibidores , Glicina Hidroximetiltransferase/genética , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Processamento de Proteína Pós-Traducional , RNA de Transferência de Metionina/genética , RNA de Transferência de Metionina/metabolismo , Serina/genética , Serina/metabolismo , Tetra-Hidrofolatos/farmacologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Recent advanced studies on flexible and stretchable electronic devices and optoelectronics have made possible a variety of soft and more functional electronic devices. With consumer demand for highly functional or free-form displays, high flexibility and stretchability in light-emitting devices are needed. Herein, we developed a unique structure of stretchable substrates with pillar arrays to reduce the stress on the active area of devices when strain is applied. We confirmed the advantages of the produced structures using mechanical simulation tools and determined that the structures effectively lessen the applied stress of interconnection as well as the active area in a stretched state. With this stress-relief stretchable substrate, we realized stretchable OLEDs that are compliant and maintain their performance under high strain deformation. Also, devices can be stretched in the biaxis, which is superior to only one-directional stretchable electronics; as such, devices can be used in practical applications like wearable electronics and health monitoring systems. We propose, for the first time, stretchable OLEDs patterned by the thermal evaporation fabrication process onto stress-relief substrates. These OLEDs can mitigate certain problems in previous studies of stretchable OLEDs without need to find new materials or to use a prestrained fabrication process.
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Silicon photonic structures have attracted a great deal of attention due to their potential benefits of efficient light management in optoelectronic applications. In this paper, we demonstrate broadband optical absorption enhancement in solution-processed amorphous silicon (a-Si) by leveraging the advantages of silicon photonic structures. Graded refractive index silicon multi-layer structures are employed by modulating optical constants with simple process optimization, resulting in significantly improved reflectance over a broad range of visible wavelengths. In addition, nanopatterning flexibility of solution-processed silicon provides benefits for tailoring silicon optical properties. With the incorporation of the two-dimensional submicron pattern into silicon films, the absorptivity of silicon films improves considerably below the wavelength of the bandgap (λ â¼ 800 nm), and the limited bandwidth of absorptivity in silicon films can be extended to near-infrared wavelengths by coating with a thin gold layer. The methodology is generally applicable to a platform for improving the broadband optical absorption of photonic and optoelectronic devices.
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This study investigates the effects of home-based Kakao Healthcare breathing exercises and stretching on respiratory function and fatigue in COVID-19-cured patients. A total of 35 participants performed four movements of home-based breathing exercises and five respiratory muscle stretching exercises four times a week for four weeks. Respiratory function was measured using forced vital capacity(FVC), forced expiratory volume in one second(FEV1), FEV1/FVC ratio, and peak expiratory flow(PEF). Fatigue was assessed using the Fatigue Severity Scale (FSS). Data analysis was performed using independent-sample and paired-sample t-tests in SPSS 24, with the significance level set at p < 0.05. After four weeks of home-based Kakao Healthcare breathing exercises, there were significant increases in respiratory FVC, FEV1, FEV1/FVC, and PEF function values observed in the training group (T.G.) after the exercise intervention (p < 0.05). Such an increase was observed when comparing these values with their corresponding pre-exercise measurements. In contrast, there were no statistically significant differences in respiratory function outcomes before and after exercise in the control group (C.G.) (p > 0.05). The FSS scores were statistically significant within the training group (T.G.) (p > 0.05). The 4-week Kakao Healthcare breathing exercise scheme was found to be capable of improving some respiratory functions in COVID-19-recovered patients, but it showed no significant improvement in fatigue levels.
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Shift work has adverse health effects such as diabetes, cardiovascular disease, sleep disturbance, depression, and breast cancer. Gastro-esophageal reflux disease (GERD) results in lesions such as reflux esophagitis (RE) and Barrett's esophagus. This study investigated the association between shift work and RE. A cohort study was conducted with 140,553 participants who were followed up at least once from 2012 to 2018. Type of working and shift types were collected using standardized questionnaires. Esophagogastroduodenoscopy (EGD) was performed by experienced endoscopists who were blinded to the aims of this study. According to the Los Angeles classification, RE was categorized based on the extent of esophageal mucosal breaks. During the 469,217.2 person-years of follow-up, 35,185 participants developed incident cases of RE. The multivariable adjusted hazard ratio (95% confidence intervals) for incident cases comparing shift work to fixed day work was 1.09 (1.04-1.13). This association was more strongly observed in the younger age group (18-39 years old) and the female group. In conclusion, shift work was significantly associated with the incidence of RE. Particularly, the results were more significant in the younger and female groups.
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Esôfago de Barrett , Esofagite Péptica , Jornada de Trabalho em Turnos , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Esofagite Péptica/etiologia , Esofagite Péptica/complicações , Estudos de Coortes , Incidência , Esôfago de Barrett/etiologia , Esôfago de Barrett/complicações , República da Coreia/epidemiologiaRESUMO
With the growing interest in companion animals and the rapidly expanding animal healthcare and pharmaceuticals market worldwide. With the advancements in RNA-sequencing (RNA-seq) technology, it has become a valuable tool for understanding biological processes in companion animals and has multiple applications in animal healthcare. Historically, veterinary diagnoses and treatments relied solely on clinical symptoms and drugs used in human diseases. However, RNA-seq has emerged as an effective technology for studying companion animals, providing insights into their genetic information. The sequencing technology has revealed that not only messenger RNAs (mRNAs) but also non-coding RNAs (ncRNAs) such as long ncRNAs and microRNAs can serve as biomarkers. Based on the examination of RNA-seq applications in veterinary medicine, particularly in dogs and cats, this review concludes that RNA-seq has significant potential as a diagnostic and research tool. It has enabled the identification of potential biomarkers for cancer and other diseases in companion animals. Further research and development are required to maximize the utilization of RNA-seq for improved disease diagnosis and therapeutic targeting in companion animals.
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Doenças do Gato , Doenças do Cão , MicroRNAs , Neoplasias , Drogas Veterinárias , Animais , Gatos , Cães , Humanos , Doenças do Gato/diagnóstico , Doenças do Gato/genética , Doenças do Gato/terapia , Doenças do Cão/diagnóstico , Doenças do Cão/genética , Doenças do Cão/terapia , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/terapia , Neoplasias/veterinária , BiomarcadoresRESUMO
AIMS: Gastric cancer (GC) is an invasive, fatal disease with a poor prognosis. Gene-directed enzyme prodrug therapy via genetically engineered neural stem cells (GENSTECs) has been widely studied in various malignancies, such as breast, ovarian, and renal cancer. In this study, the human neural stem cells expressing cytosine deaminase and interferon beta (HB1.F3.CD.IFN-ß) cells were applied to convert non-toxic 5-fluorocytosine to cytotoxic 5-fluorouracil and secrete IFN-ß. MATERIALS AND METHODS: Human lymphokine-activated killer cells (LAKs) were generated by stimulating human peripheral blood mononuclear cells (PBMCs) by interleukin-2, and we evaluated the cytotoxic activity and migratory ability of LAKs co-cultured with GNESTECs or their conditioned media in vitro. A GC-bearing human immune system (HIS) mouse model was generated by transplanting human PBMCs followed by subcutaneous engraftment of MKN45 cells in NSG-B2m mice to evaluate the involvement of T cell-mediated anti-cancer immune activity of GENSTECs. KEY FINDINGS: In vitro studies showed the presence of HB1.F3.CD.IFN-ß cells facilitated the migration ability of LAKs to MKN45 cells and activated their cytotoxic potential. In MKN45-xenografted HIS mice, treatment with HB1.F3.CD.IFN-ß cells resulted in increased cytotoxic T lymphocyte (CTL) infiltration throughout the tumor, including the central area. Moreover, the group treated to HB1.F3.CD.IFN-ß showed increased granzyme B expression in the tumor, eventually enhancing the tumor-killing potential of CTLs and significantly delaying tumor growth. SIGNIFICANCE: These results indicate that the HB1.F3.CD.IFN-ß cells exert anti-cancer effects on GC by facilitating the T cell-mediated immune response, and GENSTECs are a promising therapeutic strategy for GC.
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Antineoplásicos , Células-Tronco Neurais , Neoplasias Gástricas , Humanos , Animais , Camundongos , Interferon beta/metabolismo , Neoplasias Gástricas/terapia , Neoplasias Gástricas/metabolismo , Citosina Desaminase/genética , Citosina Desaminase/metabolismo , Leucócitos Mononucleares/metabolismo , Linhagem Celular Tumoral , Células-Tronco Neurais/metabolismo , Antineoplásicos/metabolismoRESUMO
For primary prevention, it is important for public health and clinical medicine to identify and characterize modifiable risk factors of stroke. In existing literature, the impact of occupational variables on ischemic and hemorrhagic stroke has been extensively studied. This review summarizes the available data on the significance of occupational variables in stroke. The results of this review suggest that there is sufficient evidence for the relationship between increased risk of stroke and job stress, working in extreme temperatures, long working hours, and/or shift work. The association between long working hours and occupational exposure to noise and chemicals remains inconclusive although several studies have reported this finding. This review will act as a step toward future research and provide information that may serve as a baseline for developing targeted interventions to prevent stroke in the working population.
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Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, with high mortality and recurrence rate. In this study, we generated a human immune system mouse model by transplanting human peripheral blood mononuclear cells into NSG-B2m mice followed by xenografting AsPC-1 cells, after which we assessed the role of transforming growth factor-ß2 (TGF-ß2) in T-cell-mediated anti-tumor immunity. We observed that inhibiting the TGF-ß2 production by TGF-ß2 antisense oligonucleotide (TASO) combined with IL-2 delays pancreatic cancer growth. Co-treatment of TASO and IL-2 had little effect on the SMAD-dependent pathway, but significantly inhibited the Akt phosphorylation and sequentially activated GSK-3ß. Activation of GSK-3ß by TASO subsequently suppressed ß-catenin and α-SMA expression and resulted in attenuated fibrotic reactions, facilitating the infiltration of CD8 + cytotoxic T lymphocytes (CTLs) into the tumor. TGF-ß2 inhibition suppressed the Foxp3 + regulatory T-cells in peripheral blood and tumors, thereby enhancing the tumoricidal effects of CTLs associated with increased granzyme B and cleaved caspase-3. Moreover, changes in the T-cell composition in peripheral blood and at the tumor site by TASO and IL-2 induced the increase of pro-inflammatory cytokines such as IFN-γ and TNF-α and the decrease of anti-inflammatory cytokines such as TGF-ßs. These results indicate that the TGF-ß2 inhibition by TASO combined with IL-2 enhances the T-cell mediated anti-tumor immunity against SMAD4-mutated PDAC by modulating the tumor-associated fibrosis, suggesting that TASO in combination with IL-2 may be a promising immunotherapeutic intervention for PDAC.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Humanos , Camundongos , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Citocinas , Glicogênio Sintase Quinase 3 beta , Interleucina-2 , Leucócitos Mononucleares/metabolismo , Oligonucleotídeos Antissenso/farmacologia , Neoplasias Pancreáticas/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta2/farmacologia , Neoplasias PancreáticasRESUMO
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancer types that is highly resistant to conventional treatments, such as chemotherapy and radiotherapy. As the demand for more effective therapeutics for PDAC treatment increases, various approaches have been studied to develop novel targets. The cellular communication network (CCN) family is a matricellular protein that modulates various cellular functions, including cell adhesion, proliferation, migration, and invasiveness. Despite this, little is known about the role of CCN6 in PDAC. The current study investigated the role of CCN6 in PDAC by generating CCN6-overexpressing PANC-1 cells (PANC-1-CCN6) by infecting lentivirus particles containing CCN6. PANC-1-CCN6 induces cell viability and tumorigenesis than PANC-1 cells with empty vector (control). The PANC-1-CCN6 formed more colonies, and the size of spheroids increased compared to the control. The upregulation of CCN6 enhances the expression of bone morphogenetic proteins (BMPs) genes and the upregulation of p38 mitogen-activated protein kinases (MAPKs). In PANC-1-CCN6 cells, the levels of N-cadherin, VEGF, and Snail expression were higher than the control, while E-cadherin expression was lower, which is associated with upregulation of epithelial-to-mesenchymal transition (EMT). Consistent with the changes in EMT-related proteins in PANC-1-CCN6, the migratory ability and invasiveness were enhanced in PANC-1-CCN6. Xenografted PANC-1-CCN6 in immunocompromised mice exhibited accelerated tumor growth than the control group. In immunohistochemistry (IHC), the PANC-1-CCN6 xenografted tumor showed an increased positive area of PCNA and Ki-67 than the control. These results suggest that CCN6 plays a tumorigenic role and induces the metastatic potential by the p38 MAPK and BMPs signaling pathways. Although the role of CCN6 has been introduced as an antitumor factor, there was evidence of CCN6 acting to cause tumorigenesis and invasion in PANC-1.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Humanos , Camundongos , Proteínas Morfogenéticas Ósseas , Carcinogênese , Carcinoma Ductal Pancreático/genética , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células , Transição Epitelial-Mesenquimal , Neoplasias Pancreáticas/patologia , Transdução de Sinais , Proteína Quinase 14 Ativada por Mitógeno , Neoplasias PancreáticasRESUMO
This study aimed to identify the major industries and jobs with the highest proportion of workers' compensation (WC) claims for COVID-19, characterize COVID-19 WC claims in terms of their demographic properties and disease severity, and identify factors influencing the approval of COVID-19 WC claims as occupational disease. A total of 488 workers who submitted COVID-19-related claims to the Korea Workers' Compensation and Welfare Service (KWCWS) from January 2020 to July 2021 were analyzed. A Fisher's exact test was employed to associate the severity of COVID-19 infection with demographic properties. The highest proportion of all COVID-19 WC claims compensated as occupational disease (N=462) were submitted by healthcare workers (HCW=233, 50%), while only 9% (N=41) of the total originated from manufacturing industries. The 5% (N=26) of the COVID-19 WC claims accepted were evaluated as severe (N=15) and acute respiratory distress syndrome (N=9). A total of 71% (N=329) of the COVID-19 patients compensated (N=462) were from workplaces with infection clusters. A total of 26 WC cases were rejected for various reasons, including unclear infection routes, infection at private gatherings (including within families), no diagnosis, and more. Given our findings, we suggest an official system should be established to detect and compensate more job-associated infectious diseases like COVID-19.
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COVID-19 , Doenças Profissionais , Indenização aos Trabalhadores , Humanos , COVID-19/epidemiologia , Indústrias/estatística & dados numéricos , Doenças Profissionais/epidemiologia , República da Coreia/epidemiologia , Indenização aos Trabalhadores/estatística & dados numéricosRESUMO
Chronic liver injury due to various hepatotoxic stimuli commonly leads to fibrosis, which is a crucial factor contributing to liver disease-related mortality. Despite the potential benefits of Suaeda glauca (S. glauca) as a natural product, its biological and therapeutic effects are barely known. This study investigated the effects of S. glauca extract (SGE), obtained from a smart farming system utilizing LED lamps, on the activation of hepatic stellate cells (HSCs) and the development of liver fibrosis. C57BL/6 mice received oral administration of either vehicle or SGE (30 or 100 mg/kg) during CCl4 treatment for 6 weeks. The supplementation of SGE significantly reduced liver fibrosis induced by CCl4 in mice as evidenced by histological changes and a decrease in collagen accumulation. SGE treatment also led to a reduction in markers of HSC activation and inflammation as well as an improvement in blood biochemical parameters. Furthermore, SGE administration diminished fibrotic responses following acute liver injury. Mechanistically, SGE treatment prevented HSC activation and inhibited the phosphorylation and nuclear translocation of Smad2/3, which are induced by transforming growth factor (TGF)-ß1 in HSCs. Our findings indicate that SGE exhibits anti-fibrotic effects by inhibiting TGFß1-Smad2/3 signaling in HSCs.
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Chenopodiaceae , Células Estreladas do Fígado , Animais , Camundongos , Camundongos Endogâmicos C57BL , Cirrose Hepática/tratamento farmacológicoRESUMO
Although there have been advances in cancer therapy and surgical improvement, lung cancer has the lowest survival rate (19%) at all stages. This is because most patients are diagnosed with concurrent metastasis, which occurs due to numerous related reasons. Especially, lung cancer is one of the most common and malignant cancers in the world. Although there are advanced therapeutic strategies, lung cancer remains one of the main causes of cancer death. Recent work has proposed that epithelialmesenchymal transition (EMT) is the main cause of metastasis in most cases of human cancers including lung cancer. EMT involves the conversion of epithelial cells, wherein the cells lose their epithelial abilities and become mesenchymal cells involved in embryonic development, such as gastrulation and neural crest formation. In addition, recent research has indicated that EMT contributes to altering the cancer cells into cancer stem cells (CSCs). Although EMT is important in the developmental stages, this process also activates lung cancer progression, including complicated and diverse signaling pathways. Despite the numerous investigations on signaling pathways involved in the progression of lung cancer, this malignancy is considered critical for treatment. EMT in lung cancer involves many transcription factors and inducers, for example, Snail, TWIST, and ZEB are the master regulators of EMT. EMT-related factors and signaling pathways are involved in the progression of lung cancer, proposing new approaches to lung cancer therapy. In the current review, we highlight the signaling pathways implicated in lung cancer and elucidate the correlation of these pathways, indicating new insights to treat lung cancer and other malignancies.
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Coronary artery calcium score (CACS) is a useful method for predicting coronary artery disease in asymptomatic adults. In this study, we investigated the association between prolonged sedentary time and CACS. A cohort study was conducted in 14949 men with negative CACS (CACS = 0) at baseline who were followed up at least once. Sedentary time was categorized into < 7, 7-8, and ≥ 9 h/day. CACS was calculated by cardiac tomography. During 60,112.1 person-years of follow-up, 569 participants developed positive CACS. The multivariable adjusted hazard ratios (95% confidence intervals) for incident positive CACS comparing sedentary times of 7-8 h/day and ≥ 9 h/day to sedentary time of < 7 h/day were 1.25 (0.97-1.62) and 1.28 (1.03-1.59), respectively. This association was more strongly observed in the non-obese group (BMI < 25 kg/m2). In contrast, in the obese group (BMI ≥ 25 kg/m2), there was no significant association between sedentary time and incidence of positive CACS. Prolonged sedentary time was significantly associated with incidence of positive CACS in the study. CACS is also an effective screening tool for predicting future cardiovascular events in asymptomatic patients. Therefore, CACS can be an effective screening method for predicting coronary artery diseases in people with prolonged sedentary time, especially in metabolically healthy people.
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Vasos Coronários/metabolismo , Comportamento Sedentário , Calcificação Vascular/epidemiologia , Adulto , Estudos de Coortes , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/etiologia , Correlação de Dados , Voluntários Saudáveis , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , República da Coreia/epidemiologia , Tempo , Calcificação Vascular/complicaçõesRESUMO
Metastatic prostate cancers have a high mortality rate. KiSS1 was originally identified as a metastasis suppressor gene in metastatic melanoma and breast cancer, but its role in prostate cancer has been contradictory. This study was therefore undertaken to investigate the effects of KiSS1 overexpression on the growth and migration of human metastatic prostate cancer cells. We first tested the effect of KiSS1 overexpression on the growth and migration of DU145 human metastatic prostate cancer cells in vitro. DU145 cells were infected with the culture medium of 293T cells, which produce lentivirus particles containing KiSS1. A 2.5-fold increase in proliferation of KiSS1-overexpressing cancer cells was observed, and these cells formed tumor spheroids about 3 times larger than the vector control group. qPCR and immunoblotting revealed the association between increased cell growth and regulation of the PI3K/Akt and cell cycle genes, and also that increases in ß-catenin and CD133 contribute to tumor aggregation. KiSS1 overexpression resulted in upregulation of the ß-arrestin1/2 and Raf-MEK-ERK-NF-κB pathways via KiSS1R. Moreover, the migration and invasion of KiSS1-overexpressing cells were determined to be faster than the control group, along with 1.6-fold increased metastatic colonization of the KiSS1-overexpressing cancer cells. These were associated to the regulation of EMT gene expressions, such as E-cadherin and N-cadherin, and the upregulation of MMP9. In a xenograft mouse model inoculated with DU145 cells infected GFP or KiSS1 via a lentiviral vector, KiSS1 statistically significantly increased the tumor growth, with upregulation of PCNA and Ki-67 in the tumor tissues. In addition, KiSS1 increased the angiogenic capacity by upregulating VEGF-A and CD31, both in vitro and in vivo. Taken together, our results indicate that KiSS1 not only induces prostate cancer proliferation, but also promotes metastasis by increasing the migration, invasion, and angiogenesis of malignant cells.
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Kisspeptinas , Neoplasias da Próstata , Animais , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Kisspeptinas/genética , Kisspeptinas/metabolismo , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias da Próstata/patologiaRESUMO
Liver cancer has a high prevalence, with majority of the cases presenting as hepatocellular carcinoma (HCC). The prognosis of metastatic HCC has hardly improved over the past decade, highlighting the necessity for liver cancer research. Studies have reported the ability of the KiSS1 gene to inhibit the growth or metastasis of liver cancer, but contradictory research results are also emerging. We, therefore, sought to investigate the effects of KiSS1 on growth and migration in human HCC cells. HepG2 human HCC cells were infected with lentivirus particles containing KiSS1. The overexpression of KiSS1 resulted in an increased proliferation rate of HCC cells. Quantitative polymerase chain reaction and immunoblotting revealed increased Akt activity, and downregulation of the G1/S phase cell cycle inhibitors. A significant increase in tumor spheroid formation with upregulation of ß-catenin and CD133 was also observed. KiSS1 overexpression promoted the migratory, invasive ability, and metastatic capacity of the hepatocarcinoma cell line, and these effects were associated with changes in the expressions of epithelial mesenchymal transition (EMT)-related genes such as E-cadherin, N-cadherin, and slug. KiSS1 overexpression also resulted in dramatically increased tumor growth in the xenograft mouse model, and upregulation of proliferating cell nuclear antigen (PCNA) and Ki-67 in the HCC tumors. Furthermore, KiSS1 increased the angiogenic capacity by upregulation of the vascular endothelial growth factor A (VEGF-A) and CD31. Based on these observations, we infer that KiSS1 not only induces HCC proliferation, but also increases the metastatic potential by increasing the migratory ability and angiogenic capacity.
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Carcinoma Hepatocelular , Kisspeptinas , Neoplasias Hepáticas , Animais , Humanos , Camundongos , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Kisspeptinas/genética , Kisspeptinas/metabolismo , Neoplasias Hepáticas/patologia , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
Peptide nucleic acid (PNA) is a chimeric oligonucleotide with nucleotide-derived bases and a peptide backbone. Compared with natural nucleotides, PNA has several advantages, including improved stability and high sequence discrimination during duplex formation. Despite its potential for therapeutic application, analysis technologies have not been generalized, mainly due to ambiguous physiochemical properties resembling those of nucleic acids as well as protein. Here we present a PNA detection method: sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by electrotransfer to a Western blotting membrane and then hybridization with a radiolabeled oligonucleotide probe. This method is useful for evaluating the quality of synthetic PNA and determining its intracellular localization.
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Hibridização de Ácido Nucleico/métodos , Ácidos Nucleicos Peptídicos/química , Linhagem Celular , Eletroforese em Gel de Poliacrilamida , Humanos , MicroRNAs/química , Sondas de Oligonucleotídeos/química , Ácidos Nucleicos Peptídicos/metabolismoRESUMO
In Korea, the cause of lung disease of unknown origin was identified as humidifier disinfectants in November 2011. In February 2017, the 'Special Act on Remedy for Damage Caused by Humidifier Disinfectants' was promulgated. Even though emotional and mental injuries caused by humidifier disinfectants have been reported, the focus of the special act has been on physical injury only, and criteria for recognizing mental health impact have not been considered. This case considers emotional and mental injury caused by humidifier disinfectants. After a humidifier disinfectant was used from January 2005 to April 2006, the patient's son aged 20 months was hospitalized with respiratory symptoms, and he died within two weeks. Also, the patient was hospitalized for a month with the same symptoms, and then she led a normal life with no symptoms. After both mother and son were diagnosed with definite (level 1) humidifier disinfectant lung injury (HDLI) in 2017, she took to drinking alcohol because of extreme guilt over her son's death. In March 2018 she died from acute liver failure due to alcohol use disorder. The patient's death was caused by continuous alcoholism, due to emotional and mental trauma caused by her son's death after HDLI was revealed as the cause. The government did not acknowledge her death was due to humidifier disinfectants, but the company that sold the humidifier disinfectants recognized her as a victim and compensated the family of the victim. There are still lots of psychological responses among humidifier disinfectant disaster victims. Mental health impact on humidifier disinfectant victims should be considered more carefully, and institutional improvements should be made into establish psychological interventions and measures.
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OBJECTIVES: Although the effects of long working hours on liver function remain unclear, in South Korea, there is a social perception that long working hours are associated with poor liver function. Thus, long working hours have recently become a major issue. This study aimed to determine the association between long working hours and liver function, as indicated by the alanine transaminase (ALT) levels. DESIGN: Cross-sectional study. SETTING: Large university hospitals in Seoul and Suwon, South Korea. PARTICIPANTS: Workers in formal employment who underwent a comprehensive health examination at the Kangbuk Samsung Hospital Total Healthcare Centre clinics in Seoul and Suwon, South Korea, between January 2011 and December 2018. Of the 386 488 participants, 212 421 met the inclusion criteria and were included in the analysis. PRIMARY OUTCOME MEASURE: ALT elevation. RESULTS: The participants were predominantly well-educated (86.1%), male (69.3%) and in their 30s (49.6%). In total, 13.4% of the participants presented ALT elevation (>40 IU/L). There was no significant association between working hours and ALT elevation in the general population and in the hepatitis B surface antigen (HBsAg)-negative group. Conversely, in the HBsAg-positive group, working >60 hours per week compared with 35-40 hours per week was significantly associated with ALT elevation. The association was more pronounced in those with ALT levels >80 IU/L (OR 1.94, 95% CI 1.24 to 3.01) than in those with ALT levels >40 IU/L (OR: 1.45, 95% CI 1.20 to 1.75). The p values for trend were <0.05. CONCLUSIONS: Long working hours were associated with ALT elevation only in hepatitis B virus carriers and not in the general population. Provided that there is adherence to the legal working hours, there is no need to further restrict working hours for liver health, irrespective of HBsAg status.
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Fígado , Alanina Transaminase , Estudos Transversais , Humanos , Masculino , República da Coreia/epidemiologia , SeulRESUMO
BACKGROUND: In Korea, to investigate the casual relationship between humidifier disinfectant and lung disease, four rounds of investigation and judgment were conducted. During this investigation, two adults who performed lung biopsy were recognized for their relevance between humidifier disinfectants and lung disease. At first, we did not think of the relationship to humidifier disinfectant because chest computed tomography (CT) finding of 2 cases were improved. However, they performed lung biopsy and it showed typical humidifier disinfectant lung injury (HDLI) pathologic findings, they could be recognized as HDLI. We report these cases here. CASE PRESENTATION: We selected 2 cases from the fourth-round investigation at Kangbuk Samsung Hospital. Patient of case 1 used humidifier disinfectants since September 2010. The patient was admitted 6 months later to the intensive care unit (ICU) due to severe dyspnea. Pathology following a lung biopsy revealed typical HDLI finding which was determined to be due to humidifier disinfectant exposure. Patient of case 2 used humidifier disinfectant from 2001 to 2008 for about 3 months each winter. The patient's cough and sputum production symptoms began in December of 2007. The patient was admitted to the respiratory medicine department due to worsening dyspnea. Pathology following a lung biopsy revealed typical HDLI finding. This was determined to have been caused by humidifier disinfectant exposure. CONCLUSIONS: Because the typical radiologic findings associated with HDLI can improve over time, it is necessary to consider the revision of current diagnostic criteria that the presence of radiologic findings is important.