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1.
Pancreatology ; 24(4): 584-591, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38693041

RESUMEN

OBJECTIVES: We aimed to assess the diagnostic utility of an immunohistochemical panel including calcium-binding protein P, p53, Ki-67, and SMAD family member 4 and K-ras mutation for diagnosing pancreatic solid lesion specimens obtained by endoscopic ultrasound-guided fine-needle biopsy and to confirm their usefulness in histologically inconclusive cases. METHODS: Immunohistochemistry and peptide nucleic acid-clamping polymerase chain reaction for K-ras mutation were performed on 96 endoscopic ultrasound-guided fine-needle biopsy specimens. The diagnostic efficacy of each marker and the combination of markers was calculated. The diagnostic performances of these markers were evaluated in 27 endoscopic ultrasound-guided fine-needle biopsy specimens with histologically inconclusive diagnoses. A classification tree was constructed. RESULTS: K-ras mutation showed the highest accuracy and consistency. Positivity in more than two or three of the five markers showed high diagnostic accuracy (94.6 % and 93.6 %, respectively), and positivity for more than three markers showed the highest accuracy for inconclusive cases (92.0 %). A classification tree using K-ras mutation, Ki-67, S100P, and SMAD4 showed high diagnostic performance, with only two misclassifications in inconclusive cases. CONCLUSIONS: K-ras mutation detection via peptide nucleic acid-clamping polymerase chain reaction is a stable and accurate method for distinguishing between pancreatic ductal adenocarcinoma and non-pancreatic ductal adenocarcinoma lesions. A classification tree using K-ras mutation, Ki-67, S100P, and SMAD4 helps increase the diagnostic accuracy of cases that are histologically difficult to diagnose.


Asunto(s)
Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Antígeno Ki-67 , Mutación , Neoplasias Pancreáticas , Proteína Smad4 , Humanos , Proteína Smad4/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/diagnóstico , Antígeno Ki-67/genética , Femenino , Masculino , Persona de Mediana Edad , Anciano , Reacción en Cadena de la Polimerasa/métodos , Adulto , Proteínas Proto-Oncogénicas p21(ras)/genética , Ácidos Nucleicos de Péptidos , Inmunohistoquímica , Anciano de 80 o más Años , Biomarcadores de Tumor/genética
2.
Breast Cancer Res ; 25(1): 128, 2023 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-37880751

RESUMEN

BACKGROUND: Gremlin-1 (GREM1) and Gremlin-2 (GREM2) are bone morphogenetic protein antagonists that play important roles in organogenesis, tissue differentiation, and tissue homeostasis. Although GREM1 has been reported to be involved in promoting various cancers, little has been reported about effects of GREM2 on cancer. Recently, it has been reported that GREM2 can inhibit adipogenesis in adipose-derived stromal/stem cells. However, as an inhibitor of adipogenesis, the role of GREM2 in cancer progression is not well understood yet. METHODS: Pre-adipocyte 3T3-L1 cells overexpressing mock or Grem2 were established using a lentiviral transduction system and differentiated into adipocytes-mock and adipocytes-Grem2, respectively. To investigate the effect of adipocyte-Grem2 on breast cancer cells, we analyzed the proliferative and invasion abilities of spheroids using a 3D co-culture system of breast cancer cells and adipocytes or conditioned medium (CM) of adipocytes. An orthotopic breast cancer mouse model was used to examine the role of adipocytes-Grem2 in breast cancer progression. RESULTS: Grem2 overexpression suppressed adipogenesis of 3T3-L1 cells. Proliferative and invasion abilities of spheroids formed by co-culturing MTV/TM-011 breast cancer cells and adipocytes-Grem2 were significantly reduced compared to those of spheroids formed by co-culturing MTV/TM-011 cells and adipocytes-mock. Compared to adipocytes-mock, adipocytes-Grem2 showed decreased mRNA expression of several adipokines, notably IL-6. The concentration of IL-6 in the CM of these cells was also decreased. Proliferative and invasive abilities of breast cancer cells reduced by adipocytes-Grem2 were restored by IL-6 treatment. Expression levels of vimentin, slug, and twist1 in breast cancer cells were decreased by treatment with CM of adipocytes-Grem2 but increased by IL-6 treatment. In orthotopic breast cancer mouse model, mice injected with both MTV/TM-011 cells and adipocytes-Grem2 showed smaller primary tumors and lower lung metastasis than controls. However, IL-6 administration increased both the size of primary tumor and the number of metastatic lung lesions, which were reduced by adipocytes-Grem2. CONCLUSIONS: Our study suggests that GREM2 overexpression in adipocytes can inhibit adipogenesis, reduce the expression and secretion of several adipokines, including IL-6, and ultimately inhibit breast cancer progression.


Asunto(s)
Adipogénesis , Neoplasias de la Mama , Animales , Ratones , Adipocitos/metabolismo , Adipoquinas/metabolismo , Diferenciación Celular/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Neoplasias de la Mama/metabolismo
3.
Acta Pharmacol Sin ; 43(11): 2993-3001, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35478244

RESUMEN

Vestibular schwannoma (VS), one of characteristic tumors of neurofibromatosis type 2 (NF2), is an intracranial tumor that arises from Schwann cells of the vestibular nerve. VS results in hearing loss, tinnitus, dizziness, and even death, but there are currently no FDA-approved drugs for treatment. In this study, we established a high-throughput screening to discover effective compounds that could inhibit the viability of VS cells. Among 1019 natural products from the Korea Chemical Bank screened, we found that celastrol, a pentacyclic triterpene derived from a Tripterygium Wilfordi plant, exerted potent inhibitory effect on the viability of VS cells with an IC50 value of 0.5 µM. Celastrol (0.5, 1 µM) dose-dependently inhibited the proliferation of primary VS cells derived from VS patients. Celastrol also inhibited the growth, and induced apoptosis of two other VS cell lines (HEI-193 and SC4). Aberrant activation of Wnt/ß-catenin signaling has been found in VS isolated from clinically defined NF2 patients. In HEI-193 and SC4 cells, we demonstrated that celastrol (0.1, 0.5 µM) dose-dependently inhibited TOPFlash reporter activity and protein expression of ß-catenin, but not mRNA level of ß-catenin. Furthermore, celastrol accelerated the degradation of ß-catenin by promoting the formation of the ß-catenin destruction complex. In nude mice bearing VS cell line SC4 allografts, administration of celastrol (1.25 mg · kg-1 · d-1, i.p. once every 3 days for 2 weeks) significantly suppressed the tumor growth without showing toxicity. Collectively, this study demonstrates that celastrol can inhibit Wnt/ß-catenin signaling by promoting the degradation of ß-catenin, consequently inhibiting the growth of VS.


Asunto(s)
Neuroma Acústico , beta Catenina , Ratones , Animales , beta Catenina/metabolismo , Neuroma Acústico/tratamiento farmacológico , Neuroma Acústico/metabolismo , Neuroma Acústico/patología , Ratones Desnudos , Proliferación Celular , Línea Celular Tumoral , Triterpenos Pentacíclicos/farmacología , Apoptosis , Vía de Señalización Wnt
4.
J Proteome Res ; 20(1): 740-750, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33241689

RESUMEN

Cervical cancer is the fourth most prevalent cancer among women worldwide and usually develops from cervical intraepithelial neoplasia (CIN). In the present study, we compared alterations in lipids associated with high-grade CIN and cervical cancer with those associated with a normal status and low-grade CIN by performing global lipid profiling on plasma (66 healthy controls and 55 patients with CIN1, 44 with CIN2/3, and 60 with cervical cancer) using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry. We identified 246 lipids and found 31 lipids with similar alterations in both high-grade CIN and cervical cancer. Among these 31 lipids, four lipid classes (phosphatidylcholine, phosphatidylethanolamine, diglyceride, and free fatty acids) were identified as the major lipid classes with significant differences in the patients with CIN2/3 and cervical cancer compared to the healthy controls and the patients with CIN1. Lipid metabolites belonging to the same classes were positively correlated with each other. High-grade CIN and cervical cancer induce comparable changes in lipid levels, which are closely related to the development of cervical tumors. These results suggest that lipid profiling is a useful method for monitoring progression to cervical cancer.


Asunto(s)
Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Displasia del Cuello del Útero/diagnóstico
5.
Arch Pharm (Weinheim) ; 354(9): e2100130, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34060134

RESUMEN

Toll-like receptors (TLRs) can recognize specific signatures of invading microbial pathogens and activate a cascade of downstream signals to induce the secretion of inflammatory cytokines, chemokines, and type I interferons. The activation of TLRs triggers two downstream signaling pathways: the MyD88- and the TRIF-dependent pathways. To evaluate the therapeutic potential of epoxomicin, a member of the linear peptide α',ß'-epoxyketone first isolated from an actinomycetes strain, we examined its effects on signal transduction via TLR signaling pathways. Epoxomicin inhibited the activation of NF-kB and IRF3 induced by TLR agonists, decreased the expression of interferon-inducible protein-10, and inhibited the activation of NF-kB and IRF3 induced by overexpression of downstream signaling components of TLR signaling pathways. These results suggest that epoxomicin can regulate both the MyD88- and TRIF-dependent signaling pathways of TLRs. Thus, it might have potential as a new therapeutic drug for a variety of inflammatory diseases.


Asunto(s)
Transducción de Señal/efectos de los fármacos , Receptores Toll-Like/metabolismo , Animales , Células HEK293 , Humanos , Factor 3 Regulador del Interferón/metabolismo , Ratones , Factor 88 de Diferenciación Mieloide/metabolismo , FN-kappa B/metabolismo , Oligopéptidos/farmacología , Células RAW 264.7
6.
Anesth Analg ; 124(2): 520-523, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27454066

RESUMEN

BACKGROUND: Placing the patient in the prone position frequently is required for some surgical procedures. If cardiac arrest occurs and the patient cannot be safely turned supine, cardiopulmonary resuscitation (CPR) may need to be performed with the patient in the prone position. Although clear landmarks have been defined for supine CPR, the optimal hand position for CPR in the prone position has not been clearly determined. The purpose of this study was to determine anatomically the optimal hand position for CPR in the prone position. METHODS: We reviewed retrospectively the chest computed tomography images of 100 patients taken in the prone position. The vertebral body levels crossing the medial angle of the scapula, the inferior angle of the scapula, and the spinous process of the vertebral body connected to the most inferior rib were identified, and we selected the image level at which the left ventricular (LV) cross-sectional area was the largest. This level was defined as the optimal compression level and correlated to surface anatomical landmarks. We calculated the ratio of the distance from the C7 spinous process to the level of the largest LV cross-sectional area divided by the distance from the C7 spinous process to the spinous process of the vertebral body connected with the most inferior rib. RESULTS: The level of the largest LV cross-sectional area in the prone position was 1 vertebral segment below the inferior angle of the scapula in 45% (99% confidence interval [CI], 33-58) of patients and 0 to 2 vertebral segments below that in 95% (99% CI, 86-98) of patients. The mean (SD) ratio of the distance from the C7 spinous process to the level of the largest LV cross-sectional area divided by the distance from the C7 spinous process to T12 spinous process was 67% ± 7% (99% CI, 65-69). CONCLUSIONS: When the patient is positioned prone, the largest LV cross-sectional area is 0 to 2 vertebral segments below the inferior angle of the scapula in at least 86% of patients. Further studies are needed to determine whether this position is optimal for chest compressions in the prone position.


Asunto(s)
Reanimación Cardiopulmonar/métodos , Ventrículos Cardíacos/anatomía & histología , Ventrículos Cardíacos/diagnóstico por imagen , Posición Prona , Columna Vertebral/anatomía & histología , Columna Vertebral/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Anatomía Transversal , Femenino , Corazón/anatomía & histología , Corazón/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Escápula/anatomía & histología , Escápula/diagnóstico por imagen , Vértebras Torácicas/anatomía & histología , Tomografía Computarizada por Rayos X
7.
Am J Addict ; 25(6): 466-71, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27548514

RESUMEN

BACKGROUND AND OBJECTIVES: The purpose of this study was to compare the frontal executive functions of exercise addicts, moderate exercisers, and exercise avoiders. We hypothesized that exercise addicts and avoiders would have poorer executive functions compared to moderate exercisers. METHODS: The Korean Exercise Addiction Scale was administrated to recruit participants. Electroencephalogram was recorded at the frontal scalp sites. RESULTS: The results showed that P3 and N2 latencies were shorter in the exercise addiction group than in the avoidance and moderate groups. Exercise addicts and moderate exercisers showed faster response time than exercise avoiders. DISCUSSION: P3 and N2 latencies and P3 and N2 amplitudes were discussed in terms of executive functions. SCIENTIFIC SIGNIFICANCE: This study showed that exercise addiction did not impair executive functions, but increased cognitive functioning. (Am J Addict 2016;25:466-471).


Asunto(s)
Conducta Adictiva/fisiopatología , Cognición/fisiología , Función Ejecutiva/fisiología , Ejercicio Físico , Adulto , Técnicas de Observación Conductual/métodos , Electroencefalografía/métodos , Ejercicio Físico/fisiología , Ejercicio Físico/psicología , Femenino , Humanos , Masculino , Tiempo de Reacción/fisiología , República de Corea , Estadística como Asunto
8.
J Phys Ther Sci ; 28(12): 3283-3287, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28174435

RESUMEN

[Purpose] The purpose of this study was to determine the effects of assisted aquatic movement and horseback riding therapies on emotion and brain activation in patients with cerebral palsy. [Subjects and Methods] Thirty-two right-handed patients with cerebral palsy (18 male, 14 female) whose ages ranged from 8 to 48 years participated in this experiment. Their cerebral palsy levels ranged from 1 to 3. The participants were assigned to one of three groups according to the experimental conditions: an assisted aquatic movement therapy group, a horseback riding therapy group, or a control group. Electroencephalograms, the Feeling Scale and the Felt Arousal Scale were examined as dependent variables. [Results] Analysis of self-reported data demonstrated a significant positive improvement in the emotions of participants in the assisted aquatic movement therapy group in comparison with the control group. With regard to the electroencephalogram analysis, the results of this study showed increased alpha power in the assisted aquatic movement therapy group compared with the horseback riding and control groups. [Conclusion] The results of this study suggest that professionals can consider assisted aquatic movement therapy as an effective therapeutic intervention for the improvement of mental health and brain activation.

9.
J Pathol Transl Med ; 58(4): 182-190, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38973328

RESUMEN

BACKGROUND: Acinar cell carcinoma (ACC) is a rare malignant epithelial neoplasm, which shares many cytomorphological features with other non-ductal pancreatic neoplasms such as pancreatic neuroendocrine neoplasm (PanNEN) and solid-pseudopapillary neoplasm (SPN). Due to the relative rarity of these tumors, pathologists are less familiar with the cytological features, especially on liquid-based cytology (LBC) which has been relatively recently introduced for endoscopic ultrasound-guided fine needle aspiration specimens. METHODS: We evaluated the detailed cytological features of 15 histologically confirmed ACC (7 conventional smears [CS], 8 LBC), and compared them with the LBC features of SPN (n = 9) and PanNEN (n = 9). RESULTS: Compared with CS, LBCs of ACC demonstrated significantly less bloody background. All ACCs demonstrated prominent nucleoli and macronucleoli on LBC. On comparison with the LBC features of SPN and PanNEN, most ACCs demonstrated a necrotic background with apoptotic debris while PanNEN and SPN did not show these features. Acinar structures were predominantly observed in ACC, while frequent pseudopapillary structures were seen only in SPN. Prominent nucleoli and macronucleoli were only seen in ACC. CONCLUSIONS: ACC had characteristic cytological features that could be observed on LBC preparations, such as high cellularity, necrotic/apoptotic background, nuclear tangles, acinar arrangement of cells, and macronucleoli. These findings also help distinguish ACC from PanNEN and SPN on LBC. It is important to be familiar with these features, as an accurate diagnosis on endoscopic ultrasound-guided fine needle aspiration cytology would have impact on the management of the patient.

10.
Cells ; 13(16)2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39195265

RESUMEN

Orthotospovirus tomatomaculae (tomato spotted wilt virus, TSWV) is transmitted by the western flower thrips, Frankliniella occidentalis. Epoxyoctadecamonoenoic acids (EpOMEs) function as immune-suppressive factors, particularly in insects infected by viral pathogens. These oxylipins are produced by cytochrome P450 monooxygenases (CYPs) and are degraded by soluble epoxide hydrolase (sEH). In this study, we tested the hypothesis that TSWV modulates the EpOME level in the thrips to suppress antiviral responses and enhance its replication. TSWV infection significantly elevated both 9,10-EpOME and 12,13-EpOME levels. Following TSWV infection, the larvae displayed apoptosis in the midgut along with the upregulated expression of four caspase genes. However, the addition of EpOME to the viral treatment notably reduced apoptosis and downregulated caspase gene expressions, which led to a marked increase in TSWV titers. The CYP and sEH genes of F. occidentalis were identified, and their expression manipulation using RNA interference (RNAi) treatments led to significant alternations in the insect's immune responses and TSWV viral titers. To ascertain which viral factor influences the host EpOME levels, specialized RNAi treatments targeting genes encoded by TSWV were administered to larvae infected with TSWV. These treatments demonstrated that NSS expression is pivotal in manipulating the genes involved in EpOME metabolism. These results indicate that NSs of TSWV are crucially linked with the elevation of host insect EpOME levels and play a key role in suppressing the antiviral responses of F. occidentalis.


Asunto(s)
Oxilipinas , Thysanoptera , Tospovirus , Animales , Tospovirus/fisiología , Oxilipinas/metabolismo , Thysanoptera/virología , Insectos Vectores/virología , Insectos Vectores/inmunología , Factores de Virulencia/genética , Factores de Virulencia/metabolismo , Proteínas no Estructurales Virales/metabolismo , Proteínas no Estructurales Virales/genética , Larva/virología , Larva/inmunología , Apoptosis/efectos de los fármacos , Sistema Enzimático del Citocromo P-450/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Epóxido Hidrolasas/metabolismo , Epóxido Hidrolasas/genética
11.
Healthcare (Basel) ; 12(2)2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38255041

RESUMEN

Recently, non-pharmacological treatments are gaining increasing importance for improving the quality of life in patients with chronic obstructive pulmonary disease (COPD). This pilot study aimed to evaluate the feasibility of conducting extensive research on Chuna manual therapy (CMT). This study investigated the effectiveness and safety of CMT adjuvant to Western medicine (WM) in patients with COPD. Forty patients with COPD were randomized into two groups in a 1:1 ratio: experimental (CMT plus WM) and control (WM only) groups. The CMT intervention was administered once a week for eight weeks. The primary outcome measured was the 6-min walk distance (6MWD). Secondary outcomes measured were: forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), assessments using the modified Medical Research Council (mMRC) scale and Visual Analog Scale (VAS) for dyspnea, the COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), and the EuroQoL five-dimensional questionnaire (EQ-5D). The mean differences in FEV1 (L) between Weeks 1 and 8 were statistically significant between the groups (p = 0.039). Additionally, the experimental group showed improved 6MWD, mMRC, VAS for dyspnea, CAT, SGRQ (total), and EQ-VAS scores than the control group. However, the differences between the two groups were not statistically significant. No adverse events were observed during this trial. CMT has the potential to alleviate symptoms, improve quality of life, and delay the decline in lung function in patients with COPD. The results of this pilot study could lead to large-scale clinical trials in the future.

12.
Cancer Gene Ther ; 31(4): 599-611, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38272982

RESUMEN

Irregularities in insulin signaling have significantly increased the risk of various cancers, yet the precise underlying mechanisms remain unclear. Within our study, we observed that inhibiting neddylation enhances cancer cell migration across different cancer types by activating both insulin receptor substrates 1 and 2 (IRS1 and IRS2), along with the PI3K/AKT signaling pathway. Notably, in the context of high-grade serous carcinoma (HGSC) patients, whether they had type 2 diabetes mellitus or not, IRS1 and IRS2 displayed a parallel relationship with each other while exhibiting an inverse relationship with NEDD8. We also identified C-CBL as an E3 ligase responsible for neddylating IRS1 and IRS2, with clinical evidence further confirming a reciprocal relationship between C-CBL and pAKT, thereby reinforcing the tumor suppressive role of C-CBL. Altogether, these findings suggest that neddylation genuinely participates in IRS1 and IRS2-dependent insulin signaling, effectively suppressing cancer cell migration. Thus, caution is advised when considering neddylation inhibitors as a treatment option for cancer patients, particularly those presenting with insulin signaling dysregulations linked to conditions like obesity-related type 2 diabetes or hyperinsulinemia.


Asunto(s)
Diabetes Mellitus Tipo 2 , Neoplasias , Humanos , Insulina/metabolismo , Receptor de Insulina/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal , Neoplasias/genética , Movimiento Celular
13.
Anticancer Res ; 44(10): 4283-4299, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39348965

RESUMEN

BACKGROUND/AIM: Lung adenocarcinoma (LUAD) or lung squamous cell carcinoma (LUSC) accounts for the majority of non-small cell lung cancer (NSCLC), and overexpression of programmed death ligand 1 (PD-L1) in these cells is known to induce tumor immune evasion or drug resistance. However, detailed studies are needed to determine whether microRNAs (miRNAs) that reduce PD-L1 expression can suppress drug resistance in NSCLC. MATERIALS AND METHODS: Kaplan Meier plotter and Receiver Operating Characteristic plotter were used to determine the effect of specific miRNAs on survival and chemotherapy response in NSCLC patients. Cell viability, colony formation and invasion assays, and qPCR analyses were also performed. RESULTS: The expression of miRNA-140-3p (miR-140-3p) was lower in LUAD patients, compared to the normal group, and low expression of miR-140-3p was associated with poor survival of LUAD patients, but not in LUSC. The miR-140-3p mimic inhibited proliferation, colony formation, and invasion of LUAD cells. Interestingly, the expression of miR-140-3p was significantly lower in the group of LUAD patients who did not respond to docetaxel. In LUAD cells, combined treatment with miR-140-3p and docetaxel significantly reduced cell viability as well as the expression of ABCG2 and MVP, genes associated with drug resistance, compared to either treatment alone. Additionally, combined injection of miR-140-3p mimic and docetaxel significantly inhibited tumor growth compared to treatment with docetaxel alone. CONCLUSION: These results suggest that the high expression of miR-140-3p in LUAD is correlated with good patient prognosis and may contribute to the treatment of LUAD, especially by increasing responsiveness to docetaxel.


Asunto(s)
Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Adenocarcinoma del Pulmón , Antígeno B7-H1 , Docetaxel , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares , MicroARNs , Proteínas de Neoplasias , Humanos , Docetaxel/farmacología , MicroARNs/genética , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Resistencia a Antineoplásicos/genética , Proteínas de Neoplasias/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Línea Celular Tumoral , Animales , Ratones , Proliferación Celular/efectos de los fármacos , Femenino , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Masculino , Ensayos Antitumor por Modelo de Xenoinjerto
14.
Nat Commun ; 15(1): 1301, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38346945

RESUMEN

The degradation of mechanical properties caused by grain coarsening or the formation of brittle phases during welding reduces the longevity of products. Here, we report advances in the weld quality of ultra-high strength steels by utilizing Nb and Cr instead of Ni. Sole addition of Cr, as an alternative to Ni, has limitations in developing fine weld microstructure, while it is revealed that the coupling effects of Nb and Cr additions make a finer interlocking weld microstructures with a higher fraction of retained austenite due to the decrease in austenite to acicular ferrite and bainite transformation temperature and carbon activity. As a result, an alloying design with Nb and Cr creates ultrastrong and ductile steel welds with enhanced tensile properties, impact toughness, and fatigue strength, at 45% lower material costs and lower environmental impact by removing Ni.

15.
Tissue Eng Regen Med ; 20(3): 435-446, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36809635

RESUMEN

BACKGROUND: This study aimed to identify pain-related behavior and pathological characteristics of the knee joint in rats with monosodium iodoacetate (MIA)-induced osteoarthritis (OA). METHODS: Knee joint inflammation was induced by intra-articular injection of MIA (4 mg/50 µL, n = 14) in 6-week-old male rats. Knee joint diameter, weight-bearing percentage on the hind limb during walking, the knee bending score, and paw withdrawal to mechanical stimuli were measured to evaluate edema and pain-related behavior for 28 d after MIA injection. Histological changes in the knee joints were evaluated using safranin O fast green staining on days 1, 3, 5, 7, 14, and 28 after OA induction (n = 3, respectively). Changes in bone structure and bone mineral density (BMD) were examined 14 and 28 d after OA (n = 3, respectively) using micro-computed tomography (CT). RESULTS: The knee joint diameter and knee bending scores of the ipsilateral joint significantly increased 1 d after MIA injection, and the increased knee joint diameter and knee bending score persisted for 28 d. Weight-bearing during walking and paw withdrawal threshold (PWT) decreased from 1 and 5 d, respectively, and were maintained up to 28 d after MIA. Cartilage destruction started on day 1, and Mankin scores for bone destruction significantly increased for 14 d, as shown by micro-CT imaging. CONCLUSION: The present study demonstrated that histopathological structural changes in the knee joint due to inflammation started soon after MIA injection, which induced OA pain from inflammation-related acute pain to spontaneous and evoked associated chronic pain.


Asunto(s)
Artritis Experimental , Osteoartritis , Ratas , Masculino , Animales , Ácido Yodoacético/toxicidad , Microtomografía por Rayos X , Artritis Experimental/inducido químicamente , Artritis Experimental/diagnóstico por imagen , Artritis Experimental/patología , Osteoartritis/inducido químicamente , Osteoartritis/diagnóstico por imagen , Osteoartritis/patología , Dolor/inducido químicamente , Inflamación
16.
Environ Pollut ; 317: 120705, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36410599

RESUMEN

Diesel exhaust particles (DEPs) are a major cause of cancer progression as well as a variety of acute and chronic diseases. It is well-known that programmed death-ligand 1 (PD-L1) is an immune checkpoint molecule that can induce immune escape in tumor cells. However, the function of PD-L1 in bronchial epithelial cells or how PD-L1 relates to cellular oxidation under DEPs-mediated oxidative stress is not well known. In this study, we investigated how PD-L1 affected DEPs-induced oxidative stress and cytotoxicity in human bronchial epithelial (HBE) cells, Beas-2B. DEPs not only induced intracellular reactive oxygen species (ROS) production, but also increased PD-L1 expression in HBE cells. Beas-2B cells overexpressing PD-L1 showed higher levels of ROS production, DNA damage, and apoptosis after DEPs treatment compared to control cells. In particular, the expression of an antioxidant enzyme heme-oxygenase-1 (HO-1) and nuclear translocation and transcriptional activity of Nrf2, a major regulator of HO-1, were lower in Beas-2B overexpressing PD-L1 cells than in control cells. DEPs-induced ROS generation, DNA damage and apoptosis in Beas-2B cells overexpressing PD-L1 were significantly restored by overexpressing HO-1. Collectively, our results suggest that DEPs can increase the expression of PD-L1 in HBE cells and that overexpressing PD-L1 might eventually promote DEPs-induced oxidative DNA damage and apoptosis.


Asunto(s)
Antígeno B7-H1 , Emisiones de Vehículos , Humanos , Emisiones de Vehículos/toxicidad , Antígeno B7-H1/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Estrés Oxidativo , Células Epiteliales/patología
17.
Medicine (Baltimore) ; 101(31): e29949, 2022 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-35945788

RESUMEN

Catheter ablation (CA) is a well-established therapy for rhythm control in atrial fibrillation (AF). However, CA outcomes for persistent AF remain unsatisfactory because of the high recurrence rate despite time-consuming efforts and the latest ablation technology. Therefore, the selection of good responders to CA is necessary. Surface electrocardiography (sECG)-based complexity parameters were tested for the predictive ability of procedural termination failure during CA and late recurrence of atrial arrhythmias (AA) after CA. A total of 130 patients with nonparoxysmal AF who underwent CA for the first time were investigated. A 10-second sECG of 4 leads (leads I, II, V1, and V6) was analyzed to compute the fibrillatory wave amplitude (FWA), dominant frequency (DF), spectral entropy (SE), organization index (OI), and sample entropy (SampEn). The study endpoints were procedural termination failure during CA and late (≥1 year) AA recurrence after CA. In the multivariate analysis, FWA in lead V1 and DF in lead I were independent predictors of successful AF termination during CA (P <.05). The optimal cut-off values for FWA in lead V1 and DF in lead I were 60.38 µV (area under the curve [AUC], 0.672; P = .001) and 5.7 Hz (AUC, 0.630; P = .016), respectively. The combination of FWA of lead V1 and DF of lead I had a more powerful odds ratio for predicting procedural termination failure (OR, 8.542; 95% CI, 2.938-28.834; P < .001). FWA in lead V1 was the only independent predictor of late recurrence after CA. The cut-off value is 65.73 µV which was 0.634 of the AUC (P = .009). These sECG parameters, FWA in lead V1 and DF in lead I, predicted AF termination by CA in patients with nonparoxysmal AF. In particular, FWA in lead V1 was an independent predictor of late recurrence of AA after CA.


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Área Bajo la Curva , Electrocardiografía , Humanos , Recurrencia , Resultado del Tratamiento
18.
Front Vet Sci ; 8: 796638, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35187140

RESUMEN

A 3-month-old cat weighing 2.62 kg was brought to the VIP Animal Medical Center with vomiting, diarrhea, anorexia, and depression. Laboratory findings confirmed azotemia with elevated blood urea nitrogen (BUN) (168.9 mg/dl) and creatinine (5.9 mg/dl) and symmetric dimethylarginine (SDMA) (86 µg/dl). Abdominal radiography revealed bilateral renomegaly. Ultrasonography revealed bilateral hydronephrosis and left partial and right complete ureteral obstructions with bilateral focal irregular and circumferential thickenings at ureters. Reduction of bilateral renal function was confirmed through excretory urography on computed tomography. The cat underwent subcutaneous ureteral bypass surgery on the left kidney, right nephrectomy, and bilateral ureterectomy. Histopathology of bilateral ureteral irregular and circumferential thickening revealed bilateral atypical papillary transitional mucosal hyperplasia. Three days after surgery, the left hydronephrosis resolved, and azotemia was almost resolved. This is the first report of successful management of ureteral stenosis with congenital papillary transitional mucosal hyperplasia in a kitten using multimodality imaging.

19.
Front Vet Sci ; 8: 774993, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35047584

RESUMEN

The radial joint orientation angles were calculated using the center of rotation of angulation (CORA) methodology within the frontal and sagittal planes in chondrodystrophic dog breeds, including Welsh Corgi, Dachshund, Pekinese, Poodle, Beagle and Maltese, and it was compared whether there is a statistically significant difference between the breeds. Radial joint orientation angles were obtained in eighty-eight dogs, including 23 Welsh Corgis, 16 Dachshunds, 14 Pekinese, 13 Maltese, 12 Poodles and 10 Beagles. Using the CORA methodology, the cranial proximal radial angle (CrPRA) and caudal distal radial angle (CdDRA) in the sagittal plane and medial proximal radial angle (MPRA) and lateral distal radial angle (LDRA) in the frontal plane were measured for the six breeds studied. The mean values of joint angles for each breed were compared statistically were observed. The CrPRA, CdDRA, and LDRA mean values of Dachshund and Welsh Corgi breeds were significantly smaller than other breeds, and in MPRA, Pekingese showed significantly smaller values than other breeds. This study confirms that the mean values of radial joint orientation angles can be significantly different among chondrodystrophic breeds. To accurately evaluate the degree of angular deformity of the radius, it may be helpful to refer to the average value for each breed with chondrodystrophy.

20.
Nutrients ; 12(2)2020 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-32102321

RESUMEN

Recently, diets with higher inflammatory potentials based on the dietary inflammatory index (DII®) have been shown to be associated with increased cardiovascular disease (CVD) risk in the general population. We aimed to prospectively investigate the association between the DII and CVD risk in the large Korean Genome and Epidemiology Study_Health Examination (KoGES_HEXA) cohort comprised of 162,773 participants (men 55,070; women 107,703). A validated semi-quantitative food frequency questionnaire (SQ-FFQ) was used to calculate the DII score. Statistical analyses were performed by using a multivariable Cox proportional hazard model. During the mean follow-up of 7.4 years, 1111 cases of CVD were diagnosed. Higher DII score was associated with increased risk of CVD in men (hazard ratio [HR]Quintile 5 vs. 1 1.43; 95% CI 1.04-1.96) and in women (HRQuintile 5 vs. 1 1.19; 95% CI 0.85-1.67), although not significant for women. The risk of CVD was significantly higher in physically inactive men (HRQuintile 5 vs. 1 1.80; 95% CI 1.03-3.12), obese men (HRQuintile 5 vs. 1 1.77; 95% CI 1.13-2.76) and men who smoked (HRQuintile 5 vs. 1 1.60; 95% CI 1.10-2.33), respectively. The risk of developing stroke was significantly higher for men (HRQuintile 5 vs. 1 2.06; 95% CI 1.07-3.98; p = 0.003), but not for women. A pro-inflammatory diet, as indicated by higher DII scores, was associated with increased risk of CVD and stroke among men.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Dieta , Inflamación/diagnóstico , Índice de Masa Corporal , Intervalos de Confianza , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Modelos de Riesgos Proporcionales , Estudios Prospectivos , República de Corea/epidemiología , Factores de Riesgo , Accidente Cerebrovascular/epidemiología
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