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1.
Am Surg ; 90(4): 607-615, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37768646

RESUMEN

BACKGROUND: Although hepatectomy including inferior vena cava (IVC) resection is becoming more common, some details remain uncertain such as use of artificial materials to replace a tumor-involved, damaged, or narrowed retrohepatic IVC segment. METHODS: Surgical outcomes of 12 patients who underwent hepatectomy with IVC resection including reconstruction using synthetic tubular grafts were investigated to clarify safety and feasibility. RESULTS: Operative time (median, 573 min; range, 268 to 774) and the blood loss (1076 mL; 155 to 2960) were acceptable. In-hospital mortality was 8% (1/12), and morbidity was 42% (5/12). Among the 12 patients, 2 were planned to undergo IVC reconstruction without an artificial graft. In one patient, prosthetic repair was adopted because of massive bleeding from the IVC wall during dissection of tumor from the IVC. In the other, severe stricture became evident during attempted direct closure of the partially resected IVC wall. DISCUSSION: Ongoing experience has increased our acceptance of combined liver and IVC resection. We believe that segmental IVC resection and reconstruction with a prosthetic tubular graft could be chosen more frequently in managing liver tumors suspected to involve the IVC.


Asunto(s)
Hepatectomía , Neoplasias Hepáticas , Humanos , Vena Cava Inferior/cirugía , Venas , Neoplasias Hepáticas/cirugía
2.
Cureus ; 15(7): e41496, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37551206

RESUMEN

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are mucocutaneous diseases featured by severe sequelae and high mortality rates. In addition to ocular involvement, gynecological involvement is often observed in patients with TEN with possible occurrence of partial or complete adhesions of the labia majora, labia minora, and vaginal walls as severe sequelae. Although the gynecological sequelae of TEN severely affect patients' quality of life, there is a lack of awareness among medical professionals. Moreover, preventive measures and the effectiveness of treatment have not yet been fully verified. Herein, we describe a case of TEN with severe sequelae of eyelid and vaginal adhesions.

3.
Langenbecks Arch Surg ; 408(1): 6, 2023 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-36596987

RESUMEN

PURPOSE: Histopathologic patterns at the invasion fronts of tumors predict metastatic potential and prognosis in several cancers. We examined whether such patterns at the interface between colorectal liver metastases and hepatic parenchyma have similar prognostic value. METHODS: Microscopic growth patterns at edges of metastases including desmoplasia, pushing borders, and replacement of hepatocytes were retrospectively analyzed with respect to surgical outcomes in 142 patients who underwent hepatectomy for colorectal metastases. RESULTS: Patterns included desmoplasia in 58 patients (41%), hepatocyte replacement in 41 (29%), and pushing borders in 43 (30%). Maximum metastasis diameter and serum carcinoembryonic antigen concentration in patients showing desmoplastic tumor growth were lower than those in others (P < 0.05 and P < 0.01). Disease-free survival and overall survival were better in patients showing desmoplastic growth, while a non-desmoplastic tumor growth pattern showed a negative influence. More cluster of differentiation (CD) 68-positive M1 macrophages and fewer CD206-positive M2 macrophages were demonstrated at interfaces of tumors with hepatic parenchyma when desmoplasia was present, although markers for proliferative activity (MIB1 index) and metastatic potential (E-cadherin expression) appeared uninfluenced by desmoplasia. CONCLUSION: Better long-term results were associated with metastatic tumors showing desmoplastic growth patterns at invasion fronts, which may reflect local immune state in a prognostically useful manner.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Pronóstico , Neoplasias Colorrectales/patología , Estudios Retrospectivos , Neoplasias Hepáticas/patología , Hepatectomía , Macrófagos/patología
4.
Int J Mol Sci ; 23(19)2022 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-36232471

RESUMEN

Atherosclerosis is a chronic inflammatory disease of the vascular walls related to aging. Thus far, the roles of cellular senescence and bacterial infection in the pathogenesis of atherosclerosis have been speculated to be independent of each other. Some types of macrophages, vascular endothelial cells, and vascular smooth muscle cells are in a senescent state at the sites of atherosclerotic lesions. Likewise, bacterial infections and accumulations of lipopolysaccharide (LPS), an outer-membrane component of Gram-negative bacteria, have also been observed in the atherosclerotic lesions of patients. This review introduces the integration of these two potential pathways in atherosclerosis. Previous studies have suggested that LPS directly induces cellular senescence in cultured monocytes/macrophages and vascular cells. In addition, LPS enhances the inflammatory properties (senescence-associated secretory phenotype [SASP]) of senescent endothelial cells. Thus, LPS derived from Gram-negative bacteria could exaggerate the pathogenesis of atherosclerosis by inducing and enhancing cellular senescence and the SASP-associated inflammatory properties of specific vascular cells in atherosclerotic lesions. This proposed mechanism can provide novel approaches to preventing and treating this common age-related disease.


Asunto(s)
Aterosclerosis , Lipopolisacáridos , Aterosclerosis/metabolismo , Senescencia Celular/genética , Células Endoteliales/metabolismo , Humanos , Lipopolisacáridos/farmacología
5.
Exp Ther Med ; 24(5): 682, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36185767

RESUMEN

The effects of aging on axon regeneration currently remain unclear. In addition, the up-regulated expression of neurotrophic factors that occurs within one week of peripheral nerve injury has been shown to play an important role in the axon regeneration. To investigate the effects of aging on axon regeneration, the expression of nerve-specific proteins immediately after peripheral nerve injury were compared between young and aged mice. A mouse peripheral nerve injury model was prepared using the sciatic nerve compression method. In each group, Luxol fast blue staining and immunofluorescence staining were performed to assess the degree of Wallerian degeneration in the sciatic nerve, and to evaluate the expression of repressor element 1-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), nerve growth factor (NGF), and semaphorin 3A (Sema3A) in the dorsal root ganglion, respectively. Wallerian degeneration was observed in both young and aged mice after peripheral nerve injury. Significant increases were observed in the expression of REST/NRSF (P<0.0001), NT3 (P=0.0279), and Sema3A (P=0.0175) following peripheral nerve injury in young mice, while that of BDNF (P=0.5583) and NGF (P=0.9769) remained unchanged. On the other hand, no significant differences were noted in the expression of these nerve-specific proteins in aged mice. Based on the results of the present study, compensatory changes induced by peripheral nerve injury were initiated by the up-regulated expression of REST/NRSF in young mice, but not in aged mice.

6.
J Immunol ; 208(9): 2163-2172, 2022 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-35387840

RESUMEN

Human cathelicidin LL-37 is an antimicrobial peptide that has a broad spectrum of antimicrobial activities but also acts on host cells to exert immunomodulatory functions. It has been suggested that the increase of LL-37 in atherosclerotic aortas and the dysregulated autophagy of endothelial cells are involved in the pathogenesis of atherosclerosis. In this study, to elucidate the role of LL-37 in atherosclerosis, we investigated the effect of LL-37 on autophagy in endothelial cells using HUVECs. First, LL-37 upregulated LC3-II (an autophagosomal membrane marker) and enhanced the formation of LC3-positive puncta in the cells, suggesting that LL-37 induces autophagy in endothelial cells. Second, LL-37 was associated with p62, which recognizes ubiquitinated proteins and transfers them to autophagosomes, suggesting that LL-37 is ubiquitinated and recognized by p62. Third, the degradation of LL-37 was delayed, and LL-37 induced cell death in atg7 knockdown cells, which was accompanied by the formation of protein aggregates in the cells. Taken together, these observations suggest that LL-37 induces autophagy in endothelial cells but enhances cell death in autophagy-dysfunctional conditions, in which the intracellular degradation of LL-37 is disturbed. Thus, LL-37 may exert an adverse action on autophagy-dysfunctional endothelial cells to induce cell death in the pathogenesis of atherosclerosis.


Asunto(s)
Aterosclerosis , Células Endoteliales , Péptidos Catiónicos Antimicrobianos/metabolismo , Autofagia , Muerte Celular , Células Endoteliales/metabolismo , Humanos , Catelicidinas
7.
Gan To Kagaku Ryoho ; 49(2): 195-198, 2022 Feb.
Artículo en Japonés | MEDLINE | ID: mdl-35249059

RESUMEN

We investigated the safety and efficacy of circadian chronotherapy via the hepatic artery(chrono-HAI)as a prehepatectomy chemotherapy for initially unresectable colorectal liver metastases. Five-day course of chrono-HAI using 5-FU, l-LV, and L-OHP plus systemic panitumumab with 9-day interval were administered to 24 patients with failure for previous chemotherapy. Response rate and Grade 3 adverse effect(AE) were 63% and 54%, respectively. Among 22 patients( excluding 2 CR patients), conversion surgery could be performed in 10(45%). Two-year overall survival of patients with surgery (58%)was longer in those without(20%, p=0.057). Although incidence of AE was a bit high, chrono-HAI plus systemic panitumumab is an effective prehepatectomy chemotherapy for patients with aggressive colorectal liver metastases.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Hepáticas , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/cirugía , Fluorouracilo , Arteria Hepática/patología , Arteria Hepática/cirugía , Humanos , Infusiones Intraarteriales , Leucovorina , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía
8.
Clin Cosmet Investig Dermatol ; 14: 1579-1591, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34737597

RESUMEN

PURPOSE: Alopecia areata (AA) is characterized by non-scarring, patchy hair loss caused by autoimmune reactions to anagen hair follicles. The pathogenesis of AA may be affected by the diet. However, the dietary habits of patients with AA have not been precisely examined. Therefore, the aim of this study was to investigate the dietary habits of patients with AA in comparison to those of healthy controls. PATIENTS AND METHODS: We evaluated the dietary habits of 70 adult Japanese patients with AA using a brief-type self-administered diet history questionnaire and compared them to the habits of age- and sex-matched healthy controls. RESULTS: Japanese patients with AA had a higher body mass index (BMI) and higher intakes of vitamin C and fruit than the controls. Logistic regression analysis showed that AA was associated with BMI. Retinol intake was positively correlated with severity of alopecia tool (SALT) score, and linear regression analysis revealed that retinol intake was a predictor of SALT score. Retinol intake among patients with moderate to severe AA (ie, a SALT score >25) was higher than that in patients with mild AA (a SALT score ≤25). The mean age of AA patients with atopic dermatitis (AD) was lower than that of AA patients without AD; however, there were no differences in nutrient or food intake between these two groups. Logistic regression analysis showed that the comorbidity AD was negatively associated with age. CONCLUSION: AA was associated with a high BMI, and high retinol intake was a predictor of SALT score. Further studies should be conducted to clarify whether dietary intervention to reduce BMI or limit retinol intake can alter the development or severity of AA.

10.
Jpn J Clin Oncol ; 51(1): 45-53, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-32888020

RESUMEN

BACKGROUNDS: Mutations in the isocitrate dehydrogenase (IDH)1 gene are favourable prognostic factors in newly diagnosed diffuse gliomas, whereas it remains controversial in the recurrent glioblastoma setting. METHODS: A total of 171 patients with newly diagnosed glioblastoma, either 'primary' glioblastoma or 'secondary' glioblastoma, treated at Kyorin University Hospital or Japanese Red Cross Medical Center from 2000 to 2015 were included. Patients with confirmed IDH1 status and O6-methylguanine-DNA methyltransferase promoter methylation status were retrospectively analysed for overall survival from the initial diagnosis (n = 147) and after the first progression (n = 122). RESULTS: IDH1 mutation but not IDH2 was noted in 19 of 147 patients with glioblastoma (12.9%). In patients with 'primary' glioblastoma (n = 136), median overall survival after the first progression was 13.5 and 10.5 months for mutant IDH1 and wild-type IDH1 glioblastoma, respectively (P = 0.747). Multivariate analysis revealed O6-methylguanine-DNA methyltransferase promoter methylation, and Karnofsky Performance status 60 or higher, were independent prognostic factors for better overall survival after the first progression. When 'primary' glioblastoma and 'secondary' glioblastoma were combined, median overall survival from the first progression was not significantly different between the mutant IDH1 group (10.1 months) and wild-type IDH1 group (10.5 months) (P = 0.559), whereas median overall survival from the initial diagnosis was significantly different (47.5 months vs.18.3 months, respectively; P = 0.035). CONCLUSIONS: These results suggest that IDH1 mutation may not be a prognostic factor for survival at the first progression of patients with 'primary' glioblastoma and pretreated 'secondary' glioblastoma, and further warrant investigation in prospective studies.


Asunto(s)
Progresión de la Enfermedad , Glioblastoma/enzimología , Glioblastoma/genética , Isocitrato Deshidrogenasa/genética , Mutación/genética , Adulto , Anciano , Neoplasias Encefálicas/enzimología , Neoplasias Encefálicas/genética , Metilación de ADN/genética , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia/genética , O(6)-Metilguanina-ADN Metiltransferasa/genética , Pronóstico , Regiones Promotoras Genéticas , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento
11.
Auris Nasus Larynx ; 48(4): 571-576, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33223340

RESUMEN

OBJECTIVE: Adults over the age of 65 years with balance disorders are at about twice the risk of falls, compared with those without balance disorders. Falls contribute to about 74% of the proximal femoral fractures commonly seen in the elderly. Since balance disorders are more prevalent in older adults than in younger adults, it is important to deal with balance disorders in older adults to prevent falls and the resulting deterioration in their ADL (activity of daily living). In this study, we investigated the effects of vestibular rehabilitation (VR) and cane use on improving gait and balance in patients aged over 65 years with balance disorder. METHODS: Patients aged over 65 years presenting to the Department of Otolaryngology at St. Marianna University School of Medicine between July 1 and November 1, 2018, with symptoms of dizziness for ≥ 3 months and a Japanese translation of the Dizziness Handicap Inventory score of ≥ 26 were included in the study. We quantitatively analyzed their gait before and after VR, and with and without the use of a cane. RESULTS: A total of 21 patients participated in the study (14 women; mean age 73.9 ± 6.9 years). Before VR, using a cane made no difference to step length or walking speed. After VR, using a cane increased step length from 50.5 cm (95% confidence interval [CI], 47.4-53.7 cm) to 52.0 cm (95% CI, 48.9-55.1 cm) (p = 0.039). There was no change in walking speed. A comparison of walking assessment results while using a cane before and after VR showed that step length increased from 49.9 cm (95% CI, 46.6-53.2 cm) to 52.0 cm (95% CI, 48.9-55.1 cm) (p = 0.005), and walking speed increased from 90.5 cm/s (95% CI, 82.7-98.4 cm/s) to 96.1 cm/s (95% CI, 88.3-103.9 cm/s) (p = 0.005). CONCLUSIONS: Walking speed and step length with the use of a cane significantly improved following VR. VR and cane use may act synergistically to improve walking.


Asunto(s)
Prevención de Accidentes/métodos , Accidentes por Caídas/prevención & control , Bastones , Mareo/rehabilitación , Marcha/fisiología , Enfermedades Vestibulares/rehabilitación , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Equilibrio Postural , Reflejo de Enderezamiento , Vértigo/rehabilitación , Enfermedades Vestibulares/fisiopatología , Potenciales Vestibulares Miogénicos Evocados/fisiología , Caminata/fisiología , Velocidad al Caminar/fisiología
12.
Nutrients ; 12(6)2020 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-32498372

RESUMEN

Background: In cirrhosis, a pathological gut microbiome has been linked with immune dysfunction. A pilot study of probiotic Lactobacillus casei Shirota (LcS) in alcoholic cirrhosis demonstrated significant improvement in neutrophil function. This study aimed to evaluate the efficacy of LcS on neutrophil function and significant infection rates in patients with cirrhosis. Methods: 92 cirrhotic patients (Child-Pugh score ≤10) were randomized to receive LcS or placebo, three times daily for six months. Primary end-points were incidence of significant infection and neutrophil function. Secondary end-points were cytokine profile, endotoxin, bacterial DNA positivity, intestinal permeability and quality of life. Results: Rates of infection, decompensation or neutrophil function did not differ between placebo and probiotic groups. LcS significantly reduced plasma monocyte chemotactic protein-1 and, on subgroup analysis, plasma interleukin-1ß (alcoholic cirrhosis), interleukin-17a and macrophage inflammatory protein-1ß (non-alcoholic cirrhosis), compared with placebo. No significant differences in intestinal permeability, bacterial translocation or metabolomic profile were observed. Conclusion: LcS supplementation in patients with early cirrhosis is safe. Although no significant infections were observed in either group, LcS improved cytokine profile towards an anti-inflammatory phenotype, an effect which appears to be independent of bacterial translocation.


Asunto(s)
Suplementos Dietéticos , Lacticaseibacillus casei , Cirrosis Hepática/terapia , Probióticos/administración & dosificación , Adolescente , Adulto , Anciano , Quimiocina CCL2/sangre , Quimiocina CCL4/sangre , Método Doble Ciego , Femenino , Microbioma Gastrointestinal , Humanos , Inflamación , Interleucina-17/sangre , Interleucina-1beta/sangre , Cirrosis Hepática/sangre , Cirrosis Hepática/inmunología , Cirrosis Hepática/microbiología , Masculino , Persona de Mediana Edad , Neutrófilos/inmunología , Adulto Joven
13.
Jpn J Clin Oncol ; 50(9): 999-1008, 2020 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-32469065

RESUMEN

OBJECTIVE: The optimal regimen for use of high dose-methotrexate-based chemotherapy in primary central nervous system lymphoma is still under debate. We conducted a retrospective study to evaluate the treatment outcome of a combination immunochemotherapy consisting of rituximab, methotrexate, procarbazine and vincristine followed by with or without whole brain radiotherapy and consolidation cytarabine, in comparison with high dose-methotrexate monotherapy followed by full dose whole brain radiotherapy. METHODS: Newly diagnosed primary central nervous system lymphoma patients treated with either rituximab, methotrexate, procarbazine and vincristine or high dose-methotrexate in Kyorin University Hospital were identified, and the response rates and survival were compared. Toxicities, post-treatment transition of Mini-Mental State Examination, Karnofsky performance status score, Fazekas scale and prognostic factors were analysed in the rituximab, methotrexate, procarbazine and vincristine group. RESULTS: Ninety-five patients treated with rituximab, methotrexate, procarbazine and vincristine (n = 39) or high dose-methotrexate (n = 56) were analysed. The complete response/complete response unconfirmed rate was significantly higher in the rituximab, methotrexate, procarbazine and vincristine group (74.4 vs. 15.4%, P < 0.001). Accordingly, both median progression-free survival and overall survival were significantly longer in the rituximab, methotrexate, procarbazine and vincristine group (median progression-free survival: unreached vs. 14.75 months, P < 0.001) (median overall survival: unreached vs. 63.15 months, P = 0.005). Although the rate of grade 3/4 hematologic toxicities was high both during rituximab, methotrexate, procarbazine and vincristine and consolidation cytarabine, the rate of grade 3/4 infections was low, and no treatment related deaths were observed. Deterioration in Karnofsky performance status or Mini-Mental State Examination was rare, except on disease recurrence. Although whole brain radiotherapy was associated with Fazekas scale deterioration, its association with Karnofsky performance status or Mini-Mental State Examination deterioration was not significant. CONCLUSIONS: Rituximab, methotrexate, procarbazine and vincristine was apparently promising in comparison with high dose-methotrexate monotherapy with manageable toxicity in this retrospective study, and further investigation is warranted.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Linfoma/tratamiento farmacológico , Metotrexato/uso terapéutico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias del Sistema Nervioso Central/patología , Femenino , Humanos , Linfoma/patología , Masculino , Metotrexato/administración & dosificación , Metotrexato/farmacología , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
14.
Am J Ophthalmol Case Rep ; 18: 100643, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32154441

RESUMEN

PURPOSE: To describe an intraoperative choroidal detachment due to balanced salt solution (BSS) leakage through the exit wound in a case with perforating ocular injury. OBSERVATIONS: The patient was a 22-year-old man who suffered from a left eye injury caused by a piece of wire during work. Vitrectomy was started after closure of the scleral wound, but surgical procedure could not be continued, as BSS leakage occurred into the subretinal and supra-choroidal spaces, resulting in a narrowed vitreous cavity, as we were slow to recognize the presence of the perforating ocular injury in this patient. Fluid-air exchange and air-silicone oil exchange in the vitreous cavity were performed to finish the initial surgery. Three weeks later, the reoperation was performed to remove silicone oil and insert an intraocular lens into the bag. Presently, 1 year 5 months following the second surgery, corrected visual acuity is 20/50. CONCLUSIONS AND IMPORTANCE: Our findings indicate that BSS can leak through the exit wound into the subretinal and supra-choroidal spaces intraoperatively in a case of perforating ocular injury.

15.
Int J Mol Med ; 44(4): 1187-1196, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31364735

RESUMEN

Cellular senescence is associated with the induction of a proinflammatory phenotype. Notably, senescent endothelial cells are detected at the sites of atherosclerotic lesions, suggesting the involvement of senescent endothelial cells in atherogenesis. Moreover, bacterial infection has been speculated to contribute to the pathogenesis of atherosclerosis. The present study investigated the effects of Gram­negative bacterial lipopolysaccharide (LPS) and LL­37 (a human antimicrobial peptide of the cathelicidin family), on senescent endothelial cells, using serially passaged human endothelial cells. The results indicated that senescent endothelial cells exhibited the basal proinflammatory phenotype, as evidenced by higher intercellular adhesion molecule­1 (ICAM­1) expression and NF­κB p65 phosphorylation, compared with non­senescent cells. Additionally, exposure to LPS and LL­37 further enhanced the expression of ICAM­1 in senescent endothelial cells, compared with non­senescent cells. Of note, the NF­κB p65 pathway was more activated in senescent endothelial cells stimulated with LPS and LL­37. Furthermore, the expression levels of the receptors for LPS and LL­37 [toll­like receptor 4 (TLR4) and purinergic receptor P2X 7 (P2X7), respectively] were upregulated in senescent endothelial cells. These observations indicated that LPS and LL­37 enhanced the ICAM­1 expression and NF­κB p65 activation in senescent endothelial cells, potentially via the upregulated TLR4 and P2X7. Thus, senescent endothelial cells may contribute to the pathogenesis of atherosclerosis via the basal proinflammatory phenotype and the enhanced inflammatory responses against atherogenic factors, including LPS and LL­37.


Asunto(s)
Péptidos Catiónicos Antimicrobianos/farmacología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Molécula 1 de Adhesión Intercelular/genética , Lipopolisacáridos/farmacología , Factor de Transcripción ReIA/metabolismo , Biomarcadores , Células Cultivadas , Senescencia Celular , Activación Enzimática , Técnica del Anticuerpo Fluorescente , Humanos , Molécula 1 de Adhesión Intercelular/metabolismo , Fosforilación , Catelicidinas
16.
Sci Rep ; 9(1): 11782, 2019 08 13.
Artículo en Inglés | MEDLINE | ID: mdl-31409872

RESUMEN

The N-methyl-D-aspartate (NMDA) receptor has been implicated in several neurodegenerative diseases, including stroke. Low-density lipoprotein receptor-related protein 1 (LRP1) plays pivotal roles in endocytosis and signaling in the cell. Immature LRP1 is processed by furin in the trans-Golgi network (TGN) and transported to the cell surface as its mature form. Activation of mature LRP1 exerts a protective effect against glutamate-induced degeneration of the rat retinal ganglion cells, as was shown in our previous study. However, the roles of LRP1 in the pathogenesis of excitotoxic neuronal injuries remain to be determined. The aim of this present study was to achieve further insight into the pathophysiologic roles of LRP1 after excitotoxic neuronal injuries. Our findings are the first to demonstrate that LRP1 was significantly cleaved by furin after cerebral ischemia in rats as well as after exposure of cultured cortical neurons to NMDA. It was noteworthy that the intracellular domain (ICD) of LRP1 was co-localized with TGN and furin. Furthermore, a furin inhibitor inhibited the cleavage of LRP1 and co-localization of LRP1-ICD with TGN or furin. Our findings suggest that furin-mediated cleavage of LRP1 and changes in the localization of LRP1-ICD were involved in the excitotoxic neuronal injury.


Asunto(s)
Isquemia Encefálica/genética , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , N-Metilaspartato/metabolismo , Accidente Cerebrovascular/genética , Animales , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Modelos Animales de Enfermedad , Endocitosis/efectos de los fármacos , Furina/metabolismo , Humanos , N-Metilaspartato/farmacología , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/patología , Neuronas/metabolismo , Neuronas/patología , Ratas , Receptores de LDL/genética , Transducción de Señal/efectos de los fármacos , Accidente Cerebrovascular/metabolismo , Accidente Cerebrovascular/patología , Red trans-Golgi/efectos de los fármacos , Red trans-Golgi/genética
17.
Hepatol Res ; 49(8): 872-880, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30974498

RESUMEN

AIM: Although liver biopsy is the gold standard for the diagnosis and staging of non-alcoholic fatty liver disease (NAFLD), repeated assessment of patients' liver tissue conditions are impractical. We assessed the 10-year changes in liver stiffness measurements (LSM) utilizing vibration-controlled transient elastography in NAFLD patients. METHODS: From January 2006 to September 2007, LSM was carried out for 97 biopsy-proven NAFLD patients. Of these, 34 patients underwent 10-year LSM reassessments (14 of them with paired biopsies). RESULTS: We evaluated the changes in the fibrosis stage as estimated using LSM (FS-LSM). Over a 10-year period, 32.4% had FS-LSM progression, 50% had static disease, and 17.6% had FS-LSM improvement. From among the initially diagnosed non-alcoholic steatohepatitis patients, 18% had progressed to considerable stage 4 (cirrhosis) 10 years later. In this cohort, none of the patients who had been initially diagnosed as FS-LSM stage 0 had progressed to cirrhosis 10 years later. The changes in LSM were correlated with the change in the histological fibrosis stage, the NAFLD activity score, and the change in the sum of the steatosis, activity, and fibrosis score. Improving more than 1 body mass index (kg/m2 ) and having a higher initial aspartate aminotransferase, alanine aminotransferase (ALT), or ALT responder (>30% improvement or reduction to less than 40 IU/L) were factors contributing to LSM improvements (≥2 kPa). CONCLUSIONS: Vibration-controlled transient elastography is likely to become a more clinically important tool for the long-term monitoring of NAFLD patients.

18.
Clin Ophthalmol ; 12: 2087-2093, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30410303

RESUMEN

We developed intraocular lens (IOL) fixation procedure that only uses one suture during Zinn's zonule dialysis portion of the combined surgery for IOL intracapsular fixation and unilateral loop suture for preserving the lens capsule. We treated 15 eyes in 15 patients which were confirmed to have almost 180° zonular dialysis during cataract surgery. After removing the lens, a scleral flap was created on the dialysis side. A straight needle for suturing was then inserted into the anterior chamber from the opposite side of the dialysis. The needle was used to attach the equatorial segment of the capsule on the dialysis side from the inside to the outside and then pull the suture thread under the scleral flap. After the thread was bound to a preceding loop of IOL, the IOL was inserted into the bag. Our procedure was found to be simple and less invasive, as our technique required no vitrectomy to be performed.

19.
Mol Med Rep ; 18(6): 4951-4959, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30280189

RESUMEN

LL­37 is the sole antimicrobial peptide of human cathelicidin comprising 37 amino acids, which is expressed mainly in epithelial cells and neutrophils, and activates mast cells. In the present study, in order to elucidate the mechanism of mast cell activation by LL­37, the associations between the internalization of LL­37 and Mas­related gene X2 (MrgX2)­mediated mast cell activation (degranulation) was investigated using the human mast cell line, LAD2. LL­37 was rapidly internalized into the cells, and induced degranulation, as assessed by the extracellular release of ß­hexosaminidase. Pertussis toxin, a G­protein inhibitor, significantly suppressed the internalization of LL­37 and the degranulation of LAD2 cells. Furthermore, small interfering (si)­RNA­mediated knockdown of MrgX2, a putative G protein­coupled receptor for LL­37, inhibited the internalization of LL­37 and degranulation of LAD2 cells. Notably, LL­37 internalization was enhanced by the stable expression of MrgX2 in HMC­1 and 293 cells. In addition, the internalized LL­37 mainly colocalized with MrgX2 in the perinuclear region of LAD2 cells. Furthermore, neuraminidase treatment, which removes negatively charged sialic acid from the cell surface, markedly reduced the internalization of LL­37 and degranulation of LAD2 cells, and clathrin­mediated endocytosis inhibitors (dynasore and chlorpromazine) inhibited the internalization and degranulation of LAD2 cells. Taken together, these observations indicated that LL­37 may bind the negatively charged cell surface molecules, rapidly internalize into the cells via clathrin­mediated endocytosis and interact with MrgX2 to activate mast cells (LAD2 cells).


Asunto(s)
Péptidos Catiónicos Antimicrobianos/metabolismo , Degranulación de la Célula/genética , Mastocitos/inmunología , Mastocitos/metabolismo , Proteínas del Tejido Nervioso/genética , Receptores Acoplados a Proteínas G/genética , Receptores de Neuropéptido/genética , Línea Celular , Células Cultivadas , Endocitosis , Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Proteínas del Tejido Nervioso/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Neuropéptido/metabolismo , Catelicidinas
20.
Sci Rep ; 8(1): 481, 2018 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-29323176

RESUMEN

Preparation of highly crystalline organic semiconductor films is vital to achieving high performance in electronic devices. Here we report that surface segregated monolayers (SSMs) on top of phenyl-C61-butyric acid methyl ester (PCBM) thin films induce crystal growth in the bulk, resulting in a dramatic change in the structure to form a new crystal phase. Highly ordered crystalline films with large domain sizes of several hundreds of nanometers are formed with uniaxial orientation of the crystal structure perpendicular to the substrate. The molecular rearrangements in SSMs trigger the nucleation at a lower temperature than that for the spontaneous nucleation in PCBM. The vertical charge mobility in the SSM-induced crystal domains of PCBM is five times higher than in the ordinary polycrystalline domains. Using surface monolayers may be a new strategy for controlling crystal structures and obtaining high-quality organic thin films by post-deposition crystallization.

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