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1.
Dis Colon Rectum ; 66(10): 1319-1328, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35671281

RESUMO

BACKGROUND: Colonic stenting reduces morbidity and stoma formation for left-sided colon cancer obstruction, and a prolonged interval between stenting and surgery with neoadjuvant chemotherapy administered might result in a lower stoma rate and tumor reduction. OBJECTIVE: The study aimed to evaluate the short-term outcomes of elective surgery following colonic stenting compared with elective surgery following colonic stenting and neoadjuvant chemotherapy in patients with left-sided colon cancer obstruction. DESIGN: This is a prospective multicenter cohort study. SETTINGS: This study was conducted at 5 medical centers. PATIENTS: Patients ( n = 100) with acute left-sided colon cancer obstruction undergoing colonic stenting between December 2015 and December 2019 were included. INTERVENTIONS: Patients were assigned to the stenting-alone or chemotherapy group. MAIN OUTCOME MEASURES: The primary outcomes measured were laparoscopic surgery and stoma rate. RESULTS: Of the 100 patients who underwent colonic stenting, 52 were assigned to the stenting group and 48 were assigned to the chemotherapy group. No statistically significant differences were detected in stent-related complications. The adverse events associated with neoadjuvant chemotherapy were well tolerated. The level of hemoglobin (117.2 vs 107.6 g/L; p = 0.008), albumin (34.2 vs 31.5 g/L; p < 0.001), and prealbumin (0.19 vs 0.16 g/L; p = 0.001) was significantly increased, and the bowel wall thickness (1.09 vs 2.04 mm; p < 0.001) was significantly decreased preoperatively in the chemotherapy group compared with the stenting group. The number of mean harvested lymph nodes was greater in the chemotherapy group than in the stenting group (25.6 vs 21.8; p = 0.04). Laparoscopic surgery was performed more frequently (77.1% vs 40.4%; p < 0.001) and a stoma was created less frequently (10.4% vs 28.8%; p = 0.02) in the chemotherapy group than in the stenting group. LIMITATIONS: This trial was limited by the nonrandomized design and a short follow-up period. CONCLUSIONS: This study suggests that elective surgery following neoadjuvant chemotherapy and colonic stenting is a safe, effective, and well-tolerated treatment approach with a high laparoscopic resection rate and a low stoma rate. See Video Abstract at http://links.lww.com/DCR/B980 . RESULTADOS A CORTO PLAZO DE LA CIRUGA ELECTIVA SEGUIDO DE STENT METLICO AUTOEXPANDIBLE Y QUIMIOTERAPIA NEOADYUVANTE EN PACIENTES CON OBSTRUCCIN POR CNCER DE COLON IZQUIERDO: ANTECEDENTES:La colocación de stents colónicos reduce la morbilidad y la formación de estomas por obstrucción por cáncer de colon izquierdo, y el intervalo prolongado entre la colocación de stents y la cirugía con quimioterapia neoadyuvante administrada podría resultar en una menor tasa de estomas y reducción del tumor.OBJETIVO:Evaluar los resultados a corto plazo de la cirugía electiva después de la colocación de stent en el colon en comparación con la cirugía electiva después de la colocación de stent en el colon y la quimioterapia neoadyuvante en pacientes con obstrucción por cáncer de colon izquierdo.DISEÑO:Estudio prospectivo de cohorte multicéntrico.ENTORNO CLINICO:Este estudio se realizó en 5 centros médicos.PACIENTES:Se incluyeron pacientes (n=100) con obstrucción aguda por cáncer de colon izquierdo que se sometieron a colocación de stent colónico entre diciembre de 2015 y diciembre de 2019.INTERVENCIONES:Los pacientes fueron asignados al grupo de stent solo o quimioterapia.MEDIDAS DE RESULTADO PRINCIPALES:Los resultados primarios medidos fueron la cirugía laparoscópica y la tasa de ostomía.RESULTADOS:De los 100 pacientes que se sometieron a la colocación de stent colónico, 52 fueron asignados al grupo de colocación de stent y 48 al grupo de quimioterapia. No se detectaron diferencias estadísticamente significativas en las complicaciones relacionadas con el stent. Los eventos adversos asociados con la quimioterapia neoadyuvante fueron bien tolerados. Hemoglobina (117,2 g/l vs. 107,6 g/l; p = 0,008), albúmina (34,2 g/l vs. 31,5 g/l; p < 0,001) y prealbúmina (0,19 g/l vs. 0,16 g/l; p = 0,001) aumentaron significativamente y el grosor de la pared intestinal (1,09 mm vs. 2,04 mm; p < 0,001) disminuyó significativamente antes de la operación en el grupo de quimioterapia en comparación con el grupo de colocación de stent. El número medio de ganglios linfáticos extraídos fue mayor en el grupo de quimioterapia que en el grupo de stent (25,6 vs. 21,8; p = 0,04). La cirugía laparoscópica se realizó con mayor frecuencia (77,1 % vs. 40,4 %; p < 0,001) y se creó un estoma con menos frecuencia (10,4 % vs. 28,8 % ; p = 0,02) en el grupo de quimioterapia que en el grupo de colocación de stent.LIMITACIONES:Este ensayo estuvo limitado por el diseño no aleatorio y el corto período de seguimiento.CONCLUSIONES:Este estudio sugiere que la cirugía electiva después de la quimioterapia neoadyuvante y la colocación de stent colónico es un tratamiento seguro, efectivo y bien tolerado, con una alta tasa de resección laparoscópica y una baja tasa de estoma. Consulte Video Resumen en http://links.lww.com/DCR/B980 . (Traducción- Dr. Francisco M. Abarca-Rendon ).


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Obstrução Intestinal , Humanos , Terapia Neoadjuvante/efeitos adversos , Estudos Prospectivos , Estudos de Coortes , Neoplasias do Colo/complicações , Neoplasias do Colo/terapia , Neoplasias do Colo/patologia , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Stents , Resultado do Tratamento , Estudos Retrospectivos , Neoplasias Colorretais/cirurgia
2.
Zhongguo Zhong Yao Za Zhi ; 48(12): 3224-3234, 2023 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-37382006

RESUMO

This study aims to investigate the efficacy and possible mechanism of Liuwei Dihuang Pills in the treatment of diminished ovarian reserve(DOR) by using proteomic techniques. Firstly, cyclophosphamide(60 mg·kg~(-1)) combined with busulfan(6 mg·kg~(-1)) was injected intraperitoneally to establish the mouse model of DOR. After drug injection, the mice were continuously observed and the success of modeling was evaluated by the disturbance of the estrous cycle. After successful modeling, the mice were administrated with the suspension of Liuwei Dihuang Pills by gavage for 28 days. At the end of the gavage, four female mice were selected and caged together with males at a ratio of 2∶1 for the determination of the pregnancy rate. Blood and ovary samples were collected from the remaining mice on the next day after the end of gavage. Hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM) were then employed to observe the morphological and ultrastructural changes in the ovaries. The serum levels of hormones and oxidation indicators were measured by enzyme-linked immunosorbent assay. Quantitative proteomics techniques were used to compare the ovarian protein expression before and after modeling and before and after the intervention with Liuwei Dihuang Pills. The results showed that Liuwei Dihuang Pills regulated the estrous cycle of DOR mice, elevated the serum levels of hormones and anti-oxidation indicators, promoted follicle development, protected the mitochondrial morphology of ovarian granulosa cells, and increased the litter size and survival of DOR mice. Furthermore, Liuwei Dihuang Pills negatively regulated the expression of 12 differentially expressed proteins associated with DOR, which were mainly involved in lipid catabolism, inflammatory response, immune regulation, and coenzyme biosynthesis. These differentially expressed proteins were significantly enriched in sphingolipid metabolism, arachidonic acid metabolism, ribosomes, ferroptosis, and cGMP-PKG signaling pathway. In summary, the occurrence of DOR and the treatment of DOR with Liuwei Dihuang Pills are associated with multiple biological pathways, mainly including oxidative stress response, inflammatory response, and immune regulation. "Mitochondria-oxidative stress-apoptosis" is the key to the treatment of DOR by Liuwei Dihuang Pills. YY1 and CYP4F3 may be the key upstream targets that trigger mitochondrial dysfunction and ROS accumulation, and the metabolism of arachidonic acid is the main signaling pathway of drug action.


Assuntos
Reserva Ovariana , Feminino , Masculino , Gravidez , Animais , Camundongos , Ácido Araquidônico , Proteômica , Ovário , Metabolismo dos Lipídeos
3.
Zhongguo Zhong Yao Za Zhi ; 47(11): 3059-3065, 2022 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-35718530

RESUMO

This research focused on the effect and mechanism of berberine on osteogenic differentiation of valve interstitial cells(VICs) induced by osteogenic induction medium, in order to provide new insights into the clinical treatment of calcified aortic valve disease. The expression of osteogenic and fibrotic makers in three cases of calcified valve tissues and one case of normal control was assayed by Western blot. After the porcine aortic VICs were isolated, the effects of different concentrations of berberine on their viability were examined by MTT assay for determining the optimal concentration range. VICs were cultured in osteogenic induction medium and treated with different concentrations of berberine. Western blot and q-PCR were conducted to detect the effects of berberine on the expression of osteogenic and fibrotic makers in VICs. The effects of berberine on osteogenic differentiation of VICs in the early and late stages were separately measured by ALP staining and alizarin red S staining. The effects of berberine on the phosphorylation of ERK1/2 at different time points were assayed by Western blot. And PD98059, an inhibitor of ERK1/2, was added for verification. The results suggested that related osteogenic and fibrotic makers were significantly up-regulated in calcified valve tissues as compared with those in the normal control. The up-regulated fibrosis and osteogenic makers of VICs under osteogenic conditions were reversed by berberine and the ALP activity and calcium deposition in VICs were also reduced obviously. The level of ERK1/2 phosphorylation was decreased. Similarly, the osteogenic and fibrotic makers of VICs induced by osteogenic induction medium were lowered by PD98059. This study has confirmed that berberine is able to inhibit the differentiation of VICs into myofibroblasts or osteoblast-like cells, which may be associated with the inhibition of ERK1/2 signaling pathway.


Assuntos
Estenose da Valva Aórtica , Berberina , Animais , Valva Aórtica/metabolismo , Estenose da Valva Aórtica/tratamento farmacológico , Estenose da Valva Aórtica/genética , Estenose da Valva Aórtica/metabolismo , Berberina/farmacologia , Diferenciação Celular , Células Cultivadas , Osteogênese , Suínos
4.
Anal Chem ; 92(1): 699-706, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31789017

RESUMO

Pulmonary fibrosis (PF) is a fatal disease with increasing prevalence. Nonradioactive and noninvasive diagnosis of PF at an early stage can improve the prognosis but represents a daunting challenge. Up-regulation of nitric oxide (NO) is a typical microenvironmental feature of PF. Here, we report a small-molecule probe, PNO1, that can fluorogenically sense this microenvironmental feature for PF diagnosis. We demonstrate that PNO1 fluorescence is 6-fold higher in PF-diseased mice lungs than in normal-control groups. In addition to this in vivo result, PNO1 can also be applied in vitro to detect PF-diseased cells and ex vivo to detect PF-diseased tissues from clinical patients. These results highlight PNO1 as a complement to the traditional immunostaining-based methods for PF detection to facilitate quick screening for anti-PF drug candidates.


Assuntos
Corantes Fluorescentes/química , Fibrose Pulmonar/diagnóstico , Bibliotecas de Moléculas Pequenas/química , Animais , Linhagem Celular , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/síntese química , Injeções Intravenosas , Camundongos , Estrutura Molecular , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Imagem Óptica , Fibrose Pulmonar/metabolismo , Bibliotecas de Moléculas Pequenas/administração & dosagem , Bibliotecas de Moléculas Pequenas/síntese química
5.
Stem Cells ; 37(10): 1331-1343, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31233254

RESUMO

Endothelial progenitor cells (EPCs) contribute to blood vessel formation. Canonical Wnt signaling plays an important role in physiological and pathological angiogenesis and EPC fate regulation. However, the mechanism for Wnt signaling to regulate EPC fate in neovascularization (NV) has not been clearly defined. Here, we showed that very low-density lipoprotein receptor knockout (Vldlr -/- ) mice, a model of ocular NV induced by Wnt signaling overactivation, have increased EPC numbers in the bone marrow, blood, and retina, as well as an elevated mitochondrial membrane potential indicating higher mitochondrial function of EPCs in the circulation. Isolated EPCs from Vldlr -/- mice showed overactivated Wnt signaling, correlating with increased mitochondrial function, mass, and DNA copy numbers, compared with WT EPCs. Our results also demonstrated that Wnt signaling upregulated mitochondrial biogenesis and function, while inhibiting glycolysis in EPCs, which further decreased EPC stemness and promoted EPCs to a more active state toward differentiation, which may contribute to pathologic vascular formation. Fenofibric acid, an active metabolite of fenofibrate, inhibited Wnt signaling and mitochondrial function in EPCs and decreased EPC numbers in Vldlr -/- mice. It also decreased mitochondrial biogenesis and reactive oxygen species production in Vldlr -/- EPCs, which may be responsible for its therapeutic effect on diabetic retinopathy. These findings demonstrated that Wnt signaling regulates EPC fate through metabolism, suggesting potential application of the EPC metabolic profile as predictor and therapeutic target for neovascular diseases. Stem Cells 2019;37:1331-1343.


Assuntos
Células-Tronco/metabolismo , Via de Sinalização Wnt/fisiologia , Animais , Diferenciação Celular , Células Cultivadas , Modelos Animais de Doenças , Células Progenitoras Endoteliais/metabolismo , Metaboloma , Camundongos , Neovascularização Patológica/metabolismo
6.
Am J Physiol Endocrinol Metab ; 316(3): E443-E452, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30576241

RESUMO

The purpose of this study was to explore the role of microRNA-451a (miR-451a) in diabetic retinopathy through activating transcription factor 2 (ATF2). The epiretinal membrane samples from patients with proliferative diabetic retinopathy (PDR) were immunolabeled with an antibody for Ki-67 to identify the proliferative cells. The expression of miR-451a was measured by qRT-PCR in the retina of Akita mice and in RPE cells under diabetic conditions. The potential downstream targets of miR-451a were predicted by bioinformatics and confirmed by dual luciferase assay, qRT-PCR, and Western blotting. Mitochondrial function, cell proliferation, and migration assays were used to detect the functional change after transfection of miR-451a mimic and inhibitor. Proliferative RPE cells were identified in the epiretinal membrane from PDR patients. The expression of miR-451a was downregulated both in the retina of Akita mice and 4-hydroxynonenal (4-HNE)-treated RPE cells. Bioinformatic analysis and luciferase assay identified ATF2 as a potential target of miR-451a. miR-451a inhibited proliferation and migration of RPE cells. The mitochondrial function was enhanced by miR-451a mimic, but suppressed by miR-451a inhibitor. In diabetic conditions, miR-451a showed a protective effect on mitochondrial function. The results of qRT-PCR and Western blotting revealed that overexpression of miR-451a downregulated the expression of ATF2 and its downstream target genes CyclinA1, CyclinD1, and MMP2. In conclusion, miR-451a/ATF2 plays a vital role in the regulation of proliferation and migration in RPE cells through regulation of mitochondrial function, which may provide new perspectives for developing effective therapies for PDR.


Assuntos
Fator 2 Ativador da Transcrição/genética , Retinopatia Diabética/genética , MicroRNAs/genética , Mitocôndrias/metabolismo , Fator 2 Ativador da Transcrição/metabolismo , Adulto , Idoso , Animais , Movimento Celular , Proliferação de Células , Ciclina A1/genética , Ciclina A1/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Retinopatia Diabética/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Epitélio Pigmentado da Retina
7.
BMC Ophthalmol ; 18(1): 121, 2018 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-29784048

RESUMO

BACKGROUND: This meta-analysis evaluated the effectiveness and safety of dexamethasone (DEX) implant and intravitreal anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular edema (DME). METHODS: The PubMed, Embase, clinicaltrials.gov website and Cochrane Library databases were comprehensively searched for studies comparing DEX implant with anti-VEGF in patients with DME. Best-corrected visual acuity (BCVA), central subfield thickness (CST) and adverse events were extracted from the final eligible studies. Review Manager (RevMan) 5.3 for Mac was used to analyze the data and GRADE profiler were used to access the quality of outcomes. RESULTS: Based on four randomized clinical trials assessing a total of 521 eyes, the DEX implant can achieve visual acuity improvement for DME at rates similar to those achieved via anti-VEGF treatment (mean difference [MD] = - 0.43, P = 0.35), with superior anatomic outcomes at 6 months (MD = - 86.71 µm, P = 0.02), while requiring fewer injections, in comparison to anti-VEGF treatment. Although the mean reduction in CST did not showed significant difference at 12 months (MD = - 33.77 µm, P = 0.21), the significant in BCVA from baseline to 12 months supported the anti-VEGF treatment (MD = - 3.26, P < 0.00001). No statistically significant differences in terms of the serious adverse events. However, use of the DEX implant has higher risk of intraocular pressure elevation and cataract than anti-VEGF treatment. CONCLUSIONS: Compared with anti-VEGF, DEX implant improved anatomical outcomes significantly. However, this did not translate to improved visual acuity, which may be due to the progression of cataract. Therefore, the DEX implant may be recommended as a first chioce for select cases, such as for pseudophakic eyes, anti-VEGF-resistant eyes, or patients reluctant to receive intravitreal injections frequently.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Dexametasona/administração & dosagem , Retinopatia Diabética/tratamento farmacológico , Implantes de Medicamento , Glucocorticoides/administração & dosagem , Edema Macular/tratamento farmacológico , Inibidores da Angiogênese/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Bevacizumab , Preparações de Ação Retardada , Dexametasona/efeitos adversos , Glucocorticoides/efeitos adversos , Humanos , Injeções Intravítreas , Ranibizumab , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual
8.
Zhongguo Zhong Yao Za Zhi ; 41(9): 1622-1626, 2016 May.
Artigo em Chinês | MEDLINE | ID: mdl-28891609

RESUMO

Vibrio fischeri CS234 was used to establish and optimize microtox assay system, laying a foundation for the application of this method in comprehensive acute toxicity test of traditional Chinese medicine (TCM) injections. Firstly, the Plackett-Burman method was carried out to optimize the factors which would affect Vibrio fischeri CS234 luminescence. Secondly, ZnSO4•7H2O was chosen as reference substance to establish its reaction system with quality control samples. The optimal luminescence conditions were achieved as follows: ①At a temperature of (15±1) ℃, Vibrio fischeri CS234 lyophilized powders were balanced for 15 min, then, 1 mL resuscitation fluid was added and blended for 10 min. 100 µL bacteria suspension was taken to measure the initial luminescence intensity, and then 1 mL resuscitation fluid or test sample was immediately added; after reaction for 10 min, corresponding luminescence intensity was measured again. Resuscitation diluent, osmotic pressure regulator and ZnSO4•7H2O stock solution showed no interference to the determination of Vibrio fischeri CS234 luminescence intensity, so this method was of good specificity. The within-and between-batch precisions of quality controls and the lower limit of quantification (LLOQ) samples were <5% and <10% respectively, while the accuracy ranged between 85.8% and 103.2%. The standard curve equation of ZnSO4•7H2O ranged from 3.86 mg•L⁻¹ to 77.22 mg•L⁻¹ (final concentrations) was y=21.78lnx-15.14, R2=0.998; meanwhile, IC50 of ZnSO4•7H2O to Vibrio fischeri CS234 was 19.90 mg•L⁻¹. ZnSO4•7H2O stock solution and its quality controls were continuously investigated for 120 h and 8 h respectively, and their RSD was lower than 2%, indicating stability at room temperature and 4 ℃ storage conditions. Between pH 4.5-8.0, luminescence intensity of Vibrio fischeri CS234 was controlled within ±10%, and such pH value range could meet the testing needs of the vast majority of traditional Chinese medicine injections. The Vibrio fischeri strain CS234 assay system was specific, stable, sensitive, accurate and adaptable after optimization, so it was suitable for the comprehensive acute toxicity assessment of TCM injections.


Assuntos
Aliivibrio fischeri/efeitos dos fármacos , Medicamentos de Ervas Chinesas/toxicidade , Testes de Toxicidade Aguda , Bioensaio , Luminescência , Medicina Tradicional Chinesa
9.
Tumour Biol ; 36(5): 3355-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25613066

RESUMO

The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a bona fide long noncoding RNA (lncRNA). LncRNA MALAT1 was discovered as a prognostic factor for lung cancer metastasis but also has been linked to several other human tumor entities. However, little is known about the role of lncRNA MALAT1 in glioma patients. The aim of this study was to identify the role of lncRNA MALAT1 in the pathogenesis of glioma; we analyzed the relationship of lncRNA MALAT1 expression with clinicopathological characteristics in glioma patients. In our results, lncRNA MALAT1 expression was increased in glioma tissues compared with paired adjacent brain normal tissues (P < 0.001). Furthermore, lncRNA MALAT1 was associated significantly with WHO grade (I-II vs. III-IV; P = 0.007) and tumor size (< 3 cm vs. T ≥ 3 cm; P = 0.008). However, lncRNA MALAT1 expression was not associated significantly with age (<45 vs. ≥ 45, P = 0.343), gender (female vs. male, P = 0.196), family history of cancer (yes vs. no, P = 0.665), and tumor location (supratentorial vs. infratentorial, P = 0.170). Moreover, the level of lncRNA MALAT1 expression was markedly correlated with the glioma patients' overall survival (P < 0.001). Multivariate analysis suggested that increased lncRNA MALAT1 expression was a poor independent prognostic predictor for glioma patients (P = 0.002). In conclusion, lncRNA MALAT1 plays an important role on glioma progression and prognosis and may serve as a convictive prognostic biomarker for glioma patients.


Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , RNA Longo não Codificante/fisiologia , Adulto , Idoso , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Feminino , Glioma/genética , Glioma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Longo não Codificante/genética
10.
Drug Dev Ind Pharm ; 41(12): 1997-2005, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25835068

RESUMO

The purpose of this paper was to study the influence of drug physicochemical characteristics on in vitro transdermal absorption of hydrophobic drug nanosuspensions. Four drug nanosuspensions were produced by high-pressure homogenization technique, which were the same in stabilizer and similar in particle size. Differential scanning calorimetry and powder X-ray diffraction analysis showed that the crystalline state of the nanocrystals did not change. In vitro permeation study demonstrated that the drug nanosuspensions have a higher rate of permeation that ranged from 1.69- to 3.74-fold compared to drug microsuspensions. Correlation analysis between drug physicochemical properties and Jss revealed that log P and pKa were factors that influenced the in vitro transdermal absorption of hydrophobic drug nanosuspensions, and drugs with a log P value around 3 and a higher pKa value (when pKa < pH+2) would gain higher Jss in this paper.


Assuntos
Fenômenos Químicos , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Nanopartículas/metabolismo , Absorção Cutânea/fisiologia , Administração Cutânea , Animais , Fenômenos Químicos/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Masculino , Nanopartículas/administração & dosagem , Técnicas de Cultura de Órgãos , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Absorção Cutânea/efeitos dos fármacos , Difração de Raios X
11.
Graefes Arch Clin Exp Ophthalmol ; 252(3): 423-31, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24492934

RESUMO

PURPOSE: The objective of this study was to determine whether cells from the conjunctiva could be reprogrammed into induced pluripotent stem (iPS) cells, providing an alternative source of stem cells. METHODS: We employed a doxycycline-induced reprogrammable mouse strain to generate iPS cells from conjunctiva. The identity of the stem cells was confirmed by reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence assays. Immunocytochemistry and teratoma assays are established means for scoring stem cell pluripotency. The reprogramming efficiencies of conjunctival cells and ear fibroblasts were compared. RESULTS: We confirmed the identity of the stem cells and demonstrated expression of pluripotency markers (OCT4, SOX2, NANOG, and SSEA1), as tested by RT-PCR and immunofluorescence assays. In addition, derived iPS cells differentiated successfully into embryoid bodies, and showed teratoma formation when injected into immunodeficient mice. Reprogramming conjunctival tissue is as efficient as reprogramming ear fibroblasts. Conjunctiva-iPS exhibited classic features of embryonic stem (ES) cells with respect to morphology, expression of surface antigens, and pluripotency-associated transcription factors, capacity to differentiate in vitro, and the ability to form all three germ layers in vivo. CONCLUSION: The present study demonstrated that conjunctival cells, which are readily obtained during the course of many routine conjunctival biopsies and ophthalmic procedures, can be another reliable source of iPS cells.


Assuntos
Túnica Conjuntiva/citologia , Células-Tronco Pluripotentes Induzidas/citologia , Animais , Antibacterianos/farmacologia , Biomarcadores/metabolismo , Técnicas de Cultura de Células , Técnicas de Cocultura , Túnica Conjuntiva/efeitos dos fármacos , Túnica Conjuntiva/metabolismo , Doxiciclina/farmacologia , Fibroblastos/citologia , Técnica Indireta de Fluorescência para Anticorpo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Cariotipagem , Antígenos CD15/genética , Antígenos CD15/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteína Homeobox Nanog , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo
12.
Retina ; 34(12): 2317-35, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25360790

RESUMO

BACKGROUND: Idiopathic epiretinal membrane (iERM) is a fibrocellular membrane that proliferates on the inner surface of the retina at the macular area. Membrane contraction is an important sight-threatening event and is due to fibrotic remodeling. METHODS: Analysis of the current literature regarding the epidemiology, clinical features, and pathogenesis of iERM and fibrotic tissue contraction. RESULTS: Epidemiologic studies report a relationship between iERM prevalence, increasing age, and posterior vitreous detachment. Clinically, iERM progresses through different stages characterized by an increased thickness and wrinkling of the membrane. Pathophysiologically, iERM formation is a fibrotic process in which myofibroblast formation and the deposition of newly formed collagens play key roles. Anomalous posterior vitreous detachment may be a key event initiating the formation of iERM. The age-related accumulation of advanced glycation end products may contribute to anomalous posterior vitreous detachment formation and may also influence the mechanical properties of the iERM. CONCLUSION: Remodeling of the extracellular matrix at the vitreoretinal interface by aging and fibrotic changes, plays a significant role in the pathogenesis of iERM. A better understanding of molecular mechanisms underlying this process may eventually lead to the development of effective and nonsurgical approaches to treat and prevent vitreoretinal fibrotic diseases.


Assuntos
Membrana Epirretiniana , Membrana Basal/metabolismo , Membrana Basal/patologia , Membrana Epirretiniana/etiologia , Matriz Extracelular/metabolismo , Fibrose/patologia , Humanos
13.
Retina ; 34(5): 897-906, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24077090

RESUMO

PURPOSE: To investigate the identity of collagens and cellular components in the epiretinal membrane (ERM) associated with full-thickness idiopathic macular hole and their clinical relevance. METHODS: Pars plana vitrectomy with the peeling of internal limiting membrane and ERM was performed by 2 surgeons in 40 eyes with idiopathic macular holes. The clinical data were reviewed and the surgical specimens were processed for flat-mount and immunohistochemical analysis. RESULTS: Epiretinal membrane is a GFAP-positive gliotic and fibrotic scar which contains newly formed Type I, III, and V collagens. Type VI collagen was not observed. Colocalization studies found cells coexpressing GFAP/CRALBP, GFAP/α-SMA, and α-SMA/CRALBP, which are consistent with transdifferentiation of Müller cells into fibroblasts and myofibroblasts. The clinically significant ERMs can be divided into two groups according to the amount of cells in ERM: sparse cellular proliferation and dense cellular proliferation. The latter group is associated with a higher chance of surgical difficulty during internal limiting membrane peeling (P = 0.006). Preoperative and postoperative visual function were not affected by the density of the cellular proliferation. CONCLUSION: Retinal glial cells, probably transdifferentiated Müller cells, are involved in the formation of full-thickness macular hole-associated ERMs by a gliotic and fibrotic process. Such ERMs contain newly formed Type I, III, and V collagen depositions. The cell density of ERM affects its biomechanical properties and determines the difficulty of ERM peeling.


Assuntos
Membrana Basal/metabolismo , Membrana Epirretiniana/metabolismo , Colágenos Fibrilares/metabolismo , Neuroglia/patologia , Perfurações Retinianas/complicações , Actinas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Membrana Basal/patologia , Membrana Basal/cirurgia , Proteínas de Transporte/metabolismo , Tamponamento Interno , Membrana Epirretiniana/etiologia , Membrana Epirretiniana/cirurgia , Feminino , Fibrose , Técnica Indireta de Fluorescência para Anticorpo , Proteína Glial Fibrilar Ácida/metabolismo , Gliose/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neuroglia/metabolismo , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/cirurgia , Hexafluoreto de Enxofre/administração & dosagem , Doadores de Tecidos , Tomografia de Coerência Óptica , Vitrectomia
15.
World J Diabetes ; 15(4): 654-663, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38680696

RESUMO

BACKGROUND: Neovascular glaucoma (NVG) is likely to occur after pars plana vitrectomy (PPV) for diabetic retinopathy (DR) in some patients, thus reducing the expected benefit. Understanding the risk factors for NVG occurrence and building effective risk prediction models are currently required for clinical research. AIM: To develop a visual risk profile model to explore factors influencing DR after surgery. METHODS: We retrospectively selected 151 patients with DR undergoing PPV. The patients were divided into the NVG (NVG occurrence) and No-NVG (No NVG occurrence) groups according to the occurrence of NVG within 6 months after surgery. Independent risk factors for postoperative NVG were screened by logistic regression. A nomogram prediction model was established using R software, and the model's prediction accuracy was verified internally and externally, involving the receiver operator characteristic curve and correction curve. RESULTS: After importing the data into a logistic regression model, we concluded that a posterior capsular defect, preoperative vascular endothelial growth factor ≥ 302.90 pg/mL, glycosylated hemoglobin ≥ 9.05%, aqueous fluid interleukin 6 (IL-6) ≥ 53.27 pg/mL, and aqueous fluid IL-10 ≥ 9.11 pg/mL were independent risk factors for postoperative NVG in patients with DR (P < 0.05). A nomogram model was established based on the aforementioned independent risk factors, and a computer simulation repeated sampling method was used to internally and externally verify the nomogram model. The area under the curve (AUC), sensitivity, and specificity of the model were 0.962 [95% confidence interval (95%CI): 0.932-0.991], 91.5%, and 82.3%, respectively. The AUC, sensitivity, and specificity of the external validation were 0.878 (95%CI: 0.746-0.982), 66.7%, and 95.7%, respectively. CONCLUSION: A nomogram constructed based on the risk factors for postoperative NVG in patients with DR has a high prediction accuracy. This study can help formulate relevant preventive and treatment measures.

16.
Am J Chin Med ; 52(3): 841-864, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38716618

RESUMO

A high-glucose environment is involved in the progression of diabetes mellitus (DM). This study aims to explore the regulatory effects of quercetin (QUE) on autophagy and apoptosis after myocardial injury in rats with DM. The type 2 DM rat models were constructed using low-dose streptozotocin (STZ) treatment combined with a high-carbohydrate (HC) diet in vivo. Compared with the control group, the body weight was decreased, whereas blood pressure, blood glucose, and the LVW/BW ratio were increased in the diabetic group. The results showed that the myocardial fibers were disordered in the diabetic group. Moreover, we found that the myocardial collagen fibers, PAS-positive cells, and apoptosis were increased, whereas the mitochondrial structure was destroyed and autophagic vacuoles were significantly reduced in the diabetic group compared with the control group. The expression levels of autophagy-related proteins LC3 and Beclin1 were decreased, whereas the expression levels of P62, Caspae-3, and Bax/Bcl-2 were increased in the diabetic group in vitro and in vivo. Moreover, QUE treatment alleviated the cellular oxidative stress reaction under high-glucose environments. The results of immunoprecipitation (IP) showed that the autophagy protein Beclin1 was bound to Bcl-2, and the binding capacity increased in the HG group, whereas it decreased after QUE treatment, suggesting that QUE inhibited the binding capacity between Beclin1 and Bcl-2, thus leading to the preservation of Beclin1-induced autophagy. In addition, the blood pressure, blood glucose, and cardiac function of rats were improved following QUE treatment. In conclusion, QUE suppressed diabetic myocardial injury and ameliorated cardiac function by regulating myocardial autophagy and inhibition of apoptosis in diabetes through the AMPK/mTOR signaling pathway.


Assuntos
Proteínas Quinases Ativadas por AMP , Apoptose , Autofagia , Diabetes Mellitus Experimental , Quercetina , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , Autofagia/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Quercetina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Masculino , Proteínas Quinases Ativadas por AMP/metabolismo , Ratos Sprague-Dawley , Ratos , Modelos Animais de Doenças , Miocárdio/metabolismo , Miocárdio/patologia , Estreptozocina , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/prevenção & controle , Fitoterapia , Proteína Beclina-1/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/complicações
17.
Zhonghua Nan Ke Xue ; 19(10): 890-5, 2013 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-24218941

RESUMO

OBJECTIVE: To study the correlation of azoospermia and severe oligozoospermia with Y chromosome microdeletions, chromosome karyotype and reproductive hormones in male infertility patients. METHODS: We collected semen samples from 63 patients with azoospermia, 49 with severe oligozoospermia and 60 men with normal semen parameters, and determined the incidence of Y chromosome microdeletions, chromosome karyotypes and the levels of reproductive hormones. RESULTS: The incidence rate of Y chromosome microdeletions was 11.11% in the azoospermia and 8.16% in the severe oligozoospermia patients, as compared with 0 in the normal controls (P<0.05). The rate of chromosome abnormalities was 9.52% in the azoospermia group, with statistically significant differences from the severe oligozoospermia and normal control men (both 0) (P<0.05). The levels of FSH and LH were significantly higher in the azoospermia ([20.41 +/- 19.34] IU/L and [11.44 +/- 9.48] IU/L) and the severe oligozoospermia patients ([8.88 +/- 7.04] IU/L and [6.78 +/- 3.85] IU/L) than in the normal males ([3.88 +/- 2.21] IU/L and [4.63 +/- 1.51] IU/L) (P<0.05). CONCLUSION: Examinations of genetics and reproductive hormones are necessary for infertile males with azoospermia and severe oligozoospermia, which may contribute to early diagnosis and treatment.


Assuntos
Azoospermia/genética , Oligospermia/genética , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Adulto , Estudos de Casos e Controles , Deleção Cromossômica , Cromossomos Humanos Y/genética , Hormônios/sangue , Humanos , Infertilidade Masculina , Cariótipo , Cariotipagem , Masculino , Sêmen , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/sangue , Contagem de Espermatozoides
18.
Zhonghua Yan Ke Za Zhi ; 49(11): 1052-5, 2013 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-24555214

RESUMO

Bacterial endophthalmitis is a real rare complication, perhaps the most devastating one,following pars plana vitrectomy. The most common organism responsible for it is coagulase-negative Staphylococcus. Potential predisposing factors of post-vitrectomy endophthalmitis are majorly coming from surgical procedures and compromising of the immune system. Preoperative povidone-iodine preparation received the clinical recommendation for prophylactic interventions. The main choices of bacterial endophthalmitis treatments are intravitreal injection of antibiotics according to etiological diagnoses and vitrectomy.


Assuntos
Endoftalmite , Infecções Oculares Bacterianas , Complicações Pós-Operatórias , Vitrectomia/efeitos adversos , Endoftalmite/diagnóstico , Endoftalmite/prevenção & controle , Endoftalmite/terapia , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/prevenção & controle , Infecções Oculares Bacterianas/terapia , Humanos
19.
Zhonghua Yan Ke Za Zhi ; 49(12): 1134-7, 2013 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-24499700

RESUMO

Myopic traction maculopathy is a group of ocular fundus diseases related to high myopia, which can severely impact on patients' visual function. It is well recognized that the abnormal of macular structure and function in the disease are resulted from various traction mechanisms, including the forces from posterior vitreous detachment, posterior vitreous cortex, and macular epiretinal membrane which acting on the inner retina, the force from posterior staphyloma which acting on the outer retina, and retinal intrinsic features such as the changes of inner limiting membrane and arterioles. The treatments are mainly based on surgery, including vitrectomy and scleral reinforcement surgery in order to relieve the retinal traction. The options of specific surgery procedures are still under debated. In this article, we reviewed the pathogenic mechanisms and therapeutic strategies of myopic traction maculopathy.


Assuntos
Procedimentos Cirúrgicos Eletivos , Miopia Degenerativa/patologia , Miopia Degenerativa/cirurgia , Humanos
20.
Int J Ophthalmol ; 16(5): 721-729, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37206175

RESUMO

AIM: To observe ocular surface changes after phacovitrectomy in patients with mild to moderate meibomian gland dysfunction (MGD)-type dry eye and track clinical treatment response using a Keratograph 5M and a LipiView interferometer. METHODS: Forty cases were randomized into control group A and treatment group B; the latter received meibomian gland treatment 3d before phacovitrectomy and sodium hyaluronate before and after surgery. The average non-invasive tear film break-up time (NITBUTav), first non-invasive tear film break-up time (NITBUTf), non-invasive measured tear meniscus height (NTMH), meibomian gland loss (MGL), lipid layer thickness (LLT) and partial blink rate (PBR) were measured preoperatively and 1wk, 1 and 3mo postoperatively. RESULTS: The NITBUTav values of group A at 1wk (4.38±0.47), 1mo (6.76±0.70), and 3mo (7.25±0.68) were significantly lower than those of group B (7.45±0.78, 10.46±0.97, and 11.31±0.89; P=0.002, 0.004, and 0.001, respectively). The NTMH values of group B at 1wk (0.20±0.01) and 1mo (0.22±0.01) were markedly higher than those of group A (0.15±0.01 and 0.15±0.01; P=0.008 and P<0.001, respectively); however, there was no difference at 3mo. The LLT of group B at 3mo [91.5 (76.25-100.00)] significantly exceeded that of group A [65.00 (54.50-91.25), P=0.017]. No obvious intergroup difference was found in MGL or PBR (P>0.05). CONCLUSION: Mild to moderate MGD dry eye worsens in the short term after phacovitrectomy. Preoperative cleaning, hot compresses, and meibomian gland massage as well as preoperative and postoperative sodium hyaluronate promote the rapid recovery of tear film stability.

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