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1.
Arq. bras. oftalmol ; 86(1): 52-59, Jan.-Feb. 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1403472

RESUMO

ABSTRACT Purpose: The purpose of this study was to evaluate the long-term outcomes of patients with trichiasis treated with a modified interlamellar oral mucosa graft surgery technique using fibrin glue. Methods: A prospective study was conducted at the Oculoplastic Department of Ouro Verde Hospital Complex. Patients with recurrent trichiasis without entropion who did not respond to conventional therapy, underwent intermarginal lamellar splitting of the eyelid and oral mucous graft insertion with fibrin glue replacing sutures. They were then evaluated at 1-day, 1-week, 1-month, 6-month, and 4-year follow-ups. Graft adherence, symptom resolution, esthetic satisfaction, overall patient satisfaction, and trichiasis recurrence were assessed at 6-month and 4-year follow-ups. Results: Fifteen patients (a total of 19 eyes) were included, of whom 10 (66.7%) were female and 5 (33.3%) were male. The mean age was 75.4 ± 10.5 years (range, 54-98 years). Acquired trichiasis was the main cause. Of the patients with acquired trichiasis, 12 (86.7%) had chronic blepharitis, 2 (13.3%) had an undetermined cause, and one (6.7%) had trachomatous trichiasis. Most cases involved only one eyelid segment (89.4%) and =5 lashes (84.2%; minor trichiasis). No adverse reactions from the fibrin glue were reported and no sutures were required after graft placement. At 6 months, no graft failures occurred, 17 eyes of 13 patients (89.4%) showed good graft adherence, 2 eyes of 2 patients (10.5%) showed partial graft adherence, and 2 eyes of 1 patient (10.5%) had trichiasis recurrence. At 4-year follow-up, no graft failure occurred, 3 patients (3 eyes) were lost to follow-up, and 2 eyes of 2 patients (14.2%) had trichiasis recurrence. The 4-year cumulative success rate was 78.9%. Conclusions: The modified interlamellar surgery with fibrin glue showed a good long-term success rate. This technique reduces surgical time, facilitates smaller graft insertion, and therefore, should be considered for recalcitrant minor trichiasis without entropion.>


RESUMO Objetivo: O objetivo deste estudo foi avaliar os resultados a longo prazo da técnica cirúrgica modificada de enxerto interlamelar de mucosa oral usando cola de fibrina para o tratamento de triquíase. Métodos: Um estudo prospectivo foi realizado no Departamento de Óculo-plástica do Complexo Hospital Ouro Verde. Pacientes com triquíase recorrente sem entrópio, que não responderam à terapia convencional, foram submetidos à cirurgia com separação intermarginal das lamelas das pálpebras e inserção de enxerto de mucosa oral usando cola de fibrina, substituindo a sutura. Pacientes foram avaliados 1 dia, 7 dias, 1 mês, 6 meses e 4 anos após a cirurgia. A aderência do enxerto, resolução dos sintomas, satisfação estética, satisfação geral do paciente e recorrência de triquíase foram avaliados aos 6 meses e aos 4 anos. Resultados: Quinze pacientes (total de 19 olhos) foram incluídos, dos quais 10 (66.7%) eram do sexo feminino e 5 (33.3%) do sexo masculino. A média de idade foi 75.4 ± 10.5 anos (intervalo 54-98 anos). Triquíase adquirida foi a principal causa, da qual 12 pacientes apresentaram blefarite crônica (86.7%), 2 pacientes com causa indeterminada (13.3%) e 1 paciente com triquíase tracomatosa (6.7%). A maioria dos casos envolveu apenas um segmento da pálpebra (89.4%) e com =5 cílios (84.2%; triquíase menor). Nenhuma reação adversa foi reportada com o uso da cola de fibrina e nenhum caso necessitou de sutura após inserção do enxerto. Aos 6 meses, não houve nenhuma falha de enxerto, 17 olhos de 13 pacientes (89.4%) apresentaram boa aderência de enxerto, 2 olhos de 2 pacientes (10.5%) mostraram aderência parcial do enxerto e 2 olhos de 1 paciente (10.5%) apresentaram recorrência da triquíase. Aos 4 anos, não houve nenhuma falha de enxerto, 3 olhos de 3 pacientes tiveram perda de seguimento e 2 olhos de 2 pacientes (14.2%) apresentaram recorrência da triquíase. A taxa de sucesso acumulativa após 4 anos foi de 78.9%. Conclusão: A cirurgia modificada de enxerto interlamelar de mucosa oral usando cola de fibrina mostrou uma boa taxa de sucesso a longo prazo. Esta técnica reduz o tempo cirúrgico, facilita a inserção de enxertos menores e, portanto, deve ser considerada em triquíase menor sem entrópio resistente ao tratamento convencional.

2.
Arq. bras. oftalmol ; 86(1): 74-78, Jan.-Feb. 2023. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1403474

RESUMO

ABSTRACT We describe the case of a 15-year-old girl with decreased visual acuity associated with elevated intraocular pressure in both eyes and angle closure on gonioscopy. She also presented attenuation of retinal vessels and optic disc pallor with large excavation in the left eye. Ultrasound biomicroscopy revealed an anteriorly positioned ciliary body and absence of ciliary sulcus, confirming the plateau iris configuration. Spectral-domain optical coherence tomography revealed a bilateral cystoid macular edema. Genetic screening revealed heterozygous variants of the Crumbs homolog 1 (CRB1) gene (c.2843G>A and c.2506C>A). The patient underwent trabeculectomy for intraocular pressure control and topical treatment for macular edema. This case highlights the importance of performing gonioscopy and evaluating intraocular pressure in patients with a shallow anterior chamber despite young age. In addition, it also shows the importance of genetic screening, when available, in elucidating the diagnosis and providing patients and their families' information on the patient's prognosis and possible therapeutic options.


RESUMO Nós descrevemos um caso de uma paciente de 15 anos com queda de acuidade visual e aumento da pressão intraocular em ambos os olhos, juntamente com fechamento angular no exame de gonioscopia. Na fundoscopia a paciente apresentava atenuação dos vasos retinianos, palidez de disco e aumento de escavação em olho esquerdo. Ao exame da biomicroscopia ultrassônica, foi evidenciado corpo ciliar anteriorizado e ausência de sulco ciliar em ambos os olhos, relevando presença de íris em plateau. Ao exame de tomografia de coerência óptica, visualizamos presença de edema macular cistoide bilateral. O screening genético revelou heterozigose no gene CRB1 (c.2843G>A and c.2506C>A), confirmando o diagnóstico de retinose pigmentar. Este caso reforça a importância do exame de gonioscopia e da avaliação da pressão intraocular em pacientes em câmara rasa, mesmo em pacientes jovens. Além disso, mostra a importância do screening genético como ferramenta útil para elucidação diagnóstica.

3.
Arq. bras. oftalmol ; 86(1): 71-73, Jan.-Feb. 2023. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1403476

RESUMO

ABSTRACT We report an unusual case of fulminant endogenous Clostridium septicum panophthalmitis. A 74-year-old male patient presented with sudden amaurosis in the right eye, which in a few hours, evolved into an orbital cellulitis, endophthalmitis, anterior segment ischemia, and secondary perforation of the eye. A complete diagnostic study, which included cranial and orbital contrast-enhanced computed tomography scan, contrast-enhanced magnetic resonance imaging, blood cultures, and complete blood work, were performed. No causal agent was identified. Clostridium septicum infection caused fulminant gaseous panophthalmitis. Despite broad-spectrum antibiotic treatment, evisceration of the eyeball was necessary. The extension study showed a colon adenocarcinoma as the origin of the infection. Clostridium septicum panophthalmitis is a rare but aggressive orbital infection. This infection warrants the identification of a neoplastic process in the gastrointestinal tract in many cases not previously described.


RESUMO Este é o relato de um caso incomum de panoftalmite endógena fulminante por Clostridium septicum. Um paciente do sexo masculino, 74 anos, apresentou amaurose súbita no olho direito, que em poucas horas evoluiu para celulite orbitária, endoftalmite, isquemia do segmento anterior e perfuração secundária do olho. Foi realizado um estudo diagnóstico completo, que incluiu uma tomografia computadorizada com contraste cranial e orbital, um exame de ressonância magnética, hemocultura e hemograma completo. Nenhum agente causal foi identificado. A infecção por Clostridium septicum causou uma panoftalmite gasosa fulminante. Apesar do tratamento com antibióticos de amplo espectro, foi necessário eviscerar o globo ocular. O estudo de seguimento mostrou um adenocarcinoma de cólon como a origem da infecção. A panoftalmite por Clostridium septicum é um tipo raro, mas muito agressivo de infecção orbitária. Essa infecção deve sugerir a busca por um processo neoplásico no trato gastrointestinal, em muitos casos não diagnosticado anteriormente.

4.
Arq. bras. oftalmol ; 86(1): 38-45, Jan.-Feb. 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1403477

RESUMO

ABSTRACT Purpose: The aim of this study was to evaluate the fitting process of a scleral lens that allows several parameter adjustments during trials and after the initial period of use. In addition, we verified which adjustments were needed and used the most, their indications, and how often these resources were used, and checked the results. Methods: Scleral contact lens fittings in a private clinic setting were prospectively analyzed in a sequential, non-randomized, and non-comparative manner. All the patients underwent a complete ophthalmic examination and had an indication for scleral lens use (Zenlens, Alden Optical). Results: Scleral fit was analyzed in 80 eyes of 45 patients. Regarding diagnosis, 72% of the patients had keratoconus; 12%, radial keratotomy; 5%, post-refractive surgery ectasia; 5%, dry eye; and 3%, high myopia. In 66 (82.5%) of the 80 eyes studied, parameters were modified when the lenses were ordered. The reasons that led to the modifications were apical touch or decreased sagittal height, increased sagittal height, cylindrical over-refraction, poor visual acuity, lens flexure, peripheral touch, 360° edge compression, horizontal edge compression, and vertical edge compression. Conclusion: In this study, the use of Zenlens scleral lenses was shown to be a promising corrective treatment for patients requiring the use of scleral lenses. Although the study suggests a learning curve, as many adjustments were allowed, the lens could be customized according to the patients' needs. This increased the success rates of fitting and wearing, and consequently, use of the lens became a great option for the visual rehabilitation of patients.


RESUMO Objetivo: Avaliar o processo de adaptação de uma lente escleral que permite vários ajustes de parâmetros durante os testes e após o período inicial do seu uso; verificar quais os ajustes foram necessários, quais foram os mais utilizados, as suas indicações, a frequência com que estes recursos foram utilizados, e avaliar os resultados das mudanças realizadas. Métodos: A adaptação da lente de contato escleral foi analisada prospectivamente, de forma sequencial, não aleatória e não comparativa. Todos os pacientes foram submetidos a um exame oftalmológico completo e tinham indicação para o uso de lentes esclerais. Foi utilizada a lente Zenlens (Alden Optical). Resultados: Foi analisada a adaptação de lentes de contato esclerais em 80 olhos de 45 pacientes. Quanto ao diagnóstico, 72% tinham ceratocone, 12% tinham sido submetidos a ceratotomia radial, 5% tinham ectasia pós-cirurgia refrativa, 5% tinham olho seco, e 3%, alta miopia. Em 66 dos 80 olhos estudados (82,5%), os parâmetros foram modificados quando as lentes foram encomendadas. As razões foram: toque apical ou diminuição da altura sagital, aumento da altura sagital, sobre-refração cilíndrica, baixa acuidade visual, flexão da lente, toque periférico, compressão da borda em 360° e compressão da borda horizontal e/ou vertical. Conclusão: O uso de lentes esclerais Zenlens demonstrou ser uma forma de correção muito promissora para os pacientes que requerem o uso de lentes esclerais. Embora o estudo sugira uma curva de aprendizagem, é possível personalizar as lentes de acordo com as necessidades de cada pacientes. Este fato melhora a adaptação e aumenta a chance de sucesso do uso.

5.
Arq. bras. oftalmol ; 86(1): 1-6, Jan.-Feb. 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1403480

RESUMO

ABSTRACT Purpose: To evaluate the variables possibly related to actinic keratosis and malignant skin lesions on the eyelid. Methods: A prospective study of patients with suspected eyelid malignancy was conducted. The participants underwent a 2-mm punch biopsy at two opposite sites of the lesion for diagnosis, and the results were compared with those of the histopathological study of the surgical excised specimen. The patients with an actinic keratosis component were divided into two groups (actinic keratosis-associated malignancy and actinic keratosis alone), which were compared for the following variables: age, disease duration, largest diameter, tumor area, Fitzpatrick classification, sex, tumor site and margin involvement. A cluster analysis was also performed. Results: We analyzed 174 lesions, of which 50 had an actinic keratosis component. Actinic keratosis was associated with squamous cell carcinoma in 22% of the cases and to basal cell carcinoma in 38%, which shows that both neoplasms may have contiguous actinic keratosis. Statistical analysis revealed no significant difference among the variables. In a cluster analysis, four groups were identified with malignant lesions in the medial canthus with the largest mean diameter and area. All margin involvements on the lower eyelid were related to malignancy, which means that all cases with margin involvement had an almost 100% risk of malignancy. Conclusions: Larger actinic keratosis lesions in the medial canthus and lesions with margin involvement on the lower eyelid have a greater probability of malignant association.


RESUMO Objetivo: Avaliar as possíveis variáveis relacionadas à ceratose actínica e lesões malignas cutâneas nas pálpebras. Métodos: Estudo prospectivo de pacientes com lesões palpebrais suspeitas de malignidade. Os participantes foram submetidos à biopsia por trépano (punch) de 2-mm em dois pontos opostos da lesão como método diagnóstico e os resultados foram comparados com o estudo histopatológico da peça excisada cirurgicamente. Aqueles que apresentaram ceratose actínica como resultado foram divididos em dois grupos (ceratose actínica associada com malignidade e ceratose actínica isolada) e foram comparados de acordo com as variáveis: idade, tempo de doença, maior diâmetro, área do tumor, classificação de Fitzpatrick, gênero, localização e acometimento da margem palpebral. A análise de cluster também foi realizada. Resultados: Foram analisadas 174 lesões e 50 delas tinham ceratose actínica como componente do tumor. Ceratose actínica esteve associada ao Carcinoma Espinocelular em 22% dos casos e ao Carcinoma Basocelular em 38%, mostrando que ambos podem ter ceratose actínica adjacente. A análise estatística não encontrou diferença entre as variáveis. A análise de cluster identificou quatro grupos e mostrou que lesões malignas no canto medial tinham maiores diâmetro e área. Acometimento da margem na pálpebra inferior relacionou-se em 100% com malignidade, enquanto a ausência de acometimento da margem mostrou menor chance de malignidade. Conclusões: Lesões maiores de ceratose actínica no canto medial e lesões com acometimento da margem palpebral inferior têm maiores chances de associação com malignidade.

6.
Ned Tijdschr Geneeskd ; 1672023 Jan 04.
Artigo em Holandês | MEDLINE | ID: mdl-36633055

RESUMO

PSMA PET/CT is a diagnostic technique for patients with prostate cancer. It makes use of a radioligand that specifically binds to 'prostate specific membrane antigen' (PSMA), expressed by the prostate cancer cells. PSMA PET has proven to be highly effective in prostate cancer diagnostics in both primary staging and re-staging. PSMA PET/CT has a much higher accuracy than traditional CT and skeletal scintigraphy for the detection of metastases, allowing metastases to be detected in an earlier stage. The clinical relevance of the improved detection is now under investigation. Staging with PSMA PET/CT sometimes leads to avoiding surgery because distant metastases are found that were not detected with conventional imaging. In the Netherlands, PSMA PET/CT is now indicated both in primary prostate cancer diagnostics for the detection of metastases and for the detection of biochemical recurrence after prostatectomy or after radiotherapy.


Assuntos
Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Próstata/diagnóstico por imagem , Antígeno Prostático Específico , Prostatectomia
7.
Ned Tijdschr Geneeskd ; 1672023 Jan 11.
Artigo em Holandês | MEDLINE | ID: mdl-36633084

RESUMO

A 83-year-old man presented with a large tumour on his head. He had been postponing his visit due to COVID. Physical examination revealed an ulcerating, bleeding tumour of 5.5x5x3 cm. Histologic analyses showed a poorly differentiated squamous cell carcinoma. Additional imaging displayed damage of the tabula externa without pathological lymph nodes.


Assuntos
COVID-19 , Carcinoma , Masculino , Humanos , Idoso de 80 Anos ou mais , Couro Cabeludo , Carcinoma/patologia , Linfonodos/patologia
8.
Mol Med Rep ; 27(2)2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36633126

RESUMO

Obesity is a serious medical condition worldwide, and a major risk factor for type 2 diabetes, metabolic syndrome, cancer and cardiovascular disease. In addition to changes in dietary habits and physical activity, consuming supplements to maintain good health and prevent obesity is important in modern society. Raspberry ketone (RK) is a natural phenolic ketone found in the European red raspberry (Rubus idaeus L.) and is hypothesized to prevent obesity when administered orally. The present study found that RK was reduced to rhododendrol (ROH) in human liver microsomes and cytosol. The present study investigated whether the metabolite ROH had anti­adipogenic effects using mouse 3T3­L1 cells. The effects of ROH or RK on lipid accumulation during differentiation of 3T3­L1 pre­adipocyte into adipocyte were determined using Oil Red O staining. CCAAT enhancer­binding protein α (C/EBPα) and peroxisome proliferator­activated receptor γ (PPARγ) mRNA and protein expression were examined using reverse transcription­quantitative PCR and western blotting analysis, respectively. The present study revealed that ROH suppressed lipid accumulation in the cells, similar to RK. In addition, ROH suppressed the mRNA expression levels of C/EBPα and PPARγ in 3T3­L1 adipocytes. Furthermore, ROH suppressed PPARγ protein expression in 3T3­L1 adipocytes. These findings suggested that ROH is an active metabolite with an anti­adipogenic effect, which may contribute to the anti­obesity effect of orally administered RK. The present study indicated that it is important to understand the biological activity of the metabolites of orally administered compounds.


Assuntos
Diabetes Mellitus Tipo 2 , PPAR gama , Camundongos , Animais , Humanos , Células 3T3-L1 , PPAR gama/genética , PPAR gama/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diferenciação Celular , Adipogenia , Adipócitos/metabolismo , Butanóis/metabolismo , Butanóis/farmacologia , Obesidade/metabolismo , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo
9.
Mol Med Rep ; 27(2)2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36633128

RESUMO

Lung adenocarcinoma (LUAD) is associated with high morbidity and mortality; therefore, effective biomarkers are essential. In recent years, a rapid increase in the efficiency of high­throughput sequencing technologies and the continuous improvement of comprehensive online databases have facilitated the study of the genomic changes that affect tumor progression, including the identification of tumor biomarkers. Therefore, the identification of genes that may affect the progression and prognosis of LUAD is necessary. In the present study, the CIBERSORT and ESTIMATE bioinformatics packages were used to evaluate data from The Cancer Genome Atlas, including assessment of the proportion of tumor­infiltrating immune cells in the tumor microenvironment, Cox regression analysis of differentially expressed genes and cross analysis of protein­protein interaction networks. Myeloid cell NADPH oxidase isoform 2 (NOX2), an indispensable gene in the immune system, was demonstrated to serve a vital role in LUAD pathogenesis. Western blotting and immunohistochemistry confirmed that, at the protein level, NOX2 expression was increased in normal cells compared with cancer cells. Furthermore, reverse transcription­quantitative PCR results at the mRNA level were consistent with these results, which confirmed that the abundance of NOX2 was significantly reduced in LUAD patients. NOX2 may be used as a novel marker and an independent prognostic indicator of LUAD. Its potential function was enriched in tumor immune and metabolic signaling pathways, which could provide clues for the study of the signaling pathways and molecular networks related to the disease progression of LUAD, which would be helpful for the assessment of prognosis in the clinical setting.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Prognóstico , Adenocarcinoma de Pulmão/genética , Biomarcadores Tumorais/genética , Western Blotting , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Microambiente Tumoral
10.
Mol Med Rep ; 27(2)2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36633137

RESUMO

Secreted protein acidic and rich in cysteine (SPARC), also called basement­membrane protein 40 or osteonectin, is a matricellular protein that is abundant not only in bone tissue as a non­collagenous protein but is also ubiquitously expressed in non­calcified tissue. SPARC is located intracellularly and disruption of the Sparc gene has been reported to reduce bone formation and increase fat tissue; however, the mechanism by which SPARC inhibits adipogenesis remains unclear. The present study evaluated the intracellular function of SPARC in adipogenesis using the bone marrow stromal cell line ST2. When ST2 cells with low SPARC production were cloned, intrinsic activator protein­1 (AP­1) activity was markedly higher, mineralized nodule formation was significantly lower and lipid accumulation was significantly increased compared with in the parental ST2 cells. Forced expression of secreted SPARC with the signal peptide­coding sequences of wild­type Sparc or preprotrypsin in SPARC­low ST2 cells significantly reduced AP­1 transcription activity; however, these reductions were not observed in the absence of signal peptide sequences. Recombinant SPARC, produced using Brevibacillus brevis, specifically bound to c­Fos but not c­Jun and inhibited the binding of c­Fos/c­Jun to a TPA­response element sequence. These data suggested that SPARC was incorporated into the cells from the extracellular spaces and serves an intracellular role as a decoy counterpart for c­Fos, as well as being associated with osteoblastogenesis through the inhibition of adipogenesis. These findings may provide new insights into regenerative medicine.


Assuntos
Células-Tronco Mesenquimais , Osteonectina , Osteonectina/genética , Osteonectina/metabolismo , Adipogenia/genética , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Diferenciação Celular/genética , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Sinais Direcionadores de Proteínas
11.
Oncol Rep ; 49(2)2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36633143

RESUMO

Astilbe chinensis (A. chinensis) is a perennial herb that is used to treat chronic bronchitis and pain. The anticancer activity of 3ß,6ß­dihydroxyurs­12­en­27­oic acid (ACT­3), a major component isolated from A. chinensis, has not yet been investigated in detail. The purpose of the present study was to investigate the histone deacetylase (HDAC) inhibitory and anticancer activities of ACT­3 compared with suberoylanilide hydroxamic acid (SAHA) in MCF­7 human breast cancer cells. The purity of ACT­3 was determined using high­performance liquid chromatography. In the present study, the effects of ACT­3 on anticancer effects of MCF­7 cells were determined by measuring the level of apoptotic cell death and cell cycle regulator using flow cytometry analysis and western blot analysis, respectively. The effects of ACT­3 on HDAC enzyme activity were measured using assay kits. ACT­3 and SAHA increased the levels of acetylated histone H3 and reduced the levels of HDAC1 and HDAC3 in MCF­7 cells. ACT­3 significantly decreased the cell viability in a concentration­dependent manner and induced different morphological changes at high concentrations. ACT­3 and SAHA significantly inhibited the colony formation in MCF­7 cells. ACT­3 inhibited total HDAC activity in a dose­dependent manner. ACT­3 significantly reduced the expression levels of cyclin D1 and cyclin­dependent kinase 4, and upregulated the expression levels of p21WAF1 and p53. A significant increase in the G1 phase cell population was observed in MCF­7 cells and ACT­3 induced apoptosis by reducing the ratio of B­cell lymphoma­2 (Bcl­2)/Bcl­2­associated X (Bax) and releasing cleaved caspase 9. Additionally, ACT­3 significantly increased autophagic cell death by inhibiting the serine­threonine kinase/mammalian target of the rapamycin pathway. Autophagy induction was confirmed via acridine orange staining. ACT­3 significantly increased the pERK1/2 and p21 in MCF­7 cells. Thus, the activated ERK pathway played an important role in cell cycle arrest and apoptosis via ERK­dependent induction of p21 in MCF­7 cells. These data indicated that ACT­3 can be used as a promising anticancer agent to overcome the limitations and reduce the side effects of conventional anticancer drugs.


Assuntos
Neoplasias da Mama , Inibidores de Histona Desacetilases , Humanos , Feminino , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Células MCF-7 , Proteínas Proto-Oncogênicas c-akt , Neoplasias da Mama/tratamento farmacológico , Ácidos Hidroxâmicos/farmacologia , Ácidos Hidroxâmicos/uso terapêutico , Proliferação de Células , Vorinostat/farmacologia , Apoptose , Serina-Treonina Quinases TOR , Proteínas Proto-Oncogênicas c-bcl-2 , Linhagem Celular Tumoral
12.
Oncol Rep ; 49(2)2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36633146

RESUMO

Structural alterations of collagen impact signaling that helps control tumor progression and the responses to therapeutic intervention. Integrins represent a class of receptors that include members that mediate collagen signaling. However, a strategy of directly targeting integrins to control tumor growth has demonstrated limited activity in the clinical setting. New molecular understanding of integrins have revealed that these receptors can regulate both pro­ and anti­tumorigenic functions in a cell type­dependent manner. Therefore, designing strategies that block pro­tumorigenic signaling, without impeding anti­tumorigenic functions, may lead to development of more effective therapies. In the present study, evidence was provided for a novel signaling cascade in which ß3­integrin­mediated binding to a secreted RGDKGE­containing collagen fragment stimulates an autocrine­like signaling pathway that differentially governs the activity of both YAP and (protein kinase­A) PKA, ultimately leading to alterations in the levels of immune checkpoint molecule PD­L1 by a proteasome dependent mechanism. Selectively targeting this collagen fragment, reduced nuclear YAP levels, and enhanced PKA and proteasome activity, while also exhibiting significant antitumor activity in vivo. The present findings not only provided new mechanistic insight into a previously unknown autocrine­like signaling pathway that may provide tumor cells with the ability to regulate PD­L1, but our findings may also help in the development of more effective strategies to control pro­tumorigenic ß3­integrin signaling without disrupting its tumor suppressive functions in other cellular compartments.


Assuntos
Neoplasias , Complexo de Endopeptidases do Proteassoma , Humanos , Antígeno B7-H1 , Colágeno/química , Neoplasias/tratamento farmacológico , Integrinas/metabolismo
13.
J Cell Sci ; 136(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36633090

RESUMO

The nuclear architecture of mammalian cells can be altered as a consequence of anomalous accumulation of nuclear proteins or genomic alterations. Most of the knowledge about nuclear dynamics comes from studies on cancerous cells. How normal healthy cells maintain genome stability, avoiding accumulation of nuclear damaged material, is less understood. Here, we describe that primary mouse embryonic fibroblasts develop a basal level of nuclear buds and micronuclei, which increase after etoposide-induced DNA double-stranded breaks. Both basal and induced nuclear buds and micronuclei colocalize with the autophagic proteins BECN1 and LC3B (also known as MAP1LC3B) and with acidic vesicles, suggesting their clearance by nucleophagy. Some of the nuclear alterations also contain autophagic proteins and type II DNA topoisomerases (TOP2A and TOP2B), or the nucleolar protein fibrillarin, implying they are also targets of nucleophagy. We propose that basal nucleophagy contributes to genome and nuclear stability, as well as in response to DNA damage.


Assuntos
Nucléolo Celular , Fibroblastos , Animais , Camundongos , Fibroblastos/metabolismo , Nucléolo Celular/metabolismo , Núcleo Celular/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Instabilidade Genômica , Autofagia/fisiologia , Mamíferos/metabolismo
14.
Mol Med Rep ; 27(2)2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36633133

RESUMO

The lack of specific and accurate therapeutic targets poses a challenge in the treatment of cervical cancer (CC). Global proteomics has the potential to characterize the underlying and intricate molecular mechanisms that drive the identification of therapeutic candidates for CC in an unbiased manner. The present study assessed human papillomavirus (HPV)­induced proteomic alterations to identify key cancer hallmark pathways and protein­protein interaction (PPI) networks, which offered the opportunity to evaluate the possibility of using these for targeted therapy in CC. Comparative proteomic profiling of HPV­transfected (HPV16/18 E7), HPV­transformed (CaSki and HeLa) and normal human keratinocyte (HaCaT) cells was performed using the liquid chromatography­tandem mass spectrometry (LC­MS/MS) technique. Both label­free quantification and differential expression analysis were performed to assess differentially regulated proteins in HPV­transformed and ­transfected cells. The present study demonstrated that protein expression was upregulated in HPV­transfected cells compared with in HPV­transformed cells. This was probably due to the ectopic expression of E7 protein in the former cell type, in contrast to its constitutive expression in the latter cell type. Subsequent pathway visualization and network construction demonstrated that the upregulated proteins in HPV16/18 E7­transfected cells were predominantly associated with a diverse array of cancer hallmarks, including the mTORC1 signaling pathway, MYC targets V1, hypoxia and glycolysis. Among the various proteins present in the cancer hallmark enrichment pathways, phosphoglycerate kinase 1 (PGK1) was present across all pathways. Therefore, PGK1 may be considered as a potential biomarker. PPI analysis demonstrated a direct interaction between p130 and polyubiquitin B, which may lead to the degradation of p130 via the ubiquitin­proteasome proteolytic pathway. In summary, elucidation of the key signaling pathways in HPV16/18­transfected and ­transformed cells may aid in the design of novel therapeutic strategies for clinical application such as targeted therapy and immunotherapy against cervical cancer.


Assuntos
Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/metabolismo , Neoplasias do Colo do Útero/metabolismo , Papillomavirus Humano 16/metabolismo , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/metabolismo , Proteômica , Cromatografia Líquida , Papillomavirus Humano 18 , Espectrometria de Massas em Tandem , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/metabolismo , Queratinócitos/metabolismo
15.
Oncol Rep ; 49(2)2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36633148

RESUMO

Since the completion of the KHBO1401 study, which evaluated the efficacy of the combination of gemcitabine (GEM) and cisplatin (GC) compared with GC plus S­1 (GCS), GCS has become a standard chemotherapy for patients with advanced biliary tract cancer (BTC). However, there are currently no data revealing second­line therapy options after GCS. The present study aimed to evaluate the survival outcomes of patients receiving second­line chemotherapy for advanced BTC, refractory or intolerant to GCS, using data from the KHBO1401 study. Patients who received a second­line treatment after GCS chemotherapy between July 2014 and February 2016 were retrospectively studied. Overall survival (OS) was calculated from the day of GCS treatment failure or the first day of second­line chemotherapy to the final follow­up date or until death from any cause. Among 83 patients refractory or intolerant to GCS chemotherapy, 51 (61%) received second­line chemotherapy, including GCS (n=8), GC (n=15), GEM (n=6), GEM plus S­1 (GS) (n=4) and S­1 (n=18). The 6­ and 12­month OS rates were 66.7 and 44.4%, respectively, following second­line chemotherapy, and 6.3 and 3.1%, respectively, in the best supportive care group (P<0.0001). In addition, the 12­ and 24­month OS rates were 59.3 and 36.2%, respectively, in the multidrug chemotherapy group, and 26.9 and 9.0%, respectively, in the single­agent chemotherapy group (P=0.0191). These results suggested that second­line combination chemotherapy is a viable treatment option for patients with advanced BTC that is refractory or intolerant to first­line GCS therapy.


Assuntos
Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Humanos , Cisplatino , Desoxicitidina , Estudos Retrospectivos , Neoplasias do Sistema Biliar/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Resultado do Tratamento
16.
Aging Male ; 26(1): 6-12, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36633207

RESUMO

INTRODUCTION: A positive association between benign prostate hyperplasia (BPH)/lower urinary tract symptoms (LUTS) and metabolic syndrome (MetS) was reported in several studies, but studies from Asia often showed conflicting results. MATERIALS AND METHODS: Medical records were obtained from a health promotion center database between 2021 and 2022. Men without a history of treatment for LUTS were evaluated using the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), transrectal ultrasonography. RESULTS: Of 1345 individuals, 603 (44.8%) had MetS. Older age, higher IPSS values, higher prevalence rates of BPH and overactive bladder, higher triiodothyronine, and lower testosterone and sex-hormone binding globulin were observed in individuals with MetS than in individuals without MetS. The severity of LUTS significantly increased in the individuals with MetS (p = .002). In individuals with MetS, age, HbA1c, and cerebrovascular disease (CVD) were associated with IPSS. For OABSS, age, HbA1c, thyroid-stimulating hormone (TSH), coronary artery occlusive disease, and CVD were identified as predictors. CONCLUSIONS: We confirmed the positive correlation between MetS and BPH/LUTS in Korean. Factors including TSH and atherosclerosis affected LUTS in individuals with MetS. These findings suggested a potential role of thyroid hormones and atherosclerosis in the etiology and treatment of BPH/LUTS in patients with MetS.


Assuntos
Doenças Cardiovasculares , Sintomas do Trato Urinário Inferior , Síndrome Metabólica , Hiperplasia Prostática , Bexiga Urinária Hiperativa , Masculino , Humanos , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Hiperplasia Prostática/complicações , Hiperplasia Prostática/epidemiologia , Bexiga Urinária Hiperativa/complicações , Sintomas do Trato Urinário Inferior/complicações , República da Coreia/epidemiologia , Doenças Cardiovasculares/complicações
17.
Zhongguo Zhen Jiu ; 43(1): 25-8, 2023 Jan 01.
Artigo em Chinês | MEDLINE | ID: mdl-36633235

RESUMO

OBJECTIVE: To observe the effect of Kaiqiao Jieyin acupuncture (acupuncture for opening orifices and relieving aphasia) combined with repetitive transcranial magnetic stimulation (rTMS) on language ability and daily life communication ability in patients with post-stroke aphasia (PSA). METHODS: Fifty-six patients with PSA were randomly divided into an observation group and a control group, 28 cases in each group. Both groups received routine symptomatic treatment. The control group was treated with speech rehabilitation training and rTMS. On the basis of the treatment in the control group, the observation group was treated with Kaiqiao Jieyin acupuncture at the speech area Ⅰ, Fengchi (GB 20), Tongli (HT 5), Lianquan (CV 23), Panglianquan (Extra), etc. Panglianquan (Extra) on both sides were connected to electroacupuncture, with intermittent wave, 2 Hz in frequency. The above treatment was performed once a day for 5 consecutive days, followed by 2 days of rest for 2 weeks. The scores of western aphasia battery (WAB, including scores of spontaneous speech, auditory comprehension, repetition, naming and score of aphasia quotient [AQ]) and communication abilities in daily living (CADL) in the two groups were compared before and after treatment. RESULTS: After treatment, the spontaneous speech, auditory comprehension, repetition, naming scores and AQ scores in both groups were higher than those before treatment (P<0.05), and the increase in the observation group was greater than the control group (P<0.05). The CADL scores of the two groups were higher than those before treatment (P<0.05). CONCLUSION: Kaiqiao Jieyin acupuncture combined with rTMS can improve the language ability and daily life communication ability of PSA patients.


Assuntos
Terapia por Acupuntura , Afasia , Reabilitação do Acidente Vascular Cerebral , Humanos , Estimulação Magnética Transcraniana , Resultado do Tratamento , Afasia/etiologia , Afasia/terapia
18.
Zhongguo Zhen Jiu ; 43(1): 45-50, 2023 Jan 01.
Artigo em Chinês | MEDLINE | ID: mdl-36633239

RESUMO

OBJECTIVE: To observe the effect of fire needling on prostate symptoms, quality of life, average daily number of nightly urination, urine flow rate and prostat volume in patients with mild to moderate benign prostatic hyperplasia (BPH) of kidney yang deficiency. METHODS: A total of 60 patients with mild to moderate BPH of kidney yang deficiency were randomly divided into an observation group (30 cases, 3 cases dropped off) and a control group (30 cases, 4 cases dropped off). The observation group was treated with fire needling at Guanyuan (CV 4), Shuidao (ST 28) and Qugu (CV 2) twice a week (2-3 d interval between each treatment), continuous treatment for 4 weeks. The control group received lifestyle advice and education, once a week for 4 weeks. In the two groups, the international prostate symptom score (IPSS), the quality of life (QoL) score and the average daily number of nightly urination were observed before treatment, after treatment and during the follow-up of the 4th week; the urinary maximum flow rate (Qmax), the average flow rate (Qave), and the prostate volume were assessed before and after treatment in the two groups. The safety was observed in the observation group. RESULTS: After treatment and during follow-up, the IPSS scores, QoL scores, and the average daily number of nightly urination in the observation group were decreased compared with those before treatment (P<0.05), and those in the observation group were lower than the control group (P<0.05). After treatment, there was no significant difference in Qmax, Qave and prostate volume between the two groups and within the each group (P>0.05). There were no fire needling-related adverse reactions, and no obvious abnormality was found in urine routine and coagulation function tests before and after treatment in the observation group. CONCLUSION: Fire needling can improve lower urinary tract symptoms and quality of life, reduce frequency of nightly urination in patients with mild to moderate BPH of kidney yang deficiency, and has good safety.


Assuntos
Hiperplasia Prostática , Masculino , Humanos , Hiperplasia Prostática/terapia , Qualidade de Vida , Deficiência da Energia Yang , Resultado do Tratamento , Rim
19.
Zhongguo Zhen Jiu ; 43(1): 67-71, 2023 Jan 01.
Artigo em Chinês | MEDLINE | ID: mdl-36633242

RESUMO

OBJECTIVE: To observe the effect of wheat-grain moxibustion at "Dazhui" (GV 14), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) on Wnt/ß-catenin signaling pathway in bone marrow cell in mice with bone marrow inhibition, and to explore the possible mechanism of wheat-grain moxibustion in treating bone marrow inhibition. METHODS: Forty-five SPF male CD1(ICR) mice were randomly divided into a blank group, a model group and a wheat-grain moxibustion group, 15 mice in each group. The bone marrow inhibition model was established by intraperitoneal injection of 80 mg/kg of cyclophosphamide (CTX). The mice in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6), 3 moxa cones per acupoint, 30 s per moxa cone, once a day, for 7 consecutive days. The white blood cell count (WBC) was measured before modeling, before intervention and 3, 5 d and 7 d into intervention. After intervention, the general situation of mice was observed; the number of nucleated cells in bone marrow was detected; the serum levels of interleukin-3 (IL-3), interleukin-6 (IL-6) and granulocyte macrophage colony stimulating factor (GM-CSF) were measured by ELISA; the protein and mRNA expression of ß-catenin, cyclinD1 and C-Myc in bone marrow cells was measured by Western blot and real-time PCR method. RESULTS: Compared with the blank group, the mice in the model group showed sluggish reaction, unstable gait, decreased body weight, and the WBC, number of nucleated cells in bone marrow as well as serum levels of IL-3, IL-6, GM-CSF were decreased (P<0.01), and the protein and mRNA expression of ß-catenin, cyclinD1 and C-Myc was decreased (P<0.01). Compared with the model group, the mice in the wheat-grain moxibustion group showed better general condition, and WBC, the number of nucleated cells in bone marrow as well as serum levels of IL-3, IL-6, GM-CSF were increased (P<0.01, P<0.05), and the protein and mRNA expression of ß-catenin, cyclinD1 and C-Myc was increased (P<0.05). CONCLUSION: Wheat-grain moxibustion shows therapeutic effect on bone marrow inhibition, and its mechanism may be related to activating Wnt/ß-catenin signaling pathway in bone marrow cells, improving bone medullary hematopoiesis microenvironment and promoting bone marrow cell proliferation.


Assuntos
Moxibustão , Camundongos , Masculino , Animais , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Interleucina-3 , Triticum/genética , beta Catenina/genética , Interleucina-6 , Via de Sinalização Wnt , Medula Óssea , Camundongos Endogâmicos ICR , Células da Medula Óssea , RNA Mensageiro
20.
J Appl Biomater Funct Mater ; 21: 22808000221130168, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36633288

RESUMO

BACKGROUND: To maintain and enhance the wound healing effects of mesenchymal stem cells (MSCs), a scaffold for hosting MSCs is needed, which ought to be completely biocompatible, durable, producible, and of human source. OBJECTIVE: To build a cell-extracellular matrix (ECM) complex assembled by human umbilical cord mesenchymal stem cells (HuMSCs) and to investigate its clinical potentials in promoting wound healing. METHOD: HuMSCs were isolated and expanded. When the cells of third passage reached confluency, ascorbic acid was added to stimulate the cells to deposit ECM where the cells grew in. Four weeks later, a cells-loaded ECM sheet was formed. The cell-ECM complex was observed under the scanning electron microscopy (SEM) and subjected to histological studies. The supernatants were collected and the cell-ECM complex was harvested at different time points and processed for enzyme-linked immune sorbent assay (ELISA) and mRNA analysis. The in vivo experiments were performed by means of implanting the cell-ECM complex on the mice back for up to 6 months and the specimens were collected for histological studies. RESULTS: After 4 weeks of cultivation with ascorbic stimulation, a sheet was formed which is mainly composed with HuMSCs, collagen and hyaluronic acid. The cell-ECM complex can sustain to certain tensile force. The mRNA and protein levels of vascular endothelial growth factor-α (VEGF-α), hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), and transforming growth factor-ß1 (TGF-ß1) were remarkably increased compared to monolayer-cultured cells. The implanted cell-ECM complex on mice was still noticeable with host cells infiltration and vascularization on 6 months. CONCLUSION: Our studies suggested that HuMSCs can be multi-cultivated through adding ascorbic stimulation and ECM containing collagen and hyaluronic acid were enriched around the cells which self-assembly formed a cell-ECM complex. Cell-ECM complex can improve growth factors secretion remarkably which means it may promote wound healing by paracrine.


Assuntos
Ácido Hialurônico , Fator A de Crescimento do Endotélio Vascular , Camundongos , Humanos , Animais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cicatrização/fisiologia , Colágeno , Matriz Extracelular
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