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Non-invasive optical examination plays a crucial role in various aspects of dermatology, such as diagnosis, management and research. Multiphoton microscopy uses a unique submicron technology to stimulate autofluorescence (AF), allowing for the observation of cellular structure, assessment of redox status and quantification of collagen fibres. This advanced imaging technique offers dermatologists novel insights into the skin's structure, positioning it as a promising 'stethoscope' for future development in the field. This review provides an overview of multiphoton microscopy's principles, technology and application in studying normal skin, tumour and inflammatory diseases, as well as collagen-related and pigmentary diseases.
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BACKGROUND: Superficial basal cell carcinoma (SBCC) is the rare subtype of basal cell carcinoma (BCC). BCC occurs in exposed areas such as the head and face, SCBB prone to form in trunk. Due to the manifestation of erythema and desquamation, it is prone to misdiagnosed as Bowen's disease in clinica. MATERIALS AND METHODS: A 68-year-old female presented with coin-sized erythema located on the lower abdomen for 5 years. Histopathological examination was performed, and results informed the diagnosis of SBCC. Lesions were detected by dermoscopy, reflectance confocal microscopy (RCM) and multiphoton microscopy (MPM). RESULTS: Dermoscopy revealed yellow-red background with more dendritic and linear proliferating vessels and more blue-gray nonaggregated dots structures. RCM displayed streaming of stratum spinosum, tortuous dilated vessels, highlighted inflammatory cells, and medium refraction round and oval tumor cell masses. MPM showed epidermal cells in polar arrangement, increased cell spacing, disorganized stratum granulosum and elastic fibers are gathered in clusters. CONCLUSION: We described a case of SBCC detected by dermoscopy, RCM and MPM. Noninvasive imaging features may provide a potentially tools in recognition and differentiation of SBCC.
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Doença de Bowen , Carcinoma Basocelular , Neoplasias Cutâneas , Feminino , Humanos , Idoso , Neoplasias Cutâneas/patologia , Doença de Bowen/diagnóstico por imagem , Dermoscopia/métodos , Microscopia Confocal/métodos , Carcinoma Basocelular/patologia , EritemaRESUMO
BACKGROUND: PI3K pathway is the most frequently mutated pathway in head and neck squamous cell carcinoma (HNSC), which plays a crucial role in tumorigenesis and progression. In the present study, we aimed to investigate the role of PI3K pathway mutation in clinical prognosis prediction and the relationship with immune microenvironment and response rate to immunotherapy. METHODS: We collected 129 samples with immunotherapy information from MSKCC-2019 cohort as well as 501 and 40 samples from TCGA-HNSC and MD-Anderson non-immunotherapy cohorts, respectively. Somatic mutation data was utilized to characterize the mutational status of the PI3K pathway. Subsequently, we further analyzed the differences in prognosis, immunotherapy response, genomic alterations, functional characteristics, and immune microenvironment between the mutation and wild groups. RESULTS: The Kaplan-Meier survival curves displayed that PI3K pathway mutation predicted observably prolonged overall survival (OS) in the immunotherapy cohort MSKCC-2019 (p = 0.012) but did not reach statistical significance in the non-immunotherapy cohorts TCGA-HNSC (p = 0.68) and MD-Anderson (p = 0.68). After incorporating several clinicopathologic features such as age, gender, and tumor mutation burden (TMB), the results of multivariate Cox regression analysis also demonstrated that the PI3K pathway mutation could indicate better immunotherapy outcomes in HNSC patients with a hazard ratio (HR) of 0.533 (95% CI: 0.313-0.910; p = 0.021) in the immunotherapy cohort MSKCC-2019, compared with 0.888 (95% CI: 0.636-1.241; p = 0.487) and 1.939 (95% CI: 0.483-7.781; p = 0.351) in the non-immunotherapy cohorts TCGA-HNSC and MD-Anderson. In addition, the results of the subclass mapping (SubMap) and the tumor immune dysfunction and exclusion (TIDE) also consistently suggested that patients in the mutation group are more likely to benefit from immunotherapy. And further studies showed that the mutation group owned significantly higher TMB, activated immune-related pathways, richer abundance of immune cells, and higher expression levels of immunomodulators. To improve the prognosis of the wild group, we identified five relatively sensitive potential drugs for the wild group, including "BMS-536924," "linsitinib," "NVP-TAE684," "PLX-4720," and "clonazepam." CONCLUSIONS: The PI3K pathway mutation status could be considered as a potential biomarker to predict better immunotherapeutic efficacy and clinical outcomes after immunotherapy in HNSC patients.
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Neoplasias de Cabeça e Pescoço , Fosfatidilinositol 3-Quinases , Humanos , Fosfatidilinositol 3-Quinases/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinogênese , Imunoterapia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapia , Microambiente TumoralRESUMO
Nickel-iron catalysts represent an appealing platform for electrocatalytic oxygen evolution reaction (OER) in alkaline media because of their high adjustability in components and activity. However, their long-term stabilities under high current density still remain unsatisfactory due to undesirable Fe segregation. Herein, a nitrate ion (NO3 - ) tailored strategy is developed to mitigate Fe segregation, and thereby improve the OER stability of nickel-iron catalyst. X-ray absorption spectroscopy combined with theoretical calculations indicate that introducing Ni3 (NO3 )2 (OH)4 with stable NO3 - in the lattice is conducive to constructing the stable interface of FeOOH/Ni3 (NO3 )2 (OH)4 via the strong interaction between Fe and incorporated NO3 - . Time of flight secondary ion mass spectrometry and wavelet transformation analysis demonstrate that the NO3 - tailored nickel-iron catalyst greatly alleviates Fe segregation, exhibiting a considerably enhanced long-term stability with a six-fold improvement over FeOOH/Ni(OH)2 without NO3 - modification. This work represents a momentous step toward regulating Fe segregation for stabilizing the catalytic performances of nickel-iron catalysts.
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In situ observation of the migration and structure formation of magnetic particles in polyurethane elastomers was carried out by X-ray computed tomography using synchrotron radiation. The mean diameter of the magnetic particles was 7.0 µm, and the volume fraction was Ï= 0.24 at its maximum. The exposure time was 100 ms/frame, and the pixel size was 0.458 µm/pixel. The orientation angle and the volume fraction of the maximum aggregate were analyzed using commercial software for image analysis. The orientation angle for magnetic elastomers with Ï = 0.24 was approximately 55° at 0 mT and decreased remarkably with the magnetic field. At magnetic fields above 150 mT, the orientation angle gradually decreased with the field and showed a constant value of 38° at 300 mT, suggesting that magnetic particles move and form a chain-like structure although the chains do not align perfectly in the direction of the magnetic field. On the other hand, the volume fraction of the maximum aggregate was constant at magnetic fields below 100 mT, and it significantly increased with the field, indicating that magnetic particles were connected to each other and developed into a macroscopic structure with anisotropy. Dynamic viscoelastic measurements revealed that the storage modulus of the magnetic elastomers cannot be simply scaled by the orientation angle. It was also found that the volume fraction of the maximum aggregate is a good parameter for explaining the huge increase in the storage modulus. The dynamic movement of magnetic particles when a magnetic field of 300 mT was switched on and off was also successfully observed. When the field was switched on, magnetic particles connected instantly and their aggregates were rapidly elongated in the direction of the magnetic field. When the field was switched off, some of the connections between aggregates were broken; however, most of the aggregates did not return to the original position even 5 min after being switched off.
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Breast cancer (BC) is the most dangerous female mortality all over the world, described by unavoidable spread and metastaticity of BC cells. Increasing evidences verified that lncRNA play a major role in the tumorgenesis and development of BC cell. The purpose of this study is to investigate the roles of lncRNA ceramide synthase 6 antisense RNA 1 (CERS6-AS1) and ubiquitin-conjugating enzyme E2C (UBE2C) in BC and explore the regulatory association among miR-16-5p, CERS6-AS1, and UBE2C in BC. The CERS6-AS1 and UBE2C expression levels were determined by real time quantitative PCR in cell lines and tissues of BC. The function of CERS6-AS1 and UBE2C in the apoptosis, proliferation, and migration was confirmed by cell counting kit-8, Transwell, and flowcytometry tests. We performed tumor xenograft assay to validate the roles of CERS6-AS1 in vivo. The expression of UBE2C proteins was evaluated by Western Blot analysis. Moreover, the relationship among UBE2C, CERS6-AS1, and miR-16-5p was verified by luciferase report assay. It was found that CERS6-AS1 and UBE2C were meaningfully upregulated in BC, and knockdown of both CERS6-AS1 and UBE2C inhibited the BC cell proliferation and migration, whereas induced apoptosis. Mechanistically, CERS6-AS1 could facilitate BC progression by sponging miR-16-5p for upregulation of the UBE2C expression. The CERS6-AS1/miR-16-5p/UBE2C axis might be a prospective therapeutic target in the BC treatment by sponging miR-16-5p to upregulate UBE2C, which might contribute to the development of BC.
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Neoplasias da Mama , MicroRNAs , RNA Longo não Codificante , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Membrana , MicroRNAs/genética , Oxirredutases , RNA Antissenso/genética , RNA Longo não Codificante/genética , Esfingosina N-Aciltransferase , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismoRESUMO
OBJECTIVE: The aim of this study was to describe the clinical and histopathological characteristics of seborrheic keratosis (SK) with secondary tumor and identify associated factors. METHODS: This study was a monocentric retrospective case-control study describing the factors associated with the development of tumors in SK. A total of 1365 patients with SK were admitted to our department between 2018 and 2021. All of the histopathological specimens and medical records of these patients were reviewed. We compared the data of 36 patients with tumors arising in SK with those of the remaining 1329 patients with only SK, which were designated the control group. RESULTS: The incidence of tumors arising in SK that were biopsied was 2.6%. The tumor types included squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and keratoacanthoma (KA). Compared with other patients with SK, elderly patients with immunosuppression, patients presenting surrounding erythema or ulceration, and those with SK in exposed areas had an increased possibility of developing a secondary tumor. Tumors arising within SK have the histopathological features of ulceration, cytologic atypia, mitosis, "malignant horn", trabecular cell cords, solar elastosis and severe inflammatory infiltration in the dermis. CONCLUSION: SK can show malignant progression in a small fraction of SK cases that are biopsied. This study is the first report on the clinical and histopathological characteristics of tumors arising in SK and identifies relevant factors in an Asian population.
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BACKGROUND: Heat shock proteins can protect against stress-associated cellular challenges, but they can also protect some tumors from human immune system monitoring. Heat shock protein 105 (HSP105/110) is a high molecular weight protein whose expression has been reported in many cancers, but few studies on its role in cutaneous malignant melanoma have been published. In this study, we analyzed the relationship between HSP105 expression and the clinicopathological characteristics of CMM. METHODS: This retrospective study included 91 patients with CMM. The clinicopathological characteristics of CMM patients, including age, lesion duration, location, pathological classification, Clark's level, Breslow thickness, metastasis and recurrence, were collected. Immunohistochemical staining and Western blot analysis for HSP105 were performed. Pigmented nevi (n = 20) served as a control. The staining intensity and percentage of stained cells were expressed as a histochemical score (HSCORE). RESULTS: HSP105 was overexpressed in melanoma compared with nevi. Differences in the HSCORE between nevi (HSCORE = 1.05(0.15,1.50)) and CMM (HSCORE = 2.68(1.80,3.60)) were remarkable (P<0.001). Exposed site lesions, recurrent and metastatic lesions, nodular melanoma and lentigo maligna melanoma were closely associated with higher HSP105 expression (P = 0.011, P = 0.001 and P = 0.001, respectively). Moreover, no significant difference was observed in Clark's level, Breslow thickness, or lesion duration (P>0.05). CONCLUSION: HSP105 is overexpressed in CMM. Higher HSP105 expression in lesions is associated with different clinicopathological variables. HSP105 may be a potential target for the diagnosis, treatment and prognostic prediction of CMM.
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Proteínas de Choque Térmico HSP110/genética , Melanoma/genética , Recidiva Local de Neoplasia/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Melanoma/epidemiologia , Melanoma/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Adulto Jovem , Melanoma Maligno CutâneoRESUMO
Bullous scabies (BS) is a rare atypical clinical variant of scabies and is easily confused with bullous disorders. The diagnosis of BS is always a challenge, and physicians often misdiagnose BS patients. Patients with BS admitted from 2012 to 2020 were enrolled in this study. The clinical, dermoscopic, and pathological characteristics of the patients were analyzed retrospectively. Ten patients with BS were enrolled in this study. Seven of the 10 patients were male. The bullae were most commonly found on the thighs and arms (80% of patients). Only 30% of patients (3/10) tested positive for mites and/or eggs by the initial skin scraping, but 100% (5/5) of the patients who received dermoscopy tested positive. Among these 10 patients, only five received a skin biopsy. Subepidermal (4/5) and intraepidermal (1/5) bullae with eosinophil and neutrophil infiltration were observed in five patients. Direct immunofluorescence (DIF) indicated linear deposition of IgG in the basement membrane zone in three patients. Physicians should consider the possibility of BS in patients with blisters, pruritus, and poor response to corticosteroids. Dermoscopy should be prioritized for the differential diagnosis of BS to exclude other bullous disorders. Finally, a biopsy should be performed on each patient with bullae.
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Escabiose/patologia , Dermatopatias Vesiculobolhosas/patologia , Administração Cutânea , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Dermoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prurido/fisiopatologia , Estudos Retrospectivos , Escabiose/tratamento farmacológico , Escabiose/fisiopatologia , Dermatopatias Vesiculobolhosas/tratamento farmacológico , Dermatopatias Vesiculobolhosas/fisiopatologia , Enxofre/uso terapêutico , Adulto JovemRESUMO
BACKGROUND: Heat shock proteins (HSPs), a group of heat stress proteins, are characterized by highly conserved properties. Malignant transformation is a cellular stress, and the expression of HSPs may be affected during this process. Heat shock protein 105 (HSP105) is a protective protein that has long been observed in many cancer types, but little attention has been given to cutaneous squamous cell carcinoma (CSCC). As such, the objectives of this study were to observe the expression of HSP105 on CSCC and evaluate its correlation with clinicopathological characteristics. METHODS: This retrospective study enrolled 60 patients with CSCC. The patients' clinical data, including sex, age, tumor location, tumor type, and degree of pathological differentiation, were collected. The expression of HSP105 was measured by Western blot and immunohistochemical staining. RESULTS: HSP105 expression was decreased in CSCC (HSCORE=0.65 (0.30, 1.98)) compared with normal skin (HSCORE=2.20 (1.50, 2.80)) (P<0.001). These results were consistent with the Western blot analysis. HSP105 immunostaining of Bowen disease (HSCORE=1.28 (1.08, 2.40)) revealed higher expression than in verrucous carcinoma (HSCORE=0.30 (0.23, 0.85)), keratoacanthoma (HSCORE=0.53 (0.29, 0.93)) and acantholytic squamous cell carcinoma (HSCORE=0.53 (0.41, 0.68) (P<0.01)). Poorly differentiated CSCC showed significantly higher expression of HSP105. CONCLUSION: Our study reveals for the first time that the expression of HSP105 is decreased in CSCC. We suggest that the molecular mechanisms underlying the differential expression of HSP deserve a more rigorous future study, the results of which might explain its role in carcinogenesis and its potential as a target for selective tumor therapy.
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OBJECTIVE: To explore the molecular mechanism of 17-AAG in the treatment of systemic lupus erythematosus (SLE), and the effects of the heat shock protein 90 (HSP90) inhibitor 17-AAG on the activation and proliferation of lymphocytes and the AKT/GSK3ß signaling pathway in MRL/lpr mice were detected. METHODS: MRL/lpr mice were randomly divided into the control group and the experimental group. The experimental group was injected intraperitoneally with 17-AAG, and T lymphocytes were separated by magnetic beads. Lymphocyte proliferation was detected by MTT and flow cytometry (FCM), and the expression of the HSP90 protein and PI3K/AKT signaling pathway-related proteins was detected by Western blotting. Renal histopathology and immune complex deposition were also observed in both groups. RESULTS: Immune complex deposition and inflammation decreased in kidneys from MRL/lpr mice in the experimental group. HSP90 protein expression, T lymphocyte proliferation and phosphorylated AKT and GSK3ß levels also decreased in the experimental group. CONCLUSION: 17-AAG can inhibit the activation and proliferation of T lymphocytes and downregulate the AKT/GSK3ß signaling pathway, which may be relevant for the treatment of SLE.
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Benzoquinonas/farmacologia , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Lactamas Macrocíclicas/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Linfócitos T/efeitos dos fármacos , Animais , Benzoquinonas/química , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Lactamas Macrocíclicas/química , Camundongos , Camundongos Endogâmicos MRL lpr , Estrutura Molecular , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Linfócitos T/imunologiaRESUMO
Iron phthalocyanine (FePc) is a promising non-precious catalyst for the oxygen reduction reaction (ORR). Unfortunately, FePc with plane-symmetric FeN4 site usually exhibits an unsatisfactory ORR activity due to its poor O2 adsorption and activation. Here, we report an axial Fe-O coordination induced electronic localization strategy to improve its O2 adsorption, activation and thus the ORR performance. Theoretical calculations indicate that the Fe-O coordination evokes the electronic localization among the axial direction of O-FeN4 sites to enhance O2 adsorption and activation. To realize this speculation, FePc is coordinated with an oxidized carbon. Synchrotron X-ray absorption and Mössbauer spectra validate Fe-O coordination between FePc and carbon. The obtained catalyst exhibits fast kinetics for O2 adsorption and activation with an ultralow Tafel slope of 27.5 mV dec-1 and a remarkable half-wave potential of 0.90 V. This work offers a new strategy to regulate catalytic sites for better performance.
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Objective: Adopting poly- L-lactic/glycolic acid (PLGA) and polyethylene glycol (PEG) as the material to fabricate PLGA/PEG electrospun polymer membrane by electrospinning technology. And to study its preventive effect on postoperative intraperitoneal adhesion of rat. Methods: PLGA and PEG were mixed at the ratio of 19â¶1( M/M), then dissolved in organic solvent. The PLGA/PEG electrospun polymer membrane was prepared by electrospinning technology, and then the gross observation and scanning electron microscope observation were taken. Fifty-four Sprague Dawley rats (weighing, 180-200 g), were randomly divided into 3 groups. The rats in control group ( n=6) were left intact. The rats in model group ( n=24) and PLGA/PEG group ( n=24) were treated with the method of mechanical injury of the cecal serosa in order to establish the intraperitoneal adhesion models; then the PLGA/PEG electrospun polymer membrane was used to cover the wound in PLGA/PEG group, but was not in the model group. The intraperitoneal adhesion in PLGA/PEG group and model group were observed at 3 days, 1 week, 2 weeks, and 8 weeks after operation, and the adhesion degree was assessed according to the self-generated standard. The degradation of PLGA/PEG electrospun polymer membrane was also observed in PLGA/PEG group. At each time point, the rats were harvested for histological observation. All the above indexes were compared with the control group. Results: Using the electrospinning technology, PLGA/PEG electrospun polymer membrane was prepared successfully. PLGA/PEG electrospun polymer membrane was white and opaque, with soft texture. Scanning electron microscopy observation showed that PLGA/PEG electrospun polymer membrane was mainly composed of disorderly staggered fibers, with microporous structure. All rats survived to the end of the experiment. Gross observation showed that PLGA/PEG electrospun polymer membrane gradually degraded after implantation in vivo, and the adhesion degree in PLGA/PEG group was significantly lower than that in model group ( P<0.05), but it had not yet reached to the level of the control group ( P<0.05). Histological observation showed that the proliferation of cecal fibrous connective tissue was slower in PLGA/PEG group than in model group, and adhesion severity significantly decreased, only with a small amount of inflammatory cell infiltration. Nevertheless, it was not up to the level of the control group. Conclusion: PLGA/PEG electrospun polymer membrane can effectively prevent postoperative intraperitoneal adhesion of rat, and has good biodegradability.
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Polietilenoglicóis , Polímeros , Aderências Teciduais/prevenção & controle , Animais , Ácido Láctico , Doenças Peritoneais/prevenção & controle , Ácido Poliglicólico , Complicações Pós-Operatórias/prevenção & controle , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
Neuroguidin (NGDN) is a eukaryotic translation initiation factor 4E binding protein. The purpose of this study was to clarify the function of NGDN and its possible mechanism of action in human myeloid leukemia cells. Proliferation inhibition and apoptosis in NGDN over-expressing myeloid multidrug-resistant leukemia cells (K562/A02-NGDN) was significantly higher than in control K562/A02 cells following treatment with vincristine, etoposide, and epirubicin, indicating that NGDN over-expression can increase the sensitivity of multidrug-resistant leukemia cells to chemotherapeutic drugs. Furthermore, NGDN knock-down in K562/A02 cells resulted in the activation of multiple tumor-related signaling pathways, especially the mammalian target of rapamycin (mTOR) pathway.
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Resistencia a Medicamentos Antineoplásicos/fisiologia , Leucemia Mieloide Aguda/metabolismo , Proteínas Nucleares/biossíntese , Apoptose/fisiologia , Resistência a Múltiplos Medicamentos , Citometria de Fluxo , Técnicas de Silenciamento de Genes , Humanos , Células K562 , Proteínas de Ligação a RNARESUMO
AIM OF THE STUDY: In recent years, the incidence of lung cancer, as well as the mortality rate from this disease, has increased. Moreover, because of acquired drug resistance and adverse side effects, the effectiveness of current therapeutics used for the treatment of lung cancer has decreased significantly. Chinese medicine has been shown to have significant antitumor effects and is increasingly being used for the treatment of cancer. However, as the mechanisms of action for many Chinese medicines are undefined, the application of Chinese medicine for the treatment of cancer is limited. The formula tested has been used clinically by the China National Traditional Chinese Medicine Master, Professor Zhonging Zhou for treatment of cancer. In this article, we examine the efficacy of Ke formula in the treatment of non-small cell lung cancer and elucidate its mechanism of action. METHODS: A Balb/c nude mouse xenograft model using A549 cells was previously established. The mice were randomly divided into normal, mock, Ke, cisplatin (DDP), and co-formulated (Ke + DDP) groups. After 15 days of drug administration, the animals were sacrificed, body weight and tumor volume were recorded, and the tumor-inhibiting rate was calculated. A cancer pathway finder polymerase chain reaction array was used to monitor the expression of 88 genes in tumor tissue samples. The potential antiproliferation mechanism was also investigated by Western blot analysis. RESULTS: Ke formula minimized chemotherapy-related weight loss in tumor-bearing mice without exhibiting distinct toxicity. Ke formula also inhibited tumor growth, which was associated with the downregulation of genes in the PI3K/AKT, MAPK, and WNT/ß-catenin pathways. The results from Western blot analyses further indicated that Ke blocked the cell cycle progression at the G1/S phase and induced apoptosis mainly via the PI3K/AKT pathway. CONCLUSION: Ke formula inhibits tumor growth in an A549 xenograft mouse model with no obvious side effects. Moreover, Ke exhibits synergistic antitumor effects when combined with DDP. The mechanism of action of Ke is to induce cell cycle arrest and apoptosis by suppressing the PI3K/AKT pathway. Further research will be required to determine the mechanism of action behind the synergistic effect of Ke and DDP.
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Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Fosfoinositídeo-3 Quinase , Preparações de Plantas/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Medicina Herbária/métodos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Ophiopogonin B (OP-B) is a bioactive component of Radix Ophiopogon Japonicus, which is often used in Chinese traditional medicine to treat pulmonary disease. However, whether or not OP-B has any potential antitumor activity has not been reported. Here, we show that the non-small cell lung cancer (NSCLC) cell lines NCI-H157 and NCI-H460 treated with OP-B grow more slowly and accumulate vacuoles in their cytoplasm compared to untreated control cells. Flow cytometric analysis showed that the cells were arrested in G0/G1 phase. Nuclear morphology, Annexin-V/PI staining, and expression of cleaved caspase-3 all confirm that OP-B does not induce apoptosis. Instead, based on results from both transmission electron microscopy (TEM) and the expression of microtubule-associated protein 1 light chain 3-II (LC3-II), we determined that OP-B treatment induced autophagy in both cell lines. Next, we examined the PI3K/Akt/mTOR signaling pathway and found that OP-B inhibited phosphorylation of Akt (Ser473, Thr308) in NCI-H157 cells and also inhibited several key components of the pathway in NCI-H460 cells, such as p-Akt(Ser473, Thr308), p-p70S6K (Thr389). Additionally, insulin-mediated activation of the PI3K/Akt/mTOR pathway provides evidence that activation of this pathway may correlate with induction of autophagy in H460 cells. Therefore, OP-B is a prospective inhibitor of PI3K/Akt and may be used as an alternative compound to treat NSCLC.
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Autofagia/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Extratos Vegetais/farmacologia , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Espirostanos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citoplasma , Humanos , Neoplasias Pulmonares/enzimologia , Proteínas Associadas aos Microtúbulos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Vacúolos/efeitos dos fármacosRESUMO
OBJECTIVE: To compare the double dorsal phalangeal flap (DDPF) with the combination of digital neurovascular island flap (NVIF) and first dorsal metacarpal artery flap (FDMA) in terms of repairing digit degloving injury. METHODS: From October 2005 to March 2008, DDPF was used to repair 9 patients (9 fingers) with degloving injury of the thumb and index finger and completely amputated thumb and index finger (group A). From August 1996 to June 2007, NVIF and FDMA were used to repair 13 patients (13 fingers) with the thumb degloving injury and completely amputated or necrotic thumb (group B). In group A, there were 7 males and 2 females aged 19-48 years old, there were 4 cases of thumb and index finger degloving injury repair and 5 cases of completely amputated thumb and index finger reconstruction, the skin defect ranged from 6.0 cm x 3.5 cm to 7.0 cm x 4.5 cm, and the interval between injury and operation was 3-10 hours. The size of DDPF harvested during operation was 4.0 cm x 3.5 cm-5.0 cm x 4.0 cm. In group B, there were 10 males and 3 females aged 18-50 years old, there were 5 cases of thumb degloving injury repair and 8 cases of completely amputated or necrotic thumb reconstruction, the skin defect ranged from 6.0 cm x 3.0 cm to 7.0 cm x 4.5 cm, and the interval between injury and operation was 3 hours-5 days, and the size of NVIF and FDMA harvested during operation was 3.5 cm x 3.0 cm-5.0 cm x 4.0 cm. The donor site was repaired with the full-thickness skin graft. RESULTS: All the flaps survived uneventfully except for 1 case in group A suffering from venous crisis 1 day after operation and 2 cases in group B suffering from FDMA artery crisis 4-12 hours after operation. Those flaps survived after symptomatic treatment. All the wounds healed by first intention. All patients in two groups were followed up for 1-12 years (average 3.2 years). All the donor sites were normal except for 3 cases in group B suffering from flexion contracture deformity of the proximal interphalangeal joint due to the scar contracture in the margin of NVIF donor site. According to Allen test, the skin temperature and color of the donor fingers in two groups were normal under room temperature; 1 case of group A and 6 NVIF donor fingers of group B were pale and cold under ice water. According to sensory recovery evaluation system, 16 fingers in group A were graded as S4, 1 as S3+, and 1 as S2; while in group B, 3 NVIF fingers were graded as S3, 6 NVIF fingers as S2, 4 NVIF fingers as S1, and 13 FDMA fingers as S4. The appearance of the recipient flap was satisfactory and the color was similar to the surrounding skin. The skin temperature and color of the flaps in two groups were normal under room temperature; 2 cases of group A and 4 recipient fingers of group B were pale and cold under ice water. In group A, all the palmar flap of the recipient finger achieved the reorientation of the recipient flap sensation; while in group B, 8 cases achieved the reorientation of the recipient flap sensation, and 5 cases had double sensation. For the two-point discrimination of the flap, group B was superior to that of group A in terms of the palmar aspect (P < 0.05), no significant difference was evident between two groups in terms of the dorsal aspect (P > 0.05), and the palmar aspect of each group was superior to the dorsal flap (P < 0.05). CONCLUSION: DDPF is less invasive to donor finger, easy to be operated, able to partially restore the sensory of the injured finger, and suitable for the repair of the degloving injury of the thumb and the index finger. Combination of NVIF and FDMA can restore the fine sensory of recipient palmar flap better and is applicable for those patients suffering from digital nerve defects from the proximal phalanx and with high demand for the recovery of thumb sensory.
Assuntos
Traumatismos dos Dedos/cirurgia , Transplante de Pele/métodos , Retalhos Cirúrgicos , Adulto , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Pele/lesões , Resultado do Tratamento , Adulto JovemRESUMO
Pogonatherum crinitum has long been used as a folk remedy for the treatment of many inflammatory diseases in Taiwan, and till now there is still no report concerning its active principles as well as their pharmacological studies. That prompted us to investigate the bioactive constituents of Pogonatherum crinitum. Two novel chemical entities, luteolin 6-C-beta-boivinopyranoside (1) and 6-trans-(2''-O-alpha-rhamnopyranosyl)ethenyl-5,7,3',4'-tetrahydroxyflavone (2), along with luteolin (3), kaempferol (4), luteolin 6-C-beta-fucopyranoside (5), kaempferol 3-O-alpha-L-rhamnopyranoside (6), luteolin 6-C-beta-glucopyranoside (7), rutin (8) and kaempferol 3-O-rutinoside (9) were isolated from this plant, and identified by spectroscopic analysis. The effect of these compounds on the inhibition of NO production in LPS-activated macrophages was further evaluated. All these compounds inhibited NO production in activated RAW 264.7 cells to various degrees without affecting the cellular viability. Among the compounds examined, both compounds 1 and 2 suppressed LPS-induced NO production, with E(max) values of 99.51+/-0.23% and 92.41+/-3.22%, respectively. The most potent compounds, 3 and 4, inhibited NO production with IC(50) values of 10.41+/-0.02 microM and 10.61+/-0.44 microM, respectively. These effects were attributed to suppression of mRNA expression of inducible NO synthase (iNOS). Our results clearly demonstrated that these naturally occurring iNOS inhibitors may be beneficial to the treatment of inflammatory diseases associated with overproduction of NO, which provides an explanation, at least a part, for the anti-inflammatory property of Pogonatherum crinitum.