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1.
J Craniomaxillofac Surg ; 52(3): 302-309, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38368207

RESUMO

The present study aimed to investigate outcomes following open surgery for extensive skull base ORN. Open surgery through a personalized sequential approach was employed to deal with five cases of extensive skull base ORN. Two patients with mild cases underwent regional debridement and sequestrectomy, and three patients with severe cases underwent extensive resection with reconstruction using free anterolateral thigh (ALT) flap. Biological glues and vascularized flaps were used for obturation of the skull base bony defect to prevent postoperative cerebrospinal fluid (CSF) leakage. The infections were controlled by antibiotic administrations which strictly followed the principles of antimicrobial stewardship (AMS). As results, both regional debridement plus sequestrectomy and extensive resection achieved satisfied outcomes in all patients. No severe complications and delayed hospitalization occurred. During the follow-up period (8-19 months), all patients were alive, pain free, without crusting or purulent discharge, and no sequestration or CSF leakage occurred. In conclusion, a personalized sequential approach including open surgery, pedicled/vascularized free flap reconstruction and AMS was advocated for patients with extensive skull base ORN.


Assuntos
Retalhos de Tecido Biológico , Osteorradionecrose , Procedimentos de Cirurgia Plástica , Neoplasias da Base do Crânio , Humanos , Osteorradionecrose/cirurgia , Osteorradionecrose/complicações , Base do Crânio/cirurgia , Neoplasias da Base do Crânio/cirurgia , Retalhos de Tecido Biológico/cirurgia , Vazamento de Líquido Cefalorraquidiano/cirurgia , Estudos Retrospectivos , Complicações Pós-Operatórias/cirurgia
2.
ACS Nano ; 18(5): 4189-4204, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38193384

RESUMO

cGAS-STING signaling plays a critical role in radiotherapy (RT)-mediated immunomodulation. However, RT alone is insufficient to sustain STING activation in tumors under a safe X-ray dose. Here, we propose a radiosensitization cooperated with cGAS stimulation strategy by engineering a core-shell structured nanosized radiosensitizer-based cGAS-STING agonist, which is constituted with the hafnium oxide (HfO2) core and the manganese oxide (MnO2) shell. HfO2-mediated radiosensitization enhances immunogenic cell death to afford tumor associated antigens and adequate cytosolic dsDNA, while the GSH-degradable MnO2 sustainably releases Mn2+ in tumors to improve the recognition sensitization of cGAS. The synchronization of sustained Mn2+ supply with cumulative cytosolic dsDNA damage synergistically augments the cGAS-STING activation in irradiated tumors, thereby enhancing RT-triggered local and system effects when combined with an immune checkpoint inhibitor. Therefore, the synchronous radiosensitization with sustained STING activation is demonstrated as a potent immunostimulation strategy to optimize cancer radio-immuotherapy.


Assuntos
Háfnio , Compostos de Manganês , Neoplasias , Humanos , Compostos de Manganês/farmacologia , Óxidos/farmacologia , Óxidos/uso terapêutico , Imunoterapia , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Nucleotidiltransferases
3.
J Colloid Interface Sci ; 660: 869-884, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38277843

RESUMO

Infiltration and activation of intratumoral T lymphocytes are critical for immune checkpoint blockade (ICB) therapy. Unfortunately, the low tumor immunogenicity and immunosuppressive tumor microenvironment (TME) induced by tumor metabolic reprogramming cooperatively hinder the ICB efficacy. Herein, we engineered a lactate-depleting MOF-based catalytic nanoplatform (LOX@ZIF-8@MPN), encapsulating lactate oxidase (LOX) within zeolitic imidazolate framework-8 (ZIF-8) coupled with a coating of metal polyphenol network (MPN) to reinforce T cell response based on a "two birds with one stone" strategy. LOX could catalyze the degradation of the immunosuppressive lactate to promote vascular normalization, facilitating T cell infiltration. On the other hand, hydrogen peroxide (H2O2) produced during lactate depletion can be transformed into anti-tumor hydroxyl radical (•OH) by the autocatalytic MPN-based Fenton nanosystem to trigger immunogenic cell death (ICD), which largely improved the tumor immunogenicity. The combination of ICD and vascular normalization presents a better synergistic immunopotentiation with anti-PD1, inducing robust anti-tumor immunity in primary tumors and recurrent malignancies. Collectively, our results demonstrate that the concurrent depletion of lactate to reverse the immunosuppressive TME and utilization of the by-product from lactate degradation via cascade catalysis promotes T cell response and thus improves the effectiveness of ICB therapy.


Assuntos
Estruturas Metalorgânicas , Neoplasias , Humanos , Ácido Láctico/farmacologia , Estruturas Metalorgânicas/farmacologia , Peróxido de Hidrogênio/farmacologia , Linfócitos T , Imunoterapia , Linhagem Celular Tumoral , Microambiente Tumoral
4.
ACS Nano ; 17(14): 13195-13210, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37256771

RESUMO

Radiotherapy (RT) is one of the important clinical treatments for local control of triple-negative breast cancer (TNBC), but radioresistance still exists. Ferroptosis has been recognized as a natural barrier for cancer progression and represents a significant role of RT-mediated anticancer effects, while the simultaneous activation of ferroptosis defensive system during RT limits the synergistic effect between RT and ferroptosis. Herein, we engineered a tumor microenvironment (TME) degradable nanohybrid with a dual radiosensitization manner to combine ferroptosis induction and high-Z effect based on metal-organic frameworks for ferroptosis-augmented RT of TNBC. The encapsulated l-buthionine-sulfoximine (BSO) could inhibit glutathione (GSH) biosynthesis for glutathione peroxidase 4 (GPX4) inactivation to break down the ferroptosis defensive system, and the delivered ferrous ions could act as a powerful ferroptosis executor via triggering the Fenton reaction; the combination of them induces potent ferroptosis, which could synergize with the surface decorated Gold (Au) NPs-mediated radiosensitization to improve RT efficacy. In vivo antitumor results revealed that the nanohybrid could significantly improve the therapeutic efficacy and antimetastasis efficiency based on the combinational mechanism between ferroptosis and RT. This work thus demonstrated that combining RT with efficient ferroptosis induction through nanotechnology was a feasible and promising strategy for TNBC treatment.


Assuntos
Ferroptose , Neoplasias de Mama Triplo Negativas , Humanos , Anestésicos Locais , Butionina Sulfoximina , Fibrinolíticos , Glutationa , Linhagem Celular Tumoral , Microambiente Tumoral
5.
J Stomatol Oral Maxillofac Surg ; 124(1): 101261, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35961510

RESUMO

OBJECTIVES: The semiburied design of the traditional internal distractor has a relatively high risk of infection and aesthetic problems. To reduce these potential risks, a modified internal distractor with design of pre-embedding curvilinear rail, drive screw, and universal joint was invented. Its stress distribution characteristics and the effect on curvilinear distraction osteogenesis (DO) in vivo were further tested. MATERIALS AND METHODS: Finite element analysis (FEA) was performed on a model of the human mandible and distraction device to measure the stress distribution during curvilinear DO. Six beagles underwent curvilinear DO and consolidation using the new device. Radiological and histological examinations were performed on the new bone. RESULTS: On FEA, the stress was concentrated in the condyle (128.6 MPa) and curved guide rails (324.8 MPa). Four of the six animals completed the DO period and were consolidated for 12 weeks. Secondary infections were not observed. Radiography showed that a new fan-shaped bone-15.5 ± 5.5 mm in length and 4.6 ± 1.6 mm in height-was formed in the bone gap. Micro-computed tomography and histological examinations of specimens indicated that the structure of the new bone was similar to that of the normal bone. CONCLUSIONS: The modified internal curvilinear distraction device meets the mechanical strength requirement and achieve curvilinear DO in animal experiments.


Assuntos
Experimentação Animal , Osteogênese por Distração , Cães , Humanos , Animais , Análise de Elementos Finitos , Microtomografia por Raio-X , Mandíbula/cirurgia , Mandíbula/patologia , Osteogênese por Distração/métodos , Parafusos Ósseos
6.
Inflamm Res ; 71(12): 1559-1576, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36301340

RESUMO

BACKGROUND: Myocardial inflammation and apoptosis are key processes in coxsackievirus B3 (CVB3)-induced acute viral myocarditis (AVMC). Accumulating evidence reveals the essential roles of long noncoding RNAs (lncRNAs) in the pathogenesis of AVMC. Here, we aimed to evaluate the biological functions of a novel lncRNA guanylate-binding protein 9 (lncGBP9) in AVMC progression and further explore its underlying mechanisms. METHODS: Initially, mouse models of AVMC were constructed by CVB3 infection. The expression and localization of lncGBP9 in heart tissues were analyzed using RT-qPCR and FISH. Adeno-associated virus serotype 9 (AAV9)-mediated lncGBP9 knockdown was then employed to clarify its roles in survival, cardiac function, and myocardial inflammation and apoptosis. Moreover, the mRNA and protein levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß) were detected by RT-qPCR and ELISA, and the regulation of lncGBP9 knockdown on the NF-κB signaling pathway was investigated by Western blotting. Using an in vitro model of HL-1 cardiomyocytes exposed to CVB3 infection, the effects of lncGBP9 knockdown on cell viability, inflammation, and apoptosis were further evaluated in vitro. RESULTS: Increased lncGBP9 expression was detected in the heart tissues of AVMC mice and CVB3-infected HL-1 cells, and was mainly located in the cytoplasm. Knockdown of lncGBP9 remarkably alleviated the severity of AVMC in CVB3-infected mice, as verified by improved cardiac function, and reduced myocardial inflammation and apoptosis. Additionally, lncGBP9 knockdown suppressed the NF-κB signaling pathway and consequently reduced productions of pro-inflammatory cytokines in vivo. In vitro functional assays further confirmed that lncGBP9 knockdown promoted cell viability, inhibited cell apoptosis, and reduced pro-inflammatory cytokines release in CVB3-infected HL-1 cells through suppressing NF-κB activation. CONCLUSIONS: Collectively, lncGBP9 knockdown exerts anti-inflammatory and anti-apoptotic effects in CVB3-induced AVMC, which may be mediated in part via NF-κB signaling pathway. These findings highlight lncGBP9 as an attractive target for therapeutic interventions.


Assuntos
Infecções por Coxsackievirus , Miocardite , Camundongos , Animais , Miocardite/genética , NF-kappa B/metabolismo , Enterovirus Humano B/metabolismo , Infecções por Coxsackievirus/genética , Infecções por Coxsackievirus/metabolismo , Infecções por Coxsackievirus/patologia , Transdução de Sinais , Inflamação/metabolismo , Apoptose , Citocinas/metabolismo , Camundongos Endogâmicos BALB C
7.
Gland Surg ; 11(4): 677-686, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35531114

RESUMO

Background: This paper aimed to summarize our experience in the nursing of acute graft-versus-host disease (aGVHD) after simultaneous pancreas-kidney transplantation (SPK). Methods: We retrospectively collected and analyzed the demographic characteristics, preoperative evaluation, donor evaluation, screening, and surgical methods of patients with aGVHD after SPK in our center from September 2016 to September 2019. Results: One patient developed intractable diarrhea with decline in platelet (PLT), white blood cell (WBC), and red blood cell (RBC) counts. Meanwhile, the other two patients experienced facial and trunk rashes, hepatic impairment, as well as decreased PLT, WBC, and RBC counts. We took the following nursing interventions: establishing an intensive care team and close monitoring of changes in the condition; protective isolation to minimize exogenous infections; nursing of pulmonary infections; and nutritional support. However, despite careful treatment and nursing, the conditions of the three patients subsequently worsened rapidly and became uncontrollable, and all died. Conclusions: aGVHD is extremely rare after SPK, and no literature exists concerning nursing care or management related to this condition. Clinical manifestations and histopathology are helpful for diagnosis; however, treatment outcomes might be unsatisfactory and the prognosis is poor. Early detection, diagnosis, and intervention have a positive impact on the prognosis of aGVHD, and proper nursing can benefit patients.

8.
Adv Healthc Mater ; 11(8): e2200143, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35195958

RESUMO

With the successful marriage between nanotechnology and oncology, various high-Z element containing nanoparticles (NPs) are approved as radiosensitizers to overcome radiation resistance for enhanced radiotherapy (RT). Unfortunately, NPs themselves lack specificity to tumors. Due to the inherent tropism nature of malignant cells, mesenchymal stem cells (MSCs) emerge as cell-mediated delivery vehicles for functional NPs to improve their therapeutic index. Herein, radiosensitive bismuth selenide (Bi2 Se3 ) NPs-laden adipose-derived mesenchymal stromal cells (AD-MSCs/Bi2 Se3 ) are engineered for targeted RT of non-small cell lung cancer (NSCLC). The results reveal that the optimized intracellular loading strategy hardly affects cell viability, specific surface markers, or migration capability of AD-MSCs, and Bi2 Se3  NPs can be efficiently transported from AD-MSCs to tumor cells. In vivo biodistribution test shows that the Bi2 Se3 NPs accumulation in tumor is increased 20 times via AD-MSCs-mediated delivery. Therefore, AD-MSCs/Bi2 Se3 administration synchronized with X-ray irradiation controls the tumor progress well in orthotopic A549 tumor bearing mice. Considering that MSCs migrate better to irradiated tumor cells in comparison to nonirradiated ones and MSCs preferentially accumulate within lung tissues after systemic administration into accounts, the tumor-tropic MSCs/NPs system is feasible and promising for targeted RT treatment of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Radiossensibilizantes , Animais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Linhagem Celular Tumoral , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/radioterapia , Transplante de Células-Tronco Mesenquimais/métodos , Camundongos , Distribuição Tecidual
9.
Acta Biomater ; 141: 364-373, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35063709

RESUMO

Tumor vasculature-targeting therapy either using angiogenesis inhibitors or vascular disrupting agents offers an important new avenue for cancer therapy. In this work, a tumor-specific catalytic nanomedicine for enhanced tumor ablation accompanied with tumor vasculature disruption and angiogenesis inhibition was developed through a cascade reaction with enzyme glucose oxidase (GOD) modified on Fe-based metal organic framework (Fe-MOF) coupled with anti-VEGFR2.The GOD enzyme could catalyze the intratumoral glucose decomposition to trigger tumor starvation and yet provide abundant hydrogen peroxide as the substrate for Fenton-like reaction catalyzed by Fe-MOF to produce sufficient highly toxic hydroxyl radicals for enhanced chemodynamic therapy and instantly attacked tumor vascular endothelial cells to destroy the existing vasculature, while the anti-VEGFR2 antibody guided the nanohybrids to target blood vessels and block the VEGF-VEGFR2 connection to prevent angiogenesis. Both in vitro and in vivo results demonstrated the smart nanohybrids could cause the tumor cell apoptosis and vasculature disruption, and exhibited enhanced tumor regression in A549 xenograft tumor-bearing mice model. This study suggested that synergistic targeting tumor growth and its vasculature network would be more promising for curing solid tumors. STATEMENT OF SIGNIFICANCE: Cooperative destruction of tumor cells and tumor vasculature offers a potential avenue for cancer therapy. Under this premise, a tumor-specific catalytic nanomedicine for enhanced tumor ablation accompanied with tumor vasculature disruption and new angiogenesis inhibition was developed through a cascade reaction with glucose oxidase modified on the surface of iron-based metal organic framework coupled with VEGFR2 antibody. The resulting data demonstrated that a therapeutic regimen targeting tumor growth as well as its vasculature with both existing vasculature disruption and neovasculature inhibition would be more potential for complete eradication of tumors.


Assuntos
Estruturas Metalorgânicas , Neoplasias , Animais , Catálise , Linhagem Celular Tumoral , Células Endoteliais/metabolismo , Glucose Oxidase/química , Humanos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo
10.
ACS Appl Mater Interfaces ; 13(45): 53504-53518, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34704726

RESUMO

With the recent success of immune checkpoint blockade (ICB) in cancer immunotherapy, there has been renewed interest in evaluating the combination of ICB inhibitors with radiotherapy (RT) in clinical trials in view of the localized RT-initiated vaccination effect, which can be augmented further by systemic immune-stimulating agents. Unfortunately, traditional RT/ICB accompanies severe toxicity from high-dose ionizing irradiation and low response rate from RT-aggravated immunosuppression, among which M2-type tumor-associated macrophages (TAMs) play an important role. Herein, CpG-decorated gold (Au) nanoparticles (CpG@Au NPs) were fabricated to improve the RT/ICB efficacy by immune modulation under low-dose X-ray exposure, where Au NPs served as radioenhancers to minimize the radiotoxicity, and yet acted as nanocarriers to deliver CpG, a toll-like receptor 9 agonist, to re-educate immunosuppressive M2 TAMs to immunostimulatory M1 counterparts, thus arousing innate immunity and meanwhile priming T cell activation. When combined with an anti-programmed death 1 antibody, irradiated CpG@Au led to consistent abscopal responses that efficiently suppressed distant tumors in a bilateral GL261 tumor-bearing model. This work thus demonstrates that CpG@Au-mediated macrophage reeducation could efficiently modulate the tumor-immune microenvironment for synergistic RT/ICB.


Assuntos
Glioma/terapia , Ouro/farmacologia , Inibidores de Checkpoint Imunológico/farmacologia , Imunoterapia , Nanocompostos/química , Oligodesoxirribonucleotídeos/farmacologia , Macrófagos Associados a Tumor/efeitos dos fármacos , Animais , Ouro/química , Inibidores de Checkpoint Imunológico/química , Camundongos , Oligodesoxirribonucleotídeos/química , Células Tumorais Cultivadas , Microambiente Tumoral/efeitos dos fármacos
11.
J Mater Chem B ; 9(2): 208-227, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33215626

RESUMO

Radiotherapy (RT) plays a central role in curing malignant tumors. However, the treatment outcome is often impeded by low radiation absorption coefficients and radiation resistance of tumors along with normal tissue radio-toxicity. With the development of nanotechnology, nanomaterials in combination with RT offer the possibility to improve the therapeutic efficacy yet reduce side-effects. Metal-ligand coordination nanomaterials, including nanoscale metal-organic frameworks (NMOFs) and nanoscale coordination polymers (NCPs), formed by coordination interactions between inorganic metal ions/clusters with organic bridging ligands, have shown great potential in the field of radiation oncology in recent years in view of their unique advantages including the porous structure, high surface area, periodic frameworks, and diverse selections of both metal ions/clusters and organic ligands. In this review, we summarize the recent advances in NMOF/NCP-mediated synergistic RT in combination with hypoxia relief, chemotherapy, photodynamic therapy, photothermal therapy, chemodynamic therapy or immunotherapy, which emerged in the last 3 years, and describe cooperative enhancement interactions among these synergistic combinations. Moreover, the potential challenges and future prospects of this rapidly growing direction were also addressed.


Assuntos
Imunoterapia/métodos , Estruturas Metalorgânicas/química , Nanoestruturas/química , Radioterapia/métodos , Humanos , Ligantes
12.
Sci Total Environ ; 743: 140755, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32758841

RESUMO

Wide use of plastic greenhouses for vegetable production increases human exposure to phthalate (PAEs) through vegetable intake. However, little information is available about distribution of PAEs in air-soil-vegetable systems of plastic greenhouses and PAE estrogenic effects. This study was designed to investigate PAE distributions and corresponding health risk in plastic greenhouses in Guangzhou, a subtropical city in South China. PAEs were prevalent in plastic greenhouses, with sum concentrations of 16 PAE compounds (∑16PAEs) up to 5.76 mg/kg in soils, 5.27 mg/kg in vegetables and 4393 ng/m3 in air. Di (2-ethylhexyl) phthalate, di-isobutyl phthalate, and dibutyl phthalate were predominant compounds. Average concentrations and bioconcentration factor of ∑16PAEs and the predominant PAE compounds in vegetables of greenhouses were higher than those of open fields. Plastic greenhouses exhibited significantly higher air PAE levels than those of open fields due to higher indoor temperature, which enhanced PAE accumulation by vegetables. Both carcinogenic and non-carcinogenic risks of PAEs via dietary and non-dietary exposures for farmers decreased with an order of vegetable > air > soil. Consumption of vegetables from greenhouses resulted in significantly higher estrogenic effects compared to those from open field cultivation. This study emphasizes highly potential health risks of PAEs in air-soil-vegetable systems of plastic greenhouses.

13.
Front Psychol ; 11: 1287, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32581984

RESUMO

BACKGROUND: Fear of cancer recurrence (FCR) is common among cancer patients and of high clinical relevance. This study explores the prevalence and correlates of FCR in Chinese newly diagnosed cancer population. METHODS: This is a multicentre, cross-sectional study that includes 996 patients with mixed cancer diagnosis. All recently diagnosed patients completed a questionnaire consisting of the following: Fear of Progression Questionnaire-Short Form (FoP-Q-SF), General Anxiety Disorder Questionnaire (GAD-7), and Patient Health Questionnaire (PHQ-9). Univariate analyses, multivariate logistic regression analyses, and structural equation modeling (SEM) was performed to examine the association between tested variables and FCR. RESULTS: Of the 996 patients, 643 (64.6%) reported high FCR (scored ≥ 34 in the FoP-Q-SF). Chemotherapy (OR = 1.941), Childhood severe illness experience (OR = 2.802), depressive (OR = 1.153), and anxiety (OR = 1.249) symptoms were positively associated with high FCR, while higher monthly income (OR = 0.592) was negatively associated with high FCR. SEM indicated that emotional disturbances (anxiety and depression) directly influenced FCR, while emotional disturbances partly mediated the association between personal monthly income and FCR. CONCLUSION: High FCR is a frequently reported problem among newly diagnosed cancer patients. Various factors increased the likelihood of the development of FCR. Flexible psychological interventions are needed for patients with high FCR.

14.
Cell Death Dis ; 11(5): 391, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32444644

RESUMO

Necroptosis is a recently discovered form of programmed cell death (PCD) having necrotic-like morphology. However, its presence and potential impact with respect to head and neck squamous cell carcinoma (HNSCC) are still unknown. The aim of this study was to reveal the necroptosis status and its clinicopathological relevance in HNSCC and to establish an in vitro model. We first analyzed the level of p-MLKL, MLKL, and tumor necrosis in HNSCC patient tissues as well as their correlation with clinicopathological features. Results showed that approximately half of the tumor necrosis can be attributed to necroptosis, and the extent of necroptosis is an independent prognostic marker for patient's overall survival and progression-free survival. Then we established and thoroughly verified an in vitro model of necroptosis in two HNSCC cell lines using combined treatment of TNF-α, Smac mimetic and zVAD-fmk (TSZ). At last, we adopted this model and demonstrated that necroptosis can promote migration and invasion of HNSCC cells by releasing damage-associated molecular patterns. In conclusion, our study unveiled the necroptotic status in HNSCC for the first time and provided a novel in vitro model of necroptosis in two HNSCC cell lines. In addition, our results indicated that necroptosis may be a potential cancer promoter in HNSCC. This study may serve as the foundation for future researches of necroptosis in HNSCC.


Assuntos
Neoplasias de Cabeça e Pescoço/metabolismo , Necroptose/fisiologia , Necrose/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Humanos , Proteínas Quinases/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo
15.
Sci Total Environ ; 707: 135609, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-31771853

RESUMO

Phthalate acid esters (PAEs) are of serious concern as a human health risk due to their ubiquitous presence in indoor air. In the present study, fifteen PAEs in the indoor air samples from physical, chemical, and biological laboratories in Guangzhou, southern China were analysed using gas chromatography mass spectrometry. Extremely high levels of PAEs of up to 6.39 × 104 ng/m3 were detected in some laboratories. Diisobutyl phthalate (DiBP), di(methoxyethyl) phthalate (DMEP), and di-n-butyl phthalate (DBP) were the dominant PAEs with median levels of 0.48 × 103, 0.44 × 103, and 0.39 × 103 ng/m3, respectively, followed by di-(2-propylheptyl) phthalate (DPHP) and di(2-ethylhexyl) phthlate (DEHP) (median levels: 0.16 × 103 and 0.13 × 103 ng/m3, respectively). DMEP and DPHP were found for the first time in indoor air. Principal component analysis indicated that profiles of PAEs varied greatly among laboratory types, suggesting notable variations in sources. The results of independent samples t-tests showed that levels of PAEs were significantly influenced by various environmental conditions. Both the non-carcinogenic and carcinogenic health risks from human exposure to PAEs based on the daily exposure dose in laboratory air were acceptable. Further research should be conducted to investigate the long-term health effects of exposure to PAEs in laboratories.


Assuntos
Poluição do Ar em Ambientes Fechados , China , Dibutilftalato , Ésteres , Humanos , Ácidos Ftálicos
16.
Adv Sci (Weinh) ; 5(12): 1801012, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30581704

RESUMO

Cancer stem cells (CSCs) are proposed to account for the initiation of cancer metastasis, but their accessibility remains a great challenge. This study reports deep tumor-penetrated biomimetic nanocages to augment the accessibility to CSCs fractions in tumor for anti-metastasis therapy. The nanocages can load photothermal agent of 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DBN) and chemotherapeutic epirubicin (EBN) to eradicate CSCs for photothermal-chemotherapy of breast cancer metastasis. In metastatic 4T1-indcued tumor model, both DBN and EBN can efficiently accumulate in tumor sites and feasibly permeate throughout the tumor mass. These biomimetic nanosystems can be preferentially internalized by cancer cells and effectively accessed to CSCs fractions in tumor. The DBN+laser/EBN treatment produces considerable depression of primary tumor growth, drastically eradicates around 80% of CSCs fractions in primary tumor, and results in 95.2% inhibition of lung metastasis. Thus, the biomimetic nanocages can be a promising delivery nanovehicle with preferential CSCs-accessibility for effective anti-metastasis therapy.

17.
Adv Healthc Mater ; 7(10): e1800022, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29508557

RESUMO

Owing to the progressive development of metal-organic frameworks (MOFs) synthetic processes and their unique characters associated with the excellent performance-selectable composition, tunable pore scale, large surface area, and good thermal stability, MOFs have captured the interest and the imagination of an increasing number of scientists working in different fields. In the area of biomedical applications, MOFs are especially involved in sensing, molecular imaging, and drug delivery, with strong contributions to the whole nanomedicine area. Recently, these materials have been scaled down to nanometer sizes with the advancement of chemical synthesis gradually reaching an adjustable level. This review mainly discusses and summarizes the general synthesis, properties, and biomedical applications of nanoscaled MOFs and their composites in biosensing, imaging, and cancer therapy within the latest three years. The remaining challenges and future opportunities in this field, in terms of processing techniques, maximizing composite properties, and prospects for clinical applications, are also indicated.


Assuntos
Técnicas Biossensoriais/métodos , Sistemas de Liberação de Medicamentos/métodos , Estruturas Metalorgânicas , Imagem Molecular/métodos , Nanoestruturas , Neoplasias , Animais , Humanos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/uso terapêutico , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico
18.
J Craniofac Surg ; 29(3): 651-654, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29283941

RESUMO

Extended anterolateral thigh (ALT) flap can provide a large amount of skin to reconstruct the extensively full-thickness defects of cheek. However when the width of 1 skin paddle exceeds 8 cm, it always results in that the donor site cannot be closed primarily and need to be covered by split-thickness skin grafting, which delivers lots of impacts on the functional and cosmetic outcome of the thigh. The aim of this study was to introduce the authors' modification of stacking 2 skin paddles of the tripaddled ALT flap to reconstruct the extensive full-thickness defects in the cheek after the radical ablasion of advanced buccal squamous cell carcinoma. Ten patients of advanced buccal squamous cell carcinoma between March 2014 and December 2016 were enrolled in the authors' hospital. All the patients were received the soft-tissue reconstructions for the extensively full-thickness cheek defects by using the tripaddled ALT chimeric flaps. Among 3 skin paddles, the distal paddle was used to reconstruct the inner mucosa defect, and the other 2 large skin paddles were stacked side by side for outer mega cheek defect. The mean area of the intraoral defect was 32.2 cm and the mean area of the extraoral defect was 106.34 cm. The mean width of the outer skin defect was 9.5 cm. All the flaps survived and all the donor sites were closed primarily. So, stacking 2 skin paddles of a tripaddled ALT flap as a kiss pattern is a novel modification on conventional flap design to provide customized coverage for extensive and full-thickness buccal defects while minimizing donor-site morbidity.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Bochecha/cirurgia , Neoplasias Bucais/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Transplante de Pele , Retalhos Cirúrgicos , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Coxa da Perna , Sítio Doador de Transplante/cirurgia
19.
Molecules ; 22(1)2017 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-28085062

RESUMO

Influenza remains one of the major epidemic diseases worldwide, and rapid virus replication and collateral lung tissue damage caused by excessive pro-inflammatory host immune cell responses lead to high mortality rates. Thus, novel therapeutic agents that control influenza A virus (IAV) propagation and attenuate excessive pro-inflammatory responses are needed. Polysaccharide extract from Radix isatidis, a traditional Chinese herbal medicine, exerted potent anti-IAV activity against human seasonal influenza viruses (H1N1 and H3N2) and avian influenza viruses (H6N2 and H9N2) in vitro. The polysaccharides also significantly reduced the expression of pro-inflammatory cytokines (IL-6) and chemokines (IP-10, MIG, and CCL-5) stimulated by A/PR/8/34 (H1N1) at a range of doses (7.5 mg/mL, 15 mg/mL, and 30 mg/mL); however, they were only effective against progeny virus at a high dose. Similar activity was detected against inflammation induced by avian influenza virus H9N2. The polysaccharides strongly inhibited the protein expression of TLR-3 induced by PR8, suggesting that they impair the upregulation of pro-inflammatory factors induced by IAV by inhibiting activation of the TLR-3 signaling pathway. The polysaccharide extract from Radix isatidis root therefore has the potential to be used as an adjunct to antiviral therapy for the treatment of IAV infection.


Assuntos
Antivirais/farmacologia , Medicamentos de Ervas Chinesas/química , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H9N2/efeitos dos fármacos , Polissacarídeos/farmacologia , Receptor 3 Toll-Like/antagonistas & inibidores , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antivirais/isolamento & purificação , Brônquios/citologia , Brônquios/efeitos dos fármacos , Brônquios/imunologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CCL5/genética , Quimiocina CCL5/imunologia , Quimiocina CXCL9/genética , Quimiocina CXCL9/imunologia , Galinhas , Cães , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Regulação da Expressão Gênica , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza A Subtipo H9N2/imunologia , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Células Madin Darby de Rim Canino , Polissacarídeos/isolamento & purificação , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Receptor 3 Toll-Like/genética , Receptor 3 Toll-Like/imunologia , Zigoto/virologia
20.
J Oral Maxillofac Surg ; 75(5): 1071-1080, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27875710

RESUMO

PURPOSE: Postoperative parotid fistula can occur after partial parotidectomy, which is a routine surgical procedure during neck dissection of oral cancers arising from or close to the oropharyngeal area. The aim of this study was to evaluate the reliability of vascularized fascia lata for the prevention of postoperative parotid fistula after neck dissection. MATERIALS AND METHODS: A retrospective review was conducted of patients with oral cancer who underwent ablative resection involving the parotid tail and reconstruction using the anterolateral thigh (ALT) flap with a vascularized fascia lata paddle. The vascularized fascia lata paddle was used to seal off the parotid stump by tightly suturing the edges of the fascia lata and parotid wound together. RESULTS: Twenty-three patients (18 men and 5 women) with primary oral cancer arising from or close to the oropharyngeal area were enrolled. The mean area of parotid defect was 16.7 cm2 and the mean area of fascia lata harvested was 21.8 cm2. All flaps survived. Pressure dressing or anticholinergic drugs were not used in any case. During the follow-up period, there was no clinical evidence of the development of parotid fistula. CONCLUSION: The vascularized fascia lata paddle is a reliable option for the prevention of postoperative parotid fistula after neck dissection of oral cancer.


Assuntos
Fascia Lata/irrigação sanguínea , Fístula/prevenção & controle , Cuidados Intraoperatórios , Esvaziamento Cervical , Doenças Parotídeas/prevenção & controle , Glândula Parótida/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Retalhos Cirúrgicos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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