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1.
Int J Ophthalmol ; 16(10): 1589-1594, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37854383

RESUMO

AIM: To evaluate the effectiveness of knock-down of heat shock protein 47 (HSP47) on conjunctival bleb scarring in a rat model and its possible mechanism. METHODS: Male Sprague-Dawley rats were used for glaucoma filtration surgery (GFS) and were treated with either phosphate buffered solution, shControl, mitomycin C, or sh-HSP47 using a microsyringe immediately after GFS. The morphology of filtering blebs was observed postoperatively. The levels of HSP47 were analyzed at 2, 5, 8, and 11d after GFS via real-time quantitative polymerase chain reaction (PCR) and Western blot. The silencing effect of HSP47, the expression of collagen I and III, and the potential signaling pathways of HSP47 during scarification were explored 11d post GFS. The protein levels of transforming growth factor-ß1 (TGF-ß1), phospho-Smad2 (pSmad2), phospho-Smad3 (p-Smad3), and phospho-p38 (p-p38) were also analyzed using Western blot. RESULTS: Sh-HSP47 treatment significantly prolonged the functional filtration bleb retention. The levels of HSP47 were increased significantly at 5, 8, and 11d postoperatively compared to the control group (P<0.05, P<0.01, and P<0.001). The levels of HSP47 protein at day 11 postoperatively were significantly down-regulated after HSP47 silencing using sh-HSP47 adenovirus transfection (P<0.01). Expression levels of collagen I and III within the blebs were significantly reduced in the absence of HSP47 (P<0.01). Moreover, the protein levels of TGF-ß1, p-Smad2/3, and p-p38 were dramatically inhibited after treatment with sh-HSP47 (P<0.01). CONCLUSION: The inhibitory effects of HSP47 knock-down on scarring after GFS have the potential to be an efficacious therapeutic option for the treatment of conjunctival bleb scarring.

2.
BMC Immunol ; 24(1): 17, 2023 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-37391717

RESUMO

BACKGROUND: Primary Sjogren's Syndrome (pSS) is a lymphoproliferative disease with autoimmune characteristics, which is characterized by lymphocyte infiltration of exocrine glands and involvement and dysfunction of extraglandular organs. Renal tubular acidosis (RTA) is a common renal involvement in pSS. This study investigated the phenotypic characteristics of peripheral blood lymphocyte subsets and cytokines in pSS patients complicated with RTA (pSS-RTA). METHOD: This retrospective study included 25 pSS patients complicated with RTA and 54 pSS patients without RTA (pSS-no-RTA). To examine the level of peripheral lymphocytes subsets, flow cytometry analysis was used. The level of serum cytokines were detected by flow cytometry bead array(CBA). The influencing factors related to the occurrence of pSS-RTA were identified through logistic regression analyze. RESULTS: The absolute number of CD4 + T cells and Th2 cells in peripheral blood were decreased in pSS-RTA patients than pSS-no-RTA patients. Moreover, the absolute number of NK cells and Treg cells were also decreased in pSS-RTA patients than pSS-no-RTA. The level of serum IL-2 was higher in pSS-RTA patients than pSS-no-RTA patients, and is negatively correlated with the number of NK cells, the number and percentage of Th17 cells, and Th17/Treg. Serum IL-2 level is also correlated with various cytokines. Multivariate logistic analysis proved that elevated ESR and ALP were risk factors for pSS complicated with RTA, while Treg was a protective factor. CONCLUSION: The increase of serum IL-2 level and the decrease of peripheral blood NK cells and Treg cells may be the immune mechanism of the development of pSS-RTA disease.


Assuntos
Acidose Tubular Renal , Síndrome de Sjogren , Humanos , Interleucina-2 , Estudos Retrospectivos , Células Matadoras Naturais , Citocinas
3.
Artigo em Inglês | MEDLINE | ID: mdl-37139241

RESUMO

Objective: To explore the validation of a disease-free survival (DFS) model for predicting disease progression based on the combination of ubiquitin-conjugating enzyme E2 C (UBE2C) levels and clinical indicators in breast cancer patients. Methods: We enrolled 121 patients with breast cancer, collected their baseline characteristics and follow-up data, and analyzed the UBE2C levels in tumor tissues. We studied the relationship between UBE2C expression in tumor tissues and disease progression events of patients. We used the Kaplan-Meier method for identifying the disease-free survival rate of patients, and the multivariate Cox regression analysis to study the risk factors affecting the prognosis of patients. We sought to develop and validate a model for predicting disease progression. Results: We found that the level of expression of UBE2C could effectively distinguish the prognosis of patients. In the Receiver Operating Characteristic (ROC) curve analysis, the Area under the ROC Curve (AUC) = 0.826 (0.714-0.938) indicating that high levels of UBE2C was a high-risk factor for poor prognosis. After evaluating different models using the ROC curve, Concordance index (C-index), calibration curve, Net Reclassification Index (NRI), Integrated Discrimination Improvement Index (IDI), and other methods, we finally developed a model for the expression of Tumor-Node (TN) staging using Ki-67 and UBE2C, which had an AUC=0.870, 95% CI of 0.786-0.953. The traditional TN model had an AUC=0.717, and 95% CI of 0.581-0.853. Decision Curve Analysis (DCA) and Clinical Impact Curve (CIC) analysis indicated that the model had good clinical benefits and it was relatively simple to use. Conclusion: We found that high levels of UBE2C was a high-risk factor for poor prognosis. The use of UBE2C in addition to other breast cancer-related indicators effectively predicted the possible disease progression, thus providing a reliable basis for clinical decision-making.

4.
Front Endocrinol (Lausanne) ; 14: 1098165, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36896181

RESUMO

Purpose: Intravitreal Conbercept (IVC) has been shown to be effective in treating proliferative diabetic retinopathy (PDR) as an adjuvant in pars plana vitrectomy (PPV); however, the best timing of IVC injection remains unknown. This network meta-analysis (NMA) sought to ascertain the comparative efficacy of different timings of IVC injection as an adjuvant to PPV on PDR. Methods: A comprehensive literature search was conducted in PubMed, EMBASE, and the Cochrane Library to identify relevant studies published before August 11, 2022. According to the mean time of IVC injection before PPV, the strategy was defined as very long interval if it was > 7 days but ≤ 9 days, long interval if it was > 5 days but ≤ 7 days, mid interval if it was > 3 days but ≤ 5 days, and short interval if it was ≤ 3 days, respectively. The strategy was defined as perioperative IVC if IVC was injected both before and at the end of PPV, and the strategy was intraoperative IVC if injected immediately at the end of PPV. The mean difference (MD) and odds ratio (OR) with corresponding 95% confidence interval (CI) for continuous and binary variables, respectively, were computed through network meta-analysis using Stata 14.0 MP. Results: Eighteen studies involving 1149 patients were included. There was no statistical difference between intraoperative IVC and control in treating PDR. Except for a very long interval, preoperative IVC significantly shortened operation time, and reduced intraoperative bleeding and iatrogenic retinal breaks. Long and short intervals reduced endodiathermy application, and mid and short intervals reduced postoperative vitreous hemorrhage. Moreover, long and mid intervals improved BCVA and central macular thickness. However, very long interval was associated with an increased risk of postoperative vitreous hemorrhage (RR: 3.27, 95%CI: 1.84 to 5.83). Moreover, mid interval was better than intraoperative IVC in shortening operation time (MD: -19.74, 95%CI: -33.31 to -6.17). Conclusions: There are no discernible effects of intraoperative IVC on PDR, but preoperative IVC, except for very long interval, is an effective adjuvant to PPV for treating PDR.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Humanos , Retinopatia Diabética/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Vitrectomia , Fator A de Crescimento do Endotélio Vascular , Hemorragia Vítrea/cirurgia , Metanálise em Rede , Diabetes Mellitus/etiologia
5.
Artigo em Inglês | MEDLINE | ID: mdl-36475295

RESUMO

Objective: We have found that miR-381 can regulate the proliferation of breast cancer cells by regulating TWIST protein, it can serve as a potential marker for the tumor progression. Thus, we herein establishment and validation of a model for predicting disease progression in patients with breast cancer using a combination of microRNA-381 (miR-381) and clinical indicators. Methods: Data from 160 breast cancer patients in the First People's Hospital of Lianyungang were collected, The relationship between miR-381 expression and tumor subtype was analyzed. The Kaplan-Meier (K-M) curve method was used to investigate the disease-free survival rate, while multivariate Cox regression analysis was used to investigate the risk factors affecting the prognosis of the patients. A model for predicting disease progression was subsequently established and validated. Results: The miR-381 was significantly higher in the stage I patients than stage II/III patients. The miR-381 level of triple-negative breast cancer (TNBC) type was significantly decreased. The miR-381 could be used to effectively predict the prognosis, using cut-off value of 0.2515, with a sensitivity of 65.38% (51.8-76.85%), specificity of 75.00% (46.77-91.11%). The K-M survival curve indicated that the patients with higher miR-381 expression had a better prognosis. The miR-381+Ki-67+TN model and TN (T and N in TNM staging) model were established and subsequently compared. The TN model had an area under the curve (AUC) of 0.479 (95% CI 0.329, 0.629); in comparison, the our model had an AUC of 0.719 (95% CI 0.580, 0.857), showing better performance. Conclusion: The miR-381 expression was correlated with different (TNM) stages and tumor subtypes. The higher the TNM stage, the lower the miR-381 expression in the tumor tissue, while it was significantly decreased in TNBC. A prediction model consisting of combination of miR-381 and Ki-67 and TN indicators could predict disease progression more effectively.

6.
Front Immunol ; 13: 1012513, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36524110

RESUMO

Objective: In order to determine whether the immune balance of T helper 17(Th17)/regulatory T(Treg) is related to the pathogenesis of idiopathic retroperitoneal fibrosis (IRPF), we analyzed the differences in peripheral blood lymphocytes, CD4+T cell subsets and cytokines between patients with IRPF and healthy people to clarify the CD4+T cell subsets, especially Treg cell subsets, and the role of cytokines in the pathogenesis of IRPF. Methods: This study included 22 patients with IRPF, 36 patients with IgG4-related diseases (IgG4-RD) without retroperitoneal fibrosis (RPF), and 28 healthy controls. The absolute numbers and percentage of peripheral blood lymphocyte subsets and CD4+T cell subsets in each group were detected by flow cytometry, and the serum cytokine level was detected by flow cytometric bead array (CBA). Results: Compared with the healthy group, the absolute value of B cells in peripheral blood of IRPF patients was significantly decreased, and T, natural killer (NK), CD4+ and CD8+ were not significantly abnormal. The absolute numbers of Th2 cells were lower than healthy group(p=0.043). In particular, the absolute numbers of Treg cells were significantly lower than healthy group(p<0.001), while the absolute numbers of Th17 cells increased(p=0.682). Th17/Treg was significantly higher than healthy group (p< 0.001). Cytokine analysis showed that the level of interleukin (IL)-4 in IRPF patients was higher than healthy group(p=0.011), IL-6, IL-10, IL-17, TNF-α and IFN-γ were significantly higher than healthy group (all p<0.001). Receiver operating characteristic (ROC) curves showed that IL-10 and TNF-α could distinguish bilateral ureteral dilatation in IRPF patients, with areas under the ROC curve (AUCs) of 0.813 (95% CI:0.607-1.000, p=0.026) and 0.950 (95% CI:0.856-1.000, p=0.001), respectively. IL-6 could distinguish bilateral ureteral obstruction, with an AUC of 0.861 (95% CI: 0.682-1.000, p=0.015). Conclusions: Our study showed that IRPF patients had reduced Treg cells and indeed had Th17/Treg imbalance, which may be related to the pathogenesis of the disease. The levels of IL-6, IL-10 and TNF-α appear to be associated with the progression of IRPF.


Assuntos
Fibrose Retroperitoneal , Linfócitos T Reguladores , Humanos , Citocinas , Interleucina-10 , Interleucina-6 , Fibrose Retroperitoneal/imunologia , Fibrose Retroperitoneal/metabolismo , Linfócitos T Reguladores/metabolismo , Fator de Necrose Tumoral alfa
7.
Ophthalmic Res ; 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36315987

RESUMO

INTRODUCTION: Acute primary angle closure (APAC) is often characterized by acute elevation of intraocular pressure (IOP) accompanied by severe ocular and systemic symptoms. Excessive collagen accumulation, which can be caused by upregulated heat shock protein 47 (HSP47) expression, can produce scarring in rat conjunctival blebs. Meanwhile, the presence of HSP47 in human aqueous humor and its levels are yet to be determined. METHODS: We examined 32 consecutive patients with APAC and 16 age-matched participants without APAC scheduled for cataract surgery who were enrolled as a control group. Aqueous humor samples were collected from all subjects at the time of surgery and compared between the subjects with and without APAC. RESULTS: The levels of HSP47 in the aqueous humor of patients with APAC (1,210.4 ± 450.2 pg/mL) were found to be significantly increased (P = 0.001) compared with those in the control group (863.4 ± 240.0 pg/mL). Notably, the levels of HSP47 negatively correlated with the age of patients with APAC (P = 0.023). CONCLUSION: HSP47 was upregulated in the aqueous humor of patients with APAC and may play a role in scarring after trabeculectomy for APAC.

8.
Front Immunol ; 13: 907729, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935983

RESUMO

Objective: To search for the immunological risk factors of Psoriatic arthritis (PsA) combined with nonalcoholic fatty liver disease (NAFLD), development and assessment of predictive nomograms for NAFLD risk in patients with PsA, and to further explore the correlation between risk factors and dyslipidemia. Methds: A total of 127 patients with PsA (46 with NAFLD and 81 without NAFLD) were included in this retrospective study. The clinical and serological parameters of the patients were collected. The percentage and the absolute number of lymphocytes and CD4+T cells were determined by Flow cytometry. Univariate and multivariate binary logistic regression analysis was used to screen independent risk factors of PsA complicated with NAFLD in the model population, and a nomogram prediction model was developed and assessed. Results: (1) Univariate and multivariate logistic regression analysis of the modeling population showed that the percentage of peripheral blood T helper 1 cells (Th1%) (OR=1.12, P=0.001), body mass index (BMI) (OR=1.22, P=0.005) and triglycerides (TG) (OR=4.78, P=0.003) were independent risk factors for NAFLD in patients with PsA, which were incorporated and established a nomogram prediction model. The model has good discrimination and calibration, and also has certain clinical application value. (2) The number of peripheral blood NK cells in PsA patients was significantly positively correlated with serum triglyceride (TG) (r=0.489, P<0.001), cholesterol (CHOL) (r=0.314, P=0.003) and low-density lipoprotein (LDL) (r=0.362, P=0.001) levels. Conclusions: Our study shows that the novel NAFLD nomogram could assess the risk of NAFLD in PsA patients with good efficiency. In addition, peripheral blood NK cell levels may be associated with dyslipidemia in patients with PsA.


Assuntos
Artrite Psoriásica , Dislipidemias , Hepatopatia Gordurosa não Alcoólica , Artrite Psoriásica/complicações , Humanos , Células Matadoras Naturais , Nomogramas , Hepatopatia Gordurosa não Alcoólica/etiologia , Estudos Retrospectivos , Fatores de Risco , Triglicerídeos
9.
Front Immunol ; 13: 939057, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35979346

RESUMO

Objective: This study aimed to analyze the application value of blood metagenomic next-generation sequencing (mNGS) in patients with connective tissue diseases (CTDs) to provide a reference for infection diagnosis and guidance for treatment. Methods: A total of 126 CTD patients with suspected infections who were hospitalized in the Department of Rheumatology, the Second Hospital of Shanxi Medical University from January 2020 to December 2021 were enrolled in this study. We retrospectively reviewed the results of mNGS and conventional diagnostic tests (CDTs). Results: Systemic lupus erythematosus (SLE) and polymyositis/dermatomyositis (DM/PM) had the highest incidence of infections. The positive pathogen detection rates of mNGS were higher than those of CDT. The virus infections are the most common type in CTD patients with single or mixed infection, especially Human gammaherpesvirus 4 (EBV), Human betaherpesvirus 5 (CMV), and Human alphaherpesvirus 1. The incidence of prokaryote and eukaryote infections is secondary to viruses. Bloodstream infections of rare pathogens such as Pneumocystis jirovecii should be of concern. Meanwhile, the most common mixed infection was bacterial-virus coinfection. Conclusion: mNGS has incremental application value in patients with CTD suspected of co-infection. It has a high sensitivity, and a wide detection range for microorganisms in CTD patients. Furthermore, the high incidence of opportunistic virus infections in CTD patients should be of sufficient concern.


Assuntos
Coinfecção , Doenças do Tecido Conjuntivo , Doenças do Tecido Conjuntivo/diagnóstico , Doenças do Tecido Conjuntivo/genética , Herpesvirus Humano 4 , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Metagenômica/métodos , Estudos Retrospectivos
10.
Medicine (Baltimore) ; 101(2): e28427, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35029181

RESUMO

ABSTRACT: Volumetric-modulated arc therapy (VMAT) is a novel treatment strategy that protects normal tissues and enhances target volume coverage during radiotherapy.This study aimed to clarify whether VMAT is superior to intensity-modulated radiotherapy (IMRT) in treatment planning for left-sided breast cancer patients after modified radical mastectomy.Left-sided breast cancer patients treated with modified radical mastectomy were eligible for analysis. The dose distribution of both planning target volume and organs at risk were analyzed by using dose volume histograms.Twenty-four patients were eligible for analysis. Both VMAT and IMRT plans were sufficient in planning target volume coverage. In terms of conformity, VMAT was superior to IMRT (P = .034). Dmean, V5, and V10 of the heart were significantly decreased in VMAT plans when compared with IMRT plans. VMAT was as effective as IMRT plans in sparing of other normal tissues. In addition, both the mean number of monitor units and treatment time were significantly reduced when VMAT was compared with IMRT.VMAT plans was equivalent or superior to IMRT plans in dose distribution, and was associated with slightly advantage in sparing of the heart and coronary arteries. Our analyses suggested VMAT as a preferred option in left-sided breast cancer patients treated with modified radical mastectomy.


Assuntos
Radioterapia de Intensidade Modulada , Neoplasias Unilaterais da Mama , Feminino , Humanos , Mastectomia Radical Modificada , Órgãos em Risco , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Neoplasias Unilaterais da Mama/radioterapia , Neoplasias Unilaterais da Mama/cirurgia
11.
Bioengineered ; 13(1): 1335-1345, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34983296

RESUMO

Homeodomain­containing gene 10 (HOXC10) has been identified as an oncogene in various malignancies. Nevertheless, the role and function of HOXC10 in breast cancer (BC) remain unclear. RT-qPCR and Western blot were used to detect the mRNA and protein levels of genes, respectively. CCK-8, transwell, and TUNEL assays were performed to evaluate cell viability, invasion, migration, and apoptosis of BC cells in vitro. The xenograft model was established to examine the effect of HOXC10 on tumor growth in vivo. Our results indicated that HOXC10 expression was increased in BC and correlated with an unsatisfactory prognosis. Functional assays indicated that HOXC10 overexpression promoted cell proliferation and metastasis, and suppressed cell apoptosis of BC, while HOXC10 knockdown showed opposite trends. Furthermore, in vitro and in vivo assays uncovered that HOXC10 promoted the tumorigenesis of BC via the activation of IL-6/JAK2/STAT3 signaling. Overall, our study revealed that HOXC10 could function as a tumor promotor in BC by upregulating IL-6 levels to activate the JAK2/STAT3 signaling pathway.


Assuntos
Neoplasias da Mama/patologia , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Interleucina-6/metabolismo , Janus Quinase 2/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Apoptose , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Camundongos , Estadiamento de Neoplasias , Transplante de Neoplasias , Prognóstico , Transdução de Sinais , Regulação para Cima
12.
Am J Transl Res ; 13(11): 12763-12774, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956491

RESUMO

Recent studies have shown that the expression level of PD-L1 in tumor cells positively correlates with tumor metastasis and recurrence rate. The effects of post-translational modifications (PTMs) of PD-L1 are related to immunosuppression. However, the degradation of PD-L1 in cancers has not yet been sufficiently defined. Here, we identified USP21 as a novel deubiquitinase of PD-L1. Overexpression of USP21 significantly increased PD-L1 abundance while its knockdown induced PD-L1 degradation. In vitro deubiquitination assay revealed that USP21-WT, but not USP21-C221A, reduced polyubiquitin chains of PD-L1. These results highlight the role of USP21 in the deubiquitination and stabilization of PD-L1. Furthermore, we show that USP21 is the frequently amplified deubiquitinase in lung cancer, especially in lung squamous cell carcinoma, and its amplification is accompanied by upregulation of PD-L1. This study reveals the mechanism of USP21-mediated PD-L1 degradation, and suggests that USP21 might be a potential target for the treatment of lung cancer.

13.
Nat Commun ; 12(1): 2346, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879767

RESUMO

Cancer expression of PD-L1 suppresses anti-tumor immunity. PD-L1 has emerged as a remarkable therapeutic target. However, the regulation of PD-L1 degradation is not understood. Here, we identify several compounds as inducers of PD-L1 degradation using a high-throughput drug screen. We find EGFR inhibitors promote PD-L1 ubiquitination and proteasomal degradation following GSK3α-mediated phosphorylation of Ser279/Ser283. We identify ARIH1 as the E3 ubiquitin ligase responsible for targeting PD-L1 to degradation. Overexpression of ARIH1 suppresses tumor growth and promotes cytotoxic T cell activation in wild-type, but not in immunocompromised mice, highlighting the role of ARIH1 in anti-tumor immunity. Moreover, combining EGFR inhibitor ES-072 with anti-CTLA4 immunotherapy results in an additive effect on both tumor growth and cytotoxic T cell activation. Our results delineate a mechanism of PD-L1 degradation and cancer escape from immunity via EGFR-GSK3α-ARIH1 signaling and suggest GSK3α and ARIH1 might be potential drug targets to boost anti-tumor immunity and enhance immunotherapies.


Assuntos
Antígeno B7-H1/metabolismo , Neoplasias/imunologia , Neoplasias/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Antígeno B7-H1/química , Antígeno CTLA-4/antagonistas & inibidores , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Feminino , Quinase 3 da Glicogênio Sintase/metabolismo , Células HEK293 , Ensaios de Triagem em Larga Escala , Humanos , Imunoterapia/métodos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Modelos Biológicos , Neoplasias/terapia , Fosforilação , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Transdução de Sinais , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Evasão Tumoral/fisiologia , Células U937 , Ubiquitinação/efeitos dos fármacos
14.
Onco Targets Ther ; 13: 10441-10446, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116623

RESUMO

Disulfiram (DSF), also known as "Antabuse", has been widely used in clinical practice to treat alcoholism. In the past decades, both in vivo and in vitro experiments showed that DSF has strong anti-cancer activity, there were some clinical studies indicated the administration of this drug was associated with favorable survival in breast cancer. It is also evident that DSF has a radioprotective effect on normal cells and could be utilized during the course of radiation therapy. Moreover, increasing evidences demonstrated the role of DSF in enhancing the radiosensitivity of tumor cells in number of alternative mechanisms. Recent studies have also elaborated the anticancer mechanism of DSF in tumor cells. This review summarizes the anticancer activity of DSF both in preclinical studies and clinical trials, focuses on the advances of this drug in radiobiology and the treatment of breast cancer, and reveals the promising of repurposing DSF as a novel radiosensitizer and radioprotector in further clinical trials.

15.
J Mater Chem B ; 8(13): 2673-2688, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32147674

RESUMO

An effective treatment for spinal cord injury (SCI) remains a severe clinical challenge due to the intrinsically limited regenerative capacity and complex anatomical structure of the spinal cord. The combination of biomaterials, which serve as scaffolds for axonal growth, cells and neurotrophic factors, is an excellent candidate for spinal cord regeneration. Herein, a new micropatterned conductive electrospun nanofiber mesh was constructed with poly{[aniline tetramer methacrylamide]-co-[dopamine methacrylamide]-co-[poly(ethylene glycol) methyl ether methacrylate]}/PCL (PCAT) using a rotation electrospinning technology. The aim was to study the synergistic effects of electrical stimulation (ES) and a micropatterned conductive electrospun nanofiber mesh incorporated with nerve growth factor (NGF) on the differentiation of rat nerve stem cells (NSCs). The hydrophilicity of the conductive nanofiber mesh could be tailored by changing the dopamine (DA) and aniline tetramer (AT) content from 19° to 79°. A favorable electroactivity and conductivity was achieved by the AT segment of PCAT. The as-fabricated micropatterned electrospun nanofiber mesh possessed a regularly aligned valley and ridge structure, and the diameter of the nanofiber was 312 ± 58 nm, while the width of the valley and ridge was measured to be 210 ± 17 µm and 200 ± 16 µm, respectively. The growth and neurite outgrowth of differentiated NSCs were observed along the valley of the micropatterned nanofiber mesh. In addition, the NGF loaded micropatterned conductive electrospun nanofiber mesh combined with ES exhibited the highest cell viability, and effectively facilitated the differentiation of NSCs into neurons and suppressed the formation of astrocytes, thus exhibiting a great application potential for nerve tissue engineering.


Assuntos
Nanofibras/química , Regeneração Nervosa , Células-Tronco Neurais/citologia , Engenharia Tecidual , Alicerces Teciduais/química , Animais , Adesão Celular , Diferenciação Celular , Células Cultivadas , Condutividade Elétrica , Estimulação Elétrica , Camundongos , Estrutura Molecular , Células NIH 3T3 , Fator de Crescimento Neural/química , Células PC12 , Tamanho da Partícula , Polímeros/química , Ratos , Propriedades de Superfície
16.
ACS Biomater Sci Eng ; 6(1): 634-646, 2020 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33463207

RESUMO

Electrically conducting polymers have been emerging as intelligent bioactive materials for regulating cell behaviors and bone tissue regeneration. Additionally, poor adhesion between conventional implants and native bone tissue may lead to displacement, local inflammation, and unnecessary secondary surgery. Thus, a conductive bioadhesive with strong adhesion performance provides an effective approach to fulfill fixation and regeneration of comminuted bone fracture. Inspired by mussel chemistry, we designed the conductive copolymers poly{[aniline tetramer methacrylamide]-co-[dopamine methacrylamide]-co-[poly(ethylene glycol) methyl ether methacrylate]} [poly(ATMA-co-DOPAMA-co-PEGMA); AT:conductive aniline tetramer; DOPA:dopamine; PEG:poly(ethylene glycol))] with AT content 3.0, 6.0, and 9.0 mol %, respectively. The adhesive strength of this copolymer was enhanced during tensile process perhaps due to the synergistic effects of H-bonding, π-π interactions, and polymer long-chain entanglement, reaching up to 1.28 MPa with 6 mol % AT. Biological characterizations of preosteoblasts indicated that the bioadhesives exhibited desirable biocompatibility. In addition, the osteogenic differentiation was synergistically enhanced by the conductive substrate and electrical stimulation with a square wave, frequency of 100 Hz, 50% duty cycle, and electrical potential of 500 mV, as indicated by ALP activity, calcium deposition, and expression of osteogenic genes. The ALP activity at 14 days and calcium deposition at 28 days on the 9 mol % AT group were significantly higher than that on PLGA under electrical stimulation. The expression value of OPN for 9 mol % AT group was notably upregulated by 5.9-fold compared with PLGA at 7 days under electrical stimulation. Overall, the conductive polymers with strong adhesion can synergistically upregulate the cellular activity combining with electrical stimulation and might be a promising bioadhesive for orthopedic and dental applications.


Assuntos
Adesivos , Engenharia Tecidual , Compostos de Anilina , Osso e Ossos , Osteogênese , Polímeros
17.
Macromol Biosci ; 19(10): e1900147, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31486250

RESUMO

Conducting polymers (CPs) is one of intelligent biomaterials with the specific properties of reversible redox states, which have a significant effects on the cell behaviors and nerve tissue regeneration. However, the effects of CPs with different electrical conductivity on the behaviors of nerve cells are rarely reported. Therefore, a kind of Poly(3-hexylthiophene) (P3HT) with certain molecular weight is synthesized by Kumada catalyst transfer polymerization (KCTP) method and employed to prepare bioabsorbable and electroactive intelligent composites of Poly(3-hexylthiophene)/Poly(glycolide-lactide) (P3HT/PLGA). FeCl3 doping electroactive membranes with different electrical conductivities are prepared to investigate the cell behaviors. On the substrate with higher electrical conductivity, the proliferation of rat adrenal pheochromocytoma cells (PC12 cells) is significantly promoted and neurite length is increased obviously. In particular, the most significant improvements are the neuron gene expression of Synapsin 1 and microtubule-associated protein 2 (MAP2) by the composites with high conductivity. These results suggest that P3HT/PLGA with suitable electrical conductivity have a positive role in promoting neural growth and differentiation, which is promising for advancing potential application of nerve repair and regeneration.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Cloretos , Compostos Férricos , Regeneração Nervosa , Tecido Nervoso/metabolismo , Neurônios/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Engenharia Tecidual , Animais , Cloretos/química , Cloretos/farmacologia , Condutividade Elétrica , Compostos Férricos/química , Compostos Férricos/farmacologia , Tecido Nervoso/citologia , Neurônios/citologia , Células PC12 , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia , Ratos
18.
Case Rep Endocrinol ; 2018: 7618456, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29515923

RESUMO

An 18-year-old female diagnosed finally as PTC with intrathyroid spread was reported, and the diagnosis and surgical treatment of internal spreading of PTC were discussed. One lump was found on the thyroid isthmus by physical examination and B ultrasound, and multiple nodular shadows were found by CT. This patient finally underwent total thyroidectomy with bilateral central node dissection due to multifocal papillary thyroid carcinoma except PTC in the isthmus found in right lobe by intraoperative frozen section. The pathological section showed a major thyroid carcinoma in thyroid isthmus with scattered micropapillary carcinoma around it in the whole thyroid gland. The small lesions are distributed around central lesion in a radial form and the number of small lesions decreases with increased distance from central lesion. PTC with internal spread should be distinguished from multifocal PTC and poorly differentiated PTC in pathology. Thyroid cancerous node had a large diameter; it was likely to have internal spread. Combined imaging before surgery should be valued to diagnose PTC with internal spread. Preoperative CT and intraoperative frozen section are helpful for surgical volume selection of PTC with internal spread.

19.
Mol Clin Oncol ; 7(2): 221-224, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28781789

RESUMO

Breast metastasis is extremely unusual in gastric cancer patients worldwide. We herein report the case of a 39-year-old female Chinese patient presenting with symptoms of inflammation in the left breast. A biopsy did not reveal any evidence of malignancy. A modified radical mastectomy was performed and the postoperative pathological examination revealed infiltration by signet ring cell gastric carcinoma. A review of the Chinese literature was performed, and a total of 16 patients with breast metastasis from gastric carcinoma have been reported from 1990 onwards. This condition is associated with a poor prognosis, with a survival time of 1 month to 4 years. More studies are required to determine the optimal treatment.

20.
Int J Nanomedicine ; 11: 1819-33, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27199557

RESUMO

Two-dimensional MoS2 nanosheet has been extensively explored as a photothermal agent for tumor regression; however, its surface modification remains a great challenge. Herein, as an alternative to surface polyethylene glycol modification (PEGylation), a facile approach based on "thin-film" strategy has been proposed for the first time to produce soybean phospholipid-encapsulated MoS2 (SP-MoS2) nanosheets. By simply vacuum-treating MoS2 nanosheets/soybean phospholipid/chloroform dispersion in a rotary evaporator, SP-MoS2 nanosheet was successfully constructed. Owing to the steric hindrance of polymer chains, the surface-coated soybean phospholipid endowed MoS2 nanosheets with excellent colloidal stability. Without showing detectable in vitro and in vivo hemolysis, coagulation, and cyto-/histotoxicity, the constructed SP-MoS2 nanosheets showed good photothermal conversion performance and photothermal stability. SP-MoS2 nanosheet was shown to be a promising platform for in vitro and in vivo breast tumor photothermal therapy. The produced SP-MoS2 nanosheets featured low cost, simple fabrication, and good in vivo hemo-/histocompatibility and hold promising potential for future clinical tumor therapy.


Assuntos
Dissulfetos/síntese química , Glycine max/química , Hipertermia Induzida/métodos , Neoplasias Mamárias Animais/terapia , Nanopartículas/química , Fosfolipídeos/química , Fototerapia/métodos , Animais , Coagulação Sanguínea , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Hemólise , Humanos , Imuno-Histoquímica , Neoplasias Mamárias Animais/patologia , Teste de Materiais , Camundongos Endogâmicos BALB C , Camundongos Nus , Molibdênio , Indução de Remissão
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