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1.
Anticancer Res ; 41(12): 5945-5951, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34848448

RESUMO

BACKGROUND: Melanoma is the deadliest variant of skin cancer and its incidence continues to increase. There are limited treatment options for advanced and metastatic cases of melanoma, despite advances in immunotherapy and chemotherapy. Melanoma is notorious as a radioresistant tumor. Previous studies found that phytochemicals, such as resveratrol and those found in green tea and blueberry, can sensitize various cancer cells, including melanoma, to radiotherapy. Our previous study also revealed that kiwifruit extract (KE) has antitumor activity to melanoma cells. This study was designed to expand upon our previous investigation and determine KE's potential as a radiosensitizer on CRL-11147 melanoma cancer cells and elucidate the possible mechanisms behind its potential. MATERIALS AND METHODS: Proliferation and apoptosis of CRL-11147 melanoma cells under radiation therapy (RT) plus KE versus RT alone were investigated using Proliferative cell nuclear antigen (PCNA) staining, quick cell proliferation assay, clonogenic assay, and caspase-3 activity assay. Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) were then used to investigate the mechanisms behind the observed results. RESULTS: The percentage of CRL-11147 colonies, PCNA staining intensity, and the optic density value of CRL-11147 cells decreased with RT/KE vs. RT alone. Relative caspase-3 activity was increased with RT/KE vs. RT alone. Increased expression of the anti-proliferative molecule p27 and pro-apoptotic molecule TRAILR1 correlated with the anti-tumor effect seen in the RT/KE group versus the RT alone group. CONCLUSION: KE augments radiosensitivity of CRL-11147 by up-regulating both p27 and TRAILR1 to inhibit proliferation and increase apoptosis, respectively.

2.
Front Genet ; 12: 682082, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745200

RESUMO

Background: Immune checkpoint blockers (ICBs) are increasingly being used to treat patients with advanced hepatocellular carcinoma (HCC), but only a third of these patients are sensitive to ICBs. Emerging evidence suggests that ferroptosis could be a novel target for antitumor treatment, and combined treatment with ferroptosis inducers might enhance sensitivity to immunotherapy. However, there is a lack of information on the crosstalk between ferroptosis-related lncRNAs and anti-tumor immunity. Therefore, we aim to explore prognostic value of ferroptosis-related lncRNAs and clarify potential role in ICBs of HCC. Methods: We obtained mRNA and lncRNA expression data from two independent cohorts (TCGA and GEO database). Univariate Cox, the least absolute shrinkage and selection operator (Lasso) algorithm and multivariate Cox analysis were used to construct a lncRNA signature, which was evaluated using the area under the receiver operating characteristic curve (AUC) and Kaplan-Meier curves. Tumor-infiltrating cell (TIC) profiling and the tumor immune dysfunction and exclusion (TIDE) algorithm were used to validate the signature model and immunotherapy. Finally, we adopted RT-PCR assay to evaluate the differential expression of lncRNAs in HCC tissues in our hospital. Results: The ferroptosis-related lncRNA signature included five lncRNAs, most of which were positively correlated with clinical stage and grade. The signature could stratify patients into two risk groups, with the high-risk group associated with a shorter overall survival (OS, p < 0.05) in TCGA-LIHC and GSE76427. Besides, the AUCs of the 1-, 3-, and 5-years OS were 0.772, 0.707, and 0.666, respectively. Gene set enrichment analysis (GESA) of lncRNAs revealed enrichment of oncogenic and immune-related pathways. The TIC profiling indicated a close correlation between the signature and immune cells. Furthermore, the high-risk group had a better response to immunotherapy than low-risk group. RT-PCR demonstrated these five lncRNAs were upregulated in cancerous tissue than normal tissues. Conclusions: The ferroptosis-related lncRNA signature could accurately predict the OS of HCC patients and may serve as an independent clinical factor for patients' outcomes. Ferroptosis-related lncRNAs may remodel the tumor microenvironment (TME) and affect the anti-cancer ability of ICBs, and therefore, could potentially act as an indicator for the response to immunotherapy in HCC.

3.
Med Oncol ; 39(1): 2, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34739644

RESUMO

Prostate cancer is the most common cancer among men in the USA. A peptide derived from the active site of alpha-fetoprotein (AFP), known as AFPep, has been shown to be efficacious in inhibiting breast cancer growth. The role of this derived peptide AFPep in the development of prostate cancer has yet to be studied. To investigate the role of AFPep on prostate cancer, we used the PC-3 and DU-145 cell lines. We found that through key anti-apoptosis and pro-proliferation molecules, AFPep enhances the proliferation of DU-145 prostate cancer cells. The anti-proliferative molecules p18, p21, and p27, along with the pro-apoptotic molecules Fas and Bax, were all down-regulated in DU-145 cell lines treated with AFPep. Conversely, AFPep was not found to have a proliferative effect on the PC-3 prostate cancer cell line. This finding suggests the effects of AFPep to be cell line-specific in prostate cancer. Further investigation into the effects of AFPep could lead to new areas of treating prostate cancer.

4.
BMC Health Serv Res ; 21(1): 1045, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34600531

RESUMO

BACKGROUND: To analyse the changes in curative care expenditure (CCE) associated with noncommunicable diseases (NCDs) before and after the Beijing healthcare reform, thus providing a reference for the healthcare system. METHODS: A total of 60 medical institutions were selected using multistage stratified cluster random sampling in Beijing, China. The records of approximately 100 million outpatients with NCDs in 2016-2018 were extracted. System of Health Accounts 2011 (SHA2011) was used to estimate the CCE. The segmented regression model was established to observe both the instant change and the slope change of intervention in interrupted time series analysis (ITSA). The study was conducted from December 2019 to May 2020 in Beijing, China. RESULTS: From SHA2011, we found that the CCE for outpatients with NCDs in Beijing were 58.59, 61.46 and 71.96 billion RMB in 2016, 2017 and 2018, respectively. The CCE continued to rise at all hospital levels, namely, tertiary, secondary, and community-level hospitals. However, the proportion of CCE in tertiary hospitals decreased. From ITSA, we can also conclude that the CCE showed a significant increasing trend change at the three hospital levels after the intervention. The drug proportion showed a significant decreasing trend change in secondary and tertiary hospitals. CONCLUSIONS: Beijing healthcare reform does have an impact on the CCE of NCDs.


Assuntos
Gastos em Saúde , Doenças não Transmissíveis , Pequim/epidemiologia , Reforma dos Serviços de Saúde , Humanos , Análise de Séries Temporais Interrompida , Doenças não Transmissíveis/epidemiologia , Doenças não Transmissíveis/terapia , Pacientes Ambulatoriais , Centros de Atenção Terciária
5.
Sci Rep ; 11(1): 20062, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625598

RESUMO

In this study, we investigated the effect of exenatide (EXE), a glucagon-like peptide (GLP)-1 receptor agonist, on kidney function, obesity indices, and glucose control in overweight/obese patients with type 2 diabetes mellitus (T2DM). A total of 159 overweight/obese patients with T2DM were randomized to the EXE group or insulin glargine (GLAR) control group for a total treatment period of 24 weeks. EXE intervention significantly reduced the urine albumin concentration (UAC) at week 12 and 24 endpoints (P < 0.001 at week 12 and 24). The levels of the anthropometric, glucose and lipid parameters (TG and HDL-c), and inflammation biomarkers (CRP and TNF-α) in the EXE group were improved at 12 weeks or 24 weeks, respectively. Meanwhile, a comparison between two groups showed significant changes in anthropometric parameters, glucose parameters, lipid parameters (TG and HDL-c), and Inflammation biomarkers (CRP, IL-6, and TNF-α). Serum fibroblast growth factor 21 (FGF21) was increased in the EXE group (P = 0.005) at week 24, and the change was significantly improved compared with GLAR group (P = 0.003). Correlation network analysis showed that FGF21 had a more central role in improving metabolism in the EXE group, and the change of FGF 21 was significantly negatively correlated with UAC at week 12 and week 24, respectively (r = - 0.297, P = 0.010; r = - 0.294, P = 0.012). Our results showed that EXE could help patients improve UAC, glycemic levels, and inflammatory biomarkers after a follow-up period of 24 weeks intervention. These EXE effects may be partly mediated by FGF 21, indicating that EXE is an effective and safe way to control albuminuria in overweight/obese patients with T2DM.

6.
J Nanobiotechnology ; 19(1): 344, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34706736

RESUMO

BACKGROUND: The use of magnetic nanozymes (NZs) with the ability to synchronize gas therapy through photodynamic and chemotherapy in the treatment of breast cancer has received much attention. RESULTS: Hence, in this study, we designed a bovine lactoferrin-coated iron sulfide NZs containing doxorubicin (abbreviated as: FeS-Dox@bLf NZs) by wet-chemical synthesis method. Then, the physicochemical characteristics of synthesized NZs were explored by several methods. Also, the level of Fe2+, H2S and Dox releases from FeS-Dox@Lf NZs. Also, the cytotoxic effects of FeS-Dox@Lf NZs were investigated by cellular assays. After intravenous injections of NZs and laser irradiation, significant effects of FeS-Dox@Lf NZs on mice weight and tumor status were observed. Afterwards, not only the distribution of Dox in the body was examined by fluorescent, but also the time of Fe clearance and the amount of Dox and Fe retention in vital tissues were determined. The findings confirm that FeS-Dox@Lf NZs, in addition to targeted drug distribution in tumor tissue, resulted in superior therapeutic performance compared to free Dox due to reduced Dox side effects in vital tissues, and increased level of free radicals in 4T1 cells. CONCLUSION: Overall, FeS-Dox@Lf NZs with the ability to synchronize chemotherapy and gas therapy raised hopes for more effective treatment of breast cancer.

7.
J Adv Res ; 33: 227-239, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34603792

RESUMO

Background: Because enzymes can control several metabolic pathways and regulate the production of free radicals, their simultaneous use with nanoplatforms showing protective and combinational properties is of great interest in the development of therapeutic nano-based platforms. However, enzyme immobilization on nanomaterials is not straightforward due to the toxic and unpredictable properties of nanoparticles in medical practice. Aim of review: In fact, because of the ability to load enzymes on nano-based supports and increase their renewability, scientific groups have been tempted to create potential therapeutic enzymes in this field. Therefore, this study not only pays attention to the therapeutic and diagnostic applications of diseases by enzyme-nanoparticle (NP) bio-conjugate (abbreviated as: ENB), but also considers the importance of nanoplatforms used based on their toxicity, ease of application and lack of significant adverse effects on loaded enzymes. In the following, based on the published reports, we explained that the immobilization of enzymes on polymers, inorganic metal oxide and hybrid compounds provide hopes for potential use of ENBs in medical activities. Then, the use of ENBs in bioassay activities such as paper-based or wearing biosensors and lab-on-chip/microfluidic biosensors were evaluated. Finally, this review addresses the current challenges and future perspective of ENBs in biomedical applications. Key scientific concepts of review: This literature may provide useful information regarding the application of ENBs in biosensing and therapeutic platforms.

8.
Am J Med Sci ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34534510

RESUMO

BACKGROUND: This study aims to explore the effect of mobile phone-based telemedicine management of glycemic control of type 2 diabetes mellitus (T2DM). METHODS: Patients with T2DM were followed up in Chongqing Jiulongpo District Yuzhoulu Community Health Center, and randomly divided into the telemedicine group (n=47) and the control group (n=50). The control group received regularly routine intervention. The telemedicine management group used the mobile phone to manage their health condition remotely. RESULTS: Both groups had similar baseline characteristics. After a follow-up period of 12 months intervention, the weight, body mass index, waist circumference, systolic blood pressure, body fat percentage, body fat mass, body water and muscle mass, fasting blood glucose, glycosylated hemoglobin, total costs of diabetes treatment for 1 month and the quality-of-life score were significantly improved in the telemedicine group (P<0.05). And compared with the control group, body fat composition, fasting blood glucose, glycosylated hemoglobin and the cost of change shows a significant improvement (P<0.05). Positive correlation was detected between fasting blood glucose and body composition parameters, such as body fat percentage, lean body mass and body fat mass in the telemedicine group (r=0.56, P<0.05; r=0.37, P<0.05; r=0.56, P<0.05). CONCLUSIONS: Compared with conventional intervention, the mobile phone-based telemedicine management can help patients with diabetes to improve glycemic level and quality of life.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34335816

RESUMO

Introduction: Antiviral activity is a main function of many types of traditional Chinese medicine (TCM), and they may contribute more in the process of certain viral epidemics. Therefore, based on the effectiveness and economy of TCM, we aimed to determine the situation of health economic studies about antivirals, especially the difference between TCM and non-TCM. Methods: A literature search of three databases was conducted with a time range of January 2000-December 2020, and terms related to health economics and TCM were used as key terms. QHES and CHEERS were used as quality assessment tools. Results: 203 papers were included in our research. After evaluation using QHES and CHEERS, antiviral TCM obtained an overall score of 41.37 ± 4.46/99 in QHES, compared with 48.89 ± 7.25/99 (18.18% higher than TCM) of antiviral non-TCM. Conclusion: With a statistically significant difference, the overall quality of pharmacoeconomic research about antiviral non-Chinese medicine is better than that about antiviral Chinese medicine, which may have resulted from researchers' capacities or the absence of a more suitable standard for pharmacoeconomic research. It tells that the quality of pharmacoeconomic studies about TCM still warrants improvement.

10.
J Control Release ; 338: 341-357, 2021 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-34428480

RESUMO

Microneedle arrays have recently received much attention as cancer detection and treatment platforms, because invasive injections and detection of the biopsy are not needed, and drug metabolism by the liver, as well as adverse effects of systemic drug administration, are diminished. Microneedles have been used for diagnosis, vaccination, and in targeted drug delivery of breast cancer. In this review, we summarize the recent progress in diagnosis and targeted drug delivery for breast cancer treatment, using microneedle arrays to deliver active molecules through the skin. The results not only suggest that health and well-being of patients are improved, but also that microneedle arrays can deliver anticancer compounds in a relatively noninvasive manner, based on body weight, breast tumor size, and circulation time of the drug. Moreover, microneedles could allow simultaneous loading of multiple drugs and enable controlled release, thus effectively optimizing or preventing drug-drug interactions. This review is designed to encourage the use of microneedles for diagnosis and treatment of breast cancer, by describing general properties of microneedles, materials used for construction, mechanism of action, and principal benefits. Ongoing challenges and future perspectives for the application of microneedle array systems in breast cancer detection and treatment are highlighted.


Assuntos
Neoplasias da Mama , Administração Cutânea , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Feminino , Humanos , Microinjeções , Agulhas , Pele/metabolismo
11.
Front Nutr ; 8: 651596, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34222299

RESUMO

Objective: To retrospectively investigate the comparative efficacy, safety and cost-benefits of three nutritional treatment schemes including short peptide jejunal nutrition (SPJN), whole protein jejunal nutrition (WPJN), and partial parenteral nutrition (PPN) in patients underwent esophagectomy for esophageal cancer in our hospital. This study was carried out in accordance with the conceptual framework of nutritional therapy in fast-track rehabilitation surgery. Methods: We retrospectively reviewed 305 patients who were assigned to receive esophagectomy for esophageal cancer. Eligible patients was naturally divided into SPJN group [n = 98 (32.1%)], WPJN group [n = 95 (31.1%)], and PPN group [n = 112 (36.7%)] according to the type of nutritional scheme which was actually prescribed to patients by the attendingphysician in clinical practice. The differences of the serum total protein (TP), albumin (ALB), pre-albumin (PA), hemoglobin (HGB), white blood cells (WBCs), red blood cells (RBCs) and neutrophils were compared among 3 nutritional schemes groups. We also investigated the relationship of the fluid intake, urine output, gastric juice drainage volume and thoracic drainage volume among 3 nutritional groups at 3 days after surgery. Moreover, the differences of cost-benefit indexes, complications, length of hospitalization and hospital expenditure were also compared. Results: The serum TP, ALB, and PA in the SPJN group were all higher than those in the WPJN and PPN groups (p < 0.05). The gastric juice volume of gastrointestinal decompression drainage and fluid volume of thoracic drainage in the SPJN group were all less than that in the WPJN group (p < 0.05). The overall hospital stay and post-operative hospital stay in the SPJN group were all shorter than that in WPJN group (p < 0.05). Moreover, the incidence of post-operative complications including anastomotic leakage, infection, and gastrointestinal reaction was remarkably lower in the SPJN group compared to the WPJN group (p < 0.05). Interesting, hospital expenditure in the PPN group was less than that in the SPJN and the WPJN groups (p < 0.001). Conclusion: Patients may obtain benefits in improving protein level after receiving SPJN scheme at the early stage after esophagectomy. Meanwhile, patients may obtain benefits in improving post-operative complications and hospital stay after receiving SPJN or PPN compared to WPJN protocol. However, the difference between SPJN and PPN requires further study because no difference was detected in terms of clinical outcomes including complications and the length of hospitalization although PPN may achieve a possible decrease of medical expenditure.

12.
Anticancer Res ; 41(7): 3337-3341, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230129

RESUMO

BACKGROUND/AIM: Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive type of primary brain tumor and a cornerstone in its treatment is radiotherapy (RT). However, RT for GBM is largely ineffective at clinically safe doses, thus, the study of radiosensitizers is of great significance. MATERIALS AND METHODS: With accumulating evidence for the anticancer effect of compounds from cranberry, this study was designed to investigate if cranberry extract (CE) sensitizes GBM to RT in the widely used human glioblastoma cell line U87. We utilized clonogenic survival assays, cell proliferation assays, and caspase-3 activity kits. Potential proliferative and apoptotic molecular mechanisms were evaluated by reverse transcription-polymerase chain reaction. RESULTS: We found that CE alone had little effect on the survival of U87 cells. However, RT supplemented by CE significantly inhibited proliferation and promoted apoptosis of U87 cells when compared with RT alone. The proliferation-inhibitory effect of RT/CE might be attributable to the up-regulation of p21, along with the down-regulation of cyclin B and cyclin-dependent kinase 4. This pro-apoptotic effect might additionally be attributable to the down-regulation of survivin. CONCLUSION: These results warrant further study of the potential radiosensitizing capacity of CE in glioblastoma and other cancer types.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Extratos Vegetais/farmacologia , Radiossensibilizantes/farmacologia , Vaccinium macrocarpon/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Humanos , Regulação para Cima/efeitos dos fármacos
13.
Anticancer Res ; 41(7): 3343-3348, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230130

RESUMO

BACKGROUND: Cervical cancer (CC) is one of the leading causes of mortality worldwide. Previously, we reported that blueberry extract constrains the growth of CC. Raspberry is a widely consumed fruit that exhibits antitumor properties against several cancer types but little is known about its direct effect on CC. This study was designed to investigate the potential antitumor effect of raspberry extract (RE) on CC cells and to elucidate the possible mechanisms behind it. MATERIALS AND METHODS: Clonogenic survival assay and caspase-3 activity kits were used to evaluate the effects of RE on cell survival, proliferation, and apoptosis of a widely used CC cell line, HeLa. Possible molecular mechanisms were investigated using reverse transcription-polymerase chain reaction. RESULTS: The percentage of colonies and optic density value of HeLa cells decreased in the presence of RE in comparison to controls. Relative caspase-3 activity in cancer cells increased in the presence of RE in comparison to controls. The antitumor effect displayed on HeLa cells by RE was associated with the increased expression of antiproliferative molecule P53 and the increased expression of pro-apoptotic molecule tumor necrosis factor receptor superfamily member 6 (FAS). CONCLUSION: RE displays anticancer activity against CC HeLa cells. The mechanism behind this is by up-regulation of anti-proliferative molecule P53 and pro-apoptotic molecule FAS.


Assuntos
Antineoplásicos/farmacologia , Extratos Vegetais/farmacologia , Rubus/química , Neoplasias do Colo do Útero/tratamento farmacológico , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Regulação para Cima/efeitos dos fármacos , Neoplasias do Colo do Útero/metabolismo , Receptor fas/metabolismo
14.
Neurol Res ; : 1-8, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34112057

RESUMO

Objectives: This article aimed to analyze the relationship between obesity and the efficacy of acute ischaemic stroke patients treated with IVT.Background: Stroke causes morbidity and mortality in large numbers of individuals annually. Intravenous thrombolysis (IVT)with recombinant tissue plasminogen activator (r-tPA) is currently the only approved by the FDA for treatment of acute ischaemic stroke. Researchers have focused on studying the mechanisms associated with ischaemic stroke. Obesity is an established vascular risk factor with increasing prevalence and a huge impact on public health worldwide. It is an independent predictor for ischaemic stroke with a 4% risk increase for each unit augmentation in body mass index (BMI). Therefore, obese patients will constitute an increasing subgroup of candidates for IVT. However, its impact on prognosis in acute ischaemic stroke patients with intravenous thrombolysis did not reach a consensus conclusion.Methods: Systematic literature search of PUBMED databases published before August 2020, was performed to identify studies addressing the role of obesity in acute ischaemic stroke patients treated with IVT. Studies included randomized clinical trials, observational studies, guideline statements, and review articles.Conclusions: Obesity may be related to long-term prognosis of large group of AIS patients treated with IVT. It depends on the scale of clinical study samples, follow-up time, and evaluation criteria.

15.
Cancer Lett ; 518: 94-101, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34153401

RESUMO

In recent years, tumor metabolism has become a prevalent research topic for scientists and pharmaceutical companies. As research in the field has progressed, the metabolism-based therapy of tumors has ushered in new opportunities. Most tumors emerge and evolve under selective pressure from their microenvironment, which promotes the diversification of both neoplastic and non-neoplastic compartments of the tumor microenvironment (TME), and finally reaches a certain degree of intratumoral heterogeneity. As a result of the tumor intratumoral heterogeneity, tumor cells often possess a complex energy metabolism phenotype. During tumor progression, the metabolism for both tumor parenchyma and stroma is reprogrammed. The tumor stroma mainly consists of the extracellular matrix, fibroblasts, and immune cells. Interestingly, tumor-infiltrating immune cells utilize different metabolites based on their subtype and function, and these immunometabolic pathways can be modified in the TME. In particular, interleukins play a vital role in the activation and differentiation of immune cells and have exhibited multiple effects on tumor cell neoplasia, invasion, and metastasis. In this review, we summarize the common mechanisms of interleukins affecting the tumor and tumor-infiltrating immune cells metabolically and discuss how these mechanisms may lead to novel therapeutic opportunities. This review might contribute to the novel development of cancer immunotherapy.

16.
Int J Biol Macromol ; 185: 813-820, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34186122

RESUMO

The stability of IFN-γ as a therapeutic protein can play a key role on its anticancer effects. Herein, we explored the thermodynamic parameters and conformational stability of IFN-γ in the presence of calycosin, the main active compound of Radix astragali, by different biophysical and theoretical analysis. Afterwards, the improved anticancer effects of IFN-γ-calycosin interaction relative to IFN-γ alone were assessed on hepatocellular carcinoma (HepG2) cell line by MTT and caspase assays. ITC data indicated that upon interaction of calycosin with IFN-γ the binding and thermodynamic parameters were as follows: Kd = 1.9 µM, ΔG° = -32.45 kJ/mol, ΔH° = -11.91 kJ/mol, and TΔS° = 20.54 kJ/mol. ANS/synchronous fluorescence, CD and UV-Vis spectroscopy studies indicated that the interaction between calycosin and IFN-γ caused the folding of the IFN-γ backbone in to a more packed structure with enhanced α-helix content and higher melting temperature (Tm) value. The spectroscopic outcomes were then verified by molecular docking and molecular dynamic analysis. It was also shown that after incubation of the IFN-γ samples at 50 °C for 60 min in the presence of calycosin (5 µM), the IFN-γ-calycosin system showed a significant antiproliferative effects against hepatocellular carcinoma (HepG2) cells through caspase-9/3 activation and this anticancer effect was more pronounced than free IFN-γ. This data may provide useful information about the development of IFN-γ-based therapeutic platforms.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/metabolismo , Caspase 3/metabolismo , Caspase 9/metabolismo , Interferon gama/farmacologia , Isoflavonas/química , Neoplasias Hepáticas/metabolismo , Antineoplásicos/química , Carcinoma Hepatocelular/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Estabilidade de Medicamentos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Interferon gama/química , Neoplasias Hepáticas/tratamento farmacológico , Dobramento de Proteína/efeitos dos fármacos , Termodinâmica
17.
J Mater Chem B ; 9(27): 5439-5450, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34155495

RESUMO

Nanotechnology has recently become popular due to its potential for biomedical applications, especially for cancer treatment. Nanotechnology, featuring responsiveness to stimuli and stable drug release, has been widely used for the delivery of chemotherapeutic drugs, which are commonly used in the treatment of osteosarcoma. Smart stimuli-responsive nanotechnology is expected to improve the treatment of osteosarcoma. Herein, we focus on the latest research on nanomaterials in treating osteosarcoma that respond to internal and external stimuli. We also discuss nanocarriers with targeting ligands and the use of smart nanotechnology to partially reverse the multidrug resistance of osteosarcoma.

18.
Anticancer Res ; 41(5): 2239-2245, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952450

RESUMO

BACKGROUND/AIM: This study was designed to investigate the effect of IL-39 on T24 bladder cancer (BC) cell line survival and growth. MATERIALS AND METHODS: In order to assess the direct effect of IL-39 on survival, proliferation, and apoptosis of T24 BC cells, we utilized a clonogenic survival assay, a cell proliferation assay, and caspase-3 activity kits. Potential proliferative and apoptotic molecular mechanisms were evaluated by RT-PCR. RESULTS: Treatment of T24 BC cells with IL-39 resulted in a significant reduction in the percentage of colonies. The anti-tumor effect of IL-39 on T24 bladder cancer cells correlated strongly with a decrease in cyclin E, in combination with an increase in the mRNA levels of Fas. CONCLUSION: IL-39 impedes the growth and survival of T24 BC cells by inhibiting growth and promoting apoptosis. This ability to modulate gene transcription in neoplastic cells shows promise and warrants further research in immunotherapy.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ciclina E/metabolismo , Interleucinas/farmacologia , Receptor fas/metabolismo , Apoptose/genética , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Ciclina D/genética , Ciclina D/metabolismo , Ciclina E/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptor fas/genética
19.
Front Bioeng Biotechnol ; 9: 616555, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34026739

RESUMO

Bone serves to maintain the shape of the human body due to its hard and solid nature. A loss or weakening of bone tissues, such as in case of traumatic injury, diseases (e.g., osteosarcoma), or old age, adversely affects the individuals quality of life. Although bone has the innate ability to remodel and regenerate in case of small damage or a crack, a loss of a large volume of bone in case of a traumatic injury requires the restoration of bone function by adopting different biophysical approaches and chemotherapies as well as a surgical reconstruction. Compared to the biophysical and chemotherapeutic approaches, which may cause complications and bear side effects, the surgical reconstruction involves the implantation of external materials such as ceramics, metals, and different other materials as bone substitutes. Compared to the synthetic substitutes, the use of biomaterials could be an ideal choice for bone regeneration owing to their renewability, non-toxicity, and non-immunogenicity. Among the different types of biomaterials, nanocellulose-based materials are receiving tremendous attention in the medical field during recent years, which are used for scaffolding as well as regeneration. Nanocellulose not only serves as the matrix for the deposition of bioceramics, metallic nanoparticles, polymers, and different other materials to develop bone substitutes but also serves as the drug carrier for treating osteosarcomas. This review describes the natural sources and production of nanocellulose and discusses its important properties to justify its suitability in developing scaffolds for bone and cartilage regeneration and serve as the matrix for reinforcement of different materials and as a drug carrier for treating osteosarcomas. It discusses the potential health risks, immunogenicity, and biodegradation of nanocellulose in the human body.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33981352

RESUMO

Objectives: To measure the distributed characteristics of Traditional Chinese Medicine (TCM) constitutions, as well as related factors with biased TCM constitutions among the elderly individuals in Macau. Methods: The elderly individuals from elderly healthcare centers located in Macao Peninsula, Taipa, and Coloane were selected as research samples. The basic information questionnaire and the Constitution in Chinese Medicine Questionnaire (CCMQ) for elderly were employed. Descriptive analysis was applied to illustrate demographical characteristics and TCM constitution distribution. Exploratory factor analysis (EFA) was conducted to explore potential factors influencing biased constitutions, and weight of each variable for constitution was further calculated. Results: A total of 313 participants were recruited. Eighty-six (27.48%) elderly were identified as balanced constitution; others were biased constitutions accounting for 72.52%. Distribution differences related to gender and age were identified among participants with unbalanced constitutions. Four biased constitutions were further analyzed with EFA. For qi-stagnation and yang-deficiency constitutions, three similar factors were determined in the domains of education, sleeping habits, and lifestyle behaviors, successively. Although four factors were identified in phlegm-dampness constitution, the latter two belonged to lifestyle behaviors and the former two were education and sleeping habits. For yin-deficiency constitution, education, tobacco-alcohol consumption, sleeping habits, and exercise were four dimensions of potential influential factors. Tobacco consumption, sleep, and exercise duration weighted the most for qi-stagnation constitution; sleep duration, education level, and sugar-containing beverage intake for phlegm-dampness; length of education, alcohol consumption, and education level for yang-deficiency constitution; and weekly exercise hours, sleep duration, and education level for yin-deficiency constitution. Conclusion: The prevalence rate of biased constitutions was relatively high among elderly residents in Macau. Relations between demographical and lifestyle behavioral factors and biased constitutions were identified in this study. Controlling these influential factors might be beneficial for health management of Macau elderly individuals.

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