Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 31
Filtrar
Mais filtros

Base de dados
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Trends Analyt Chem ; 143: 116342, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34602681

RESUMO

There have been many efforts to synthesize advanced materials that are capable of real-time specific recognition of a molecular target, and allow the quantification of a variety of biomolecules. Scaffold materials have a porous structure, with a high surface area and their intrinsic nanocavities can accommodate cells and macromolecules. The three-dimensional structure (3D) of scaffolds serves not only as a fibrous structure for cell adhesion and growth in tissue engineering, but can also provide the controlled release of drugs and other molecules for biomedical applications. There has been a limited number of reports on the use of scaffold materials in biomedical sensing applications. This review highlights the potential of scaffold materials in the improvement of sensing platforms and summarizes the progress in the application of novel scaffold-based materials as sensor, and discusses their advantages and limitations. Furthermore, the influence of the scaffold materials on the monitoring of infectious diseases such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and bacterial infections, was reviewed.

2.
J Cell Physiol ; 234(11): 19393-19405, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31004363

RESUMO

The prevalence of diabetes mellitus is increasing all over the world and it is apparent that treatment of diabetic complications has the same importance as primary diabetes treatment and glycemic control. Diabetic complications occur as a result of prolonged hyperglycemia and its consequences, such as advanced glycation end products and reactive oxygen species. Impairment of lipid profile is also contributed to worsening diabetic complications. Therefore, it seems that the application of lipid-lowering agents may have positive effects on reversing diabetic complications besides glycemic control. Statins, a group of lipid-lowering compounds, have been shown to exert antioxidant, immunomodulatory, anti-inflammatory, and antiproliferative properties beyond their lipid-lowering effects. Furthermore, they have been reported to improve diabetic complications with different pathways. In this review, we will discuss the clinical importance, molecular biology of the most important microvascular/macrovascular diabetic complications, possible application of statins and their mechanism of action in retarding these complications.


Assuntos
Complicações do Diabetes/tratamento farmacológico , Hidroximetilglutaril-CoA Redutases/genética , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperglicemia/tratamento farmacológico , Complicações do Diabetes/metabolismo , Complicações do Diabetes/patologia , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Hidroximetilglutaril-CoA Redutases/metabolismo , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/genética , Espécies Reativas de Oxigênio/metabolismo
3.
J Cell Physiol ; 234(8): 12267-12277, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30697727

RESUMO

Clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRISPR-Cas9) is an RNA-guided gene editing tool which offers several advantageous characteristics in comparison with the conventional methods (e.g., zinc finger nucleases and transcription activator-like effector nucleases) such as cost-effectiveness, flexibility, and being easy-to-use. Despite some limitations such as efficient delivery and safety, CRISPR-Cas9 is still the most convenient tool for gene editing purposes. Due to the potential capability of the CRISPR-Cas9 system in genome editing and correction of casual mutations, it can be considered as a possible therapeutic system in the treatment of disorders associated with the genome mutations and in particular cancer treatment. In this review, we will discuss CRISPR-Cas-based gene editing along with its classifications and mechanism of action. Furthermore, the therapeutic application of the CRISPR-Cas9 system in mutational disorders, delivery systems, as well as its advantages and limitations with a special emphasis on cancer treatment will be discussed.


Assuntos
Sistemas CRISPR-Cas/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Edição de Genes/métodos , Terapia Genética/métodos , Neoplasias/terapia , Marcação de Genes/métodos , Humanos , Neoplasias/genética , Interferência de RNA
4.
J Cell Biochem ; 120(9): 15719-15729, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31087712

RESUMO

Overcoming multidrug resistance (MDR) is a final goal of various recent studies, in which combination of different compounds and conventional chemotherapeutics results in circumventing MDR and hence cancer progression. Therefore, we aimed to investigate the effects of peroxisome proliferator-activated receptors (PPARs)-γ on MDR in doxorubicin-resistant human myelogenous leukemia cells. The effect of doxorubicin on cell viability following treatment with ciglitazone was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The activity of P-glycoprotein (P-gp), as one of the membrane transporters, was determined by the rhodamine 123 (Rho 123) assay. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot were used for the measurement of P-gp, and tensin homolog deleted on chromosome ten (PTEN) expression at mRNA and protein, respectively. For evaluation of doxorubicin (DOX)-induced apoptosis by annexin V/PI staining was used. Ciglitazone significantly increases the cytotoxic effects of DOX. In addition, ciglitazone considerably decreased the expression levels and activity of P-gp in DOX-resistant K562 cells. Furthermore, upon the ciglitazone treatment, PTEN expression could be increased in K562/DOX cells in a PPARγ-dependent manner. Moreover, ciglitazone significantly enhanced DOX-induced apoptosis in K562/DOX cells. The combination treatment of K562/DOX leukemia cancer cells with doxorubicin and ciglitazone might be an effective strategy in inducing apoptosis and reversing developed MDR, and more importantly decreasing the adverse side effects of these agents.


Assuntos
Doxorrubicina/farmacologia , Leucemia Mieloide/metabolismo , PTEN Fosfo-Hidrolase/genética , Tiazolidinedionas/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Células K562 , Leucemia Mieloide/tratamento farmacológico , Leucemia Mieloide/genética , PPAR gama/metabolismo , PTEN Fosfo-Hidrolase/metabolismo
5.
Pharm Res ; 36(5): 68, 2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-30887127

RESUMO

PURPOSE: Chemotherapy as an important tool for cancer treatment faces many obstacles such as multidrug resistance and adverse toxic effects on healthy tissues. Drug delivery systems have opened a new window to overcome these problems. METHODS: A polyelectrolyte carboxymethyl cellulose polymer as a magnetic nanocarrier was synthesized for enhancing delivery and uptake of doxorubicin in MCF7 breast cancer cells and decreasing the adverse toxic effects to healthy tissues. RESULTS: The physicochemical properties of developed nanocarrier showed that it can be used in drug delivery purposes. The efficiency of the delivery system was assessed by loading and release studies. Besides, biological assays including protein-particle interaction, hemolysis assay, cytotoxicity study, cellular uptake, and apoptosis analysis were performed. All results persuaded us to investigate the cytotoxic effects of nanocarrier in an animal model by determining the biochemical parameters attributed to organ injuries, and hematoxylin and eosin (H&E) staining for histopathological manifestations. We observed that the nanocarrier has no toxic effect on healthy tissues, while, it is capable of reducing the toxic side effects of doxorubicin by more cellular internalization. CONCLUSION: Chemical characterizations and biological studies confirmed that developed nanocarrier with permanent cationic groups of imidazolium and anionic carboxylic acid groups is an effective candidate for anticancer drug delivery.


Assuntos
Antineoplásicos/administração & dosagem , Carboximetilcelulose Sódica/química , Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Polieletrólitos/química , Animais , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Carboximetilcelulose Sódica/toxicidade , Permeabilidade da Membrana Celular , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/toxicidade , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Humanos , Células MCF-7 , Nanopartículas de Magnetita/química , Masculino , Camundongos , Tamanho da Partícula , Polieletrólitos/toxicidade , Propriedades de Superfície
6.
Pharm Res ; 35(6): 119, 2018 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-29671072

RESUMO

PURPOSE: P-glycoprotein (P-gp) mediated multidrug resistance (MDR) has been recognized as the main obstacle against successful cancer treatment. To address this problem, co-encapsulated doxorubicin (DOX) and metformin (Met) in a biodegradable polymer composed of poly(lactide-co-glycolide) (PLGA) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was prepared. We reported in our previous study that Met inhibits P-gp in DOX resistant breast cancer (MCF-7/DOX) cells. TPGS is a bioactive compound which has also been shown to inhibit P-gp, further to its pharmaceutical advantages. METHODS: The DOX/Met loaded PLGA-TPGS nanoparticles (NPs) were prepared by double emulsion method and characterized for their surface morphology, size and size distribution, and encapsulation efficiencies of drugs in NPs. RESULTS: All NPs were found to be spherical-shaped with the size distribution below 100 nm and encapsulation efficiencies were 42.26 ± 2.14% for DOX and 7.04 ± 0.52% for Met. Dual drug loaded NPs showed higher cytotoxicity and apoptosis in MCF-7/DOX cells in comparison to corresponding free drugs. The higher cytotoxicity of dual drug loaded NPs was attributed to the enhanced intracellular drug accumulation due to enhanced cellular uptake and reduced drug efflux which was obtained by combined effects of Met and TPGS in reducing cellular ATP content and inhibiting P-gp. CONCLUSION: Simultaneous delivery of DOX and Met via PLGA-TPGS NPs would be a promising approach to overcome MDR in breast cancer chemotherapy.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/administração & dosagem , Composição de Medicamentos/métodos , Metformina/administração & dosagem , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Células MCF-7 , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Vitamina E/química
7.
Tumour Biol ; 39(10): 1010428317716501, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28978268

RESUMO

Multidrug resistance in tumor cells is still a big challenge in cancer treatment. Therefore, identification ofsafe and effective multidrug resistance-reversing compounds with minimal side effects is an important approach in cancer treatment. Here, we investigated the role and potential mechanisms of peroxisome proliferator-activated receptor γ in doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells. The effect of doxorubicin on cell viability following treatment with balaglitazone, a peroxisome proliferator-activated receptor γ agonist, was evaluated using trypan blue and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Rhodamine123 assay was used to determine the activity of two common drug efflux membrane transporters P-glycoprotein and multidrug resistance protein-1. P-glycoprotein, multidrug resistance protein-1, and phosphatase and tensin homolog deleted on chromosome 10 messenger RNA/protein expression levels were measured by quantitative reverse transcription polymerase chain reaction and western blot analyses. Annexin V/fluorescein isothiocyanate assay was also employed to investigate apoptosis. We showed that balaglitazone considerably enhanced the cytotoxicity of doxorubicin. Balaglitazone also significantly downregulated P-glycoprotein expression and activity in K562/DOX cells and reduced multidrug resistance through elevation of intracellular doxorubicin in cells. Furthermore, upon balaglitazone treatment, phosphatase and tensin homolog deleted on chromosome 10 expression could be restored in K562/DOX cells in a peroxisome proliferator-activated receptor γ-dependent manner. We concluded that peroxisome proliferator-activated receptor γ agonist, balaglitazone, could reverse multidrug resistance by inducing phosphatase and tensin homolog deleted on chromosome 10 and peroxisome proliferator-activated receptor/ phosphatase and tensin homolog deleted on chromosome 10 signaling pathway. These findings suggest that targeting peroxisome proliferator-activated receptor γ might serve as an effective approach for circumventing multidrug resistance in chemotherapy of cancerous patients.


Assuntos
Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , PPAR gama/metabolismo , PTEN Fosfo-Hidrolase/biossíntese , Quinazolinas/farmacologia , Tiazolidinedionas/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Western Blotting , Sobrevivência Celular/efeitos dos fármacos , Citometria de Fluxo , Humanos , Células K562 , Reação em Cadeia da Polimerase , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima
8.
Environ Sci Pollut Res Int ; 30(13): 35757-35768, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36538225

RESUMO

Long-term exposure to ionizing radiation (IR) can cause dire health consequences even less than the dose limits. Previous biomonitoring studies have focused more on complete blood counts (CBCs), with non-coherent results. In this study, we aimed to investigate the association between exposure to IR and cytokine interleukin-6 (IL-6) along with hematological parameters in Tabriz megacity's radiation workers. In this hospital-based study, blood samples were taken from 33 radiation workers (exposed group) and 34 non-radiation workers (control group) in 4 hospitals. Absorbed radiation dose was measured by a personal film badge dosimeter in radiation workers. The studied biomarkers and all of the selected covariates were measured and analyzed using adjusted multiple linear regression models. The exposed doses for all radiation workers were under the dose limits (overall mean = 1.18 mSv/year). However, there was a significant association between exposure to ionizing radiation and IL-6 (49.78 vs 36.17; t = 2.4; p = 0.02) and eosinophils (0.17 vs 0.14; t = 2.02; p = 0.049). The difference between the mean of the other biomarkers in radiation workers was not statistically significant compared to the control group. This study demonstrated that long-term exposure to ionizing radiation, even under the dose limits, is related to a significantly increased level of some blood biomarkers (Il-6 and eosinophil) that, in turn, can cause subsequent health effects such as cancer.


Assuntos
Exposição Ocupacional , Exposição à Radiação , Interleucina-6 , Radiação Ionizante , Células Sanguíneas , Biomarcadores , Exposição Ocupacional/análise , Doses de Radiação
9.
Mol Neurobiol ; 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38057641

RESUMO

Inflammation during pregnancy may occur due to various factors. This condition, in which maternal immune system activation occurs, can affect fetal brain development and be related to neurodevelopmental diseases. MIA interacts with the fetus's brain development through maternal antibodies, cytokines, chemokines, and microglial cells. Antibodies are associated with the development of the nervous system by two mechanisms: direct binding to brain inflammatory factors and binding to brain antigens. Cytokines and chemokines have an active presence in inflammatory processes. Additionally, glial cells, defenders of the nervous system, play an essential role in synaptic modulation and neurogenesis. Maternal infections during pregnancy are the most critical factors related to MIA; however, several studies show the relation between these infections and neurodevelopmental diseases. Infection with specific viruses, such as Zika, cytomegalovirus, influenza A, and SARS-CoV-2, has revealed effects on neurodevelopment and the onset of diseases such as schizophrenia and autism. We review the relationship between maternal infections during pregnancy and their impact on neurodevelopmental processes.

10.
Iran J Pharm Res ; 21(1): e126918, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36060916

RESUMO

For the first time, nitrogen, sulfur, phosphorus, and boron-doped carbon dots (N, S, P, B-codoped CDs) were synthesized through a hydrothermal reaction. The produced CDs were utilized to develop an optical sensor to determine methotrexate (MTX) in cell lysates and patients' plasma samples. Basically, in the presence of MTX, the fluorescence emission of the CD-based probe was quenched. Under optimum conditions, a good proportional relationship was obtained between the quenched fluorescence signal and MTX concentrations from 74.9 ng/mL to 99.9 µg/mL with a limit of detection of 74.9 ng/mL. The developed nanoprobe provided a wide linear range and high accuracy and was successfully utilized in the routine therapeutic drug monitoring of MTX in plasma samples. The obtained results proposed the developed nanoprobe for the on-time and specific detection of MTX in blood samples. As another application, N, S, P, B-codoped CDs were utilized for bioimaging MCF-7 cancer cells and could be proposed as efficient bioimaging agents for tumor cells.

11.
Int J Biol Macromol ; 215: 346-367, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-35718150

RESUMO

Bone is an alive and dynamic organ that is well-differentiated and originated from mesenchymal tissues. Bone undergoes continuous remodeling during the lifetime of an individual. Although knowledge regarding bones and their disorders has been constantly growing, much attention has been devoted to effective treatments that can be used, both from materials and medical performance points of view. Polymers derived from natural sources, for example polysaccharides, are generally biocompatible and are therefore considered excellent candidates for various biomedical applications. This review outlines the development of chitosan-based biomaterials for the treatment of bone disorders including bone fracture, osteoporosis, osteoarthritis, arthritis rheumatoid, and osteosarcoma. Different examples of chitosan-based formulations in the form of gels, micro/nanoparticles, and films are discussed herein. The work also reviews recent patents and important developments related to the use of chitosan in the treatment of bone disorders. Although most of the cited research was accomplished before reaching the clinical application level, this manuscript summarizes the latest achievements within chitosan-based biomaterials used for the treatment of bone disorders and provides perspectives for future scientific activities.


Assuntos
Quitosana , Nanopartículas , Materiais Biocompatíveis/uso terapêutico , Quitosana/uso terapêutico , Nanopartículas/uso terapêutico , Polímeros , Polissacarídeos , Engenharia Tecidual
12.
Eur J Pharmacol ; 910: 174455, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34461125

RESUMO

Memantine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist that was initially indicated for the treatment of moderate to severe Alzheimer's disease. It is now also considered for a variety of other pathologies in which activation of NMDA receptors apparently contributes to the pathogenesis and progression of disease. In addition to the central nervous system (CNS), NMDA receptors can be found in non-neuronal cells and tissues that recently have become an interesting research focus. Some studies have shown that glutamate signaling plays a role in cell transformation and cancer progression. In addition, these receptors may play a role in cardiovascular disorders. In this review, we focus on the most recent findings for memantine with respect to its pharmacological effects in a range of diseases, including inflammatory disorders, cardiovascular diseases, cancer, neuropathy, as well as retinopathy.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Antagonistas de Aminoácidos Excitatórios/farmacologia , Memantina/farmacologia , Neoplasias/tratamento farmacológico , Doenças do Sistema Nervoso/tratamento farmacológico , Animais , Doenças Cardiovasculares/metabolismo , Antagonistas de Aminoácidos Excitatórios/farmacocinética , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Memantina/farmacocinética , Memantina/uso terapêutico , Neoplasias/metabolismo , Doenças do Sistema Nervoso/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/metabolismo , Doenças Retinianas/tratamento farmacológico , Doenças Retinianas/metabolismo
13.
Anal Methods ; 13(37): 4280-4289, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34591952

RESUMO

A novel strategy was developed for the detection of methotrexate (MTX) via the quenching effect of MTX on the fluorescence intensity of terbium-doped dendritic silica particles (Tb@KCC-1). The fluorescence intensity of Tb@KCC-1 can be effectively quenched by MTX at 546 nm under an excitation wavelength of 233 nm. The quenched fluorescence is proportional to the amount of MTX in both plasma and exhaled breath condensate (EBC) samples. Under the optimal conditions, the linear dynamic ranges of the developed method were 44 nM to 2.2 µM for EBC, 44 nM to 0.22 µM and 0.22-2.2 µM for plasma samples. The limit of detection (LOD) and limit of quantification (LOQ) in both plasma and EBC media are 35 and 116 nM, respectively. The developed method has the benefits of fast analysis time, simple approach, high specificity, and sensitivity for the detection of MTX in both media. This nanoprobe has been successfully utilized for the quantification of MTX in patients' plasma and spiked EBC samples, proving the applicability of the nanoprobe for MTX detection in real samples.


Assuntos
Antineoplásicos , Térbio , Humanos , Metotrexato , Dióxido de Silício , Espectrometria de Fluorescência
14.
Mater Sci Eng C Mater Biol Appl ; 121: 111691, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33579435

RESUMO

A wide variety of species, such as different ions, reactive oxygen species, and biomolecules play critical roles in many cell functions. These species are responsible for a range of cellular functions such as signaling, and disturbed levels could be involved in many diseases, such as diabetes, cancer, neurodegeneration etc. Thus, sensitive and specific detection methods for these biomarkers could be helpful for early disease detection and mechanistic investigations. New ultrasensitive sensors for detection of markers within living cells are a growing field of research. The present review provides updates in live cell-based biosensing, which have been published within the last decade. These sensors are mainly based on carbon, gold and other metals, and their physicochemical advantages and limitations are discussed. Advanced materials can be incorporated into probes for the detection of various analytes in living cells. The sensitivity is strongly influenced by the intrinsic properties of the nanomaterials as well their shape and size. The mechanisms of action and future challenges in the developments of new methods for live cell based biosensing are discussed.


Assuntos
Técnicas Biossensoriais , Nanoestruturas , Carbono , Ouro
15.
Front Immunol ; 12: 762782, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34975853

RESUMO

Coagulopathy is a frequently reported finding in the pathology of coronavirus disease 2019 (COVID-19); however, the molecular mechanism, the involved coagulation factors, and the role of regulatory proteins in homeostasis are not fully investigated. We explored the dynamic changes of nine coagulation tests in patients and controls to propose a molecular mechanism for COVID-19-associated coagulopathy. Coagulation tests including prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen (FIB), lupus anticoagulant (LAC), proteins C and S, antithrombin III (ATIII), D-dimer, and fibrin degradation products (FDPs) were performed on plasma collected from 105 individuals (35 critical patients, 35 severe patients, and 35 healthy controls). There was a statically significant difference when the results of the critical (CRT) and/or severe (SVR) group for the following tests were compared to the control (CRL) group: PTCRT (15.014) and PTSVR (13.846) (PTCRL = 13.383, p < 0.001), PTTCRT (42.923) and PTTSVR (37.8) (PTTCRL = 36.494, p < 0.001), LACCRT (49.414) and LACSVR (47.046) (LACCRL = 40.763, p < 0.001), FIBCRT (537.66) and FIBSVR (480.29) (FIBCRL = 283.57, p < 0.001), ProCCRT (85.57%) and ProCSVR (99.34%) (ProCCRL = 94.31%, p = 0.04), ProSCRT (62.91%) and ProSSVR (65.06%) (ProSCRL = 75.03%, p < 0.001), D-dimer (p < 0.0001, χ2 = 34.812), and FDP (p < 0.002, χ2 = 15.205). No significant association was found in the ATIII results in groups (ATIIICRT = 95.71% and ATIIISVR = 99.63%; ATIIICRL = 98.74%, p = 0.321). D-dimer, FIB, PT, PTT, LAC, protein S, FDP, and protein C (ordered according to p-values) have significance in the prognosis of patients. Disruptions in homeostasis in protein C (and S), VIII/VIIIa and V/Va axes, probably play a role in COVID-19-associated coagulopathy.


Assuntos
Transtornos da Coagulação Sanguínea/sangue , Testes de Coagulação Sanguínea/métodos , Coagulação Sanguínea , COVID-19/complicações , Adulto , Idoso , Transtornos da Coagulação Sanguínea/complicações , Transtornos da Coagulação Sanguínea/diagnóstico , Fatores de Coagulação Sanguínea/metabolismo , COVID-19/virologia , Feminino , Fibrina/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Homeostase , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Prognóstico , Proteína C/metabolismo , Tempo de Protrombina , SARS-CoV-2/genética , SARS-CoV-2/fisiologia
16.
Biochem Pharmacol ; 174: 113787, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31884044

RESUMO

Immunotherapy-based cancer treatment has revolutionized the era of cancer patients recuperation and it has brought a strong hope to treatment of some types of cancers. Metformin, a widely used antidiabetic drug, which has intensely been studied for its anticancer effects, is believed to have positive influences on immune responses against tumor cells. Metformin can affect metabolic pathways within cells mainly through activation of AMPK. Metabolic restriction of tumor microenvironment on effector immune cells is one of the important strategies favoring tumor cells to escape from immunogenic cell death. The metabolism of T cells has an axial role in shaping and supporting immune responses and may have an important role in anticancer immunity, suggesting that the functionality and durability of tumor-specific T cells need sufficient energy and nutrients. Energy biogenesis of tumor-specific cytotoxic T cells has become an interesting field of study and it is suggested that activation and maintenance of effector T cell responses in tumor microenvironment may occur by metabolic reprogramming of T cells. AMPK has been noticed as the main intracellular energy sensor and mitochondrial biogenesis key regulator which can control and regulate metabolic reprogramming in immune cells and increase antitumor immunity. Metabolic reprogramming of T cells to overcome metabolic restriction in tumor microenvironment, maiming effector T cell responses against tumor cells, has been noticed by several studies. Here we represent metformin, an AMPK activator, as a new candidate drug for metabolic reprogramming of tumor-specific T cells to increase the efficacy and accountability of cancer immunotherapy.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Antineoplásicos/farmacologia , Metformina/farmacologia , Neoplasias/tratamento farmacológico , Linfócitos T/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Antineoplásicos/uso terapêutico , Metabolismo Energético/efeitos dos fármacos , Humanos , Imunoterapia/métodos , Metformina/uso terapêutico , Neoplasias/imunologia , Neoplasias/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo
17.
Chem Biol Drug Des ; 95(2): 215-223, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31512406

RESUMO

Ovarian cancer is considered as one of the most lethal gynecological cancers, and cisplatin-based therapy has an important role as the first-line option for chemotherapy. Resistance to chemotherapy is the main obstacle against successful cancer chemotherapy with cisplatin. Therefore, identifying potent compositions and molecules with fewer side-effects is a big challenge to overcome cisplatin resistance. In this study, we investigated the possible mechanism and potency of sanguinarine, a plant-derived alkaloid, in human cisplatin-resistant ovarian cancer (A2780/R) cells. The effect of sanguinarine on cytotoxicity of cisplatin was determined by MTT assay. Apoptosis-inducing effect of sanguinarine alone and in combination with cisplatin was evaluated by annexin V/PI assay and DAPI staining. Intracellular glutathione (GSH) content was quantitated using GSH assay kit after treatment with sanguinarine. Results indicated that sanguinarine enhances the sensitivity of A2780/R cells to cisplatin. Apoptosis-inducing effect of cisplatin was also enhanced when combined with sanguinarine. Furthermore, sanguinarine reduced intracellular GSH content in a dose-dependent but not time-dependent manner. These findings suggest that sanguinarine could reverse cisplatin resistance in A2780/R cells through GSH reduction. Therefore, sanguinarine can be used as one of the potent adjuvants for ovarian cancer chemotherapy.


Assuntos
Antineoplásicos/farmacologia , Benzofenantridinas/farmacologia , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Glutationa/metabolismo , Isoquinolinas/farmacologia , Neoplasias Ovarianas/patologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Humanos , Neoplasias Ovarianas/metabolismo
18.
Eur J Med Chem ; 190: 112121, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32061960

RESUMO

The history, properties, and characteristics of para-sulfonato-calixarenes are described. On the one hand, the inherent antibacterial and antifungal properties against microorganisms, and on the other hand non-toxicity of these supramolecules toward human organs are analyzed. The resulting biocompatibility of para-sulfonato-calixarenes makes them potential candidates for diverse life sciences and pharmaceutical applications without significant side effects. The interactions with different drugs, the capability of drug encapsulation, delivery, and release, the formation of host-quest assemblies and inclusion complexation between para-sulfonato-calixarenes and drugs were also investigated in detail. Besides, their function in cancer treatment and their toxicity against different cancer cell lines were fully reviewed and summarized. Afterward, the capability of these macrocyclic compounds for biosensing of organic compounds, peptides and enzymes activity was highlighted. In this review, we also take a brief look at recent reports on the applications of para-sulfonato-calixarenes in fluorescence imaging and their usage as highly stable and bright probes for in vivo and in vitro imaging and sensing.


Assuntos
Materiais Biocompatíveis/farmacologia , Calixarenos/farmacologia , Ácidos Sulfônicos/farmacologia , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Materiais Biocompatíveis/química , Técnicas Biossensoriais , Calixarenos/química , Linhagem Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologia , Humanos , Imagem Óptica , Ácidos Sulfônicos/química
19.
Immunol Lett ; 220: 32-37, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31982460

RESUMO

Despite the prominent progress in understanding cancer immunosurveillance mechanisms, there are some types of problems which have been identified to hinder effective and successful immunotherapy of cancers. Such problems have been ascribed to the tumor abilities in the creation of a tolerant milieu that can impair immune responses against cancer cells. In the present study, we represent possible approaches for metabolic reprogramming of T cells in cancer immunotherapy to overcome tumor metabolic impositions on immune responses against cancer cells. Metabolic suppression of effector immune cells in tumor milieu is one of the important strategies recruited by tumor cells to escape from immunogenic cell death. We have investigated the metabolic reprogramming of T cells as a method and a possible new target for cancer immunotherapy. Synergic effects of PPAR ligands in immunotherapy of cancers on the metabolic reprogramming of T cells have been noticed by several studies as a new target of cancer immunotherapy. The current wealth of data like this promises a future scenario which the consideration of metabolic restriction in the tumor microenvironment and administration of therapeutic agents such as PPAR ligands to overcome metabolic restrictions on T cells (refreshing their functionality) may be effective and enhance the accountability and efficacy of cancer immunotherapy.


Assuntos
Imunoterapia/métodos , Neoplasias/terapia , Receptores Ativados por Proliferador de Peroxissomo/agonistas , Linfócitos T/metabolismo , Humanos , Ligantes , Microambiente Tumoral/imunologia
20.
Carbohydr Polym ; 231: 115696, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31888835

RESUMO

Wound healing is a dynamic and complex process which affects the quality of life in patients and annually causes high costs for the health system, worldwide. Polymers from natural origins such as polysaccharides have gained particular interest between researchers for wound dressing applications due to their abundance in nature, biocompatibility with human tissues, and ideal physicochemical properties. Aside from their supportive effect in wound care, polysaccharides and their derivatives can actively contribute to the healing process. Silver nanoparticles are widely used noble metal nanoparticles incorporated in wound dressings due to their low toxicity for human cells, naturally availability, and strong antimicrobial effects. In the present study, we will review the most frequently used polysaccharides in wound dressing procedure with silver or silver nanoparticles accommodated. The methods of synthesis, physicochemical properties, healing efficiencies, toxicity against human tissues, antibacterial and antifungal effects of each material will also be discussed.


Assuntos
Bandagens , Carboidratos/química , Polímeros/química , Cicatrização , Anti-Infecciosos/química , Anti-Infecciosos/uso terapêutico , Carboidratos/uso terapêutico , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Nanocompostos/química , Nanocompostos/uso terapêutico , Polímeros/uso terapêutico , Prata/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA