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1.
Funct Integr Genomics ; 24(5): 150, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39222264

RESUMO

MicroRNAs (miRNAs) are a group of small non-coding RNAs and play an important role in controlling vital biological processes, including cell cycle control, apoptosis, metabolism, and development and differentiation, which lead to various diseases such as neurological, metabolic disorders, and cancer. Chemotherapy consider as gold treatment approaches for cancer patients. However, chemotherapeutic is one of the main challenges in cancer management. Doxorubicin (DOX) is an anti-cancer drug that interferes with the growth and spread of cancer cells. DOX is used to treat various types of cancer, including breast, nervous tissue, bladder, stomach, ovary, thyroid, lung, bone, muscle, joint and soft tissue cancers. Also recently, miRNAs have been identified as master regulators of specific genes responsible for the mechanisms that initiate chemical resistance. miRNAs have a regulatory effect on chemotherapy resistance through the regulation of apoptosis process. Also, the effect of miRNAs p53 gene as a key tumor suppressor was confirmed via studies. miRNAs can affect main biological pathways include PI3K pathway. This review aimed to present the current understanding of the mechanisms and effects of miRNAs on apoptosis, p53 and PTEN/PI3K/Akt signaling pathway related to DOX resistance.


Assuntos
Doxorrubicina , Resistencia a Medicamentos Antineoplásicos , MicroRNAs , Neoplasias , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias/genética , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Apoptose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genética , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Animais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética
2.
Cancer Cell Int ; 24(1): 233, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965615

RESUMO

MicroRNAs (miRNAs) are small RNA molecules that regulate genes and are involved in various biological processes, including cancer development. Researchers have been exploring the potential of miRNAs as therapeutic agents in cancer treatment. Specifically, targeting the mammalian target of the rapamycin (mTOR) pathway with miRNAs has shown promise in improving the effectiveness of radiotherapy (RT), a common cancer treatment. This review provides an overview of the current understanding of miRNAs targeting mTOR as therapeutic agents to enhance RT outcomes in cancer patients. It emphasizes the importance of understanding the specific miRNAs that target mTOR and their impact on radiosensitivity for personalized cancer treatment approaches. The review also discusses the role of mTOR in cell homeostasis, cell proliferation, and immune response, as well as its association with oncogenesis. It highlights the different ways in which miRNAs can potentially affect the mTOR pathway and their implications in immune-related diseases. Preclinical findings suggest that combining mTOR modulators with RT can inhibit tumor growth through anti-angiogenic and anti-vascular effects, but further research and clinical trials are needed to validate the efficacy and safety of using miRNAs targeting mTOR as therapeutic agents in combination with RT. Overall, this review provides a comprehensive understanding of the potential of miRNAs targeting mTOR to enhance RT efficacy in cancer treatment and emphasizes the need for further research to translate these findings into improved clinical outcomes.

3.
BMC Infect Dis ; 24(1): 757, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39085793

RESUMO

BACKGROUND: Understanding the factors influencing disease progression and severity in pediatric COVID-19 cases is essential for effective management and intervention strategies. This study aimed to evaluate the discriminative ability of clinical and laboratory parameters to identify predictors of COVID-19 severity and mortality in hospitalized children. METHODS: In this multicenter retrospective cohort study, we included 468 pediatric patients with COVID-19. We developed a predictive model using their demographic, clinical, and laboratory data. The performance of the model was assessed using various metrics including sensitivity, specificity, positive predictive value rates, and receiver operating characteristics (ROC). RESULTS: Our findings demonstrated strong discriminatory power, with an area under the curve (AUC) of 0.818 for severity and 0.873 for mortality prediction. Key risk factors for severe COVID-19 in children include low albumin levels, elevated C-reactive protein (CRP), lactate dehydrogenase (LDH), and underlying medical conditions. Furthermore, ROC curve analysis highlights the predictive value of CRP, LDH, and albumin, with AUC values of 0.789, 0.752, and 0.758, respectively. CONCLUSION: Our study indicates that laboratory values are valuable in predicting COVID-19 severity in children. Various factors, including CRP, LDH, and albumin levels, demonstrated statistically significant differences between patient groups, suggesting their potential as predictive markers for disease severity. Implementing predictive analyses based on these markers could aid clinicians in making informed decisions regarding patient management.


Assuntos
Proteína C-Reativa , COVID-19 , SARS-CoV-2 , Índice de Gravidade de Doença , Humanos , COVID-19/mortalidade , COVID-19/diagnóstico , COVID-19/sangue , Masculino , Feminino , Criança , Estudos Retrospectivos , Pré-Escolar , Lactente , Fatores de Risco , Proteína C-Reativa/análise , Curva ROC , Adolescente , L-Lactato Desidrogenase/sangue , Criança Hospitalizada/estatística & dados numéricos , Hospitalização/estatística & dados numéricos
4.
J Food Sci Technol ; 61(6): 1126-1137, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38562596

RESUMO

Herein, a novel voltammetry taste sensor array (VTSA) using pencil graphite electrode, screen-printed electrode, and glassy carbon electrode was used to identify heavy metals (HM) including Cad, Pb, Sn and Ni in soybean and rapeseed oils. HMs were added to edible oils at three concentrations of 0.05, 0.1 and 0.25 ppm, and then, the output of the device was classified using a chemometric classification method. According to the principal component analysis results, PG electrode explains 96% and 81% of the variance between the data in rapeseed and soybean edible oils, respectively. Additionally, the SP electrode explains 91% of the variance between the data in rapeseed and soybean oils. Moreover, the GC electrode explains 100% and 99% of the variance between the data in rapeseed and soybean edible oils, respectively. K-nearest neighbor exhibited high capability in classifying HMs in edible oils. In addition, partial least squares in the combine of VTSA shows a predict 99% in rapeseed oil. The best electrode for soybean edible oil was GC.

5.
Cell Biol Int ; 47(5): 833-847, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36571107

RESUMO

Today, cancer is one of the main health-related challenges, and in the meantime, breast cancer (BC) is one of the most common cancers among women, with an alarming number of incidences and deaths every year. For this reason, the discovery of novel and more effective approaches for the diagnosis, treatment, and monitoring of the disease are very important. In this regard, scientists are looking for diagnostic molecules to achieve the above-mentioned goals with higher accuracy and specificity. RNA interference (RNAi) is a posttranslational regulatory process mediated by microRNA intervention and small interfering RNAs. After transcription and edition, these two noncoding RNAs are integrated and activated with the RNA-induced silencing complex (RISC) and AGO2 to connect the target mRNA by their complementary sequence and suppress their translation, thus reducing the expression of their target genes. These two RNAi categories show different patterns in different BC types and stages compared to healthy cells, and hence, these molecules have high diagnostic, monitoring, and therapeutic potentials. This article aims to review the RNAi pathway and diagnostic and therapeutic potentials with a special focus on BC.


Assuntos
Neoplasias da Mama , MicroRNAs , Humanos , Feminino , Interferência de RNA , Neoplasias da Mama/genética , RNA Interferente Pequeno/metabolismo , MicroRNAs/metabolismo , Complexo de Inativação Induzido por RNA/genética , Complexo de Inativação Induzido por RNA/metabolismo
6.
Int J Clin Pract ; 2022: 1918177, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35685588

RESUMO

Objective: In this study, by using clinical and paraclinical characteristics, we have aimed to predict the severity of the disease in hospitalized COVID-19 children. Method: This cross-sectional study was conducted on medical records about epidemiologic data, underlying diseases, symptoms, and laboratory tests from March to October, 2020, on 238 hospitalized confirmed COVID-19 paediatric cases in several children's hospitals of Tehran, Ahwaz, Isfahan, and Bandar Abbas. Results: From 238 patients, 140 (59%) were male and most of them were in the age group of 1 to 5 years (34.6%). Among all hospitalized patients, 38% had an underlying disease and in total, 5% of cases were expired. Conclusion: Determining patient severity is essential for appropriate clinical decision making; our results showed that in hospitalized pediatric patients, by using several variables such as SGOT, CRP, ALC, LDH, WBC, O2sat, and ferritin, we can use clinical and paraclinical characteristics for predicting the severity of COVID-19.


Assuntos
COVID-19 , COVID-19/diagnóstico , COVID-19/epidemiologia , Criança , Criança Hospitalizada , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Irã (Geográfico)/epidemiologia , Masculino , SARS-CoV-2
7.
Cancer Cell Int ; 21(1): 470, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488747

RESUMO

Understanding the molecular mechanisms of cancer biology introduces targeted therapy as a complementary method along with other conventional therapies. Recombinant immunotoxins are tumor specific antibodies that their recognizing fragment is utilized for delivering modified toxins into tumor cells. These molecules have been considered as a targeted strategy in the treatment of human cancers. HER2 tumor biomarker is a transmembrane tyrosine kinase receptor that can be used for targeted therapies in the forms of anti-HER2 monoclonal antibodies, antibody-drug conjugates and immunotoxins. There have been many studies on HER2-based immunotoxins in recent years, however, little progress has been made in the clinical field which demanded more improvements. Here, we summarized the HER2 signaling and it's targeting using immunotherapeutic agents in human cancers. Then, we specifically reviewed anti-HER2 immunotoxins, and their strengths and drawbacks to highlight their promising clinical impact.

8.
J Cell Physiol ; 235(6): 5429-5444, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31912904

RESUMO

Due to the presence of cancer stem cells (CSCs), breast cancer often relapsed after conventional therapies. Strategies that induce differentiation of CSCs will be helpful in eradication of tumor cells, so we designed an oligodeoxynucleotide (ODNs) for targeting of signal transducer and activator of transcription 3 (STAT3) transcription factor which is involved in stemness, and constitutively activated in triple-negative breast cancer. Molecular docking and electrophoretic mobility shift assay analysis showed that decoy ODN bound specifically to the DNA binding site of STAT3 protein. The prevalent uptake of Cy3-labeled ODNs is in the cytoplasm and the nucleus of MDA-MB-231 treated cells. STAT3 decoy ODNs treatment showed cell growth inhibition by decreasing cell viability (17%), increasing the percentage of arrested cells in G0/G1 phases (18%), and triggering apoptosis (29%). Migration and invasion potential decreased from 10.77 to 6.76 µm/hr, by wound closure rate, and migrated/invaded percentage by 26.4% and 15.4% in the transwell assays, respectively. CD44 protein expression level on the cell surface also decreased, while CD24 increased. Mammosphere formation efficiency reduced in terms of tumorsphere size by 47%, while the required time increased. Cells morphology was changed, and lipid droplets were accumulated in the cytoplasm compared to the control and scrambled groups, in all assays (repeated triplicate). Furthermore, the gene expression of all downstream targets significantly decreased owing to suppressing the STAT3 transcription factor. Overall, the results confirmed the antitumor effects of STAT3 decoy in MDA-MB-231 cells. Thus, it seems that STAT3 decoy ODNs might be considered as an auxiliary tool for breast cancer eradicating by the differentiation therapy approach.


Assuntos
Neoplasias da Mama/terapia , Células-Tronco Neoplásicas/efeitos dos fármacos , Oligodesoxirribonucleotídeos/farmacologia , Fator de Transcrição STAT3/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Simulação de Acoplamento Molecular , Metástase Neoplásica , Células-Tronco Neoplásicas/patologia , Oligodesoxirribonucleotídeos/química , Proteólise , RNA Interferente Pequeno/química , RNA Interferente Pequeno/farmacologia , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/química
9.
Langmuir ; 36(34): 10175-10186, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32787026

RESUMO

Droplet impact on arbitrary inclined surfaces is of great interest for applications such as antifreezing, self-cleaning, and anti-infection. Research has been focused on texturing the surfaces to alter the contact time and rebouncing angle upon droplet impact. In this paper, using propagating surface acoustic waves (SAWs) along the inclined surfaces, we present a novel technique to modify and control key droplet impact parameters, such as impact regime, contact time, and rebouncing direction. A high-fidelity finite volume method was developed to explore the mechanisms of droplet impact on the inclined surfaces assisted by SAWs. Numerical results revealed that applying SAWs modifies the energy budget inside the liquid medium, leading to different impact behaviors. We then systematically investigated the effects of inclination angle, droplet impact velocity, SAW propagation direction, and applied SAW power on the impact dynamics and showed that by using SAWs, droplet impact on the nontextured hydrophobic and inclined surface is effectively changed from deposition to complete rebound. Moreover, the maximum contact time reduction up to ∼50% can be achieved, along with an alteration of droplet spreading and movement along the inclined surfaces. Finally, we showed that the rebouncing angle along the inclined surface could be adjusted within a wide range.

10.
Protein Expr Purif ; 174: 105650, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32360597

RESUMO

•Spy Tag-Protein covalent interaction is rapid and specific method for protein immobilization.•Column free purification of SpyCatcher protein enables develop a universal solid support for SpyTag protein purification.•This method is highly simple and applicable to other proteins.


Assuntos
Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/isolamento & purificação , Ensaio de Imunoadsorção Enzimática
11.
Cell Biol Int ; 44(12): 2499-2511, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32841450

RESUMO

Resistance to radiotherapy and chemotherapy has been a major problem of conventional cancer therapies, which consequently leads to cancer relapse and cancer-related death. It is known that cancer stem cells (CSCs) play a key role in therapy resistance and CSC-based targeted therapies have been considered as a powerful tool for cancer treatment. In the current study, we investigated the synergistic effects of suppressing signal transducer and activator of transcription (STAT3) function by decoy ODNs on X-irradiation (XI) and methotrexate (MTX) exposure as a combinational therapy in triple-negative breast cancer (TNBC) MDA-MB-231 cells. Lipofectamine 2000® was used as a transfecting agent and the cells treated with Scramble ODNs (SCR) and decoy ODNs were subjected to irradiation with 2 Gy at single/fractionated (XI group) doses, different concentration of MTX group, and X-irradiation-methotrexate (XI/MTX group). Synergistic effects of STAT3 SCR and decoy ODNs on cells were investigated by cell viability (MTT), cell cycle profile, apoptosis rate, migration, and invasion assays. Statistical analysis of obtained data showed that STAT3 decoy ODNs significantly decreased the cell viability, arrested the growth at G0/G1 phase, increased apoptosis rate, and reduced migrated and invaded cells through transwell membrane, in XI, MTX, and XI/MTX exposed groups. Since STAT3 is a master transcription factor in breast cancer cells stemness, aggressiveness, TNBC's heterogeneity, and therapy resistance; therefore, inhibition of this transcription factor by decoy ODNs could increase antitumor efficiencies of XI and MTX exposure strategies. Accordingly, this method could have the potential to increase the efficiency of combination therapies.


Assuntos
Oligodesoxirribonucleotídeos/farmacologia , Fator de Transcrição STAT3/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Células-Tronco Neoplásicas/patologia , Radiação , Fator de Transcrição STAT3/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
12.
J Electrocardiol ; 60: 15-22, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32208176

RESUMO

OBJECTIVE: The purpose of this study was to investigate the effects of 12-week of moderate-intensity aerobic exercise and 5-month detraining on electrocardiogram (ECG) indices and serum levels of 25-hydroxivitamin D (Vit D), parathyroid hormone (PTH), calcium (Ca2+), and phosphorus (P) in postmenopausal women (PMWs). MATERIALS AND METHODS: Thirty-one PMWs (aged 50-70 yrs) were randomized to exercise (EX, n = 16) and control (C, n = 15) groups. EX group performed of 12-week of warm up- walking/jogging moderate intensity aerobic exercise training program- recovery (60 min/day, 3 days/week at 70% of maximal heart rate reserve), and then 5-month detraining remained. C group maintain their normal lifestyle during 8 months. The ECG indices and cardiac serum levels were measured at baseline, after 12-week exercise, and after 5-month detraining. RESULTS: After 12-week exercise intervention, P-R interval, serum PTH and serum Vit D were significantly increased in the EX group compared to the C group (P = 0.020, P = 0.001 and P = 0.001, respectively). After 5-month detraining, P-R segment and S-T interval were significantly decreased (P = 0.042 and P = 0.001, respectively) while serum Vit D was significantly increased (P = 0.014) in the EX group compared to the C group. CONCLUSIONS: The results suggested that 12-week of moderate intensity aerobic exercise increased the P-R interval, PTH and Vit D, as severe Vit D deficiency status (below 10 ng/ml) improved to Vit D deficiency status (between 10 and 20 ng/ml) in PMWs. Also, long-term positive adaptations to aerobic exercise such as increased Vit D were observed even after 5-month detraining. In addition, P-R segment and S-T interval decreased after 5-month detraining in sedentary PMWs, which may be a sign of atrial positive adaptations to aerobic exercise.


Assuntos
Sistema Cardiovascular , Eletrocardiografia , Exercício Físico/fisiologia , Pós-Menopausa , Adaptação Fisiológica , Idoso , Biomarcadores , Feminino , Humanos , Pessoa de Meia-Idade
13.
J Cell Physiol ; 234(12): 22765-22774, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31115051

RESUMO

Expression of master transcriptional regulators of stem cells (Oct4 and Sox2) is associated with mediating tumor proliferation and tumor differentiation. The main goal of this study is the investigation of specific binding of designed Oct4-Sox2 transcription factors decoy oligodeoxynucleotides (ODNs) sequence to their nucleus-extracted proteins in HT29-ShE cells containing enriched cancer stem-like cells (SCLCs). First, gene expression of Oct4, Sox2, and E-cadherin revealed the overexpression of Oct4 and Sox2 and downregulation of E-cadherin in HT29-ShE cells compared with HT29 wild-type and HT29-ShC cells. Next, Oct4-Sox2 complex decoy ODNs were designed according to their elements in the promoter region of Sox2 gene. Then, the interactions of Oct4 and Sox2 proteins to designed ODNs were evaluated in silico. Finally, DNA-protein interactions of decoy ODNs and their corresponding proteins were examined by electrophoretic mobility shift assay (EMSA). Analysis of gel shift retardation assay admitted the specific binding of designed ODNs sequence to the nuclear extracted Oct4 and Sox2 proteins. The results will be a promising approach to target cancer stem cells for potential use in differentiation therapy before chemotherapy and radiotherapy of cancers.


Assuntos
Antineoplásicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Células-Tronco Neoplásicas/efeitos dos fármacos , Fator 3 de Transcrição de Octâmero/metabolismo , Oligodesoxirribonucleotídeos/farmacologia , Fatores de Transcrição SOXB1/metabolismo , Antígenos CD/genética , Antígenos CD/metabolismo , Antineoplásicos/metabolismo , Sítios de Ligação , Caderinas/genética , Caderinas/metabolismo , Forma Celular/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Desenho de Fármacos , Regulação Neoplásica da Expressão Gênica , Células HT29 , Humanos , Simulação de Acoplamento Molecular , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Fator 3 de Transcrição de Octâmero/genética , Oligodesoxirribonucleotídeos/genética , Oligodesoxirribonucleotídeos/metabolismo , Regiões Promotoras Genéticas , Fatores de Transcrição SOXB1/genética , Transdução de Sinais
15.
Mol Biol Rep ; 45(6): 2869-2881, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30145641

RESUMO

PTEN (Phosphatase and tensin homolog deleted on chromosome ten) is a tumor suppressor that is frequently mutated in most human cancers. PTEN is a lipid and protein phosphatase that antagonizes PI3K/AKT pathway through lipid phosphatase activity at the plasma membrane. More recent studies showed that, in addition to the putative role of PTEN as a PI(3,4,5)P3 3-phosphatase, it is a PI(3,4)P2 3-phosphatase during stimulation of class I PI3K signaling pathway by growth factor. Although PTEN tumor suppressor function via it's lipid phosphatase activity occurs primarily in the plasma membrane, it can also be found in the nucleus, in cytoplasmic organelles and extracellular space. PTEN has also shown phosphatase independent functions in the nucleus. PTEN can exit from the cell through exosomal export or secretion and has a tumor suppressor function in adjacent cells. PTEN has a critical role in growth, the cell cycle, protein synthesis, survival, DNA repair and migration. Understanding the regulation of PTEN function, activity, stability, localization and its dysregulation outcomes and also the intracellular and extracellular role of PTEN and paracrine role of PTEN-L in tumor cells as an exogenous therapeutic agent can help to improve clinical conceptualization and treatment of cancer.


Assuntos
PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Animais , Ciclo Celular/fisiologia , Núcleo Celular/enzimologia , Citoplasma/enzimologia , Genes Supressores de Tumor , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
16.
Anticancer Drugs ; 28(3): 263-270, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27861173

RESUMO

Overexpression of epidermal growth factor receptor (EGFR) plays a significant role in the development and metastasis of many solid tumors. Strategies based on anti-EGFR immunotoxins have shown promising results in several studies, but immunogenicity of antibody and toxin moieties is a limitation of this type of therapeutics. In the present study, a novel humanized anti-EGFR immunotoxin (huscFv-PE25) was developed by genetic fusing of a humanized anti-EGFR single-chain variable fragment (huscFv) with a modified Pseudomonas aeruginosa exotoxin A (PE25KDEL). The reactivity and toxicity of this immunotoxin with tumor cells were assessed by dot-blot, enzyme-linked immunosorbent assay, and MTT procedures. Results of enzyme-linked immunosorbent assay and dot-blot assay indicated that the immunotoxin recognizes and efficiently binds to EGFR-overexpressing tumor cells. MTT assay showed a specific growth-inhibitory effect of huscFv-PE25 on EGFR-overexpressing A431 cells, without any inhibitory effect on EGFR-negative cells. In conclusion, the results of this study indicated that huscFv-PE25 can recognize and exert an inhibitory effect on EGFR-overexpressing cancer cells, despite its smaller size and lower immunogenicity. This may provide a basis for the development of novel clinical therapeutic agents against EGFR-overexpressing tumor cells.


Assuntos
ADP Ribose Transferases/farmacologia , Toxinas Bacterianas/farmacologia , Receptores ErbB/imunologia , Exotoxinas/farmacologia , Imunotoxinas/química , Imunotoxinas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Fatores de Virulência/farmacologia , Células A549 , ADP Ribose Transferases/química , Animais , Toxinas Bacterianas/química , Células CHO , Linhagem Celular Tumoral , Cetuximab/farmacologia , Cricetulus , Ensaio de Imunoadsorção Enzimática , Receptores ErbB/biossíntese , Exotoxinas/química , Região Variável de Imunoglobulina/química , Região Variável de Imunoglobulina/imunologia , Imunotoxinas/imunologia , Imunotoxinas/isolamento & purificação , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/imunologia , Anticorpos de Cadeia Única/química , Anticorpos de Cadeia Única/imunologia , Neoplasias Cutâneas/enzimologia , Neoplasias Cutâneas/imunologia , Fatores de Virulência/química , Exotoxina A de Pseudomonas aeruginosa
17.
Protein Expr Purif ; 127: 8-15, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27298212

RESUMO

Various strategies have been attempted for targeting of epidermal growth factor receptor (EGFR), as an essential biomarker in a variety of cancers. Several anti-EGFR antibodies including cetuximab are used in clinics for treatment of EGFR-overexpressing colorectal and head and neck cancers but the efficiency of these antibodies is threatened by their large size and chimeric nature. Humanized single chains antibodies (huscFv) are smaller generation of antibodies with lower immunogenicity may overcome these limitations. This article reports production and evaluation of a novel humanized anti-EGFR scFv. The CDRs of cetuximab heavy and light chains were grafted onto human antibody frameworks as framework donors. To maintain the antigen binding affinity of murine antibody, the murine vernier zone residues were retained in framework regions of huscFv. Additionally, two point mutations in CDR-L1 and CDR-L3 and three point mutations in CDR-H2 and CDR-H3 loops of the humanized scFv (huscFv) were introduced to increase affinity of the huscFv to EGFR. Analysis of results demonstrated that the humanness degree of resultant huscFv was increased as 19%. HuscFv was expressed in BL21 (DE3) and affinity purified via Ni-NTA column. The reactivity of huscFv with EGFR was evaluated by ELISA and dot blot techniques. Analysis by ELISA and dot blot showed that the huscFv was able to recognize and react with EGFR. Toxicity analysis by MTT assay indicated an inhibitory effect on growth of EGFR-overexpressing A431 cells. In conclusion, the huscFv produced in this study revealed decreased immunogenicity while retained growth inhibitory effect on EGFR-overexpressing tumor cells.


Assuntos
Anticorpos Monoclonais Humanizados , Receptores ErbB/antagonistas & inibidores , Anticorpos de Cadeia Única , Animais , Anticorpos Monoclonais Humanizados/biossíntese , Anticorpos Monoclonais Humanizados/química , Anticorpos Monoclonais Humanizados/genética , Anticorpos Monoclonais Humanizados/farmacologia , Linhagem Celular Tumoral , Cetuximab/biossíntese , Cetuximab/química , Cetuximab/genética , Receptores ErbB/metabolismo , Humanos , Camundongos , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Anticorpos de Cadeia Única/biossíntese , Anticorpos de Cadeia Única/química , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/farmacologia
18.
Nat Prod Res ; : 1-7, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38907660

RESUMO

The genus of Lonicera is the largest genus of Caprifoliaceae family. This study revealed the composition, antioxidant, and antibacterial actions of essential oils of Lonicera caprifolium L. in different areas of Iran; Qom, Mashhad, Shiraz. Gas chromatography-mass spectrometry examination was applied to recognise the oil conformation. The essential oils of Qom included a high number of monoterpenes, with linalool as the significant constituent. In the essential oil of Mashhad, the main elements were methyl linoleate. The essential oil of Shiraz displayed a similar profile, including a large quantity of fatty acid, with methyl palmitate as the main component. The antioxidant activity was assessed via the DPPH exam, and the antimicrobial action was verified using the broth microdilution procedure. The essential oils of Qom revealed the maximum antimicrobial and antioxidant actions between the three regions, ascribed to its high concentration of monoterpenes and phenolic composites. Moreover, principal component analysis (PCA) and heat map successfully revealed the variation and correlation between metabolites of the three oils. These conclusions highlight the potential of L. caprifolium as natural foundations of antimicrobial and antioxidant representatives, with investigation required to reveal their therapeutic requests.

19.
Artigo em Inglês | MEDLINE | ID: mdl-39107672

RESUMO

Transdermal drug delivery provides therapeutic benefits over enteric or injection delivery because its transdermal routes provide more consistent concentrations of drug and avoid issues of drugs affecting kidneys and liver functions. Many technologies have been evaluated to enhance drug delivery through the relatively impervious epidermal layer of the skin. However, precise delivery of large hydrophilic molecules is still a great challenge even though microneedles or other energized (such as electrical, thermal, or ultrasonic) patches have been used, which are often difficult to be integrated into small wearable devices. This study developed a flexible surface acoustic wave (SAW) patch platform to facilitate transdermal delivery of macromolecules with fluorescein isothiocyanates up to 2000 kDa. Two surrogates of human skin were used to evaluate SAW based energized devices, i.e., delivering dextran through agarose gels and across stratum corneum of pig skin into the epidermis. Results showed that the 2000 kDa fluorescent molecules have been delivered up to 1.1 mm in agarose gel, and the fluorescent molecules from 4 to 2000 kDa have been delivered up to 100 µm and 25 µm in porcine skin tissue, respectively. Mechanical agitation, localised streaming, and acousto-thermal effect generated on the skin surface were identified as the main mechanisms for promoting drug transdermal transportation, although micro/nanoscale acoustic cavitation induced by SAWs could also have its contribution. SAW enhanced transdermal drug delivery is dependent on the combined effects of wave frequency and intensity, duration of applied acoustic waves, temperature, and drug molecules molecular weights.

20.
Int J Biol Macromol ; 260(Pt 2): 129633, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38253146

RESUMO

Here, mitochondria were isolated from mesenchymal stem cells (MSCs) after being treated with mitochondria-stimulating substrates, 50 µM metformin (Met), and 40 µM dichloroacetic acid (DCA). The isolated mitochondria (2 × 107 particles) were characterized and encapsulated inside 100 µl hydrogel composed of alginate (3 % w/v; Alg)/gelatin (Gel; 1 % w/v) enriched with 1 µM pyrrole (Pyr) solidified in the presence of 0.2 M FeCl3. The physicochemical properties and cytocompatibility of prepared hydrogels were assessed using FTIR, swelling, biodegradation, porosity assays, and scanning electron microscopy (SEM). The mitochondria-bearing hydrogel was injected into the ischemic area of rat hearts. FTIR absorption bands represented that the addition of FeCl3 led to polypyrrole (PPy) formation, polysaccharide oxidation, and interaction between Alg and Gel. SEM images exhibited porous structure and the size of pores was reduced in Alg/Gel + PPy group compared to Alg + PPy hydrogel. Based on the data, both Alg + PPy and Alg/Gel + PPy hydrogels can preserve the integrity and morphology of loaded mitochondria. It was noted that Alg/Gel + PPy hydrogel possessed a higher swelling ratio, degradation, and porosity compared to Alg + PPy group. Data confirmed that Alg/Gel + PPy hydrogel containing 1 µM Pyr yielded the highest survival rate compared to groups with 2 and 4 µM Pyr (p < 0.05). Injection of mitochondria-loaded Alg/Gel + PPy hydrogel yielded significant restoration of left ventricle thickness compared to the infarction, mitochondria, and Alg/Gel + PPy hydrogel groups 14 days post-injection (p < 0.05). Histological analyses revealed a significant increase of vWF+ capillaries and α-SMA+ arterioles in the mitochondria-loaded Alg/Gel + PPy hydrogel group (p < 0.05). Immunofluorescence imaging revealed the ability of rat cardiomyocytes to uptake mitochondria alone or after being loaded into Alg/Gel + PPy hydrogel. These effects were evident in the Alg/Gel + PPy group. Taken together, electroconductive Alg-based hydrogels are suitable platforms for the transplantation of cells and organelles and the regeneration of ischemic heart changes.


Assuntos
Alginatos , Cloretos , Compostos Férricos , Infarto do Miocárdio , Ratos , Animais , Alginatos/química , Polímeros/química , Hidrogéis/farmacologia , Hidrogéis/química , Angiogênese , Pirróis/química , Infarto do Miocárdio/tratamento farmacológico , Mitocôndrias
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