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1.
Int J Mol Sci ; 25(6)2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38542131

RESUMO

A chemo-drug such as cisplatin is effective for cancer treatment but remains non-specific, is susceptible to drug resistance, and induces several side effects on organ systems. Zeolitic imidazolate framework-8, a type of MOF, has gained attention, including as a drug delivery method for targeted cancer therapeutics. In this study, ZIF-8/Silica nanocomposite was synthesized using a one-pot hydrothermal technique using the Stober technique. We studied the effect of phyto-synthesized GPt and chemo-drug cisplatin CPt on ZIF-8/Silica for targeted efficacy of cancer therapy. The texture, morphology, and chemical environment of Pt on ZIF-8/Silica were analyzed using different characterization techniques such as XRD, FT-IR, BET, diffuse reflectance spectroscopy, SEM-EDX, TEM, zeta potential, and TGA analysis. The isothermal behavior of CPt and GPt adsorption was investigated using isotherm models like Langmuir, Freundlich, and Temkin isotherm. The adsorption kinetics indicating the adsorption efficiency of GPt and CPt are influenced by the concentration of Pt complex and the adsorption sites of ZIF-8/Silica. A high entrapment efficiency and loading capacity of GPt (86% and 4.3%) and CPt (91% and 4.5%) were evident on ZIF-8/Silica. The nanocomposite showed a pH-sensitive Pt release using a dialysis membrane technique. For instance, a high release of GPt (93%) was observed under pH = 6.6 in 72 h, while the release reduced to 50% at pH 7.4 in 72 h. The anti-cancer activity of nanoformulations was studied in vitro using MCF7 (breast cancer cells) and HFF-1 (human foreskin fibroblast) cells. The findings demonstrated that GPt is as effective as CPt; the EC50 value for MCF7 cells treated with ZIF-8/Silica/Cp/PEG was 94.86 µg/mL, whereas for ZIF-8/Silica/GPt/PEG it was 60.19 µg/mL.


Assuntos
Antineoplásicos , Nanocompostos , Neoplasias , Zeolitas , Humanos , Cisplatino/farmacologia , Platina , Zeolitas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Dióxido de Silício/química , Antineoplásicos/farmacologia , Imidazóis/farmacologia , Imidazóis/química , Neoplasias/tratamento farmacológico
3.
Cancers (Basel) ; 15(3)2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36765654

RESUMO

In nanotherapeutics, gaining insight about the drug interaction with the pore architecture and surface functional groups of nanocarriers is crucial to aid in the development of targeted drug delivery. Manganese ferrite impregnated graphene oxide (MnFe2O4/GO) with a two-dimensional sheet and spherical silica with a three-dimensional interconnected porous structure (MnFe2O4/silica) were evaluated for cisplatin release and cytotoxic effects. Characterization studies revealed the presence of Mn2+ species with a variable spinel cubic phase and superparamagnetic effect. We used first principles calculations to study the physisorption of cisplatin on monodispersed silica and on single- and multi-layered GO. The binding energy of cisplatin on silica and single-layer GO was ~1.5 eV, while it was about double that value for the multilayer GO structure. Moreover, we treated MCF-7 (breast cancer cells) and HFF-1 (human foreskin fibroblast) with our nanocomposites and used the cell viability assay MTT. Both nanocomposites significantly reduced the cell viability. Pt4+ species of cisplatin on the spinel ferrite/silica nanocomposite had a better effect on the cytotoxic capability when compared to GO. The EC50 for MnFe2O4/silica/cisplatin and MnFe2O4/GO/cisplatin on MCF-7 was: 48.43 µg/mL and 85.36 µg/mL, respectively. The EC50 for the same conditions on HFF was: 102.92 µg/mL and 102.21 µg/mL, respectively. In addition, immunofluorescence images using c-caspase 3/7, and TEM analysis indicated that treating cells with these nanocomposites resulted in apoptosis as the major mechanism of cell death.

4.
Vasc Health Risk Manag ; 19: 1-11, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36647392

RESUMO

Background: Obesity is a global pandemic that is associated with high morbidity and mortality. Natural herbs are commonly used for weight reduction and appetite suppression. Therefore, we aim to investigate the role and mechanism of Nigella sativa (NS) and ginger on weight reduction and appetite regulation. Methods: This experimental study was performed at Imam Abdulrahman Bin Faisal University. Twenty-five female rats were distributed into 5 groups: NS (oral 1000mg/kg), Ginger (500 mg/kg), NS-ginger (both interventions), a positive control (intraperitoneal 50 µg/kg Liraglutide), and a negative control. Each intervention was given for 9 weeks. Food intake and body weight were assessed weekly. Serum lipid profile and peptides involved in appetite control (cholecystokinin (CCK), glucagon-like peptide 1(GLP-1), gastric inhibitory polypeptide (GIP), ghrelin, peptide YY, and orexin) were assayed at the end of the experiment. Results: None of the interventions showed a statistically significant difference regarding food consumption or weight gain (p > 0.05). However, the three interventions significantly reduced total cholesterol (TC), NS and NS-ginger significantly increased HDL, NS increased ghrelin and ginger increased orexin. Conclusion: The present dose and duration of NS, ginger, or in combination did not demonstrate a significant change in body weight or food consumption in comparison to the negative or positive controls. However, NS or ginger has improved the lipid profile by reducing TC and increasing HDL. In addition, NS or ginger can influence some of the peptides involved in appetite regulation such as the increase in ghrelin induced by NS and the reduction of orexin induced by ginger. We believe that these latter effects are novel and might indicate a promising effect of these natural products on appetite regulation.


Assuntos
Depressores do Apetite , Nigella sativa , Zingiber officinale , Animais , Feminino , Ratos , Apetite , Depressores do Apetite/farmacologia , Peso Corporal , Grelina/farmacologia , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Lipídeos , Orexinas/farmacologia , Ratos Wistar , Redução de Peso
5.
Medicina (Kaunas) ; 58(10)2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36295630

RESUMO

Background and Objectives: Sickle cell anemia (SCA) is a hereditary monogenic disease due to a single ß-globin gene mutation that codes for the production of sickle hemoglobin. Its phenotype is modulated by fetal hemoglobin (HbF), a product of γ-globin genes. Exploring the molecules that regulate γ-globin genes at both transcriptional and translational levels, including microRNA (miRNA), might help identify alternative therapeutic targets. Materials and Methods: Using next-generation sequencing we identified pre-miRNAs and mature miRNA expression signatures associated with different HbF levels in patients homozygous for the sickle hemoglobin gene. The involvement of identified miRNAs in potential SCD-related pathways was investigated with the DIANA TOOL and miRWalk 2.0 database. Results: miR-184 were most highly upregulated in reticulocytes. miR-3609 and miR-483-5p were most highly downregulated in sickle cell anemia with high HbF. miR-370-3p that regulates LIN28A, and miR-451a which is effective in modulating α- and ß- globin levels were also significantly upregulated. miRNA targeted gene pathway interaction identified BCL7A, BCL2L1, LIN28A, KLF6, GATA6, solute carrier family genes and ZNF genes associated with erythropoiesis, cell cycle regulation, glycosphingolipid biosynthesis, cAMP, cGMP-PKG, mTOR, MAPK and PI3K-AKT signaling pathways and cancer pathways. Conclusions: miRNA signatures and their target genes identified novel miRNAs that could regulate fetal hemoglobin production and might be exploited therapeutically.


Assuntos
Anemia Falciforme , MicroRNAs , Humanos , Hemoglobina Fetal/genética , Hemoglobina Fetal/metabolismo , gama-Globinas/genética , gama-Globinas/uso terapêutico , Hemoglobina Falciforme/uso terapêutico , Arábia Saudita , Fosfatidilinositol 3-Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-akt , Anemia Falciforme/genética , MicroRNAs/genética , MicroRNAs/uso terapêutico , Globinas beta/genética , Globinas beta/uso terapêutico , Serina-Treonina Quinases TOR/uso terapêutico , Glicoesfingolipídeos/uso terapêutico
6.
Semin Cancer Biol ; 86(Pt 2): 1056-1065, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-34843989

RESUMO

Colorectal cancer is one of the most aggressive types of cancer with about two million new cases and one million deaths in 2020. The side effects of the available chemotherapies and the possibility of developing resistance against treatment highlight the importance of developing new therapeutic options. The development in the field of nanotechnology have introduced the application of nanoparticles (NPs) as a promising approach in the diagnosis and treatments of colorectal cancer and other types of cancer. Gold nanoparticles (AuNPs) are currently one of the most studied materials as they possess unique tunable properties allowing them to play a role in colorectal cancer bioimaging, diagnosis, and therapy. The high surface-to-volume ratio of AuNPs mediates their utilization in drug delivery as well as functionalization to provide specific targeting. Moreover, depending on their physical properties (size, shape), AuNPs can be modified to fit the intended application. However, there are contradictory results around the pharmacokinetics of AuNPs including their biodistribution, clearance, and toxicity. This variation of opinions is most likely due to the development of different AuNPs that vary in shape, size, and surface chemistry, in addition to the conditions under which each research was carried out. The conflicting data represent a challenge in the clinical use of AuNPs suggesting the need to understand the toxicity, fate, and long-term exposure of AuNPs in vivo. Thus, there is an unmet need for the establishment of a publicly available data base for extensive analysis. In this review, we discuss the recent advances in AuNP applications in the treatment and diagnosis of colorectal cancer, mechanisms of action, and clinical challenges.


Assuntos
Neoplasias do Colo , Nanopartículas Metálicas , Humanos , Ouro/química , Ouro/farmacocinética , Ouro/toxicidade , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Distribuição Tecidual , Sistemas de Liberação de Medicamentos , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/tratamento farmacológico
7.
Biomed Pharmacother ; 139: 111557, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243621

RESUMO

Migraine is a neurological ailment that is characterized by severe throbbing unilateral headache and associated with nausea, photophobia, phonophobia and vomiting. A full and clear mechanism of the pathogenesis of migraine, though studied extensively, has not been established yet. The current available information indicates an intracranial network activation that culminates in the sensitization of the trigemino-vascular system, release of inflammatory markers, and initiation of meningeal-like inflammatory reaction that is sensed as headache. Genetic factors might play a significant role in deciding an individual's susceptibility to migraine. Twin studies have revealed that a single gene polymorphism can lead to migraine in individuals with a monogenic migraine disorder. In this review, we describe recent advancements in the genetics, pathophysiology, diagnosis, treatment, management, and prevention of migraine. We also discuss the potential roles of genetic and abnormal factors, including some of the metabolic triggering factors that result in migraine attacks. This review will help to accumulate current knowledge about migraine and understanding of its pathophysiology, and provides up-to-date prevention strategies.


Assuntos
Transtornos de Enxaqueca/genética , Transtornos de Enxaqueca/patologia , Animais , Genética , Humanos , Inflamação/diagnóstico , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/patologia , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/tratamento farmacológico , Polimorfismo de Nucleotídeo Único/genética
8.
Saudi Med J ; 42(7): 793-797, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34187925

RESUMO

OBJECTIVES: To assess the sex hormone levels in young Saudi female migraineurs during a migraine attack and during pain-free periods and compare them with control subjects. METHODS: A case-control study involving 14 Saudi female migraineurs and 21 control subjects was conducted between December 2019 and March 2020. Demographic and disease history data were collected through participant interviews. Blood samples were drawn during the migraine attack and pain-free periods. RESULTS: Follicular (30.00±19.60; p<0.001) and luteal (39.79±11.45; p=0.037) estrogen levels were significantly higher in patients with non-menstrual related migraine (NMM), while luteal testosterone levels (1.10±0.31; p=0.023) were significantly higher in patients with menstrually related migraine (MM). Body mass index (BMI) was higher in patients with NMM (25.77±6.53; p=0.013), and it was found to be associated with follicular estrogen (p=0.016), progesterone (p=0.018), and pain intensity (p=0.042). Luteal estrogen level was significantly lower (13.96±7.88; p=0.036) in patients with luteal onset of attack. CONCLUSION: High estrogen levels were found to mediate NMM, their effect being more pronounced with increase in BMI; whereas low luteal estrogen levels mediated MM. Young females with MM might have high luteal testosterone levels, and a compensatory protective role could be surmised accordingly.


Assuntos
Transtornos de Enxaqueca , Progesterona , Estudos de Casos e Controles , Feminino , Hormônios Esteroides Gonadais , Humanos , Transtornos de Enxaqueca/epidemiologia , Arábia Saudita/epidemiologia
9.
Int J Gen Med ; 14: 851-856, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33737829

RESUMO

BACKGROUND: A reliable, migraine-specific biomarker has not been identified so far. Calcitonin Gene-Related Peptide (CGRP) and Apolipoprotein E (ApoE) might serve as migraine biomarkers due to their roles in migraine pathophysiology. However, their diagnostic usefulness has not been explored yet. Present study explored the diagnostic accuracy of CGRP and ApoE in migraine. METHODS: A cross-sectional, case-control study was conducted from November 2019 to April 2020 at Physiology department of our university. Fourteen female migraine patients, 18-25 years old, with confirmed "Migraine" diagnosis by a neurologist, were recruited. Control group consisted of 14 age-matched healthy females with no personal/family history of migraine. Blood was drawn once from control subjects and twice from migraine patients (ictal and interictal phase). Serum CGRP and ApoE levels were assessed by ELISA. Statistical analysis involved paired t-test, one-way ANOVA, Receiver operating characteristic (ROC) curves and cross-tabs. RESULTS: ApoE (mg/dl) was higher significantly in interictal (1.90±0.50) and ictal (1.97±0.65) phases of migraine compared to control (1.07±0.26) (p ≤ 0.001). ROC curves for ApoE were significant in migraine ictal vs control (AUC= 0.91, AUC 95% CI: 0.78-1.0) and migraine interictal vs control (AUC=0.92, AUC 95% CI: 0.8-1.0) subjects. ROC curve for CGRP (pg/mL) was significant in migraine ictal vs control subjects only (AUC=0.79, AUC 95% CI: 0.6-0.97). CONCLUSION: Serum ApoE has "excellent" accuracy to diagnose migraine patients whether in ictal or interictal phase, from healthy subjects. ApoE levels of patients in these two phases of migraine are raised significantly than healthy subjects. CGRP has "fair" diagnostic accuracy to discriminate between migraine ictal phase and healthy subjects. Its levels do not differ significantly among migraine ictal, interictal phase and healthy controls.

11.
Nat Commun ; 12(1): 836, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33547321

RESUMO

Dynamic regulation of intestinal cell differentiation is crucial for both homeostasis and the response to injury or inflammation. Sprouty2, an intracellular signaling regulator, controls pathways including PI3K and MAPKs that are implicated in differentiation and are dysregulated in inflammatory bowel disease. Here, we ask whether Sprouty2 controls secretory cell differentiation and the response to colitis. We report that colonic epithelial Sprouty2 deletion leads to expanded tuft and goblet cell populations. Sprouty2 loss induces PI3K/Akt signaling, leading to GSK3ß inhibition and epithelial interleukin (IL)-33 expression. In vivo, this results in increased stromal IL-13+ cells. IL-13 in turn induces tuft and goblet cell expansion in vitro and in vivo. Sprouty2 is downregulated by acute inflammation; this appears to be a protective response, as VillinCre;Sprouty2F/F mice are resistant to DSS colitis. In contrast, Sprouty2 is elevated in chronic colitis and in colons of inflammatory bowel disease patients, suggesting that this protective epithelial-stromal signaling mechanism is lost in disease.


Assuntos
Colite/genética , Glicogênio Sintase Quinase 3 beta/genética , Homeostase/genética , Interleucina-33/genética , Proteínas de Membrana/genética , Proteínas Serina-Treonina Quinases/genética , Animais , Contagem de Células , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Criança , Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Feminino , Regulação da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/metabolismo , Células Caliciformes/efeitos dos fármacos , Células Caliciformes/metabolismo , Células Caliciformes/patologia , Células HT29 , Homeostase/efeitos dos fármacos , Humanos , Interleucina-33/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Dodecilsulfato de Sódio/administração & dosagem
12.
Polymers (Basel) ; 12(7)2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32650474

RESUMO

Tamoxifen (TAM) is a hormonal drug and is mainly used as an anti-estrogen in breast cancer patients. TAM binds to estrogen receptors (ERs), resulting in inhibition of estrogen signaling pathways and thus, a downregulation of cell proliferation. Cancer cells with negative or low ER expression will not uptake TAM and will show low response. Poly (methyl methacrylate) (PMMA) nanoparticles were prepared using surfactant-free emulsion polymerization, then were loaded with Nile red (NR), which resulted in PMMA-NR. To enhance TAM delivery to cervical cancer cells (HELA), which is considered ER-negative, we loaded TAM and polymethyl methacrylate nanoparticles-Nile-red into silica (PMMA-NR-Si-TAM). The uptake and intracellular distribution were visualized by confocal laser scanning microscopy, and the in vitro cytotoxic activity was evaluated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay using HELA and non-tumorigenic cell line HFF-1. The sensitivity of HELA (LC50: 207.31 µg/mL) and HFF-1 (LC50: 234.08 µg/mL) to free TAM was very low. However, after the encapsulation of TAM with PMMA-NR, the sensitivity significantly increased HELA (LC50: 71.83 µg/mL) and HFF-1 (LC50: 37.36 µg/mL). This indicates that TAM can be used for the treatment of ER-negative cervical cancer once conjugated to PMMA-NR nanoparticles. In addition, the PMMA-NR formulation appears to be highly suitable for cancer imaging and drug delivery.

13.
Beilstein J Nanotechnol ; 10: 2217-2228, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31807407

RESUMO

The combination of magnetic nanoparticles with a porous silica is a composite that has attracted significant attention for potential multifunctional theranostic applications. In this study, 30 wt % CuFe2O4 was impregnated into a matrix of monodispersed spherical hydrophilic silica (HYPS) nanoparticles through a simple dry impregnation technique. The chemotherapy drug cisplatin was loaded through electrostatic equilibrium adsorption over 24 h in normal saline solution. The presence of cubic spinel CuFe2O4 on HYPS was confirmed through powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR) and diffuse reflectance UV-vis spectroscopy (DR UV-vis) analysis. The HYPS particles showed a surface area of 170 m2/g, pore size of 8.3 nm and pore volume of 0.35 cm3/g. The cisplatin/CuFe2O4/HYPS nanoformulation showed the accumulation of copper ferrite nanoparticles on the surface and in the pores of HYPS with a surface area of 45 m2/g, pore size of 16 nm and pore volume of 0.18 cm3/g. Transmission electron microscopy (TEM) and energy dispersive X-ray (EDX) mapping analysis showed the presence of homogeneous silica particles with nanoclusters of copper ferrite distributed on the HYPS support. Vibrating sample magnetometry (VSM) analysis of CuFe2O4/HYPS showed paramagnetic behavior with a saturated magnetization value of 7.65 emu/g. DRS UV-vis analysis revealed the functionalization of cisplatin in tetrahedral and octahedral coordination in the CuFe2O4/HYPS composite. Compared to other supports such as mesocellular foam and silicalite, the release of cisplatin using the dialysis membrane technique was found to be superior when CuFe2O4/HYPS was applied as the support. An in vitro experiment was conducted to determine the potential of CuFe2O4/HYPS as an anticancer agent against the human breast cancer cell line MCF-7. The results show that the nanoparticle formulation can effectively target cancerous cells and could be an effective tumor imaging guide and drug delivery system.

14.
Curr Pharm Des ; 25(34): 3599-3607, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31612821

RESUMO

The in-vitro experimental model for the development of cancer therapeutics has always been challenging. Recently, the scientific revolution has improved cell culturing techniques by applying three dimensional (3D) culture system, which provides a similar physiologically relevant in-vivo model for studying various diseases including cancer. In particular, cancer cells exhibiting in-vivo behavior in a model of 3D cell culture is a more accurate cell culture model to test the effectiveness of anticancer drugs or characterization of cancer cells in comparison with two dimensional (2D) monolayer. This study underpins various factors that cause resistance to anticancer drugs in forms of spheroids in 3D in-vitro cell culture and also outlines key challenges and possible solutions for the future development of these systems.


Assuntos
Antineoplásicos/farmacologia , Técnicas de Cultura de Células , Resistencia a Medicamentos Antineoplásicos , Neoplasias , Esferoides Celulares/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos
15.
Cells ; 8(6)2019 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-31234505

RESUMO

Hematopoietic stem cells (HSCs) are multipotent, self-renewing cells that can differentiate into myeloid or lymphoid cells. The mobilization and differentiation processes are affected by the external environment, such as extracellular matrix and soluble molecules in the niche, where the lipid rafts (LRs) of the HSCs act as the receptors and control platforms for these effectors. LRs are membrane microdomains that are enriched in cholesterol, sphingolipid, and proteins. They are involved in diverse cellular processes including morphogenesis, cytokinesis, signaling, endocytic events, and response to the environment. They are also involved in different types of diseases, such as cancer, Alzheimer's, and prion disease. LR clustering and disruption contribute directly to the differentiation, homing, hibernation, or mobilization of HSCs. Thus, characterization of LR integrity may provide a promising approach to controlling the fate of stem cells for clinical applications. In this review, we show the critical role of LR modification (clustering, disruption, protein incorporation, and signal responding) in deciding the fate of HSCs, under the effect of soluble cytokines such as stem cell factor (SCF), transforming growth factor- ß (TGF-ß), hematopoietic-specific phospholipase Cß2 (PLC-ß2), and granulocyte colony-stimulating factor (G-CSF).


Assuntos
Diferenciação Celular , Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Microdomínios da Membrana/metabolismo , Animais , Humanos , Modelos Biológicos
16.
Artif Cells Nanomed Biotechnol ; 47(1): 1533-1542, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31007071

RESUMO

Poly (methyl methacrylate) (PMMA) is basically biocompatible polyester with high resistance to chemical hydrolysis, and high drug permeability and the most important characteristics of PMMA is that it does not produce any toxicity. There is not much information about PMMA action on the colon cancer cells. In the present study, we have synthesized PMMA nanoparticles. The distribution pattern of PMMA particles was analysed by Zeta sizer and the size of the particles was calculated by using quasi elastic light scattering (QELS). The surface structure and the morphology of PMMA were characterized by transmission electron microscope (TEM) and scanning electron microscope (SEM), respectively. We have also analysed their effects on cancerous cells (human colorectal carcinoma cells, HCT-116) and normal, healthy cells (human embryonic kidney cells, HEK-293) by using morphometric, MTT, DAPI and wound healing methods. We report that PMMA particles inhibited the cancer cell viability in a dose-dependent manner. The lower dose (1.0 µg/ml) showed a moderate decrease in cancer cell viability, whereas higher dosages (2.5 µg/ml, 5.0 µg/mL and 7.5 µg/mL) showed steadily decrease in the cancer cell viability. We also report that PMMA is highly selective to cancerous cells (HCT-116), as we did not find any action on the normal healthy cells (HEK-293). In conclusion, our results suggest PMMA particles are potential biomaterials to be used in the treatment of colon cancer.


Assuntos
Neoplasias do Colo/patologia , Polimetil Metacrilato/química , Polimetil Metacrilato/farmacologia , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/patologia , Proliferação de Células/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Células HCT116 , Células HEK293 , Humanos , Nanopartículas/química , Tamanho da Partícula , Polimetil Metacrilato/metabolismo , Cicatrização/efeitos dos fármacos
17.
PLoS One ; 14(2): e0212492, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30768627

RESUMO

BACKGROUND: B-cell lymphoma/leukaemia 11A (BCL11A) is a C2H2-type zinc-finger transcription factor protein that is a critical modulator of haemoglobin switching and suppresses the production of foetal haemoglobin. Variation in the BCL11A gene ameliorates the severity of sickle cell disease (SCD) and ß-thalassemia (ß-thal). The BCL11A gene is located on chromosome 2p16.1 and encodes an 835-amino acid protein. METHOD: Using state-of-the-art in silico tools, this study examined the most pathogenic non-synonymous single nucleotide polymorphisms (nsSNPs) that disrupt the BCL11A protein and mediate foetal-to-adult globin switching. A total of 11,463 SNPs were retrieved from the Single Nucleotide Polymorphism database (dbSNP). These included 799 in the 5' untranslated region (UTR), 486 in the 3' UTR, and 266 non-synonymous, 189 coding synonymous, six nonsense, and six stop-gained SNPs. RESULTS AND DISCUSSION: In silico tools (SIFT, SNAP, PolyPhen-2, PANTHER, I-Mutant, PROVEAN, SNPs&GO, mCSM, and PhD-SNP) predicted the five most-deleterious nsSNPs: rs61742690, rs62142605, rs17028351, rs115666026, and rs74987258. Molecular dynamic simulation and homology modelling of the mutated proteins (S783N, D643N, G451S, K670R, and M313L) of the most deleterious nsSNPs revealed their functional and structural impact. nsSNP rs61742690 was predicted to be the most deleterious, as supported by eight of the nine in silico tools. CONCLUSIONS: Complete failure in the protein-protein interactions with functional partners (KLF1 and others) and significant changes (±100% variation) in the interface energy revealed that rs61742690 (S783N) in the zinc-finger domain is a suitable target for disrupting BCL11A-mediated foetal-to-adult globin switching.


Assuntos
Proteínas de Transporte/genética , Globinas/genética , Proteínas Nucleares/genética , Algoritmos , Proteínas de Transporte/química , Proteínas de Transporte/metabolismo , Simulação por Computador , Bases de Dados de Ácidos Nucleicos , Hemoglobina Fetal/biossíntese , Hemoglobina Fetal/genética , Globinas/metabolismo , Humanos , Simulação de Dinâmica Molecular , Proteínas Mutantes/química , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Polimorfismo de Nucleotídeo Único , Domínios e Motivos de Interação entre Proteínas/genética , Proteínas Repressoras , Homologia de Sequência de Aminoácidos , Dedos de Zinco/genética
18.
Stem Cells Int ; 2018: 1429351, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30254679

RESUMO

Human embryonic stem cells (hESCs) hold great potential for the treatment of various degenerative diseases. Pluripotent hESCs have a great ability to undergo unlimited self-renewal in culture and to differentiate into all cell types in the body. The journey of hESC research is not that smooth, as it has faced several challenges which are limited to not only tumor formation and immunorejection but also social, ethical, and political aspects. The isolation of hESCs from the human embryo is considered highly objectionable as it requires the destruction of the human embryo. The issue was debated and discussed in both public and government platforms, which led to banning of hESC research in many countries around the world. The banning has negatively affected the progress of hESC research as many federal governments around the world stopped research funding. Afterward, some countries lifted the ban and allowed the funding in hESC research, but the damage has already been done on the progress of research. Under these unfavorable conditions, still some progress was made to isolate, culture, and characterize hESCs using different strategies. In this review, we have summarized various strategies used to successfully isolate, culture, and characterize hESCs. Finally, hESCs hold a great promise for clinical applications with proper strategies to minimize the teratoma formation and immunorejection and better cell transplantation strategies.

19.
Int J Biomater ; 2018: 8479439, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30210543

RESUMO

Both nanoparticles and cloves (Syzygium aromaticum) possess anticancer properties, but they do not elicit a significant response on cancer cells when treated alone. In the present study, we have tested fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles) in combination with crude clove extracts on human breast cancer cells (MCF-7) to examine whether the combination approach enhance the cancer cell death. The MCF-7 cells were treated with different concentrations (1.25 µg/mL, 12.5 µg/mL, 50 µg/mL, 75 µg/mL, and 100 µg/mL) of FMSP-nanoparticles alone and in combination with 50 µg/mL crude clove extracts. The effects of FMSP-nanoparticles alone and combined with clove extracts were observed after 24 hrs and 48 hrs intervals. The response of FMSP-nanoparticles-treated cells was evaluated by Trypan Blue, 4',6-diamidino-2-phenylindole (DAPI), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, respectively. We have demonstrated that cancer cell viability was decreased to 55.40% when treated with FMSP-nanoparticles alone, whereas when cancer cells were treated with FMSP-nanoparticles along with crude clove extracts, the cell viability was drastically decreased to 8.50%. Both morphological and quantitative data suggest that the combination of FMSP-nanoparticles plus crude clove extracts are more effective in treating cancer cells and we suggest that the combination treatment of nanoparticles along with clove extracts hold a great promise for the cancer treatments.

20.
Artif Cells Nanomed Biotechnol ; 46(sup3): S247-S253, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30043653

RESUMO

Nanoparticles have many advantages such as high biocompatibility, bioavailability and effective therapeutic capabilities. The aim of the present study is to examine whether fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles) have any impact on human colorectal cancer cells. In the present study, we have tested FMSP-nanoparticles with an average size of 100-200 nm on human colorectal carcinoma cells (HCT-116) to check their cytotoxic and anti-cancer capabilities. The effects of FMSP-nanoparticles on cancer cells were observed after 6 h, 24 h and 48 h intervals. The response of FMSP-nanoparticles-treated cells was evaluated by Trypan Blue, 4lue-diamidino-2-phenylindole (DAPI) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Our MTT analysis results revealed that FMSP-nanoparticles produced dose-dependent effects on cancer cells, FMSP-nanoparticles with dose of 1.25 µg/mL did not decrease cell survivability, whereas dosages of 12.5 µg/mL and 50 µg/mL respectively showed 23.59% and 59.47% decrease in the cancer cell survivability. In conclusion, our results demonstrate FMSP-nanoparticles have a potential anti-cancer capability and hold a great promise for colon cancer treatments.


Assuntos
Antineoplásicos , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais , Corantes Fluorescentes , Nanopartículas de Magnetita , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologia , Células HCT116 , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico
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