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Acylpyrazolone-based Schiff base ligands (HLn) and their corresponding Pt(II) complexes with the general formula [Pt(Ln)(Cl)] (n = 1-3) were synthesized and characterized by different spectroscopic techniques including 1H-NMR, 195Pt-NMR, LC-Mass, FT-IR, and UV-Vis spectroscopy, as well as elemental analysis. The crystal structure of one of the Schiff base ligands was also obtained. Based on the ADMET comparative results and the bioavailability radar charts, the complexes are completely drug-like. The Schiff base complexes with a structural difference of one methyl group in ligand were used as anticancer agents against human breast cancer cell lines SKBR3 and MDA-MB-231. The IC50 values after treatment by [Pt(L1)Cl] and [Pt(L2)Cl] were obtained more than cisplatin and less than carboplatin on cancer cells MDA-MB-231 and SKBR3, while the IC50 value of [Pt(L3)Cl] was more than both other complexes and clinical Pt drugs. Molecular docking data showed that the groove binding is the main interaction with DNA double strands with a minor contribution from electrostatic interactions. To investigate the structure-activity relationship, DFT computational was done. All quantum chemical parameters display the drug approaching biomacromolecule and more biological activity of [Pt(L1)Cl] > [Pt(L2)Cl] > [Pt(L3)Cl]. So, three Schiff base platinum complexes can be suitable candidates as anticancer drugs. Schiff-base ligands (HLn) and their Pt(II) complexes ([Pt(Ln)(Cl)], n=1-3) were obtained. To investigate their biological property and main interactions with DNA, ADMET, and cytotoxicity against MDA-MB-231 and SKBR3, DFT, and Molecular docking were done.
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Antineoplásicos , Neoplasias da Mama , Complexos de Coordenação , Humanos , Feminino , Platina/química , Neoplasias da Mama/tratamento farmacológico , Simulação de Acoplamento Molecular , Raios X , Bases de Schiff/química , Ligantes , Espectroscopia de Infravermelho com Transformada de Fourier , Antineoplásicos/farmacologia , Antineoplásicos/química , DNA/metabolismo , Complexos de Coordenação/farmacologia , Complexos de Coordenação/químicaRESUMO
BACKGROUND: The present research was performed to assess N-heteroaryl acetic acid salts' anticancer activity against the breast cancer cell in order to introduce new inhibitory agents for histone deacetylase. METHODS AND RESULTS: A molecular docking simulation was performed to design the rational novel compounds. Afterward, the best compounds were selected for synthesis. The cytotoxic effects and mechanism of action have been studied via (Methyl Thiazol-Tetrazolium) MTT assay. Flow cytometry and gene expression analyses were performed to introduce an effective acetic acid derivative as an anticancer agent. Molecular docking simulations demonstrated that all compounds have the best interaction with histone deacetylase. The fold changes of Bcl-2, Bak, Bim, Caspase-3, and Caspase-8 gene expressions were investigated and compared with reference gene using real-time PCR. The cytotoxic studies showed the best anticancer activity of 4-benzyl-1-(carboxymethyl) pyridinium bromide (compound 2) with a low IC50 value (32 µM, p < 0.05). Also, the best anti HDAC activity was obtained for compound 2 with IC50 value of 1.1 µM. Furthermore, this compound showed a high percentage of apoptosis among all tested compounds after 72 h incubation which was associated with the significant increase in mRNA level of Bim, Bax, Bak, Caspase-3, and Caspase-8 and the considerable decrease in Bcl2 gene expression. CONCLUSION: These results suggest that compound 2 with the benzyl ring could be an effective anticancer compound for further investigation in breast cancer treatment.
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Antineoplásicos/síntese química , Neoplasias da Mama/enzimologia , Inibidores de Histona Desacetilases/síntese química , Histona Desacetilases/metabolismo , Compostos de Piridínio/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Movimento Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/química , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/química , Humanos , Concentração Inibidora 50 , Células MCF-7 , Modelos Moleculares , Simulação de Acoplamento Molecular , Compostos de Piridínio/química , Compostos de Piridínio/farmacologia , Relação Estrutura-AtividadeRESUMO
In this study, [111 In]In-DOTA-PR81 was developed, and its preliminary preclinical qualifications were assessed for single photon emission computed tomography (SPECT) imaging of breast cancer. DOTA-NHS-ester was practiced and successively purified by molecular filtration. The chelate:mAb ratio was determined by spectrophotometry. DOTA-PR81 was radiolabeled with In-111 and its radiochemical yield, in vitro stability, in vitro internalization, and immunoreactivity tests were performed. SPECT imaging and tissue counting were applied to evaluate the tissue distribution of [111 In]In-DOTA-hIgG and [111 In]In-DOTA-PR81 in BALB/c mice bearing breast tumors. The radiochemical yield of [111 In]In-DOTA-PR81 complex was >95.0 ± 0.5% (ITLC), and the specific activity was 170 ± 44 MBq/mg. Conjugation reaction resulted in the average number of chelators attached to a mAb (c/a) of 3.4 ± 0.3:1. The radioimmunoconjugate showed immunoreactivity towards MCF7 cell line and MUC1 antigen while its significant in vitro and in vivo stability were investigated over 48 h, respectively (93.0 ± 1.2% in phosphate-buffered saline (PBS) and 84.0 ± 1.3% in human serum). The peak concentration of internalized activity of [111 In]In-DOTA-PR81 was between 4 to 6 h. In comparison with control probes, the complex was accumulated with high specificity and sensitivity at the tumor site. Achieved results indicated that [111 In]In-DOTA-PR81 could be contemplated as an appropriate radiotracer for prognostic imaging of antigens in oncology.
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Imunoconjugados/química , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Mucina-1/imunologia , Compostos Radiofarmacêuticos/farmacocinética , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Células CHO , Cricetinae , Cricetulus , Feminino , Humanos , Radioisótopos de Índio/química , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Compostos Organometálicos/química , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/síntese química , Distribuição TecidualRESUMO
Tyrosinase is a multi-copper enzyme which is widely distributed in different organisms and plays an important role in the melanogenesis and enzymatic browning. Therefore, its inhibitors can be attractive in cosmetics and medicinal industries as depigmentation agents and also in food and agriculture industries as antibrowning compounds. For this purpose, many natural, semi-synthetic and synthetic inhibitors have been developed by different screening methods to date. This review has focused on the tyrosinase inhibitors discovered from all sources and biochemically characterised in the last four decades.
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Chalcona/farmacologia , Cumarínicos/farmacologia , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Resveratrol/farmacologia , Agaricales/enzimologia , Animais , Chalcona/química , Cumarínicos/química , Inibidores Enzimáticos/química , Flavonoides/química , Humanos , Monofenol Mono-Oxigenase/metabolismo , Resveratrol/químicaRESUMO
Propensity of two different silver nanoparticles (Ag-NPs) to bovine hemoglobin (BHb) was investigated by means of spectroscopic methods. We have combined spectrophotometric and calorimetric methods to show that there is no significant interaction between citrate-coated Ag-NPs and BHb at physiological pH and 20°C. However, our previous results show that polyethylene glycol-coated Ag-NPs strongly bind to Hb and effect on the secondary and tertiary structures of BHb. Thus, a suitable surface coating and modification of surface charge would increase the NPs safety and reduce adverse biological responses.
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Ácido Cítrico/metabolismo , Hemoglobinas/metabolismo , Nanopartículas Metálicas/química , Prata/química , Animais , Bovinos , Polietilenoglicóis/metabolismo , Ligação Proteica , Análise EspectralRESUMO
This study aimed to carry out the preclinical studies of [89Zr]Zr-DFO-Bevacizumab. The radiolabeled compound was prepared with radiochemical purity >99% (ITLC), and a specific activity of 74 GBq/g. Cellular studies indicated the great capability of [89Zr]Zr-DFO-Bevacizumab for binding to SKOV3 cell lines. High accumulation was observed in the tumor. The liver and spleen received the highest absorbed dose with 1.12 and 0.72 mGy/MBq, respectively. This radiopharmaceutical can be considered as a suitable PET agent for VEGF-expressing ovarian cancer imaging.
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Bevacizumab , Neoplasias Ovarianas , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Fator A de Crescimento do Endotélio Vascular , Zircônio , Bevacizumab/farmacocinética , Bevacizumab/química , Tomografia por Emissão de Pósitrons/métodos , Animais , Humanos , Feminino , Zircônio/química , Compostos Radiofarmacêuticos/farmacocinética , Linhagem Celular Tumoral , Fator A de Crescimento do Endotélio Vascular/metabolismo , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/metabolismo , Camundongos , Distribuição Tecidual , Radioisótopos , Desferroxamina/químicaRESUMO
Non-alcoholic fatty liver disease (NAFLD) is a common long-lasting liver disease that affects millions of people around the world. It is best identified with a hepatic fat build-up that ultimately leads to inflammation and damage. The classification and nomenclature of NAFLD have long been a controversial topic, until 2020 when a group of international experts recommended substituting NAFLD with MAFLD (metabolic dysfunction-associated FLD). MAFLD was then terminologically complemented in 2023 by altering it to MASLD, i.e., metabolic dysfunction-associated steatotic liver disease (MASLD). Both the MAFLD and the MASLD terminologies comprise the metabolic element of the disorder, as they offer diagnostic benchmarks that are embedded in the metabolic risk factors that underlie the disease. MASLD (as a multisystemic disease) provides a comprehensive definition that includes a larger population of patients who are at risk of liver morbidity and mortality, as well as adverse cardiovascular and diabetes outcomes. MASLD highlights metabolic risks in lean or normal weight individuals, a factor that has not been accentuated or discussed in previous guidelines. Novel antihyperglycemic agents, anti-hyperlipidemic drugs, lifestyle modifications, nutritional interventions, and exercise therapies have not been extensively studied in MAFLD and MASLD. Nutrition plays a vital role in managing both conditions, where centralizing on a diet rich in whole vegetables, fruits, foods, healthy fats, lean proteins, and specific nutrients (e.g., omega-3 fatty acids and fibers) can improve insulin resistance and reduce inflammation. Thus, it is essential to understand the role of nutrition in managing these conditions and to work with patients to develop an individualized plan for optimal health. This review discusses prevention strategies for NAFLD/MAFLD/MASLD management, with particular attention to nutrition and lifestyle correction.
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Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/terapia , Hepatopatia Gordurosa não Alcoólica/complicações , Fatores de RiscoRESUMO
Purpose: One of the most interesting methods to deliver therapeutic doses of ionizing radiation to tumor sites is radiolabeled compounds. Bombesin peptide binds to gastrin-releasing peptide receptors (GRPRs) with great affinity. Through its appropriate physical characteristics and accessibility as the 188W/188Re generator, 188Re can be effectively used to develop a therapeutic radio complex. In this study, 188Re-HYNIC-BBN was prepared under optimal conditions. Methods: Optimization of the effective parameters on 188Re-HYNIC-BBN radio-labeling yield like ligand concentration, pH, reaction time, and temperature were performed. The final product's radiochemical purity was measured by RTLC and HPLC. The stability of the radio-complex was checked in PBS buffer (4 °C) and human blood serum (37 °C). The partition coefficient of the final radio-complex was studied using standard procedure. Finally, the biodistribution of 188Re-HYNIC-BBN and free 188Re in different organs of the rats were compared in various intervals. Results: The final product was prepared with a specific activity of 7.11 TBq/mmol and radiochemical purity > 95% at the optimized conditions (pH = 4-5, reaction time = 45 min, temp = 95â). This radio-complex was found to be stable in PBS and blood serum over 24 h. LogPo/w was - 1.78, showing the high hydrophilic nature of the radio-complex. The biodistribution of 188Re-HYNIC-BBN demonstrated the fast clearance of the radio-peptide from the blood circulation. The most portion of the radioactivity was excreted from the body via the urinary tract and the remaining activity was accumulated in GRPR-expressing organs. Conclusion: The special characteristics of the complex introduce 188Re-HYNIC-BBN as a new therapeutic agent for targeting GRPRs, however, more biological data is still needed.
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Background: Current treatment methods are not successful in restoring the lost cardiomyocytes after injury. Stem cell-based strategies have attracted much attention in this regard. Smoking, as a strong cardiovascular risk factor, not only affects the cardiac cells adversely but also deteriorates the function of stem cells. Since mesenchymal stem cells (MSCs) are one of the popular candidates in cardiovascular disease (CVD) clinical trials, we investigated the impact of nicotine on the regenerative properties (viability and cardiac differentiation) of these cells. Methods: MSCs were isolated from rat bone marrow and characterized based on morphology, differentiation capability, and the expression of specific mesenchymal markers. The MTT assay was used to assess the viability of MSCs after being exposed to different concentrations of nicotine. Based on MTT findings and according to the concentration of nicotine in smokers' blood, the growth curve and population doubling time were investigated for eight consecutive days. Cells were treated with 5-azacytidine (an inducer of cardiac differentiation), and then the expressions of cardiac-specific markers were calculated by qPCR. Results: MSCs were spindle-shaped, capable of differentiating into adipocyte and osteocyte, and expressed CD73 and CD90. The viability of MSCs was reduced upon exposure to nicotine in a concentration- and time-dependent manner. The growth curve showed that nicotine reduced the proliferation of MSCs, and treated cells needed more time to double. In addition, the expressions of GATA4 and troponin were downregulated in nicotine-treated cells on day 3. However, these two cardiac markers were overexpressed on day 7. Conclusion: Nicotine decreased normal growth and reduced the expression of cardiac markers in MSCs. This aspect is of eminent importance to smokers with cardiovascular disease who are candidates for stem cell therapy.
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INTRODUCTION: Hyperglycemia may be a stumbling block for delivery of regenerative benefits of mesenchymal stem cells (MSCs) to diabetic patients with cardiovascular diseases. Our study aims to assess the viability and cardiac differentiation potential of MSCs after being exposed to diabetic glucose concentration. METHODS: MSCs were extracted from rat bone marrow. Cells were characterized based on morphology, differentiation potential, and expression of mesenchymal specific markers. MTT assay was done to evaluate the viability of MSCs after treatment with different glucose concentrations. Case group was MSCs treated with diabetic concentration of glucose versus cells treated with PBS as the control group. Growth curve and population doubling time were calculated in both groups. Expression of GATA4 and troponin, as the early and late markers during cardiac differentiation, were measured following 5-azacytidine exposure. RESULTS: Proliferated cells at passage three had fibroblastic-shape, was able to differentiate into adipocytes or osteocytes, and expressed CD73 and CD90. MSCs viability was gradually decreased by increasing glucose concentration. Irrespective of nicotine concentration, three-day exposure imposed more severe detrimental effects on viability compared with one-day treatment. Proliferation rate of the MSCs was lower in the case group, and they need more time for population doubling. Expression of both cardiac markers were downregulated in the case group at day three. However, their expression became higher at day seven. CONCLUSION: Diabetic glucose concentration inhibits normal proliferation and cardiac differentiation of MSCs. This effect should be considered in stem cell therapy of cardiovascular patients who are concurrently affected by hyperglycemia, a common comorbidity in such individuals. Why carry out this study? What was learned from the study?
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Diferenciação Celular , Sobrevivência Celular , Glucose , Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Animais , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ratos , Glucose/farmacologia , Glucose/metabolismo , Proliferação de Células/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/citologia , MasculinoRESUMO
Preeclampsia (PE) is a pregnancy-related disorder characterized by high blood pressure and proteinuria in the third trimester. The disease is associated with many metabolic and biochemical changes. There is a need for new biomarkers for diagnosis and follow-up. The present study examined the diagnostic ability of tryptophan catabolites (TRYCATs) and insulin resistance (IR) parameters in women with PE. This case-control study recruited sixty women with preeclampsia and 60 healthy pregnant women as a control group. Serum levels of TRYCATs (tryptophan, kynurenic acid, kynurenine, and 3-hydroxykynurenine) and IR parameters (insulin and glucose) were measured by ELISA and spectrophotometric methods. The results showed that PE women have a significantly lower tryptophan level than healthy pregnant women. However, there was a significant increase in kynurenic acid, kynurenic acid/kynurenine, kynurenine/tryptophan, and 3-hydroxykynurenine levels. PE women also have a state of IR. The correlation study indicated various correlations of IR and TRYCATs with clinical data and between each other, reflecting the role of these parameters in the pathophysiology of PE. The ROC study showed that the presence of IR state, reduced tryptophan, and increased 3-HK predicted PE disease in a suspected woman with moderate sensitivities and specificities. In conclusion, the pathophysiology of PE involves a state of IR and an alteration of the TRYCAT system. These changes should be taken into consideration when PE is diagnosed or treated.
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Resistência à Insulina , Pré-Eclâmpsia , Complicações na Gravidez , Humanos , Feminino , Gravidez , Triptofano/metabolismo , Cinurenina/metabolismo , Estudos de Casos e Controles , Ácido CinurênicoRESUMO
Platinum (Pt) derivatives are good candidates for discovering new anti-tumor agents. The present research aims to explore the in-vivo and in-vitro anticancer activity of two platinum complexes with 1,3-dimethyl pentyl glycine ligand (DMPG), [Pt(bpy)(13DMPG)]NO3 and [Pt(dach)(13DMPG)]NO3, against breast cancer cells. The present study was conducted to investigate the cytotoxic potential of these compounds (2-400 µM) compared to standard drugs (cisplatin, oxaliplatin, and carboplatin) on SKBR3 cells using the methyl thiazol-tetrazolium (MTT) assay. Furthermore, the gene expression changes of Bak, Bim, Bcl-2, Caspase-3, and Caspase-9 were carried out by real-time polymerase chain reaction (PCR), and flow cytometric analysis was performed to confirm the cell apoptosis in the presence of the compounds. For more validation, in-vivo anticancer activities of both compounds were investigated against breast transplanted tumors in the BALB/c mice model. The cytotoxic studies by MTT assay revealed the anti-proliferative potential of both derivatives. [Pt(dach)(13DMPG)]NO3 with an IC50 value of 15 µM, exhibited higher cytotoxicity against SKBR3 cells as compared to [Pt(bpy)(13DMPG)]NO3, oxaliplatin, and carboplatin. Based on the flow cytometry analysis, both derivatives demonstrated apoptotic effects. Also, real-time PCR analysis revealed an up-regulation of Bak, Bim, Bax, Caspases-3, and Caspase-9 genes and a significant reduction in Bcl-2 gene expression in treated cells with both compounds compared to the control group. In-vivo results validated in-vitro analysis and showed the anticancer activity of compounds against breast transplanted tumors in the BALB/c mice model. According to the results, [Pt(dach)(13DMPG)]NO3 displayed a significant anticancer activity.
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Antineoplásicos , Neoplasias , Camundongos , Animais , Platina , Carboplatina , Oxaliplatina , Caspase 9 , Glicina , Ligantes , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológicoRESUMO
Arterial stiffness is often increased in overweight/obese subjects before the development of hypertension. It is also one of the earliest indicators of increased cardiovascular disease risk and can be considered a good predictor of the development of subclinical cardiovascular dysfunction. Arterial stiffness is a significant prognostic factor influencing cardiovascular risk, which dietary habits can modify. Obese patients should use the caloric-restricted diet because it augments aortic distensibility, diminishes pulse wave velocity (PWV), and increases the activity of endothelial nitric oxide synthases. High intake of saturated fatty acids (SFA), trans fats, and cholesterol, typical for the Western diet, impairs endothelial function and raises brachial-ankle PWV. The replacement of SFA with monounsaturated (MUFA) or polyunsaturated fatty acids (PUFA) derived from seafood and plants diminishes the risk of arterial stiffness. The dairy product intake (excluding butter) decreases PWV in the general population. The high-sucrose diet causes toxic hyperglycemia and increases arterial stiffness. Complex carbohydrates with a low glycemic index (including isomaltose) should be recommended to keep vascular health. The high sodium intake (>10 g/day), particularly associated with low potassium consumption, has a deleterious effect on arterial stiffness (↑ baPWV). Since vegetables and fruits are good sources of vitamins and phytochemicals, they should be recommended in patients with high PWV. Thus, the dietary recommendation to prevent arterial stiffness should be similar to the Mediterranean diet, which is rich in dairy products, plant oils, and fish, with a minimal red meat intake and five servings of fruits and vegetables daily.
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Sobrepeso , Rigidez Vascular , Humanos , Fatores de Risco , Análise de Onda de Pulso , Obesidade , Ácidos Graxos , VerdurasRESUMO
Objectives: Due to the suitable physical characteristics of 89Zr as a PET radionuclide and affinity of Trastuzumab monoclonal antibody against HER2, [89Zr]Zr-Trastuzumab was prepared and went through preclinical evaluations for ultimate human applications. Methods: 89Zr was produced by using 89Y(p,n)89Zr reaction at a 30 MeV cyclotron (radionuclide purity>99.9%, specific activity of 17 GBq/µg). p-SCN-Bn-Deferoxamine (DFO); was conjugated to trastuzumab, followed by labeling with 89Zr in oxalate form at optimized condition. Cell binding, internalization and, radioimmuno-activity assays were studied using HER2+ BT474 and HER2- CHO cell lines. Finally, the biodistribution of the radioimmunoconjugate was assessed in normal and HER2+ BT474 tumor-bearing mice using tissue counting and imaging at different intervals after injection. Also, a woman with HER2-positive metastatic breast cancer under treatment with Herceptin underwent both [89Zr]Zr-Trastuzumab and, [18F]FDG PET/CTs. Results: 89Zr was produced with high radionuclidic and radiochemical purities (>99%) and [89Zr]Zr-DFO-Trastuzumab was prepared with radiochemical purity of >98% and specific activity of 9.85 GBq/µmol. The radioimmunoconjugate was stable both in PBS buffer and in human serum for at least 48 h. The radioimmunoactivity assay demonstrated about 70% of [89Zr]Zr-DFO-Trastuzumab is bound to the BT474 cells at the number of 250×106 cells. Cell binding studies showed that about 28% of radioimmunoconjugate is attached to BT474 cells after 90 min. Internalization studies showed that 50% of [89Zr]Zr-Trastuzumab is internalized to BT474 cells only in 6 h. The biodistribution study of the labeled compound in normal mice demonstrated the same pattern of the monoclonal antibodies which is entirely different from the biodistribution of free 89Zr. Biodistribution and imaging studies in tumor-bearing mice showed the significant uptake values of [89Zr]Zr-Trastuzumab in tumor sites. [89Zr]Zr-Trastuzumab PET/CT revealed metastatic lesions documented previously with [18F]FDG PET/CT scan in a woman with breast cancer who was under treatment with Herceptin. Although the [18F]FDG PET/CT scan had better quality images, the valuable and unique advantage of [89Zr]Zr-Trastuzumab PET/CT is delineating HER2+ metastasis, which is essential in diagnosis and HER2-based treatments. Conclusion: The prepared [89Zr]Zr-Trastuzumab has a high potential radio-pharmaceutical for immune-PET imaging of the patients with HER2+ tumors.
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In the present study, an Iranian natural zeolite (Sabzevar region) was evaluated as a natural adsorbent for the elimination and immobilization of strontium ions from an aqueous solution. For improving the adsorption efficiency of strontium ion, the zeolite surface was modified by the Schiff base ligand of bis (2-hydroxybenzaldehyde)1,2-diaminoethane (H2L). The natural zeolite and zeolite/H2L were characterized using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), X-ray fluorescence (XRF), BET and scanning electron microscope (SEM). Analysis of the natural zeolite showed that the zeolite is from the type of clinoptilolite and has a crystalline structure with the specific surface area 29.74 m2/g. The results showed that strontium adsorption onto modified zeolite increases compared to unmodified zeolite from 64.5% to 97.2% (at pH = 6). The effective parameters pH, adsorbent dosage, initial concentration of strontium ions, contact time, temperature, and interfering ions, were studied and optimized. The maximum adsorption efficiency was confirmed by modified zeolite and found to be 97.5% after 60 min of equilibrium time at pH 6, 0.05g as adsorbent dosage, and at 25 °C. Adsorption of strontium was confirmed by Langmuir model with maximum adsorption capacity of 10.31 mg/g. Kinetic studies showed that the adsorption of strontium ions on the adsorbent follows pseudo-second-order (PSO) model. Also, the thermodynamics of the adsorption process indicated that the adsorption of strontium on zeolite/H2L is an endothermic and spontaneous process, and the adsorption mechanism is a combination of physical and chemical adsorption. Finally, to manage the secondary waste generated from the adsorption process, strontium ions were immobilized in a zeolite structure. The results showed that the stabilization is well done with the thermal preparation process. After thermal treatment at 25-900 °C, modified zeolite satisfactorily retains strontium during back-exchange tests with NaCl solution. According to the results, the amount of strontium released from the adsorbent phase decreases from 52.6 to 1.6% with increasing heat treatment temperature.
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Hyperpigmentation is a common and distressing dermatologic condition. Since tyrosinase (TYR) plays an essential role in melanogenesis, its inhibition is considered a logical approach along with other therapeutic methods to prevent the accumulation of melanin in the skin. Thus, TYR inhibitors are a tempting target as the medicinal and cosmetic active agents of hyperpigmentation disorder. Among TYR inhibitors, hydroquinone is a traditional lightening agent that is commonly used in clinical practice. However, despite good efficacy, prolonged use of hydroquinone is associated with side effects. To overcome these shortcomings, new approaches in targeting TYR and treating hyperpigmentation are desperately requiredessentialneeded. In line with this purpose, several non-hydroquinone lightening agents have been developed and suggested as hydroquinone alternatives. In addition to traditional approaches, nanomedicine and nanotheranostic platforms have been recently proposed in the treatment of hyperpigmentation. In this review, we discuss the available strategies for the management of hyperpigmentation with a focus on TYR inhibition. In addition, alternative treatment options to hydroquinone are discussed. Finally, we present nano-based strategies to improve the therapeutic effect of drugs prescribed to patients with skin disorders.
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Hiperpigmentação , Preparações Clareadoras de Pele , Humanos , Hiperpigmentação/tratamento farmacológico , Melaninas/metabolismo , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Pele , Preparações Clareadoras de Pele/uso terapêutico , Preparações Clareadoras de Pele/farmacologiaRESUMO
Cardiomyopathy, a disorder of electrical or heart muscle function, represents a type of cardiac muscle failure and culminates in severe heart conditions. The prevalence of dilated cardiomyopathy (DCM) is higher than that of other types (hypertrophic cardiomyopathy and restrictive cardiomyopathy) and causes many deaths. Idiopathic dilated cardiomyopathy (IDCM) is a type of DCM with an unknown underlying cause. This study aims to analyze the gene network of IDCM patients to identify disease biomarkers. Data were first extracted from the Gene Expression Omnibus (GEO) dataset and normalized based on the RMA algorithm (Bioconductor package), and differentially expressed genes were identified. The gene network was mapped on the STRING website, and the data were transferred to Cytoscape software to determine the top 100 genes. In the following, several genes, including VEGFA, IGF1, APP, STAT1, CCND1, MYH10, and MYH11, were selected for clinical studies. Peripheral blood samples were taken from 14 identified IDCM patients and 14 controls. The RT-PCR results revealed no significant differences in the expression of the genes APP, MYH10, and MYH11 between the two groups. By contrast, the STAT1, IGF1, CCND1, and VEGFA genes were overexpressed in patients more than in controls. The highest expression was found for VEGFA, followed by CCND1 (p < 0.001). Overexpression of these genes may contribute to disease progression in patients with IDCM. However, more patients and genes need to be analyzed in order to achieve more robust results.
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Cardiomiopatias , Cardiomiopatia Dilatada , Insuficiência Cardíaca , Humanos , Cardiomiopatia Dilatada/genética , Miocárdio , Cardiomiopatias/genética , Biomarcadores , Ciclina D1RESUMO
Natural compounds such as gallic acid (GA) have attracted more attention in cosmetic and pharmaceutical skin care products. However, the low solubility and poor stability of GA have limited its application. This study aimed to synthesize and characterize the GA niosomal dispersion (GAN) and investigate the potential of an optimal formulation as a skin drug delivery system for GA. For this purpose, GAN formulations were synthesized using the thin layer evaporation method with different molar ratios of Tween 60/Span 60, along with a constant molar ratio of polyethylene glycol 4000 (PEG-4000) and cholesterol in a methanol and chloroform solvent (1:4 v/v). The physicochemical properties of nanosystems in terms of size, zeta potential, drug entrapment, drug release, morphology, and system-drug interaction were characterized using different methods. In addition, in vitro cytotoxicity, anti-tyrosinase activity, and antibacterial activity were evaluated by MTT assay, the spectrophotometric method, and micro-well dilution assay. All formulations revealed a size of 80-276 nm, polydispersity index (PDI) values below 0.35, and zeta potential values below-9.7 mV. F2 was selected as the optimal formulation due to its smaller size and high stability. The optimal formulation of GAN (F2) was as follows: a 1:1 molar ratio of Span 60 to cholesterol and 1.5 mM GA. The release of the F2 drug showed a biphasic pattern, which was fast in the first 12 h until 58% was released. Our results showed the high antibacterial activity of GAN against Escherichia coli and Pseudomonas aeruginosa. The MTT assay showed that GA encapsulation increased its effect on B6F10 cancer cells. The F2 formulation exhibited potent anti-tyrosinase activity and inhibited melanin synthesis. These findings suggest that it can be used in dermatological skin care products in the cosmetic and pharmaceutical industries due to its significant antibacterial, anti-melanoma, and anti-tyrosinase activity.
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Obesity has consistently been associated with an increased risk of metabolic abnormalities such as diabetes, hyperlipidemia, and cardiovascular diseases, as well as the development of several types of cancer. In recent decades, unfortunately, the rate of overweight/obesity has increased significantly among adults and children. A growing body of evidence shows that there is a relationship between metabolic disorders such as obesity and the composition of the gut microbiota. Additionally, inflammation is considered to be a driving force in the obesity-gut microbiota connection. Therefore, it seems that anti-inflammatory nutrients, foods, and/or diets can play an essential role in the management of obesity by affecting the intestinal flora and controlling inflammatory responses. In this review, we describe the links between the gut microbiota, obesity, and inflammation, and summarize the benefits of anti-inflammatory diets in preventing obesity.
Assuntos
Microbioma Gastrointestinal , Doenças Metabólicas , Anti-Inflamatórios/farmacologia , Criança , Dieta , Dieta Hiperlipídica , Humanos , Inflamação/complicações , Inflamação/prevenção & controle , Doenças Metabólicas/complicações , Obesidade/metabolismoRESUMO
Purpose: In this study, the human absorbed dose of 111In-DOTA-PR81 as a new radioimmunoconjugate for single-photon emission computed tomography (SPECT) imaging of MUC1 + breast cancer was determined. Materials and Methods: The complex was prepared at optimized conditions in about 1 h and 38°C. The radiochemical purity of the tracer was investigated using the instant thin-layer chromatography method method, showing purity of higher than 96%. After evaluating the stability of the product in human serum and room temperature, the biological distribution of the radiolabeled compound was studied in normal rats and tumor-bearing mice. Finally, the human absorbed dose of the complex was estimated based on animals' data using radiation dose assessment resource and Spark et al. methods. Results: High uptake of the complex in MUC1 + breast tumors compared to other nontarget organs shows that the radioimmunoconjugate is a beneficial agent for SPECT imaging of MUC1 + breast cancer. Human organs absorbed dose estimation of the complex demonstrated the highest amounts of the absorbed dose are in the liver and kidneys with 0.384 and 0.245 mGy/MBq, respectively. Conclusions: 111In-DOTA-PR81 radioimmunoconjugate is a high potential agent for MUC1 + breast cancer SPECT imaging and estimated absorbed dose values could helpfully use for the determination of the maximum injectable dose.