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1.
Mol Biol Rep ; 48(11): 7361-7370, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34665399

RESUMO

BACKGROUND: C. vespertiliomis extracts were evaluated for antiproliferative and apoptosis effect on breast cancer (MCF7) cells. METHODS AND RESULTS: The leaves extracts were analysed for its antiproliferative effect on breast cancer (MCF7) cells and normal epithelial breast (MCF 10A) cells using Sulforhodamine B (SRB) assay. The selective extract was evaluated for its ability to induce apoptosis using Annexin V-FITC apoptosis staining and the expression of molecular genes using qualitative reverse transcription-polymerase chain reaction (RT-PCR) against MCF7 cells. Gas chromatography-mass spectrometry (GC-MS) was used to identify the compounds from the selective extract. The findings showed that dichloromethane fraction (CV-Dcm) extract had high antiproliferative effect against MCF7 cells (IC50 = 24 µg/mL, selective index (SI) = 8.17). The percentages of apoptosis cells in CV-Dcm-treated MCF7 cells was 58.8%. The CV-Dcm extract induced downregulation of PCNA level. The apoptotic genes were also triggered in both extrinsic and intrinsic signaling pathways, affecting a 1.5-fold increase in BAX, 1.4-fold increase in cytochrome c, 1.3-fold increase in caspase-8, 1.7-fold increase in caspase-3 and 0.5-fold-decrease in BCL-2. Treated MCF7 cells also activated P53-dependent apoptotic death pathway. CONCLUSIONS: The present work strongly suggests that high efficacy of CV-Dcm extract was attributed to its antiproliferative and apoptosis-inducing activation in MCF7 cells, most likely due to its favourable compounds.


Assuntos
Apoptose , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células , Fabaceae/química , Extratos Vegetais/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/fisiopatologia , Caspase 3 , Feminino , Humanos , Células MCF-7 , Extratos Vegetais/uso terapêutico
2.
Chirality ; 33(1): 37-50, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33197086

RESUMO

A chiral separation method coupled with capillary electrophoresis (CE) analysis for ketoconazole and miconazole enantiomers using chiral selectors such as ß-cyclodextrin (ß-CD) and hydroxypropyl-ß-CD (HP-ß-CD) was developed in this study, which included the optimisation, validation and application of the method on the antifungal cream samples. The formation of inclusion complex between the hosts (ß-CD and HP-ß-CD) and guests (ketoconazole and miconazole) were compared and analysed using ultraviolet-visible spectrophotometry, nuclear magnetic resonance (NMR) spectroscopy and molecular docking methods. Results from the study showed that in a concentration that ranged between 0.25 and 50 mg L-1 , the linear calibration curves of each enantiomer had a high coefficient of regression (R2 > 0.999), low limit of detection (0.075 mg L-1 ) and low limit of quantification (0.25 mg L-1 ). The relative standard deviation (RSD) of the intraday and interday analyses ranged from 0.79% to 8.01% and 3.30% to 11.43%, respectively, while the recoveries ranged from 82.0% to 105.7% (RSD < 7%, n = 3). The most probable structure of the inclusion complexes was proposed based on the findings from the molecular docking studies conducted using the PatchDock server.

3.
Biomed Chromatogr ; 35(5): e5050, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33314228

RESUMO

A simple and sensitive preconcentration strategy using sequential electrokinetic and hydrodynamic injection modes in micellar electrokinetic chromatography with diode array detection was developed and applied for the separation and determination of anticancer agent, 5-fluorouracil and its metabolite, 5-fluoro-2'-deoxyuridine, in human plasma. Sequential injection modes with increased analyte loading capacity using the anionic pseudo-stationary phase facilitated collection of the dispersed neutral and charged analytes into narrow zones and improved sensitivity. Several important parameters affecting sample enrichment performance were evaluated and optimized in this study. Under the optimized experimental conditions, 614- and 643-fold and 782- and 803-fold sensitivity improvement were obtained for 5-fluorouracil and its metabolite when compared with normal hydrodynamic and electrokinetic injection, respectively. The method has good linearity (1-1,000 ng/ml) with acceptable coefficient of determination (r2 > 0.993), low limits of detection (0.11-0.14 ng/ml) and satisfactory analyte relative recovery (97.4-99.7%) with relative standard deviations of 4.6-9.3% (n = 6). Validation results as well as the application to analysis of human plasma samples from cancer patients demonstrate the applicability of the proposed method to clinical studies.


Assuntos
Antineoplásicos/sangue , Cromatografia Capilar Eletrocinética Micelar/métodos , Desoxiuridina/análogos & derivados , Fluoruracila/sangue , Desoxiuridina/sangue , Humanos
4.
Molecules ; 25(9)2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32365508

RESUMO

Clinacanthus nutans is a well-known herb that has been used as an alternative and therapeutic medicine, however more selective C. nutans extracts are needed. In this study, leaves were extracted with 80% methanol and further fractionated with n-hexane, dichloromethane, chloroform, n-butanol, and aqueous residue. Subsequently, the total phenolic content (TPC), total flavonoid content (TFC), antioxidant scavenging activity, and antiproliferative effects on breast cancer (Michigan Cancer Foundation-7 [MCF7]) and normal breast (Michigan Cancer Foundation-10A [MCF 10A]) cells of the extracts were measured. Additionally, molecular docking simulation of the major compounds from C. nutans extracts was conducted. The aqueous residue had the highest TPC and TFC, whereas the crude extract had the highest scavenging activity. Among the extracts, dichloromethane extract (CN-Dcm) was selected as it had the highest selectivity index (SI) (1.48). Then, the chosen extract (CN-Dcm) was proceed for further analysis. The compounds from CN-Dcm were identified using gas chromatography-mass spectrometry (GC-MS). The major compounds from CN-Dcm were further investigated through molecular docking studies. Palmitic acid and linolenyl alcohol were the compounds found in the CN-Dcm extract that exhibited the highest binding affinities with p53-binding protein Mdm-2. These results highlight the potential of C. nutans as a source of anticancer activities.


Assuntos
Acanthaceae/química , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Extratos Vegetais/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Linhagem Celular Tumoral , Fracionamento Químico , Relação Dose-Resposta a Droga , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Conformação Molecular , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química
5.
Molecules ; 25(18)2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32971740

RESUMO

A bottom-up approach for synthesizing silver nanoparticles (AgNPs-GA) phytomediated by Garcinia atroviridis leaf extract is described. Under optimized conditions, the AgNPs-GA were synthesized at a concentration of 0.1 M silver salt and 10% (w/v) leaf extract, 1:4 mixing ratio of reactants, pH 3, temperature 32 °C and 72 h reaction time. The AgNPs-GA were characterized by various analytical techniques and their size was determined to be 5-30 nm. FTIR spectroscopy indicates the role of phenolic functional groups in the reduction of silver ions into AgNPs-GA and in supporting their subsequent stability. The UV-Visible spectrum showed an absorption peak at 450 nm which reflects the surface plasmon resonance (SPR) of AgNPs-GA and further supports the stability of these biosynthesized nanoparticles. SEM, TEM and XRD diffractogram analyses indicate that AgNPs-GA were spherical and face-centered-cubic in shape. This study also describes the efficacy of biosynthesized AgNPs-GA as anti-proliferative agent against human breast cancer cell lines, MCF-7 and MCF-7/TAMR-1. Our findings indicate that AgNPs-GA possess significant anti-proliferative effects against both the MCF-7 and MCF-7/TAMR-1 cell lines, with inhibitory concentration at 50% (IC50 values) of 2.0 and 34.0 µg/mL, respectively, after 72 h of treatment. An induction of apoptosis was evidenced by flow cytometry using Annexin V-FITC and propidium iodide staining. Therefore, AgNPs-GA exhibited its anti-proliferative activity via apoptosis on MCF-7 and MCF-7/TAMR-1 breast cancer cells in vitro. Taken together, the leaf extract from Garcinia atroviridis was found to be highly capable of producing AgNPs-GA with favourable physicochemical and biological properties.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Nanopartículas Metálicas/química , Prata/química , Prata/farmacologia , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Química Sintética , Garcinia/química , Química Verde , Humanos , Células MCF-7 , Extratos Vegetais/química
6.
Int J Mol Sci ; 19(6)2018 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-29891772

RESUMO

In the field of medicine, nanomaterials, especially those derived using the green method, offer promise as anti-cancer agents and drug carriers. However, the biosafety of metallic nanoparticles used as anti-cancer agents remains a concern. The goal of this systematic review was to compare the cytotoxicity of different plant-mediated syntheses of metallic nanoparticles based on their potency, therapeutic index, and cancer cell type susceptibility in the hopes of identifying the most promising anti-cancer agents. A literature search of electronic databases including Science Direct, PubMed, Springer Link, Google Scholar, and ResearchGate, was conducted to obtain research articles. Keywords such as biosynthesis, plant synthesis, plant-mediated, metallic nanoparticle, cytotoxicity, and anticancer were used in the literature search. All types of research materials that met the inclusion criteria were included in the study regardless of whether the results were positive, negative, or null. The therapeutic index was used as a safety measure for the studied compound of interest. Data from 76 selected articles were extracted and synthesised. Seventy-two studies reported that the cytotoxicity of plant-mediated synthesis of metallic nanoparticles was time and/or dose-dependent. Biosynthesised silver nanoparticles demonstrated higher cytotoxicity potency compared to gold nanoparticles synthesised by the same plants (Plumbago zeylanica, Commelina nudiflora, and Cassia auriculata) irrespective of the cancer cell type tested. This review also identified a correlation between the nanoparticle size and morphology with the potency of cytotoxicity. Cytotoxicity was found to be inversely proportional to nanoparticle size. The plant-mediated syntheses of metallic nanoparticles were predominantly spherical or quasi-spherical, with the median lethal dose of 1⁻20 µg/mL. Nanoparticles with other shapes (triangular, hexagonal, and rods) were less potent. Metallic nanoparticles synthesised by Abutilon inducum, Butea monosperma, Gossypium hirsutum, Indoneesiella echioides, and Melia azedarach were acceptably safe as anti-cancer agents, as they had a therapeutic index of >2.0 when tested on both cancer cells and normal human cells. Most plant-mediated syntheses of metallic nanoparticles were found to be cytotoxic, although some were non-cytotoxic. The results from this study suggest a focus on a selected list of potential anti-cancer agents for further investigations of their pharmacodynamic/toxicodynamic and pharmacokinetic/toxicokinetic actions with the goal of reducing the Global Burden of Diseases and the second leading cause of mortality.


Assuntos
Ouro/toxicidade , Nanopartículas Metálicas/toxicidade , Plantas/metabolismo , Animais , Humanos , Tamanho da Partícula
7.
Artigo em Inglês | MEDLINE | ID: mdl-38466777

RESUMO

Poly(methyl methacrylate-vinyl imidazole bromide) (poly-MMA-IL)-grafted magnetic nanoparticles were successfully developed and applied in the micro-magnetic solid phase extraction (µ-MSPE) for 16 types of polycyclic aromatic hydrocarbons (PAHs) from tea, fried food, and grilled food samples via gas chromatography flame ionization detector (GC-FID). One variable at a time (OVAT) and response surface methodology (RSM) were used for efficient optimization. The validation method showed a good coefficient of determination (R2) ranging from 0.9901 to 0.9982 (n = 3) with linearity of 0.2 µg L-1-500 µg L-1. Detection and quantification limits were 0.06 µg L-1-0.32 µg L-1 and 0.18 µg L-1-0.97 µg L-1. Additionally, satisfactory reproducibility was attained with intra-day and inter-day precisions having RSD ranges of 3.6%-11.1%. The spiked recovery value of 16 PAHs in fried food, grilled food and tea samples obtained from the night market in Malaysia ranged from 80%-12%, respectively.


Assuntos
Análise de Alimentos , Contaminação de Alimentos , Líquidos Iônicos , Nanopartículas de Magnetita , Hidrocarbonetos Policíclicos Aromáticos , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/química , Contaminação de Alimentos/análise , Nanopartículas de Magnetita/química , Líquidos Iônicos/química , Microextração em Fase Sólida , Extração em Fase Sólida , Chá/química , Polímeros/química
8.
Immunother Adv ; 4(1): ltae002, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38826586

RESUMO

Humanised xenograft models and cancer cell lines are widely used for preclinical drug evaluation, biological studies, and targeted therapy strategies in cancer research. A humanised mouse model is a laboratory mouse that has been genetically modified to contain specific human genes, cells, or tissues. By introducing human-specific elements into rodents, researchers can create a more accurate representation of human physiological and pathological processes. Lacking an appropriate animal model for osteosarcoma (OS), hindered understanding of underlying mechanisms in OS metastasis progression. Markedly, metastasis influences the prognosis and treatment of osteosarcoma. Gaining insight into the mechanisms and occurrences of metastasis could potentially facilitate oncologists in improving therapies. Hence, it is important to develop a lung metastatic OS model to study the basic biology of its progression. This study has established a tumour-bearing mouse model using HOS-143B cell line which was injected into male NOD.SCID gamma (NSG) mice at two locations; intramuscularly (hind leg) and subcutaneously (back) respectively. The primary and metastatic tumour size was monitored by palpating the area of tumour induced and quantified using digital calliper. H&E staining was performed by pathologist to confirm metastasis. Our results showed that mice injected with 1 million cancer cells were unable to produce tumours. Meanwhile, mice injected with three million cancer cells showed tumour development and lung metastasis after 25 days of cancer cell inoculation. In conclusion, this study has successfully established a lung metastatic OS mouse model that could be useful for biological studies of OS. These findings imply that this model is essential for safety and efficacy before clinical trials, accelerate the translation from basic research to therapeutic applications.

9.
Talanta ; 254: 124188, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36521327

RESUMO

A paper-based polymeric ionic liquid (p-Poly-(MMA-IL)) was successfully developed by grafting the polymeric ionic liquid on the surface of commercial filter paper (FP) by using the dipping method, presenting a new cost-effective film. The newly developed p-Poly-(MMA-IL) FP was then applied as a paper-based thin-film microextraction (p-TFME) analytical device to extract 14 compounds as representative of five groups of antibiotic drugs, which were sulfonamides, tetracyclines, fluoroquinolones, penicillin and macrolides in environmental water samples. Besides, p-Poly-(MMA-IL) FP, p-Poly-(MMA) FP, and unmodified filter paper were successfully characterised by FTIR, NMR, FESEM, TGA, and XRD techniques. They underwent significant parameters optimisation, which affected the extraction efficiency. Under optimal conditions, the proposed (p-Poly-(MMA-IL) FP-TFME) device method was evaluated and applied to analyse multi-class antibiotic drugs in environmental water samples by using a liquid chromatography-mass spectrometry (LC-MS). The validation method showed that a good linearity (0.1 µg L-1 - 500 µg L-1) was noted (R2 > 0.993, n = 3). Detection and quantification limits were within 0.05 µg L-1 - 4.52 µg L-1 and 0.15 µg L-1 - 13.6 µg L-1, respectively. The relative standard deviation (RSD) values ranged at 1.4%-12.2% (intra-day, n = 15) and 4.4%-11.0% (inter-day, n = 10). The extraction recoveries of environmental water samples ranged from 79.1% to 126.8%, with an RSD of less than 15.4% (n = 3). The newly developed paper-based polymeric ionic liquid (p-Poly-(MMA-IL) FP) for analysis of multi-class antibiotic drugs under the p-TFME analytical device procedure was successfully achieved with limited sample volume and organic solvent, fast extraction, and feasible in daily analysis. The detection concentration and relative RSD of multi-class antibiotics determined in various environmental water samples by the proposed method (n = 5) were within 0.44 µg L-1 - 54.41 µg L-1 and 0.69%-15.56%, respectively. These results signified the potential of the p-Poly-(MMA-IL) FP-TFME device as an efficient, sensitive and environmentally friendly approach for analysing antibiotics.


Assuntos
Líquidos Iônicos , Microextração em Fase Líquida , Cromatografia Líquida/métodos , Antibacterianos , Cromatografia Líquida de Alta Pressão , Líquidos Iônicos/química , Espectrometria de Massas em Tandem/métodos , Água/química , Microextração em Fase Líquida/métodos , Limite de Detecção
10.
Cureus ; 15(11): e48692, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38090459

RESUMO

Sacubitril/valsartan is a drug commonly prescribed for the management of hypertension. However, the complete understanding of its efficacy and safety as an antihypertensive agent remains a subject of ongoing investigation. To address this gap, a meta-analysis was conducted to assess and compare the efficacy and safety of sacubitril/valsartan in relation to olmesartan, an angiotensin receptor blocker (ARB). A thorough search of PubMed, Google Scholar, and Cochrane databases was performed to identify relevant randomized controlled trials (RCTs) and observational studies that could contribute to this meta-analysis. The selected studies were evaluated for their efficacy and safety parameters, including mean sitting and ambulatory blood pressure measurements, common side effects, adverse events, and drug discontinuation rates. A total of eight studies, involving 4488 hypertensive patients, were included in this analysis. Among the participants, 63.5% were administered sacubitril/valsartan, while 36.5% received olmesartan. The analysis revealed significant changes in mean sitting systolic blood pressure (MsSBP), mean sitting diastolic blood pressure (MsDBP), and mean sitting pulse pressure (MsPP) favoring sacubitril/valsartan, with p-values <0.00001, 0.07, and <0.00001, respectively. Additionally, sacubitril/valsartan demonstrated a significant reduction in mean ambulatory systolic blood pressure (MaSBP), mean ambulatory diastolic blood pressure (MaDBP), and mean ambulatory pulse pressure (MaPP) with p-values of 0.001, 0.001, and 0.02, respectively. However, it is important to note that safety outcomes indicated that sacubitril/valsartan was associated with slightly less favorable results compared to olmesartan. This meta-analysis highlights that sacubitril/valsartan exhibits superior efficacy in reducing blood pressure parameters compared to olmesartan in hypertensive patients. Nevertheless, its safety profile appears to be slightly less favorable. To reinforce these findings and provide more robust evidence, further studies with larger sample sizes should be conducted in the future. This comprehensive review serves as a valuable resource for healthcare professionals and researchers seeking to make informed decisions regarding antihypertensive treatment options.

11.
J Biomol Struct Dyn ; 41(13): 6104-6120, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35899385

RESUMO

Clinacanthus nutans is a medicinal plant recognised for its anticancer properties. We previously discovered that the C. nutans extract had the most potent inhibitory effect on MCF7 breast cancer cell and significantly induced apoptosis. However, there is a scarcity of studies demonstrating the molecular interactions of C. nutans-derived chemical compounds associated with apoptosis-related proteins. Therefore, the objective of this study was to determine the potential chemical compounds found in the C. nutans extract and examine their interactions with the targeted apoptotic proteins using molecular docking and molecular dynamic simulations. To address this objective, the compounds found in the SF2 extract of C. nutans were analysed using Gas Chromatography-Mass Spectrometry (GC-MS). The molecular interaction of the compounds with the targeted apoptotic proteins were determined using molecular docking and molecular dynamic simulations. GC-MS analysis revealed a total of 32 compounds in the SF2 extract. Molecular docking analysis showed that compound ß-amyrenol had the highest binding affinity for MDM2-P53 (-7.26 kcal/mol), BCL2 (-11.14 kcal/mol), MCL1-BAX (-6.42 kcal/mol), MCL1-BID (-6.91 kcal/mol), and caspase-9 (-12.54 kcal/mol), whereas campesterol had the highest binding affinity for caspase-8 (-10.11 kcal/mol) and caspase-3 (-10.14 kcal/mol). These selected compounds were subjected to molecular dynamic simulation at 310 K for 100 ns. The results showed that the selected protein-ligand conformation complexes were stable, compact, and did not alter much when compared to the protein references. The findings indicate that ß-amyrenol and campesterol are potentially significant compounds that might provide insight into the molecular interactions of the compounds with the apoptosis-related proteins.Communicated by Ramaswamy H. Sarma.


Assuntos
Simulação de Dinâmica Molecular , Extratos Vegetais , Cromatografia Gasosa-Espectrometria de Massas , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Simulação de Acoplamento Molecular , Proteína de Sequência 1 de Leucemia de Células Mieloides , Proteínas Reguladoras de Apoptose , Apoptose
12.
Nat Prod Res ; 36(11): 2848-2852, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33949277

RESUMO

Clinacanthus nutans has been reported to have many medicinal properties and it is traditionally used in treating viral lesions. This study aims to determine the molecular docking of C. nutans compounds detected by Gas Chromatography-Mass Spectrometry (GC-MS) with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 main protease) protein and its host receptor angiotensin-converting enzyme 2 (ACE2) protein using the AutoDock 4.2 tool. The drug-likeness and molecular docking analyses showed that fourteen compounds of C. nutans satisfied the Lipinski's rule of five and they exhibited good inhibitory effects against the SARS-Cov-2 main protease and ACE2 proteins. In addition, the glyceryl 2-linolenate compound was found to have the most potent binding affinities with both proteins. The results provide useful insights into the molecular inhibitory interactions of C. nutans compounds detected by GC-MS analysis with the targeted SARS-CoV-2 main protease and ACE2 protein.


Assuntos
Acanthaceae , Tratamento Farmacológico da COVID-19 , Acanthaceae/química , Enzima de Conversão de Angiotensina 2 , Antivirais/farmacologia , Proteases 3C de Coronavírus , Cromatografia Gasosa-Espectrometria de Massas , Simulação de Acoplamento Molecular , Extratos Vegetais/farmacologia , SARS-CoV-2
13.
Environ Sci Pollut Res Int ; 29(54): 81685-81702, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35737268

RESUMO

Clinacanthus nutans dichloromethane fraction (CN-Dcm) extract has previously been proven to suppress breast cancer (MCF7) cell proliferation. Despite this, the extrinsic and intrinsic apoptosis mechanisms involved in C. nutans extract-treated MCF7 cells are still unknown. This study was intended to subfractionate CN-Dcm extract using column chromatography and analyse the treated MCF7 cells using the CellTiter 96® AQueous One Solution Cell Proliferation (MTS) assay, Annexin V/propidium iodide (PI) assay, western blot, and reverse transcription-qualitative polymerase chain reaction (RT-qPCR). Out of nine subfraction extracts (SF1 to SF9), SF2 extract strongly inhibited MCF7 cells with the lowest IC50 value (23.51 ± 1.00 µg/mL) and substantially induced apoptosis in the MCF7 cells. In treated MCF7 cells, SF2 extract significantly upregulated the expression of P53, BAX, BID, caspase-8, caspase-9, and caspase-3, while downregulating the expression of BCL2. The presence of potential bioactive chemical compounds in the SF2 extract was identified using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Thus, the SF2 extract has the potential to induce apoptosis in MCF7 cells through intrinsic and extrinsic pathways.


Assuntos
Acanthaceae , Neoplasias da Mama , Humanos , Feminino , Caspase 3 , Caspase 9 , Caspase 8 , Cloreto de Metileno , Anexina A5 , Propídio , Proteína Supressora de Tumor p53 , Proteína X Associada a bcl-2 , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Acanthaceae/química , Apoptose
14.
Biomed Res Int ; 2022: 4165808, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35800225

RESUMO

Lapatinib, an orally administered small-molecule tyrosine kinase inhibitor (SM-TKI), is an effective treatment for ErbB2-positive breast cancer. However, its efficacy as one of the targeted cancer therapies has been hampered by several adverse effects, especially gastrointestinal toxicity, commonly manifested as diarrhoea. Although it can be generally tolerated, diarrhoea is reported as the most common and most impactful on a patient's quality of life and associated with treatment interruption. Severe diarrhoea can result in malabsorption, leading to dehydration, fatigue, and even death. ErbB1 is an epidermal growth factor profoundly expressed in normal gut epithelium while lapatinib is a dual ErbB1/ErbB2 tyrosine kinase inhibitor. Thus, ErbB1 inhibition by lapatinib may affect gut homeostasis leading to diarrhoea. Nevertheless, the underlying mechanisms remain unclear. This review article provides evidence of the possible mechanisms of lapatinib-induced diarrhoea that may be related to/or modulated by ErbB1. Insight regarding the involvement of ErbB1 in the pathophysiological changes such as inflammation and intestinal permeability as the underlying cause of diarrhoea is covered in this article.


Assuntos
Antineoplásicos , Neoplasias da Mama , Antineoplásicos/efeitos adversos , Diarreia/induzido quimicamente , Feminino , Humanos , Lapatinib/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Qualidade de Vida , Quinazolinas/farmacologia , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo
15.
Micromachines (Basel) ; 13(1)2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35056243

RESUMO

In this present work, we aim to improve the hydrophobicity of a polydimethylsiloxane (PDMS) surface. Various heights of 3D PDMS micropillars were fabricated via grayscale photolithography, and improved wettability was investigated. Two approaches of PDMS replication were demonstrated, both using a single master mold to obtain the micropillar arrays. The different heights of fabricated PDMS micropillars were characterized by scanning electron microscopy (SEM) and a surface profiler. The surface hydrophobicity was characterized by measuring the water contact angles. The fabrication of PDMS micropillar arrays was shown to be effective in modifying the contact angles of pure water droplets with the highest 157.3-degree water contact angle achieved by implementing a single mask grayscale lithography technique.

16.
Toxics ; 10(6)2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35736905

RESUMO

Since the major route of BPA exposure is via the oral route, BPA may have effects on the gastrointestinal tract, especially on the intestinal barrier, where most digestion and absorption processes occur. In this study, the effects of BPA-treated water on the small intestine (SI) and SI tight junction proteins (TJPs) of both pregnant Sprague-Dawley rats and their fetuses were investigated. Previously, hybrid photocatalytic filtration treatment by a visible light driven N-doped TiO2 membrane has successfully removed up to 81.6% of BPA in water. The effect of BPA-untreated (5.00 ± ppm) and BPA-treated water (0.9 ± ppm) after 21 days of exposure on the jejunum and ileum, as well as the expressions of claudin proteins, were investigated by Western blotting (WB) and hematoxylin and eosin (H&E) in order to investigate the potential of the photocatalytic membrane in removing the detrimental effect of BPA. The results suggest that BPA exposure altered the morphology of villi, and affected the expression level of claudin-2, -3, and -4 proteins in the jejunum and ileum of both pregnant rats and their fetuses. Interestingly, villi and claudins expressions were undisrupted in a treated-BPA water group, which indicated that the degradation of BPA via membranes effectively mitigates the effect on BPA on gastrointestinal tract.

17.
Talanta ; 236: 122833, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635223

RESUMO

A dynamic pH junction was used in capillary electrophoresis (CE-DAD) to on-line preconcentrate, separate, and determine trace amounts of sulfonamide antibiotics (SAs) in milk and yoghurt samples in this study. A sample matrix with 0.15% acetic acid and 10% methanol (MeOH) at a pH of 4.0, and a background electrolyte (BGE) that contained 35 mM sodium citrate with 10% MeOH at a pH of 8.5, and an acidic barrage of 0.4% acetic acid with 10% MeOH at a pH of 2.5 were utilised to achieve a stacking effect for SAs through a dynamic pH junction. Under optimised conditions, the proposed preconcentration method showed good linearity (30-500 ng/mL, r2 ≥ 0.9940), low limits of detection (LODs) of 4.1-6.3 ng/mL, and acceptable analytes recovery (81.2-106.9%) with relative standard deviations (RSDs) within 5.3-13.7 (n = 9). The limits of quantification (LOQs) were below the maximum residue limit approved by the European Union (EU) in this type of matrices. Sensitivity enhancement factors of up to 129 were reached with the optimised dynamic pH junction using CE with a diode array detector (DAD). The method was used to determine SAs in fresh milk, low-fat milk, full-cream milk, and yoghurt samples.


Assuntos
Antibacterianos , Iogurte , Animais , Eletroforese Capilar , Concentração de Íons de Hidrogênio , Leite , Sulfonamidas
18.
Microbiol Resour Announc ; 11(10): e0046822, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36043870

RESUMO

Here, we present two 7.1- and 7.3-bp near-complete genome sequences of Burkholderia pseudomallei strains of HTAA077 and HRPB058, isolated from a pus culture from a confirmed melioidosis patient at Hospital Tengku Ampuan Afzan, Kuantan, Malaysia, and from blood culture from a patient at Hospital Raja Permaisuri Bainun, Ipoh, Malaysia, using a Nanopore MinION instrument.

19.
Saudi Dent J ; 33(2): 105-111, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33551624

RESUMO

The objective of this study is to determine the therapeutic efficacy of allicin against Candida albicans (C. albicans) and Staphylococcus aureus (S. aureus), the common etiological agents for denture stomatitis (DS). The minimum inhibitory concentration (MICs), minimum bactericidal concentrations (MBCs) and minimum fungicidal concentration (MFCs) of allicin were determined by the broth microdilution method followed by checkerboard microdilution method for a synergistic interaction between allicin + nystatin and allicin + CHX. The potential of allicin to eradicate C. albicans and S. aureus biofilms was assessed by treating biofilm formed on self- polymerized acrylic resin with allicin at a sub-MIC concentration for 5 min. The commercial denture cleanser (brand X) was used as a positive control. A Kruskal-Wallis test followed by the post-hoc Mann-Whitney U test was applied (SPSS 20.0), and the level of significance was set at P < 0.05. Allicin exhibited antimicrobial activity against C. albicans (MIC:8 µg/ml and MFC:16 µg/ml) and S. aureus (MIC:8 µg/ml and MBC:8 µg/ml). A synergistic interaction was observed between allicin + nystatin and allicin + CHX (FICI ≤ 0.5). Allicin exhibited significant biofilm eradication against C. albicans and S. aureus biofilms with percentages of 50.0% and 52.6%, respectively. The results of this study suggest a possible application of allicin in treating C. albicans and S. aureus infection in DS.

20.
Bioinorg Chem Appl ; 2021: 9920890, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093698

RESUMO

Silver nanoparticles (AgNPs) previously synthesised using leaf (AgNP-L) and stem (AgNP-S) extracts of Clinacanthus nutans (C. nutans) were tested to evaluate antimicrobial, antioxidant, and cytotoxicity activities. The AgNPs showed good inhibition against bacteria, but not fungi. The inhibition results showed the highest activity against Staphylococcus aureus (S. aureus) with 11.35 mm (AgNP-L) and 11.52 mm (AgNP-S), while the lowest inhibition was against Escherichia coli (E. coli) with 9.22 mm (AgNP-L) and 9.25 mm (AgNP-S) in the disc diffusion method. The same trend of results was noted in the well diffusion method. The IC50 of AgNP-L and AgNP-S in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays was 417.05 µg/mL and 434.60 µg/mL, as well as 304.31 µg/mL and 326.83 µg/mL, respectively. Ferric reducing power (FRAP) assay showed that AgNP-L [872.389 µmol/L Fe(II)] and AgNP-S [612.770 µmol/L Fe(II)] exhibited significantly (p < 0.05) greater antioxidant activities than leaf extract (CNL) [152.260 µmol/L Fe(II)] and stem extract (CNS) [110.445 µmol/L Fe(II)] of C. nutans. The AgNPs were also proven to possess cytotoxic effects on the breast (MCF-7), cervical (HeLa), and colon (HT-29) cancer cells in a dose-dependent manner. AgNP-S and AgNP-L showed significantly (p < 0.05) higher cytotoxicity against MCF-7 (117.43 µg/mL) and HT-29 (78.47 µg/mL), respectively. In conclusion, the biosynthesised AgNPs from aqueous extract leaves and stem of C. nutans have demonstrated promising potential towards antioxidant, antimicrobial, and cytotoxicity activities.

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