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1.
Environ Res ; 259: 119500, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38950814

RESUMO

Monitoring fenitrothion (FNT) residues in food and the environment is crucial due to its high environmental toxicity. In this study, we developed a sensitive, reliable electrochemical method for detecting FNT by using screen-printed carbon electrodes (SPCE) modified with porous graphene oxide (PGO) nanosheets. PGO surface properties have been meticulously characterized using advanced spectroscopic techniques. Electrochemical impedance spectroscopy and cyclic voltammetry were used to test the electrochemical properties of the PGO-modified sensor. The PGO-modified sensor exhibited remarkable sensitivity, achieving a detection limit as low as 0.061 µM and a broad linear range of 0.02-250 µM. Enhanced performance is due to PGO's high surface area and excellent electrocatalytic properties, which greatly improved electron transfer. Square wave voltammetry was used to demonstrate the sensor's efficacy as a real-time, on-site monitoring tool for FNT residues in fruit and water. The outstanding performance of the PGO/SPCE sensor underscores its applicability in ensuring food safety and environmental protection.

2.
Environ Res ; : 119543, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964574

RESUMO

This research was designed to isolate the predominant L-asparaginase-producing fungus from rhizosphere soil of tapioca field and assess the suitable growth conditions required to produce maximum L-asparaginase activity. The Aspergillus tubingensis was identified as a predominant L-asparaginase producing fungal isolate from 15 isolates, and it was characterized by 18S rRNA sequencing. The L-asparaginase-producing activity was confirmed by pink color zone formation around the colonies in modified Czapek Dox agar plate supplemented with 1% L-asparagine. The optimal growth conditions required for the L-asparaginase production by A. tubingensis were optimized as pH 6.0, temperature 30°C, glucose as carbon source, 1.5% of L-asparagine, ammonium sulphate as nitrogen source, rice husk as natural L-asparagine enriched source, and 8 days of the incubation period. The L-asparaginase activity from A. tubingensis was excellent under these optimal growth conditions. It significantly used rice husk as an alternative to synthetic L-asparagine. As a result, this may be considered a sustainable method of converting organic waste into valuable raw material for microbial enzyme production.

3.
Environ Res ; : 119566, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38971355

RESUMO

Cultivating productive paddy crops on salty soil to maximise production is a challenging approach to meeting the world's growing food demand. Thus, determining salinity tolerance rates in specific paddy cultivars is urgently needed. In this study, the salt tolerance traits of selected paddy cultivars, ADT45 and ADT39, were investigated by analysing germination, metabolites (pigments and biomolecules), and enzymatic (Superoxide dismutase (SOD), Catalase (CAT), and Peroxidase (POD) adaptation strategies as salt-stress tolerance mechanisms. This study found that salinity-induced reactive oxygen species (ROS) were efficiently detoxified by the antioxidant enzymes Superoxide dismutase (SOD), Catalase (CAT), and Peroxidase (POD) in ADT45 paddy varieties, followed by ADT39. Salinity stress had a significant impact on pigments and essential biomolecules in ADT45 and ADT39 paddy cultivars, including total chlorophyll, anthocyanin, carotenoids, ascorbic acid, hydrogen peroxide (H2O2), malondialdehyde, and proline. ADT45 demonstrated a significant relationship between H2O2 and antioxidant enzyme levels, followed by ADT39 paddy but not IR64. Morphological, physiological, and biochemical analyses revealed that ADT45, followed by ADT39, is a potential salt-tolerant rice cultivar.

4.
Environ Res ; 257: 119287, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38823610

RESUMO

Heavy metal pollution in soil has emerged as a major environmental concern. This can be attributed to human activities such as mining, modern agriculture, and industrialization. This study was conducted to determine how heavy metals spread from mine tailings to surrounding farmland. Metal absorption and accumulation were also investigated in the root and shoot biomass of tapioca crops grown in those farmlands. Metal concentrations in MTAS1 were 85.3 ± 1.2, 45.8 ± 1.5, 134.8 ± 1.7, 92.4 ± 2.2, and 78.95 ± 1.4 mg kg-1, respectively. Heavy metal concentrations in MTAS2 and MTAS3 were found to be 79.62 ± 1.6, 75.4 ± 1.5, 41.31 ± 1.1, 47.8 ± 1.6, 142.5 ± 2.1, 128.4 ± 1.4, 86.2 ± 1.9, 79.5 ± 1.3, and 83.4 ± 1.2 mg kg-1, respectively. Tapioca crop shoot and root biomass grown at these metal polluted sites absorbed and accumulated significant amounts of Cd, Cu, Zn, Pb, Ni, and Mn. Notably, the metal content of the tapioca crop's root and shoot biomass exceeded national standards.

5.
Front Cell Infect Microbiol ; 14: 1351303, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38881736

RESUMO

Introduction: Fowl adenovirus (FAdV) is a significant pathogen in poultry, causing various diseases such as hepatitis-hydropericardium, inclusion body hepatitis, and gizzard erosion. Different serotypes of FAdV are associated with specific conditions, highlighting the need for targeted prevention strategies. Given the rising prevalence of FAdV-related diseases globally, effective vaccination and biosecurity measures are crucial. In this study, we explore the potential of structural proteins to design a multi-epitope vaccine targeting FAdV. Methods: We employed an in silico approach to design the multi-epitope vaccine. Essential viral structural proteins, including hexon, penton, and fiber protein, were selected as vaccine targets. T-cell and B-cell epitopes binding to MHC-I and MHC-II molecules were predicted using computational methods. Molecular docking studies were conducted to validate the interaction of the multi-epitope vaccine candidate with chicken Toll-like receptors 2 and 5. Results: Our in silico methodology successfully identified potential T-cell and B-cell epitopes within the selected viral structural proteins. Molecular docking studies revealed strong interactions between the multi-epitope vaccine candidate and chicken Toll-like receptors 2 and 5, indicating the structural integrity and immunogenic potential of the designed vaccine. Discussion: The designed multi-epitope vaccine presents a promising approach for combating FAdV infections in chickens. By targeting essential viral structural proteins, the vaccine is expected to induce a robust immunological response. The in silico methodology utilized in this study provides a rapid and cost-effective means of vaccine design, offering insights into potential vaccine candidates before experimental validation. Future studies should focus on in vitro and in vivo evaluations to further assess the efficacy and safety of the proposed vaccine.


Assuntos
Infecções por Adenoviridae , Galinhas , Epitopos de Linfócito B , Epitopos de Linfócito T , Simulação de Acoplamento Molecular , Doenças das Aves Domésticas , Vacinas de Subunidades Antigênicas , Animais , Vacinas de Subunidades Antigênicas/imunologia , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/virologia , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito B/imunologia , Infecções por Adenoviridae/prevenção & controle , Infecções por Adenoviridae/veterinária , Infecções por Adenoviridae/imunologia , Vacinas Virais/imunologia , Proteínas Estruturais Virais/imunologia , Proteínas Estruturais Virais/genética , Aviadenovirus/imunologia , Aviadenovirus/genética , Simulação por Computador , Vacinas de Subunidades Proteicas
6.
Int J Biol Macromol ; 270(Pt 2): 132284, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38734353

RESUMO

Liposomes and nanofibers have been implemented as efficacious vehicles for delivering anticancer drugs. With this view, this study explores the antiproliferative efficacy and apoptosis induction in leukemia cancer cells utilizing irinotecan-loaded liposome-embedded nanofibers fabricated from chitosan, a biological source. Specifically, we investigate the effectiveness of poly(ε-caprolactone) (PCL)/chitosan (CS) (core)/irinotecan (CPT)nanofibers (termed PCL-CS10 CPT), PCL/chitosan/irinotecan (core)/PCL/chitosan (shell) nanofibers (termed CS/CPT/PCL/CS), and irinotecan-coloaded liposome-incorporated PCL/chitosan-chitosan nanofibers (termed CPT@Lipo/CS/PCL/CS) in releasing irinotecan in a controlled manner and treating leukemia cancer. The fabricated formulations were characterized utilizing Fourier transform infrared analysis, transmission electron microscopy, scanning electron microscopy, dynamic light scattering, zeta potential, and polydispersity index. Irinotecan was released in a controlled manner from nanofibers filled with liposomes over 30 days. The cell viability of the fabricated nanofibrous materials toward Human umbilical vein endothelial cells (HUVECs) non-cancerous cells after 168 h was >98 % ± 1 %. The CPT@Lipo/CS/PCL/CS nanofibers achieved maximal cytotoxicity of 85 % ± 2.5 % against K562 leukemia cancer cells. The CPT@Lipo/CS/PCL/CS NFs exhibit a three-stage drug release pattern and demonstrate significant in vitro cytotoxicity. These findings indicate the potential of these liposome-incorporated core-shell nanofibers for future cancer therapy.


Assuntos
Apoptose , Proliferação de Células , Quitosana , Irinotecano , Leucemia , Lipossomos , Nanofibras , Quitosana/química , Humanos , Lipossomos/química , Irinotecano/farmacologia , Irinotecano/química , Irinotecano/administração & dosagem , Nanofibras/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Leucemia/tratamento farmacológico , Leucemia/patologia , Células Endoteliais da Veia Umbilical Humana , Liberação Controlada de Fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Poliésteres/química , Antineoplásicos/farmacologia , Antineoplásicos/química
7.
Biochem Genet ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802693

RESUMO

Paired homologous domain transcription factor 2 (PITX2) is critically involved in ocular and cardiac development. Mutations in PITX2 are consistently reported in association with Axenfeld-Rieger syndrome, an autosomal dominant genetic disorder and atrial fibrillation, a common cardiac arrhythmia. In this study, we have mined missense mutations in PITX2 gene from NCBI-dbSNP and Ensembl databases, evaluated the pathogenicity of the missense variants in the homeodomain and C-terminal region using five in silico prediction tools SIFT, PolyPhen2, GERP, Mutation Assessor and CADD. Fifteen homeodomain mutations G42V, G42R, R45W, S49Y, R53W, E53D, E55V, R62H, P65S, R69H, G75R, R84G, R86K, R87W, R91P were found to be highly pathogenic by both SIFT, PolyPhen2 were further functionally characterized using I-Mutant 2.0, Consurf, MutPred and Project Hope. The findings of the study can be used for prioritizing mutations in the context of genetic studies.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38061618

RESUMO

Silica nanoparticles (SNPs) are widely explored as drug carriers, gene delivery vehicles, and as nanoparticles intended for bone and tissue engineering. SNPs are highly evident through various clinical trials for a wide range of biomedical applications. SNPs are biocompatible and promising nanoparticles for next-generation therapeutics. However, despite the well-established importance of SNPs, metabolomics methods for the SNPs remain elusive which renders its maximal clinical translation. We applied 1H nuclear magnetic resonance (1H NMR) spectroscopy to investigate the metabolomics profile in Zebrafish (Danio rerio) exposed to SNPs. Zebrafish were exposed to the SNPs (10.0, 25.0, and 50.0 µg/mL) for 72 h and whole-body samples were subjected for targeted profiling. Pattern recognition of 1H NMR spectral data depicted alterations in the metabolomic profiles between control and SNPs exposed zebrafish. We found that tryptophane, lysine, methionine, phenylalanine, tyrosine, sn-glycero-3-phosphocholine (G3PC), and o-phosphocholine were decreased. The metabolic expression of niacinamide, nicotinamide adenine dinucleotide (NAD+), citrate, adenosine triphosphate (ATP), and xanthine were increased in zebrafish with SNPs treatment. We are report for the first time on metabolite alterations and phenotypic expression in zebrafish via 1H NMR. These results demonstrate that SNPs can adversely affect the significant metabolic pathways involved in energy, amino acids, cellular membrane, lipids, and fatty acid metabolisms. Metabolomics profiling may be able to detect metabolic dysregulation in SNPs-treated zebrafish and establish a foundation for further toxicological studies.


Assuntos
Fosforilcolina , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Fosforilcolina/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Metabolômica/métodos
9.
J Pharm Sci ; 113(6): 1536-1545, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38147911

RESUMO

In today's context, prolonged exposure to sunlight is widely recognized as a threat to human health, leading to a range of adverse consequences, including skin cancers, premature skin aging, and erythema. To mitigate these risks, preventive actions mainly focus on advocating the application of sunscreen lotions and minimizing direct exposure to sunlight. This research study specifically centered on ensulizole (ENS), a prominent ingredient in sunscreens. The objective was to create inclusion complexes (ICs) with Beta-cyclodextrin (B-CD) and its hydroxypropyl derivatives (H-CD). Using phase solubility measurements, we determined that both B-CD and H-CD form 1:1 stoichiometric ICs with ENS. Proton nuclear magnetic resonance spectral (1H NMR) analysis confirmed that the phenyl portion of ENS is encapsulated within the B-CD cavity. Significant changes in surface morphology were observed during the formation of these ICs compared to ENS and CDs alone. Quantum mechanical calculations were employed to further support the formation of ICs by providing energy data. Particularly, the photostability of the ENS:B-CD ICs remained intact for up to four hours of UV exposure, with no significant alterations in the structure of ENS. Furthermore, comprehensive biocompatibility assessments yielded encouraging results, suggesting the potential application of these inclusion complexes in cosmetics as a UVB sunscreen. In summary, our research underscores the successful creation of inclusion complexes characterized by enhanced photostability and safe biocompatibility.


Assuntos
Solubilidade , Protetores Solares , beta-Ciclodextrinas , Protetores Solares/química , beta-Ciclodextrinas/química , Humanos , Composição de Medicamentos/métodos , Química Farmacêutica/métodos , Materiais Biocompatíveis/química , Estabilidade de Medicamentos
10.
Artigo em Inglês | MEDLINE | ID: mdl-37987950

RESUMO

Zinc oxide nanoparticles (ZnO NPs) are used in various fields, including biological ones. ZnO NPs are eventually disposed of in the environment where they may affect natural systems, and there is no international law to regulate their manufacture, usage, and disposal. Hence, this present study is carried out to synthesise a more non-toxic and bioactive ZnO NPs from the marine algae Sargassum polycystum. The ZnO NPs were biologically produced using the marine algae Sargassum polycystum. The dynamic light scattering result describes that synthesised particles' average size is about 100 nm in diameter. Transmission electron microscopy (TEM) analysis demonstrated the rod-like morphology of ZnO NPs. Fourier tranform-infrared spectroscopy (FT-IR) results revealed the presence of functional groups in ZnO NPs. The selected area electron diffraction (SAED) results strongly suggested the ZnO NPs crystallinity. ZnO NPs surface morphology and compositions were identified by scanning electron microscopy (SEM- EDX) values. To analyse the toxicity of synthesised nanoparticles, zebra fish larvae were used, which involved subjecting embryos to various ZnO NPs concentrations at 1 hpf and analysing the results at 96 hpf. The 60 and 80 ppm sub-lethal doses were chosen for further studies based on the LC50 (82.23 ppm). In the ZnO NPs-treated groups, a significant slowdown in pulse rate and a delay in hatching were seen, both of which impacted the embryonic processes. A teratogenic study revealed a dose-dependent increase in the incidence of developmental deformities in the treated groups. Along with increased oxidants and a corresponding reduction in antioxidant enzymes, Na+ K+-ATPase and AChE activity changes were seen in ZnO NPs-treated zebra fish larvae groups. The apoptosis process was increased in ZnO NPs-treated groups revealed by acridine orange staining. These results indicate that the green synthesis process cannot mitigate the oxidative stress induced by ZnO NPs on oxidative signalling.

11.
Environ Res ; 239(Pt 2): 117370, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37827374

RESUMO

The current research investigates the utilization of spirulina microalgae biodiesel blends in a naturally aspirated constant speed compression ignition engine with Ce2O3 nanoparticles at the concentration of 50 ppm under diverse engine loading conditions. Blends of microalgae dispersed with neat diesel at the volume of 20% and 40%. A series of tests were conducted to evaluate the combined effects of microalgae and nanoparticles on engine performance, combustion efficiency, and emission characteristics. The study revealed that increasing the microalgae concentration in the diesel fuel resulted in reduced brake thermal efficiency due to less effective atomization and lower calorific value. Surprisingly, the 20% biodiesel blend with nanoparticles exhibited the highest brake thermal efficiency across various engine loads, while the 40% blend showed higher brake specific fuel consumption compared to both the 20% blend and neat diesel, primarily because of its lower heating value necessitating increased fuel consumption. Furthermore, the biodiesel blends led to lower in-cylinder pressure than pure diesel, mainly attributable to suboptimal atomization. In terms of emissions, the utilization of microalgae-based fuel led to a significant reduction in NOx, CO, and smoke emissions, attributed to the lower cylinder temperatures associated with these blends. In conclusion, this study underscores the potential of spirulina microalgae, particularly when combined with nanoparticles at an optimal concentration, as a promising and environmentally friendly alternative for compression ignition engines.


Assuntos
Microalgas , Nanopartículas , Spirulina , Biocombustíveis , Emissões de Veículos , Gasolina , Monóxido de Carbono/análise
12.
Environ Res ; 235: 116676, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37453504

RESUMO

The current study demonstrates the potential of Cassia fistula seed carbon (CFSC), a waste lignocellulosic biomass, to eliminate Cd (II) ion-from saturated liquid samples. The efficient removal of about 93.2% (w/v) of Cd (II) ions from 10 mg/L concentration was achieved within 80 min of treatment. The CFSC dosage of 100 mg/50 mL accounted as optimal for enhanced Cd (II) removal. Cd (II) adsorption onto CFSC was observed to be maximum at pH 6. The investigational trials were assessed with three isotherm models such Dubinin-Radushkevich, Freundlich, and Langmuir. The specifications obtained from this experimental study align well with the Langmuir isotherm model, which describes the maximal adsorption capacity of 68.02 mg/g. Cd (II) adsorption data from this study exhibited the R2 of 0.9 under pseudo-second-order. Maximum desorption (76.3% w/v) was obtained with 0.3 M HCL. This study revealed that thermally activated C. fistula seed carbon (CFSC) can be tuned to be lucrative adsorbent for Cd (II) elimination from water and waste-water.


Assuntos
Cassia , Poluentes Químicos da Água , Cádmio/análise , Carbono , Adsorção , Poluentes Químicos da Água/análise , Cinética , Íons , Carvão Vegetal , Água , Concentração de Íons de Hidrogênio , Termodinâmica
13.
J Biomol Struct Dyn ; : 1-9, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37254288

RESUMO

The intercalative yeast t-RNA binding behavior of some metallo-surfactant complexes, Co(ip)2(TA)2](ClO4)3 (1) and [Co(dpq)2(TA)2](ClO4)3 (2) where TA = Tetradecylamine (Myristylamine), ip = imidazo[4,5-f][1,10]phenanthroline and dpq = dipyrido[3,2-d:2'-3'-f]quinoxaline containing π-conjugated systems (both below and above critical micelle concentration) have been investigated by means of absorption spectral titration, competitive binding, circular dichroism, cyclic voltammetry, and viscometry measurements. Absorption spectral titration results implicate yeast tRNA has significant effects on the binding behaviors of two surfactant complexes via intercalative mode showed a significant absorption band of hypochromicity with red shift. The intrinsic binding constant values below and above CMC were determined as Kb = 6.12 × 105 M-1, 2.31 × 106 M-1, for complex (1) and 7.23 × 105 M-1, 3.57 × 106 M-1, for complex (2). In both sets of complexes (1) and (2), the complexes bind more strongly to yeast tRNA in the above critical micelle concentration can be hydrophobic and confirm intercalation. Competitive displacement studies confirmed that complexes bind to yeast tRNA via intercalative mode. Cyclic voltammetry studies suggest the increasing amounts of yeast tRNA, the cathodic potential Epc for the two complexes shows a positive shift in peak potential indicated the process of binding via intercalation. These observations were further validated by CD, and hydrodynamic measurements. All these studies suggesting that a surfactant complex binds to yeast tRNA appear to be mainly intercalative because of hydrophobicity due to extending aromaticity of the π system of the ligand and planarity of the complex has a significant effect on tRNA binding affinity increasing in the order of complexes containing ligands ip < dpq.Communicated by Ramaswamy H. Sarma.

14.
Environ Res ; 231(Pt 3): 116216, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37224944

RESUMO

The present investigation explores the feasibility of generating biogas from water hyacinth (WH) through a pretreatment process. The WH samples were subjected to a high concentration of H2SO4 pretreatment to enhance biogas production. The H2SO4 pretreatment aids in breaking down the lignocellulosic materials found in the WH. Additionally, it helps modify the cellulose, hemicellulose, and lignin, which assists in the anaerobic digestion process. The samples underwent pretreatment with 5% v/v H2SO4 for 60 min. Biogas production was conducted for both untreated and pretreated samples. Furthermore, sewage sludge and cow dung were used as inoculants to promote fermentation in the absence of oxygen. The results of this study demonstrate that the pretreatment of water hyacinth with 5% v/v H2SO4 for 60 min considerably enhances biogas production through the anaerobic co-digestion process. The maximum biogas production was recorded by T. Control-1, with a production rate of 155 mL on the 15th day compared to all other controls. All the pretreated samples showed the highest biogas production on the 15th day, which is comparatively five days earlier than the untreated samples. In terms of CH4 production, the maximum yield was observed between the 25th and 27th days. These findings suggest that water hyacinth is a viable source of biogas production, and the pretreatment method significantly improves biogas yield. This study presents a practical and innovative approach to biogas production from water hyacinth and highlights the potential for further research in this area.


Assuntos
Biocombustíveis , Eichhornia , Anaerobiose , Metano , Esgotos , Nutrientes , Digestão
15.
Front Plant Sci ; 14: 1298880, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38322423

RESUMO

Mycoplasma gallisepticum (MG) is responsible for chronic respiratory disease in avian species, characterized by symptoms like respiratory rales and coughing. Existing vaccines for MG have limited efficacy and require multiple doses. Certain MG cytoadherence proteins (GapA, CrmA, PlpA, and Hlp3) play a crucial role in the pathogen's respiratory tract colonization and infection. Plant-based proteins and therapeutics have gained attention due to their safety and efficiency. In this study, we designed a 21.4-kDa multi-epitope peptide vaccine (MEPV) using immunogenic segments from cytoadherence proteins. The MEPV's effectiveness was verified through computational simulations. We then cloned the MEPV, introduced it into the plant expression vector pSiM24-eGFP, and expressed it in Nicotiana benthamiana leaves. The plant-produced MEPV proved to be immunogenic when administered intramuscularly to chickens. It significantly boosted the production of immunoglobulin Y (IgY)-neutralizing antibodies against cytoadherence protein epitopes in immunized chickens compared to that in the control group. This preliminary investigation demonstrates that the plant-derived MEPV is effective in triggering an immune response in chickens. To establish an efficient poultry health management system and ensure the sustainability of the poultry industry, further research is needed to develop avian vaccines using plant biotechnology.

16.
Biochimie ; 200: 119-130, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35654241

RESUMO

Renal cell carcinoma (RCC), also called kidney cancer, is one of the most common malignancies worldwide, including the United States and China. Because of the characteristics of RCC that are both insidious and largely insensitive to chemo-radiation, the incidence and mortality of RCC are increasing every year. However, there are few studies describing anti-cancer effects of the natural compounds on RCC as compared to other cancers. Here, we analyzed the anti-neoplastic impact of Tanshinone IIA (TSN) on RCC cells. We noted that TSN increased the expression of LC3 proteins while having little effect on PARP and Alix protein expression. We found that TSN up-regulated the expression of autophagy-related proteins such as Atg7 and Beclin-1. Moreover, TSN promoted the formation of autophagic vacuoles such as autophagosomes and autolysosomes. However, treatment with 3-Methyladenine (3-MA) or Chloroquine (CQ), slightly decreased the ability of TSN to induce autophagy, but still autophagy occurred. In addition, TSN inhibited translocation of ß-catenin into the nucleus, and ß-catenin deletion and TSN treatment in RCC increased the expression of LC3 protein. Overall, our findings indicate that TSN can exert significant anti-tumor effects through down-regulation of ß-catenin to induce autophagic cell death.


Assuntos
Morte Celular Autofágica , Carcinoma de Células Renais , Neoplasias Renais , Abietanos , Apoptose , Autofagia , Carcinoma de Células Renais/tratamento farmacológico , Linhagem Celular Tumoral , Regulação para Baixo , Humanos , Neoplasias Renais/tratamento farmacológico , beta Catenina/metabolismo
17.
Eur J Pharmacol ; 928: 175113, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35750234

RESUMO

Withaferin A (WFA), a withanolide, is isolated from plants of Withania somnifera (L.) Dual (Solanaceae), known as Indian ginseng, Indian winter cherry or Ashwagandha. It has been reported to exert multifaceted anti-neoplastic effects. Here, we analyzed the impact of WFA on apoptosis and autophagy activation in different human colorectal cancer cell lines. We observed that WFA exposure caused an increased aggregation of cells in the subG1 arrest in cell cycle, and increased the number of late apoptotic cells. WFA also induced the apoptosis via PARP and caspase-3 cleavage accompanied with suppression of levels of anti-apoptotic proteins like Bcl-2 and Bcl-xl. The influence of WFA on autophagy was validated by acridine orange, MDC staining, and immunocytochemistry of LC3. It was found that 24 h treatment of WFA increased the acridine and MDC stained autophagosome with induced the LC3 and other autophagy markers Atg7 and beclin-1 activation. We used Z-DEVD-FMK, a caspase-3 blocker, and 3-MA, an autophagy inhibitor, to confirm whether these effects were specific to apoptosis and autophagy, and observed the recovery of both these processes upon exposure to WFA. Moreover, the activation of ß-catenin protein was attenuated by WFA. Interestingly, small interfering RNA (siRNA)-promoted ß-catenin knockdown augmented the WFA-induced active form of p-GSK-3ß, and stimulated autophagy and apoptosis through PARP and LC3 activation. These findings suggested that WFA could stimulate activation of both apoptosis and autophagy process via modulating ß-catenin pathway.


Assuntos
Neoplasias Colorretais , Vitanolídeos , Apoptose , Autofagia , Caspase 3/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Glicogênio Sintase Quinase 3 beta , Humanos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Vitanolídeos/farmacologia , Vitanolídeos/uso terapêutico , beta Catenina
18.
Nutr Cancer ; 74(9): 3375-3387, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35579498

RESUMO

Mitogen­activated protein kinase (MAPK) pathway is a prominent signaling cascade that modulates cell proliferation, apoptosis, stress response, drug resistance, immune response, and cell motility. Activation of MAPK by various small molecules/natural compounds has been demonstrated to induce apoptosis in cancer cells. Herein, the effect of leelamine (LEE, a triterpene derived from bark of pine trees) on the activation of MAPK in hepatocellular carcinoma (HCC) and breast cancer (BC) cells was investigated. LEE induced potent cytotoxicity of HCC (HepG2 and HCCLM3) and BC (MDA-MB-231 and MCF7) cells over normal counterparts (MCF10A). LEE significantly enhanced the phosphorylation of p38 and JNK MAPKs in a dose-dependent fashion and it did not affect the phosphorylation of ERK in HCC and BC cells. The apoptosis-driving effect of LEE was further demonstrated by cleavage of procaspase-3/Bid and suppression of prosurvival proteins (Bcl-xL and XIAP). Furthermore, LEE also reduced the SDF1-induced-migration and -invasion of HCC and BC cells. Taken together, the data demonstrated that LEE promotes apoptosis and induces an anti-motility effect by activating p38 and JNK MAPKs in HCC and BC cells.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Abietanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Neoplasias Hepáticas/patologia , Sistema de Sinalização das MAP Quinases , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
19.
Biology (Basel) ; 11(3)2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35336740

RESUMO

Leelamine (LEE) has recently attracted significant attention for its growth inhibitory effects against melanoma, breast cancer, and prostate cancer cells; however, its impact on hematological malignancies remains unclear. Here, we first investigate the cytotoxic effects of LEE on several human chronic myeloid leukemia (CML) cells. We noted that LEE stimulated both apoptosis and autophagy in CML cells. In addition, the constitutive activation of signal transducer and activator of transcription 5 (STAT5) was suppressed substantially upon LEE treatment. Moreover, STAT5 knockdown with small interfering RNA (siRNA) increased LEE-induced apoptosis as well as autophagy and affected the levels of various oncogenic proteins. Thus, the targeted mitigation of STAT5 activation by LEE can contribute to its diverse anticancer effects by enhancing two distinct cell death pathways.

20.
Environ Res ; 208: 112684, 2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-34995544

RESUMO

The Azadirachta indica is an excellent and pharmaceutically valuable phytochemicals enriched traditional medicinal plant. The purpose of the research was to assess the ability of A. indica aqueous kernel extract to synthesize silver nanoparticles as well as their anti-inflammatory and anti-diabetic activity in vitro. The obtained results state that the aqueous kernel extract of A. indica can fabricate the silver nanoparticles and be confirmed by standard analytical techniques. Under UV-visible spectrophotometer analysis, the absorbance peak was found at 430 nm was related to the surface plasmon resonance of silver nanoparticles. The FTIR (Fourier-transform infrared spectroscopy) analysis revealed that numbers of functional groups belong to the pharmaceutically valuable phytochemicals, which act as reducing, capping, and stabilizing agent on silver nanoparticles synthesis. The size and shape of the silver nanoparticles were examined as 19.27-22.15 nm and spherical in shape. Interestingly, this kernel fabricated silver nanoparticles possess a reasonable anti-inflammatory (69.77%) and anti-diabetic (73.5%) activity at 100 µg mL-1 and these were partially comparable with standards (anti-inflammatory: 81.15%; anti-diabetic: 87.9%). Thus, the aqueous kernel extract fabricated silver nanoparticles can be considered for further in-vivo study to assess the practical possibility to promote as a pharmaceutical agent.


Assuntos
Azadirachta , Nanopartículas Metálicas , Anti-Inflamatórios/farmacologia , Azadirachta/química , Nanopartículas Metálicas/química , Extratos Vegetais/farmacologia , Folhas de Planta , Prata/química , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
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