RESUMEN
The increasing demand for plastic in our daily lives has led to global plastic pollution. The improper disposal of plastic has resulted in a massive amount of atmospheric microplastics (MPs), which has further resulted in the production of atmospheric nanoplastics (NPs). Because of its intimate relationship with the environment and human health, microplastic and nanoplastic contamination is becoming a problem. Because microplastics and nanoplastics are microscopic and light, they may penetrate deep into the human lungs. Despite several studies demonstrating the abundance of microplastics and nanoplastics in the air, the potential risks of atmospheric microplastics and nanoplastics remain unknown. Because of its small size, atmospheric nanoplastic characterization has presented significant challenges. This paper describes sampling and characterization procedures for atmospheric microplastics and nanoplastics. This study also examines the numerous harmful effects of plastic particles on human health and other species. There is a significant void in research on the toxicity of airborne microplastics and nanoplastics upon inhalation, which has significant toxicological potential in the future. Further study is needed to determine the influence of microplastic and nanoplastic on pulmonary diseases.
Asunto(s)
Microplásticos , Contaminantes Químicos del Agua , Humanos , Microplásticos/toxicidad , Plásticos/toxicidad , Contaminación Ambiental , Pulmón/química , Contaminantes Químicos del Agua/toxicidadRESUMEN
The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with the most contagious variants, alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2), and Omicron (B.1.1.529) has continuously added a higher number of morbidity and mortality, globally. The present integrated bioinformatics-cheminformatics approach was employed to locate potent antiviral marine alkaloids that could be used against SARS-CoV-2. Initially, 57 antiviral marine alkaloids and two repurposing drugs were selected from an extensive literature review. Then, the putative target enzyme SARS-CoV-2 main protease (SARS-CoV-2-Mpro) was retrieved from the protein data bank and carried out a virtual screening-cum-molecular docking study with all candidates using PyRx 0.8 and AutoDock 4.2 software. Further, the molecular dynamics (MD) simulation of the two most potential alkaloids and a drug docking complex at 100 ns (with two ligand topology files from PRODRG and ATB server, separately), the molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) free energy, and contributions of entropy were investigated. Then, the physicochemical-toxicity-pharmacokinetics-drug-likeness profiles, the frontier molecular orbitals energies (highest occupied molecular orbital, lowest unoccupied molecular orbital, and ΔE), and structural-activity relationship were assessed and analyzed. Based on binding energy, 8-hydroxymanzamine (-10.5 kcal/mol) and manzamine A (-10.1 kcal/mol) from all alkaloids with darunavir (-7.9 kcal/mol) and lopinavir (-7.4 kcal/mol) against SARS-CoV-2-Mpro were recorded. The MD simulation (RMSD, RMSF, Rg, H-bond, MM/PBSA binding energy) illustrated that the 8-hydroxymanzamine exhibits a static thermodynamic feature than the other two complexes. The predicted physicochemical, toxicity, pharmacokinetics, and drug-likeness profiles also revealed that the 8-hydroxymanzamine could be used as a potential lead candidate individually and/or synergistically with darunavir or lopinavir to combat SARS-CoV-2 infection after some pharmacological validation.
Asunto(s)
Alcaloides , Tratamiento Farmacológico de COVID-19 , Alcaloides/farmacología , Antivirales/química , Antivirales/farmacología , Quimioinformática , Biología Computacional , Proteasas 3C de Coronavirus , Cisteína Endopeptidasas/química , Darunavir , Humanos , Lopinavir , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Inhibidores de Proteasas/química , SARS-CoV-2RESUMEN
The key to bacterial virulence relies on an exquisite balance of signals between microbe and hosts. Bacterial toxin-antitoxin (TA) system is known to play a vital role in response to stress adaptation, drug resistance, biofilm formation, intracellular survival, persistence as well as pathogenesis. In the present study, we investigated the role of Hha-TomB TA system in regulating virulence of Salmonella enterica serovar Typhimurium (S. Typhimurium) in a host model system, where we showed that deletion of hha and tomB genes displayed impaired cell adhesion, invasion, and uptake. The isogenic hha and tomB mutant strain was also found to be deficient in intracellular replication in vitro, with a highly repressed Salmonella Pathogenicity Island-2 (SPI-2) genes and downregulation of Salmonella Pathogenicity Island-1 (SPI-1) genes. In addition, the Δhha and ΔtomB did not show acute colitis in C57BL/6 mice and displayed less dissemination to systemic organs followed by their cecal pathology. The TA mutants also showed reduction in serum cytokine and nitric oxide levels both in vitro and in vivo. However, the inflammation phenotype was restored on complementing strain of TA gene to its mutant strain. In silico studies depicted firm interaction of Hha-TomB complex and the regulatory proteins, namely, SsrA, SsrB, PhoP, and PhoQ. Overall, we demonstrate that this study of Hha-TomB TA system is one of the prime regulating networks essential for S. Typhimurium pathogenesis. 1. Role of Hha-TomB toxin-antitoxin (TA) system in Salmonella pathogenesis was examined. 2. The TA mutants resulted in impaired invasion and intracellular replication in vitro. 3. The TA mutants displayed alteration in SPI-1 and SPI-2 regulatory genes inside host cells. 4. Mutation in TA genes also limited systemic colonization and inflammatory response in vivo.
Asunto(s)
Antitoxinas , Salmonella typhimurium , Animales , Antitoxinas/genética , Antitoxinas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica , Inmunidad , Ratones , Ratones Endogámicos C57BL , Salmonella typhimurium/genética , Salmonella typhimurium/metabolismo , SerogrupoRESUMEN
Molecular electronic devices based on few and single-molecules have the advantage that the electronic signature of the device is directly dependent on the electronic structure of the molecules as well as of the electrode-molecule junction. In this work, we use a two-step approach to synthesise functionalized nanomolecular electronic devices (nanoMoED). In first step we apply an organic solvent-based gold nanoparticle (AuNP) synthesis method to form either a 1-dodecanethiol or a mixed 1-dodecanethiol/ω-tetraphenyl ether substituted 1-dodecanethiol ligand shell. The functionalization of these AuNPs is tuned in a second step by a ligand functionalization process where biphenyldithiol (BPDT) molecules are introduced as bridging ligands into the shell of the AuNPs. From subsequent structural analysis and electrical measurements, we could observe a successful molecular functionalization in nanoMoED devices as well as we could deduce that differences in electrical properties between two different device types are related to the differences in the molecular functionalization process for the two different AuNPs synthesized in first step. The same devices yielded successful NO2gas sensing. This opens the pathway for a simplified synthesis/fabrication of molecular electronic devices with application potential.
RESUMEN
Hexachlorocyclohexane (HCH) has been recognized as an effective insecticide to protect crops against grasshoppers, cohort insects, rice insects, wireworms, and other agricultural pests and; for the control of vector-borne diseases such as malaria. It is a cyclic, saturated hydrocarbon, which primarily exists as five different stable isomers in the environment. Though the use of HCH is banned in most countries owing to its adverse effects on the environment, its metabolites still exist in soil and groundwater, because of its indiscriminate applications. In this study, a dose-dependent toxicity assay of the HCH isomers isolated from soil and water samples of different regions of Odisha, India was performed to assess the in vivo developmental effects and oxidative stress in zebrafish embryos. Toxicity analysis revealed a significant reduction in hatching and survivability rate along with morphological deformities (edema, tail malformations, spinal curvature) upon an increase in the concentration of HCH isomers; beta isomer exhibiting maximum toxicity (p < 0.05). Oxidative stress assay showed that ROS and apoptosis were highest in the fish exposed to ß-2 and δ-2 isomers of HCH in comparison to the untreated one. Zebrafish proved to be a useful biological model to assess the biological effects of HCH isomers. In addition, the results suggest the implementation of precautionary measures to control the use of organochlorine compounds that can lead to a decrease in the HCH isomers in the field for a healthier environment.
Asunto(s)
Hexaclorociclohexano , Pez Cebra , Animales , Apoptosis , Biodegradación Ambiental , Hexaclorociclohexano/toxicidad , Humanos , Estrés Oxidativo , Suelo , Pez Cebra/metabolismoRESUMEN
High-quality point-of-care is critical for timely decision of disease diagnosis and healthcare management. In this regard, biosensors have revolutionized the field of rapid testing and screening, however, are confounded by several technical challenges including material cost, half-life, stability, site-specific targeting, analytes specificity, and detection sensitivity that affect the overall diagnostic potential and therapeutic profile. Despite their advances in point-of-care testing, very few classical biosensors have proven effective and commercially viable in situations of healthcare emergency including the recent COVID-19 pandemic. To overcome these challenges functionalized magnetic nanoparticles (MNPs) have emerged as key players in advancing the biomedical and healthcare sector with promising applications during the ongoing healthcare crises. This critical review focus on understanding recent developments in theranostic applications of functionalized magnetic nanoparticles (MNPs). Given the profound global economic and health burden, we discuss the therapeutic impact of functionalized MNPs in acute and chronic diseases like small RNA therapeutics, vascular diseases, neurological disorders, and cancer, as well as for COVID-19 testing. Lastly, we culminate with a futuristic perspective on the scope of this field and provide an insight into the emerging opportunities whose impact is anticipated to disrupt the healthcare industry.
Asunto(s)
Tratamiento Farmacológico de COVID-19 , COVID-19 , Nanopartículas de Magnetita , Nanopartículas , COVID-19/diagnóstico , Prueba de COVID-19 , Enfermedad Crónica , Humanos , Nanopartículas de Magnetita/uso terapéutico , Nanomedicina , PandemiasRESUMEN
Presently, nanocarriers (NCs) have gained huge attention for their structural ability, good biocompatibility, and biodegradability. The development of effective NCs with stimuli-responsive properties has acquired a huge interest among scientists. When developing drug delivery NCs, the fundamental goal is to tackle the delivery-related problems associated with standard chemotherapy and to carry medicines to the intended sites of action while avoiding undesirable side effects. These nanocarriers were able of delivering drugs to tumors through regulating their pH, temperature, enzyme responsiveness. With the use of nanocarriers, chemotherapeutic drugs could be supplied to tumors more accurately that can equally encapsulate and deliver them. Material carriers for chemotherapeutic medicines are discussed in this review keeping in viewpoint of the structural properties and targeting methods that make these carriers more therapeutically effective, in addition to metabolic pathways triggered by drug-loaded NCs. Largely, the development of NCs countering to endogenous and exogenous stimuli in tumor regions and understanding of mechanisms would encourage the progress for tumor therapy and precision diagnosis in future.
Asunto(s)
Nanopartículas , Neoplasias , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Humanos , Nanopartículas/química , Neoplasias/tratamiento farmacológico , TemperaturaRESUMEN
The ecotoxicological effect of after-usage released TiO2 nanoparticles in aquatic resources has been a major concern owing to their production and utilization in different applications. Addressing the issue, this study investigates the detailed in vivo molecular toxicity of TiO2 nanoparticles with Paramecium caudatum. TiO2 nanoparticles were synthesized at a lab scale using high energy ball milling technique; characterized for their physicochemical properties and investigated for their ecotoxicological impact on oxidative stress, steatosis, and apoptosis of cells through different biochemical analysis, flow cytometry, and fluorescent microscopy. TiO2 nanoparticles; TiO2 (N15); of size 36 ± 12 nm were synthesized with a zeta potential of - 20.2 ± 8.8 mV and bandgap of 4.6 ± 0.3 eV and exhibited a blue shift in UV-spectrum. Compared to the Bulk TiO2, the TiO2 (N15) exhibited higher cytotoxicity with a 24 h LC50 of 202.4 µg/ml with P. Caudatum. The mechanism was elucidated as the size and charge-dependent internalization of nanoparticles leading to abnormal physiological metabolism in oxidative stress, steatosis, and apoptosis because of their influential effect on the activity of metabolic proteins like SOD, GSH, MDA, and catalase. The study emphasized the controlled usage TiO2 nanoparticles in daily activity with a concern for ecological and biomedical aspects.
Asunto(s)
Nanopartículas , Paramecium caudatum , Apoptosis , Nanopartículas/química , Nanopartículas/toxicidad , Estrés Oxidativo , Titanio/toxicidadRESUMEN
The mortality and morbidity rates for prostate cancer have recently increased to alarming levels, rising higher than lung cancer. Due to a lack of drug targets and molecular probes, existing theranostic techniques are limited. Human LIN28A and its paralog LIN28B overexpression are associated with a number of tumors resulting in a remarkable increase in cancer aggression and poor prognoses. The current review aims to highlight recent work identifying the key roles of LIN28A and LIN28B in prostate cancer, and to instigate further preclinical and clinical research in this important area.
Asunto(s)
Terapia Molecular Dirigida , Medicina de Precisión , Neoplasias de la Próstata/terapia , Proteínas de Unión al ARN/metabolismo , Humanos , Masculino , Neoplasias de la Próstata/patologíaRESUMEN
The identification of reactive intermediates during molecule-to-nanoparticle (NP) transformation has great significance in comprehending the mechanism of NP formation and, therefore, optimizing the synthetic conditions and properties of the formed products. We report here the room temperature (RT) synthesis of AgCuSe NPs from the reaction of di-tert-butyl selenide with trifluoroacetates (TFA) of silver(I) and copper(II). The isolation and characterization of a molecular species during the course of this reaction, [Ag2Cu(TFA)4(tBu2Se)4] (1), which shows extraordinary reactivity and interesting thermochromic behavior (blue at 0 °C and green at RT), confirmed that ternary metal selenide NPs are formed via this intermediate species. Similar reactions with related dialkyl chalcogenide R2E resulted in the isolation of molecular species of similar composition, [Ag2Cu(TFA)4(R2E)4] [R = tBu, E = S (2); R = Me, E = Se (3); R = Me, E = S (4)], which are stable at RT but can be converted to ternary metal chalcogenides at elevated temperature. Density functional theory calculations confirm the kinetic instability of 1 and throw light on its thermochromic properties.
RESUMEN
In the present study, we systematically investigated the adsorption mechanism of canonical DNA nucleobases and their two nucleobase pairs on a single-layer gallium sulfide (GaS) substrate using DFT+D3 methods. The GaS substrate has chemical interactions with molecules 0.02 |e| 0.11 |e| from molecules to the monolayer GaS surface. Due to the chemical interactions of adenine, cytosine, guanine, and thymine on the monolayer GaS surface, the work function is decreased by 0.69, 0.60, 0.97, and 0.20 eV, respectively. It is displayed that the bandgap of the monolayer GaS sheet can be significantly affected as induced molecular electronic states tend to appear near the Fermi level region due to chemical and physisorption mechanism. We have also investigated the transport properties of DNA nucleobases, namely, AT and GC pair molecules on the GaS surface, which shows significant reduction in the zero-bias transmission spectra. Moreover, with and without DNA nucleobases, namely, AT and GC pair molecules' absorptions on the GaS surface, clearly expressed in terms of distinct current signals, can be observed as ON and OFF states for this device. The distinctive nucleobase adsorption energies and different I-V responses may serve as potential probes for the selective detection of nucleobase molecules in imminent DNA sequencing applications based on a monolayer GaS surface.
Asunto(s)
Secuencia de Bases , ADN/química , Galio/química , Sulfuros/química , ADN/análisis , Estructura MolecularRESUMEN
Day to day consumption of black pepper raise concern about the detailed information about their medicinal, pharmaceutical values and knowledge about the biocompatibility with respect to ecosystem. This study investigates the in vivo selective molecular biocompatibility of its seed cover (SC) and seed core (SP) powder extract using embryonic zebrafish model. Gas chromatography mass spectrometry (GCMS) analysis of the extract prepared by grinding showed presence of different components with "piperine" as principle component. Biocompatibility analysis showed dose and time dependent selective effect of SC and SP with LC50 of 30.4 µg/ml and 35.6 µg/ml, respectively on survivability, hatching and heartbeat rate in embryonic zebrafish. Mechanistic investigation elucidated it as effect of accumulation and internalization of black pepper leading to their influence on structure and function of cellular proteins hatching enzyme (he1a), superoxide dismutase (sod1) and tumor protein (tp53) responsible for delayed hatching, oxidative stress induction and apoptosis. The study provided insight to selective biocompatibility of black pepper expedient to produce higher quality spices with respect to pharmaceutical, clinical and environmental aspects.
Asunto(s)
Alcaloides/química , Apoptosis/efectos de los fármacos , Benzodioxoles/química , Estrés Oxidativo/efectos de los fármacos , Piper nigrum/toxicidad , Piperidinas/química , Alcamidas Poliinsaturadas/química , Alcaloides/análisis , Animales , Benzodioxoles/análisis , Piper nigrum/química , Piper nigrum/embriología , Piperidinas/análisis , Extractos Vegetales/química , Extractos Vegetales/toxicidad , Alcamidas Poliinsaturadas/análisis , Semillas/química , Semillas/toxicidad , Superóxido Dismutasa/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Pez Cebra/embriología , Pez Cebra/fisiología , Proteínas de Pez Cebra/química , Proteínas de Pez Cebra/metabolismoRESUMEN
The investigation of the biocompatibility of potential and commercially available dental material is a major challenge in dental science. This study demonstrates that the zebrafish model is a novel in vivo model for investigating the biocompatibility of dental materials. Two commercially available dental materials, mineral trioxide aggregate (MTA) and Biodentine, were assessed for their biocompatibility. The biocompatibility analysis was performed in embryonic zebrafish with the help of standard toxicity assays measuring essential parameters such as survivability and hatching. The mechanistic and comparative analysis of toxicity was performed by oxidative stress analysis by measuring ROS induction and apoptosis in zebrafish exposed to dental materials at different concentrations. The molecular investigation at the protein level was done by a computational approach using in silico molecular docking and pathway analysis. The toxicity analysis showed a significant reduction in hatching and survivability rates along with morphological malformations with an increase in the concentration of exposed materials. ROS and apoptosis assay results revealed a greater biocompatibility of Biodentine as compared to that of MTA which was concentration-dependent. In silico analysis showed the significant role of the tricalcium silicate-protein ( Sod1, tp53, RUNX2B) interaction in an exhibition of toxicity. The study provides a new vision and standard in dental material sciences for assessing the biocompatibility of potential novel and commercially available dental materials.
Asunto(s)
Compuestos de Aluminio/toxicidad , Compuestos de Calcio/toxicidad , Cementos Dentales/toxicidad , Embrión no Mamífero/efectos de los fármacos , Óxidos/toxicidad , Silicatos/toxicidad , Pez Cebra/embriología , Animales , Simulación por Computador , Combinación de Medicamentos , Femenino , Masculino , Simulación del Acoplamiento MolecularRESUMEN
HIV-1 being the most widespread type worldwide, its accounts for almost 95% of all infections including HIV associated dementia (HAD) that triggers neurological dysfunction and neurodegeneration in patients. The common features associated with HAD and other neurodegenerative diseases are accumulation of amyloid plaques, neuronal loss and deterioration of cognitive abilities, amongst which amyloid fibrillation is considered to be a hallmark. The success of effective therapeutics lies in the understanding of mechanisms leading to neurotoxicity. Few viral proteins like gp-120 are known to be involved in aggregation and enhancement of viral infectivity while comprehending the neurotoxic role of some other proteins is still underway. In the current study, amyloidogenic potential of HIV-1 Vpu protein from brain isolate is investigated through computational approaches. The aggregation propensity of brain derived HIV-1 Vpu was assessed by several amyloid prediction servers that projected the region 4-35 to be amyloidogenic. The protein structure was modeled and subjected to 70â¯ns molecular dynamics (MD) simulation to investigate the transformation of α-helical conformation of the predicted aggregate region into ß-sheet, proposing the protein's ability to initiate fibril formation that is central to amyloidogenic proteins. The structural features of brain derived HIV-1 Vpu were consistent with the in silico amyloid prediction results that depicts the conformational change in the region 8-28 of which residues Ala8, Ile9, Val10, Ala19, Ile20 and Val21 constitutes ß-sheet formation. The α-helix/ß-sheet discordance of the predicted region was reflected in the simulation study highlighting the possible structural transition associated with HIV-1 Vpu protein of brain isolate.
Asunto(s)
Amiloide/química , Proteínas del Virus de la Inmunodeficiencia Humana/química , Proteínas Reguladoras y Accesorias Virales/química , Encéfalo/metabolismo , VIH-1/química , Proteínas del Virus de la Inmunodeficiencia Humana/aislamiento & purificación , Humanos , Modelos Moleculares , Simulación de Dinámica Molecular , Agregación Patológica de Proteínas , Conformación Proteica , Estructura Secundaria de Proteína , Proteínas Reguladoras y Accesorias Virales/aislamiento & purificaciónRESUMEN
Pulp therapy has been emerged as a one of the efficient therapies in the field of endodontics. Among different types of new endodontic materials, pulpotec has been materialized as a recognized material for vital pulp therapy. However, its efficacy has been challenged due to lack of information about its cellular biocompatibility. This study evaluates the mechanistic biocompatibility of pulpotec cement with macrophage cells (RAW 264.7) at cellular and molecular level. The biocompatibility was evaluated using experimental and computational techniques like MTT assay, oxidative stress analysis and apoptosis analysis through flow cytometry and fluorescent microscopy. The results showed concentration-dependent cytotoxicity of pulpotec cement extract to RAW 264.7 cells with an LC 50 of X/10-X/20. The computational analysis depicted the molecular interaction of pulpotec cement extract components with metabolic proteins like Sod1 and p53. The study revealed the effects of Pulpotec cement's extract, showing a concentration-dependent induction of oxidative stress and apoptosis. These effects were due to influential structural and functional abnormalities in the Sod1 and p53 proteins, caused by their molecular interaction with internalized components of Pulpotec cement. The study provided a detailed view on the utility of Pulpotec in endodontic applications, highlighting its biomedical aspects.
Asunto(s)
Apoptosis , Materiales Biocompatibles , Macrófagos , Estrés Oxidativo , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Ratones , Animales , Células RAW 264.7 , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Materiales Biocompatibles/farmacología , Ensayo de Materiales , Supervivencia Celular/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismo , Cementos Dentales/farmacología , Cementos Dentales/química , Superóxido Dismutasa-1/metabolismoRESUMEN
Current methods of cancer therapy have demonstrated enormous potential in tumor inhibition. However, a high dosage regimen of chemotherapy results in various complications which affect the normal body cells. Tumor cells also develop resistance against the prescribed drugs in the whole treatment regimen increasing the risk of cancer relapse. Metronomic chemotherapy is a modern treatment method that involves administering drugs at low doses continuously, allowing the drug sufficient time to take its effect. This method ensures that the toxicity of the drugs is to a minimum in comparison to conventional chemotherapy. Nanoparticles have shown efficacy in delivering drugs to the tumor cells in various cancer therapies. Combining nanoparticles with metronomic chemotherapy can yield better treatment results. This combination stimulates the immune system, improving cancer cells recognition by immune cells. Evidence from clinical and pre-clinical trials supports the use of metronomic delivery for drug-loaded nanoparticles. This review focuses on the functionalization of nanoparticles for improved drug delivery and inhibition of tumor growth. It emphasizes the mechanisms of metronomic chemotherapy and its conjunction with nanotechnology. Additionally, it explores tumor progression and the current methods of chemotherapy. The challenges associated with nano-based metronomic chemotherapy are outlined, paving the way for prospects in this dynamic field.
Asunto(s)
Administración Metronómica , Nanopartículas , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Nanopartículas/administración & dosificación , Antineoplásicos/administración & dosificación , Animales , Sistemas de Liberación de Medicamentos/métodos , Portadores de FármacosRESUMEN
Bioaccumulation of Chlorpyrifos (CP) as pesticides due to their aggrandized use in agriculture has raised serious concern on the health of ecosystem and human beings. Moreover, their degraded products like 3,5,6-trichloro-2-pyridinol (TCP) has enhanced the distress due to their unpredictable biotoxicity. This study evaluates and deduce the comparative in vivo mechanistic biotoxicity of CP and TCP with zebrafish embryos through experimental and computational approach. Experimental cellular and molecular analysis showed higher induction of morphological abnormalities, oxidative stress and apoptosis in TCP exposed embryos compared to CP exposure due to upregulation of metabolic enzymes like Zhe1a, Sod1 and p53. Computational analysis excavated the differential discrepancies in intrinsic atomic interaction as a reason of disparity in biotoxicity of CP and TCP. The mechanistic differences were deduced due to the differential accumulation and internalisation leading to variable interaction with metabolic enzymes for oxidative stress and apoptosis causing physiological and morphological abnormalities. The study unravelled the information of in vivo toxicity at cellular and molecular level to advocate the attention of taking measures for management of CP as well as TCP for environmental and human health.
Asunto(s)
Cloropirifos , Animales , Humanos , Cloropirifos/toxicidad , Cloropirifos/análisis , Pez Cebra , Ecosistema , Piridonas/toxicidadRESUMEN
The aggrandised advancement in utility of advanced day-to-day materials and nanomaterials has raised serious concern on their biocompatibility with human and other biotic members. In last few decades, understanding of toxicity of these materials has been given the centre stage of research using many in vitro and in vivo models. Zebrafish (Danio rerio), a freshwater fish and a member of the minnow family has garnered much attention due to its distinct features, which make it an important and frequently used animal model in various fields of embryology and toxicological studies. Given that fertilization and development of zebrafish eggs take place externally, they serve as an excellent model organism for studying early developmental stages. Moreover, zebrafish possess a comparable genetic composition to humans and share almost 70% of their genes with mammals. This particular model organism has become increasingly popular, especially for developmental research. Moreover, it serves as a link between in vitro studies and in vivo analysis in mammals. It is an appealing choice for vertebrate research, when employing high-throughput methods, due to their small size, swift development, and relatively affordable laboratory setup. This small vertebrate has enhanced comprehension of pathobiology and drug toxicity. This review emphasizes on the recent developments in toxicity screening and assays, and the new insights gained about the toxicity of drugs through these assays. Specifically, the cardio, neural, and, hepatic toxicology studies inferred by applications of nanoparticles have been highlighted.
Asunto(s)
Nanoestructuras , Pez Cebra , Animales , Humanos , Modelos Animales , Hígado , MamíferosRESUMEN
Cell fate determination is a complex process that is frequently described as cells traveling on rugged pathways, beginning with DNA damage response (DDR). Tumor protein p53 (p53) and phosphatase and tensin homolog (PTEN) are two critical players in this process. Although both of these proteins are known to be key cell fate regulators, the exact mechanism by which they collaborate in the DDR remains unknown. Thus, we propose a dynamic Boolean network. Our model incorporates experimental data obtained from NSCLC cells and is the first of its kind. Our network's wild-type system shows that DDR activates the G2/M checkpoint, and this triggers a cascade of events, involving p53 and PTEN, that ultimately lead to the four potential phenotypes: cell cycle arrest, senescence, autophagy, and apoptosis (quadra-stable dynamics). The network predictions correspond with the gain-and-loss of function investigations in the additional two cell lines (HeLa and MCF-7). Our findings imply that p53 and PTEN act as molecular switches that activate or deactivate specific pathways to govern cell fate decisions. Thus, our network facilitates the direct investigation of quadruplicate cell fate decisions in DDR. Therefore, we concluded that concurrently controlling PTEN and p53 dynamics may be a viable strategy for enhancing clinical outcomes.
Asunto(s)
Daño del ADN , Fosfohidrolasa PTEN , Proteína p53 Supresora de Tumor , Humanos , Apoptosis , Puntos de Control del Ciclo Celular , Células HeLa , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Nanoscience has emerged as a fascinating field of science, with its implementation in multiple applications in the form of nanotechnology. Nanotechnology has recently been more impactful in diverse sectors such as the pharmaceutical industry, agriculture sector, and food market. The peculiar properties which make nanoparticles as an asset are their large surface area and their size, which ranges between 1 and 100 nanometers (nm). Various technologies, such as chemical and biological processes, are being used to synthesize nanoparticles. The green chemistry route has become extremely popular due to its use in the synthesis of nanoparticles. Nanomaterials are versatile and impactful in different day to day applications, resulting in their increased utilization and distribution in human cells, tissues, and organs. Owing to the deployment of nanoparticles at a high demand, the need to produce nanoparticles has raised concerns regarding environmentally friendly processes. These processes are meant to produce nanomaterials with improved physiochemical properties that can have significant uses in the fields of medicine, physics, and biochemistry. Among a plethora of nanomaterials, silver nanoparticles have emerged as the most investigated and used nanoparticle. Silver nanoparticles (AgNPs) have become vital entities of study due to their distinctive properties which the scientific society aims to investigate the uses of. The current review addresses the modern expansion of AgNP synthesis, characterization, and mechanism, as well as global applications of AgNPs and their limitations.