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Nickel ferrite nanoparticles (NiFe2O4 NPs) were synthesized using the medicinally important plant Aloe vera leaf extract, and their structural, morphological, and magnetic properties were characterized by x-ray diffraction (XRD), fourier transform infrared (FTIR), scanning electron microscopy (SEM), energy dispersive x-ray (EDX), and vibrating sample magnetometer (VSM). The synthesized NPs were soft ferromagnetic and spinel in nature, with an average particle size of 22.2 nm. To the best of our understanding, this is the first comprehensive investigation into the antibacterial, anticandidal, antibiofilm, and antihyphal properties of NiFe2O4 NPs against C. albicans as well as drug-resistant gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and gram-negative multidrug resistant Pseudomonas aeruginosa (MDR-P. aeruginosa) bacteria. NiFe2O4 NPs showed potent antimicrobial activity (MIC 1.6-2 mg/mL) against the test pathogens. NiFe2O4 NPs at 0.5 mg/mL suppressed biofilm formation by 49.5-53.1 % in test pathogens. The study found that the NPs not only prevent the formation of biofilm, but also eliminate existing mature biofilms by 50.5-75.79 % at 0.5 mg/mL, which was further validated by SEM. SEM examination revealed a reduction in the number of cells that form biofilms and adhere to the surface. Additionally, it considerably impeded the colonization and aggregation of the biofilm strains on the glass surface. Light microscopic examination demonstrated that NPs effectively prevent the expansion of hyphae, filaments, and yeast-to-hyphae transformation in C. albicans, resulting in a substantial decrease in their ability to cause infection. Moreover, SEM images of the treated cells exhibited the presence of wrinkles, deformities, and impaired cell walls, which suggests an alteration and instability of the membrane. This study demonstrated the efficacy of the greenly manufactured NPs in suppressing the proliferation of candida, drug-resistant bacteria, and their preexisting biofilms, as well as yeast-to-hyphae transformation. Therefore, these NPs with broad spectrum applications could be utilized in health settings to mitigate biofilm-related health conditions caused by pathogenic microbial strains.
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Antibacterianos , Biopelículas , Candida albicans , Compuestos Férricos , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Níquel , Pseudomonas aeruginosa , Biopelículas/efectos de los fármacos , Níquel/química , Níquel/farmacología , Compuestos Férricos/farmacología , Compuestos Férricos/química , Candida albicans/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Hojas de la Planta/química , Hojas de la Planta/microbiología , Aloe/química , Difracción de Rayos X , Tamaño de la Partícula , Microscopía Electrónica de Rastreo , Antifúngicos/farmacología , Antifúngicos/química , Espectroscopía Infrarroja por Transformada de Fourier , Nanopartículas/químicaRESUMEN
Cancer patients face a significant clinical and socio-economic burden due to increased incidence, mortality, and poor survival. Factors like late diagnosis, recurrence, drug resistance, severe side effects, and poor bioavailability limit the scope of current therapies. There is a need for novel, cost-effective, and safe diagnostic methods, therapeutics to overcome recurrence and drug resistance, and drug delivery vehicles with enhanced bioavailability and less off-site toxicity. Advanced nanomaterial-based research is aiding cancer biologists by providing solutions for issues like hypoxia, tumor microenvironment, low stability, poor penetration, target non-specificity, and rapid drug clearance. Currently, nanozymes and carbon-dots are attractive due to their low cost, high catalytic activity, biocompatibility, and lower toxicity. Nanozymes and carbon-dots are increasingly used in imaging, biosensing, diagnosis, and targeted cancer therapy. Integrating these materials with advanced diagnostic tools like CT scans and MRIs can aid in clinical decision-making and enhance the effectiveness of chemotherapy, photothermal, photodynamic, and sonodynamic therapies, with minimal invasion and reduced collateral effects.
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Nanoestructuras , Neoplasias , Humanos , Carbono , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Microambiente TumoralRESUMEN
This study emphasized on the synthesis of zinc oxide nanoparticles (ZnO NPs) in an environmentally friendly manner from the extract of Catharanthus roseus leaves and its antibacterial assessment against the pneumonia-causing pathogen Klebsiella pneumoniae. This simple and convenient phytosynthesis approach is found to be beneficial over conventional methods, wherein plants serve as excellent reducing, capping, and stabilizing agents that enables the formation of ZnO NPs without the use of harmful chemicals. The formation of ZnO NPs was confirmed through several characterization techniques such as UV-visible spectroscopy, XRD, FT-IR, SEM, HR-TEM, and EDX. XRD analysis revealed high polycrystallinity with crystallite size of approximately 13 nm. SEM and HR-TEM revealed the hexagonal structure of ZnO NPs with the particle size range of 20-50 nm. The EDX shows the elemental purity without any impurity. Furthermore, the antibacterial efficacy by the technique of disc diffusion exhibited clear inhibition zones in ZnO NPs-treated discs. In addition, 125 µg/mL of ZnO NP concentration showed minimum inhibition by the microbroth dilution method. The potent inhibitory activity was further validated with trypan blue dye exclusion and fluorescence microscopy. Finally, SEM examination confirmed the efficient antibacterial potential of ZnO NPs through disruption of the intact morphology of Klebsiella pneumoniae.
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Antibacterianos , Catharanthus , Klebsiella pneumoniae , Nanopartículas del Metal , Óxido de Zinc , Klebsiella pneumoniae/efectos de los fármacos , Óxido de Zinc/química , Óxido de Zinc/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Catharanthus/química , Nanopartículas del Metal/química , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/química , Extractos Vegetales/farmacología , Difracción de Rayos XRESUMEN
Cancer is one of the dreadful diseases worldwide. Surgery, radiation and chemotherapy, are the three basic standard modes of cancer treatment. However, difficulties in cancer treatment are increasing due to immune escape, spreading of cancer to other places, and resistance of cancer cells to therapies. Various signaling mechanisms, including PI3K/Akt/mTOR, RAS, WNT/ß-catenin, TGF-beta, and notch pathways, are involved in cancer resistance. The adaptive inflammatory response is the initial line of defence against infection. However, chronic inflammation can lead to tumorigenesis, malignant transformation, tumor growth, invasion, and metastasis. The most commonly dysregulated inflammatory pathways linked to cancer include NF-κB, MAPK, JAK-STAT, and PI3K/AKT. To overcome major hurdles in cancer therapy, nanomedicine is receiving much attention due to its role as a vehicle for delivering chemotherapeutic agents that specifically target tumor sites. Several biocompatible nanocarriers including polymer and inorganic nanoparticles, liposomes, micellar nanoparticles, nanotubes, and exosomes have been extensively studied. Exosome has been reported as an important potential system that could be effectively used as a bioinspired, bioengineered, and biomimetic drug delivery solution considering its toxicity, immunogenicity, and rapid clearance by the mononuclear phagocyte system. Exosome-mimetic vesicles are receiving much interest for developing nano-sized delivery systems. In this review, exosomes in detail as well as certain other nanocarriers, and their potential therapeutic roles in cancer therapy has been thoroughly discussed. Additionally, we also reviewed on oncogenic and tumor suppressor proteins, inflammation, and their associated signaling pathways and their interference by exosomes based nanomedicine.
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Exosomas , Neoplasias , Humanos , Nanomedicina , Exosomas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Inflamación/metabolismoRESUMEN
Diabetes is a serious health issue that causes a progressive dysregulation of carbohydrate metabolism due to insufficient insulin hormone, leading to consistently high blood glucose levels. According to the epidemiological data, the prevalence of diabetes has been increasing globally, affecting millions of individuals. It is a long-term condition that increases the risk of various diseases caused by damage to small and large blood vessels. There are two main subtypes of diabetes: type 1 and type 2, with type 2 being the most prevalent. Genetic and molecular studies have identified several genetic variants and metabolic pathways that contribute to the development and progression of diabetes. Current treatments include gene therapy, stem cell therapy, statin therapy, and other drugs. Moreover, recent advancements in therapeutics have also focused on developing novel drugs targeting these pathways, including incretin mimetics, SGLT2 inhibitors, and GLP-1 receptor agonists, which have shown promising results in improving glycemic control and reducing the risk of complications. However, these treatments are often expensive, inaccessible to patients in underdeveloped countries, and can have severe side effects. Peptides, such as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are being explored as a potential therapy for diabetes. These peptides are postprandial glucose-dependent pancreatic beta-cell insulin secretagogues and have received much attention as a possible treatment option. Despite these advances, diabetes remains a major health challenge, and further research is needed to develop effective treatments and prevent its complications. This review covers various aspects of diabetes, including epidemiology, genetic and molecular basis, and recent advancements in therapeutics including herbal and synthetic peptides.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/genética , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Incretinas/uso terapéutico , Incretinas/metabolismo , Polipéptido Inhibidor Gástrico , Insulina/metabolismo , Péptidos/uso terapéutico , Glucosa/metabolismo , Glucemia/metabolismoRESUMEN
Central nervous system disorders, especially neurodegenerative diseases, are a public health priority and demand a strong scientific response. Various therapy procedures have been used in the past, but their therapeutic value has been insufficient. The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier is two of the barriers that protect the central nervous system (CNS), but are the main barriers to medicine delivery into the CNS for treating CNS disorders, such as brain tumors, Parkinson's disease, Alzheimer's disease, and Huntington's disease. Nanotechnology-based medicinal approaches deliver valuable cargos targeting molecular and cellular processes with greater safety, efficacy, and specificity than traditional approaches. CNS diseases include a wide range of brain ailments connected to short- and long-term disability. They affect millions of people worldwide and are anticipated to become more common in the coming years. Nanotechnology-based brain therapy could solve the BBB problem. This review analyzes nanomedicine's role in medication delivery; immunotherapy, chemotherapy, and gene therapy are combined with nanomedicines to treat CNS disorders. We also evaluated nanotechnology-based approaches for CNS disease amelioration, with the intention of stimulating the immune system by delivering medications across the BBB.
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Enfermedades del Sistema Nervioso Central , Nanopartículas , Humanos , Nanomedicina , Sistemas de Liberación de Medicamentos/métodos , Encéfalo , Barrera Hematoencefálica , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Nanopartículas/uso terapéuticoRESUMEN
Breast cancer is one of the most prevalent and reoccurring cancers and the second most common reason of death in women. Despite advancements in therapeutic strategies for breast cancer, early tumor recurrence and metastasis in patients indicate resistance to chemotherapeutic medicines, such as paclitaxel due to the abnormal expression of ER and EGF2 in breast cancer cells. Therefore, the development of alternatives to paclitaxel is urgently needed to overcome challenges involving drug resistance. An increasing number of studies has revealed miRNAs as novel natural alternative substances that play a crucial role in regulating several physiological processes and have a close, adverse association with several diseases, including breast cancer. Due to the therapeutic potential of miRNA and paclitaxel in cancer research, the current review focuses on the differential roles of various miRNAs in breast cancer development and treatment. miRNA delivery to a specific target site, the development of paclitaxel and miRNA formulations, and nanotechnological strategies for the delivery of nanopaclitaxel in the management of breast cancer are discussed. These strategies involve improving the cellular uptake and bioavailability and reducing the toxicity of free paclitaxel to achieve accumulation tumor site. Furthermore, a molecular docking study was performed to ascertain the enhanced anticancer activity of the nanoformulation of ANG1005 and Abraxane. An in silico analysis revealed that ANG1005 and Abraxane nanoformulations have superior and significantly enhanced interactions with the proteins α-tubulin and Bcl-2. Therefore, ANG1005 and Abraxane may be more suitable in the therapeutic management of breast cancer than the existing free paclitaxel. miRNAs can revert abnormal gene expression to normalcy; since miRNAs serve as tumor suppressors. Therefore, restoration of particular miRNAs levels as a replacement therapy may be an effective endocrine potential strategy for treating ER positive/ negative breast cancers.
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Neoplasias de la Mama/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , MicroARNs/genética , Nanopartículas/administración & dosificación , Nanotecnología/métodos , Paclitaxel/análogos & derivados , Péptidos/administración & dosificación , Receptores de Estrógenos/metabolismo , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/química , Neoplasias de la Mama/patología , Simulación por Computador , Manejo de la Enfermedad , Resistencia a Antineoplásicos , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Simulación del Acoplamiento Molecular , Nanopartículas/química , Paclitaxel/administración & dosificación , Paclitaxel/química , Péptidos/químicaRESUMEN
Epilepsy is a chronic brain disorder, with anti-epileptic drugs (AEDs) providing relief from hyper-excitability of neurons, but largely failing to restrain neurodegeneration. We investigated a progressive preclinical trial in rats, whereby the test drugs; sodium valproate (SVP; 150 and 300 mg/kg), baclofen (BFN; 5 and 10 mg/kg), and thymoquinone (THQ; 40 and 80 mg/kg) were administered (i.p, once/day for 15 days) alone, and as low dose combinations, and subsequently tested for antiseizure and neuroprotective potential using electrical stimulation of neurons by Maximal electroshock (MES). The seizure stages were monitored, and hippocampal levels of m-TOR, IL-1ß, IL-6 were measured. Hippocampal histopathology was also performed. Invitro and Insilco studies were run to counter-confirm the results from rodent studies. We report the synergistic effect of trio-drug combination; SVP (150 mg/kg), BFN (5 mg/kg) and THQ (40 mg/kg) against generalized seizures. The Insilco results revealed that trio-drug combination binds the Akt active site as a supramolecular complex, which could have served as a delivery system that affects the penetration and the binding to the new target. The potential energy of the ternary complex in the Akt active site after dynamics simulation was found to be -370.426 Kcal/mol, while the supramolecular ternary complex alone was -38.732 Kcal/mol, with a potential energy difference of -331.694 Kcal/mol, which favors the supramolecular ternary complex at Akt active site binding. In addition, the said combination increased cell viability by 267% and reduced morphological changes induced by Pentylenetetrazol (PTZ) in HEK-293 cells, which indicates the neuroprotective property of said combination. To conclude, we are the first to report the anti-convulsant and neuroprotective potential of the trio-drug combination.
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Hydrogen sulfide (H2S) is an endogenous biologically active gas produced in mammalian tissues. It plays a very critical role in many pathophysiological processes in the body. It can be endogenously produced through many enzymes analogous to the cysteine family, while the exogenous source may involve inorganic sulfide salts. H2S has recently been well investigated with regard to the onset of various carcinogenic diseases such as lung, breast, ovaries, colon cancer, and neurodegenerative disorders. H2S is considered an oncogenic gas, and a potential therapeutic target for treating and diagnosing cancers, due to its role in mediating the development of tumorigenesis. Here in this review, an in-detail up-to-date explanation of the potential role of H2S in different malignancies has been reported. The study summarizes the synthesis of H2S, its roles, signaling routes, expressions, and H2S release in various malignancies. Considering the critical importance of this active biological molecule, we believe this review in this esteemed journal will highlight the oncogenic role of H2S in the scientific community.
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Sulfuro de Hidrógeno , Neoplasias , Animales , Biología , Cisteína , Sulfuro de Hidrógeno/metabolismo , Mamíferos/metabolismo , Neoplasias/tratamiento farmacológico , Transducción de Señal/fisiologíaRESUMEN
Biofunctionalized TiO2 nanoparticles with a size range of 18.42±1.3â nm were synthesized in a single-step approach employing Grape seed extract (GSE) proanthocyanin (PAC) polyphenols. The effect of PACs rich GSE corona was examined with respect to 1)â the stability and dispersity of as-synthesized GSE-TiO2 -NPs, 2)â their antiproliferative and antibiofilm efficacy, and 3)â their propensity for internalization and reactive oxygen species (ROS) generation in urinary tract infections (UTIs) causing Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcusâ saprophyticus strains. State-of-the-art techniques were used to validate GSE-TiO2 -NPs formation. Comparative Fourier transformed infrared (FTIR) spectral analysis demonstrated that PACs linked functional -OH groups likely play a central role in Ti4+ reduction and nucleation to GSE-TiO2 -NPs, while forming a thin, soft corona around nascent NPs to attribute significantly enhanced stability and dispersity. Transmission electron microscopic (TEM) and inductively coupled plasma mass-spectroscopy (ICP-MS) analyses confirmed there was significantly (p<0.05) enhanced intracellular uptake of GSE-TiO2 -NPs in both Gram-negative and -positive test uropathogens as compared to bare TiO2 -NPs. Correspondingly, compared to bare NPs, GSE-TiO2 -NPs induced intracellular ROS formation that corresponded well with dose-dependent inhibitory patterns of cell proliferation and biofilm formation in both the tested strains. Overall, this study demonstrates that -OH rich PACs of GSE corona on biogenic TiO2 -NPs maximized the functional stability, dispersity and propensity of penetration into planktonic cells and biofilm matrices. Such unique merits warrant the use of GSE-TiO2 -NPs as a novel, functionally stable and efficient antibacterial nano-formulation to combat the menace of UTIs in clinical settings.
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Nanopartículas del Metal , Nanopartículas , Antibacterianos/farmacología , Bacterias , Biopelículas , Proliferación Celular , Especies Reactivas de Oxígeno , TitanioRESUMEN
The study was undertaken to investigate the antioxidant, genotoxic, and cytotoxic potentialities of phyto-fabricated zinc oxide nanoparticles (ZnO-NPs) from Ipomoea obscura (L.) Ker Gawl. aqueous leaf extract. The UV-visible spectral analysis of the ZnO-NPs showed an absorption peak at 304 nm with a bandgap energy of 3.54 eV, which are characteristics of zinc nanoparticles. Moreover, the particles were of nano-size (~24.26 nm) with 88.11% purity and were agglomerated as observed through Scanning Electron Microscopy (SEM). The phyto-fabricated ZnO-NPs offered radical scavenging activity (RSA) in a dose-dependent manner with an IC50 of 0.45 mg mL-1. In addition, the genotoxicity studies of ZnO-NPs carried out on onion root tips revealed that the particles were able to significantly inhibit the cell division at the mitotic stage with a mitotic index of 39.49%. Further, the cytotoxic studies on HT-29 cells showed that the phyto-fabricated ZnO-NPs could arrest the cell division as early as in the G0/G1 phase (with 92.14%) with 73.14% cells showing early apoptotic symptoms after 24 h of incubation. The results of the study affirm the ability of phyto-fabricated ZnO-NPs from aqueous leaf extract of I. obscura is beneficial in the cytotoxic application.
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Ipomoea/metabolismo , Nanopartículas/química , Óxido de Zinc/química , Óxido de Zinc/farmacología , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/toxicidad , Compuestos de Bifenilo/química , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/metabolismo , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/toxicidad , Tecnología Química Verde , Células HT29 , Humanos , Pruebas de Mutagenicidad , Cebollas/efectos de los fármacos , Cebollas/genética , Picratos/química , Óxido de Zinc/metabolismo , Óxido de Zinc/toxicidadRESUMEN
Background and Objectives: Recently, many studies have focused on the early detection of Parkinson's disease (PD). This disease belongs to a group of neurological problems that immediately affect brain cells and influence the movement, hearing, and various cognitive functions. Medical data sets are often not equally distributed in their classes and this gives a bias in the classification of patients. We performed a Hybrid feature selection framework that can deal with imbalanced datasets like PD. Use the SOMTE algorithm to deal with unbalanced datasets. Removing the contradiction from the features in the dataset and decrease the processing time by using Recursive Feature Elimination (RFE), and Principle Component Analysis (PCA). Materials and Methods: PD acoustic datasets and the characteristics of control subjects were used to construct classification models such as Bagging, K-nearest neighbour (KNN), multilayer perceptron, and the support vector machine (SVM). In the prepressing stage, the synthetic minority over-sampling technique (SMOTE) with two-feature selection RFE and PCA were used. The PD dataset comprises a large difference between the numbers of the infected and uninfected patients, which causes the classification bias problem. Therefore, SMOTE was used to resolve this problem. Results: For model evaluation, the train-test split technique was used for the experiment. All the models were Grid-search tuned, the evaluation results of the SVM model showed the highest accuracy of 98.2%, and the KNN model exhibited the highest specificity of 99%. Conclusions: the proposed method is compared with the current modern methods of detecting Parkinson's disease and other methods for medical diseases, it was noted that our developed system could treat data bias and reach a high prediction of PD and this can be beneficial for health organizations to properly prioritize assets.
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Enfermedad de Parkinson , Algoritmos , Análisis por Conglomerados , Humanos , Redes Neurales de la Computación , Enfermedad de Parkinson/diagnóstico , Máquina de Vectores de SoporteRESUMEN
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a global pandemic and is posing a serious challenge to mankind. As per the current scenario, there is an urgent need for antiviral that could act as a protective and therapeutic against SARS-CoV-2. Previous studies have shown that SARS-CoV-2 is much similar to the SARS-CoV bat that occurred in 2002-03. Since it is a zoonotic virus, the exact source is still unknown, but it is believed bats may be the primary reservoir of SARS-CoV-2 through which it has been transferred to humans. In this review, we have tried to summarize some of the approaches that could be effective against SARS-CoV-2. Firstly, plants or plant-based products have been effective against different viral diseases, and secondly, plants or plant-based natural products have the minimum adverse effect. We have also highlighted a few vitamins and minerals that could be beneficial against SARS-CoV-2.
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Antivirales/uso terapéutico , Productos Biológicos/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Nutrientes/uso terapéutico , SARS-CoV-2/efectos de los fármacos , Virosis/tratamiento farmacológico , Animales , Quirópteros/virología , HumanosRESUMEN
In ovarian cancer, the prometastatic RTK AXL promotes motility, invasion and poor prognosis. Here, we show that reduced survival caused by AXL overexpression can be mitigated by the expression of the GPI-anchored tumour suppressor OPCML Further, we demonstrate that AXL directly interacts with OPCML, preferentially so when AXL is activated by its ligand Gas6. As a consequence, AXL accumulates in cholesterol-rich lipid domains, where OPCML resides. Here, phospho-AXL is brought in proximity to the lipid domain-restricted phosphatase PTPRG, which de-phosphorylates the RTK/ligand complex. This prevents AXL-mediated transactivation of other RTKs (cMET and EGFR), thereby inhibiting sustained phospho-ERK signalling, induction of the EMT transcription factor Slug, cell migration and invasion. From a translational perspective, we show that OPCML enhances the effect of the phase II AXL inhibitor R428 in vitro and in vivo We therefore identify a novel mechanism by which two spatially restricted tumour suppressors, OPCML and PTPRG, coordinate to repress AXL-dependent oncogenic signalling.
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Moléculas de Adhesión Celular/metabolismo , Neoplasias Ováricas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Proteínas Tirosina Fosfatasas Clase 5 Similares a Receptores/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Animales , Benzocicloheptenos/farmacología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Pollos , Colesterol/metabolismo , Activación Enzimática/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Trompas Uterinas/patología , Femenino , Proteínas Ligadas a GPI/metabolismo , Silenciador del Gen/efectos de los fármacos , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Microdominios de Membrana/metabolismo , Invasividad Neoplásica , Neoplasias Ováricas/patología , Fosforilación/efectos de los fármacos , Unión Proteica/efectos de los fármacos , Resultado del Tratamiento , Triazoles/farmacología , Tirosina Quinasa del Receptor AxlRESUMEN
This work aimed at improving the targeting and cytotoxicity of simvastatin (SMV) against colon cancer cells. SMV was encapsulated in chitosan polymers, followed by eudragit S100 microparticles. The release of SMV double coated microparticles was dependent on time and pH. At pH 7.4 maximum release was observed for 6 h. The efficiency of the double coat to target colonic tissues was confirmed using real-time X-ray radiography of iohexol dye. Entrapment efficiency and particle size were used in the characterization of the formula. Cytotoxicity of SMV microparticles against HCT-116 colon cancer cells was significantly improved as compared to raw SMV. Cell cycle analysis by flow cytomeric technique indicated enhanced accumulation of colon cancer cells in the G2/M phase. Additionally, a significantly higher cell fraction was observed in the pre-G phase, which highlighted enhancement of the proapoptotic activity of SMV prepared in the double coat formula. Assessment of annexin V staining was used for confirmation. Cell fraction in early, late and total cell death were significantly elevated. This was accompanied by a significant elevation of cellular caspase 3 activity. In conclusion, SMV-loaded chitosan coated with eudragit S100 formula exhibited improved colon targeting and enhanced cytotoxicity and proapoptotic activity against HCT-116 colon cancer cells.
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Antineoplásicos/administración & dosificación , Quitosano/química , Neoplasias del Colon/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Simvastatina/administración & dosificación , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Portadores de Fármacos/química , Células HCT116 , Humanos , Concentración de Iones de Hidrógeno , Masculino , Microesferas , Tamaño de la Partícula , Ácidos Polimetacrílicos/química , Conejos , Simvastatina/farmacologíaRESUMEN
Parkinson's disease (PD) is a devastating neurodegenerative disorder predominantly affecting the elderly, characterized by the loss of dopaminergic neurons in the substantia nigra. Reactive oxygen species (ROS) generation plays a central role in the pathogenesis of PD and other neurodegenerative diseases. An imbalance between cellular antioxidant activity and ROS production leads to oxidative stress, contributing to disease progression. Dopamine metabolism, mitochondrial dysfunction, and neuroinflammation in dopaminergic neurons have been implicated in the pathogenesis of Parkinson's disease. Consequently, there is a pressing need for therapeutic interventions capable of scavenging ROS. Current pharmacological approaches, such as L-dihydroxyphenylalanine (levodopa or L-DOPA) and other drugs, provide symptomatic relief but are limited by severe side effects. Researchers worldwide have been exploring alternative compounds with less toxicity to address the multifaceted challenges associated with Parkinson's disease. In recent years, plant-derived polyphenolic compounds have gained significant attention as potential therapeutic agents. These compounds exhibit neuroprotective effects by targeting pathophysiological responses, including oxidative stress and neuroinflammation, in Parkinson's disease. The objective of this review is to summarize the current understanding of the neuroprotective effects of various polyphenols in Parkinson's disease, focusing on their antioxidant and anti-inflammatory properties, and to discuss their potential as therapeutic candidates. This review highlights the progress made in elucidating the molecular mechanisms of action of these polyphenols, identifying potential therapeutic targets, and optimizing their delivery and bioavailability. Well-designed clinical trials are necessary to establish the efficacy and safety of polyphenol-based interventions in the management of Parkinson's disease.
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Enfermedades Neuroinflamatorias , Fármacos Neuroprotectores , Estrés Oxidativo , Enfermedad de Parkinson , Polifenoles , Humanos , Estrés Oxidativo/efectos de los fármacos , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Polifenoles/farmacología , Polifenoles/uso terapéutico , Animales , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Antioxidantes/farmacología , Antioxidantes/uso terapéuticoRESUMEN
Two-dimensional (2D) nanomaterials have garnered enormous attention seemingly due to their unusual architecture and properties. Graphene and graphene oxide based 2D nanomaterials remained the most sought after for several years but the quest to design superior 2D nanomaterials which can find wider application gave rise to development of non-graphene 2D materials as well. Consequently, in addition to graphene based 2D nanomaterials, 2D nanostructures designed using macromolecules (such as DNAs, proteins, peptides and peptoids), transition metal dichalcogenides, transition-metal carbides and/or nitrides (MXene), black phosphorous, chitosan, hexagonal boron nitrides, and graphitic carbon nitride, and covalent organic frameworks have been developed. Interestingly, these 2D nanomaterials have found applications in diagnosis and treatment of various diseases including Alzheimer's disease (AD). Although AD is one of the most debilitating neurodegenerative conditions across the globe; unfortunately, there remains a paucity of effective diagnostic and/or therapeutic intervention for it till date. In this scenario, nanomaterial-based biosensors, or therapeutics especially 2D nanostructures are emerging to be promising in this regard. This review summarizes the diagnostic and therapeutic platforms developed for AD using 2D nanostructures. Collectively, it is worth mentioning that these 2D nanomaterials would seemingly provide an alternative and intriguing platform for biomedical interventions.
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Enfermedad de Alzheimer , Técnicas Biosensibles , Grafito , Nanoestructuras , Humanos , Grafito/química , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/tratamiento farmacológico , Nanoestructuras/uso terapéutico , Nanoestructuras/química , Técnicas Biosensibles/métodosRESUMEN
The rapid advancement of nanotechnology has led to unprecedented innovations across diverse industries, including pharmaceuticals, agriculture, cosmetics, electronics, textiles, and food, owing to the unique properties of nanoparticles. The extensive production and unregulated release of synthetic nanoparticles may contribute to nanopollution within the ecosystem. In the agricultural sector, nanotechnology is increasingly utilized to improve plant productivity, enhance resistance to stressors, and reduce the usage of chemicals. However, the uncontrolled discharge of nanoparticles into the natural environment raises concerns regarding possible plant toxicological impacts. The review focuses on the translocation of these particles within the plants, emphasizing their phytotoxicological effects at morphological, physiological, biochemical, and molecular levels. Eventhough the beneficial aspects of these nanoparticles are evident, excessive usage of nanoparticles at higher concentrations may lead to potential adverse effects. The phytotoxicity resulting from excessive amounts of nanoparticles affects seed germination and biomass production, disrupts the photosynthesis system, induces oxidative stress, impacts cell membrane integrity, alters gene expression, causes DNA damage, and leads to epigenetic variations in plants. Nanoparticles are found to directly associate with the cell membrane and cell organelles, leading to the dissolution and release of toxic ions, generation of reactive oxygen species (ROS) and subsequent oxidative stress. The present study signifies and accumulates knowledge regarding the application of nanoparticles in agriculture and illustrates a clear picture of their possible impacts on plants and soil microbes, thereby paving the way for future developments in nano-agrotechnology. The review concludes by addressing current challenges and proposing future directions to comprehend and mitigate the possible biological risks associated with nanoparticles in agriculture.
Asunto(s)
Nanopartículas , Plantas , Nanopartículas/toxicidad , Nanopartículas/química , Plantas/efectos de los fármacos , Plantas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Estrés Oxidativo/efectos de los fármacosRESUMEN
Cerium oxide nanoparticles (CeO2NPs) have a broad scale of applications in the biomedical field due to their excellent physicochemical and catalytic properties. The present study aims to synthesize the CeO2NPs from Centella asiatica (C. asiatica) leaf extract, which has been used in Indian traditional medicine for its neuroprotective properties. The CeO2NPs were characterized by ultraviolet-visible, X-ray diffraction, Fourier transform infrared, Raman spectroscopy, scanning electron microscopy- energy dispersive X-ray spectroscopy, and high-resolution transmission electron microscopy. The antioxidant property was evaluated by 2,2-di (4-tert-octyl phenyl)-1-picrylhydrazyl and OH radical assays. The neuroprotective potential was assessed against the oxidative stress (OS) induced by H2O2 in the human neuroblastoma (SH-SY5Y) cell line. CeO2NPs exhibited significant DPPH and OH radical scavenging activity. Our results revealed that CeO2NPs significantly increased H2O2-induced cell viability, decreased lactate dehydrogenase, protein carbonyls, reactive oxygen species generation, apoptosis, and upregulated antioxidant enzyme activity. Our findings suggest that the CeO2NPs protect the SH-SY5Y cells from OS and apoptosis, which could potentially counter OS-related neurodegenerative disorders.
RESUMEN
The journal retracts the article, "Optimized Ellagic Acid-Ca Pectinate Floating Beads for Gastroprotection against Indomethacin-Induced Gastric Injury in Rats" [...].