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BACKGROUND: Cancer treatment often involves the use of potent antineoplastic drugs like Capecitabine [CAP], which can lead to serious toxicities. There is a need for dosage forms to manage these toxicities that can deliver the medication effectively to the target site while maintaining therapeutic efficacy at lower doses. To achieve the aforesaid objective, NLC containing capecitabine [NANOBIN] was prepared and evaluated. Different formulations of NANOBIN, denoted as CaTS, CaT1S, CaT2S, CaTS1, and CaTS2, were designed and evaluated to improve drug delivery and therapeutic outcomes. METHODS: The NANOBIN formulations were prepared using the hot homogenization method. The characterization of these formulations was conducted based on various parameters such as particle size, Polydispersity Index [PDI], Zeta Potential [ZP], Transmission Electron Microscopy [TEM] imaging, and Encapsulation Efficiency [EE]. In vitro evaluations included stability testing, release studies to assess drug release kinetics, and a cytotoxicity assay [MTT assay] to evaluate the efficacy of these formulations against human breast cancer cells [MCF-7]. RESULTS: The characterization results revealed that all NANOBIN formulations exhibited particle sizes ranging from 65 to 193 nm, PDI values within the range of 0.26-0.37, ZP values between 46.47 to 61.87 mV [-ve], and high EE percentages ranging from 94.121% to 96.64%. Furthermore, all NANOBIN formulations demonstrated sustained and slow-release profiles of CAP. The MTT assay showed that the NANOBINs exhibited significantly enhanced cytotoxic efficacy, approximately 10 times greater than free CAP when tested on MCF-7 cells. These findings indicate the potential of NANOBINs to deliver CAP effectively to the target site, enabling prolonged drug availability and enhanced therapeutic effects at lower doses. CONCLUSION: The study demonstrates that NANOBINs can effectively deliver CAP to target sites, prolonging drug exposure and enhancing therapeutic efficacy while reducing the required dose. Further studies are necessary to validate these findings and establish NANOBINs as a preferred treatment option for cancer therapy.
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Background: It has been reported that a deadly virus known as COVID-19 has arisen in China and has spread rapidly throughout the country. The globe was shattered, and a large number of people on the planet died. It quickly became an epidemic due to the absence of apparent symptoms and causes for patients, confusion appears due to the lack of sufficient laboratory results, and its intelligent algorithms were used to make decisions on clinical outcomes. Methods: This study developed a new framework for medical datasets with high missing values based on deep-learning optimization models. The robustness of our model is achieved by combining: Data Missing Care (DMC) Framework to overcome the problem of high missing data in medical datasets, and Grid-Search optimization used to develop an improved deep predictive training model for patients with COVID-19 by setting multiple hyperparameters and tuning assessments on three deep learning algorithms: ANN (Artificial Neural Network), CNN (Convolutional Neural Network), and Recurrent Neural Networks (RNN). Results: The experiment results conducted on three medical datasets showed the effectiveness of our hybrid approach and an improvement in accuracy and efficiency since all the evaluation metrics were close to ideal for all deep learning classifiers. We got the best evaluation in terms of accuracy 98%, precession 98.5%, F1-score 98.6%, and ROC Curve (95% to 99%) for the COVID-19 dataset provided by GitHub. The second dataset is also Covid-19 provided by Albert Einstein Hospital with high missing data after applying our approach the accuracy reached more than 91%. Third dataset for Cervical Cancer provided by Kaggle all the evaluation metrics reached more than 95%. Conclusions: The proposed formula for processing this type of data can replace the traditional formats in optimization while providing high accuracy and less time to classify patients. Whereas, the experimental results of our approach, supported by comprehensive statistical analysis, can improve the overall evaluation performance of the problem of classifying medical data sets with high missing values. Therefore, this approach can be used in many areas such as energy management, environment, and medicine.
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Inflammation and resolution are highly programmed processes involving a plethora of immune cells. Lipid mediators synthesized from arachidonic acid metabolism play a pivotal role in orchestrating the signaling cascades in the game of inflammation. The majority of the studies carried out so far on inflammation were aimed at inhibiting the generation of inflammatory molecules, whereas recent research has shifted more towards understanding the resolution of inflammation. Owing to chronic inflammation as evident in neuropathophysiology, the resolution of inflammation together with the class of lipid mediators actively involved in its regulation has attracted the attention of the scientific community as therapeutic targets. Both omega-three polyunsaturated fatty acids, eicosapentaenoic acid and docosahexaenoic acid, orchestrate a vital regulatory role in inflammation development. Resolvins derived from these fatty acids comprise the D-and E-series resolvins. A growing body of evidence using in vitro and in vivo models has revealed the pro-resolving and anti-inflammatory potential of resolvins. This systematic review sheds light on the synthesis, specialized receptors, and resolution of inflammation mediated by resolvins in Alzheimer's and Parkinson's disease.
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Doença de Alzheimer , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Alzheimer/tratamento farmacológico , Ácido Eicosapentaenoico/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Inflamação/metabolismo , Mediadores da InflamaçãoRESUMO
The inhibition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) and papain-like protease (PLpro) prevents viral multiplications; these viral enzymes have been recognized as one of the most favorable targets for drug discovery against SARS-CoV-2. In the present study, we screened 225 phytocompounds present in 28 different Indian spices to identify compounds as potential inhibitors of SARS-CoV-2 Mpro and PLpro. Molecular docking, molecular dynamics simulation, molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding free energy calculations, and absorption, distribution, metabolism, excretion and toxicity (ADMET) studies were done. Based on binding affinity, dynamics behavior, and binding free energies, the present study identifies pentaoxahexacyclo-dotriacontanonaen-trihydroxybenzoate derivative (PDT), rutin, and dihyroxy-oxan-phenyl-chromen-4-one derivative (DOC), luteolin-7-glucoside-4'-neohesperidoside as promising inhibitors of SARS-CoV-2 Mpro and PLpro, respectively.
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Parkinson's disease is a neurodegenerative disease caused by the death of neurons, ie, cells critical to the production of dopamine, an important neurotransmitter in the brain. Here, we present a brief review of the dopamine synthetic pathway, binding to the dopamine receptors, and subsequent action. The production of dopamine (a monoamine neurotransmitter) occurs in the ventral tegmental area (VTA) of the substantia nigra, specifically in the hypothalamic nucleus and midbrain. Compared to other monoamines, dopamine is widely distributed in the olfactory bulb, midbrain substantia nigra, hypothalamus, VTA, retina, and the periaqueductal gray area. Dopamine receptors are large G-protein coupled receptor family members, of which there are five subtypes including D1, D2, D3, D4, and D5. These subtypes are further divided into two subclasses: D1-like family receptors (types 1 and 5) and D2-like family receptors (types 2, 3, and 4). Four different pathways and functions of the dopaminergic system are presented in this review. In the oxidation of dopamine, 5,6-indolequinone, dopamine-o-quinone, and aminochrome are formed. It is difficult to separate the roles of 5,6-indolequinone and dopamine-o-quinone in the degenerative process of Parkinson's diseases due to their instability. The role of aminochrome in Parkinson's disease is to form and stabilize the neurotoxic protofibrils of alpha-synuclein, mitochondrial dysfunction, oxidative stress, and the degradation of protein by lysosomal systems and proteasomes. The neurotoxic effects of aminochrome can be inhibited by preventing the polymerization of 5,6-indolequinone, dopamine-o-quinone, and aminochrome into neuromelanin, by reducing aminochrome catalysis by DT-diaphorase, and by preventing dopamine oxidative deamination catalyzed by monoamine oxidase. In addition to these, the conversion of dopamine in the neuromelanin (NM) shows both protective and toxic roles. Therefore, the aims of this review were to discuss and explain the role of dopamine and explore its physiology and specificity in Parkinson's disease, as well as its role in other physiological functions.
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Doenças Neurodegenerativas , Doença de Parkinson , Dopamina , Humanos , Neurônios , Oxirredução , Doença de Parkinson/tratamento farmacológicoRESUMO
The current study proposes a bio-directed approach for the formation of titanium oxide and silver nanoparticles (TiO2 and Ag NPs), using a wild mushroom, Fomitopsis pinicola, identified by 18S ribosomal RNA gene sequencing (gene accession no. MK635350) and phenotypic examination. NP synthesis was confirmed by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), diffuse reflectance UV-visible spectroscopy (DR-UV), and scanning and transmission electron microscopy (SEM/TEM). Furthermore, the impact of NPs on Escherichia coli and Staphylococcus aureus and a human colon cancer cell line (HCT) were evaluated by MIC/MBC and MTT assays, respectively, along with structural morphogenesis by different microscopy methods. The results obtained showed that TiO2 and Ag NPs were found to be significantly active, however, slightly enhanced antibacterial and anticancer action was seen with Ag NPs (10-30 nm). Such NPs can be utilized to control and treat infectious diseases and colon cancer and therefore have potential in a range of biomedical applications.
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OBJECTIVES: Citrullus colocynth (CTC) is a wild medicinal plant with proven antimicrobial activity. The aim of this study is to investigate the use of its aqueous extract in producing magnetic iron oxide nanoparticles (MNPs) with improved antimicrobial activity. The cold and hot aqueous extract of seed and pulp parts of CTC, respectively, were used to produce MNPs. The particles were characterized by transmission electron microscope, energy dispersion x-ray, FTIR and their surface charge were measured. The antimicrobial activity of the produced particles was assessed against two Gram positive (Bacillus subtillis and Staphylococcus aureus) and two Gram negative (Escherichia coli and Pseudomonas aeruginosa) bacteria and well as against Candida albicans. RESULTS: MNPs synthesized using cold seed extract (S-MNP) and pulp extract (P-MNP) were spherical in shape. The size distribution was more uniform in the S-MNP (6-15 nm) compared to the P-MNP (12-45 nm). Both particles showed comparable anti-microbial potential against the tested microorganisms. At a concentration range of 0.48-1000 µg/mL, S-MNP inhibited bacterial growth by 16.0-99.0% and 10.0-91.0%; while P-MNP inhibition was 11.0-100.0% and 11.0-99.0% for Gram positive and negative bacteria; respectively. Candida albicans was the least affected microorganism with maximum inhibition of 63-88% after treatment with S-MNP and P-MNP (1 mg/mL), respectively. CONCLUSIONS: The aqueous extract of CTC can be used for synthesis of MNPs with antimicrobial activity. The described procedures are simple and can be modified for large scale green synthesis of MNPs.
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Anti-Infecciosos/farmacologia , Citrullus colocynthis/química , Compostos Férricos/química , Extratos Vegetais/farmacologia , Anti-Infecciosos/química , Bacillus subtilis/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Química Verde , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Extratos Vegetais/química , Pseudomonas aeruginosa/efeitos dos fármacos , Sementes/química , Staphylococcus aureus/efeitos dos fármacosRESUMO
A considerable amount of bioactive compounds have been used for the biopharmaceutical engineering to help human health and nutrition. Hairy root culture (HRC) or transgenic root is a favourable alternative technique for phytochemical production. Ligularia fischeri is a significant source of pharmaceutically important active compounds with an enormous range of health care applications. HRC of L. fischeri was developed using Agrobacterium rhizogenes for the production of polyphenolic compounds with antioxidant, antimicrobial, antidiabetic, anticancer and anti-inflammatory pharmaceutical activities. Hairy roots (HRs) were selected by morphological assessment, genetic and molecular analyses. The maximum accumulation of fresh mass (94.15 g/L) and dry mass (9.45 g/L) was recorded in MS liquid medium supplemented with 30 g/L sucrose at 28 days. Furthermore, HRs successfully produced numerous polyphenolic compounds, including six hydroxycinnamic acids, seven flavonols, seven hydroxybenzoic acids, vanillin, resveratrol, pyrogallol, homogentisic, and veratric acids, which were identified by UHPLC analysis. HRs produced higher total phenolic (185.65 mg/g), and flavonoid (5.25 mg/g) contents than non-transformed roots (125.55 mg/g and 3.75 mg/g). As a result of these metabolic changes, pharmaceutical activities were found higher in HRs than non-transformed roots (NTRs). The present study indicates that HRC has the potential to increase the content of beneficial polyphenolic compounds with higher potential pharmaceutical activities. To the best of our knowledge, the present study is the first report on enhancing the production of polyphenolic compounds with pharmaceutical activities from the HRCs of L. fischeri.