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1.
Front Big Data ; 7: 1369895, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38784675

RESUMO

Introduction: The cryptocurrency market is captivating the attention of both retail and institutional investors. While this highly volatile market offers investors substantial profit opportunities, it also entails risks due to its sensitivity to speculative news and the erratic behavior of major investors, both of which can provoke unexpected price fluctuations. Methods: In this study, we contend that extreme and sudden price changes and atypical patterns might compromise the performance of technical signals utilized as the basis for feature extraction in a machine learning-based trading system by either augmenting or diminishing the model's generalization capability. To address this issue, this research uses a bagged tree (BT) model to forecast the buy signal for the cryptocurrency market. To achieve this, traders must acquire knowledge about the cryptocurrency market and modify their strategies accordingly. Results and discussion: To make an informed decision, we depended on the most prevalently utilized oscillators, namely, the buy signal in the cryptocurrency market, comprising the Relative Strength Index (RSI), Bollinger Bands (BB), and the Moving Average Convergence/Divergence (MACD) indicator. Also, the research evaluates how accurately a model can predict the performance of different cryptocurrencies such as Bitcoin (BTC), Ethereum (ETH), Cardano (ADA), and Binance Coin (BNB). Furthermore, the efficacy of the most popular machine learning model in precisely forecasting outcomes within the cryptocurrency market is examined. Notably, predicting buy signal values using a BT model provides promising results.

2.
BMC Chem ; 18(1): 96, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38725069

RESUMO

Alfuzosin hydrochloride and tadalafil fixed-dose combination tablets were recently formulated for the treatment of individuals with lower urinary tract symptoms caused by benign prostatic hyperplasia. Herein, the first spectrophotometric methods for quantitative analysis of alfuzosin hydrochloride and tadalafil in their binary mixture were established. The spectral overlapping of alfuzosin hydrochloride and tadalafil made direct simultaneous analysis unfeasible. Therefore, two mathematical methods were used to solve these overlapping spectra: absorbance subtraction and ratio difference. The absorbance subtraction method manipulates the zero absorption spectra of the studied drugs at the isoabsorptive point (272 nm) and uses the absorbance factor of pure ALF to calculate the absorbance of the studied drugs in the mixture at the isoabsorptive point. The ratio spectra method, on the other hand, manipulates the ratio spectra of the studied drugs, which are obtained by dividing each drug's zero absorption spectra by a divisor spectrum from the second drug. The ratio amplitude difference between 251 nm and 211 nm was directly proportional to alfuzosin hydrochloride, whereas between 292 nm and 222 nm it was directly proportional to tadalafil. The methods used were verified in accordance with the recommendations of the ICH and demonstrated adequate linear regression in working ranges of 1-15 µg/mL for alfuzosin hydrochloride and 3-40 µg/mL for tadalafil. The methods were accurate, precise, and selectively employed to quantify alfuzosin hydrochloride and tadalafil in their combined tablets.

3.
Spectrochim Acta A Mol Biomol Spectrosc ; 317: 124398, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38710140

RESUMO

In this study, graphene quantum dots (GQDs) were employed for quantitatively analyzing lamivudine using a fluorescence quenching technique. This approach allows for sensitive determination of the concentration of lamivudine in different matrices without requiring derivatization. The mechanism behind the fluorescence intensity quenching between GQDs and lamivudine molecules was explored using the Stern Volmer equation, revealing dynamic quenching behavior. Additionally, various factors affecting fluorescence quenching efficiency such as pH, GQDs concentration, and incubation time were carefully tuned. Moreover, our developed method successfully met ICH guidelines for validation parameters including linearity, accuracy, precision, and selectivity demonstrating excellent performance. The results showed good accuracy and precision, with a mean recovery value of 101.91% for method accuracy and a relative standard deviation of 0.682 and 1.489 for intraday and interday precision, respectively. Finally, the greenness and blueness of the developed method were also investigated to assess its environmental friendliness and analytical practicality. Greenness evaluation using the AGREE tool demonstrated that the developed method has a low environmental impact with an AGREE score of 0.75, Besides, the blueness evaluating using the BAGI tool indicated that the developed method is practical, reliable, and well-suited for routine analysis of lamivudine in various samples.


Assuntos
Grafite , Lamivudina , Pontos Quânticos , Espectrometria de Fluorescência , Grafite/química , Pontos Quânticos/química , Lamivudina/análise , Espectrometria de Fluorescência/métodos , Química Verde/métodos , Reprodutibilidade dos Testes , Limite de Detecção , Concentração de Íons de Hidrogênio , Corantes Fluorescentes/química
4.
Saudi Pharm J ; 32(5): 102048, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38585197

RESUMO

Memory loss or dementia is a progressive disorder, and one of its common forms is Alzheimer's disease (AD), effecting mostly middle aged and older adults. In the present study, we developed Rivastigmine (RIV) nanoparticles using poly(lactic-co-glycolic acid) (RIV-loaded PLGA NPs) and polyvinyl alcohol (PVA). The prepared RIV-PLGA nanoparticles was evaluated for the management of Alzheimer's disease (AD). The nanoparticles were prepared by the slightly modified nano-precipitation technique. The developed formulations were evaluated for particle size, zeta potential (ZP), polydispersibility index (PDI) and surface morphology and drug content. The experimental result revealed that prepared RIV-loaded PLGA NPs (F1) was optimized having particle size (61.2 ± 4.6 nm), PDI (0.292), ZP (-11.2 ± 1.2). SEM study confirms the prepared nanoparticles depicted non-aggregated as well smooth surface particles without any fracture. This formulation (F1) was further assessed for in vivo studies on animal model. A pharmacological screening on an animal model of Alzheimer's disease revealed that RIV-loaded PLGA NPs formulations treat CNS disorders like Alzheimer's effectively. In addition to that, an in-vivo brain cholinesterase estimation study found that, animals treated with optimized formulation significantly (p < 0.01) reduced brain cholinesterase activity when compared to scopolamine-treated animals. According to the above results, it can be concluded that RIV-loaded PLGA NPs are ideal carriers for delivering the drug at a specific target site in the brain, thus may treat Alzheimer's disease efficiently and improve patient compliance.

5.
Saudi Pharm J ; 32(5): 102050, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38577488

RESUMO

This study aimed to formulate nano-cubosomes (NCs) co-loaded with capsaicin (CAP) and thiocolchicoside (TCS) to enhance their bioavailability and minimize associated potential side effects through transdermal delivery alongside their synergistic activity. Twenty seven (27) nano-cubosomal dispersions were prepared according to Box-Behnken factorial design and the effect of CAP, TCS, glyceryl mono oleate (GMO) and poloxamer 407 (P407) concentrations on particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency were assessed. The results revealed that the optimized formulation exhibited a mean droplet size of 503 ± 10.3 nm, PDI of 0.405 ± 0.02, zeta potential of -10.0 ± 1.70 mV and entrapment efficiency of 86.9 ± 3.56 %. The in vivo anti-inflammatory effect of optimized formulation was studied in rats by injecting carrageenan to induce edema. The results of in vivo study showed that transdermal application of nano-cubosomes co-loaded with CAP and TCS significantly (p value < 0.05) improved carrageenan induced inflammation compared with standard treatment. The analgesic activity of optimized formulation was evaluated in rats by using Eddy's hot plate method. The findings of analgesic activity illustrated that the analgesic effects exhibited by test formulation may be associated with increased licking period and inhibition of prostaglandins level. In conclusion, the transdermal application of NCs co-loaded with CAP and TCS may be a promising delivery system for enhancing their bioavailability as well as synergistic analgesic and anti-inflammatory activity in gout management.

6.
PLoS One ; 19(4): e0298699, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38574042

RESUMO

Sign language recognition presents significant challenges due to the intricate nature of hand gestures and the necessity to capture fine-grained details. In response to these challenges, a novel approach is proposed-Lightweight Attentive VGG16 with Random Forest (LAVRF) model. LAVRF introduces a refined adaptation of the VGG16 model integrated with attention modules, complemented by a Random Forest classifier. By streamlining the VGG16 architecture, the Lightweight Attentive VGG16 effectively manages complexity while incorporating attention mechanisms that dynamically concentrate on pertinent regions within input images, resulting in enhanced representation learning. Leveraging the Random Forest classifier provides notable benefits, including proficient handling of high-dimensional feature representations, reduction of variance and overfitting concerns, and resilience against noisy and incomplete data. Additionally, the model performance is further optimized through hyperparameter optimization, utilizing the Optuna in conjunction with hill climbing, which efficiently explores the hyperparameter space to discover optimal configurations. The proposed LAVRF model demonstrates outstanding accuracy on three datasets, achieving remarkable results of 99.98%, 99.90%, and 100% on the American Sign Language, American Sign Language with Digits, and NUS Hand Posture datasets, respectively.


Assuntos
Algoritmo Florestas Aleatórias , Língua de Sinais , Humanos , Reconhecimento Automatizado de Padrão/métodos , Gestos , Extremidade Superior
7.
Sci Rep ; 14(1): 9614, 2024 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671304

RESUMO

The abnormal heart conduction, known as arrhythmia, can contribute to cardiac diseases that carry the risk of fatal consequences. Healthcare professionals typically use electrocardiogram (ECG) signals and certain preliminary tests to identify abnormal patterns in a patient's cardiac activity. To assess the overall cardiac health condition, cardiac specialists monitor these activities separately. This procedure may be arduous and time-intensive, potentially impacting the patient's well-being. This study automates and introduces a novel solution for predicting the cardiac health conditions, specifically identifying cardiac morbidity and arrhythmia in patients by using invasive and non-invasive measurements. The experimental analyses conducted in medical studies entail extremely sensitive data and any partial or biased diagnoses in this field are deemed unacceptable. Therefore, this research aims to introduce a new concept of determining the uncertainty level of machine learning algorithms using information entropy. To assess the effectiveness of machine learning algorithms information entropy can be considered as a unique performance evaluator of the machine learning algorithm which is not selected previously any studies within the realm of bio-computational research. This experiment was conducted on arrhythmia and heart disease datasets collected from Massachusetts Institute of Technology-Berth Israel Hospital-arrhythmia (DB-1) and Cleveland Heart Disease (DB-2), respectively. Our framework consists of four significant steps: 1) Data acquisition, 2) Feature preprocessing approach, 3) Implementation of learning algorithms, and 4) Information Entropy. The results demonstrate the average performance in terms of accuracy achieved by the classification algorithms: Neural Network (NN) achieved 99.74%, K-Nearest Neighbor (KNN) 98.98%, Support Vector Machine (SVM) 99.37%, Random Forest (RF) 99.76 % and Naïve Bayes (NB) 98.66% respectively. We believe that this study paves the way for further research, offering a framework for identifying cardiac health conditions through machine learning techniques.


Assuntos
Arritmias Cardíacas , Eletrocardiografia , Aprendizado de Máquina , Humanos , Eletrocardiografia/métodos , Arritmias Cardíacas/diagnóstico , Algoritmos , Monitorização Fisiológica/métodos , Cardiopatias/diagnóstico
8.
Cureus ; 16(2): e53366, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38435149

RESUMO

Background and objective Given its ever-increasing burden, chronic kidney disease (CKD) represents a significant public health threat. CKD is characterized by a gradual alteration in the kidney's normal glomerular filtration rate, which results in the progressive loss of kidney function over a period of time ranging from a few months to years. Diabetes mellitus (DM) and hypertension (HTN) are well-known risk factors for developing CKD and end-stage renal failure. In light of this, this study aimed to assess the awareness, prevalence, and risk factors of CKD in patients with diabetes and those with HTN in the Aseer region, the Kingdom of Saudi Arabia. Methods A correlational cross-sectional study was conducted among a sample of people across Saudi Arabia. The data collection was conducted via an online questionnaire circulated on social media platforms. The study questionnaire included socioeconomic and demographic information and medical history of DM, HTN, and CKD. Also, patients' awareness of and attitude towards CKD were assessed. Results A total of 301 diabetic or hypertensive patients fulfilling the inclusion criteria completed the study questionnaire. Of them, 174 (57.8%) were aged less than 55 years, while 127 (42.2%) were aged more than 55 years; 200 (66.4%) patients were males. A total of 94 (31.2%) study patients were diabetic, 64 (21.3%) were hypertensive, and 143 (47.5%) were both diabetic and hypertensive; 226 (75.1%) study patients had an overall good awareness of CKD while only 75 (24.9%) showed a poor awareness level. Higher awareness was associated with patients' age, education, and having CKD, DM, or HTN (p<0.05). Conclusion Our findings revealed that CKD was not common among study patients, and its prevalence was found to be less than estimated based on many studies in the literature. Also, diabetic and hypertensive patients showed a higher than satisfactory level of awareness of CKD, especially young patients with high levels of education.

9.
Saudi Pharm J ; 32(5): 102023, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38550333

RESUMO

The escalation of many coronavirus variants accompanied by the lack of an effective cure has motivated the hunt for effective antiviral medicines. In this regard, 18 Saudi Arabian medicinal plants were evaluated for SARS CoV-2 main protease (Mpro) inhibition activity. Among them, Terminalia brownii and Acacia asak alcoholic extracts exhibited significant Mpro inhibition, with inhibition rates of 95.3 % and 95.2 %, respectively, at a concentration of 100 µg/mL. Bioassay-guided phytochemical study for the most active n-butanol fraction of T. brownii led to identification of eleven compounds, including two phenolic acids (1, and 2), seven hydrolysable tannins (3-10), and one flavonoid (11) as well as four flavonoids from A. asak (12-15). The structures of the isolated compounds were established using various spectroscopic techniques and comparison with known compounds. To investigate the chemical interactions between the identified compounds and the target Mpro protein, molecular docking was performed using AutoDock 4.2. The findings identified compounds 4, 5, 10, and 14 as the most potential inhibitors of Mpro with binding energies of -9.3, -8.5, -8.1, and -7.8 kcal mol-1, respectively. In order to assess the stability of the protein-ligand complexes, molecular dynamics simulations were conducted for a duration of 100 ns, and various parameters such as RMSD, RMSF, Rg, and SASA were evaluated. All selected compounds 4, 5, 10, and 14 showed considerable Mpro inhibiting activity in vitro, with compound 4 being the most powerful with an IC50 value of 1.2 µg/mL. MM-GBSA free energy calculations also revealed compound 4 as the most powerful Mpro inhibitor. None of the compounds (4, 5, 10, and 14) display any significant cytotoxic activity against A549 and HUVEC cell lines.

10.
Int J Gen Med ; 17: 1007-1015, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505144

RESUMO

Background: Nearly half of the Systemic lupus erythematosus (SLE) patients develop lung involvement. The study assessed the extent of pulmonary involvement among SLE patients and to identify the associated factors in the population. Methodology: This retrospective cohort study was conducted at Aseer Hospital and Khamis Myshat Hospital in the Southern region of Saudi Arabia. The study spanned from January 1, 2016, to June 3, 2023. Patient inclusion criteria encompassed individuals who received a definitive diagnosis and classification as per American College of Rheumatology criteria, while patients under 18 years of age and those with mixed connective tissue diseases were exclude. Results: A total of 247 participants were included. 41.7% (n=103) aged 41 years and older, 95.1% (n = 235) were females. Around 10.10% had diabetes mellitus and 17.00% had hypertension and hypothyroidism. Lupus Nephritis was in 15.40%. Chest involvement was reported in 21.9%, in the form of pleuritis (6.10%), pleural effusion (4.00%), and lupus pneumonitis (4.00%), interstitial lung disease (4.00%), pulmonary embolism (3.60%) of individuals, and pulmonary hemorrhage (2.80%). The respiratory symptoms reported by SLE were; dyspnea, cough, and chest pain each having a prevalence of around 18.0%. Palpitations have a relatively high occurrence at 13.80%. Meanwhile, hemoptysis (blood coughing) has a lower prevalence of 1.20%, and fever is reported at 2.80%. Having chronic kidney disease and hypertension were significantly associated with having pulmonary involvement; (χ2=3.308, p=0.027) and (χ2=7.782, Fisher's p=0.002) respectively. The seropositivity for antiphospholipid Abs, anti-CCP, and antids-DNA were significantly associated with pulmonary involvement (χ2=3.239, =p=0.049), (χ2=4.621, Fisher's p=0.023), and (χ2=8.248, p=0.010) respectively. Conclusion: The study found that 21.9% of SLE patients experience chest involvement, with varying degrees of pulmonary symptoms. Factors such as chronic kidney disease, hypertension, antiphospholipid antibodies, Anti-CCP positivity, and seropositivity for Anti-dsDNA were found to be significant associations with lung involvement, contributing to our understanding of SLE.

11.
Int J Biol Macromol ; 264(Pt 1): 130278, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38373565

RESUMO

Ribophorin-1 serves as one of the subunits of the oligosaccharyltransferase (OST) complex located in the endoplasmic reticulum (ER). Until now, RPN-1 was considered an ER protein. However, our findings reveal that a minor fraction of RPN-1 escapes from the lumen of the ER and is ectopically expressed on the surface of different cell lines. The precise mechanism of protein translocation is unknown. The expression of RPN-1 was demonstrated through the isolation of membrane proteins using surface biotinylation and sucrose density gradient techniques. The confirmation of RPN-1 was obtained through surface staining using a specific antibody, revealing its expression on various cell lines. Additionally, we examined the expression of RPN-1 in different populations of PBMCs and observed a differential regulation of RPN-1 within PBMC subpopulations. Notably, there was a significant expression of RPN-1 on monocytes and B cells, but there was little to no population of T cells expressing RPN-1. We confirmed the expression of RPN-1 on THP-1, U937, and Jurkat cells. We also confirmed their surface expression through si-RNA knockdown. Our study shows RPN-1 expression on various cell surfaces, suggesting varied regulation among cell types. In the future, we may uncover its roles in immune function, signaling, and differentiation/proliferation.


Assuntos
Leucócitos Mononucleares , Proteínas de Membrana , Humanos , Leucócitos Mononucleares/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Retículo Endoplasmático/metabolismo , Membrana Celular/metabolismo , Glicosiltransferases/metabolismo
13.
Cureus ; 16(1): e51745, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38187028

RESUMO

Introduction and aim Gout, the most common form of inflammatory arthritis, arises from hyperuricemia, a condition where elevated levels of uric acid lead to the deposition of monosodium urate (MSU) crystals in the joints. Nevertheless, it's important to note that not all cases of hyperuricemia result in gout. Methodology This cross-sectional study was conducted in the Asir region of Saudi Arabia, targeting primary healthcare physicians (PHPs) specializing in family medicine and general practice. The study utilized a modified electronic questionnaire, inspired by similar studies and aligned with recent guidelines, to assess PHPs' knowledge and practices concerning asymptomatic hyperuricemia (AH) and gout. The questionnaire encompassed the PHPs' demographic data and their knowledge and practices for AH and gout management. Results Out of 201 participating PHPs, the majority were male (68.2%), predominantly aged 25-34 years (73.1%), and practicing as general practitioners (61.2%). A significant proportion of PHPs had less than five years of experience (63.7%). In terms of education, 36.8% attended continuing medical education (CME) on AH or gout, and 66.7% were aware of the related management guidelines. The study revealed that the total knowledge score among PHPs averaged 5.18 out of seven, indicating a moderate level of knowledge. However, their practice level was moderate, with a mean practice score of 6.75 out of 12. The study also found no significant differences in knowledge scores based on gender, age, or years of experience, but significant variations were noted based on medical specialty. Conclusion There is a moderate level of knowledge and practice among PHPs in managing AH and gout in the Asir region. Despite adequate knowledge levels, there appears to be a gap in implementing this knowledge into practice, particularly in long-term management strategies. The findings emphasize the need for ongoing medical education and specialized training programs to bridge these gaps. The study provides a valuable framework for identifying and addressing similar challenges in other regions and medical practices.

14.
Sensors (Basel) ; 24(2)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38257527

RESUMO

Switched filter banks find widespread application in frequency-hopping radar systems and communication networks with multiple operating frequencies, especially in situations demanding elevated filter element isolation. In this paper, the design and implementation of a highly isolated switchable narrow-bandpass filter bank architecture using hairpin microstrip topology is presented. The filter bank has four discrete bandpass filters with passbands of 2.0-2.2 GHz, 2.3-2.5 GHz, 3.1-3.3 GHz, and 3.9-4.1 GHz. These filters span the radar S-frequency band (2.0-4.0 GHz). In order to switch between channels with a switching speed of nanoseconds, low-loss and highly isolated SP4T switches are implemented. Advanced design system (ADS) software is used to design the various filter functionalities, and the entire system is tested on a vector network analyzer (VNA). The proposed architecture makes it much easier to put the filter bank into practice and switch it to the desired frequency, which is useful for radar receiver applications.

15.
J Biomol Struct Dyn ; : 1-20, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38234048

RESUMO

Marburg virus infections are extremely fatal with a fatality range of 23% to 90%, therefore there is an urgent requirement to design and develop efficient therapeutic molecules. Here, a comprehensive temperature-dependent molecular dynamics (MD) simulation method was implemented to identify the potential molecule from the anti-dengue compound library that can inhibit the function of the VP24 protein of Marburg. Virtual high throughput screening identified five effective binders of VP24 after screening 484 anti-dengue compounds. These compounds were treated in MD simulation at four different temperatures: 300, 340, 380, and 420 K. Higher temperatures showed dissociation of hit compounds from the protein. Further, triplicates of 100 ns MD simulation were conducted which showed that compounds ID = 118717693, and ID = 5361 showed strong stability with the protein molecule. These compounds were further validated using ΔG binding free energies and they showed: -30.38 kcal/mol, and -67.83 kcal/mol binding free energies, respectively. Later, these two compounds were used in steered MD simulation to detect its dissociation. Compound ID = 5361 showed the maximum pulling force of 199.02 kcal/mol/nm to dissociate the protein-ligand complex while ID = 118717693 had a pulling force of 101.11 kcal/mol/nm, respectively. This ligand highest number of hydrogen bonds with varying occupancies at 89.93%, 69.80%, 57.93%, 52.33%, and 50.63%. This study showed that ID = 5361 can bind with the VP24 strongly and has the potential to inhibit its function which can be validated in the in-vitro experiment.Communicated by Ramaswamy H. Sarma.

16.
Saudi Pharm J ; 32(1): 101898, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38192384

RESUMO

Dodonaea viscosa grows widely in Saudi Arabia, but studies evaluating its neuroprotective activity are lacking. Thus, this study aimed to isolate and identify the secondary metabolites and evaluate the neuroprotective effects of D. viscosa leaves. The isolation and identification of phytochemicals were performed using chromatographic and spectroscopic techniques. The neuroprotective potential of the extract was evaluated against focal cerebral ischaemia-reperfusion injury in rat model. Neurobehavioural deficits in the rats were evaluated, and their brains were harvested to measure infarct volume and oxidative biomarkers. Results revealed the presence of three compounds: a novel isoprenylated phenolic derivative that was elucidated as 4-hydroxy-3-(3'-methyl-2'-butenyl) phenyl 1-O-ß-D-apiosyl-(1''' â†’ 6'')- ß-D-glucopyranoside (named Viscomarfadol) and two known compounds (isorhamnetin-3-O-rutinoside and epicatechin (4-8) catechin). Pre-treatment of the rats with the extract improved neurological outcomes. It significantly reduced neurological deficits and infarct volume; significantly reduced lipid peroxidation, as evidenced by decreased malondialdehyde levels; and significantly elevated antioxidant (superoxide dismutase, catalase, and glutathione) activities. These results indicate that D. viscosa is a promising source of bioactive compounds that can improve neurological status, decrease infarct volume, and enhance antioxidant activities in rats with cerebral ischaemic injury. Thus, D. viscosa could be developed into an adjuvant therapy for ischaemic stroke and other oxidative stress-related neurodegenerative disorders. Further investigations are warranted to explore other bioactive compounds in D. viscosa and evaluate their potential neuroprotective activities.

17.
J Biomol Struct Dyn ; : 1-23, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38174404

RESUMO

Recent monkeypox virus (MPXV) infections show the risk of MPXV transmission that persists today and the significance of surveillance and quick response methods to stop the virus's spread. Currently, the monkeypox virus infection is not specifically treated. In this study, QSAR models were designed using known inhibitors of cysteine proteinase from the vaccinia virus, where the Random Forest model and Ridge model had showed the best correlation between predicted and observed EC50. These models were used to screen Maliaceae family phytochemicals against MPXV cysteine proteinase. The compound, IMPHY010637 was detected in top 5 from both the QSAR screening models and showed best docked score (-8.6 kcal/mol) and thus selected for further investigation. Further, the IMPHY010637 showed interaction with the catalytic residue His241 of the protein as reported in earlier studies. The ADMET analysis of the compound showed the acceptable drug-like properties of IMPHY010637. However, these properties could be improved after experimental validation of protein-ligand binding. Both docked complex and poses created in 100 ns MD simulation of the protein-ligand complex showed the presence of multiple hydrogen bonds. RMSD and conformation analysis showed stable binding of IMPHY010637 with the cysteine proteinase of MPXV at its active site. Compared to the known inhibitor, IMPHY010637 showed better binding with the protein as observed by the PCA and MM/GBSA analysis. This study concluded IMPHY010637 as a potential inhibitor for the cysteine proteinase of MPXV using computational methods that could be tested in in-vitro experiments.Communicated by Ramaswamy H. Sarma.

18.
Spectrochim Acta A Mol Biomol Spectrosc ; 308: 123710, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38043294

RESUMO

Augmented least squares models such as concentration residual augmented classical least squares (CRACLS) and spectral residual augmented classical least squares (SRACLS) are powerful chemometric approaches that can be applied for spectroscopic analysis of many pharmaceutical compounds. Herein, both CRACLS and SRACL have been employed for UV spectral analysis of three antiretroviral therapy namely abacavir (ACV), lamivudine (LMV) and dolutegravir (DTG) in their ternary mixture. A partial factorial design has been utilized for calibration set construction then both CRACLS and SRACLS models have been optimized regarding the number of iterations and principal components, respectively, using a leave-one-out cross-validation procedure. It was found that a higher number of iterations and principal components were required for modelling the minor component DTG indicating more augmentation procedures to improve the models' accuracy. Validation of the proposed models was performed using external validation set of 13 mixtures and different validation parameters have been evaluated regarding models' predictive abilities. Both models showed excellent performance for analyzing ACV and LMV with relative root mean square error of prediction (RRMSEP) below 2 %. However, higher RRMSEP values around 5 % were observed for the minor component DTG suggesting that these models should be utilized with caution when analyzing minor components in mixtures. Furthermore, the suggested models have been applied for analyzing ACV, LMV and DTG in their pharmaceutical formulation and excellent agreement was observed between the suggested models and the reported chromatographic method posing these models as powerful chemometric approaches for quality control analysis of many pharmaceutical compounds.


Assuntos
Ciclopropanos , Didesoxiadenosina/análogos & derivados , Infecções por HIV , Compostos Heterocíclicos com 3 Anéis , Lamivudina , Oxazinas , Piperazinas , Piridonas , Humanos , Quimiometria , Análise dos Mínimos Quadrados , Espectrofotometria Ultravioleta/métodos , Preparações Farmacêuticas
19.
Spectrochim Acta A Mol Biomol Spectrosc ; 308: 123711, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38042122

RESUMO

Histamine is crucial for controlling a variety of physiological processes and its dysregulation is linked to various pathological conditions, including allergic disorders, autoimmune diseases and inflammatory conditions. Herein, a novel fluorescence chemo sensor was produced to measure histamine in the pure form and spiked human plasma matrix. The proposed method is based on chemical transformation of histamine into a fluorescent product, N-(2-(1H-imidazol-4-yl) ethyl)-2-bromoacetamide, exhibiting unique fluorescence properties compared to non-fluorescent histamine molecule. This transformation occurs through a sequence of chemical reactions involving the interaction of histamine with trimethylamine, resulting in the formation of a nucleophilic intermediate that subsequently reacts with electrophilic bromoacetyl bromide. The transformed fluorescent product demonstrates an emission at 340 nm after being excited at 250 nm. Significant concentration-dependent fluorescence enhancement was obtained enabling histamine determination. The procedures were examined for accuracy, precision, selectivity, and robustness in line with the ICH M10 recommendations. The method exhibits a lower limit of quantification at 0.25 ng/mL and dynamic detection throughout a linearity range of 1-200 ng/mL, providing accurate assessment of histamine in the plasma matrix.


Assuntos
Histamina , Humanos , Espectrometria de Fluorescência/métodos
20.
Eur J Pharm Sci ; 195: 106665, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38056779

RESUMO

This study aimed to fabricate and characterize feboxostat (FXT) loaded nanoemulgel (NEG) for transdermal delivery. NEG was prepared by high sheared homogenization technique and characterized for thermodynamic stability, pH analysis, drug content, zeta analysis, viscosity, spreadability, FTIR, in-vitro drug release and ex-vivo permeation. In vivo anti-inflammatory activity was evaluated in albino rats by inducing edema in hind paws using carrageenan. The formulations showed optimum thermodynamic stability, having no phase separation and color change. The pH was in the range of human skin range i.e. 5.5-6.5. The drug content of F3 and F4 formulations were 97.56 ± 3.45 % and 83.88 ± 3.12 % respectively which were in official limit of USP i.e. 90 ± 10 %. No interaction was found between the FXT and various components after FTIR analysis. The viscosity of NEG was 4587 cp at 6 rpm and 2681 cp at 12 rpm. The droplet sizes of F1 (Blank NE), F2 (Blank NEG), F3 (Drug loaded NE) and F4 (Drug loaded NEG) were 148.6 nm, 153.4 nm, 402.1 nm and 498.3 nm respectively. The percent drug release of F3 was 82 ± 0.97 %, while F4 released 78 ± 0.91 % after 24 h. The drug permeation was 77 ± 1.28 % and 74 ± 1.10 % for F3 and F4 respectively. The optimized formulation significantly (p < 0.05; ANOVA) inhibited the paw edema in albino rats as compared to the control and standard group. It has been concluded that FXT loaded NEG can be a safe and effective alternative to the oral therapy of FXT.


Assuntos
Absorção Cutânea , Pele , Ratos , Animais , Humanos , Administração Cutânea , Pele/metabolismo , Portadores de Fármacos/química , Edema/induzido quimicamente , Edema/tratamento farmacológico
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