Search

Aim: To develop and characterize doxorubicin-loaded sodium selenite nanoparticles (SSNP-DOX) and their surface attachment with cetuximab (mAb-SSNP-DOX). Methods: SSNP-DOX was formulated by gelation and then conjugated with cetuximab to form mAb-SSNP-DOX. Characterization included DLS, SEM, TEM, DSC, Raman spectroscopy and XRD. In vitro, the kinetics of doxorubicin release and cytotoxicity in MCF-7 breast cancer cells were investigated. Results: The zeta potential for SSNP-DOX and mAb-SSNP-DOX was -14.4 ± 10.1 mV and -27.5 ± 7.28 mV, with particle sizes of 181.3 nm and 227.5 nm, respectively. The formulation intensity was 89.7% for SSNP-DOX and 100% for mAb-SSNP-DOX, with PDI values of 0.419 and 0.251, respectively. SEM and TEM showed that mAb-SSNP-DOX was smooth and spherical. The DSC analysis revealed exothermic peaks at 102.44°C for SSNP-DOX and 144.21°C for mAb-SSNP-DOX, along with endothermic peaks at 269.19°C and 241.6°C, respectively. Raman spectroscopy showed a higher intensity for mAb-SSNP-DOX. The XRD study showed different peaks for each formulation. Both followed zero order kinetics for doxorubicin release. Cytotoxicity studies showed significant effects and high apoptosis in MCF-7 cells for both formulations. Conclusion: The mAb-SSNP-DOX showed promising properties, more effective doxorubicin release and higher cytotoxicity against breast cancer cells compared with SSNP-DOX. Article highlights Breast cancer Breast cancer is a significant cause of morbidity and mortality worldwide and is characterized by high heterogeneity and treatment resistance. MCF-7 cells are a commonly used human breast cancer cell line in research and a model for studying the efficacy of therapeutic interventions. Nanoparticle drug delivery system Drug delivery systems in the form of nanoparticles improve drugs' therapeutic efficacy and stability while minimizing unwanted side effects by enabling precise delivery to cancer cells. Targeted nanoparticle drug delivery systems, such as those incorporating monoclonal antibodies, further improve treatment outcomes by selectively targeting cancer cells and causing less damage to healthy tissue. Targeted breast cancer treatment The study focused on developing injectable nanoparticle formulations, SSNP-DOX and mAb-SSNP-DOX, which effectively target MCF-7 breast cancer cells. Combining cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), with SSNP-DOX improved the specificity and efficacy of the treatment. Characterization & physicochemical stability The nanoparticle formulations were comprehensively characterized using dynamic light scattering (DLS), differential scanning calorimetry (DSC), Raman spectroscopy, x-ray diffraction (XRD) and nuclear magnetic resonance spectroscopy (NMR). These techniques confirmed the formulations' stability and uniformity, ensuring their suitability for targeted drug delivery. In vitro performance & enhanced efficacy The release profiles of doxorubicin from SSNP-DOX and mAb-SSNP-DOX showed sustained drug release over a prolonged period. In vitro, cytotoxicity studies showed that both formulations effectively suppressed the growth of MCF-7 breast cancer cells. Of the two, mAb-SSNP-DOX was the superior formulation, performing better on all parameters tested. Target specificity & overcoming drug resistance mAb-SSNP-DOX showed increased specificity in targeting breast cancer cells due to cetuximab. This combination of nanoparticles with cetuximab represents a promising approach to overcoming drug resistance in the treatment of breast cancer, offering improved efficacy and targeting of breast cancer cells. Future directions Future research should focus on optimizing these formulations, investigating the underlying molecular mechanisms and conducting extensive in vivo studies to validate the therapeutic potential of mAb-SSNP-DOXstance and conducting extensive in vivo studies to validate these findings. [ABSTRACT FROM AUTHOR]

A new approach to predicting the geometrical characteristics of the mixing behavior of an inclined dense jet for angles ranging from 15° to 85° is proposed in this study. This approach is called the group method of data handling (GMDH) and is based on the artificial neural network (ANN) technique. The proposed model was trained and tested using existing experimental data reported in the literature. The model was then evaluated using statistical indices, as well as being compared with analytical models from previous studies. The results of the coefficient of determination (R2) indicate the high accuracy of the proposed model, with values of 0.9719 and 0.9513 for training and testing for the dimensionless distance from the nozzle to the return point x r / D and 0.9454 and 0.9565 for training and testing for the dimensionless terminal rise height y t / D . Moreover, four previous analytical models were used to evaluate the GMDH model. The results showed the superiority of the proposed model in predicting the geometrical characteristics of the inclined dense jet for all tested angles. Finally, the standard error of the estimate (SEE) was applied to demonstrate which model performed the best in terms of approaching the actual data. The results illustrate that all fitting lines of the GMDH model performed very well for all geometrical parameter predictions and it was the best model, with an approximately 10% error, which was the lowest error value among the models. Therefore, this study confirms that the GMDH model can be used to predict the geometrical properties of the inclined negatively buoyant jet with high performance and accuracy. [ABSTRACT FROM AUTHOR]

Faidherbia albida (Delile) A. Chev, a type of tree in the Leguminosae family, has several traditional uses. This study investigates the antioxidant properties, phenolic and flavonoid contents, nitric acid modulatory effects, and cytotoxicity of methanolic and chloroform extracts of the bark and fruits of Faidherbia albida. Various assays were performed to evaluate the antioxidant properties of the extracts, including the Folin-Ciocalteu and AlCl3 tests, the oxygen radical absorbance capacity (ORAC), the purple diphenyl picrylhydrazine (DPPH) scavenging ability, and the Ferric Reducing/Antioxidant Power (FRAP). The ability of the extracts to modulate the production of nitric oxide (NO) was assessed, and the cytotoxicity of the extracts was evaluated in cultured cells. Additionally, a bibliometric analysis was performed on related research documents. The 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the cytotoxicity of the extracts in cultivated RAW 264.7 cells. A bibliometric analysis of 362 research documents related to F. albida published since 1913 was performed to understand the current state of knowledge to identify areas for further research using bibliometric computer packages. The results showed that the bark methanolic extract had the highest phenolic content, while the chloroform extract of the fruits had the highest flavonoid content. The chloroform extract of the fruits exhibited the highest inhibition of NO production. The extracts exhibited low cytotoxicity. The methanolic extract of the bark exhibited the strongest radical scavenging activities for FRAP and DPPH. The ORAC assay revealed that the antioxidant capacity of the methanolic extract of the fruits and the chloroform extract of the bark were approximately four times greater than that of quercetin, which is a known antioxidant compound. F. albida exhibits a significant antioxidant activity, which is influenced by both solvent polarity and specific botanical components. [ABSTRACT FROM AUTHOR]

Alfaifi, H.; Mohammadian, A., and Bonakdari, H., 2020. Experimental investigation and model development of geometric characteristics of negatively buoyant jets inclined at 15° and 52° using GMDH method. Journal of Coastal Research, 36(3), 636–653. Coconut Creek (Florida), ISSN 0749-0208. The goal of this study was to provide more experimental data on the main geometric characteristics of an inclined negatively buoyant jet discharged into deep stagnant water, as well as to use the data for developing and evaluating the performance of the proposed model. Series of laboratory experiments were performed using a high-resolution digital camera to determine the main geometric characteristics of two jet discharge angles, 15° and 52°. Various densimetric Froude numbers (Frd) were used in this study, ranging from 11 to 75. The results showed that the behavior of the jet is significantly affected by the Frd and the initial discharge angle (θ). A comparison of the present results with previously reported data showed good agreement for all geometric parameters, especially for the angle of 15°, while the 52° values differed slightly. A nonlinear method (artificial neural network, ANN) called the group method of data handling (GMDH) was employed in this study to develop explicit equations for the geometric characteristics of the two studied angles. This method has not previously been used in the prediction of mixing of inclined dense jets. Moreover, different statistical indices were utilized to evaluate the accuracy of the proposed equations. The values of R-squared (R2) and the mean absolute percentage error (MAPE) for the geometric characteristic ranged between 0.964 to 0.995 and from 2.6% to 8.4% respectively, which indicate that the GMDH model performed very well. The GMDH results provided good predictions for both angles for the data used within this study. [ABSTRACT FROM AUTHOR]

Background: Catha edulis Forsk. (Khat) is traditionally used for treating various disorders. Nevertheless there are no reports of any scientific assessment of its psychopharmacological properties. Objective: Therefore, the current study was designed to evaluate the antidepressant-like activity of Khat ethanolic extract using established animal models of depression and stress. Materials and Methods: Ninety healthy male albino mice were used in this study. Forced swim, tail suspension and head poking tests were utilized to evaluate the antidepressant-like activity of the ethanolic extract of Khat (100, 200 and 400 mg/kg, i.p.) and escitalopram (standard drug) which were administered 30 min prior to the tests. Phytochemical analysis of the standardized extract was conducted using liquid chromatography-mass spectroscopy (LC-MS). Results: A significant decrease in the head-dipping behavior was noticed after administration of 100, 200 and 400 mg/kg of Khat extract. Moreover, the extract significantly decreased the immobility time in tail suspension and forced swim tests. The presence of cathinone and cathine were detected in the extract using LC-MS. Conclusion: The current results suggest that the extract of Khat leaves has acute antidepressant properties and may have sedative effects. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the cholinergic, muscarinic and antagonistic effects of Khat (Catha edulis) on native nicotinic acetylcholine receptors (nAChR) and understand its associated mechanism. Methods: Fresh leaves of Catha edulis (50 g) were pulverized and subjected to extraction using 200 mL of methanol and filtered. The filtrate was reconstituted with 0.02 N sulfuric acid, and then chloroform extraction. Properties of the crude alkaloid extract of khat (CAEK) were assessed in skeletal muscles isolated from frog rectus abdominis. In silico analysis of the effects of cathine (CAT) and cathinone (CATO) on muscle-type nicotinic acetylcholine receptors (nAChRs) and molecular docking to predict their potential binding sites on nAChR subunits were carried out. Results: Pre-treatment of isolated muscles with CAEK inhibited carbachol-induced contractility in a dose-dependent manner. At 10, 20, 40 and 80 mg/mL concentrations of CAEK, inhibition percentages were 74.4, 85.2, 95.4 and 99.5 %, respectively. Molecular docking studies show that CAT and CATO modulate the function of nAChRs through competitive antagonism. Conclusion: These results reveal that khat consumption could contribute to the development of skeletal muscle-associated ailments; hence, detailed studies emphasizing cardiac complications and muscular toxicity mechanisms should be conducted. [ABSTRACT FROM AUTHOR]

Background: Crohn's disease is a chronic, relapsing form of inflammatory bowel disease marked by severe gastrointestinal inflammation and a broad range of debilitating symptoms. Despite advances in medical treatments, achieving sustained remission remains challenging for many patients. This umbrella review aims to consolidate evidence from various systematic reviews to evaluate the efficacy and safety of stem cell therapies in treating Crohn's disease., Methods: This review followed the Joanna Briggs Institute methodology and adhered to PRISMA guidelines. A literature search of PubMed, Web of Science, Embase, and the Cochrane Library covered records up to 20 April 2024. Only systematic reviews and meta-analyses on stem cell therapy for Crohn's disease were considered. Data were extracted and analyzed for clinical efficacy indicators like remission induction and safety metrics, including adverse events and mortality rates., Results: Sixteen systematic reviews were included, spanning studies conducted between 2009 and 2023. Stem cell therapy showed a pooled risk ratio (RR) of 1.299 (95% CI: 1.192-1.420) for clinical remission, indicating a 29.9% increased likelihood of remission compared to controls. The pooled RR for healing perianal Crohn's disease was 1.358 (95% CI: 1.13-1.631), suggesting a 35.8% increased likelihood of healing. A pooled RR of 1.481 (95% CI: 1.036-2.116) shows a 48.1% higher immediate fistula closure rate with stem cell therapy. For long-term outcomes, a RR of 1.422 (95% CI: 1.091-1.854) indicates a 42.2% increased likelihood of maintaining closure. However, stem cell therapy did not significantly impact Crohn's Disease Activity Index (CDAI) (RR: 1.154, 95% CI: 0.193-6.883) and Perianal Disease Activity Index (PDAI) scores (mean difference at 12 weeks: -0.505, 95% CI: -2.481 to 1.471; mean difference at 24 weeks: -0.338, 95% CI: -1.638 to 0.963). The safety profile was comparable to conventional therapies, with a pooled RR of 0.972 (95% CI: 0.739-1.278) for adverse events and 1.136 (95% CI: 0.821-1.572) for serious adverse events., Conclusion: Stem cell therapy offers significant progress in treating Crohn's disease, particularly in complex cases, by improving fistula closure rates and suggesting potential as a supplementary therapy. Its safety profile aligns with conventional treatments, yet ongoing clinical trials are crucial to optimize its use. Continual research will enable healthcare providers to tailor more effective treatment strategies for this challenging condition., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Dengue fever, caused by the dengue virus and transmitted through Aedes mosquitoes, is a growing public health concern, particularly in tropical and subtropical regions. Traditionally associated with febrile and hemorrhagic symptoms, recent research suggests a potential link between dengue and cognitive impairments. This systematic review assessed existing research to understand the association between dengue virus infection and cognitive impairments, including dementia, Alzheimer disease, memory loss, and confusion. This systematic review followed preferred reporting items for systematic reviews and meta-analyses guidelines. A comprehensive literature search was conducted in PubMed, EMBASE, and Web of Science up to January 18, 2024. Studies examining the prevalence and association of cognitive impairments in dengue patients were included. Data extraction and quality assessment were performed using Nested Knowledge software and the Newcastle-Ottawa Scale. Of the 1129 articles identified, 5 were included in the review, covering a total of 200 873 participants from Taiwan, Brazil, and France. Evidence from population-based cohort studies indicated short-term cognitive impairments, including confusion and memory loss, in some dengue patients. Additionally, long-term risks of dementia, including Alzheimer disease and vascular dementia, were observed, particularly among older adults. Although the findings suggest there might be an association between dengue infection and cognitive decline, the mechanisms underlying this link remain unclear. This systematic review suggests that dengue virus infection may affect cognitive function in both acute and long-term contexts. However, the current evidence is not strong enough to establish a conclusive link. Further research with larger sample sizes and longitudinal studies is essential to confirm the impact of dengue virus on cognitive health., (© The Author(s) 2024. Published by Oxford University Press on behalf of CINP.)

Background: Fistulas, abnormal connections between two anatomical structures, significantly impact the quality of life and can result from a variety of causes, including congenital defects, inflammatory conditions, and surgical complications. Stem cell therapy has emerged as a promising alternative due to its potential for regenerative and immunomodulatory effects. This overview of systematic reviews aimed to assess the safety and efficacy of stem cell therapy in managing fistulas, drawing on the evidence available., Methods: This umbrella review was conducted following the Joanna Briggs Institute (JBI) methodology to assess the efficacy and safety of stem cell therapy for treating various types of fistulas. A comprehensive search was performed across multiple electronic databases including PubMed, Embase, Cochrane Register, and Web of Science up to 5 May 2024. Systematic reviews focusing on stem cell therapy for fistulas were included, with data extracted on study design, stem cell types, administration methods, and outcomes. The quality of the reviews was assessed using the AMSTAR 2 tool, and meta-analyses were conducted using R software version 4.3., Results: Nineteen systematic reviews were included in our umbrella review. The stem cell therapy demonstrated by significant improvements in clinical remission rates, with a relative risk (RR) of 1.299 (95% CI: 1.192-1.420). Stem cell therapy enhanced fistula closure rates, both short-term (RR=1.481; 95% CI: 1.036-2.116) and long-term (RR=1.422; 95% CI: 1.091-1.854). The safety analysis revealed no significant increase in the risk of adverse events with stem cell therapy, showing a pooled RR of 0.972 (95% CI: 0.739-1.278) for general adverse events and 1.136 (95% CI: 0.821-1.572) for serious adverse events, both of which indicate a safety profile comparable to control treatments. Re-epithelialization rates also improved (RR=1.44; 95% CI: 1.322-1.572)., Conclusion: Stem cell therapy shows promise as an effective and safe treatment for fistulas, particularly in inducing remission and promoting closure of complex fistulas. The findings advocate for further high-quality research to confirm these benefits and potentially incorporate stem cell therapy into standard clinical practice for fistula management. Future studies should focus on long-term outcomes and refining stem cell treatment protocols to optimize therapeutic efficacy., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Artificial intelligence (AI) and microbiome have emerged in recent years as transformative fields with far-reaching implications for various biomedical domains. This paper presents a comprehensive bibliometric analysis examining the intersection of AI and the microbiome (AIM). The study aims to provide information on this interdisciplinary field's research landscape, trends, and emerging topics. Using a systematic approach, data-driven studies were extracted from the Scopus database on 23 November 2023 and analyzed using the VOSviewer and Bibliometrix applications. The regression coefficient of 0.94 and the yearly growth rate of 7.46% in AIM production indicate a consistent increase over time. Identification of essential contributors, organizations, and nations illuminated cooperative networks and research hotspots. The trend themes are the gut microbiome, disease prediction, machine learning, transfer learning, categorization, big data, artificial neural networks, chronic rhinosinusitis, epidemiology, COPD, and bronchoalveolar lavage. These hot issues in AIM reflect the present emphasis on research and developments in our knowledge of the microbiome's function in health, sickness, and individualized treatment. The findings give researchers, policymakers, and industry experts a thorough picture of the research environment and guide future paths in AIM's fascinating and promising subject.

The search for new treatments for Alzheimer's disease (AD) has led to the exploration of plant-based drugs as potential options. Acetylcholinesterase (AChE) inhibitors are widely used as anti-AD medications. This study aimed to investigate the inhibitory mechanism of girinimbine, a constituent of Murraya koenigii, on AChE. AChE inhibition was assessed by in vitro experiments using the modified Ellman method, as well as in silico molecular docking and molecular dynamic simulation. The results were compared to those of the well-known anti-AChE agents tacrine and propidium iodide. Girinimbine, propidium, and tacrine at concentrations of 3.8X10-5M, 1.1x10-5M, and 6.1x10-7M showed percentages of inhibition percentages of 35.6%, 28.2%, and 76.6%, respectively. The docking and molecular dynamics simulation analyses indicated that girinimbine exhibited a higher binding affinity to AChE compared to propidium and tacrine. This finding was further confirmed by the docking, root mean square deviation (RMSD), root mean square fluctuation (RMSF), and radius of rotation analyses. In conclusion, M. koenigii girinimbine shows promise as an acetylcholinesterase inhibitor for Alzheimer's disease. Further research, including in vivo studies and clinical trials, is needed to explore its potential as a plant-based drug candidate for AD treatment.

BACKGROUND This study examined the effects of khat extract on the proinflammatory cytokines, liver, and kidneys of rats. Unlike previous research that focused on broad immune markers and general effects, this study investigated specific proinflammatory cytokines (IL-1ß, IL-2, IL-4, IL-6, and TNF-alpha) and considered gender differences in the immune response. Fresh khat plants and nontoxic doses were used to obtain clear observations relevant to human health. MATERIAL AND METHODS Extracts were prepared from young shoots of khat plants and fresh leaves. 150-gram male and female rats were randomly divided into 8 groups (5 rats per group). Six groups received the extract orally for 8 weeks at doses of 100, 300, and 500 mg/kg/day. Blood samples were collected after 56 days and assayed for cytokines using ELISA, while liver enzymes and kidney markers were assayed using kinetics and colorimetric methods. RESULTS Khat extract increased the levels of most cytokines, with higher doses causing greater increase. This effect was consistent across sexes for some cytokines (IL-1ß, IL-2), but not others (IL-4, IL-6, TNF-alpha), where sex played a role at specific doses. Various doses of the extract influenced glucose levels in both male and female rats. In addition, liver enzyme markers showed some variations. CONCLUSIONS This study, with its intriguing findings, illuminates the complex effects of khat on various systems. Variations in AST and ALT levels in the liver support earlier hepatotoxicity research and suggest possible khat-induced damage. This study revealed consistently increased levels of all cytokines as the dose of khat extract increased.