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1.
Future Med Chem ; : 1-15, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39263964

RESUMEN

New pyridine-O-glycosides and their acyclic nucleoside analogues were prepared by heterocyclization and glycosylation. The anticancer activity against HCT-116, HepG2 and MCF-7 human cancer cells and BJ-1 cell revealed that the galacto- and xylopyranosyl glycosides possessing 4-bromophenyl have superior cytotoxic activities against HepG2 cell while glycosides 7-9 resulted in superior cytotoxic activities regarding MCF-7 breast cell. In case of HCT-116 colorectal carcinoma cells, two products and the derived glycosides and acyclic analogues showed potent activities. The most potent compounds were investigated for their possible binding affinities to the active site of CDK2 enzyme via in silico molecular docking simulation in addition to computational studies. The results support the antiproliferative effect and elucidate the interactions of 3a and 8 with catalytic sites.


[Box: see text].

2.
Environ Sci Nano ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39263008

RESUMEN

Nanomaterials (NMs) are increasingly used in medical treatments, electronics, and food additives. However, nanosafety-the possible adverse effects of NMs on human health-is an area of active research. This review provides an overview of the influence of biomolecular coronas on NM transformation following various exposure routes. We discuss potential exposure pathways, including inhalation and ingestion, describing the physiology of exposure routes and emphasising the relevance of coronas in these environments. Additionally, we review other routes to NM exposure, such as synovial fluid, blood (translocation and injection), dermal and ocular exposure, as well as the dose and medium impact on NM interactions. We emphasize the need for an in-depth characterisation of coronas in different biological media, highlighting the need and opportunity to study lung and gastric fluids to understand NM behaviour and potential toxicity. Future research aims to predict better in vivo outcomes and address the complexities of NM interactions with biological systems.

3.
Am J Trop Med Hyg ; 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39106853

RESUMEN

In an open randomized controlled trial, we compared one vial (10 mL) to two vials (20 mL) of EchiTAb-plus-ICP (EPI) antivenom among children with systemic carpet viper (Echis romani) envenoming of moderate severity in northeastern Nigeria. Systemic envenoming, presenting with incoagulable blood, was diagnosed using the 20-minute whole blood clotting test (20WBCT). Eligible patients with positive 20WBCT whose guardians assented were recruited and randomly allocated to receive either one vial or two vials of EPI administered either as a bolus or as a slow continuous infusion. The primary outcome was permanent restoration of blood coagulability 6 hours after the start of treatment, assessed by the 20WBCT and repeated at 6, 12, 24, and 48 hours after treatment. Secondary outcomes were the incidences of early adverse reactions to antivenom treatment. Initial doses permanently restored blood coagulability at 6 hours in 34/39 (87.2%) of those treated with one vial and 39/41 (95.1%) of those treated with two vials of EPI (P = 0.258). However, the proportion with permanent restoration of clotting at 6 hours among patients randomized to bolus administration was 41 of 42 (97.6%) patients compared with 32 of 38 (84.2%) patients randomized to slow infusion of EPI antivenom (P = 0.049); however, the difference was not sustained through the remaining time points. There was no difference in early adverse reactions between those treated with the two different doses or modes of delivery. We conclude that the one-vial dose compared favorably to two vials of EPI antivenom with regards to effectiveness and safety among children with carpet viper envenoming of moderate severity in Nigeria.

4.
Front Toxicol ; 6: 1393330, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39109300

RESUMEN

Engineered nanoparticles (NPs) pose a broad spectrum of interesting properties that make them useful for many applications. However, continuous exposure to NPs requires the need to deeply understand the outcomes when these NPs interact with different biological environments. After exposure within (to) these environments, the pristine surfaces of NPs strongly interact with the molecules from the surrounding medium, including metabolites, lipids, glycan, and proteins, forming the so-called protein corona (PC). It is well established that the NP-PC strongly influences the biological fate of various NPs types, including cellular uptake, toxicity, and biodistribution. Thus, for a proper assessment of potential hazards associated with engineered NPs, it is mandatory to study and evaluate the PC that forms around NPs. Herein, we describe protocols in detail for the isolation and characterization of NP-PC complexes and cover the following aspects: 1) isolation protocols for different nanomaterials in a range of exposing media, including magnetic isolation methods for superparamagnetic NPs, 2) NP physico-chemical characterization using advanced and standard techniques available in regular laboratories, and 3) NP- PC characterization of the protein and glycan components.

5.
Res Sq ; 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38978569

RESUMEN

Firearm injuries are a common and major public health problem in Baltimore, Maryland. The city is also one of the first U.S. cities in which the 1930s discriminatory practice of redlining first emerged. This study examines the association between current day firearm injuries and residence in these historically redlined areas at a neighborhood level using zip codes. Firearm injury outcomes in patients who presented to a hospital in Maryland from 2015 to 2020 were measured from the Health Services Cost Review Commission (HSCRC) in conjunction with both geospatial data from Richmond's Digital Scholarship Lab's Mapping Inequality project and population data from the U.S. Census. A redlining score was calculated to represent the extent of redlining in each zip code. Negative binomial regression models were utilized to measure the association between neighborhood zip codes and rate of firearm injuries. Our adjusted regression model shows that for every one-unit increase of the Home Owners' Loan Corporation (HOLC) redlining score, there is a 2.24-fold increase in the rate of firearm injuries (RR 2.24; 95% CI: 0.31, 1.31, p < 0.001). These findings suggest a strongassociation between historically redlined areas and population risk of firearm injury today. Further research is needed to investigate the underlying mechanisms that may contribute to this relationship, such as access to firearms or social and economic factors. Overall, our study highlights the potential impact of historical redlining policies on contemporary health outcomes in Baltimore.

6.
ACS Omega ; 9(27): 29666-29681, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-39005820

RESUMEN

The corrosion inhibition of (N 1 E)-N 1,N 2-bis(4-(dimethylamino)benzylidene)-ethane-1,2-diamine, DMAB, against the destruction of C-steel in dilute HCl media (1.0 M) was examined. The techniques of gravimetry, gasometry, potentiodynamic, and electrochemical impedance spectroscopy are utilized. The rate of corrosion is found to decrease with more additions of the DMAB compound. The inhibition efficacy increases with concentrations to reach 97.7% at 5.0 mM and 298 K. The protection of metal destruction is controlled by the adsorption of the DMAB molecules on the metallic surface obeying Langmuir's pattern. The computed ΔG°ads values are characterized by negative sign, explaining the spontaneity of the adsorption process. These values vary between -38.70 and -35.13 kJ mol-1 depending on the temperature, which proves the physio- and chemisorption mechanisms. The reduction in K ads values with T can be attributed to the desorption of some DMAB molecules from the electrode surface. Theoretical quantum computation confirms the adsorption of the DMAB compound in concurrence with the data obtained by practical techniques.

7.
BMC Vet Res ; 20(1): 276, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926724

RESUMEN

BACKGROUND: Trace elements play a crucial role in fish nutrition, with zinc (Zn) being one of the most important elements. BIO-sourced zinc nanoparticles were synthesized using the green microalga Pediastrum boryanum (BIO-ZnNPs, 29.35 nm). 30 or 60 mg/ kg dry feed of the BIO-ZnNPs (BIO-ZnNPs30 and BIO-ZnNPs60) were mixed with the Nile tilapia (Oreochromis niloticus) basal diet and fed to the fish for 8 weeks to evaluate their impact on fish growth, digestion, intestinal integrity, antioxidative status, and immunity. RESULTS: A significant enhancement was observed in all investigated parameters, except for the serum protein profile. BIO-ZnNPs at 60 mg/kg feed elevated the activities of reduced glutathione (GSH) and catalase (CAT), enzymatic antioxidants, but did not induce oxidative stress as reflected by no change in MDA level. Fish intestinal immunity was improved in a dose-dependent manner, in terms of improved morphometry and a higher count of acid mucin-producing goblet cells. Interleukin-8 (IL-8) was upregulated in BIO-ZnNPs30 compared to BIO-ZnNPs60 and control fish groups, while no significant expressions were noted in tumor necrosis factor-alpha (TNFα), nuclear factor kappa B (NFkB), and Caspase3 genes. CONCLUSION: Overall, BIO-ZnNPs inclusion at 60 mg/kg feed showed the most advantage in different scenarios, compared to BIO-ZnNPs at 30 mg/kg feed. The positive effects on growth and intestinal health suggest that BIO-ZnNPs supplementation of aquafeeds has many benefits for farmed fish.


Asunto(s)
Alimentación Animal , Cíclidos , Dieta , Intestinos , Zinc , Animales , Zinc/farmacología , Zinc/administración & dosificación , Alimentación Animal/análisis , Cíclidos/inmunología , Cíclidos/crecimiento & desarrollo , Intestinos/efectos de los fármacos , Intestinos/inmunología , Dieta/veterinaria , Suplementos Dietéticos , Nanopartículas del Metal , Antioxidantes , Chlorophyta/química , Microalgas
8.
J Neuroinflammation ; 21(1): 124, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38730498

RESUMEN

Traumatic brain injury (TBI) is a chronic and debilitating disease, associated with a high risk of psychiatric and neurodegenerative diseases. Despite significant advancements in improving outcomes, the lack of effective treatments underscore the urgent need for innovative therapeutic strategies. The brain-gut axis has emerged as a crucial bidirectional pathway connecting the brain and the gastrointestinal (GI) system through an intricate network of neuronal, hormonal, and immunological pathways. Four main pathways are primarily implicated in this crosstalk, including the systemic immune system, autonomic and enteric nervous systems, neuroendocrine system, and microbiome. TBI induces profound changes in the gut, initiating an unrestrained vicious cycle that exacerbates brain injury through the brain-gut axis. Alterations in the gut include mucosal damage associated with the malabsorption of nutrients/electrolytes, disintegration of the intestinal barrier, increased infiltration of systemic immune cells, dysmotility, dysbiosis, enteroendocrine cell (EEC) dysfunction and disruption in the enteric nervous system (ENS) and autonomic nervous system (ANS). Collectively, these changes further contribute to brain neuroinflammation and neurodegeneration via the gut-brain axis. In this review article, we elucidate the roles of various anti-inflammatory pharmacotherapies capable of attenuating the dysregulated inflammatory response along the brain-gut axis in TBI. These agents include hormones such as serotonin, ghrelin, and progesterone, ANS regulators such as beta-blockers, lipid-lowering drugs like statins, and intestinal flora modulators such as probiotics and antibiotics. They attenuate neuroinflammation by targeting distinct inflammatory pathways in both the brain and the gut post-TBI. These therapeutic agents exhibit promising potential in mitigating inflammation along the brain-gut axis and enhancing neurocognitive outcomes for TBI patients.


Asunto(s)
Antiinflamatorios , Lesiones Traumáticas del Encéfalo , Eje Cerebro-Intestino , Humanos , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/metabolismo , Eje Cerebro-Intestino/fisiología , Eje Cerebro-Intestino/efectos de los fármacos , Animales , Antiinflamatorios/uso terapéutico , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/fisiología , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/etiología
9.
J Econ Entomol ; 117(3): 809-816, 2024 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-38568949

RESUMEN

In this study, we investigated the biological aspects and predation efficiency of 3 aphidophagous ladybird beetles, Coccinella novemnotata, Hippodamia variegata, and Coccinella septempunctata, on the cotton aphid, Aphis gossypii, reared on cucumber plants (Cucumis sativus L. cultivar barracuda) under laboratory conditions. The developmental periods of C. novemnotata, H. variegata, and C. septempunctata were observed to be 16.00 ±â€…0.25, 16.00 ±â€…0.25, and 20.58 ±â€…0.40 days, respectively. The larvae of these ladybird beetles consumed an average of 218.93 ±â€…8.86, 254.77 ±â€…8.86, and 537.36 ±â€…10.49 aphids, respectively. Fourth-instar larvae were particularly efficient, consuming 53.68%, 52.68%, and 52.64% of total aphids for C. novemnotata, H. variegata, and C. septempunctata, respectively. Adult emergence rates were promising, with 91.67%, 100.00%, and 92.86%, accompanied by sex ratios of 63.64%, 53.84%, and 61.54%, respectively. Notably, a single female of C. novemnotata, H. variegata, and C. septempunctata consumed an average of 2,215.30, 2,232.00, and 3,364.50 aphids, respectively, over its lifespan. Coccinella septempunctata demonstrated the highest predation efficiency among the 3 species, suggesting its potential for biological control of A. gossypii in both open fields and greenhouses, promoting sustainable agricultural practices.


Asunto(s)
Áfidos , Escarabajos , Larva , Control Biológico de Vectores , Conducta Predatoria , Animales , Áfidos/fisiología , Escarabajos/fisiología , Larva/crecimiento & desarrollo , Larva/fisiología , Cucumis sativus , Femenino , Masculino , Cadena Alimentaria , Ninfa/crecimiento & desarrollo , Ninfa/fisiología
10.
BMC Vet Res ; 20(1): 107, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38500172

RESUMEN

BACKGROUND: Feed supplements, including essential trace elements are believed to play an important role in augmenting fish immune response. In this context, selenium nanoparticles (SeNPs) in fish diets via a green biosynthesis strategy have attracted considerable interest. In this investigation, selenium nanoparticles (SeNPs, 79.26 nm) synthesized from the green microalga Pediastrum boryanum were incorporated into Nile tilapia diets to explore its beneficial effects on the immune defense and intestinal integrity, in comparison with control basal diets containing inorganic Se source. Nile tilapia (No. 180, 54-57 g) were fed on three formulated diets at concentrations of 0, 0.75, and 1.5 mg/kg of SeNPs for 8 weeks. After the trial completion, tissue bioaccumulation, biochemical indices, antioxidant and pro-inflammatory cytokine-related genes, and intestinal histological examination were analyzed. RESULTS: Our finding revealed that dietary SeNPs significantly decreased (P < 0.05) serum alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and cholesterol, while increasing (P < 0.05) high-density lipoproteins (HDL). The Se concentration in the muscle tissues showed a dose-dependent increase. SeNPs at a dose of 1.5 mg/kg significantly upregulated intestinal interleukin 8 (IL-8) and interleukin 1 beta (IL-1ß) gene transcription compared with the control diet. Glutathione reductase (GSR) and glutathione synthetase (GSS) genes were significantly upregulated in both SeNPs-supplemented groups compared with the control. No apoptotic changes or cell damages were observed as indicated by proliferating cell nuclear antigen (PCNA) and caspase-3 gene expression and evidenced histopathologically. SeNPs supplementation positively affects mucin-producing goblet cells (GCs), particularly at dose of 1.5 mg/kg. CONCLUSION: Therefore, these results suggest that Green synthesized SeNPs supplementation has promising effects on enhancing Nile tilapia immunity and maintaining their intestinal health.


Asunto(s)
Cíclidos , Microalgas , Nanopartículas , Selenio , Animales , Selenio/farmacología , Selenio/metabolismo , Microalgas/metabolismo , Suplementos Dietéticos , Dieta/veterinaria , Antioxidantes/metabolismo , Expresión Génica , Alimentación Animal/análisis
11.
Cell Death Dis ; 15(2): 140, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38355725

RESUMEN

Immune checkpoints (CTLA4 & PD-1) are inhibitory pathways that block aberrant immune activity and maintain self-tolerance. Tumors co-opt these checkpoints to avoid immune destruction. Immune checkpoint inhibitors (ICIs) activate immune cells and restore their tumoricidal potential, making them highly efficacious cancer therapies. However, immunotolerant organs such as the liver depend on these tolerogenic mechanisms, and their disruption with ICI use can trigger the unintended side effect of hepatotoxicity termed immune-mediated liver injury from ICIs (ILICI). Learning how to uncouple ILICI from ICI anti-tumor activity is of paramount clinical importance. We developed a murine model to recapitulate human ILICI using CTLA4+/- mice treated with either combined anti-CTLA4 + anti-PDL1 or IgG1 + IgG2. We tested two forms of antisense oligonucleotides to knockdown caspase-3 in a total liver (parenchymal and non-parenchymal cells) or in a hepatocyte-specific manner. We also employed imaging mass cytometry (IMC), a powerful multiplex modality for immunophenotyping and cell interaction analysis in our model. ICI-treated mice had significant evidence of liver injury. We detected cleaved caspase-3 (cC3), indicating apoptosis was occurring, as well as Nod-like receptor protein 3 (NLRP3) inflammasome activation, but no necroptosis. Total liver knockdown of caspase-3 worsened liver injury, and induced further inflammasome activation, and Gasdermin-D-mediated pyroptosis. Hepatocyte-specific knockdown of caspase-3 reduced liver injury and NLRP3 inflammasome activation. IMC-generated single-cell data for 77,692 cells was used to identify 22 unique phenotypic clusters. Spatial analysis revealed that cC3+ hepatocytes had significantly closer interactions with macrophages, Kupffer cells, and NLRP3hi myeloid cells than other cell types. We also observed zones of three-way interaction between cC3+ hepatocytes, CD8 + T-cells, and macrophages. Our work is the first to identify hepatocyte apoptosis and NLRP3 inflammasome activation as drivers of ILICI. Furthermore, we report that the interplay between adaptive and innate immune cells is critical to hepatocyte apoptosis and ILICI.


Asunto(s)
Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Ratones , Humanos , Animales , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inhibidores de Puntos de Control Inmunológico/farmacología , Antígeno CTLA-4/metabolismo , Caspasa 3/metabolismo , Hígado/metabolismo , Apoptosis , Hepatocitos/metabolismo , Comunicación Celular
12.
Foods ; 13(4)2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38397501

RESUMEN

A milk drink flavored with date syrup produced at a lab scale level was evaluated. The production process of date syrup involves a sequence of essential unit operations, commencing with the extraction, filtration, and concentration processes from two cultivars: Sukkary and Khlass. Date syrup was then mixed with cow's and camel's milk at four percentages to form a nutritious, natural, sweet, and energy-rich milk drink. The sensory, physical, and chemical characteristics of the milk drinks flavored with date syrup were examined. The objective of this work was to measure the physiochemical properties of date fruits and milk drinks flavored with date syrup, and then to evaluate the physical properties of milk drinks utilizing non-destructive visible-near-infrared spectra (VIS-NIR). The study assessed the characteristics of the milk drink enhanced with date syrup by employing VIS-NIR spectra and utilizing a partial least-square regression (PLSR) and artificial neural network (ANN) analysis. The VIS-NIR spectra proved to be highly effective in estimating the physiochemical attributes of the flavored milk drink. The ANN model outperformed the PLSR model in this context. RMSECV is considered a more reliable indicator of a model's future predictive performance compared to RMSEC, and the R2 value ranged between 0.946 and 0.989. Consequently, non-destructive VIS-NIR technology demonstrates significant promise for accurately predicting and contributing to the entire production process of the product's properties examined.

13.
Pharmaceuticals (Basel) ; 17(2)2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38399412

RESUMEN

The SARS-CoV-2 pandemic at the end of 2019 had major worldwide health and economic consequences. Until effective vaccination approaches were created, the healthcare sectors endured a shortage of operative treatments that might prevent the infection's spread. As a result, academia and the pharmaceutical industry prioritized the development of SARS-CoV2 antiviral medication. Pyranopyrazoles have been shown to play a prominent function in pharmaceutical chemistry and drug sighting because of their significant bioactive properties. We provide herein a novel sequence of pyranopyrazoles and their annulated systems whose antiviral efficacy and cytotoxicity were explored versus human coronavirus 229E (HCoV-229E) Vero-E6 cell lines as a model for the Coronaviridae family. Fifteen synthetic congeners pointed out miscellaneous antiviral efficacies against HCoV-229E with variable inhibition degrees. Compound 18 showed a high selectivity index (SI = 12.6) that established spectacular inhibitory capacity against human coronavirus 229E. Compounds 6, 7, and 14 exposed moderate efficacies. Compounds 6, 7, 14, and 18 exhibited substantial antiviral action through the replication phase with reduction percentages extending from 53.6%, 60.7%, and 55% to 82.2%, correspondingly. Likewise, when assessed to the positive control tipranavir (88.6%), the inhibitory efficiency of compounds 6, 7, 14, and 18 versus the SARS-CoV2 Mpro provided high percentages of 80.4%, 73.1%, 81.4% and up to 84.5%, respectively. In silico studies were performed to investigate further the biological activity and the target compounds' physical and chemical features, including molecular dynamic (MD) simulations, protein-ligand docking, ADME studies, and density functional theory (DFT) calculations. These inquiries demonstrated that this series of metabolically stable pyranopyrazoles and their annulated systems are effective human coronavirus inhibitors that inhibit the viral Mpro protein and may have emerged as a novel COVID-19 curative option.

14.
Environ Toxicol Pharmacol ; 106: 104353, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38163529

RESUMEN

A substantial increase in engineered nanoparticles in consumer products has been observed, heightening human and environmental exposure. Inhalation represents the primary route of human exposure, necessitating a focus on lung toxicity studies. However, to avoid ethical concerns the use of in vitro models is an efficient alternative to in vivo models. This study utilized an in vitro human alveolar barrier model at air-liquid-interface with four cell lines, for evaluating the biological effects of different gold nanoparticles. Exposure to PEGylated gold nanospheres, nanorods, and nanostars did not significantly impact viability after 24 h, yet all AuNPs induced cytotoxicity in the form of membrane integrity impairment. Gold quantification revealed cellular uptake and transport. Transcriptomic analysis identified gene expression changes, particularly related to the enhancement of immune cells. Despite limited impact, distinct effects were observed, emphasizing the influence of nanoparticles physicochemical parameters while demonstrating the model's efficacy in investigating particle biological effects.


Asunto(s)
Oro , Nanopartículas del Metal , Humanos , Oro/toxicidad , Oro/química , Nanopartículas del Metal/toxicidad , Nanopartículas del Metal/química , Línea Celular
15.
J Trauma Acute Care Surg ; 97(3): 356-364, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38189659

RESUMEN

BACKGROUND: Traumatic brain injury (TBI) leads to acute gastrointestinal dysfunction and mucosal damage, resulting in feeding intolerance. C-C motif chemokine receptor 2 (Ccr2 + ) monocytes are crucial immune cells that regulate the gut's inflammatory response via the brain-gut axis. Using Ccr2 ko mice, we investigated the intricate interplay between these cells to better elucidate the role of systemic inflammation after TBI. METHODS: A murine-controlled cortical impact model was used, and results were analyzed on postinjury days 1 and 3. The experimental groups included (1) sham C57Bl/6 wild type (WT), (2) TBI WT, (3) sham Ccr2 ko , and (4) TBI Ccr2 ko . Mice were euthanized on postinjury days 1 and 3 to harvest the ileum and study intestinal dysfunction and serotonergic signaling using a combination of quantitative real-time polymerase chain reaction, immunohistochemistry, fluorescein isothiocyanate-dextran motility assays, and flow cytometry. Student's t test and one-way analysis of variance were used for statistical analysis, with significance achieved when p < 0.05. RESULTS: Traumatic brain injury resulted in severe dysfunction and dysmotility of the small intestine in WT mice as established by significant upregulation of inflammatory cytokines iNOS , Lcn2 , TNFα , and IL1ß and the innate immunity receptor toll-like receptor 4 ( Tlr4 ). This was accompanied by disruption of genes related to serotonin synthesis and degradation. Notably, Ccr2 ko mice subjected to TBI showed substantial improvements in intestinal pathology. Traumatic brain injury Ccr2 ko groups demonstrated reduced expression of inflammatory mediators ( iNOS , Lcn2 , IL1ß , and Tlr4 ) and improvement in serotonin synthesis genes, including tryptophan hydroxylase 1 ( Tph1 ) and dopa decarboxylase ( Ddc ). CONCLUSION: Our study reveals a critical role for Ccr2 + monocytes in modulating intestinal homeostasis after TBI. Ccr2 + monocytes aggravate intestinal inflammation and alter gut-derived serotonergic signaling. Therefore, targeting Ccr2 + monocyte-dependent responses could provide a better understanding of TBI-induced gut inflammation. Further studies are required to elucidate the impact of these changes on brain neuroinflammation and cognitive outcomes.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Ratones Endogámicos C57BL , Ratones Noqueados , Monocitos , Receptores CCR2 , Serotonina , Transducción de Señal , Animales , Receptores CCR2/metabolismo , Receptores CCR2/genética , Ratones , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/complicaciones , Monocitos/metabolismo , Serotonina/metabolismo , Modelos Animales de Enfermedad , Masculino , Inflamación/metabolismo
16.
J Colloid Interface Sci ; 659: 503-519, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38184993

RESUMEN

The adsorption of proteins onto the surface of nanoparticle (NP) leads to the formation of the so-called "protein corona" as consisting both loosely and tightly bound proteins. It is well established that the biological identity of NPs that may be acquired after exposure to a biological matrix is mostly provided by the components of the hard corona as the pristine surface is generally less accessible for binding. For that reason, the isolation and the characterisation of the NP-corona complexes and identification of the associated biomolecules can help in understanding its biological behaviour. Established methods for the isolation of the NP-HC complexes are time-demanding and can lead to different results based on the isolation method applied. Herein, we have developed a fast and simple method using ferromagnetic beads isolated from commercial MACS column and used for the isolation of superparamagnetic NP following exposure to different types of biological milieu. We first demonstrated the ability to easily isolate superparamagnetic iron oxide NPs (IONPs) from different concentrations of human blood plasma, and also tested the method on the corona isolation using more complex biological matrices, such as culture medium containing pulmonary mucus where the ordinary corona methods cannot be applied. Our developed method showed less than 20% difference in plasma corona composition when compared with centrifugation. It also showed effective isolation of NP-HC complexes from mucus-containing culture media upon comparing with centrifugation and MACS columns, which failed to wash out the unbound proteins. Our study was supported with a full characterisation profile including dynamic light scattering, nanoparticle tracking analysis, analytical disk centrifuge, and zeta potentials. The biomolecules/ proteins composing the HC were separated by vertical gel electrophoresis and subsequently analysed by liquid chromatography-tandem mass spectrometry. In addition to our achievements in comparing different isolation methods to separate IONPs with corona from human plasma, this is the first study that provides a complete characterisation profile of particle protein corona after exposure in vitro to pulmonary mucus-containing culture media.


Asunto(s)
Nanopartículas , Corona de Proteínas , Humanos , Corona de Proteínas/química , Proteínas/química , Nanopartículas Magnéticas de Óxido de Hierro , Nanopartículas/química , Medios de Cultivo
17.
Biol Trace Elem Res ; 202(4): 1752-1766, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37491615

RESUMEN

The current study evaluated the potential ameliorative effect of a dietary immune modulator, Nannochloropsis oculata microalga, on the mercuric chloride (HgCl2)-induced toxicity of Nile tilapia. Nile tilapia (45-50 g) were fed a control diet or exposed to » LC50 of HgCl2 (0.3 mg/L) and fed on a medicated feed supplemented with N. oculata (5% and 10% (50 or 100 g/kg dry feed)) for 21 days. Growth and somatic indices, Hg2+ bioaccumulation in muscles, and serum acetylcholinesterase (AChE) activity were investigated. Antioxidant and stress-related gene expression analyses were carried out in gills and intestines. Histopathological examinations of gills and intestines were performed to monitor the traits associated with Hg2+ toxicity or refer to detoxification. Hg2+ toxicity led to significant musculature bioaccumulation, inhibited AChE activity, downregulated genes related to antioxidants and stress, and elicited histopathological changes in the gills and intestine. Supplementation with N. oculata at 10% was able to upregulate the anti-oxidative-related genes while downregulated the stress apoptotic genes in gills and intestines compared to the unexposed group. In addition, minor to no histopathological traits were detected in the gills and intestines of the N. oculata-supplemented diets. Our data showed the benefit of dietary N. oculata in suppressing Hg2+ toxicity, which might support its efficacy as therapeutic/preventive agent to overcome environmental heavy metal pollution in aquatic habitats.


Asunto(s)
Cíclidos , Mercurio , Animales , Mercurio/toxicidad , Mercurio/metabolismo , Acetilcolinesterasa/genética , Acetilcolinesterasa/metabolismo , Dieta , Suplementos Dietéticos , Antioxidantes/farmacología , Antioxidantes/metabolismo , Estrés Oxidativo , Inmunidad , Alimentación Animal/análisis
18.
Cureus ; 15(10): e47390, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38022006

RESUMEN

Background During the COVID-19 pandemic, universities worldwide pivoted to distance education, primarily online, using various blended learning tools. In the contemporary era, characterized by widespread high-speed internet and the ubiquity of social media (SM), SM has become an essential tool, especially among students. This study aimed to assess the perception, impact, and preferences of various SM platforms for learning among health sciences students in the post-COVID-19 era. Methodology The study was conducted at constituent colleges of Jouf University and Northern Border University between January and June 2022. Responses from 560 students were assessed using a self-administered, pre-validated questionnaire comprising 31 questions. These questions addressed students' perceptions, preferences, and learning modes derived from SM. Descriptive and inferential statistics evaluated the influence of SM on student learning. Results On average, students spent 3.18 hours daily on SM. YouTube (41.1%) and Instagram (37.1%) emerged as the most preferred platforms for learning. A significant 86.4% of students utilized SM for accessing subject-related texts and watching related videos. Moreover, 78.6% believed that SM platforms enhanced their subject knowledge following lectures. Logistic regression analysis indicated maximum learning benefits for students who used SM between two to three hours daily. Conclusion Social media platforms, when used judiciously, can enhance the learning experience for health sciences students in the post-COVID era. While offering opportunities to acquire new knowledge and skills, care must be taken to prevent misuse, abuse, or related health hazards.

19.
J Enzyme Inhib Med Chem ; 38(1): 2241674, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37548154

RESUMEN

Hexahydroquinoline (HHQ) scaffold was constructed and recruited for development of new series of anticancer agents. Thirty-two new compounds were synthesised where x-ray crystallography was performed to confirm enantiomerism. Thirteen compounds showed moderate to good activity against NCI 60 cancer cell lines, with GI % mean up to 74% for 10c. Expending erlotinib as a reference drug, target compounds were verified for their inhibiting activities against EGFRWT, EGFRT790M, and EGFRL858R where compound 10d was the best inhibitor with IC50 = 0.097, 0.280, and 0.051 µM, respectively, compared to erlotinib (IC50 = 0.082 µM, 0.342 µM, and 0.055 µM, respectively). Safety profile was validated using normal human lung (IMR-90) cells. 10c and 10d disrupted cell cycle at pre-G1 and G2/M phases in lung cancer, HOP-92, and cell line. Molecular docking study was achieved to understand the potential binding interactions and affinities in the active sites of three versions of EGFRs.


New 32 hexahydroquinoline (HHQ) analogues 6a­i, 8a­m, 10a­d, and 12a­f having the same features of EGFR inhibitors were synthesised in racemic mixtures.The antiproliferative activities were assessed towards 60 cancer cell lines which were efficiently inhibited by compound 10c.Compound 10d remarkably inhibited EGFRWT, EGFRT790M, and EGFRL858R.Cell cycle analysis and Annexin V-based flow cytometry in the HOP-92 lung cancer cells were performed.The safety profile of compounds 10c and 10d was validated using normal human lung (IMR-90) cells.Molecular docking studies revealed that the S-isomers exhibited higher affinity than R-isomers to active sites.


Asunto(s)
Antineoplásicos , Neoplasias Pulmonares , Quinolinas , Humanos , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Receptores ErbB/metabolismo , Clorhidrato de Erlotinib/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Simulación del Acoplamiento Molecular , Mutación , Inhibidores de Proteínas Quinasas/química , Quinolinas/química
20.
BMC Chem ; 17(1): 98, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37582756

RESUMEN

Mathematical filtration is an efficient tool to resolve the overlapping spectra of binary mixtures in zero or first order form. Herein, a comparative study was conducted between six economic, accurate and precise spectrophotometric methods for determination of Triclabendazole (TCB) and Levamisole HCl (LVM). Each component was resolved with minimum mathematical steps in its zero-order absorption spectrum by ratio subtraction, constant multiplication, and the recent factorized response method; coupled with spectrum subtraction. In addition, the mixture was resolved in its first derivative form by derivative subtraction, D1 constant multiplication, and the recent D1 factorized response method; coupled with spectrum subtraction. Results obtained were also compared to those obtained from constant value, concentration value, and derivative ratio methods. The linearity range was found to be either 1.0-10.0 µg/mL or 2.0-20.0 µg/mL for TCB, and 2.0-14.0 µg/mL for LVM with LOD of 0.08 µg/mL and 0.19 µg/mL, respectively. Validation of the proposed methods was performed according to VICH guidelines. Results obtained from the statistical data showed no significant difference regarding accuracy and precision compared to the reported methods. The developed spectrophotometric methods followed the principles of green analytical chemistry, in which the green assessment was done through four tools, called, National Environmental Methods Index (NEMI), Analytical Eco-Scale (AES), Green Analytical Procedure Index (GAPI) and Analytical greenness metric (AGREE). Also, a white assessment was performed using RGB model. The proposed methods could offer an economic alternative for the routine analysis of bulk materials and combined veterinary dosage form.

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