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1.
J Clin Exp Hepatol ; 15(1): 102381, 2025.
Article in English | MEDLINE | ID: mdl-39262566

ABSTRACT

Purpose: We aimed to perform a meta-analysis with the intention of evaluating the reliability and test accuracy of the aMAP risk score in the identification of HCC. Methods: A systematic search was performed in PubMed, Scopus, Cochrane, Embase, and Web of Science databases from inception to September 2023, to identify studies measuring the aMAP score in patients for the purpose of predicting the occurrence or recurrence of HCC. The meta-analysis was performed using the meta package in R version 4.1.0. The diagnostic accuracy meta-analysis was conducted using Meta-DiSc software. Results: Thirty-five studies 102,959 participants were included in the review. The aMAP score was significantly higher in the HCC group than in the non-HCC group, with a mean difference of 6.15. When the aMAP score is at 50, the pooled sensitivity, specificity, negative likelihood ratio, and positive likelihood ratio with 95% CI was 0.961 (95% CI 0.936, 0.976), 0.344 (95% CI 0.227, 0.483), 0.114 (95% CI 0.087, 0.15), and 1.464 (95% CI 1.22, 1.756), respectively. At a cutoff value of 60, the pooled sensitivity, specificity, negative likelihood ratio, and positive likelihood ratio with 95% CI was 0.594 (95% CI 0.492, 0.689), 0.816 (95% CI 0.714, 0.888), 0.497 (95% CI 0.418, 0.591), and 3.235 (95% CI 2.284, 4.582), respectively. Conclusion: The aMAP score is a reliable, accurate, and easy-to-use tool for predicting HCC patients of all stages, including early-stage HCC. Therefore, the aMAP score can be a valuable tool for surveillance of HCC patients and can help to improve early detection and reduce mortality.

2.
Heliyon ; 10(16): e35791, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39220931

ABSTRACT

Nickel-iron-based spinel oxide was prepared and supported on multi-walled carbon nanotubes to enhance the electrochemical oxidation of ethylene glycol in an alkaline medium. NiFe2O4 was prepared using facile sol-gel techniques. Then the prepared material was characterized using different bulk and surface techniques like powder X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM), and transmitted electron microscope (TEM). Different electrodes of NiFe2O4/CNT ratios were prepared to find out the optimum spinel oxide/CNT ratio. The activity of the metal spinel oxides composite was characterized toward ethylene glycol conversion by different electrochemical techniques like cyclic voltammetry (CV), Chronoamperometry (CA), and electrochemical impedance spectroscopy (EIS). The modified electrode reached an oxidation current of 43 mA cm-2 in a solution of 1.0 M ethylene glycol and 1.0 M NaOH. Furthermore, some kinetics parameters (like diffusion coefficient, and rate constant) were calculated to evaluate the catalytic performance. Additionally, the electrode showed extreme stability for long-term ethylene glycol oxidation.

3.
Molecules ; 29(15)2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39125114

ABSTRACT

In this study, magnetic copper ferrite (CuFe2O4) nanoparticles were synthesized via the Pechini sol-gel method and evaluated for the removal of Cd(II) ions from aqueous solutions. PF600 and PF800 refer to the samples that were synthesized at 600 °C and 800 °C, respectively. Comprehensive characterization using FTIR, XRD, FE-SEM, HR-TEM, and EDX confirmed the successful formation of CuFe2O4 spinel structures, with crystallite sizes of 22.64 nm (PF600) and 30.13 nm (PF800). FE-SEM analysis revealed particle diameters of 154.98 nm (PF600) and 230.05 nm (PF800), exhibiting spherical and irregular shapes. HR-TEM analysis further confirmed the presence of aggregated nanoparticles with average diameters of 52.26 nm (PF600) and 98.32 nm (PF800). The PF600 and PF800 nanoparticles exhibited exceptional adsorption capacities of 377.36 mg/g and 322.58 mg/g, respectively, significantly outperforming many materials reported in the literature. Adsorption followed the Langmuir isotherm model and pseudo-second-order kinetics, indicating monolayer adsorption and strong physisorption. The process was spontaneous, exothermic, and predominantly physical. Reusability tests demonstrated high adsorption efficiency across multiple cycles when desorbed with a 0.5 M ethylenediaminetetraacetic acid (EDTA) solution, emphasizing the practical applicability of these nanoparticles. The inherent magnetic properties of CuFe2O4 facilitated easy separation from the aqueous medium using a magnet, enabling efficient and cost-effective recovery of the adsorbent. These findings highlight the potential of CuFe2O4 nanoparticles, particularly PF600, for the effective and sustainable removal of Cd(II) ions from water.

4.
Proc Natl Acad Sci U S A ; 121(32): e2400153121, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39088391

ABSTRACT

Although many cytokine pathways are important for dendritic cell (DC) development, it is less clear what cytokine signals promote the function of mature dendritic cells. The signal transducer and activator of transcription 4 (STAT4) promotes protective immunity and autoimmunity downstream of proinflammatory cytokines including IL-12 and IL-23. In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), Stat4-/- mice are resistant to the development of inflammation and paralysis. To define whether STAT4 is required for intrinsic signaling in mature DC function, we used conditional mutant mice in the EAE model. Deficiency of STAT4 in CD11c-expressing cells resulted in decreased T cell priming and inflammation in the central nervous system. EAE susceptibility was recovered following adoptive transfer of wild-type bone marrow-derived DCs to mice with STAT4-deficient DCs, but not adoptive transfer of STAT4- or IL-23R-deficient DCs. Single-cell RNA-sequencing (RNA-seq) identified STAT4-dependent genes in DC subsets that paralleled a signature in MS patient DCs. Together, these data define an IL-23-STAT4 pathway in DCs that is key to DC function during inflammatory disease.


Subject(s)
Dendritic Cells , Encephalomyelitis, Autoimmune, Experimental , Interleukin-23 , STAT4 Transcription Factor , Signal Transduction , Animals , STAT4 Transcription Factor/metabolism , Dendritic Cells/immunology , Dendritic Cells/metabolism , Interleukin-23/metabolism , Interleukin-23/immunology , Mice , Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/metabolism , Mice, Knockout , Multiple Sclerosis/immunology , Multiple Sclerosis/metabolism , Multiple Sclerosis/pathology , Central Nervous System/metabolism , Central Nervous System/immunology , Inflammation/metabolism , Inflammation/immunology , Adoptive Transfer , Mice, Inbred C57BL , Humans , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
5.
J Clin Med ; 13(16)2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39201088

ABSTRACT

Background: Subclinical myocardial injury (SCMI) is associated with an increased risk of poor cardiovascular disease (CVD) outcomes. Understanding the underlying risk factors for SCMI is crucial for the prevention and management of CVD. We hypothesized that atherogenic dyslipidemia, a combination of high triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C), is associated with an increased risk of SCMI. Methods: This analysis from the third National Health and Nutrition Examination Survey (NHANES-III) included 7093 participants (age 59.3 ± 13.4 years, 52.8% women, and 49.4% White) free of CVD. Atherogenic dyslipidemia was defined as TG ≥ 150 mg/dL and HDL-C < 40 mg/dL in men or <50 mg/dL in women. A validated electrocardiographic-based cardiac infarction injury score (CIIS) ≥ 10 was considered positive for SCMI. Multivariable logistic regression analysis was used to examine the association of different combinations of TG and HDL-C groups, including atherogenic dyslipidemia with SCMI. Results: About 22.5% (n = 1594) of participants had atherogenic dyslipidemia, and 26.3% (n = 1862) had SCMI. Compared to participants with normal TG and normal HDL-C, those with atherogenic dyslipidemia had a higher prevalence of SCMI (31.2% vs. 23.9%, p-value < 0.001). In a multivariable logistic regression model, atherogenic dyslipidemia was associated with the highest odds of SCMI followed by high TG/normal HDL-C, then low HDL-C/normal TG [OR (95% CI): 131 (1.14, 1.52), 1.13 (0.97, 1.33), and 1.01 (0.86, 1.20), respectively). Conclusions: Atherogenic dyslipidemia is associated with a higher risk of SCMI, which highlights the role of nontraditional risk factors in the development of subclinical CVD.

6.
Article in English | MEDLINE | ID: mdl-38980411

ABSTRACT

Eight Novel chalcones were synthesized and their structures were confirmed by different spectral tools. All the prepared compounds were subjected to SRB cytotoxic screening against several cancer cell lines. Compound 5c exerted the most promising effect against MCF7 and HEP2 cells with IC50 values of 9.5 and 12 µg/mL, respectively. Real-time PCR demonstrated the inhibitory effect of compound 5c on the expression level of Antigen kiel 67 (KI-67), Survivin, Interleukin-1beta (IL-1B), Interleukin-6 (IL-6), Cyclooxygenase-2 (COX-2) and Protein kinase B (AKT1) genes. Flow-cytometric analysis of the cell cycle indicated that compound 5c stopped the cell cycle at the G0/G1 and G2/M phases in MCF7 and HEP2 treated cells, respectively. ELISA assay showed that Caspase 8, Caspase 9, P53, BAX, and Glutathione (GSH) were extremely activated and Matrix metalloproteinase 2 (MMP2), Matrix metalloproteinase 9 (MMP9), BCL2, Malondialdehyde (MDA), and IL-6 were deactivated in 5c treated MCF7 and HEP2 cells. Wound healing revealed that chalcone 5c reduced the ability to close the scrape wound and decreased the number of migrating MCF7 and HEP2 cells compared to the untreated cells after 48 h. Theoretical molecular modeling against P53 cancer mutant Y220C and Bcl2 showed binding energies of -22.8 and -24.2 Kcal/mole, respectively, which confirmed our ELISA results.

7.
Onco Targets Ther ; 17: 521-536, 2024.
Article in English | MEDLINE | ID: mdl-38948385

ABSTRACT

Introduction: The increasing incidence of cancer diseases necessitates the urgent exploration of new bioactive compounds. One of the trends in drug discovery is marine sponges which is gaining significant support due to the abundant production of natural pharmaceutical compounds obtained from marine ecosystems. This study evaluates the anticancer properties of an organic extract from the Red Sea sponge Callyspongia siphonella (C. siphonella) on HepG-2 and MCF-7 cancer cell lines. Methods: C. siphonella was collected, freeze-dried, and extracted using a methanol-dichloromethane mixture. The extract was analyzed via Liquid Chromatography-Mass Spectrometry. Cytotoxic effects were assessed through cell viability assays, apoptosis detection, cell cycle analysis, mitochondrial membrane potential assays, scratch-wound healing assays, and 3D cell culture assays. Results: Fifteen compounds were identified in the C. siphonella extract. The extract showed moderate cytotoxicity against MCF-7 and HepG-2 cells, with IC50 values of 35.6 ± 6.9 µg/mL and 64.4 ± 8 µg/mL, respectively, after 48 hours of treatment. It induced cell cycle arrest at the G2/M phase in MCF-7 cells and the S phase in HepG-2 cells. Apoptosis increased significantly in both cell lines, accompanied by reduced mitochondrial membrane potential. The extract inhibited cell migration, with notable reductions after 24 and 48 hours. In 3D cell cultures, the extract had IC50 values of 5.1 ± 2 µg/mL for MCF-7 and 166.4 ± 27 µg/mL for HepG-2 after 7 days of treatment, showing greater potency in MCF-7 spheres compared to HepG-2 spheres. Discussion and Conclusion: The anticancer activity is attributed to the bioactive compounds. The C. siphonella extract's ability to induce apoptosis, disrupt mitochondrial membrane potential, and arrest the cell cycle highlights its potential as a novel anticancer agent. Additional research is required to investigate the underlying mechanism by which this extract functions as a highly effective anticancer agent.

8.
Mar Pollut Bull ; 205: 116668, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38972217

ABSTRACT

Two concentrations (6.25 and 1.25 mg/L) were used for two Parkinson's disease medications, Benserazide, and Trihexyphenidyl, to test their effects on the meiobenthic nematofauna. It is predicted that these highly hydrosoluble drugs will end up in marine environments. The results showed that both medications when added alone, induced (i) important changes in the numbers and (ii) taxonomic composition. The impact of Benserazide and Trihexyphenidyl was also reflected in the (iii) functional traits of nematofauna, with the most affected categories following exposure being the trophic group 1B, the clavate tails, the circular amphids, the c-p2 life history, and the body length of 1-2 mm. These results were supported by the molecular interactions of the studied drugs with both GLD-3 and SDP proteins of Caenorhabditis elegans. (iv) The mixtures of both drugs did not show any changes in the nematode communities, suggesting that no synergistic or antagonistic interactions exist between them.


Subject(s)
Antiparkinson Agents , Benserazide , Caenorhabditis elegans , Trihexyphenidyl , Animals , Antiparkinson Agents/pharmacology , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/physiology , Water Pollutants, Chemical , Nematoda/drug effects
9.
Noncoding RNA Res ; 9(4): 1249-1256, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39036602

ABSTRACT

Background: Type I diabetes mellitus (T1DM) is one of the most common chronic autoimmune diseases worldwide. miRNAs are a class of small non-coding RNA molecules that have been linked to immune system functions, ß-cell metabolism, proliferation, and death, all of which contribute to pathogenesis of TIDM. Dysregulated miRNAs have been identified in Egyptian TIDM patients. Aim: Several miRNAs were profiled in Egyptian TIDM patients to determine whether they can be used as molecular biomarkers for T1DM. The relationship between the investigated miRNAs and pro-inflammatory cytokines (TNF-α and IL-6) has also been evaluated in the development of TIDM, in addition to the creation of a proposed model for TIDM prediction. Patients & methods: Case-control study included 177 Egyptian patients with confirmed type I diabetes mellitus and 177 healthy individuals. MiRNA-34 and miRNA-146 were detected in serum samples using real-time PCR, whereas TNF-α and IL-6 levels were assessed using ELIZA. Results: Patients with TIDM showed a significant decrease in the expression of miRNA-146, with a cut-off value ≤ 3.3, 48 % specificity, and 92.1 % sensitivity, whereas miRNA-34 had the highest sensitivity (95.5 %) and specificity (97.2 %) for differentiating diabetic patients from controls. Furthermore, other diagnostic proinflammatory markers showed lower sensitivity and specificity. Conclusion: Serum levels of miRNA-34a, miRNA-146, IL-6, and TNF-α provide new insights into T1DM pathogenesis and could be used for screening and diagnosis purposes. They can be also a potential therapeutic target, as well as allowing for more strategies to improve T1DM disease outcomes.

10.
Bioinorg Chem Appl ; 2024: 8180102, 2024.
Article in English | MEDLINE | ID: mdl-38962162

ABSTRACT

Background: Magnesium oxide nanoparticles (MgONPs) have been fabricated by several approaches, including green chemistry approach due to diverse application and versatile features. Objectives: The current study aimed to prepare a convenient, biocompatible, and economically viable MgONPs using waste citron peel extract (CP-MgONPs) to evaluate their biological applications. Methods: The CP-MgONPs were synthesized by a sustainable approach from extract of waste citron peel both as capping and reducing agents without use of any hazardous material. The physicochemical features of formed CP-MgONPs were determined by sophisticated analytical and microscopic techniques. The biogenic CP-MgONPs were examined for their antibacterial, anticarcinogenic, and photocatalytic attributes. Results: A prominent absorption peak in the UV-Vis spectra at 284 nm was the distinguishing characteristic of the CP-MgONPs. The scanning electron microscopy (SEM) reveals polyhedral morphology of nanoparticles with slight agglomeration of CP-MgONPs. The CP-MgONPs exerted excellent antibacterial potencies against six bacterial strains. The CP-MgONPs displayed significant susceptibility towards E. coli (20.72 ± 0.33 mm) and S. aureus (19.52 ± 0.05 mm) with the highest inhibition zones. The anticancer effect of CP-MgONPs was evaluated against HepG2 (IC50 : 15.3 µg·mL-1) cancer cells and exhibited potential anticancer activity. A prompt inversion of cellular injury manifested as impairment of the integrity of the cell membrane, apoptosis, and oxidative stress was observed in treated cells with CP-MgONPs. The biosynthesized CP-MgONPs also conducted successful photocatalytic potential as much as MgO powder under the UV-light using acid orange 8 (AO-8) dye. The degradation performance of CP-MgONPs showed over 94% photocatalytic degradation efficiency of acid orange 8 (AO-8) dyes within a short time. Conclusions: Outcomes of this research signify that biogenic CP-MgONPs may be advantageous at low concentrations, with positive environmental impacts.

11.
Front Immunol ; 15: 1354055, 2024.
Article in English | MEDLINE | ID: mdl-39007143

ABSTRACT

Recombinant adeno-associated virus (AAV) vectors have emerged as the preferred platform for gene therapy of rare human diseases. Despite the clinical promise, host immune responses to AAV vectors and transgene remain a major barrier to the development of successful AAV-based human gene therapies. Here, we assessed the human innate immune response to AAV9, the preferred serotype for AAV-mediated gene therapy of the CNS. We showed that AAV9 induced type I interferon (IFN) and IL-6 responses in human blood from healthy donors. This innate response was replicated with AAV6, required full viral particles, but was not observed in every donor. Depleting CpG motifs from the AAV transgene or inhibiting TLR9 signaling reduced type I IFN response to AAV9 in responding donors, highlighting the importance of TLR9-mediated DNA sensing for the innate response to AAV9. Remarkably, we further demonstrated that only seropositive donors with preexisting antibodies to AAV9 capsid mounted an innate immune response to AAV9 in human whole blood and that anti-AAV9 antibodies were necessary and sufficient to promote type I IFN release and plasmacytoid dendritic (pDC) cell activation in response to AAV9. Thus, our study reveals a previously unidentified requirement for AAV preexisting antibodies for TLR9-mediated type I IFN response to AAV9 in human blood.


Subject(s)
Dependovirus , Genetic Vectors , Immunity, Humoral , Interferon Type I , Toll-Like Receptor 9 , Humans , Toll-Like Receptor 9/immunology , Toll-Like Receptor 9/genetics , Dependovirus/genetics , Dependovirus/immunology , Interferon Type I/immunology , Genetic Vectors/genetics , Immunity, Innate , Dendritic Cells/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Genetic Therapy , Interleukin-6/blood , Interleukin-6/immunology
12.
ACS Omega ; 9(29): 31601-31610, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39072071

ABSTRACT

Ten new compounds based on the methineazo-azomethine (CH=N-N=CH) and ester linking groups were prepared and investigated for their mesophase behavior and optical stability, and liquid crystals of 4-substituted phenyl methineazo-azomethine phenyl 4-alkoxybenzoates, I n a-e , were investigated. An alkoxy group with a length between 8 and 12 carbons is attached to the phenyl eater wing, while the other terminal ring is substituted in its 4-position with one of the polar NO2, F, Cl, CH3O, and N(CH3)2 groups. The molecular structures of the newly prepared compounds were verified by using 1H NMR, 13C NMR, and elemental analysis. Differential scanning calorimetry and polarized optical microscopy were applied to investigate their mesophase behavior. All members of the prepared homologous series showed excellent thermal mesomorphic stability over wide temperature ranges. The geometrical and thermal properties of the investigated compounds were verified via density functional theory (DFT). The theoretical results revealed that all of the compounds are almost planar. Finally, the experimentally established values of the mesophase data were correlated with the predicted quantum chemical characteristics evaluated by DFT.

13.
Sci Rep ; 14(1): 11131, 2024 05 15.
Article in English | MEDLINE | ID: mdl-38750140

ABSTRACT

This study aimed to investigate the potential anti-fibrotic activity of vinpocetine in an experimental model of pulmonary fibrosis by bleomycin and in the MRC-5 cell line. Pulmonary fibrosis was induced in BALB/c mice by oropharyngeal aspiration of a single dose of bleomycin (5 mg/kg). The remaining induced animals received a daily dose of pirfenidone (as a standard anti-fibrotic drug) (300 mg/kg/PO) and vinpocetine (20 mg/kg/PO) on day 7 of the induction till the end of the experiment (day 21). The results of the experiment revealed that vinpocetine managed to alleviate the fibrotic endpoints by statistically improving (P ≤ 0.05) the weight index, histopathological score, reduced expression of fibrotic-related proteins in immune-stained lung sections, as well as fibrotic markers measured in serum samples. It also alleviated tissue levels of oxidative stress and inflammatory and pro-fibrotic mediators significantly elevated in bleomycin-only induced animals (P ≤ 0.05). Vinpocetine managed to express a remarkable attenuating effect in pulmonary fibrosis both in vivo and in vitro either directly by interfering with the classical TGF-ß1/Smad2/3 signaling pathway or indirectly by upregulating the expression of Nrf2 enhancing the antioxidant system, activating PPAR-γ and downregulating the NLRP3/NF-κB pathway making it a candidate for further clinical investigation in cases of pulmonary fibrosis.


Subject(s)
Alveolar Epithelial Cells , Pulmonary Fibrosis , Signal Transduction , Vinca Alkaloids , Animals , Humans , Male , Mice , Alveolar Epithelial Cells/drug effects , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/pathology , Bleomycin/adverse effects , Cell Line , Disease Models, Animal , Mice, Inbred BALB C , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Oxidative Stress/drug effects , PPAR gamma/metabolism , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/pathology , Pulmonary Fibrosis/chemically induced , Signal Transduction/drug effects , Smad2 Protein/metabolism , Smad3 Protein/metabolism , Transforming Growth Factor beta1/metabolism , Vinca Alkaloids/pharmacology
14.
Cancer Immunol Res ; 12(8): 1074-1089, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38810242

ABSTRACT

The specific BCL-2 small molecule inhibitor venetoclax induces apoptosis in a wide range of malignancies, which has led to rapid clinical expansion in its use alone and in combination with chemotherapy and immune-based therapies against a myriad of cancer types. While lymphocytes, and T cells in particular, rely heavily on BCL-2 for survival and function, the effects of small molecule blockade of the BCL-2 family on surviving immune cells is not fully understood. We aimed to better understand the effect of systemic treatment with venetoclax on regulatory T cells (Treg), which are relatively resistant to cell death induced by specific drugging of BCL-2 compared to other T cells. We found that BCL-2 blockade altered Treg transcriptional profiles and mediated Treg plasticity toward a TH17-like Treg phenotype, resulting in increased IL17A production in lymphoid organs and within the tumor microenvironment. Aligned with previously described augmented antitumor effects observed when combining venetoclax with anti-PD-1 checkpoint inhibition, we also demonstrated that Treg-specific genetic BCL-2 knockout combined with anti-PD-1 induced tumor regression and conferred overlapping genetic changes with venetoclax-treated Tregs. As long-term combination therapies using venetoclax gain more traction in the clinic, an improved understanding of the immune-modulatory effects caused by venetoclax may allow expansion of its use against malignancies and immune-related diseases.


Subject(s)
Bridged Bicyclo Compounds, Heterocyclic , Proto-Oncogene Proteins c-bcl-2 , Sulfonamides , T-Lymphocytes, Regulatory , Th17 Cells , Sulfonamides/pharmacology , Sulfonamides/therapeutic use , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/drug effects , Animals , Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors , Proto-Oncogene Proteins c-bcl-2/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Mice , Th17 Cells/immunology , Humans , Tumor Microenvironment/immunology , Tumor Microenvironment/drug effects , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Cell Line, Tumor , Mice, Inbred C57BL , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use
16.
Chem Biol Interact ; 394: 110996, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38593908

ABSTRACT

Diabetic retinopathy is not cured efficiently and changes of lifestyle measures may delay early retinal injury in diabetes. The aim of our study was to investigate the effects of reduced daily light exposure on retinal vascular changes in streptozotocin (STZ)-induced model of DM with emphasis on inflammation, Aqp4 expression, visual cycle and cholesterol metabolism-related gene expression in rat retina and RPE. Male Wistar rats were divided into the following groups: 1. control; 2. diabetic group (DM) treated with streptozotocin (100 mg/kg); 3. group exposed to light/dark cycle 6/18 h (6/18); 4. diabetic group exposed to light/dark cycle 6/18 h (DM+6/18). Retinal vascular abnormalities were estimated based on lectin staining, while the expression of genes involved in the visual cycle, cholesterol metabolism, and inflammation was determined by qRT-PCR. Reduced light exposure alleviated vasculopathy, gliosis and the expression of IL-1 and TNF-α in the retina with increased perivascular Aqp4 expression. The expression of genes involved in visual cycle and cholesterol metabolism was significantly up-regulated in RPE in DM+6/18 vs. DM group. In the retina only the expression of APOE was significantly higher in DM+6/18 vs. DM group. Reduced light exposure mitigates vascular changes and gliosis in DM via its anti-inflammatory effect, increased retinal cholesterol turnover and perivascular Aqp4 expression.


Subject(s)
Cholesterol , Diabetes Mellitus, Experimental , Diabetic Retinopathy , Gliosis , Light , Rats, Wistar , Retina , Streptozocin , Animals , Male , Diabetic Retinopathy/metabolism , Diabetic Retinopathy/pathology , Retina/metabolism , Retina/pathology , Retina/radiation effects , Cholesterol/metabolism , Rats , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/complications , Gliosis/pathology , Gliosis/metabolism , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/genetics , Anti-Inflammatory Agents/pharmacology , Aquaporin 4/metabolism , Aquaporin 4/genetics , Retinal Vessels/metabolism , Retinal Vessels/pathology
17.
Cureus ; 16(2): e55186, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38562270

ABSTRACT

Background DiGeorge syndrome, a common genetic microdeletion syndrome, is associated with multiple congenital anomalies, including congenital cardiac diseases. This study aims to identify the short and midterm outcomes of cardiac surgery performed on children with DiGeorge syndrome. Methods A retrospective cohort study was conducted between the period of 2018-2022, which included children divided into two groups with a 1:2 ratio. Group one included DiGeorge syndrome patients who were diagnosed using fluorescence in situ hybridization (FISH). Group two included the control group of patients who were clear of genetic syndromes. The two groups were matched based on similar cardiac surgery, age of surgery, and Risk Adjustment in Congenital Heart Surgery (RACHS-1) score. The two groups were compared based on the demographical data and postoperative complications. Results The study consisted of 81 children; 27 were DiGeorge syndrome patients, and 54 were in the control group. DiGeorge syndrome patients showed an increase in mechanical ventilation duration (p=0.0047), intensive care unit (ICU) length of stay (p=0.0012), and hospital length of stay (p=0.0391). Moreover, they showed an increased risk for bacteremia (p=0.0414), ventilator-associated pneumonia (VAP; p=0.0036), urinary tract infections (UTI; p=0.0064), and surgical site infection (SSI; p≤0.0001). They were also more susceptible to postoperative seizures (p=0.0049). Furthermore, patients with DiGeorge syndrome had a higher prevalence of congenital renal anomalies. However, there was no mortality in either group.  Conclusion This study shows a variability in the postoperative outcomes between the two groups. The study demonstrates that patients with DiGeorge syndrome have higher risks of infections and longer hospital stay during the postoperative period. Further research with a larger sample is needed to confirm our findings.

18.
Molecules ; 29(6)2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38542852

ABSTRACT

The production of green hydrogen using water electrolysis is widely regarded as one of the most promising technologies. On the other hand, the oxygen evolution reaction (OER) is thermodynamically unfavorable and needs significant overpotential to proceed at a sufficient rate. Here, we outline important structural and chemical factors that affect how well a representative nickel ferrite-modified graphene oxide electrocatalyst performs in efficient water splitting applications. The activities of the modified pristine and graphene oxide-supported nickel ferrite were thoroughly characterized in terms of their structural, morphological, and electrochemical properties. This research shows that the NiFe2O4@GO electrode has an impact on both the urea oxidation reaction (UOR) and water splitting applications. NiFe2O4@GO was observed to have a current density of 26.6 mA cm-2 in 1.0 M urea and 1.0 M KOH at a scan rate of 20 mV s-1. The Tafel slope provided for UOR was 39 mV dec-1, whereas the GC/NiFe2O4@GO electrode reached a current of 10 mA cm-2 at potentials of +1.5 and -0.21 V (vs. RHE) for the OER and hydrogen evolution reaction (HER), respectively. Furthermore, charge transfer resistances were estimated for OER and HER as 133 and 347 Ω cm2, respectively.

19.
Cureus ; 16(2): e53572, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38445133

ABSTRACT

Background Herpes zoster (HZ) is a viral infection resulting from the reactivation of the varicella-zoster virus. The vaccination was proven to prevent herpes zoster and its complications for individuals over the age of 50 since they are more susceptible to herpes zoster infection. Therefore, it is essential to understand and acknowledge the herpes zoster infection and vaccine. This study aims to assess the level of knowledge and attitude towards herpes zoster and its vaccination among individuals at risk in Saudi Arabia. Methods A cross-sectional study was conducted between February 2023 and June 2023 among the general population in Saudi Arabia, using a self-administered online questionnaire adapted from a previous study after translating it into Arabic. Results A total of 1883 participants were included in this study, almost equally distributed across the five regions of Saudi Arabia. Females represented 62.4% (n=1175), and 56% (n=1062) of participants reported a positive history of chickenpox, while 3.6% (n=67) reported a history of herpes zoster. Furthermore, 78.9% (n=1486) have heard of herpes zoster, while 68.8% (n=1296) have at least one of the herpes zoster risk factors. Only 7.8% (n=147) had high knowledge about HZ, and only 3.1% (n=58) had adequate knowledge regarding the HZ vaccine. Conclusion Our study findings show that the general population of Saudi Arabia has inadequate knowledge about herpes zoster and its vaccine. For that reason, awareness and education programs targeting individuals at high risk of herpes zoster are required to enhance awareness and knowledge about herpes zoster and to improve their attitudes toward the herpes zoster vaccination.

20.
BMC Chem ; 18(1): 15, 2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38254234

ABSTRACT

Preserving the environment, reducing the amount of waste resulting from chemical trials, and reducing the amount of energy consumed have currently become a pivotal global trend. An analytical quality by design (AQbD) based eco-friendly TLC-densitometric method was implemented for quantifying two antihypertensive agents, captopril (CPL) and hydrochlorothiazide (HCZ), along with their impurities; captopril disulphide (CDS), chlorothiazide (CTZ) and salamide (SMD). The analytical target profile (ATP) was first identified, followed by selecting the critical analytical attributes (CAAs), such as retardation factors and resolution between the separated peaks. Critical method parameters (CMPs) that may have a crucial influence on CAAs were identified and emanated through the quality risk assessment phase. A literature survey-based preliminary studies were performed, followed by optimization of the selected CMPs through a custom experimental design to attain the highest resolution with optimum retardation factors. Moreover, method robustness was also tested by testing the design space. Complete separation of the drugs and their impurities was achieved using ethyl acetate: glacial acetic acid (6: 0.6, v/v) as a developing system applied to a 12 cm length TLC plate at room temperature with UV scanning at 215 nm. Calibration graphs were found to be linear in the ranges of (0.70-6.00), (0.10-2.00), (0.20-1.00), (0.07-1.50) and (0.05-1.00) µg/band corresponding to CPL, HCZ, CDS, CTZ, and SMD, respectively. Four different green metric tools were used to evaluate the greenness profile of the proposed method, and results showed that it is greener than the reported HPLC method. Method whiteness assessment was also conducted. Moreover, the method performance was evaluated following the ICH guidelines, and the outcomes fell within the acceptable limits. The developed method could be approved for routine assay of the cited components in their pharmaceutical formulations and bulk powder without interference from the reported impurities. The issue of concern is saving money, especially in developing countries.

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