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1.
RSC Adv ; 14(42): 30673-30686, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39324037

RESUMEN

The current work reports the synthesis of Cr(iii), Mn(ii), Co(ii), Ni(ii) and Cu(ii) chelates of the Schiff base ligand named hydroxy-phenyl-acetic acid (2-hydroxy-naphthalen-1-ylmethylene)-hydrazide with multi-chelation centre toward metal ions. The spectral tools, 1H-NMR, FTIR, mass, UV-vis spectra, and the analytical elemental and thermal analysis, in addition to magnetic moment and conductivity measurements all combined have been applied to conclude the structure and geometry of the synthesized metal complexes. The formed metal chelates have been assured to be formed with the molar compositions of 1 L : 1 M for PANH-Cr, PANH-Mn, PANH-Co, PANH-Ni and 2 L : 1 M for PANH-Cu. All the complexes have been confirmed to be non-electrolytic except the PANH-Mn and PANH-Ni which are 1 : 1 electrolytes. FTIR spectral analysis assured the ligand to act as mono basic bi or tridentate ligand leading to the formation of octahedral complexes with all metals except Cu(ii) complex which assured to has square planar structure. Except PANH-Cr, all the synthesized metal chelates exhibited phenoxazinone synthase like efficacy with varying activity with dramatically high activity for PANH-Mn complex with TOF number of 169.89 h-1.

2.
J Prim Care Community Health ; 15: 21501319241288029, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39344982

RESUMEN

BACKGROUND: There are many challenges that entail caring for an individual with dementia, affecting not only the individual with the condition but also their caregivers. This can lead to increased burden, frustration, and depression among those taking care of them. A research gap exists concerning the care of people with dementia in Egypt, particularly regarding the mental health of caregivers. Limited studies have been conducted in Egypt, particularly focusing on the mental health of caregivers. This lack highlights the need to understand the prevalence and impact of caregiver burden in this population. OBJECTIVES: The research aimed to evaluate the burden of dementia, levels of depression, and anxiety among family caregivers of individuals with dementia. METHODS: A cross-sectional study was conducted at a geriatric unit clinic of a psychiatric hospital in Cairo University, Egypt. Caregiver burden, anxiety, and depression were assessed using questionnaires. These questionnaires included the Zarit Burden Interview (ZBI), Generalized Anxiety Disorder scale (GAD-7), and Patient Health Questionnaire-9 (PHQ-9), together with demographic data on the patients and caregivers. RESULTS: The majority of the 141 participants (73% (n = 103)) were female, mostly daughters, with an average age of 40 years. Approximately 50% (n = 71) of the subjects exhibited mild to moderate burden, whereas 30% (n = 43) showed moderate to severe burden. About 31% (n = 44) of the subjects exhibited symptoms of moderate depression, whereas 9% (n = 13) had symptoms of severe depression. Furthermore, almost 43% (n = 60) of caregivers exhibited a moderate level of anxiety. Furthermore, a significant association was seen between caregiver burden and the presence of anxiety and depression. CONCLUSION: This study showed a substantial burden in providing care, elevated levels of despair, and anxiety among caregivers of PWD. The findings highlight how important it is to develop targeted therapies and support systems in order to lessen the load on caregivers, advance their mental health, and improve overall care for both caregivers and their patients in Egypt. Policy-makers should prioritize investing in dementia-related support systems and services to empower caregivers and improve the quality of life for both caregivers and their patients.


Asunto(s)
Ansiedad , Cuidadores , Demencia , Depresión , Humanos , Femenino , Masculino , Estudios Transversales , Egipto , Cuidadores/psicología , Depresión/epidemiología , Ansiedad/epidemiología , Adulto , Persona de Mediana Edad , Carga del Cuidador/psicología , Anciano , Encuestas y Cuestionarios , Costo de Enfermedad
3.
Heliyon ; 10(16): e35791, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39220931

RESUMEN

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.

4.
Heliyon ; 10(14): e34540, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39130476

RESUMEN

Peptic ulcer disease (PUD), often caused by Helicobacter pylori infection, is a prevalent gastrointestinal condition characterized by the erosion of the gastric or duodenal mucosal lining. H. pylori adheres to gastric epithelial cells, secreting toxins and disrupting the stomach's defenses. H. pylori relies on various receptors to establish infection, making these molecules attractive therapeutic targets. This study aimed to develop novel anti-ulcer compounds by combining benzothiazole, pyrazoline, and chalcone pharmacophores. A series of chalcone derivatives 4a-c were synthesized via Claisen-Schmidt condensation and characterized using spectroscopic techniques such as FT-IR, NMR and elemental analysis. The DFT calculations, using B3LYP method with 6-311G basis set, revealed the p-tolyl derivative 4b exhibited the highest thermal stability while the p-bromophenyl derivative 4c showed the lowest stability but highest chemical reactivity. The HOMO-LUMO energy gaps as well as the dipole moments decreased in the order: 4b > 4a > 4c, reflecting a similar reactivity trend. Molecular docking showed ligands 4a-c bound effectively to the H. pylori urease enzyme, with docking scores from -5.3862 to -5.7367 kcal/mol with superior affinity over lansoprazole. Key interactions involved hydrogen bonds and hydrophobic pi-hydrogen bonds with distances ranging 3.46-4.34 Å with active site residues ASN666, SER714 and ASN810. The combined anti-inflammatory, antimicrobial, and H. pylori anti-adhesion properties make these novel chalcones promising PUD therapeutic candidates.

5.
Front Pharmacol ; 15: 1394557, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39170697

RESUMEN

Introduction: Isoproterenol (ISO) is regarded as an adrenergic non-selective ß agonist. It regulates myocardial contractility and may cause damage to cardiac tissues. Alchemilla vulgaris (AV) is an herbal plant that has garnered considerable attention due to its anti-inflammatory and antioxidant bioactive components. The present investigation assessed the cardioprotective potential of AV towards ISO-induced myocardial damage. Methods: Four groups of mice were utilized: control that received saline, an ISO group (85 mg/kg, S.C.), ISO + AV100, and ISO + AV200 groups (mice received 100 or 200 mg/kg AV orally along with ISO). Results and discussion: ISO induced notable cardiac damage demonstrated by clear histopathological disruption and alterations in biochemical parameters. Intriguingly, AV treatment mitigates ISO provoked oxidative stress elucidated by a substantial enhancement in superoxide dismutase (SOD) and catalase (CAT) activities and reduced glutathione (GSH) content, as well as a considerable reduction in malondialdehyde (MDA) concentrations. In addition, notable downregulation of inflammatory biomarkers (IL-1ß, TNF-α, and RAGE) and the NF-κB/p65 pathway was observed in ISO-exposed animals following AV treatment. Furthermore, the pro-apoptotic marker Bax was downregulated together with autophagy markers Beclin1 and LC3 with in ISO-exposed animals when treated with AV. Pre-treatment with AV significantly alleviated ISO-induced cardiac damage in a dose related manner, possibly due to their antioxidant and anti-inflammatory properties. Interestingly, when AV was given at higher doses, a remarkable restoration of ISO-induced cardiac injury was revealed.

6.
Parasitol Res ; 123(8): 293, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39105851

RESUMEN

Side effects and low efficacy of current anti-toxoplasmosis therapeutics against encysted bradyzoites necessitate research into alternative safe therapeutic options. The safety, immunostimulatory, and antimicrobial properties of alginate nanoparticle formulation (Alg-NP) highlight its potential as an oral therapy against acute toxoplasmosis. In the current study, Alg-NP was formulated and characterized and then assessed for its anti-Toxoplasma effects using parasitological, ultrastructural, immunological, and histopathological studies. Treatment with Alg-NP significantly prolonged mice survival and reduced the parasite burden in both peritoneal fluid and tissue impression smears. In addition, it altered parasite viability and caused severe tachyzoite deformities as evidenced by ultrastructural studies. Alg-NP induced high levels of serum IFN-γ in infected mice with significant amelioration in histopathological changes in both hepatic and splenic tissue sections. In conclusion, Alg-NP could be considered a promising therapeutic agent against acute murine toxoplasmosis, and owing to its safety, it could potentially be enlisted for human use.


Asunto(s)
Alginatos , Modelos Animales de Enfermedad , Nanopartículas , Toxoplasma , Toxoplasmosis Animal , Animales , Alginatos/química , Ratones , Administración Oral , Toxoplasma/efectos de los fármacos , Toxoplasmosis Animal/tratamiento farmacológico , Antiprotozoarios/farmacología , Antiprotozoarios/administración & dosificación , Antiprotozoarios/uso terapéutico , Ácido Glucurónico , Femenino , Ácidos Hexurónicos , Hígado/parasitología , Hígado/patología , Hígado/efectos de los fármacos , Bazo/efectos de los fármacos , Bazo/parasitología , Líquido Ascítico/parasitología , Carga de Parásitos , Análisis de Supervivencia , Interferón gamma/sangre , Ratones Endogámicos BALB C , Resultado del Tratamiento
7.
Am J Physiol Endocrinol Metab ; 327(3): E313-E327, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39017682

RESUMEN

Thyroid dysfunction and diabetes mellitus are prevalent endocrine disorders that often coexist and influence each other. The role of spexin (SPX) in diabetes and obesity is well documented, but its connection to thyroid function is less understood. This study investigates the influence of exercise (EX) and SPX on thyroid hypofunction in obese type 2 diabetic rats. Rats were divided into normal control, obese diabetic sedentary, obese diabetic EX, and obese diabetic SPX groups, with subdivisions for M871 and HT-2157 treatment in the latter two groups. High-fat diet together with streptozotocin (STZ) injection induced obesity and diabetes. The EX group underwent swimming, and the SPX group received SPX injections for 8 wk. Results showed significant improvements in thyroid function and metabolic, oxidative, and inflammatory states with EX and SPX treatment. The study also explored the involvement of galanin receptor isoforms (GALR)2/3 in SPX effects on thyroid function. Blocking GALR2/3 receptors partially attenuated the beneficial effects, indicating their interaction. These findings underscore the importance of EX and SPX in modulating thyroid function in obesity and diabetes. Comprehending this interplay could enable the development of new treatment approaches for thyroid disorders associated with obese type 2 diabetes. Additional research is necessary to clarify the exact mechanisms connecting SPX, EX activity, and thyroid function.NEW & NOTEWORTHY This study proves, for the first time, the beneficial effects of SPX on thyroid dysfunction in obese diabetic rats and suggests that SPX mediates the EX effect on thyroid gland and exerts its effect mainly via GALR2.


Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Dieta Alta en Grasa , Obesidad , Hormonas Peptídicas , Condicionamiento Físico Animal , Glándula Tiroides , Animales , Ratas , Obesidad/metabolismo , Obesidad/terapia , Condicionamiento Físico Animal/fisiología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/terapia , Masculino , Hormonas Peptídicas/metabolismo , Glándula Tiroides/metabolismo , Glándula Tiroides/efectos de los fármacos , Ratas Wistar
8.
ACS Omega ; 9(29): 31601-31610, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39072071

RESUMEN

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.

9.
FASEB J ; 38(14): e23816, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39072779

RESUMEN

Acetaminophen (APAP) is one of the most clinically relevant medications associated with acute liver damage. A prolific deal of research validated the hepatoprotective effect of empagliflozin (EMPA); however, its effect on APAP-induced hepatotoxicity has still not been investigated. In this study, the prospective hepatoprotective impact of EMPA against APAP-induced hepatotoxicity was investigated. Twenty-eight Balb-C mice were assigned to four groups: control, APAP, EMPA10/APAP, and EMPA25/APAP. At the end of the experiment, serum hepatotoxicity biomarkers, MDA level, and GSH content were estimated. Hepatic mitofusin-2 (MFN2), optic atrophy 1 (OPA1), dynamin-related protein 1 (Drp1), and mitochondrial fission 1 protein (FIS1) were immunoassayed. PGC-1α, cGAS, and STING mRNA expression were assessed by real-time PCR. Histopathological changes and immunohistochemistry of INF-ß, p-NF-κB, and iNOS were evaluated. APAP treatment caused significant hepatic functional impairment and increased hepatic MDA levels, as well as a concomitant decrease in GSH content. Marked elevation in Drp1 and FIS1 levels, INF-ß, p-NF-κB, and iNOS immunoreactivity, and reduction in MFN2 and OPA1 levels in the APAP-injected group, PGC-1α downregulation, and high expression of cGAS and STING were also documented. EMPA effectively ameliorated APAP-generated structural and functional changes in the liver, restored redox homeostasis and mitochondrial dynamics balance, and enhanced mitochondrial biogenesis, remarkably diminished hepatic expression of cGAS and STING, and elicited a reduction in hepatic inflammation. Moreover, the computational modeling data support the interaction of APAP with antioxidant system-related proteins as well as the interactions of EMPA against Drp1, cGAS, IKKA, and iNOS proteins. Our findings demonstrated for the first time that EMPA has an ameliorative impact against APAP-induced hepatotoxicity in mice via modulation of mitochondrial dynamics, biogenesis, and cGAS/STING-dependent inflammation. Thus, this study concluded that EMPA could be a promising therapeutic modality for acute liver toxicity.


Asunto(s)
Acetaminofén , Compuestos de Bencidrilo , Enfermedad Hepática Inducida por Sustancias y Drogas , Dinaminas , GTP Fosfohidrolasas , Glucósidos , Proteínas de la Membrana , Dinámicas Mitocondriales , Nucleotidiltransferasas , Animales , Masculino , Ratones , Acetaminofén/toxicidad , Acetaminofén/efectos adversos , Compuestos de Bencidrilo/farmacología , Compuestos de Bencidrilo/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Dinaminas/metabolismo , Dinaminas/genética , Glucósidos/farmacología , GTP Fosfohidrolasas/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Ratones Endogámicos BALB C , Dinámicas Mitocondriales/efectos de los fármacos , Proteínas Mitocondriales/metabolismo , FN-kappa B/metabolismo , Nucleotidiltransferasas/metabolismo , Biogénesis de Organelos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Transducción de Señal/efectos de los fármacos
10.
Mol Biol Rep ; 51(1): 766, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38877370

RESUMEN

BACKGROUND: Myotonia Congenita (MC) is a rare disease classified into two major forms; Thomsen and Becker disease caused by mutations in the CLCN1 gene, which affects muscle excitability and encodes voltage-gated chloride channels (CLC-1). While, there are no data regarding the clinical and molecular characterization of myotonia in Egyptian patients. METHODS: Herein, we report seven Egyptian MC patients from six unrelated families. Following the clinical diagnosis, whole-exome sequencing (WES) was performed for genetic diagnosis. Various in silico prediction tools were utilized to interpret variant pathogenicity. The candidate variants were then validated using Sanger sequencing technique. RESULTS: In total, seven cases were recruited. The ages at the examination were ranged from eight months to nineteen years. Clinical manifestations included warm-up phenomenon, hand grip, and percussion myotonia. Electromyography was performed in all patients and revealed myotonic discharges. Molecular genetic analysis revealed five different variants. Of them, we identified two novel variants in the CLCN1 gene ( c.1583G > C; p.Gly528Ala and c.2203_2216del;p.Thr735ValfsTer57) and three known variants in the CLCN1 and SCN4A gene. According to in silico tools, the identified novel variants were predicted to have deleterious effects. CONCLUSIONS: As the first study to apply WES among Egyptian MC patients, our findings reported two novel heterozygous variants that expand the CLCN1 mutational spectrum for MC diagnosis. These results further confirm that genetic testing is essential for early diagnosis of MC, which affects follow-up treatment and prognostic assessment in clinical practice.


Asunto(s)
Canales de Cloruro , Secuenciación del Exoma , Mutación , Miotonía Congénita , Humanos , Miotonía Congénita/genética , Miotonía Congénita/diagnóstico , Secuenciación del Exoma/métodos , Canales de Cloruro/genética , Femenino , Masculino , Egipto , Niño , Adolescente , Mutación/genética , Preescolar , Adulto Joven , Lactante , Canal de Sodio Activado por Voltaje NAV1.4/genética , Adulto , Linaje , Electromiografía
11.
Arch Pharm (Weinheim) ; 357(9): e2400256, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38889397

RESUMEN

Green and white chemistry are vital to revolutionizing the chemical industry through their unparalleled potential to enhance sustainability and efficiency. In this study, nine sustainability tools of both green and white metrics, including green analytical procedure index (GAPI), ComplexGAPI, analytical greenness, analytical greenness metric for sample preparation, Analytical Eco-Scale (ESA), analytical method greenness score, high-performance liquid chromatography- environmental assessment tool (HPLC-EAT), analytical method volume intensity, and blue applicability grade index (BAGI), have been developed for appraising environmental friendliness for both innovative and straightforward mean centering of ratio spectra (MCR) and reversed-phase high-performance liquid chromatography (RP-HPLC) strategies utilized for concurrent analysis and separation of cyclopentolate (CYC) and C12 and C14 homologs of benzalkonium chloride (BNZ) in pure and ophthalmic solution. The mobile phase, formed of buffer phosphate and acetonitrile (35:65, v/v), was adjusted to pH 6.3, and 215-nm UV detection was used. The experimental flow rate was 2.0 mL min-1, and the analytical column was L11 Inertsil Ph-3 (150 mm × 4.6 mm, 5 µm). All sequences were run at 25°C in the column oven. The MCR approach effectively resolved the drug's spectral overlapping. CYC and BNZ employed this approach at 227.5 and 220.4 nm, respectively. As part of the HPLC analysis, an isocratic method was employed with phosphate buffer and acetonitrile in the mobile phase at 35:65. A correlation coefficient greater than 0.999 was observed between the calibration curves for the HPLC and MCR methods in the ranges of 20-320 µg mL-1 and 5-30 µg mL-1 for all drugs. The technique yields excellent primary recovery rates, ranging from 97.2% to 100.5%. The recommended approach has been validated according to International Council for Harmonization guidelines.


Asunto(s)
Antagonistas Colinérgicos , Cromatografía Líquida de Alta Presión , Antagonistas Colinérgicos/análisis , Antagonistas Colinérgicos/química , Cromatografía de Fase Inversa/métodos , Tecnología Química Verde , Soluciones Oftálmicas/química , Estructura Molecular
12.
Int J Biol Macromol ; 273(Pt 2): 132815, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38825279

RESUMEN

Modern environmental organic chemistry is focused on developing cost-efficient, versatile, environmentally acceptable catalytic chemicals that are also highly effective. Herein, hybrid calcium-chitosan nanocomposite films was prepared by doping calcium oxide molecules into a chitosan matrix at weight percentage (15, 20, and 25 % wt. chitosan­calcium) using an easy and affordable simple co-precipitation process. The CS-CaO nanocomposite's structure was elucidated using analytical techniques such as Fourier transform infrared (FTIR), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS). Based on the X ray diffraction (XRD) measurements, the crystallinity was reduced by the incorporation of the CaO molecules. Also, from the calculation of the Debye-Scherrer equation on this X-ray diffraction (XRD) pattern, the crystallite size was found to be 17.2 nm for the nanocomposite film with 20 % wt. The energy dispersive spectroscopy graph demonstrated the presence of the distinctive Ca element signals within the chitosan, with the amount in a sample of 20 % wt. being discovered to be 21.32 % wt. For the synthesis of bis-hydrazono[1,2,4]thiadiazoles, the obtained CS-CaO nanocomposite could be employed as a potent heterogeneous recyclable catalyst. Better reaction yields, quicker reactions, softer reaction conditions, and green reusable efficient biocatalysts for several uses are just a few advantages of this approach.


Asunto(s)
Compuestos de Calcio , Quitosano , Tecnología Química Verde , Nanocompuestos , Óxidos , Quitosano/química , Nanocompuestos/química , Compuestos de Calcio/química , Óxidos/química , Tiadiazoles/química , Difracción de Rayos X , Espectroscopía Infrarroja por Transformada de Fourier , Catálisis
13.
Diabetol Metab Syndr ; 16(1): 131, 2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38880916

RESUMEN

BACKGROUND: Type 2 diabetes is an endocrine disorder characterized by compromised insulin sensitivity that eventually leads to overt disease. Adipose stem cells (ASCs) showed promising potency in improving type 2 diabetes and its complications through their immunomodulatory and differentiation capabilities. However, the hyperglycaemia of the diabetic microenvironment may exert a detrimental effect on the functionality of ASCs. Herein, we investigate ASC homeostasis and regenerative potential in the diabetic milieu. METHODS: We conducted data collection and functional enrichment analysis to investigate the differential gene expression profile of MSCs in the diabetic microenvironment. Next, ASCs were cultured in a medium containing diabetic serum (DS) or normal non-diabetic serum (NS) for six days and one-month periods. Proteomic analysis was carried out, and ASCs were then evaluated for apoptosis, changes in the expression of surface markers and DNA repair genes, intracellular oxidative stress, and differentiation capacity. The crosstalk between the ASCs and the diabetic microenvironment was determined by the expression of pro and anti-inflammatory cytokines and cytokine receptors. RESULTS: The enrichment of MSCs differentially expressed genes in diabetes points to an alteration in oxidative stress regulating pathways in MSCs. Next, proteomic analysis of ASCs in DS revealed differentially expressed proteins that are related to enhanced cellular apoptosis, DNA damage and oxidative stress, altered immunomodulatory and differentiation potential. Our experiments confirmed these data and showed that ASCs cultured in DS suffered apoptosis, intracellular oxidative stress, and defective DNA repair. Under diabetic conditions, ASCs also showed compromised osteogenic, adipogenic, and angiogenic differentiation capacities. Both pro- and anti-inflammatory cytokine expression were significantly altered by culture of ASCs in DS denoting defective immunomodulatory potential. Interestingly, ASCs showed induction of antioxidative stress genes and proteins such as SIRT1, TERF1, Clusterin and PKM2. CONCLUSION: We propose that this deterioration in the regenerative function of ASCs is partially mediated by the induced oxidative stress and the diabetic inflammatory milieu. The induction of antioxidative stress factors in ASCs may indicate an adaptation mechanism to the increased oxidative stress in the diabetic microenvironment.

15.
J Mol Histol ; 55(4): 481-490, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38777994

RESUMEN

A growing body of evidence suggests that elevated sucrose intake may contribute to the development of neurological disorders. Recognizing that regular exercise has the potential to reduce the occurrence of neuromuscular disorders, the present research investigated the impact of exercise on the redox status of the hypothalamus in mitigating the adverse effects associated with high sucrose intake. Forty Wistar albino rats were subjected to a high sucrose diet, with some groups engaging in exercise for a duration of 3 months. The exercise regimen was found to sustain the redox balance in the hypothalamus. In summary, the consumption of a high sucrose diet resulted in the disturbance of the histological morphology of the hypothalamus, accompanied by an increased percentage of caspase-3 positive cells. Additionally, the high sucrose diet disrupted the oxidant/antioxidant ratio in favor of oxidants, leading to elevated levels of AOPPs and AGEP. Conversely, exercise was effective in restoring most of these values to levels approximating the control group, indicating a potential protective effect of regular exercise against the detrimental impacts of high sucrose dietary consumption on the hypothalamus. Graphical abstract.


Asunto(s)
Hipotálamo , Condicionamiento Físico Animal , Ratas Wistar , Animales , Hipotálamo/metabolismo , Condicionamiento Físico Animal/fisiología , Ratas , Masculino , Estrés Oxidativo , Caspasa 3/metabolismo , Oxidación-Reducción , Sacarosa en la Dieta/efectos adversos , Sacarosa en la Dieta/administración & dosificación , Antioxidantes/metabolismo , Sacarosa/efectos adversos , Sacarosa/administración & dosificación
16.
Inflammopharmacology ; 32(4): 2541-2553, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38763983

RESUMEN

Ulcerative colitis (UC) is a chronic colonic inflammation with a significant health hazard. Aspergillus awamori (A. awamori) is a microorganism with various bioactive compounds with natural antioxidant and anti-inflammatory properties. The present work aimed to elucidate the protective and therapeutic effects of varying concentrations of A. awamori against acetic acid (AA)-induced ulcerative colitis (UC) in rats. Nine groups of albino male rats were established: a control negative group (G1), a control positive group (G2,AA), and preventive protocol groups (including G3A, G4A, and G5A) that received 100 mg, 50 mg, and 25 mg/kg b.w, respectively, of A. awamori orally and daily from the 1st day of the experiment and for 7 consecutive days. Then, they were subjected to one dose of AA intrarectally on day 8th. G3B, G4B, and G5B were termed as curative protocol groups that received one dose of AA on day 8th and then administered 100 mg, 50 mg, and 25 mg/kg b.w. of A. awamori, respectively, on day 9th and continued receiving these doses daily until day 16th. Rats in the AA group exhibited marked histopathological alterations of the distal colon, with an exaggeration of the DAI. In addition, a remarkable increase in oxidative stress was represented by the elevation of MDA and NO levels with a decline in SOD and GPx activities. In addition, upregulation of TNF-α, IL-6, and IL-1ß mRNA expressions and downregulation of Muc2 and Nrf2 levels were detected. Unambiguously, a remarkable anti-inflammatory effect was noticed either in A. awamori prevented or treated groups expounded by reducing and regulating TNF-α, IL-6, and IL-1ß with improved pathological lesion scoring. The Muc2, Nrf2, and bcl-2 gene levels were upregulated and restored also. In summary, the findings in this work reveal that A. awamori supplementation successfully alleviated the UC induced by AA, which had a better effect when administered before colitis induction.


Asunto(s)
Ácido Acético , Antiinflamatorios , Antioxidantes , Apoptosis , Aspergillus , Colitis Ulcerosa , Animales , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Masculino , Ratas , Antioxidantes/farmacología , Antiinflamatorios/farmacología , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Colon/efectos de los fármacos , Colon/patología , Colon/metabolismo
17.
Arch Pharm (Weinheim) ; 357(8): e2400025, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38644337

RESUMEN

A novel environmentally friendly reversed-phase high-performance liquid chromatography (RP-HPLC) method has been effectively validated for simultaneously measuring a prospective conjunction of tizanidine (TIZ) and etoricoxib (ETC), the combined medicine, in rat plasma. The technique employs diclofenac potassium as the internal standard, guaranteeing dependable and precise outcomes. This study aimed to assess the impact of the suggested combination therapy on treating inflammation resulting from rheumatoid arthritis (RA) in a rat model. The procedure was performed using an Agilent series 1200 model HPLC apparatus. The chromatographic conditions consist of isocratic elution mode, C18 column with dimensions of 150 mm × 4.6 mm × 5 µm, flow rate of 1.5 mL/min, wavelength of 230 nm, temperature of 50°C, and injection volume of 10 µL. The elution was performed using a mobile phase consisting of a phosphate buffer with a pH of 3.5 and acetonitrile in a ratio of 80:20 v/v. Calibration curves were conducted for TIZ and ETC within the 1-50 µg/mL range, demonstrating linear trends with R2 values over 0.999. The effectiveness and eco-friendliness of the proposed method were evaluated using eight separate environmentally conscious metrics. The addition of TIZ and ETC to arthritic rodents amplified these effects significantly. Furthermore, TIZ and ETC significantly reduced serum levels in arthritic rodents, and safety investigations revealed normal complete blood count, liver, and renal functions. TIZ and ETC appear to have antiarthritic, anti-inflammatory, and safe combinations, making them viable future treatment options for RA that are also safe and efficacious. Following validation by United States Food and Drug Administration (US-FDA) rules, all goods met the criteria.


Asunto(s)
Artritis Reumatoide , Cromatografía de Fase Inversa , Clonidina , Etoricoxib , Animales , Cromatografía Líquida de Alta Presión , Ratas , Masculino , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/sangre , Clonidina/análogos & derivados , Clonidina/sangre , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/sangre , Artritis Experimental/inducido químicamente , Reproducibilidad de los Resultados
18.
Int J Pharm X ; 7: 100245, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38633410

RESUMEN

Infected wounds pose a significant challenge in healthcare, requiring innovative therapeutic strategies. Therefore, there is a critical need for innovative pharmaceutical materials to improve wound healing and combat bacterial growth. This study examined the efficacy of azithromycin-loaded silver nanoparticles (AZM-AgNPs) in treating infected wounds. AgNPs synthesized using a green method with Quinoa seed extract were loaded with AZM. Characterization techniques, including X-ray Powder Diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), and Uv-Vis analysis were utilized. The agar diffusion assay and determination of the MIC were used to assess the initial antibacterial impact of the formulations on both MRSA and E. coli. In addition, the antimicrobial, wound-healing effects and histological changes following treatment with the AZM-AgNPs were assessed using an infected rat model. The nanoparticles had size of 24.9 ± 15.2 nm for AgNPs and 34.7 ± 9.7 nm for AZM-AgNPs. The Langmuir model accurately characterized the adsorption of AZM onto the AgNP surface, indicating a maximum loading capacity of 162.73 mg/g. AZM-AgNPs exhibited superior antibacterial properties in vivo and in vitro compared to controls. Using the agar diffusion technique, AZM-AgNPs showed enhanced zones of inhibition against E. coli and MRSA, which was coupled with decreased MIC levels. In addition, in vivo studies showed that AZM-AgNP treated rats had the best outcome characterized by improved healing process, lower bacterial counts and superior epithelialization, compared to the control group. In conclusion, AZM-AgNPs can be synthesized using a green method with Quinoa seed with successful loading of azithromycin onto silver nanoparticles. In vitro and in vivo studies suggest the promising use of AZM-AgNPs as an effective therapeutic agent for infected wounds.

19.
J Genet Eng Biotechnol ; 22(1): 100341, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38494255

RESUMEN

BACKGROUND: Spondyloepimetaphyseal dysplasias (SEMD) are a large group of skeletal disorders represented by abnormalities of vertebrae in addition to epiphyseal and metaphyseal areas of bones. Several genes have been identified underlying different forms. ACAN gene mutations were found to cause Aggrecan-related bone disorders (spondyloepimetaphyseal dysplasias,spondyloepiphyseal dysplasias, familial osteochondritis dissecans and short stature syndromes). This study aims to find the disease causing variant in Egyptian patient with SEMD using whole exome sequencing. METHODS: Whole-exome sequencing was performed for an Egyptian male patient who presented with short stature, clinical and radiological features suggestive of unclassified SEMD. RESULTS: The study identified a novel de novo heterozygous ACAN gene variant (c.7378G>A; p.Gly2460Arg) in G3 domain. Mutations in ACAN gene have been more commonly associated with short stature than SEMD. The phenotype of our patient was intermediate in severity between spondyloepiphyseal dysplasia presentation; Kimberley type(SEDK) and Spondyloepimetaphyseal dysplasias Aggrecan (SEMDAG) CONCLUSIONS: Whole exome sequencing revealed a novel de novo ACAN gene variant in patient with SEDK. The clinical and skeletal phenotype of our patient was much severe than those reported originally and showed more metaphyseal involvement. To the best of our knowledge, two previous studies reported a heterozygous variant in ACAN with spondyloepiphyseal dysplasia presentation; Kimberley type.

20.
Molecules ; 29(6)2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38542852

RESUMEN

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.

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