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1.
Curr Issues Mol Biol ; 46(10): 10991-11020, 2024 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-39451533

RESUMEN

Ceratonia siliqua L. is a medicinal plant that has long been used in traditional Moroccan medicine to treat many diseases. This study aimed to assess the impact of the stages of the immature phase of carob pulp (M1, M2, M3, M4, and M5) on phytochemical composition, antioxidant activity, and antidiabetic activity of Ceratonia siliqua L. The identification of the phenolic profile by HPLC-UV/MS-MS and the study of the antidiabetic effect by in silico, in vitro, and in vivo studies were carried out for extracts with high contents of phenolic compounds from immature wild carob pulp from the communes of Timoulit (TM), Bin Elouidane (AW), and Ouaouizerth (TG) in the province of Azilal in the Béni Mellal-Khénifra region. The results revealed a gradual increase in total sugar content over the pulp's ripening period, reaching a value of 2134 ± 56.23 mg GE/100 g fresh weight (FW) for TG. The three locations showed peak values for total polyphenol content (TPC), total flavonoid content (TFC), and total condensed tannin (TCT) at the M2 stage. AW had the highest concentrations of TPC (3819 ± 226.4 mg GAE/100 g FM), TFC (1034 ± 57.08 mg QE/100 g FM), and TCT (1472 ± 28.46 mg CE/100 g FM). The DPPH assay (7892 ± 296.1 mg TE/100 g FM) and the FRAP assay (278.2 ± 7.85 mg TE/100 g FM) both demonstrated that the TG zone is a highly potent antioxidant zone. In contrast, the AW site exhibited a markedly elevated value of 725.4 ± 103.6 mg TE/100 g FM in the ABTS assay. HPLC-UV-MS/MS analysis showed that the methanolic extracts of immature carob pulp (MEICP) from the three areas contained several different chemical compounds. The most prevalent were 3-O-p-coumaroyl-5-O-caffeoylquinic acid, quercetin 3-methyl ether, gallic acid, and galloylquinic acid. Immature carob pulp extract (ICPE) from AW showed the strongest in vitro inhibition of pancreatic α-amylase (IC50 = 0.405 µg/mL) and TG extracts were most potent against intestinal α-glucosidase (IC50 = 0.063 µg/mL). In vivo, AW, TG, and TM extracts significantly reduced postprandial glycemia in rats, with AW having the greatest effect. These results highlight the antidiabetic potential of ICPE. The 3-O-p-Coumaroyl-5-O-caffeoylquinic acid showed better affinity for α-amylase compared to acarbose and interacted significantly with several amino acid residues of the enzyme. Similarly, this molecule and 3,4-Dicaffeoylquinic acid demonstrated a strong affinity for α-glucosidase, suggesting their potential as natural inhibitors of enzymes involved in carbohydrate metabolism. Most of the compounds are not substrates of P-glycoprotein and exhibited high intestinal absorption. Furthermore, the majority of these compounds did not act as inhibitors or substrates of CYP450 enzymes, reinforcing their suitability for development as oral medications. These results underscore the potential of immature carob pulp as a promising antidiabetic agent.

2.
Afr J Disabil ; 13: 1376, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39114452

RESUMEN

Background: Multiple sclerosis (MS), fatigue is among the leading clinical symptoms. It is one of the most disabling symptoms for most MS people. Objectives: This research measures the prevalence of fatigue and its impact on the physical, cognitive, and psychosocial abilities of individuals with MS in Morocco. Method: This cross-sectional and descriptive study included 152 participants. Data were collected via an online survey using the snowball method, incorporating sociodemographic characteristics and the Arabic version of the Modified Fatigue Impact Scale. Results: According to the results, 89.4% of respondents experienced pathological fatigue, with an average score of 65.52 (± 18.00). There was a significant relationship between pathological fatigue, age (p = 0.0324), and clinical phenotype (p = 0.041). Fatigue negatively impacted participants' physical, cognitive, and psychological capacities, with average scores of 70.38 (± 8.15), 62.28 (± 10.23), and 73.87 (± 1.86), respectively. Conclusion: The results of our study confirmed a high prevalence of fatigue among people with MS in Morocco. Sustained research in this field remains crucial, as it enables the formulation of strategies aimed at enhancing the quality of life for those impacted by MS. Contribution: This study is the first in Morocco to examine fatigue prevalence in people with MS and its impact on their physical, cognitive, and psychosocial abilities. High fatigue levels hinder the integration of people with MS into professional and student life. The findings emphasize the need for effective symptom and fatigue management.

3.
Arch Physiol Biochem ; : 1-17, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38982878

RESUMEN

This work investigated the biochemical disturbances and histological alteration in Psammomys obesus animal model fed different high calorie diets (HCDs) during three months. Four diets were used: a low-calorie natural diet, Chenopodiaceae halophyte plant used as control (LCD), a high standard carbohydrate diet rich in protein, HCD 0, a high carbohydrate diet rich in two concentrations of fat, HCD 1 and HCD 2. All animals having received HCDs developed dyslipidemia after one month of experiment with distinction of different sub-groups developing or not obesity and diabetes. HCDs induced a remarkable increasing in blood cholesterol, LDL-cholesterol and triglyceride levels indicating a fast induction of dyslipidemia and a significant increase of aminotransaminases activities revealing a pronounced hepatotoxicity. Animal developing diabetes showed a severe hepatic injury, a degeneration of the adipose tissue and a significant reduction of retinal thickness. P. obesus seems to be an excellent animal model to investigate nutritional metabolic diseases.

4.
Molecules ; 29(13)2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38999038

RESUMEN

This study focuses on synthesizing a new series of isoxazolinyl-1,2,3-triazolyl-[1,4]-benzoxazin-3-one derivatives 5a-5o. The synthesis method involves a double 1,3-dipolar cycloaddition reaction following a "click chemistry" approach, starting from the respective [1,4]-benzoxazin-3-ones. Additionally, the study aims to evaluate the antidiabetic potential of these newly synthesized compounds through in silico methods. This synthesis approach allows for the combination of three heterocyclic components: [1,4]-benzoxazin-3-one, 1,2,3-triazole, and isoxazoline, known for their diverse biological activities. The synthesis procedure involved a two-step process. Firstly, a 1,3-dipolar cycloaddition reaction was performed involving the propargylic moiety linked to the [1,4]-benzoxazin-3-one and the allylic azide. Secondly, a second cycloaddition reaction was conducted using the product from the first step, containing the allylic part and an oxime. The synthesized compounds were thoroughly characterized using spectroscopic methods, including 1H NMR, 13C NMR, DEPT-135, and IR. This molecular docking method revealed a promising antidiabetic potential of the synthesized compounds, particularly against two key diabetes-related enzymes: pancreatic α-amylase, with the two synthetic molecules 5a and 5o showing the highest affinity values of 9.2 and 9.1 kcal/mol, respectively, and intestinal α-glucosidase, with the two synthetic molecules 5n and 5e showing the highest affinity values of -9.9 and -9.6 kcal/mol, respectively. Indeed, the synthesized compounds have shown significant potential as antidiabetic agents, as indicated by molecular docking studies against the enzymes α-amylase and α-glucosidase. Additionally, ADME analyses have revealed that all the synthetic compounds examined in our study demonstrate high intestinal absorption, meet Lipinski's criteria, and fall within the required range for oral bioavailability, indicating their potential suitability for oral drug development.


Asunto(s)
Benzoxazinas , Inhibidores de Glicósido Hidrolasas , Simulación del Acoplamiento Molecular , alfa-Glucosidasas , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/síntesis química , Benzoxazinas/química , Benzoxazinas/farmacología , Benzoxazinas/síntesis química , alfa-Glucosidasas/metabolismo , alfa-Glucosidasas/química , alfa-Amilasas Pancreáticas/antagonistas & inhibidores , alfa-Amilasas Pancreáticas/metabolismo , Reacción de Cicloadición , Estructura Molecular , Simulación por Computador , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Hipoglucemiantes/síntesis química , Humanos , Relación Estructura-Actividad , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/farmacología , Compuestos Heterocíclicos/síntesis química , alfa-Amilasas/antagonistas & inhibidores , alfa-Amilasas/metabolismo , alfa-Amilasas/química , Intestinos/enzimología
5.
Int J MS Care ; 26: 140-143, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38872996

RESUMEN

BACKGROUND: Multiple sclerosis (MS) is an acquired chronic, autoimmune, and neurodegenerative disease of the central nervous system. In addition to conventional MS therapy, patients are interested in traditional and complementary medicine (T&CM). Our study aims to describe the use of T&CM in a cohort of Moroccan patients with MS. METHODS: A quantitative descriptive study was adopted to study this subject. For data collection, we opted for an anonymous questionnaire for 98 patients with MS. We gathered data via an electronic survey, using multivariable analysis to examine the effect of specific factors on T&CM use. Data collection took place from March 2022 to June 2022. RESULTS: The results show that 52% of patients use T&CM. Of those, 29.6% use cupping, 23.5% recite the Holy Quran, 15.3% use phytotherapy, 13.2% use apitherapy, and 10.2% use acupuncture. In addition, 66.3% of the surveyed respondents stated that alternative medicine positively affects their health. Finally, 49.1% of surveyed patients who use alternative medicine are between 30 and 40 years old. The results also show that the rate of T&CM use is higher in patients with progressive MS (OR = 2.540) and patients without financial access to disease-modifying therapy (OR = 2.100). CONCLUSIONS: This study invites us to consider societal, cultural, and economic factors when studying the use of T&CM among people with MS. Further research is needed to understand the motivations for using T&CM.

6.
Behav Brain Res ; 468: 115025, 2024 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-38710451

RESUMEN

Prenatal stress (PS), in both humans and animals, presents a potential risk to the mother and her fetus throughout gestation. PS is always associated with physiological changes that alter embryonic development and predispose the individual to lifelong health problems, including susceptibility to mental illness. This study aims to identify the harmful effects of prenatal restraint stress (PRS), commonly employed to induce stress painlessly and without any lasting debilitation during gestation. This stress is applied to pregnant Swiss albino mice from E7.5 to delivery for three hours daily. Our results show that PS affects dams' weight gain during the gestational period; moreover, the PS dams prefer passive nursing, exhibit a lower percentage of licking and grooming, and impair other maternal behaviors, including nesting and pup retrieval. Concerning the offspring, this stress induces neurobehavioral impairments, including a significant increase in the time of recovery of the young stressed pups in the surface righting reflex, the latency to avoid the cliff in the cliff avoidance test, longer latencies to accomplish the task in negative geotaxis, and a lower score in swimming development. These alterations were accompanied by increased Malondialdehyde activity (MDA) at PND17 and 21 and downregulation of AchE activity in the whole brain of pups on postnatal days 7 and 9. These findings demonstrated that PS causes deleterious neurodevelopmental impairments that can alter various behaviors later in life.


Asunto(s)
Conducta Materna , Estrés Oxidativo , Efectos Tardíos de la Exposición Prenatal , Restricción Física , Estrés Psicológico , Animales , Embarazo , Femenino , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Ratones , Estrés Psicológico/metabolismo , Estrés Psicológico/fisiopatología , Estrés Oxidativo/fisiología , Conducta Materna/fisiología , Malondialdehído/metabolismo , Animales Recién Nacidos , Encéfalo/metabolismo , Masculino , Acetilcolinesterasa/metabolismo , Conducta Animal/fisiología , Reflejo de Enderezamiento/fisiología , Reacción de Prevención/fisiología
7.
Iran J Pharm Res ; 23(1): e143703, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38655071

RESUMEN

Background: The utilization of amorphous silica nanoparticles (SiNPs) is gaining popularity in various applications, but it poses a potential risk to human and environmental health. However, the underlying causes and mechanisms of SiNPs-induced kidney damage are still largely unknown. Objectives: This study aimed to investigate the SiNPs-induced damage in the kidney and further explore the possible mechanisms of SiNPs-induced nephrotoxicity. Methods: Thirty adult male rats were divided into 3 different groups. Rats in groups 2 and 3 were administered SiNPs at 2 dosage levels (25 and 100 mg/kg of body weight), while the rats in the control group received no treatment for 28 days. Reactive oxygen species (ROS), antioxidant enzyme activities (glutathione peroxidase [GPx], superoxide dismutase [SOD], and catalase [CAT]), glutathione (GSH) levels, and oxidation markers (such as lipid peroxidation [malondialdehyde (MDA)] and protein oxidation [protein carbonyl (PCO)]) were analyzed in the kidney tissue. Additionally, renal fibrogenesis was studied through histopathological examination and the expression levels of fibrotic biomarkers. Results: The findings revealed that in vivo treatment with SiNPs significantly triggered oxidative stress in kidney tissues in a dose-dependent manner. This was characterized by increased production of ROS, elevated levels of MDA, PCO, and nitric oxide (NO), along with a significant decline in the activities of SOD, CAT, GPx, and reduced GSH. These changes were consistent with the histopathological analysis, which indicated interstitial fibrosis with mononuclear inflammatory cell aggregation, tubular degeneration, glomerulonephritis, and glomerular atrophy. The fibrosis index was confirmed using Masson's trichrome staining. Additionally, there was a significant upregulation of fibrosis-related genes, including transforming growth factor-beta 1 (TGF-ß1), matrix metalloproteinases 2 and 9 (MMP-2/9), whereas the expression of tissue inhibitor of metalloproteinase 2 (TIMP2) was downregulated. Conclusions: This study provided a new research clue for the role of ROS and deregulated TGF-ß signaling pathway in SiNPs nephrotoxicity.

8.
Physiol Behav ; 280: 114548, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38615729

RESUMEN

Corn and soybean oils are among the most frequently used vehicles for water-insoluble compounds in toxicological studies. These two vegetable oils are nutrients and may induce some biological effects on animals that might interfere with the experimental results. However, their chronic effects on a developing brain have not been reported. This study aims to evaluate the neurobehavioral and brain biochemical effects of both oils on male and female Swiss albino mice. Pregnant female mice were exposed to 1 µl/g/d of either tap water, corn oil (CO), or soybean oil (SO) from early gestation (GD1) until weaning then offspring mice were exposed to the same treatment regimen until adulthood (PND70). Our results showed that developmental exposure to both oils induced body weight changes in offspring mice. In addition, we detected some behavioral abnormalities where both oil-treated groups showed a significant decrease in locomotor activity and greater levels of anxiety behavior. Moreover, our results suggest that continuous exposure to these oils may alter motor coordination, spatial memory and induce depression-like behavior in adult mice. These alterations were accompanied by increased malondialdehyde, superoxide dismutase, and glutathione peroxidase activities in specific brain regions. Together, these data suggest that exposure to CO and SO as vehicles in developmental studies may interfere with the behavioral response and brain redox homeostasis in offspring mice.


Asunto(s)
Encéfalo , Aceite de Maíz , Estrés Oxidativo , Efectos Tardíos de la Exposición Prenatal , Aceite de Soja , Animales , Femenino , Aceite de Maíz/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Ratones , Embarazo , Masculino , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/crecimiento & desarrollo , Glutatión Peroxidasa/metabolismo , Peso Corporal/efectos de los fármacos , Malondialdehído/metabolismo , Superóxido Dismutasa/metabolismo , Actividad Motora/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Ansiedad/inducido químicamente , Aprendizaje por Laberinto/efectos de los fármacos , Vehículos Farmacéuticos
9.
Naunyn Schmiedebergs Arch Pharmacol ; 397(9): 6591-6609, 2024 09.
Artículo en Inglés | MEDLINE | ID: mdl-38466353

RESUMEN

Glyphosate-based Herbicide (GBH) is a widely used pesticide that functions as a broad-spectrum, non-selective herbicide. Despite advanced research to describe the neurotoxic potential of GBH, the harmful effects on maternal behavior and neurodevelopment of offspring remain unclear. This study was conducted to highlight the effects of GBH on the antioxidant system, anxiety traits, social interaction, and cognitive and sensorimotor functions in pups exposed to 25 or 50 mg/l daily via their mother's milk. Concerning the biochemical biomarkers, GBH administered during the early stages of development negatively affected the status of antioxidant enzymes and lipid peroxidation in the brain structures of the pups. Furthermore, our results showed a significant decrease in acetylcholinesterase (AChE) specific activity within the brains of treated pups. The results of the behavioral tests indicated that the treated offspring developed anxiety, memory, and sociability disorders, as evidenced by the Open Field, Y-maze, object recognition task, and social interaction tests. Through neurodevelopmental testing, we also showed sensorimotor impairment (righting reflex and negative geotaxis) and abnormal maternal behavior. Altogether, our study clearly demonstrates that the developing brain is sensitive to GBH.


Asunto(s)
Antioxidantes , Conducta Animal , Encéfalo , Glicina , Glifosato , Herbicidas , Efectos Tardíos de la Exposición Prenatal , Animales , Glicina/análogos & derivados , Glicina/toxicidad , Herbicidas/toxicidad , Femenino , Conducta Animal/efectos de los fármacos , Embarazo , Antioxidantes/metabolismo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Masculino , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/crecimiento & desarrollo , Ratas Wistar , Leche , Acetilcolinesterasa/metabolismo , Conducta Materna/efectos de los fármacos , Ansiedad/inducido químicamente , Aprendizaje por Laberinto/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Exposición Materna/efectos adversos
11.
Naunyn Schmiedebergs Arch Pharmacol ; 397(4): 2215-2231, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-37804342

RESUMEN

Malathion is an organophosphate pesticide (OP) commonly used in agriculture, industry, and veterinary medicine. Sex is a crucial factor in responding to neurotoxicants, yet the sex-specific effects of OP exposure, particularly neurological impairments following chronic low-level exposure remains limited. Our study aims to evaluate the neurobehavioral and biochemical effects of developmental exposure to Malathion across sexes. Pregnant mice were exposed to a low oral dose of Malathion from gestation up to the weaning of the pups, which were individually gavaged with a similar dose regimen until postnatal day 70. Our results show that Malathion decreased body weight and food intake, reduced locomotor activity and recognition memory. Motor coordination and special memory were only altered in females, whereas we found a male-specific effect of Malathion on social behavior and marble burying. These alterations were accompanied by increased malondialdehyde (MDA), decreased brain acetylcholinesterase activity (AChE), and disrupted brain redox homeostasis. Our findings about the effects of Malathion exposure across sexes may, in part, contribute to understanding the dimorphic susceptibilities observed in neurological disorders.


Asunto(s)
Insecticidas , Malatión , Femenino , Embarazo , Ratones , Masculino , Animales , Malatión/farmacología , Acetilcolinesterasa/metabolismo , Insecticidas/farmacología , Encéfalo , Conducta Social
12.
Mult Scler Relat Disord ; 81: 105347, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38061315

RESUMEN

OBJECTIVE: This study aims to describe the clinical, therapeutic, and epidemiological profiles of MS patients in Morocco. METHODS: This descriptive study involved 170 patients representing four Morocco regions. We collected the data using an electronic survey. RESULTS: The results show female dominance in patients with MS. Besides, most patients present with relapsing-remitting MS (RRMS). The main clinical symptoms reported by patients are fatigue, cognitive issues, spasticity, bowel or bladder complaints, and visual issues. Furthermore, the findings show that almost half of the patients use Interferon bêta-1a and azathioprine as disease-modifying therapies; 60.5 % use traditional and complementary medicine, of which 30.6 % use cupping, 30 % recite the Holy Quran, and 28.2 % use apitherapy. The findings show that there is a statistically significant relationship between specific MS factors such as professional activity (p = 0.0071), degree of satisfaction with treatment (p = 0.005), stress (p = 0.014), and the frequency of relapses. CONCLUSIONS: In addition to DMT, patients also use traditional and complementary medicine. There is also a relationship between some epidemiological characteristics and the frequency of relapses in patients with MS.


Asunto(s)
Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Humanos , Femenino , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/epidemiología , Marruecos/epidemiología , Interferón beta-1a/uso terapéutico , Recurrencia
13.
Chem Biol Interact ; 385: 110745, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37806379

RESUMEN

Myocardial infarction (MI) is a life-threatening ischemic disease and is one of the leading causes of morbidity and mortality worldwide. Punicalagin (PU), the major ellagitannin found in pomegranates, is characterized by multiple antioxidant activities. The aim of this study is to assess the protective effects of PU against isoproterenol (ISO)-induced acute myocardial damage and to investigate its underlying vascular mechanisms using rat model. METHODS: Rats were randomly divided into five groups and were treated orally (p.o.) with PU (25 and 50 mg/kg) for 14 days. ISO was administered subcutaneously (S.C.) (85 mg/kg) on the 15th and 16th days to induce Myocardial infarction. Cardiac markers, oxidative stress markers, and inflammatory cytokines levels were determined in the heart tissue. Immunohistochemistry analysis was performed to determine the protein expression pathways of inflammation, apoptosis and oxidative stress (Nuclear factor erythroid 2-related factor 2 (Nrf-2), and heme oxygenase-1 (HO-1) in all the groups. In silico study was carried out to evaluate the molecular interaction of PU with some molecular targets. RESULTS: Our results showed that ISO-induced cardiac tissue injury was evidenced by increased serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), and lactate dehydrogenase (LDH), associated with several histopathological changes. ISO also induced an increase of MDA, PCO, NO, and 8-hydroxy-2-deoxyguanosine (8-OHdG), along with a decrease of antioxidant enzyme activities in the myocardial tissues. In addition, an increase of TNF-α, NF-κB, IL-6, IL-1ß, iNOS, Nrf2 and (HO-1) was observed. Pre-treatment with PU reduced myocardial infract area, ameliorated histopathological alterations in myocardium, and decreased activities of myocardial injury marker enzymes in ISO-induced rats. In addition, PU remarkably restored ISO-induced elevation of lipid peroxidation and decrease of antioxidants, significantly reduced myocardial pro-inflammatory cytokines concentrations in this animal model. Molecular docking analysis of PU with protein targets showed potent interactions with negative binding energies. In conclusion, PU can protect the myocardium from oxidative injury, inflammatory response, and cell death induced by ISO by upregulating Nrf2/HO-1 signaling and antioxidants.


Asunto(s)
Taninos Hidrolizables , Infarto del Miocardio , Ratas , Animales , Isoproterenol/toxicidad , Taninos Hidrolizables/farmacología , Simulación del Acoplamiento Molecular , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Factor 2 Relacionado con NF-E2/metabolismo , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/tratamiento farmacológico , Miocardio/metabolismo , Estrés Oxidativo , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Citocinas/metabolismo , Apoptosis
14.
Medicina (Kaunas) ; 59(10)2023 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-37893530

RESUMEN

Background and Objectives: Alzheimer's disease (AD) stands as a pervasive neurodegenerative ailment of global concern, necessitating a relentless pursuit of remedies. This study aims to furnish a comprehensive exposition, delving into the intricate mechanistic actions of medicinal herbs and phytochemicals. Furthermore, we assess the potential of these compounds in inhibiting human acetylcholinesterase through molecular docking, presenting encouraging avenues for AD therapeutics. Materials and Methods: Our approach entailed a systematic exploration of phytochemicals like curcumin, gedunin, quercetin, resveratrol, nobiletin, fisetin, and berberine, targeting their capability as human acetylcholinesterase (AChE) inhibitors, leveraging the PubChem database. Diverse bioinformatics techniques were harnessed to scrutinize molecular docking, ADMET (absorption, distribution, metabolism, excretion, and toxicity), and adherence to Lipinski's rule of five. Results: Results notably underscored the substantial binding affinities of all ligands with specific amino acid residues within AChE. Remarkably, gedunin exhibited a superior binding affinity (-8.7 kcal/mol) compared to the reference standard. Conclusions: These outcomes accentuate the potential of these seven compounds as viable candidates for oral medication in AD treatment. Notably, both resveratrol and berberine demonstrated the capacity to traverse the blood-brain barrier (BBB), signaling their aptitude for central nervous system targeting. Consequently, these seven molecules are considered orally druggable, potentially surpassing the efficacy of the conventional drug, donepezil, in managing neurodegenerative disorders.


Asunto(s)
Enfermedad de Alzheimer , Berberina , Plantas Medicinales , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Acetilcolinesterasa , Berberina/uso terapéutico , Plantas Medicinales/metabolismo , Resveratrol/farmacología , Resveratrol/uso terapéutico , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/uso terapéutico , Inhibidores de la Colinesterasa/química , Fitoquímicos/uso terapéutico
15.
Neuroendocrinology ; 113(2): 193-207, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35066506

RESUMEN

BACKGROUND: Selenoprotein T (SELENOT), a PACAP-regulated thioredoxin-like protein, plays a role in catecholamine secretion and protects dopaminergic neurons. However, the role of SELENOT in the establishment of the catecholaminergic (CA) neuronal system is not known yet. METHODS: We analyzed by immunohistochemistry and RNAscope in situ hybridization the distribution of SELENOT and the expression of its mRNA, respectively. In addition, 3D imaging involving immunostaining in toto, clearing through the iDISCO+ method, acquisitions by light-sheet microscopy, and processing of 3D images was performed to map the CA neuronal system. A semi-automatic quantification of 3D images was carried out. RESULTS: SELENOT protein and mRNA are widely distributed in the mouse brain, with important local variations. Three-dimensional mapping, through tyrosine hydroxylase (TH) labeling, and semi-automated quantification of CA neurons in brain-specific SELENOT knockout mice showed a significant decrease in the number of TH-positive neurons in the area postrema (AP-A2), the A11 cell group (A11), and the zona incerta (ZI-A13) of SELENOT-deficient females, and in the hypothalamus (Hyp-A12-A14-A15) of SELENOT-deficient females and males. CONCLUSION: These results showed that SELENOT is diffusely expressed in the mouse brain and that its deficiency impacts CA neuron distribution in different brain areas including Hyp-A12-A14-A15, in both male and female mice.


Asunto(s)
Imagenología Tridimensional , Neuronas , Ratones , Femenino , Masculino , Animales , Neuronas/metabolismo , Encéfalo/metabolismo , Hibridación in Situ , Ratones Noqueados , ARN Mensajero/metabolismo , Tirosina 3-Monooxigenasa/metabolismo
16.
Port J Public Health ; 40(3): 163-171, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39469255

RESUMEN

Introduction: The widespread lockdown due to the COVID-19 pandemic was insured by Moroccan authorities in early 2020 to preserve the health of citizens. The lockdown and the pandemic imposed psychological effects on the population including anxiety. Celiac disease (CeD), a chronic disease among the most common inflammatory intestinal disorders, has been linked to adult emotional disturbances. Hence, CeD patients may suffer from anxiety or increase this condition due to the concomitant situation. The objective of this study was to assess COVID-19-related anxiety in a sample of adults with CeD in comparison with a matched healthy group. Method: CeD patients (103) and matched healthy group (101) were investigated using a web-based COVID-19 and related lockdown anxiety survey. Anxiety was assessed with the State and Trait Anxiety Inventory (STAI test: Y1 for state anxiety and Y2 for trait anxiety). Results: State anxiety was present among 65.3% of CeD and 41.6% of the comparison group, and the difference was statistically significant. CeD women suffered more from state anxiety than their compeers in the comparison group (t = 3.23; p = 0.002), and a significant correlation between good compliance to GFD and less state anxiety was found among CeD patients (r = 0.31; p = 0.002). 61.8% of CeD participants thought they were at higher risk of contamination by COVID-19, and they were mostly women (χ2 = 7.66, p < 0.006) and had significantly higher state anxiety mean scores than their compatriots who did not express these thoughts (t = 2.93; p = 0.004). Additionally, 41.5% of CeD participants had anxiety as a trait against 26.7% in the comparison group and the difference between the two groups was statistically significant. Conclusion: Results of this survey allow a better understanding of the health-related pandemic effects on Moroccan CeD patients. It demonstrates that COVID-19 and related lockdowns had a serious impact on the psychological balance of these patients by increasing their anxiety. The survey results underlined the need to improve the psychological care of CeD patients notably by considering remote medical visits during this ongoing pandemic to provide mental health support.


Introdução: O confinamento generalizado devido à pandemia de COVID-19 foi instaurado pelas autoridades marroquinas no início de 2020 para preservar a saúde dos cidadãos. O confinamento e a pandemia determinaram efeitos psicológicos na população, incluindo ansiedade. A doença celíaca (CeD), uma doença crónica caracterizada por alterações inflamatórias intestinais, tem sido associada a distúrbios emocionais em adultos. Assim, os pacientes com CeD podem sofrer de ansiedade ou sofrer ainda mais desta condição, como consequência da situação concomitante. O objetivo deste estudo foi avaliar a ansiedade relacionada ao COVID-19 numa amostra de adultos com CeD em comparação com um grupo saudável emparelhado. Método: Doentes com CeD (103) e um grupo saudável emparelhado (101) responderam através da internet a um questionário sobre ansiedade relacionada com o confinamento devido à COVID-19. A ansiedade foi avaliada com o State and Trait Anxiety Inventory (teste STAI: y1 para ansiedade-estado e y2 para ansiedade-traço). Resultados: A ansiedade-estado esteve presente em 65,3% dos CeD e 41,6% do grupo de comparação e a diferença foi estatisticamente significativa. As mulheres com CeD referem maiores níveis de ansiedade-estado do que seus pares no grupo de comparação (t = 3,23; p = 0,002) e foi encontrada correlação significativa entre boa adesão à DSG e menos ansiedade-estado (r = 0,31; p = 0,002). 61,8% dos participantes com CeD achavam que estavam em maior risco de contaminação por COVID-19, eram principalmente mulheres (χ2 = 7,66, p < 0,006) e apresentaram um score médio de ansiedade-estado significativamente maior do que seus pares que não expressaram esses pensamentos (t = 2,93; p = 0,004). Além disso, 41,5% dos participantes com CeD tinham ansiedade como traço contra 26,7% no grupo de comparação e a diferença entre os dois grupos foi estatisticamente significativa. Conclusão: Os resultados desta investigação permitem compreender melhor os efeitos pandémicos relacionados com a saúde em pacientes com doença celíaca. Demonstra que a COVID-19 e o confinamento relacionado tiveram um sério impacto no equilíbrio psicológico desses pacientes, piorando a sua ansiedade. Os resultados destacaram também a necessidade de melhorar o atendimento psicológico dos pacientes com CeD, principalmente considerando o uso da telemedicina durante a actual pandemia para suporte à sua saúde mental.

17.
Port J Public Health ; 41(3): 179-187, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39469614

RESUMEN

Introduction: Breakfast skipping is an unhealthy eating behavior reportedly common among adolescents. The aim of the present study was to determine the prevalence and factors associated with breakfast skipping among schoolchildren aged 12-19 years in Beni Mellal city, Morocco, and to assist in the design of interventions to improve breakfast consumption habits of school-aged children in this region. Methods: A school-based cross-sectional study was carried out. A total of 550 children were included in the study. Multivariable logistic regression analysis was used to identify factors associated with skipping breakfast consumption. The association between dependent and independent variables was assessed using an odds ratio (OR) with a 95% confidence interval and p value <0.05 was considered statistically significant. Results: Among 550 Moroccan adolescents evaluated, 25.6% reported not consuming breakfast every day. Breakfast eating was statistically associated with gender (OR = 7.13 [95% CI 1.32-3.84], p = 0.008); mother's low educational level (OR = 2.86 [95% CI 1.89-4.71], p = 0.091); nonworking mothers (OR = 13.71 [95% CI 1.16-5.29], p < 0.001); not eating between meals (OR = 15.49 [95% CI 2.15-5.49], p < 0.001); eating dinner regularly each day (OR = 17.79 [95% CI 2.81-8.01], p = 0.005); eating vegetables 1-3 times per week (OR = 10.21 [95% CI 1.44-4.67], p = 0.001); consuming milk and dairy product 1-3 times per week (OR = 13.88 [95% CI 1.59-5.56], p < 0.001); and never consuming sodas and soft drink in week (OR = 3.12 [95% CI 1.90-4.50], p = 0.003). Conclusions: This study revealed that the prevalence of skipping breakfast consumption among school-aged children in Beni Mellal city was high. Thus, the findings suggest a community health education program, conducted by school nurses, nutritionists, and other health professionals, is needed.


Introdução: Não tomar o pequeno-almoço é um comportamento alimentar não saudável supostamente comum entre adolescentes. O objetivo do presente estudo foi determinar a prevalência e os fatores associados com o não consumo do pequeno-almoço entre crianças em idade escolar dos 12 aos 19 anos na cidade de Beni Mellal, Marrocos, e contribuir para o desenho de intervenções para melhorar os hábitos de consumo do pequeno-almoço de crianças em idade escolar em esta região. Métodos: Foi realizado um estudo transversal de base escolar. Um total de 550 crianças foram incluídas no estudo. A análise de regressão logística multivariada foi usada para identificar os fatores associados à omissão do consumo do pequeno-almoço. A associação entre variáveis dependentes e independentes foi avaliada por meio de odds ratio com intervalo de confiança de 95% e valor de p < 0.05 foi considerado estatisticamente significativo. Resultados: Entre os 550 adolescentes marroquinos avaliados, 25.6% relataram não tomar o pequeno-almoço todos os dias. Tomar o pequeno-almoço foi estatisticamente associado ao sexo (Odds Ratio (OR) = 7.13 [IC 95% 1.32­3.84], p = 0.008); à baixa escolaridade da mãe (OR = 2.86 [IC 95% 1.89­4.71], p = 0.091); mães não trabalhadoras (OR = 13.71 [IC 95% 1.16­5.29], p < 0.001), não comer entre as refeições (OR = 15.49 [IC 95% 2.15­5.49], p < 0.001); jantar regularmente todos os dias (OR = 17.79 [IC 95% 2.81­8.01], p = 0.005); comer vegetais 1 a 3 vezes por semana (OR = 10.21 [IC 95% 1.44­4.67], p = 0.001); consumir leite e derivados de 1 a 3 vezes por semana (OR = 13.88 [IC 95% 1.59­5.56], p < 0.001) e nunca beber refrigerantes durante a semana (OR = 3.12 [IC 95% 1.90­4.50], p = 0.003). Conclusões: Este estudo revelou que a prevalência da falta de consumo de pequeno-almoço entre crianças em idade escolar na cidade de Beni Mellal foi alta. Assim, os resultados sugerem que é necessário um programa de educação em saúde da comunidade, conduzido por nutricionistas e outros profissionais de saúde.

18.
Mult Scler Relat Disord ; 67: 104193, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36179556

RESUMEN

OBJECTIVE: This study aims to determine the link between sociodemographic factors, diagnosis, and access to disease-modifying treatment for patients with multiple sclerosis (MS) in Morocco. METHODS: This study concerned a sample of 520 patients representing seven regions of Morocco. We obtained data from the patient record registers, the patient's files, and a questionnaire. RESULTS: The results showed female dominance (69.4%) in patients with MS (69.4%). Besides, patients with this disease are generally young; their mean age is 35.36. The employment rate among the surveyed population was 24.9%. More than 74.6% have no health care coverage, and 70.4% of the patients investigated live without treatment. The results show a significant association between access to treatment and several sociodemographic factors, such as the patient's job, health care coverage, region, and marital status. There is also a link between these sociodemographic factors and access to diagnosis. CONCLUSIONS: Diagnosis and access to treatment are associated with certain sociodemographic factors such as health insurance coverage, the patient's job, regional belonging, and marital status.


Asunto(s)
Esclerosis Múltiple , Humanos , Femenino , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/terapia , Marruecos/epidemiología , Atención a la Salud , Encuestas y Cuestionarios , Empleo
19.
AIMS Neurosci ; 9(1): 57-75, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35434276

RESUMEN

Exposure to certain acute stressors results in an immediate behavioral and physiological response to these situations during a significant period of days. The goal of the current study is to evaluate the long-lasting effect of single exposure of restraint stress among mice after 0 h, 24 h, 48 h and 72 h. Five groups of mice are under experiment: a control group and four groups exposed to one session of restraint stress. All these groups have been studied for behavioral tests in order to evaluate their memories. This is done through a Y-labyrinth and an object recognition test, and anxiety by using open field device. In the second part of the study, enzymatic assays (concerning catalase, glutathione s transferase, glutathione peroxidase and superoxide dismutase) are used to evaluate oxidative stress. The enzymatic activity of the antioxidant system is assessed in five brain structures, including the cerebellum, olfactory bulb, spinal bulb, hypothalamus, and hippocampus. The obtained results show that acute restraint stress leads to a decrease in memory function and to the development of an anxious state; concomitant to an increase of locomotor activity afterword. It causes disturbance of antioxidant balance in the brain by developing a state of oxidative stress. Indeed, restraint stress causes a change in anti-oxidant stress enzymatic activity in the brain, notably in post-stress period. In conclusion, acute restraint stress is responsible for altering cognitive functions, especially memory, and the development of anxious behavior, which could be a result of the generation of oxidative stress; effects that are persistent over an important period after the cessation of stress.

20.
Int Health ; 14(4): 390-397, 2022 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-31957782

RESUMEN

BACKGROUND: Diabetes remains poorly controlled in a high proportion of diabetes patients. This study examines the prevalence of poor glycaemic control and associated factors in type 2 diabetes patients in the Beni-Mellal Khenifra region in Morocco. METHODS: A cross-sectional survey was conducted in 2017 among 1456 diabetes patients attending primary health centres. Demographic and clinical data were collected through face-to-face interviews using structured and pre-tested questionnaires. Anthropometric measurements, including body weight, height and waist circumference were taken using standardized techniques and calibrated equipment. Glycaemic control was assessed in terms of the glycated haemoglobin (HbA1c) level and poor glycaemic control was defined as HbA1c ≥7% and a level <7% reflects good glycaemic control. RESULTS: Of the total participants, 66.3% had poor glycaemic control. Bivariate analysis showed that sex (p=0.010), education level (p=0.013), body mass index (p=0.048), duration of diabetes (p<0.0001) and type of therapeutic regimen (p<0.0001) were significantly associated with HbA1c level. However, multiple logistic regression analyses revealed that only a longer duration of diabetes (OR 1.525 [95% confidence interval {CI} 1.183-1.967], p=0.001) and receiving insulin therapy alone (OR 1.589 [95% CI 1.157-2.183], p=0.004) or a combination of oral antidiabetics with insulin (OR 2.554 [95% CI 1.786-3.653], p<0.001) were significantly associated with inadequate glycaemic control. CONCLUSIONS: Despite the particularities of the region, the findings about glycaemic control and its cross-sectionally associated factors are in line with findings from other regions of Morocco. In this subgroup, the longer duration of diabetes and insulin treatment could constitute a cause leading to poor glycaemic control. However, inverse causality cannot be excluded.

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