Dental pulp stem cells ameliorate D-galactose-induced cardiac ageing in rats.

Background: Ageing is a key risk factor for cardiovascular disease and is linked to several alterations in cardiac structure and function, including left ventricular hypertrophy and increased cardiomyocyte volume, as well as a decline in the number of cardiomyocytes and ventricular dysfunction, emphasizing the pathological impacts of cardiomyocyte ageing. Dental pulp stem cells (DPSCs) are promising as a cellular therapeutic source due to their minimally invasive surgical approach and remarkable proliferative ability. Aim: This study is the first to investigate the outcomes of the systemic transplantation of DPSCs in a D-galactose (D-gal)-induced rat model of cardiac ageing. Methods. Thirty 9-week-old Sprague-Dawley male rats were randomly assigned into three groups: control, ageing (D-gal), and transplanted groups (D-gal + DPSCs). D-gal (300 mg/kg/day) was administered intraperitoneally daily for 8 weeks. The rats in the transplantation group were intravenously injected with DPSCs at a dose of 1 × 106 once every 2 weeks. Results: The transplanted cells migrated to the heart, differentiated into cardiomyocytes, improved cardiac function, upregulated Sirt1 expression, exerted antioxidative effects, modulated connexin-43 expression, attenuated cardiac histopathological alterations, and had anti-senescent and anti-apoptotic effects. Conclusion: Our results reveal the beneficial effects of DPSC transplantation in a cardiac ageing rat model, suggesting their potential as a viable cell therapy for ageing hearts.

Impact of NMDA receptors block versus GABA-A receptors modulation on synaptic plasticity and brain electrical activity in metabolic syndrome.

PURPOSE: Metabolic syndrome (MetS) is a common disorder associated with disturbed neurotransmitter homeostasis. Memantine, an N-methyl-d-aspartate receptor (NMDAR) antagonist, was first used in Alzheimer's disease. Allopregnanolone (Allo), a potent positive allosteric modulator of the Gamma-Amino-Butyric Acid (GABA)-A receptors, decreases in neurodegenerative diseases. The study investigated the impact of Memantine versus Allo administration on the animal model of MetS to clarify whether the mechanism of abnormalities is related more to excitatory or inhibitory neurotransmitter dysfunction. MATERIALS AND METHODS: Fifty-six male rats were allocated into 7 groups: 4 control groups, 1 MetS group, and 2 treated MetS groups. They underwent assessment of cognition-related behavior by open field and forced swimming tests, electroencephalogram (EEG) recording, serum markers confirming the establishment of MetS model and hippocampal Glial Fibrillary Acidic Protein (GFAP) and Brain-Derived Neurotrophic Factor (BDNF). RESULTS: Allo improved anxiety-like behavior and decreased grooming frequency compared to Memantine. Both drugs increased GFAP and BDNF expression, improving synaptic plasticity and cognition-related behaviors. The therapeutic effect of Allo was more beneficial regarding lipid profile and anxiety. We reported progressive slowing of EEG waves in the MetS group with Memantine and Allo treatment with increased relative theta and decreased relative delta rhythms. CONCLUSIONS: Both Allo and Memantine boosted the outcome parameters in the animal model of MetS. Allo markedly improved the anxiety-like behavior in the form of significantly decreased grooming frequency compared to the Memantine-treated groups. Both drugs were associated with increased hippocampal GFAP and BDNF expression, indicating an improvement in synaptic plasticity and so, cognition-related behaviors.

Evaluating cognitive and affective abilities among medical students: behavioural and medicolegal perspectives.

Medical students attending university for the first time experience a new environment, full of significant social, cultural, and intellectual challenges. Moreover, drug abuse and bullying among university students are major global concerns. The aim of the current study was to assess the impact of medicolegal issues on undergraduate and postgraduate students. It is a cross-sectional survey-based study, with each set of questions investigating cognitive functions, aggression, personality, and exposure to medicolegal issues. Males and those with a chronic disease have been significantly exposed to medicolegal issues; exposed students were significantly older than nonexposed ones. The scores of aggression were significantly higher among exposed and male students. The cognitive scores were higher for the students from rural areas than in urban areas, and females were more neurotic than males. The current study recommends conducting campaigns to educate university students on the importance of formally disclosing unethical behaviors and listening to the victims to facilitate overcoming their negative feelings. As many victims feel comfortable disclosing victimization to their friends, we recommend conducting peer educational programs to help friends support their colleagues regarding unethical misconduct.

Comparing MitoQ10 and heat therapy: Evaluating mechanisms and therapeutic potential for polycystic ovary syndrome induced by circadian rhythm disruption.

Environmental factors, such as sleep restriction, contribute to polycystic ovary syndrome (PCOS) by causing hyperinsulinemia, hyperandrogenism, insulin resistance, and oligo- or anovulation. This study aimed to evaluate the effects of circadian rhythm disruption on reproductive and metabolic functions and investigate the potential therapeutic benefits of MitoQ10 and hot tub therapy (HTT). Sixty female rats were divided into six groups: control, MitoQ10, HTT, and three groups with PCOS induced by continuous light exposure(L/L). The reproductive, endocrine, and structural manifestations ofL/L-induced PCOS were confirmed by serum biochemical measurements, ultrasound evaluation of ovarian size, and vaginal smear examination at week 14. Subsequently, the rats were divided into the L/L (untreated), L/L+MitoQ10-treated, andL/L+HTT-treated groups. At the end of week 22, all rats were sacrificed. Treatmentwith MitoQ10 or HTT partially reversed the reproductive, endocrine, and structural features of PCOS, leading to a decreased amplitude of isolated uterine contractions, ovarian cystic changes and size, and endometrial thickness. Furthermore, both interventions improved the elevated serum levels of anti-Mullerian hormone (AMH), kisspeptin, Fibulin-1, A disintegrin and metalloproteinase with thrombospondin motifs 19 (ADAMTS-19), lipid profile, homeostatic model assessment for insulin resistance (HOMA-IR), oxidative stress markers, androgen receptors (AR) and their transcription target genes, FKBP52 immunostaining in ovarian tissues, and uterine estrogen receptor alpha (ER-α) and PRimmunostaining. In conclusion, MitoQ10 supplementation and HTT demonstrated the potential for ameliorating metabolic, reproductive, and structural perturbations associated with PCOS induced by circadian rhythm disruption. These findings suggest a potential therapeutic role for these interventions in managing PCOS in women.

Inhibition of notch signalling and mesangial expansion by combined glucagon like peptide-1 agonist and crocin therapy in animal model of diabetic nephropathy.

Diabetic nephropathy (DN) is one of the devastating complications in diabetes mellitus (DM). Glucagon-like peptide-1 (GLP-1) is one of the incretins secreted from L cells in the intestine. Crocin (a carotenoid component of saffron) has antioxidants properties. We investigated the renal effects of Exendin-4 as a GLP-1 agonist and Crocin in DN.Thirty male rats were divided into five groups: control, type II DM, type II DM + Exendin-4, type II DM + Crocin and type II DM + Exendine-4 + Crocin. At the end of the experimental period, systolic and diastolic blood pressures were measured, and GFR was calculated. Blood and urine samples were collected for biochemical analysis. Tissue samples were collected from the kidney for histological examination and biochemical measurements of protein expression.Treatment with GLP-1 agonist or Crocin caused a significant improvement in renal function. Better results were achieved with simultaneous administration of both drugs with inhibition of notch signalling pathway and the related proteins.

Effect of Allopregnanolone on Spatial Memory and Synaptic Proteins in Animal Model of Metabolic Syndrome.

Metabolic Syndrome (MetS) is considered a common disorder, especially with a sedentary lifestyle and unhealthy food consumption. Cognitive impairment is one of the MetS consequences that worsens the quality of life of the patients. The study aimed to assess the therapeutic effect of the neurosteroid Allopregnalonone on spatial memory and, therefore, the expression of two synaptic plasticity markers in the hippocampus. Thirty-two male rats were divided into four groups: control groups, MetS, and MetS + Allopregnalone. Spatial memory has been evaluated by the Y-maze task and blood pressure measured by the rat tail method. Biochemical evaluation of serum glucose, insulin, lipid profile, and hippocampal expression of Synaptophysin and Associated Protein 43 (GAP-43) were performed for assessing Allopregnanolone on serum and hippocampal markers. Allopregnanolone therapy improved working spatial memory, hypertension, and biochemical markers measured in the serum and hippocampus.

Melatonin-Pretreated Mesenchymal Stem Cells Improved Cognition in a Diabetic Murine Model.

Diabetes mellitus (DM) is a multisystem endocrine disorder affecting the brain. Mesenchymal stem cells (MSCs) pretreated with Melatonin have been shown to increase the potency of MSCs. This work aimed to compare Melatonin, stem cells, and stem cells pretreated with Melatonin on the cognitive functions and markers of synaptic plasticity in an animal model of type I diabetes mellitus (TIDM). Thirty-six rats represented the animal model; six rats for isolation of MSCs and 30 rats were divided into five groups: control, TIDM, TIDM + Melatonin, TIDM + Stem cells, and TIDM + Stem ex vivo Melatonin. Functional assessment was performed with Y-maze, forced swimming test and novel object recognition. Histological and biochemical evaluation of hippocampal Neuroligin 1, Sortilin, Brain-Derived Neurotrophic Factor (BDNF), inducible nitric oxide synthase (iNOS), toll-like receptor 2 (TLR2), Tumor necrosis factor-alpha (TNF-α), and Growth Associated Protein 43 (GAP43). The TIDM group showed a significant decrease of hippocampal Neuroligin, Sortilin, and BDNF and a significant increase in iNOS, TNF-α, TLR2, and GAP43. Melatonin or stem cells groups showed improvement compared to the diabetic group but not compared to the control group. TIDM + Stem ex vivo Melatonin group showed a significant improvement, and some values were restored to normal. Ex vivo melatonin-treated stem cells had improved spatial working and object recognition memory and depression, with positive effects on glucose homeostasis, inflammatory markers levels and synaptic plasticity markers expression.

Platelets: the peripheral donor of mitochondria for diabetes-induced cognitive impairment.

This commentary highlights the research entitled: Transplantation of platelet-derived mitochondria alleviates cognitive impairment and mitochondrial dysfunction in db/db mice, presented by Ma et al. appearing in Clinical Science (2020) 134(16), https://doi.org/10.1042/CS20200530. The authors evaluated the effect of xenograft transplantation of mitochondria isolated from peripheral blood platelets in an animal model of type II diabetes and evaluated the effects of transplantation on diabetes-associated cognitive impairment (DACI). They showed cognitive and molecular improvement in response to mitochondrial transplantation to db/db mice brains. Besides, they showed better internalization of the transplanted mitochondria into the diseased animals' hippocampal cells compared with the healthy normal control.

Gastroprotective effects of nebivolol and simvastatin against cold restraint stress-induced gastric ulcer in rats.

Gastric ulcer is one of the most serious diseases. Nebivolol (Neb), a ß1-blocker, exhibits vasodilator and anti-oxidative properties, simvastatin (Sim) antihyperlipidemic drug, exhibits anti-oxidative, anti-inflammatory properties and promote endogenous nitric oxide (NO) production. The aim of this study was to evaluate the gastroprotective effects of Neb and Sim against cold restraint stress (CRS)-induced gastric ulcer in rats. Rats were restrained, and maintained at 4°C for 3 hours. Animals were divided into six groups; control group, CRS group, and four treatment groups received ranitidine (Ran), Neb, Sim and both Neb and Sim. Treatments were given orally on a daily basis for 7 days prior to CRS. The gastroprotective effects of Neb and Sim were assessed biochemically by measuring variations in prostaglandins E2, NO, reduced glutathione and malondialdehyde, and functionally by estimating force of contractions of isolated rat fundus in the studied groups in response to acetylecholine stimulation and morphologically using hematoxylin and eosin staining, periodic acid Schiff's reaction and immunohistochemistry for cyclooxygenase 2 in gastric mucosa. CRS caused significant ulcerogenic effect. Alternatively, pretreatment with Ran, Neb, and Sim significantly corrected biochemical findings, pharmacological and histological studies.

Metformin protects against thioacetamide induced liver injury in rats / La metformina protege contra la lesión hepática inducida por tioacetamida en ratas

Potent heptatotoxic chemicals such as carbon tetrachloride and thioacetamide (TAA) are used to evaluate hepatoprotective agents. Here we sought to investigate the potential protective effect of the antidiabetic and antioxidant drug, metformin against liver injury induced by TAA. Model group rats received several injections of TAA (200 mg/kg) before being sacrificed after 10 weeks and the protective group started the treatment two weeks prior to TAA injections and continued receiving both agents, metformin and TAA until the end of the experiment, week 10. Harvested liver tissues were examined using light microscopy and liver homogenates were assayed for oxidative and anti-oxidative stress markers that are known to be modulated in liver injury. Profound damage in the hepatic tissue of the model group such as liver fibrosis and destruction of hepatic architectures were revealed, which were protected by metformin comparable to the control group. TAA augmented the oxidative stress biomarker, malondialdehyde (MDA) and ameliorated the antioxidant superoxide dismutase (SOD), which were significantly (p<0.05) protected by metformin treatment. These results indicate that metformin effectively protects against TAA-induced hepatotoxicity in a rat model.

Para evaluar los agentes hepatoprotectores se usan químicos heptatotóxicos potentes como el tetracloruro de carbono y la tioacetamida (TAA). En este estudio tratamos de investigar el efecto protector potencial de la droga antidiabética y antioxidante, la metformina contra la lesión hepática inducida por TAA. Las ratas del grupo modelo recibieron varias inyecciones de TAA (200 mg/kg) durante 10 semanas antes de ser sacrificadas, y el grupo protector comenzó el tratamiento dos semanas antes de las inyecciones TAA y continuó recibiendo ambos agentes, metformina y TAA, hasta el final del experimento. Los tejidos hepáticos se examinaron usando microscopía óptica y se analizaron los homogeneizados hepáticos en busca de marcadores de estrés oxidativo y antioxidante los que están modulados en la lesión hepática. Se observaron daños significativos en el tejido hepático del grupo modelo como la fibrosis hepática y destrucción de la arquitectura hepática, que estaban protegidas por la metformina comparable al grupo control. TAA aumentó el biomarcador de estrés oxidativo, malondialdehído (MDA) y mejoró la enzima antioxidante superóxido dismutasa (SOD), que fueron protegidas significativamente (p <0,05) por el tratamiento con metformina. Estos resultados indican que la metformina protege eficazmente contra la hepatotoxicidad inducida por TAA en un modelo de rata.

Does posttreatment thymoquinone reverse high-dose atorvastatin-induced hepatic oxidative injury in rats?

Atorvastatin (ATO) was commonly used to lower blood cholesterol, but it caused harmful effects to organs, including the liver. Thymoquinone (TQ), a prominent constituent of Nigella sativa, has antioxidant, antiinflammatory, antiapoptotic, antimicrobial, and anticancer activity. The current study investigated the mechanism of ATO-induced hepatotoxicity, whether posttreatment TQ could reverse ATO-induced hepatic injury, and the mechanism of action of TQ as a hepatoprotective agent. Forty adult male Sprague Dawley rats were divided into four equal groups: control, TQ-treated, ATO-treated, and combined ATO/TQ-treated. Rats were treated for 8 weeks and 10 days and euthanized by cervical dislocation 3 days after the last treatment. Blood samples and livers were tested for liver enzymes, oxidative stress, and apoptosis markers and used for histopathological and ultrastructural examination. The ATO-treated group showed an increase in liver enzymes, decreases in reduced glutathione and catalase, and increases in the malondialdehyde lipid peroxidation marker, protein carbonylation, and caspase 3 activity. Posttreatment TQ in the ATO/TQ-treated group seemed to reverse these changes. Histopathological and ultrastructural examination supported these data. Results from the current study suggested that posttreatment TQ may reverse oxidative stress injury in rat liver produced by ATO, suggesting a potential clinical application of using TQ to prevent ATO-induced hepatic injury.

Effects of chronic aspartame consumption on MPTP-induced Parkinsonism in male and female mice.

BACKGROUND: Parkinson's disease is a progressive neurodegenerative disorder. Aspartame (l-aspartyl-l-phenylalanine methyl ester), a low calorie sweetener used in foods and beverages. OBJECTIVES: This study investigated the effect of chronic aspartame intake on Parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). METHOD: Forty-eight mice (24 males and 24 females): control, aspartame, MPTP, and aspartame + MPTP groups tested by Y-maze, stepping, forced swimming and olfactory preference tests. Brain tissues examined for dopamine content, tyrosine hydroxylase, inducible nitric oxide synthase (iNOS), glutathione peroxidase, phosphorylated tau and α-synuclein protein. Histopathological evaluation of brain sections at the level of basal ganglia was done. RESULTS: Decreased dopamine content, tyrosine hydroxylase expression, glutathione peroxidase expression and increased iNOS, tau and α-synuclein expression in groups received aspartame, MPTP or both agents simultaneously in both males and females group. CONCLUSIONS: Increased dopaminergic degeneration and complications with chronic aspartame consumption and more injury in male groups.

Effect of melatonin supplemented at the light or dark period on recovery of sciatic nerve injury in rats.

Peripheral nerve injuries can cause disabilities, social or economic problems. Melatonin, the secretory product of the pineal gland has antioxidant and anti-inflammatory actions. The aim of the present study was to investigate the effect of melatonin on the recovery of sciatic nerve after injury, comparing its effect when given in the light or the dark periods. Forty adult male Albino rats were allocated into four groups: control, nerve injury, nerve injury + melatonin given at light and nerve injury + melatonin given at dark. Nerve injury was initiated by clamping the sciatic nerve. Sciatic functional index (SFI) was measured preoperatively and postoperatively. Melatonin was given daily for six weeks. Recovery of the function was analyzed by functional analysis, electrophysiological analysis and biochemical measurement of Superoxide dismutase (SOD), Interleukin 1-beta (IL-1 ß), Nerve growth factor (NGF), and bcl-2. Melatonin improved SFI, nerve conduction velocity (NCV) and the force of gastrocnemius muscle contraction as compared to the untreated rats. SOD activity, NGF, and bcl-2 were significantly increased, while IL-1ß was significantly decreased after melatonin treatment as compared to the untreated injury group. SFI reached the control level; muscle contraction and IL-1B were significantly improved in the group treated with melatonin in the dark. Melatonin fastened the neural recovery and may be used in the treatment of nerve injury and it induced better nerve regeneration when the rats were treated during the dark period.

Hepatoprotective effect of blocking N-methyl-d-aspartate receptors in male albino rats exposed to acute and repeated restraint stress.

Stress affects many organs in addition to the brain, including the liver. We assessed the effects on the liver of blocking N-methyl-d-aspartate (NMDA) glutamate receptors with memantine in acute and repeated restraint stress. Forty-two male albino rats were divided into 7 groups; control, acute restraint stress (ARS), ARS + memantine, repeated restraint stress, repeated restraint + memantine, and positive control groups. We measured serum iron, zinc, alanine transferase and aspartame transferase, hepatic malondialdehyde, tumor necrosis factor-α (TNF-α), glutathione peroxidase, superoxide dismutase, metallothionein content, zinc transporter ZRT/IRT-like protein 14 mRNA expression, and hepcidin expression. We conducted a histopathological evaluation via histological staining and immunostaining for glial fibrillary acidic protein and synaptophysin expression, both of which are markers of hepatic stellate cell (HSC) activation. Both ARS and repeated stress increased markers of hepatic cell injury, oxidative stress, and HSC activation. Blocking NMDA with memantine provided a hepatoprotective effect in acute and repeated restraint stress and decreased hepatic cell injury, oxidative stress, and HSC activation.

Effect of undifferentiated versus hepatogenic partially differentiated mesenchymal stem cells on hepatic and cognitive functions in liver cirrhosis.

Liver cirrhosis is the outcome of chronic liver injury. The current study aimed to investigate the therapeutic effect of undifferentiated mesenchymal stem cells versus in vitro partially differentiated mesenchymal stem cells on liver cirrhosis and hepatic encephalopathy. 50 adult male albino rats constituted the animal model and were divided into the following groups: control, thioacetamide, undifferentiated mesenchymal stem cells and hepatocyte growth factor-differentiated mesenchymal stem cells groups. Cognitive assessment was achieved by open field test and Y-maze task. We measured serum alanine aminotransferase, albumin and transforming growth factor-beta1, gene expression of α-smooth muscle actin, matrix metalloprotein-2, its tissue inhibitor and apoptotic markers: Bax and Bcl2, brain glial fibrillary acidic protein, synaptophysin, and dopaminergic receptors.

Modification of hippocampal markers of synaptic plasticity by memantine in animal models of acute and repeated restraint stress: implications for memory and behavior.

Stress is any condition that impairs the balance of the organism physiologically or psychologically. The response to stress involves several neurohormonal consequences. Glutamate is the primary excitatory neurotransmitter in the central nervous system, and its release is increased by stress that predisposes to excitotoxicity in the brain. Memantine is an uncompetitive N-methyl D-aspartate glutamatergic receptors antagonist and has shown beneficial effect on cognitive function especially in Alzheimer's disease. The aim of the work was to investigate memantine effect on memory and behavior in animal models of acute and repeated restraint stress with the evaluation of serum markers of stress and the expression of hippocampal markers of synaptic plasticity. Forty-two male rats were divided into seven groups (six rats/group): control, acute restraint stress, acute restraint stress with Memantine, repeated restraint stress, repeated restraint stress with Memantine and Memantine groups (two subgroups as positive control). Spatial working memory and behavior were assessed by performance in Y-maze. We evaluated serum cortisol, tumor necrotic factor, interleukin-6 and hippocampal expression of brain-derived neurotrophic factor, synaptophysin and calcium-/calmodulin-dependent protein kinase II. Our results revealed that Memantine improved spatial working memory in repeated stress, decreased serum level of stress markers and modified the hippocampal synaptic plasticity markers in both patterns of stress exposure; in ARS, Memantine upregulated the expression of synaptophysin and brain-derived neurotrophic factor and downregulated the expression of calcium-/calmodulin-dependent protein kinase II, and in repeated restraint stress, it upregulated the expression of synaptophysin and downregulated calcium-/calmodulin-dependent protein kinase II expression.

Cognitive effects of acute restraint stress in male albino rats and the impact of pretreatment with quetiapine versus ghrelin.

Stress is any condition that seriously affects the balance of the organism physiologically and psychologically. Stress activates the hypothalamic-pituitary-adrenal (HPA) releasing glucocorticoid hormones that produce generalized effects on different body systems including the nervous system. This study aimed to investigate the effect of acute restraint stress (ARS) on cognitive performance by measuring spatial working memory in Y-maze, behavior (anxiety and exploratory behavior) in open field test, expression of synaptophysin and glial fibrillary acidic protein (GFAP) in the hippocampus by immunohistochemistry, dopaminergic receptors (D2) in the basal ganglia by gene expression and comparing the effect of ghrelin and quetiapine on the previous parameters. 36 adult male albino rats constituted the animal model of this work and have been divided into six groups: control group, control group exposed to ARS, quetiapine group, quetiapine group exposed to ARS, ghrelin group and ghrelin group exposed to ARS. We demonstrated more neuroprotective effect for quetiapine compared to ghrelin on stress response, anxiety behavior and working spatial memory impairment due to ARS.