Treating severe bone deformities and abnormalities continues to be a major clinical hurdle, necessitating the adoption of suitable materials that can actively stimulate bone regeneration. Magnesium phosphate (MP) is a material that has the ability to stimulate the growth of bones. The current study involved the synthesis of mesoporous MP and lanthanum (La)-doped nanopowders using a chemical precipitation approach. The nanopowders were analyzed using several techniques, including XRD, FTIR, HR-TEM, BET, XPS, and FE-SEM. The results confirmed the nanopowders' size of less than 40 nm and the successful incorporation of La3+ ions into the MP structure. The bioactivity of the materials was assessed in vitro using simulated bodily fluid (SBF) at 37°C for a duration of 14 days in a shaker incubator (50 rpm). The SEM showed that a bone-like apatite layer formed quickly on the nanopowders' surface, proving that they have unique bioactive properties. The EDX spectra confirmed the presence of Ca, P, Mg, and La elements after immersion in SBF. The MP nanopowders, both with and without La doping, demonstrated the capacity to stimulate bone formation in a rat femoral bone defect model over a 28-day duration. Radiographic and histological studies showed that the La-doped MP nanopowders greatly improved bone repair and regeneration in comparison to the La-free nanopowders. Finally, the readily producible mesoporous MP nanomaterials, especially those with increased La doping (up to 7 wt%), exhibit significant potential for the restoration of large bone defects. Hence, fabricated nanopowders have immense promise for repairing bone criterion defects.

The current study investigated the pharmacokinetic profile of a newly developed biodegradable subcutaneous tramadol implant and shed some light on neurochemical changes. Ribbons of polycaprolactone polymer were loaded with tramadol HCl in two quantities (T350, T650) and implanted in back skin of rats. Plasma tramadol levels were monitored for 45 days and pharmacokinetic parameters were evaluated in addition to analgesic activity. Cortical oxidative stress indicators, orexin, and serotonin levels were determined. The CB-1 receptor and PPAR-alpha receptor protein levels were assayed. Both T350 and T650 loaded ribbons attained a sustained release profile for 45 days. T650 implants achieved higher bioavailability than T350. However, the analgesic efficacy of tramadol started once it was implanted and decreased along time indicating accelerated tolerance. Oxidative biomarkers were of normal range. The ventrolateral periaqueductal gray (vlPAG) analgesic pathway involving orexin, endocannabinoid, and serotonin was found to be affected in relation to developing tolerance. Induced cortical 5-HT and orexin-A and decreased level of DA after implanting T350 and T650 were observed. PPAR-alpha and CB-1R were of elevated abundance in cortex after T650 implants.However, pharmacodynamics reported a sensitizing effect related to vlPAG pathway. The implant achieved long stable release profile but of diminished analgesic activity.

While autologous transplants are the traditional standard intervention for non-healing bone defect regeneration, they carry many risks and limitations. Regenerative composite biomaterials are promising alternatives to conventional autograft and allograft implants. This study aimed to overcome these challenges by creating a novel biodegradable 3D biomaterial scaffold that mimics the structural and physiological properties of native bone. Scaffolds composed of magnesium phosphate (MgP) doped with copper oxide (CuO) in specific proportions (3, 5, or 7% [w/w]) were homogenously distributed in an alginate polymer matrix for the repair of calvarial bone defects in a rat model. The scaffolds were fabricated using a 3D bioprinting technique, and their physical properties were characterized through X-ray diffraction, Fourier transform infrared spectroscopy, and mechanical strength assessments. The bioactivity of the scaffolds was evaluated in vitro for biomineralization and cytotoxicity, revealing high biomineralization and cell viability. Female rats were used for the in vivo experiments, and the defects were examined using microscopic and histological analysis, computed tomography imaging, as well as serum markers including osteocalcin and procollagen III. The in vivo results demonstrated high efficacy of the scaffolds in promoting bone regeneration and enhanced healing in the calvarial defect model. The incorporation of CuO not only improved the scaffolds' mechanical properties but also exhibited angiogenic effects, fostering an environment conducive to bone healing. Our results indicated that the Alg-MgP-CuO scaffolds have great promise for bone tissue engineering applications and repair, especially with 7% (w/w) CuO doping.

Developing and evaluating enhanced biocomposites for medication delivery and bone regeneration is the main goal of this research. A unique wet precipitation chemical process was used to create calcium silicate (CaO–SiO₂) biocomposites, with different amounts of calcium hexaboride (CaB₆) incorporated as an additive. The biocomposite samples were subjected to varying compositions, and their physicochemical properties were assessed by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), and zeta potential tests. The samples' microstructures show submicron and nanoscale particles scattered or arranged in regular or irregular clusters. After adding CaB6, the tested biocomposites' negative zeta potential dropped because of the positively charged Ca2+ ions from the compound on the material's surface. The biocomposites' drug loading and release capacities were assessed using the anti-cancer medication of 5-fluorouracil (5-FU). The biocomposites were evaluated for their capacity to regenerate bone through in vivo experiments conducted on a rat model. The healing score (7 for the WB7.5 sample) and the degree of bone formation were compared with the concentration of CaB₆ in the bio-composites. The findings revealed that the presence of CaB₆ had a substantial impact on both the healing score and bone formation. Increased amounts of CaB₆ resulted in higher healing scores and better bone production. Moreover, the bio-composites demonstrated prolonged drug release profiles (up to 45

Alzheimer’s disease (AD) is a growing challenge worldwide, with current treatments largely symptomatic and limited. The current study aimed to introduce coated nanoporous membranes for localized drug delivery of donepezil, combining both antifouling activity and sustained drug release, unlike traditional Alzheimer’s treatments that rely on systemic administration. Nanoporous membranes were prepared by electrochemical anodization, coated with Polymethyl methacrylate (PMMA) or a PMMA/polyurethane (PU) mixture to mitigate biofouling. The fabricated nanoporous membranes before and after coating were characterized using SEM/EDX, FTIR, BET, and contact angle measurements. In vitro drug release and release kinetics were studied in artificial cerebrospinal fluid (ACSF). Coated and donepezil loaded membranes were implanted on the dura surface in Wistar rats AD model via intracerebral streptozotocin (STZ) injection. The activity was evaluated on behavioral, biochemical and histological levels. PMMA enhanced membrane hydrophobicity (contact angle increased from 62.8° to 79°) and sustained drug release over 7 days, making it the preferred coating. The PMMA membrane demonstrated a reduction in beta-amyloid levels without being loaded with donepezil, while the donepezil-loaded membrane showed cognitive function improvement in Morris water maze and Y-maze. Acetylcholinesterase activity was elevated after STZ-induction of AD and got ameliorated by the membranes implantation. Brain-Derived Neurotrophic Factor (BDNF) was lowered by STZ, while increased in treated animals. Histological examination revealed the neuronal regeneration after donepezil-loaded PMMA coated membrane. These findings suggest that coated nanoporous membranes are promising systems for localized active donepezil drug delivery for AD-like symptoms modulation in STZ-induced AD model, warranting further validation in other AD paradigms.

Polydrug use among teenagers is widespread and emergent either among athletes or non-athletes. It is reported that stanzolol (Stanz) is commonly abused with cannabis (Cann), this combination probably affects the testicular functions negatively. Aim The present study aimed to evaluate the toxic effects of Stanz and or Cann on reproductive hormones and testicular enzymes. Male Wistar rats were administered Stanz (5 mg/kg, s.c., once per week) and Cann (20 mg/kg, i.p., daily) either alone or in combination for two months, in exercise or sedentary conditions. Swimming exercise protocol was applied. Administration of both Stanz and Cann induced testicular damage, as evidenced by altered hormones, oxidative stress, and testicular enzymes. The testis tissue was significantly injured by the combined administration. In serum, levels of free testosterone, follicular stimulating hormone (FSH), lutenizing hormone (LH) were markedly reduced, while sorbitol dehydrogenase level increased. Moreover, tissue malondialdehyde (MDA) was significantly increased, glutathione (GSH) content decreased, testicular N-acetyl-β-glucosaminidase (NAG) and Myeloperoxidase (MPO) were increased. SIRT1 and STS mRNA expression were downregulated. Besides, distinct histopathological changes were detected in testis of Stanz and Cann injected rats. Nevertheless, Stanz, Cann or combined treatment showed a considerable up-regulation of immunoexpression of inducible nitric oxide synthase (iNOS) and caspase-3 in testes tissue. Oxidative stress and inflammation played a significant role in the observed pathological changes. Training was partially ameliorating for the observed effects. Use of the drugs in sedentary rats had more detrimental effects on testes. Although exercise could palliate the damage partially, it was not fully protective.

Workers are increasingly being exposed to the fumes of toluene, which is used extensively in many industrial processes. Toluene exposure has been connected to heart disorders such as ventricular tachycardia, coronary vasospasm, sinus bradycardia, and atrioventricular conduction difficulties. Alpha lipoic acid (ALA) and L-carnitine (LC) are antioxidants that may have cardioprotective benefits against chronic cardiotoxicity caused by toluene in male rats, therefore this study investigates these effects over a month in male rats. Toluene was administered for one month to male Sprague Dawley rats. ALA (50 and 100 mg/kg i.p.) and LC (150 mg/kg and 300 mg/kg i.p.) were administered during the last 15 days of treatment. Treatment with antioxidants had a strong therapeutic impact against myocardial damage caused by toluene, as evidenced by elevated levels of cardiotoxicity markers: The isoenzyme CK-MB (creatine kinase) and LDH (lactate dehydrogenase). Toluene significantly reduced glutathione levels, increased lipid peroxidation, and decreased the activities of glutathione reductase (GR) and glutathione peroxidase (GPx), antioxidant enzymes that are markers of oxidative stress. ALA and LC treatment significantly attenuated toluene-mediated-cardiac damage as well as oxidative damage, with LC being more effective than ALA. Furthermore, toluene induced apoptotic cardiac damage as evidenced by increased caspase-3 and caspase-12 activities. ALA and LC treatment attenuated these apoptotic actions of toluene. In addition, toluene increased calpain-2 activity, while ALA and LC ameliorated this effect. All of these results suggest that ALA and LC have a strong protective effect against the cardiotoxic effects of toluene by reducing oxidative stress, apoptotic tissue damage, and calpain-2 activity.

Drug dependence is a chronic brain disease characterized by craving and recurrent episodes of relapse. Tramadol HCl is a promising agent for withdrawal symptoms management, considering its relatively low abuse potential and safety. Oral administration, however, is not preferred in abstinence maintenance programs. Introducing an implantable, long-lasting formula is suggested to help outpatient abstinence programs achieve higher rates of treatment continuation. Tramadol implants (T350 and T650) were prepared on polycaprolactone polymer ribbons by the wet method. Male Wistar rats were adapted to heroin-conditioned place preference (CPP) at escalating doses (3–30 mg/kg, intraperitoneally, for 14 days). Implants were surgically implanted in the back skin of rats. After 14 days, the CPP score was recorded. Naloxone (1 mg/kg, intraperitoneally) was used to induce withdrawal on day 15, and symptoms were scored. Elevated plus maze and open field tests were performed for anxiety-related symptoms. Striata were analyzed for neurochemical changes reflected in dopamine, 3,4-dihydroxyphenyl acetic acid, gamma-aminobutyric acid, and serotonin levels. Brain oxidative changes including glutathione and lipid peroxides were assessed. The tramadol implants (T350 and T650) reduced heroin CPP and limited naloxone-induced withdrawal symptoms. The striata showed increased levels of 3,4-dihydroxyphenyl acetic acid, and serotonin and decreased levels of gamma-aminobutyric acid and dopamine after heroin withdrawal induction, which were reversed after implanting T350 and T650. Implants restore the brain oxidative state. Nonsignificant low naloxone-induced withdrawal score after the implant was used in naive subjects indicating low abuse potential of the implants. The presented tramadol implants were effective at diminishing heroin CPP and withdrawal in rats, suggesting further investigations for application in the management of opioid withdrawal.

Calvarial defects of bone present difficult clinical situations, and their restoration using biocompatible materials requires special treatments that enable bone regeneration. Magnesium phosphate (MgP) is known as an osteoinductive biomaterial because it contains Mg2+ ions and P ions that enhance the activity of osteoplast cells and help in bone regeneration. In this study, MgP and CuO-doped MgP were fabricated and characterized for their physicomechanical properties, particle size, morphology, surface area, antibacterial test, and in vitro bioactivity evaluation using the following techniques: X-rays diffraction, Fourier-transformer infrared, TEM, and Brunauer, Emmett and Teller (BET) surface area, X-rays photoelectron spectroscopy (XPS), and Scanning electron microscopy (SEM). Furthermore, these nanopowders were implanted in adult inbred male Wistar rats and studied after two periods (28 and 56 days). The results demonstrated that the obtained semiamorphous powders are in nanoscale (<= 50 nm). XPS analysis ensured the preparation of MgP as mono MgP and CuO were incorporated in the structure as Cu2+. The bioactivity was supported by the observation of calcium phosphate layer on the nanopowders' surface. The in vivo study demonstrated success of MgP nanopowders especially those doped with CuO in restoration of calvarial defect bone. Therefore, fabricated biomaterials are of great potential in restoration of bone calvarial defects.

The aim of the present study was to prepare and evaluate Piperine (PP) loaded chitosan lipid nanoparticles (PP-CLNPs) to evaluate its biological activity alone or in combination with the antidiabetic drug Metformin (MET) in the management of cognitive deficit in diabetic rats. Piperine was successfully loaded on CLNPs prepared using chitosan, stearic acid, Tween 80 and Tripolyphosphate (TPP) at different concentrations. The developed CLNPs exhibited high entrapment efficiency that ranged from 85.12 to 97.41%, a particle size in the range of 59.56–414 nm and a negatively charged zeta potential values (− 20.1 to − 43.9 mV). In vitro release study revealed enhanced PP release from CLNPs compared to that from free PP suspensions for up to 24 h. In vivo studies revealed that treatment with the optimized PP-CLNPs formulation (F2) exerted a cognitive enhancing effect and ameliorated the oxidative stress associated with diabetes. PP-CLNPs acted as an effective bio-enhancer which increased the potency of metformin in protecting brain tissue from diabetes-induced neuroinflammation and memory deterioration. These results suggested that CLNPs could be a promising drug delivery system for encapsulating PP and thus can be used as an adjuvant therapy in the management of high-risk diabetic cognitive impairment conditions.

Adolescents commonly co-abuse many drugs including anabolic androgenic steroids either they are athletes or non-athletes. Stanozolol is the major anabolic used in recent years and was reported grouped with cannabis. The current study aimed at evaluating the biochemical and histopathological changes related to the hypertrophic effects of stanozolol and/or cannabis whether in condition of exercise practice or sedentary conditions. Adult male Wistar albino rats received either stanozolol (5 mg/kg, s.c), cannabis (10 mg/kg, i.p.), and a combination of both once daily for two months. Swimming exercise protocol was applied as a training model. Relative heart weight, oxidative stress biomarkers, cardiac tissue fibrotic markers were evaluated. Left ventricular morphometric analysis and collagen quantification was done. The combined treatment exhibited serious detrimental effects on the heart tissues. It increased heart tissue fibrotic markers (Masson’s trichrome stain (p < 0.001), cardiac COL3 (p < 0.0001), and VEGF-A (p < 0.05)), lowered heart glutathione levels (p < 0.05) and dramatically elevated oxidative stress (increased malondialdehyde (p < 0.0001) and 8-OHDG (p < 0.0001)). Training was not ameliorating for the observed effects. Misuse of cannabis and stanozolol resulted in more hypertrophic consequences of the heart than either drug alone, which were at least largely assigned to oxidative stress, heart tissue fibrotic indicators, histological alterations, and morphometric changes.

Background Seizures are considered to be the most common symptom encountered in emergency- rushed tramadol-poisoned patients; accounting for 8% of the drug-induced seizure cases. Although, diazepam clears these seizures, the risk of central respiratory depression cannot be overlooked. Henceforth, three adsorbing composites were examined in a tramadol acute intoxication mouse model. Methods Calcium Silicate (Wollastonite) either non-doped or wet doped with iron oxide (3%Fe 2 O 3 ) or zinc oxide (30% ZnO) were prepared. The composites’ adsorption capacity for tramadol was determined in vitro. Tramadol intoxication was induced in Swiss albino mice by a parenteral dose of 120 mg/kg. Proposed treatments were administered within 1 min at 5 increasing doses, i.p. The next 30 min, seizures were monitored as an intoxication symptom. Plasma tramadol concentration was recorded after two hours of administration. Results The 3% Fe 2 O 3 -containing composite (CSFe3), was found to be composed of mainly wollastonite with very little alpha–hematite. On the other hand, hardystonite and wellimite were developed in the 30%ZnO-containing composite (CSZn3). Micro-round and irregular nano-sized microstructures were established (The particle size of CS was 56 nm, CSFe3 was 49 nm, and CSZn3 was 42 nm). The CSZn3 adsorption capacity reached 1497 mg of tramadol for each gram. Tramadol concentration was reduced in plasma and seizures were inhibited after its administration to mice at three doses. Conclusion The calcium silicate composite doped with ZnO presented a good resolution of tramadol-induced seizures accompanied by detoxification of blood, indicating its potential for application in such cases. Further studies are required.

Nowadays energy drinks (EDs) are widely used among teenagers. One of the most popular EDs in Egypt is Red BullR (RB). The aim of this study was to evaluate the chronic effects of RB on gastric acidity, oxidative stress, and inflammation in pylorus-ligated rats. Thirty-two adult male albino rats were divided into 4 groups; Control animals were given distilled water instead of a beverage. RB was given in doses of 5, 7.5, and 10 ml/kg, p.o., twice daily for 28 days in pylorus-ligated rats. The effects of different doses of RB were investigated on body weight, gastric acidity, and volume and pH of gastric secretions. Biochemical indices of oxidative status including malondialdehyde (MDA), glutathione (GSH), and nitric oxide (NO) were also measured. In addition, interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) were evaluated. Pretreatment with RB significantly increased body weight, gastric juice volume, acidity, and decreased pH in a dose-dependent manner. Moreover, oral administration of RB resulted in a significant increase in levels of MDA, NO, IL-6, and TNF-α along with decreasing GSH in stomach homogenate. The stomach of rats treated with RB showed sporadic focal records of apoptotic bodies in lining mucosal cells. Moreover; higher records of mucosal/submucosal inflammatory cell infiltrate were observed with more severe submucosal edema. Chronic consumption of RB increased gastric acidity, oxidative stress, and inflammation along with decreasing mucus secretion in rat stomach.

The current study was conducted to examine an innovative method for synthesizing gold nanoparticles (AuNPs) from an aqueous sweet granadilla (Passiflora ligularis Juss) P. ligularis. Furthermore, the synthesized AuNPs were used to explore their potential neuroprotective impact against propionic acid (PPA)-induced autism. A sweet granadilla extract was used to achieve the synthesis of AuNPs. The structural and dimensional dispersion of AuNPs were confirmed by different techniques, including UV–Vis spectrophotometer (UV–Vis), X-ray Diffraction (XRD) Pattern, Energy Dispersive X-ray (EDX), Zeta potential, and High-Resolution Transmission Electron Microscopy (HRTEM) analysis. The AuNPs mediated by P. ligularis adopt a spherical shape morphology and the particle size was distributed in the range of 8.43–13 nm without aggregation. Moreover, in vivo, the anti-autistic effects of AuNPs administration were higher than those of P. ligularis extract per second. In addition, the reduced anxiety and neurobehavioral deficits of AuNPs were observed in autistic rats which halted the brain oxidative stress, reduced inflammatory cytokines, ameliorated neurotransmitters, and neurochemical release, and suppressed apoptotic genes (p < 0.05). The alleviated antiapoptotic gene expression and histopathological analysis confirmed that the treatment of AuNPs showed significant neural pathways that aid in reducing tissue damage and necrosis. The results emphasize that the biomedical activity was increased by using the green source synthesis P. ligularis -AuNPs. Additionally, the formulation of AuNPs demonstrates strong neuroprotective effects against PPA-induced autism that were arbitrated by a range of different mechanisms, such as anti-inflammatory, antioxidant, neuromodulator, and antiapoptotic effects.

Background/aim Regular and excessive use of general household disinfectants and hand sanitizers has increased since coronavirus disease 2019 (COVID-19) hit as per World Health Organization (WHO) recommendations. However, existing knowledge about hypochlorite use as a disinfectant is inadequate for the applied experimental conditions are generally not translated to real life. This study explores the effect of the regular use of the commonly recommended disinfectants such as alcohol-based solutions and 0.1% hypochlorite on the lung and liver tissues of rats. Materials and methods Sixteen Wistar rats were assigned to two housing conditions, first group cages were cleaned regularly with tap water. The second group was exposed to regular sanitization of the cages twice daily for 2 months using 70% alcohol followed by 1% hypochlorite solution, 30 min apart. Serum redox state was evaluated and serum liver enzymes were assessed. Lung and liver tissues were examined biochemically for inflammatory markers such as IL-1B, NF-kB, VEGF, and oxidant biomarkers such as MDA and antioxidant markers including GSH, SOD, and GPx. A histological examination was performed. Results Serum liver enzymes, antioxidants in serum or liver tissues and the inflammatory biomarkers in liver tissue were insignificantly changed, while lung tissue was inflamed and proceeded to fibrotic changes and the inflammatory biomarkers of IL-1β and NF-kβ, and VEGF of lung tissue were significantly elevated ( P < 0.05) after surface disinfectant exposure to alcohol followed by 0.1% hypochlorite solution for two months. Moreover, the GSH and GPx levels were significantly reduced ( P < 0.05), while the MDA level was significantly increased ( P < 0.05) in the serum and lungs of a disinfectant exposed group of rats. Conclusion Frequent and excessive exposure to alcohol followed by 0.1% hypochlorite solution even as recommended can pose a risk to the respiratory system. Their application in cleaning routine should be wisely considered.

We have examined the effects of four different polyphenols in attenuating heroin addiction using a conditioned place preference (CPP) paradigm. Adult male Sprague Dawley rats received heroin (alternating with saline) in escalating doses starting from 10 mg/kg, i.p. up to 80 mg/kg/d for 14 consecutive days. The rats were treated with distilled water (1 mL), quercetin (50 mg/kg/d), β-catechin (100 mg/kg/d), resveratrol (30 mg/kg/d), or magnolol (50 mg/kg/d) through oral gavage for 7 consecutive days, 30 min before heroin administration, starting on day 8. Heroin withdrawal manifestations were assessed 24 h post last heroin administration following the administration of naloxone (1 mg/kg i.p). Heroin CPP reinstatement was tested following a single dose of heroin (10 mg/kg i.p.) administration. Striatal interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) were quantified (ELISA) after naloxone-precipitated heroin withdrawal. Compared to the vehicle, the heroin-administered rats spent significantly more time in the heroin-paired chamber (p < 0.0001). Concomitant administration of resveratrol and quercetin prevented the acquisition of heroin CPP, while resveratrol, quercetin, and magnolol blocked heroin-triggered reinstatement. Magnolol, quercetin, and β-catechin blocked naloxone-precipitated heroin withdrawal and increased striatal IL-6 concentration (p < 0.01). Resveratrol administration was associated with significantly higher withdrawal scores compared to those of the control animals (p < 0.0001). The results of this study show that different polyphenols target specific behavioral domains of heroin addiction in a CPP model and modulate the increase in striatal inflammatory cytokines TNF-α and IL-6 observed during naloxone-precipitated heroin withdrawal. Further research is needed to study the clinical utility of polyphenols and to investigate the intriguing finding that resveratrol enhances, rather than attenuates naloxone-precipitated heroin withdrawal.

This study aimed to evaluate the antidepressant-like effects of aqueous extracts of miswak ( Salvadora persica ) and date palm ( Phoenix dactylifera ) and their combination on depression-like behaviors using a chronic unpredictable mild stress (CUMS) rat model of depression and to investigate the underlying possible mechanisms. Results showed that CUMS induced depression-like behaviors and anxiety in male rats, as determined by behavioral tests (FST, EPM, and OFT). CUMS significantly increased the levels of plasma malondialdehyde (MDA), cortisol, and pro-inflammatory cytokines (TNF-α and IL-6), in addition to enhancing acetylcholinesterase (ACHE) activity while plasma total antioxidant capacity and serotonin level were reduced. In the prefrontal cortex, CUMS decreased the expression of CREB and BDNF mRNA. However, aqueous extracts of miswak and date palm and their combination effectively ameliorated depressive-like behaviors, body weight loss, and oxidative stress induced by CUMS and restored serotonin and cortisol secretion to normal levels. Furthermore, the studied extracts improved the levels of plasma pro-inflammatory cytokines and CREB and BDNF mRNA expression in the prefrontal cortex. In conclusion, aqueous extracts of miswak and date palm have significant antidepressant-like effects on depression-like behaviors in CUMS model in rats. Moreover, their combination has higher antidepressant-like effects than either extract alone, suggesting that it may be an effective treatment for stress-induced depression-like behaviors acting through modulating pro-inflammatory cytokines and CREB/BDNF signaling pathway in the prefrontal cortex. Chronic stress is a major contributor to the development of depression. In recent years, there has been a significant increase in the use of herbal remedies for the treatment of a variety of diseases, particularly mood disorders. Because of the side effects encountered by antidepressant drugs such as anxiety, sexual dysfunction, loss of appetite, and inadequate response or developing tolerance to these medications, there is a need for more efficient and convenient antidepressant treatments. According to this study, aqueous extracts of miswak and date palm are effective treatments for stress-induced depression-like behaviors.

In ischemic stroke, the third most frequent cause of mortality in industrialized countries, therapeutic options have until now been limited to the first hours after disease onset. Cell transplantation has emerged in various neurological disorders, including experimental stroke, as a successful recovery-promoting approach also in the post-acute stroke phase. However, before envisaging any translation into humans of such promising cell-based approaches we still need to clarify: (i) the ideal cell source for transplantation, (ii) the most appropriate route of cell administration, and, last but not least, (iii) the best approach to achieve an appropriate and functional integration of transplanted cells into the host tissue. Here we discuss, with special emphasis on neural stem/precursor cells, potential mechanisms that may be involved in the action of cell-based therapies in stroke.

Pesticide residues in food is a major health hazard. Contamination of pesticide residues in common Egyptian fruits was studied. Samples of peach and cantaloupe (500g each) from five different local markets were examined. Fruit samples were liquid-liquid extracted. Thiamethoxam was detected in three cantaloupe samples at 0.085 mg/kg and acetamiprid in two samples at 0.24 mg/kg, whereas acetamiprid was detected in all the peach samples at 0.08 mg/kg. Detected levels were below MRL. Male albino rats were given either distilled water (0.2 ml) or acetamiprid (17 µg/kg) or thiamethoxam (6 µg/kg) orally for 6 consecutive days. Doses were calculated according to the estimated average daily intake of fruits (~100 g) and extrapolated to rats. Thereafter, oxidative state of liver and brain was evaluated besides liver function tests and assessment of histopathological features. Serum GPT was in normal range in thiamethoxam-exposed rats, while it showed a marked increase in acetamiprid-exposed rats. sGOT was elevated after exposure to both compounds, though total protein and sGSH were not affected. Oxidative insult was expressed in liver tissue through increased MDA, NO and protein carbonyl contents, although the antioxidant GSH pool was not depleted after pesticide exposure. Acetamiprid boosted the cytokine IL-1 level. Histopathological examination of liver tissue showed inflammatory degenerative changes. Acetamiprid affected the DNA integrity in blood. Brain oxidative state was not changed. These pesticides should be further studied for guiding local regulations towards safer use to avoid long term associated health hazards.

Objectives: Natural antioxidants particularly carotenoids have been associated with a lowered risk for stroke and cerebrovascular diseases.The present study proposes a new microbial source of carotenoid-rich bio-pigment and investigates its potency in mitigating ischemic stroke in an animal model. Methods:A yeast isolate rich in carotenoid pigment was defined morphologically and physiologically, recognized by 18S rDNA as Rhodotorula mucilaginosa G20with a similarity of 100%, then submitted to Gen Bank (accession number KY271337.1).The extracted pigment was analyzed using high-performance liquid chromatography invitro.Furthermore, an in-vivo rat model was assessed to investigate the effect of the extracted pigment against Endothelin-1 (ET-1) induced focal cerebral ischemia.Rats were assigned into four groups: Group (1) normal control rats received saline.Group (2): sham-operated rats received saline, Group (3): rats received ET-1.Group (4): rats received extracted pigment and ET.Results: HPLC results revealed that the extracted yeast pigment consists mainly of neoxanthin and β-carotene.Invivo, pretreatment with extracted pigment significantly enhanced the grip strength, restored impaired vertical forelimb use induced by ET-1 in rats, halted oxidants biomarkers, and triggered antioxidant mediators.Moreover, it suppressed inflammatory and apoptotic markers.The histological and structural deterioration in the ventral subiculum was deterred. Conclusions:Based on these encouraging results, The extracted microbial carotenoid pigment production can be considered efficient and economical and proves to be a promising approach for ameliorating cerebral ischemic injuries.