Protein click chemistry and its potential for medical applications.

A revolution in chemical biology occurred with the introduction of click chemistry. Click chemistry plays an important role in protein chemistry modifications, providing specific, sensitive, rapid, and easy-to-handle methods. Under physiological conditions, click chemistry often overlaps with bioorthogonal chemistry, defined as reactions that occur rapidly and selectively without interfering with biological processes. Click chemistry is used for the posttranslational modification of proteins based on covalent bond formations. With the contribution of click reactions, selective modification of proteins would be developed, representing an alternative to other technologies in preparing new proteins or enzymes for studying specific protein functions in different biological processes. Click-modified proteins have potential in diverse applications such as imaging, labeling, sensing, drug design, and enzyme technology. Due to the promising role of proteins in disease diagnosis and therapy, this review aims to highlight the growing applications of click strategies in protein chemistry over the last two decades, with a special emphasis on medicinal applications.

Cell-Penetrating Peptides: Promising Therapeutics and Drug-Delivery Systems for Neurodegenerative Diseases.

Currently, one of the most significant and rapidly growing unmet medical challenges is the treatment of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). This challenge encompasses the imperative development of efficacious therapeutic agents and overcoming the intricacies of the blood-brain barrier for successful drug delivery. Here we focus on the delivery aspect with particular emphasis on cell-penetrating peptides (CPPs), widely used in basic and translational research as they enhance drug delivery to challenging targets such as tissue and cellular compartments and thus increase therapeutic efficacy. The combination of CPPs with nanomaterials such as nanoparticles (NPs) improves the performance, accuracy, and stability of drug delivery and enables higher drug loads. Our review presents and discusses research that utilizes CPPs, either alone or in conjugation with NPs, to mitigate the pathogenic effects of neurodegenerative diseases with particular reference to AD and PD.

Effects of land use/cover change on heavy metal distribution of soils in wetlands and ecological risk assessment.

This study aimed to determine the impact of land use/cover changes on the heavy metal content in the Sultan Marshland and surrounding area and assess the pollution status. 54 topsoil samples (0-20 cm) were collected from the Rangeland, Farmland, Scrubland, Southern Marshland, Northern Marshland, and Dry Lake areas. The heavy metal contents of the soil samples (Cr, Pb, Fe, Zn, Cu, Co, Mn, Cd, Mo, As, and Ni) were determined using ICP-MS and ICP-OES devices. The impact of land use/cover change on soil heavy metal content was evaluated using variance analysis, while differences between groups were identified using the Duncan test. Principal Component Analysis (PCA) was conducted to identify potential sources of heavy metals. The contamination status of the soils was evaluated based on land use/cover using the Contamination Factor (Cf), Pollution Load Index (PLI), Ecological Risk Factor (Er), and Potential Ecological Risk Index (PERI). Changes in land use/cover around the Sultan Marshlands affected heavy metal distribution of the soils except for Cd. Among all land use/cover types, Fe concentration was the highest in the soils, while Cd concentration was the lowest. Soils in Southern Marshland exhibited higher average concentrations of Cr, Fe, Zn, Co, Cu, and Ni compared to other land uses/covers. Farmlands and rangelands had higher concentrations of Cd, As and Pb. Land use/cover was ranked based on the total heavy metal load in the following order in terms of average values: Southern Marshland > Scrubland > Farmland > Rangeland > Northern Marshland > Dry Lake. According to Cf, the soils in the Dry Lake were exposed to considerable levels of As contamination. Based on PLI, half of the soil sampling points in the Southern Marshland soils showed a degradation in environmental quality. Er indicated that all land uses moderately polluted with Cd. According to the average PERI, all soils under different land use/cover types were categorized as having a low ecological risk. It was believed that heavy metals originated from both natural and human activities. To ensure the sustainability of the ecosystem and to mitigate the risk of heavy metal pollution entering the food chain, it is recommended to manage farming and mining activities and land use habits.

Evaluation of the frequency of ABO and Rh-Hr blood-group systems in different acquired cataracts type.

OBJECTIVES: This study evaluated the relationship between acquired cataract's different types and the ABO and Rh blood classes. METHODS: Overall, 520 patients, by randomized sampling method, participated in this retrospective cross-sectional study. After reviewing the patient's medical records and laboratory results, the patient's demographics, ABO group, Rh, and cataract type were documented. RESULTS: A total of 520 patients were included in the research, with a mean age of 67.57 ± 11.85. Most of them were female (n = 286, 55%). Mix (n = 230, 44%) and nuclear sclerotic (NS) (n = 167, 32%) cataracts were the most common types. The posterior subcapsular cataract (PSC) prevalence in females was significantly higher than in males (16.1% vs.7.3% p = 0.002). Also, men had more NS cataracts than females (89, 38% vs. 78, 27.3%) (p = 0.009). Patients with PSC were significantly younger than others (all p-values < 0.001). Our results showed that cataract types are independent of blood group types and Rh (P > 0.05). CONCLUSION: Although our findings showed that cataract types are independent of blood group types and Rh, they can be compared with future studies on the association of other Blood-Group Systems in developing acquired cataracts.

The Upregulation of HLA-G1 and miRNA-34a in Lens Epithelial Cells of Diabetic Retinopathy Patients.

Background: Retinopathy of diabetes is a chronic diabetes mellitus complication affecting retinal vessels, and some ocular complications' molecular mechanisms remain obscure. Objective: To evaluate the expression of HLA-G1, HLA-G5, miRNA-181a, and miRNA-34a in the lens epithelial cells of patients with retinopathy of diabetes. Methods: In a case-control study, 30 diabetic patients with retinopathy, 30 diabetic patients without retinopathy, and 30 cataract patients without diabetes mellitus as the control group were enrolled after a full description with details about the study methods and objectives. The expression of HLA G1, HLA G5, miRNA-181a, and miRNA-34a in lens epithelial cells was assessed by quantitative RT PCR. Moreover, the levels of HLA-G protein in aqueous humor were evaluated by the ELISA method. Results: HLA-G1 expression was significantly upregulated in the retinopathy group (P=0.003). The aqueous humor of diabetic retinopathy patients contained significantly higher levels of HLA-G protein compared with the non-diabetic patients (P=0.001). miRNA-181a was significantly downregulated in the diabetic retinopathy group compared with the patients without diabetes (P=0.001). In addition, miRNA-34a was upregulated in the retinopathy group (P=0.009). Conclusion: Taken together, the present results showed that HLA-G1 and miRNA-34a can be valuable markers for diabetic retinopathy. Our data offers new perspectives for improving the control of inflammation in the lens epithelial cells by considering HLA-G and miRNA.

Selective detection of aspartic acid in human serum by a fluorescent probe based on CuInS2@ZnS quantum dots.

The importance of amino acids identification in biological systems has created expectation to develop a sensitive method for their detection. In this work, an efficient core-shell fluorescent quantum dots (QDs) probe based on CuInS2 (CIS) core and ZnS shell with the formula of CIS@ZnS QDs were synthesised and characterised by FT-IR, UV-Vis, TEM and DLS techniques. The probe was used for detection of Aspartic Acid (Asp) in an aqueous media. The probe shows a remarkable fluorescence response toward Asp over the other amino acids such as valine (Val), glycine (Gly), phenylalanine (Phe), leucine (Leu), alanine (Ala), serine (Ser), isoleucine (Iso), threonine (Thr), methionine (Met), Glutamic acid (Glu), histidine (His), arginine (Arg), cysteine (Cys), asparagine (Asn), glutamine (Gln), citrolline (Cit), sarcosine (Sar) and ornithine (Orn) the fluorescence intensity quenches significantly upon addition of Asp in an aqueous media. The CIS@ZnS QDs probe showed a selective and sensitive response by fluorescence quenching toward Asp in the concentration range of 8.3 × 10-7 M to 3.3 × 10-4 M with the detection limit of 7.8 × 10-8 M. The application of the sensor in determination of Asp in real human serum sample was also investigated. Based on our library search, the all reported fluorescent sensors for detection of Asp, either show a remarkable sensitivity to Glu acid. Luckily, this is the first presented optical probe able to detect just Asp from the solutions containing various amino acids.

Multifunctional Quasi-Solid-State Zinc-Sulfur Battery.

The introduction of structural energy storage devices into emerging markets, such as electric vehicles, is predominately hindered by weak energy density, safety concerns, and immaturity of the field in materials. Herein, fabrication and testing of a freeze-resistant, multifunctional quasi-solid-state zinc-sulfur battery (ZnS) are reported. To this end, an electrostatic spray coating technique was used to deposit a thin layer of sulfur on the highly porous, unidirectional activated carbon nanofibers (A-CNFs) as a load-bearing cathode. This technique could fill micro- and mesopores, and microsized channels with sulfur, achieving an extensive sulfur loading of 60 wt %. Several drawbacks of structural energy storage devices (applicability under varied climate conditions, poor electrochemical performance and mechanical properties) are addressed by initiating an antifreezing hydrogel electrolyte with a failure strain of over 200%. This electrolyte possesses ethylene glycol and an I2 additive as an antifreezing agent and redox mediator, respectively. The as-assembled ZnS battery offers a high energy density of 283 Wh/kg based on the CNF-S cathode (149 Wh/kg based on the ZnS cell) and mechanical properties beyond state-of-the-art structural energy storage devices with a tensile strength of 377 MPa, Young's modulus of 16.7 GPa, and energy-to-failure of 4.5 MJ/m3. The electrochemomechanical properties of the ZnS battery were also investigated to elucidate the effects of electrochemical energy storage on mechanical properties and vice versa. Overall, the ZnS battery outperforms state-of-the-art structural energy storage devices in terms of energy storage and load-bearing capabilities.

Impact of Ionic Liquid Additives and Inorganic Fullerene-Like Tungsten Disulfide on Friction and Wear under Aqueous Environments.

Aqueous lubricants are gaining attention due to significant advantages such as being environmentally friendly, tunable, and thermally stable. The oil and gas industry can use such additives to utilize in water-based fluids for applications where small sliding velocities and large lateral forces require enhanced lubrication. This investigation aims to compare the effects of two different additives: (i) inorganic fullerene-like tungsten disulfide (IF-WS2) and (ii) an alkanolamine ionic liquid denoted as AA-IL. Both additives were paired with three different base fluids, deionized water (DIW), aqueous NaCl, and aqueous CaCl2, to measure the impact on fluids commonly utilized in the field. The addition of IF-WS2 to all three solutions resulted in a 30-60% decrease in the coefficient of friction (COF) and wear. Surface analysis by X-ray photoelectron spectroscopy (XPS) and energy-dispersive X-ray spectroscopy (EDS) showed that the formation of a tribofilm (tungsten oxide layer) is primarily responsible for tribological improvements. The AA-IL did not show evidence of any chemical interaction. Instead, a physically bonded film of the AA-IL on the steel surface enabled the improved COF (40-50% reduction) and wear response. Both additives are effective in very small amounts and provide excellent wear and friction reduction properties.

Conversion of 2D MXene to Multi-Low-Dimensional GerMXene Superlattice Heterostructure.

Integration of 2D structures into other low-dimensional materials results in the development of distinct van der Waals heterostructures (vdWHSs) with enhanced properties. However, obtaining 2D-1D-0D vdWHSs of technologically useful next generation materials, transition-metal carbide MXene and monoelemental Xene nanosheets in a single superlattice heterostructure is still challenging. Here, the fabrication of a new multidimensional superlattice heterostructure "GerMXene" from exfoliated M3X2T x MXene and hydrogenated germanane (GeH) crystals, is reported. Direct experimental evidence for conversion of hydrothermally activated titanium carbide MXene (A-MXene) to GerMXene heterostructure through the rapid and spontaneous formation of titanium germanide (TiGe2 and Ti6Ge5) bonds, is provided. The obtained GerMXene heterostructure possesses enhanced surface properties, aqueous dispersibility, and Dirac signature of embedded GeH nanosheets as well as quantum dots. GerMXene exhibits functional bioactivity, electrical conductivity, and negative surface charge, paving ways for its applications in biomedical field, electronics, and energy storage.

An On-off Supramolecular Fluorescence Switch for Detection of Pb2+ Ions and Vitamin C.

ß-cyclodextrin-hydroxyquinoline functionalized graphene oxide (GO-CD-HQ) was facilely fabricated to monitor and quantitatively analyze cations in aqueous media. The optical probe was notably selective enhanced toward Pb2+ ions over the other tested ions like Cu2+, Hg2+, Ca2+, Na+, K+, Zn2+, Fe2+, Fe3+, Ag+, Mg2+, and Cd2+ at 468 nm as an emission wavelength. The probe was shown the best performance in pH value, 5, and optimum time 1 min. Absorption spectra have clearly confirmed the static type fluorescence enhancement mechanism of GO-CD-HQ. Under the optimal conditions, the detection limit of it and linear concentration range for Pb2+ ions were obtained as 3.72 × 10-5 M and (5-60) × 10-5 M, respectively. Additionally, the developed assay exhibited logic gate behavior with Pb2+ ions and vitamin C as a masking agent for cited ions.

In Silico Design and Evaluation of PRAME+FliCΔD2D3 as a New Breast Cancer Vaccine Candidate.

Background: The most prevalent cancer in women over the world is breast cancer. Immunotherapy is a promising method to effectively treat cancer patients. Among various immunotherapy methods, tumor antigens stimulate the immune system to eradicate cancer cells. Preferentially expressed antigen in melanoma (PRAME) is mainly overexpressed in breast cancer cells, and has no expression in normal tissues. FliCΔD2D3, as truncated flagellin (FliC), is an effective toll-like receptor 5 (TLR5) agonist with lower inflammatory responses. The objective of the present study was to utilize bioinformatics methods to design a chimeric protein against breast cancer. Methods: The physicochemical properties, solubility, and secondary structures of PRAME+FliCΔD2D3 were predicted using the tools ProtParam, Protein-sol, and GOR IV, respectively. The 3D structure of the chimeric protein was built using I-TASSER and refined with GalaxyRefine, RAMPAGE, and PROCHECK. ANTIGENpro and VaxiJen were used to evaluate protein antigenicity, and allergenicity was checked using AlgPred and Allergen FP. Major histocompatibility complex )MHC( and cytotoxic T-lymphocytes )CTL( binding peptides were predicted using HLApred and CTLpred. Finally, B-cell continuous and discontinuous epitopes were predicted using ABCpred and ElliPro, respectively. Results: The stability and solubility of PRAME+FliCΔD2D3 were analyzed, and its secondary and tertiary structures were predicted. The results showed that the derived peptides could bind to MHCs and CTLs. The designed chimeric protein possessed both linear and conformational epitopes with a high binding affinity to B-cell epitopes. Conclusion: PRAME+FliCΔD2D3 is a stable and soluble chimeric protein that can stimulate humoral and cellular immunity. The obtained results can be utilized for the development of an experimental vaccine against breast cancer.

Aldose reductase (AC)n gene polymorphism in Iranian patients with type 2 diabetic microangiopathy; a case-control study.

AIM: (AC)n promoter region of the aldose reductase (ALR) genes polymorphism has been associated with diabetic microvascular complications (MVCs). The aim of this study was to find the relationship between dinucleotide repeat (AC)n polymorphisms of the ALR gene and the occurrence of MVCs, such as diabetic retinopathy, neuropathy, and nephropathy in Iranian type 2 diabetic (T2D) patients. METHODS: This prospective case-control study was performed on T2D patients who were categorized into two groups based on the presence or absence of diabetic microangiopathy. All patients were provided informed consent. After extracting genomic DNA, the (AC)n of the ALR gene was determined using Polymerase chain reaction (PCR). RESULTS: Thirteen alleles of the (AC)n gene polymorphism were detected including Z + 16, Z + 14, Z + 8, Z + 6, Z + 4, Z + 2, Z, Z - 2, Z - 4, Z - 6, Z - 8, Z - 10, and Z - 12. The frequency of the Z - 4 allele was significantly higher in patients with retinopathy, nephropathy, and autonomic neuropathy compared with those with long-term uncomplicated diabetes (P < 0.001, P < 0.001, P = 0.031, respectively). After controlling for baseline risk factors, we found that the carrier of the Z - 4 allele of ALR (AC)n polymorphism had a higher risk of diabetic retinopathy and diabetic nephropathy (P < 0.001). The homozygosity for the Z - 4 allele was found to be associated with diabetic microangiopathy. CONCLUSION: Our results showed that ALR (AC)n gene polymorphism in Iranian patients with type 2 diabetes independently, predispose retinal, renal and neural microvascular to diabetic complications.

Development of Fluorine-Free Tantalum Carbide MXene Hybrid Structure as a Biocompatible Material for Supercapacitor Electrodes.

The application of nontoxic 2D transition-metal carbides (MXenes) has recently gained ground in bioelectronics. In group-4 transition metals, tantalum possesses enhanced biological and physical properties compared to other MXene counterparts. However, the application of tantalum carbide for bioelectrodes has not yet been explored. Here, fluorine-free exfoliation and functionalization of tantalum carbide MAX-phase to synthesize a novel Ta4C3Tx MXene-tantalum oxide (TTO) hybrid structure through an innovative, facile, and inexpensive protocol is demonstrated. Additionally, the application of TTO composite as an efficient biocompatible material for supercapacitor electrodes is reported. The TTO electrode displays long-term stability over 10 000 cycles with capacitance retention of over 90% and volumetric capacitance of 447 F cm-3 (194 F g-1) at 1 mV s-1. Furthermore, TTO shows excellent biocompatibility with human-induced pluripotent stem cells-derived cardiomyocytes, neural progenitor cells, fibroblasts, and mesenchymal stem cells. More importantly, the electrochemical data show that TTO outperforms most of the previously reported biomaterials-based supercapacitors in terms of gravimetric/volumetric energy and power densities. Therefore, TTO hybrid structure may open a gateway as a bioelectrode material with high energy-storage performance for size-sensitive applications.

Chemoprevention of Prostate Cancer Cells by Vitamin C plus Quercetin: role of Nrf2 in Inducing Oxidative Stress.

To assess the effect of sequential treatment with Vitamin C (VC) and Quercetin (Q) on Nrf2-related oxidative stress in PC3 and DU145 cells, viability was measured by MTT assay. Intracellular ROS levels were determined, using 2'-7'-dichlorodihydrofluorescein diacetate fluorescent as a probe. Nrf2 gene expression was investigated by quantitative reverse transcription polymerase chain reaction, and Nrf2 protein levels were defined by western blot analysis. The activity of glutathione peroxidase (GPx), glutathione reductase (GR), nicotinamide adenine dinucleotide phosphate dehydrogenase quinone 1 (NQO1) and hemeoxygenase 1 (HO-1) enzymes were measured. The IC50 values for VC + Q were 263.03-372.1 µM and 144.2-194.1 µM respectively and 200 µM VC + 50 µM Q (dose no.1) and 100 µM VC + 75 µM Q (dose no.2) were selected. Sequential treatment of PC3 cells led to a significant reduction of Nrf2 mRNA expression and protein levels in addition to a significant reduction of GPx, GR and NQO1 enzymatic activity. Although the data was slightly different for DU145 cells after the treatments, in terms of Nrf2 gene expression, we obtained the same results. Our study revealed the significant effects of sequential treatment with VC + Q on Nrf2 suppression in prostate cancer cells.

Heerfordt-Waldenström Syndrome, A Rare Presentation of Sarcoidosis in a Patient with Old Ocular Toxoplasmosis.

BACKGROUND: There are similarities between the ophthalmic presentation of toxoplasmosis and sarcoidosis, and there are some concerns of immunosuppressive treatments for sarcoidosis, which may lead to T. gondii reactivation. We report a rare case with acute sarcoidosis (Heerfordt- Waldenström syndrome) with a history of ocular toxoplasmosis from the North of Iran. CASE PRESENTATION: The patient was a 36-year-old woman with left painful eye and swollen parotid, right facial paresis, maculopapular rash in left eyebrow and erythema nodosa on both legs. Anti-Toxoplasma IgG antibody was positive, and IgM was not detectable. Radiographic findings on the chest revealed bilateral hilar lymphadenopathy. The initial treatment was sulfamethoxazole- trimethoprim to prevent the recurrence of retinal toxoplasmosis and corticosteroid and mycophenolate mofetil for sarcoidosis. The patient showed clinical and vision improvement without recurrences during three months follow-up. DISCUSSION: Ophthalmological examinations and laboratory tests to rule out toxoplasmosis could be considered in known cases of sarcoidosis, particularly in ocular sarcoidosis status. To the best of our knowledge, this is the first report of comorbidity of ocular toxoplasmosis/sarcoidosis from Iran and possibly the world.

Darolutamide as a Second-Generation Androgen Receptor Inhibitor in the Treatment of Prostate Cancer.

Prostate cancer (PC) is known as the most frequent cancer among men in the world. Androgen Deprivation Therapy (ADT) is one of the initial treatment approaches in the PC therapy and various drugs can be used in routine Hormonal therapy for PC therapy. Nevertheless, PC cells can survive and continue their growth via different mechanisms which lead to their resistance to common treatments i.e., Enzalutamide. olutamide (ODM-201) is a second-generation androgen receptor (AR) inhibitor with a new chemical structure and has a high affinity to the AR. Darolutamide does not cross the blood-brain barrier and for this reason, reduces the possibility of seizures. Darolutamide can also inhibit the transcriptional activity of several AR mutant variants (F877L, F877L/T878A, and H875Y/T878A), which are Enzalutamide resistant. In this review, we reviewed the results of different studies: in vitro, animal model and phase 1, 2 and 3 clinical trials (ARADES, ARAFOR and ARAMIS). We shall discuss worldwide phase 2 and 3 clinical trials (ARASENS and ODENZA) that are in progress, in order to demonstrate the advantages of Darolutamide consumption in different groups of patients. Darolutamide has shown high potential in inhibiting the growth of MR49F (Enzalutamide resistant PC cells) and VCaP (Castration-resistant PC cells) cell lines and transcriptional activities of AR. Fewer doses of Darolutamide are needed compared to Enzalutamide. The drug had significant anti-tumor activity and no effect on serum testosterone levels in animal models. Darolutamide demonstrates its safety and efficacy in different studies and was well tolerated nearly in all of the patients.

Reply to: "Agreement analysis" / Respuesta a: "Análisis de concordancia"

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Novel Biocompatible Amino Acids-Functionalized Three-dimensional Graphene Foams: As the Attractive and Promising Cisplatin Carriers for Sustained Release Goals.

Application of amino acids-immobilized porous materials for drug delivery studies has been attracted a lot of attention in the recent years. In this study, amino acids-grafted graphene foams were prepared by anchoring of Alanine (Ala), Cysteine (Cys) and Glycine (Gly) amino acids on the surface of graphene oxide (GO) nanostructures and used as the novel biocompatible carriers to control releasing of the cisplatin as the cytotoxic anticancer drug. The characterization of prepared compounds was done by the FT-IR, Raman, TGA, N2 adsorption-desorption isotherms, SEM, and TEM techniques. Adsorption and in vitro release behavior of amino acids-functionalized foams were studied using ICP standard method. The results show that the drug loading amount and the drug releasing rate are significantly enhanced upon functionalization process. The Ala-Foam sample with the larger surface area and pore volume showed a higher loading content (4.53%) than other samples. In addition, the MTT test on the two MCF-7 and HepG2 human cancer cell lines exhibited an acceptable biocompatibility and sustainable drug releasing from the carriers up to 48 h, leading to the dosage frequency decrease and the patient compliance improvement.

Prevalence of Sleep Disturbance and Potential Associated Factors among Medical Students from Mashhad, Iran.

METHODS: In this cross-sectional study, 315 medical students chosen by stratified random sampling participated in the academic year 2018-2019. The Pittsburgh Instrument and DASS-21 questionnaire were used to evaluate sleep quality and anxiety, depression, and stress, respectively. Also, demographic, educational, and socioeconomic information was collected. SPSS 16 software was used for data analysis. RESULTS: Out of 300 students who completed the questionnaires, 165 (55%) were male, with a mean age of 21.94 ± 2.28 years old. The prevalence of poor sleep quality was 51.3%. We did not find significant associations among age, sex, and poor sleep quality. Concurrent psychological symptoms such as stress, depression, and anxiety were significantly associated with sleep disorders. After adjusting variables in the multivariable regression model, depression (OR = 2.81, 95% CI: 1.35-5.87; p = 0.006) and the number of hours spent on using smartphones in 24 hours (OR = 1.13, 95% CI: 1.02-1.25; p = 0.01) were significantly associated with poor sleep quality among medical students. CONCLUSION: The prevalence of poor sleep quality among medical students was high, and we found that increased use of smartphones during the day and depression were associated with sleep disorders.

Rutin via Increase in the CA3 Diameter of the Hippocampus Exerted Antidepressant-Like Effect in Mouse Model of Maternal Separation Stress: Possible Involvement of NMDA Receptors.

METHODS: Mouse neonates were exposed to MS paradigm 3 hours daily from postnatal days (PND) 2 to 14. The control and MS mice were divided separately into 16 groups (n = 8) (8 groups for each set) including mice that received normal saline, mice that received rutin at doses of 10, 50, and 100 mg/kg, mice that received NMDA at a dose of 150 mg/kg, mice that received ketamine (NMDA antagonist) at a dose of 0.25 mg/kg, mice that received NMDA antagonist plus a subeffective dose of rutin, and mice that received NMDA plus an effective dose of rutin. Forced swimming test (FST) was performed. Afterwards, the hippocampus was evaluated in cases of histopathological changes as well as expression of NR2A and NR2B genes. RESULTS: Rutin significantly reduced immobility time in the FST. The expression of NR2A and NR2B subunits of NMDA receptor in MS mice was significantly higher than that in the control group. Rutin significantly decreased the expression of NR2B and NR2A subunits in the hippocampus. The CA3 diameter and percentage of dark neurons in the hippocampus of MS mice significantly decreased and increased, respectively, which partially reversed following rutin administration. CONCLUSION: Rutin, partially, through a neuroprotective effect on the hippocampus exerted antidepressant-like effect. We concluded that NMDA receptors, at least in part, mediated the beneficial effect of rutin.