The link between serum neuregulin-1 and atherogenic index in type 2 diabetes mellitus.

BACKGROUND: Neuregulin-1(NRG-1) is a protein that belongs to the group of epidermal growth factors. It plays vital roles in anti-fibrotic effects on the myocardium. The current paper explores the role of NRG-1 in type 2 diabetes mellitus (T2DM) and its relation to atherogenic index as a factor for increasing cardiovascular disease(CVD) risk. MATERIAL AND METHODS: In this study, 79 diabetes mellitus patients are independent insulin. These patients consisted of 53 females and 26 males their age were ranged 40-67 years. They were divided into two groups depending on the atherogenic index of plasma (AIP). Group I including48 diabetic patient with high risk of CVD and group II including 31 diabetic patients without risk CVD. Forty healthy individuals were included as control. RESULT: When compared to the control group, the serum levels of NRG-1 were significantly lower (p = 0.01). Additionally, group I had a much lower NRG-1level than group II. The results of multiple stepwise regression showed that the only independent predictor for NRG-1 level prediction was AIP (ß = - 0.600, P = 0.040). When comparing the diabetic patients with high risk factors for CVD to the healthy subject group, the AUC was outstanding (AUC = 0.889, P = 0.001) and had a high diagnosis. CONCLUSIONS: We proved low NRG-1 levels in diabetic patients and the association of highest NRG-1 amounts to a better AIP. Moreover, the measurement of NRG-1 levels could be beneficial as laboratory markers to monitor for increasing CVD risk in type 2 diabetes mellitus.

Heterologous DNA Prime/Protein Boost Immunization Targeting Nef-Tat Fusion Antigen Induces Potent T-cell Activity and in vitro Anti-SCR HIV-1 Effects.

BACKGROUND: Heterologous combinations in vaccine design are an effective approach to promote T cell activity and antiviral effects. The goal of this study was to compare the homologous and heterologous regimens targeting the Nef-Tat fusion antigen to develop a human immunodeficiency virus-1 (HIV-1) therapeutic vaccine candidate. METHODS: At first, the DNA and protein constructs harboring HIV-1 Nef and the first exon of Tat as linked form (pcDNA-nef-tat and Nef-Tat protein) were prepared in large scale and high purity. The generation of the Nef-Tat protein was performed in the E. coli expression system using an IPTG inducer. Then, we evaluated and compared immune responses of homologous DNA prime/ DNA boost, homologous protein prime/ protein boost, and heterologous DNA prime/protein boost regimens in BALB/c mice. Finally, the ability of mice splenocytes to secret cytokines after exposure to single-cycle replicable (SCR) HIV-1 was compared between immunized and control groups in vitro. RESULTS: The nef-tat gene was successfully subcloned in eukaryotic pcDNA3.1 (-) and prokaryotic pET-24a (+) expression vectors. The recombinant Nef-Tat protein was generated in the E. coli Rosetta strain under optimized conditions as a clear band of ~ 35 kDa detected on SDS-PAGE. Moreover, transfection of pcDNA-nef-tat into HEK-293T cells was successfully performed using Lipofectamine 2000, as confirmed by western blotting. The immunization studies showed that heterologous DNA prime/protein boost regimen could significantly elicit the highest levels of Ig- G2a, IFN-γ, and Granzyme B in mice as compared to homologous DNA/DNA and protein/protein regimens. Moreover, the secretion of IFN-γ was higher in DNA/protein regimens than in DNA/DNA and protein/protein regimens after exposure of mice splenocytes to SCR HIV-1 in vitro. CONCLUSION: The chimeric HIV-1 Nef-Tat antigen was highly immunogenic, especially when applied in a heterologous prime/ boost regimen. This regimen could direct immune response toward cellular immunity (Th1 and CTL activity) and increase IFN-γ secretion after virus exposure.

Physio-biochemical and DNA methylation analysis of the defense response network of wheat to drought stress.

In the present work, physio-biochemical and DNA methylation analysis were conducted in wheat (Triticum aestivum L.) cultivars "Bolani" (drought-tolerant) and "Sistan" (drought-sensitive) during drought treatments: well-watered (at 90% field capacity (FC)), mild stress (at 50% FC, and severe stress (at 25% FC). During severe stress, O2•- and H2O2 content in cultivar Sistan showed significant increase (by 1.3 and 2.5-fold, respectively) relative to cultivar Bolani. In Bolani, the increased levels of radical scavenging activity (by 32%), glycine betaine (GB) (by 11.44%), proline (4-fold), abscisic acid (by 63.76%), and more stability of relative water content (RWC) (2-fold) were observed against drought-induced oxidative stress. Methylation level significantly decreased from 70.26% to 60.64% in Bolani and from 69.06% to 59.85% in Sistan during stress, and higher decreased tendency was related to CG and CHG in Bolani but CG in Sistan under severe stress. Methylation patterns showed that the highest polymorphism in Bolani was mainly as CG. As the intensity of stress increased, the enhanced physio-biochemical responses of Bolani cultivar were accompanied by a more decrease in the number of unchanged bands. According to heat map analysis, the highest difference (84.38%) in methylation patterns was observed between control and severe stress. Multivariate analysis using principal component analysis (PCA) showed a cultivar-specific methylation during stress and that methylation changes between cultivars are much higher than that of within a cultivar. Higher methylation to demethylation in Bolani (30.06 vs. 22.12%) compared to that of cultivar Sistan (23.21 vs. 30.15%) indicated more demethylation did not induce tolerance responses in Sistan. Sequencing differentially methylated fragments along with qRT-PCR analysis showed the efficient role of various DNA fragments, including demethylated fragments such as phosphoenol pyruvate carboxylase (PEPC), beta-glucosidase (BGlu), glycosyltransferase (GT), glutathione S-transferase (GST) and lysine demethylase (LSD) genes and methylated fragments like ubiquitin E2 enzyme genes in the development of drought tolerance. These results suggested the specific roles of DNA methylation in development of drought tolerance in wheat landrace.

Production of alkaline protease by Aspergillus niger in a new combinational paper waste culture medium.

Enzymes derived from microbial sources have gained increasing popularity in industrial applications over the past decades. Despite the high production cost, alkaline proteases have wide applications in industries such as tanneries, food production, and detergents. In recent years, there has been a shift towards utilizing natural carbon sources for cultivating microorganisms and extracting proteases in order to reduce production costs. This study aimed to investigate the biochemical and kinetic properties of protease enzymes obtained from Aspergillus niger cultivated in a paper waste medium and compare with the enzyme produced in a basal medium. Glucose is a more favorable carbon source compared to cellulose, so paper waste was pretreated with cellulose-degrading bacteria to convert cellulose into smaller carbohydrates. After the growth of A. niger in basal and combinational media, the enzymatic properties were compared between the extracted enzymes by using casein as substrate. The results demonstrated that A. niger could produce protease enzymes in the paper waste medium similar to the basal medium with more than 5-fold cost saving. The specific activity of the enzymes isolated from the basal and paper waste media was calculated to be 184.95 ± 10.56 U ml-1 and 169.88 ± 11.05 U ml-1, respectively. Carbon sources did not affect the optimum pH and temperature of the protease enzyme, which were found to be 8 and 37 °C, respectively. This study provides valuable insights into the production of alkaline protease from A. niger using a combinational medium (paper waste pretreated by cellulose-degrading bacteria), offering a cost-effective approach for industrial applications.

Investigation of the Iron Oxide Nanoparticle Effects on Amyloid Precursor Protein Processing in Hippocampal Cells.

Introduction: Iron oxide nanoparticles (Fe2O3-NPs) are small magnetic particles that are widely used in different aspects of biology and medicine in modern life. Fe2O3-NP accumulated in the living cells due to the absence of an active system to excrete the iron ions and damages cellular organelles by high reactivity. Methods: Herein cytotoxic effects of Fe2O3-NP with a size of 50 nm on the primary culture of neonatal rat hippocampus were investigated using 2,5-diphenyltetrazolium bromide (MTT) assay. Pathophysiological signs of Alzheimer's disease such as amyloid precursor protein (APP) expression, Aß aggregation, soluble APPα, and APPß secretion were also investigated in hippocampal cells treated with various concentrations of nanoparticle (NP) for different exposure times. Results: Our results revealed that Fe2O3-NP treatment causes oxidative stress in cells which is accompanied by upregulation of the APP and Aß in a concentration-dependent manner. NP exposure also leads to more secretion of sAPPß rather than sAPPα, leading to increased activation of ß-secretase in NP-received cells. All the harmful effects accumulate in neurons that cannot be renovated, leading to neurodegeneration in Alzheimer's disease. Conclusion: This study approved iron-based NPs could help to develop Alzheimer's and related neurological disorders and explained why some of the iron chelators have therapeutic potential in Alzheimer's disease. Highlights: Fe2O3-NP induced oxidative stress in hippocampal cells in a concentration dependent manner.Fe2O3-NP imposed up-regulation of APP in hippocampal cells.Fe2O3-NP activated ß-secretase and elevated sAPPß/sAPPα ratio.Cumulative effects of Fe2O3-NP damages increased cell death in neurons. Plain Language Summary: The most common type of dementia is Alzheimer's disease (AD), which is characterized by chronic neurodegeneration, impairment of memory, and disturbed planning, language, and thinking ability. In recent years, the use of nanoparticles has been increased in all aspects of life. Among these nanoparticles, iron oxide nanoparticles (Fe2O3-NP) are vital in biological sciences, medicine, magnetic resonance imaging, ultrasound, and optical imaging. Considering the general application and high reactivity of iron, growing concerns exist about the Fe2O3-NP application harms, especially in the central nervous system. Hippocampus tissue is one of the affected tissues in AD, which is widely investigated in recent years. This study aimed to investigate the cytotoxic effects of Fe2O3-NP on the primary culture of the hippocampus as one of the main tissues damaged in patients with AD. Our results revealed that treatment with different concentrations of Fe2O3-NP caused cellular damage in hippocampal cells. Exposure to Fe2O3-NP also caused oxidative stress. Our results showed a close association between oxidative stress and AD's pathological symptoms. The Fe2O3-NP application in medicine and biology should be limited.

Recent advances in various bio-applications of bacteria-derived outer membrane vesicles.

Outer membrane vesicles (OMVs) are spherical nanoparticles released from gram-negative bacteria. OMVs were originally classified into native 'nOMVs' (produced naturally from budding of bacteria) and non-native (produced by mechanical means). nOMVs and detergent (dOMVs) are isolated from cell supernatant without any detergent cell disruption techniques and through detergent extraction, respectively. Growth stages and conditions e.g. different stress factors, including temperature, nutrition deficiency, and exposure to hazardous chemical agents can affect the yield of OMVs production and OMVs content. Because of the presence of bacterial antigens, pathogen-associated molecular patterns (PAMPs), various proteins and the vesicle structure, OMVs have been developed in many biomedical applications. OMVs due to their size can be phagocytized by APCs, enter lymph vessels, transport antigens efficiently, and induce both T and B cells immune responses. Non-engineered OMVs have been frequently used as vaccines against different bacterial and viral infections, and various cancers. OMVs can also be used in combination with different antigens as an attractive vaccine adjuvant. Indeed, foreign antigens from target microorganisms can be trapped in the lumen of nonpathogenic vesicles or can be displayed on the surface through bacterial membrane protein to increase the immunogenicity of the antigens. In this review, different factors affecting OMV production including time of cultivation, growth media, stress conditions and genetic manipulations to enhance vesiculation will be described. Furthermore, recent advances in various biological applications of OMVs such as vaccine, drug delivery, cancer therapy, and enzyme carrier are discussed. Generally, the application of OMVs as vaccine carrier in three categories (i.e., non-engineered OMVs, OMVs as an adjuvant, recombinant OMVs (rOMVs)), as delivery system for small interfering RNA and therapeutic agents, and as enzymes carrier will be discussed.

Investigation of Coronavirus disease 2019 virus in vaginal fluid and menses blood and the effect on menstrual cycle duration and sexual desire: A cross-sectional study.

Background: Coronavirus disease 2019 (COVID-19) was detected in the throat, urine, and feces but has little evidence documented of sexual transmission. Objective: Here, we aimed to diagnose the presence of COVID-19 in vaginal fluids and menses blood. Menstrual cycle duration and sexual desire were the other aims. Materials and Methods: In this cross-sectional study, 300 individuals with clinical approval of COVID-19 infection who were referred to the Alzahra hospital of Tabriz University of Medical Sciences, Tabriz, Iran were divided into mild (n = 178, partial pressure of oxygen ≥ 91) and severe (n = 122, partial pressure of oxygen ≤ 91) groups, also based on clinical signs and hospitalization, from January to May 2021. Demographic characteristics, menstruation, and sexual desire of individuals were recorded in the questionnaire blood sampling was done on days 2-4 for menses, and vaginal fluid after menses for polymerase chain reaction by using a Dacron tip swab. Results: Participants were studied in the mild (mean age: 43.32 ± 7.41) and severe (mean age: 47.15 ± 6.9) groups. COVID-19 infection resulted in shortening the menstrual cycle duration in the severe group (30.15 ± 2.9 vs. 25.12 ± 2.1 days, p = 0.01). Polymerase chain reaction test for vaginal fluid and menses blood was negative for all cases. Sexual desire declined in both groups, significantly. Conclusion: This virus was not present in the menses blood and vaginal fluid of women with COVID-19 infection, which proposed a low risk of virus transmission via vaginal tracts. Severe COVID-19 infection may affect the menstrual duration.

A treatment approach of severe vulvar edema in ovarian hyperstimulation syndrome patient: A case report.

Background: Ovarian hyperstimulation syndrome (OHSS) is a serious life-threatening complication of infertility treatment. Vulvar edema is a disease with various causes and frequent phenomena seen in physiological and pathologic conditions like pregnancy, inflammatory disorders, tumors, idiopathic reasons, and most importantly, in the severe form of OHSS. Case Presentation: Here, we report a 26-yr-old woman with severe OHSS, recombinant follicle-stimulating hormone therapy. 8 days later, we observed a mild and asymmetrical swelling of the vulva with severe edema in the right labia. Due to the worsening of the vulvar edema even after 15 days of conservative treatment, hand massage and compressive bandaging of the vulva were performed, which caused rapid recovery within 20 min of the case. Conclusion: Treatment with a hand massage with lubricant gel followed by compressive bandaging resolved the vulvar edema immediately; it is an easy procedure without any adverse events.

Lateralization of the hippocampus: A review of molecular, functional, and physiological properties in health and disease.

The hippocampus is a part of the brain's medial temporal lobe that is located under the cortex. It belongs to the limbic system and helps to collect and transfer information from short-term to long-term memory, as well as spatial orientation in each mammalian brain hemisphere. After more than two centuries of research in brain asymmetry, the hippocampus has attracted much attention in the study of brain lateralization. The hippocampus is very important in cognitive disorders, related to seizures and dementia, such as epilepsy and Alzheimer's disease. In addition, the motivation to study the hippocampus has increased significantly due to the asymmetry in the activity of the left and right hippocampi in healthy people, and its disruption during some neurological diseases. After a general review of the hippocampal structure and its importance in related diseases, the asymmetry in the brain with a focus on the hippocampus during the growth and maturation of healthy people, as well as the differences created in patients at the molecular, functional, and physiological levels are discussed. Most previous work indicates that the hippocampus is lateralized in healthy people. Also, lateralization at different levels remarkably changes in patients, and it appears that the most complex cognitive disorder is caused by a new dominant asymmetric system.

A novel loss of function mutation in the PHD domain of the RAG2 gene, affecting zinc-binding affinity.

BACKGROUND: Severe combined immune deficiencies (SCIDs) are genetically heterogeneous disorders that lead to the absence or malfunction of adaptive immune cells, including T- and B-cells. Pathogenic variants in the RAG2 gene are associated with this disease. METHODS: A couple with consanguineous marriage from the Iranian-Azeri-Turkish ethnic group was referred to the genetic lab. Two children of this family died due to SCID disease with symptoms of skin granulomas, lack of developed T- and B-cells, and intact NK cells. To infer their genotypes, DNA samples obtained from the parents were subjected to whole-exome sequencing (WES). RESULTS: WES data analysis revealed that both parents were carriers of a pathogenic variant, NC_000011.10 (NM_000536.4):c.1268G > C, in the RAG2 gene. This variant was absent in our cohort of 400 healthy individuals from the same ethnic group. To gain insight into the consequence of the variant on the protein function, further analysis was performed by applying bioinformatics tools. This study revealed that the replacement of cysteine with serine at the zinc-binding domain diminished the domain's affinity to zinc ion, resulting in the loss of the mutant protein's ability to bind to the recombination signal sequence (RSS). The formation of the RAG2-RSS complex is vital for T- and B-cell development. CONCLUSION: The identification of a novel pathogenic variant, c.1268G > C, revealed that this variant in the zinc-binding domain diminished the affinity of the zinc ion to the mutant protein and consequently led to the loss of its ability to bind to the RSS.

The relationship between thyroid deficiency and blood-based biomarkers of cognitive disorders.

OBJECTIVE: Thyroid hormones play an essential role in metabolism regulation and circadian rhythm control. Recent studies approved their role in normal development and healthy function of central nervous system (CNS). The thyroid gland is a component of the hypothalamic-pituitary-thyroid axis disrupted during thyrotoxicosis and hypothyroidism, two main clinical conditions that induce more liability against dementia-related disease. METHOD: In the first step, this study evaluated the circular level of neuropeptide Y (NPY), leptin, oxytocin, and vasopressin in hyperthyroidism and hypothyroidism patients. In the second step, we investigated neurological and cognitive abnormalities by assessment of the hallmark proteins and peptides such as amyloid ß (Aß) variants, glycogen synthase kinase 3ß (GSK-3ß), and tau protein in thyroid-deficient samples. RESULTS: The results show increased content of leptin hormone in patients with hypothyroidism who also manifested high levels of vasopressin. Underactivation and overactivation of the thyroid gland are accompanied by reduced circular oxytocin. We may conclude that thyroid deficiency is associated with neurohormone dysregulation. Interestingly, both patient groups exhibited significant increases in Aß40 and Aß42 levels relative to the control group, which was also accompanied by the rise in GSK-3ß; this might be interpreted as cholinergic system dysfunction and cognitive impairment. The results revealed tau content increased considerably in thyrotoxicosis but did not change significantly in hypothyroidism compared to the control group. CONCLUSION: Therefore, our results have shown that thyroid gland dysfunction is a risk factor for cognitive impairment, mainly through neuroendocrine dysregulation. This study provides a relationship between hyperthyroidism/hypothyroidism and biomarkers of neurological abnormalities in blood serum.

Intraovarian Injection of Autologous Platelet-Rich Plasma Improves Therapeutic Approaches in The Patients with Poor Ovarian Response: A before-after Study.

In this article published in Int J Fertil Steril, Vol 16, No 2, April-June 2022, Pages: 90-94, the authors found that this sentence "Also, AMH level was not statistically significantly different after PRP treatment (0.38 ± 0.039) in comparison with before of treatment (0.39 ± 0.04, Fig.1C)" was incorrect. The corrected one is "Also, AMH level was not significantly different before PRP treatment (0.38 ± 0.039) in comparison with after of treatment (0.39 ± 0.04, Fig.1C)" in the first paragraph of the result section.
The authors would like to apologies for any inconvenience caused.

Iranian Mesobuthus Eupeus Crude Venom Induces Selective Toxicity in Chronic Lymphocytic Leukemia B-Lymphocytes Through Lysosomal/Mitochondrial Dysfunction and Reactive Oxygen Species Formation.

From ancient times to the present-day animal venoms had been used as medicinal and therapeutic agents. Recently it has been reported that the scorpion venom is a potential source of active and therapeutic compounds to design potent drugs against variety of cancerous cells and other diseases. The current study aimed to evaluate the selective toxicity of Iranian Mesobuthus eupeus (IMe) crude venom as a potential source of anticancer compounds on cancerous CLL B-lymphocytes and normal lymphocytes. For this purpose, we isolated cancerous CLL B-lymphocytes and normal lymphocytes from chronic lymphocytic leukemia patients and healthy volunteers. Cancerous CLL B-lymphocytes and normal lymphocytes were treated with different concentration (0, 5, 10, 20, 40 and 80 µg/ml) of IMe crude venom for 12 hours and cytotoxicity, reactive oxygen species (ROS) production, collapse of mitochondrial membrane potential (MMP) and lysosomal membrane integrity were determined. The data demonstrated the significant cytotoxic effect of IMe crude venom on cancerous CLL B-lymphocytes, with a concentration value (IC50) that inhibits 50% of the cell viability of 60 µg/ ml after 12 h of incubation. MTT assay proved that the IMe crude venom is selectively toxic to cancerous CLL B-lymphocytes, and IMe crude venom induced selective cell death via activation of ROS formation and mitochondrial/lysosomal dysfunction. These finding showed that IMe crude venom has a selective mitochondrial/lysosomal-mediated cell death effect on cancerous CLL B-lymphocytes. Therefore, the IMe crude venom and its fractions may be promising in the future anticancer drug development for treatment of CLL and variety of cancers.

Intraovarian Injection of Autologous Platelet-Rich Plasma Improves Therapeutic Approaches in The Patients with Poor Ovarian Response: A Before-After Study.

Background: Advanced age is associated with a decline in the natural oocytes, low oocyte yield, and also increases the assisted reproductive technology (ART) failure rate, and consequently resulted in a pregnancy rate decrease. Platelet-rich plasma (PRP) is one of the proposed therapeutic strategies for women with poor ovarian response (POR). Because of the autologous source of PRP, the lowest risks of disease transmission, immunogenic and allergic reactions have been expected. This study aimed to evaluate the single-dose intraovarian injection of autologous PRP in poor ovarian reserve. Materials and Methods: We conducted a clinical trial study in the Al-Zahra hospital and Milad Infertility Clinic, Tabriz, Iran (April and May, 2021). A total of thirty-five women with a POR and mean age 40.68 ± 0.34 enrolled in this study. After injection of autologous PRP into the ovaries, the number of oocytes, antral follicles, and level of estradiol, anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteal hormone (LH), FSH/LH ratio also were evaluated while, these parameters were evaluated before PRP administration. Results: At the 2-month follow-up, women treated with PRP showed a significant elevation in the number of oocytes (3.68 ± 0.24, P=0.0043) and embryos (3.17 ± 0.14, P=0.0001), as well as in the estradiol levels (404.1 ± 16.76 vs. 237.7 ± 13.14, P=0.0003). Conclusion: Single PRP injection is effective and might be a promising therapeutic approach in the patients with POR to conceive with their own oocytes, although further evidence is required to assess the influence of PRP on the live birth rate.

Interaction of bovine serum albumin with ellagic acid and urolithins A and B: Insights from surface plasmon resonance, fluorescence, and molecular docking techniques.

Human serum albumin (HSA) shows the sequence homology and structural similarity with bovine serum albumin (BSA). Therefore, here, the interaction of natural phenolic antioxidants, ellagic acid (ELA), and its derivatives-urolithins A (ULA) and B (ULB)-with BSA was investigated. The results of surface plasmon resonance (SPR) indicated a high affinity of ELA, ULA, and ULB to BSA, with KD value < 1 × 10-6 M. The KD values of binding of the studied compounds to BSA increased with temperature, revealing a reduction in affinity with an increase in temperature. Fluorescence data showed that the quenching of BSA by tested compounds occurred via a static quenching. However, the affinity of ELA for BSA was higher than that of ULA and ULB, which may be because of the presence of a large number of hydroxyl groups in its structure. The assessment of the antioxidant activity of BSA and BSA-ELA/ULA/ULB complexes using the DPPH assay indicated that the DPPH scavenging activity of BSA increased after complex formation with ELA/ULA/ULB in the following order: BSA-ELA > BSA-ULA > BSA-ULB > BSA, which was due to their structural differences. The results of the docking analysis were in agreement with the experimental results.

The role of non-enzymatic glycation on Tau-DNA interactions: Kinetic and mechanistic approaches.

Despite the regulatory role of Tau protein in the stabilization and assembly of microtubules, this protein has an important function in the protection and stabilizing of DNA molecules in the cell nucleus. In the present study, it has been indicated that glycation of lysine residues (Lys-267, Lys-274, and Lys-280) in the microtubule-binding domain (MBD) can considerably decrease its binding affinity to DNA molecules. The structural analysis also confirmed that the decreased glycated tau-DNA complex's stability was due to structural modification of this protein after the glycation process. The study of hippocampal cells under hyperglycemic conditions showed that near to 70% of Tau proteins glycated in these cells, although the expression of Tau remained unaffected. The assessment of H3K9me2, as a marker for binding of Tau to pericentromeric heterochromatin (PCH), indicated that localization of Tau protein on PCH was remarkably decreased at high glucose conditions relative to the controls. It is suggested that increasing the structural stability of Tau protein limits the ability of this protein for DNA binding, while the molecular and physical barrier of glycated Lys residues should not be neglected.

Ecballium elaterium attenuates neuroinflammation in an animal model of Alzheimer's disease through modulation of nuclear factor κB pathway.

OBJECTIVE: Sustained inflammation, which could be promoted by Aß aggregation and tau hyperphosphorylation, is a critical player in Alzheimer's disease (AD) pathogenesis. In the first phase, this study was designed to evaluate the anti-inflammatory properties of Ecballium elaterium (EE), as a Mediterranean therapeutic plant, and its effects on biochemical and behavioral signs of nucleus basalis of Meynert lesioned (NBML) rats, as an approved model of AD. In the second phase, we investigated the effect of EE on nuclear factor (NF)-κB pathway which is responsible for encoding proteins involved in the inflammatory cascade. MATERIALS AND METHODS: Animals were divided randomly into four groups as following: control, NBML rats (AD), AD rats that were treated by high- and low-dose EE. Prostaglandins (PGs) levels were measured by enzyme-linked immunosorbent assay (ELISA) kits. Cyclooxygenase-2 (COX-2) and acetylcholinesterase (AChE) levels were assessed by fluorometric kit and Elman method, respectively. Behavioral signs were evaluated by Morris Water Maze (MWM) test and inflammatory proteins content was analyzed by immunoblotting method. RESULTS: According to the results, treatment of NBML rats with EE fruit juice reduced PGs and cytokines more than 2-fold in comparison with AD rats through inhibition of COX-2 enzyme. Attenuation of inflammatory response in NBML rats was accompanied by reduced AChE activity (about 3-fold) and improved learning ability. Interestingly, EE reduced NF-κB expression for about 3-fold which resulted in a more than 10-fold increase in IκBα/P-IκBα ratio. CONCLUSION: Our results confirmed the TNF-α/cytokines/NF-κB/COX-2 pathway involves as the main inflammatory response in NBML rats. We also provided biochemical and behavioral evidence which introduces EE as an anti-inflammatory adjuvant to improve pathophysiological signs in patients suffering from AD and related dementia.

Proteomic profiling of the rat hippocampus from the kindling and pilocarpine models of epilepsy: potential targets in calcium regulatory network.

Herein proteomic profiling of the rat hippocampus from the kindling and pilocarpine models of epilepsy was performed to achieve new potential targets for treating epileptic seizures. A total of 144 differently expressed proteins in both left and right hippocampi by two-dimensional electrophoresis coupled to matrix-assisted laser desorption-mass spectrometry were identified across the rat models of epilepsy. Based on network analysis, the majority of differentially expressed proteins were associated with Ca2+ homeostasis. Changes in ADP-ribosyl cyclase (ADPRC), lysophosphatidic acid receptor 3 (LPAR3), calreticulin, ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), synaptosomal nerve-associated protein 25 (SNAP 25) and transgelin 3 proteins were probed by Western blot analysis and validated using immunohistochemistry. Inhibition of calcium influx by 8-Bromo-cADP-Ribose (8-Br-cADPR) and 2-Aminoethyl diphenylborinate (2-APB) which act via the ADPRC and LPAR3, respectively, attenuated epileptic seizures. Considering a wide range of molecular events and effective role of calcium homeostasis in epilepsy, polypharmacy with multiple realistic targets should be further explored to reach the most effective treatments.

Frequency of Cytomegalovirus Viral Load in Iranian Human Immunodeficiency Virus-1-Infected Patients with CD4+ Counts <100 Cells/mm3.

OBJECTIVES: The aim of present work was to assess cytomegalovirus (CMV) viremia in Iranian human immunodeficiency virus (HIV)-1-infected patients with a CD4+ count <100 cells/mm3 and to explore whether CMV DNA loads correlate with CD4+ cell counts or associated retinitis. METHODS: This study was conducted at the AIDS research center in Iran on HIV-1-infected patients with CD4+ count <100 cells/mm3, antiretroviral therapy-naive, aged ≥18 years with no previous history of CMV end-organ disease (CMV-EOD). RESULTS: Thirty-nine of 82 patients (47.56%) had detectable CMV viral load ranging from 66 to 485,500 IU/mL. CMV viral load in patients with retinitis ranges from 352 to 2,720 IU/mL, and it was undetectable in 2 patients. No significant associations between CMV viremia and CD4+ cell count was found (p value = 0.31), whereas significant association of CMV viremia in HIV-infected patients with retinitis was found (p < 0.02). CONCLUSIONS: We estimated the frequency of CMV viral load infection in Iranian HIV-1-infected patients with a CD4+ cell count <100 mm3/mL in the largest national referral center for HIV-1 infection in Iran. Further research is required on the relevance of CMV viral load in diagnostic and prognostic value of CMV-EOD.

Structural and kinetic insights into HIV-1 reverse transcriptase inhibition by farnesiferol C.

Human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) is the key enzyme for the virus gene replication and the most important target for antiviral therapy. Toxicity, drug resistance and side effects have led to search for new antiviral agents. Farnesiferol C (FC) is a well-known biologically active sesquiterpene coumarin derivative from genus Ferula. The current study was designed to examine the impacts of FC on the structure and function of HIV-1 RT, using some theoretical and experimental methods. FC inhibited HIV-1RT activity via mixed inhibition mechanism (IC50 = 30 µM). Spectroscopic data showed some conformational changes in the secondary as well as tertiary structure of HIV-1RT following the interaction with FC. Results showed that FC could quench the intrinsic fluorescence emission of HIV-1RT through static quenching mechanism. Thermodynamic parameters revealed that hydrogen bondings and van der Waals forces are the major forces in the binding reaction and the low equilibrium constants (KD) value obtained from surface plasmon resonance data, confirmed the high affinity of FC for HIV-1RT. Molecular docking studies indicated that FC interacts with enzyme through hydrophobic pocket. Taken together, the outcomes of this research revealed that, sesquiterpene coumarines can be used to design natural remedies as anti-HIV agents.