Indomethacin attenuates neuroinflammation and memory impairment in an STZ-induced model of Alzheimer's like disease.

Objective: Non-steroidal anti-inflammatory drugs (NSAIDs) exposure might be considerably associated with a decreased risk of Alzheimer's disease (AD). Therefore, we conducted an experiment to investigate the impact of indomethacin (IND) on inflammasome as a key player of neuroinflammation.Methods: The Alzheimer's-like condition was induced by streptozotocin (STZ) in rats. IND was injected intraperitoneally 1 d prior to STZ administration and resumed with 2 d interval up to 60 d. Morris water maze (MWM) was utilized to assess learning and memory. The expression level of genes that contribute to the inflammasome pathway was measured using real-time polymerase chain reaction (PCR). To authenticate the obtained outcomes, immunostaining for caspase-1, interleukin-1ß (IL-1ß), and phosphorylated tau (p-Tau) protein was conducted.Results: Behavioral experiments indicated that IND treatment was able to improve learning and memory performance (p<.05). A significant decrease in C-terminal caspase recruitment domain [CARD] domain-containing protein 4 (NLRC4), nucleotide-binding oligomerization domain [NOD]-like receptor protein 3 (NLRP3), IL-1ß, and apoptosis-associated speck-like protein containing CARD (ASC) mRNA expression was recorded in IND administered group compared with the STZ group (p<.05). Furthermore, expression levels of IL-18 and caspase-1 in the hippocampus of IND-treated group tended to decrease. Immunostaining evaluations showed that few positive cells for caspase-1, IL-1ß, and p-Tau protein in IND treated animals, whereas the number of positive cells was considerably increased in STZ treated animals (p<.05).Conclusion: It could be deduced that IND improves neuroinflammation and memory impairment in AD through decreasing IL-1ß and caspase-1 that are associated with suppression of NLRC4 and NLRP3 inflammasome genes. This holds the potential to introduce valuable targets in the field for successful combat against AD.

Contribution of inflammasome complex in inflammatory-related eye disorders and its implications for anti-inflammasome therapy.

Inflammasome complex is regarded as a major molecular regulator that exerts a significant function in caspase-1 activation and consequently, the development of cytokines like interleukin-1ß (IL-1ß) and interleukin-18 (IL-18). The secretion of these cytokines may induce inflammation. The role of inflammasomes in the pathologic process of eye-related illnesses like glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy has been well studied over the past decade. However, the detailed pathogenic mechanism of inflammasomes in these retinal diseases is still unknown. Therefore, further investigation and understanding various aspects of inflammasome complexes as well as their pivotal roles in the immunopathology of human ocular illnesses are essential. The present review aims to describe the significant involvement of inflammasomes in the immunopathology of important inflammatory retinal illnesses, including glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy focusing on anti-inflammasome therapy as a promising approach in the treatment of inflammation-related eye diseases.

Decrease of intracellular ROS by arbutin is associated with apoptosis induction and downregulation of IL-1ß and TNF-α in LNCaP; prostate cancer.

Increased reactive oxygen species (ROS) along with inflammation are involved in the prostate cancer (PCa). Therefore, this study was conducted to investigate the molecular mechanisms that were affected by arbutin as an antioxidant on prostate cancer cell line; LNCap. The intracellular ROS measurement confirmed that arbutin significantly (p < .05) decreased the ROS levels in a dose-dependent manner. Detection of cell death profile established that 1,000 µM of arbutin could remarkably induced apoptosis (p < .05), while tert-butyl hydroperoxide (tBHP) as ROS inducer prompted necrosis. In addition, 1,000 µM of arbutin successfully decreased expressions of IL-1ß and TNF-α genes (p < .05). Furthermore, evaluation of the IL-1ß protein level showed that arbutin could significantly decrease this cytokine (p < .05). In summary, reduction of ROS along with increasing apoptosis and decreasing expression of pro-inflammatory genes following arbutin treatment can open new visions in the treatment of prostate cancer using complementary medicine. PRACTICAL APPLICATIONS: Nowadays, arbutin as a glycosylated hydroquinone is available commercially in both natural and synthetic forms. Arbutin is of interest because of its skin-lightening effect, and used in cosmetic products for cutaneous hyperpigmentation. Arbutin inhibited tyrosinase in melanocytes competitively. Moreover, arbutin was able to attenuate oxidative stress and, its anti-inflammatory activities has been established. In addition, arbutin has represented useful activities for suppression of malignant melanoma development. In addition, arbutin exhibits several pharmacological effects, including antimicrobial, antihyperlipidemic, antihyperglycemic, and alpha amylase inhibitory effects. In this study, we showed its effect on prostate cancer in vitro. Therefore, it opens new insights in the complementary medicine that can maintain or improve human health.

Elevated expression of IL-18 but not IL-1ß gene is associated with NALP3 and AIM2 inflammasome in Polycystic Ovary Syndrome.

Inflammasome complex mediated interleukin 1ß (IL-1ß) and interleukin 18 (IL-18) production may be involved in immunopathogenesis of polycystic ovary syndrome (PCOS). Therefore, this study was conducted to investigate involved inflammasome pathways in PCOS. Therefore, inflammasome genes expression and serum level of IL-1ß were evaluated in 30 patients with confirmed PCOS and 30 women without PCOS. A remarkable increase in expression of the nucleotide binding and oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NALP3), absent in melanoma 2 (AIM2), IL-18 and associated speck-like protein containing a caspase recruitment domain (CARD); (ASC) genes in PCOS were observed (p < 0.05). In contrast, expression level of NALP1, NALP12, NLR family apoptosis inhibitory proteins (NAIP), NLR family caspase recruitment domain (CARD) domain containing 4 (NLRC4) and IL-1ß genes was not significant. Although the IL-1ß protein level in serum of COS patients with BMI ≥ 25 was significantly higher than PCOS patient with BMI < 25, but there was no significant difference in non-PCOS individuals with BMI < 25 or ≥25. Furthermore, significant correlation between expression of AIM2 (r = 0.83, p = 0.032) and NALP3 (r = 0.59, p = 0.0001) was observed with IL-18, while a positive correlation (r = 0.84, p = 0.0001) was revealed between NAIP and IL-1ß. Based on the obtained results on inflammasome components along with increased expression of IL-1ß especially in overweight patients, it can be concluded that IL-18 expression as well as IL-1ß is probably due to activation of AIM2, NALP3 or NAIP inflammasome, which may play a critical role in immunopathology of PCOS.

Novel Computational Approaches to Developing Potential STAT4 Silencing siRNAs for Immunomodulation of Atherosclerosis.

BACKGROUND: Small interfering RNAs (siRNAs) are known as commonly used targeting mRNAs tools for suppressing gene expression. Since Signal Transducer and Activator of Transcription 4 (STAT4) is considered as a significant transcription factor for generation and differentiation of Th1 cells during vascular dysfunction and atherosclerosis, suppressing STAT4 could represent novel immunomodulatory therapies against atherosclerosis. OBJECTIVE: Therefore, the current study was conducted to design efficient siRNAs specific for STAT4 and to evaluate different criteria affecting their functionality. METHODS: In the present study, all related sequences of STAT4 gene were retrieved from Gen Bank database. Multiple sequence alignment was carried out to recognize Open Reading Frame (ORF) and conserved region. Then, siDirect 2.0 server was applied for the development of candidate siRNA molecules and confirmation of predicted molecules was performed using Dharma siRNA technology and GeneScript siRNA targetfinder. In addition, BLAST tool was used against whole Genebank databases to identify potential off-target genes. DNA/RNA GC content calculator and mfold server were used to calculate GC content and secondary structure prediction of designed siRNA, respectively. Finally, IntaRNA program was used to study the thermodynamics of interaction between predicted siRNA and target gene. RESULTS: Based on the obtained results, three efficient siRNA molecules were designed and validated for STAT4 gene silencing using computational methods, which may result in suppressing STAT4 gene expression. CONCLUSION: According to our results, this study shows that siRNA targeting STAT4 can be considered as a therapeutic agent in many Th1-mediated pathologic conditions specially atherosclerosis.

Involvement of NLRC4 inflammasome through caspase-1 and IL-1ß augments neuroinflammation and contributes to memory impairment in an experimental model of Alzheimer's like disease.

Inflammatory response through interleukin-1ß (IL-1ß) plays a key role in the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanism of pro-IL-1ß processing in AD is not clearly defined. The current study was designed to investigate which of the inflammasome complexes are critical for IL-1ß production in AD. An experimental model for Alzheimer like disease was induced in male Wistar rats and Morris Water Maze was used to evaluate the function of learning and memory. The expression of genes involved in inflammasome complex including NLRP1, NLRP3, NLRC4, AIM2, ASC, IL18, IL-1ß and caspase-1 was determined via Real-time PCR. Hematoxylin and Eosin (H&E) staining and Immunohistochemistry (IHC) for CD45 was applied to assess inflammatory cells infiltration. Furthermore, caspase-1, IL-1ß and phosphorylated tau (p-Tau) protein expressing cells were investigated in the lesion area using immunofluorescence staining technique. The behavioral study revealed that streptozotocin (STZ) injection significantly impaired learning and memory function. In addition, the infiltration of inflammatory cells was confirmed in the hippocampus region of STZ-treated animals. Furthermore, a significant increase in the expression level of NLRC4 inflammasome, ASC and IL-1ß was identified in STZ-treated animals. In contrast, no significant difference was observed in other inflammasome components including NLRP1, NLRP3, AIM2, IL-18 and caspase-1 in STZ-treated group compared with the control group. Moreover, the number of caspase-1, IL-1ß and p-Tau protein positive cells were remarkably increased in STZ-treated animals. Based on the obtained results, it can be concluded that increased production of IL-1ß, caspase-1 and p-Tau through association with NLRC4 inflammasome may be involved in neuroinflammation and memory impairment in AD, which creates a new horizon in this regard. Hence, strategies targeting NLRC4 inflammasome could be beneficial for the treatment of AD.

Development of a conserved chimeric vaccine based on helper T-cell and CTL epitopes for induction of strong immune response against Schistosoma mansoni using immunoinformatics approaches.

Currently, three recombinant antigens based vaccines are under clinical trials against Schistosomiasis, but there is no vaccine available for prophylaxis or therapeutic. This study was conducted to construct a multi-epitope based vaccine against Schistosoma mansoni via utilizing Sm14, Sm21.7, Sm23, Sm29, Smp80, Sm-CB and SM-TSP-2 antigens. Helper T lymphocyte (HTL), cytotoxic T lymphocyte (CTL) and IFN-γ epitopes were predicted. Furthermore, Pan HLA DR-binding epitope was added to the vaccine. Moreover, 50S ribosomal protein L7/L12 of Mycobacterium tuberculosis as a novel TLR4 agonist was applied. The TAT peptide was added to the vaccine to augment intracellular delivery. The selected epitopes were linked together through appropriate linkers and chimeric vaccine was constructed with 617 amino acids with molecular weight of 65.43 kDa. Physico-chemical properties revealed a soluble protein with antigenic and non-allergic properties. Further analyses validated the stability of the construct that was able to interact with TLR4. Immunoinformatics analysis demonstrated the strong potential of constructed vaccine to stimulate T and B-cell mediated immune responses. In summary, obtained data indicated that the proposed vaccine can properly induce both T and B cells immune responses and could possibly be utilized for prophylactic or therapeutic aims in response to infection caused by S. mansoni.

Development a multi-epitope driven subunit vaccine for immune response reinforcement against Serogroup B of Neisseria meningitidis using comprehensive immunoinformatics approaches.

Serogroup B of Neisseria meningitidis is the main cause of mortality due to meningococcal meningitis. Despite of many investigations, there is still no effective vaccine to prevent this serious infection. Therefore, this study was conducted to design a multi-epitope based vaccine through immunoinformatics approaches. The T CD4+ and TCD8+ cells along with IFN-γ inducing epitopes were selected from TspA, FHbp, NspA, TbpB, PilQ and NspA antigens form serogroup B of Neisseria meningitidis. Furthermore, to induce strong helper T lymphocytes (HTLs) responses, Pan HLA DR-binding epitope (PADRE) was used. In addition, loop 5 and 7 of the PorB as a TLR2 agonist were added to the vaccine construct. Physico-chemical properties, secondary and tertiary structures of the proposed construct were assessed. Finally, homology modeling, refinement and molecular docking were carried out to evaluated the construct tertiary structure and protein-protein interaction, respectively. By fusing the CTL, HTL and IFN-γ predicted epitopes along with suitable adjuvant and linkers, a multi-epitope vaccine was constructed with a TAT sequence of HIV at the N-terminal. Immunoinformatics analyses confirmed a soluble and non-allergic protein with a molecular weight of 62.5 kDa and high antigenicity. Furthermore, the stability of the multi-epitope construct was established and showed strong potential to generate humoral and cell-mediated immune responses. In addition, through molecular docking and dynamic simulation, the microscopic interaction between the vaccine construct and TLR-2 were verified. In summary, immunoinformatics analysis demonstrated that the constructed multi-epitope vaccine had a strong potential of T and B-cell stimulation and it could possibly be used for prophylactic or therapeutic aims to protect against serogroup B of N. meningitidis.

Influenza Vaccination and Guillain-Barré Syndrome: Reality or Fear.

Guillain-Barré syndrome (GBS) is an inflammatory disorder and an acute immune-mediated demyelinating neuropathy that causes reduced signal transmissions, progressive muscle weakness, and paralysis. The etiology of the syndrome still remains controversial and uncertain. GBS can be initiated and triggered by respiratory tract infections such as influenza, and intestinal infections such as Campylobacter jejuni. In addition, there is considerable evidence suggesting links between influenza vaccination and GBS. As reported previously, the incidence of GBS in individuals receiving swine flu vaccine was about one to two cases per million. Despite the influenza vaccine efficacy, its association with an immune-mediated demyelinating process can be challenging as millions of people get vaccinated every year. In this review we will discuss the association between influenza infection and vaccination with GBS by focusing on the possible immunopathological mechanisms.

Helicobacter pylori evasion strategies of the host innate and adaptive immune responses to survive and develop gastrointestinal diseases.

Helicobacter pylori (H. pylori) is a bacterial pathogen that resides in more than half of the human population and has co-evolved with humans for more than 58,000 years. This bacterium is orally transmitted during childhood and is a key cause of chronic gastritis, peptic ulcers and two malignant cancers including MALT (mucosa-associated lymphoid tissue) lymphoma and adenocarcinoma. Despite the strong innate and adaptive immune responses, H. pylori has a long-term survival in the gastric mucosa. In addition to the virulence factors, survival of H. pylori is strongly influenced by the ability of bacteria to escape, disrupt and manipulate the host immune system. This bacterium can escape from recognition by innate immune receptors via altering its surface molecules. Moreover, H. pylori subverts adaptive immune response by modulation of effector T cell. In this review, we discuss the immune-pathogenicity of H. pylori by focusing on its ability to manipulate the innate and acquired immune responses to increase its survival in the gastric mucosa, leading up to gastrointestinal disorders. We also highlight the mechanisms that resulted to the persistence of H. pylori in gastric mucosa.

Immuno-informatics based approaches to design a novel multi epitope-based vaccine for immune response reinforcement against Leptospirosis.

Leptospirosis is known as a zoonotic disease of global importance originated from infection with the spirochete bacterium Leptospira. Although several leptospirosis vaccines have been tested, the vaccination is relatively unsuccessful in clinical application despite decades of research. Therefore, this study was conducted to construct a novel multi-epitope based vaccine against leptospirosis by using Hap1, LigA, LAg42, SphH and HSP58 antigens. T cell and IFN gamma epitopes were predicted from these antigens. In addition, to induce strong CD4+ helper T lymphocytes (HTLs) responses, Pan HLA DR-binding epitope (PADRE) and helper epitopes selected from Tetanus toxin fragment C (TTFrC) were applied. Moreover, for boosting immune response, Heparin-Binding Hemagglutinin (HBHA), a novel TLR4 agonist was added to the construct as an adjuvant. Finally, selected epitopes were linked together using EAAAK, GPGPG, AAY and HEYGAEALERAG linkers. Based on the predicted epitopes, a multi-epitope vaccine was construct with 490 amino acids. Physico-chemical properties, secondary and tertiary structures, stability, intrinsic protein disorder, solubility, and allergenicity of this vaccine construct were assessed by applying immunoinformatics analyses. A soluble, and non-allergic protein with a molecular weight of 53.476 kDa was obtained. Further analyses validated the stability of the chimeric protein and the predicted epitopes in the chimeric vaccine indicated strong potential to induce B-cell and T-cell mediated immune response. Therefore, immunoinformatics analysis showed that the modeled multi-epitope vaccine can properly stimulate the both T and B cells immune responses and could potentially be used for prophylactic or therapeutic usages.

Psychosocial Predictors of Cognitive Impairment in the Elderly: A Cross-Sectional Study.

Objective: Cognitive impairment is a major public health problem among elderly population. The aim of this study was to assess some psychosocial predictors of cognitive impairment (age, education, living alone, smoking, depression and social support) in the Iranian elderly population. Method : A total of 1612 elderly (over 60 years) were enrolled in this cross-sectional study. Cognitive function was assessed using Mini Mental State Examination (MMSE). In addition, data from psychological tests and demographic characteristics were analyzed. Results: Older age, low education level, living alone, smoking, depressive symptoms, and lower social support were associated with an increased risk of cognitive impairment. Ages 70 to 74 (OR = 3.47; 95% CI, 2.13-5.65), 75 to79 (OR = 3.05; 95% CI, 2.11-4.41) and 80 to 85 (OR = 5.81; 95% CI, 2.99-11.22) and depression symptoms (OR = 1.64; 95% CI, 1.27-2.13) were significant positive predictors, whereas social support with scores ranging from 26 to 30 (OR =0. 32; 95% CI, 0.16-0.62) and 31 to 33 (OR =0.29; 95% CI, 0.14-0.61) and more than 5 years of education (OR = 0.19; 95% CI, 0.14-0.27) were the negative predictors of cognitive impairment. Conclusion: The findings suggest older age and depression as positive predictive factors and higher education level and social support as negative predictive factors of cognitive impairment in the elderly population.

Zika virus: epidemiology, clinical aspects, diagnosis, and control of infection.

Zika virus (ZIKV) is an emerging pathogen of huge public health significance to human beings. Although majority of infections are benign with self-limiting symptoms, the recent outbreak has established an association with the increased incidence of some congenital anomalies such as microcephaly. In other words, due to the large extent of the virus and mosquito vectors, the infection has become a thoughtful health problem for human societies, though now, there are no antiviral therapies or vaccines against this virus. In spite of extensive research carried out by scientists, not so much information has been gathered about this viral infection. In the current review, we prepared an overview of the remarkable progress made in understanding about the epidemiology, immunology, clinical presentation, and diagnosis methods of ZIKV infection.

The significance role of regulatory T cells in the persistence of infections by intracellular bacteria.

Regulatory T cells (Treg cells), are considered as effective immune cells playing a key role in immune response during cancers, autoimmune and infectious diseases. Regulatory T lymphocytes are divided into two main subgroups: natural Treg cells that generated during maturation in the thymus and have the suppressive activity that is critical for the establishment and maintenance of homeostasis in the body and induced Treg cells (iTreg) that are originated from naive T cells following the self-antigen recognition. In recent years, the roles of Treg in immune responses to microbial infections have received increased attention in researches. Several reports suggested the pivotal role of Treg cells in controlling responses to bacterial infections and demonstrated the impact of regulatory cells on one or more stages in the pathogenesis of bacterial infections. In this review, we describe the significance of regulatory T cells in the immunopathology of bacterial infections by focusing on specific bacterial infections including Mycobacteria, Listeria monocytogenes, and Bordetella pertussis. Moreover, suppressive mechanisms of regulatory T cells during bacterial infection including cell-cell contact, local secretion of inhibitory cytokines and local competition for growth factors will be discussed.

Association of TNF-α but not IL-1ß levels with the presence of Helicobacter pylori infection increased the risk of peptic ulcer development.

Peptic ulcer is a lesion in the mucosa of the digestive tract affecting many people all around the world. Recent investigations have indicated that produced inflammatory cytokines such as TNF-α and IL-1ß in response to gastric infection by Helicobacter pylori play an important role in the development of peptic ulcer. With regard to the significance of these cytokines in peptic ulcer development and the high prevalence of this disease in the developing countries, this study aimed to investigate the association of TNF-α and IL-1ß with peptic ulcer in the presence of H. pylori. This case-control study enrolled 61 patients with peptic ulcer disease (PUD) as cases and 59 people without peptic ulcer (NPUD) as controls. Blood samples and endoscopic biopsies were collected. H. pylori infection was confirmed by using rapid urease test (RUT), specific IgG measurement and histopathological examination. Then, IL-1ß and TNF-α levels were evaluated using enzyme linked immunosorbent assay (ELISA). The seropositivity of H. pylori was 62.5% in the studied population, while by considering RUT and histopathological examination along with specific-IgG antibody, H. pylori infection decreased to 56.7%. In addition, H. pylori infection was significantly (OR = 0.37; 95% CI = 0.17-0.82; P = .02) associated with peptic ulcer development. The TNF-α level in PUD and infected H. pylori subjects was significantly higher than that of control and un-infected H. pylori individuals. However, no significant difference of IL1ß level was observed between PUD and control groups as well as between H. pylori infected and un-infected individuals. Interestingly, IL-1ß level in PUD patients without H. pylori infection was significantly higher than infected ones. Moreover, a significant correlation between specific-IgG antibody with TNF-α level was observed. Taken together, our results showed that increased level of TNF-α could probably play pivotal role in pathogenesis of peptic ulcer in the presence of H. pylori infection. These findings also highlighted the importance of IL-1ß in the absence of H. pylori infection in peptic ulcer development.

Influence of Helicobacter pylori virulence factors CagA and VacA on pathogenesis of gastrointestinal disorders.

Helicobacter Pylori (H. pylori) is a gram-negative bacteria infecting numerous people all over the world. It has been established that H. pylori play an important role in pathogenesis of gastritis, peptic ulcer and gastric cancer. Pathogenic features of this bacterium are mainly attributes to the existence of pathogenic islands (PAI) genes. The most known genes in these islands are cytotoxin-associated gene A (CagA) and vacuolating cytotoxin gene (VacA). Most studies demonstrated various frequency of CagA and VacA in patient with peptic ulcer or gastritis in different countries. This variation in CagA and VacA frequency may be due to the capability of this bacterium to be genetically versatile and can alter the expression of these genes with geographic diversity. Although H. pylori infection is not usually associated with any clinical symptoms, but sometimes leads to inflammation in gastrointestinal system and resulted in peptic ulcer and gastric cancer. In this regard, this review will illustrate the importance of Helicobacter pylori in pathogenesis of gastrointestinal disorders with focusing on CagA and VacA virulence factors.

The role of regulatory T cells in immunopathogenesis and immunotherapy of viral infections.

Two hepatotropic viruses hepatitis C virus (HCV) and hepatitis B virus (HBV) have been considered as the main cause of chronic viral infections. In addition, human immunodeficiency virus (HIV) attacks the immune system by eradication of some white blood cell (T-helper cell). The role of Tregs in HCV, HBV and HIV infections ranges from suppressing antiviral T cell responses to protecting tissues as liver and immune cells from immune mediated injury. In this review, we discuss the influence of regulatory T cells in immunopathology of specific viral infections including HCV, HBV and HIV by focusing on targeting Tregs as novel approach in vaccinology against viral infections.

Three cycles of AC chemotherapy regimen increased oxidative stress in breast cancer patients: A clinical hint.

BACKGROUND: Recent studies have suggested the importance of oxidant/antioxidant status in initiation and progression of breast cancer. The aim of this study was to evaluate oxidative stress markers in breast cancer patients before and after 3 cycles of chemotherapy with adriamycin and cytoxan (AC). Also, in this study the effect of age and the stage of disease on oxidative stress markers were compared and evaluated. METHODS: This study included 60 women with newly diagnosed stage II-III breast cancer who underwent chemotherapy with AC as the therapy-first strategy after surgery. Serum samples were obtained before treatment and after the third chemotherapy. Then, serum total antioxidant status (TAS) and malondialdehyde (MDA) as lipid peroxidation marker were analyzed. Moreover, the effects of the subject's age and clinical disease stage were investigated. RESULTS: A concurrent significant increase in MDA (p<0.001) and a significant decrease in TAS (p<0.001) were also observed after 3 cycles of AC chemotherapy. In addition, some changes were found in the status of oxidative stress markers which were associated with age and clinical disease stage. CONCLUSION: Our data indicated that chemotherapy with AC increase the oxidative stress in breast cancer patients. The present study indicated that higher stages of the breast cancer are associated with significant increases of oxidative stress markers.

Morphine pre- and post-conditioning exacerbates apoptosis in rat hippocampus cells in a model of homocysteine-induced oxidative stress.

Recent investigations indicated that morphine has protective effects in different ischemia/reperfusion models and may protect against neuronal cell death, while other evidence showed that morphine induces apoptosis in neurons. Therefore, the current study was conducted to investigate pre- and post-conditioning effects of morphine on hippocampal cell apoptosis in a rat model of homocysteine (Hcy)-induced oxidative stress. In the present study, 0.5 µmol/µl Hcy was injected into bilateral intrahipocampal in the rat brain and morphine at a therapeutic dose of 10 mg/kg was injected intraperitoneally 5 days before and after Hcy injection in rats. The left and right rat hippocampus were removed for biochemical and histopathological analysis. In addition, hippocampal cell apoptosis was assayed by the TUNEL kit. Our results indicated that malondialdehyde (MDA) and superoxide anion (SOA) levels in the Hcy group were increased significantly compared to the control group (P<0.001). In addition, morphine pre- and post-treatment increased the MDA and SOA levels significantly in rat hippocampus compared with other groups (P<0.001). It was found that Hcy alone induced apoptosis in hippocampus cells and significantly increased the number of TUNEL-positive cells in rat hippocampus compared to the other group (P<0.001). Notably, our results indicated that pre- and post-treatment by morphine increased apoptosis in hippocampus cells compared with the other group (P<0.001). In conclusion, morphine neuroprotection and neurotoxicity needs to be further investigated to determine morphine side-effects in medical applications and to identify new targets for potential therapies.

Development of an epitope-based vaccine inhibiting immune cells rolling and migration against atherosclerosis using in silico approaches.

Atherosclerosis is a chronic inflammatory disease characterized by formation of pro-oxidative lipids in large and medium-sized vessels. Over the years, many treatments and drugs have entered the market to improve atherosclerosis and autoantigen-mediated active immunization is currently considered as a beneficial method. Therefore, this study was conducted to design a novel epitope-based vaccine against atherosclerosis employing CD99, CD81 and CD99L2 antigens. In this way, structural vaccinology approaches were used to design a novel multi-epitope vaccine against atherosclerosis. Six epitopes were predicted from CD99, CD81 and CD99L2 proteins. In addition, helper epitopes selected from Tetanus toxin fragment C (TTFrC)ion were applied to induce CD4+ helper T lymphocytes (HTLs) responses. Moreover, cholera toxin B (CTB) was employed as an adjuvant. Finally, EAAAK AND GPGPG sequences as linkers were considered to make a linkage between favorite peptide sequences. A multi-epitope construction was designed based on the predicted epitopes which was 270 residues in length. Further immunoinformatic analyses were carried out to assess physicochemical properties, secondary and tertiary structures, stability, intrinsic protein disorder, solubility, and allergenicity of this chimeric protein. Based on the obtained results, a soluble, and non-allergic protein with a molecular weight of 28.7kDa was designed. Further analyses revealed that the chimeric protein is a stable protein and the predicted epitopes indicated strong potential to induce B-cell and T-cell mediated immune response. Our immunoinformatic analyses revealed that the modeled multi-epitope vaccine had appropriate properties,which can properly stimulate the immune responses of both T and B cells.