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.

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.

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.

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.

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.

Elevated expression of DNMT1 is associated with increased expansion and proliferation of hematopoietic stem cells co-cultured with human MSCs.

BACKGROUND: Mesenchymal stem cells (MSCs) play an important role in hematopoietic stem cell (HSC) maintenance, proliferation, and apoptosis. DNA methyltransferase 1 (DNMT1) is considered an essential factor in the maintenance of HSCs in mammalian cells. Therefore, this study was conducted to evaluate the mRNA expression level of DNMT1 during cord blood (CB)-HSC ex vivo expansion with MSCs. METHODS: Ex vivo cultures of CB-HSCs were performed in three culture conditions for 7 days: cytokines, cytokines with MSCs, and only MSCs. Total and viable cell numbers were counted after 5 and 7 days using trypan blue stain, and the stem cell percentage was then evaluated by flow cytometry. Moreover, in vitro colony-forming unit assay was carried out to detect clonogenic potential of HSCs at days 0 and 7 using MethoCult H4434. Finally, DNMT1 mRNA expression level was evaluated by real-time polymerase chain reaction. RESULTS: Maximum CB-CD34+ cell expansion was observed on day 7 in all the three cultures. After 7 days, ex vivo expansion of CB-CD34+ cells indicated a significant decrease in DNMT1 expression in the cytokine cultures, whereas in the two co-culture conditions DNMT1 expression was increased. A significant difference between the number of CD34+ and CD34- cells in the cytokine co-culture system was observed. CONCLUSION: These data indicated that an elevated expression of DNMT1 is associated with increased expansion and proliferation of HSCs co-cultured with human MSCs. Hence, DNMT1 may be a potential factor in the maintenance of expanded HSCs co-cultured with human MSCs.

Helicobacter pylori cagL amino acid polymorphism D58E59 pave the way toward peptic ulcer disease while N58E59 is associated with gastric cancer in north of Iran.

The cagL protein of Helicobacter pylori involving in pathogenesis of gastroduodenal disorders. Therefore, the current study was conducted to determine the cagL amino acid polymorphisms in patients with gastric diseases. One hundred gastric biopsies were collected from gastritis, peptic ulcer (PUD) and gastric cancer (GC) patients and were screened for cagL using polymerase chain reaction (PCR). Also, sequence variations of the cagL were assessed via sequence translation. The cagL geneopositivity was 71.6% in patients were infected with H. pylori. The cagL from PUD indicated a higher rate of D58 amino acid sequence polymorphism than those of the GC and gastritis (P < 0.05). The D58 polymorphism showed an increased risk of PUD up to 6.5-fold (95% CI: 1.2-35.7). This position was occupied with amino acid N58 in GC. The E59 polymorphism was more frequently found in PUD and GC than gastritis patients. Additionally, presence of Q62 and N122 significantly observed in PUD and GC, whereas I60 was detected in PUD patients. Our results demonstrated that presence of the D, I, Q and N at position 58, 60, 62 and 122, respectively increased the risk of peptic ulcer. However, amino acid N, M, Q and N at the same position alongside V134 increased the risk of gastric cancer.