Evaluation of Beclin1 and mTOR genes and p62 protein expression in breast tumor tissues of Iranian patients.

Autophagy is a cellular process that plays a major role in the fate of tumor cells. Understanding the role of autophagy in cancer therapy is a major challenge, particularly for breast cancer as the sole top cause of mortality among women. In this study, we evaluated the gene expression of mTOR and Beclin1 and the levels of p62 protein, in breast tumors and compared them to a control condition. To explore the role of autophagy in breast cancer, we acquired tumor biopsies from 41 new cases of breast cancer patients. We extracted total RNA from each biopsy and used real-time PCR to quantify Beclin1 and mTOR-specific RNA expression. In addition, we evaluated the expression of the p62 protein in paraffin-embedded tumor tissue using the immunohistochemistry technique. The data revealed an upregulation of Beclin1 and a downregulation of mTOR in tumor tissues compared to the control condition. The correlation between p62 expression and Beclin1/mTOR showed a negative and positive correlation, respectively, confirming autophagy activation in the tumor tissues. However, there was no correlation between autophagy markers and tumor size, grade and stage. The findings revealed that autophagy activation was found in breast tumor tissues, suggesting that autophagy can be a target for breast cancer therapy.

Perceived Stress and Cfognition Function Quantification in a Scary Video Game: An Electroencephalogram Features and Biochemical Measures.

Introduction: Video games affect the stress system and cognitive abilities in different ways. Here, we evaluated electrophysiological and biochemical indicators of stress and assessed their effects on cognition and behavioral indexes after playing a scary video game. Methods: Thirty volunteers were recruited into two groups as control and experimental. The saliva and blood samples were collected before and after intervention (watching/playing the scary game for control and experimental groups respectively). To measure cortisol and salivary alpha-amylase (sAA) levels, oxytocin (OT), and brain-derived neurotrophic factor (BDNF) plasma levels, dedicated ELISA kits were used. Electroencephalography recording was done before and after interventions for electroencephalogram (EEG)-based emotion and stress recognition. Then, the feature extraction (for mental stress, arousal, and valence) was done. Matrix laboratory (MATLAB) software, version 7.0.1 was used for processing EEG-acquired data. The repeated measures were applied to determine the intragroup significance level of difference. Results: Scary gameplay increases mental stress (P<0.001) and arousal (P<0.001) features and decreases the valence (P<0.001) one. The salivary cortisol and alpha-amylase levels were significantly higher after the gameplay (P<0.001 for both). OT and BDNF plasma levels decreased after playing the scary game (P<0.05 for both). Conclusion: We conclude that perceived stress considerably elevates among players of scary video games, which adversely affects the emotional and cognitive capabilities, possibly via the strength of synaptic connections, and dendritic thorn construction of the brain neurons among players. Highlights: The mental stress level increases in players of scary video games.The salivary cortisol and alpha-amylase levels are significantly higher after the scary gameplay.Plasma levels of oxytocin and brain-derived neurotrophic factor decrease after the scary gameplay.The arousal and valence features increase in players of scary video game.Cognitive capabilities are adversely affected by the scary gameplay. Plain Language Summary: Nowadays, video games have become an important part of human life at different ages. Therefore, assessing their effects (improving and/or damaging) on cognition and behavior is important for understanding how they affect the nervous system. The results of such studies can be used to design a variety of games in the future in a way that minimizes the harmful side effects of video games on human cognitive functions and maximizes their beneficial effects.

The Effect of Electrical Fields From High-voltage Transmission Line on Cognitive, Biological, and Anatomical Changes in Male Rhesus macaque Monkeys Using MRI: A Case Report Study.

Introduction: Living near high-voltage power lines and exposure to high-frequency electromagnetic fields (EMFs) is a potentially serious hazard to animal and human health. The present study was conducted to evaluate the effect of high-frequency EMFs from simulated high-voltage electric towers on cognitive, anatomical, and biological changes in the male macaque. Methods: In this study, two Rhesus macaque were recruited, one experimental and one control. The experimental subject was exposed to EMFs from 3 kV/m simulated electric towers with a specific protocol and the control subject was tested without irradiation (4h per day, for 30 days). All required tests were performed before and after the intervention on experimental and control monkeys. The anatomical alternation of the prefrontal area (PFA) was measured by MRI images. All tests were performed on irradiated and control animals before and after the intervention and the results were compared between irradiated and control animals. Results: The results of the present study indicated increased white blood cell counts after high-frequency EMFs irradiation. Also, the red blood cell counts showed a decreasing trend after irradiation. The plasma adrenaline level increased after irradiation. Besides, the blood glucose levels increased after irradiation. The PFA was different before and after the irradiation. Moreover, some behavioral disorders, such as fatigue, drowsiness, anorexia, and insomnia were observed after irradiation. Conclusion: The results of biological tests and MRI showed an elevated risk of immunodeficiency disorders, weakness, and behavioral disorders. People who live or work near high-voltage electric towers with high-frequency EMFs are warned. Highlights: Magnetic, and electric fields from high pressure towers caused negative effects in terms of biology and even anatomical changes in the prefrontal part of the brain.Disturbance in the prefrontal part of the brain caused the monkey's cognitive and behavioral disorder.An increase in white blood cells, a decrease in red blood cells, and an increase in the adrenaline and blood sugar were indicative of biological disorders after wave exposure in male rhesus monkeys.The effects of magnetic and electric fields resulting from high pressure towers on the nerves and psyche require health researchers to do more studies. Plain Language Summary: Today, one of the factors that threaten the cognitive and behavioral health of humans and animals is living in the vicinity of magnetic and electric fields resulting from the power transmission of high-pressure towers. These fields cause cognitive and behavioral disorders in living beings. Therefore, because it threatens the cognitive health of creatures, it needs more research.

Serum Concentrations of Thyroid-Stimulating Hormone, Triiodothyronine, and Thyroxine in Outpatients Infected with SARS-CoV2 in Khuzestan Province, Iran: A Disease Clinical Course Approach.

Background and Objectives: The virus SARS-CoV2, which causes COVID-19, affects the endocrine system. This study investigated serum concentrations of the thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) in 53 outpatients infected with SARS-CoV2 and 53 non-infected matched participants in Khuzestan Province, Iran. We also examined the possible association of clinical symptoms progression and disease severity with serum concentrations of TSH, T3, and T4. Materials and Methods: A checklist was applied to collect demographic and clinical data. Blood samples were taken for biochemical analysis of serum concentrations of TSH, T3, and T4. Clinical symptoms of the infected outpatients were monitored weekly for 28 days. Results: Our results indicated that, as the severity of the disease increased, the respiratory and pulse rates raised significantly. Additionally, disease severity was significantly different between genders. Specifically, 79.5% of the asymptomatic/mild, and 38.5% of moderate outpatients were men. We also found significantly lower serum T3 but higher T4 in infected outpatients, compared with controls. However, serum TSH did not significantly differ between the two groups. The generalized estimating equation (GEE) analysis revealed no relationship between clinical symptoms progression and disease severity with serum concentrations of TSH, T3, and T4 in our study population. Additionally, GEE analysis showed that the odds ratio of neurological symptoms among women was 2.5 times that of men, the odds ratio of neurological symptoms in illiterates was 10 times higher than that of those without a high-school diploma, and the chance of developing pulmonary symptoms in those without high-school diploma was about 21 times higher than illiterates. Conclusion: In conclusion, this study showed that infected outpatients had significantly lower serum T3 but higher T4 than non-infected participants. There was no relation between symptom progression and disease severity with serum concentrations of TSH, T3, and T4, but educational status and sex significantly affected the chance of neurological and pulmonary symptoms occurring over 28 days. Our results may be used to develop potential therapies to treat COVID-19 disease.

Oxidative Stress and Inflammatory Status in COVID-19 Outpatients: A Health Center-Based Analytical Cross-Sectional Study.

The antioxidant system can be critical in reducing exacerbated inflammation in COVID-19. This study compared the antioxidant and inflammatory responses between COVID-19 outpatients and seemingly healthy individuals. This descriptive-analytical cross-sectional study was conducted on 53 COVID-19 outpatients and 53 healthy individuals as controls. The serum concentrations of amyloid A (SAA), total antioxidant capacity (TAC), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were measured and compared between COVID-19 patients and controls using the independent sample t-test before and after controlling for dietary supplement use. A generalized estimating equation (GEE) regression model, limited to COVID-19 patients, was used to evaluate the odds ratios (ORs) and 95% confidence intervals (95% CIs) of disease symptoms on days 1, 7, 14, 21, and 28 after the disease onset. Serum concentrations of SOD (p ≤ 0.001) and GPx (p = 0.001) were significantly higher in COVID-19 patients than in controls before adjustment for dietary supplement use. GPx remained significantly higher among COVID-19 patients than in controls after adjustment for all dietary supplements (p = 0.005). Moreover, serum concentrations of GPx (p = 0.003), SOD (p = 0.022), and TAC (p = 0.028) remained significantly higher among COVID-19 patients than in controls after adjustment for vitamin D supplementation. This study showed higher GPx in COVID-19 outpatients than in controls after adjustment for dietary supplement use. Moreover, elevated SOD, GPx, and TAC concentrations were shown in COVID-19 outpatients compared to controls after adjusting for vitamin D supplementation. These results may provide a useful therapeutic target for treating oxidative stress in COVID-19 disease, which may help ameliorate the pandemic.

A Green Approach for the Biosynthesis of Gold Nanoparticles Using Cuminum cyminum L. Seed and Its Application for Pain Management in Rats.

Background: This study investigated the antinociceptive effect of cumin and its biosynthesized gold nanoparticles (AuNPs). Methods: Cumin extract (E) and cumin-AuNPs (GN) were prepared and administered intraperitoneally at the concentrations of 200, 500, and 1000 mg/ml to 27 male rats. Ultraviolet-visible spectroscopy and atomic force microscopy were applied for AuNPs synthesis confirmation. The nociceptive behavior was assessed, and IL-6 serum levels were measured. Results: Cumin-AuNPs showed a peak absorption of 515 nm, and a size of about 40 nm. Three different concentrations of extract had no significant effect on acute and chronic nociceptive behavior. GN + E200 (46.00 ± 10.59) showed a significant acute anti-nociceptive effect compared to the control (98.66 ± 4.91; p = 0.029) and SS300 (98.33 ± 20.30; p = 0.029) groups. Also, GN + E500 (42.00 ± 11.84) significantly reduced acute nociceptive behavior compared to the control (98.66 ± 4.91; p = 0.019), SS300 (98.33 ± 20.30; p = 0.020), and GN + E1000 (91.00 ± 26.00; p = 0.040) groups. IL-6 serum levels reduced significantly in GN + E500 (24.65 ± 10.38; p = 0.002) and SS300 (33.08 ± 1.68; p = 0.039) compared to the controls (46.24 ± 3.02). Chronic nociceptive behavior was significantly lower in the SS300 (255.33 ± 26.30) compared to E200 (477.00 ± 47.29; p = 0.021), E500 (496.25 ± 46.29; p = 0.013), and GN + E500 (437.00 ± 118.03; p = 0.032) groups. Conclusion: Our findings suggest the potential effects of cumin-AuNPs on formalin-induced nociceptive behavior, which is independent of IL-6serum levels.

Profiling serum levels of glutathione reductase and interleukin-10 in positive and negative-PCR COVID-19 outpatients: A comparative study from southwestern Iran.

Since the outbreak of COVID-19 in China, it has rapidly spread across many other countries. We evaluated antioxidant defense systems and inflammatory status related to the SARS-CoV2 infection in a population from southwestern Iran. Comorbidities and clinical symptoms of 104 subjects (comprising negative and positive-PCR COVID-19 outpatients) were assessed. Serum concentrations of glutathione reductase (GR) and interleukin-10 (IL-10) were measured using ELISA. In the positive-PCR group, follow-ups on clinical symptoms were carried out for 28 days at 7-day intervals. In the positive-PCR group, hypertension, diabetes, liver disease, chronic heart disease, and chronic kidney disease were the most common comorbidities. In the general category of symptoms, we found a significant difference between negative and positive-PCR groups, except regarding runny noses. In the pulmonary category, there was a significant difference between the two groups except in terms of chest pain. We also determined a significant difference in neurologic symptoms, except for ear pain, between negative and positive-PCR groups. We also found significantly lower levels of GR but higher levels of IL-10 in the positive-PCR group (p = 0.000 for both). In the positive-PCR group, serum levels of IL-10 (odds ratio = 0.914, p = 0.012) decreased the chances of neurological symptoms occurring over time. The antioxidant defense systems of positive-PCR outpatients failed as demonstrated by a reduction in the serum levels of GR. We also indicated a dysregulation in the immune response against COVID-19, characterized by changes in serum IL-10 levels.

The Effect of 12 Hz Extremely Low-frequency Electromagnetic Field on Visual Memory of Male Macaque Monkeys.

Introduction: Today, humans live in a world surrounded by electromagnetic fields. Numerous studies have been conducted to discover the biological, physiological, and behavioral effects of electromagnetic fields on humans and animals. Given the biological similarities between monkeys and humans, The present research aimed to examine Visual Memory (VM), hormonal, genomic, and anatomic changes, in the male rhesus macaques exposed to an Extremely Low-Frequency Magnetic Field (ELF-MF). Methods: Four male rhesus macaques (Macaca mulatta) were used. For the behavioral tests, the animals should be fasting for 17 hours. For the tests such as visual memory, the animal's cooperation was necessary. Using the radiation protocol, we exposed two monkeys to a 12-Hz electromagnetic field with a magnitude of 0.7 µT (electromagnetic radiation) four hours a day for a month. Before and after the exposure, a visual memory test was conducted using a coated device (visible reward) on a movable stand. Ten milliliters of blood was obtained from the femoral artery of each monkey, and half of it was used to examine cortisol serum levels using the MyBioSource kit (made in the USA). The other half of the blood was used to extract lymphocytes for assaying expressions of Glucocorticoid Receptor (GR) genes before and after radiation using the PCR method. Anatomic studies of the amygdala were carried out based on pre- and post-radiation Magnetic Resonance Imaging (MRI). Results: Research results indicated that visual memory in male primates increased significantly after exposure to the 12-Hz frequency. Hormonal analysis at the 12-Hz frequency showed a decrease in cortisol serum levels. However, visual memory and serum cortisol levels did not change considerably in male primates in the control group. There was no considerable amygdala volumetric difference after exposure to the 12-Hz frequency. The expression of the GR genes decreased in the 12-Hz group compared to the control group. Conclusion: In short, these results indicated that ELF might benefit memory enhancement because exposure to the 12-HZ ELF can enhance visual memory. This outcome may be due to a decrease in plasma cortisol and or expression of GR genes. Moreover, direct amygdala involvement in this regard cannot be recommended. Highlights: The effects of Extremely Low-Frequency Electromagnetic Fields (ELF-EMF) of 12 Hz on monkeys were studied.The results showed a reduction in the serum cortisol levels and the expression of GR genes.The amygdala anatomical area changes were not significant in the experimental group.In the experimental group, visual memory (delay of 30- and 60-s evaluation) improved after exposure to a frequency of 12 Hz. Plain Language Summary: Extremely low-frequency electromagnetic fields are among the most important factors affecting humans. This study aimed to determine the fields of 12-Hz frequency on the visual memory changes of male monkeys. The importance of research is due to the cognitive similarity of monkeys to humans. The findings of the research can be attributed to humans. Behavioral, hormonal, genetic, and anatomical studies indicated improvement in visual memory (test monkeys versus control monkeys). This study demonstrates the effect of the 12-Hz frequency on the monkey's visual memory. Researchers can study 12-Hz frequency in other cognitive indices.

The Association between Vitamin D and Zinc Status and the Progression of Clinical Symptoms among Outpatients Infected with SARS-CoV-2 and Potentially Non-Infected Participants: A Cross-Sectional Study.

Vitamin D and zinc are important components of nutritional immunity. This study compared the serum concentrations of 25-hydroxyvitamin D (25(OH)D) and zinc in COVID-19 outpatients with those of potentially non-infected participants. The association of clinical symptoms with vitamin D and zinc status was also examined. A checklist and laboratory examination were applied to collect data in a cross-sectional study conducted on 53 infected outpatients with COVID-19 and 53 potentially non-infected participants. Serum concentration of 25(OH)D were not significantly lower in patients with moderate illness (19 ± 12 ng/mL) than patients with asymptomatic or mild illness (29 ± 18 ng/mL), with a trend noted for a lower serum concentration of 25(OH)D in moderate than asymptomatic or mild illness patients (p = 0.054). Infected patients (101 ± 18 µg/dL) showed a lower serum concentration of zinc than potentially non-infected participants (114 ± 13 µg/dL) (p = 0.01). Patients with normal (odds ratio (OR), 0.19; p ≤ 0.001) and insufficient (OR, 0.3; p = 0.007) vitamin D status at the second to seventh days of disease had decreased OR of general symptoms compared to patients with vitamin D deficiency. This study revealed the importance of 25(OH)D measurement to predict the progression of general and pulmonary symptoms and showed that infected patients had significantly lower zinc concentrations than potentially non-infected participants.

Associations between traditional and non-traditional anthropometric indices and cardiometabolic risk factors among inpatients with type 2 diabetes mellitus: a cross-sectional study.

OBJECTIVE: We aimed to evaluate whether traditional and non-traditional adiposity indicators are associated with cardiometabolic risk factors among adult patients with type 2 diabetes mellitus (DM). METHODS: In this cross-sectional study among 240 inpatients with type 2 DM, we determined traditional anthropometric indicators including body mass index, waist circumference, hip circumference (HC), waist-to-hip ratio (WHR), waist-to-height ratio, and non-traditional anthropometric indicators including lipid accumulation product (LAP), visceral adiposity index (VAI), deep abdominal adipose tissue (DAAT), and Després indices. Lipid profile, fasting blood glucose, glycated hemoglobin (HbA1c), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured to evaluate cardiometabolic parameters. RESULTS: In overweight patients, DAAT was positively correlated with total triglycerides. LAP was negatively correlated with serum HDL-C levels. WHR and DAAT were associated with total triglycerides, HbA1c, total cholesterol, total cholesterol/HDL-C, and total triglycerides/HDL-C, after adjustment for age and duration of disease. VAI, DAAT, LAP, and Després index were significant determinants of lipid profile and SBP. CONCLUSION: Traditional and non-traditional anthropometric indices are associated with cardiometabolic risk factors in patients with type 2 DM.

Application of community-based nutrition education needs assessment in reviewing the course plan of medical and nursing students.

Background: Training needs assessment is the process of recognizing educational needs. This study aimed to apply a community-based nutrition education needs assessment to revise the nutrition course plan in the curriculum of the doctorate of medicine and that of the baccalaureate of nursing. Methods: The study was designed in 2 phases: (1) nutritional needs assessment; (2) community-based revision of nutrition course plan. In the first phase, 13 nutrition professionals working in the region set out 5 priorities of nutrition-related health problems in the community by a training need assessment based on a survey and scoring system. Then, an expert panel determined the priorities of behavioral and nonbehavioral causes of the nutrition-related health problems by the nominal group technique (NGT). The results of the first phase were used to review the topics of nutrition course plans up to 20%. Results: The priorities identified in Abadan, Khorramshahr, and Shadegan were obesity and type 2 diabetes mellitus in adults as well as anemia in pregnant women, respectively. Also, wrong eating habits and insufficient nutrition knowledge were among the most important behavioral causes of nutrition-related health problems in the target community. These results were applied to a community-based review of nutrition course plans for medical and nursing students. Conclusion: The use of nutritional needs assessment approaches by a survey and nominal group technique with a group of professionals provided an opportunity for a community-based review of the nutrition course plan for medical and nursing students as a first phase in the development of a community-based nutrition course plane.

Role of the mesenchymal stem cells derived from adipose tissue in changing the rate of breast cancer cell proliferation and autophagy, in vitro and in vivo.

OBJECTIVES: Autophagy is an intracellular degradation system of damaged proteins and organelles; however, the role of autophagy in the progression of cancer remains unclear. In recent years, mesenchymal stem cell (MSC)-based approaches have attracted considerable attention for anti-cancer therapy. The present study aimed to examine the interaction of MSCs with the breast cancer cells under autophagy-induced conditions. MATERIALS AND METHODS: In this study, MSCs isolated from human adipose tissue were co-cultured with MDA-MB 231, a breast cancer cell line, and the autophagy process was induced by tunicamycin treatment. The cell viability was monitored by the MTT assay, and the cells were recovered at different time intervals (24 or 48 hours) to determine autophagy markers such as Beclin, mTOR and the ratio of LC3II/I expression. Additionally, the animal study was conducted using a mouse model of breast cancer treated with isogenic adipose-derived MSCs, and the expression of Beclin and Ki67 was determined using immunohistochemistry in breast tumor tissue. RESULTS: In cancer cells co-cultured with MSCs, the cell proliferation was increased, the Beclin expression and the LC3II/I protein ratio were decreased, and the mTOR expression was increased in MDA-MB 231 upon co-cultured with MSCs. Direct injection of MSCs to a mouse model of breast cancer showed an increase in tumor volume, an increase in the accumulation of Ki67 and a decrease in the Beclin expression in tumor tissues. CONCLUSION: The data may suggest that suppressed autophagy in breast cancer cells is probably a mechanism by which MSCs can induce cancer cell proliferation.

Cuminum cyminum L.-Mediated Synthesis of Silver Nanoparticles: Their Characterization and Effect on Formalin-Induced Nociceptive Response in Male Rats.

In this study, a simple, low-cost, rapid, and eco-friendly approach for the biosynthesis of silver nanoparticles (AgNPs) using the aqueous extract of Cuminum cyminum L. (cumin) seed (CcAgNPs) was developed. Also, the anti-nociceptive properties of these synthesized AgNPs were evaluated in vivo. The CcAgNPs characterized using Ultraviolet-visible (UV-Vis) spectrophotometer, X-ray diffraction analysis (XRD), Fourier transform infrared (FTIR) spectroscopy, atomic force microscopy (AFM), and transmission electron microscopy (TEM). The analysis of phytochemical components in the aqueous extract of cumin seeds showed high concentrations of total phenols and ascorbic acid and low concentrations of total flavonoids. The analysis of phytochemical components and FTIR spectroscopy confirmed the presence of functional groups responsible for the bioreduction of Ag+ to AgNPs. The UV-Vis absorbance spectrum of CcAgNPs showed a maximum wavelength at 442 nm. The analysis of TEM images showed a spherical shape with a size of less than 50 nm, while XRD spectra revealed the crystallinity of CcAgNPs. The analysis of anti-nociceptive properties of CcAgNPs showed that the first phase of formalin-induced pain was significantly reduced in the groups receiving 200, 500, and 1000 mg/kg CcAgNPs compared with the controls and the group receiving 300 mg/kg of sodium salicylate (SS300). The second phase of formalin pain was also significantly reduced in the groups receiving 200 and 500 mg/kg CcAgNPs compared to the controls and SS300 group. Overall, we introduced a new AgNPs synthesized from cumin seeds (CcAgNPs) and showed their anti-nociceptive properties in the formalin-induced pain.

The Effect of Brain Teaser Games on the Attention of Players Based on Hormonal and Brain Signals Changes.

INTRODUCTION: Computer games as an interactive media play a significant role in the cognitive and behavioral health of the players. Computer games have either positive or negative effects on cognitive indices among players. They also directly influence the lifestyle and quality of life of children, adolescents, and young adults. The present study aimed to evaluate the short-term effects of the brain teaser game on players. METHODS: Among 45 male volunteers, 40 subjects with an average age of 20 years were recruited and divided into two groups: the experimental group and the control group. All required tests were conducted before and after the intervention (playing the game) on the experimental group. Also, the same tests were performed on the control group, in which the participants were not allowed to play the game. All participants completed a questionnaire comprised demographic characteristics and specific information regarding the game (e.g., game style and hours spent on playing the game). The saliva samples were collected to measure levels of cortisol and α-amylase. The salivary α-amylase (sAA) and cortisol levels were analyzed using the relevant ELISA kits. The cognitive tests were performed using PASAT software before and after the game to assess the perceptual-cognitive abilities of the players. The brain waveforms were acquired by a 14-channel Emotiv brain signal recording device before and after the game. Data analysis was conducted in R and MATLAB software. RESULTS: PASAT test suggested that mental health and sustained attention were significantly improved after the intervention. In addition, the sAA and salivary cortisol levels were significantly higher before the intervention. The results of the brainwave analysis revealed that stress index and attention were significantly higher before the intervention. CONCLUSION: Findings of the present study suggest that brain teaser games positively influence the central nervous system and activate stress path, leading to changes in brain signals and subsequently improved cognitive elements, such as attention among players.

Synovial interlukin-6 affects apoptosis induction via nuclear factor kappa-B and fractalkine pathway during adjuvant arthritis.

Background: Apoptosis disruptions play substantial roles in pathogenesis of arthritis and its symptoms. Cytokines and their intracellular signaling have pivotal roles in arthritis pathophysiology. This study aimed to investigate the relationship between synovial Interleukin-6 (IL-6), nuclear factor kappa-B (NF-ĸB), and fractalkine (FKN) in the changes of edema and apoptosis during adjuvantinduced knee arthritis. Methods: A total of 240 male Wistar rats were divided into different groups. Arthritis was evoked and the knee edema changes were evaluated by Vernier caliper. Synovial IL-6 was assayed by rat standard ELISA kit. Levels of NF-ĸB, fractalkine, and apoptotic indicators in the synovium were evaluated by Western blot method. Results were expressed as Mean± SEM. To analyze within-group variations, repeated measures ANOVA, followed by post hoc Tukey's test was used (SPSS, 16). Independent samples t test was used to designate significant differences in knee diameter, synovial level of IL-6, apoptotic markers, NF-ĸB, and FKN between groups. Significance level was set at P≤ 0.05. Results: The injection of Complete Freund's Adjuvant (CFA) caused intense knee edema (P< 0.001), which was reduced by implementing anti-IL-6 (P< 0.001), anti-FKN (P< 0.001), Inh-NF-ĸB (P< 0.001), and anti-FKN+ Inh NF-kB (P< 0.001). The results indicated elevated levels of apoptotic markers during the acute phase (P = 0.010), along with an increase in IL-6 (P< 0.001), NF-ĸB (P< 0.001), and FKN (P= 0.030). Although IL-6 (P< 0.001), NF-ĸB (P= 0.001), and FKN (P= 0.007) levels elevation continued during the chronic phase, the apoptosis markers decreased in this phase (P= 0.050). The findings revealed that Anti-IL-6 treatment during different phases of the study could change the synovial NF-ĸB and FKN. Conclusion: It seems that time-dependent variations in apoptotic markers level may be involved in pathogenesis of adjuvant-induced knee arthritis. In conclusion, synovial IL-6 through NF-ĸB- FKN pathway can play an important role in this process.

The Impact of Synovial NF-κB Activation on Apoptosis Pattern Change During Adjuvant-induced Inflammation.

INTRODUCTION: Apoptosis dysregulation plays a substantial role in the pathophysiology of chronic inflammation and its related symptoms such as edema. Regulation of NF-κB activation is involved in apoptosis pattern change. The current study aimed at verifying the effects of local inflammation on edema and changes in apoptotic markers, and investigating the possible role of NF-κB in apoptosis pattern change during different stages of complete Freund's adjuvant (CFA)-induced knee arthritis in rats. METHODS: A total of 96 male Wistar rats were divided into different experimental groups. Arthritis was evoked into the right knee articular joint. Changes made in knee edema were assessed by caliper on the days 0, 7, 14, and 21 of the study. Synovial NF-κB and levels of apoptotic markers were evaluated during different stages of the study using Western blot technique. RESULTS: CFA injection caused intense edema during the whole study period. Synovial NF-κB level increased during the whole study period. The level of apoptotic markers increased during the acute phase of study. But during chronic phase, the apoptosis level decreased. Inh-NF-κB administration increased synovial apoptosis during the whole study period. CONCLUSION: It seems that apoptosis pattern change plays an important role in the progression and modulation of CFA-induced inflammation and its related symptoms. Also, it can be concluded that synovial NF-κB had a crucial role in synovial apoptosis change during the study period.

The Role of C Fibers in Spinal Microglia Induction and Possible Relation with TRPV3 Expression During Chronic Inflammatory Arthritis in Rats.

INTRODUCTION: Stimulation of peptidergic fibers activates microglia in the dorsal horn. Microglia activation causes fractalkine (FKN) release, a neuron-glia signal, which enhances pain. The transient vanilloid receptor 1 (TRPV1) mediates the release of neuropeptides, which can subsequently activate glia. TRPV1 and TRPV2 are generally expressed on C and Aδ fibers, respectively. Expression of both proteins is upregulated during inflammation, but expression of TRPV3 after induction of inflammation is unclear. METHODS: Adult male Wistar rats were used in all experiments. Arthritis was induced in them by single subcutaneous injection of complete Freund's adjuvant (CFA) in their right hindpaws. Resiniferatoxin (RTX) was used to eliminate peptidergic fibers. We examined the relation between FKN and TRPV3 expression by administration of anti-FKN antibody. RESULTS: Our study findings indicated that 1) spinal TRPV3 was mostly expressed on nonpeptidergic fibers, 2) expression of spinal TRPV3 increased following inflammation, 3) elimination of peptidergic fibers decreased spinal TRPV3 expression, 4) alteration of hyperalgesia was compatible with TRPV3 changes in RTX-treated rat, and 5) anti-FKN antibody reduced spinal TRPV3 expression. DISCUSSION: It seems that the hyperalgesia variation during different phases of CFA-induced arthritis correlates with spinal TRPV3 expression variation on peptidergic fibers. Moreover, spinal microglial activation during CFA inflammation is involved in TRPV3 expression changes via FKN signaling.

Evaluation of placental epigenetic changes due to morphine consumption / Evaluación de cambios epigenéticos de la placenta por consumo de morfina

Based on previous studies, a variety of bioenvironmental elements including inappropriate nutrition, diseases, infections, stressors, and medications are involved in epigenetic changes. Drug abuse is one of the most important causes of epigenetic changes and a concern in today's world. Studies have shown that morphine use by pregnant mothers causes several disorders in mothers in addition to transferring abnormalities to the next generation (placenta and embryo). Epigenetic factors such as morphine cause changes in gene expression in placenta as the first embryonic defense barrier. Because placenta does all the nutritional exchanges between mother's and embryo's blood, placental health guarantees normal embryonic development. Many studies have been conducted on defects caused by epigenetic factors including medication use. Opioid abuse including morphine abuse has endangered health of many people. Morphine changes gene expression by binding to opioid receptors on placental villi. Based on the studies, major epigenetic changes due to drug use are mediated by DNA methylation and histone changes. Recognizing different epigenetic factors and their effect on placental and embryonic development is among modern studies. The importance of recognizing epigenetic changes caused by drug abuse by pregnant mothers can be the most important way to prevent adulthood diseases in the embryo and in some cases miscarriage. Changes induced by epigenetic factors can be moderated or reversed by controlling the epigenetic factors. This study is a review of changes caused by morphine use by pregnant rats on development of placenta.

Basado en estudios anteriores, una variedad de elementos bioambientales incluyendo la nutrición inadecuada, enfermedades, infecciones, factores de estrés, y los medicamentos están involucrados en los cambios epigenéticos. El abuso de drogas es una de las causas más importantes de los cambios epigenéticos y una preocupación en el mundo actual. Los estudios han demostrado que el uso de la morfina por parte de las madres embarazadas es la causa de varios trastornos en las madres, además de la transferencia de anormalidades a la siguiente generación (la placenta y el embrión). Factores epigenéticos como la morfina causan cambios en la expresión génica en la placenta como la primera barrera de defensa embrionaria. Debido a que la placenta es el medio de todos los intercambios nutricionales entre la madre y la sangre del embrión, la salud de la placenta garantiza el desarrollo embrionario normal. Muchos estudios se han realizado sobre los defectos causados por factores epigenéticos que incluyen el uso de medicamentos. El abuso de opioides, incluyendo la morfina ha puesto en peligro la salud de muchas personas. La morfina produce cambios de expresión génica mediante la unión a los receptores opioides en vellosidades placentarias. Basado en los estudios, los principales cambios epigenéticos debido al consumo de drogas están mediadas por metilación del ADN y los cambios en las histonas. En la actualidad se han publicado estudios referente al conocimiento de diferentes factores epigenéticos y su efecto sobre la placenta y el desarrollo embrionario. La importancia de reconocer los cambios epigenéticos causados por el abuso de drogas por mujeres embarazadas puede ser la forma más importante para prevenir las enfermedades de la edad adulta en el embrión y en algunos casos del aborto espontáneo. Los cambios inducidos por factores epigenéticos pueden ser moderados o revertidos mediante el control de los factores epigenéticos. Este estudio es una revisión de los cambios en el desarrollo de la placenta causados por el uso de morfina en ratas preñadas.

Serum IL-10 involved in morphine tolerance development during adjuvant-induced arthritis

Opioid receptors play an important role in modulation of hyperalgesia in inflamed tissues, but chronic morphine application induces such side effects as tolerance. There is near communications between cytokines and mu opioid receptor expression. This study was aimed to assess the role of serum IL-10 in morphine tolerance development during adjuvant-induced arthritis. Adjuvant arthritis (AA) was induced on day 0 by single injection of Complete Freund’s Adjuvant (CFA) into the rats’ hindpaw. Hyperalgesia, edema, and spinal mu opioid receptor (mOR) variations were assessed on 0, 7, 14, and 21 days of the study. For assessment of the morphine tolerance development, morphine effective dose (4 mg/kg) was administered from the 14th day after CFA injection and continued until the morphine post-dose paw withdrawal latency (PWL); it did not significantly differ from the baseline. For assessment of the effects of IL-10 on tolerance induction, a neutralizing dose (ND50) of anti-IL-10 was administered daily during different stages of the study. AA induction in the right hindpaw of rats resulted in unilateral inflammation and hyperalgesia within 21 days of the study. Anti-IL-10 antibody administration in the AA rats induced marked elevation of hyperalgesia compared to the AA control group. Our data also indicated that morphine effective anti-hyperalgesic dose significantly decreased in the AA rats compared to the control group, which this symptom was aligned with spinal mu opioid receptor (mOR) expression increase during AA. Moreover, there was a significant difference in morphine tolerance induction between the AA and control rats, and our results also demonstrated that IL-10 played an important role in tolerance-induction process. It can be concluded that morphine tolerance slowly progressed when administered morphine effective dose was reduced during AA chronic inflammation. On the other hand, it seems that increased level of serum IL-10 may affect morphine tolerance development during inflammation

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