A3 receptor agonist, Cl-IBMECA, potentiate glucose-induced insulin secretion from MIN6 insulinoma cells possibly through transient Ca2+ entry

Diabetes incidence showed ascending trends in recent years indicating urgent need for new therapeutic agents. Extracellular adenosine signaling showed promising results. However, role of its A3 receptor in pancreatic -cells proliferation and insulin secretion is not well established. Thus, we aimed to determine its main signaling mediators in MIN6 insulinoma cell line. A3 adenosine receptor (A3AR) expression was confirmed using RT-PCR. Receptor functionality was evaluated by measurements of cAMP, using ELISA kit, and intracellular Ca2+ levels, using Fura 2/AM probe in response to the specific A3AR agonist (Cl-IBMECA). Insulin ELISA kit was used to measure insulin release. Herein, we mentioned that MIN6 cells express active form of A3AR, which decreased cAMP levels with the half maximal effective concentration (EC50) value of 5.61. Ca2+i Levels transiently (approximately 120 sec) increased in response to the agonist. Cl-IBMECA increase insulin secretion at 0.01-1 mu M, but showed an inhibitory effects at higher concentrations (1-10 mu M). Altogether, we found that in MIN6 cells, A3AR, possibly through Ca2+ mediated signaling pathways, potentiated glucose-induced insulin secretion

IPP-1 controls Akt/CREB phosphorylation extension in A(2a) adenosine receptor signaling cascade in MIN6 pancreatic beta-cell line

Signaling through A(2a) adenosine receptor specifically prevent pancreatic beta-cells (PBCs) loses under diabetogenic conditions. However, signaling mediators of this receptor in PBCs remained unidentified. Thus, we aimed to investigate the possible involvement of PKA/Akt/IPP-1/CREB pathway in MIN6 beta-cells. In addition, we investigated IPP-1 role in A(2a) receptor signaling pathway. The expression of A(2a) receptor in MIN6 cell line was evaluated by RT-PCR and its functionality confirmed by quantification of cAMP in response to the CGS 21680, an A(2a) receptor agonist. MTT and Brdu assays were used to evaluate cell viability and proliferation, respectively. PKA activity and insulin release were evaluated using ELISA methods. P-Akt/Akt, p-IPP-1/IPP-1, and p-CREB/CREB levels were assessed using western blotting. IPP-1 knock down assessments was performed using specific siRNA. Our result revealed that MIN6 cells express A(2a) receptor which actively increased cAMP levels (with EC50 = 2.41 mu M) and PKA activity. Activation of this receptor increased cell viability, proliferation and insulin release. Moreover, we mentioned A(2a) receptor stimulation increased p-Akt, p-IPP-1, and p-CREB levels in dose (max at 10 mu M of CGS 21680) and time (max at 30 min after CGS 21680 treatment) dependent manner. Interestingly, herein, we found in IPP-1 knocked down cells, A(2a) receptor failed to activate Akt and CREB. Altogether, we mentioned that in MIN6 cells A(2a) receptor increase cell viability, proliferation and insulin release through PKA/Akt/IPP-1/CREB signaling pathway. In addition, we conclude A(2a) receptor signaling through this pathway is dependent to activation of IPP-1

Adenosine A2a Receptor Polymorphisms and Susceptibility to Anxiety Disorders

Anxiety disorders (ADs) are a group of mental disorders characterized by feelings of tension, fear, and excessive worrying in the face of life experiences. Aberrant signaling of adenosine A2a receptor (ADORA2A) is believed to be involved in the pathogenesis of ADs. Polymorphisms in the ADORA2A gene were shown to be associated with some of the patterns presented by ADs. The results of these studies have been inconsistent, making it hard to draw definitive conclusions. Therefore, this study performed a systematic review to clarify the associations between ADORA2A gene polymorphisms and ADs susceptibility. PubMed/Medline, Web of Science, and Scopus database using appropriate keywords, then screened for separation of suitable studies based on inclusion/exclusion criteria. Collectively, rs5751876 (1976T>C or previously 1083C>T) and rs35060421 (2592C>Tins) polymorphisms of ADORA2A were associated with an increased susceptibility to ADs. Moreover, rs2298383 TT genotype may be the causal regulatory factor, and ADORA2A T/C (rs2298383/rs3761422) haplotypes have significant susceptibility to ADs development. Additional research is needed to further define the role of ADORA2A gene polymorphisms in the pathogenesis of ADs

Psychometric evaluation of Persian version of Diabetes Acceptance Scale (DAS)

Background: Acceptance of diabetes is a psychological adaptation to the potential limitations of the disease. Poor acceptance of diabetes impairs efective self-management of diabetes, leading to worsening metabolic control. This study aimed at determining the psychometric properties of the Persian version of the Diabetes Acceptance Scale. Methods: This cross-sectional methodological study was performed on diabetic patients in Iran in 2021. The ques tionnaire consisted of two parts: demographic characteristics and Diabetes Acceptance Scale. The questionnaire was translated into Persian through the forward–backward translation method. The face validity and content validity were performed qualitatively and quantitatively. Exploratory (n=200) and confrmatory (n=200) factor analysis were performed to evaluate the validity of the structure. Internal consistency and temporal stability were estimated to determine reliability. Results: Exploratory factor analysis on the polychoric correlation matrix obtained three factors: Rational dealing, Resentment and Avoidance, which explained 68.8% of the total DAS variance. Confrmatory factor analysis showed that the 3-fractor model had a good ft to a second independent data set. Finally, Ordinal Cronbach’s alpha coefcient was 0.96, 0.94 and 0.93, respectively for the Rational dealing, Resentment, and Avoidance factor. Also, using intraclass correlation coefcient, the stability of the instrument was 0.97. Conclusion: Based on the fndings of this study, the Persian version of DAS has sufcient validity and reliability to measure the admission of Iranian diabetic patientsinfo:eu-repo/semantics/publishedVersio

Exploring the Relationship among EFL Teachers’ Critical Thinking, Autonomy and Experience in Public and Private Schools

The research delved into the connection between English Language instructors’ critical thinking, autonomy, and teaching experience among some public and private instructors. Two different sets of instructors including some private institute and high school instructors were selected from two major cities in Khorasan Razavi, Iran. The results from Path Analysis indicated that all subcomponents of instructors’ thinking critically except deduction could significantly predict instructors’ independence. Moreover, experience more effectively and remarkably predicted their independence. Accordingly, from among the five subcomponents of instructors’ CT, four sub-constituents were predicated by experience. Nevertheless, assessment and evaluation could not be properly predicted by experience. Findings also indicated that thinking critically could rightly and moderately be related to autonomy whereas there was a positively weak association between thinking critically and experience. Accordingly, findings pointed to a sizeable distinction between the two EFL settings regarding instructors’ autonomous behavior with non-public EFL instructors being more self-sufficient, selfdirected, and self-reliant than their counterparts in public high schools. In the same vein, there was no substantial distinction between the two settings concerning thinking critically

Increased Glutathione Reductase Expression and Activity in Colorectal Cancer Tissue Samples: An Investigational Study in Mashhad, Iran

Background: Glutathione reductase is an important enzyme in oxidative metabolism that provides reduced glutathione from its oxidized form in the cells. The role of oxidative stress in tumor tissues has led us to investigate the gene expression and activity of this enzyme in tumor and adjacent resected margins of colorectal cancer tissues, one of the most common malignancies in humans. Methods: We conducted this study on 15 Iranian colorectal cancer patients. RNA was extracted from fresh colon tissues that included tumor and anatomically normal margin tissue. Expression of the glutathione reductase gene was determined using realtime PCR by the ΔΔCt relative quantification method. The gene expression results were standardized with glyceraldehyde 3-phosphate dehydrogenase as the endogenous reference gene. In addition, we measured enzyme activity of glutathione reductase with a commercial kit based on a colorimetric assay. Results: The tumor tissue had higher expression of glutathione reductase compared to the margin tissue (P=0.005). There was significantly greater glutathione reductase enzyme activity in the tumor tissue (116.9±34.31 nmol/min/ml) compared to the noncancerous adjacent tissues (76.7±36.85 nmol/min/ml; P=0.003). Conclusion: These data showed increased glutathione reductase expression and enzyme activity in colorectal tumor tissue. Given the key role of glutathione in synthesis of dNTPs for DNA repair with the glutaredoxin system, the increased glutathione reductase expression and activity might be a reflection of hyperactivity of this enzyme in DNA synthesis and the repair process in colorectal cancer cells

Effect of Drying Temperature on Iron Fischer-Tropsch Catalysts Prepared by Solvent Deficient Precipitation

A novel solvent deficient precipitation (SDP) method to produce nanoparticles was studied for its potential in Fischer-Tropsch synthesis (FTS) catalysis. Using Fe(NO3)3·9H2O as the iron-containing precursor, this method produces ferrihydrite particles which are then dried, calcined, reduced, and carbidized to form the active catalytic phase for FTS. Six different drying profiles, including final drying temperatures ranging between 80 and 150°C, were used to investigate the effect of ammonium nitrate (AN), a major by-product of reaction between Fe(NO3)3·9H2O and NH4HCO3 in the SDP method. Since AN has two phase-transitions within this range of drying temperatures, three different AN phases can exist during the drying of the catalyst precursors. These AN phases, along with physical changes occurring during the phase transitions, may affect the pore structure and the agglomeration of ferrihydrite crystallites, suggesting possible reasons for the observed differences in catalytic performance. Catalysts dried at 130°C showed the highest FTS rate and the lowest methane selectivity. In general, better catalytic performance is related to the AN phase present during drying as follows: phase III &gt; phase II &gt; phase I. However, within each AN phase, lower drying temperatures led to better catalytic properties.</jats:p

Caregiving consequences in cancer family caregivers: a narrative review of qualitative studies

BackgroundCancer is a significant public health issue, causing various challenges for individuals affected by it. As cancer progresses, patients often become dependent on others for support. Family caregivers and members play a crucial role in the recovery and rehabilitation of these patients. However, caregivers themselves face numerous challenges throughout the course of their family member’s illness. Exploring the experiences of family caregivers can inform long-term planning and supportive interventions to address their caregiving difficulties. This study reviews previous literature on caregiving outcomes.MethodThis study presents a narrative review of qualitative studies, analyzing a total of 23 articles. The results were extracted and organized into subcategories. After revision by the research team, main categories were identified. These categories encompass both positive and negative outcomes of caregiving.ResultsThe findings of this review demonstrate that caring for a family member with cancer has significant implications for caregivers. These implications include: (A) Positive outcomes of caregiving (such as achieving self-management and balance, promoting kinship intimacy, finding meaning and purpose, and experiencing spiritual growth) and (B) Negative outcomes of caregiving (including care-related physical exhaustion, disruption of personal life plans, psycho-emotional consequences, and socio-economic burden).ConclusionThe results of this study highlight the challenges faced by family caregivers and emphasize the importance of addressing their needs within the healthcare system. By providing support and attention to their well-being, caregivers can enhance their resilience and adaptability in managing caregiving difficulties