The protective effect of α7-nACh receptor and its interaction with 5-HT1B/1D receptors in acute intestinal ischemia-reperfusion injury in rats.

Over the past decades, great attention has been given to the nervous system modulating effects on the immune response in inflammation-associated injuries, such as acute intestinal ischemia-reperfusion (IR). Recently, we proved the anti-inflammatory and antioxidant effects of 5-hydroxytryptamine (5-HT)1B/1D receptors in intestinal IR injury in rats. Also, the alpha7 nicotinic acetylcholine (α7-nACh) receptor has anti-inflammatory effects in different inflammation-associated injuries. Starting from these premises, we aimed to examine the function of the α7-nACh receptors and the functional interactions between the anti-inflammatory and antioxidant effects of α7-nACh and 5-HT1B/1D receptors in acute intestinal IR injury. To confirm the expression and localization of α7-nACh receptors on the ileum nerves, an immunofluorescence-based method was applied. Then, intestinal IR injury was induced by 30-min occlusion of superior mesenteric artery and reperfusion for 2 h in rats. Acute systemic administration of α7-nACh receptor agonist PNU-282987 and antagonist methyllycaconitine, and 5-HT1B/1D receptors agonist (sumatriptan) and antagonist (GR127, 935) were used in the model of intestinal IR injury. Finally, biochemical and histological parameters were assessed. Α7-nACh receptors were expressed by 9% on the ileum nerves. Likewise, activation of the α7-nACh receptor showed anti-inflammatory and antioxidant effects in intestinal IR injury but not as well as 5-HT1B/1D receptors. Interestingly, 5-HT1B/1D receptors via attenuation of glutamate (Glu) release indirectly activated the α7-nACh receptor and its protective effects against inflammation and oxidative stress. The protective effect of the α7-nACh receptor on intestinal IR injury was activated indirectly through the 5-HT1B/1D receptors' modulatory impact on Glu release.

Epidemiology of diabetes in Iran: A scoping review of studies published during 2015-2019.

Background: Proper synthesis of existing epidemiologic studies on diabetes in Iran can guide future research efforts. We aimed to conduct a comprehensive scoping review on all research articles that investigated any aspect of diabetes epidemiology in Iran during 2015-2019. Methods: This work was conducted as a part of the Iran Diabetes Research Roadmap and completed under Arksey and O'Malley's framework for scoping reviews. The Scopus and PubMed databases were searched on Feb 15th, 2020. Eligible document types on diabetes epidemiology in the Iranian population, in Persian or English, that published during the 2015-2019 period underwent eligibility assessment. A total of 315 relevant articles were included and further analysis was performed on the original studies (n = 268). Through classifying them into six domains: Diabetes incidence; the prevalence of diabetes and associated factors; the incidence/prevalence of complications/comorbid conditions; mortality/survival; burden; and prediction modeling. Results: In total, 64 (20.3%) papers were published in Q1 journals, and 40 (12.6%) were international collaborations. No clear annual trend was present in the number of published primary or secondary articles, the portion of papers published in Q1 journals, international collaborations or relative domain proportions. Few review articles were found on prediction modeling, mortality or burden (excluding global studies). Conclusions: Our findings show a minor portion of works on diabetic epidemiology in Iran meets the quality standards of Q1 journals. Researchers have neglected some critical subjects and have occasionally fallen for common pitfalls of epidemiologic research. In particular, adhering to established guidelines can help authors implement rigorous methods to develop, validate, and deploy practical clinical prediction models. Researchers should prioritize investigating longitudinally collected data that aid in measuring disease incidence and enable casual inference. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01094-0.

Knowledge gaps in diabetes research: an evidence mapping of the literature.

Background: Mapping the available evidence can be used to inform current diabetes research, identify relevant gaps, and prioritize future research. In this regard, we mapped diabetes research performed in Iran. Method: We searched the Scopus and PubMed databases from 01/01/2015 till 01/01/2020 using keywords such as diabetes and Iran. The included articles were classified according to their document types, level of evidence, and subject areas. Results: The majority of the included articles (53%) were related to diabetes types, followed by complications (28%). Most of the documents were original articles (82%), and reviews were 18% of the publications. Systematic reviews constitute only 6% of the total documents. Observational studies were the most common types of study designs (26%), followed by clinical trials (20%). Moreover, topics on control and management of diabetes were the most prevalent subject areas (58%), and fewer studies were on preventive strategies (6%). In diabetes management studies, less attention has been paid to evaluate psychological (10%), educational (9%), and physical activity-related (7%) interventions. There was a shortage of secondary studies related to physical activity, psychology, diagnostic, and screening-related studies. Conclusion: To fill diabetes research gaps, more investment in cost-effectiveness interventions, such as preventive strategies and behavioral self-management programs, need. Moreover, we need to pay more attention on applied sciences and real world evidence to bridge translational gaps from bench to bedside. In this regard, further data synthesis can be helpful in evaluating the effectiveness of the available studies and avoiding unnecessary investigations.

Involvement of 5-HT1B/1D receptors in the inflammatory response and oxidative stress in intestinal ischemia/reperfusion in rats.

Acute mesenteric ischemia (AMI) is caused by an abrupt cessation of blood flow to the small intestine. Reperfusion is the return of blood flow to the ischemic bowel. Intestinal ischemia/reperfusion (I/R) leads to the formation of reactive oxygen species, local inflammatory response, and may lead to the patient's death. Pre-treatment of the intestinal may reduce the high mortality associated with AMI. 5-Hydroxytryptamine 1B (5-HT1B) and 5-HT1D receptors have anti-inflammatory and neuroprotective effects in different experimental studies. We aimed to investigate the potential involvement of these receptors in intestinal I/R injury. Firstly, we assessed the expression and localization of 5-HT1B and 5-HT1D receptors in the enteric nervous system using an immunofluorescence-based method. Intestinal I/R in rats was induced by 30 min occlusion of superior mesenteric artery and reperfusion for 2 h. Rats were randomly divided in different control and I/R groups (n = 6) receiving either vehicle, sumatriptan (5-HT1B/1D receptors agonist; 0.1 mg/kg), GR127,935 (5-HT1B/1D receptors antagonist; 0.1 mg/kg) and combination of sumatriptan (0.1 mg/kg) + GR127,935 (0.1 mg/kg) before determination of biochemical and histological parameters. In the enteric nervous system, 5-HT1B and 5-HT1D receptors were expressed 17% and 11.5%, respectively. Pre-treatment with sumatriptan decreased 5-hydroxytryptamine (5HT) level by 53%, and significantly decreased calcitonin gene-related peptide (CGRP) levels, lipid pereoxidation, neutrophil infiltration, and level of pro-inflammatory markers in the serum. Histopathologic studies also showed a remarkable decrease in intestinal tissue injury. These findings suggest that sumatriptan may inhibit intestinal injury induced by I/R through modulating the inflammatory response by activation of 5-HT1B/1D receptors.

Evaluation of Neutrophil Gelatinase-Associated Lipocalin and Cystatin C in Early Diagnosis of Chronic Kidney Disease in the Absence of the Gold Standard.

BACKGROUND: Glomerular filtration rate (GFR) is considered as a gold standard of kidney function. However, using GFR as the gold standard is not common in clinical practice, because its direct measurement is usually expensive, cumbersome, and invasive. In the present study, we assessed the predictive power of two other biomarkers, Cystatin-C (Cys-C) and Neutrophil Gelatinase-Associated Lipocalin (NGAL) for early detection of chronic kidney diseases (CKD) in the absence of a gold standard. MATERIALS AND METHODS: In this study, 72 patients who referred to the Shohadaye Tajrish Hospital of Tehran, Iran, for measuring their kidney function were studied. The ELISA method was utilized for measuring plasma NGAL (PNGAL) and serum Cys-C (SCys-C). The Bayesian latent class modeling approach was applied to asses the predictive power of these biomarkers. RESULTS: While both the biomarkers had rather high sensitivities (PNGAL=91%, SCys-C= 89%), the specificity of SCys-C biomarker was very lower than the one of PNGAL (SCys-C=56%, PNGAL=94%). The estimated area under the receiver operating characteristic (ROC) curve for SCys-C as the single biomarker for the diagnosis of CKD was about 0.76, while a similar estimate for PNGAL was 0.93. The added value of PNGAL to SCys-C for the diagnosis of CKD in terms of the ROC curve was about 0.19, while the added value of SCys-C to PNGAL was less than 0.02. CONCLUSION: In general, our findings suggest that PNGAL can be utilized as a single reliable biomarker for early detection of CKD. In addition, results showed that when a perfect gold standard is not available, Bayesian approaches to latent class models could lead to more precise sensitivity and specificity estimates of imperfect tests.

Comparative assessment of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C as early biomarkers for early detection of renal failure in patients with hypertension.

BACKGROUND: Hypertension is one the most common causes of chronic kidney disease (CKD). One of the major concerns in hypertensive patients is early detection of renal disorders. In the past, serum creatinine (Scr) concentration was used as a marker of kidney function, but it proffers a late reflection of reduced glomerular filtration rate. Cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) have been recently proven to be useful for quantification of CKD. Therefore, we compared the diagnostic value of NGAL with cystatin C and creatinine to evaluate kidney function in hypertensive patients. METHODS: In this study, 42 hypertensive patients and 30 healthy volunteers were recruited. Serum cystatin C (Scys C) and plasma NGAL were measured using ELISA method. Creatinine, urea, hemoglobin, fibrinogen, and C-reactive protein were measured according to the routine methods. Estimated glomerular filtration rate (eGFR) was considered as the gold standard method (cut-off value of < 78 ml/min/1.73 m². RESULTS: In the patient group, plasma NGAL, cystatin C, and creatinine were all significantly correlated with eGFR, and plasma NGAL correlated best with eGFR. Receiver-operating characteristics analysis indicated that plasma NGAL was a better indicator than creatinine and cystatin C for predicting a GFR < 78 ml/min/1.73 m2. The sensitivity and specificity for NGAL were 96% and 100%, for cystatin C were 92% and 60% and for creatinine were 76% and 47%, respectively. CONCLUSION: Plasma NGAL demonstrated a higher diagnostic value to detect kidney impairment in the early stages of CKD as compared to Scys C and Scr in hypertensive patients.