The clinical significance of the glucocorticoid receptors: Genetics and epigenetics.

The impacts of glucocorticoids (GCs) are mainly mediated by a nuclear receptor (GR) existing in almost every tissue. The GR regulates a wide range of physiological functions, including inflammation, cell metabolism, and differentiation playing a major role in cellular responses to GCs and stress. Therefore, the dysregulation or disruption of GR can cause deficiencies in the adaptation to stress and the preservation of homeostasis. The number of GR polymorphisms associated with different diseases has been mounting per year. Tackling these clinical complications obliges a comprehensive understanding of the molecular network action of GCs at the level of the GR structure and its signaling pathways. Beyond genetic variation in the GR gene, epigenetic changes can enhance our understanding of causal factors involved in the development of diseases and identifying biomarkers. In this review, we highlight the relationships of GC receptor gene polymorphisms and epigenetics with different diseases.

Comparison between C4d immunohistochemical staining and other clinical-histopathological findings in IgA nephropathy.

INTRODUCTION: IgAN occurs following abnormal IgA deposition in the glomerular mesangial regions. It is the most common primary glomerular disease and one of the causes of ESRD, so it is necessary to identify clinical and histopathological findings that predict progression to ESRD. In the physiopathology of this disease, C4d causes serious renal injuries and should be counted as a significant prognostic factor too. This study examined C4d biomarker and compare it with findings affecting prognosis, to determine the predictive value of C4d in progression to ESRD in IgAN. MATERIALS AND METHODS: In this study, all biopsy samples of IgAN patients who referred to Imam Reza Hospital in Tabriz were collected for four years. Their samples were evaluated C4d immunohistochemical staining and positive samples have compared with Clinical-histopathological findings affecting prognosis. RESULTS: In this study, C4d positivity showed a significant association with mesangial hypercellularity (p = 0.001), segmental glomerulosclerosis (p = 0.003), and endocapillary hypercellularity (p = 0.001); however, it did not show a significant relationship with tubular atrophy/interstitial fibrosis (p = 0.08). The study also found that C4d positivity was significantly (p < 0.05) correlated with hypertension, increased proteinuria, hematuria, high creatinine, and decreased mean eGFR. CONCLUSION: This study showed that immunohistochemical staining of C4d is a useful method for evaluating the prognosis of the severity of renal injuries in patients with IgAN and could be a valuable alternative for most Clinical-histopathological factors routinely used as predictive factors for its progression to ESRD, especially when the biopsy specimen size is small and insufficient for other studies.

Oral spirochetes: Pathogenic mechanisms in periodontal disease.

Periodontitis is an infectious inflammatory disease resulting from infection of biofilm forming bacteria. Several bacterial factors regulate inflammatory response and cause to tissue damage and loss of connection between gingival and tooth. Since bacterial virulence factors and also host immune responses have role, understanding of periodontal disease is complex, in overall we can say that in this disease epithelium is deleted by bacteria. Oral spirochetes are related to periodontitis, among them, Treponema denticola, have been associated with periodontal diseases such as early-onset periodontitis, necrotizing ulcerative gingivitis, and acute pericoronitis. This review will analyse mechanisms of pathogenesis of spirochetes in periodontitis. Microorganisms cause destruction of gingival tissue by two mechanisms. In one, damage results from the direct action of bacterial enzymes and cytotoxic products of bacterial metabolism. In the other, only bacterial components have role, and tissue destruction is the inevitable side effect of a subverted and exaggerated host inflammatory response to plaque antigens.

Plasma levels of miR-21, miR-150, miR-423 in patients with lupus nephritis.

INTRODUCTION: MicroRNAs (miRNA) are involved in the pathogenesis of systemic lupus erythematosus (SLE), an autoimmune disease, and can be considered as diagnostic and prognostic biomarkers. Lupus nephritis (LN) remains a major challenge of SLE since it damages the kidneys in the course of the disease. METHODS: The aim of this study was to investigate the diagnostic values of circulating miR-21, miR-148a, miR-150, and miR-423 involved in autoimmunity and kidney fibrosis in plasma samples of LN cases (N = 26) and healthy controls (N = 26) using quantitative- PCR (qPCR). The possible associations between the microRNAs and clinical parameters and their diagnostic values were also calculated. RESULTS: The levels of circulating miR-21 (P < .001) and miR-423 (P < .05) significantly increased, while miR-150 decreased in LN (P > .05) patients as compared with healthy controls. Receiver operating characteristic (ROC) analysis indicated that miR-21 was superior in discriminating LN patients from controls with an Area Under Curve (AUC) of 0.912 [95% CI = 0.83 to 0.99, P < .001], whereas the multivariate ROC curve analysis revealed the high accuracy [AUC = 0.93, P < .001, 79% sensitivity and 83% specificity] of the miR-21, -150, and -423 to differentiate LN from controls. CONCLUSION: The involvement of the studied miRNAs in renal fibrosis and the obtained results make it rational to speculate that they may be used as potential biomarkers in LN.

Comparison of edema and ecchymosis in rhinoplasty candidates after lateral nasal osteotomy using piezosurgery and external osteotomy.

Rhinoplasty is done with external and endonasal methods. One of the main stages of rhinoplasty in both external and endonasal methods is the lateral nasal osteotomy. Lateral nasal osteotomy is the main cause of edema and ecchymosis after rhinoplasty, which is annoying and unpleasant for patients. Piezosurgery is a new method that uses electronic-ultrasonic waves to perform nasal osteotomies. The aim of this study was to compare of edema and ecchymosis after lateral nasal osteotomy using piezosurgery with external osteotomy in rhinoplasty candidates. In this clinical trial, 66 experimental patients for rhinoplasty surgery were selected from Imam Reza hospital in Tabriz, Iran. After examination, the patients were randomly divided into two groups. One group of patients had lateral nasal osteotomy by using the piezosurgery technique, and the other group had a lateral osteotomy with the conventional method of external subcutaneous. On the third and 7 days after the operation, the level of edema and ecchymosis in the patients were examined as per the Gökalan questionnaire (adopted by Yucel) by two persons who were not aware of the goals of the study, and then, they evaluated and scored the questionnaire. The obtained data were analyzed by the SPSS 19 software. The highest level of edema and ecchymosis was observed 3 days after surgery in both groups. Meanwhile, the findings revealed a significant difference between the two groups in the amount of edema and ecchymosis on day 3 after surgery. Furthermore on day 7, the amount of edema and ecchymosis compared to that of the 3rd day was statistically significant for both groups. In general, in all studied groups, edema, and ecchymosis decreased in 7 days compared to 3 days and also piezosurgery is more promising and effective than osteotomy.

Altered levels of immune-regulatory microRNAs in plasma samples of patients with lupus nephritis.

Introduction: Lupus nephritis (LN) is a major cause of mortality and morbidity in the patients with lupus, a chronic autoimmune disease. The role of genetic and epigenetic factors is emphasized in the pathogenesis of LN. The aim of the present study was to evaluate the levels of immune-regulatory microRNAs (e.g., miR-31, miR-125a, miR-142-3p, miR-146a, and miR-155) in plasma samples of patients with LN. Methods: In this study, 26 patients with LN and 26 healthy individuals were included. The plasma levels of the microRNAs were evaluated by a quantitative real-time PCR. Moreover, the correlation of circulating plasma microRNAs with disease activity and pathological findings along with their ability to distinguish patients with LN were assessed. Results: Plasma levels of miR-125a (P = 0.048), miR-146a (P = 0.005), and miR-155 (P< 0.001) were significantly higher in comparison between the cases and controls. The plasma level of miR-146a significantly correlated with the level of anti-double strand-DNA antibody and proteinuria. Moreover, there was a significant correlation between miR-142-3p levels and disease chronicity and activity index (P <0.05). The multivariate ROC curve analysis indicated the plasma circulating miR-125a, miR-142-3p, miR-146, and miR-155 together could discriminate most of the patients with LN from controls with area an under curve (AUC) of 0.89 [95% CI, 0.80-0.98, P<0.001], 88% sensitivity, and 78% specificity. Conclusion: Based on the findings of the present study, the studied microRNAs may be involved in the pathogenesis and development of LN and have the potential to be used as diagnostic and therapeutic markers in LN.

A Comparative Study of Macrophage Density in Odontogenic Cysts and Tumors with Diverse Clinical Behavior.

STATEMENT OF THE PROBLEM: Macrophages are the target of attention in numerous diseases. Many studies reported them as the regulators of the growth, dissemination, and clinical behavior of various lesions. There are relatively scarce data regarding the role of macrophages in oral lesions, particularly odontogenic lesions. PURPOSE: This study investigated the macrophage density in odontogenic lesions of diverse biologic performance. MATERIALS AND METHOD: In this comparative analytical study, 60 cases of odontogenic lesions including ameloblastoma, keratocystic odontogenic tumor, dentigerous cyst, and radicular cyst were immunohistochemically stained with anti-CD68 antibody. One-way ANOVA and Tukey's HSD test were used for statistical analysis. RESULTS: The results showed that the macrophage density in keratocystic odontogenic tumor (35.72±7.74) and ameloblastoma (46.12±9.84) was not significantly different from that in dentigerous cyst (43.87±8.13). Interestingly, the macrophage density in keratocystic odontogenic tumor was lower than that in dentigerous cyst. No significant difference was observed in macrophage density between the ameloblastoma and much less aggressive lesions like dentigerous cyst (p= 0.59). Macrophage density in radicular cyst (81.53±11.04) was significantly higher than other odontogenic lesions (p< 0.001). CONCLUSION: The lack of significant differences in macrophage density between the known aggressive odontogenic tumors and much less aggressive lesions implied that macrophages might not contribute to the biological behavior of the odontogenic lesions. Therefore, it could support the notion that targeted therapy would not have prominent clinical potential to decrease the extent of mutilating surgeries in odontogenic lesions.

EXTENDED-SPECTRUM BETA-LACTAMASE PRODUCING GRAM NEGATIVE BACTERIA IN IRAN: A REVIEW.

BACKGROUND: The emergence and spread of extended spectrum ß-lactamase (ESBL)-producing Gram- negative bacteria (GNB), particularly in Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa, have increased all over the world. ESBLs are characterized by their ability to hydrolyze ß-lactams, early cephalosporins, oxyimino-thiazolyl cephalosporins, and monobactams, but not cephamycins or carbapenems. The rate of nosocomial infections caused by ESBL-producing GNB in Asia Pacific has increased and several studies have identified their prevalence in the region. The aim of this study is to review the prevalence of ESBL-producing GNB in the West Asia and the Middle East with a particular focus on Iran. MATERIALS AND METHODS: The available evidence from various studies (Microbia and clinical studies, retrieved from the PubMed, and Scopus databases) regarding the ESBL producing Gram negative bacteria in Iran were evaluated. RESULTS: In almost all parts of the country, high resistance has been observed, especially in the central part of Iran. Up to 89.8% Escherichia coli, 72.1% Klebsiella pneumonia, 84.2% Acinetobacter baumannii, and 83.8% Pseudomonas aeruginosa isolates are ESBL positive. CONCLUSION: The present study showed the increasing prevalence of ESBLs in different regions of Iran, which could be useful to strategic policy towards reducing reduce their prevalence.

The Prevalence of CTX-M-15 Extended-spectrum ß-Lactamases Among Salmonella spp. and Shigella spp. Isolated from three Iranian Hospitals.

Bacterial antimicrobial resistance mediated by the production of extended-spectrum ß-lactamases (ESBLs) is considered a major threat for treatment of Salmonella and Shigella infections. This study aimed to investigate antibiotic resistance patterns of Salmonella and Shigella spp. and presence of CTX-M from three teaching hospitals in Iran. In the present study, 58 clinical Shigella and 91 Salmonella isolates were recovered between 2009 and 2013 from 3 teaching hospitals in Iran. After culture and antimicrobial susceptibility testing, ESBL-positive isolates were subjected to further investigations. These included polymerase chain reaction (PCR) amplification and DNA sequencing of blaCTX-M-15 encoding plasmid. In both genera, high sensitivity to gentamicin and amikacin, but high resistance to ampicillin, tetracycline, and trimethoprim-sulfamethoxazole, was found. Molecular investigation showed that 31.8% isolates of Salmonella spp. and 34.48% isolates of Shigella spp. were CTX-M positive and all of them were also positive for ISEcpI. Protein translation, comparing with reference sequences, showed that all CTX-M isolates belong to CTX-M-15. The present study suggests that the resistance of ESBLs-producing Salmonella and Shigella spp. in Iran hospitals is very serious. Therefore, strategies to minimize the spread of ESBL-producing isolates should be implemented.

Evaluation of EBV transformation of human memory B-cells isolated by FACS and MACS techniques.

Several studies have been performed to develop effective neutralizing monoclonal antibodies. The Epstein-Barr virus (EBV) can efficiently immortalize B-cells to establish lymphoblastoid cell lines (LCL) and so it has been used extensively for transformation of B-cells to produce and secrete immunoglobulin. The present study addressed the effect of TLR7/8 agonist (R848), feeder cells layer and fluorescence-activated cell sorting (FACS) and magnetic-activated cell sorting (MACS) cell separation methods on the transformation efficiency of antibody-producing memory B-cells. For these studies, the antigen used for analyses of antibody formation was the tetanus neurotoxin (TeNT) derived from Clostridium tetani. The results here showed that employing an HFFF.PI6 feeder cell layer, R848 agonist and FACS-mediated purification of memory B-cells led to increased transformation efficiency. Altogether, the effects of the R848 and the feeder cells provided an efficient method for EBV transformation of human B-cells. Moreover, there was an advantage in using FACS sorting of B-cells over the MACS method in the context of EBV transformation and immortalization of precursors of antigen-specific B-cells.

Microscopic polyangiitis complicated with bilateral brachial plexopathy: a case report and review of the literature.

Microscopic polyangiitis is a small-vessel necrotizing vasculitis associated with anti-neutrophil cytoplasmic antibodies and presents itself with glomerulonephritis and hemorrhagic pulmonary capillaritis. Peripheral nervous system involvement is common in anti-neutrophil cytoplasmic antibodies-associated vasculitis, but brachial plexopathy is unusual. We present the case of a 22-year-old man with known microscopic polyangiitis who was under maintenance therapy with prednisolone and cyclophosphamide and developed cough, dyspnea, and hemoptysis which increased in 6 days accompanying pain and paresthesia in the upper limbs. His physical examination revealed hypoesthesia, absence of deep tendon reflexes, and decreased muscle strength in the upper limbs. His chest computed tomography scan showed ground glass pattern in the lower and middle lobes. Electromyography and nerve conduction study showed bilateral brachial plexopathy with involvement of all of the cervical roots that were more severe in the lower roots and left side.

Primary Pulmonary Fibrosarcoma With Bone Metastasis: a Successful Treatment With Post-Operation Adjuvant Chemotherapy.

INTRODUCTION: Pulmonary fibrosarcoma has been an extremely rare tumor in children. Wide surgical resection of infantile fibrosarcoma would be the treatment of choice. CASE PRESENTATION: Post-operative chemotherapy has shown the benefit in the cases of residual disease after initial surgery and metastatic disease in the literature. We have presented the case of a 70-days old male child with primary infantile fibrosarcoma of the left lung and distant metastasis of skull. CONCLUSIONS: The aim of this publication was to highlight the role of adjuvant chemotherapy to improve outcome of infantile fibrosarcoma with residual tumor and / or metastatic disease.