Integrating protein interaction and pathway crosstalk network reveals a promising therapeutic approach for psoriasis through apoptosis induction.

Psoriasis is a complex inflammatory skin disease manifested by altered proliferation and differentiation of keratinocytes with dysfunctional apoptosis. This study aimed to identify regulatory factors and comprehend the underlying mechanisms of inefficient apoptosis to open up promising therapeutic approaches. Incorporating human protein interactions, apoptosis proteins, and physical relationships of psoriasis-apoptosis proteins helped us to generate a psoriasis-apoptosis interaction (SAI) network. Subsequently, topological and functional analyses of the SAI network revealed effective proteins, functional modules, hub motifs, dysregulated pathways and transcriptional gene regulatory factors. Network pharmacology, molecular docking and molecular dynamics simulation methods identified the potential drug-target interactions. RELA, MAPK1, MAPK3, MMP9, IL1B, AKT1 and STAT1 were revealed as effective proteins. The MAPK1-MAPK3-RELA motif was identified as a hub regulator in the crosstalk between 41 pathways. Among all pathways, "lipid and atherosclerosis" was found to be the predominant pathway. Acetylcysteine, arsenic-trioxide, ß-elemene, bortezomib and curcumin were identified as potential drugs to inhibit pathway crosstalk. Experimental verifications were performed using the literature search, GSE13355 and GSE14905 microarray datasets. Drug-protein-pathway interactions associated with apoptosis were deciphered. These findings highlight the role of hub motif-mediated pathway-pathway crosstalk associated with apoptosis in the complexity of psoriasis and suggest crosstalk inhibition as an effective therapeutic approach.

Effect of university policies on research productions: a scientometric study.

BACKGROUND: This study aimed to assess the effect of new package of interventions on scientific productions rate in Shahid Beheshti University of Medical Sciences. METHODS: Through a health system research, we extracted policies from the strategic plan of the university and 10 interventions were developed to increase the scientific productions in terms of quality, quantity and commercialization and to develop infrastructure for research in health service provision and education. For evaluating the effectiveness of interventions, citation and publication indicators for individuals and schools were analyzed using descriptive statistics and t-test. They were extracted from Scopus and ISI web of knowledge during period of 1/1/2009 to 30/5/2012. RESULTS: There was an increasing trend in scientific productions from 2009 to mid-2012. We found 60 percent of total scientific productions of the university were published during last 3.5 years. During this 3.5 years, 10 more percentile of faculty members involved in research. Schools of pharmacy, Medicine and Health had the highest scientific products. Mean for h-index was 1.5 (SD=2.49) in ISI and 1.9 (SD=2.89) in Scopus database (p<0.001). CONCLUSION: Effective policies and interventions lead to 46% increase in scientific productions from 2009 to 2010 and 56% increase from 2010 to 2011.

The healing effect of unrestricted somatic stem cells loaded in collagen-modified nanofibrous PHBV scaffold on full-thickness skin defects.

Unrestricted somatic stem cells (USSCs) loaded in nanofibrous PHBV scaffold can be used for skin regeneration when grafted into full-thickness skin defects of rats. Nanofibrous PHBV scaffolds were designed using electrospinning method and then, modified with the immobilized collagen via the plasma method. Afterward, the scaffolds were evaluated using scanning electron microscopy, physical and mechanical assays. In this study; nanofibrous PHBV scaffolds loaded with and without USSCs were grafted into the skin defects. The wounds were subsequently investigated at 21 days after grafting. Results of mechanical and physical analyses showed good resilience and compliance to movement as a skin graft. In animal models; all study groups excluding the control group exhibited the most pronounced effect on wound closure, with the statistically significant improvement in wound healing being seen on post-operative Day 21. Histological and immunostaining examinations of healed wounds from all groups, especially the groups treated with stem cells, showed a thin epidermis plus recovered skin appendages in the dermal layer. Thus, the graft of collagen-coated nanofibrous PHBV scaffold loaded with USSC showed better results during the healing process of skin defects in rat model.

Association of psoriasis severity with serum prolactin, thyroid hormones, and cortisol before and after treatment.

BACKGROUND: Prolactin (PRL) level is proposed to be associated with the severity of psoriasis although the previous studies reported different results. OBJECTIVE: To find the association between PRL levels and severity of psoriasis before and after treatment. In addition, we aimed to find a difference in prolactin, thyroid stimulating hormone (TSH), thyroid hormones (T3 and T4), and cortisol levels between patients with psoriasis and normal controls. METHODS: First, the levels of hormones were measured in 30 patients with psoriasis and 30 matched controls. The severity was assessed by psoriasis area and severity index (PASI). Then, patients were treated, and PASI was assessed every week until achieving PASI-75 response. At this time, the hormones were measured again and compared to the baseline. RESULTS: No statistical significant difference was observed in the mean PRL, T3, T4, TSH, and cortisol levels between cases and controls. Comparing to the baseline, a significant decrease in PRL levels and a significant increase in T3 and serum cortisol levels were observed after treatment (P < 0.05), while the changes in other hormones were not significant. CONCLUSION: After treatment, PRL significantly decreased, and T3 and cortisol levels significantly increased. No correlation between hormone levels and improvement of PASI score existed.

Mucosal manifestations of pemphigus vulgaris in ear, nose, and throat; before and after treatment.

BACKGROUND: Pemphigus vulgaris (PV) is a life-threatening autoimmune bullous disease, mediated by autoantibodies directed against antigens on the keratinocyte cell surface of stratified squamous epithelia. The frequency of ear, nose, and throat (ENT) involvement in PV is not clearly identified. OBJECTIVE: We sought to evaluate the ENT involvement in new patients with PV examined by ENT endoscopy before and after treatment. METHODS: This study included 41 new patients with PV. All patients were evaluated for ENT manifestations by otoscopic and endoscopic examination before treatment. After these examinations, the patients received proper treatment according to standard protocols. Thirty patients were re-evaluated by endoscopic examination after clinical remission of mucocutaneous signs. RESULTS: A total of 41 (33 [80.5%] male and 8 [19.5%] female) patients with mean age of 44.56 ± 12.76 years entered this study. In ENT examination of patients before the treatment, 11 (26.8%) patients showed ear, 15 (36.6%) nasal, 37 (90.3%) oral, 25 (61%) pharyngeal, and 24 (58.5%) laryngeal involvement. Thirty patients underwent the posttreatment ENT examination. We found ear signs in 2 (6.7%), nasal involvement in 1 (3.3%), oral signs in 4 (13.3%), pharyngeal manifestations in 6 (20%), and laryngeal signs in 3 (10%) patients after treatment. The treatment was significantly effective in the improvement of mucosal lesion in different sites (P < .01). LIMITATION: Eleven patients refused to undergo posttreatment ENT examination. CONCLUSION: ENT evaluation may be worthwhile to evaluate the disease extension in patients with PV more definitely and exclude other potential etiologies in recalcitrant patients.

Facial and bilateral acral porokeratosis with nail dystrophy: A case report.

Porokeratosis is a rare disorder of keratinization with unknown etiology. It exhibits both sporadic and autosomal dominant inheritance. The lesions are sharply demarcated, hyperkeratotic, and annular with distinct keratotic edges. The cornoid lamella is the histological hallmark of porokeratosis. Porokeratosis lesions on the face may have a superficial or a destructive nature. To our knowledge there are only a few cases of facial porokeratosis that have been reported. We report a sporadic form of facial and bilateral acral porokeratosis with nail dystrophy.

Four familial cases of epidermodysplasia verruciformis: mother and three sons.

Epidermodysplasia verruciformis (EV) is a rare genodermatosis associated with a high risk of skin cancer. In this report, we present three Iranian brothers and their mother with extensive seborrheic keratosis-like (SK-like) viral warts. Initial facial lesions developed in the first decade and disseminated with time. The patients showed SK-like viral warts characterized by dark brown or black pigmented proliferative lesions with hyperkeratotic surfaces. The histopathological findings were consistent with the diagnosis of EV. There are few reports of familial epidermodysplasia verruciformis especially in a mother and her three sons.

On the mechanism of apoptosis-inducing activity of human calprotectin: zinc sequestration, induction of a signaling pathway, or something else?

Calprotectin, a heterodimer present in neutrophil cytoplasm, has antimicrobial and apoptosis-inducing activities. At the moment, there are two general hypotheses about the mechanism of action of calprotectin: (i) exclusion of extracellular zinc by calprotectin, and consequently induction of apoptosis; (ii) binding of calprotectin to a cell membrane receptor, and consequently, activation of a signaling pathway for apoptosis. Here, we introduce another hypothesis, i.e. inhibition or destruction of "target" inside cells. We suggest that calprotectin might become internalized non-specifically, maybe in a process like pinocytosis. This process is probably independent of the zinc concentration. We also demonstrated that the internal target hypothesis successfully predicts cell survival behavior of cultured cells as a function of calprotectin concentration. Additional analyses should be performed to elucidate the real calprotectin "target".