Association between the Treatment of Rosacea and Eradication of Helicobacter Pylori Infection.

Background: Rosacea is a multifactorial skin inflammatory disorder with an unknown cure. Genetics and environmental factors such as microorganisms are involved in the rosacea etiology, for example, Helicobacter pylori have been suggested in rosacea progression. The present study investigated the relationship between H. pylori eradication and rosacea patient's improvement. Materials and Methods: H. pylori infection was investigated in 60 rosacea patients and 65 sex- and age-matched healthy control through enzyme-linked immunosorbent assay (ELISA) and HpSag tests. After infection confirmation, randomly half of the rosacea patients were treated for H. pylori eradication (test), and others received standard treatment (control). HpSag and ELISA tests were repeated after infection eradication and disease flow was surveyed for 60 days. The groups were compared using the ANOVA (Analysis Of Variance) test at the significant level of P < 0.05. Results: At the baseline, the mean of immunoglobulin G (IgG) (59.27 ± 41.4 RU/mL) and immunoglobulin M (IgM) (11.55 ± 6.1 RU/mL) in rosacea patients was higher than the level of IgG (41.38 ± 54.33 RU/mL) and IgM (8.11 ± 8.91 RU/mL) in healthy control (P < 0.04) and (P < 0.01), respectively. Also, the values for H. pylori infection were positive in all patients and 10 healthy controls. The mean titer of IgM and IgG in the test and control patients groups were different at baseline and after treatment. Furthermore, in the test patients group, the mean of IgG was reduced in active rosacea after treatment, and 63.9% of active patients showed rosacea remission after H. pylori eradication. Conclusion: Data suggest the exacerbating role of H. pylori in rosacea, and its eradication along with other therapeutic methods causes rosacea improvement.

Chlamydia pneumoniae Seropositivity in the Iranian Patients with the Skin Inflammatory Disorder of Rosacea.

Background: Rosacea is a skin chronic inflammation with an unknown cause and cure. Environmental and genetic factors could not entirely explain the disease pathogenesis. Recently, infections like Chlamydia pneumoniae are of more attention in the rosacea progression. This study investigated the relationship between the C. pneumoniae seropositivity and the rosacea disorder. Materials and Methods: We aimed at a cohort of 100 patients with the rosacea disorder (60 active and 40 inactive) and from 100 sex- and age-matched healthy controls in Isfahan and determined the immunoglobulin M (IgM)/IgG antibodies titers to C. pneumoniae in the serum using the enzyme-linked immunosorbent assay method. The groups were compared using the analysis of variance procedure at the significant level of P < 0.05, statistically. Results: The mean of IgG in the controls was significantly higher than the levels in both the active and the inactive rosacea patients (p < 0.022). Also, the titer of serum IgM to C. pneumoniae in the controls was different, compared with the active (p < 0.019) and the inactive (p < 0.02) rosacea patients. In addition, the median titer of serum IgG (not IgM) to C. pneumoniae in the females with the inactive rosacea disorder was lower than the active rosacea disorder (p < 0.019) and controls women (p < 0.008). Furthermore, the serum level of IgG or IgM to C. pneumoniae in the controls males was higher than the males with the rosacea disorder (p < 0.05) and (p < 0.02), alternatively. Conclusion: C. pneumoniae seropositivity in the rosacea patients and controls was insignificant.

New molecular insights into the A218V variant impact on the steroidogenic acute regulatory protein (STAR) associated with 46, XY disorders of sexual development.

Disorders of sexual development (DSD) are an abnormal congenital conditions associated with atypical development of the urogenital tract and external genital structures. The steroidogenic acute regulatory (STAR) gene, associated with congenital lipoid adrenal hyperplasia (CLAH), is included in the targeted gene panel for the DSD diagnosis. Therefore, the genetic alterations of the STAR gene and their molecular effect were examined in the CLAH patients affected with DSD. Ten different Iranian families including twelve male pseudo-hermaphroditism patients with CLAH phenotype were studied using genetic linkage screening and STAR gene sequencing in the linked families to the STAR locus. Furthermore, the structural, dynamical, and functional impacts of the variants on the STAR in silico were analyzed. Sanger sequencing showed the pathogenic variant p.A218V in STAR gene, as the first report in Iranian population. Moreover, modeling and simulation analysis were performed using tools such as radius of gyration, root mean square deviation (RMSD), root mean square fluctuation (RMSF), and molecular docking showed that p.A218V variant affects the residues interaction in cholesterol-binding site and the proper folding of STAR through increasing H-bound and the amount of α-Helix, deceasing total flexibility and changing fluctuations in some residues, resulting in reduced steroidogenic activity of the STAR protein. The study characterized the structural and functional changes of STAR caused by pathogenic variant p.A218V. It leads to limited cholesterol-binding activity of STAR, ultimately leading to the CLAH disease. Molecular dynamics simulation of STAR variants could help explain different clinical manifestations of CLAH disease.

A Novel Homozygous Pathogenic Variant in CYP11B1 in a Female Iranian Patient with 11B Hydroxylase Deficiency.

OBJECTIVE: Congenital adrenal hyperplasia (CAH) addresses a number of autosomal recessive disorders characterized by the enzyme defects in steroid hormones biosynthesis. The second common form of CAH is caused by mutations in the CYP11B1 gene. Here, we reveal a novel mutation in the CYP11B1 gene related to the 11ßOHD phenotype. METHODS AND RESULTS: Sequence analysis of the CYP11B1 gene in a 19-year-old Iranian woman with the 11ßOHD phenotype was performed. In silico analysis and molecular docking were done. A novel missense homozygous variant c.1351C > T (p.L451F) in the CYP11B1 gene was identified in the patient and, according to American College of Medical Genetics and Genomics criteria, was categorized as likely pathogenic. Protein docking showed destructive effects of the variant on the CYP11B1 protein-ligand interactions. CONCLUSION: This study broadens the CYP11B1 mutation spectrum and introduces the novel p.L451F likely pathogenic variant leading to destructive effects on protein-ligand interactions. Our results provide reliable information for genetic counseling and molecular diagnostics of CAH.

Characterization of a novel androgen receptor gene variant identified in an Iranian family with complete androgen insensitivity syndrome (CAIS): a molecular dynamics simulation study.

Androgen insensitivity syndrome (AIS) is a common form of 46, XY disorder in sex development disease (DSD). It is due to the androgen receptor (AR) gene mutations and includes clinical subgroups of complete AIS (CAIS) and partial AIS (PAIS), along with a vast area of clinical heterogeneity of completely normal female external genitalia to male infertility. In this study, the Whole Exome Sequencing (WES) was utilized to detect the cause of DSD in a consanguineous Iranian family with two female patients with normal external genitalia and 46, XY karyotype. Sanger sequencing was applied to validate the candidate variant. Next, we predicted the structural alteration induced by the variant on AR protein using bioinformatics analysis such as molecular dynamic (MD) and molecular docking simulations. WES results identified a novel hemizygous p.L763V variant in the AR gene in the proband that was compatible with the X-linked recessive pattern of inheritance. Bioinformatics studies confirmed the loss of AR function. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, it was categorized as pathogenic. This study broadens the AR mutation spectrum and introduces the novel p.L763V missense pathogenic variant leading to AR failure to bind to its ligand, and the resulting CAIS clinical subgroup. This study presents a prosperous application of WES and bioinformatics analysis to recognize the underlying cause of DSD in Iran, necessary for its clinical/psychological management.Communicated by Ramaswamy H. Sarma.

Corrigendum to "Functional analysis of recombinant codon-optimized bovine neutrophil ß-defensin" [J. Adv. Res. 7(5) (2016) 815-821].

[This corrects the article DOI: 10.1016/j.jare.2015.12.003.].

Effect of transgenic Leishmania major expressing mLLO-Bax-Smac fusion gene in the apoptosis of the infected macrophages.

Objectives: Leishmaniasis is a complex infection against which no confirmed vaccine has been reported so far. Transgenic expression of proteins involved in macrophage apoptosis-like BAX through the parasite itself accelerates infected macrophage apoptosis and prevents Leishmania differentiation. So, in the present research, the impact of the transgenic Leishmania major including mLLO-BAX-SMAC proapoptotic proteins was assayed in macrophage apoptosis acceleration. Materials and Methods: The coding sequence mLLO-Bax-Smac was designed and integrated into the pLexyNeo2 plasmid. The designed sequence was inserted under the 18srRNA locus into the L. major genome using homologous recombination. Then, mLLO-BAX-SMAC expression was studied using the Western blot, and the transgenic parasite pathogenesis was investigated compared with wild-type L. major in vitro and also in vivo. Results: Western blot and PCR results approved mLLO-BAX-SMAC expression and proper integration of the mLLO-Bax-Smac fragment under the 18srRNA locus of L. major, respectively. The flow cytometry results revealed faster apoptosis of transgenic Leishmania-infected macrophages compared with wild-type parasite-infected macrophages. Also, the mild lesion with the less parasitic burden of the spleen was observed only in transgenic Leishmania-infected mice. The delayed progression of leishmaniasis was obtained in transgenic strain-injected mice after challenging with wild-type Leishmania. Conclusion: This study recommended transgenic L. major including mLLO-BAX-SMAC construct as a pilot model for providing a protective vaccine against leishmaniasis.

Evaluation of transgenic Leishmania infantum expressing mLLO-BAX-SMAC in the apoptosis of the infected macrophages in vitro and in vivo.

BACKGROUND: Leishmaniasis is an important infectious disease that develops because of escaping parasite from the host immune system or preventing host macrophages apoptosis. Recently, the development of transgenic methods and the manipulation of the parasite genome has provided many advantages. So, in this study, the effect of the transgenic Leishmania infantum expressing mLLO-BAX-SMAC proteins was examined in accelerating host cell apoptosis. METHOD: The entire coding sequence of designed codon-optimized mLLO-Bax-Smac was cloned in the pLexyNeo2 vector and integrated downstream of the 18srRNA locus of L infantum genome by homologous recombination. Next, the expression of mLLO-BAX-SMAC fusion protein was evaluated by the Western blotting technique and the pathogenesis of transgenic parasite was surveyed in vitro and in vivo. RESULTS: The results of PCR and Western blot confirmed proper integration and expression of mLLO-Bax-Smac sequence into the 18srRNA locus of L infantum. Flow cytometry showed accelerating apoptosis of transgenic Leishmania-infected macrophages compared to wild-type parasite. Also, transgenic parasites were less virulent as a fewer parasitic burden was found in the spleen and liver of transgenic-infected mice compared to the control. CONCLUSION: The data suggested that the transgenic L infantum expressing BAX-SMAC can be used as an experimental model for developing vaccination against leishmaniasis.

The role of Bax in the apoptosis of Leishmania-infected macrophages.

BACKGROUND: Leishmania is a protozoan parasite that nests in macrophages and is responsible for the Leishmaniasis disease. In spite of different defense pathways, last strategy of macrophage for killing parasite is apoptosis process. By permeableizing the mitochondrial outer membrane (MOM). As breaching MOM releases apoptogenic factors like cytochrome-c which activate caspases that result in the destruction of the cell. In this review, we summarized the appropriate manuscripts regarding the bax includes, its different types and the effect of bax on the apoptosis of Leishmania and parasite-infected macrophages. METHODS: Information about the role of BAX in the apoptosis of parasite-infected macrophage of recent articles were surveyed by searching computerized bibliographic database PubMed and Google Scholar entering the keywords BAX and leishmaniasis. RESULTS: The common studies revealed Leishmania use different survival strategies for inhibiting macrophage apoptosis. As Leishmania by preventing homooligomerization or upregulating the anti-apoptotic molecule Bcl-2 can prohibits proteins of host-cell apoptosis such as Bax that is required for mitochondrial permeabilisation during apoptosis. CONCLUSION: With regard to the supportive role of bax in apoptosis and the preventive role of Leishmania in its function, it seems that expression of bax gene in parasite by technologies like transgenic or down regulating of anti-apoptotic molecule Bcl-2 by miRNA could be prompted the apoptosis process of infected-macrophages and inhibited extensive spread of Leishmania and the resulting lesions.

The therapeutic effect of ozonated olive oil plus glucantime on human cutaneous leishmaniasis.

OBJECTIVES: Leishmaniasis is one of the main health problems in developing countries, caused by intracellular protozoan parasites of the Leishmania genus. Although research has been successful in discovering vaccines and anti-parasitic drugs like antimony compounds, their side effects like high toxicity, prolonged regeneration, etc., have raised the replacement importance of natural products with antioxidant and antibacterial properties. It can be said that an appropriate alternative to this is the ozonated olive oil. Ozone by introducing O2 in involved tissues and bloodstream could degrade parasite amastigotes and lead to cleared leishmaniasis infections. So, the present study aimed to evaluate the effect of ozonated olive oil in Iranian leishmaniasis patients compared to glucantime, a choice drug for the treatment of Leishmaniasis. MATERIALS AND METHODS: Thirty patients with confirmed leishmaniasis lesions were included and divided into two groups, 15 cases as control and 15 cases as test with lesions of 30-50 mm2 in diameter. The control group received glucantime intralesionally and the test group ozonated olive oil plus glucantime, 2 times daily. RESULTS: The mean of lesion size was (50.94±33.20) before and (15±14.34) after treatment in control (P<0.00) and (50.88±31.74) before and (9.93±14.18) after treatment in the test group (P<0.00). Moreover, the mean course of therapy was 10.4(±1.84) weeks and 8.93(±2.15) weeks in control and test groups, respectively (P=0.636). Significant differences were reported in lesion size after treatment between the two groups (P<0.00). CONCLUSION: Data suggested ozonated olive oil can have synergistic effects with glucantime in the treatment of cutaneous leishmaniasis.

An update of spectrum and frequency of GJB2 mutations causing hearing loss in the south of Iran: A literature review.

OBJECTIVE: Mutations in the GJB2 gene are a major cause of autosomal recessive non-syndromic HL (ARNSHL) in many populations. Previous studies have estimated the average frequency of GJB2 mutations to be between 16 and 18% in Iran, but would vary among different ethnic groups. Here, we have taken together and reviewed results from our three previous publications and data from search other published mutation reports to provide a comprehensive collection of data for GJB2 mutations and HL in the south of Iran. METHODS: In all, 447 unrelated families were included and analyzed for the prevalence and type of the GJB2 gene mutations. RESULTS: Totally, the frequency of GJB2 mutations was found to be 11.5% in the southern provinces studied which is significantly lower than that identified in Northern populations of Iran, and also a southwest to southeast Iranian gradient in the frequency of GJB2 mutations is suggested. CONCLUSIONS: This study highlights the importance of establishing prevalence, based on the local population for screening and diagnostic programs of live births in Iran.

The role of peroxisome proliferator-activated receptor-coactivator-1 gene in skin aging.

Skin aging is a continuous process that exhibits fine and deep wrinkles, thin and transparent skin, loss of underlying fat, dry skin and itch, following decreased collagen and elastin synthesis. Both extrinsic and intrinsic agents are considered in the pathogenesis on skin aging. Extrinsic factors such as sun exposure, windy and dry weather, nutrition, and lifestyle may induce premature aging, toxic-free radicals, and reactive oxygen species due to decreasing normal function of mitochondria which play the major intrinsic factors in premature skin aging. One of the major genetic factors in mitochondrial function is peroxisome proliferator-activated receptor-coactivator-1 (PGC-1) gene. This factor could delay skin aging by increasing the mitochondrial biogenesis and replication and oxidative phosphorylation and so may induce free radical scavenging. This review is focused on intrinsic skin aging and the role of PGC-1 protein in decreasing effect of aging causes.