Molecular epidemiology of cutaneous leishmaniasis and heterogeneity of Leishmania major strains in Iran

Objective To determine the geographical distribution of Leishmania species causing cutaneous leishmaniasis (CL) and to study the genetic heterogeneity of Leishmania major isolates from different endemic areas of Iran. Methods A total of 341 isolates from lesions of patients living in 11 provinces of Iran were grown in culture medium and inoculated to BALB/c mice to detect possible visceralisation. The species were identified by isoenzyme analysis using a battery of six enzymes and kinetoplast (k) DNA‐PCR technique. Genetic variation among L. major isolates was analysed by random amplified polymorphic DNA (RAPD) technique. Results Of the total 341 isolates, 283 isolates were L. major and 58 isolates were Leishmania tropica. In rural areas, the causative agent of CL was mainly L. major (95%L. major vs. 5%L. tropica), in urban areas it was L. tropica (65%L. tropica vs. 35%L. major). All isolates of L. major and 8.6% of L. tropica isolates showed visceralisation in BALB/c mice. There is considerable genetic diversity between L. major strains from different endemic areas and even between some isolates of the same endemic area. Conclusion Leishmania major is the most frequent species in the endemic areas of CL in eleven provinces of Iran, and genetic diversity is a common feature of L. major in the country.     

Tracer kinetic modeling of [11C]AFM,a new PET imaging agent for the serotonin transporter

[¹¹C]AFM, or [¹¹C]2-[2-(dimethylaminomethyl)phenylthio]-5-fluoromethylphenylamine, is a new positron emission tomography (PET) radioligand with high affinity and selectivity for the serotonin transporter (SERT). The purpose of this study was to determine the most appropriate kinetic model to quantify [¹¹C]AFM binding in the healthy human brain. Positron emission tomography data and arterial input functions were acquired from 10 subjects. Compartmental modeling and the multilinear analysis-1(MA1) method were tested using the arterial input functions. The one-tissue model showed a lack of fit in low-binding regions, and the two-tissue model failed to estimate parameters reliably. Regional time–activity curves were well described by MA1. The rank order of [¹¹C]AFM binding potential (BP_ND) matched well with the known regional SERT densities. For routine use of [¹¹C]AFM, several noninvasive methods for quantification of regional binding were evaluated, including simplified reference tissue models (SRTM and SRTM2), and multilinear reference tissue models (MRTM and MRTM2). The best methods for region of interest (ROI) analysis were MA1, MRTM2, and SRTM2, with fixed population kinetic values ( or b′) for the reference methods. The MA1 and MRTM2 methods were best for parametric imaging. These results showed that [¹¹C]AFM is a suitable PET radioligand to image and quantify SERT in humans.     

Calorie restriction promotes remyelination in a Cuprizone-Induced demyelination mouse model of multiple sclerosis

Metabolic Brain Disease - Over the past few decades several attempts have been made to introduce a potential and promising therapy for Multiple sclerosis (MS). Calorie restriction (CR) is a dietary...     

Distribution and molecular analysis of Blastocystis subtypes from gastrointestinal symptomatic and asymptomatic patients in Iran

IntroductionBlastocystis is a common intestinal parasite of human and animal hosts. The parasite has 17 subtypes, and among those at least nine subtypes (ST1-ST9) are found in human hosts.ObjectiveThe aim of the present study was to investigate the presence of different subtypes of Blastocystis spp. among the patients referred to Velayat hospital of Qazvin province, Iran.MethodsOverall, 864 stool samples were examined by using formalin-ethyl acetate concentration method and Trichrome staining. All specimens were cultured in clotted fetal bovine medium. Later, DNA extraction and PCR amplification of 18S ribosomal RNA gene region was conducted and phylogenetic tree constructed.ResultsThe results revealed 7.9% (68/864) of the study population were infected with Blastocystis. Intestinal symptoms were observed in 61% (36/59) of individuals positive for Blastocystis, with abdominal pain in 58% (21/36) of cases which was more frequent than other intestinal signs. No significant relationship was observed among the study variables. By molecular and phylogenetic analysis, three subtypes ST1 (45%), ST2 (30%) and ST3 (23%) of parasite were identified.ConclusionThis study showed ST1 subtype was the predominant subtype among the positive specimens, meanwhile the highest haplotype and nucleotide diversity were clarified in ST3 subtype.     

Potential Roles of MyomiRs in Cardiac Development and Related Diseases

Muscle-specific miRNAs, which are known as MyomiRs, are crucial regulatory elements for cardiovascular development. MyomiRs are abundantly expressed in the myocardium and regulate certain aspects of physiological and pathological processes in myocardiocytes, including cardiovascular development, myocardial remodeling, and arise for cardiovascular diseases through different mechanisms, such as epigenetic pathways. Clinical and experimental studies have confirmed the myomiRs as promising diagnostic biomarkers for the early diagnosis of cardiac disorders. In this review, we have summarized recent findings in the field of epigenetic modulations of myomiRs and cardiac regeneration associated with cardiac diseases.     

Oxidative stress parameters and keap 1 variants in T2DM: Association with T2DM,diabetic neuropathy,diabetic retinopathy,and obesity

IntroductionChronic hyperglycemia activates the inflammatory pathways and oxidative stress mechanisms with consequent damage to nerve tissue and retina. The Keap1‐Nrf2 pathway acts as one of the most important antioxidant pathways of the organism. Variants of Keap1 could affect susceptibility to diabetes and its complications.MethodsIn a case‐control study, 400 individuals included type 2 diabetes mellitus (T2DM) patients without complication, with neuropathy, with retinopathy, and healthy individuals were investigated. The levels of glutathione (GSH), glutathione peroxidase (GPx), malondialdehyde (MDA), and total antioxidant capacity (TAC) were measured using chemical methods. Using the PCR‐RFLP method, the Keap1 (rs11085735) variants were identified.ResultsNeuropathic patients had significantly lower levels of GSH, GPx, and TAC and higher levels of total oxidative status (TOS), MDA, and oxidative stress index (OSI) compared to T2DM patients without complication and controls. Lower levels of GSH and GPx and a higher level of MDA were observed in patients with retinopathy compared with controls. Obesity was associated with significantly lower GPx activity and higher TOS. A significantly higher Keap1 AA genotype was found in patients with neuropathy than T2DM without complication and controls. The presence of Keap1 AA genotype correlated with lower GPx activity compared to CC genotype.ConclusionsOur study suggests the role of reduced antioxidant system and Keap1 variants in the pathogenesis of T2DM and its complications of neuropathy and retinopathy and also obesity in enhanced oxidative stress. Monitoring oxidative stress parameters in diabetic patients, especially those with complication and their treatment with antioxidants is suggested.     

Neutrophil/platelet to lymphocyte ratio in monitoring of response to TNF‐α inhibitors in psoriatic patients

Neutrophil or platelet to lymphocyte ratio (NLR and PLR) has been proposed to be used as prognostic purposes in a variety of diseases. The aim of this study was to evaluate the usefulness of these ratios in monitoring of response to TNF‐α‐inhibitors in psoriatic patients. Eighty psoriatic patients were included and treated with TNF‐α‐inhibitors for 12 months based on drug protocol. Hematologic indices, including NLR and PLR values were assessed before and after treatment. Data on psoriasis area and severity index (PASI), smoking behavior, alcohol intake habit, nail abnormality, body mass index (BMI), joint involvement, and disease duration were also recorded. PASI scores were improved significantly after one‐year treatment (P = .000). Furthermore, this type of treatment significantly reduced the NLR and PLR (P = .000). These changes were in accordance with PASI scores. Patients with BMI greater than 24.9 had higher, but non‐significant NLR and PLR than normal or lean individuals. Cigarette smokers and alcohol consumers had lower NLR and PLR values than other individuals (P < .05). There was no significant association between NLR and PLR and joint or nail involvement. Although NLR and PLR will not be helpful in primary diagnosis of inflammatory diseases, they could be accounted as monitoring tools in management of psoriasis or globally indicators of inflammation.     

Neuregulin‐1 positively modulates glial response and improves neurological recovery following traumatic spinal cord injury

Spinal cord injury (SCI) results in glial activation and neuroinflammation, which play pivotal roles in the secondary injury mechanisms with both pro‐ and antiregeneration effects. Presently, little is known about the endogenous molecular mechanisms that regulate glial functions in the injured spinal cord. We previously reported that the expression of neuregulin‐1 (Nrg‐1) is acutely and chronically declined following traumatic SCI. Here, we investigated the potential ramifications of Nrg‐1 dysregulation on glial and immune cell reactivity following SCI. Using complementary in vitro approaches and a clinically‐relevant model of severe compressive SCI in rats, we demonstrate that immediate delivery of Nrg‐1 (500 ng/day) after injury enhances a neuroprotective phenotype in inflammatory cells associated with increased interleukin‐10 and arginase‐1 expression. We also found a decrease in proinflammatory factors including IL‐1β, TNF‐α, matrix metalloproteinases (MMP‐2 and 9) and nitric oxide after injury. In addition, Nrg‐1 modulates astrogliosis and scar formation by reducing inhibitory chondroitin sulfate proteoglycans after SCI. Mechanistically, Nrg‐1 effects on activated glia are mediated through ErbB2 tyrosine phosphorylation in an ErbB2/3 heterodimer complex. Furthermore, Nrg‐1 exerts its effects through downregulation of MyD88, a downstream adaptor of Toll‐like receptors, and increased phosphorylation of Erk1/2 and STAT3. Nrg‐1 treatment with the therapeutic dosage of 1.5 μg/day significantly improves tissue preservation and functional recovery following SCI. Our findings for the first time provide novel insights into the role and mechanisms of Nrg‐1 in acute SCI and suggest a positive immunomodulatory role for Nrg‐1 that can harness the beneficial properties of activated glia and inflammatory cells in recovery following SCI.