Fine-scale population genetic structure of Endangered Caspian Sea trout,Salmo caspius: implications for conservation

Hydrobiologia - Many populations of Caspian Sea trout (Salmo caspius)—a nationally endangered species in Iran—have been extirpated or depleted due to anthropogenic impacts. The Lar...     

Effects of crocin in reducing DNA damage,inflammation, and oxidative stress in multiple sclerosis patients: A double‐blind,randomized, and placebo‐controlled trial

Multiple sclerosis (MS) is an autoimmune disease in which the immune system attacks the nerve cells, resulting in neurological disorders. Oxidative stress, free radicals, and neuritis have important roles in MS pathogenesis. Here, we aim to evaluate the effect of crocin on inflammatory markers, oxidative damage, and deoxyribonucleic acid (DNA) damage in the blood of patients with MS. A total of 40 patients were divided into two groups, drug and placebo‐treated groups, using random assignment. Participants of the intervention and control groups received two crocin capsules or placebo per day for 28 days, respectively. Findings revealed a significant decrease in the level of important pathogenic factors in MS, including lipid peroxidation, DNA damage, tumor necrosis factor‐alpha, and interleukin 17 as well as a significant increase in the total antioxidant capacity in the serum of patients treated with crocin compared with the placebo group. Our results suggest the beneficial and therapeutic effects of crocin in MS.     

Efficacy of intra-lesional injections of meglumine antimoniate once a week vs. twice a week in the treatment of cutaneous leishmaniasis caused by L. tropica in Iran: A randomized controlled clinical trial

Treatment of Cutaneous leishmaniasis (CL) is based on using antimoniate derivatives; patients’ compliance for systemic injections is low due to the pain and systemic complications. In this randomized open trial, the efficacy of intra-lesional (IL) injections of meglumine antimoniate (MA) once a week vs. twice a week in the treatment of Anthrpoponothic CL caused by L. tropica was studied. Eligible volunteer patients were selected according to inclusion/exclusion criteria. The included patients were randomly allocated to receive IL-MA injections once a week or twice a week. The primary outcome was set as complete healing of the lesion(s), and defined as complete re-epithelialization and absence of induration in the lesions. A total of 180 parasitologicaly proven CL patients caused by L. tropica were recruited, 90 patients were treated with weekly IL-MA and 90 patients received IL-MA twice a week. The complete cure was 87.9% vs. 89.2% in the group received weekly and twice a week IL-MA injections, respectively (P = 0.808). Patients’ compliance was acceptable and side effects were limited to a few local allergic reactions to MA. Median time to healing was significantly shorter in patients who received IL-MA twice a week (median ± SE) 37±3.8, (CI: 29.6–44.4) days compared to whom received IL-MA once a week 60±2.3, (CI: 55.6–64.5) days (P< 0.001), however the number of injections was higher in group who received IL-MA twice a week (12 vs. 9 injections). In conclusion, the rate of cure in the group of CL patients with IL-MA twice a week was not significantly different from the group who received IL-MA once a week shorten, but the duration of healing was shorter in the group who received IL-MA twice a week while the group received more injections so is recommended to use IL-MA once a week due to the fact the compliance is acceptable with limited side effects.Clinical Trial Registration: IRCT20081130001475N13; https://en.irct.ir/.     

Ras oncogene mutations in urine sediments of patients with bladder cancer

Early detection of bladder cancer is particularly important since it dramatically affects the survival rates. However, neither urinary cytology nor tumor markers that are currently used are sensitive enough for the early detection of bladder cancer or recurrent disease. The ras genes are frequently mutated in cancer. In this study, we investigated the diagnostic potential of ras mutation analysis in urinary sediments of patients with bladder cancer using a single-strand conformation polymorphism analysis and polymerase chain reaction. Mutation in codon 12 of the H-ras gene was observed in 39% of the patients. Our results indicate that this approach may significantly improve diagnostic sensitivity in detecting bladder tumors.     

Exploring the role of circadian clock gene and association with cancer pathophysiology

ABSTRACT

Most of the processes that occur in the mind and body follow natural rhythms. Those with a cycle length of about one day are called circadian rhythms. These rhythms are driven by a system of self-sustained clocks and are entrained by environmental cues such as light-dark cycles as well as food intake. In mammals, the circadian clock system is hierarchically organized such that the master clock in the suprachiasmatic nuclei of the hypothalamus integrates environmental information and synchronizes the phase of oscillators in peripheral tissues.

The circadian system is responsible for regulating a variety of physiological and behavioral processes, including feeding behavior and energy metabolism. Studies revealed that the circadian clock system consists primarily of a set of clock genes. Several genes control the biological clock, including BMAL1, CLOCK (positive regulators), CRY1, CRY2, PER1, PER2, and PER3 (negative regulators) as indicators of the peripheral clock.

Circadian has increasingly become an important area of medical research, with hundreds of studies pointing to the body’s internal clocks as a factor in both health and disease. Thousands of biochemical processes from sleep and wakefulness to DNA repair are scheduled and dictated by these internal clocks. Cancer is an example of health problems where chronotherapy can be used to improve outcomes and deliver a higher quality of care to patients.

In this article, we will discuss knowledge about molecular mechanisms of the circadian clock and the role of clocks in physiology and pathophysiology of concerns.     

Homozygous mutations in fibroblast growth factor 3 are associated with a new form of syndromic deafness characterized by inner ear agenesis, microtia, and microdontia

We identified nine individuals from three unrelated Turkish families with a unique autosomal recessive syndrome characterized by type I microtia, microdontia, and profound congenital deafness associated with a complete absence of inner ear structures (Michel aplasia). We later demonstrated three different homozygous mutations (p.S156P, p.R104X, and p.V206SfsX117) in the fibroblast growth factor 3 (FGF3) gene in affected members of these families, cosegregating with the autosomal recessive transmission as a completely penetrant phenotype. These findings demonstrate the involvement of FGF3 mutations in a human malformation syndrome for the first time and contribute to our understanding of the role this gene plays in embryonic development. Of particular interest is that the development of the inner ear is completely disturbed at a very early stage--or the otic vesicle is not induced at all--in all of the affected individuals who carried two mutant FGF3 alleles.     

The cardioprotective effect of different doses of vasopressin (AVP) against ischemia-reperfusion injuries in the anesthetized rat heart

The aim of the present study was to investigate the protective effect of various doses of exogenous vasopressin (AVP) against ischemia–reperfusion injury in anesthetized rat heart. Anesthetized rats were randomly divided into seven groups (n = 4–13) and all of them subjected to prolonged 30 min regional ischemia and 120 min reperfusion. Group I served as saline control with ischemia, in treatment groups II, III, IV and V, respectively different doses of AVP (0.015, 0.03, 0.06 and 1.2 μg/rat) were infused within 10 min prior to ischemia, in group VI, an AVP-selective V1 receptor antagonist (SR49059, 1 mg/kg, i.v.) was administrated prior to effective dose of AVP injection and in group VII, SR49059 (1 mg/kg, i.v.) was only administrated prior to ischemia. Various doses of AVP significantly prevented the decrease in heart rate (HR) at the end of reperfusion compared to their baseline and decreased infarct size, biochemical parameters [LDH (lactate dehydrogenase), CK-MB (creatine kinase-MB) and MDA (malondialdehyde) plasma levels], severity and incidence of ventricular arrhythmia, episodes and duration of ventricular tachycardia (VT) as compared to control group. Blockade of V1 receptors by SR49059 attenuated the cardioprotective effect of AVP on ventricular arrhythmias and biochemical parameters, but partially returned infarct size to control. AVP 0.03 μg/rat was known as effective dose. Our results showed that AVP owns a cardioprotective effect probably via V1 receptors on cardiac myocyte against ischemia/reperfusion injury in rat heart in vivo.     

ARLTS1, MDM2 and RAD51 gene variations are associated with familial breast cancer

Genetic factors that contribute to the risk of breast cancer are largely not known and association studies have revealed several genes with low penetrance risk alleles for breast cancer. Analysis of these genes may provide important information on the risk factors affecting carcinogenesis. Variations in the ARLTS1, RAD51 and MDM2 genes have been associated with increased risk of different cancer types but for breast cancer the results are not consistent. In this study we investigated the role of the allelic variants in candidate genes acting in the tumor suppressor, DNA repair and p53 pathways as risk factors for familial breast cancer in 147 patients displaying characteristics of familial disease. Presence of the polymorphic variants were investigated by amplification of the corresponding regions and restriction fragment length polymorphism analysis. Genotype and allele frequencies in the patients were significantly different for all three variants. Our results indicate that the polymorphic variants might affect individual susceptibility towards breast cancer.     

Detection and Identification of Aster Yellows Phytoplasma Associated with Lipstick Yellow Frond Disease in Malaysia

Yellowing symptoms similar to coconut yellow decline phytoplasma disease were observed on lipstick palms (Cyrtostachys renda) in Selangor state, Malaysia. Typical symptoms were yellowing, light green fronds, gradual collapse of older fronds and decline in growth. Polymerase chain reaction assay was employed to detect phytoplasma in symptomatic lipstick palms. Extracted DNA was amplified from symptomatic lipstick palms by PCR using phytoplasma‐universal primer pair P1/P7 followed by R16F2n/R16R2. Phytoplasma presence was confirmed, and the 1250 bp products were cloned and sequenced. Sequence analysis indicated that the phytoplasmas associated with lipstick yellow frond disease were isolates of ‘Candidatus Phytoplasma asteris’ belonging to the 16SrI group. Virtual RFLP analysis of the resulting profiles revealed that these palm‐infecting phytoplasmas belong to subgroup 16SrI‐B and a possibly new 16SrI‐subgroup. This is the first report of lipstick palm as a new host of aster yellows phytoplasma (16SrI) in Malaysia and worldwide.     

Dichotomous effects of IFN-γ on dendritic cell function determine the extent of IL-12-driven antitumor T cell immunity

Sustained intratumoral delivery of IL-12 and GM-CSF can overcome tumor immune suppression and promote T cell-dependent eradication of established disease in murine tumor models. However, the antitumor effector response is transient and rapidly followed by a T suppressor cell rebound. The mechanisms that control the switch from an effector to a regulatory response in this model have not been defined. Because dendritic cells (DC) can mediate both effector and suppressor T cell priming, DC activity was monitored in the tumors and the tumor-draining lymph nodes (TDLN) of IL-12/GM-CSF-treated mice. The studies demonstrated that therapy promoted the recruitment of immunogenic DC (iDC) to tumors with subsequent migration to the TDLN within 24-48 h of treatment. Longer-term monitoring revealed that iDC converted to an IDO-positive tolerogenic phenotype in the TDLN between days 2 and 7. Specifically, day 7 DC lost the ability to prime CD8(+) T cells but preferentially induced CD4(+)Foxp3(+) T cells. The functional switch was reversible, as inhibition of IDO with 1-methyl tryptophan restored immunogenic function to tolerogenic DC. All posttherapy immunological activity was strictly associated with conventional myeloid DC, and no functional changes were observed in the plasmacytoid DC subset throughout treatment. Importantly, the initial recruitment and activation of iDC as well as the subsequent switch to tolerogenic activity were both driven by IFN-γ, revealing the dichotomous role of this cytokine in regulating IL-12-mediated antitumor T cell immunity.