Punicic acid: A potential compound of pomegranate seed oil in Type 2 diabetes mellitus management

Diabetes is one of the most prevalent diseases in the worldwide. Type 2 diabetes mellitus (T2DM), the most common form of the disease, has become a serious threat to public health and is a growing burden on global economies. Due to the unexpected adverse effects of antidiabetic medicines, the use of nutraceuticals as a complementary therapy has drawn extensive attention by investigators. In this issue, a novel nutraceutical, Punicic acid (PA)—the main ingredient of pomegranate seed oil (PSO) that has potential therapeutic effects in T2DM—has been investigated. PA is a peroxisome proliferator-activated receptor gamma agonist, and unlike synthetic ligands, such as thiazolidinediones, it has no side effects. PA exerts antidiabetic effects via various mechanisms, such as reducing inflammatory cytokines, modulating glucose homeostasis, and antioxidant properties. In this review, we discussed the potential therapeutic effects of PSO and PA and represented the related mechanisms involved in the management of T2DM.     

Dynamical features of the Plasmodium falciparum ribosome during translation

Plasmodium falciparum, the mosquito-transmitted Apicomplexan parasite, causes the most severe form of human malaria. In the asexual blood-stage, the parasite resides within erythrocytes where it proliferates, multiplies and finally spreads to new erythrocytes. Development of drugs targeting the ribosome, the site of protein synthesis, requires specific knowledge of its structure and work cycle, and, critically, the ways they differ from those in the human host. Here, we present five cryo-electron microscopy (cryo-EM) reconstructions of ribosomes purified from P. falciparum blood-stage schizonts at sub-nanometer resolution. Atomic models were built from these density maps by flexible fitting. Significantly, our study has taken advantage of new capabilities of cryo-EM, in visualizing several structures co-existing in the sample at once, at a resolution sufficient for building atomic models. We have discovered structural and dynamic features that differentiate the ribosomes of P. falciparum from those of mammalian system. Prompted by the absence of RACK1 on the ribosome in our and an earlier study we confirmed that RACK1 does not specifically co-purify with the 80S fraction in schizonts. More extensive studies, using cryo-EM methodology, of translation in the parasite will provide structural knowledge that may lead to development of novel anti-malarials.     

Association of interleukin-18 gene variants with susceptibility to visceral leishmaniasis in Iranian population

Host resistance to Leishmania infection is mediated by cellular immune responses leading to macrophage activation and parasite killing. Interleukin-18 (IL-18) known as interferon-γ (IFN-γ) inducing factor, stimulates IFN-γ production by T cells. Taking into account the important role of IL-18 in the defense against visceral leishmaniasis (VL) and the known effect of IL-18 gene polymorphisms on its production, the aim of this study was to investigate the probable relationship between IL-18 gene polymorphisms and the susceptibility to VL. The study groups included 118 pediatric patients who suffered from VL and 156 non-relative healthy people as the controls from the same endemic area. IL-18 gene polymorphisms at the positions ?656 G/T, ?137 G/C and +105A/C (codon 35/3) were analyzed by polymerase chain reaction-restricted fragment length polymorphism (PCR–RFLP). The results showed that the frequency of T allele at the position -656 was significantly higher in the controls, compared with that in the patients (P = 0.047), but it couldn’t tolerate Bonferroni correction. Regarding the IL-18 genotypes, there was no significant difference between the patients and controls. Although the frequencies of ATG single haplotype and AGG/ATG double haplotype were significantly higher in the controls (P = 0.043) and the patients (P = 0.044), respectively, the two P values couldn’t tolerate Bonferroni correction. Furthermore, a strong linkage disequilibrium was observed among the ?656, ?137 and +105 single nucleotide polymorphisms of IL-18 gene (all Ps < 0.001). In conclusion, this study suggests that the inheritance of T allele at the position ?656 may be considered as a genetic factor for resistance to VL.     

Drinking Water Fluoride and Blood Pressure? An Environmental Study

The relationship between intakes of fluoride (F) from drinking water and blood pressure has not yet been reported. We examined the relationship of F in ground water resources (GWRs) of Iran with the blood pressure of Iranian population in an ecologic study. The mean F data of the GWRs (as a surrogate for F levels in drinking water) were derived from a previously conducted study. The hypertension prevalence and the mean of systolic and diastolic blood pressures (SBP & DBP) of Iranian population by different provinces and genders were also derived from the provincial report of non-communicable disease risk factor surveillance of Iran. Statistically significant positive correlations were found between the mean concentrations of F in the GWRs and the hypertension prevalence of males (r?=?0.48, p?=?0.007), females (r?=?0.36, p?=?0.048), and overall (r?=?0.495, p?=?0.005). Also, statistically significant positive correlations between the mean concentrations of F in the GWRs and the mean SBP of males (r?=?0.431, p?=?0.018), and a borderline correlation with females (r?=?0.352, p?=?0.057) were found. In conclusion, we found the increase of hypertension prevalence and the SBP mean with the increase of F level in the GWRs of Iranian population.     

Degree of modification of Ro60 by the lipid peroxidation by-product 4-hydroxy-2-nonenal may differentially induce Sjögren syndrome or systemic lupus erythematosus in BALB/c mice

Our previous work showed that immunization of rabbits with 4-hydroxy-2-nonenal-modified Ro60 (HNE-Ro60) accelerates autoimmunity. We extended this model into mice, hypothesizing that the severity of autoimmunity would be dependent on the degree of HNE modification of Ro60. Five groups of BALB/c mice (10/group) were used. Group I was immunized with Ro60. Groups II to IV were immunized with Ro60 modified with 0.4 mM (low), 2 mM (medium), and 10 mM (high) HNE, respectively. Group V controls received Freund's adjuvant. A rapid abrogation of tolerance to Ro60/La antigens occurred in mice immunized with HNE-modified Ro60, especially in the low and medium HNE-Ro60 groups. Lymphocytic infiltration and significantly high decrement in salivary flow (37%) compared to controls was observed only in the high HNE-Ro60 group, suggesting induction of a Sjögren syndrome-like condition in this group. Anti-dsDNA occurred only in mice immunized with medium HNE-Ro60. This group did not have a significant decrement in salivary flow, suggesting induction of a systemic lupus erythematosus-like manifestation in this group. Significantly high antibodies to Ro60 were found in saliva of mice in the low and medium HNE-Ro60 and the Ro60 groups, as well as anti-HNE Ro60 in the low and medium HNE-Ro60 groups. Understanding the mechanism of this differential induction may help discriminate between these two autoimmune diseases.     

Assessment of hemolytic activity of bee venom against some physicochemical factors

Bee venom (BV) is a biotoxin with biologically active peptides which have cell lysis and hemolytic activity properties. These properties can be affected under different storage conditions or during the production process. In present study, we investigated effects of a number of physicochemical factors, including temperature, pH, UV radiation, ultrasound waves and storage time on hemolytic activity of BV. Maximum absorption and melting temperature of BV solution were obtained as 280 nm and ~70 °C, respectively. Cell hemolysis 50 (CH₅₀) -concentration of BV that can lyse 50% of red blood cells- was determined as 0.94 μg/ml at ambient temperature. CH₅₀ was shown not to be importantly varied at temperature up to 60 °C, pH value 2 to 13 and under UV/ ultrasound radiation. Storage at ?20, 6 and 25 °C for 6 months made about 2.5, 35 and 1000 times increase in CH₅₀. From the results, it may be concluded that BV is a relatively resistant hemolytic agent and can be used in a variety of laboratory research and product manufacturing methods.     

Validity of using recombinant melon profilin,Cuc m 2, for diagnosis of melon allergy

Background:

Allergy is a clinical disorder affecting humans worldwide. Allergenic extracts prepared from natural source materials remain heterogeneous in composition and content, but are regularly used for diagnosis and immunotherapy. Recombinant allergens are suitable candidates to use in place of natural allergens; however, the recombinant allergens should be assessed and compared with the natural ones. Cuc m 2 (profilin), one of the most important allergens of melon (Cucumis melo), has been cloned and was expressed in Escherichia coli (E. coli). We aimed to evaluate the validity of recombinant Cuc m 2 (rCuc m 2) in the diagnosis of melon allergy and investigate whether rCuc m 2 could be used as a replacement for natural Cuc m 2 (nCuc m 2).

Methods:

nCuc m 2 was purified by immuno-affinity chromatography and rCuc m 2 was purified by metal-affinity chromatography. SDS-PAGE and western blotting were carried out to evaluate the purification methods. Skin prick tests (SPT), and enzyme immunoassays to determine specific IgE, were performed with the natural and recombinant purified allergens on 53 patients with melon allergy.

Results:

rCuc m 2 elicited no significantly different responses in skin compared with nCuc m 2. All patients'' sera showed similar ODs in ELISAs with natural and recombinant profilin.

Conclusion:

rCuc m 2 evoked strong immuno-reactivity equivalent to nCuc m 2, and has potential for diagnosis of melon allergy. Key Words: Allergy, Cuc m 2, Melon, Natural allergen, Recombinant allergen     

Reverse remodeling and recovery from cachexia in rats with aldosteronism

The congestive heart failure (CHF) syndrome with soft tissue wasting, or cachexia, has its pathophysiologic origins rooted in neurohormonal activation. Mechanical cardiocirculatory assistance reveals the potential for reverse remodeling and recovery from CHF, which has been attributed to device-based hemodynamic unloading whereas the influence of hormonal withdrawal remains uncertain. This study addresses the signaling pathways induced by chronic aldosteronism in normal heart and skeletal muscle at organ, cellular/subcellular, and molecular levels, together with their potential for recovery (Recov) after its withdrawal. Eight-week-old male Sprague-Dawley rats were examined at 4 wk of aldosterone/salt treatment (ALDOST) and following 4-wk Recov. Compared with untreated, age-/sex-/strain-matched controls, ALDOST was accompanied by 1) a failure to gain weight, reduced muscle mass with atrophy, and a heterogeneity in cardiomyocyte size across the ventricles, including hypertrophy and atrophy at sites of microscopic scarring; 2) increased cardiomyocyte and mitochondrial free Ca(2+), coupled to oxidative stress with increased H(2)O(2) production and 8-isoprostane content, and increased opening potential of the mitochondrial permeability transition pore; 3) differentially expressed genes reflecting proinflammatory myocardial and catabolic muscle phenotypes; and 4) reversal to or toward recovery of these responses with 4-wk Recov. Aldosteronism in rats is accompanied by cachexia and leads to an adverse remodeling of the heart and skeletal muscle at organ, cellular/subcellular, and molecular levels. However, evidence presented herein implicates that these tissues retain their inherent potential for recovery after complete hormone withdrawal.     

Derivation and propagation of human embryonic stem cell lines from frozen embryos in an animal product-free environment

The protocols described here are comprehensive instructions for deriving human embryonic stem (hES) cell lines in xeno-free conditions from cryopreserved embryos. Details are included for propagation, cryopreservation and characterization. Initial derivation is on feeder cells and is followed by adaptation to a feeder-free environment; competent technicians can perform these simplified methods easily. From derivation to cryopreservation of fully characterized initial stocks takes 3-4 months. These protocols served as the basis for standard operating procedures (SOPs), with both operational and technical components, that we set to meet good manufacturing practice (GMP) and UK regulatory body requirements for derivation of clinical-grade cells. As such, these SOPs are currently used in our current GMP compliant facility to derive hES cell lines ab initio, in an animal product-free environment; these lines are suitable for research and potentially for clinical use in cell therapy. So far, we have derived eight clinical-grade lines, which will be freely available to the scientific community after submission/accession to the UK Stem Cell Bank.