Natural low- and high-density lipoproteins as mighty bio-nanocarriers for anticancer drug delivery

Cancer Chemotherapy and Pharmacology - Lipoproteins (LPs) are a set of naturally occurring bio-nanoparticles consisting of Apo-LPs, phospholipids, a highly hydrophobic core of cholesteryl esters...     

Association of catalase (rs7943316) and glutathione peroxidase-1 (rs1050450) polymorphisms with the risk of type 2 diabetes (T2DM)

Reactive oxygen species are involved in the pathogenesis of type 2 diabetes mellitus (T2DM). Catalase and Glutathione peroxidase-1 are antioxidant enzymes and the activity of them is essential for the protection against damage caused by reactive oxygen species. The aim of this study was to investigate the association between genetic polymorphisms of CAT gene (rs7943316) and GPx-1 gene (rs1050450) in patients with type 2 diabetes. In this case-control study, a total of 120 Iranian patients with T2DM and 120 healthy individuals as control were included. Genotypes were determined by PCR-RFLP. A significant difference was found between genotyping distribution of CAT (–21 A/T) polymorphism.The frequency of TT genotype was increased in patients compared to controls and we observed a statistically significant difference (OR = 1.797, 95% CI = 0.975–3.318, P = 0.044). Distribution of genotypes did not differ for GPx-1 (198 C/T) polymorphism between the cases and controls subjects. This study indicated that CAT rs7943316 genotype (TT) was associated with an increased risk of T2DM. No evidence was found to support an association between GPx-1 (198 C/T) polymorphism and T2DM.     

Association of Lysyl oxidase (LOX) Polymorphisms with the Risk of Keratoconus in an Iranian Population

Background: Keratoconus is a connective tissue-related eye disease with unknown etiology that causes the loss of visual acuity. Lysyl oxidase (LOX) is an amine oxidase that catalyzes the covalent cross-link of collagens and elastin in the extracellular environment, thus determining the mechanical properties of connective tissue. The current study aimed to investigate the possible associations between two LOX polymorphisms, rs1800449 and rs2288393, and susceptibility to keratoconus.

Methods: A total of 262 Iranian subjects including 112 patients with keratoconus and 150 healthy individuals as controls were recruited. Genotyping for the LOX variants was performed using allele-specific PCR.

Results: A significant difference was found between two groups regarding allelic and genotyping distribution of LOX polymorphism at position rs1800449 G>A. The frequency of AA and GA?+?AA genotypes were increased in patients compared to controls (17% versus 8% and 62.5% versus 50%, respectively), showing a statistically significant difference (OR?=?2.827, 95% CI: 1.251–6.391, p?=?0.012). The A allele was associated with an increased risk for keratoconus, with the frequency of 39.9% and 29% in patients and controls, respectively (OR?=?1.614, 95% CI: 1.119–2.326, p?=?0.011). Furthermore, the haplotype analysis revealed that the rs1800449G/rs2288393C is a protective factor against keratoconus (OR?=?0.425, 95% CI?=?0.296–0.609, p?=?0.001). Conversely, the +473A/rs2288393C (OR?=?3.703, 95% CI?=?2.230–6.149, p?=?0.001) and +473G/rs2288393G (OR?=?15.48, 95% CI?=?3.805–63.03, p?=?0.001) haplotypes were identified as risk factors for keratoconus.

Conclusion: Our study demonstrated that the LOX rs1800449 genotypes (AA and GA?+?AA) and allele (A) appears to confer risk for susceptibility to keratoconus.     

Characteristics,sources, and health risks of atmospheric PM10-bound heavy metals in a populated middle eastern city

ABSTRACT

This study reports on the characteristics, sources, and health risks of atmospheric PM₁₀-bound heavy metals (HMs) on citizenship living in different regions of Ahvaz, Southwest of Iran were investigated during 2016–2017. A total of 84 samples were analyzed from different regions: (S1) industrial, (S2) high traffic, and (S3) residential. Blood samples were collected from people who came to the east health center of Ahvaz. High volume air samplers, equipped with quartz fiber filters (8?×?10) were utilized for sampling in this study. Inductively coupled plasma optical emission spectroscopy (ICP-OES) was also used for HMs. Risk assessment and hazard index of these pollutants were estimated, using USEPA’s exposure parameters. Based on the results, the highest and the lowest concentration of HM were observed in industrial and residential areas. Blood’s HMs concentration for chromium (Cr), nickel (Ni), lead (Pb), and zinc (Zn) were 2.932, 4.199, 8.425, and 71.2?μg/dL, respectively. In conclusion, increasing exposure concentration of HMs would have a significant potential for increased cancer and risk of diseases. The results of this study show that increasing exposure concentration to HM in the studied scenarios have a significant potential for generating different health endpoints, although exposing to HMs led to generating diseases in individuals particularly in polluted and populated districts; so, environmental measures should be considered by urban air authorities to mitigate the concentration of these pollutants in ambient air.     

Novel mutation in MAPT exon 13 (p.N410H) causes corticobasal degeneration

In order to determine the frequency of microtubule-associated protein tau gene (MAPT) mutations and rare variants in CBD, we performed a systematic sequence analysis of MAPT coding and 3′ untranslated region (3′UTR) in a large cohort of autopsy-confirmed CBD patients (N = 109). This identified a novel MAPT mutation in exon 13, p.N410H, in a case that is neuropathologically indistinguishable from sporadic CBD. On immunoblot, the p.N410H mutation carrier had the same insoluble tau profile as seen in CBD. Additionally, tau expression analysis in brain tissue found a significant increase in the 4R/3R tau mRNA ratio (P = 0.04), indicating that p.N410H disrupts tau isoform homeostasis. Biochemically, recombinant tau protein with p.N410H showed a marked increase in tau filament formation compared to wild-type tau (P < 0.001), had a 19.2 % decrease in rate of microtubule assembly (P < 0.05), and a 10.3 % reduction in the extent of total microtubule polymerization (P < 0.01). Sequence analysis of the complete MAPT 3′UTR in autopsy-confirmed CBD cases further identified two rare variants with nominally significant association with CBD. An ATC nucleotide insertion (“MAPTv8”) was found in 4.6 % of CBD patients compared to 1.2 % of controls (P = 0.031, OR = 3.71), and rs186977284 in 4.6 % CBD patients, but only 0.9 % of controls (P = 0.04, OR = 3.58). Rs186977284 was also present in 2.7 % of a large cohort of autopsy-confirmed PSP patients (N = 566) and only 0.9 % of an additional control series (P = 0.034, OR = 3.08), extending the association to PSP. Our findings show that mutations in MAPT can cause CBD and MAPT non-coding variants may increase the risk of complex 4R tauopathies.     

Aggression–impulsivity,mental pain,and communication difficulties in medically serious and medically non-serious suicide attempters

Background

Unbearable mental pain, depression, and hopelessness have been associated with suicidal behavior in general, while difficulties with social communication and loneliness have been associated with highly lethal suicide attempts in particular. The literature also links aggression and impulsivity with suicidal behavior but raises questions about their influence on the lethality and outcome of the suicide attempt.

Objectives

To evaluate the relative effects of aggression and impulsivity on the lethality of suicide attempts we hypothesized that impulsivity and aggression differentiate between suicide attempters and non-attempters and between medically serious and medically non-serious suicide attempters.

Method

The study group included 196 participants divided into four groups: 43 medically serious suicide attempters; 49 medically non-serious suicide attempters, 47 psychiatric patients who had never attempted suicide; and 57 healthy control subjects. Data on sociodemographic parameters, clinical history, and details of the suicide attempts were collected. Participants completed a battery of instruments for assessment of aggression–impulsivity, mental pain, and communication difficulties.

Results

The medically serious and medically non-serious suicide attempters scored significantly higher than both control groups on mental pain, depression, and hopelessness (p < .001 for all) and on anger-in, anger-out, violence, and impulsivity (p < .05 for all), with no significant difference between the two suicide attempter groups. Medically serious suicide attempters had significantly lower self-disclosure (p < .05) and more schizoid tendencies (p < .001) than the other three groups and significantly more feelings of loneliness than the medically non-serious suicide attempters and nonsuicidal psychiatric patients (p < .05). Analysis of aggression–impulsivity, mental pain, and communication variables with suicide lethality yielded significant correlations for self-disclosure, schizoid tendency, and loneliness. The interaction between mental pain and schizoid traits explained some of the variance in suicide lethality, over and above the contribution of each component alone.

Conclusions

Aggression–impulsivity and mental pain are risk factors for suicide attempts. However, only difficulties in communication differentiate medically serious from medically non-serious suicide attempters. The combination of unbearable mental pain and difficulties in communication has a magnifying effect on the risk of lethal suicidal behavior.     

HLA Antigens Shed from the Surface of Synthetic or Naturally Occurred Platelet-Derived Microparticles During Storage of Platelet Concentrate

The demand for standard platelet concentrates (PCs) has continued to increase in the recent years. Infusible platelet membranes (IPM) prepared from new or outdated human platelets have been developed as an alternative to standard PCs, with the additional advantage of long shelf life and increased viral safety. Reduction of HLA antigens on the IPM has been assigned as one of the probable advantages of this product. In re-examining this issue, we studied the existence of HLA class I on the surface of IPM microparticles. In comparison we also surveyed HLA expression on the surface of the naturally occurred platelet-derived microparticles (nPMPs) during 7 days storage. Intended for producing IPM, PCs obtained from Iranian blood transfusion organization were lysed; virally inactivated with wet heat in the presence of a heat stabilizer and then sonicated. IPMs were separated using centrifugation and liquid-stored in 4°C. The expression of HLA class I antigens was surveyed using flow cytometry technique. HLA molecules were present on the microparticles. Shedding of HLA antigens was demonstrated from the surface of the both liquid-stored IPM and nPMPs during storage. Storage of IPM in 4°C was accompanied with significant reduction of HLA molecules. It seemed that achievement of HLA-free IPM could be impossible unless chloroquine treated platelets were used to prepare these microvesicles.     

Efficacy of Crocus sativus L. on reduction of cadmium‐induced toxicity on spermatogenesis in adult rats

Cadmium is a toxic heavy metal element, which probably cause infertility by impairment in spermatogenesis. The present work aimed (i) to study the toxic effect of cadmium on spermatogenesis in rat, as well as (ii) the protective effect of Crocus sativus L. on cadmium‐intoxicated rats. Cadmium chloride was administered intraperitoneally during 16 days at intervals of 48 h between subsequent treatments. Crocus sativus L. was pre‐treated in both of control and cadmium‐injected rats. Animals were sacrificed on day 17 after the first treatment. The left cauda epididymis was removed and immediately immersed into Hank's balanced salt solution for the evaluation of sperm count and viability, and left testis was fixed in 10% formalin for histological evaluation. Following contamination with cadmium, a decrease was observed in the number and viability of cauda epididymis sperm, which were increased by Crocus sativus L. pre‐treatment (P < 0.05). In addition, cadmium decreased both cell proliferation and Johnsen Scores in the seminiferous tubules, which were reversed by Crocus sativus pre‐treatment (P < 0.05). Furthermore, cadmium‐induced decrease in the amount of free serum testosterone as well as an increase in lipid peroxidation activity in the testicular tissue was reversed by Crocus sativus L. (P < 0.05). These findings may support the concept that Crocus sativus L. can improve the cadmium toxicity on spermatogenesis.     

Association of toxicochemical and microbiological quality of bottled mineral water in Birjand city,Iran

Water is one of the pivotal, both in natural ecosystems and human development. Inadequate and unsafe water is still one of the major challenges in most developing countries. Due to the growing trends of bottled water (BW) consumption in Iran, especially in dry regions, regular monitoring of the quality of bottled mineral water is necessary. Therefore, this cross-sectional study was carried out to evaluate the chemical and microbiological quality of bottled mineral water which was sold in the markets of Birjand city, Iran in 2015. Samples were selected randomly from 12 most popular brands of national BW in autumn and winter. Then, 12 most popular brands were selected for analysis. Finally, parameters including total hardness, levels of calcium, magnesium, pH, bicarbonate, sulfate, alkalinity, residual chlorine and total and fecal coliforms were examined for each brand. The results of the present study revealed that most of the chemical and microbiological parameters of BW in Birjand city were lower than maximum contaminant levels which are set by Iranian mineral water quality standards and WHO guidelines. Furthermore, total and fecal coliforms were within the standards. Overall, the results of this study revealed that the health status of the bottled mineral water which is sold in the markets of Birjand city was good. But, regular monitoring of the above mentioned parameters would be helpful to improve the water quality and to provide good portable water for the dwellers and very effective to enhance public health on citizens.