Prediction of new chromene-based inhibitors of tubulin using structure-based virtual screening and molecular dynamics simulation methods

Multidrug resistance (MDR) is one of the serious problems in cancer research that causes failure in chemotherapy. Chromene-based compounds have been proven to be the novel anti-MDR agents for inhibiting proliferation of tumor cells through tubulin polymerization inhibition of by binding at the colchicine binding site. In this study, we screened a chromene-based database of small molecules using physicochemical, ADMET properties and molecular docking to identify potential hit compounds. In order to validate our hit compounds, molecular dynamics simulations and related analysis were carried out and the results suggest that our hit compounds (PubChem CIDs: 16814409, 17594471, 57367244 and 69899719) can prove to be potential inhibitors of tubulin. The in silico results show that the present hits, like colchicine, effectively suppressed the dynamic instability of microtubules and induced microtubuledepolymerization and cell cycle arrest

The Effect of Stevia Rebaudiana on Serum Omentin and Visfatin Level in STZ-Induced Diabetic Rats

Recently the role of adipocytokines in relationship to incidence of diabetes has been demonstrated. One of the medicinal plants that are used in the treatment of diabetes is stevia. This study investigates the effect of stevia on serum omentin and visfatin levels as novel adipocytokines in diabetic induced rats to find potential mechanisms for the anti hyperglycemic effect of stevia. Forty male wistar rats weighing 180–250 g were induced with diabetes by intraperitoneal injection of streptozotocin (STZ). The animals were divided into 5 groups of 8. Rats in group 1 (non-diabetic control) and group 2 (diabetic control) were treated with distilled water, and the rats in the treated groups, group 3 (T250), group 4 (T500), and group 5 (T750) were treated with stevia, gavaged every day at 9 a.m. in doses of 250, 500, and 750 mg/kg, respectively. At the end of the study significant reductions in fasting blood sugar (FBS), the homeostasis model assessment insulin resistance (HOMA-IR), triglyceride (TG), alkaline phosphatase (ALP), and Omentin level were found in groups 3 and 4 in comparison with group 2. Pancreatic histopathology slides demonstrated that stevia extract did not induce any increase in the number of β-cells. The conclusion is that prescription of stevia in the doses of 250 and 500 mg/kg/d decreases the omentin level indirectly via activating insulin sensitivity and lowering blood glucose in STZ-induced diabetic rats. KEYWORDS. Diabetes, omentin, stevia, visfati

Long-Term Exposure of Lead Acetate on Rabbit Renal Tissue

Background: Lead has been widely used in different industries for ages. It is one of the heavy metals, highly poisonous even at low doses, and has biochemical, physiological and behavioral side effects on human and animals. It has been shown that lead has toxic effects on different tissues such as neural and genitourinary tissues, cardiovascular systems and blood. Therefore, high attention has been paid to its environmental pollutions. Objectives: Although many histological and biochemical studies have reported about the effects of lead on the renal tissue, there are a few studies about the ultrastructure and morphometric effects of lead on the kidney. Hence, the aim of this study was the evaluation of morphology and morphometrics of rabbit renal urinary barrier ultrastructure following long-term exposure to lead acetate. Materials and Methods: In this experimental study, 20 male New Zealand rabbits were divided into control and test groups (10 in each). The test group was injected intraperitoneally with chronic dose (8.5 mg/kg of body weight) of lead acetate and for the control group the same volume of normal saline was used, every other day for 10 weeks. After anesthetizing, the biopsies of renal tissues were taken for light and electron microscopic morphometric and morphologic analyses. Results: Long-term exposure to lead acetate caused histopathology effects including dilatation, congestion, nuclei heterochromatic effects, increase in diameter of renal tubules and urinary barrier thickness in rabbit renal tissue. Conclusions: Quantitative and qualitative results of long-term lead acetate exposure showed many histopathology side-effects, especially in the urinary barrier. Keywords: Kidney, Lead Acetate, Morphologic, Morphometric, Urinary Barrier, Glomerul

Effect of noise pollution on testicular tissue and hormonal assessment in rat

Many studies have focused on the effect of noise stress on the health. So far, few studies have been conducted on the effect of noise on reproductive system. The aim of study was to investigate the effect of noise pollution on morphometric parameters of testicular tissue and hormonal assessment (ACTH, cortisol and testosterone). In this study, 40 male rats were exposed to control, 95, 105 and 115 dB noise intensity for sixty days. At the end of study, blood sampling was performed and ACTH, cortisol and testosterone concentrations were assessed. The results showed that noise stress decreased testosterone levels in the 115 dB-treated group, while it increased the ACTH and cortisol levels. Histological sections of testis showed that the mean diameter of the seminiferous tubules and thickness of the germinal epithelium reduced compared to the control group. Also the ratio of the interstitial tissue area to the total testicular tissue area was increased significantly. Our study shows that noise stress may have negative influences on male fertility

Effect of shark cartilage derived protein on the NK cells activity

Context: Shark cartilage has been used for its beneficial effects on various diseases. There are evidences, that shark cartilage stimulates cellular and humoral immune responses, which makes it an anti-tumor and immunomodulator candidate. Objective: The immunostimulatory effect of shark cartilage derived proteins on the cytotoxic activity of natural killer (NK) cells from healthy human peripheral blood mononuclear cells was studied. Material and methods: The shark cartilage was extracted and its bioactive proteins were purified using ion-exchange chromatography (DE-52) and sequential fractionation on Amicon ultrafiltration membranes. The effect of each protein fraction on the modulation of cytotoxic activity of NK cells, as effectors, against K562, as target cells, was assayed by enzymatic lactate dehydrogenase test. Results: The most immunostimulatory effect on the cytotoxic activity of NK cells was observed for AR10 fraction, containing proteins with molecular weight of about 14.5kDa on the reducible discontinuous sodium dodecyl sulfate polyacrylamide gel electrophoresis. Discussion: Among the examined shark cartilage derived proteins, the most immunostimulatory effects on the NK cells cytotoxicity was found for AR10 fraction with molecular weight of about 14kDa. We propose—the direct interactions of shark cartilage derived proteins with NK cells surface receptors may lead to the enhancing in the cytotoxic activity of NK cells. Conclusion: Thus AR10 fraction, proteins of about 14.5kDa, has a novel immunostimulatory effect on the NK cells activity in vitro and if confirmed by in vivo trials, it may lead to its future clinical applications as, immunotherapy of cancer, HIV, and augmentation of host immune system related immunodeficiency disorders. Keywords: Immunostimulation, purification, shark cartilage, K562, NK cel

Anti-inflammatory and Wound Healing Activities of Aloe vera, Honey and Milk Ointment on Second-Degree Burns in Rats

The aim of the present study was morphological and morphometric investigation of burn healing impacts of an honey, milk, and Aloe vera (HMA) ointment on experimentally induced second-degree burns, to approve the medicinal basis of its use in Iranian traditional medicine. A total of 21 male Albino rats weighing 200 to 300 g were divided into 3 groups of 7, including (1) control group, (2) positive control group, and (3) the treatment group that were treated with eucerin, silver sulfadiazine 3% and HMA ointment 5% respectively. After anesthetizing, the second-degree burns (1 cm2 areas) were made on the back of the animals using a digital controlled hot plaque, and each group was treated topically, based on the time scheduled. Then, skin punch biopsies were obtained on the 1st, 14th, and 28th days of post–burn induction; processed; and stained using hematoxylin and eosin and Masson’s trichrome methods. The results showed that HMA ointment induces cell proliferation, increasing the wound closure rate, blood vessel counts, and collagen fiber density in treated animals. It also reduced the wound secretions, inflammation, and scar formation. According to the obtained morphological, morphometric results, we concluded that the traditional HMA ointment, which is rich in therapeutic biomaterials and minerals, has multiple healing effects on burn wounds in rats. Keywords burn, wound healing, biomaterial, morphometri

Phospholipase A2 activity of the Persian Gulf upside-down jellyfish venom (Cassiopea andromeda)

Background: The venomous jellyfish Cassiopea andromeda can produce envenomation and different toxicological and biological effects by their nematocysts. The phospholipase A2 enzymes (PLA2) are toxic and induce various pharmacological effects including neurotoxicity, myotoxicity, and anticoagulant activities. The main aim of the current project was to screen the in vitro PLA2 activity of the C. andromeda crude venom. To better understand the experimental result; a molecular docking study was also performed. Materials and methods: The live specimens were collected from Nayband lagoon, by a trawl net, and separation of their tentacles was done according to Bloom 's et al., method. The PLA2 activity of crude venom was performed according to the acidimetric method of Tan and Tan. The lyophilized venom was subjected to Gas Chromatography/ Mass Spectroscopy, and the obtained structures were used for docking study against PLA2. The indoxam was considered as standard control. Results: The PLA2 activity of the jellyfish crude venom was 413 ±0.08 µmol/min/mg. Analysis of the crude venom detected seven compounds (i-vii) using GC-MS. Docking data was also confirmed the experimental results. According to the docking results, the highest affinity [-6.7 (kcal/mol)] was observed in the compound “Pregn-5-ene-3,11-dione, 17,20:20,21 bis [methylenebis(oxy)]-, cyclic 3-(1,2-ethane diyl acetal”. Conclusions: A high PLA2 level was found in the venom of C. andromeda. There was a good correlation between in vitro and in silico studies

The normoglycemic first-degree relatives of patients with type 2 diabetes mellitus have low circulating omentin-1 and adiponectin levels

Objective: It has been suggested that adipose-derived cytokines act as insulin sensitizers/insulin-mimetics and some others may induce insulin resistance. In order to elucidate the potential role of novel adipocytokines in the pre-diabetes states, circulating levels of novel adipocytokines were evaluated in first-degree relatives of subjects with type 2 diabetes mellitus (FDRs). Method: Serum omentin-1, adiponectin and retinol-binding protein 4 (RBP4) levels were measured in 179 subjects (90 glucose tolerant FDRs and 89 age- and sex-matched healthy controls) using enzymelinked immunosorbent assay (ELISA) methods. Results: There was no significant difference between the two groups regarding serum RBP4 concentrations. However, serum omentin-1 (median [interquartile range], 6.18 [4.06–11.52] ng/ml versus 10.50 [4.30– 20.60] ng/ml, p = 0.004) and adiponectin (mean ± SD, 10.07 ± 4.0 lg/ml versus 20.66 ± 8.12 lg/ml, p < 0.0001) levels were significantly lower in FDRs when compared with the controls. In multiple logistic regression analysis, FDRs showed a significant association with lower circulating omentin-1 and adiponectin levels, even after adjustments were made for age, sex, body mass index, blood pressure measures, and biochemical parameters including glucose status, lipid profile, insulin levels and HOMA-IR (OR = 0.49, CI [0.30–0.79]; p = 0.004 and OR = 0.74, CI [0.67–0.82]; p < 0.0001, respectively). However, FDRs did not show a significant association with serum RBP4 levels in different models of regression analyses. Conclusions: The FDRs showed significant associations with lower omentin-1 and adiponectin levels. A potential role for these adipokines in the FDRs’ increased risk of diabetes needs to be further elucidated

Reduced serum osteocalcin concentrations are associated with type 2 diabetes mellitus and the metabolic syndrome components in postmenopausal women: the crosstalk between bone and energy metabolism

Although it has been shown that osteocalcin functions as a hormone in the regulation of glucose metabolism and fat mass, no population-based study to date has addressed serum osteocalcin levels in relation to energy metabolism concurrent with bone metabolism in postmenopausal women. In a population-based study, cardiovascular risk factors, high-sensitivity C-reactive protein (hs-CRP), osteoprotegerin, receptor activator of nuclear factor-jB ligand, osteocalcin, CrossLaps, alkaline phosphatase, and bone mineral density (BMD) at the lumbar spine (L2–L4) and the proximal femur were measured in 382 Iranian postmenopausal women. In multiple logistic regression analysis, lower osteocalcin and CrossLaps levels were associated with a higher odds ratio (OR) of having type 2 diabetes mellitus when adjustments were made for age, hs-CRP, cardiovascular risk factors, BMD, and markers of bone metabolism [OR 5.17, CI (2.66–10.04), p\0.0001 and OR 2.51, CI (1.37–4.61), p = 0.003, respectively]. However, lower alkaline phosphatase levels were associated with a lower OR of having type 2 diabetes mellitus [OR 0.28, CI (0.15–0.52), p\0.0001] in regression analysis. No significant difference was found between serum osteocalcin levels of those with and without metabolic syndrome. Among the metabolic syndrome components, low osteocalcin levels had significant associations with elevated blood glucose [OR 1.89, CI (1.16–3.07), p = 0.010] and elevated waist circumference [OR 2.53, CI (1.13–5.67), p = 0.024] in multivariate analyses. In conclusion, serum osteocalcin was independently associated with glucose intolerance and abdominal obesity as the components of metabolic syndrome and type 2 diabetes mellitus in postmenopausal women. Since CrossLaps and alkaline phosphatase levels were independently associated with the presence of type 2 diabetes mellitus, the unique contribution of osteocalcin in glucose metabolism could not be concluded

Sensing of Alzheimer’s Disease and Multiple Sclerosis Using Nano-Bio Interfaces

It is well understood that patients with different diseases may have a variety of specific proteins (e.g., type, amount, and configuration) in their plasmas. When nanoparticles (NPs) are exposed to these plasmas, the resulting coronas may incorporate some of the disease-specific proteins. Using gold (Au) NPs with different surface properties and corona composition, we have developed a technology for the discrimination and detection of two neurodegenerative diseases, Alzheimer's disease (AD) and multiple sclerosis (MS). Applying a variety of techniques, including UV-visible spectra, colorimetric response analyses and liquid chromatography-tandem mass spectrometry, we found the corona-NP complexes, obtained from different human serums, had distinct protein composition, including some specific proteins that are known as AD and MS biomarkers. The colorimetric responses, analyzed by chemometrics and statistical methods, demonstrate promising capabilities of the technology to unambiguously identify and discriminate AD and MS. The developed colorimetric technology might enable a simple, inexpensive and rapid detection/discrimination of neurodegenerative diseases. KEYWORDS: Alzheimer’s disease; colorimetric technology; disease-specific protein corona; gold nanoparticles; multiple sclerosi