Resveratrol Protects Purkinje Neurons and Restores Muscle Activity in Rat Model of Cerebellar Ataxia

Cerebellar ataxia (CA) is regarded as a miscellaneous cluster of brain disorders related to the cerebellum. Resveratrol is a naturally occurring polyphenolic compound. Previous reports suggest that resveratrol confers neuroprotection in various animal models of brain damage. Indeed, we considered it invaluable to investigate whether a treatment with resveratrol has a therapeutic role against CA induced by 3-acetylpyridine (3-AP) in rats. In addition, no investigation has examined neuroprotective effect of resveratrol in rat model of CA. Initially, 3-AP administration generated CA rat models followed by intraperitoneal injection with resveratrol. Then, motor performance and muscle electromyography (EMG) activity were assessed. Moreover, the anti-apoptotic role of resveratrol in CA and its relationship to protection of Purkinje cells were explored. According to what we have found, resveratrol administration improved the muscle activity and movement coordination in 3-AP-lesioned rats. Also under resveratrol treatment, the total number of the Purkinje neurons increased whereas a reduction in apoptotic bodies was observed. In conclusion, post-treatment with resveratrol evidently ameliorated motor performance as well as muscle activity accompanied by a protection of Purkinje cells in ataxic rats.     

Atrial natriuretic peptide is negatively regulated by microRNA-425

Numerous common genetic variants have been linked to blood pressure, but no underlying mechanism has been elucidated. Population studies have revealed that the variant rs5068 (A/G) in the 3′ untranslated region of NPPA, the gene encoding atrial natriuretic peptide (ANP), is associated with blood pressure. We selected individuals on the basis of rs5068 genotype (AG vs. AA) and fed them a low- or high-salt diet for 1 week, after which they were challenged with an intravenous saline infusion. On both diets, before and after saline administration, ANP levels were up to 50% higher in AG individuals than in AA individuals, a difference comparable to the changes induced by high-salt diet or saline infusion. In contrast, B-type natriuretic peptide levels did not differ by rs5068 genotype. We identified a microRNA, miR-425, that is expressed in human atria and ventricles and is predicted to bind the sequence spanning rs5068 for the A, but not the G, allele. miR-425 silenced NPPA mRNA in an allele-specific manner, with the G allele conferring resistance to miR-425. This study identifies miR-425 as a regulator of ANP production, raising the possibility that miR-425 antagonists could be used to treat disorders of salt overload, including hypertension and heart failure.     

Association of G22A and A4223C ADA1 gene polymorphisms and ADA activity with PCOS

Adenosine deaminase-1 (ADA1) regulates the concentration of adenosine as the main modulator of oocyte maturation. There is compelling evidence for the association of ADA1 gene polymorphisms with many diseases but the importance of ADA1 polymorphisms in polycystic ovary syndrome (PCOS) has not been studied before. This study investigates serum total ADA activity (tADA), ADA1 and ADA2 isoenzyme activities, and genotype and allele frequencies of G22A and A4223C polymorphisms in healthy and PCOS women. In this case-control study 200 PCOS patients and 200 healthy women were enrolled. Genomic DNA was extracted from whole blood and the PCR-RFLP technique was used to determine the G22A and A4223C variants. The genotype frequencies were calculated and the association between polymorphic genotypes and enzyme activities were determined. tADA activity was significantly lower in the PCOS group compared with the control group (27.76±6.0 vs. 39.63±7.48, respectively). PCOS patients also showed reduced activity of ADA1 and ADA2. PCOS was not associated with G22A polymorphism whereas AA, AC, and CC genotypes of A4223C polymorphism were found distributed differently between the control and the PCOS women where the C allele showed a strong protective role for PCOS (odds ratio=1.876, p=0.033). The present study for the first time showed that lower ADA activity may be involved in pathogenesis of PCOS by maintaining a higher concentration of adenosine affecting follicular growth. As a novel finding, we also showed great differences in genotype distribution and allele frequencies of A4223C polymorphism between groups indicating a protective role for C allele against PCOS.

AbbreviationsADA: adenosine deaminase PCOS: polycystic ovary syndrome PCR-RFLP: polymerase chain reaction–restriction fragment length polymorphism tADA: total adenosine deaminase     

Evaluation of dose enhancement in presence of gold nanoparticles in eye brachytherapy by <Superscript>103</Superscript>Pd source

In recent years, the use of gold nanoparticles in radiation therapy has been introduced as a new approach in radiotherapy. The aim of this study is to investigate the effect of gold nanoparticles (GNPs) in plaque brachytherapy for choroidal melanoma using Monte Carlo (MC) simulation. MCNPX code was used for simulation of human eye, ¹⁰³Pd (model 200) brachytherapy source and the 20 mm COMS eye plaque that was loaded with 24 ¹⁰³Pd seeds and standardized by Collaborative Ocular Melanoma Study (COMS). The tumour was defined from the inner surface of choroid with 0.55 cm height and latticed with gold nanospheres and it was filled with different concentrations of 5, 10 and 15 mg/g GNPs, separately. Dose rate and dose enhancement factor in tumour and normal tissues of the eye (without gold) was examined for this case and compared with gold–water mixture of the same concentrations distributed in the tumour. The results show that with increasing the concentration of GNPs, the dose in the tumour increases and the dose to the normal tissues decreases. Furthermore, the time that is required to deliver the prescribed dose to the tumour decreases. In the gold nanosphere case for 5, 10 and 15 mg/g concentrations, the DEF in the apex of the tumour are 1.28, 1.46, 1.44 and at the distance of 6.5 mm in the normal tissue (outside the tumour) this factor would be 0.82, 0.73 and 0.68. The comparison between two cases of gold nanospheres and gold–water mixture shows that when the gold concentrations are defined as mixed with water, the dose enhancement in the first depths are higher than when the gold-nanoparticles are distributed inside the tumour. Furthermore due to more reduced particle flux for water-mixture case, by an increase in the depth the dose enhancement in gold-nanosphere increases compared with gold–water mixture case.     

Haematology, morphology and blood cells characteristics of male and female Siamese fighting fish (Betta splendens)

The aim of the present study was to obtain baseline data on blood cell size, morphology and haematological parameters in Siamese fighting fish (Betta splendens) since there is limited information in the published literature. Blood samples from the caudal vein of apparently healthy Siamese fighting fish (male: n = 40 and female: n = 36) were collected. Haematological values of the blood samples were determined using standard techniques. The morphological features of blood cells were described according to observations made by light microscopy. The various types of blood cells measurement were carried out with the help of a stage and an ocular micrometre at a magnification of ×1,000. Erythrocytes, thrombocytes and four types of leucocytes: lymphocytes, monocytes, heterophils and eosinophils, were distinguished and characterised. The average size of the erythrocyte cell and nucleus was 97.33 and 16.28 μm², respectively. Results showed a positive correlation between erythrocyte size and nucleus size for Siamese fighting fish (r = 0.470, p < 0.01). We also found sex-dependent differences for total white blood cell count, lymphocytes and heterophils in Siamese fighting fish (p < 0.05). Statistical analysis revealed that differences in other haematological parameters and blood cell morphology, between male and female fish were not statistically significant (p > 0.05).     

Effects of open rhinoplasty on upper lip position in profile and frontal views

Examining the upper lip position is a key indicator of facial beauty. This study aimed to examine the upper lip position following cosmetic rhinoplasty at the frontal and profile views. The medical records of 67 patients who underwent rhinoplasty with no history of any facial skeletal surgery were obtained from archives. Complete preoperative and postoperative photos including the profile view at rest and the frontal view at rest, were prepared and analysed using Adobe Photoshop CC 2015 software. Interpupillary distances of two eyes in frontal views and Glabella to Pogonion (POG) distance in profile views were considered as fixed landmarks to calibrate the preoperative and postoperative photos. Upper lip length, subnasal area, and vermilion points were marked and compared between preoperative and postoperative photos. Data analysis was carried out using one-sample t-test and p < 0.05% was considered as the significant level. Lip length (frontal view) was increased in 46 subjects. There were changes in the profile view of vermilion and subnasal positions in 56 patients and 53 patients, respectively. In surgical procedures on columella strut, maxillary augment, alar resection, spreader graft, columella retraction, and depressor septi muscle release, vermilion and subnasal protrusion in the profile view was statistically significant and lip length increased significantly in the frontal view. In tip rotation surgery techniques, the vermilion and subnasal position showed also significant protrusion. The depressor septi muscle cutting methods had only led to a significant protrusion of the vermilion position and upper lip length. Despite all covariants interfering in rhinoplasty, this cosmetic surgery most often may increases maxillary lip length and helps that maxilla look more protruded.     

A Combined Epidemiologic and Metabolomic Approach Improves CKD Prediction

Metabolomic approaches have begun to catalog the metabolic disturbances that accompany CKD, but whether metabolite alterations can predict future CKD is unknown. We performed liquid chromatography/mass spectrometry–based metabolite profiling on plasma from 1434 participants in the Framingham Heart Study (FHS) who did not have CKD at baseline. During the following 8 years, 123 individuals developed CKD, defined by an estimated GFR of <60 ml/min per 1.73 m². Numerous metabolites were associated with incident CKD, including 16 that achieved the Bonferroni-adjusted significance threshold of P≤0.00023. To explore how the human kidney modulates these metabolites, we profiled arterial and renal venous plasma from nine individuals. Nine metabolites that predicted CKD in the FHS cohort decreased more than creatinine across the renal circulation, suggesting that they may reflect non–GFR-dependent functions, such as renal metabolism and secretion. Urine isotope dilution studies identified citrulline and choline as markers of renal metabolism and kynurenic acid as a marker of renal secretion. In turn, these analytes remained associated with incident CKD in the FHS cohort, even after adjustment for eGFR, age, sex, diabetes, hypertension, and proteinuria at baseline. Addition of a multimarker metabolite panel to clinical variables significantly increased the c-statistic (0.77–0.83, P<0.0001); net reclassification improvement was 0.78 (95% confidence interval, 0.60 to 0.95; P<0.0001). Thus, the addition of metabolite profiling to clinical data may significantly improve the ability to predict whether an individual will develop CKD by identifying predictors of renal risk that are independent of estimated GFR.Given the significant morbidity and mortality attributable to established CKD, early markers of CKD risk are needed.¹ The kidneys can modulate circulating small-molecule levels through a variety of mechanisms, such as filtration, reabsorption, secretion, and metabolism (including both catabolism and anabolism). Currently available metrics of kidney function (serum creatinine and urea) primarily reflect relatively advanced impairment in renal filtration. In contrast, early and specific disease markers may reflect impairments along other axes of renal small-molecule handling.Metabolite profiling technologies enable high-throughput, high-resolution metabolic phenotyping of human plasma. Applied to well-characterized human cohorts, these techniques have the potential to identify novel disease biomarkers and to highlight their underlying metabolic pathways. For example, we have previously applied liquid chromatography-mass spectrometry (LC-MS)–based metabolite profiling to identify numerous metabolite alterations that accompany ESRD.² Similar findings have been observed using capillary electrophoresis-MS–based metabolite profiling of plasma obtained from individuals across a spectrum of extant kidney disease.^3,4 Whether any of these metabolite perturbations presage the development of clinically overt kidney disease is unknown.Here, we report the application of metabolite profiling to plasma obtained from participants in the Framingham Heart Study (FHS). Prior work in the FHS has highlighted branched-chain and aromatic amino acids as robust predictors of future type 2 diabetes.⁵ Because of access to archived plasma samples, detailed phenotyping, and longitudinal follow-up on clinical outcomes, this sample provides an ideal opportunity to identify novel markers of CKD risk. To explore how select CKD predictors are modulated by the human kidney, we also performed metabolite profiling of plasma and urine samples obtained from individuals undergoing aortic and renal vein catheterization. Taken together, these studies demonstrate the broad effect kidney function has on the plasma metabolome and show how this perspective can improve CKD prediction beyond estimated GFR (eGFR) and other established CKD risk factors.     

Clinical and experimental studies on polyherbal formulations for diabetes： current status and future prospective

Diabetes is a leading cause of morbidity an active search for antidiabetic drugs with greater and mortality in the world. There is currently effectiveness with fewer and less adverse side effects. Although numerous individual herbs have been experimentally or clinically reported to possess antidiabetic effects, considerably less research has been conducted on polyherbal compounds. It is believed that herbal compounds containing multiple plant products have synergistic antidiabetic effects and could enhance the desired actions. Several polyherbal formulations have been studied as therapeutic agents in diabetes management. To describe the current state of research on polyherbal compounds in the treatment of diabetes, an extensive review of literature was undertaken on several major databases. This paper presents what is known about the efficacy of these polyherbal formulations and compare their antidiabetic effects with those of current oral hypoglycemic drugs as reference. The percent decrease in blood glucose, lipids and other biochemical parameters achieved by each product in diabetic animals and patients is reported. Also, the possible mechanisms responsible for hypoglycemic action of polyherbal formulations are discussed.