Oxytocin protective effects on zebrafish larvae models of autism-like spectrum disorder.

Objectives: Autism is a complicated neurodevelopmental disorder characterized by social interaction deficiencies, hyperactivity, anxiety, communication disorders, and a limited range of interests. The zebrafish (Danio rerio) is a social vertebrate used as a biomedical research model to understand social behavior mechanisms. Materials and Methods: After spawning, the eggs were exposed to sodium valproate for 48 hr, after which the eggs were divided into eight groups. Except for the positive and control groups, there were six treatment groups based on oxytocin concentration (25, 50, and 100 µM) and time point (24 and 48 hr). Treatment was performed on days 6 and 7, examined by labeling oxytocin with fluorescein-5-isothiocyanate (FITC) and imaging with confocal microscopy and the expression levels of potential genes associated with the qPCR technique. Behavioral studies, including light-dark background preference test, shoaling behavior, mirror test, and social preference, were performed on 10, 11, 12, and 13 days post fertilization (dpf), respectively. Results: The results showed that the most significant effect of oxytocin was at the concentration of 50 µM and the time point of 48 hr. Increased expression of shank3a, shank3b, and oxytocin receptor genes was also significant at this oxytocin concentration. Light-dark background preference results showed that oxytocin in the concentration of 50 µM significantly increased the number of crosses between dark and light areas compared with valproic acid (positive group). Also, oxytocin showed an increase in the frequency and time of contact between the two larvae. We showed a decrease in the distance in the larval group and an increase in time spent at a distance of one centimeter from the mirror. Conclusion: Our findings showed that the increased gene expression of shank3a, shank3b, and oxytocin receptors improved autistic behavior. Based on this study some indications showed that oxytocin administration in the larval stage could significantly improve the autism-like spectrum.

Plasma Concentration of Taurine Changes following Acetaminophen Overdose in Male Patients during Hospitalization.

Changes in plasma concentration of taurine during hospitalization of acetaminophen poisoned patients have not been studied. Hepatotoxicity is a common consequence of acetaminophen overdose that may lead to acute liver failure. Numerous biomarkers for drug-induced liver injury have been explored. All biomarkers are usually obtainable 48 h following acetaminophen overdose. We have already introduced taurine as a non-specific early biomarker of acetaminophen overdose. This study aimed to follow up changes in plasma concentration of taurine during the first three days of acetaminophen overdose. Sixty-four male patients suffering from acetaminophen overdose were selected for the study. Four blood samples were taken from the patients every 12 h. Sixty blood samples were also taken from sixty healthy humans. The plasma concentration of taurine in both groups was analyzed an already developed HPLC method. Analysis of regression showed a significant correlation between means of plasma concentrations of taurine and acetaminophen, aspartate aminotransferase, Alanine aminotransferase, glutathione peroxidase, and prothrombin time during hospitalization. The high plasma concentration of taurine, 6 h or more after acetaminophen overdose, could be a useful early indicator of liver damage.

Recent Advances in Nanotechnology-Based Biosensors Development for Detection of Arsenic, Lead, Mercury, and Cadmium.

Heavy metals cause considerable environmental pollution due to their extent and non-degradability in the environment. Analysis and trace levels of arsenic, lead, mercury, and cadmium as the most toxic heavy metals show that they can cause various hazards in humans' health. To achieve rapid, high-sensitivity methods for analyzing ultra-trace amounts of heavy metals in different environmental and biological samples, novel biosensors have been designed with the participation of strategies applied in nanotechnology. This review attempted to investigate the novel, sensitive, efficient, cost-benefit, point of care, and user-friendly biosensors designed to detect these heavy metals based on functional mechanisms. The study's search strategies included examining the primary databases from 2015 onwards and various keywords focusing on heavy metal biosensors' performance and toxicity mechanisms. The use of aptamers and whole cells as two important bio-functional nanomaterials is remarkable in heavy metal diagnostic biosensors' bioreceptor design. The application of hybridized nanomaterials containing a specific physicochemical function in the presence of a suitable transducer can improve the sensing performance to achieve an integrated detection system. Our study showed that in addition to both labeled and label-free detection strategies, a wide range of nanoparticles and nanocomposites were used to modify the biosensor surface platform in the detection of heavy metals. The detection limit and linear dynamic range as an essential characteristic of superior biosensors for the primary toxic metals are studied. Furthermore, the perspectives and challenges facing the design of heavy metal biosensors are outlined. The development of novel biosensors and the application of nanotechnology, especially in real samples, face challenges such as the capability to simultaneously detect multiple heavy metals, the interference process in complex matrices, the efficiency and stability of nanomaterials implemented in various laboratory conditions.

High-Performance Voltammetric Aptasensing Platform for Ultrasensitive Detection of Bisphenol A as an Environmental Pollutant.

Bisphenol A (BPA) as a pervasive endocrine-disrupting compound (EDC) has been shown to cause multiple detrimental effects including cardiovascular disorders, pregnancy complications, obesity, glucose metabolism disorders, and reproductive toxicity even at a concentration as low as tolerable daily intake (TDI) (4 µg/kg/day). In the present study, a novel ultra-sensitive, electrochemical aptasensor was designed using a screen-printed carbon electrode (SPCE) modified by gold nanoparticles (Au NPs) conjugated to thiolated aptamers for accurate determination of BPA in biological, industrial and environmental samples. To characterize the electrochemical properties of the aptasensor, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were implemented. Detection of BPA was also performed through differential pulse voltammetry (DPV) in [Fe(CN)6]3-/4- electrolyte solution. Under optimum condition, the present electrochemical aptasensor demonstrated an outstanding linear response in the concentration range of 1 pM to 10 nM with a remarkably low limit of detection of 0.113 pM. Due to the superb affinity between anti-BPA aptamers and BPA molecules, the designed aptasensor did not show any significant interaction with other analytes in real samples. Also, fabricated biosensor remained perfectly stable in long-term storage. The analytical results of the fabricated aptasensor are well compatible with those obtained by the ELISA method, indicating the trustworthiness and reasonable accuracy of the application of aptasensor in real samples. Overall, the proposed aptasensor would be a credible and economical method of precise, reproducible, and highly selective detection of minimum levels of BPA in food containers and clinical samples. This would be a promising strategy to enhance the safety of food products and reduce the risk of BPA daily exposure.

A Sensitive Aptamer-Based Biosensor for Electrochemical Quantification of PSA as a Specific Diagnostic Marker of Prostate Cancer.

PURPOSE: The current project aimed to design a simple, highly sensitive, and economical label-free electrochemical aptasensor for determination of prostate-specific antigen (PSA), as the gold standard biomarker for prostate cancer diagnosis. The aptasensor was set up using a screen-printed carbon electrode (SPCE) modified by gold nanoparticles (Au NPs) conjugated to thiolated aptamers. METHODS: Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were implemented for electrochemical (EC) characterization of the aptasensor. The determination of PSA was also performed through differential pulse voltammetry (DPV) in [Fe (CN) 6]3-/4- electrolyte solution. RESULTS: The present aptasensor was shown an outstanding linear response in the concentration range of 1 pg/mL - 200 ng/mL with a remarkably lower limit of detection of 0.077 pg/mL. The optimum concentration for PSA separation and the optimum incubation time for antigen-aptamer binding were determined by observing and electing the highest electrochemical responses in a specified time or concentration. CONCLUSION: According to the results of the specificity tests, the designed aptasensor did not show any significant interactions with other analytes in real samples. Clinical functionality of the aptasensor was appraised in serum samples of healthy individuals and patients examining the PSA level through the fabricated aptasensor and the reference methods. Both methods are comparable in sensitivity. The present fabricated PSA aptasensor with substantial characteristics of ultra- sensitivity and cost-effectiveness can be conventionally built and used for the routine check-up of the men for prostate problems.

An Electrochemical Aptasensor Platform Based on Flower-Like Gold Microstructure-Modified Screen-Printed Carbon Electrode for Detection of Serpin A12 as a Type 2 Diabetes Biomarker.

PURPOSE: In the present study, a highly sensitive and simple electrochemical (EC) aptasensor for the detection of serpin A12 as a novel biomarker of diabetes was developed on a platform where flower-like gold microstructures (FLGMs) are electrodeposited onto a disposable screen-printed carbon electrode. Meanwhile, serpin A12-specific thiolated aptamer was covalently immobilized on the FLGMs. METHODS: The electrochemical activity of a fabricated aptasensor under various conditions were examined by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Aptamer concentration, deposition time, self-assembly time, and incubation time were optimized for assay of serpin A12. The differential pulse voltammetry (DPV) was implemented for quantitative detection of serpin A12 in K3 [Fe (CN) 6]/K4 [Fe (CN) 6] solution (redox probe). RESULTS: The label-free aptasensor revealed a linear range of serpin A12 concentration (0.039-10 ng/mL), detection limit of 0.020 ng/mL (S/N=3), and 0.031 ng/mL in solution buffer and plasma, respectively. CONCLUSION: The results indicate that this aptasensor has a high sensitivity, selectivity, stability, and acceptable reproducibility for detection of serpin A12 in diabetic patients.

Effects of mercuric chloride on spatial memory deficit-induced by beta-amyloid and evaluation of mitochondrial function markers in the hippocampus of rats.

Mercury is a highly poisonous heavy metal abundantly found in the environment in its inorganic form. Although evidence have been provided about the possible role of inorganic mercury in the pathology of Alzheimer's disease (AD), its effect on cognitive and mitochondrial functions have not yet been completely understood. Thus, the purpose of the present study was to examine the effects of the chronic exposure to mercuric chloride (0.4, 0.8 and 1.6 mg kg-1 per day for 3 weeks) through drinking water (by gavage) on spatial learning and memory and hippocampal mitochondrial function in beta-amyloid treated rats (1 µg per µL per side, intrahippocampally). The acquisition and retention of spatial memory were evaluated by the Morris water maze (MWM) test. Several parameters of hippocampal mitochondrial function were also measured. The results indicated that mercury impaired spatial learning and memory as well as aggravated Aß-induced memory impairments in a concentration-dependent manner. Furthermore, mercury exposure resulted in a significant increase in ROS generation, MMP collapse, mitochondrial swelling, glutathione oxidation, lipid peroxidation, and outer membrane damage. In addition, a reduced cytochrome c oxidase (complex IV) activity and elevated ADP/ATP ratio in the rats' hippocampus was also observed. The findings of the current study revealed that chronic mercury exposure led to mitochondrial dysfunction, which resulted in spatial memory impairments. The results also showed that mercury can exacerbate the toxic effects of Aß on spatial memory and hippocampal mitochondrial function.

Polyphenols targeting diabetes via the AMP-activated protein kinase pathway; future approach to drug discovery.

Regarding the widespread progression of diabetes, its related complications and detrimental effects on human health, investigations on this subject seems compulsory. AMP-activated protein kinase (AMPK) is a serine/threonine kinase and a key player in energy metabolism regulation. AMPK is also considered as a prime target for pharmaceutical and therapeutic studies on disorders such as diabetes, metabolic syndrome and obesity, where the body energy homeostasis is imbalanced. Following the activation of AMPK (physiological or pharmacological), a cascade of metabolic events that improve metabolic health is triggered. While there are several publications on this subject, this is the first report that has focused solely on polyphenols targeting diabetes via AMPK pathway. The multiple characteristics of polyphenolic compounds and their favorable influence on diabetes pathogenesis, as well as their intersections with the AMPK signaling pathway, indicate that these compounds have a beneficial effect on the regulation of glucose homeostasis. PPs could potentially occupy a significant position in the future anti-diabetic drug market.

Biochemical and molecular evidence on the role of vaspin in early detection of the insulin resistance in a rat model of high-fat diet and use of diazinon.

Vaspin, as a newly discovered adipocytokine, can modulate obesity with insulin-sensitizing effects. This study mainly focused on the plasma level of vaspin in insulin resistant rats, which received high-fat diet (HFD) and diazinon (DZN) (70 mg/kg). Upon 30-day experiment, related oxidative stress and inflammatory markers of plasma, the toxic effects of DZN and HFD on the histological structure of the liver, as well as the expression levels of potential genes associated with insulin resistance, phosphatase and tensin homolog (PTEN) and Forkhead box protein O1 (FoxO1) were evaluated. Metabolic parameters implicated to the glucose and insulin statues such as homeostatic model assessment of insulin resistance (HOMA-IR), oral glucose tolerance test (OGTT) and fasting blood glucose (FBG) were determined. DZN significantly inhibited almost 50% of the plasma cholinesterase (ChE) activity. A remarkable increase of MDA level was observed in groups that received DZN and DZN + HFD. Animals treated with DZN or DZN + HFD showed significant changes in reactive oxygen species (ROS) level. The level of plasma tumor Necrosis Factor alpha (TNF-α) was noticeably elevated in the exposed groups. The highest elevation in vaspin level was observed in HFD group followed by DZN treated animals. In all treated groups, insulin level significantly increased and also, the area under the curve (AUC0-180) values of plasma glucose heightened considerably. The histopathological micrographs of HFD + DZN treated group indicated a severe fatty change. The plasma concentration of DZN was significantly higher in the DZN-treated group in comparison to the DZN + HFD group. FoxO1 and PTEN mRNA levels were significantly overexpressed in the DZN and HFD exposed groups. In HFD treated group, PTEN expression significantly increased compared with the DZN and DZN + HFD groups. Consequently, in contrast to oxidative stress and inflammatory biomarkers, vaspin level would be a more reliable diagnostic factor when it comes to the insulin resistance.

Novel label-free electrochemical aptasensor for determination of Diazinon using gold nanoparticles-modified screen-printed gold electrode.

The present study aimed to develop a highly sensitive label-free electrochemical aptasensor for the detection of Diazinon (DZN), as one of the most widespread organophosphorus compounds. The aptasensor was assembled using screen-printed gold electrode modified by thiolated aptamers which were immobilized on gold nanoparticles (Au NPs). Optimum deposition time, in which the highest electrochemical response occurred, was found in 150 s. Electrochemical impedance spectroscopy and cyclic voltammetry were used to characterize electrochemical properties of the novel aptasensor. Electrochemical detection was carried out through differential pulse voltammetry in [Fe(CN)6]3-/4- solution. Fluctuation of the current was examined in the DZN concentration range of 0.1-1000 nM. According to the results, the designed aptasensor provided an extremely lower limit of detection (0.0169 nM) compared with HPLC and other colorimetric techniques for DZN detection. The present highly specific designed aptasensor doesn't interact with other analytes in the real sample. Consequently, the present aptasensor is easy to use and relatively inexpensive with a good sensitivity, stability, and reproducibility for this application. We are now evaluating all approaches to make a portable device for fast and sensitive quantification of DZN and related OPs.

Alteration of hepatocellular antioxidant gene expression pattern and biomarkers of oxidative damage in diazinon-induced acute toxicity in Wistar rat: A time-course mechanistic study.

In the present survey, the plasma level of diazinon after acute exposure was measured by HPLC method at a time-course manner. In addition, the impact of diazinon on the expression of the key genes responsible for hepatocellular antioxidative defense, including PON1, GPx and CAT were investigated. The increase in oxidative damages in treated rats was determined by measuring LPO, protein carbonyl content and total antioxidant power in plasma. After administration of 85 mg/kg diazinon in ten groups of male Wistar rats at different time points between 0-24 hours, the activity of AChE enzyme was inhibited to about 77.94 %. Significant increases in carbonyl groups and LPO after 0.75 and 1 hours were also observed while the plasma antioxidant power was significantly decreased. Despite the dramatic reduction of GPX and PON1 gene expression, CAT gene was significantly upregulated in mRNA level by 1.1 fold after 4 hours and 1.5-fold after 24 hours due to diazinon exposure, compared to control group. Furthermore, no significant changes in diazinon plasma levels were found after 4 hours in the treated rats. The limits of detection and quantification were 137.42 and 416.52 ng/mL, respectively. The average percentage recoveries from plasma were between 90.62 % and 95.72 %. In conclusion, acute exposure to diazinon increased oxidative stress markers in a time-dependent manner and the changes were consistent with effects on hepatic antioxidant gene expression pattern. The effect of diazinon even as a non-lethal dose was induced on the gene expression of antioxidant enzymes. The change in antioxidant defense system occurs prior to diazinon plasma peak time. These results provide biochemical and molecular evidence supporting potential acute toxicity of diazinon and is beneficial in the evaluation of acute toxicity of other organophosphorus pesticides as well.

Recent advances in biosensor technology in assessment of early diabetes biomarkers.

Discovery of biosensors has acquired utmost importance in the field of healthcare. Recent advances in biological techniques and instrumentation involving nanomaterials, surface plasmon resonance, and aptasensors have developed innovative biosensors over classical methods. Integrated approaches provided a better perspective for developing specific and sensitive devices with wide potential applications. Type 2 diabetes mellitus is a complex disease affecting almost every tissue and organ system, with metabolic complications extending far beyond impaired glucose metabolism. Although there is no known cure for Type 2 diabetes, early diagnosis and interventions are critical to prevent this disease and can postpone or even prevent the serious complications that are associated with diabetes. Biomarkers for type 2 diabetes are useful for prediction and intervention of the disease at earlier stages. Proper selection of biomarkers that represent health and disease states is vital for disease diagnosis and treatment by detecting it before it manifests. In this respect, we provide an overview of different types of biosensors being used, ranging from electrochemical, fluorescence-based, nanomonitors, SPR-based, and field-effect transistor biosensors for early detection and management of diabetes with focus on prediabetes. In the future, novel non-invasive technologies combined with blood and tissue-based biomarkers will enable the detection, prevention, and treatment of diabetes and its complications long before overt disease develops.