Metal-Organic Framework Fluorescence Sensors for Rapid and Accurate Detection of Melamine in Milk Powder.

In this research, a simple, label-free, and ultra-sensitive fluorescent platform based on a metal-organic framework (MOF) has been developed to detect melamine in milk powder. This fluorescence sensor was fabricated from sensitized terbium (Tb)@NH2-MIL-253 (Al) MOF using a hydrothermal method that involved combining the green emission of Tb (λem = 545 nm) with the blue emission of NH2-MIL-253(Al) MOF (λem = 430 nm) under a single excitation wavelength (λex = 335 nm). The fluorescence sensor was then used under optimized conditions (pH = 9.0; sensor concentration = 30 mg/L; response time = 30 s) to quantify melamine in milk powder. The accuracy, sensitivity, and reproducibility of this sensor were established compared to the high-performance liquid chromatography (HPLC) method. The linear range and lower limit of detection (LLOD, computed with 3σ/S) of the sensor were between 40-396.45 nM (equal to 25 µg/kg-0.25 mg/kg) and 40 nM (equal to 25 µg/kg), respectively, which is much less than the maximum residual level (MRL) for the detection of melamine in infant formula (1 mg/kg) and other foods/feeds (2.5 mg/kg). Additionally, the results had good agreement with the HPLC outcomes, suggesting that the NH2-MIL-253(Al) MOF sensing probe has great precision and repeatability. To conclude, the new fluorescence sensor developed in this study can accurately and sensitively detect melamine in food samples, which may be useful for screening for adulteration of milk powders and other foods.

Mechanistic Approach for Protective Effect of ARA290, a Specific Ligand for the Erythropoietin/CD131 Heteroreceptor, against Cisplatin-Induced Nephrotoxicity, the Involvement of Apoptosis and Inflammation Pathways.

ARA 290, an 11-amino acid linear nonhematopoietic peptide derived from the three-dimensional structure of helix B of the erythropoietin (EPO), interacts selectively with the innate repair receptor (IRR) that arbitrates tissue protection. The aim of this study was to investigate the protective effects of ARA290 against cisplatin-induced nephrotoxicity. For this purpose, HEK-293 and ACHN cells were treated with ARA290 (50-400 nM) and cisplatin (2.5 µM) in pretreatment condition. Then, cytotoxicity, genotoxicity, oxidative stress parameters (ROS, GPx, SOD, and MDA), and inflammatory markers (TNFα, IL6, and IL1ß) were evaluated. Furthermore, apoptotic cell death was assessed via caspase-3 activity and tunnel assay. To determine the molecular mechanisms of the possible nephroprotective effects of ARA290, gene and protein expressions of TNFα, IL1ß, IL6, Caspase-3, Bax, and Bcl2 were evaluated by real-time PCR and western blot assay, respectively. The findings indicated that ARA290 significantly reduced the DNA damage parameters of comet assay and the frequency of micronuclei induced by cisplatin. Besides, ARA290 improved cisplatin-induced oxidative stress by reducing MDA/ROS levels and enhancing antioxidant enzyme levels. In addition, reduced levels of pro-inflammatory cytokines indicated that cisplatin-induced renal inflammation was mitigated upon the treatment with ARA290. Besides, ARA290 ameliorates cisplatin-induced cell injury by antagonizing apoptosis. Furthermore, the molecular findings indicated that gene and protein levels of TNFα, IL1ß, IL6, Caspase-3, and Bax were significantly decreased and gene and protein levels of Bcl2 significantly increased in the ARA290 plus cisplatin group compared with the cisplatin group. These findings revealed that ARA290 as a potent chemo-preventive agent exerted a protective effect on cisplatin-induced nephrotoxicity mostly through its anti-apoptotic, anti-inflammatory, and antioxidant potentials and also suggested that ARA290 might be a new therapeutic approach for patients with acute kidney injury.

Lead inhibits the odontogenic differentiation potential of dental pulp stem cells by affecting WNT1/ß-catenin signaling and related miRNAs expression.

Lead (Pb) is ubiquitous in environment that accumulates in teeth and calcified tissues from where it releases gradually with aging and adversely affects dental health. This study aimed to determine the effect of Pb exposure on odontogenic differentiation potential of isolated human dental pulp stem cells and investigate the possible underlying epigenetic factors. In the absence of Pb exposure, stem cells displayed significant odontogenic markers including elevated Alkaline Phosphatase (ALP) activity, Alizarin red staining intensity, and increased expression of odontogenic DMP1 and DSPP genes. Exposure to 60 µM Pb resulted in reduced ALP activity and calcium deposition. Also, diminished expression of RUNX2, DMP1, and DSPP, as well as Wnt signaling mediators including WNT1, and ß-catenin were detected. The expression of Wnt signaling related microRNAs, miRNA-139-5p and miRNA-142-3p, on the other hand, were shown to have a significant increase. We concluded that Pb could adversely affect the odontogenic differentiation potential of dental pulp stem cell. The underlying mechanism might related to Pb-induced epigenetic dysregulation of WNT1/ß-catenin pathway-related miRNAs leading to down-regulation of Wnt/ß-catenin related odontogenic genes and eventually impaired odontogenic differentiation process.

Molecular Evidence of the Inhibitory Potential of Melatonin against NaAsO2-Induced Aging in Male Rats.

Arsenic (As) poisoning is widespread due to exposure to pollution. The toxic level of (As) causes oxidative stress-induced aging and tissue damage. Since melatonin (MLT) has anti-oxidant and anti-aging properties, we aimed to evaluate the protective effect of MLT against the toxicity of sodium arsenite (NaAsO2). Healthy male NMRI mice were divided into eight different groups. The control group received a standard regular diet. Other groups were treated with varying diets, including MLT alone, NaAsO2, and NaAsO2 plus MLT. After one month of treatment, biochemical and pathological tests were performed on blood, heart, and lung tissue samples. NaAsO2 increased the levels of TNF-α, 8-hydroxy-2-deoxy guanosine (8OHdG), malondialdehyde (MDA), reactive oxygen species (ROS), and high mobility group box 1 (HMGB1), increased the expression of TNF receptor type 1-associated death domain (TRADD) mRNA and telomerase reverse transcriptase, and decreased the expression of Klotho (KL) mRNA in both plasma and tissues. In contrast, MLT reduced MDA, ROS, HMGB1, lactate, and TNF-α enhanced the mRNA expression of KL, and suppressed the mRNA expression of the TERT and TRADD genes. Thus, MLT confers potent protection against NaAsO2- induced tissue injury and oxidative stress.

The rise of deep learning and transformations in bioactivity prediction power of molecular modeling tools.

The search and design for the better use of bioactive compounds are used in many experiments to best mimic compounds' functions in the human body. However, finding a cost-effective and timesaving approach is a top priority in different disciplines. Nowadays, artificial intelligence (AI) and particularly deep learning (DL) methods are widely applied to improve the precision and accuracy of models used in the drug discovery process. DL approaches have been used to provide more opportunities for a faster, efficient, cost-effective, and reliable computer-aided drug discovery. Moreover, the increasing biomedical data volume in areas, like genome sequences, medical images, protein structures, etc., has made data mining algorithms very important in finding novel compounds that could be drugs, uncovering or repurposing drugs and improving the area of genetic markers-based personalized medicine. Furthermore, deep neural networks (DNNs) have been demonstrated to outperform other techniques such as random forests and SVMs for QSAR studies and ligand-based virtual screening. Despite this, in QSAR studies, the quality of different data sources and potential experimental errors has greatly affected the accuracy of QSAR predictions. Therefore, further researches are still needed to improve the accuracy, selectivity, and sensitivity of the DL approach in building the best models of drug discovery.

Assessment of arsenic-induced modifications in the DNA methylation of insulin-related genes in rat pancreatic islets.

Extended exposure to inorganic arsenic through contaminated drinking water has been linked with increased incidence of diabetes mellitus. The most common exposure occurs through the consumption of contaminated drinking water mainly through geogenic sources of inorganic arsenic. Epigenetic modifications are important mechanisms through which environmental pollutants could exert their toxic effects. Bisulfite sequencing polymerase chain reaction method followed by Sanger sequencing was performed for DNA methylation analysis. Our results showed that sodium arsenite treatment significantly reduced insulin secretion in pancreatic islets. It was revealed that the methylation of glucose transporter 2 (Glut2) gene was changed at two cytosine-phosphate-guanine (CpG) sites (-1743, -1734) in the promoter region of the sodium arsenite-treated group comparing to the control. No changes were observed in the methylation status of peroxisome proliferator-activated receptor-gamma (PPARγ), pancreatic and duodenal homeobox 1 (Pdx1) and insulin 2 (Ins2) CpG sites in the targeted regions. Measuring the gene expression level showed increase in Glut2 expression, while the expression of insulin (INS) and Pdx1 were significantly affected by sodium arsenite treatment. This study revealed that exposure to sodium arsenite changed the DNA methylation pattern of Glut2, a key transporter of glucose entry into the pancreatic beta cells (ß-cells). Our data suggested possible epigenetic-mediated toxicity mechanism for arsenite-induced ß-cells dysfunction. Further studies are needed to dissect the precise epigenetic modulatory activity of sodium arsenite that affect the biogenesis of insulin.

Cannabinoids as anti-ROS in aged pancreatic islet cells.

AIMS: Cannabinoids are the chemical compounds with a high affinity for cannabinoid receptors affecting the central nervous system through the release of neurotransmitters. However, the current knowledge related to the role of such compounds in the regulation of cellular aging is limited. This study aimed to investigate the effect of cannabidiol and tetrahydrocannabinol on the function of aged pancreatic islets. MAIN METHODS: The expression of p53, p38, p21, p16, and Glut2 genes and ß-galactosidase activity were measured as hallmarks of cell aging applying real-time PCR, ELISA, and immunocytochemistry techniques. Pdx1 protein expression, insulin release, and oxidative stress markers were compared between young and aged rat pancreatic islet cells. KEY FINDINGS: Upon the treatment of aged pancreatic islets cells with cannabidiol and tetrahydrocannabinol, the expression of p53, p38, p21 and the activity of ß-galactosidase were reduced. Cannabidiol and tetrahydrocannabinol increase insulin release, Pdx1, Glut2, and thiol molecules expression, while the oxidative stress parameters were decreased. The enhanced expression of Pdx1 and insulin release in aged pancreatic islet cells reflects the extension of cell healthy aging due to the significant reduction of ROS. SIGNIFICANCE: This study provides evidence for the involvement of cannabidiol and tetrahydrocannabinol in the oxidation process of cellular aging.

Nanoformulations of Herbal Extracts in Treatment of Neurodegenerative Disorders.

Nanotechnology is one of the methods that influenced human life in different ways and is a substantial approach that assists to overcome the multiple limitations of various diseases, particularly neurodegenerative disorders (NDs). Diverse nanostructures such as polymer nanoparticles, lipid nanoparticles, nanoliposomes, nano-micelles, and carbon nanotubes (CNTs); as well as different vehicle systems including poly lactic-co-glycolic acid, lactoferrin, and polybutylcyanoacrylate could significantly increase the effectiveness, reduce the side effects, enhance the stability, and improve the pharmacokinetics of many drugs. NDs belong to a group of annoying and debilitating diseases that involve millions of people worldwide. Previous studies revealed that several nanoformulations from a number of natural products such as curcumin (Cur), quercetin (QC), resveratrol (RSV), piperine (PIP), Ginkgo biloba, and Nigella sativa significantly improved the condition of patients diagnosed with NDs. Drug delivery to the central nervous system (CNS) has several limitations, in which the blood brain barrier (BBB) is the main drawback for treatment of NDs. This review discusses the effects of herbal-based nanoformulations, their advantages and disadvantages, to manage NDs. In summary, we conclude that herbal-based nano systems have promising proficiency in treatment of NDs, either alone or in combination with other drugs.

Poisoning by Medical Plants.

BACKGROUND: Herbal medications are becoming increasingly popular with the impression that they cause fewer side effects in comparison with synthetic drugs; however, they may considerably contribute to acute or chronic poisoning incidents. Poison centers receive more than 100000 patients exposed to toxic plants. Most of these cases are inconsiderable toxicities involving pediatric ingestions of medicinal plants in low quantity. In most cases of serious poisonings, patients are adults who have either mistakenly consumed a poisonous plant as edible or ingested the plant regarding to its medicinal properties for therapy or toxic properties for illegal aims. METHODS: In this article, we review the main human toxic plants causing mortality or the ones which account for emergency medical visits. Articles addressing "plant poisoning" in online databases were listed in order to establish the already reported human toxic cases. RESULTS: The current review introduces herbal plants toxicity and herb-drug interactions to warn the health professionals about possible consequences of unconscious uses of medicinal plants. The reported cases extracted from our prepared database were classified on the basis of the main toxic effects of plants, and the most prominent constituents of the plants which are responsible for specific toxic effects. CONCLUSION: Considering the long history of consumption of herbal medicines in different societies, people may wrongly think that medicinal plants are fully harmless and nontoxic. Prescription, preparation and consumption regulations of medicinal plants are not clear and strict as well as their marketing regulations that differ from country to country. The extensive and various consumption of medicinal plants without adequate observation is the most important reason for poisoning by medicinal plants.

Bio-guided fractionation and isolation of active component from Tragopogon graminifolius based on its wound healing property.

ETHNOPHARMACOLOGICAL RELEVANCE: Tragopogon graminifolius (T. graminifolius) from Asteraceae family has been used as a remedy in Persian traditional medicine for the treatment of various disorders such as wound healing. AIM OF THE STUDY: The purpose of this study is to investigate the compounds of T. graminifolius, which are responsible for its wound healing activity. MATERIALS AND METHODS: The experiment was performed in three phases; each phase consisted of fractionation of extracts followed by scratch assay. The results of the scratch assay were expressed using scratch closure index (SCI), representing the contraction of scratch. RESULTS: In phase I, Ethyl acetate fraction (E) showed the maximum SCI (61.7 ±â€¯3.5) that was selected for more fractionation in the next phase. In phase II, 12 fractions were obtained and labeled as fractions E- A to L, respectively. Based on the SCI of fractions, EF (SCI=68.9 ±â€¯0.6) was the most active fraction in phase II and selected for further fractionation in phase III. In phase III, 8 fractions were resulted by fractionation of EF and labeled as EF- 1-8. Fraction EF5 with the highest SCI (30.8 ±â€¯3.0) was the most effective fraction and Luteolin was the main component. Luteolin significantly improved viability of fibroblast cells and increased cell population that was accompanied by decreased cell apoptosis. Luteolin-induced cell number increase in the S and G2M phases of the cell cycle, further confirms the proliferative effect of this compound. CONCLUSION: The results showed that the total extract and fractions of T. graminifolius stimulate proliferation and migration of skin fibroblast cells and Luteolin is one of the active compounds responsible for these effects.

Cerium and yttrium oxide nanoparticles against lead-induced oxidative stress and apoptosis in rat hippocampus.

Due to numerous industrial applications, lead has caused widespread pollution in the environment; it seems that the central nervous system (CNS) is the main target for lead in the human body. Oxidative stress and programmed cell death in the CNS have been assumed as two mechanisms related to neurotoxicity of lead. Cerium oxide (CeO2) and yttrium oxide (Y2O3) nanoparticles have recently shown antioxidant effects, particularly when used together, through scavenging the amount of reactive oxygen species (ROS) required for cell apoptosis. We looked into the neuroprotective effects of the combinations of these nanoparticles against acute lead-induced neurotoxicity in rat hippocampus. We used five groups in this study: control, lead, CeO2 nanoparticles + lead, Y2O3 nanoparticles + lead, and CeO2 and Y2O3 nanoparticles + lead. Nanoparticles of CeO2 (1000 mg/kg) and Y2O3 (230 mg/kg) were administered intraperitoneally during 2 days prior to intraperitoneal injection of the lead (25 mg/kg for 3 days). At the end of the treatments, oxidative stress markers, antioxidant enzymes activity, and apoptosis indexes were investigated. The results demonstrated that pretreatments with CeO2 and/or Y2O3 nanoparticles recovered lead-caused oxidative stress markers (ROS, lipid peroxidation, and total thiol molecules) and apoptosis indexes (Bax/Bcl-2 and caspase-3 protein expression). Besides, these nanoparticles reduced the activities of lead-induced superoxide dismutase and catalase as well as the ADP/ATP ratio. Interestingly, the best recovery resulted from the compound of these nanoparticles. Based on these outcomes, it appears that this combination may potentially be beneficial for protection against lead-caused acute toxicity in the brain through improving the oxidative stress-mediated programmed cell death pathway.

On the benefit of magnetic magnesium nanocarrier in cardiovascular toxicity of aluminum phosphide.

The present study was designed to determine the effect of a new (25)Mg(2+)-carrying nanoparticle ((25)MgPMC16) on energy depletion, oxidative stress, and electrocardiographic (ECG) parameters on heart tissue of the rats poisoned by aluminum phosphide (AlP). (25)MgPMC16 at doses of 0.025, 0.05, and 0.1 median lethal dose (LD50 = 896 mg/kg) was administered intravenously (iv) 30 min after a single intragastric administration of AlP (0.25 LD50). Sodium bicarbonate (Bicarb; 2 mEq/kg, iv) was used as the standard therapy. After anesthesia, the animals were rapidly connected to an electronic cardiovascular monitoring device for monitoring of ECG, blood pressure (BP), and heart rate (HR). Later lipid peroxidation, antioxidant power, ATP/ADP ratio, and Mg concentration in the heart were evaluated. Results indicated that after AlP administration, BP and HR decreased while R-R duration increased. (25)MgPMC16 significantly increased the BP and HR at all doses used. We found a considerable increase in antioxidant power, Mg level in the plasma and the heart and a reduction in lipid peroxidation and ADP/ATP ratio at various doses of (25)MgPMC16, but (25)MgPMC16-0.025 + Bicarb was the most effective combination therapy. The results of this study support that (25)MgPMC16 can increase heart energy by active transport of Mg inside the cardiac cells.(25)MgPMC16 seems ameliorating AlP-induced toxicity and cardiac failure necessitating further studies.

Observance of ethical codes in selecting supervisor by postgraduate students.

Nowadays, with development of medical sciences, several ethical challenges have raised which make research more complicated. Observance of student's right in selecting interested research topic and the supervisor, in addition to its positive effect on the research process, will cause satisfaction and quality promotion in the educational system. To observe that issue, during a confidential survey of a number of postgraduate students in 2009, students were asked to confidentially describe any displeasure they might get during their study and research. The most important items included: imposing thesis by a supervisor without informing the student, compulsory assignment of students to a specific supervisor, little time allocated for students by the supervising team who may be selected without students interests, prolongation of the research time, and non-cooperation in publishing the results. Establishment of a proper way to transfer student's displeasure or criticism to supervisors and establishing a continuous program for informing research teams including supervisors and students about ethical codes can positively affect the issue.

Prevention of malathion-induced depletion of cardiac cells mitochondrial energy and free radical damage by a magnetic magnesium-carrying nanoparticle.

The present work was designed to examine the effect of a new (25)Mg(2+)-carrying nanoparticle (PMC16) on energy and oxidative stress parameters inside the heart of the rats exposed to acute mild toxic dose of malathion, a widely used organophosphate. Post a single intraperitoneal (ip) injection of malathion (0.25 of LD50), PMC16 at different doses (0.05, 0.1, and 0.2 of LD50) was administered intravenously (iv) as a supplement to standard therapy of atropine and pralidoxime. MgSO(4) was used as another supplement for comparison with PMC16. Oxidative stress biomarkers including lipid peroxidation (LPO) and reactive oxygen species (ROS), antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), ATP/ADP ratio, and Mg in the cardiac cells were determined. Results indicated a significant increase in LPO, ROS, ADP/ATP ratio, and a decrease in Mg post-malathion poisoning in comparison to controls. All of these parameters were improved by use of standard therapy either with MgSO4 or various doses of PMC16. The activities of SOD, CAT, and GPx did not change significantly in the present acute malathion poisoning model and neither MgSO(4) or PMC16 had no considerable improvement on these parameters. Comparing groups that received normal Mg and those of various doses of PMC16, a significant difference was found with the PMC16 (0.2 LD50) group. PMC16 0.2 reduced cardiac cells LPO and ROS of Mal-exposed animals rather than that of MgSO4. PMC16 0.2 was also significantly better than MgSO(4) in improving MAL-induced changes in ADP/ATP ratio and also intracellular Mg levels. This study illustrates that malathion-induced cardiac cells toxicity is improved by administration of Mg as a result of increasing cardiac ATP through active transport of Mg inside the cells. Finally, the results of this study support positive effects of this magnetic Mg nanoparticle carrier but do not confirm its absolute efficacy that remains to be explored by further tests in different animal models and organs before moving to a phase I human trial.

Study on clinical and biochemical toxicity biomarkers in a zinc-lead mine workers.

The aim of this study was to determine oxidative stress status as well as blood lead (Pb) and zinc (Zn) levels and clinical markers in workers of a Zn-Pb mine. A comparative cross-sectional analysis was performed in 67 mine workers who have been in contact with Zn and Pb in comparison to a control group containing 67 healthy subjects with the same age and sex. Lipid peroxidation, superoxide dismutase, catalase, glutathione reductase, myleoperoxidase, DNA damage, total antioxidant capacity, Zn, and Pb levels were measured in blood of workers and controls. Clinical examination was accomplished to record any abnormal sign or symptoms. Comparing with controls, the workers showed higher blood levels of superoxide dismutase, myleoperoxidase, glutathione reductase, lipid peroxidation, Pb, and Zn. Workers showed lower DNA-damage as compared with controls. Workers showed clinical symptoms such as memory impairment, less of concentration, insomnia, headache, claudication, epigasteric, inappetence, agitation, tremor, decreasing of reflection of deep tendon, conduction deafness of ear, and fatigue. The workers had extra normal levels of Pb (0.9-3 microg/dL) and showed oxidative stress. Taken together, the results indicate that exposure to combination of Pb and Zn in mine elevates total antioxidant capacity of body in a reflex to overcome to oxidative stress. Especially, in the present case, it seems that toxic effect of Pb has been greater than positive effects of Zn, but the combination exposure has resulted in not such a critical toxicity situation.

Restoration of morphine-induced alterations in rat submandibular gland function by N-methyl-D-aspartate agonist.

The effects of morphine, 1-aminocyclobutane-cis-1,3-dicarboxylic (ACBD; NMDA agonist) and 3-((R)2-carboxypiperazin-4-yl)-propyl-l-phosphoric acid (CPP; NMDA antagonist) and their concurrent therapy on rat submandibular secretory function were studied. Pure submandibular saliva was collected intraorally by micro polyethylene cannula from anaesthetized rats using pilocarpine as secretagogue. Intraperitoneal injection of morphine (6 mg/kg) induced significant inhibition of salivary flow rate, total protein, calcium, and TGF-beta1 concentrations. Administration of ACBD (10 mg/kg) and CPP (10 mg/kg) alone did not influence secretion of submandibular glands. In combination therapy, coadministration of CPP with morphine did not influence morphine-induced changes in salivary function while ABCD could restore all morphine-induced changes. In combination treatment, ACBD prevented morphine-induced reduction of flow rate, total protein, calcium, and TGF-beta1 and reached control levels. It is concluded that morphine-induced alterations in submandibular gland function are mediated through NMDA receptors.