Application of polysaccharide biopolymers as natural adsorbent in sample preparation.

Preparing samples for analyses is perhaps the most important part to analyses. The varied functional groups present on the surface of biopolymers bestow them appropriate adsorption properties. Properties like biocompatibility, biodegradability, presence of different surface functional group, high porosity, considerable absorption capacity for water, the potential for modification, etc. turn biopolymers to promising candidates for varied applications. In addition, one of the most important parts of determination of an analyte in a matrix is sample preparation step and the efficiency of this step in solid phase extraction methods is largely dependent on the type of adsorbent used. Due to the unique properties of biopolymers they are considered an appropriate choice for using as sorbent in sample preparation methods that use from a solid adsorbent. Many review articles have been published on the application of diverse adsorbents in sample preparation methods, however despite the numerous advantages of biopolymers mentioned; review articles in this field are very few. Thus, in this paper we review the reports in different areas of sample preparation that use polysaccharides-based biopolymers as sorbents for extraction and determination of diverse organic and inorganic analytes.

Rolipram and pentoxifylline combination ameliorates the morphological abnormalities of dorsal root ganglion neurons in experimental diabetic neuropathy by reducing mitochondrial dysfunction and apoptosis.

Diabetic neuropathy (DN) is the most prevalent complication of diabetes. Pharmacological treatments for DN are often limited in efficacy, so the development of new agents to alleviate DN is essential. The aim of this study was to evaluate the effects of rolipram, a selective phosphodiesterase-4 inhibitor (PDE-4I), and pentoxifylline, a general PDE inhibitor, using a rat model of DN. In this study, a diabetic rat model was established by i.p. injection of STZ (55 mg/kg). Rats were treated with rolipram (1 mg/kg), pentoxifylline (100 mg/kg), and combination of rolipram (0.5 mg/kg) and pentoxifylline (50 mg/kg), orally for 5 weeks. After treatments, sensory function was assessed by hot plate test. Then rats were anesthetized and dorsal root ganglion (DRG) neurons isolated. Cyclic adenosine monophosphate (cAMP), adenosine triphosphate (ATP, adenosine diphosphate and mitochondrial membrane potential (MMP) levels, Cytochrome c release, Bax, Bcl-2, caspase-3 proteins expression in DRG neurons were assessed by biochemical and ELISA methods, and western blot analysis. DRG neurons were histologically examined using hematoxylin and eosin (H&E) staining method. Rolipram and/or pentoxifylline significantly attenuated sensory dysfunction by modulating nociceptive threshold. Rolipram and/or pentoxifylline treatment dramatically increased the cAMP level, prevented mitochondrial dysfunction, apoptosis and degeneration of DRG neurons, which appears to be mediated by inducing ATP and MMP, improving cytochrome c release, as well as regulating the expression of Bax, Bcl-2, and caspase-3 proteins, and improving morphological abnormalities of DRG neurons. We found maximum effectiveness with rolipram and pentoxifylline combination on mentioned factors. These findings encourage the use of rolipram and pentoxifylline combination as a novel experimental evidence for further clinical investigations in the treatment of DN.

Dual action anti-inflammatory/antiviral isoquinoline alkaloids as potent naturally occurring anti-SARS-CoV-2 agents: A combined pharmacological and medicinal chemistry perspective.

In the search for compounds that inhibit the SARS-CoV-2 after the onset of the COVID-19 pandemic, isoquinoline-containing alkaloids have been identified as compounds with high potential to fight the disease. In addition to having strong antiviral activities, most of these alkaloids have significant anti-inflammatory effects which are often manifested through the inhibition of a promising host-based anti-COVID-19 target, the p38 MAPK signaling pathway. In the present review, our pharmacological and medicinal chemistry evaluation resulted in highlighting the potential of anti-SARS-CoV-2 isoquinoline-based alkaloids for the treatment of COVID-19 patients. Considering critical parameters of the antiviral and anti-inflammatory activities, mechanism of action, as well as toxicity/safety profile, we introduce the alkaloids emetine, cephaeline, and papaverine as high-potential therapeutic agents for use in the treatment of COVID-19. Although preclinical studies confirm that some isoquinoline-based alkaloids reviewed in this study have a high potential to inhibit the SARS-CoV-2, their entry into drug regimens of COVID-19 patients requires further clinical trial studies and toxicity evaluation.

Chemotherapy: a double-edged sword in cancer treatment.

Chemotherapy is a well-known and effective treatment for different cancers; unfortunately, it has not been as efficient in the eradication of all cancer cells as been expected. The mechanism of this failure was not fully clarified, yet. Meanwhile, alterations in the physiologic conditions of the tumor microenvironment (TME) were suggested as one of the underlying possibilities. Chemotherapy drugs can activate multiple signaling pathways and augment the secretion of inflammatory mediators. Inflammation may show two opposite roles in the TME. On the one hand, inflammation, as an innate immune response, tries to suppress tumor growth but on the other hand, it might be not powerful enough to eradicate the cancer cells and even it can provide appropriate conditions for cancer promotion and relapse as well. Therefore, the administration of mild anti-inflammatory drugs during chemotherapy might result in more successful clinical results. Here, we will review and discuss this hypothesis. Most chemotherapy agents are triggers of inflammation in the tumor microenvironment through inducing the production of senescence-associated secretory phenotype (SASP) molecules. Some chemotherapy agents can induce systematic inflammation by provoking TLR4 signaling or triggering IL-1B secretion through the inflammasome pathway. NF-kB and MAPK are key signaling pathways of inflammation and could be activated by several chemotherapy drugs. Furthermore, inflammation can play a key role in cancer development, metastasis and exacerbation.

Rolipram and pentoxifylline combination ameliorates experimental diabetic neuropathy through inhibition of oxidative stress and inflammatory pathways in the dorsal root ganglion neurons.

Diabetic neuropathy (DN) is the most challenging microvascular complication of diabetes and there is no suitable treatment for it, so the development of new agents to relieve DN is urgently needed. Since oxidative stress and inflammation play an essential role in the development of DN, clearance of these factors are good strategies for the treatment of this disease. According to key role of cyclic adenosine monophosphate (cAMP) in the regulation of oxidative stress and inflammatory pathways, it seems that phosphodiesterase inhibitors (PDEIs) can be as novel drug targets for improving DN through enhancement of cAMP level. The aim of this study was to evaluate the effects of rolipram, a selective PDE4 inhibitor, and pentoxifylline, a general PDE inhibitor on experimental model of DN and also to determine the possible mechanisms involved in the effectiveness of these agents. We investigated the effects of rolipram (1 mg/kg) and pentoxifylline (100 mg/kg) and also combination of rolipram (0.5 mg/kg) and pentoxifylline (50 mg/kg), orally for five weeks in rats that became diabetic by STZ (55 mg/kg, i.p.). After treatments, motor function was evaluated by open-field test, then rats were anesthetized and dorsal root ganglion (DRG) neurons isolated. Next, oxidative stress biomarkers and inflammatory factors were assessed by biochemical and ELISA methods, and RT-PCR analysis in DRG neurons. Rolipram and/or pentoxifylline treatment significantly attenuated DN - induced motor function deficiency by modulating distance moved and velocity. Rolipram and/or pentoxifylline treatment dramatically increased the cAMP level, as well as suppressed DN - induced oxidative stress which was associated with decrease in LPO and ROS and increase in TAC, total thiol, CAT and SOD in DRG neurons. On the other hand, the level of inflammatory factors (TNF-α, NF-kB and COX2) significantly decreased following rolipram and/or pentoxifylline administration. The maximum effectiveness was with rolipram and/or pentoxifylline combination on mentioned factors. These findings provide novel experimental evidence for further clinical investigations on rolipram and pentoxifylline combination for the treatment of DN.

Evaluation of the hepatoprotective effects of curcumin and nanocurcumin against paraquat-induced liver injury in rats: Modulation of oxidative stress and Nrf2 pathway.

Paraquat (PQ) is a widely used herbicide all over the world, which is highly toxic for animals and humans. Its cytotoxicity is based on reactive radical generation. The aim of this study is to evaluate and compare the hepatoprotective effects of curcumin and nanocurcumin against liver damage caused by sub-acute exposure with PQ via modulation of oxidative stress and genes expression of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Rats were exposed to PQ (5 mg/kg/day, orally) + curcumin or nanocurcumin (100 mg/kg/day, orally) for 7 days. Then rats were anesthetized and serum and liver samples were collected. Next, serum enzymatic activities, liver histopathology, oxidative stress, and expression of genes involved in Nrf2 signaling pathway were assessed by biochemical and enzyme-linked immunosorbent assay methods, hematoxylin and eosin staining, and real-time polymerase chain reaction analysis. PQ significantly increased malondialdehyde, alanine transaminase, aspartate aminotransferase, alkaline phosphatase levels, and Kelch-like ECH-associated protein 1 gene expression and also decreased total antioxidant capacity, total thiol group levels, Glutathione S-transferases, heme oxygenase 1, Nrf2, and NAD(P)H:quinone oxidoreductase 1 genes expression, causing histological damages to liver tissue. These changes were significantly modulated by curcumin and nanocurcumin treatments. Our findings showed that nanocurcumin had better hepatoprotective effect than curcumin in liver damage after PQ exposure most likely through modulation of oxidative stress and genes expression of Nrf2 pathway.

Phosphodiesterase 4 and 7 inhibitors produce protective effects against high glucose-induced neurotoxicity in PC12 cells via modulation of the oxidative stress, apoptosis and inflammation pathways.

Diabetic neuropathy (DN) is the most common diabetic complication. It is estimated diabetic population will increase to 592 million by the year 2035. This is while at least 50-60% of all diabetic patients will suffer from neuropathy in their lifetime. Oxidative stress, mitochondrial dysfunction, apoptosis, and inflammation are crucial pathways in development and progression of DN. Since there is also no selective and effective therapeutic agent to prevent or treat high glucose (HG)-induced neuronal cell injury, it is crucial to explore tools by which one can reduce factors related to these pathways. Phosphodiesterase 4 and 7 (PDE 4 and 7) regulate oxidative damage, neurodegenaration, and inflammatory responses through modulation of cyclic adenosine monophosphate (cAMP) level, and thus can be as important drug targets for regulating DN. The aim of this study was to evaluate the protective effects of inhibitors of PDE 4 and 7, named rolipram and BRL5048, on HG-induced neurotoxicity in PC12 cells as an in vitro cellular model for DN and determine the possible mechanisms for theirs effects. We report that the PC12 cells pre-treatment with rolipram (2 µM) and/or BRL5048 (0.2 µM) for 60 min and then exposing the cells to HG (4.5 g/L for 72 h) or normal glucose (NG) (1 g/L for 72 h) condition show: (1) significant attenuation in ROS, MDA and TNF-a levels, Bax/Bcl-2 ratio, expression of caspase 3 and UCP2 proteins; (2) significant increase in viability, GSH/GSSG ratio, MMP and ATP levels. All these data together led us to propose PDE 4 and 7 inhibitors, and specifically, rolipram and BRL5048, as potential drugs candidate to be further studied for the prevention and treatment of DN.

Protective effects of alpha lipoic acid on high glucose-induced neurotoxicity in PC12 cells.

Hyperglycemia plays an important role in the development of diabetic neuropathy. In this study, we investigated the protective effects of alpha lipoic acid (ALA) against high glucose-induced neurotoxicity in PC12 cells as a suitable in vitro model for studying neuronal functions. PC12 cells were treated with high glucose (25 mg/ml for 24 h) in the absence and presence of ALA (100 µM for 24 h). The viability of PC12 cells was estimated by using MTT assay. The expression of pro- apoptotic Bax, anti- apoptotic Bcl-2 and caspase 3 protein were evaluated by western blotting. The reactive oxygen species (ROS) levels were determined with 2,7-dichlorodihydro- fluorescein diacetate (H2DCFDA). Biochemical markers of oxidative stress were assessed by using the total antioxidant power (TAP), lipid peroxidation (LPO), ADP/ATP ratio, activity of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD). Pretreatment of PC12 cells with ALA, significantly improved high glucose-induced toxicity by increasing activity of antioxidant enzymes CAT and SOD in the PC12 cell. It also increased the concentrations of TAP. An elevated level of cell death and ROS in high glucose conditions, diminished with ALA treatment. Over expression of Bax and caspase 3 protein, elevation of ADP/ATP ratio and LPO level in high glucose- treated PC12 cells, were significantly reduced by ALA. It was concluded that ALA attenuates neurotoxicity induced by high glucose in PC12 cells.

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.

Improvement of isolated rat pancreatic islets function by combination of cerium oxide nanoparticles/sodium selenite through reduction of oxidative stress.

Insulin Dependent Diabetes Mellitus (IDDM) is a disease with high incidence with no pure cure therapy yet. In most of cases, these patients need pancreatic islets transplantation that is not completely successful because of oxidative stress happening during isolation and transplantation procedures. In the present study, effective factors in transplantation procedure such as viability, insulin secretion, production of reactive oxygen molecules (ROM), and mitochondrial energy as ATP/ADP ratio were examined in the isolated islets exposed to sodium selenite (Na2SeO3; 0 30 nmol/L), metal form of cerium oxide (100 nm), cerium oxide nanoparticles (100 nm) and combination of Na2SeO3 (30 nmol/L)/cerium oxide nanoparticles (100 nm) in a time course (1, 2, 4 and 6 days posttreatment) manner. The results showed a significant increase of cells viability, secretion of insulin, and ATP/ADP ratio and a reduction in ROM by use of sodium selenite, cerium oxide nanoparticles, and especially combination of cerium oxide nanoparticles/sodium selenite. Interestingly, not only no improvement was found with metal form of cerium oxide but also deterioration occurred in tested markers. Results suggest that pretreatment with combination of cerium oxide nanoparticles/sodium selenite can improve transplantation outcome and graft function by control of oxidative stress damage.

Evaluation of Cytotoxic, Necrotic, Apoptotic, and Autophagic Effects of Methamphetamine and 3,4-Methylenedioxymethamphetamine on U-87 MG (Glial) and B104-1-1 (Neuronal) Cell Lines.

Methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA) are empathogen (entactogen) psychoactive designer drugs which are mainly used for recreational purposes. Both MA and MDMA are central nervous system stimulants which are classified as monoamine neurotransmitter reuptake inhibitors. They have strong cytotoxic effects on dopaminergic and serotonergic neurons. Neurotoxicities of MA and MDMA by glial activation have been shown. The present work has investigated and measured cytotoxic, necrotic and apoptotic, and autophagic effects of MA and MDMA on U-87 MG (glial) and B104-1-1 (neuronal) cell lines by janus green, ethidium bromide/acridine orange, and monodansylcadaverine/propidium iodide staining to evaluate and compare their effects on glial and neuronal cells, respectively. The results of the present work showed that: (1) MDMA induced more potent mitochondrial toxicity, stronger necrotic and autophagic effects than MA in both B104-1-1 (neuronal) and U-87 MG (glial) cell lines; (2) although MDMA induced stronger apoptotic effect than MA on U-87 MG cell line, it had equal apoptotic effect on B104-1-1 cell line with MA; and (3) MDMA induced more potent mitochondrial toxicity, stronger necrotic, apoptotic, and autophagic effects than MA in B104-1-1 cell line than U-87 MG cell line.

The neuroprotective effects of melatonin against diabetic neuropathy: A systematic review of non-clinical studies.

Backgrounds: Diabetes can cause diabetic neuropathy (DN), a nerve injury. High blood sugar (glucose) levels can harm nerves all over your body. The nerves in your legs and feet are the most commonly affected by DN. The purpose of this study was to conduct a review of melatonin's potential neuroprotective properties against DN. Method: A full systematic search was conducted in several electronic databases (Scopus, PubMed, and Web of Science) up to March 2022 under the PRISMA guidelines. Forty-seven studies were screened using predefined inclusion and exclusion criteria. Finally, the current systematic review included nine publications that met the inclusion criteria. Result: According to in vivo findings, melatonin treatment reduces DN via inhibition of oxidative stress and inflammatory pathways. However, compared to the diabetes groups alone, melatonin treatment exhibited an anti-oxidant trend. According to other research, DN also significantly produces biochemical alterations in neuron cells/tissues. Additionally, histological alterations in neuron tissue following DN were detected. Conclusion: Nonetheless, in the majority of cases, these diabetes-induced biochemical and histological alterations were reversed when melatonin was administered. It is worth noting that the administration of melatonin ameliorates the neuropathy caused by diabetes. Melatonin exerts these neuroprotective effects via various anti-oxidant, anti-inflammatory, and other mechanisms.

Evaluation of Protective Effects of Curcumin and Nanocurcumin on Aluminium Phosphide­Induced Subacute Lung Injury in Rats: Modulation of Oxidative Stress through SIRT1/FOXO3 Signalling Pathway.

OBJECTIVE: Aluminum phosphide (AlP) is widely used to protect stored food products and grains from pests and rodents. The availability of AlP, especially in Asian countries it has become a desirable factor to commit suicide. The phosphine produced from ALP is a very reactive radical and a respiratory inhibitor that causes oxidative damage. There is no dedicated antidote or effective drug to manage AlP-induced lung toxicity. The present study aims to evaluate and compare the protective effects of curcumin and nanocurcumin on ALP­induced subacute lung injury and determine the underlying mechanism. METHODS: Rats were exposed to AlP (2 mg/kg/day, orally)+curcumin or nanocurcumin (100 mg/kg/day, orally) for 7 days. Then rats were anesthetized and lung tissues were collected. Oxidative stress biomarkers, genes expression of antioxidant enzymes, participated genes in the SIRT1/FOXO3 pathway, and lung histopathology were assessed by biochemical and ELISA methods, Real-Time PCR analysis, and H&E staining. RESULTS: Curcumin and nanocurcumin produced a remarkable improvement in AlP-induced lung damage through reduction of MDA, induction of antioxidant capacity (TAC, TTG) and antioxidant enzymes (CAT, GPx), modulation of histopathological changes, and up-regulation of genes expression of SIRT1, FOXO3, FOXO1 in lung tissue. CONCLUSION: Nanocurcumin had a significantly more protective effect than curcumin to prevent AlP-induced lung injury via inhibition of oxidative stress. Nanocurcumin could be considered a suitable therapeutic choice for AlP poisoning.

Insights Into Parkin-Mediated Mitophagy in Alzheimer's Disease: A Systematic Review.

Background: Parkin-mediated mitophagy is the dominant mitophagy pathway of neural cells. Its restoration will result in prevention of cognitive decline, including Alzheimer's disease (AD). The role of this mitophagy pathway in neurodegenerative diseases has drawn attention in recent years. The two main pathological proteins in AD, amyloid ß (Aß) and human Tau (hTau), interfere with mitochondrial dynamics through several pathways. However, taking into consideration the specific interactions between Aß/hTau and Parkin, special focus is required on this mitophagy pathway and AD. In this review, these interactions are fully discussed, and an overview of the neuroprotective drugs that enhance Parkin-mediated mitophagy is presented. Methods: This systematic review was performed according to PRISMA guidelines, and a comprehensive literature search was done in the electronic databases up to September 2020, using search terms in the titles and abstracts to identify relevant studies. One hundred eighty-six articles were found, and 113 articles were screened by title and abstract. Finally, 25 articles were included in this systematic review according to our inclusion and exclusion criteria. Results: Accumulation of Aß and hTau affects mitophagy, including Parkin-mediated. Tau seems to prevent Parkin translocation directly. A Parkin level in the cell appears to be of importance in determining the damage caused by Aß and hTau and in the future therapeutic approaches. Parkin controls the PINK1 level via the presenillins, suggesting that mutations in presenillins affect Parkin mitophagy. Significance: Parkin mitophagy is a process affected by several AD pathological events multidimensionally.

LncRNA-miRNA-mRNA Networks of Gastrointestinal Cancers Representing Common and Specific LncRNAs and mRNAs.

Gastrointestinal (GI) cancers are responsible for approximately half of cancer-related deaths, highlighting the need for the identification of distinct and common features in their clinicopathological characteristics. Long ncRNA (lncRNAs), which are involved in competitive endogenous RNA (ceRNA) networks with critical roles in biological processes, constitute a substantial number of non-coding RNAs. Therefore, our study aimed to investigate the similarities and differences in the ceRNA networks of The Cancer Genome Atlas (TCGA)-GI cancers. We performed a comprehensive bioinformatics analysis of ceRNA networks for TCGA-GI cancers in terms of the deferential mRNA, lncRNA, and miRNA expression levels, ceRNA networks, overall survival analysis, correlation analysis, pathological cancer stages, and gene set enrichment analysis. Our study revealed several common and distinct mRNAs and lncRNAs with prognostic values in these networks. It was specifically noteworthy that MAGI2-AS3 lncRNA was found to be shared in almost all GI cancers. Moreover, the most common shared mRNAs between GI cancers were MEIS1, PPP1R3C, ADAMTSL3, RIPOR2, and MYLK. For each cancer ceRNA network, we found that the expression level of a number of lncRNAs and mRNAs was specific. Furthermore, our study provided compelling evidence that several genes, most notably KDELC1, can act as novel proto-oncogenes in cancers. This, in turn, can highlight their role as new prognostic and therapeutic targets. Moreover, we found cell cycle and extracellular matrix structural constituent as the top shared KEGG and molecular function, respectively, among GI cancers. Our study revealed several known lncRNAs and known and unknown mRNAs in GI cancers with diagnostic and prognostic values.

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.

Barium- and Bismuth-loaded Clinoptilolite Micro- and Nano-Particles as Proposed New Efficient Contrast Agents.

AIMS AND OBJECTIVE: Clinoptilolite is one of the natural zeolites. Clinoptilolite particles have a high surface area, negative surface charge, cation adsorption and exchange capacities. Barium sulfate (BaSO4) and bismuth subnitrate (Bi5H9N4O22) suspensions have been used for upper and lower gastrointestinal imaging but Ba2+ and Bi3+ ions are toxic. In the present study, the feasibility of the application of Ba2+- and Bi3+-loaded clinoptilolite micro- and nano-particles in medical imaging was investigated. MATERIALS AND METHODS: Nanoparticles and microparticles of natural clinoptilolite were loaded with Ba2+ and Bi3+ ions. Radiopacities of loaded particles were measured and compared with those of BaSO4 and Bi5H9N4O22. RESULTS: Ba2+- and Bi3+-loaded clinoptilolite nanoparticles and microparticles showed more intense X-ray opacities than BaSO4 and Bi5H9N4O22 with equimolar concentrations. Moreover, Ba2+- and Bi3+-loaded clinoptilolite nanoparticles more intensely absorbed X-ray than respective loaded microparticles. CONCLUSION: The present study proposes Ba2+- and Bi3+-loaded clinoptilolite nanoparticles and microparticles as new, safe, efficient, and inexpensive contrast agents.

Effects of Securigera Securidaca seed extract in combination with glibenclamide on antioxidant capacity, fibroblast growth factor 21 and insulin resistance in hyperglycemic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Undesired effects of synthetic antidiabetic agents have made researchers to seek for safer and healthier resources. With this aspect, herbal materials have attracted substantial research interest and are being extensively investigated. Considering that herb-drug interactions can be a double-edged sword presenting both risks and benefits, investigation of such interactions is greatly in demand. AIM OF THE STUDY: to investigate possible beneficial effects of hydroalcoholic extract of SecurigeraSecuridaca seed (HESS) on antioxidant capacity, fibroblast growth factor 21 (FGF21) and insulin resistance in Streptozotocin (STZ)-induced diabetic rats, alone and in combination with glibenclamide. MATERIALS AND METHODS: Forty male Wistar rats were randomly divided in to eight equal groups including healthy and diabetic controls and six treated groups with a various doses of HESS alone and in combination with glibenclamide, for 35 consecutive days. Serum samples were taken and analyzed for biochemical profile, HOMA indexes, FGF21, oxidative/nitrosative stress and inflammatory biomarkers as compared with the controls. Moreover, total phenolic and flavonoid contents of herbal extract were assessed. RESULTS: The herbal extract was found to be rich in flavonoid and phenolic components. Both of glibenclamide and the HESS decreased glucose and insulin resistance, as well as increased body weight and insulin sensitivity. Moreover, the extract could mitigate oxidative/nitrosative stress and inflammation dose-dependently, however, the standard drug was less effective than HESS. Induction of diabetes increased FGF21 levels and both of the treatments could reduce its contents, however, glibenclamide was more effective than HESS. CONCLUSIONS: The results clearly show that there is no contradiction between HESS and glibenclamide. Moreover, the herbal extract could augment antioxidant and anti-inflammatory properties of the standard drug.