Evaluation of Date Extract on Nerve Conduction Velocity in Male Rats.

Introduction: Neuropathy is a condition in which the Peripheral Nervous System (PNS) is disordered. Studying the effects of antioxidants on the performance improvement of this system is vital. This study aimed to investigate the effects of date extract on Nerve Conduction Velocity (NCV), Distal Motor Latency (DML), and wave height of the sciatic nerve in male rats. Methods: This laboratory study used 24 male Wistar rats weighing 250-300 g, divided into the test and control groups. The test group received 10% date extract daily, at 4 mL/kg of body weight, for three weeks. In the beginning, nerve Conduction Velocity (NCV), Distal Motor Latency (DML), and wave height of the sciatic nerve were examined in all animals and reexamined for NCV three weeks later. P-values lower than 0.05 were considered significant. Results: Sciatic NCV and wave height were significantly increased; however, compared to the control group, DML of the knee significantly declined in the test group. Conclusion: The compositions of date extract accelerate electrical signal transmission. Highlights: Irreparable damages to the Peripheral Nervous System (PNS) are major problems in societies.Different therapeutic methods have been adopted for peripheral nerve repair.According to FAO, the production and use of dates are rising.Dates are used in traditional medicine for curing hoarseness, paralysis, backache, and rheumatic pains. Plain Language Summary: Dates are highly important in our nutrition. There have been studies on the positive antioxidative effects of date extract in preventing diabetic neuropathy. Dates are used in traditional medicine for curing hoarseness, paralysis, backache, and rheumatic pains, among others. The importance of dates is derived from their rich compositions of carbohydrates, salts and minerals, dietary fiber, vitamins, fatty acids, amino acids, and proteins. Different therapeutic methods have been adopted for PNS, still, 50% of these damages become permanent and cause disability. Date palms are in the palm family native to Iran, and found in relatively tropical regions.Dates are used in traditional medicine for curing hoarseness, paralysis, backache, and rheumatic pains, among others. In short, the compositions of date extract accelerate electrical signal transmission.

Antioxidant, cytotoxic and hyperalgesia-suppressing activity of a native Shilajit obtained from Bahr Aseman mountains.

Shilajit, a blackish-brown exudation obtained from steep rocks of different mountains, has been longly used as a therapeutic agent in traditional medicine. The present study was designed to evaluate the antioxidant, cytotoxic and hyperalgesia-suppressing activity of the aqueous and DMSO extracts of a native Shilajit. The antioxidant and cytotoxic effects of Shilajit extracts was determined using DPPH scavenging activity and MTT assay methods, respectively. In order to examine the hyperalgesia-suppressing activity of the Shilajit aqueous extract the STZ-induced diabetic animals were subjected to oral administration of the extract (50, 100 and 200 mg/kg daily) for six weeks followed by evaluating the behavioral examination (hot plate and tail flick tests) compared to those of diabetic control (Sham) and vehicle groups. The obtained results of antioxidant evaluation of Shilajit represented scavenging activity of 50% at concentration of 2500 µg/mL and 6000 µg/mL in the case of aqueous and DMSO extracts, respectively. Cytotoxic study of water extract of Shilajit revealed IC50 of 727.5±1.9 µg/mL and 1103±3.2 µg/mL on cell lines of MCF-7 (breast cancer) and A549 (lung cancer), respectively. Thermal pain response examination of diabetic rats treated with aqueous extract of Shilajit (100 mg/kg and 200 mg/kg) for six weeks reduced hyperalgesia compared to vehicle and Sham groups. To sum up, considering the moderate antioxidant and hyperalgesia-suppressing activity of this native Shilajit make it as a suitable candidate for further investigation after isolation and characterization of the active compounds.

Distinct genetic variation and heterogeneity of the Iranian population.

Iran, despite its size, geographic location and past cultural influence, has largely been a blind spot for human population genetic studies. With only sparse genetic information on the Iranian population available, we pursued its genome-wide and geographic characterization based on 1021 samples from eleven ethnic groups. We show that Iranians, while close to neighboring populations, present distinct genetic variation consistent with long-standing genetic continuity, harbor high heterogeneity and different levels of consanguinity, fall apart into a cluster of similar groups and several admixed ones and have experienced numerous language adoption events in the past. Our findings render Iran an important source for human genetic variation in Western and Central Asia, will guide adequate study sampling and assist the interpretation of putative disease-implicated genetic variation. Given Iran's internal genetic heterogeneity, future studies will have to consider ethnic affiliations and possible admixture.

Impact of Ondansetron on Withdrawal Signs, Fentanyl Requirement and Pain Relief in Opioid-addicted Patients under General Anesthesia.

BACKGROUND: Serotonin 5-HT3 receptor antagonists such as ondansetron have been investigated to attenuate opioid withdrawal signs in studies. OBJECTIVE: Therefore, we designed a randomized double-blinded placebo-controlled trial to evaluate this effect on opioid-addicted patients who were admitted to the orthopedic department for surgery due to bone fractures. METHODS: Male adults who were addicted to opioids, aged 18 to 79 years were enrolled (n=96) and randomized into intravenous doses (4 & 8 mg) of ondansetron (n=32) and placebo (n=32). The vital signs, withdrawal symptoms and the frequency requirement of fentanyl were recorded during anesthesia, and opioid (pethidine) analgesic was received during the recovery period. Outcome parameters were analyzed for reduction of withdrawal symptoms in addicted adults. RESULTS: We indicated that ondansetron demonstrated significant differences with few vital outcomes including systolic blood pressure (SBP) 20 (SBP3) and 50 min (SBP4) after injection of ondansetron during the period of surgery. Ondansetron could also significantly reduce the frequency requirement of fentanyl at 20 min (dose 3) in general anesthesia. Furthermore, requirement for further administration of opioid analgesic drugs such as pethidine was significantly reduced in the ondansetron groups. Objective opioid withdrawal scale (OOWS) results indicated that few clinical parameters including tremor, hot and cold flushes and anxiety were significantly attenuated in addicted patients who received ondansetron. CONCLUSION: This study demonstrated supporting evidence for the beneficial treatment of ondansetron for the control of withdrawal symptoms and pain in addicted patients, and more clinical studies are suggested in this regard.

Metronidazole aryloxy, carboxy and azole derivatives: Synthesis, anti-tumor activity, QSAR, molecular docking and dynamics studies.

A series of novel metronidazole aryloxy, carboxy and azole derivatives has been synthesized and their cytotoxic activities on three cancer cell lines were evaluated by MTT assay. Compounds 4m, 4l and 4d showed the most potent cytotoxic activity (IC50s less than 100 µg/mL). Apoptosis was also detected for these compounds by flow cytometry. Docking studies were performed in order to propose the probable target protein. In the next step, molecular dynamics simulation was carried out on the proposed target protein, focal adhesion kinase (FAK, PDB code: 2ETM), bound to compound 4m. As, 4m showed a potent cytotoxic activity and an acceptable apoptotic effect, it can be a potential anticancer candidate that may work through inhibition of FAK.

Cytotoxicity of biologically synthesised bismuth nanoparticles against HT-29 cell line.

This study was purposed to examine the cytotoxicity and functions of biologically synthesised bismuth nanoparticles (Bi NPs) produced by Delftia sp. SFG on human colon adenocarcinoma cell line of HT-29. The structural properties of Bi NPs were investigated using transmission electron microscopy, energy dispersive X-ray, and X-ray diffraction techniques. The cytotoxic effects of Bi NPs were analysed using flow cytometry cell apoptosis while western blot analyses were applied to analyse the cleaved caspase-3 expression. Oxidative stress (OS) damage was determined using the measurement of the glutathione (GSH) and malondialdehyde (MDA) levels and antioxidant activity of superoxide dismutase (SOD) and catalase (CAT) levels. The half maximal inhibitory concentration (IC50) value of Bi NPs was measured to be 28.7 ± 1.4 µg/ml on HT-29 cell line. The viability of HT-29 represented a concentration-dependent pattern (5-80 µg/ml). The mode of Bi NPs induced apoptosis was found to be mainly related to late apoptosis or necrosis at IC50 concentration, without the effect on caspase-3 activities. Furthermore, Bi NPs reduced the GSH and increased the MDA levels and decreased the SOD and CAT activities. Taken together, biogenic Bi NPs induced cytotoxicity on HT-29 cell line through the activation of late apoptosis independent of caspase pathway and may enhance the OS biomarkers.

Design, synthesis and evaluation of novel multi-target-directed ligands for treatment of Alzheimer's disease based on coumarin and lipoic acid scaffolds.

A novel series of coumarin-lipoic acid conjugates were synthesized via cycloaddition click reaction to find out new multi-target-directed ligands (MTDLs) for treatment of Alzheimer's disease (AD). All of synthesized compounds were screened for neuroprotective and anti-cholinesterase activities. Based on primary screening, two compounds (5 and 11) were subjected to further biological evaluations. In particular, compound 11 which was the most potent AChE inhibitor showed good inhibitory effect on Aß-aggregation and intracellular ROS (reactive oxygen species) formation, as well as the ability of selective bio-metal chelation and neuroprotection against H2O2- and Aß1-42-induced cytotoxicity. In the light of these results, the applied hybridization approach introduced new promising lead compound with desired multifunctional properties, being useful in the treatment of Alzheimer's disease.

Cytotoxicity investigations of biogenic tellurium nanorods towards PC12 cell line.

The authors evaluated the cytotoxicity underlying mechanisms of biogenic tellurium (Te) nanorods (NRs) produced by the Pseudomonas pseudoalcaligenes strain Te on the PC12 cell line. The half-maximal inhibitory concentration (IC50) value was estimated at 5.05 ± 0.07 ng/ml for biogenic Te NRs and 2.44 ± 0.38 ng/ml for K2TeO3, respectively. The viability of PC12 was inhibited concentration dependent at doses of 1, 2.5, 5, 10, and 20 ng/ml. Te NRs principally induced late apoptosis or necrosis at IC50 concentration, without effect on caspase-3 activities. Furthermore, Te NRs reduced glutathione and enhanced malondialdehyde levels, and also reduced superoxide dismutase and catalase activities. These findings revealed that biogenic Te NRs were less toxic than K2TeO3. Additionally, they induced cytotoxity towards the PC12 cell line through the activation of late apoptosis independent of the caspase pathway, and may also enhance oxidative stress in the nervous system.

New racemic annulated pyrazolo[1,2-b]phthalazines as tacrine-like AChE inhibitors with potential use in Alzheimer's disease.

A novel series of tacrine-like compounds 7a-u possessing a fused pyrazolo[1,2-b]phthalazine structure were designed and synthesized as potent and selective inhibitors of AChE. The in-vitro biological assessments demonstrated that several compounds had high anti-AChE activity at nano-molar level. The more promising compound 7l with IC50 of 49 nM was 7-fold more potent than tacrine and unlike tacrine, it was highly selective against AChE over BuChE. The cell-based assays against hepatocytes (HepG2) and neuronal cell line (PC12) revealed that 7l had significantly lower hepatotoxicity compared to tacrine, with additional neuroprotective activity against H2O2-induced damage in PC12 cells. This compound could also inhibit AChE-induced and self-induced Aß peptide aggregation. The advantages including synthetic accessibility, high potency and selectivity, low toxicity, adjunctive neuroprotective and Aß aggregation inhibitory activity, make this compound as a new multifunctional lead for Alzheimer's disease drug discovery.

Probiotic and antioxidant properties of selenium-enriched Lactobacillus brevis LSe isolated from an Iranian traditional dairy product.

The present study was designed to isolate a highly selenium-tolerant lactobacillus strain from an Iranian traditional dairy product named as Spar. Different criteria such as tolerance to the low pH, simulated gastric juice (SGJ), simulated intestinal juice (SIJ) and bile salts tolerance as well as Caco-2 cell adhesion assay were examined to evaluate the probiotic potentials of the selected isolate. Furthermore, the antioxidant properties of the isolate cultivated in medium containing and free of SeO32- ions were evaluated using DPPH scavenging and reducing power assays. The isolate was identified using conventional identification and 16S rDNA gene sequencing methods as Lactobacillus brevis LSe. The obtained results showed that the isolate was able to tolerate high concentration of sodium selenite (3.16mM). By decreasing the pH of the SGJ from 6 to 3, the survival percent of L. brevis LSe was not significantly changed over the time (p>0.05). In addition, the survival percent of the isolate in the SIJ (pH 6 and pH 8) was not statistically altered after 3h, 6h and 24h of incubation (p>0.05). In the presence of bile salts (0.3% and 0.6%) the survival rate of L. brevis LSe was not significantly decreased (p>0.05).L. brevis LSe also demonstrated the satisfactory ability to adhere to Caco-2 cells which were similar to that of the reference strain L. plantarum. The obtained results of antioxidant evaluation showed that L. brevis LSe containing elemental Se exhibited significantly higher radical scavenging ability (36.5±1.31%) and reducing power (OD700, 0.14) than L. brevis LSe cultured in selenite-free medium (p<0.05). To sum up, further investigations should be conducted to merit the probable potential health benefit of Se-enriched L. brevis LSe and its application as Se-containing supplements or fermented foods.

Microwave-assisted biosynthesis of zinc nanoparticles and their cytotoxic and antioxidant activity.

The present study was designed for microwave assisted synthesis of zinc nanoparticles (Zn NPs) using Lavandula vera leaf extract in the presence of ZnSO4 (1mM). The biogenic Zn NPs were then characterized using scanning electron microscopy (SEM), energy dispersive X-ray (EDX), X-ray diffraction spectroscopy (XRD), UV-visible spectroscopy, and Fourier transform infrared spectroscopy (FTIR) techniques. Thereafter, the cytotoxic effect of ZnSO4 and Zn NPs on different cell lines was investigated by MTT-based cytotoxicity assay and their antioxidant properties were assessed using DPPH scavenging activity and reducing power assay. The SEM micrograph showed that the Zn NPs had spherical shape with the size range of 30-80nm. For A549, MCF-7, HT-29, and Caco-2 cell lines treated with Zn NPs, the concentration necessary causing 50% cell death (IC50) was found to be 22.3±1.1µgmL-1, 86±3.7µgmL-1, 10.9±0.5µgmL-1, and 56.2±2.8µgmL-1, respectively. In the case of ZnSO4, the same results (IC50) were observed at concentration of 81.6±1.3µgmL-1 (A549), 121.0±2.4µgmL-1 (MCF-7), 43.0±1.4µgmL-1 (HT-29), and 85.7±2.3µgmL-1 (Caco-2). The obtained results of antioxidant activity showed that the IC50 values of butylated hydroxyanisole (BHA) and Zn NPs were 44µgmL-1and 65.3µgmL-1, respectively, while ZnSO4 at concentration of 200µgmL-1 exhibited only 10.9% DPPH radical scavenging effect. Moreover, the reducing power of Zn NPs and BHA were significantly higher than ZnSO4 (p<0.05). To sum up, application of L. vera leaf extract combined with microwave heating energy led to simple and fast formation of Zn nanostructures exhibited higher antioxidant and cytotoxic activity compared to soluble Zn+2 ions. However, identification of the related mechanisms merit further studies.

Selection of Suitable Reference Genes for Analysis of Salivary Transcriptome in Non-Syndromic Autistic Male Children.

Childhood autism is a severe form of complex genetically heterogeneous and behaviorally defined set of neurodevelopmental diseases, collectively termed as autism spectrum disorders (ASD). Reverse transcriptase quantitative real-time PCR (RT-qPCR) is a highly sensitive technique for transcriptome analysis, and it has been frequently used in ASD gene expression studies. However, normalization to stably expressed reference gene(s) is necessary to validate any alteration reported at the mRNA level for target genes. The main goal of the present study was to find the most stable reference genes in the salivary transcriptome for RT-qPCR analysis in non-syndromic male childhood autism. Saliva samples were obtained from nine drug naïve non-syndromic male children with autism and also sex-, age-, and location-matched healthy controls using the RNA-stabilizer kit from DNA Genotek. A systematic two-phased measurement of whole saliva mRNA levels for eight common housekeeping genes (HKGs) was carried out by RT-qPCR, and the stability of expression for each candidate gene was analyzed using two specialized algorithms, geNorm and NormFinder, in parallel. Our analysis shows that while the frequently used HKG ACTB is not a suitable reference gene, the combination of GAPDH and YWHAZ could be recommended for normalization of RT-qPCR analysis of salivary transcriptome in non-syndromic autistic male children.

Microbial-assisted synthesis and evaluation the cytotoxic effect of tellurium nanorods.

The present study was designed to isolate bacterial strain capable of tellurium nanorods' (Te NRs) production followed by purification and evaluation of the cytotoxic effect of Te NRs. Among 25 environmental samples collected for screening of Te NR-producer bacterial strains one bacterial colony (isolated from hot spring and identified as Pseudomonas pseudoalcaligenes strain Te) was selected and applied for biosynthesis of Te NRs. Thereafter, an organic-aqueous partitioning system was applied for the purification of the biogenic Te NRs and the purified Te NRs were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive X-ray (EDX), X-ray diffraction spectroscopy (XRD), UV-visible spectroscopy, and Fourier transform infrared spectroscopy (FTIR) techniques. The cytotoxic effect of biologically synthesized Te NRs and potassium tellurite on four cell lines of MCF-7, HT1080, HepG2 and A549 was then determined using the MTT assay method. The obtained results revealed lower toxicity for the rod-shaped biogenic tellurium nanostructures (~22nm diameter by 185nm length) compared to K2TeO3.

One-pot, four-component synthesis of novel cytotoxic agents 1-(5-aryl-1,3,4-oxadiazol-2-yl)-1-(1H-pyrrol-2-yl)methanamines.

A series of N-benzyl-1-(5-aryl-1,3,4-oxadiazol-2-yl)-1-(1H-pyrrol-2-yl)methanamines were synthesized via one-pot reaction of appropriate benzylamine, pyrrole-2-carbaldehyde, (N-isocyanimino)triphenylphosphorane, and a carboxylic acid. The anti-tumor potential of title compounds was tested against several cancer cell lines by using MTT assay. Some tested compounds including 5e, 5p and 5q exhibited comparable or better cytotoxic activity against A549, HT29 or HT1080 cells in comparison to the reference drug doxorubicin. Also, the cytotoxic activity of compounds 5d and 5n against MCF-7 was better than that of doxorubicin. Compound 5n with IC50 value of 4.3 µM was 4-fold more potent than doxorubicin. The structure-activity relationship study revealed that the introduction of halogen atoms on both 5-phenyl ring and N-benzyl part improved the cytotoxic activity against all tested cell lines.

Preparation and evaluation of the effect of Fe3 O4 @piroctone olamine magnetic nanoparticles on matrix metalloproteinase-2: a preliminary in vitro study.

In the present study, Fe3 O4 magnetic nanoparticles were synthesized by the coprecipitation of Fe(2+) and Fe(3+) ions and used as a nanocarrier for the production of piroctone-olamine-loaded Fe3 O4 nanoparticles (Fe3 O4 @PO NPs). The nanocrystalline structure of the prepared iron oxide species was confirmed by the X-ray diffraction spectroscopy method. Particle size distribution analysis showed that the size of Fe3 O4 @PO NPs was in the range of 5-55 nm. The magnetization curve of Fe3 O4 @PO NPs (with saturation magnetization of 28.2 emu/g) confirmed its ferromagnetic property. Loading of PO on the surface of Fe3 O4 NPs qualitatively verified by Fourier transform infrared spectrum obtained from Fe3 O4 @PO NPs. Cytotoxicity studies on the human fibrosarcoma cell line (HT-1080) revealed higher inhibitory effect of Fe3 O4 @PO NPs (50% cell death [IC50 ] of 8.1 µg/mL) as compared with Fe3 O4 NPs (IC50 of 117.1 µg/mL) and PO (IC50 of 71.2 µg/mL) alone. In the case of human normal fibroblast (Hs68), the viability percentage was found to be 75% in the presence of Fe3 O4 @PO NPs (120 µg/mL). Gelatin zymography showed 17.2% and 34.6% inhibition of matrix metalloproteinase-2 (MMP-2) in the presence of Fe3 O4 @PO and PO, respectively, at the same concentration of 40 µg/mL, whereas Fe3 O4 NPs did not inhibit MMP-2 at any concentration.

The effect of Angipars on diabetic neuropathy in STZ-induced diabetic male rats: a study on behavioral, electrophysiological, sciatic histological and ultrastructural indices.

Diabetes mellitus is the most common metabolic disease with a high prevalence rate in human society that eventually leads to the peripheral nervous system complications in a great number of patients. In the present study, the effects of Angipars on nerve conduction velocity, histological alterations, and behavioral indices were investigated. Diabetes was induced in male rats by intraperitoneal injection of streptozotocin (STZ). Six weeks after STZ injection, animals were divided into five groups control, vehicle, and 3 experimental groups. The vehicle group received 1 mL distilled water daily for two weeks and three experimental groups received, respectively, intraperitoneal injection of 5, 10, and 20 mg/kg Angipars daily for two weeks. Intraperitoneal injection of Angipars, in some extent, could significantly improve behavioral indices of the experimental groups as compared to the vehicle group. Furthermore, mean nerve conduction velocity in the vehicle group showed significant difference with that in the control and the 2nd experimental groups; therefore, Angipars could increase nerve conduction velocity in neuropathic rats. Overall, Angipars exerted positive effects on the treatment and reduction of physiologic symptoms and improvement of sciatic morphological injuries in neuropathic rats.

Date fruit extract is a neuroprotective agent in diabetic peripheral neuropathy in streptozotocin-induced diabetic rats: a multimodal analysis.

BACKGROUND: To study the effects of an aqueous extract of date fruit (Phoenix dactylifera L. Arecaceae) diet on diabetic polyneuropathy (DPN) in streptozotocin- (STZ-) induced diabetic rats. METHODS: The effects of a date fruit extract (DFE) diet on diabetic neuropathy in STZ-induced diabetic rats were evaluated and compared with a nondiabetic control group, diabetic control group (sham), and vehicle group with respect to the following parameters: open field behavioral test, motor nerve conduction velocity (MNCV), and morphological observations. RESULTS: In the model of STZ-induced of diabetic neuropathy, chronic treatment for 6 weeks with DFE counteracted the impairment of the explorative activity of the rats in an open field behavioral test and of the conduction velocity of the sciatic nerve (MNCV). In addition, pretreatment with DFE significantly reversed each nerve diameter reduction in diabetic rats. CONCLUSION: DFE treatment shows efficacy for preventing diabetic deterioration and for improving pathological parameters of diabetic neuropathy in rats, as compared with control groups.