Therapeutic Potential of Iron Chelators in Viral Diseases: A Systematic Review.

BACKGROUND: Iron chelators (ICs) have recently emerged as one of the new methods of treatment for viral infections. This study aimed to evaluate the efficiency and safety of natural ICs compared to synthetic ICs. Natural and synthetic ICs are the most common therapeutic agents tested for the treatment of viral infections. When evaluated against synthetic ICs, natural ICs are probably favored owing to their lower toxicity and safer properties. The main objective of the present systematic review was to assess the current evidence on the role of pharmacological mechanisms in the treatment of viral infections. METHOD: This study was designed as a systematic review in which search strategies were focused on two electronic databases, PubMed, and Scopus, between 2017 and 2021. A search filter with two subjects, "iron chelators" and "viral infection", was employed. RESULTS: According to the results, both natural and synthetic chelators had a considerable impact on the treatment of viral infections via various mechanisms, with natural ICs being the most extensively used. CONCLUSION: Natural and synthetic ICs exert their effects through different pharmacological mechanisms. Among these compounds, natural chelators are more widely used due to their safety, efficacy, and a wider range of applications.

Evaluating the effects of curcumin nano-chitosan on miR-221 and miR-222 expression and Wnt/ß-catenin pathways in MCF-7, MDA-MB-231 and SKBR3 cell lines.

BACKGROUND: Breast cancer is one of the most common diseases worldwide that affects women of reproductive age. miR-221 and miR-222 are two highly homogeneous microRNAs that play pivotal roles in many cellular processes and regulate the Wnt/ß-catenin signaling pathway. Curcumin (CUR), a yellow polyphenolic compound, targets numerous signaling pathways relevant to cancer therapy. The main aim of this study was to compare the ability of chitosan curcumin nanoparticle (CC-CUR) formulation with the curcumin in modulating miR-221 and miR-222 expression through Wnt/ß-catenin signaling pathway in MCF-7, MDA-MB-231 and SK-BR-3 breast cancer cell lines. METHOD: Chitosan-cyclodextrin-tripolyphosphate containing curcumin nanoparticles (CC-CUR) were prepared. Cytotoxicity of the CUR and CC-CUR was evaluated. Experimental groups including CC-CUR, CUR and negative control were designed. The expression of miR-221 and miR-222 and Wnt/ß-catenin pathway genes was measured. RESULTS: The level of miR-221 and miR-222 and ß-catenin genes decreased in MCF-7 and MDA-MB-231 cells and WIF1 gene increased in all cells in CC-CUR group. However, the results in SK-BR-3 cell line were unexpected; since miRs and WIF1 gene expressions were increased following CC-CUR administration and ß-catenin decreased by administration of CUR. CONCLUSION: Although the composite form of curcumin decreased the expression of miR-221 and miR-222 in MCF-7 and MDA cells, with significant decreasing of ß-catenin and increasing of WIF1 gene in almost all three cell lines, we can conclude than this formulation exerts its effect mainly through the Wnt/ß-catenin pathway. These preliminary findings may pave the way for the use of curcumin nanoparticles in the treatment of some known cancers.

Synthesis and physicochemical characterization of mesoporous hydroxyapatite and its application in toothpaste formulation.

The key characteristics of mesoporous hydroxyapatite, such as high porosity and expansive surface area, along with its biocompatibility with dental tissues and potential as a delivery vehicle for active ingredients, have recently garnered significant research focus. In the present study, mesoporous hydroxyapatite was synthesized using a precipitation technique and was subsequently characterized via X-ray diffraction, Fourier transform infrared, dynamic light scattering, field emission scanning electron microscopy and N2 adsorption-desorption isotherms. The results revealed that the synthesized mesopore particles exhibited significant adsorption potential, and were thereby considered a carrier of thymol, an effective antibacterial on oral pathogens. Specifically, mesoporous hydroxyapatite's surface area and pore volume were approximately 2.66-fold and 1.95-fold higher than hydroxyapatite's. A statistically significant divergence in the release profiles of thymol from thymol-loaded mesoporous hydroxyapatite and thymol-loaded hydroxyapatite was noted, as indicated by the similarity factor (f2 < 50). Evaluation of organoleptic parameters (taste, odor, smoothness, appearance) showed that thymol-loaded mesoporous hydroxyapatite toothpaste had superior organoleptic attributes compared to thymol-loaded hydroxyapatite toothpaste. However, both formulations were acceptable regarding pH and stability and were desirable regarding abrasiveness with no significant difference compared to the standard formulation (p > 0.05). Overall, the findings demonstrate the suitability of mesoporous hydroxyapatite as an abrasive material for developing hydroxyapatite-based toothpaste formulations.

Lavender improves fatigue symptoms in multiple sclerosis patients: A double-blind, randomized controlled trial.

BACKGROUND: Fatigue is one of the most common complications of Multiple Sclerosis (MS) patients. Several pharmacological and non-pharmacological interventions have been recommended to control this complication. Lavender is one of the plants considered by Persian Medicine (PM) and recommended by scholars of past centuries in the treatment of neurological diseases. This study aimed to investigate the efficacy of lavender capsule on improving fatigue symptoms in MS patients. MATERIAL AND METHODS: In a double-blind, controlled trial, using a computer block randomization approach, 48 confirmed MS patients with eligibility criteria of being 18 years or older, Modified Fatigue Impact Scale (MFIS) ≥25, relapsing-remitting MS patients, EDSS ≤6, not pregnant, not breastfeeding, and not suffering from other diseases that cause fatigue, were randomized to receive capsules containing 600mg of lavender flowers as the intervention group or capsules containing 600mg cornstarch as the control group. Patients were randomized after completing the MFIS and were asked to take one capsule three times daily for 60 days. The MFIS again checked to assess the impact of two interventions. Analysis of Covariance (ANCOVA) was used to assess the impact of two interventions. RESULTS: 24 patients included in each group. The mean (standard deviation) of MFIS was 40.56 (7.63) in the intervention and 41.43 (7.89) in the control groups (p=0.706) before the intervention. However, there was a significant reduction (p0.001˂) in the intervention group, 7.04 (4.91) compared to the control group, 38.17 (9.78) after the intervention. CONCLUSION: In comparison to cornstarch capsules, consuming the capsules of lavender flowers decreased the MFIS in MS patients.

Pesticide residues in dates using a modified QuEChERS method and GC-MS/MS.

The aim of this study was to develop a convenient, fast, effective and safe analytical method (QuEChERS) to determine 198 pesticide residues in multi-source date palm fruits using gas chromatography-tandem mass spectrometry (GC-MS/MS). The calibration curves for most pesticides were linear in the range of 15-150 µg/kg, with r2 values higher than 0.9934 and the relative standard deviation for all pesticides was ≤20%. The mean recovery rate of pesticides was 70-120% and limits of detection (LODs) and limits of quantification (LOQs) were in the range of 5-14 µg/kg and 14-40 µg/kg, respectively. The validated procedure was used to monitor pesticide residues in 30 fresh date samples. It could be concluded that the modified QuEChERS extraction method was efficient in analysing pesticide residues in dates palm and none of the samples contained residues above the MRLs.

Evaluation of the anticandidal activity of clotrimazole using Lactobacillus caseie ghosts as biological drug carrier.

BACKGROUND: Candida albicans cause oral and vaginal mucosa infections as well as bloodstream and deep-tissue infections. Commonly, clotrimazole as a broad-spectrum antimitotic drug applied for treatment of Candida albicans infections. Bacterial ghosts are dead cells that have the broad potential to target the various body tissues and cells as drug vector. OBJECTIVES: We hope to conquest this resistance by using clotrimazole loaded on bacterial ghosts. METHODS: Lactobacillus ghosts were produced by using tween 80 and lactic acid according to the protocol and the amount of the DNA and protein in supernatant was measured by Nano-drop spectrophotometry. Ghost's morphological characteristics were detected by using light microscopy, SEM and AFM. Antifungal activities of the synthesized ghosts were measured by plate methods. Three independent vertical Franz cells were used to evaluate drug release profile. BG-clotrimazole was added into cream base and was examined for dispensability as well as uniformity of the formulation on the skin. RESULTS: Results of the Nano-drop analysis showed that protein and DNA was seen in supernatant of treatment compared to control groups. AFM results showed well-dispersed and rod-shaped L. casei ghost cells. Lysis pores formation in the L. casei ghosts was indicated by SEM micrographs. BGs represent an excellent drug delivery system because of the high loading capability. Nearly, 50% of clotrimazole was released from BGs during 90 min. Highest anticandidal activity occurred using 100 mg/l clotrimazole-BG, while toxic effects were also seen with 10 mg/l clotrimazole. IC50 clotrimazole-BG was found at 0.001 mg/l. Chemical stability results showed that about 90% of clotrimazole remained in the formulation. CONCLUSION: It could be concluded that the bacterial ghosts are very talented to high loading capability, keeping and releasing drug during six months, therefore these could act as an excellent drug delivery system.

Clinical evaluation of the effect of Zataria multiflora Boiss and Trachyspermum copticum (L.) on the patients with irritable bowel syndrome.

BACKGROUND AND AIM: Irritable Bowel Syndrome (IBS) is the most common gastrointestinal dysfunction characterized by abdominal pain or discomfort, as well as changes in bowel movements and stool shape. Given the global trend towards the increased use of complementary and alternative medicine (CAM), the high prevalence of IBS, the lack of a standard treatment for all IBS subtypes, and patients' willingness to use CAM treatments, investigations into CAM treatments are needed. Accordingly, the present study aimed to investigate the effect of a mix of two herbal medicines (Zataria-Trachyspermum, ZT) on the clinical symptoms of patients with IBS. EXPERIMENTAL PROCEDURE: The present study was performed on 3 groups including the positive control, experimental, and placebo groups. The sample size was calculated as 150 participants. Fifty patients were assigned to one of three parallel groups (ZT capsule, placebo, and mebeverine capsule) by block randomization. All three groups were treated for 4 weeks. The patients were monitored in the follow-up stage for 2 additional weeks. RESULTS: After the fourth week of intervention, symptoms of pain, bloating, and reflux showed a significant decrease in the ZT group compared to the placebo and mebeverine groups (P <0.05). Moreover, the participants in the ZT group reported a significant decrease in fatigue compared to the other two groups (P <0.05). CONCLUSION: This study confirmed the positive effect of ZT on IBS symptoms, especially pain, bloating, constipation, and bowel movements.

Investigating the protective role of metformin on lithium-induced hypothyroidism.

Induction of oxidative stress events has been shown to be associated with lithium (Li) hypothyroidism induction. Metformin (MET) is a commonly used antidiabetic drug with multiple properties including antiproliferative activity, antioxidant potency, and is used in polycystic ovarian syndrome treatment. Here, in this study, we aimed to investigate the effect of different doses of MET on Li-induced hypothyroidism for elucidating its mechanism of action. The obtained results demonstrated the oxidative stress reduction in thyroid tissues upon MET treatment. Besides this, the biochemical analysis revealed a significant reduction in T3 and TSH levels (down to 2 ng/ml and 0.05 µU/ml, respectively) in coordination with an observable reduction in T4 level (up to 2.1 ng/ml). Also, a significant reduction in Li-related tissue damages including changes in the morphology and the size of follicles, rate of vascularity, detachment of follicular cells, inflammatory cells infiltration, and follicular cells hypertrophy and disruption was observed. Ultimately, regarding the significant improvement in thyroid tissues and valuable antioxidant activity determined in tissues treated with MET, it is concluded that MET co-administration with Li can significantly reduce the negative effects of Li and enhance the efficacy of Li therapy.

Computational modeling, fabrication, and characterization of the deep eutectic solvent-based green molecular cage for selective metronidazole extraction from plasma followed by UHPLC with diode array detector determination.

Four ternary deep eutectic solvents were computationally designed and synthesized, being used as candidate functional monomers in metronidazole molecular imprinting polymer synthesis, allowing selective extraction and determination by ultra high performance liquid chromatography with diode array detection. In terms of metronidazole selective extraction, the best results were obtained by (deep eutectic solvent)2 :(ethylene glycol dimethacrylate)11 , in which deep eutectic solvent is the functional monomer constructed by combining three components in 6:6:2 ratios of choline chloride:ethylene glycol:methacrylic acid. The effects of different parameters on molecular imprinted solid-phase extraction of metronidazole were thoroughly explored through screening design and response surface methodology. The adsorption mechanism findings show that the adsorption data are primarily fitted on the Freundlich model based on higher correlation coefficient. Kinetic experiments have shown that the mechanism of adsorption fits the pseudo-second-order model. The best extraction recovery (96.5%) was obtained in 25-min elution time, desorption temperature of 40°C, and 1.0 mL ACN as eluent. Metronidazole was measured by a validated ultra high performance liquid chromatography with diode array detection method. The calibration of the method was linear in the range of 0.1-10 µg/mL with limits of detection and quantification of 0.03 and 0.1 µg/mL, respectively. The method was successfully applied for the determination of metronidazole in human plasma.

A comparative study of 3D printing and heat-compressing methods for manufacturing the thermoplastic composite bone fixation plate: Design, characterization, and in vitro biomechanical experimentation.

Metallic bone fixations, due to their high rigidity, can cause long-term complications. To alleviate metallic biomaterials' drawbacks, in this research new Glass Fiber/Polypropylene (GF/PP) composite internal fixations were developed, and an investigation of their mechanical behavior was performed through in vitro biomechanical experiments. Short randomly oriented, long unidirectional prepreg, and long unidirectional fiber yarn were considered as reinforcements, and the effects on their mechanical properties of different manufacturing processes, that is, 3D printing and heat-compressing, were investigated. The constructed fixation plates were tested in the transversely fractured diaphysis of bovine tibia under axial compression loading. The overall stiffness and the Von Mises strain field of the fixation plates were obtained within stable and unstable fracture conditions. The samples were loaded until failure to determine their failure loads, strains, and mechanisms. Based on the results, the GF/PP composite fixation plates can provide adequate interfragmentary movement to amplify bone ossification, so they can provide proper support for bone healing. Moreover, their potential for stress shielding reduction and their load-bearing capacity suggest their merits in replacing traditional metallic plates.

The effect of educational intervention based on health belief model and social support on testicular self-examination in sample of Iranian men.

BACKGROUND: Testicular Self-Examination (TSE) causes earlier diagnosis of Testicular cancer (TC). Hence, all men aged between15 to 35 years should perform TSE every month. This study aims to survey the effect of educational intervention based on health belief model and social support on testicular self-examination in men aged between 15 to 35 years of Fasa City, Fars province, Iran. METHODS: In this quasi-experimental study, 200 men (100 in the experimental group and 100 in the control group) in Fasa City, Fars, Iran, were conducted from June 2018 to August 2019. The educational intervention for the experimental group consisted of six training sessions (testicular cancer, its prevalence and types, its risk factors, symptoms, infected areas, diagnosis, side-effects and its severity, understanding about testicular self-examination and its importance, benefits, and barriers of self-examination and correct way of doing TSE were discussed, role of social support). A questionnaire consisting of demographic information, knowledge, HBM construct, and social support was used to measure testicular self-examination before, 3 months after the intervention, and 6 months later. Data were analyzed using SPSS-22 via chi-squared, independent samples t-test, Mann-Whitney, and repeated measures ANOVA at a significance level of 0.5. RESULTS: The mean age of the men was 27.26 ± 3.16 years in the experimental group and 27.39 ± 3.12 years in the control group. Three months after the intervention and 6 months after the intervention, the experimental group showed a significant increase in knowledge, perceived susceptibility, perceived severity, perceived benefits, self-efficacy, cues to action, social support, and testicular self-examination performance compared to the control group. CONCLUSION: This study showed the effectiveness of the intervention based on the HBM constructs and social support in the adoption of testicular self-examination in 3 and 6 months post-intervention in men aged between 15 to 35 years. Hence, these models can act as a framework for designing and implementing educational interventions for testicular self-examination.

Leishmanicidal potentials of Gossypium hirsutum extract and its fractions on Leishmania major in a murine model: parasite burden, gene expression, and histopathological profile.

Introduction. Leishmaniasis is a neglected tropical and subtropical disease caused by over 20 protozoan species.Hypothesis. Treatment of this complex disease with traditional synthetic drugs is a major challenge worldwide. Natural constituents are unique candidates for future therapeutic development.Aim. This study aimed to assess the in vivo anti-leishmanial effect of the Gossypium hirsutum extract, and its fractions compared to the standard drug (Glucantime, MA) in a murine model and explore the mechanism of action.Methodology. Footpads of BALB/c mice were infected with stationary phase promastigotes and treated topically and intraperitoneally with G. hirsutum extract, its fractions, or Glucantime, 4 weeks post-infection. The extract and fractions were prepared using the Soxhlet apparatus with chloroform followed by the column procedure.Results. The crude extract significantly decreased the footpad parasite load and lesion size compared to the untreated control group (P<0.05), as revealed by dilution assay, quantitative real-time PCR, and histopathological analyses. The primary mode of action involved an immunomodulatory role towards the Th1 response in the up-regulation of IFN-γ and IL-12 and the suppression of IL-10 gene expression profiling against cutaneous leishmaniasis caused by Leishmania major.Conclusion. This finding suggests that the extract possesses multiple combinatory effects of diverse bioactive phytochemical compositions that exert its mechanisms of action through agonistic-synergistic interactions. The topical extract formulation could be a suitable and unique candidate for future investigation and pharmacological development. Further studies are crucial to evaluate the therapeutic potentials of the extract alone and in combination with conventional drugs using clinical settings.

Cytotoxicity Effects of Curcumin Loaded on Chitosan Alginate Nanospheres on the KMBC-10 Spheroids Cell Line.

PURPOSE: Breast cancer is one of the most lethal types of cancer in women. Curcumin showed therapeutic potential against breast cancer, but applying that by itself does not lead to the associated health benefits due to its poor bioavailability, which appears to be primarily due to poor absorption, rapid metabolism, and rapid elimination. Moreover, poor water solubility of curcumin causes accumulation of a high concentration of curcumin and so decrease its permeability to the cell. Many strategies are employed to reduce curcumin metabolism such as adjuvants and designing novel delivery systems. Therefore, in this study sodium alginate and chitosan were used to synthesize the hydrogels that are known as biocompatible, hydrophilic and low toxic drug delivery systems. Also, folic acid was used to link to chitosan in order to actively targetfolate receptors on the cells. METHODS: Chitosan-ß-cyclodextrin-TPP-Folic acid/alginate nanoparticles were synthesized and then curcumin was loaded on them. Interaction between the constituents of the particles was characterized by FTIR spectroscopy. Morphological structures of samples were studied by FE-SEM. Release profile of curcumin was determined by dialysis membrane. The cytotoxic test was done on the Kerman male breast cancer (KMBC-10) cell line by using MTT assay. The viability of cells was detected by fluorescent staining. Gene expression was investigated by real-time PCR. RESULTS: The encapsulation of curcumin into nano-particles showed an almost spherical shape and an average particle size of 155 nm. In vitro cytotoxicity investigation was indicated as dose-respond reaction against cancer breast cells after 24 h incubation. On the other hand, in vitro cell uptake study revealed active targeting of CUR-NPs into spheroids. Besides, CXCR 4 expression was detected about 30-fold less than curcumin alone. The CUR-NPs inhibited proliferation and increased apoptosis in spheroid human breast cancer cells. CONCLUSION: Our results showed the potential of NPs as an effective candidate for curcumin delivery to the target tumor spheroids that confirmed the creatable role of folate receptors.

Embryo-toxicity of docosahexaenoic and eicosapentaenoic acids: In vivo and in silico investigations using the chick embryo model.

OBJECTIVE: The objective of the current study was to evaluate the embryo-toxicity of omega-3 fatty acids. METHODS: Firstly, the embryo-toxicity of docosahexaenoic (DHA) and eicosapentaenoic acids (EPA), as well as their interaction with Bcl-2 family members, were predicted using an in silico assay. In the next step, the embryonic pathological lesions and amniotic fluid biochemical changes following omega-3 treatment were investigated using a chick embryo model. Finally, the drug's vascular apoptotic effect on the chick's yolk sac membrane (YSM) was assessed. RESULTS: In silico simulations revealed the embryo-toxicity, tissue-toxicity (respiratory and cardiovascular), and vascular-toxicity (apoptotic activity) of DHA and EPA. There was also an accurate interaction between DHA and EPA with Bax (Binding affinity: -7.6 and -10.6 kcal/mol) and Bcl-2 (Binding affinity: -8.0 and -12.2 kcal/mol), respectively. Moreover, DHA and EPA administrations were related to various adverse consequences, including weight loss and lesions in the respiratory and cardiovascular systems. Histopathological findings consisted of pulmonary edema, airway dilatation, increased interstitial tissue, and hyperemia in the lungs, heart, liver, kidney, and brain. Morphometric evaluation of the YSM vasculature revealed that the vascular apoptotic effect of omega-3was associated with a significant reduction in mean capillary area. In immunohistochemistry assay, increased expression of BAX and low expression of Bcl-2 affirmed apoptosis in YSM vessels. CONCLUSION: According to the results of this study, one could confirm that the possible embryo-toxicity of omega-3 was approved by data presented in this research. The obtained results also support the suspicion that alteration of the apoptotic-related proteins in vessels is an essential pathway in embryo-toxicity of omega-3.

Determination of trigonelline in human plasma by magnetic solid-phase extraction: a pharmacokinetic study.

Aim: To develop a novel method for the bioanalytical extraction of trigonelline (TRG) from human plasma samples using a magnetic nanocomposite and to evaluate its pharmacokinetic profile. Materials & methods: Magnetic bentonite/ß-cyclodextrine (ß-CD) nanoparticles, coupled with a validated ion-pairing reversed-phase high-performance liquid chromatography method, were used to determine TRG concentration from plasma samples following a single oral administration. Results: The developed reversed-phase high-performance liquid chromatography method was accurate, precise, specific, selective and reproducible. TRG showed rapid absorption, middle rate of elimination and mean residence time of ∼24 h. The data were best fitted on a two-compartment model in which tmax was 1.0 h, Cmax 0.115 µg/ml, area under the curve (AUC)0-24 1.72 µg/ml.h, Cl 0.0293 l/h/kg, t1/2α 0.79 h, t1/2ß 13.68 h and ka 1.63 h-1. Conclusion: The findings of this study could provide useful information to promote the future study of TRG and aid optimal dose finding.

Pharmacokinetic profile of diosgenin and trigonelline following intravenous and oral administration of fenugreek seed extract and pure compound in rabbit.

Diosgenin (DI) and trigonelline (TRG) are the main bioactive compounds of fenugreek seed. A micro-extraction method using magnetic nanocomposites coupled with ion-pairing reversed phase HPLC (RP-HPLC) method was used to determine the analytes in rabbit plasma. The main PK parameters after oral administration of pure DI and the extract were: Cmax: 0.48, 0.057 µg/ml; tmax: 1, 2 h; and t1/2ß: 6.23, 15.04 h, respectively. Pure TRG and the extract PK parameters were: Cmax: 0.121, 0.081 µg/ml; tmax: 1.30, 1.30 h; and t1/2ß: 20.06, 24.70 h, respectively. Generally, the PK profile of the two compounds was best fitted on the two-compartment model.[Formula: see text].

Simultaneous Spectrophotometric Determination of Trigonelline, Diosgenin and Nicotinic Acid in Dosage Forms Prepared from Fenugreek Seed Extract.

Mathematical algorithms offer a useful method for quantitative analysis of compounds in multi-component mixtures to overcome the overlapping problems occurred in UV spectrophotometry. The aim of this study is to develop a method for simultaneous determination of bioactive compounds in herbal dosage forms produced from fenugreek extract. A UV- spectrophotometric method based on mathematical algorithm was used to simultaneous determination of trigonelline (TRG), diosgenin (DI), and nicotinic acid (NA). The maximum absorbance (λmax) was determined to be 232.65 nm, 296.23 nm, and 262.60 nm for TRG, DI, and NA, respectively. The calibration curves showed good linearity for all analytes in the concentration range of 1-20 µg/mL (R2=0.9995, 0.9997, 0.9994 for TRG, DI and NA, respectively). The Intra- and inter-day precisions were in the range of 1.1-10.7% and 1.2-8.2%, respectively. The accuracy of the method was 96.0% for TRG, 92.9% for DI, and 104.2% for NA. The limits of detection (LOD) and quantification (LOQ) were found to be 0.91 and 3.06 µg/mL for TRG, 0.99, and 3.30 µg/mL for DI and 0.33 and 1.10 µg/mL for NA. The validated method was applied for determination of the analytes in the tablet, capsule and thin film dosage forms prepared from the fenugreek seed extract. The mean recovery percentages of the analytes were in the range of 90.0-97.4%, 85.6-105.4%, and 90.0-99.0% for tablet, capsule, and film dosage forms, respectively. Generally, the validated method could be a good candidate for routine spectrophotometric determination of the analytes without any necessity for pre-analysis extraction.

Nano-Graphene Oxide-supported APTES-Spermine, as Gene Delivery System, for Transfection of pEGFP-p53 into Breast Cancer Cell Lines.

PURPOSE: Genetic diseases can be the result of genetic dysfunctions that happen due to some inhibitory and/or environmental risk factors, which are mostly called mutations. One of the most promising treatments for these diseases is correcting the faulty gene. Gene delivery systems are an important issue in improving the gene therapy efficiency. Therefore, the main purpose of this study was modifying graphene oxide nanoparticles by spermine in order to optimize the gene delivery system. METHODS: Graphene oxide/APTES was modified by spermine (GOAS) and characterized by FT-IR, DLS, SEM and AFM techniques. Then pEGFP-p53 was loaded on GOAS, transfected into cells and evaluated by fluorescent microscopy and gene expression techniques. RESULTS: FT-IR data approved the GOAS sheet formation. Ninety percent of the particles were less than 56 nm based on DLS analysis. SEM analysis indicated that the sheets were dispersed with no aggregation. AFM results confirmed the dispersed structures with thickness of 1.25±0.87 nm. STA analysis showed that GOAS started to decompose from 400°C and was very unstable during the heating process. The first weight loss up to 200°C was due to the evaporation of absorbed water, the second one observed in the range of 200-550°C was assigned to the decomposition of labile oxygen- and nitrogen-containing functional groups, and the third one above 550°C was attributed to the removal of oxygen functionalities. In vitro release of DNA demonstrated the efficient activity of the new synthesized system. Ninety percent of the cells were transfected and showed the GFP under fluorescence microscopy, and TP53 gene was expressed 51-fold in BT-20 cells compared to ß-actin as the reference gene. Flow cytometry analysis confirmed the apoptosis of the cells rather than necrosis. CONCLUSION: It could be concluded that the new synthesized structure could transfer a high amount of the therapeutic agent into cells with best activity.

Dispersive solid-phase extraction of buprenorphine from biological fluids using metal-organic frameworks and its determination by ultra-performance liquid chromatography.

In this work, various types of metal-organic frameworks were synthesized, and their affinities toward buprenorphine were evaluated using dispersive solid-phase extraction. The extracted buprenorphine was determined by ultra high performance liquid chromatography-ultraviolet detection system. The highest extraction recovery was observed by employing zeolitic imidazole framework-67. Then, a facile and fast extraction method was designed for the extraction and purification of the target drug. Optimization of the extraction method was carried out by the design of experiment approach. A linearity range of 1-1000 µg/L with the limit of detection of 0.15 µg/L and relative standard deviations (50 µg/L, n = 5) of 3.4% was obtained for standard sample analysis. Under optimized experimental and instrumental conditions, the relative recoveries were in the range of 95 to 111%. Eventually, zeolitic imidazole framework-67 was successfully employed for the extraction and determination of buprenorphine in the biological fluids with satisfactory results.

The effect of antimicrobial activity of Teucrium Polium on Oral Streptococcus Mutans: a randomized cross-over clinical trial study.

BACKGROUND: The purpose of this study is to determine the effect of a mouthwash containing Teucriumpolium herb on Streptococcus mutans in mouth. METHODS: This study was a randomized, crossover, double-blind clinical trial, where we selected 22 volunteers (dental students) randomly and we divided them into two groups. The study had two phases. In each phase, one group acted as the intervention group, while the other one was the control group. Both the intervention and control groups were given the mouthwash with and without Teucriumpolium, respectively. S. mutans of saliva were measured before and after each phase to compare the effects of the mouthwashes. A three-week washout period was considered between the two phases. An independent two-sample t-test was utilized to compare the mean of S. mutans colonies. Additionally, we used a standard AB/BA crossover model to find the results of the treatment and the impact of carryover on the residual's biological effects. The significance level was considered 0.05 in this experiment. RESULTS: There is no significant difference observed between the two groups in the number of S. mutans before using the mouthwashes. When the mouthwash containing Teucriumpolium was used, there was a significant decrease in the number of S. mutans colonies in both phases' extract (P = 0.002). CONCLUSION: The results of this study indicate the mouthwash containing aqueous extract of Teucrium polium can majorly reduce the colonization of S. mutans in human saliva. TRIAL REGISTRATION: Ethical issues approved by the Ethics Committee of the Rafsanjan University of Medical Sciences with the approval number of 937/9/31, IRCT code Number of IRCT2013121815842N1 and it was approved on 06/16/2014. The study was conducted in the period of September to November 2014.