Targeted delivery of interleukin-12 plasmid into HepG2 cells through folic acid conjugated graphene oxide nanocarrier.

Successful gene therapy relies on carriers to transfer genetic materials with high efficiency and low toxicity in a targeted manner. To enhance targeted cell binding and uptake, we developed and synthesized a new gene delivery vector based on graphene oxide (GO) modified by branched polyethyleneimine (BPEI) and folic acid (FA). The GO-PEI-FA nanocarriers exhibit lower toxicity compared to unmodified PEI, as well as having the potential to efficiently condense and protect pDNA. Interestingly, increasing the polymer content in the polyplex formulation improved plasmid transfer ability. Substituting graphene oxide for PEI at an N/P ratio of 10 in the HepG2 and THP1 cell lines improved hIL-12 expression by up to approximately eightfold compared to simple PEI, which is twice as high as GO-PEI-FA in Hek293 at the same N/P ratio. Therefore, the GO-PEI-FA described in this study may serve as a targeting nanocarrier for the delivery of the hIL-12 plasmid into cells overexpressing folic acid receptors, such as those found in hepatocellular carcinoma.

Green and low-temperature synthesis of the magnetic modified biochar under the air atmosphere for the adsorptive removal of heavy metal ions from wastewater: CCD-RSM experimental design with isotherm, kinetic, and thermodynamic studies.

The accumulation of heavy metal ions in living cells leads to biological damage, which makes the necessity of using new methods to effectively remove heavy metal ions from the environment more vital. In this work, a magnetic modified biochar was prepared under regular air atmosphere and low temperature (220 ºC) and used as a low-cost and green adsorbent for efficient adsorptive removal of cobalt (Co(II)) and Lead (Pb(II)) ions from contaminated waters. The adsorption process was modeled and optimized using CCD-RSM to maximize the removal efficiency of heavy metal ions, as well as was monitored in detail by isotherm, kinetic, and thermodynamic studies. The results show that the Langmuir maximum adsorption capacity of the adsorbent reached 237.92 mg g-1 (single) and 121.23 mg g-1 (binary) for Co(II) and 207.21 mg g-1 (single) and 106.56 mg g-1 (binary) for Pb(II) under the short time of 25 min and solution pH of 6.0. The kinetic studies revealed that the pseudo-first-order model was the best-fitted model to experimental data and indicated that the adsorption process was mostly through chemisorption. Also, thermodynamic studies showed that that adsorptive removal of Co(II)and Pb(II)ions followed an endothermic and spontaneous process. The reusability studies demonstrated that the adsorbent could be successfully regenerated with 5 mL of 0.1 mol L-1 HNO3 solution, and the adsorption efficiency was retaining about 90% after four adsorption-desorption cycles. Also, the results from using real water samples, including drinking water, groundwater, and river water, implied that the synthesized magnetic modified biochar was highly efficient for practical treatment processes. Overall, the results indicated that the proposed magnetic biochar can be considered as a cost-effective and efficient adsorbent for adsorptive removal of heavy metal ions from contaminated waters.

Evaluation of the Biodistribution of Arginine, glycine, aspartic acid peptide-modified Nanoliposomes Containing Curcumin in Rats.

Background: Liposomes, as a biological membrane, is successfully used for drug delivery, reduces toxicity in normal cells and improves bio-accessibility of the drug to the target cells. Curcumin, as a bioactive substance with pleiotropic biological activities, is an anti-inflammatory compound and has several anticancer effects in different cancers such as pancreatic and breast cancer. Objectives: This study was conducted to determine the bio-distribution of arginine-glycine-aspartic acid (RGD)-modified nanoliposomes containing curcumin in different tissues of rats. Materials and Methods: The amount of curcumin in each tissue was examined by HPLC analysis. The distribution of liposomal Hoechst in the rats was evaluated by using fluorescence spectrophotometry, live animal imaging analyses and histological methods. Results: HPLC analysis showed the mean of curcumin in the blood significantly increased in the liposomal curcumin modified with RGD compared to free curcumin. These results were confirmed by fluorescence measurement for RGD modified liposome containing Hoechst dye. There was negligible fluorescent intensity in the blood rats, which received Hoechst alone. Live animal imaging analysis showed the presence of fluorescent color in heart tissue for all groups. It was also detected in kidney tissue for liposomal Hoechst modified with RGD group. Conclusions: The present study demonstrated that RGD-modified nano-liposomes can significantly improve drug retention time in the blood of rats.

Stachys pilifera Benth: A Review of Its Botany, Phytochemistry, Therapeutic Potential, and Toxicology.

Background: Stachys L. (Lamiaceae) includes more than 300 annual or perennial species growing in temperate regions of Southern Africa, the Mediterranean, America, and Asia. Stachys pilifera Benth (S. pilifera), also known as Marzeh Kuhi, is an endemic species from Iran. It is found in the mountainous habitats of the Zagros area. It has various traditional uses, and the phytochemical ingredients and some biological activities of this species have been examined in previous studies. Methods: PubMed, Science Direct, Google Scholar, Scopus, and Science Web databases were used to gather the data. The purpose of this review is to consolidate the scattered knowledge reported in the literature about botany, traditional uses, phytochemistry, pharmacological properties, and safety of S. pilifera and suggest its potential medicinal properties. Key Findings. In traditional Iranian medicine, S. pilifera manages various illnesses, such as rheumatoid arthritis, common cold, infections, asthma, and tussive. More than 30 compounds have been identified in S. pilifera essential oil. The compounds found in S. pilifera are phenolic compounds, monoterpenes, sesquiterpenes, flavonoids, alkaloids, and terpenoids, which have various properties such as antioxidant, nephroprotective, anti-inflammatory, antimicrobial, hepatoprotective, and anticancer properties. Conclusions: The literature reveals that S. pilifera is an essential source of bioactive phytochemicals and illustrates the unknown area of this plant for new investigations. Moreover, we recommend that future research focus on toxicology and quality control studies for S. pilifera to fill the knowledge gap and provide theoretical support for the plant's possible functional and clinical uses.

Nano-sized Fe3O4@SiO2-molecular imprinted polymer as a sorbent for dispersive solid-phase microextraction of melatonin in the methanolic extract of Portulaca oleracea, biological, and water samples.

In this study, a magnetic molecularly imprinted polymer (MMIP (Fe3O4@SiO2-MIP)) was used for the dispersive magnetic solid-phase microextraction (d-MSP-µ-E) to design an easy and effective method for melatonin (MLT) extraction in the methanolic extract of Portulaca oleracea, human urine and plasma, and water samples. HPLC with UV detection was utilized, and pH, the type and volume of eluent, MMIP mass, and contact time were considered as effective factors in the study of MLT separation and pre-concentration. These factors were optimized by Plackett-Burman and multi-objective response surface methodology (RSM). The values were 10 mg, 14 min, 4.2, methanol, 0.180 mL, 2.5 min, for the MMIP mass, time of sorption, sample pH, eluent type, eluent volume, and time of elution, respectively. At the optimum conditions, the limit of detection (LOD) was 0.046 ng mL-1, and the limit of quantification (LOQ) was 0.156 ng mL-1. The sorption capacity of the proposed MMIP sorbent was 109.1 mg g-1 at the optimum conditions. Besides, linear dynamic range (LDR) was 0.2-4200 ng mL-1, and the precision of the method (RSD %) for triplicate measurements was <6.1%. The MMIP showed saturation magnetization of 19.75 emu g-1, resulting in fast separation of the sorbent. The sorption test revealed the high sorption capacity of the MMIP for MLT and its homogeneous binding sites. In all spiked levels (50, 100, 200, and 500 ng mL-1), 93.07-104.1% was the range obtained for the recovery of MLT. The relative selectivity factor (ß) values of MLT/tryptophan, MLT/serotonin, MLT/ferulic acid, MLT/mefenamic acid, MLT/quercetin, MLT/luteolin, and MLT/chlorogenic acid were 1.60, 1.68, 2.02, 2.38, 2.32, 2.40, and 2.50, respectively. The results of desorption-regeneration cycles (seven times) by employing the MMIP showed the high stability of the resultant material. In conclusion, the MMIP combined with the magnetic separation showed a specific sorption behavior for MLT and suggested a simple, flexible, selective, and powerful analytical tool.

Rapid ultrasound-assisted microextraction of atorvastatin in the sample of blood plasma by nickel metal organic modified with alumina nanoparticles.

In the present work, nickel-1,4-benzenedioxyacetic acid was synthesized as a rod-like metal organic material and then modified with alumina nanoparticles to synthesize nickel metal organic modified-Al2 O3 nanoparticles. The material was found as an efficient sorbent for the enrichment of atorvastatin in human blood plasma. After the extraction of the sample of plasma by ultrasound-assisted dispersive solid phase extraction, high performance liquid chromatography-ultraviolet was used to determine the quantitatively pre-concentrated interest analyte. The conditions for optimum extraction were achieved by the optimization of the volume of eluent, dosage of the sorbent, and time of sonication. Solution pH of 7.0, 250 µL of ethanol, 45 mg of the sorbent, and 10 min of sonication time were the conditions for extracting the atorvastatin maximum recovery of higher than 97.0%. By using desirability function for the optimization of the process, the present method showed a response that was linear ranging from 0.2 to 800 ng/mL with regression coefficient of 0.999 in the plasma of human blood with a satisfactory detection limit of 0.05 ng/mL, while the precision of interday for the current method was found to be <5%. It can be concluded that dispersive solid phase extraction method is effective for the extraction of atorvastatin from human plasma samples (97.4-102%) due to its easy operation, simplicity, repeatability, and reliability.

Protective effect of Nasturtium officinale R. Br and quercetin against cyclophosphamide-induced hepatotoxicity in rats.

Cyclophosphamide (CPA) is used in the management of autoimmune conditions and malignant illnesses. However, its therapeutic use is limited because of its severe side effects, especially hepatotoxicity attributed to oxidative stress. Nasturtium officinale R. Br (watercress or WC) has pharmacological properties, such as anti-inflammation, and antioxidant activities. Therefore, the present study was design to assess effects of WC or its active ingredient, quercetin (QE), against CPA-induced hepatotoxicity. For this study, 49 male Wistar rats (200-250 g) were randomly selected and categorized into seven equal groups. The animals were pre- and post-treated with both hydroalcoholic extract of WC (500 mg/kg) and quercetin (75 mg/kg) for 10 consecutive days, and intraperitoneal administration of CPA (200 mg/kg) was performed on only day 10, one hour before the last dose of WC or quercetin. On day 11, all the animals were sacrificed, and their blood and liver were gathered for evaluation of the liver enzyme, hepatic oxidative stress markers, antioxidant enzymes activity, and hematoxylin and eosin staining. CPA significantly increased malondialdehyde (MDA), protein carbonyl (PCO) and nitric oxide (NO) levels and liver biomarkers. Otherwise, hepatic catalase (CAT), reduced glutathione (GSH), total thiol content (tSH), and ferric reducing antioxidant power (FRAP) were considerably lower than the control group. Results showed that WC has the ability to reduce the changes (MDA, PCO, FRAP, CAT, ALT and AST) and QE (MDA, PCO, AST) induced by CPA (p < 0.05). Histopathological finding confirmed the indicated results. These findings propose that WC and QE have protective effect against the CPA-induced hepatotoxicity by decreasing oxidative stress.

Antioxidant and protective effect of Stachys pilifera Benth against nephrotoxicity induced by cisplatin in rats.

The aim of current study was to assess the antioxidant and renoprotective effects of Stachys pilifera Benth (S.P.B.) hydroalcoholic extract on nephrotoxicity induced with cisplatin (CP). Adult rats with bodyweight of 180-220 g were divided into five groups (n = 7) treated as follows: group 1, control; group 2, CP; group 3, pretreatment with S.P.B. before CP; group 4, posttreatment with S.P.B. after CP; and, group 5, S.P.B. extract. A single dose of CP (7 mg/kg) was intraperitoneally injected on the fifth day and hydroalcoholic extract of S.P.B. (500 mg kg-1  day-1 ) was orally administered. The levels of oxidative stress markers, biochemical tests, and histopathological staining were assayed in serum and renal tissue. Also, the chemical composition of S.P.B. extract was determined by GC-MS analysis. The main compositions of S.P.B. extract identified by GC-MS analysis, were hexadeca-2,6,10,14-tetraen-1-ol, 3,7,11,16-tetramethyl (24.77%), thymol (14.1%), and linolenic acid (13.4%). In groups treated and pretreated with S.P.B., blood urea nitrogen, creatinine, malondialdehyde, and nitric oxide metabolite in serum as well as malondialdehyde and protein carbonyl content of kidney tissues were significantly decreased in comparison to CP group; in contrast, total thiol group showed a significant increase in treated group as compared to CP group. Furthermore, histological investigation indicated that treatment with S.P.B. improved renal damages induced by CP. The current study showed that S.P.B. hydroalcoholic extract improved the biochemical parameters and kidney function as well as restored antioxidant activity in CP-induced nephrotoxicity. However, it needs more investigations to define the mechanism of S.P.B. action. PRACTICAL APPLICATIONS: In different regions of Iran, Stachys is demonstrated by 34 species, out of which 13 are endemic, one of these endemic species is Stachys pilifera Benth (S.P.B.). The oil of S.P.B. is mainly consisted of cis-chrysanthenyl acetate, cis-chrysanthenol, spathulenol, ß-caryophyllene, linalool, and terpinen-4-ol. Moreover, phytochemical studies have shown the presence of compounds such as diterpenes, phenylethanoid glycosides, saponins, terpenoides, and flavonoids in Stachys species. The aerial parts of S.P.B. are consumed as herbal tea to treat several disorders, for example, infections, asthma, and rheumatoid arthritis in Iranian folk medicine. The aim of current study was to evaluate the antioxidant and protective effects of S.P.B. hydroalcoholic extract on nephrotoxicity induced with cisplatin (CP). The current study showed that S.P.B. hydroalcoholic extract improved the biochemical parameters and kidney function as well as restored antioxidant activity in CP-induced nephrotoxicity. However, it needs more researches to define the mechanism of S.P.B. action.

Ultrasound wave assisted adsorption of congo red using gold-magnetic nanocomposite loaded on activated carbon: Optimization of process parameters.

In this study, gold-magnetic nanocomposite in the presence of ultrasound wave assisted was synthesized and loaded on activated carbon (Au-Fe3O4-NCs-AC) by simple, fast and low-cost process. This novel material was applied for ultrasound assisted adsorption of congo red (CR) as model of toxic and even carcinogenic substance from aqueous solution. The detail of morphology and identity of Au-Fe3O4-AC was characterized by SEM and TEM techniques and correlation among response to variables such as pH (2-10), adsorbent mass (0.005-0.025 g), initial CR concentration (10-30 mg L-1) and ultrasound time (2-6 min) was investigated by response surface methodology (RSM) under central composite design (CCD). Analysis of variance (ANOVA) exhibit a high R2 value of 0.999 and confirm suitability of constructed second-order regression model for excellent evaluation and prediction of the experimental data. The interaction and main factor and optimum conditions of the under study process were determined from response surface plots based on desirability function. The maximum CR adsorption were achieved at pH of 4, 15 mg L-1 of CR, 0.017 g of Au-Fe3O4-AC and 5 min sonication which owing to 99.49% removal efficiency is highly recommended for future CR removal from different matrixes. Adsorption kinetic follow second-order rate expression in combination to inter particle diffusion and equilibrium adsorption data best represented by the Langmuir isotherm with maximum mono-layer adsorption capacity of 43.88 mg g-1.

Synthesis of nanocomposites of iron oxide/gold (Fe3O4/Au) loaded on activated carbon and their application in water treatment by using sonochemistry: Optimization study.

This paper focuses on the finding best operational conditions using response surface methodology (RSM) for Rhodamine123 (R123) and Disulfine blue (DSB) dyes removal by ultrasound assisted adsorption onto Au-Fe3O4 nanoparticles loaded on activated carbon (Au-Fe3O4 NPs-AC). The influences of variables such as initial R123 (X1) and DSB concentration (X2), pH (X3), adsorbent mass (X4) and sonication time (X5) on their removal were investigated by small central composite design (CCD) under response surface methodology. The significant variables and the possible interactions among variables were investigated and estimated accordingly. The best conditions were set as: 4min, 4.0, 0.025g, 13.5 and 26.5mgL-1 for sonication time, pH, adsorbent weight, initial R123 and DSB concentration, respectively. At above conditions, the adsorption equilibrium and kinetic follow the Langmuir isotherm and pseudo-second-order kinetic model, respectively. The maximum monolayer capacity (Qmax) of 71.46 and 76.38mgg-1 for R123 and DSB show sufficiency of model for well presentation of experimental data.