Ferulic acid grafted into ß-cyclodextrin nanosponges ameliorates Paraquat-induced human MRC-5 fibroblast injury.

Paraquat (PQ) is a commercially important and effective herbicide in the world. Nevertheless, it has higher toxicity causing acute organ damage and different complications, mainly in the lungs and kidneys. Ferulic acid (FA), 4-hydroxy-3-methoxycinnamic acid imposes multiple pharmacological impacts. No protective effect of FA on PQ poisoning-caused human embryonic lung fibroblast damage has not been reported. Despite their many beneficial effects, FA is characterized by poor water solubility, low bioavailability, and phytochemical instability. To solve the problem, ß-cyclodextrin nanosponge (ß-CD NSs) was utilized to increase the solubility of FA so that it was grafted into ß-CD NSs to establish ß-CD@FA NSs. The purpose of this work was to examine for the first time the protective effect of ß-CD@FA NS on MRC-5 human lung cells damages induced by PQ poisoning. MTS assay was performed to investigate the viability of MRC-5 cells at different concentrations of FA/ß-CD@FA NSs when cells were co-cultured with 0.2 µg/mL PQ. The flow cytometry study was carried out to determine apoptosis. Malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels were detected using appropriate biochemistry kits. Compared with the PQ group, the cell activity, CAT, and SOD levels were significantly increased in the FA and chiefly in ß-CD@FA NSs intervention groups, whereas apoptosis and MDA levels were markedly decreased. The inflammatory factors tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and interleukin 22 (IL-22) were detected. The results demonstrate that ß-CD@FA NSs can inhibit PQ-induced cell damage by enhancing antioxidant stress capacity and regulation of inflammatory responses.

Occurrence of some common carbapenemase genes in carbapenem-resistant Klebsiella pneumoniae isolates collected from clinical samples in Tabriz, northwestern Iran.

OBJECTIVES: This study aimed to evaluate the antibiotic resistance patterns and prevalence of carbapenemase genes in Klebsiella pneumoniae isolates in different clinical samples from Tabriz city, northwestern Iran. RESULTS: This cross-sectional study was conducted in the Department of Microbiology, Islamic Azad University, Ahar Branch, Iran, in 2020. K. pneumoniae isolates were collected from different clinical samples, including blood, wounds, sputum, and urine. The isolates were identified using a series of standard bacteriological tests. Antibiotic resistance was determined by the disc diffusion method. The presence of blaVIM, blaNDM, blaKPC, blaOXA, and blaIMP genes were screened by polymerase chain reaction (PCR). A total of 100 non-duplicated K. pneumoniae isolates were collected from 57 urine samples, 27 blood samples, 13 wound samples, and 3 sputum samples. Overall, 70.0% of the samples were from inpatients, while 30.0% were from outpatients. The most resistance rate was related to ampicillin (94.0%), while the lowest resistance rate was related to imipenem (18.0%) and meropenem (20.0%). Overall, 25.0% of the isolates were carbapenem-resistant, of which 13.0% were resistant to both imipenem and meropenem. The PCR showed the total prevalence of 23.0% for carbapenemase genes, including 18.0% for blaKPC, 3.0% for blaVIM, 1.0% for blaIMP, and 1.0% for blaOXA gene. The blaNDM gene was not detected in any isolate. The prevalence of carbapenemase-producing K. pneumoniae isolates was relatively lower in northwestern Iran than in other regions of the country. However, special attention should be paid to the proper use of antibiotics, particularly carbapenems, to prevent further spread of antibiotic resistance and its related genes.

Cognitive decline prevention in offspring of Pb+2 exposed mice by maternal aerobic training and Cur/CaCO3@Cur supplementations: In vitro and in vivo studies.

Heavy metals are considered contaminants that hazardously influence the healthy life of humans and animals as they are widely used in industry. Contact of youngsters and women at ages of parturition with lead (Pb+2) is a main related concern, which passes through the placental barricade and its better absorption in the intestine leads to flaws in the fetal developfment. However, the metals threaten animal and human life, in particular throughout developmental stages. Products existing in the nature have a major contribution to innovating chemo-preventives. As a naturally available polyphenol and necessary curcuminoid, curcumin (Cur) is a derivative of the herb Curcuma longa (L.) rhizome, which globally recognized as "wonder drug of life"; however, Cur has a limited clinical use as it is poorly dissolved in water. Therefore, to enhance its clinically relevant parameters, curcumin-loaded calcium carbonate (CaCO3@Cur) was synthesized by one step coprecipitation method as a newly introduced in this research. Initially, its structure was physio chemically characterized using FT-IR, FESEM and DLS equipment and then the cytotoxicity of lead when it was pretreated with Cur/CaCO3@Cur were assessed by MTT assay. Both Cur and CaCO3@Cur diminished the toxic effects of Pb+2 while the most protective effect on the Pb+2 cytotoxicity was achieved by pre-incubation of cells with CaCO3@Cur. Besides, the morphological changes of Pb+2-treated cells that were pre-incubated with or without Cur/CaCO3@Cur were observed by normal and florescent microscopes. A non-pharmacologic method that lowers the hazard of brain damage is exercise training that is capable of both improving and alleviating memory. In the current study, the role of regular aerobic training and CaCO3@Cur was assessed in reducing the risk of brain damage induced by lead nitrate contact. To achieve the mentioned goal, pregnant Balb/C mice were assigned to five groups (six mice/group) at random: negative and positive controls, aerobic training group and Cur and CaCO3@Cur treated (50 mg/kg/b.wt) trained groups that exposed to Pb+2 (2 mg/kg) by drinking water during breeding and pregnancy. With the completion of study, offspring were subjected to the behavioral tasks that was tested by step-through ORT, DLB, MWM and YM tests. As a result, having regular aerobic training and CaCO3@Cur co-administration with lead nitrate could reverse the most defected behavioral indicators; yet, this was not visible for both sexes and it seems that gender can also be a source of different effects in the animal's body. In fact, having regular aerobic training along with CaCO3@Cur supplementation during pregnancy may be encouraging protecting potential agents towards the toxicity of Pb+2 that could be recommended in the areas with high pollution of heavy metals.

Efficacy of fresh frozen plasma transfusion in comparison with conventional regimen in organophosphate poisoning treatment: a meta-analysis study.

OBJECTIVE: To evaluating the efficacy of fresh frozen plasma (FFP) in comparison with conventional regimen in the treatment of organophosphate (OP) poisoning. METHODS: PubMed, ScopeMed, Cochrane, Scopus, and Google Scholar databases were searched. The search strategy used the following key words "organophosphate" and "poisoning or toxicity", "(atropine and oxime)", "fresh frozen plasma", "clinical trial", "outcome". The treatment with atropine or/and oxime was considered conventional therapy. The length of hospitalization, the length of ICU admission, need for mechanical ventilation and its duration, clinical recovery point, choline esterase level, mortality rate, and intermediate syndrome (IMS) occurrence were the key outcomes of interest. Databases were searched during the period of 2003-2019. Five studies were included in the analysis. RESULTS: Pooling of data showed that the relative risk (RR) of mortality in OP poisoning for five included trials comparing FFP-treated group with conventional regimen therapy was [0.563 (95% CI (0.252, 1.255)]. The summary of RR for IMS in two studies was [RR: 1.34, 95% CI (0.655, 2.742)]. In addition, there was a non-significant mean difference (MD) in hospital stay [MD: -0.106, 95% CI (-0.434, 0.223)] in three included trials. A significant MD was observed in the length of ICU admission in two trials between FFP-treated group compared to the conventional treatment group [MD: -2.672, 95% CI (-4.189, -1.154)], but after random effects meta-analysis, the changes were not significant [MD: -2.015, 95% CI (-6.308, 2.277)]. The summary of fixed-effect meta-analysis for choline esterase level in three trails was [MD: -0.117, 95% CI (-0.468, 0.234)]. The RR of ventilation requirement for two included trials in the FFP-treated group comparing to the conventional regimen therapy was [0.84, 95% CI (0.691, 1.022)] while for ventilation duration in two studies was [MD: -0.183, 95% CI (-0.567, 0.201)]. CONCLUSION: The addition of FFP to conventional therapy did not improve the outcomes of mortality, IMS, hospital length of stay, cholinesterase levels, need or duration of mechanical ventilation, and only the length of ICU stay could affect in the treated group.

Papain grafted into the silica coated iron-based magnetic nanoparticles 'IONPs@SiO2-PPN' as a new delivery vehicle to the HeLa cells.

The present study aims at engineering, fabrication, characterization, and qualifications of papain (PPN) conjugated SiO2-coated iron oxide nanoparticles 'IONPs@SiO2-PPN'. Initially fabricated iron oxide nanoparticles (IONPs) were coated with silica (SiO2) using sol-gel method to hinder the aggregation and to enhance biocompatibility. Next, PPN was loaded as an anticancer agent into the silica coated IONPs (IONPs@SiO2) for the delivery of papain to the HeLa cancer cells. This fabricated silica-coated based magnetic nanoparticle is introduced as a new physiologically-compatible and stable drug delivery vehicle for delivering of PPN to the HeLa cancer cell line. The IONPs@SiO2-PPN were characterized using FT-IR, AAS, FESEM, XRD, DLS, and VSM equipment. Silica was amended on the surface of iron oxide nanoparticles (IONPs, γ-Fe2O3) to modify its biocompatibility and stability. The solvent evaporation method was used to activate PPN vectorization. The following tests were performed to highlight the compatibility of our proposed delivery vehicle: in vitro toxicity assay, in vivo acute systemic toxicity test, and the histology examination. The results demonstrated that IONPs@SiO2-PPN successfully reduced the IC50 values compared with the native PPN. Also, the structural alternations of HeLa cells exposed to IONPs@SiO2-PPN exhibited higher typical hallmarks of apoptosis compared to the cells treated with the native PPN. The in vivo acute toxicity test indicated no clinical signs of distress/discomfort or weight loss in Balb/C mice a week after the intravenous injection of IONPs@SiO2 (10 mg kg-1). Besides, the tissues architectures were not affected and the pathological inflammatory alternations detection failed. In conclusion, IONPs@SiO2-PPN can be chosen as a potent candidate for further medical applications in the future, for instance as a drug delivery vehicle or hyperthermia agent.

Nanoencapsulation of Andrographolide Rich Extract for the Inhibition of Cervical and Neuroblastoma Cancer Cells.

Andrographis paniculata is traditionally used for many diseases and scientifically proven for anti-cancer property. Andrographolide which is the marker compound is believed to be the main contributor to the pharmacological activities. The poor solubility and bioavailability of this diterpenoid lactone could be overcome by nanoencapsulation. Reflux extraction, and followed by successive Soxhlet fractionation were used to obtain andrographolide rich extract from the herb. Spontaneous emulsion solvent diffusion was used to nanoencapsulate andrographolide using poly(lactic-co-glycolic acid) with 1% polyvinyl alcohol as emulsifier. Nanospheres loaded with andrographolide was found to have the particle size, 163 nm; polydispersity index, 0.26 and zeta potential, - 57.85 mV. The encapsulation efficiency and in vitro drug release were 80.0% and 84.2%, respectively. The andrographolide nanoparticles could inhibit the proliferation of cervical and neuroblastoma cells with no adverse effect on normal human skin cells. Andrographolide rich extract loaded nanoparticles could inhibit the proliferation of HeLa and SH-SY5Y cells, mainly through Bax-induced apoptosis. The result was consistent with the low expression of anti-apoptotic genes (Bcl-2 and Bcl-xL) and prognostic factor (Ki-67). The tumour size of HeLa bearing mice was significantly reduced (73%) after treated with andrographolide rich nanoparticles (10 mg/kg body weight) for a month.

Fabrication and performance evaluation of blood compatible hemodialysis membrane using carboxylic multiwall carbon nanotubes and low molecular weight polyvinylpyrrolidone based nanocomposites.

This study focused to optimize the performance of polyethersulfone (PES) hemodialysis (HD) membrane using carboxylic functionalized multiwall carbon nanotubes (c-MWCNT) and lower molecular weight grade of polyvinylpyrrolidone (PVP-k30). Initially, MWCNT were chemically functionalized by acid treatment and nanocomposites (NCs) of PVP-k30 and c-MWCNT were formed and subsequently blended with PES polymer. The spectra of FTIR of the HD membranes revealed that NCs has strong hydrogen bonding and their addition to PES polymer improved the capillary system of membranes as confirmed by Field Emission Scanning Electron Microscope (FESEM) and leaching of the additive decreased to 2% and hydrophilicity improved to 22%. The pore size and porosity of NCs were also enhanced and rejection rate was achieved in the establish dialysis range (<60 kDa). The antifouling studies had shown that NCs membrane exhibited 30% less adhesion of protein with 80% flux recovery ratio. The blood compatibility assessment disclosed that NCs based membranes showed prolonged thrombin and prothrombin clotting times, lessened production of fibrinogen cluster, and greatly suppressed adhesion of blood plasma than a pristine PES membrane. The results also unveiled that PVP-k30/NCs improved the surface properties of the membrane and the urea and creatinine removal increased to 72% and 75% than pure PES membranes. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 513-525, 2019.

Bio-corrosion behavior and mechanical characteristics of magnesium-titania-hydroxyapatite nanocomposites coated by magnesium-oxide flakes and silicon for use as resorbable bone fixation material.

This study was aimed to improve of the corrosion resistance and mechanical properties of Mg/15TiO2/5HA nanocomposite by silicon and magnesium oxide coatings prepared using a powder metallurgy method. The phase evolution, chemical composition, microstructure and mechanical properties of uncoated and coated samples were characterized. Electrochemical and immersion tests used to investigate the in vitro corrosion behavior of the fabricated samples. The adhesion strength of ~36MPa for MgO and ~32MPa for Si/MgO coatings to substrate was measured by adhesion test. Fabrication a homogenous double layer coating with uniform thicknesses consisting micro-sized particles of Si as outer layer and flake-like particles of MgO as the inner layer on the surface of Mg/15TiO2/5HA nanocomposite caused the corrosion resistance and ductility increased whereas the ultimate compressive stress decreased. However, after immersion in SBF solution, Si/MgO-coated sample indicates the best mechanical properties compared to those of the uncoated and MgO-coated samples. The increase of cell viability percentage of the normal human osteoblast (NHOst) cells indicates the improvement in biocompatibility of Mg/15TiO2/5HA nanocomposite by Si/MgO coating.

Trastuzumab-decorated nanoparticles for in vitro and in vivo tumor-targeting hyperthermia of HER2+ breast cancer.

In this study, a magnetic core-shell modified tumor-targeting nanocarrier (MNPs-PEG-TRA) was engineered and demonstrated for the efficient in vitro and in vivo hyperthermia treatment of breast cancer. Magnetic nanoparticles were used as the initial nanocarriers and modified via PEGylation followed by immobilization of Trastuzumab (TRA) with tumor-targeting function towards cancer cells. The hyperthermia performance of the developed targeting drug delivery system was explored using an in vitro study with SK-BR-3 cancer cells and an in vivo study using animal models (mouse) with DMBA-induced breast cancer. The average size of the engineered system was about 100 nm and its zeta potential was about +13 mV, whereby the stability of the system in biological media is enormously enhanced while the possibility of it being removed via the immune system is diminished. The investigation was pursued based on comparing the changes in growth inhibition rates of HSF 1184, MDA-MB-231, MDA-MB-468 and SK-BR-3 cell lines at different temperatures (37 °C, 40 °C, 42 °C, and 45 °C). Compared with bare MNPs and MNPs-PEG, a remarkably enhanced hyperthermia effect using MNPs-PEG-TRA was observed not only in cultured SK-BR-3 cells in vitro but also in an in vivo DMBA tumor bearing mice model. These results are attributed to an about 4 fold higher concentration of MNPs-PEG-TRA carriers in the tumor site compared to the other organs confirming the considerable potential of the magnetic tumor-targeting hyperthermia concept for breast cancer treatment.

In vitro evaluation of actively targetable superparamagnetic nanoparticles to the folate receptor positive cancer cells.

Engineering of a physiologically compatible, stable and targetable SPIONs-CA-FA formulation was reported. Initially fabricated superparamagnetic iron oxide nanoparticles (SPIONs) were coated with citric acid (CA) to hamper agglomeration as well as to ameliorate biocompatibility. Folic acid (FA) as a targeting agent was then conjugated to the citric acid coated SPIONs (SPIONs-CA) for targeting the specific receptors expressed on the FAR+ cancer cells. Physiochemical characterizations were then performed to assure required properties like stability, size, phase purity, surface morphology, chemical integrity and magnetic properties. In vitro evaluations (MTT assay) were performed on HeLa, HSF 1184, MDA-MB-468 and MDA-MB-231cell lines to ensure the biocompatibility of SPIONs-CA-FA. There were no morphological changes and lysis in contact with erythrocytes recorded for SPIONs-CA-FA and SPIONs-CA. High level of SPIONs-CA-FA binding to FAR+ cell lines was assured via qualitative and quantitative in vitro binding studies. Hence, SPIONs-CA-FA was introduced as a promising tool for biomedical applications like magnetic hyperthermia and drug delivery. The in vitro findings presented in this study need to be compared with those of in vivo studies.

Antioxidant Activity and ROS-Dependent Apoptotic Effect of Scurrula ferruginea (Jack) Danser Methanol Extract in Human Breast Cancer Cell MDA-MB-231.

Scurrula ferruginea (Jack) Danser is one of the mistletoe species belonging to Loranthaceae family, which grows on the branches of many deciduous trees in tropical countries. This study evaluated the antioxidant activities of S. ferruginea extracts. The cytotoxic activity of the selected extracts, which showed potent antioxidant activities, and high phenolic and flavonoid contents, were investigated in human breast cancer cell line (MDA-MB-231) and non-cancer human skin fibroblast cells (HSF-1184). The activities and characteristics varied depending on the different parts of S. ferruginea, solvent polarity, and concentrations of extracts. The stem methanol extract showed the highest amount of both phenolic (273.51 ± 4.84 mg gallic acid/g extract) and flavonoid contents (163.41 ± 4.62 mg catechin/g extract) and strong DPPH• radical scavenging (IC50 = 27.81 µg/mL) and metal chelation activity (IC50 = 80.20 µg/mL). The stem aqueous extract showed the highest ABTS•+ scavenging ability. The stem methanol and aqueous extracts exhibited dose-dependent cytotoxic activity against MDA-MB-231 cells with IC50 of 19.27 and 50.35 µg/mL, respectively. Furthermore, the extracts inhibited the migration and colony formation of MDA-MB-231 cells in a concentration-dependent manner. Morphological observations revealed hallmark properties of apoptosis in treated cells. The methanol extract induced an increase in ROS generation and mitochondrial depolarization in MDA-MB-231 cells, suggesting its potent apoptotic activity. The present study demonstrated that the S. ferruginea methanol extract mediated MDA-MB-231 cell growth inhibition via induction of apoptosis which was confirmed by Western blot analysis. It may be a potential anticancer agent; however, its in vivo anticancer activity needs to be investigated.

Synthesis, characterization and in vitro evaluation of exquisite targeting SPIONs-PEG-HER in HER2+ human breast cancer cells.

A stable, biocompatible and exquisite SPIONs-PEG-HER targeting complex was developed. Initially synthesized superparamagnetic iron oxide nanoparticles (SPIONs) were silanized using 3-aminopropyltrimethoxysilane (APS) as the coupling agent in order to allow the covalent bonding of polyethylene glycol (PEG) to the SPIONs to improve the biocompatibility of the SPIONs. SPIONs-PEG were then conjugated with herceptin (HER) to permit the SPIONs-PEG-HER to target the specific receptors expressed over the surface of the HER2+ metastatic breast cancer cells. Each preparation step was physico-chemically analyzed and characterized by a number of analytical methods including AAS, FTIR spectroscopy, XRD, FESEM, TEM, DLS and VSM. The biocompatibility of SPIONs-PEG-HER was evaluated in vitro on HSF-1184 (human skin fibroblast cells), SK-BR-3 (human breast cancer cells, HER+), MDA-MB-231 (human breast cancer cells, HER-) and MDA-MB-468 (human breast cancer cells, HER-) cell lines by performing MTT and trypan blue assays. The hemolysis analysis results of the SPIONs-PEG-HER and SPIONs-PEG did not indicate any sign of lysis while in contact with erythrocytes. Additionally, there were no morphological changes seen in RBCs after incubation with SPIONs-PEG-HER and SPIONs-PEG under a light microscope. The qualitative and quantitative in vitro targeting studies confirmed the high level of SPION-PEG-HER binding to SK-BR-3 (HER2+ metastatic breast cancer cells). Thus, the results reflected that the SPIONs-PEG-HER can be chosen as a favorable biomaterial for biomedical applications, chiefly magnetic hyperthermia, in the future.

γ-Fe2O3 nanoparticles filled polyvinyl alcohol as potential biomaterial for tissue engineering scaffold.

Maghemite (γ-Fe2O3) nanoparticle with its unique magnetic properties is recently known to enhance the cell growth rate. In this study, γ-Fe2O3 is mixed into polyvinyl alcohol (PVA) matrix and then electrospun to form nanofibers. Design of experiments was used to determine the optimum parameter settings for the electrospinning process so as to produce elctrospun mats with the preferred characteristics such as good morphology, Young's modulus and porosity. The input factors of the electrospinnning process were nanoparticles content (1-5%), voltage (25-35 kV), and flow rate (1-3 ml/h) while the responses considered were Young's modulus and porosity. Empirical models for both responses as a function of the input factors were developed and the optimum input factors setting were determined, and found to be at 5% nanoparticle content, 35 kV voltage, and 1 ml/h volume flow rate. The characteristics and performance of the optimum PVA/γ-Fe2O3 nanofiber mats were compared with those of neat PVA nanofiber mats in terms of morphology, thermal properties, and hydrophilicity. The PVA/γ-Fe2O3 nanofiber mats exhibited higher fiber diameter and surface roughness yet similar thermal properties and hydrophilicity compared to neat PVA PVA/γ-Fe2O3 nanofiber mats. Biocompatibility test by exposing the nanofiber mats with human blood cells was performed. In terms of clotting time, the PVA/γ-Fe2O3 nanofibers exhibited similar behavior with neat PVA. The PVA/γ-Fe2O3 nanofibers also showed higher cells proliferation rate when MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was done using human skin fibroblast cells. Thus, the PVA/γ-Fe2O3 electrospun nanofibers can be a promising biomaterial for tissue engineering scaffolds.

Communal microaerophilic-aerobic biodegradation of Amaranth by novel NAR-2 bacterial consortium.

A novel bacterial consortium, NAR-2 which consists of Citrobacter freundii A1, Enterococcus casseliflavus C1 and Enterobacter cloacae L17 was investigated for biodegradation of Amaranth azo dye under sequential microaerophilic-aerobic condition. The NAR-2 bacterial consortium with E. casseliflavus C1 as the dominant strain enhanced the decolorization process resulting in reduction of Amaranth in 30 min. Further aerobic biodegradation, which was dominated by C. freundii A1 and E. cloacae L17, allowed biotransformation of azo reduction intermediates and mineralization via metabolic pathways including benzoyl-CoA, protocatechuate, salicylate, gentisate, catechol and cinnamic acid. The presence of autoxidation products which could be metabolized to 2-oxopentenoate was elucidated. The biodegradation mechanism of Amaranth by NAR-2 bacterial consortium was predicted to follow the steps of azo reduction, deamination, desulfonation and aromatic ring cleavage. This is for the first time the comprehensive microaerophilic-aerobic biotransformation pathways of Amaranth dye intermediates by bacterial consortium are being proposed.