IGF-1 and PDGF-bb suppress IL-1β-induced cartilage degradation through down-regulation of NF-κB signaling: involvement of Src/PI-3K/AKT pathway.

Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that plays a key role in the pathogenesis of osteoarthritis (OA). Growth factors (GFs) capable of antagonizing the catabolic actions of cytokines may have therapeutic potential in the treatment of OA. Herein, we investigated the potential synergistic effects of insulin-like growth factor (IGF-1) and platelet-derived growth factor (PDGF-bb) on different mechanisms participating in IL-1β-induced activation of nuclear transcription factor-κB (NF-κB) and apoptosis in chondrocytes. Primary chondrocytes were treated with IL-1β to induce dedifferentiation and co-treated with either IGF-1 or/and PDGF-bb and evaluated by immunoblotting and electron microscopy. Pretreatment of chondrocytes with IGF-1 or/and PDGF-bb suppressed IL-1β-induced NF-κB activation via inhibition of IκB-α kinase. Inhibition of IκB-α kinase by GFs led to the suppression of IκB-α phosphorylation and degradation, p65 nuclear translocation and NF-κB-regulated gene products involved in inflammation and cartilage degradation (COX-2, MMPs) and apoptosis (caspase-3). GFs or BMS-345541 (specific inhibitor of the IKK) reversed the IL-1β-induced down-regulation of collagen type II, cartilage specific proteoglycans, β1-integrin, Shc, activated MAPKinase, Sox-9 and up-regulation of active caspase-3. Furthermore, the inhibitory effects of IGF-1 or/and PDGF-bb on IL-1β-induced NF-κB activation were sensitive to inhibitors of Src (PP1), PI-3K (wortmannin) and Akt (SH-5), suggesting that the pathway consisting of non-receptor tyrosine kinase (Src), phosphatidylinositol 3-kinase and protein kinase B must be involved in IL-1β signaling. The results presented suggest that IGF-1 and PDGF-bb are potent inhibitors of IL-1β-mediated activation of NF-κB and apoptosis in chondrocytes, may be mediated in part through suppression of Src/PI-3K/AKT pathway, which may contribute to their anti-inflammatory effects

Zinc phthalocyanine tetrasulfonate-loaded Ag@mSiO2 nanoparticles for active targeted photodynamic therapy of colorectal cancer

Colorectal cancer has high morbidity and mortality rate, with a high level of metastasis and recurrence due to the poor therapeutic effects. Photodynamic therapy (PDT) as an emerging clinical modality for cancer treatment provides remarkable advantages over existing treatments by generating reactive oxygen species (ROS) through light irradiating photosensitizers (PSs) in the presence of oxygen. PDT can induce immunity against recurrence and destruction of metastases. The application of nanoparticles (NPs) in targeted cancer therapy is coming to light to circumvent the limitations associated with low physiological solubility and lack of selectivity of the PS towards tumor sites. In this in vitro study, we proved the added value of NP systems on PS efficacy and a tumor-targeting ligand. Using core/shell Ag@mSiO2 NPs loaded with ZnPcS4 PS and folic acid (FA), stronger cellular localization in the human colorectal cancer cell line (Caco-2) was observed compared to the passive NC and free PS. Additionally, light-induced photodynamic activation of the ZnPcS4/Ag@mSiO2-FA nanoconjugate (NC) elicited a strong cytotoxicity effect mediated by post-PDT. The results also revealed that the active NC was able to decrease the cell viability remarkably to 38.0% ± 4.2 *** compared to the passive NC (67.0% ± 7.4*) under 0.125 µM ZnPcS4 (IC50). More importantly, the actively targeted NC-induced apoptosis where cell cycle analysis elaborated on cell death through the G0 phase, indicating the final NC’s efficacy 20 hr post-PDT treatment

Development of a Thiol-capped Core/Shell Quantum Dot Sensor for Acetaminophen

Acetaminophen (AC) is a frequently used pharmaceutical which has been detected in water systems and is of concern due to its potential environmental impacts. In this study, three quantum dot (QD)-ligand systems, namely L-cysteine (L-cys)-, N-acetyl- L-cysteine (NAC)- and glutathione (GSH)-capped CdSe/ZnS quantum dots, were synthesized and tested for the fluorescence detection of acetaminophen. Among the synthesized aqueous core/shell quantum dots, L-cys-CdSe/ZnS QDs were found to be optimal with high sensitivity for the fluorescence detection of acetaminophen. The L-cys-CdSe/ZnS QDs were of a zinc blende crystal structure and displayed excellent fluorescence intensity and photostability and provided a photoluminescence quantum yield of 77 % . The fluorescence of L-cys-CdSe/ZnS QDs was enhanced by the introduction of AC enabling the development of a fast and simple method for the detection of AC. Under optimal conditions, F-F0 was linearly proportional to the concentration of AC from 3.0–100 nmol L–1 with limits of detection and quantification of 1.6 and 5.3 nmol L–1, respectively. Some related pharmaceutical compounds including epinephrine hydrochloride (EP), L-ascorbic acid (AA), uric acid (UA), dopamine hydrochloride (DA) and 4-aminophenol (4-AP) did not interfere with the sensing ofAC. The probe was also successfully applied in the determination of AC in tap and river water matrices.The University of Pretoria, the Water Research Commission (Grant K5/2438/1 and K5/2752) as well as the Photonics Initiative of South Africa (Grant PISA-15-DIR-06).http://www.journals.co.za/sajchemam2019Chemistr

Recent advances in porphyrin-based inorganic nanoparticles for cancer treatment

Abstract: The application of porphyrins and their derivatives have been investigated extensively over the past years for phototherapy cancer treatment. Phototherapeutic Porphyrins have the ability to generate high levels of reactive oxygen with a low dark toxicity and these properties have made them robust photosensitizing agents. In recent years, Porphyrins have been combined with various nanomaterials in order to improve their bio-distribution. These combinations allow for nanoparticles to enhance photodynamic therapy (PDT) cancer treatment and adding additional nanotheranostics (photothermal therapy—PTT) as well as enhance photodiagnosis (PDD) to the reaction. This review examines various porphyrin-based inorganic nanoparticles developed for phototherapy nanotheranostic cancer treatment over the last three years (2017 to 2020). Furthermore, current challenges in the development and future perspectives of porphyrin-based nanomedicines for cancer treatment are also highlighted

Assessment of the rate and etiology of pharmacological errors by nurses of two major teaching hospitals in Shiraz

Medication errors have serious consequences for patients, their families and care givers. Reduction of these faults by care givers such as nurses can increase the safety of patients. The goal of study was to assess the rate and etiology of medication error in pediatric and medical wards. This cross-sectional-analytic study is done on 101 registered nurses who had the duty of drug administration in medical pediatric and adults’ wards. Data was collected by a questionnaire including demographic information, self report faults, etiology of medication error and researcher observations. The results showed that nurses’ faults in pediatric wards were 51/6% and in adults wards were 47/4%. The most common faults in adults wards were later or sooner drug administration (48/6%), and administration of drugs without prescription and administering wrong drugs were the most common medication errors in pediatric wards (each one 49/2%). According to researchers’ observations, the medication error rate of 57/9% was rated low in adults wards and the rate of 69/4% in pediatric wards was rated moderate. The most frequent medication errors in both adults and pediatric wards were that nurses didn’t explain the reason and type of drug they were going to administer to patients. Independent T-test showed a significant change in faults observations in pediatric wards (p=0.000) and in adults wards (p=0.000). Several studies have shown medication errors all over the world, especially in pediatric wards. However, by designing a suitable report system and use a multi disciplinary approach, we can be reduced the occurrence of medication errors and its negative consequences.Keyword: Etiology,Teaching hospital,Pharmcological error, Medication errors, Nurse.</p

Quantum dot - molecularly imprinted polymer nanomaterials for the fluorescence sensing of selected pharmaceutical and personal care products

This research was aimed at fabricating and applying cadmium based core/shell quantum dots (QDs) as fluorescence probes for the detection in aquatic compartments of triclosan (TCS) and acetaminophen (AC) which fall within the pharmaceutical and personal care products (PPCPs) subclass of emerging chemical pollutants (ECPs). Semiconductor quantum dots possess significant advantages such as high fluorescence intensity, long-term photostability, narrow emission and broad absorption as well as high photoluminescence quantum yields, and they have thus attracted considerable research attention for environmental monitoring and sensing applications. Core/shell CdSe/ZnS QDs were synthesized through the one-pot organometallic approach in order to explore the fluorescence sensing of the QDs towards triclosan. A ligand exchange reaction was also performed with glutathione (GSH) as a surface capping agent to convert hydrophobic QDs to water soluble QDs, where the mercapto moiety of GSH binds onto the surface of the QDs and their carboxyl groups provide water solubility. The resultant quantum dots were characterized using various state of the art instruments including fluorescence and UV/Vis spectroscopy, powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), high resolution transmission electron microscopy (HRTEM), and energy dispersive X-ray spectroscopy (EDS). Characterization techniques confirmed the successful synthesis of QDs and the formation of a GSH coating thereon. The synthesized GSH-CdSe/ZnS QDs had a high photoluminescence quantum yield of 89% and an average particle size of 3.3±1.3 nm, as determined by HRTEM analysis, which agreed well with the size determined from the first excitonic absorption peak (3.7 nm). In addition, the QDs exhibited strong and narrow fluorescence intensity with an estimated full width at half maximum of 32.7 nm. The presence of triclosan in the proximity of the QDs enhanced the fluorescence intensity of the QDs. The experimental results showed that under optimum conditions (i.e. 1.5 mg GSH-CdSe/ZnS QDs in 3.0 mL of Millipore water with an incubation time of 5 min and excitation and emission wavelengths of 300 nm and 598 nm, respectively), the calibration plot of F-F0/F0 of the GSH-CdSe/ZnS QDs was proportional to triclosan concentration in the range of 10-300 nmol L-1 (F and F0 are the fluorescence intensity of the QDs in the presence and absence of triclosan respectively). The mechanism was likely based on Förster resonance energy transfer (FRET) from the analyte to the QDs which provided a fluorescence “turn-on” nanosensor for the sensing of triclosan. The Förster distance in the system of GSH-CdSe/ZnS QDs-TCS was found to be approximately 4.0 nm which meets the distance required (<10 nm) for FRET to occur. The developed QDs were found to be a sensitive probe for the determination of triclosan with a very low detection limit of 3.7 nmol L-1 in the presence of other structurally related compounds. The applicability of the probe was evaluated for the determination of triclosan in South African tap and river water matrices which indicated good recoveries of 94%-117.5%. In the next study, the performance of three QD-ligand systems were tested to find the optimum system with high sensitivity to acetaminophen. In this regard, three water-soluble QDs were synthesized through the use of hot, coordinating solvents of octadec-1-ene and oleic acid. In addition, ligand exchange reactions using L-cysteine (L-cys), N-acetyl-L-cysteine (NAC) and glutathione (reported earlier for triclosan detection) as thiol capping agents were performed. L-cys-CdSe/ZnS QDs produced enough sensitivity and were utilized as the optimized system for the determination of acetaminophen. Therefore, characterizations and analytical performance of the sensor for acetaminophen detection were investigated by using aqueous L-cys-CdSe/ZnS QDs. L-cys bound efficiently to the surface of the QDs which was confirmed by different characterisation techniques such as Fourier-transform infrared spectroscopy, high resolution transmission electron microscopy, and energy dispersive X-ray spectroscopy. The photoluminescence properties of the synthesized L-cys-CdSe/ZnS QDs included a quantum yield of 77% with a low full width at half maxima value of 38.5 nm for L-cys-CdSe/ZnS QDs, which indicated the formation of a uniform and homogenous particle size distribution. The average particle size of the L-cys-CdSe and L-cys-CdSe/ZnS QDs determined from HRTEM were 2.1±0.5 and 5.1±0.8 nm, respectively which correlated well with the size from the first excitonic absorption peaks (2.8 nm and 4.0 nm respectively). The utilization of the L-cys-CdSe/ZnS QDs as fluorescent probes for the determination of acetaminophen in water samples was optimised for various parameters including concentration of L-cys-CdSe/ZnS QDs and incubation time. The optimum amount of L-cys-CdSe/ZnS QDs was found to be 1.0 mg in 3.0 mL Millipore water with an incubation time of 5 min. The reaction mechanism proved that the fluorescence “turn-on” effect of the L-cys-CdSe/ZnS QDs in the presence of acetaminophen was due to Förster resonance energy transfer from acetaminophen (donor) to the QDs (acceptor) with a Förster distance of 6.1 nm. Experimental investigation showed that the FRET-sensitized QD emission intensity at 595 nm was enhanced with the introduction of acetaminophen over the linear range of 3.0-100 nmol L-1. The applicability of the QDs to determine AC concentrations in the presence of some related pharmaceuticals including epinephrine hydrochloride, L-ascorbic acid, uric acid, dopamine hydrochloride and 4-aminophenol were tested and no significant interferences were found. In addition, the probe could be applied for the detection of acetaminophen in water matrices at concentrations as low as 1.6 nmol L-1 with recoveries of 90-108% which is environmentally relevant.Thesis (PhD)--University of Pretoria, 2018.ChemistryPhDUnrestricte

Litmus Tests for Comparing Memory Consistency Models: How Long Do They Need to Be?

Even though the general problem of comparing two memory models is infeasible, in this paper we show that checking the equivalence of two memory models becomes feasible when we consider a more restricted class of memory models. We define a class of memory models that is expressive enough to include most known hardware memory models, and we establish a bound of two threads and no more than six memory access instructions for contrasting litmus tests in this class of models. Thus, we can compare memory models in this class by checking a small number of litmus tests. We build a tool for comparing memory models based on this theorem and use the tool to explore and map the space of this class of models

Passivating effect of ternary alloyed AgZnSe shell layer on the structural and luminescent properties of CdS quantum dots

The surface passivation of luminescent CdS quantum dots (QDs) via epitaxial overgrowth of new alloyed ternary AgZnSe shell layer is reported here. Two synthetic fabrication strategies were used to tune the optical properties of CdS/AgZnSe core/alloyed shell QDs across the visible region. Transmission electron microscopy, powder X-ray diffraction, Raman, UV/vis and fluorescence spectrophotometric techniques were used to characterize the nanocrystals. Analysis of the internal structure of the QDs revealed that homogeneity of the particle reduced as the size increased, thus indicating that the QDs growth transitioned from an interfacial epitaxial homogenous state to a heterogeneous state. The crystal structure of the QDs revealed a distinct zinc-blende diffraction pattern for CdS while CdS/AgZnSe core/alloyed shell QDs kinetically favoured a phase change process from the zinc-blende phase to a wurtzite phase. Analysis of the photophysical properties revealed varying degrees of interfacial defect state suppression in CdS/AgZnSe QDs which was dependent on the QDs size. Specifically, the fluorescence quantum yield (QY) of CdS/AgZnSe QDs was at most ~5-fold higher than the CdS core and varied from 35% to 73%. We found that band gap modulation via the synthetic fabrication strategy employed, influenced the optical properties of the core/alloyed shell QDs. The CdS/AgZnSe QDs produced in this work hold great promise in light-emitting optoelectronic applications.The Water Research Council (WRC) project K5/2752, South Africa and the University of Pretoria.http://www.elsevier.com/locate/mssphj2020Chemistr