DNA sequencing validation by PCR-RFLP for evaluating butyrophilin-like 2 rs2076530 polymorphism in Iranian patients with sarcoidosis

Background:Sarcoidosis is a multifactorial immune disorder with an uncertain origin. A single nucleotide polymorphism (G→A, rs2076530) in the butyrophilin-like 2 (BTNL2) gene results in the formation of truncating protein. This study aimed to genotype the predisposition of the BTNL2 rs2076530 polymorphism in Iranian patients with sarcoidosis using the RFLP technique.Materials and Methods:In this study, 80 patients with sarcoidosis and 80 healthy individuals were included. The rs2076530 polymorphism of the BTNL2 gene was genotyped using the PCR-RFLP method by AvrII restriction enzyme and confirmed by DNA sequencing (Capillary electrophoresis 3130, ABI).Results:There was a statistically significant difference between proportions of patients with AA (47,5%) and controls (27.5%) (OR=2.38, 95%CI:1.23-4.61, P=0.009). In addition, a significant difference was observed in the frequency of the A allele (62.5%) in sarcoidosis (OR=2.14, 95%CI:1.37-3.35, P=0.001). A Bonferroni correction with P<0.0038 indicates a statistical difference for genotype AA (P=0.009). In an effective model, binary logistic regression analysis indicates a statistical association between AA genotype and sarcoidosis (P=0.018 with 60% prediction). Based on the gene analysis study using DNA sequencing, all of the mentioned mutations were seen via RFLP.Conclusion:According to our findings, the BTNL2 rs2076530 A allele in the Iranian population is associated with susceptibility to sarcoidosis. This designed PCR-RFLP method for detecting SNPs is effective as DNA sequencing.     

Randomised phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer

Background This multi-center RP2 study assessed activity/safety of ixabepilone + bevacizumab compared to ixabepilone in platinum-resistant/refractory ovarian/fallopian tube/primary peritoneal cancer. Additional objectives were to examine the role of prior bevacizumab and taxanes, and explore class III-ß-tubulin (TUBB3) as a predictive biomarker.Methods Participants were randomised to receive ixabepilone 20 mg/m² days 1, 8, 15 with (IXA + BEV) or without (IXA) bevacizumab 10 mg/kg days 1, 15 every 28 days. Patients were stratified by prior BEV. The primary endpoint was PFS. OS, safety, and ORR served as secondary endpoints.Results Among 76 evaluable patients who received IXA + BEV (n = 39) compared to IXA (n = 37), the ORR was 33% (n = 13) versus 8% (n = 3)(P = 0.004), durable at 6 months in 37% (n = 14) and 3% (n = 1) (P < 0.001). BEV significantly improved PFS (median:5.5 vs 2.2 months, HR = 0.33, 95%CI 0.19–0.55, P < 0.001) and OS (median:10.0 vs 6.0 months, HR = 0.52, 95%CI 0.31–0.87, P = 0.006). Both regimens were well-tolerated. TUBB3 expression did not predict response. Subgroup analyses revealed minimal effect of prior BEV or taxane resistant/refractory status on response to IXA + BEV.Conclusions IXA + BEV is a well-tolerated, effective combination for platinum/taxane-resistant ovarian cancer that extends PFS and likely OS relative to IXA monotherapy. Prior receipt of BEV should not preclude the use of IXA + BEV. TUBB3 is not a predictive biomarker.Clinical trial registration NCT3093155.Subject terms: Translational research, Phase II trials     

In vitro study of alginate–gelatin scaffolds incorporated with silica NPs as injectable,biodegradable hydrogels

Porous substrates composed of biodegradable polymers and nanoparticles have found extensive use as three-dimensional (3D) scaffolds to regenerate damaged tissues through the incorporation of cells or growth factors. Here, injectable thermally responsive hydrogels based on SiO₂ nanoparticles (NPs), alginate, and gelatin biopolymers, with possible utilization for cartilage tissue engineering, are introduced. The nanocomposites contain different amounts of SiO₂ NPs for reinforcement and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)/N-hydroxysuccinimide (NHS) for chemical crosslinking of polymer chains in the 3D hydrogel network. The cross-sectional structure of the hydrogels containing 0.25, 1.5, and 3.0% SiO₂ NPs was observed by FE-SEM, confirming porous morphology with interconnected pores. Based on the rheometer analyses, by increasing the amount of SiO₂ NPs, the mechanical strength of the gels can be found. In addition, in vitro biodegradation studies show that the hydrogels without SiO₂ are more unstable than the hydrogels containing SiO₂ NPs. In vitro biocompatibility of the products tested by MTT assay indicates that cell viability and attachment depend on the presence of SiO₂ NPs.

Thermoresponsive oxidized alginate/gelatin/SiO₂ NPs injectable hydrogels have great potential in cartilage tissue engineering due to low gelation time (120 s) and body temperature gelation (37 °C).     

Preparation and study of characteristics of LiCoO2/Fe3O4/Li2B2O4 nanocomposites as ideal active materials for electrochemical hydrogen storage

The nanocomposites of LiCoO₂/Fe₃O₄/Li₂B₂O₄ were designed by the Pechini route using different fuels for the optimization of their morphology and structure. Compared to other fuels, citric acid can act as both an ideal fuel and a capping agent. The ratio of the EG : H₂O mixture is another parameter, which was studied in terms of its effects on the structural characterization. The optimized sample with a rod shape was selected to compare with the bulk sample through electrochemical hydrogen storage capacity. The discharge capacity for rod-shaped nanocomposites measured was 1284 mA h g⁻¹. However, the discharge capacity for the bulk morphology was calculated to be about 694 mA h g⁻¹. The magnetic, electrochemical and structural analyses were performed to investigate the properties of LiCoO₂/Fe₃O₄/Li₂B₂O₄ nanocomposites.

To the best of our knowledge, for the first time, the effects of LiCoO₂/Fe₃O₄/Li₂B₂O₄ nanocomposites as a favorable hydrogen capacitor were investigated to enhance hydrogen storage performance.     

Photocatalytic and antibacterial activities of Tl–Hg–I nanocomposites: sonochemical synthesis and characterization

Efforts to find new and practical solutions to improve water quality and treatment of industrial effluents are ongoing. In this study, Tl₄HgI₆/HgI₂ nanocomposites were synthesized by a rapid ultrasonic method to investigate their photocatalytic and antibacterial activity. Various synthesis conditions such as changes in the ratio of precursors, use of surfactants, and changes in the power and time of sonication to achieve particles with optimal size and morphology were performed. X-ray diffraction (XRD) and energy dispersive spectroscopy (EDS) analysis confirmed the purity and formation of the nanocomposite. Optimal nanoparticles in terms of size and morphology were selected by examining the images obtained from scanning electron microscopy (SEM) analysis. The nanocomposites obtained in the presence of PVP (polyvinylpyrrolidone) as a surfactant (sample no. 8) were selected as the optimal sample. Transmission electron microscopy (TEM), differential reflectance spectroscopy (DRS), Raman, N₂ adsorption/desorption analyzes were performed for the optimal sample to evaluate the properties of nanocomposites. The band-gap for Tl₄HgI₆/HgI₂ nanocomposites was calculated to be about 2.3 eV for HgI₂ and 3.1 eV for Tl₄HgI₆. The optimal sample was used to evaluate the photocatalytic activity for decolorizing an aqueous solution of six different organic dyes. Finally, for rhodamine B, the decolorization was about 80%. Also, Tl₄HgI₆/HgI₂ nanocomposite showed a significant inhibition zone in the antibacterial test. The maximum inhibition diameter of 50 mm was obtained against Streptococcus pyogenes. The results showed that Tl₄HgI₆/HgI₂ nanocomposites have good potential for many industrial applications.

In this work, Tl₄HgI₆/HgI₂ nanocomposites were synthesized by a rapid ultrasonic method. The photocatalytic properties of the nanocomposites were evaluated for the first time. Photocatalytic properties were performed for six industrial dyes.     

2-Benzylidenebenzofuran-3(2H)-ones as a new class of alkaline phosphatase inhibitors: synthesis,SAR analysis,enzyme inhibitory kinetics and computational studies

The excelling role of organic chemistry in the medicinal field continues to be one of the main leads in the drug development process. Particularly, this industry requires organic chemists to discover small molecular structures with powerful pharmacological potential. Herein, a diverse range of chalcone (1–11) and aurone (12–22) derivatives was designed and synthesized and for the first time, and both motifs were evaluated as potent inhibitors of alkaline phosphatases (APs). Structural identification of the target compounds (1–22) was accomplished using common spectroscopic techniques. The effect of the nature and position of the substituent was interestingly observed and justified based on the detailed structure–activity relationship (SAR) of the target compounds against AP. It was concluded from the obtained results that all the newly synthesized compounds exhibit high inhibitory potential against the AP enzyme. Among them, compounds 12 (IC₅₀ = 2.163 ± 0.048 μM), 15 (IC₅₀ = 2.146 ± 0.056 μM), 16 (IC₅₀ = 2.132 ± 0.034 μM), 18 (IC₅₀ = 1.154 ± 0.043 μM), 20 (IC₅₀ = 1.055 ± 0.029 μM) and 21 (IC₅₀ = 2.326 ± 0.059 μM) exhibited excellent inhibitory activity against AP, and even better/more active than KH₂PO₄ (standard) (IC₅₀ = 2.80 ± 0.065 μM). Remarkably, compound 20 (IC₅₀ = 1.055 ± 0.029 μM) may serve as a lead structure to design more potent inhibitors of alkaline phosphatase. To the best of our knowledge, these synthetic compounds are the most potent AP inhibitors with minimum IC₅₀ values reported to date. Furthermore, a molecular modeling study was performed against the AP enzyme (1EW2) to check the binding interaction of the synthesized compounds 1–22 against the target protein. The Lineweaver–Burk plots demonstrated that most potential derivative 20 inhibited h-IAP via a non-competitive pathway. Finally, molecular dynamic (MD) simulations were performed to evaluate the dynamic behavior, stability of the protein–ligand complex, and binding affinity of the compounds, resulting in the identification of compound 20 as a potential inhibitor of AP. Accordingly, excellent correlation was observed between the experimental and theoretical results. The pharmacological studies revealed that the synthesized analogs 1–22 obey Lipinski''s rule. The assessment of the ADMET parameters showed that these compounds possess considerable lead-like characteristics with low toxicity and can serve as templates in drug design.

Aurones are the plant secondary metabolites belonging to the flavonoid’s family. The bioactivities of aurones are very promising, thus these heterocyclic compounds can be considered as an alluring scaffold for drug design and development.     

A new phase transfer nanocatalyst NiFe2O4–PEG for removal of dibenzothiophene by an ultrasound assisted oxidative process: kinetics,thermodynamic study and experimental design

In this study, NiFe₂O₄–PEG, an effective nanocatalyst was synthesized via a hydrothermal method using different PEG concentrations and synthesis times. The synthesized nanocatalyst was used in the ultrasound assisted oxidative desulfurization (UAOD) of model fuels (e.g. n-hexane and dibenzothiophene (DBT)) for the first time. The nanocatalyst was then characterized by XRD, FTIR, BET, SEM, VSM and TEM analyses. In addition, central composite design was used to evaluate the effective variables on the UAOD process. The optimal values of effective factors such as catalyst dose, oxidant amount, irradiation time and ultrasonic power to maximize of the percentage of sulfur removal were 0.149 g, 15 mL, 11.96 min, and 70 MHz, respectively. Moreover, the kinetic aspects of the oxidation reaction of DBT in the UAOD process were investigated using a pseudo-first-order model. Furthermore, using the Arrhenius equation, an activation energy of 35.86 kJ mol⁻¹ was obtained. Additionally, thermodynamic analysis showed that the oxidation reaction of DBT was endothermic with a positive Gibbs free of energy, indicating the non-spontaneity of oxidation of DBT in the UAOD process. Moreover, the conversion rate of DBT has increased from 57% at 35 °C to 85% at 65 °C.

In this study, NiFe₂O₄–PEG, an effective nanocatalyst was synthesized via a hydrothermal method using different PEG concentrations and synthesis times.     

Thermosensitive alginate–gelatin–nitrogen-doped carbon dots scaffolds as potential injectable hydrogels for cartilage tissue engineering applications

Hybrid injectable and biodegradable hydrogels based on oxidized alginate/gelatin and containing nitrogen-doped carbon dots (NCDs) as a reinforcement have been fabricated and crosslinked by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS) as the chemical crosslinking agents in the hydrogel system. The idea of composite hydrogels relies on the assumption that they supply a microenvironment that is convenient for the exchange of nutrients via a porous structure and cell proliferation and have mechanical characteristics that approximately match natural tissue. The effect of the NCD content on the morphology structure, mechanical strength, swelling ratio, and biodegradation has been investigated. The results indicate that nanocomposite hydrogels containing a higher content of NCDs have smaller pore sizes and higher mechanical properties. The in vitro biodegradation and swelling behavior demonstrated that increasing the amount of NCDs up to 0.06% decreased the swelling ratio and weight loss of the hydrogels. The composite hydrogels are biocompatible, as verified by the MTT assay of MG-63 cells. The N-doped graphene quantum dots considerably affect degradation and interaction within the cells and hydrogels.

The low gelation time (120 s) and gelation temperature at body temperature (37 °C) make oxidized alginate/gelatin/NCDs hydrogels suitable as temperature-sensitive injectable hydrogels for cartilage tissue engineering.     

Magnetic Lu2Cu2O5-based ceramic nanostructured materials fabricated by a simple and green approach for an effective photocatalytic degradation of organic contamination

Designing and fabricating an efficient photocatalytic compound with an appropriate band gap to eliminate toxic contaminants is necessary to remediate the environment. This article presents the development of a new type of nanostructure, Lu₂Cu₂O₅–Lu₂O₃ nanocomposites to photo-catalytically degrade different kinds of toxic pollutants under sunlight. The oxide nanocomposites were fabricated via a quick and eco-friendly approach. In order to fabricate oxide nanostructures with appropriate features in terms of morphology and particle size, the effects of the kind of green reactant and its quantity were examined. Amylum was an appropriate and green reactant for the efficient synthesis of Lu₂Cu₂O₅–Lu₂O₃ nanobundles with the most organized morphology. The features of Lu₂Cu₂O₅-based nanostructures were carefully investigated utilizing multiple characterization methods. Then, the catalytic role of the fabricated nanobundles was evaluated for the removal of various kinds of toxic contaminants. The effects of the quantity of photocatalytic nanostructure, the concentration of the contaminant compound, and the type of light source in the catalytic degradation process were screened. The findings of this research demonstrated that utilizing 0.05 g of Lu₂Cu₂O₅–Lu₂O₃ nanobundles, 98.5% of the contaminant with a concentration of 10 ppm can be degraded in 2 h under ultraviolet light irradiation. The experimental results also certified that, during the photocatalytic pathway, superoxide radicals play a meaningful role in the elimination of toxic pollutants. To our knowledge, this is the first report of the fabrication of Lu₂Cu₂O₅–Lu₂O₃ nanocomposite through a facile and eco-friendly approach and its photocatalytic efficiency.

The synthesis of Lu₂Cu₂O₅–Lu₂O₃ nanocomposites via a simple auto-combustion approach and their excellent performance in the removal of organic pollutants under sunlight is presented for the first time.