Single-pill sofosbuvir and daclatasvir for treating hepatis C in patients co-infected with human immunodeficiency virus.

BACKGROUND: The current recommendation for treating hepatitis C virus (HCV) in HIV patients includes the combination of sofosbuvir (SOF) and daclatasvir (DCV). DCV should be used at different doses to compensate for interactions with antiretroviral therapy (ART). Up to three pills a day might be required which will significantly add to the pill burden of these patients. In this study, we have used a single-tablet approach to treating HCV-HIV coinfection. METHODS: Patients coinfected with HIV and HCV were prospectively enrolled from 10 centers throughout the country. Patients received a single once-daily fixed dose combination (FDC) pill containing 400 mg SOF and 30, 60 or 90 mg DCV depending on the type of ART they were receiving for 12 or 24 weeks. (ClinicalTrials.gov ID: NCT03369327). RESULTS: Two hundred thirty-three patients were enrolled from 10 centers. Twenty-three patients were lost to follow-up and two patients died from causes unrelated to treatment. Two hundred eight patients completed the treatment course of which 201 achieved SVR (96.6%). CONCLUSION: Single-tablet combination of DCV and SOF is an effective and safe treatment for patients coinfected with HIV and HCV. The combination works well in patients on ART in which dose adjustment is required. Patients with cirrhosis, previous treatment failure and various genotypes respond identically. The expenses of genotyping can be saved.

Pd Nanocatalyst Adorned on Magnetic Chitosan@N-Heterocyclic Carbene: Eco-Compatible Suzuki Cross-Coupling Reaction.

A novel magnetic-functionalized-multi-walled carbon nanotubes@chitosan N-heterocyclic carbene-palladium (M-f-MWCNTs@chitosan-NHC-Pd) nanocatalyst is developed in two steps. The first step entails the fabrication of a three-component cross-linking of chitosan utilizing the Debus-Radziszewski imidazole approach. The second step comprised the covalent grafting of prepared cross-linked chitosan to the outer walls of magnetically functionalized MWCNTs (M-f-MWCNTs) followed by introducing PdCl2 to generate the m-f-MWCNTs@cross-linked chitosan with a novel NHC ligand. The repeated units of the amino group in the chitosan polymer chain provide the synthesis of several imidazole units which also increase the number of Pd linkers thus leading to higher catalyst efficiency. The evaluation of catalytic activity was examined in the expeditious synthesis of biaryl compounds using the Suzuki cross-coupling reaction of various aryl halides and aryl boronic acids; ensuing results show the general applicability of nanocatalyst with superior conversion reaction yields, high turnover frequencies (TOFs) and turnover numbers (TON). Meanwhile, nanocatalyst showed admirable potential in reusability tests, being recycled for five runs without losing significant activities under optimum reaction conditions. The successfully synthesis of catalyst and its characterization was confirmed using the Fourier transform infrared spectrometer (FT-IR), spectrometer transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray photo-electron spectroscopy (XPS) and thermogravimetric analysis (TGA).

Application of poly 1,8-diaminonaphthalene/multiwalled carbon nanotubes-COOH hybrid material as an efficient sorbent for trace determination of cadmium and lead ions in water samples.

Poly 1,8-diaminonaphthalene/multiwalled carbon nanotubes-COOH hybrid material as an effective sorbents in solid phase extraction has been developed for the separation and preconcentration of Cd(II) and Pb(II) at trace levels in environmental water samples. The results indicate that the novel nanocomposite show a high affinity for these heavy metals due to the presence of several good extractive sites, which are introduced to the synthesized nanocomposite The maximum adsorption capacity of the synthesized sorbent for cadmium and lead ions was found to be 101.2 and 175.2 mg g(-1) , respectively. The detection limits of this method were 0.09 and 0.7 ng ml(-1) for Cd(II) and Pb(II), respectively.

Thin-film solid-phase microextraction of pesticides from cereal samples using electrospun polyvinyl alcohol/modified chitosan/porous organic framework nanofibers.

In this study, a coating of electrospun polyvinyl alcohol/modified chitosan/hydroxy-containing porous organic framework (PVA/MCS/HC-POF) was fabricated and applied as a novel sorbent for thin-film solid-phase microextraction of pesticides from cereal samples, followed by HPLC-UV. The successful fabrication of PVA/MCS/HC-POF was confirmed through characterization tests. The functional group of MCS and a large number of hydroxyl groups on the HC-POF structure contributed to the co-extraction of pesticides. Under the optimum conditions, the calibration plots were linear within the range of 5.0-800 ng mL-1 (r2 ≥ 0.978), and the limits of detection were obtained below 4.0 ng mL-1. The method's precision was investigated through intra-day, inter-day, and film-to-film RSD (%) measurements, all of which were less than 6.5 %, 8.2 %, and 10.0 %, respectively. Furthermore, satisfactory recoveries ranging from 63.3 % to 79.0 % were obtained. Accordingly, the proposed method can be considered a suitable alternative for measuring trace amounts of pesticides in cereal samples.

Highly selective and sensitive recognition of multi-ions in aqueous solution based on polymer-grafted nanoparticle as visual colorimetric sensor.

A novel, selective and sensitive colorimetric sensor for naked-eye detection and adsorption of multi-ions in aqueous solution was synthesized using hybridization of organic-inorganic phase. The polymer-grafted nanoparticles (PGNPs) was synthesized via atom transfer radical polymerization (ATRP) of monomers on modified TiO2 NPs and applied under optimized conditions for naked-eye detection: sensor mass: 15 mg; response time: 30 s with limits of detection (LODs) as small as 10, 1, 0.5, and 1 ppb Hg (II), Cd (II), Cu (II), and UO2 (II) at pH = 8, 9, 6, and 7, respectively. The efficient selectivity of the naked eye sensor to multi-ions in the presence of various ions was affirmed wherein the color of the chemosensor in the presence of Hg (II), Cd (II), Cu (II), and UO2 (II) shifted from gray to violet, orange, green and yellow, respectively. The salient advantages of this method comprise expeditious, selectable, high reproducibility, with reasonable adsorption capacity (133 mg g-1) and inexpensive nature for rapid detection of heavy metal ions contamination in aqueous solution in an inexpensive manner. The adsorption mechanism was studied via adsorption kinetics and adsorption isotherm models and the accuracy of the chemosensor has been confirmed and supported by XRD, FT-IR, TGA, 1H-NMR, SEM, TEM, EDX mapping, DLS, BET, and EDS analysis.

Thermoresponsive in situ forming and self-healing double-network hydrogels as injectable dressings for silymarin/levofloxacin delivery for treatment of third-degree burn wounds.

Our study aimed to introduce a novel double-cross-linked and thermoresponsive hydrogel with remarkable potential for accelerating third-degree burn wound healing. Burn injuries are recognized as challenging, critical wounds. Especially in third-degree burns, treatment is demanding due to extended wounds, irregular shapes, significant exudation, and intense pain during dressing changes. In this work, hydrogels made of zwitterionic chitosan and dialdehyde starch (ZCS and ZDAS) were created to deliver silymarine (SM) and levofloxacin (LEV). The hydrogels were effortlessly produced using dynamic Schiff base linkages and ionic interactions between ZCS and ZDAS at appropriate times. The pore uniformity, gel fraction, and commendable swelling properties can imply a suitable degree of Schiff base cross-link. The hydrogel demonstrated outstanding shape retention, and significant self-healing and flexibility abilities, enabling it to uphold its form even during bodily movements. After injecting biocompatible hydrogel on the wound, a notable acceleration in wound closure was observed on day 21 (98.1 ± 1.10 %) compared to the control group (75.1 ± 6.13 %), and histopathological analysis revealed a reduction of inflammation that can be linked to remarkable antioxidant and antibiotic properties. The results demonstrate the hydrogel's efficacy in promoting burn wound healing, making it a promising candidate for medical applications.

Development of PVA/Chitosan-g-Poly (N-vinyl imidazole)/TiO2/curcumin nanofibers as high-performance wound dressing.

In this study, electrospun Poly(vinyl alcohol)/Chitosan-g-Poly (N-vinyl imidazole) (PVA/CS-g-PNVIM) wound dressing containing Titanium dioxide/Curcumin (CUR) was prepared as a novel wound healing system with multifunctional properties, including wound closure, drug release, and antibacterial activity. The wound dressing nanofibers system's mechanical, structural, and biological properties were investigated using tensile testing, degradation, X-ray diffraction, Scanning electron microscopy, Fourier transformed infrared spectroscopy, drug release, and in vivo studies. The nanofiber dressing showed excellent mechanical and hydrolytic degradation stability. CS-g-PNVIM-based nanofibers showed excellent antibacterial activity against both Escherichia coli and Staphylococcus aureus in just 1 h with 90 % growth inhibition, with no cytotoxicity to normal fibroblast cells. The animal studies showed that the wound healing and tissue regeneration process by CS-g-PNVIM-based nanofibers were faster than the control group and was completed in 14 days. In conclusion, the CS-g-PNVIM-based nanofibers are potentially promising for biocompatible antibacterial wound dressing applications with proper exudate absorption.

Preparation of chitosan biguanidine/PANI-containing self-healing semi-conductive waterborne scaffolds for bone tissue engineering.

Electrically conducting self-healing scaffolds are known as a new series of intelligent biomaterial for regulating Human Adipose Mesenchymal Stem Cells biological behaviors, especially their differentiation to bone cells. Herein, we developed a novel hydrophilic semi-conductive chitosan derivative (CP) and loaded it into the self-healing waterborne polyurethane structure, as a new osteogenic agent. The fabricated scaffolds exhibited excellent shape memory properties with shape fixity (> 97 %) and shape recovery ratio (> 98 %) with excellent self-healing value (> 93 %) at a temperature close to the body temperature. The results of MTT, cell attachment, alkaline phosphatase activity, and alizarin red staining analysis demonstrated that the CP-contained scaffolds promote proliferation of hADSCs and matrix mineralization. Also, by introducing the CP the gene expression level of COL-1, ALP, RUNX2, and OCN were significantly enhanced, in line with matrix mineralization. These multifunctional engineered constructs are promising biomaterials for repairing various bone defects.

Bioactive chitosan biguanidine-based injectable hydrogels as a novel BMP-2 and VEGF carrier for osteogenesis of dental pulp stem cells.

Nowadays, vascularization and mineralization of bone defects is the main bottleneck in the bone regeneration field that is needed to be overcome and developed. Here, we prepared novel in-situ formed injectable hydrogels based on chitosan biguanidine and carboxymethylcellulose loaded with vascular endothelial growth factor (VEGF) and recombinant Bone morphogenetic protein 2 (BMP-2) and studied its influence on osteoblastic differentiation of dental pulp stem cells (DPSCs). The sequential release behavior of the VEGF and BMP-2 from hydrogels adjusted with the pattern of normal human bone growth. MTT assay exhibited that these hydrogels were non-toxic and significantly increased DPSCs proliferation. The Real-time PCR and Western blot analysis on CG11/BMP2-VEGF showed significantly higher gene and protein expression of ALP, COL1α1, and OCN. These results were confirmed by mineralization assay by Alizarin Red staining and Alkaline phosphatase enzyme activity. Based on these evaluations, these hydrogel holds potential as an injectable bone tissue engineering platform.

Electrospun triazole-based chitosan nanofibers as a novel scaffolds for bone tissue repair and regeneration.

For the first time, the novel type of guided bone regeneration composite nanofibers were prepared by grafting polycaprolactone (PCL) to chitosan (CS) using the copper (I) - catalyzed azide-alkyne cycloaddition (CuAAC) reaction. For improve the bioactivity of scaffolds the magnesium-doped hydroxyapatite (Mg-HA) was used. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and proton nuclear magnetic resonance (1H NMR) were applied to characterize the prepared scaffolds. The SEM observations show defect-free uniform composite nanofibers with about 419-495 nm diameter. The in vitro cell viability test (MTT assay) show that fabricated scaffolds don't have any significant cytotoxicity. Also, osteoblast-like MG63 cells cultured on the nanofibers which prepared through CuAAC reaction (CS-g-PCL/Mg-HA) show higher antibacterial activity, mechanical properties, and cell attachment compared to CS/PCL/Mg-HA blend scaffolds. Moreover, the Alkaline phosphatase (ALP) activity and Alizarin red S (ARS) staining showed that the introduction of the triazole ring into the chemical structure of the copolymer enhanced bone mineralization ability of the scaffolds. These results suggested that this novel scaffold provides an interesting option for bone repair and regeneration.

Efficacy of Sovodak in the Management of Patients Co-infected with HIV/HCV.

Purpose: Sofosbuvir (SOF) and daclatasvir (DOC) are suggested for the treatment of hepatitis C virus (HCV) in patients with concomitant HCV and human immunodeficiency virus (HIV). In 2016, Sovodak tablet a combination of SOF and DOC was introduced. In the present study we assessed the effectiveness of SOF in the treatment of HCV in patients co-infected with HIV. Methods: A total of 26 HCV patients co-infected with HIV received SOF for 3 months. One patient did not adhere to the drug protocol and was removed from the final analysis. The blood sample for qualitative polymerase chain reaction (PCR) was obtained after treatment and sustained virological response (SVR) was calculated. Results: Twenty five patients finished the study. The mean patients' age was 44.16±6.21 years. About 72% of participants had HCV genotype 1a, 8% genotype 1b, and 20% genotype 3a. After 3 months of intervention with Sovodak, the SVR12 was about 96%. None of the patients reported any adverse events. Conclusion: For the first time, the results of the present study showed that Sovodak had high SVR12 in HCV patients co-infected with HIV. However, for a precise conclusion, there is a need for larger studies and an equal number of patients with different virus genotypes.

Fabrication of nanochitosan incorporated polypyrrole/alginate conducting scaffold for neural tissue engineering.

The utilization of conductive polymers for fabrication of neural scaffolds have attracted much interest because of providing a microenvironment which can imitate nerve tissues. In this study, polypyrrole (PPy)-alginate (Alg) composites were prepared using different percentages of alginate and pyrrole by oxidative polymerization method using FeCl3 as an oxidant and electrical conductivity of composites were measured by four probe method. In addition, chitosan-based nanoparticles were synthesized by ionic gelation method and after characterization merged into PPy-Alg composite in order to fabricate a conductive, hydrophilic, processable and stable scaffold. Physiochemical characterization of nanochitosan/PPy-Alg scaffold such as electrical conductivity, porosity, swelling and degradation was investigated. Moreover, cytotoxicity and proliferation were examined by culturing OLN-93 neural and human dermal fibroblasts cells on the Nanochitosan/PPy-Alg scaffold. Due to the high conductivity, the film with ratio 2:10 (PPy-Alg) was recognized more suitable for fabrication of the final scaffold. Results from FT-IR and SEM, evaluation of porosity, swelling and degradation, as well as viability and proliferation of OLN-93 neural and fibroblast cells confirmed cytocompatiblity of the Nanochitosan/PPy-Alg scaffold. Based on the features of the constructed scaffold, Nanochitosan/PPy-Alg scaffold can be a proper candidate for neural tissue engineering.

Efficient Optical and UV-Vis Chemosensor Based on Chromo Probes-Polymeric Nanocomposite Hybrid for Selective Recognition of Fluoride Ions.

A novel colorimetric sensor based on the TiO2/poly(acrylamide-co-methylene bis acrylamide-co-2-(3-(4-nitro-phenyl)thioureido)ethyl methacrylate) nanocomposite was synthesized via a surface modification strategy; methacryloxypropyltrimethoxysilane was used to provide reactive vinyl groups on the surface of TiO2 nanoparticles for the successful surface polymerization of Am (acrylamide), MBA (methylenbisacrylamide), and NPhM (2-(3-(4-nitrophenyl)thioureido)ethyl methacrylate) components. The successful preparation of nanocomposites was confirmed using Fourier transform infrared, 1H NMR, 13C NMR, scanning electron microscopy, transmission electron microscopy, thermogravimetry analysis, and X-ray diffraction methods, and the sensing ability of the probe toward fluoride ions was investigated using naked-eye detection and UV-vis measurement. The interaction of the prepared polymeric nanocomposite with fluoride ions elicited a significant visible change in color from pale yellow to orange and was further affirmed by a clean interconversion of the two absorption bands at 330 and 485 nm. The selective binding ability of the polymeric nanocomposite towards fluoride over other anions, such as I-, Cl-, Br-, AcO-, H2PO4 -, and H2SO4 - was further explored; the prepared chemosensor could detect fluoride ions in acetonitrile with a detection limit of 3 µM.

Estimation of formaldehyde occupational exposure limit based on genetic damage in some Iranian exposed workers using benchmark dose method.

The present study evaluated an occupational exposure level for formaldehyde employing benchmark dose (BMD) approach. Dose-response relationship was determined by utilizing cumulative occupational exposure dose and DNA damage. Based on this goal, outcome of comet assay for some Iranian exposed people in occupational exposure individuals was used. In order to assess formaldehyde exposure, 53 occupationally exposed individuals selected from four melamine tableware workshops and 34 unexposed subjects as a control group were examined. The occupational exposure dose was carried out according to the NIOSH-3500 method, and the DNA damage was obtained by employing comet assay in peripheral blood cells. EPA Benchmark Dose Software was employed for calculating BMD and BMDL. Cumulative exposure dose of formaldehyde was between of 2.4 and 1972 mg. According to the findings of the current study, the induction of DNA damage in the exposed persons was increased tail length and tail moment (p < 0.001), when compared to controls. Finally, an acceptable dose-response relationship was obtained in three-category information between formaldehyde cumulative exposure doses and genetic toxicity. BMDL was 0.034 mg/m3 (0.028 ppm), corresponding to genetic damage of peripheral blood cells. It can be concluded that the occupational permissible limit in Iranian people could be at levels lower than OSHA standards.

Thermo-responsive molecularly imprinted polymer containing magnetic nanoparticles: Synthesis, characterization and adsorption properties for curcumin.

A novel intelligent thermoresponsive-magnetic molecularly imprinted polymer (TMMIP) nanocomposite based on N-isopropylacrylamide (NIPAM) & Fe3O4 was designed for the controlled & sustained release of Curcumin (CUR) with the ability to response external stimulus. The TMMIP nanocomposite was prepared using acryl functionalized ß-cyclodextrin (ß-CD) and NIPAM as functional monomers and CUR as target molecule. The recognition cavities which caused by host-guest interactions had direct influence to enhanced drug loading and sustained release of CUR. According to in-vitro release experiment in two different temperatures (below & above LCST of NIPAM) the prolonged & controlled release of CUR were observed. The release rate could be controlled by changing the temperature because of the phase transition behavior of NIPAM monomer. Also, the proposed biosensor displayed effective role in separation science, reasonable adsorption capacity (77mgg-1), fast recognition (10min equilibration), selective extraction toward CUR in the presence of structural analogues and easily separation using external magnetic field. Moreover, the synthesized TMMIP was confirmed by various characterization.

Novel magnetic ion-imprinted polymer: an efficient polymeric nanocomposite for selective separation and determination of Pb ions in aqueous media.

A novel ion-imprinted polymer (IIP) toward Pb(II) recognition was synthesized on the surface of magnetic multi-walled carbon nanotubes (magnetic MWCNTs). In order to prepare magnetic functionalized-MWCNT/IIP (magnetic f-MWCNT/IIP), copolymerization of methylenebisacrylamide (MBAm) and acrylamide (AM) in the presence of dithizone-Pb(II) complex was carried out on the surface of the magnetic f-MWCNTs. Selectivity of the new synthesized sorbent toward Pb(II) and the influence of a variety of foreign ions on the recognition, preconcentration, and removal of Pb(II) were evaluated using adsorption experiments in aqueous solution. The synthesized sorbent exhibited a good affinity with high adsorption capacity (Q = 80.81 mg/g) and an excellent selectivity toward Pb(II) in comparison with other common cations including alkaline, alkaline earth, and transition metals such as Na+, K+, Mg2+, Ca2+, Cd2+, and Ni2+. The parameters such as adsorption and desorption time, adsorption capacity, effect of the sorbent mass, eluent type, concentration and volume, and also pH of the solutions were investigated. The result demonstrated that the proposed sorbent provided a fast removal and higher maximum binding capacity compared to other reported synthesized sorbents. The characteristics of the magnetic f-MWCNT/IIP were analyzed using Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), X-ray diffraction (XRD), energy-dispersive spectroscopy (EDS), vibrating sample magnetometer (VSM), and elemental analysis (EA). Graphical abstract ᅟ.

Novel molecularly imprinted polymer based on ß-cyclodextrin@graphene oxide: Synthesis and application for selective diphenylamine determination.

A sensitive and selective molecularly imprinted polymer (MIP) for the determination of diphenylamine (DPA) was developed based on host-guest interactions of a cyclodextrin-based polymer which possesses an inherent affinity for the target. The proposed GO@MIP has been prepared using the graphene oxide (GO) sheets as surface of polymerization, DPA as target molecule, ß-cyclodextrin (ß-CD) and acrylamide (AM) as functional monomers, azobisisobutyronitrile (AIBN) as initiator and N, N methylene bisacrylamide (MBAm) as crosslinker which denoted as GO@MIP nanocomposite. The MIP sites were formed by the inclusion complex through interaction of DPA and ß-CD, followed by extraction of target. The resulting GO@MIP nanocomposite possess a fast adsorption kinetics, highly improved imprinting effect, high adsorption capacity, and it can be applied to fast extraction of DPA. The resultant GO@MIP nanocomposite was characterized using the Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA) scanning electron microscope (SEM) and energy-dispersive spectroscopy (EDS) analysis. On the other hand, the non-imprinted polymer (GO@NIP nanocomposite) has been synthesized and was used in the adsorption experiments. The MIP exhibited good affinity with a maximum adsorption capacity of 95.98mgg-1 and excellent selectivity toward DPA than other structural analogues such as 2-amino benzophenone and dithizone.

Biocompatible electrospinning chitosan nanofibers: A novel delivery system with superior local cancer therapy.

In this study, an electrospinning technique was used for the fabrication of novel biomedicated nanofibers which are applied for preventing wound infections and local chemotherapy. CURs containing nanofibers with a crosslinking agent (Si-O-Si network) have been produced through functionalization of graphene oxide with APTES. In vitro drug release profile results showed the novel nanofibers could limit the drug's initial burst release and provide better sustainability in comparison with the blend nanofibers without modified GO. The novel delivery vehicle can inhibit the growth of MRSA and S. epidermidis up to 94% and 88%. Also in vitro cell toxicity experiments which were performed by XTT method on MCF-7, HEP G2 and L929 cell lines showed that anticancer activity of CUR remained intact even after loading into nanofibers. This result suggested that the fGO-Si-CUR including nanofibers were a promising candidate for postoperative chemotherapy.

Synthesis, characterization and application of poly(acrylamide-co-methylenbisacrylamide) nanocomposite as a colorimetric chemosensor for visual detection of trace levels of Hg and Pb ions.

In this study, a new colorimetric chemosensor based on TiO2/poly(acrylamide-co-methylenbisacrylamide) nanocomposites was designed for determination of mercury and lead ions at trace levels in environmental samples. The removal and preconcentration of lead and mercury ions on the sorbent was achieved due to sharing an electron pair of N and O groups of polymer chains with the mentioned heavy metal ions. The hydrogel sensor was designed by surface modification of a synthesized TiO2 nanoparticles using methacryloxypropyltrimethoxysilan (MAPTMS), which provided a reactive C=C bond that polymerized the acrylamide and methylenbisacrylamide. The sorbent was characterized using X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscope (SEM), EDS analysis and Fourier transform in frared (FT-IR) spectrometer. This nanostructured composite with polymer shell was developed as a sensitive and selective sorbent for adsorption of mercury and lead ions from aqueous solution at optimized condition. This method involves two-steps: (1) preconcentration of mercury and lead ions by the synthesized sorbent and (2) its selective monitoring of the target ions by complexation with dithizone (DZ). The color of the sorbent in the absence and presence of mercury and lead ions shifts from white to violet and red, respectively. The detection limit of the synthesized nanochemosensor for mercury and lead ions was 1 and 10 µg L(-1), respectively. The method was successfully applied for trace detection of mercury and lead ions in tap, river, and sea water samples.