Reactive Oxygen Species Responsive Naturally Occurring Phenolic-Based Polymeric Prodrug.

Reactive Oxygen Species (ROS) play a vital role in the biological system. Exaggerated, ROS have devastating effects on the human body leading to the pathophysiological condition including the transformation of a normal cell into a cancer phenotype. Nature has blessed us with various biomolecules that we use along with our dietary supplements. Using such therapeutic small molecules covalently incorporated into biodegradable polyoxalate polymer backbone with a responsive group forms an efficient drug delivery vehicle. This chapter "Reactive oxygen species responsive naturally occurring phenolic-based polymeric prodrug" will be focusing on redox-responsive polymers incorporated with naturally occurring phenolics and clinical application.

Diastereomers of Coibamide A Show Altered Sec61 Client Selectivity and Ligand-Dependent Activity against Patient-Derived Glioma Stem-like Cells.

Coibamide A (CbA) is a cyanobacterial lariat depsipeptide that selectively inhibits multiple secreted and integral membrane proteins from entering the endoplasmic reticulum secretory pathway through binding the alpha subunit of the Sec61 translocon. As a complex peptide-based macrocycle with 13 stereogenic centers, CbA is presumed to adopt a conformationally restricted orientation in the ligand-bound state, resulting in potent antitumor and antiangiogenic bioactivity. A stereochemical structure-activity relationship for CbA was previously defined based on cytotoxicity against established cancer cell lines. However, the ability of synthetic isomers to inhibit the biosynthesis of specific Sec61 substrates was unknown. Here, we report that two less toxic diastereomers of CbA, [L-Hiv2]-CbA and [L-Hiv2, L-MeAla11]-CbA, are pharmacologically active Sec61 inhibitors. Both compounds inhibited the expression of a secreted reporter (Gaussia luciferase), VEGF-A, and a Type 1 membrane protein (VCAM1), while [L-Hiv2]-CbA also decreased the expression of ICAM1 and BiP/GRP78. Analysis of 43 different chemokines in the secretome of SF-268 glioblastoma cells revealed different inhibitory profiles for the two diastereomers. When the cytotoxic potential of CbA compounds was compared against a panel of patient-derived glioblastoma stem-like cells (GSCs), Sec61 inhibitors were remarkably toxic to five of the six GSCs tested. Each ligand showed a distinct cytotoxic potency and selectivity pattern for CbA-sensitive GSCs, with IC50 values ranging from subnanomolar to low micromolar concentrations. Together, these findings highlight the extreme sensitivity of GSCs to Sec61 modulation and the importance of ligand stereochemistry in determining the spectrum of inhibited Sec61 client proteins.

Wide linear-range detecting nonenzymatic glucose biosensor based on CuO nanoparticles inkjet-printed on electrodes.

Inkjet-printed copper oxide nanoparticles (CuO NPs) on silver electrodes were used to fabricate the nonenzymatic glucose biosensor. The inkjet-printed CuO NPs electrodes produced high and reproducible sensitivity of 2762.5 µAm M(-1) cm(-2) at an applied potential of +0.60 V with the wide linear-detecting range of 0.05-18.45 mM and the detection limit of ~0.5 µM (S/N = 3). The long-term stability and reproducibility of sensor in glucose electro-oxidation resulted from the chemical stability of CuO NPs and pore-like structure formed on Ag surface, which prevented the CuO NPs from conglomeration and the interference of oxygen in the air. Significantly, the effect of interfering species, such as AA, UA, and DA were negligible, whereas sugar derivatives (lactose, fructose, and mannose) show insignificant interference. Finally, the electrode was applied to analyze glucose concentration in human serum samples.

Time-dependent control of hole-opening degree of porous ZnO hollow microspheres.

Well-designed, monodispersed porous ZnO hollow microspheres with controlled hole-opening were successfully synthesized by a facile two-step solution route at low temperature. The hollow microspheres having average diameter of 3-4 µm showed time-dependent hole-opening, i.e. 4-100% for 15-75 min. The hole-opening percentage increases linearly with time until complete opening. The ZnO hollow microspheres also exhibited a high surface area (34 m(2) g(-1)), a large pore volume (0.19 cm(3) g(-1)) and an average pore diameter of 3.8 nm. A plausible growth mechanism for the formation of ZnO hollow microspheres was also proposed.

Biosynthesized gold nanoparticles maintained nitrogen metabolism, nitric oxide synthesis, ions balance, and stabilizes the defense systems to improve salt stress tolerance in wheat.

Green synthesis of nanoparticles (NPs) is competent in inducing physiological responses in plants for combating the abiotic stresses. Considering this, salt stress is one of the most alarming conditions that exerts complex and polygenic impacts on morph-physiological functioning of plants; resulting in reduced crop productivity and yield. Therefore, understanding the salt responses and tolerance mechanisms are important for sustaining crop productivity. In the current study, we have examined the effects of biosynthesized gold nanoparticles (AuNPs) on wheat (Triticum aestivum) plants under salt stress. Green-synthesized AuNPs were found beneficial in modulating the K+/Na+ ratio, chlorophyll concentration, defense systems, nitrogen assimilation, stomatal dynamics and growth traits under salt stress condition. Furthermore, the excessive accumulation of oxidative stress markers including reactive oxygen/nitrogen species was controlled in response of AuNPs treatment under salt stress. Overall, modulation of these traits commanded to induce salt stress tolerance in wheat plants.

Targeting and therapeutic peptide-based strategies for polycystic kidney disease.

Polycystic kidney disease (PKD) is characterized by progressive cyst growth and is a leading cause of renal failure worldwide. Currently, there are limited therapeutic options available to PKD patients, and only one drug, tolvaptan, has been FDA-approved to slow cyst progression. Similar to other small molecule drugs, however, tolvaptan is costly, only moderately effective, and causes adverse events leading to high patient dropout rates. Peptides may mitigate many drawbacks of small molecule drugs, as they can be highly tissue-specific, biocompatible, and economically scaled-up. Peptides can function as targeting ligands that direct therapies to diseased renal tissue, or be potent as therapeutic agents themselves. This review discusses various aberrant signaling pathways in PKD and renal receptors that can be potential targets of peptide-mediated strategies. Additionally, peptides utilized in other kidney applications, but may prove useful in the context of PKD, are highlighted. Insights into novel peptide-based solutions that have potential to improve clinical management of PKD are provided.

Transdermal Delivery of Kidney-Targeting Nanoparticles Using Dissolvable Microneedles.

INTRODUCTION: Chronic kidney disease (CKD) affects approximately 13% of the world's population and will lead to dialysis or kidney transplantation. Unfortunately, clinically available drugs for CKD show limited efficacy and toxic extrarenal side effects. Hence, there is a need to develop targeted delivery systems with enhanced kidney specificity that can also be combined with a patient-compliant administration route for such patients that need extended treatment. Towards this goal, kidney-targeted nanoparticles administered through transdermal microneedles (KNP/MN) is explored in this study. METHODS: A KNP/MN patch was developed by incorporating folate-conjugated micelle nanoparticles into polyvinyl alcohol MN patches. Rhodamine B (RhB) was encapsulated into KNP as a model drug and evaluated for biocompatibility and binding with human renal epithelial cells. For MN, skin penetration efficiency was assessed using a Parafilm model, and penetration was imaged via scanning electron microscopy. In vivo, KNP/MN patches were applied on the backs of C57BL/6 wild type mice and biodistribution, organ morphology, and kidney function assessed. RESULTS: KNP showed high biocompatibility and folate-dependent binding in vitro, validating KNP's targeting to folate receptors in vitro. Upon transdermal administration in vivo, KNP/MN patches dissolved within 30 min. At varying time points up to 48 h post-KNP/MN administration, higher accumulation of KNP was found in kidneys compared with MN that consisted of the non-targeting, control-NP. Histological evaluation demonstrated no signs of tissue damage, and kidney function markers, serum blood urea nitrogen and urine creatinine, were found to be within normal ranges, indicating preservation of kidney health. CONCLUSIONS: Our studies show potential of KNP/MN patches as a non-invasive, self-administrable platform to direct therapies to the kidneys.

Metal oxide modified ZnO nanomaterials for biosensor applications.

Advancing as a biosensing nanotechnology, nanohybrids present a new class of functional materials with high selectivity and sensitivity, enabling integration of nanoscale chemical/biological interactions with biomedical devices. The unique properties of ZnO combined with metal oxide nanostructures were recently demonstrated to be an efficient approach for sensor device fabrication with accurate, real-time and high-throughput biosensing, creating new avenues for diagnosis, disease management and therapeutics. This review article collates recent advances in the modified ZnO nanostructured metal oxide nanohybrids for efficient enzymatic and non-enzymatic biosensor applications. Furthermore, we also discussed future prospects for nanohybrid materials to yield high-performance biosensor devices.

Quercetin Inlaid Silk Fibroin/Hydroxyapatite Scaffold Promotes Enhanced Osteogenesis.

There is a significant rise in the bone grafts demand worldwide to treat bone defects owing to continuous increase in conditions such as injury, trauma, diseases, or infections. Therefore, development of three-dimensional scaffolds has evolved as a reliable technology to address the current limitations for bone tissue regeneration. Mimicking the natural bone, in this study, we have designed a silk fibroin/hydroxyapatite scaffold inlaid with a bioactive phytochemical (quercetin) at different concentrations for promoting osteogenesis, especially focusing on quercetin ability for enhancing bone health. Characterization of the quercetin/silk fibroin/hydroxyapatite (Qtn/SF/HAp) scaffolds showed an increased pore size and irregular porous microstructure with good mechanical strength. The Qtn (low-content)/SF/HAp scaffold was found to be an efficient cell carrier facilitating cellular growth, osteogenic differentiation, and proliferation as compared to SF/HAp and Qtn (high-content)/SF/HAp scaffolds. However, Qtn (high-content)/SF/HAp was observed to inhibit cell proliferation without any effects on cell viability. In vitro and in vivo outcomes studied using bone marrow-derived mesenchymal stem cells (rBMSCs) confirm the cytocompatibility, osteogenic differentiation ability, and prominent upregulation of the bone-specific gene expressions for the rBMSCs-seeded Qtn/SF/HAp scaffolds. In particular, the implanted Qtn (low-content)/SF/HAp scaffolds at the bone defect site were found to be well-attached and amalgamated with the surrounding tissues with approximately 80% bone volume recovery at 6 weeks after surgery as compared with other groups. Based on the aforementioned observations highlighting the quercetin efficiency for bone regeneration, the as-synthesized Qtn (low-content)/SF/HAp scaffolds can be envisioned to provide a biomimetic bone-like microenvironment promoting rBMSCs differentiation into osteoblast, thus suggesting a potential alternative graft for high-performance regeneration of bone tissues.

Preparation of a Highly Conductive Seed Layer for Calcium Sensor Fabrication with Enhanced Sensing Performance.

The seed layer plays a crucial role in achieving high electrical conductivity and ensuring higher performance of devices. In this study, we report fabrication of a solution-gated field-effect transistor (FET) sensor based on zinc oxide nanorods (ZnO NRs) modified iron oxide nanoparticles (α-Fe2O3 NPs) grown on a highly conductive sandwich-like seed layer (ZnO seed layer/Ag nanowires/ZnO seed layer). The sandwich-like seed layer and ZnO NRs modification with α-Fe2O3 NPs provide excellent conductivity and prevent possible ZnO NRs surface damage from low pH enzyme immobilization, respectively. The highly conductive solution-gated FET sensor employed the calmodulin (CaM) immobilization on the surface of α-Fe2O3-ZnO NRs for selective detection of calcium ions (Ca2+). The solution-gated FET sensor exhibited a substantial change in conductance upon introduction of different concentrations of Ca2+ and showed high sensitivity (416.8 µA cm-2 mM-1) and wide linear range (0.01-3.0 mM). In addition, the total Ca2+ concentration in water and serum samples was also measured. Compared to the analytically obtained data, our sensor was found to measure Ca2+ in the water and serum samples accurately, suggesting a potential alternative for Ca2+ determination in water and serum samples, specifically used for drinking/irrigation and clinical analysis.

Three-dimensional duck's feet collagen/PLGA scaffold for chondrification: role of pore size and porosity.

An ideal tissue-engineered scaffold must provide sufficient porosity to allow free movement of cells, nutrients, and oxygen for proper cell growth and further maintenance. Owing to variation in pore sizes and shapes of as-fabricated scaffold, the amount of oxygen available for the cells attached to the scaffold and transfer of by-products and excrement will be different, which ultimately results in cell activity. Thus, optimizing pore size and porosity of a scaffold for a specific tissue regeneration are one of the key highlights, which should be considered while designing a scaffold as well as choosing a specific cell type. In this study, three-dimensional (3D) scaffolds based on blends of duck's feet collagen (DC) and poly (lactic-co-glycolic acid) (PLGA) with different pore sizes i.e. 90-180, 180-250, 250-355 and 355-425 µm were prepared using solvent casting/salt leaching approach and examined its effects on chondrification. The morphological analysis of the as-fabricated scaffolds was performed using SEM for studying porosity and pore size. The cell proliferation and gene expression were investigated after culturing costal chondrocytes on each scaffolds using 3-(4, 5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay and qRT-PCR. Histological staining of in vivo implants was performed in nude mice as models. The biological evaluation showed a pore-size dependent chondrification at different time points. Especially, the 355-425 µm DC/PLGA scaffold showed a highest positive impact on maintenance of cell proliferation, costal chondrocyte phenotype and increased glycosaminoglycan accumulation than the other groups. These results indicated that DC/PLGA scaffolds with pore size ranging from 250 to 425 µm can be considered as highly-suitable constructs for enhanced chondrification.

Highly stable hydrazine chemical sensor based on vertically-aligned ZnO nanorods grown on electrode.

Herein, we report a binder-free, stable, and high-performance hydrazine chemical sensor based on vertically aligned zinc oxide nanorods (ZnO NRs), grown on silver (Ag) electrode via low-temperature solution route. The morphological characterizations showed that the NRs were grown vertically in high density and possess good crystallinity. The as-fabricated hydrazine chemical sensors showed an excellent sensitivity of 105.5 µAµM-1cm-2, a linear range up to 98.6µM, and low detection limit of 0.005µM. It also showed better long-term stability, good reproducibility and selectivity. Furthermore, the fabricated electrodes were evaluated for hydrazine detection in water samples. We found the approach of directly growing nanostructures as a key factor for enhanced sensing performance of our electrodes, which effectively transfers electron from ZnO NRs to conductive Ag electrode. Thus it holds future prospective applications as binder-free, cost-effective, and stable sensing devices fabrication.

Development of highly-stable binder-free chemical sensor electrodes for p-nitroaniline detection.

Herein, pre-seeded fluorine doped tin oxide (FTO) glass substrates were used as an electrode for zinc oxide nanorods (ZnO NRs) growth by a low-temperature solution route in order to fabricate binder-free high-sensitive chemical sensor. The vertically-grown ZnO NRs exhibited a more favorable active morphology and improved sensing properties for p-nitroaniline (pNA) detection. On investigation with different concentrations of pNA, the ZnO NRs/FTO electrode showed an excellent sensitivity (10.18µAµM-1cm-2) and low detection limit (0.5µM) with good selectivity, outstanding long-term stability, and high reproducibility. Collectively, the present work emphasizes the potency of ZnO NRs/FTO electrodes for fabrication of an efficient and reliable chemical sensing device with improved performances.

Solution Process Synthesis of High Aspect Ratio ZnO Nanorods on Electrode Surface for Sensitive Electrochemical Detection of Uric Acid.

This study demonstrates a highly stable, selective and sensitive uric acid (UA) biosensor based on high aspect ratio zinc oxide nanorods (ZNRs) vertical grown on electrode surface via a simple one-step low temperature solution route. Uricase enzyme was immobilized on the ZNRs followed by Nafion covering to fabricate UA sensing electrodes (Nafion/Uricase-ZNRs/Ag). The fabricated electrodes showed enhanced performance with attractive analytical response, such as a high sensitivity of 239.67 µA cm-2 mM-1 in wide-linear range (0.01-4.56 mM), rapid response time (~3 s), low detection limit (5 nM), and low value of apparent Michaelis-Menten constant (Kmapp, 0.025 mM). In addition, selectivity, reproducibility and long-term storage stability of biosensor was also demonstrated. These results can be attributed to the high aspect ratio of vertically grown ZNRs which provides high surface area leading to enhanced enzyme immobilization, high electrocatalytic activity, and direct electron transfer during electrochemical detection of UA. We expect that this biosensor platform will be advantageous to fabricate ultrasensitive, robust, low-cost sensing device for numerous analyte detection.

Osteogenesis evaluation of duck's feet-derived collagen/hydroxyapatite sponges immersed in dexamethasone.

BACKGROUND: The aim of this study was to investigate the osteogenesis effects of DC and DC/HAp sponge immersed in without and with dexamethasone. METHODS: The experimental groups in this study were DC and DC/HAp sponge immersed in without dexamethasone (Dex(-)DC and Dex(-)-DC/HAp group) and with dexamethasone (Dex(+)-DC and Dex(+)-DC/HAp group). We characterized DC and DC/HAp sponge using compressive strength, scanning electron microscopy (SEM). Also, osteogenic differentiation of BMSCs on sponge (Dex(-)DC, Dex(-)-DC/HAp, Dex(+)-DC and Dex(+)-DC/HAp group) was assessed by SEM, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide (MTT) assay, alkaline phosphatase (ALP) activity assay and reverse transcription-PCR (RT-PCR). RESULTS: In this study, we assessed osteogenic differentiation of BMSCs on Duck's feet-derived collagen (DC)/HAp sponge immersed with dexamethasone Dex(+)-DC/HAp. These results showed that Dex(+)-DC/HAp group increased cell proliferation and osteogenic differentiation of BMSCs during 28 days. CONCLUSION: From these results, Dex(+)-DC/HAp can be envisioned as a potential biomaterial for bone regeneration applications.

Highly Efficient Non-Enzymatic Glucose Sensor Based on CuO Modified Vertically-Grown ZnO Nanorods on Electrode.

There is a major challenge to attach nanostructures on to the electrode surface while retaining their engineered morphology, high surface area, physiochemical features for promising sensing applications. In this study, we have grown vertically-aligned ZnO nanorods (NRs) on fluorine doped tin oxide (FTO) electrodes and decorated with CuO to achieve high-performance non-enzymatic glucose sensor. This unique CuO-ZnO NRs hybrid provides large surface area and an easy substrate penetrable structure facilitating enhanced electrochemical features towards glucose oxidation. As a result, fabricated electrodes exhibit high sensitivity (2961.7 µA mM-1 cm-2), linear range up to 8.45 mM, low limit of detection (0.40 µM), and short response time (<2 s), along with excellent reproducibility, repeatability, stability, selectivity, and applicability for glucose detection in human serum samples. Circumventing, the outstanding performance originating from CuO modified ZnO NRs acts as an efficient electrocatalyst for glucose detection and as well, provides new prospects to biomolecules detecting device fabrication.

Enhanced osteogenesis of ß-tricalcium phosphate reinforced silk fibroin scaffold for bone tissue biofabrication.

Scaffolds, used for tissue regeneration are important to preserve their function and morphology during tissue healing. Especially, scaffolds for bone tissue engineering should have high mechanical properties to endure load of bone. Silk fibroin (SF) from Bombyx mori silk cocoon has potency as a type of biomaterials in the tissue engineering. ß-tricalcium phosphate (ß-TCP) as a type of bioceramics is also critical as biomaterials for bone regeneration because of its biocompatibility, osteoconductivity, and mechanical strength. The aim of this study was to fabricate three-dimensional SF/ß-TCP scaffolds and access its availability for bone grafts through in vitro and in vivo test. The scaffolds were fabricated in each different ratios of SF and ß-TCP (100:0, 75:25, 50:50, 25:75). The characterizations of scaffolds were conducted by FT-IR, compressive strength, porosity, and SEM. The in vitro and in vivo tests were carried out by MTT, ALP, RT-PCR, SEM, µ-CT, and histological staining. We found that the SF/ß-TCP scaffolds have high mechanical strength and appropriate porosity for bone tissue engineering. The study showed that SF/ß-TCP (75:25) scaffold exhibited the highest osteogenesis compared with other scaffolds. The results suggested that SF/ß-TCP (75:25) scaffold can be applied as one of potential bone grafts for bone tissue engineering.

Rapid methyl orange degradation using porous ZnO spheres photocatalyst.

Porous zinc oxide (ZnO) spheres were synthesized by facile low temperature solution route. The as-synthesized porous ZnO spheres were characterized in detail in terms of their morphological, structural, optical and photocatalytic properties using field-emission scanning electron microscopy (FESEM, equipped with energy dispersive spectroscopy (EDS)), transmission electron microscopy (TEM), high-resolution TEM (HRTEM), X-ray diffractometer (XRD), UV-visible spectroscopy and Raman-scattering measurements. Nitrogen adsorption-desorption analysis was performed to determine pore size distribution from the adsorption isotherm curves using the Barrett-Joyner-Halenda (BJH) method. Morphological and structural characterizations showed porous nature of ZnO spheres with high surface area, good crystallinity, wurtzite hexagonal phase and good optical features. Next, ZnO spheres were studied as photocatalyst for photodegradation of harmful dye, methyl orange (MO). Under ultraviolet light irradiation, the decrease in MO dye concentration was monitored by UV-visible spectroscopy at different time intervals until the dye was completely degraded to colorless end product. Rapid MO dye decomposition was observed with a degradation rate of ~96.3% within the initial 120min, which is attributed to the porous nature, large specific surface area (114.6m(2)g(-1)), narrow pore size distribution (~2.5 to 25nm) evaluated from N2 adsorption-desorption isotherms analysis and excellent electron accepting features of the engineered porous ZnO spheres.

Outstanding Antibiofilm Features of Quanta-CuO Film on Glass Surface.

Intelligently designed surface nanoarchitecture provides defined control over the behavior of cells and biomolecules at the solid-liquid interface. In this study, CuO quantum dots (quanta-CuO; ∼3-5 nm) were synthesized by a simple, low-temperature solution process and further formulated as paint to construct quanta-CuO thin film on glass. Surface morphological characterizations of the as-coated glass surface reveal a uniform film thickness (∼120 ± 10 nm) with homogeneous distribution of quanta-CuO. The antibiofilm assay showed a very high contact bacteria-killing capacity of as-coated quanta-CuO glass surfaces toward Staphylococcus aureus and Escherichia coli. This efficient antibacterial/antibiofilm activity was ascribed to the intracellular reactive oxygen species (ROS) generated by the quanta-CuO attached to the bacterial cells, which leads to an oxidative assault and finally results in bacterial cell death. Although there is a significant debate regarding the CuO nanostructure's antibacterial mode of action, we propose both contact killing and/or copper ion release killing mechanisms for the antibiofilm activity of quanta-CuO paint. Moreover, synergism of quanta-CuO with conventional antibiotics was also found to further enhance the antibacterial efficacy of commonly used antibiotics. Collectively, this state-of-the-art design of quanta-CuO coated glass can be envisioned as promising candidates for various biomedical and environmental device coatings.

Inflammatory response study of gellan gum impregnated duck's feet derived collagen sponges.

Tissue engineered biomaterials have biodegradable and biocompatible properties. In this study, we have fabricated sponges using duck's feet derived collagen (DC) and gellan gum (GG), and further studied its inflammatory responses. The as-prepared duck's feet DC/GG sponges showed the possibility of application as a tissue engineering material through in vitro and in vivo experiments. The physical and chemical properties of sponges were characterized by compression strength, porosity, and scanning electron microscopy, etc. In vitro cell viability were investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. An inflammatory response was studied after seeding RAW264.7 cells on as-fabricated sponges using reverse transcriptase-polymerase chain reaction. In vivo studies were carried out by implanting in subcutaneous nude mouse followed by extraction, histological staining. Collectively, superior results were showed by DC/GG sponges than GG sponge in terms of physical property and cell proliferation and thus can be considered as a potential candidate for future tissue engineering applications.