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Bone tissue engineering is a promising technology being studied globally to become an effective and sustainable method to treat the problems of damaged or diseased bones. In this work, we developed an in situ cross-linking hydrogel system that combined N-succinyl chitosan (NSC) and oxidized alginate (OA) at varying mixing ratios through Schiff base cross-linking. The hydrogel system also contains biphasic calcium phosphate (BCP) and ascorbic acid (AA), which could enhance biological characteristics and accelerate bone repair. The hydrogels' properties were examined through physicochemical tests such as scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FT-IR), x-ray diffraction (XRD), pore size and porosity measurement, swelling ratio, degradation rate, AA release study, as well as cytocompatibility, including live/dead and cytotoxicity assays. The results revealed that the supplementation of AA and BCP components can affect the physico-mechanical properties of the hydrogel system. However, they exhibited noncytotoxic properties. Overall, the results demonstrated that the hydrogel composed of 3% (w/v) NSC and 3% (w/v) OA (NSC: OA volume ratio is 8:2) loaded with 40% (w/w) BCP and 0.3 mg/mL AA has the potential for bone regeneration., (© 2024 Wiley Periodicals LLC.)

Introduction: The emergence of colistin resistance threatens the treatment of Pseudomonas aeruginosa infections., Methods: In this study, in vitro development of colistin resistance was investigated using comparative phenotypic and proteomic analysis of P. aeruginosa ATCC 9027, its 14-day colistin sub-MIC exposed strain (Col-E1), and 10-day antibiotic-free cultured Col-E1 strain (Col-E2). Antibiotic susceptibility, morphology, virulence factors, and proteomic changes were assessed using disc-diffusion, agar-based, spectrophotometry, SEM, and iTRAQ-LC-MS/MS methods., Results: Colistin-exposed strains decreased susceptibility to colistin while remaining susceptible to other antibiotics. Col-E1 reduced the cell lengths by 17.67% and the colony size by 36.16% compared to the initial strain. The reduction remained in Col-E2. The pyocyanin production was reduced in Col-E1 (p=0.025, Tukey HSD) and increased again in Col-E2 (p=0.005, Tukey HSD). In contrast, no significant changes in elastase, protease, rhamnolipid, pyoverdine, and biofilm production were observed (p>0.05, Tukey HSD). In Col-E1, the proteome analysis showed 135 differentially expressed proteins (DEPs) of which 94 DEPs (69.23%) maintained their expression change in Col-E2. Among DEPs, 82 were involved in metabolism and protein synthesis. Some DEPs (6/135) played a role in stress response such as GrpE (fold change: 14.93) and Hmp (fold change: 12.08). In particular, membrane proteins like OprD, DdlB, and OprI showed significant colistin response with fold change of -8.47, 6.43 and 6.19, respectively., Conclusions: In summary, colistin response in P. aeruginosa seemed to affect morphology, production of pyocyanin, and proteins of metabolism, protein synthesis, stress response and membrane., Competing Interests: Conflicts of interest: All authors – none to declare., (GERMS.)

Transdermal drug delivery (TDD) has significantly advanced medical practice in recent years due to its ability to prevent the degradation of substances in the gastrointestinal tract and avoid hepatic metabolism. Among different available approaches, microneedle arrays (MNAs) technology represents a fascinating delivery tool for enhancing TDD by penetrating the stratum corneum painless and minimally invasive for delivering antibacterial, antifungal, and antiviral medications. Polymeric MNAs are extensively utilized among many available materials due to their biodegradability, biocompatibility, and low toxicity. Therefore, this review provides a comprehensive discussion of polymeric MNAs, starting with understanding stratum corneum and developing MNA technology. Furthermore, the engineering concepts, fundamental considerations, challenges, and future perspectives of polymeric MNAs in clinical applications are properly outlined, offering a comprehensive and unique overview of polymeric MNAs and their potential for a broad spectrum of clinical applications., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The design of three-dimensional (3D) scaffolds should focus on creating highly porous, 3D structures with an interconnected pore network that supports cell growth. The scaffold's pore interconnectivity is directly linked to vascularization, cell seeding, guided cell migration, and transportation of nutrients and metabolic waste. In this study, different types of food flavors including monosodium glutamate, sugar, and sodium chloride were used as the porogens along with PCL/PVP blend polymer for solvent casting/particulate leaching method. The morphology, porosity, interconnectivity, chemical composition, water absorption, and mechanical properties of the fabricated scaffolds are carefully characterized. The scaffolds are biocompatible in both in vitro and in vivo experiments and do not trigger any inflammatory response while enhancing new bone formation and vascularization in rabbit calvaria critical-sized defects. The new bone merges and becomes denser along with the experiment timeline. The results indicate that the 3D PCL/PVP scaffolds, using monosodium glutamate as porogen, exhibited suitable biological performance and held promise for bone tissue engineering in oral and maxillofacial surgery., (© 2024 IOP Publishing Ltd.)

Understanding the evolution of antibiotic resistance is important for combating drug-resistant bacteria. In this work, we investigated the adaptive response of Pseudomonas aeruginosa to ciprofloxacin. Ciprofloxacin-susceptible P. aeruginosa ATCC 9027, CIP-E1 ( P. aeruginosa ATCC 9027 exposed to ciprofloxacin for 14 days) and CIP-E2 (CIP-E1 cultured in antibiotic-free broth for 10 days) were compared. Phenotypic responses including cell morphology, antibiotic susceptibility, and production of pyoverdine, pyocyanin and rhamnolipid were assessed. Proteomic responses were evaluated using comparative iTRAQ labelling LC-MS/MS to identify differentially expressed proteins (DEPs). Expression of associated genes coding for notable DEPs and their related regulatory genes were checked using quantitative reverse transcriptase PCR. CIP-E1 displayed a heterogeneous morphology, featuring both filamentous cells and cells with reduced length and width. By contrast, although filaments were not present, CIP-E2 still exhibited size reduction. Considering the MIC values, ciprofloxacin-exposed strains developed resistance to fluoroquinolone antibiotics but maintained susceptibility to other antibiotic classes, except for carbapenems. Pyoverdine and pyocyanin production showed insignificant decreases, whereas there was a significant decrease in rhamnolipid production. A total of 1039 proteins were identified, of which approximately 25 % were DEPs. In general, there were more downregulated proteins than upregulated proteins. Noted changes included decreased OprD and PilP, and increased MexEF-OprN, MvaT and Vfr, as well as proteins of ribosome machinery and metabolism clusters. Gene expression analysis confirmed the proteomic data and indicated the downregulation of rpoB and rpoS . In summary, the response to CIP involved approximately a quarter of the proteome, primarily associated with ribosome machinery and metabolic processes. Potential targets for bacterial interference encompassed outer membrane proteins and global regulators, such as MvaT.

Introduction: Vitamin D 3 plays a vital role in bone health, with low levels of vitamin D 3 being related to skeletal fragility, fractures, and metabolic disorders such as diabetes. Metformin is known as an antihyperglycemic agent for regulating blood sugar. A correlation between diabetes mellitus and osteoporosis is attracting considerable interest, and research to find the prevention and treatment is gradually being studied. In this study, we investigated the effect of metformin and vitamin D 3 on osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells (AT-MSCs) under high d-glucose concentrations and optimized by combining vitamin D 3 and metformin in the process., Methods: ROS production of AT-MSCs under high d-glucose conditions was measured by DCFH-DA assay. The differentiated AT-MSCs were analyzed by Alizarin Red S staining and optical density measurement. The investigation involved the examination of osteogenic master genes' expressions using quantitative reverse transcription polymerase chain reaction (qRT-PCR) techniques., Results: Interestingly, the results have shown that human AT-MSCs will exhibit high ROS accumulation and low osteogenic differentiation capabilities, indicated by low calcium deposition, as well as low expression of indicative genes such as ALP , Runx-2 under high d-glucose conditions. The combination of vitamin D 3 and metformin remarkedly accelerated the osteogenic differentiation of AT-MSCs under high d-glucose concentrations more effectively than the administration of either agent., Conclusions: This study partially explains an aspect of an in vitro model for pre-clinical drug screening for osteoporosis-related diabetic pathological mechanisms, which can be applied for further research on the prevention or treatment of osteoporosis in diabetic patients., Competing Interests: The authors have no competing financial interests to declare., (© 2023 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Dynamic hydrogel systems from N,O-carboxymethyl chitosan (NOCC) are investigated in the past years, which has facilitated their widespread use in many biomedical engineering applications. However, the influence of the polymer's oxidation levels on the hydrogel biological properties is not fully investigated. In this study, chitosan is converted into NOCC and introduced to react spontaneously with oxidized xanthan gum (OXG) to form several injectable hydrogels with controlled degradability. Different oxidation levels of xanthan gum, as well as NOCC/OXG volume ratios, are trialed. The infrared spectroscopy spectra verify chemical modification on OXG and successful crosslinking. With increasing oxidation levels, more dialdehyde groups are introduced into the OXG, resulting in changes in physical properties including gelation, swelling, and self-healing efficiency. Under different volume ratios, the hydrogel shows a stable structure and rigidity with higher mechanical properties, and a slower degradation rate. The shear-thinning and self-healing properties of the hydrogels are confirmed. In vitro assays with L929 cells show the biocompatibility of all formulations although the use of a high amount of OXG15 and OXG25 limited the cell proliferation capacity. Findings in this study suggested a suitable amount of OXG at different oxidation levels in NOCC hydrogel systems for tissue engineering applications., (© 2023 Wiley-VCH GmbH.)

Dual-drug delivery systems for anticancer therapy have recently attracted substantial attention due to their potency to overcome limitations of conventional anti-cancer drugs, tackle drug resistance problems, as well as improve the therapeutic efficacy. In this study, we introduced a novel nanogel based on folic acid-gelatin-pluronic P123 (FA-GP-P123) conjugate to simultaneously deliver quercetin (QU) and paclitaxel (PTX) to the targeted tumor. The results indicated that the drug loading capacity of FA-GP-P123 nanogels was significantly higher than that of P123 micelles. The kinetic release profiles of QU and PTX from the nanocarriers were governed by Fickian diffusion and swelling behavior, respectively. Notably, FA-GP-P123/QU/PTX dual-drug delivery system induced higher toxicity to MCF-7 and Hela cancer cells than either QU or PTX individual delivery system, and the non-targeted dug delivery system (GP-P123/QU/PTX), indicating the synergistic combination of dual drugs and FA positive targeting effect. Furthermore, FA-GP-P123 could effectively deliver QU and PTX to tumors in vivo after administration into MCF-7 tumor-bearing mice, which resulted in 94.20 ± 5.90 % of tumor volume reduced at day 14. Moreover, the side effects of the dual-drug delivery system were significantly reduced. Overall, we suggest FA-GP-P123 as potential nanocarrier for dual-drug delivery for targeted chemotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: This study investigated post-traumatic stress disorder (PTSD), anxiety, depression and their related factors among coronavirus disease 2019 (COVID-19) patients during the fourth wave of the pandemic in Vietnam., Methods: Vietnamese-fluent confirmed COVID-19 patients for at least 3 d were recruited in this online cross-sectional study to answer a three-part questionnaire including participants' sociodemographic characteristics, PTSD (Impact of Event Scale-Revised) and anxiety and depression (Hospital Anxiety and Depression Scale). Associated factors were determined using multivariable binary logistic regression models., Results: Of 1544 responses, the majority were female (53.0%), ages 18-39 y (74.8%) and were isolated and treated at field hospitals (72.2%). Family or friends were the greatest sources of mental support (68.2%), followed by healthcare providers (51.1%). The overall prevalence rates of PTSD, anxiety and depression among COVID-19 patients were 22.9%, 11.2% and 17.4%, respectively. Risk factors included older age, higher education, getting infected from the public, knowing someone who died from COVID-19 and high perception of life threat. Meanwhile, mental assistance from family or friends, a greater number of supporters, living with someone not vulnerable and higher salaries were significantly protective factors., Conclusions: The psychological responses associated with some sociodemographic details. Family or friends should be the first line of mental interventions for COVID-19 patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

The adsorption ability of hydrogen, hydroxide, and oxygenic intermediates plays a crucial role in electrochemical water splitting. Electron-deficient metal-active sites can prompt electrocatalytic activity by improving the adsorption ability of intermediates. However, it remains a significant challenge to synthesize highly abundant and stable electron-deficient metal-active site electrocatalysts. Herein, we present a general approach to synthesizing a hollow ternary metal fluoride (FeCoNiF 2 ) nanoflake array as an efficient and robust bifunctional electrocatalyst for the hydrogen evolution reaction (HER) and urea oxidation reaction (UOR). We find that the F anion withdraws electrons from the metal centers, inducing an electron-deficient metal center catalyst. The rationally designed hollow nanoflake array exhibits the overpotential of 30 mV for HER and 130 mV for UOR at a current density of 10 mA cm -2 and superior stability without decay events over 150 h at a large current density of up to 100 mA cm -2 . Remarkably, the assembled urea electrolyzer using a bifunctional hollow FeCoNiF 2 nanoflake array catalyst requires cell voltages of only 1.352 and 1.703 V to afford current densities of 10 and 100 mA cm -2 , respectively, which are 116 mV less compared with that required for overall water splitting.

Kesterite Cu 2 ZnSnS 4 (CZTS) thin films in which the Cu site was partially replaced with Ag were prepared by spray deposition on an Mo-coated glass substrate. Successful replacement of Cu components in the CZTS lattice with Ag up to an Ag/(Cu + Ag) ratio of 0.20 was achieved. Samples with relatively low contents of Ag (Ag/(Cu + Ag) ratios of 0.05 and 0.10) showed obvious grain growth compared to that of bare CZTS, whereas samples with higher Ag contents showed an appreciable decrease in grain sizes. Photoelectrochemical properties for water reduction (H 2 production), which was examined after surface modifications with an In 2 S 3 /CdS double layer and Pt catalyst for H 2 evolution, depended strongly on such morphological differences; a maximum conversion efficiency, i.e. , half-cell solar to hydrogen efficiency, of 2.4% was achieved by the photocathode based on the film with an Ag/(Cu + Ag) ratio of 0.10. Minority carrier dynamics examined by photoluminescence measurements indicated that such an active sample of PEC H 2 production had a relatively long carrier lifetime, suggesting that the suppression of carrier recombination at grain boundaries in the bulk of these kesterite films is one of the important factors for enhancing PEC functions.

Background and Objective: Influenza virus (FLU), rhinovirus (RV) and respiratory syncytial virus (RSV) are the most common acute respiratory infections worldwide. Infection can cause severe health outcomes, while therapeutic options are limited, primarily relieving symptoms without attenuating the development of lesions or impaired lung function. We therefore examined the inflammatory response to these infections with the intent to identify common components that are critical drivers of immunopathogenesis and thus represent potential therapeutic targets., Methods: BALB/c mice were infected with FLU, RV or RSV, and lung function, airway inflammation and immunohistopathology were measured over a 10-day period. Anti-IL-17A mAb was administered to determine the impact of attenuating this cytokine's function on the development and severity of disease., Results: All three viruses induced severe airway constriction and inflammation at 2 days post-infection (dpi). However, only FLU induced prolonged inflammation till 10 dpi. Increased IL-17A expression was correlated with the alterations in lung function and its persistence. Neutralization of IL-17A did not affect the viral replication but led to the resolution of airway hyperresponsiveness. Furthermore, anti-IL-17A treatment resulted in reduced infiltration of neutrophils (in RV- and FLU-infected mice at 2 dpi) and lymphocytes (in RSV-infected mice at 2 dpi and FLU-infected mice at 10 dpi), and attenuated the severity of immunopathology., Conclusion: IL-17A is a common pathogenic molecule regulating disease induced by three prevalent respiratory viruses. Targeting the IL-17A pathway may provide a unified approach to the treatment of these respiratory infections alleviating both inflammation-induced lesions and difficulties in breathing., (© 2021 Asian Pacific Society of Respirology.)

(1) Background: Wounds with damages to the subcutaneous are difficult to regenerate because of the tissue damages and complications such as bacterial infection. (2) Methods: In this study, we created burn wounds on pigs and investigated the efficacy of three biomaterials: polycaprolactone-gelatin-silver membrane (PCLGelAg) and two commercial burn dressings, Aquacel ® Ag and UrgoTul TM silver sulfadiazine. In vitro long-term antibacterial property and in vivo wound healing performance were investigated. Agar diffusion assays were employed to evaluate bacterial inhibition at different time intervals. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill assays were used to compare antibacterial strength among samples. Second-degree burn wounds in the pig model were designed to evaluate the efficiency of all dressings in supporting the wound healing process. (3) Results: The results showed that PCLGelAg membrane was the most effective in killing both Gram-positive and Gram-negative bacteria bacteria with the lowest MBC value. All three dressings (PCLGelAg, Aquacel, and UrgoTul) exhibited bactericidal effect during the first 24 h, supported wound healing as well as prevented infection and inflammation. (4) Conclusions: The results suggest that the PCLGelAg membrane is a practical solution for the treatment of severe burn injury and other infection-related skin complications.

The use of naturally occurring materials with antibacterial properties has gained a great interest in infected wound management. Despite being an abundant resource in Vietnam, chitosan and its derivatives have not yet been intensively explored for their potential in such application. Here, we utilized a local chitosan source to synthesize chitosan oligomers (OCS) using hydrogen peroxide (H 2 O 2 ) oxidation under the microwave irradiation method. The effects of H 2 O 2 concentration on the physicochemical properties of OCS were investigated through molecular weight, degree of deacetylation, and heavy metal contamination for optimization of OCS formulation. Then, the antibacterial inhibition was examined; the minimum inhibitory concentration and minimum bactericidal concentration (MIC and MBC) of OCS-based materials were determined against common skin-inhabitant pathogens. The results show that the local Vietnamese chitosan and its derivative OCS possessed high-yield purification while the molecular weight of OCS was inversely proportional and proportional to the concentration of H 2 O 2 , respectively. Further, the MIC and MBC of OCS ranged from 3.75 to less than 15 mg/mL and 7.5-15 mg/mL, respectively. Thus, OCS-based materials induce excellent antimicrobial properties and can be attractive for wound dressings and require further investigation.

Biodegradable periodic mesoporous organosilica nanoparticles (B-PMO) are an outstanding nanocarrier due to their biodegradability and high drug load capacities. The present study describes a synthesis of a phenylene-containing tetrasulfide based B-PMO, named P4S. The incorporation of aromatic phenylene groups into the framework creates a strong interaction between nanoparticles (NPs) with aromatic rings in the cordycepin molecules. This results in the low release profile under various conditions. In addition, the replacement of this linker slowed the degradation of nanoparticles. The physicochemical properties of the nanoparticles are evaluated and compared with a biodegradable ethane-containing tetrasulfide based PMO and a non-degradable MCM-41. The biodegradability of P4S is also demonstrated in a reducing environment and the 100 nm spherical nanoparticles completely decomposed within 14 days. The porous structure of P4S has a high loading of hydrophilic cordycepin (approximately 731.52 mg g -1 ) with a slow releasing speed. The release rates of P4S NPs are significantly lower than other materials, such as liposomes, gelatin nanoparticles, and photo-crosslinked hyaluronic acid methacrylate hydrogels, in the same solution. This specific release behavior could guarantee drug therapeutic effects with minimum side-effects and optimized drug dosages. Most importantly, according to the in vitro cytotoxicity study, cordycepin-loaded P4S NPs could retain the toxicity against liver cancer cell (HepG2) while suppressed the cytotoxicity against normal cells (BAEC)., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aim: This study measured the level of knowledge, attitudes and practices towards COVID-19 prevention and examined associated factors among patients at a national tertiary general hospital in Vietnam., Methods: Adult patients admitted to University Medical Center during research period were recruited in a cross-sectional study, which employed a convenience sampling method with a 4-component questionnaire in order to examine the patients' consciousness towards COVID-19 spreading prevention based on four aspects: demographic characteristics (10 items), knowledge (14 items), attitudes (6 items), and practices (7 items)., Results: The study involved 2769 respondents (18-90 years) with the mean age of 38.05±13.91 years. About two thirds of the respondents obtained diploma degree or higher (63.4%) and shared their living space with others (64.4%). The majority of patients settled in urban area (74.9%). All participants stayed informed about COVID-19, with the most commonly used channels like television (75.2%), the Internet (72.2%) and phone (69.8%). The vast majority showed sufficient knowledge (93.7%) and positive attitudes (76.3%). Just over half of participants remained good practiced of COVID-19 prevention (57.7%). On average, the factors of younger age, higher educational level, frequency and department of admission, and the number of COVID-19 informative channels were significantly associated with sufficient knowledge, positive attitudes, and good practices regarding preventive action against COVID-19 spreading. The optimistic attitude and having more undergoing chronic diseases were associated with the likelihood of well-practiced COVID-19 preventive measures (OR 3.63, 95% CI 1.54-8.55, p=0.003 and OR 0.86, 95% CI 0.78-0.98, p=0.02, respectively)., Conclusion: The results of this study demonstrated that the likelihood of good preventive practices in the fight against COVID-19 pandemic was influenced by attitudes and several sociodemographic factors. More drastic interventions for the prevention of COVID-19 should be widely furnished and equipped in hospitals, through various routes to maximize the efficiency and adherence to prevention practices., Competing Interests: The authors reported no conflicts of interest for this work., (© 2021 Nguyen et al.)

Hematin has been used as an alternative enzyme catalyst to horseradish peroxidase (HRP) due to its iron-containing activity center. Although hematin and it derivatives have been widely used for polymerization of phenol/analine compounds, it has some drawbacks such as the limited solubility and reaction only at high pH condition. Herein, we report a nanosized biomimetic catalyst, hematin-decorated polyamidoamine dendrimer (G3.0-He) that can effectively catalyze the in situ hydrogelation of phenol-conjugated polymers under neutral pH condition. We demonstrate that G3.0-He particles are smaller than 100 nm and have excellent enzyme-mimetic functions. Interestingly, the nanosized catalyst is not inactivated at high H 2 O 2 concentration. Compared to pure hematin, G3.0-He has significantly higher dispersion in acidic and neutral media, and preserves the percentage of survival of fibroblasts over 90%. Notably, G3.0-He possesses an exquisite HRP-mimicking activity in gelation of gelatin derivative with phenolic hydroxyl (tyamine) moieties under mild physiological conditions. The in vitro study demonstrated that Gel-Tyr hydrogel by G3.0-He catalyzed reaction had excellent cytocompatibility and an excellent scaffold for adhesion to fibroblast cells. Therefore, the designed minimalistic G3.0-He catalyst could serve as an effective catalytic alternative for HRP enzyme in the preparation of biomedical hydrogels., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Virus-induced respiratory tract infections are a major health burden in childhood, and available treatments are supportive rather than disease modifying. Rhinoviruses (RVs), the cause of approximately 80% of common colds, are detected in nearly half of all infants with bronchiolitis and the majority of children with an asthma exacerbation. Bronchiolitis in early life is a strong risk factor for the development of asthma. Here, we found that RV infection induced the expression of miRNA 122 (miR-122) in mouse lungs and in human airway epithelial cells. In vivo inhibition specifically in the lung reduced neutrophilic inflammation and CXCL2 expression, boosted innate IFN responses, and ameliorated airway hyperreactivity in the absence and in the presence of allergic lung inflammation. Inhibition of miR-122 in the lung increased the levels of suppressor of cytokine signaling 1 (SOCS1), which is an in vitro-validated target of miR-122. Importantly, gene silencing of SOCS1 in vivo completely reversed the protective effects of miR-122 inhibition on RV-induced lung disease. Higher miR-122 expression in nasopharyngeal aspirates was associated with a longer time on oxygen therapy and a higher rate of treatment failure in 87 infants hospitalized with moderately severe bronchiolitis. These results suggest that miR-122 promotes RV-induced lung disease via suppression of its target SOCS1 in vivo. Higher miR-122 expression was associated with worse clinical outcomes, highlighting the potential use of anti-miR-122 oligonucleotides, successfully trialed for treatment of hepatitis C, as potential therapeutics for RV-induced bronchiolitis and asthma exacerbations.

Wound dressings are typically used to provide a favorable environment supporting the intricate process of wound healing. This research aims to fabricate and evaluate an electrospun polycaprolactone (EsPCL) membrane coated with various densities of chitosan oligomers (COS) - a biological agent - for application as bioactive wound dressing. Weight calculation was employed to investigate the density of COS coated onto the electrospun PCL membrane. Physicochemical characteristics of the prepared membranes, such as hydrophilicity and mechanical properties were demonstrated and evaluated through standard experimental methods. In vitro assays and mice model were used to investigate the antibacterial activities, cytocompatibility, hemostasis and the in vivo interaction of the membranes. The results showed that COS was coated successfully on the surface of the polymeric membrane, altering its morphology and associated characteristics. The greater concentration of COS led to an increase in the thickness of the membrane, which resulted in stronger antibacterial activities. Moreover, the increase of chitosan oligomers density in the membrane induced faster hemostasis and affected the re-epithelialization and wound healing in mice. Thus, the membrane as a whole and particularly chitosan oligomers were shown to be potential for further studies regarding wound dressing., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Bone cement is used as a mortar for securing bone implants, as bone void fillers or as spacers in orthopaedic surgery. Antibiotic-loaded bone cements (ALBCs) have been used to prevent and treat prosthetic joint infections by providing a high antibiotic concentration around the implanted prosthesis. High antibiotic concentrations are, on the other hand, often associated with tissue toxicity. Controlling antibiotic release from ALBCS is key to achieving effective infection control and promoting prosthesis integration with the surrounding bone tissue. However, current ALBCs still need significant improvement in regulating antibiotic release. In this review, we first provide a brief introduction to prosthetic joint infections, and the background concepts of therapeutic efficacy and toxicity in antibiotics. We then review the current state of ALBCs and their release characteristics before focusing on the research and development in controlling the antibiotic release and osteo-conductivity/inductivity. We then conclude by a discussion on the need for better in vitro experiment designs such that the release results can be extrapolated to predict better the local antibiotic concentrations in vivo.

Bacterial biofilms are involved in most device-associated infections and remain a challenge for modern medicine. One major approach to addressing this problem is to prevent the formation of biofilms using novel antimicrobial materials, device surface modification or local drug delivery; however, successful preventive measures are still extremely limited. The other approach is concerned with treating biofilms that have already formed on the devices; this approach is the focus of our manuscript. Treating biofilms associated with medical devices has unique challenges due to the biofilm's extracellular polymer substance (EPS) and the biofilm bacteria's resistance to most conventional antimicrobial agents. The treatment is further complicated by the fact that the treatment must be suitable for applying on devices surrounded by host tissue in many cases. Nanomaterials have been extensively investigated for preventing biofilm formation on medical devices, yet their applications in treating bacterial biofilm remains to be further investigated due to the fact that treating the biofilm bacteria and destroying the EPS are much more challenging than preventing adhesion of planktonic bacteria or inhibiting their surface colonization. In this highly focused review, we examined only studies that demonstrated successful EPS destruction and biofilm bacteria killing and provided in-depth description of the nanomaterials and the biofilm eradication efficacy, followed by discussion of key issues in this topic and suggestion for future development.

Rhinovirus (RV) infections in asthmatic patients are often associated with asthma exacerbation, characterized by worsened airways hyperreactivity and increased immune cell infiltration to the airways. The C-X-C chemokines, CXCL3 and CXCL5, regulate neutrophil trafficking to the lung via CXCR2, and their expression in the asthmatic lung is associated with steroid-insensitive type 2 inflammatory signatures. Currently, the role of CXCL3 and CXCL5 in regulating neutrophilic and type 2 responses in viral-induced asthma exacerbation is unknown. Inhibition of CXCL3 or CXCL5 with silencing RNAs in a mouse model of RV-induced exacerbation of asthma attenuated the accumulation of CXCR2 + neutrophils, eosinophils, and innate lymphoid cells in the lung and decreased production of type 2 regulatory factors IL-25, IL-33, IL-5, IL-13, CCL11, and CCL24. Suppression of inflammation was associated with decreased airways hyperreactivity, mucus hypersecretion, and collagen deposition. Similar results were obtained by employing RC-3095, which has been shown to bind to CXCR2, or by depletion of neutrophils. Our data demonstrate that CXCL3 and CXCL5 may be critical in the perpetuation of RV-induced exacerbation of asthma through the recruitment of CXCR2-positive neutrophils and by promoting type 2 inflammation. Targeting the CXCL3/CXCL5/CXCR2 axis may provide a new therapeutic approach to attenuating RV-induced exacerbations of asthma., (Copyright © 2020 by The American Association of Immunologists, Inc.)

The development of improved methods for the synthesis of monodisperse gold nanoparticles (Au NPs) is of high priority because they can be used as substrates for surface-enhanced Raman scattering (SERS) applications relating to biological lipids. Herein, Au NPs have been successfully synthesized via a seed-mediated growth method. The LSPR peak is controlled via adjusting the gold nanoseed component, and different fabrication methods were studied to establish the effect of sonication time on NP size. The simple, facile, and room-temperature method is based on a conventional ultrasonic bath, which leads to ultrasonic energy effects on the size and morphology of the Au NPs. This research offers new opportunities for the production of highly monodispersed spherical Au NPs without the use of a magnetic stirrer method, as evidenced by ultraviolet-visible reflectance spectra and scanning electron microscopy (SEM) analysis. SEM images indicate that the spherical Au NP colloidal particles are stable and reliable, which paves the way for their use as a nanostructured biosensor platform that can be exploited for multiple applications, for example, in materials science, sensing, catalysis, medicine, food safety, biomedicine, etc. The highest enhancement factor that could be achieved in terms of the SERS enhancement activity of these Au NP arrays was determined using 10 -9 M serotonin (5-hydroxytryptamine, 5-HT) as the Raman probe molecules., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Purpose: The aim of this study is to develop a new coating for wound dressings that is comprised of antimicrobial silver (Ag) and antioxidant flavonoid quercetin (Q)., Methods: Dip-coating was used to apply the coating on cotton gauge as a model dressing. Ag was immobilised using polydopamine as a priming and catalytic layer followed by coating of quercetin that was incorporated in a functionalized polydimethylsiloxane. The coating was investigated using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX) and release assay. The antimicrobial activity of quercetin and Ag was tested against Staphylococcus aureus ( S. aureus ). A surgical wound model on mice was used to evaluate the effects of the coated dressing on wound healing rates and tissue histology., Results: Ag and quercetin showed enhanced antimicrobial activity against S. aureus when used in combination. Ag and quercetin were successfully immobilized onto the fibre of the dressing using the dip-coating process. The coating released Ag and quercetin over 8 days and showed strong antioxidant activity. In the wound healing model, complete wound closure was achieved in 12 days in the group receiving coated dressing and was associated with an enhancement in tissue remodelling and neo-angiogenesis and the reduction in tissue inflammation., Conclusion: These new antimicrobial-antioxidant coatings may be promising in the development of advanced wound care therapies., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Tran et al.)

The purpose of this research is to investigate the effect of different oxidation degrees and volume ratios of components on the physical properties and biocompatibility of an in situ cross-linking chitosan-hyaluronic acid-based hydrogel for skin wound healing applications. Carboxymethyl groups (-CH 2 COOH) were introduced to the polymer chain of chitosan, producing N,O - Carboxymethyl Chitosan (NOCC). Hyaluronic acid was oxidized to obtain aldehyde hyaluronic acid (AHA) with three oxidation degrees (AHA40, AHA50 and AHA60). The gelation was induced by forming Schiff base linkage between aldehyde groups of AHA and amino groups of NOCC. Then, the polysaccharide derivatives were combined at three NOCC:AHA volume ratios (3:7, 5:5 and 7:3) to form composite hydrogels without using any additional cross-linker. FT-IR analysis, surface morphology observation and wettability test, in vitro degradation test and rheological analysis were carried out to characterize the hydrogels. Additionally, in vitro cytotoxicity and in vivo wound healing evaluations were also conducted to study the biocompatibility of the composite. Our findings showed that when increasing the volume of NOCC, the homogeneity and hydrophobicity of the resulting hydrogels were also improved and their pore walls became thicker, leading to slower degradation rate. On the other hand, when raising the oxidation degree of AHA, the hydrophilicity of the gels decreased and less time was required to form the gel matrix. Besides, the obtained in vitro and in vivo results indicated that lower oxidation degree of AHA supports cell proliferation, cell attachment and wound healing process better. It is also concluded that NOCC-AHA40 5:5 hydrogel is most suitable for skin wound healing applications since it possesses superior morphology with high uniformity, favorable pore size and suitable density along with appropriate wettability. The NOCC-AHA gel matrix is expected to be used as a delivery system for other factors and employed as an effective bio-glue in further tissue engineering applications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This study aimed to fabricate the potential therapeutic scaffold to efficiently and safely fastening skin wound healing. A biocompatible grafting polymer-based thermal sensitive hybrid hydrogel (Chitosan-P123, CP) containing gelatin and curcumin was designed to be suitable stiffness for tissue regeneration. A detailed in the rheological study found that the encapsulated agents induced the change in the stiffness of the hydrogel from the hard to the soft. Especial, the thermally induced phase transition of CP hydrogel was governed by the participant of gelatin rather than curcumin. For example, at 25 wt% gelatin, CP hydrogel exhibited a unique gel-sol-gel transition following the function of temperature. Moreover, in vitro investigation revealed that the hybrid hydrogel provides the capacity of especially induced curcumin release with a sustainable rate as well as the excellent biocompatibility scaffold. Altogether with in vivo study, the hybrid hydrogel highlighted the advance of the dual synergistic of curcumin and gelatin in development of smart scaffold system, which promoted the efficacy in the regeneration of the structure and the barrier's function of damaged skin such as wound or skin cancer., (Copyright © 2019. Published by Elsevier Masson SAS.)

Phyllanthus emblica is an edible nutraceutical and functional food in the Asia area with medicinal and nutritive importance. The fruit extract of P. emblica is currently considered to be one of the effective functional foods for flesh maintenance and disease treatments because of its antioxidative and immunomodulatory properties. We examined the antioxidant abilities of the fruit extract powder by carrying out 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging, iron reducing power, and metal chelating activity analysis and showed excellent antioxidative results. In 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the result showed that the samples had no cytotoxic effect on RAW 264.7 cells even at a high concentration of 2 mg/mL. To investigate its immunomodulatory function, our estimation was to treat it with lipopolysaccharide (LPS) in RAW 264.7 cells to present anti-inflammatory capacities. The extract decreased reactive oxygen species (ROS) production levels in a dose-dependent manner measured by flow cytometry. We also examined various inflammatory mRNAs and proteins, including nuclear factor-κB (NF-κB), inducible nitric oxide synthases (iNOS), and cyclooxygenase-2 (COX-2). In quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting assay, all three targets were decreased by the extract, also in a dose-dependent manner. In conclusion, P. emblica fruit extract powder not only lessened antioxidative stress damages, but also inhibited inflammatory reactions.

In this study, chitosan nanoparticles were used as a carrier for Protocatechuic acid (PCA) to resist Pyricularia oryzae against rice blast. The final compound was characterized using zeta potentials for its surface electricity, Fourier transform infrared (FT-IR) analysis and transmission electron microscopy (TEM) were conducted for functional groups and for particle sizes and shape, respectively. The zeta potential results showed that loading PCA causes chitosan nanoparticle (CSNP) to decrease in surface electrons. The TEM images revealed that the particle size of chitosan (CS), although increasing in size when carrying PCA molecules, showed sufficient size for reasonable penetration into fungal cells. The FT-IR analysis showed that all functional group in CSNP carried PCA matched with previous studies. The antifungal test showed that diameters of inhibition zone of CS increases significantly after loading PCA, exhibiting the strongest antimicrobial effect on the Pyricularia oryzae fungus compared with weaker effects exhibited by CSNP alone or PCA. Our results suggested that CSNP loaded with PCA could be a potential compound for eradication of Pyricularia oryzae and that further testing on in vitro rice plants is recommended to reaffirm this possibility.

The development of nanomaterials in the field of biomedical has attracted much attention in the past decades. New mesoporous nanosilica (MNS) generation, called multi functionalized MNS, presents the promising applications for efficient encapsulation, controlled release, and intracellular delivery of therapeutic agents due to their unique physiochemical properties, such as large surface area and pore volume, tunable particle size, biocompatibility, and high loading capacity. In this review, we intensively discussed the multi functionalized MNSs that respond to the demand of physical stimuli (thermo, light, magnetic field, ultrasound, and electricity), chemical stimuli (pH, redox, H 2 O 2 ), and biological stimuli (enzyme, glucose, ATP), individual or in combination. Moreover, the recent applications of multi functionalized MNSs, focusing on drug and other therapeutic agents delivery, diagnostic imaging, and catalysis are also summarized in order to promote the further development of MNSs as a universal platform in the bright upcoming future., (Copyright © 2018. Published by Elsevier B.V.)

Bacterial infection and damage caused by dressing removal are two concerning problems which prolong the healing process in treatment of skin injuries. In this study, plasma treated electrospun polycaprolactone (PCL) scaffold was coated with silver nanoparticles (AgNPs) embedded in gelatin (Gel) by multi-immersion technique to optimize its antibacterial performance and reduce wound-scaffold adhesion. Water interaction test was used to examine the hydrophilization of PCL electrospun fibers after plasma treatment. Scanning Electron Microscopy (SEM) and weight calculation were employed to investigate the morphology and absorptive ability of the GelAg multi-coated PCL membrane (EsPCLGelAg). Antibacterial property of the membrane was evaluated using agar diffusion method against gram positive and gram negative bacteria. Mice model was also used to examine the efficiency of the membrane in healing process and its ability to prevent damage of newly formed tissue when peeling off. SEM results showed that the thickness of GelAg layer on EsPCL membrane increases correspondingly to the number of coating times. In vitro and in vivo data also demonstrated that the greater number of GelAg coating times, the more significant the antibacterial property of the membrane while not sticking to the wound site. These results suggest that multi-coating technique can be applied to optimize the antibacterial property of EsPCLGelAg scaffold and prevent removal-induced damage for wound dressing applications., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: Shear stress can activate platelet integrin-mediated signaling that leads to shear-induced platelet aggregation (SIPA) and eventually contribute to acute myocardial infarction. The major platelet integrin αIIbβ3 is polymorphic at residue 33 [Leu33Pro (PlA) polymorphism]. The Pro33 isoform has been shown to have a prothrombotic phenotype. In this work, we studied the impact of Leu33/Pro33 polymorphism on the shear-induced integrin-mediated Src and FAK activation in platelets., Methods: Platelets of both genotypes were placed on immobilized fibrinogen or heat activated BSA and were exposed to physiological (500/s) or abnormally high (5000/s) shear rates for 2-10 min. Platelets after exposure to shear were analysed for Src pY418 and FAK pY397 activities., Results: Whereas physiological shear stress does not affect platelet signaling, abnormally high-shear stress considerably elevates Src and FAK phosphorylation in both Pro33 and Leu33 platelets. Both under static and flow conditions, Pro33 platelets exhibited a significantly higher Src and FAK activities than Leu33 platelets. Interestingly, even in the absence of the αIIbβ3-fibrinogen interaction, we could detect a shear-induced integrin-mediated signaling of Src and FAK in platelets. In parallel experiments in which platelets were pretreated with abciximab, an integrin αIIbβ3 antagonist, activation of both kinases by shear was inhibited., Conclusion: Taken together, our data indicates an important role of αIIbβ3 and shows that Leu33Pro polymorphism modulates the integrin-mediated Src and FAK signaling in platelets in response to shear stress.

Rice (Oryza sativa L.) is one of the major staple food crops of nearly two-third of the world's population. However, rice blast caused by fungus Pyricularia oryzae is generally considered the most serious disease of cultivated rice worldwide due to its extensive distribution and destructiveness under favourable climatic conditions. In this report, the combination between chitosan (CS) and silver (Ag), Ag@CS, was introduced for antifungal activity against Pyricularia oryzae extracted from blast-infected leaves. In detail, Ag@CS nanoparticles (NPs) were first synthesized and further mixed with Trihexad 700 WP (Tri), Ag@CS-Tri, against the fungus by agar diffusion method. The prepared Ag@CS-Tri NPs were characterized by Fourier transform infrared (FTIR), dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). In aqueous condition, Ag@CS-Tri NPs were successfully prepared and existed as spherical NPs with particle size of 17.26 ± 0.89 nm, which is an ideal size for their uptake into plant cells, indicating that the size of their parentally Ag@CS NPs is small enough to combine Tri, and their diameter is large enough to effectively penetrate the cellular membrane and kill fungi. More importantly, the antifungal property of Ag@CS-Tri NPs was significantly increased with inhibition zone around 25 nm compared with only around 12 nm of Ag@CS at the same concentration of Ag (2 ppm) and CS (4000 ppm). These results demonstrated that the synergistic effect of Tri and Ag@CS NPs can be a potential candidate with high antifungal activity for the use of antibiotics in agriculture.

The aim of the present study was to improve the penetration during in vitro fertilization (IVF) of a frozen lot of epididymal sperm with a notoriously low fertilization ability of a Ban boar which is a native Vietnamese breed by optimizing different parameters of the IVF system. In Experiment 1, we determined that Pig-fertilization medium was superior medium to Tyrode's albumin lactate pyruvate-polyvinyl alcohol medium for IVF and defined the optimum the sperm concentration (1 × 10 6  sperm/ml). In Experiment 2, we clarified that partial removal of cumulus cells from cumulus-oocyte complexes by hyaluronidase treatment before IVF enhances sperm penetration, whereas complete cumulus removal reduces penetration. Finally, in Experiment 3 the elevation of concentration of caffeine in Pig-fertilization medium from 2 to 5 mmol/L and the prolongation of the co-culture of gametes from 3 to 5 hr significantly increased the total penetration rate from 15.2% to over 50%. In conclusion, the combination of partial oocyte denudation, an elevated caffeine concentration in Pig-fertilization medium and an extended interval of IVF with using an optimized sperm concentration was a potent way to improve the fertilization results for a frozen epididymal Ban sperm lot with low fertility., (© 2018 Japanese Society of Animal Science.)

Influenza is a major health burden worldwide and is caused by influenza viruses that are enveloped and negative stranded RNA viruses. Little progress has been achieved in targeted intervention, either at a population level or at an individual level (to treat the cause), due to the toxicity of drugs and ineffective vaccines against influenza viruses. MicroRNAs (miRNAs) are small non-coding RNAs that play critical roles in gene expression, cell differentiation, and tissue development and have been shown to silence viral replication in a sequence-specific manner. Investigation of these small endogenous nucleotides may lead to new therapeutics against influenza virus infection. Here, we describe our current understanding of the role of miRNAs in host defense response against influenza virus, as well as their potential and limitation as new therapeutic approaches.

Burn wound healing is a complex multifactorial process that relies on coordinated signaling molecules to succeed. Curcumin is believed to be a potent antioxidant and anti-inflammatory agent; therefore, it can prevent the prolonged presence of oxygen free radicals which is a significant factor causing inhabitation of optimum healing process. This study describes an extension of study about the biofunctional nanocomposite hydrogel platform that was prepared by using curcumin and an amphiphilic chitosan-g-pluronic copolymer specialized in burn wound healing application. This formular (nCur-CP, nanocomposite hydrogel) was a free-flowing sol at ambient temperature and instantly converted into a nonflowing gel at body temperature. In addition, the storage study determined the great stability level of nCur-CP in long time using UV-Vis and DLS. Morphology and distribution of nCur in its nanocomposite hydrogels were observed by SEM and TEM, respectively. In vitro studies suggested that nCur-CP exhibited well fibroblast proliferation and ability in antimicrobacteria. Furthermore, second- and third-degree burn wound models were employed to evaluate the in vivo wound healing activity of the nCur-CP. In the second-degree wound model, the nanocomposite hydrogel group showed a higher regenerated collagen density and thicker epidermis layer formation. In third degree, the nCur-CP group also exhibited enhancement of wound closure. Besides, in both models, the nanocomposite material-treated groups showed higher collagen content, better granulation, and higher wound maturity. Histopathologic examination also implied that the nanocomposite hydrogel based on nanocurcumin and chitosan could enhance burn wound repair. In conclusion, the biocompatible and injectable nanocomposite scaffold might have great potential to apply for wound healing.

Porous nanosilica (PNS) has been regarded as a promising candidate for controlled delivery of anticancer drugs. Unmodified PNS-based nanocarriers, however, showed a burst release of encapsulated drugs, which may limit their clinical uses. In this report, PNS was surface conjugated with adamantylamine (ADA) via disulfide bridges (-SS-), PNS-SS-ADA, which was further modified with cyclodextrin-poly(ethylene glycol) methyl ether conjugate (CD-mPEG) to form a core@shell structure PNS-SS-ADA@CD-mPEG for redox triggered delivery of doxorubicin (DOX), DOX/PNS-SS-ADA@CD-mPEG. The prepared PNS-SS-ADA@CD-mPEG nanoparticles were spherical in shape with an average diameter of 55.5 ± 3.05 nm, a little larger than their parentally PNS nanocarriers, at 49.6 ± 2.56 nm. In addition, these nanoparticles possessed high drug loading capacity, at 79.2 ± 3.2%, for controlled release. The release of DOX from DOX/PNS-SS-ADA@CD-mPEG nanoparticles was controlled and prolonged up to 120 h in PBS medium (pH 7.4), compared to less than 40 h under reducing condition of 5 mM DTT. Notably, the PNS-SS-ADA@CD-mPEG was a biocompatible nanocarrier, and the toxicity of DOX was dramatically reduced after loading drugs into the porous core. This redox-sensitive PNS-SS-ADA@CD-mPEG nanoparticle could be considered a potential candidate with high drug loading capacity and a lower risk of systemic toxicity.

A silver (Ag)-incorporated kesterite Cu 2 ZnSnS 4 (CZTS) thin film was fabricated by a facile spray pyrolysis method. Crystallographic analyses indicated successful incorporation of various amounts of Ag up to a Ag/(Ag + Cu) ratio of ca. 0.1 into the crystal lattice of CZTS in a homogeneous manner without formation of other impurity compounds. From the results of morphological investigations, Ag-incorporated films had larger crystal grains than the CZTS film. The sample with a relatively low Ag content (Ag/(Ag + Cu) of ca. 0.02) had a compact morphology without appreciable voids and pinholes. However, an increase in the Ag content in the CZTS film (Ag/(Ag + Cu) ca. 0.10) induced the formation of a large number of pinholes. As can be expected from these morphological properties, the best sunlight conversion efficiency was obtained by the solar cell based on the film with Ag/(Ag + Cu) of ca. 0.02. Electrostructural analyses of the devices suggested that the Ag-incorporated film in the device achieved reduction in the amounts of unfavorable copper on zinc antisite defects compared to the bare CZTS film. Moreover, the use of a Ag-incorporated film improved band alignment at the CdS(buffer)-CZTS interface. These alterations should also contribute to enhancement of device properties.

Respiratory syncytial virus (RSV) infection induces asthma exacerbations, which leads to worsening of clinical symptoms and may result in a sustained decline in lung function. Exacerbations are the main cause of morbidity and mortality associated with asthma, and significantly contribute to asthma-associated healthcare costs. Although glucocorticoids are used to manage exacerbations, some patients respond to them poorly. The underlying mechanisms associated with steroid-resistant exacerbations remain largely unknown. We have previously established a mouse model of RSV-induced exacerbation of allergic airways disease, which mimics hallmark clinical features of asthma. In this study, we have identified key roles for macrophage IFN-γ and IL-27 in the regulation of RSV-induced exacerbation of allergic airways disease. Production of IFN-γ and IL-27 was steroid-resistant, and neutralization of IFN-γ or IL-27 significantly suppressed RSV-induced steroid-resistant airway hyperresponsiveness and airway inflammation. We have previously implicated activation of pulmonary macrophage by TNF-α and/or MCP-1 in the mechanisms of RSV-induced exacerbation. Stimulation of pulmonary macrophages with TNF-α and/or MCP-1 induced expression of both IFN-γ and IL-27. Our findings highlight critical roles for IFN-γ and IL-27, downstream of TNF-α and MCP-1, in the mechanism of RSV-induced exacerbation. Thus, targeting the pathways that these factors activate may be a potential therapeutic approach for virus-induced asthma exacerbations., (Copyright © 2017 by The American Association of Immunologists, Inc.)

In this report, poly(amide amine) (PAMAM) dendrimer and Heparin-grafted-monomethoxy polyethylene glycol (HEP-mPEG) were synthesized and characterized. In aqueous solution, the generation 4 PAMAM dendrimers (G4.0-PAMAM) existed as nanoparticles with particle size of 5.63nm. However, after electrostatic complexation with HEP-mPEG to form a core@shell structure G4.0-PAMAM@HEP-mPEG, the size of nanoparticles was significantly increased (73.82nm). The G4.0-PAMAM@HEP-mPEG nanoparticles showed their ability to effectively encapsulate doxorubicin (DOX) for prolonged and controlled release. The cytocompatibility of G4.0-PAMAM@HEP-mPEG nanocarriers was significantly increased compared with its parentally G4.0-PAMAM dendrimer in both mouse fibroblast NIH3T3 and the human tumor HeLa cell lines. DOX was effectively encapsulated into G4.0-PAMAM@HEP-mPEG nanoparticles to form DOX-loaded nanocarriers (DOX/G4.0-PAMAM@HEP-mPEG) with high loading efficiency (73.2%). The release of DOX from DOX/G4.0-PAMAM@HEP-mPEG nanocarriers was controlled and prolonged up to 96h compared with less than 24h from their parentally G4.0-PAMAM nanocarriers. Importantly, the released DOX retained its bioactivity by inhibiting the proliferation of monolayer-cultured cancer HeLa cells with the same degree of fresh DOX. This prepared G4.0-PAMAM@HEP-mPEG nanocarrier can be a potential candidate for drug delivery systems with high loading capacity and low systemic toxicity in cancer therapy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

: Shear stress alone can activate platelets resulting in a subsequent platelet aggregation, so-called 'shear-induced platelet aggregation'. In our work, we analyzed how differently elevated shear stress impacts the Src and focal adhesion kinase (FAK) activation in fibrinogen-adherent human platelets. We detected the extents of Src pY418 and FAK pY397 activations in platelets on immobilized fibrinogen and over BSA under shear conditions. Moreover, we analyzed the role of αIIbβ3 in the shear-induced platelet signaling by performing our experiments in the presence of the αIIbβ3-antagonist Abciximab. Abnormally high shear rates (5000 s) significantly increased the extent of phosphorylation of both tyrosine kinases after short (2 min) incubation time independently of the presence or absence of the integrin αIIbβ3 ligand, fibrinogen. We could see considerably greater Src activation on immobilized fibrinogen than on BSA, but the extent of FAK Y397 phosphorylation was independent on the matrix. Abciximab not only reduced the Src and FAK signaling in platelets exposed to 5000 s on immobilized fibrinogen, but in platelets exposed to 5000 s over BSA as well. Our data indicate that whereas Src activation under shear stress is dominantly ligand-dependent, FAK signaling seems to be mostly shear induced.

Background: Severe steroid-insensitive asthma is a substantial clinical problem. Effective treatments are urgently required, however, their development is hampered by a lack of understanding of the mechanisms of disease pathogenesis. Steroid-insensitive asthma is associated with respiratory tract infections and noneosinophilic endotypes, including neutrophilic forms of disease. However, steroid-insensitive patients with eosinophil-enriched inflammation have also been described. The mechanisms that underpin infection-induced, severe steroid-insensitive asthma can be elucidated by using mouse models of disease., Objective: We sought to develop representative mouse models of severe, steroid-insensitive asthma and to use them to identify pathogenic mechanisms and investigate new treatment approaches., Methods: Novel mouse models of Chlamydia, Haemophilus influenzae, influenza, and respiratory syncytial virus respiratory tract infections and ovalbumin-induced, severe, steroid-insensitive allergic airway disease (SSIAAD) in BALB/c mice were developed and interrogated., Results: Infection induced increases in the levels of microRNA (miRNA)-21 (miR-21) expression in the lung during SSIAAD, whereas expression of the miR-21 target phosphatase and tensin homolog was reduced. This was associated with an increase in levels of phosphorylated Akt, an indicator of phosphoinositide 3-kinase (PI3K) activity, and decreased nuclear histone deacetylase (HDAC)2 levels. Treatment with an miR-21-specific antagomir (Ant-21) increased phosphatase and tensin homolog levels. Treatment with Ant-21, or the pan-PI3K inhibitor LY294002, reduced PI3K activity and restored HDAC2 levels. This led to suppression of airway hyperresponsiveness and restored steroid sensitivity to allergic airway disease. These observations were replicated with SSIAAD associated with 4 different pathogens., Conclusion: We identify a previously unrecognized role for an miR-21/PI3K/HDAC2 axis in SSIAAD. Our data highlight miR-21 as a novel therapeutic target for the treatment of this form of asthma., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Heparin (Hep) conjugated to poly (amidoamine) dendrimer G3.5 (P) via redox-sensitive disulfide bond (P-SS-Hep) was studied. The redox and pH dual-responsive nanocarriers were prepared by a simple method that minimized many complex steps as previous studies. The functional characterization of G3.5 coated Hep was investigated by the proton nuclear magnetic resonance spectroscopy. The size and formation were characterized by the dynamic light scattering, zeta potential, and transmission electron microscopy. P-SS-Hep was spherical in shape with average diameter about 11 nm loaded with more than 20% letrozole. This drug carrier could not only eliminate toxicity to cells and improve the drugs solubility but also increase biocompatibility of the system under reductive environment of glutathione. In particular, P-SS-Hep could enhance the effectiveness of cancer therapy after removing Hep from the surface. These results demonstrated that the P-SS-Hep conjugates could be a promising candidate as redox and pH responsive nanocarriers for cancer chemotherapy., Competing Interests: The authors declare that they have no competing interests.

Platelet integrin αIIbβ3 possesses a Leu/Pro polymorphism at residue 33 (Leu33/HPA-1a or Pro33/HPA-1b). The Pro33 isoform has been suggested to exhibit prothrombotic features. αIIbβ3-expressing CHO (Chinese hamster ovary) cells on immobilized fibrinogen show activation of the MAP kinase family member ERK2, with an enhanced ERK2 activity in Pro33 cells compared to Leu33 cells. In our present work, we examined how the Leu/Pro polymorphism modulates the ERK2 activation stimulated by 2 differently triggered outside-in signalings. We either treated the CHO cells with Mn2+ or allowed them to adhere to fibrinogen. Moreover, we studied which signaling cascades are involved in ERK2 activation. In contrast to immobilized fibrinogen, Mn2+ did not significantly increase ERK2 activation. However, Mn2+ had a synergistic effect on ERK2 phosphorylation when combined with immobilized fibrinogen. Pro33 cells adherent to fibrinogen exhibited a significantly greater ERK2 activity than Leu33 cells in the presence of Mn2+, which peaked after 10 min of adhesion. Our data showed that Src family and rho kinases play a crucial role in the integrin αIIbβ3-dependent outside-in signaling to ERK2., (© 2016 S. Karger AG, Basel.)

The formulation of a potential delivery system based on liposomes (Lips) formulated from soy lecithin (SL) for paclitaxel (PTX) was achieved (PTX-Lips). At first, PTX-Lips were prepared by thin film method using SL and cholesterol and then were characterized for their physiochemical properties (particle size, polydispersity index, zeta potential, and morphology). The results indicated that PTX-Lips were spherical in shape with a dynamic light scattering (DLS) particle size of 131 ± 30.5 nm. Besides, PTX was efficiently encapsulated in Lips, 94.5 ± 3.2% for drug loading efficiency, and slowly released up to 96 h, compared with free PTX. More importantly, cell proliferation kit I (MTT) assay data showed that Lips were biocompatible nanocarriers, and in addition the incorporation of PTX into Lips has been proven successful in reducing the toxicity of PTX. As a result, development of Lips using SL may offer a stable delivery system and promising properties for loading and sustained release of PTX in cancer therapy., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

In the study, four kinds of pluronics (P123, F68, F127 and F108) with varying hydrophilic-lipophilic balance (HLB) values were modified and conjugated on 4th generation of polyamidoamine dendrimer (PAMAM). The obtained results from FT-IR, 1 H NMR and GPC showed that the pluronics effectively conjugated on the dendrimer. The molecular weight of four PAMAM G4.0-Pluronics and its morphologies are in range of 200.15-377.14kDa and around 60-180nm in diameter by TEM, respectively. Loading efficiency and release of hydrophobic fluorouracil (5-FU) anticancer drug were evaluated by HPLC; Interesting that the dendrimer nanocarrier was conjugated with the highly lipophilic pluronic P123 (G4.0-P123) exhibiting a higher drug loading efficiency (up to 76.25%) in comparison with another pluronics. Live/dead fibroblast cell staining assay mentioned that all conjugated nanocarriers are highly biocompatible. The drug-loaded nanocarriers also indicated a highly anti-proliferative activity against MCF-7 breast cancer cell. The obtained results demonstrated a great potential of the highly lipophilic pluronics-conjugated nanocarriers in hydrophobic drugs delivery for biomedical applications., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Exacerbations of asthma are linked to significant decline in lung function and are often poorly controlled by corticosteroid treatment. Clinical investigations indicate that viral and bacterial infections play crucial roles in the onset of steroid-resistant inflammation and airways hyperresponsiveness (AHR) that are hallmark features of exacerbations. We have previously shown that interferon γ (IFNγ) and lipopolysaccharide (LPS) cooperatively activate pulmonary macrophages and induce steroid-resistant airway inflammation and AHR in mouse models. Furthermore, we have established a mouse model of respiratory syncytial virus (RSV)-induced exacerbation of asthma, which exhibits macrophage-dependent, steroid-resistant lung disease. Emerging evidence has demonstrated a key role for bromo- and extra-terminal (BET) proteins in the regulation of inflammatory gene expression in macrophages. We hypothesised that BET proteins may be involved in the regulation of AHR and airway inflammation in our steroid-resistant exacerbation models., Methodology/principal Findings: We investigated the effects of a BET inhibitor (I-BET-762) on the development of steroid-resistant AHR and airway inflammation in two mouse models. I-BET-762 administration decreased macrophage and neutrophil infiltration into the airways, and suppressed key inflammatory cytokines in both models. I-BET treatment also suppressed key inflammatory cytokines linked to the development of steroid-resistant inflammation such as monocyte chemoattractant protein 1 (MCP-1), keratinocyte-derived protein chemokine (KC), IFNγ, and interleukin 27 (IL-27). Attenuation of inflammation was associated with suppression of AHR., Conclusions/significance: Our results suggest that BET proteins play an important role in the regulation of steroid-resistant exacerbations of airway inflammation and AHR. BET proteins may be potential targets for the development of future therapies to treat steroid-resistant inflammatory components of asthma., Competing Interests: The authors have declared that no competing interests exist.

Pure sulfide Cu2 ZnSnS4 thin films were fabricated on Mo-coated glass substrates by facile spray deposition of aqueous precursor solutions containing Cu(NO3 )2 , Zn(NO3 )2 , Sn(CH3 SO3 )2 , and thiourea followed by annealing at 600 °C. When a precursor solution containing a stoichiometric composition of Cu, Zn, and Sn was used, the resulting Cu2 ZnSnS4 thin film contained a Cu2-x S impurity phase owing to the evaporation of Sn components during the annealing process. The Cu2-x S impurity in the Cu2 ZnSnS4 thin film was removed by reducing the concentration of Cu in the precursor solution. This resulted in an improvement of the structural features (i.e., grain sizes and compactness) as well as the electric properties such as acceptor densities, the nature of the acceptor defects, and carrier lifetimes. A solar cell based on the Cu2 ZnSnS4 film with an empirically optimal composition showed conversion efficiency of 8.1 %. The value achieved was one of the best efficiencies of Cu2 ZnSnS4 -based cells derived from a non-vacuum process., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Viral respiratory infections trigger severe exacerbations of asthma, worsen disease symptoms, and impair lung function. To investigate the mechanisms underlying viral exacerbation, we established a mouse model of respiratory syncytial virus (RSV)-induced exacerbation after allergen sensitization and challenge. RSV infection of OVA-sensitized/challenged BALB/c mice resulted in significantly increased airway hyperresponsiveness (AHR) and macrophage and neutrophil lung infiltration. Exacerbation was accompanied by increased levels of inflammatory cytokines (including TNF-α, MCP-1, and keratinocyte-derived protein chemokine [KC]) compared with uninfected OVA-treated mice or OVA-treated mice exposed to UV-inactivated RSV. Dexamethasone treatment completely inhibited all features of allergic disease, including AHR and eosinophil infiltration, in uninfected OVA-sensitized/challenged mice. Conversely, dexamethasone treatment following RSV-induced exacerbation only partially suppressed AHR and failed to dampen macrophage and neutrophil infiltration or inflammatory cytokine production (TNF-α, MCP-1, and KC). This mimics clinical observations in patients with exacerbations, which is associated with increased neutrophils and often poorly responds to corticosteroid therapy. Interestingly, we also observed increased TNF-α levels in sputum samples from patients with neutrophilic asthma. Although RSV-induced exacerbation was resistant to steroid treatment, inhibition of TNF-α and MCP-1 function or depletion of macrophages suppressed features of disease, including AHR and macrophage and neutrophil infiltration. Our findings highlight critical roles for macrophages and inflammatory cytokines (including TNF-α and MCP-1) in viral-induced exacerbation of asthma and suggest examination of these pathways as novel therapeutic approaches for disease management., (Copyright © 2016 by The American Association of Immunologists, Inc.)

Fibronectin (FN), a dimeric adhesive glycoprotein, which is present both in plasma and the extracellular matrix can interact with platelets and thus contribute to platelet adhesion and aggregation. It has been shown that FN can decrease platelet aggregation but enhance platelet adhesion, suggesting a dual role of FN in haemostasis. The prevalent function(s) of FN may be determined by its fibril form. To explore the suggested dual role of this adhesive protein for haemostasis in further detail, we now tested for any differences of adherent and suspended platelets with regard to their effect to unfold and assemble FN upon interaction. Platelet aggregation and adhesion assays were performed using washed platelets in the presence of exogenous FN. Addition of plasma FN reduced platelet aggregation in response to collagen or PMA by 50% or 25% but enhanced platelet adhesion onto immobilized collagen, as compared to control experiments. Analyses by fluorescence resonance energy transfer (FRET) demonstrated that adherent platelets but not suspended platelets were capable of unfolding FN during 3h incubation. Fluorescence microscopy and deoxycholate (DOC) solubility assays demonstrated that FN fibrils formed only on the surfaces of adherent platelets. In addition, platelets adherent onto FN revealed a significantly higher activity of specific Src phosphorylation (pY418) than platelets in suspension. These data suggest (1) that the function of FN in haemostasis is prevalent to its assembly, unfolding and subsequent fibril formation on the surface of adherent platelets and (2) that outside-in signaling contributes to the interaction of platelets and FN., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A common and prevailing complication for patients with abdominal surgery is the peritoneal adhesion that follows during the post-operative recovery period. Biodegradable polymers have been suggested as a barrier to prevent the peritoneal adhesion. In this work, as a preventive method, PVA/Gelatin hydrogel-based membrane was investigated with various combinations of PVA and gelatin (50/50, 30/70/, and 10/90). Membranes were made by casting method using hot PVA-gelatin solution and the gelatin was cross-linked by exposing UV irradiation for 5 days to render stability of the produced sheathed form in the physiological environment. Physical crosslinking was chosen to avoid the problems of potential cytotoxic effect of chemical crosslinking. Their materials characterization and mechanical properties were evaluated by SEM surface characterization, hydrophilicity, biodegradation rate, and so forth. Cytocompatibility was observed by in vitro experiments with cell proliferation using confocal laser scanning microscopy and the MTT assay by L-929 mouse fibroblast cells. The fabricated PVA/Gel membranes were implanted between artificially defected cecum and peritoneal wall in rats and were sacrificed after 1 and 2 weeks post-operative to compare their tissue adhesion extents with that of control group where the defected surface was not separated by PVA/Gel membrane. The PVA/Gel membrane (10/90) significantly reduced the adhesion extent and showed to be a potential candidate for the anti-adhesion application., (Copyright © 2013 Wiley Periodicals, Inc.)