Mucosal Adhesive Chitosan Nanogel Formulations of Antibiotics and Adjuvants (Terpenoids, Flavonoids, etc.) and Their Potential for the Treatment of Infectious Diseases of the Gastrointestinal Tract.

Bacterial infections are usually found in the stomach and the first part of the small intestine in association with various pathologies, including ulcers, inflammatory diseases, and sometimes cancer. Treatment options may include combinations of antibiotics with proton pump inhibitors and anti-inflammatory drugs. However, all of them have high systemic exposure and, hence, unfavorable side effects, whereas their exposure in stomach mucus, the predominant location of the bacteria, is limited. Chitosan and nanogels based on chitosan presumably are not absorbed from the gastrointestinal tract and are known to adhere to the mucus. Therefore, they can serve as a basis for the local delivery of antibacterial drugs, increasing their exposure at the predominant location of therapeutic targets, thus improving the risk/benefit ratio. We have used E. coli ATCC 25922 (as a screening model of pathogenic bacteria) and Lactobacilli (as a model of a normal microbiome) to study the antibacterial activity of antibacterial drugs entrapped in a chitosan nanogel. Classical antibiotics were studied in a monotherapeutic regimen as well as in combination with individual terpenoids and flavonoids as adjuvants. It has been shown that levofloxacin (LF) in combination with zephirol demonstrate synergistic effects against E. coli (cell viability decreased by about 50%) and, surprisingly, a much weaker effect against Lactobacilli. A number of other combinations of antibiotic + adjuvant were also shown to be effective. Using FTIR and UV spectroscopy, it has been confirmed that chitosan nanogels with the drug are well adsorbed on the mucosal model, providing prolonged release at the target location. Using an ABTS assay, the antioxidant properties of flavonoids and other drugs are shown, which are potentially necessary to minimize the harmful effects of toxins and radicals produced by pathogens. In vivo experiments (on sturgeon fish) showed the effective action of antibacterial formulations developed based on LF in chitosan nanogels for up to 11 days. Thus, chitosan nanogels loaded with a combination of drugs and adjuvants can be considered as a new strategy for the treatment of infectious diseases of the gastrointestinal tract.

Evaluation of Retinal Ganglion Cell via Visual Evoked Potential.

Visual Evoked Potential (VEP) is an electrical signal recorded from the visual cortex in response to light stimulation. It can be used as an in vivo method to objectively access the functional integrity of the retinogeniculocortical pathway. Here we describe the methods to perform flash VEP (FVEP) recording in rodents and goat and pattern VEP (PVEP) recording in rhesus macaque.

Unilateral cross-incompatibility between Camellia oleifera and C. yuhsienensis provides new insights for hybridization in Camellia spp.

Camellia yuhsienensis was used to cross with Camellia oleifera to improve the resistance of oil camellia anthracnose. However, unilateral cross-incompatibility (UCI) between C. oleifera and C. yuhsienensis was found during the breeding process. Five C.oleifera cultivars and four C. uhsienensis materials were tested to confirm the UCI between C. oleifera and C. yuhsienensis. 'Huashuo' (HS) and 'Youza 2' (YZ2) were used to represent these two species to characterize the UCI, including pollen tube growth, fertilization and fruit development. The results demonstrated that UCI was prevalent between C. oleifera and C. yuhsienensis. The asynchronous flowering period was a pre-pollination barrier that limited mating between these two species under natural conditions. Interspecific pollen tubes were observed through the styles of these two plants, though the growth rates differed considerably. At 96 hours after pollination, the pollen tube of YZ2 barely entered the ovule, but remained at the base of the style and became swollen. However, the HS pollen tube entered the ovule 48 hours after pollination, double fertilization was observed, and the fruit and seeds developed commonly. Relative to compatible combinations, most unfertilized ovules in incompatible combinations failed to grow, turned brown 150 days after pollination, and the fruits were smaller than expected with uneven enlargement. Investigations on both semi-in vivo and in vitro pollen tubes gave us new idea for thought: the HS style has a stronger inhibitory effect on the interspecific pollen tubes, while calcium alleviates the inhibitory of styles but failed to prevent the appearance of abnormal pollen tube morphology. This study provides useful information on interspecific hybridization between C. oleifera and C. yuhsienensis for understanding reproductive isolation mechanisms and breeding programs in genus Camellia.

Flexible self-healing nanocomposite based gelatin/tannic acid/acrylic acid reinforced with zinc oxide nanoparticles and hollow silver nanoparticles based on porous silica for rapid wound healing.

In this research, gelatin (Ge), tannic acid (TA), acrylic acid (AA) as a matrix are used. Zinc oxide (ZnO) nanoparticles (10, 20, 30, 40 and 50 wt%) and hollow silver nanoparticles along with ascorbic acid (1, 3, and 5 wt%) are considered as reinforcement. In order to prove the functional groups of nanoparticles made from Fourier-transform infrared spectroscopy (FTIR), and determine the existing phases of the powders in the hydrogel, X-ray diffraction (XRD) is used, also to investigate the morphology, size, and porosity of the holes and in the scaffolds, scanning electron microscope analysis is used (FESEM). Then, mechanical tests such as tension and compression test are performed to determine the most optimal state of the composite. Also, the antibacterial test is performed for the manufactured powders and hydrogel, as well as the toxicity test for the fabricated hydrogel. The results show that the sample (30 wt% of zinc oxide and 5 wt% of hollow nanoparticles) is the most optimal hydrogel based on mechanical tests and biological properties.

Short-term in vivo testing to discriminate genotoxic carcinogens from non-genotoxic carcinogens and non-carcinogens using next-generation RNA sequencing, DNA microarray, and qPCR.

Next-generation RNA sequencing (RNA-Seq) has identified more differentially expressed protein-coding genes (DEGs) and provided a wider quantitative range of expression level changes than conventional DNA microarrays. JEMS·MMS·Toxicogenomics group studied DEGs with targeted RNA-Seq on freshly frozen rat liver tissues and on formalin-fixed paraffin-embedded (FFPE) rat liver tissues after 28 days of treatment with chemicals and quantitative real-time PCR (qPCR) on rat and mouse liver tissues after 4 to 48 h treatment with chemicals and analyzed by principal component analysis (PCA) as statics. Analysis of rat public DNA microarray data (Open TG-GATEs) was also performed. In total, 35 chemicals were analyzed [15 genotoxic hepatocarcinogens (GTHCs), 9 non-genotoxic hepatocarcinogens (NGTHCs), and 11 non-genotoxic non-hepatocarcinogens (NGTNHCs)]. As a result, 12 marker genes (Aen, Bax, Btg2, Ccnf, Ccng1, Cdkn1a, Gdf15, Lrp1, Mbd1, Phlda3, Plk2, and Tubb4b) were proposed to discriminate GTHCs from NGTHCs and NGTNHCs. U.S. Environmental Protection Agency studied DEGs induced by 4 known GTHCs in rat liver using DNA microarray and proposed 7 biomarker genes, Bax, Bcmp1, Btg2, Ccng1, Cdkn1a, Cgr19, and Mgmt for GTHCs. Studies involving the use of whole-transcriptome RNA-Seq upon exposure to chemical carcinogens in vivo have also been performed in rodent liver, kidney, lung, colon, and other organs, although discrimination of GTHCs from NGTHCs was not examined. Candidate genes published using RNA-Seq, qPCR, and DNA microarray will be useful for the future development of short-term in vivo studies of environmental carcinogens using RNA-Seq.

Bioactive bacterial cellulose wound dressings for burns with collagen in-situ and chitosan ex-situ impregnation.

Bacterial cellulose (BC) is a biopolymer that commonly used for wound dressings regarding to its high in-vitro and in-vivo biocompatibility. Moreover, the three-dimensional fibers in BC become an advantageous for bioactive wound dressing application as they serve as templates for impregnation other supportive materials. Chitosan and collagen are two of the materials that can be impregnated to optimize the BC properties for serve as wound dressing material. Collagen can help skin cells grow on the wound sites, where chitosan has anti-bacterial properties and can bind red blood cells. BC-based wound dressings were made by impregnating collagen via in-situ method followed by immersing chitosan via ex-situ method into BC fibers for 24 h. The intermolecular interactions of amine groups in the wound dressing were confirmed by FTIR. The XRD diffractogram showed wider peaks at 14.2°, 16.6°, and 22.4° due to the presence of collagen and chitosan molecules in the BC fibers. SEM images confirmed that chitosan and collagen could penetrate BC fibers well. Other tests, such as water content, porosity, antibacterial properties, and haemocompatibility, indicated that the wound dressing was non-hemolytic. In-vivo test indicated that BC/collagen/chitosan wound dressing supported the wound healing process on second degree burn.

Cytotoxicity and Anti-Plasmodium berghei Activity of Emodin Loaded Nanoemulsion.

Background: Malaria parasites cause a tremendous burden of disease in both the tropics and subtropics areas. Growing of drugs resistance in parasites is one of the most threats to malaria control. The aim of study was to investigate the anti-malarial activity of nano-emodin isolated from Rhamnus cathartica on Plasmodium berghei in mice to evaluate parasites inhibition rate using in-vivo test. Methods: The study was conducted in the School of Public Health, Tehran University of Medical Sciences, during 2020. Nano-emodin particles were prepared from Rhamnus cathartica, and confirmed by Zeta Potential Analyzer, DLS and electron microscopy techniques. Mice were infected with P. berghei and treated by emodin nano-particles. Parasitemia was evaluated in each group in comparison with control group. Toxicity test was done using twice the highest concentration of emodin extract on a separate group of mice and ED50 was calculated. Results: Emodin extract was significantly effective in all concentrations on D4 (P<0.05). The most effective on parasitemia was observed in 400 mg/kg of Liquid Nano-emodin and solid (non-Nano) emodin. ED50 for emodin extract was determined 220 mg/kg. Toxicity test showed no toxic effect on the subjects. Conclusion: The emodin extract is safe, lack of side effects. So, it can be used for more and longer period of time and in higher doses. Emodin extract, either in form of liquid and nanoparticle or in a solid form, has the same therapeutic effect on P. berghei in infected Balb/c mice.

Anthelmintic Properties of Essential Oils to Control Gastrointestinal Nematodes in Sheep-In Vitro and In Vivo Studies.

Herbal products such as essential oils may play a promising role in the treatment of infections caused by gastrointestinal nematodes (GINs). The aim of this study was to evaluate the in vitro potential of 11 essential oils (EOs) and one binary combination of isolated EO compounds, as well as the in vivo anthelmintic efficacy of two EO formulations. Four GIN genera were identified in the coproculture examination: Haemonchus, Trichostrongylus, Teladorsagia and Chabertia. The in vitro egg hatch test (EHT) was performed at six different concentrations (50, 12.5, 3.125, 0.781, 0.195 and 0.049 mg/mL) for each EO, whereas in the in vivo faecal egg count reduction test (FECRT), each EO sample was diluted in sunflower oil and orally administrated at a dose of 100 mg/kg to the different group of animals. In the EHT, the EOs of Origanum vulgare, Foeniculum vulgare, Satureja montana, Satureja hortensis and two types of Thymus vulgaris were the most effective. The dominant compounds of these EOs were carvacrol, thymol, anethol, p-cymene and γ-terpinene, indicating their importance for the anthelmintic activity. In the FECRT, both T. vulgaris EO type 1 and linalool:estragole combination show an anthelmintic potential with a mean effect on FECR of approximately 25%. The results suggest the possible role of tested EOs as anthelmintic agents in sheep farms, although further in vivo tests are needed.

A Potential Anthelmintic Phytopharmacological Source of Origanum vulgare (L.) Essential Oil against Gastrointestinal Nematodes of Sheep.

The development of anthelmintic resistance in sheep gastrointestinal nematodes (GINs) requires novel strategies for the sustainable control of these parasites. This study aimed to evaluate the anthelmintic efficacy of the Origanum vulgare (L.) essential oil (EO) against sheep GINs and to evaluate the possibility of its use in control practice. The in vitro egg hatch test was conducted at eight different concentrations (50, 12.5, 3.125, 0.781, 0.195, 0.049, 0.025, and 0.0125 mg/mL) of the tested EO. For the in vivo fecal egg count reduction test, the EO of O. vulgare was administrated orally at a mean single dose of 150 mg/kg to sheep from two farms in Southern Italy, whereby potential toxic effects to the hosts were also evaluated. In the egg hatch test, the inhibition of egg hatchability varied from 71.3% to 93.7%, depending on the concentration used. The high anthelmintic potential was confirmed in the fecal egg count reduction test with an average reduction of nematode eggs in feces of 43.2% and 60.1% on days 7 and 14 after treatment, respectively. In addition, no toxic effects were noticed during the clinical examination of sheep or by observing blood count and liver or kidney function test results. The obtained results suggest the strong activity of the O. vulgare EO against sheep GINs, probably due to a high percentage of carvacrol (76.21%), whereby it can be considered safe for sheep at the dose tested in vivo. Therefore, it is suitable for use in veterinary practice as a part of an integrated strategy for the control of sheep GINs.

In vivo biocompatibility and degradability of a Zn-Mg-Fe alloy osteosynthesis system.

Zinc is generally considered to be one of the most promising materials to be used in biodegradable implants, and many zinc alloys have been optimized to improve implant biocompatibility, degradation, and mechanical properties. However, long-term degradation leads to the prolonged presence of degradation products, which risks foreign body reactions. Herein, we investigated the in vivo biocompatibility and degradation of a biodegradable Zn-Mg-Fe alloy osteosynthesis system in the frontal bone, mandible, and femur in beagles for 1 year. Results of the routine blood, biochemical, trace element, and histological analyses of multiple organs, peripheral blood CD4/CD8a levels, and serum interleukin 2 and 4 levels showed good biocompatibility of the Zn-Mg-Fe alloy. Zinc content analysis revealed zinc accumulation in adjacent bone tissue, but not in the liver, kidney, and spleen, which was related to the degradation of the Zn-Mg-Fe alloy. The alloy demonstrated a uniform slowing degradation rate in vivo. No degradation differences in the frontal bone, mandible, and femur were observed. The degradation products included zinc oxide [ZnO], zinc hydroxide [Zn(OH)2], hydrozincite [Zn5(OH)6(CO3)2], and hopeite [Zn3(PO4)2·4H2O]. The good biocompatibility and degradation properties of the Zn-Mg-Fe alloy render it a very attractive osteosynthesis system for clinical applications.

Evaluation of the skin phototoxicity of systemically administered pharmaceuticals in Sprague-Dawley rats.

In vivo phototoxicity testing is important for predicting drug-induced phototoxicity in humans. Currently, there is no internationally validated in vivo test method for the photosafety evaluation of pharmaceuticals. In this study, we evaluated the phototoxicity of systemically administered drugs using SD rats. We first determined the appropriate ultraviolet A (UVA) dose using 8-methoxypsoralen, a well-known phototoxic drug. Compared to lower and higher UVA doses, we found that a UVA dose of 10 J/cm2 allowed for the detection of phototoxic responses in both a dose- and time-dependent manner. We next performed a phototoxicity study using seven pharmaceutical drugs which included known phototoxic and non-phototoxic drugs using a UVA dose of 10 J/cm2. In order to improve the accuracy of our assessment, we evaluated both gross skin findings as well as histopathological findings. Using gross skin findings alone resulted in an accuracy of 85.7% which could be increased to 100% accuracy when the gross skin findings were combined with histopathological findings. This study suggests that the inclusion of histopathological findings increases the accuracy of the phototoxicity evaluation of systemically administered drugs in SD rats. In conclusion, we found that for studying drug-induced phytotoxicity, a 10 J/cm2 UVA dose serves as the optimal radiation dose, and that the inclusion of histopathological findings increases the accuracy of the phototoxicity evaluation of the drugs.

Developmental Neurotoxicity of Environmentally Relevant Pharmaceuticals and Mixtures Thereof in a Zebrafish Embryo Behavioural Test.

Humans are exposed daily to complex mixtures of chemical substances via food intake, inhalation, and dermal contact. Developmental neurotoxicity is an understudied area and entails one of the most complex areas in toxicology. Animal studies for developmental neurotoxicity (DNT) are hardly performed in the context of regular hazard studies, as they are costly and time consuming and provide only limited information as to human relevance. There is a need for a combination of in vitro and in silico tests for the assessment of chemically induced DNT in humans. The zebrafish (Danio rerio) embryo (ZFE) provides a powerful model to study DNT because it shows fast neurodevelopment with a large resemblance to the higher vertebrate, including the human system. One of the suitable readouts for DNT testing in the zebrafish is neurobehaviour (stimulus-provoked locomotion) since this provides integrated information on the functionality and status of the entire nervous system of the embryo. In the current study, environmentally relevant pharmaceuticals and their mixtures were investigated using the zebrafish light-dark transition test. Zebrafish embryos were exposed to three neuroactive compounds of concern, carbamazepine (CBZ), fluoxetine (FLX), and venlafaxine (VNX), as well as their main metabolites, carbamazepine 10,11-epoxide (CBZ 10,11E), norfluoxetine (norFLX), and desvenlafaxine (desVNX). All the studied compounds, except CBZ 10,11E, dose-dependently inhibited zebrafish locomotor activity, providing a distinct behavioural phenotype. Mixture experiments with these pharmaceuticals identified that dose addition was confirmed for all the studied binary mixtures (CBZ-FLX, CBZ-VNX, and VNX-FLX), thereby supporting the zebrafish embryo as a model for studying the cumulative effect of chemical mixtures in DNT. This study shows that pharmaceuticals and a mixture thereof affect locomotor activity in zebrafish. The test is directly applicable in environmental risk assessment; however, further studies are required to assess the relevance of these findings for developmental neurotoxicity in humans.

A Target-Based In Vivo Test System to Identify Novel Fungicides with Mode of Action in the HOG Pathway.

Resistance management plays a key role in modern plant protection. There is a growing need to identify new fungicide targets and new modes of action. In this context, it is also mandatory to find new compounds acting on successful target locations. For the latter, so-called target-site-specific test systems emerged to search for inhibitors. Most of them are based on in vitro assays, in which interaction between a compound and a purified target protein is demonstrated. Consequently, getting essential information about potentially toxic effects in the living cell or in the whole organism is not possible. Thus, we present a fluorescent-labelled mutant strain of the rice blast fungus Magnaporthe oryzae as a rapid tool for fluorescence-based identification and visualization of fungicides in vivo with the mode of action in the high osmolarity glycerol (HOG)-signaling pathway. The HOG pathway represents an excellent target for antifungal agents such as the phenylpyrrole fungicides, since almost no relevant resistances have occurred to date, despite 30 years of extensive usage of this fungicide class.

Collaborative study for the validation of cell line assays for in-process toxicity and antigenicity testing of Clostridium septicum vaccine antigens - Part 2: Optimisation of cell line assays.

During the production of clostridial vaccines large numbers of mice are used for various in-process control tests. Replacement in vitro assays had been developed for the testing of the toxins and toxoids of several clostridial species, but none of these assays had been assessed in an international collaborative study. Under the common aegis of the European Partnership for Alternative Approaches to Animal Testing (EPAA) and of the European Directorate for the Quality of Medicines & HealthCare (EDQM), a project on clostridial vaccines for veterinary use was started as part of the EDQM-co-ordinated Biological Standardisation Programme (BSP). Within the framework of this project (coded BSP130) a collaborative study was organised to evaluate Vero cell-based alternative methods to the current mouse tests used to measure: i) the toxicity of Clostridium septicum toxin, ii) the absence of toxicity of C. septicum toxoid and iii) the antigenicity of C. septicum toxoid. The principal aims of the study were to determine the repeatability and reproducibility of the in vitro assays and to demonstrate concordance of the in vitro and current in vivo tests. The study results demonstrated good concordance, but the information gathered through the study (later on called Part 1) and the participants' workshop prompted the extension of the project in order to further optimise the in vitro protocols and improve their repeatability and reproducibility, which were comparable to but not better than those of the in vivo assays in Part 1. The 3 in vitro assays to be optimised in the extension of the BSP130 project were : i) the in vitro toxin neutralisation equivalence plus (TNE+), as a replacement for the in vivo minimum lethal dose (MLD) test for quantification of the toxicity of toxin; ii) the in vitro MLD, as a replacement for the in vivo MLD test for detection of residual toxicity associated with toxoid; iii) the in vitro total combining power (TCP), as a replacement for the in vivo TCP test for quantification of the antigenicity of toxoid. At this point, the Analytical Method Transfer Laboratory of Ceva-Phylaxia (Hungary), supported by the project management team, developed suitable SOPs for the 3 in vitro assays. These optimised methods were further assessed in BSP130 through a second international collaborative study (Part 2) aimed at defining repeatability and reproducibility in different laboratories and determining the levels of improvement compared with the original in vivo tests and the initial in vitro assays used in Part 1 of the project. Fourteen laboratories, comprising 4 public sector and 10 manufacturers' medicines control laboratories, from 11 countries participated in the collaborative Part 2 study, each testing 6 different C. septicum toxins and 6 C. septicum toxoids. Improved repeatability and reproducibility were observed for the optimised assays. The results of this study confirm the suitability of these assays for in-process control of C. septicum vaccines, with better repeatability and reproducibility than their in vivo equivalents. It is expected that, with appropriate minor changes and the use of relevant reagents, these optimised in vitro assays could be used not only for the assessment of C. septicum toxins and toxoids but for all cytotoxin-based clostridial antigens. The development and implementation of such in vitro assays would offer a great opportunity to significantly reduce animal usage, shorten the duration of QC test procedures and increase the precision of toxicity and antigenicity assays in clostridial veterinary vaccine in-process control. This would also provide more accurate and reproducible dosing of antigens in the final vaccine products, help to promote compendial acceptance and to proffer a basis for improved international harmonisation across this area of product testing.

In vivo bioresorbability and bone formation ability of sintered highly pure calcium carbonate granules.

Calcium carbonate-based bone substitutes derived from natural coral exoskeleton (aragonite) are resorbed and remodeled faster than calcium phosphate-based substitutes. However, coral species with structures appropriate for use as bone substitutes are very limited. Therefore, it is important to evaluate potential of artificial calcium carbonate ceramics as a bone substitute. In this study, calcium carbonate granules with various porosities and pore sizes were prepared by sintering a highly pure (>99.98%) calcium carbonate powder (calcite), and their resorption properties and bone formation abilities were examined in vivo for the first time. The sintered calcium carbonate was resorbed faster than ß-tricalcium phosphate, which has a similar structure. However, sintered calcium carbonate did not promote new bone formation during long-term implantation. Furthermore, both resorption and new bone formation were affected by the pore structure. The optimal structures of the artificially sintered calcium carbonate bone substitute were also discussed.

Comprehensive review of genotoxicity data for diclofenac.

Diclofenac is a non-steroidal anti-inflammatory drug discovered several decades ago, which has since been used by an estimated one billion patients and has demonstrated an acceptable safety profile. In support of its marketing approval, a comprehensive set of genotoxicity studies were conducted in vitro and in vivo. Despite the fact that these studies preceded both Good Laboratory Practice (GLP) requirements and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines on genotoxicity testing, they were conducted using the best scientific principles and are considered appropriate by contemporary standards. In addition to bacterial mutagenicity and mammalian in vitro assays, repeat-dose somatic, germ cell and dominant lethal assays were conducted. These data are made available for the first time to offer researchers an opportunity to review the existing data set that unequivocally demonstrates that diclofenac sodium is not genotoxic. This is further substantiated by long-term bioassay data demonstrating that diclofenac sodium has no carcinogenic potential in rodents. However, more recently, new studies have been published showing a genotoxic potential for diclofenac in novel or modified in vitro test systems. These new publications are discussed in the context of the existing comprehensive data package.

Skin Sensitization Tests: The LLNA and the RhE IL-18 Potency Assay.

Contact allergy is of considerable importance to the toxicologist, and regulatory authorities worldwide require testing for skin sensitization potential and appropriate hazard labeling to enable management of the risk to human health. Although traditionally the identification of skin-sensitizing chemicals has been carried out using animal models, in Europe legislative changes have promoted, and now require, the use of non-animal methods (i.e., Cosmetic Directive, REACH). Several in vitro alternatives for hazard identification have now been validated, but do not provide information on the potency of a skin sensitizer. Here, we describe an animal model, the local lymph node assay (LLNA), and an in vitro model, the RhE IL-18 potency assay, in the context of the identification and potency classification of skin sensitizers. These two assays have been chosen among the different available tests as representative of an alternative in vivo model (the LLNA) and a promising in vitro method with the potential of both hazard identification and potency classification.

Fabrication and characterization of mucoadhesive bioplastic patch via coaxial polylactic acid (PLA) based electrospun nanofibers with antimicrobial and wound healing application.

Polylactic acid (PLA) is the second-highest consumed bioplastic in the world. PVP/PLA-PEO complex nanofibers encapsulating collagen and cefazolin dressing scaffold were fabricated using a coaxial electrospinning method to target the release of the encapsulated compounds. It was observed that in collagen doses of 10 and 20%, the speed of healing showed a significant difference with the control sample, but the dose of 40% caused a decrease in wound healing rate in mice. The nanofibers' morphology and surface roughness were investigated by scanning electron microscopy (SEM) and atomic force microscopy (AFM), respectively. The mechanical properties and adhesion strength of the scaffolds were investigated. The scaffolds' antimicrobial activity was evaluated by disk diffusion method against the E. coli, S. aureus, and P. aeruginosa. The results indicated a positive effect on the antimicrobial activity of the samples. In this study, we were able to prolong the effect of scaffolds by changing the pattern of release of cefazolin from inside the nanofibers. Possible interactions between the polymers and the encapsulated compounds were investigated using Fourier-transform infrared spectroscopy (FTIR). Finally, in-vivo and histological tests were performed to evaluate the efficacy of the scaffolds in accelerating wound healing.

Reduced Graphene Oxide-Polypyrrole Aerogel-Based Coaxial Heterogeneous Microfiber Enables Ultrasensitive Pressure Monitoring of Living Organisms.

Pressure sensors for living organisms can monitor both the movement behavior of the organism and pressure changes of the organ, and they have vast perspectives for the health management information platform and disease diagnostics/treatment through the micropressure changes of organs. Although pressure sensors have been widely integrated with e-skin or other wearable systems for health monitoring, they have not been approved for comprehensive surveillance and monitoring of living organisms due to their unsatisfied sensing performance. To solve the problem, here, we introduce a novel structural design strategy to manufacture reduced graphene oxide-polypyrrole aerogel-based microfibers with a typical coaxial heterogeneous structure, which significantly enhances the sensitivity, resolution, and stability of the derived pressure microsensors. The as-fabricated pressure microsensors exhibit ultrahigh sensitivities of 12.84, 18.27, and 4.46 kPa-1 in the pressure ranges of 0-20, 20-40, and 40-65 Pa, respectively, high resolution (0.2 Pa), and good stability in 450 cycles. Furthermore, the microsensor is applied to detect the movement behavior and organic micropressure changes for mice and serves as a platform for monitoring micropressure for the integrative diagnosis both in vivo and in vitro of organisms.

Diagnostic Tools in Allergic Rhinitis.

Allergic mechanisms account for most cases of chronic rhinitis. This condition is associated with significant impairment of quality of life and high indirect costs. The identification of the allergic triggers of rhinitis has been historically based on the performance of atopy test [skin prick test (SPT) and serum allergen-specific (s)IgE]. Nevertheless, these tests only denote sensitization, and atopy and allergy represent two different phenomena. It is now clear that allergic phenotypes of rhinitis can exist in both atopic (allergic rhinitis, AR) and non-atopic (local allergic rhinitis, LAR) individuals. Moreover, both allergic phenotypes can coexist in the same rhinitis patient (dual allergic rhinitis, DAR). Therefore, a diagnostic approach merely based on atopy tests is associated with a significant rate of misdiagnosis. The confirmation of the allergic etiology of rhinitis requires the performance of in vivo test like the nasal allergen challenge (NAC). NAC is mandatory for the diagnosis of LAR and DAR, and helps decide the best management approach in difficult cases of AR. Nevertheless, NAC is a laborious technique requiring human and technical resources. The basophil activation test (BAT) is a patient-friendly technique that has shown promising results for LAR and DAR diagnosis. In this review, the diagnostic usefulness for chronic rhinitis of SPT, NAC, olfactory tests, serum sIgE, BAT and the quantification of inflammatory mediators in nasal samples will be discussed. The accurate performance of an etiologic diagnosis of rhinitis patients will favor the prescription of specific therapies with disease-modifying potential like allergen immunotherapy.