A double-layer cellulose/pectin-soy protein isolate-pomegranate peel extract micro/nanofiber dressing for acceleration of wound healing.

Multi-layered wound dressings can closely mimic the hierarchical structure of the skin. Herein, a double-layer dressing material is fabricated through electrospinning, comprised of a nanofibrous structure as a healing-support layer or the bottom layer (BL) containing pectin (Pec), soy protein isolate (SPI), pomegranate peel extract (P), and a cellulose (Cel) microfiber layer as a protective/monitoring layer or top layer (TL). The formation of a fine bilayer structure was confirmed using scanning electron microscopy. Cel/Pec-SPI-P dressing showed a 60.05 % weight loss during 7 days of immersion in phosphate buffered solution. The ultimate tensile strength, elastic modulus, and elongation at break for different dressings were within the range of 3.14-3.57 MPa, 32.26-36.58 MPa, and 59.04-63.19 %, respectively. The release of SPI and phenolic compounds from dressings were measured and their antibacterial activity was evaluated. The fabricated dressing was non-cytotoxic following exposure to human keratinocyte cells. The Cel/Pec-SPI-P dressing exhibited excellent cell adhesion and migration as well as angiogenesis. More importantly, in vivo experiments on Cel/Pec-SPI-P dressings showed faster epidermal layer formation, blood vessel generation, collagen deposition, and a faster wound healing rate. Overall, it is anticipated that the Cel/Pec-SPI-P bilayer dressing facilitates wound treatment and can be a promising approach for clinical use.

Advances in Stimuli-Responsive Chitosan Hydrogels for Drug Delivery Systems.

Sustainable and controllable drug transport is one of the most efficient ways of disease treatment. Due to high biocompatibility, good biodegradability, and low costs, chitosan and its derivatives are widely used in biomedical fields. Specifically, chitosan hydrogel enables drugs to pass through biological barriers because of their abundant amino and hydroxyl groups that can interact with human tissues. Moreover, the multi-responsive nature (pH, temperature, ions strength, and magnetic field, etc.) of chitosan hydrogels makes precise drug release a possibility. Here, the synthesis methods, modification strategies, stimuli-responsive mechanisms of chitosan-based hydrogels, and their recent progress in drug delivery are summarized. Chitosan hydrogels that carry and release drugs through subcutaneous (dealing with wound dressing), oral (dealing with gastrointestinal tract), and facial (dealing with ophthalmic, ear, and brain) are reviewed. Finally, challenges toward clinic application and the future prospects of stimuli-responsive chitosan-based hydrogels are indicated.

Keratin- and VEGF-Incorporated Honey-Based Sponge-Nanofiber Dressing: An Ideal Construct for Wound Healing.

To overcome the drawbacks of single-layered wound dressings, bilayer dressings are now introduced as an alternative to achieve effective and long-term treatment. Here, a bilayer dressing composed of electrospun nanofibers in the bottom layer (BL) and a sponge structure as the top layer (TL) is presented. Hydrophilic poly(acrylic acid) (PAAc)-honey (Hny) with interconnected pores of 76.04 µm was prepared as the TL and keratin (Kr), Hny, and vascular endothelial growth factor (VEGF) were prepared as the BL. VEGF indicates a gradual release over 7 days, promoting angiogenesis, as proven by the chick chorioallantoic membrane assay and in vivo tissue histomorphology observation. Additionally, the fabricated dressing material indicated a satisfactory tensile profile, cytocompatibility for human keratinocyte cells, and the ability to promote cell attachment and migration. The in vivo animal model demonstrated that the full-thickness wound healed faster when it was covered with PAAc-Hny/Hny-Kr-VEGF than in other groups. Additionally, faster blood vessel formation, collagen synthetization, and epidermal layer generation were also confirmed, which have proven efficient healing acceleration in wounds treated with synthesized bilayer dressings. Our findings indicated that the fabricated material can be promising as a functional wound dressing.

Antinociceptive effects of vitamin B-complex: A behavioral and histochemical study in rats.

B-vitamins have been evaluated as a useful adjuvant therapy to treat pain. In spite of clinical and experimental evidence indicating the analgesic effect of B-vitamins, few studies have investigated their effect on aspects of the inflammatory pain response. In the present study, we investigated the analgesic effect of chronic application of B-complex vitamins (Neurobion) using an inflammatory experimental pain model in rats. Nociceptive behavioral responses were evaluated in male Wistar rats after plantar injection of formalin, comparing the treatment group (TG) with Neurobion pretreatment to the control group (CG) without the pretreatment. In addition, neuronal activity in the central pain pathway was evaluated using c-Fos immunohistochemical reactivity and NADPH-d histochemistry. A highly significant reduction of painful behaviors such as licking and flinching were observed in TG, especially during the secondary phase of the formalin test compared to CG. Results suggest that long-term pre-treatment using Neurobion can have a beneficial effect in reducing the chronic phase of pain. In addition, we observed a downregulation of c-Fos and NADPH-d in dorsal spinal neurons, suggesting that the antinociceptive effect induced by Neurobion could be due to a suppression of nociceptive transmission at the spinal level, particularly in the afferent regions of the dorsal spinal horn, which these neurons utilizing nitric oxide at least as one of their pain neurotransmitters.

Angiogenesis, hemocompatibility and bactericidal effect of bioactive natural polymer-based bilayer adhesive skin substitute for infected burned wound healing.

Thermal wounds are complex and lethal with irregular shapes, risk of infection, slow healing, and large surface area. The mortality rate in patients with infected burns is twice that of non-infected burns. Developing multifunctional skin substitutes to augment the healing rate of infected burns is vital. Herein, we 3D printed a hydrogel scaffold comprising carboxymethyl chitosan (CMCs) and oxidized alginate grafted catechol (O-AlgCat) on a hydrophobic electrospun layer, forming a bilayer skin substitute (BSS). The functional layer (FL) was fabricated by physiochemical crosslinking to ensure favorable biodegradability. The gallium-containing hydrophobic electrospun layer or backing layer (BL) could mimic the epidermis of skin, avoiding fluid penetration and offering antibacterial activity. 3D printed FL contains catechol, gallium, and biologically active platelet rich fibrin (PRF) to adhere to both tissue and BL, show antibacterial activity, encourage angiogenesis, cell growth, and migration. The fabricated bioactive BSS exhibited noticeable adhesive properties (P ≤ 0.05), significant antibacterial activity (P ≤ 0.05), faster clot formation, and the potential to promote proliferation (P ≤ 0.05) and migration (P ≤ 0.05) of L929 cells. Furthermore, the angiogenesis was significantly higher (P ≤ 0.05) when evaluated in vivo and in ovo. The BSS-covered wounds healed faster due to low inflammation and high collagen density. Based on the obtained results, the fabricated bioactive BSS could be an effective treatment for infected burn wounds.

Asymmetric tri-layer sponge-nanofiber wound dressing containing insulin-like growth factor-1 and multi-walled carbon nanotubes for acceleration of full-thickness wound healing.

To more closely resemble the structure of natural skin, multi-layered wound dressings have been developed. Herein, a tri-layer wound dressing was prepared containing a polyacrylamide (PAAm)-Aloe vera (Alo) sponge that had been incorporated with insulin-like growth factor-1 (IGF1) to provide a porous absorbent layer, which was able to promote angiogenesis. Alo nanofibers with multi-walled carbon nanotubes (MWCNT) were electrospun into the bottom layer to increase cell behavior, and a small film of stearic acid was put as a top layer to avoid germy penetration. In comparison to bilayer dressing, the tensile strength increased by 17.0 % (from 0.200 ± 0.010 MPa to 0.234 ± 0.022 MPa) and the elastic modulus by 45.6 % (from 0.217 ± 0.003 MPa to 0.316 ± 0.012 MPa) in the presence of Alo nanofibers containing 0.5 wt% of MWCNT at the bottom layer of Trilayer0.5 dressing. The release profile of IGF1, the antibacterial activity and the degradability of different wound dressings were investigated. Trilayer0.5 indicated the highest cell viability, cell adhesion and angiogenic potential among the prepared dressing materials. In-vivo rat model revealed that the Trilayer0.5 dressing treated group had the highest rate of wound closure and wound healing within 10 days compared to other groups.

Advanced biomaterials for human glioblastoma multiforme (GBM) drug delivery.

Glioblastoma multiforme (GBM) has several distinctive characteristics linked to a poor early-stage prognosis. The crucial obstacle in the treatment of GBM is the inability of chemo drugs or other anticancer medicines to reach brain tumors due to the blood-brain tumor barrier (BBTB), leading to weak cytotoxic activity and drug resistance. Additionally, there is a limited number of clinically approved anticancer medicines for GBM because of the heterogeneity of this type of tumor. Presently, four FDA-approved drugs are available for the treatment of GBM, i.e., temozolomide, lomustine, carmustine, and bevacizumab. These drugs are primarily used to treat recurrent high-grade gliomas and their symptoms. Unfortunately, despite efforts to treat GBM over the last 60 years, no significant progress has been made in extending the overall survival (OS) of patients with this disease. Therefore, possible treatments and accessible drugs must be modified or advanced medicines developed to treat GBM. Several innovative strategies have been used to overcome these challenges, such as combining traditional therapies with emerging nanoscale-based biomaterials for multifunctional characteristics. These modified nanoscale biomaterials can cross the blood-brain barrier (BBB) and increase chemo-drug sensitivity through improved accumulation and efficiency. Herein, we review the recent developments in organic and inorganic biomaterial-based nanoparticles for GBM drug delivery. Firstly, we present a brief overview of the FDA-approved drugs and some additional chemo drugs for treating GBM, followed by a discussion on the drawbacks of the delivery of these drugs in GBM. Further, the current challenges in the field of GBM drug delivery, significant advancements in biomaterials research to overcome these obstacles, and subsequent considerations and opportunities for the application of biomaterials in the clinical treatment of GBM are highlighted.

Functionalization of aminoalkylsilane-grafted cotton for antibacterial, thermal, and wettability properties.

Multifunctional cotton fabrics are considered a significant challenge, hindering their commercialization through a scalable and eco-friendly method. The main drawbacks that limit their wide application are the lack of antibacterial activity, wettability, and being easily damaged by fire. Herein, we report a facile synthesis technique of superhydrophobic, flame resistant and antibacterial cotton fabric production using APTES agents to achieve all the above-mentioned properties. This study optimized the chemical grafting of aminoalkylsilane on the cotton surface with different reaction times and APTES concentrations to get the highest grafting content. Chemical characterization confirmed successful aminoalkylsilane grafting on the surface of cotton fabric. Subsequently, the antibacterial activity, wettability, and flame resistance properties of aminoalkylsilane grafted cotton fabric were accurately investigated. The obtained results showed that samples at 10 h reaction time with 14% APTES concentration indicated higher grafting content which showed high enhancement. Additionally, all produced aminoalkylsilane grafted cotton demonstrated a water contact angle of higher than 115° with low surface energy as well as impressive antibacterial activity. The obtained grafted cotton could be used as a promising filter screen for separating oils from contaminated water with more than 90% separation efficiency. This method is easy, environmentally friendly, cost-effective, and practical. It can be widely used to produce superhydrophobic cotton fabric on a large scale, which holds great potential in oil-water separation energy-saving clothing and healthcare products.

A poly-l-lysine-bonded TEMPO-oxidized bacterial nanocellulose-based antibacterial dressing for infected wound treatment.

Oxidized bacterial nanocellulose (O-BNC) is a favorable material to subdue bacterial infection because of the carboxylate content that not only has a weak antibacterial activity but also is capable of bonding electrostatically to polycationic antibacterial agents. In this study, the 2,2,6,6-Tetramethylpiperidinyloxy radical (TEMPO)-mediated oxidation of BNC was optimized to achieve high carboxylate content while retaining an acceptable tensile profile. To develop an O-BNC-based functional wound dressing, ε-poly-l-lysine (PLL) was then covalently bonded with O-BNC via 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS) reaction after homogeneous distribution by ultrasonication. The antibacterial activity of the obtained wound dressing was significantly higher (p < 0.05), and no toxicity was observed. The infected full-thickness wounds of rats were healed faster (p < 0.05) covered by the dressing due to less inflammation, faster blood vessel proliferation, and epidermal layer formation. The material is an effective and promising functional dressing for the treatment of infected wounds.

Fibrous Aerogels for Solar Vapor Generation.

Solar-driven vapor generation is emerging as an eco-friendly and cost-effective water treatment technology for harvesting solar energy. Aerogels are solid materials with desirable high-performance properties, including low density, low thermal conductivity, and high porosity with a large internal surface, which exhibit outstanding performance in the area of solar vapor generation. Using fibers as building blocks in aerogels could achieve unexpected performance in solar vapor generation due to their entangled fibrous network and high surface area. In this review, based on the fusion of the one-dimensional fibers and three-dimensional porous aerogels, we discuss recent development in fibrous aerogels for solar vapor generation based on building blocks synthesis, photothermal materials selection, pore structures construction and device design. Thermal management and water management of fibrous aerogels are also evaluated to improve evaporation performance. Focusing on materials science and engineering, we overview the key challenges and future research opportunities of fibrous aerogels in both fundamental research and practical application of solar vapor generation technology.

Different Methods for Cell Viability and Proliferation Assay: Essential Tools in Pharmaceutical Studies.

BACKGROUND AND OBJECTIVE: The ratio of live cells to total cells in a sample is a definition for cell viability or cell toxicity. The assessment of the viable cells plays a critical role in all processes of the cell culture workflows. Overall, they are used to evaluate the survival of cells and also to optimize culture or experimental conditions following treatment with different agents or compounds, like during a drug screen. In most cases, the measurement of cell viability is the primary purpose of the experiments, for example, in pharmaceutical studies to evaluate agents' toxicity. METHODS: A literature research was conducted on cell viability assays from MEDLINE (PubMed), Web of Science and Scopus. RESULTS: There is a wide range of cell viability assays and different parameters such as cost, speed, and complexity of a test effect to determine the choosing method. However, each method has some advantages and disadvantages and none of them are 100% perfect. CONCLUSION: Accordingly, it seems that the simultaneous utility of at least two assays will cover disadvantages to demonstrate the effects of different agents on different cell types. For instance, when one assay measures cell metabolic health, the other one checks cells permeability. Therefore, by this strategy, a researcher can report with more confidence the effective doses of the examined therapeutic agents.

Evaluation of cell adhesion and osteoconductivity in bone substitutes modified by polydopamine.

Bones damaged due to disease or accidents can be repaired in different ways. Tissue engineering has helped with scaffolds made of different biomaterials and various methods. Although all kinds of biomaterials can be useful, sometimes their weakness in cellular activity or osteoconductivity prevents their optimal use in the fabrication of bone scaffolds. To solve this problem, we need additional processes, such as surface modification. One of the common methods is coating with polydopamine. Polydopamine can not only cover the weakness of the scaffolds in terms of cellular properties, but it can also create or increase osteoconductivity properties. Polydopamine creates a hydrophilic layer on the surface of scaffolds due to a large number of functional groups such as amino and hydroxyl groups. This layer allows bone cells to anchor and adheres well to the surfaces. In addition, it creates a biocompatible environment for proliferation and differentiation. Besides, the polydopamine coating makes the surfaces chemically active by catechol and amine group, and as a result of their presence, osteoconductivity increases. In this mini-review, we investigated the characteristics, structure, and properties of polydopamine as a modifier of bone substitutes. Finally, we evaluated the cell adhesion and osteoconductivity of different polydopamine-modified bone scaffolds.

Functionalization of Aminoalkylsilane-Grafted Bacterial Nanocellulose with ZnO-NPs-Doped Pullulan Electrospun Nanofibers for Multifunctional Wound Dressing.

High moisture permeability, excellent mechanical properties in a wet state, high water-holding capability, and high exudate absorption make bacterial nanocellulose (BNC) a favorable candidate for biomedical device production, especially wound dressings. The lack of antibacterial activity and healing-promoting ability are the main drawbacks that limit its wide application. Pullulan (Pul) is a nontoxic polymer that can promote wound healing. Zinc oxide nanoparticles (ZnO-NPs) are well-known as a safe antibacterial agent. In this study, aminoalkylsilane was chemically grafted on a BNC membrane (A-g-BNC) and used as a bridge to combine BNC with Pul-ZnO-NPs hybrid electrospun nanofibers. FTIR results confirmed the successful production of A-g-BNC/Pul-ZnO. The obtained dressing demonstrated blood clotting performance better than that of BNC. The dressing showed an ability to release ZnO, and its antibacterial activity was up to 5 log values higher than that of BNC. The cytotoxicity of the dressing toward L929 fibroblast cells clearly showed safety due to the proliferation of fibroblast cells. The animal test in a rat model indicated faster healing and re-epithelialization, small blood vessel formation, and collagen synthesis in the wounds covered by A-g-BNC/Pul-ZnO. The new functional dressing, fabricated with a cost-effective and easy method, not only showed excellent antibacterial activity but could also accelerate wound healing.

Polypropylene/Lignin/POSS Nanocomposites: Thermal and Wettability Properties, Application in Water Remediation.

Compositing is an interesting strategy that has always been employed to introduce or enhance desired functionalities in material systems. In this paper, sponges containing polypropylene, lignin, and octavinyl-polyhedral oligomeric silsesquioxane (OV-POSS) were successfully prepared via an easy and elegant strategy called thermally induced phase separation (TIPS). To fully explore the behaviour of different components of prepared sponges, properties were characterized by a thermogravimetric analyser (TGA), differential scanning calorimetry (DSC), Fourier transform infrared measurement (FTIR), and scanning electron microscopy (SEM). Furthermore, wettability properties toward an organic liquid and oil were investigated. The FTIR analysis confirmed the chemical modification of the components. TGA and DSC measurements revealed thermal stability was much better with an increase in OV-POSS content. OV-POSS modified sponges exhibited ultra-hydrophobicity and high oleophilicity with water contact angles of more than 125°. The SEM revealed that POSS molecules acted as a support for reduced surface roughness. Moreover, OV-POSS-based blend sponges showed higher sorption capacities compared with other blend sponges without OV-POSS. The new blend sponges demonstrated a potential for use as sorbent engineering materials in water remediation.

Application of Bacterial Nanocellulose in Cancer Drug Delivery: A Review.

Bacterial nanocellulose (BNC) is one of the natural biopolymers with unique features, such as nontoxicity, biocompatibility, high tensile profile, nanofiber structure, and purity. The current review aimed to summarize the latest development in BNC-based biomaterials in cancer drug delivery. The original articles were found by searching key databases, including PubMed, Scopus, and Web of Scientific and using key terms such as "bacterial nanocellulose OR bacterial cellulose OR BNC" AND "cancer OR carcinoma OR tumor". The obtained data were in a wide timeframe and the English language. Totally, 350 articles were found from the three main databases (i.e., 106, 251, and 173 articles from PubMed, Scopus, and the Web of Science, respectively). In general, 32 articles met the inclusion criteria after duplicate removal and screening according to the aim of the study. In this review study, different applications of the BNC were considered for cancer drug delivery in addition to describing advanced methods that may be applied to improve therapeutic potency while reducing the adverse effects of chemodrugs by decreasing their dosages. The high ratio of the surface area-to-volume and easy modifications of their chemical components lead to BNC potential use as an appropriate matrix structure for the binding and controlled release of various pharmaceutical agents, specifically for topical or transdermal administrations. In addition, BNC-based products regulate the release of hydrophobic and hydrophilic compounds, thus providing appropriate materials related to cancer drug delivery. However, undoubtedly, further developments of BNC-based products as cancer drug delivery systems require more extensive investigations.

Multifunctional bioactive core-shell electrospun membrane capable to terminate inflammatory cycle and promote angiogenesis in diabetic wound.

Diabetic wound (DW) healing is a major clinical challenge due to multifactorial complications leading to prolonged inflammation. Electrospun nanofibrous (NF) membranes, due to special structural features, are promising biomaterials capable to promote DW healing through the delivery of active agents in a controlled manner. Herein, we report a multifunctional composite NF membrane loaded with ZnO nanoparticles (NP) and oregano essential oil (OEO), employing a new loading strategy, capable to sustainedly co-deliver bioactive agents. Physicochemical characterization revealed the successful fabrication of loaded nanofibers with strong in vitro anti-bacterial and anti-oxidant activities. Furthermore, in vivo wound healing confirmed the potential of bioactive NF membranes in epithelialization and granulation tissue formation. The angiogenesis was greatly prompted by the bioactive NF membranes through expression of vascular endothelial growth factor (VEGF). Moreover, the proposed NF membrane successfully terminated the inflammatory cycle by downregulating the pro-inflammatory cytokines interleukin -6 (IL-6) and matrix metalloproteinases-9 (MMP-9). In vitro and in vivo studies revealed the proposed NF membrane is a promising dressing material for the healing of DW.

Bacterial Nanocellulose-Enhanced Alginate Double-Network Hydrogels Cross-Linked with Six Metal Cations for Antibacterial Wound Dressing.

Alginate (Alg) and bacterial nanocellulose (BNC) have exhibited great potential in biomedical applications, especially wound dressing. Non-toxicity and a moisture-maintaining nature are common features making them favorable for functional dressing fabrication. BNC is a natural biopolymer that promotes major advances to the current and future biomedical materials, especially in a flat or tubular membrane form with excellent mechanical strength at hydrated state. The main drawback limiting wide applications of both BNC and Alg is the lack of antibacterial activity, furthermore, the inherent poor mechanical property of Alg leads to the requirement of a secondary dressing in clinical treatment. To fabricate composite dressings with antibacterial activity and better mechanical properties, sodium alginate was efficiently incorporated into the BNC matrix using a time-saving vacuum suction method followed by cross-linking through immersion in separate solutions of six cations (manganese, cobalt, copper, zinc, silver, and cerium). The results showed the fabricated composites had not only pH-responsive antibacterial activities but also improved mechanical properties, which are capable of acting as smart dressings. All composites showed non-toxicity toward fibroblast cells. Rat model evaluation showed the skin wounds covered by the dressings healed faster than by BNC.

Apo AI Nanoparticles Delivered Post Myocardial Infarction Moderate Inflammation.

RATIONALE: Decades of research have examined immune-modulatory strategies to protect the heart after an acute myocardial infarction and prevent progression to heart failure but have failed to translate to clinical benefit. OBJECTIVE: To determine anti-inflammatory actions of n-apo AI (Apo AI nanoparticles) that contribute to cardiac tissue recovery after myocardial infarction. METHODS AND RESULTS: Using a preclinical mouse model of myocardial infarction, we demonstrate that a single intravenous bolus of n-apo AI (CSL111, 80 mg/kg) delivered immediately after reperfusion reduced the systemic and cardiac inflammatory response. N-apo AI treatment lowered the number of circulating leukocytes by 30±7% and their recruitment into the ischemic heart by 25±10% (all P<5.0×10-2). This was associated with a reduction in plasma levels of the clinical biomarker of cardiac injury, cardiac troponin-I, by 52±17% (P=1.01×10-2). N-apo AI reduced the cardiac expression of chemokines that attract neutrophils and monocytes by 60% to 80% and lowered surface expression of integrin CD11b on monocytes by 20±5% (all P<5.0×10-2). Fluorescently labeled n-apo AI entered the infarct and peri-infarct regions and colocalized with cardiomyocytes undergoing apoptosis and with leukocytes. We further demonstrate that n-apo AI binds to neutrophils and monocytes, with preferential binding to the proinflammatory monocyte subtype and partially via SR-BI (scavenger receptor BI). In patients with type 2 diabetes, we also observed that intravenous infusion of the same n-apo AI (CSL111, 80 mg/kg) similarly reduced the level of circulating leukocytes by 12±5% (all P<5.0×10-2). CONCLUSIONS: A single intravenous bolus of n-apo AI delivered immediately post-myocardial infarction reduced the systemic and cardiac inflammatory response through direct actions on both the ischemic myocardium and leukocytes. These data highlight the anti-inflammatory effects of n-apo AI and provide preclinical support for investigation of its use for management of acute coronary syndromes in the setting of primary percutaneous coronary interventions.

Candidalysin Is Required for Neutrophil Recruitment and Virulence During Systemic Candida albicans Infection.

BACKGROUND: Candidalysin is a cytolytic peptide toxin secreted by Candida albicans hyphae and has significantly advanced our understanding of fungal pathogenesis. Candidalysin is critical for mucosal C albicans infections and is known to activate epithelial cells to induce downstream innate immune responses that are associated with protection or immunopathology during oral or vaginal infections. Furthermore, candidalysin activates the NLRP3 inflammasome and causes cytolysis in mononuclear phagocytes. However, the role of candidalysin in driving systemic infections is unknown. METHODS: In this study, using candidalysin-producing and candidalysin-deficient C albicans strains, we show that candidalysin activates mitogen-activated protein kinase (MAPK) signaling and chemokine secretion in endothelial cells in vitro. RESULTS: Candidalysin induces immune activation and neutrophil recruitment in vivo, and it promotes mortality in zebrafish and murine models of systemic fungal infection. CONCLUSIONS: The data demonstrate a key role for candidalysin in neutrophil recruitment and fungal virulence during disseminated systemic C albicans infections.