A description of long-lived photodoped states in Mott insulators is challenging, as it needs to address exponentially separated timescales. We demonstrate how properties of such states can be computed using numerically exact steady state techniques, in particular, the quantum Monte Carlo algorithm, by using a time-local ansatz for the distribution function with separate Fermi functions for the electron and hole quasiparticles. The simulations show that the Mott gap remains robust to large photodoping, and the photodoped state has hole and electron quasiparticles with strongly renormalized properties.
We study bulk particle transport in a Fermi-Hubbard model on an infinite-dimensional Bethe lattice, driven by a constant electric field. Previous numerical studies showed that one dimensional analogs of this system exhibit a breakdown of diffusion due to Stark many-body localization at least up to time that scales exponentially with the system size. Here, we consider systems initially in a spin density wave state using a combination of numerically exact and approximate techniques. We show that for sufficiently weak electric fields, the wave's momentum component decays exponentially with time in a way consistent with normal diffusion. By studying different wavelengths, we extract the dynamical exponent and the generalized diffusion coefficient at each field strength. Interestingly, we find a nonmonotonic dependence of the dynamical exponent on the electric field. As the field increases toward a critical value proportional to the Hubbard interaction strength, transport slows down, becoming subdiffusive. At large interaction strengths, however, transport speeds up again with increasing field, exhibiting superdiffusive characteristics when the electric field is comparable to the interaction strength. Eventually, at the large field limit, localization occurs and the current through the system is suppressed.
Phase-change memory (PCM) devices have great potential as multilevel memory cells and artificial synapses for neuromorphic computing hardware. However, their practical use is hampered by resistance drift, a phenomenon commonly attributed to structural relaxation or electronic mechanisms primarily in the context of bulk effects. In this study, we reevaluate the electrical manifestation of resistance drift in sub-100 nm Ge2Sb2Te5 (GST) PCM devices, focusing on the contributions of bulk vs interface effects. We employ a combination of measurement techniques to elucidate the current transport mechanism and the electrical manifestation of resistance drift. Our steady-state temperature-dependent measurements reveal that resistance in these devices is predominantly influenced by their electrical contacts, with conduction occurring through thermionic emission (Schottky) at the contacts. Additionally, temporal current-voltage characterization allows us to link the resistance drift to a time-dependent increase in the Schottky barrier height. These findings provide valuable insights, pinpointing the primary contributor to resistance drift in PCM devices: the Schottky barrier height for hole injection at the interface. This underscores the significance of contacts (interface) in the electrical manifestation of drift in PCM devices.
Jojoba (Simmondsia chinensis L.) wax was previously reported to increase cutaneous wound healing, ameliorate acne and psoriasis manifestations, and reduce oxidative stress and inflammation. However, its potential cosmetic properties have not been fully investigated. Thus, the current study aimed to evaluate the anti-inflammatory activities of jojoba wax and its impact on the synthesis of extracellular components following topical application. The fatty acid and fatty alcohol profiles of two industrial and two lab-scale cold-press jojoba waxes were analyzed along with total tocopherol and phytosterol content. The dermo-cosmetic effect of all jojoba wax preparations was evaluated ex-vivo, using the human skin organ culture model, which emulates key features of intact tissue. The ability of jojoba wax to reduce secreted levels of key pro-inflammatory cytokines and the safety of the applications in the ex-vivo model were evaluated. In addition, the impact on the synthesis of pro-collagen and hyaluronic acid levels upon treatment was investigated. The results demonstrate that topically applied jojoba wax can reduce LPS-induced secretion of IL-6, IL-8, and TNFα by approx. 30% compared to untreated skin. This effect was enhanced when treatment was combined with low non-toxic levels of Triton X-100, and its efficacy was similar to the anti-inflammatory activity of dexamethasone used as a positive control. In addition, mRNA and protein levels of collagen III and synthesis of hyaluronic acid were markedly increased upon topical application of jojoba. Moreover, the enhanced content of extracellular matrix (ECM) components correlated with the enhanced expression of TGFß1. Collectively, our results further demonstrate that jojoba can reduce local skin inflammation, and this effect may be increased by emulsifier which increases its bioavailability. In addition, the finding that topical application of jojoba wax enhances the synthesis of pro-collagen and hyaluronic acid and may be beneficial in the treatment of age-related manifestations.
Nonequilibrium quantum transport is of central importance in nanotechnology. Its description requires the understanding of strong electronic correlations that couple atomic-scale phenomena to the nanoscale. So far, research in correlated transport has focused predominantly on few-channel transport, precluding the investigation of cross-scale effects. Recent theoretical advances enable the solution of models that capture the interplay between quantum correlations and confinement beyond a few channels. This problem is the focus of this study. We consider an atomic impurity embedded in a metallic nanosheet spanning two leads, showing that transport is significantly altered by tuning only the phase of a single local hopping parameter. Furthermoreâdepending on this phaseâcorrelations reshape the electronic flow throughout the sheet, either funneling it through the impurity or scattering it away from a much larger region. This demonstrates the potential for quantum correlations to bridge length scales in the design of nanoelectronic devices and sensors.
BACKGROUND: Skin aging manifestation, such as coarse wrinkles, loss of elasticity, pigmentation, and rough-textured appearance, is a multifactorial process that can be exacerbated by air pollution, smoking, poor nutrition, and sun exposure. Exposure to UV radiation is considered the primary cause of extrinsic skin aging and accounts for about 80% of facial aging. Extrinsic skin aging signs can be reduced with demo-cosmetic formulations. Both cannabidiol (CBD) and eicosapentaenoic acid (EPA) have been previously suggested as potent active dermatological ingredients. AIMS: The objective of the current research was to evaluate the compatibility of both agents in the prevention and treatment of skin aging. First, the impact of both agents was assessed using standard photoaging models of UV-induced damage, both in vitro (HaCaT cells) and ex vivo (human skin organ culture). Then, a clinical validation study (n = 33) was performed using an optimized topical cream formulation tested at different time points (up to Day 56). RESULTS: EPA was found to potentiate the protective effects of CBD by reducing the secretion of prostaglandin E2 (PGE2 ) and interleukin-8 (IL-8), two primary inflammatory agents associated with photoaging. In addition, a qualitative histological examination signaled that applying the cream may result in an increase in extracellular matrix (ECM) remodeling following UV radiation. This was also evidenced clinically by a reduction of crow's feet wrinkle area and volume, as well as a reduction of fine line wrinkle volume as measured by the AEVA system. The well-established age-dependent subepidermal low-echogenic band (SLEB) was also reduced by 8.8%. Additional clinical results showed significantly reduced red spots area and count, and an increase in skin hydration and elasticity by 31.2% and 25.6% following 56 days of cream application, respectively. These impressive clinical results correlated with high satisfaction ratings by the study participants. DISCUSSION AND CONCLUSIONS: Collectively, the results show a profound anti-aging impact of the developed formulation and strengthen the beneficial derm-cosmetic properties of CBD-based products.
The quantum many-body problem is ultimately a curse of dimensionality: the state of a system with many particles is determined by a function with many dimensions, which rapidly becomes difficult to efficiently store, evaluate and manipulate numerically. On the other hand, modern machine learning models like deep neural networks can express highly correlated functions in extremely large-dimensional spaces, including those describing quantum mechanical problems. We show that if one represents wavefunctions as a stochastically generated set of sample points, the problem of finding ground states can be reduced to one where the most technically challenging step is that of performing regression-a standard supervised learning task. In the stochastic representation the (anti)symmetric property of fermionic/bosonic wavefunction can be used for data augmentation and learned rather than explicitly enforced. We further demonstrate that propagation of an ansatz towards the ground state can then be performed in a more robust and computationally scalable fashion than traditional variational approaches allow.
Machine Learning , Neural Networks, Computer , Reproduction , Upper Extremity
Herein, we report biocompatible hydrogel for wound healing that was prepared using nature-sourced building blocks. For the first time, OCS was employed as a building macromolecule to form bulk hydrogels along with the nature-sourced nucleoside derivative (inosine dialdehyde, IdA) as the cross-linker. A strong correlation was obtained between the mechanical properties and stability of the prepared hydrogels with a cross-linker concentration. The Cryo-SEM images of IdA/OCS hydrogels showed an interconnected spongy-like porous structure. Alexa 555 labeled bovine serum albumin was incorporated into the hydrogels matrix. The release kinetics studies under physiological conditions indicated that cross-linker concentration could also control the release rate. The potential of hydrogels in wound healing applications was tested in vitro and ex vivo on human skin. Topical application of the hydrogel was excellently tolerated by the skin with no impairment of epidermal viability or irritation, determined by MTT and IL-1α assays, respectively. The hydrogels were used to load and deliver epidermal growth factor (EGF), showing an increase in its ameliorating action, effectively enhancing wound closure inflicted by punch biopsy. Furthermore, BrdU incorporation assay performed in both fibroblast and keratinocyte cells revealed an increased proliferation in hydrogel-treated cells and an enhancement of EGF impact in keratinocytes.
Epidermal Growth Factor , Nucleosides , Humans , Epidermal Growth Factor/pharmacology , Hydrogels/pharmacology , Hydrogels/chemistry , Wound Healing
Acne vulgaris, the most common form of acne, is characterized by a mixed eruption of inflammatory and noninflammatory skin lesions primarily affecting the face, upper arms, and trunk. The pathogenesis of acne is multifactorial and includes abnormal keratinization and plugging of the hair follicles, increased sebum production, proliferation and activation of Cutibacterium acnes (C. acnes; formerly Propionibacterium acnes, P. acnes), and finally inflammation. Recent studies have found that cannabidiol (CBD) may be beneficial in the treatment of acne. The aim of this study was to explore natural plant extracts that, when combined with CBD, act synergistically to treat acne by targeting different pathogenic factors while minimizing side effects. The first stage of the study investigated the capacity of different plant extracts and plant extract combinations to reduce C. acnes growth and decrease IL-1ß and TNFα secretion from U937 cells. The results found that Centella asiatica triterpene (CAT) extract as well as silymarin (from Silybum marianum fruit extract) had significantly superior anti-inflammatory activity when combined with CBD compared to either ingredient alone. In addition, the CAT extract helped potentiate CBD-induced C. acnes growth inhibition. The three ingredients were integrated into a topical formulation and evaluated in ex vivo human skin organ cultures. The formulation was found to be safe and effective, reducing both IL-6 and IL-8 hypersecretion without hampering epidermal viability. Finally, a preliminary clinical study of this formulation conducted on 30 human subjects showed a statistically significant reduction in acne lesions (mainly inflammatory lesions) and porphyrin levels, thereby establishing a tight correlation between in vitro, ex vivo, and clinical results. Further studies must be conducted to verify the results, including placebo-controlled clinical assessment, to exclude any action of the formulation itself.
BACKGROUND: The Dead Sea basin is the lowest terrestrial site on the globe and is internationally recognized as a photoclimatotherapy center. Since the last century, questions were raised regarding a possible presence of unique incident ultraviolet irradiation, allowing the successful treatment of psoriasis, atopic dermatitis and other dermatological diseases. AIM: This research study aims to determine the characteristics of solar ultraviolet irradiation and to understand the mechanism of action of photoclimatotherapy while applying results to clinical protocols of treatments. METHODS: A meteorological station was established at the Dead Sea basin to continuously measure global, UVB and UVA irradiation. The same irradiation parameters are also monitored continuously by a set of identical ultraviolet irradiation instruments installed on the campus of the Ben-Gurion University of the Negev in Beer Sheva. RESULTS: This study details the results of these long-term measurements, as well as their correlation with the success obtained by clinicians treating psoriasis patients. CONCLUSIONS: A database of more than 25 years has enabled medical staff to establish tailor-made protocols for sun-exposure time intervals as a function of particular month and hour of day. The availability of such information significantly improved the results of photoclimatotherapy for psoriasis and simultaneously increased the safety of sun exposure at the Dead Sea.
Dermatitis, Atopic , Psoriasis , Ultraviolet Therapy , Humans , Psoriasis/therapy , Ultraviolet Rays , Ultraviolet Therapy/methods
In this work, we present biocompatible nanocarriers based on modified polysaccharides capable of transporting insulin macromolecules through human skin without any auxiliary techniques. N-Alkylamidated carboxymethyl cellulose (CMC) derivatives CMC-6 and CMC-12 were synthesized and characterized using attenuated total reflectance Fourier transform infrared (ATR-FTIR) and nuclear magnetic resonance (NMR) spectroscopy, gel permeation chromatography and thermogravimetric, calorimetric and microscopic techniques. The prepared modified polysaccharides spontaneously assemble into soft nanoaggregates capable of adjusting to both aqueous and lipid environments. Due to this remarkable self-adjustment ability, CMC-6 and CMC-12 were examined for transdermal delivery of insulin. First, a significant increase in the amount of insulin present in lipid media upon encapsulation in CMC-12 was observed in vitro. Then, ex vivo studies on human skin were conducted. Those studies revealed that the CMC-12 carrier led to an enhancement of transdermal insulin delivery, showing a remarkable 85% insulin permeation. Finally, toxicity studies revealed no alteration in epidermal viability upon treatment and the absence of any skin irritation or amplified cytokine release, verifying the safety of the prepared carriers. Three-dimensional (3D) molecular modeling and conformational dynamics of CMC-6 and CMC-12 polymer chains explained their binding capacities and the ability to transport insulin macromolecules. The presented carriers have the potential to become a biocompatible, safe and feasible platform for the design of effective systems for transdermal delivery of bioactive macromolecules in medicine and cosmetics. In addition, transdermal insulin delivery reduces the pain and infection risk in comparison to injections, which may increase the compliance and glycemic control of diabetic patients.
The skin barrier and its endogenous protective mechanisms cope daily with exogenous stressors, of which ultraviolet radiation (UVR) poses an imminent danger. Although the skin is able to reduce the potential damage, there is a need for comprehensive strategies for protection. This is particularly important when developing pharmacological approaches to protect against photocarcinogenesis. Activation of NRF2 has the potential to provide comprehensive and long-lasting protection due to the upregulation of numerous cytoprotective downstream effector proteins that can counteract the damaging effects of UVR. This is also applicable to photodermatosis conditions that exacerbate the damage caused by UVR. This review describes the alterations caused by UVR in normal skin and photosensitive disorders, and provides evidence to support the development of NRF2 activators as pharmacological treatments. Key natural and synthetic activators with photoprotective properties are summarized. Lastly, the gap in knowledge in research associated with photodermatosis conditions is highlighted.
Photosensitivity Disorders , Ultraviolet Rays , Humans , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Photosensitivity Disorders/drug therapy , Skin/metabolism , Ultraviolet Rays/adverse effects
Environmental risk factors, including noise, air pollution, chemical agents, ultraviolet radiation (UVR) and mental stress have a considerable impact on human health. Oxidative stress and inflammation are key players in molecular pathomechanisms of environmental pollution and risk factors. In this review, we delineate the impact of environmental risk factors and the protective actions of the nuclear factor erythroid 2-related factor 2 (NRF2) in connection to oxidative stress and inflammation. We focus on well-established studies that demonstrate the protective actions of NRF2 and its downstream pathways against different environmental stressors. State-of-the-art mechanistic considerations on NRF2 signaling are discussed in detail, e.g. classical concepts like KEAP1 oxidation/electrophilic modification, NRF2 ubiquitination and degradation. Specific focus is also laid on NRF2-dependent heme oxygenase-1 induction with detailed presentation of the protective down-stream pathways of heme oxygenase-1, including interaction with BACH1 system. The significant impact of all environmental stressors on the circadian rhythm and the interactions of NRF2 with the circadian clock will also be considered here. A broad range of NRF2 activators is discussed in relation to environmental stressor-induced health side effects, thereby suggesting promising new mitigation strategies (e.g. by nutraceuticals) to fight the negative effects of the environment on our health.
Heme Oxygenase-1 , NF-E2-Related Factor 2 , Heme Oxygenase-1/genetics , Heme Oxygenase-1/metabolism , Humans , Inflammation/chemically induced , Kelch-Like ECH-Associated Protein 1/genetics , Kelch-Like ECH-Associated Protein 1/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Ultraviolet Rays
Mass vaccination with a safe and effective vaccine may be the best way to control the COVID-19 pandemic. Heterologous prime-boost vaccination with the CoronaVac and AZD1222 vaccines may increase the immunogenicity elicited by either vaccine alone. This study sought to compare the immunogenicity of a heterologous CoronaVac and AZD1222 prime-boost with a homologous CoronaVac prime-boost. From July 13 to September 2, 2021, 88 participants were enrolled in the study. Half (n = 44) of the participants were assigned to the AZD1222/CoronaVac cohort and half were assigned to the CoronaVac/AZD1222 cohort. Both cohorts had a prime-boost interval of 4 weeks. A control group of 136 health care personnel who received the homologous CoronaVac/CoronaVac prime-boost was matched by age and sex to the experimental cohorts. The primary endpoint was the geometric mean ratio (GMR) of the anti-receptor binding domain (RBD) antibody concentration 4 weeks after the booster dose was administered. The CoronaVac/CoronaVac cohort served as the reference group. Baseline age and sex were similar, and the median age was 42.5 years. The GMR was 2.58 (95% confidence interval [CI] 1.80-3.71) and 8.69 (95% CI 6.05-12.47) in the AZD1222/CoronaVac and CoronaVac/AZD1222 cohorts, respectively. Reactogenicity was similar following prime and booster doses with the same vaccine. Findings indicated that the heterologous CoronaVac and AZD1222 prime-boost combination elicited a more robust immune response than the homologous CoronaVac prime-boost. While both heterologous prime-boost combinations showed similar reactogenicity, the immunogenicity of the CoronaVac/AZD1222 cohort was higher, indicating that the order of prime-boost vaccine administration was important.
COVID-19 , ChAdOx1 nCoV-19 , Immunogenicity, Vaccine , Adult , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Humans , Immunization, Secondary , Pandemics , Vaccination
IFN-ß is a cytokine that plays a significant role in the immune system. Inhibition of IFN-ß might be used as a therapeutic approach to treat septic shock. A peptidomimetic previously developed by our research team, 1-benzyl-5-methyl-4-(n-octylamino)pyrimidin-2(1H)-one (LT87), was used as an cardioprotective agent in a myocardial ischemia (MI) mouse model. We have developed new LT87 derivatives by synthetizing its dimers in an attempt to extend its structural variety and enhance its biological activity. A dimeric derivative, LT127, exhibited a dose-dependent inhibition of LPS-mediated IFN-ß and subsequent CXCL10 mRNA transcription. The effect was selective and transduced through TLR4- and TRAM/TRIF-mediated signaling, with no significant effect on MyD88-dependent signaling. However, this effect was not specific to TLR4, since a similar effect was observed both on TLR8- and MDA5/RIG-I-stimulated IFN-ß expression. Nevertheless, LT127 might serve as a drug candidate, specifically as an inhibitor for IFN-ß production in order to develop a novel therapeutic approach to prevent septic shock.
Interferon-beta , Peptidomimetics , Shock, Septic , Animals , Cytokines/metabolism , Interferon-beta/metabolism , Mice , Peptidomimetics/pharmacology , Shock, Septic/drug therapy , Signal Transduction , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism
Air pollution has been repeatedly linked to numerous health-related disorders, including skin sensitization, oxidative imbalance, premature extrinsic aging, skin inflammation, and increased cancer prevalence. Nrf2 is a key player in the endogenous protective mechanism of the skin. We hypothesized that pharmacological activation of Nrf2 might reduce the deleterious action of diesel particulate matter (DPM), evaluated in HaCaT cells. SK-119, a recently synthesized pharmacological agent as well as 2,2'-((1E,1'E)-(1,4-phenylenebis(azaneylylidene))bis(methaneylylidene))bis(benzene-1,3,5-triol) (SH-29) were first evaluated in silico, suggesting a potent Nrf2 activation capacity that was validated in vitro. In addition, both compounds were able to attenuate key pathways underlying DPM damage, including cytosolic and mitochondrial reactive oxygen species (ROS) generation, tested by DC-FDA and MitoSOX fluorescent dye, respectively. This effect was independent of the low direct scavenging ability of the compounds. In addition, both SK-119 and SH-29 were able to reduce DPM-induced IL-8 hypersecretion in pharmacologically relevant concentrations. Lastly, the safety of both compounds was evaluated and demonstrated in the ex vivo human skin organ culture model. Collectively, these results suggest that Nrf2 activation by SK-119 and SH-29 can revert the deleterious action of air pollution.
Air Pollution , NF-E2-Related Factor 2 , HaCaT Cells , Humans , Keratinocytes/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Particulate Matter/toxicity , Reactive Oxygen Species
Jojoba (Simmondsia chinensis (Link) Schneider) wax is used for various dermatological and pharmaceutical applications. Several reports have previously shown beneficial properties of Jojoba wax and extracts, including antimicrobial activity. The current research aimed to elucidate the impact of Jojoba wax on skin residential bacterial (Staphylococcus aureus and Staphylococcus epidermidis), fungal (Malassezia furfur), and virus infection (herpes simplex 1; HSV-1). First, the capacity of four commercial wax preparations to attenuate their growth was evaluated. The results suggest that the growth of Staphylococcus aureus, Staphylococcus epidermidis, and Malassezia furfur was unaffected by Jojoba in pharmacologically relevant concentrations. However, the wax significantly attenuated HSV-1 plaque formation. Next, a complete dose-response analysis of four different Jojoba varieties (Benzioni, Shiloah, Hatzerim, and Sheva) revealed a similar anti-viral effect with high potency (EC50 of 0.96 ± 0.4 µg/mL) that blocked HSV-1 plaque formation. The antiviral activity of the wax was also confirmed by real-time PCR, as well as viral protein expression by immunohistochemical staining. Chemical characterization of the fatty acid and fatty alcohol composition was performed, showing high similarity between the wax of the investigated varieties. Lastly, our results demonstrate that the observed effects are independent of simmondsin, repeatedly associated with the medicinal impact of Jojoba wax, and that Jojoba wax presence is required to gain protection against HSV-1 infection. Collectively, our results support the use of Jojoba wax against HSV-1 skin infections.
Anti-Infective Agents/pharmacology , Antiviral Agents/pharmacology , Herpes Simplex/drug therapy , Herpesvirus 1, Human/drug effects , Waxes/pharmacology , Acetonitriles/pharmacology , Animals , Cell Survival/drug effects , Chlorocebus aethiops , Cyclohexanes/pharmacology , Dose-Response Relationship, Drug , Fatty Acids/chemistry , Fatty Acids/pharmacology , Fatty Alcohols/chemistry , Fatty Alcohols/pharmacology , Glucosides/pharmacology , Humans , Malassezia/drug effects , Microbial Sensitivity Tests , Staphylococcus aureus/drug effects , Staphylococcus epidermidis/drug effects , Vero Cells , Waxes/chemistry
In this study, we address three important challenges related to disease transmissions such as the COVID-19 pandemic, namely, (a) providing an early warning to likely exposed individuals, (b) identifying individuals who are asymptomatic, and (c) prescription of optimal testing when testing capacity is limited. First, we present a dynamic-graph based SEIR epidemiological model in order to describe the dynamics of the disease propagation. Our model considers a dynamic graph/network that accounts for the interactions between individuals over time, such as the ones obtained by manual or automated contact tracing, and uses a diffusion-reaction mechanism to describe the state dynamics. This dynamic graph model helps identify likely exposed/infected individuals to whom we can provide early warnings, even before they display any symptoms and/or are asymptomatic. Moreover, when the testing capacity is limited compared to the population size, reliable estimation of individual's health state and disease transmissibility using epidemiological models is extremely challenging. Thus, estimation of state uncertainty is paramount for both eminent risk assessment, as well as for closing the tracing-testing loop by optimal testing prescription. Therefore, we propose the use of arbitrary Polynomial Chaos Expansion, a popular technique used for uncertainty quantification, to represent the states, and quantify the uncertainties in the dynamic model. This design enables us to assign uncertainty of the state of each individual, and consequently optimize the testing as to reduce the overall uncertainty given a constrained testing budget. These tools can also be used to optimize vaccine distribution to curb the disease spread when limited vaccines are available. We present a few simulation results that illustrate the performance of the proposed framework, and estimate the impact of incomplete contact tracing data.
COVID-19 , Contact Tracing , Data Analysis , Humans , Pandemics , Prescriptions , SARS-CoV-2
Whole organ perfusion decellularization has been proposed as a promising method to generate non-immunogenic organs from allogeneic and xenogeneic donors. However, the ability to recellularize organ scaffolds with multiple patient-specific cells in a spatially controlled manner remains challenging. Here, we propose that replacing donor endothelial cells alone, while keeping the rest of the organ viable and functional, is more technically feasible, and may offer a significant shortcut in the efforts to engineer transplantable organs. Vascular decellularization was achieved ex vivo, under controlled machine perfusion conditions, in various rat and porcine organs, including the kidneys, liver, lungs, heart, aorta, hind limbs, and pancreas. In addition, vascular decellularization of selected organs was performed in situ, within the donor body, achieving better control over the perfusion process. Human placenta-derived endothelial progenitor cells (EPCs) were used as immunologically-acceptable human cells to repopulate the luminal surface of de-endothelialized aorta (in vitro), kidneys, lungs and hind limbs (ex vivo). This study provides evidence that artificially generating vascular chimerism is feasible and could potentially pave the way for crossing the immunological barrier to xenotransplantation, as well as reducing the immunological burden of allogeneic grafts.
Endothelial Cells/cytology , Regenerative Medicine/methods , Tissue Engineering/methods , Tissue Scaffolds , Transplantation Chimera/anatomy & histology , Transplantation, Heterologous/methods , Animals , Chimerism , Female , Hindlimb/blood supply , Hindlimb/transplantation , Organ Culture Techniques , Rats , Rats, Sprague-Dawley , Swine , Tissue and Organ Harvesting , Viscera/blood supply , Viscera/transplantation
Psoriasis and atopic dermatitis (AD) are two common chronic inflammatory skin diseases. Although showing different etiology and clinical manifestations, patients with either disease suffer from low health-related quality of life due to pruritus (dermal itch). Recent studies have revealed that more than 85% of psoriasis patients suffer from pruritus, and it is also the dominating symptom of AD. However, as this is a non-life treating symptom, it was partly neglected for years. In this review, we focus on current findings as well as the impact and potential treatments of pruritus in these two skin diseases. We first distinguish the type of itch based on involved mediators and modulators. This clear delineation between the types of pruritus based on involved receptors and pathways allows for precise treatment. In addition, insights into recent clinical trials aimed to alleviate pruritus by targeting these receptors are presented. We also report about novel advances in combinatorial treatments, dedicated to the type of pruritus linked to a causal disease. Altogether, we suggest that only a focused treatment tailored to the primary disease and the underlying molecular signals will provide fast and sustained relief of pruritus associated with psoriasis or AD.
Dermatitis, Atopic/drug therapy , Pruritus/drug therapy , Psoriasis/drug therapy , Animals , Antipruritics/pharmacology , Dermatitis, Atopic/physiopathology , Humans , Pruritus/etiology , Psoriasis/physiopathology , Quality of Life
