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Background Adipogenesis, glycosaminoglycan hyaluronan (HA) production, inflammation, and fibrosis are the main pathogenic mechanisms responsible for Graves’ orbitopathy (GO). We hypothesized that d...

Objective To assess the actual xylitol content in sugar-free chewing gums available in a market of Saudi Arabia and investigate its effect on acid production and pH change in vitro. Materials and methods: A total of 29 different brands of xylitol-containing sugar-free chewing gums were collected from five major grocery stores in Saudi Arabia. Xylitol was extracted and its concentration was determined using the D-Sorbitol/Xylitol Enzymatic Kit (Megazyme; Bray, Wicklow, Ireland). The pH of the extracts and the amount of acid production for each product was measured after 15-minute and 30-minute incubation with Streptococcus mutans. Descriptive analysis, concentrations, and one-way analysis of variance (ANOVA) with the least significant difference (LSD) as multiple comparisons were performed. Results: The xylitol content in grams was clearly stated on the labels of 16 products, while it was stated in percentages on the labels of ten products. The mean pH of most of the tested products was 5.857 ± 0.096. Significant differences in pH were recorded among 20 products (p ≤ 0.05). Highly significant differences in pH (p = 0.001) were observed in five of the products. Conclusion: The results of this study indicate, using an in vitro model, that xylitol can significantly affect salivary pH. The actual xylitol content in most brands of chewing gums currently available in the markets of Saudi Arabia is less than the concentration recommended for prevention of caries. Accurate information with proper labeling is required to enable dental professionals to take correct and informed decisions about recommending the use of these products.

Fibrinolysis can be abnormally activated in several critical care settings but it's often misdiagnosed by standard laboratory tests. Although rotational thromboelastometry can assess the whole coagulative process, its ability to detect fibrinolysis has been questioned. Aim of this study was to investigate the ability of thromboelastometry in detecting induced fibrinolysis in an in-vitro model. Whole blood samples were taken from 18 healthy volunteers. Each sample was split and added with increasing urokinase concentrations till to reach 0, 50, 75 and 100 IU/ml. Thromboelastometry tests, extem and aptem, were performed on the obtained samples. If significant lysis at 50 IU/ml was recorded, also 10, 25 and 35 IU/ml drug concentrations were tested. No lytic effects were detected in 10 IU/ml samples. Lysis variables were the most sensitive in detecting fibrinolysis even at 25 IU/ml (P

Abstract. Wound healing consists of a series of highly orderly overlapping processes characterized by hemostasis, inflammation, proliferation, and remodeling. Prolongation or interruption in each phase can lead to delayed wound healing or a non-healing chronic wound. Vitamin A is a crucial nutrient that is most beneficial for the health of the skin. The present study was undertaken to determine the effect of vitamin A on regeneration, angiogenesis, and inflammation characteristics in an in vitro model system during wound healing. For this purpose, mouse skin normal fibroblast (L929), human umbilical vein endothelial cell (HUVEC), and monocyte/macrophage-like cell line (RAW 264.7) were considered to evaluate proliferation, angiogenesis, and anti-inflammatory responses, respectively. Vitamin A (0.1–5 μM) increased cellular proliferation of L929 and HUVEC (p

Heart failure is a major health risk, and with limited availability of donor organs, there is an increasing need for developing cardiac assist devices (CADs). Mock circulatory loops (MCL) are an important in-vitro test platform for CAD’s performance assessment and optimisation. The MCL is a lumped parameter model constructed out of hydraulic and mechanical components aiming to simulate the native cardiovascular system (CVS) as closely as possible. Further development merged MCLs and numerical circulatory models to improve flexibility and accuracy of the system; commonly known as hybrid MCLs. A total of 128 MCLs were identified in a literature research until 25 September 2020. It was found that the complexity of the MCLs rose over the years, recent MCLs are not only capable of mimicking the healthy and pathological conditions, but also implemented cerebral, renal and coronary circulations and autoregulatory responses. Moreover, the development of anatomical models made flow visualisation studies possible. Mechanical MCLs showed excellent controllability and repeatability, however, often the CVS was overly simplified or lacked autoregulatory responses. In numerical MCLs the CVS is represented with a higher order of lumped parameters compared to mechanical test rigs, however, complex physiological aspects are often simplified. In hybrid MCLs complex physiological aspects are implemented in the hydraulic part of the system, whilst the numerical model represents parts of the CVS that are too difficult to represent by mechanical components per se. This review aims to describe the advances, limitations and future directions of the three types of MCLs.

Obesity is associated with the development of liver disease and its progression to hepatocellular carcinoma. This link may be attributed to adipocytokines such as visfatin and resistin which have been shown to promote liver cancer incidence and progression. Studies have yet to determine the role of visfatin and resistin in liver cancer, specifically in the context of obesity. The objective of this study was to investigate the effect of neutralizing visfatin and resistin in obese (OB) or normal weight (NW) sera to determine the contribution of these proteins in obesity-induced invasive liver cancer. Sera from OB or NW males was used to determine the efficacy of neutralizing visfatin and resistin to reduce the obesity-induced liver cancer phenotype. HepG2 and SNU-449 cells were exposed to OB and NW sera ± antibodies for visfatin or resistin. The neutralizing antibodies differentially suppressed invasion, reactive oxygen species production, and matrix metalloproteinase-9 secretion. These changes corresponded with a decrease in phosphorylated extracellular signal-regulated kinases and protein kinase B in HepG2 cells, but differences were not observed in CAP1 or β-catenin. In conclusion, visfatin and resistin have differential roles in obesity-associated liver cancer and may be potential targets to reverse the impact of obesity on liver cancer progression.

Immunotherapies have been heavily explored in the last decade, ranging from new treatments for cancer to allergic diseases. These therapies target the immune system, a complex organ system consisting of tissues with intricate structures and cells with a multitude of functions. To better understand immune functions and develop better therapeutics, many cellular and 2-dimensional (2D) tissue models have been developed. However, research has demonstrated that the 3-dimensional (3D) tissue structure can significantly affect cellular functions, and this is not recapitulated by more traditional 2D models. Microfluidics has been used to design 3D tissue models that allow for intricate arrangements of cells and extracellular spaces, thus allowing for more physiologically relevant in vitro model systems. Here, we summarize the multitude of microfluidic devices designed to study the immune system with the ultimate goal to improve existing and design new immunotherapies. We have included models of the different immune organs, including bone marrow and lymph node (LN), models of immunity in diseases such as cancer and inflammatory bowel disease, and therapeutic models to test or engineer new immune-modulatory treatments. We particularly emphasize research on how microfluidic devices are used to better understand different physiological states and how interactions within the immune microenvironment can influence the efficacy of immunotherapies.

Idiopathic pulmonary fibrosis (IPF) is a severe health problem characterized by progressive fibroblast proliferation and aberrant vascular remodeling. However, the lack of a suitable in vitro model...

Introduction: High-power lasers (100–120 W) have widely expanded the available settings for laser lithotripsy and facilitated tailoring of treatment for individual cases. Previous in vitro and in v...

Lysophosphatidic acid (LPA) is a common glycerol phospholipid and an important extracellular signaling molecule. LPA binds to its receptors and mediates a variety of biological effects, including the pathophysiological process underlying ischemic brain damage and traumatic brain injury. However, the molecular mechanisms mediating the pathological role of LPA are not clear. Here, we found that LPA activates cyclin-dependent kinase 5 (CDK5). CDK5 phosphorylates tau, which leads to neuronal cell death. Inhibition of LPA production or blocking its receptors reduced the abnormal activation of CDK5 and phosphorylation of tau, thus reversing the death of neurons. Our data indicate that the LPA-CDK5-Tau pathway plays an important role in the pathophysiological process after ischemic stroke. Inhibiting the LPA pathway may be a potential therapeutic target for treating ischemic brain injury.

Objective To evaluate differences in pro-inflammatory and degradative mediator production from osteoarthritic knee articular cartilage explants treated with a hyperosmolar saline solution supplemented with anti-inflammatory components (l-glutamine, ascorbic acid, sodium pyruvate, epigallocatechin gallate [EGCG], and dexamethasone) or normal saline using an in vitro model for knee arthroscopy. Design Full-thickness 6 mm articular cartilage explants ( n = 12/patient) were created from femoral condyle and tibial plateau samples collected from patients who received knee arthroplasty. One explant half was treated for 3 hours with hyperosmolar saline (600 mOsm/L) supplemented with anti-inflammatory components and the corresponding half with normal saline (308 mOsm/L). Explants were cultured for 3 days and then collected for biomarker analyses. Media biomarker concentrations were normalized to the wet weight of the tissue (mg) and were analyzed by a paired t test with significance set at P < 0.05. Results Cartilage was collected from 9 females and 2 males (mean age = 68 years). Concentrations of MCP-1 ( P < 0.001), IL-8 ( P = 0.03), GRO-α ( P = 0.02), MMP-1 ( P < 0.001), MMP-2 ( P < 0.001), and MMP-3 ( P < 0.001) were significantly lower in explant halves treated with the enhanced hyperosmolar solution. When considering only those cartilage explants in the top tercile of tissue metabolism, IL-6 ( P = 0.005), IL-8 ( P = 0.0001), MCP-1 ( P < 0.001), GRO-α ( P = 0.0003), MMP-1 ( P < 0.001), MMP-2 ( P < 0.001), MMP-3 ( P < 0.001), and GAG expression ( P = 0.0001) was significantly lower in cartilage explant halves treated with the enhanced hyperosmolar solution. Conclusions Treatment of cartilage explants with a hyperosmolar saline arthroscopic irrigation solution supplemented with anti-inflammatory components was associated with significant decreases in inflammatory and degradative mediator production and mitigation of proteoglycan loss.

Ductal carcinoma in situ (DCIS) is a precancerous stage breast cancer, where abnormal cells are contained within the duct, but have not invaded into the surrounding tissue. However, only 30–40% of ...

Organoids are self-organizing, self-renewing three-dimensional cellular structures that resemble organs in structure and function. They can be derived from adult stem cells, embryonic stem cells, or induced pluripotent stem cells. They contain most of the relevant cell types with a topology and cell-to-cell interactions resembling that of the in vivo tissue. The widespread and increasing adoption of organoid-based technologies in human biomedical research is testament to their enormous potential in basic, translational- and applied-research. In a similar fashion there appear to be ample possibilities for research applications of organoids from livestock and companion animals. Furthermore, organoids as in vitro models offer a great possibility to reduce the use of experimental animals. Here, we provide an overview of studies on organoids in livestock and companion animal species, with focus on the methods developed for organoids from a variety of tissues/organs from various animal species and on the applications in veterinary research. Current limitations, and ongoing research to address these limitations, are discussed. Further, we elaborate on a number of fields of research in animal nutrition, host-microbe interactions, animal breeding and genomics, and animal biotechnology, in which organoids may have great potential as an in vitro research tool.

The protective effect of antioxidant SkQR1 was examined on the model of left-sided compression ischemia in rat sensorimotor cortex. The special tests aimed to determine the neurologic deficit in the limbs and assess performance of the forelimbs showed that a 2.5-min ischemia produced no disturbance in the limb functions on postsurgery days 1, 3, and 7. Elevation of compression time resulted in neurologic deficit in animals, and its severity depended on this time. A single intravenous injection of SkQR1 (250 nmol/kg body weight) performed 30 min after ischemia significantly reduced the degree of neurologic deficit. In vitro model of ischemia in surviving rat hippocampal slices showed that a 15-min-long ischemia significantly inhibited the population excitatory postsynaptic potentials, which did not restore during reperfusion. Preincubation of the slices with SkQR1 did not significantly affect recovery of these potentials.

Introduction Foldable hydrophobic acrylic intraocular lenses (IOLs) are prone to develop a long-term postoperative material change called glistenings. The aim of this study was to investigate the changes in the predisposition for glistening formation in one type of hydrophobic acrylic IOL material from its introduction to the present day. Methods In a laboratory setup, an in vitro model was used to induce glistenings in hydrophobic acrylic IOLs manufactured by one company (Alcon, Fort Worth, TX, USA) in different years: 23 1990s-manufacture hydrophobic acrylic three-piece IOLs (MA30BA/MA60AC) that were explanted in 1996 and 1997, and five of each of the newer AcrySof IOL models (MA60AC, SA60AT, TFNT00 and SN60WF) from 2014 to 2017. Furthermore, five Clareon (SY60WF) IOLs were put through the same accelerated aging procedure. The number of microvacuoles per square millimeter (MV/mm2) was determined in the central part of each IOL optic and compared between the groups. Results The mean number of MV was highest in the 1990s-manufacture Alcon acrylic IOLs, with 1289 (± 738) MV/mm2. The number decreased to 650 (± 101), 192 (± 105), 175 (± 112) and 47 (± 26) for MA60AC, SA60AT, TFNT00 and SN60WF, respectively. The lowest count was obtained in the Clareon group, with 1 (± 1) MV/mm2. Conclusions A high number of glistenings was induced in the explanted IOLs from the 1990s. The propensity for glistening formation decreased considerably after that decade and now in current use. Even though in vitro glistening formation in today’s AcrySof material was low, the Clareon material was essentially glistenings-free.

Hemorrhage is the phenomenon of blood loss caused by vascular trauma or other pathological reasons, which is life-threatening in severe cases. Because microhemorrhage is difficult to visually monitor and pre-treat in vivo, it is necessary to establish in vitro prediction methods to study the hemostasis mechanism in different physiological environments. In this study, a microfluidic bleeding model was developed to investigate the effect of blood flow shear on microvascular hemostasis. The results indicated that the regulation of blood shear rate on platelet aggregation affected the growth and morphology of hemostatic thrombus, and finally regulated the process of hemostasis. This in vitro model is significant to studies on hemostatic mechanisms, a reliable prediction of microhemorrhages, and an adjustment of the treatment scheme.

Irregular hemodynamics affects the progression of various vascular diseases, such atherosclerosis or aneurysms. Despite the extensive hemodynamics studies on animal models, the inter-species differences between humans and animals hamper the translation of such findings. Recent advances in vascular tissue engineering and the suitability of in vitro models for interim analysis have increased the use of in vitro human vascular tissue models. Although the effect of flow on endothelial cell (EC) pathophysiology and EC-flow interactions have been vastly studied in two-dimensional systems, they cannot be used to understand the effect of other micro- and macro-environmental parameters associated with vessel wall diseases. To generate an ideal in vitro model of the vascular system, essential criteria should be included: 1) the presence of smooth muscle cells or perivascular cells underneath an EC monolayer, 2) an elastic mechanical response of tissue to pulsatile flow pressure, 3) flow conditions that accurately mimic the hemodynamics of diseases, and 4) geometrical features required for pathophysiological flow. In this paper, we review currently available in vitro models that include flow dynamics and discuss studies that have tried to address the criteria mentioned above. Finally, we critically review in vitro fluidic models of atherosclerosis, aneurysm, and thrombosis.

The SOCS1/JAK2/STAT3 axis is strongly associated with tumor growth and progression, and participates in cytokine secretion in many diseases. However, the effects of the SOCS1/JAK2/STAT3 axis in experimental subarachnoid hemorrhage remain to be studied. A subarachnoid hemorrhage model was established in rats by infusing autologous blood into the optic chiasm pool. Some rats were first treated with JAK2/STAT3 small interfering RNA (Si-JAK2/Si-STAT3) or overexpression plasmids of JAK2/STAT3. In the brains of subarachnoid hemorrhage model rats, the expression levels of both JAK2 and STAT3 were upregulated and the expression of SOCS1 was downregulated, reaching a peak at 48 hours after injury. Simultaneously, the interactions between JAK2 and SOCS1 were reduced. In contrast, the interactions between JAK2 and STAT3 were markedly enhanced. Si-JAK2 and Si-STAT3 treatment alleviated cortical neuronal cell apoptosis and necrosis, destruction of the blood–brain barrier, brain edema, and cognitive functional impairment after subarachnoid hemorrhage. This was accompanied by decreased phosphorylation of JAK2 and STAT3 protein, decreased total levels of JAK2 and STAT3 protein, and increased SOCS1 protein expression. However, overexpression of JAK2 and STAT3 exerted opposite effects, aggravating subarachnoid hemorrhage-induced early brain injury. Si-JAK2 and Si-STAT3 inhibited M1-type microglial conversion and the release of pro-inflammatory factors (inducible nitric oxide synthase, interleukin-1β, and tumor necrosis factor-α) and increased the release of anti-inflammatory factors (arginase-1, interleukin-10, and interleukin-4). Furthermore, primary neurons stimulated with oxyhemoglobin were used to simulate subarachnoid hemorrhage in vitro, and the JAK2 inhibitor AG490 was used as an intervention. The in vitro results also suggested that neuronal protection is mediated by the inhibition of JAK2 and STAT3 expression. Together, our findings indicate that the SOCS1/JAK2/STAT3 axis contributes to early brain injury after subarachnoid hemorrhage both in vitro and in vivo by inducing inflammatory responses. This study was approved by the Animal Ethics Committee of Anhui Medical University and the First Affiliated Hospital of University of Science and Technology of China (approval No. LLSC-20180202) on March 1, 2018.

Using a novel in vitro model system combining biochemical/histologic with bioengineering approaches has provided significant insights into the physiology of fetal membrane weakening and rupture along with potential mechanistic reasons for lack of efficacy of currently clinically used agents to prevent preterm premature rupture of the membranes (pPROM) and preterm births. Likewise, the model has also facilitated screening of agents with potential for preventing pPROM and preterm birth.

Purpose Additive manufacturing (AM) is an innovation in today's medical field. It helps create a patient-specific 3D model of bones, nerves, organs and blood vessel. Now, doctors and surgeons have successfully applied this technology to plan different types of treatments and also cancers. The purpose of this paper is to study the requirements and applications of AM for cancer treatment. Methods Today AM is used for the application of regenerative medicine. It can help develop and improve in-vitro models in the tumour microenvironment. Thus, to identify its applications, related research papers on AM for cancer are studied. Results 3D printing technology has a unique capability to manufacture tumour models. It helps to understand the status of the whole tumor. Here in this paper, we studied the capabilities of AM technologies for cancer treatment. This study discusses necessary process steps, followed by 3D printing and finally identified significant applications of these technologies for cancer treatment with a brief description. Conclusion 3D printed tumor helps to provide faithful studies on metastasis. These models create a promising platform to construct biomimetic models. By accurate manufacturing of in vitro model, this technology seems to be the best tool to facilitate complex treatment, surgery and therapies. It shows great potential for the printing of organs. This technology is time-saving and avoids time-consuming processes. It has been analysed that AM helps in reducing the duration of treatment of a cancer patient. Researchers are focusing on reducing pain during therapies. They have also tested 3D printed tumor models for different drugs, to eliminate the risks. These models play a significant role in courses of treatments.

BACKGROUND AND PURPOSE: Endovascular embolization using liquid embolic agents is a safe and effective treatment option for AVMs and dural arteriovenous fistulas. The aim of this study was to assess the degree of artifact inducement by the most frequently used liquid embolic agents in conventional CT in an experimental in vitro model. MATERIALS AND METHODS: Dimethyl-sulfoxide–compatible tubes were filled with the following liquid embolic agents (n = 10, respectively): Onyx 18, all variants of Squid, PHIL 25%, PHIL LV, and n-BCA mixed with iodized oil. After inserting the tubes into a CT imaging phantom, we acquired images. Artifacts were graded quantitatively by the use of Hounsfield units in a donut-shaped ROI using a customized software application that was specifically designed for this study and were graded qualitatively using a 5-point scale. RESULTS: Quantitative and qualitative analyses revealed the most artifacts for Onyx 18 and the least artifacts for n-BCA, PHIL 25%, and PHIL LV. Squid caused more artifacts compared with PHIL, both for the low-viscosity and for the extra-low-viscosity versions (eg, quantitative analysis, Squid 18: mean ± SD, 30.3 ± 9.7 HU versus PHIL 25%: mean ± SD, 10.6 ± 0.8 HU; P

The removal of antibiotics from the feeds used in the livestock industry has resulted in the use of a wide range of alternative antimicrobial products that aim to deliver the productivity and health benefits that have traditionally been associated with antibiotics. Amongst the most popular alternatives are phytogenic product-based extracts from herbs and spices with known antimicrobial properties. Despite embracing such alternatives, the industry is still largely unaware of modes of action, their overall effects on animal health, and interactions with other feed additives such as probiotics. To address some of these issues, three phytogenic products were selected and their interactions with caecal microbiota of layers, grown under six different production systems, were investigated in vitro. Caecal microbiotas were grown with and without phytogenic products, and the changes in microbiota composition were monitored by sequencing of 16S rRNA gene amplicons. Phytogenic products and production system both significantly influenced microbiota composition. The three phytogenic products all altered the relative abundance of species within the Lactobacillus genus, by promoting the growth of some and inhibiting other Lactobacillus species. There were also significant alterations in the Bacillus genus. This was further investigated by comparing the effects of the phytogenic products on the growth of a commercially used Bacillus-based probiotic. The phytogens affected the probiotic mix differently, with some promoting the growth of Bacillus sp. at lower phytogenic concentrations, and fully suppressing growth at higher concentrations, indicating the importance of finding an optimal concentration that can control pathogens while promoting beneficial bacteria. Key points • After removal of antibiotics from animal feed, urgent solutions for pathogen control were needed. • Alternative products entered the market without much knowledge on their effects on animal health. • Probiotic products are used in combination with phytogens despite the possible incompatibility.

Advances in the complexity and functionality of in vitro models of the CNS mean that such models now have the potential to overcome many of the limitations of traditional model systems. Nikolakopoulou et al. provide an overview and user guide for in vitro CNS models, with a focus on ‘Organ-on-a-Chip’ technologies., The complexity of the human brain poses a substantial challenge for the development of models of the CNS. Current animal models lack many essential human characteristics (in addition to raising operational challenges and ethical concerns), and conventional in vitro models, in turn, are limited in their capacity to provide information regarding many functional and systemic responses. Indeed, these challenges may underlie the notoriously low success rates of CNS drug development efforts. During the past 5 years, there has been a leap in the complexity and functionality of in vitro systems of the CNS, which have the potential to overcome many of the limitations of traditional model systems. The availability of human-derived induced pluripotent stem cell technology has further increased the translational potential of these systems. Yet, the adoption of state-of-the-art in vitro platforms within the CNS research community is limited. This may be attributable to the high costs or the immaturity of the systems. Nevertheless, the costs of fabrication have decreased, and there are tremendous ongoing efforts to improve the quality of cell differentiation. Herein, we aim to raise awareness of the capabilities and accessibility of advanced in vitro CNS technologies. We provide an overview of some of the main recent developments (since 2015) in in vitro CNS models. In particular, we focus on engineered in vitro models based on cell culture systems combined with microfluidic platforms (e.g. ‘organ-on-a-chip’ systems). We delve into the fundamental principles underlying these systems and review several applications of these platforms for the study of the CNS in health and disease. Our discussion further addresses the challenges that hinder the implementation of advanced in vitro platforms in personalized medicine or in large-scale industrial settings, and outlines the existing differentiation protocols and industrial cell sources. We conclude by providing practical guidelines for laboratories that are considering adopting organ-on-a-chip technologies.

Mitral regurgitation (MR) is the most prevalent valvulopathy in the USA and the second most prevalent valvulopathy in Europe. Despite excellent clinical results of surgical mitral valve repair (SMVR), transcatheter-based mitral valve repair (MVR) procedures emerged as a feasible treatment option for surgically inoperable or high-risk patients suffering from clinically relevant MR. The current study investigates the impact of device-induced coaptationwidth on the hydrodynamic performance of insufficient mitral valves (MV) during left ventricular (LV) systole. A non-calcified, pathological MV model (MVM) featuring a D-shaped MV annulus with an area of 7.6 cm2 and a flail gap in the A2-P2 region was employed in an experimental setup. Pressure gradient-volumetric flow rate (Δp-Q) relations were investigated for steady-state backward flow with transvalvular pressure gradients ranging from (0.75 ≤ Δp ≤ 177.36) mmHg. Glycerol-water mixture (36 % (v/v) glycerol in water) at 37 °C with a density of (1 098.2 ± 1.3) kg·m-3 and a dynamic viscosity of 3.5 mPa∙s was used as circulatory fluid. In order to determine the impact of the width of transcatheter MVR devices during LV-systole Δp-Q relations were investigated for three MVM-configurations: (i) MVM without MVR device, (ii) MVM with one MVR device and (iii) MVM with two MVR devices implanted in the A2-P2 region. The MVR devices were manufactured from steel sheets with a thickness of 0.2 mm and feature arm lengths of 9.0 mm and a width of 5.0 mm. The conducted investigations show that the implantation of MVR devices in the A2-P2 region prevents the manifestation of an A2-P2 flail gap and thereby effectively reduces the retrograde blood flow during the LV-systole by 13 % with one MVR device and 27 % with two MVR devices implanted. Thus, the application of two MVR devices with a combined device-induced width of 10 mm results in a better MR reduction than the implantation of one MVR device with a device-induced width of 5 mm.

INTRODUCTION Lesion size and continuity in dragging laser balloon (LB) ablation, which may enable fast and durable pulmonary vein isolation for atrial fibrillation, are unknown. We evaluated the differences in size and continuity of linear lesions formed by dragging ablation and conventional point-by-point ablation using an LB in vitro model. METHODS AND RESULTS Chicken muscles were cauterized using the first-generation LB in dragging and point-by-point fashion. Dragging ablation was manually performed with different dragging speeds (0.5-2°/s) using an overlap ratio of the beginning and last site during one application at 12 W/20 s and 8.5 W/30 s. Point-by-point ablation was performed with 25% and 50% overlap ratios at six energy settings (5.5 W/30 s to 12 W/20 s). Lesion depth, width, and continuity were compared. Lesion continuity was assessed by the surface and deep visible gap degree categorized from 1 (perfect) to 3 (poor). Twenty lesions were evaluated for each ablation protocol. Lesion depth and width in dragging ablation at high power (12 W) were comparable with most measurements in point-by-point ablation. Lesion depth and width were smaller at faster-dragging speed and lower power (8.5 W) in dragging ablation. The surface visible gap degree was better in dragging ablation at all dragging speeds than a 25% overlapped point-by-point ablation (p

Skin drug delivery is an emerging route in drug development, leading to an urgent need to understand the behaviour of active pharmaceutical ingredients within the skin. Given, As one of the body's first natural defences, the barrier properties of skin provide an obstacle to the successful outcome of any skin drug therapy. To elucidate the mechanisms underlying this barrier, reductionist strategies have designed several models with different levels of complexity, using non-biological and biological components. Besides the detail of information and resemblance to human skin in vivo, offered by each in vitro model, the technical and economic efforts involved must also be considered when selecting the most suitable model. This review provides an outline of the commonly used skin models, including healthy and diseased conditions, in-house developed and commercialized models, their advantages and limitations, and an overview of the new trends in skin-engineered models.

Background Luteolin has been demonstrated to possess numerous biological effects. However, the effect of luteolin on LPS (Lipopolysaccharides) stimulation in CPEK cells has not been investigated. Hypothesis/Objectives An in vitro model of atopic canine dermatitis was used to identify the antioxidant effect of luteolin as a new treatment that is capable of improving the conditions of veterinary patients. Methods CPEK cells were treated with or without luteolin in the presence or absence of LPS. A cell viability assay was performed to test luteolin toxicity and the protective effect of luteolin after LPS stimulation. Additionally, enzyme‐linked immunosorbent assay (ELISA) kits were used to detect the levels of IL‐33, IL‐1β, IL‐6, and IL‐8. Results Luteolin was capable to significantly decrease levels expression of IL‐33, IL 1β, IL‐6, and IL‐8. Conclusions and clinical importance Luteolin could be a new pharmacological treatment for canine atopic dermatitis., Luteolin has been demonstrated to possess numerous biological effects. Low‐dose luteolin inhibited the release of IL‐33 and other pro‐inflammatory cytokines 3.Luteolin could be a new pharmacological treatment for canine atopic dermatitis

Traumatic brain injury (TBI) is the primary cause of death and disability affecting over 10 million people in the industrialized world. TBI causes a wide spectrum of secondary molecular and cellula...

Cutaneous squamous cell carcinoma (cSCC) causes approximately 10,000 deaths annually in the U. S. Current therapies are largely ineffective against metastatic and locally advanced cSCC. There is a need to identify novel, effective, and less toxic small molecule cSCC therapeutics. We developed a 3-dimensional bioprinted skin (3DBPS) model of cSCC tumors together with a microscopy assay to test chemotherapeutic effects in tissue. The full thickness SCC tissue model was validated using hematoxylin and eosin (H&E) and immunohistochemical histological staining, confocal microscopy, and cDNA microarray analysis. A nondestructive, 3D fluorescence confocal imaging assay with tdTomato-labeled A431 SCC and ZsGreen-labeled keratinocytes was developed to test efficacy and general toxicity of chemotherapeutics. Fluorescence-derived imaging biomarkers indicated that 50% of cancer cells were killed in the tissue after 1μM 5-Fluorouracil 48-hour treatment, compared to a baseline of 12% for untreated controls. The imaging biomarkers also showed that normal keratinocytes were less affected by treatment (11% killed) than the untreated tissue, which had no significant killing effect. Data showed that 5-Fluorouracil selectively killed cSCC cells more than keratinocytes. Our 3DBPS assay platform provides cellular-level measurement of cell viability and can be adapted to achieve nondestructive high-throughput screening (HTS) in bio-fabricated tissues.

Background Infections are challenging complications of implant-based breast reconstruction and augmentation. They pose a clinical challenge, with significant economic implications. One proposed solution is implant irrigation at the time of placement. There is no consensus on the optimal irrigant solution. Methods The authors tested the relative efficacy of 10% povidone-iodine, Clorpactin, Prontosan, triple-antibiotic solution, or normal saline (negative control) against two strains each of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. Sterile, smooth silicone implant disks were immersed in irrigant solution, then incubated in suspensions of methicillin-resistant S. aureus or S. epidermidis overnight. The disks were rinsed and sonicated to displace adherent bacteria from the implant surface, and the displaced bacteria were quantified. Normalized values were calculated to characterize the relative efficacy of each irrigant. Results Povidone-iodine resulted in reductions of the bacterial load by a factor of 10 to 10 for all strains. Prontosan-treated smooth breast implant disks had a 10-fold reduction in bacterial counts for all but one methicillin-resistant S. aureus strain. In comparison to Prontosan, triple-antibiotic solution demonstrated a trend of greater reduction in methicillin-resistant S. aureus bacterial load and weaker activity against S. epidermidis strains. Clorpactin reduced the recovered colony-forming units for only a single strain of S. epidermidis. Povidone-iodine demonstrated the greatest efficacy against all four strains. However, Clorpactin, triple-antibiotic solution, and Prontosan demonstrated similar efficacies. Conclusions Povidone-iodine was the most efficacious of the irrigants at reducing methicillin-resistant S. aureus and S. epidermidis contamination. Given the recent lifting of the U.S. Food and Drug Administration moratorium, larger clinical studies of povidone-iodine as a breast implant irrigant solution are warranted. Clinical question/level of evidence Therapeutic, V.

Made available in DSpace on 2020-12-12T02:07:46Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Preeclampsia (PE) is a pregnancy-specific disorder that affects 3-8% expecting mothers worldwide being one of the main causes of maternal and fetal morbidity and mortality. The search for altered circulating molecules in PE is an important target to better understand the pathophysiology of this disease. Therefore, we evaluated Sirtuin-1 (SIRT1) concentration in plasma from healthy pregnant (HP) women, gestational hypertensive women (GH), and preeclampsia women (PE) via enzyme-linked immunosorbent assay (ELISA). We also measured intracellular SIRT1 in HUVECs incubated with plasma from PE patients compared to HP and GH via Western Blot Assay. Statistical differences were considered when p

Few studies reported the extent of heavy metal accumulation in traditional Chinese medicines (TCMs). Currently, oral bioaccessibility of lead (Pb), cadmium (Cd), arsenic (As), mercury (Hg), and copper (Cu) present in traditional animal medicines was investigated with physiologically based extraction test-extracted in vitro model. We are the first to develop a health risk assessment strategy by combinational analysis of bioaccessible heavy metal levels to calculate target hazard quotient (THQ), target hazard index (THI) and cancer risk (CR), which has capacity to evaluate the heavy metal associated heath risk of traditional animal medicines. To precisely acquire a realistic risk assessment, questionnaire data was adopted to measure the frequency and duration of the exposure to traditional animal medicines, and the safety factor was highlighted as well. Our data revealed that the bioaccessibility of Hg was the lowest among the five heavy metals. After the adjustment with the bioaccessibility of each heavy metal to target hazard index (THI) values, excitingly, the results manifested that the consumption of traditional animal medicines might not exert an unacceptable health risk in a broad community. In addition, the CR values of As and Pb indicated that the risk of developing cancers was quite lower than their acceptable levels in the clinic.

Purpose: To assess in silicone juxtarenal aneurysm models the gutter characteristics and compression of different types of chimney graft (CG) configurations. Materials and Methods: Fifty-seven combinations of Excluder C3 or Conformable Excluder stent-grafts (23, 26, and 28.5 mm) were deployed in 2 silicone juxtarenal aneurysm models with 3 types of CGs: Viabahn self-expanding (VSE; 6 and 13 mm) or Viabahn balloon-expandable (VBX; 6, 10, and 12 mm) stent-grafts and Advanta V12 balloon-expandable stent-grafts (ABX; 6 and 12 mm). Setups were divided into 4 groups on the basis of increasing CG and main graft (MG) diameters. Two independent observers assessed gutter size and type as well as CG compression on computed tomography scans using postprocessing software. Results: In the smaller diameter combinations (6-mm CG and 23-, 26-, and 28.5-mm MGs), both VSE (p=0.006 to 0.050) and ABX (p=0.045 to 0.050) showed lower gutter areas and volumes compared with VBX. In turn, the VBX showed a nonsignificant tendency to decreased compression, especially compared to ABX. Use of the Excluder C3 showed a 6-fold increase in type A1 gutters (related to type Ia endoleak) as compared to the Conformable Excluder (p=0.018). Balloon-expandable stent-grafts (both ABX and VBX) showed a 3-fold increase in type A1 gutters in comparison with self-expanding stent-grafts (p=0.008). Conclusion: The current study suggests that use of the Conformable Excluder in combination with VSE chimney grafts is superior to the other tested CG/MG combinations in terms of gutter size, gutter type, and CG compression.

Purpose Despite proven benefits of in-utero spina bifida (SB) repair, ≥ 30% of children at birth have Chiari II malformation or cerebrospinal fluid (CSF) leakage from the repair site. Our study's purpose was to determine CSF pressures in the myelomeningocele sac during mid-gestation in order to design an in-vitro model for evaluating different surgical methods used for watertight closure during in-utero SB repair. Methods CSF pressures were measured during in-utero SB repair at mid-gestation. An in-vitro chicken thigh model, simulating fetal tissue, tested watertight closure when attached to the base of a water column. Primary closure methods were evaluated using defect sizes of 20 × 3 mm for minimal traction or 20 × 8 mm for moderate traction. Additionally, 3 common in-utero repair patches were compared using 15 × 15 mm defects. Results Using 6–12.5 cm pre-determined CSF pressures, 165 in-vitro experiments were performed. Regardless of methodology we found that in 66 primary-based closures that minimal versus moderate wound edge traction provided better seals. The locking method was superior to the non-locking technique for watertight closure in 99 patch-based closures. Conclusions Minimal wound edge traction was best for primary closures, and locking sutures ideal for patch-based closures, however surgical techniques should be individualized to improve upon clinical outcomes.

Background The diagnosis of nondisplaced longitudinal fractures [vertical root fractures (VRFs)] is challenging in clinical practice. Radiographic techniques showed a difficulty in detection of VRFs. Cone-beam computed tomography (CBCT) is a new diagnostic imaging modality that provides high-quality three-dimensional (3D) images for dental diagnosis. Aims The aim of this in vitro study is to compare accuracy of three different imaging modalities: conventional periapical radiographs, digital radiographs, and CBCT in detecting VRFs in teeth that are endodontically as well as nonendodontically treated. Materials and methods An in vitro model consisting of 60 recently extracted human mandibular lower premolars were used. Root canal treatment was carried out for 30 teeth. Root fractures were created in 30 teeth (15 root canal treated and 15 non-treated) by mechanical force. Other 30 teeth remain intact. The teeth were mounted and images were taken with a periapical, digital, and CBCT X-ray unit. Three endodontists separately evaluated the images. Results Interobserver κ values showed a very good interobserver agreement (0.98 for CBCT, 0.88 for digital, and 0.93 for conventional periapical X-rays). There was an overall statistically significant difference (p = 0.00) in detecting of root fracture among the three imaging modalities and the highest accuracy with CBCT images. Conclusions In in vitro model, CBCT scan appears to give the highest accuracy in detecting VRFs when compared with the periapical systems in both endodontically and nonendodontically treated teeth. Clinical significance The CBCT scan shows higher sensitivity in detection of VRFs in comparison with periapical images.

Background Intrathecal drug delivery has a significant role in pain management and central nervous system (CNS) disease therapeutics. A fluid-physics based tool to assist clinicians in choosing specific drug doses to the spine or brain may help improve treatment schedules. Methods This study applied computational fluid dynamics (CFD) and in vitro model verification to assess intrathecal drug delivery in an anatomically idealized model of the human CSF system with key anatomic features of the CNS. Key parameters analyzed included the role of (a) injection location including lumbar puncture (LP), cisterna magna (CM) and intracerebroventricular (ICV), (b) LP injection rate, injection volume, and flush volume, (c) physiologic factors including cardiac-induced and deep respiration-induced CSF stroke volume increase. Simulations were conducted for 3-h post-injection and used to quantify spatial–temporal tracer concentration, regional area under the curve (AUC), time to maximum concentration (Tmax), and maximum concentration (Cmax), for each case. Results CM and ICV increased AUC to brain regions by ~ 2 logs compared to all other simulations. A 3X increase in bolus volume and addition of a 5 mL flush both increased intracranial AUC to the brain up to 2X compared to a baseline 5 mL LP injection. In contrast, a 5X increase in bolus rate (25 mL/min) did not improve tracer exposure to the brain. An increase in cardiac and respiratory CSF movement improved tracer spread to the brain, basal cistern, and cerebellum up to ~ 2 logs compared to the baseline LP injection. Conclusion The computational modeling approach provides ability to conduct in silico trials representative of CSF injection protocols. Taken together, the findings indicate a strong potential for delivery protocols to be optimized to reach a target region(s) of the spine and/or brain with a needed therapeutic dose. Parametric modification of bolus rate/volume and flush volume was found to have impact on tracer distribution; albeit to a smaller degree than injection location, with CM and ICV injections resulting in greater therapeutic dose to brain regions compared to LP. CSF stroke volume and frequency both played an important role and may potentially have a greater impact than the modest changes in LP injection protocols analyzed such as bolus rate, volume, and flush.

Background Onychomycosis affects almost 6% of the world population. Topical azoles and systemic antifungal agents are of low efficacy and can have undesirable side effects. An effective, non-invasive therapy for onychomycosis is an unmet clinical need. Objective Determine the efficacy threshold of non-thermal atmospheric plasma (NTAP) to treat onychomycosis in an in vitro model. Methods A novel toe/nail-plate model using cadaver nails and agarose media inoculated with Candida albicans was exposed to a range of NTAP doses. Results Direct exposure of C albicans and Trichophyton mentagrophytes to 12 minutes of NTAP results in complete killing at doses of 39 and 15 kPulses, respectively. Onset of reduced viability of C albicans to NTAP treatment through the nail plate occurs at 64 kPulses with 10× and 100× reduction at 212 and 550 kPulses, respectively. Conclusions NTAP is an effective, non-invasive therapeutic approach to onychomycosis that should be evaluated in a clinical setting.

International audience; Drug-induced liver injury (DILI) is a patient-specific, temporal, multifactorial pathophysiological process that cannot yet be recapitulated in a single in vitro model. Current preclinical testing regimes for the detection of human DILI thus remain inadequate. A systematic and concerted research effort is required to address the deficiencies in current models and to present a defined approach towards the development of new or adapted model systems for DILI prediction. This Perspective defines the current status of available models and the mechanistic understanding of DILI, and proposes our vision of a roadmap for the development of predictive preclinical models of human DILI.

Drinks and foods may be thickened to improve swallowing safety for dysphagia patients, but the resultant consistencies are not always palatable. Characterising alternative appetising foods is an important task. The study aims to characterise the in vitro swallowing behaviour of specifically formulated thickened dysphagia fluids containing xanthan gum and/or starch with standard jellies and yoghurt using a validated mechanical model, the “Cambridge Throat”. Observing from the side, the model throat can follow an experimental oral transit time (in vitro-OTT) and a bolus length (BL) at the juncture of the pharynx and larynx, to assess the velocity and cohesion of bolus flow. Our results showed that higher thickener concentration produced longer in vitro-OTT and shorter BL. At high concentration (spoon-thick), fluids thickened with starch-based thickener showed significantly longer in vitro-OTT than when xanthan gum-based thickener was used (84.5 s ± 34.5 s and 5.5 s ± 1.6 s, respectively, p

Alzheimer’s disease (AD) is an aging-dependent neurodegenerative disease that impairs cognitive function. Although the main pathologies of AD are the aggregation of amyloid-beta (Aβ) and phosphorylated Tau protein, the mechanisms that lead to these pathologies and their effects are believed to be heterogeneous among patients. Many epidemiological studies have suggested that sex is involved in disease prevalence and progression. The reduction of sex hormones contributes to the pathogenesis of AD, especially in females, suggesting that the supplementation of sex hormones could be a therapeutic intervention for AD. However, interventional studies have revealed that hormone therapy is beneficial under limited conditions in certain populations with specific administration methods. Thus, this suggests the importance of identifying crucial factors that determine hormonal effects in patients with AD. Based on these factors, it is necessary to decide which patients will receive the intervention before starting it. However, the long observational period and many uncontrollable environmental factors in clinical trials made it difficult to identify such factors, except for the APOE ε4 allele. Induced pluripotent stem cells (iPSCs) derived from patients can differentiate into neurons and recapitulate some aspects of AD pathogenesis. This in vitro model allows us to control non-cell autonomous factors, including the amount of Aβ aggregates and sex hormones. Hence, iPSCs provide opportunities to investigate sex-dependent pathogenesis and predict a suitable population for clinical trials of hormone treatment.

Adolescent neuropsychiatric disorders have been recently increasing due to genetic and environmental influences. Abnormal brain development before and after birth contribute to the pathology of neuropsychiatric disorders. However, it is difficult to experimentally investigate because of the complexity of brain and ethical constraints. Recently generated human brain organoids from pluripotent stem cells are considered as a promising in vitro model to recapitulate brain development and diseases. To better understand how brain organoids could be applied to investigate neuropsychiatric disorders, we analyzed the key consideration points, including how to generate brain organoids from pluripotent stem cells, the current application of brain organoids in recapitulating neuropsychiatric disorders and the future perspectives. This review covered what have been achieved on modeling the cellular and neural circuit deficits of neuropsychiatric disorders and those challenges yet to be solved. Together, this review aims to provide a fundamental understanding of how to generate brain organoids to model neuropsychiatric disorders, which will be helpful in improving the mental health of adolescents.

The wide use of antibacterial drugs in the agricultural and veterinary industries as growth stimulants and antimicrobial therapies has led to increased resistance of pathogens and opportunistic pathogens to many chemotherapy drugs. The purpose of our study is to assess the additive effect of these compounds to enhance the inhibitory action of antibiotics. Antibacterial drugs of various chemical groups, extracts from medicinal plants with microbicide and anti-quorum effects, inorganic copper and zinc salts, as well as probiotic strains of the genus Bacillus of veterinary purpose, were used to achieve the goal. The main methodical approach to assessing the additive effect of complex compounds in the work was the method of diffusion into agar, combined with the method of serial dilution. The selection of antibacterial drugs was carried out using the disk diffusion method. S. enteritidis, S. typhimurium, and P. aeruginosa were used as the test organisms in studies. The main criterion for the selection of antibacterial drugs was the resistance of probiotic strains and the moderate sensitivity of the test organisms in relation to their action. Cefixime was experimentally selected for the study against S. enteritidis and S. typhimurium and Fosfomycin against P. aeruginosa. Of all the studied phytobiotics, the most promising for further study was the oak bark extract. Against P. aeruginosa, the most significant chemical compound is CuSO4 at a concentration of 40 mg/ml, which does not affect the growth of probiotic strains. The pronounced additive effect of the combined compound based on cefixime, oak bark, and B. subtilis 534 was observed against S. enteritidis and S. typhimurium by 23% and 25%, respectively. The combined use of fosfomycin, B. subtilis 534, CuSO4, and the oak bark extract increases P. aeruginosa growth suppression by 19 % compared to the control of the growth suppression of this antibiotic.

Background Stem cells and their secreted extracellular vesicles (EVs) have shown different cardioprotective effects. However, their impact on the electrophysiological properties of the heart tissue remains controversial. While the use of some progenitor cells seems to have antiarrhythmic potential, the use of cardiomyocyte-like cells may be proarrhythmic. The mechanisms behind, and whether these effects are linked to cell engraftment and not to their secreted products is not fully known. Purpose The aim of this study was to investigate the electrophysiological modifications induced by extracellular vesicles secreted by human cardiosphere-derived cells (CDC-EVs) in an in vitro model of atrial fibrillation in order to explore their potential antiarrhythmic effect. Methods CDCs were derived from cardiac biopsies of patients who underwent cardiac surgery for other reasons. Purified CDC-EVs resuspended in serum-free media (SFM) vs. SFM alone were added to HL-1 atrial myocyte monolayers presenting spontaneous fibrillatory activity. After 48 hours, the monolayers were fully confluent, and the electrophysiological properties were analysed through optical mapping in both the treated (n=9) and control plates (n=9). Optical mapping recordings of the monolayers were analysed with Matlab for the activation frequency, activation complexity, rotor dynamics (curvature and meandering) and conduction velocity. Results CDC-EVs reduced activation complexity of the fibrillating atrial monolayers by ∼40% (2.74±0.59 vs. 1.61±0.16 PS/cm2, p Conclusions CDC-EVs significantly modify conduction velocity and rotor dynamics, therefore reducing fibrillation complexity and remodelling to drive atrial myocytes to a less arrhythmogenic profile. Testing CDC-EVs in more robust models of atrial fibrillation, the most common sustained arrhythmia in humans with significant morbidity and mortality, is of special interest. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III, Ministerio de Ciencia e Innovaciόn,CIBERCV, Spain Figure 1

Introduction The echocardiographic diagnosis of aortic stenosis (AS) is established by assessing its maximal opening area (OA). The behavior of OA is dependent on transvalvular flow which can be low in case of low-flow, low-gradient AS. However, current guidelines for the assessment of AS do not consider flow but rather a stroke volume. This experiment was designed to create a graphical representation of the OA versus flow for various valve stiffness values to eventually build a model with iso-stiffness lines. Methods We filmed harvested porcine aortic valve mounted in a pulsatile flow loop during the ejection time with a high speed camera (2000Hz), measured for each time point OA and the instantaneous flow through the aortic valve at 10 different mean flow rates (ranging from 0.5 to 5.0 liters/min) and divided both, OA and flow, by the area of left ventricular outflow tract (LVOT) in order to account for different valve sizes. We plotted each OA against its corresponding flow after correcting for the intersignal delay. Due to a time lag between flow onset and the valve opening caused by a ballooning of the valve, we only included the points corresponding to the 5% highest instantaneous flow rates (for each of the 10 mean flow rates). We stiffened the valve by treating it with a protein cross-linking agent (formaldehyde) to yield a total of three stiffness grades (a, b, c) and repeated the procedure for each of those grades. Results We generally observed an asymptotic appearance of the flow-OA relationship as well as a flattening of this relationship with increasing valve stiffening. This visually matches well simulated data generated with a sigmoid model. Conclusions We could obtain all flow/OA pairs at different stiffness grades. This will allow us to fit a sigmoid function capturing the flow-OA relationship for each stiffness grade and create iso-stiffness line that will allow classifying valve stenosis grade irrespective of the flow and the size of the valve in one single graph, potentially simplifying the grading system of aortic stenosis, especially for patient with low-flow, low-gradient AS. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Bern Center for Precision Medicine (BCPM) Stiffness stage 1All stiffness stages combined

Management of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) remains highly challenging due to highly variable therapeutic responses. By establishing an in vitro model for LHSCC based on conditional reprogramming (CR), a cell-culture technique, we aim to investigate its potential value on personalized cancer therapies. Herein, a panel of 28 human LHSCC CR cells were established from 50 tumor tissues using the CR method. They retained tumorigenic potential upon xenotransplantation and recapitulated molecular characteristics of LHSCC. Differential responses to anticancer drugs and radiotherapy were detected in vitro. CR cells could be transformed to xenograft and organoid, and they shared comparable drug responses. The clinical drug responses were consistent with in vitro drug responses. Collectively, the patient-derived CR cell model could promisingly be utilized in clinical decision-making and assisted in the selection of personalized therapies for LHSCC.

The aim of the work is to propose a methodology for the stimulation of a 3D in vitro skin model to activate wound healing. The presented work is in the frame of the national research project, CronXCov, “Checking the CHRONIC to prevent COVID-19”, devoted to understand how physiologic and inflamed skin on chip 3D models evolve upon a range of physical (e.g., electrical, mechanical, optical) stimulations, over time. Thanks to the 3D modelling, using Next Generation Sequencing and the network medicine frame of analysis to process the data, we will systematically characterize the effects of the applied stimuli, offering new insight for the exploitation of wound healing.

The aim of this present study is to investigate the role of damaged Trabecular Meshwork (TM) in triggering neuron-like cell apoptosis. Preliminary results showed that stressed TM releases harmful signals to neuron-like cells, suggesting its pivotal role in glaucoma cascade.