Publications by authors named "Chiara Ghezzi"

The gold standard treatment in anterior cruciate ligament (ACL) reconstruction involves autologous tissue transplantation, but this can have complications. Artificial grafts are an alternative, but the best option is debated. This study aimed to assess the biocompatibility and integration of a silk fibroin textile prosthesis (SF-TP) with peri-implant bone tissue and the native ACL.

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Article Synopsis
  • The study investigates the effects of Jardiance® (Empagliflozin), a specific SGLT2 inhibitor, on glucose uptake in astrocytomas by using a glucose tracer and PET imaging.
  • Five patients participated, four with grade IV glioblastomas and one with grade II astrocytoma, undergoing two PET scans before and after taking Jardiance.
  • Results showed a significant reduction in tumor glucose accumulation after treatment, suggesting SGLT2 is an active glucose transporter in astrocytomas and prompting recommendations for further clinical trials.
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Studies on gamma radiation-induced injury have long been focused on hematopoietic, gastrointestinal, and cardiovascular systems, yet little is known about the effects of gamma radiation on the function of human cortical tissue. The challenge in studying radiation-induced cortical injury is, in part, due to a lack of human tissue models and physiologically relevant readouts. Here, a physiologically relevant 3D collagen-based cortical tissue model (CTM) is developed for studying the functional response of human iPSC-derived neurons and astrocytes to a sub-lethal radiation exposure (5 Gy).

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Sample pooling is a promising strategy to facilitate COVID-19 surveillance testing for a larger population in comparison to individual single testing due to resource and time constraints. Increased surveillance testing capacity will reduce the likelihood of outbreaks as the general population is returning to work, school, and other gatherings. We have analyzed the impact of three variables on the effectiveness of pooling test samples: swab type, workflow, and positive sample order.

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The oral cavity contains distinct microenvironments that serve as oral barriers, such as the non-shedding surface of the teeth (e.g., enamel), the epithelial mucosa and gingival tissue (attached gingiva) where microbial communities coexist.

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Squamous cell lung cancer maintains its growth through elevated glucose consumption, but selective glucose consumption inhibitors are lacking. Here, we discovered using a high-throughput screen new compounds that block glucose consumption in three squamous cell lung cancer cell lines and identified 79 compounds that block glucose consumption in one or more of these cell lines. Based on its ability to block glucose consumption in all three cell lines, pacritinib, an inhibitor of FMS Related Receptor Tyrosine Kinase 3 (FLT3) and Janus Kinase 2 (JAK2), was further studied.

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Article Synopsis
  • Small molecule inhibitors targeting kinases are crucial for treating non-small cell lung cancer (NSCLC), but they have limitations like varying patient responses, side effects, and lack of reliable biomarkers for efficacy.
  • Early changes in tumor glucose consumption, tracked with [F]FDG PET imaging, may predict how well these inhibitors work, but this area is still not fully understood.
  • The study shows that effective targeted kinase inhibitors consistently reduce glucose consumption early on, which is important for inhibiting cancer cell growth in NSCLC models.
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Large-scale population testing is a key tool to mitigate the spread of respiratory pathogens, such as the current COVID-19 pandemic, where swabs are used to collect samples in the upper airways (e.g., nasopharyngeal and midturbinate nasal cavities) for diagnostics.

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Microbial communities are eubiotic ecosystems that interact dynamically and synergistically with the human body. Imbalances in these interactions may cause dysbiosis by enhancing the occurrence of inflammatory conditions, such as periodontal or inflammatory bowel diseases. However, the mechanisms that lie behind eubiosis-dysbiosis transitions are still unclear and constantly being redefined.

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During the COVID-19 public health emergency, many actions have been undertaken to help ensure that patients and health care providers have timely and continued access to high-quality medical devices to respond effectively. The development and validation of new testing supplies and equipment, including collection swabs, has helped to expand the availability and capability for various diagnostic, therapeutic, and protective medical devices in high demand during the COVID-19 emergency. Here, we report the initial validation of a new injection-molded anterior nasal swab, ClearTip™, that was experimentally validated in a laboratory setting as well as in independent clinical studies in comparison to gold standard flocked swabs.

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Large-scale population testing is a key tool to mitigate the spread of respiratory pathogens, as in the current COVID-19 pandemic, where swabs are used to collect samples in the upper airways (e.g. nasopharyngeal and mid-turbinate nasal cavities) for diagnostics.

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Faced with the COVID-19 pandemic, the US system for developing and testing technologies was challenged in unparalleled ways. This article describes the multi-institutional, transdisciplinary team of the "RADx Tech Test Verification Core" and its role in expediting evaluations of COVID-19 testing devices. Expertise related to aspects of diagnostic testing was coordinated to evaluate testing devices with the goal of significantly expanding the ability to mass screen Americans to preserve lives and facilitate the safe return to work and school.

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Biomaterial scaffold designs are needed for self-organizing features related to tissue formation while also simplifying the fabrication processes involved. Toward this goal, silk protein-based self-folding scaffolds to support 3D cell culture, while providing directional guidance and promotion of cell growth and differentiation, are reported. A simple and robust one-step self-folding approach is developed using bilayers consisting of a hydrogel and silk film in aqueous solution.

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Multiple ophthalmic pathologies, such as retinal detachment and diabetic retinopathy, require the removal and replacement of the vitreous humor. Clinical tamponades such as silicone oil and fluorinated gases are utilized but limited due to complications and toxicity. Therefore, there is a need for biocompatible, stable, vitreous humor substitutes.

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Elevated glucose consumption is fundamental to cancer, but selectively targeting this pathway is challenging. We develop a high-throughput assay for measuring glucose consumption and use it to screen non-small-cell lung cancer cell lines against bioactive small molecules. We identify Milciclib that blocks glucose consumption in H460 and H1975, but not in HCC827 or A549 cells, by decreasing SLC2A1 (GLUT1) mRNA and protein levels and by inhibiting glucose transport.

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Brain-infiltrating leukocytes contribute to multiple sclerosis (MS) and autoimmune encephalomyelitis and likely play a role in traumatic brain injury, seizure, and stroke. Brain-infiltrating leukocytes are also primary targets for MS disease-modifying therapies. However, no method exists for noninvasively visualizing these cells in a living organism.

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The cornea provides a functional barrier separating the outside environment from the intraocular environment, thereby protecting posterior segments of the eye from infection and damage. Pathological changes that compromise the structure or integrity of the cornea may occur as a result of injury or disease and can lead to debilitating effects on visual acuity. Over 10 million people worldwide are visually impaired or blind due to corneal opacity.

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Cervical insufficiency (CI) is an important cause of preterm birth, which leads to severe newborn complications. Standard treatment for CI is cerclage, which has variable success rates, resulting in a clinical need for alternative treatments. Our objective was to develop an ex vivo model of softened cervical tissue to study an injectable silk-based hydrogel as a novel alternative treatment for CI.

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Sodium-dependent glucose transporters (SGLTs) exploit sodium gradients to transport sugars across the plasma membrane. Due to their role in renal sugar reabsorption, SGLTs are targets for the treatment of type 2 diabetes. Current therapeutics are phlorizin derivatives that contain a sugar moiety bound to an aromatic aglycon tail.

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Diabetes mellitus is a disease caused by innate or acquired insulin deficiency, resulting in altered glucose metabolism and high blood glucose levels. Chronic hyperglycemia is linked to development of several ocular pathologies affecting the anterior segment, including diabetic corneal neuropathy and keratopathy, neovascular glaucoma, edema, and cataracts leading to significant visual defects. Due to increasing disease prevalence, related medical care costs, and visual impairment resulting from diabetes, a need has arisen to devise alternative systems to study molecular mechanisms involved in disease onset and progression.

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The cornea is a valuable tissue for studying peripheral sensory nerve structure and regeneration due to its avascularity, transparency, and dense innervation. Somatosensory innervation of the cornea serves to identify changes in environmental stimuli at the ocular surface, thereby promoting barrier function to protect the eye against injury or infection. Due to regulatory demands to screen ocular safety of potential chemical exposure, a need remains to develop functional human tissue models to predict ocular damage and pain using in vitro-based systems to increase throughput and minimize animal use.

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The concentration of glucose in plasma is held within narrow limits (4-10 mmol/l), primarily to ensure fuel supply to the brain. Kidneys play a role in glucose homeostasis in the body by ensuring that glucose is not lost in the urine. Three membrane proteins are responsible for glucose reabsorption from the glomerular filtrate in the proximal tubule: sodium-glucose cotransporters SGLT1 and SGLT2, in the apical membrane, and GLUT2, a uniporter in the basolateral membrane.

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New in vitro tissue models to mimic in vivo conditions are needed to provide insight into mechanisms involved in peripheral pain responses, potential therapeutic strategies to address these responses, and to replace animal models for such indications. For example, the rabbit cornea Draize test has become the standard method used for decades to screen ophthalmic drug and consumer product toxicity. In vitro tissue models with functional innervation have the potential to replace in vivo animal testing and provide sophisticated bench tools to study ocular nociception and its amelioration.

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Key Points: The goal was to determine the importance of the sodium-glucose cotransporter SGLT1 and the glucose uniporter GLUT2 in intestinal glucose absorption during oral glucose tolerance tests (OGTTs) in mice. Glucose absorption was determined in mice using positron emission tomography and three non-metabolizable glucose probes: one specific for SGLTs, one specific for GLUTs, and one a substrate for both SGLTs and GLUTs. Absorption was determined in wild-type, Sglt1 and Glut2 mice.

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It has been 30 years since the intestinal sodium glucose cotransporter SGLT1 was cloned, and, in the intervening years, there have been many advances that have influenced physiology and medicine. Among the first was that SGLT1 is the founding member of the human gene family SLC5, containing 11 diverse transporters and a glucose sensor. Equally surprising was that SGLTs are members of a structural family of cotransporters and exchangers in different gene families.

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