Miracle-dz/UniFAR-FTUs huggingface dataset:
A Huge Plantar Intramuscular Hemangioma in the Plantar Area Treated Surgically: A Case Report and Literature Review

Intramuscular hemangioma (IH) is rare, accounting for only 0.8% of all hemangioma cases. In particular, IH of the foot has only been reported a few times. In such cases, the symptoms typically include tenderness and swelling, often in relation to physical activity, but tingling or impaired function may also be present. Here, we report a patient who presented with a significant IH in the plantar area treated surgically. A 25-year-old female visited our hospital with pain in the plantar aspect of the right foot. She had noticed a mass about 10 years prior. She had previously experienced pain only when pressing the mass, but the pain subsequently became more regular pain and was exacerbated by exercise. In fact, the pain became so intense that she could not sleep well. Upon physical examination, mild swelling and tenderness of the plantar area were noted in the second to the fourth metatarsal. Sensation and motor reflexes were normal and the results of Tinel’s test were negative. Plain radiographs of the right foot revealed phleboliths scattered throughout the first to third intermetatarsal spaces. Magnetic resonance imaging revealed a space-occupying multilobulated mass (5.6 × 2.8 × 2.5 cm) located in the flexor digitorum brevis (FDB) muscle, which penetrated the plantar fascia and spread to the subcutaneous layer. In T2-weighted images, the lesion displayed a hyperintense signal compared to the surrounding skeletal muscle. Based on radiological findings, we suspected IH. The mass surrounded by the FDB muscle was exposed and completely removed via wide excision. IH consisting of cavernous-like vascular structures was diagnosed on pathology. At 1-year follow-up, the patient was almost asymptomatic and had recovered almost full range of motion in the plantar area. Histological analysis and surgery are recommended to remove intramuscular hemangiomas in the plantar area, but if the patient is not suitable for surgery, sclerotherapy or combination treatment should also be considered.
Renal and Extra Renal Manifestations in Adult Zebrafish Model of Cystinosis

Cystinosis is a rare, incurable, autosomal recessive disease caused by mutations in the CTNS gene. This gene encodes the lysosomal cystine transporter cystinosin, leading to lysosomal cystine accumulation in all cells of the body, with kidneys being the first affected organs. The current treatment with cysteamine decreases cystine accumulation, but does not reverse the proximal tubular dysfunction, glomerular injury or loss of renal function. In our previous study, we have developed a zebrafish model of cystinosis through a nonsense mutation in the CTNS gene and have shown that zebrafish larvae recapitulate the kidney phenotype described in humans. In the current study, we characterized the adult cystinosis zebrafish model and evaluated the long-term effects of the disease on kidney and extra renal organs through biochemical, histological, fertility and locomotor activity studies. We found that the adult cystinosis zebrafish presents cystine accumulation in various organs, altered kidney morphology, impaired skin pigmentation, decreased fertility, altered locomotor activity and ocular anomalies. Overall, our data indicate that the adult cystinosis zebrafish model reproduces several human phenotypes of cystinosis and may be useful for studying pathophysiology and long-term effects of novel therapies.
Doxorubicin-Induced Autophagolysosome Formation Is Partly Prevented by Mitochondrial ROS Elimination in DOX-Resistant Breast Cancer Cells

Since its discovery, mitophagy has been viewed as a protective mechanism used by cancer cells to prevent the induction of mitochondrial apoptosis. Most cancer treatments directly or indirectly cause mitochondrial dysfunction in order to trigger signals for cell death. Elimination of these dysfunctional mitochondria by mitophagy could thus prevent the initiation of the apoptotic cascade. In breast cancer patients, resistance to doxorubicin (DOX), one of the most widely used cancer drugs, is an important cause of poor clinical outcomes. However, the role played by mitophagy in the context of DOX resistance in breast cancer cells is not well understood. We therefore tried to determine whether an increase in mitophagic flux was associated with the resistance of breast cancer cells to DOX. Our first objective was to explore whether DOX-resistant breast cancer cells were characterized by conditions that favor mitophagy induction. We next tried to determine whether mitophagic flux was increased in DOX-resistant cells in response to DOX treatment. For this purpose, the parental (MCF-7) and DOX-resistant (MCF-7dox) breast cancer cell lines were used. Our results show that mitochondrial reactive oxygen species (ROS) production and hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression are higher in MCF-7dox in a basal condition compared to MCF-7, suggesting DOX-resistant breast cancer cells are prone to stimuli to induce a mitophagy-related event. Our results also showed that, in response to DOX, autophagolysosome formation is induced in DOX-resistant breast cancer cells. This mitophagic step following DOX treatment seems to be partly due to mitochondrial ROS production as autophagolysosome formation is moderately decreased by the mitochondrial antioxidant mitoTEMPO.
Preliminary Insight of Pyrrolylated-Chalcones as New Anti-Methicillin-Resistant Staphylococcus aureus (Anti-MRSA) Agents

Bacterial infections are regarded as one of the leading causes of fatal morbidity and death in patients infected with diseases. The ability of microorganisms, particularly methicillin-resistant Staphylococcus aureus (MRSA), to develop resistance to current drugs has evoked the need for a continuous search for new drugs with better efficacies. Hence, a series of non-PAINS associated pyrrolylated-chalcones (1–15) were synthesized and evaluated for their potency against MRSA. The hydroxyl-containing compounds (8, 9, and 10) showed the most significant anti-MRSA efficiency, with the MIC and MBC values ranging from 0.08 to 0.70 mg/mL and 0.16 to 1.88 mg/mL, respectively. The time-kill curve and SEM analyses exhibited bacterial cell death within four hours after exposure to 9, suggesting its bactericidal properties. Furthermore, the docking simulation between 9 and penicillin-binding protein 2a (PBP2a, PDB ID: 6Q9N) suggests a relatively similar bonding interaction to the standard drug with a binding affinity score of −7.0 kcal/mol. Moreover, the zebrafish model showed no toxic effects in the normal embryonic development, blood vessel formation, and apoptosis when exposed to up to 40 µM of compound 9. The overall results suggest that the pyrrolylated-chalcones may be considered as a potential inhibitor in the design of new anti-MRSA agents.
The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases

The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems. In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development. The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development. The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases. This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as “C. sativa L.” or “medical cannabis”), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.
Biosynthesis and Cytotoxic Properties of Ag, Au, and Bimetallic Nanoparticles Synthesized Using Lithospermum erythrorhizon Callus Culture Extract

The present study reports a green chemistry approach for the rapid and easy biological synthesis of silver (Ag), gold (Au), and bimetallic Ag/Au nanoparticles using the callus extract of Lithospermum erythrorhizon as a reducing and capping agent. The biosynthesized nanoparticles were characterized with ultraviolet-visible (UV-Vis) spectroscopy, X-ray diffraction (XRD) analysis, and transmission electron microscopy (TEM). Our results showed the formation of crystalline metal nanostructures of both spherical and non-spherical shape. Energy dispersive X-ray (EDX) spectroscopy showed the characteristic peaks in the silver and gold regions, confirming the presence of the corresponding elements in the monometallic particles and both elements in the bimetallic particles. Fourier-transform infrared (FTIR) spectroscopy affirmed the role of polysaccharides and polyphenols of the L. erythrorhizon extract as the major reducing and capping agents for metal ions. In addition, our results showed that the polysaccharide sample and the fraction containing secondary metabolites isolated from L. erythrorhizon were both able to produce large amounts of metallic nanoparticles. The biosynthesized nanoparticles demonstrated cytotoxicity against mouse neuroblastoma and embryonic fibroblast cells, which was considerably higher for Ag nanoparticles and for bimetallic Ag/Au nanoparticles containing a higher molar ratio of silver. However, fibroblast migration was not significantly affected by any of the nanoparticles tested. The obtained results provide a new example of the safe biological production of metallic nanoparticles, but further study is required to uncover the mechanism of their toxicity so that the biomedical potency can be assessed.
Role of Serum E-Selectin as a Biomarker of Infection Severity in Coronavirus Disease 2019

Introduction: E-selectin is a recognized marker of endothelial activation; however, its place in Coronavirus Disease 2019 (COVID-19) has not been fully explored. Aims of the study are to compare sE-selectin values among the Intensive Care Unit (ICU)-admitted and non-admitted, survived and non-survived patients and those with or without thrombosis. Methods: A single-center study of patients with COVID-19 hospitalized at Policlinico Umberto I (Rome) from March to May 2020 was performed. Simple and multiple logistic regression models were developed. Results: One hundred patients were included, with a median age (IQR) of 65 years (58–78). Twenty-nine (29%) were admitted to ICU, twenty-eight (28%) died and nineteen (19%) had a thrombotic event. The median value (IQR) of sE-selectin was 26.1 ng/mL (18.1–35). sE-selectin values did not differ between deceased and survivors (p = 0.06) and among patients with or without a thrombotic event (p = 0.22). Compared with patients who did not receive ICU treatments, patients requiring ICU care had higher levels of sE-selectin (36.6 vs. 24.1 ng/mL; p < 0.001). In the multiple logistic regression model, sE-selectin levels > 33 ng/mL, PaO2/FiO2 < 200 and PaO2/FiO2 200–300 were significantly associated with an increased risk of ICU admission. sE-selectin values significantly correlated with a neutrophil count (R = 0.32 (p = 0.001)) and the number of days from the symptoms onset to hospitalization (R = 0.28 (p = 0.004)). Conclusions: sE-selectin levels are predictive of ICU admission in COVID-19 patients. Since data on the relation between sE-selectin and COVID-19 are scarce, this study aims to contribute toward the comprehension of the pathogenic aspects of COVID-19 disease, giving a possible clinical marker able to predict its severity.
(Dys)function Follows Form: Nucleic Acid Structure, Repeat Expansion, and Disease Pathology in FMR1 Disorders

Fragile X-related disorders (FXDs), also known as FMR1 disorders, are examples of repeat expansion diseases (REDs), clinical conditions that arise from an increase in the number of repeats in a disease-specific microsatellite. In the case of FXDs, the repeat unit is CGG/CCG and the repeat tract is located in the 5′ UTR of the X-linked FMR1 gene. Expansion can result in neurodegeneration, ovarian dysfunction, or intellectual disability depending on the number of repeats in the expanded allele. A growing body of evidence suggests that the mutational mechanisms responsible for many REDs share several common features. It is also increasingly apparent that in some of these diseases the pathologic consequences of expansion may arise in similar ways. It has long been known that many of the disease-associated repeats form unusual DNA and RNA structures. This review will focus on what is known about these structures, the proteins with which they interact, and how they may be related to the causative mutation and disease pathology in the FMR1 disorders.
Chronic kidney disease recognition amongst physicians and advanced practice providers

Abstract Objective Chronic kidney disease is a worldwide public health issue, with increasing prevalence resulting in high morbidity and mortality. As a result, recognizing and treating it early can lead to improved outcomes. We hypothesized that some providers might be more comfortable making this diagnosis than others. Methods Retrospective study of 380 patients with chronic kidney disease seen between 2012 and 2016 in an outpatient setting. Results Three hundred and sixteen patients were treated by physicians and sixty-four by advanced practice providers. Chronic kidney disease was identified by the primary care providers in 318 patients (83.6%). Patients recognized with chronic kidney disease were older, 76 ± 8.8 vs 72 ± 7.45 years, p = 0.001; had lower GFR, 37 [29, 46] vs 57 [37, 76] ml/min/1.73 m2, p < 0.0001 and were more likely to be seen by a physician compared to an advanced practice provider: 272/316 (86%) vs 46/64 (71.8%), p = 0.008. In multivariate analyses, care by a physician, OR = 2.27 (1.13–4.58), p = 0.02 was associated with increased recognition of chronic kidney disease. On the other hand, higher GFR was associated with decreased diagnosis of chronic kidney disease, OR = 0.95 (0.93–0.96), p < 0.0001. Conclusion The odds of chronic kidney disease recognition were higher amongst physicians in comparison to non-physician providers.
Anisotropic Chitosan Scaffolds Generated by Electrostatic Flocking Combined with Alginate Hydrogel Support Chondrogenic Differentiation

The replacement of damaged or degenerated articular cartilage tissue remains a challenge, as this non-vascularized tissue has a very limited self-healing capacity. Therefore, tissue engineering (TE) of cartilage is a promising treatment option. Although significant progress has been made in recent years, there is still a lack of scaffolds that ensure the formation of functional cartilage tissue while meeting the mechanical requirements for chondrogenic TE. In this article, we report the application of flock technology, a common process in the modern textile industry, to produce flock scaffolds made of chitosan (a biodegradable and biocompatible biopolymer) for chondrogenic TE. By combining an alginate hydrogel with a chitosan flock scaffold (CFS+ALG), a fiber-reinforced hydrogel with anisotropic properties was developed to support chondrogenic differentiation of embedded human chondrocytes. Pure alginate hydrogels (ALG) and pure chitosan flock scaffolds (CFS) were studied as controls. Morphology of primary human chondrocytes analyzed by cLSM and SEM showed a round, chondrogenic phenotype in CFS+ALG and ALG after 21 days of differentiation, whereas chondrocytes on CFS formed spheroids. The compressive strength of CFS+ALG was higher than the compressive strength of ALG and CFS alone. Chondrocytes embedded in CFS+ALG showed gene expression of chondrogenic markers (COL II, COMP, ACAN), the highest collagen II/I ratio, and production of the typical extracellular matrix such as sGAG and collagen II. The combination of alginate hydrogel with chitosan flock scaffolds resulted in a scaffold with anisotropic structure, good mechanical properties, elasticity, and porosity that supported chondrogenic differentiation of inserted human chondrocytes and expression of chondrogenic markers and typical extracellular matrix.
Caspase-1 Inhibition Impacts the Formation of Chondrogenic Nodules, and the Expression of Markers Related to Osteogenic Differentiation and Lipid Metabolism

Caspase-1, as the main pro-inflammatory cysteine protease, was investigated mostly with respect to inflammation-related processes. Interestingly, caspase-1 was identified as being involved in lipid metabolism, which is extremely important for the proper differentiation of chondrocytes. Based on a screening investigation, general caspase inhibition impacts the expression of Cd36 in chondrocytes, the fatty acid translocase with a significant impact on lipid metabolism. However, the engagement of individual caspases in the effect has not yet been identified. Therefore, the hypothesis that caspase-1 might be a candidate here appears challenging. The primary aim of this study thus was to find out whether the inhibition of caspase-1 activity would affect Cd36 expression in a chondrogenic micromass model. The expression of Pparg, a regulator Cd36, was examined as well. In the caspase-1 inhibited samples, both molecules were significantly downregulated. Notably, in the treated group, the formation of the chondrogenic nodules was apparently disrupted, and the subcellular deposition of lipids and polysaccharides showed an abnormal pattern. To further investigate this observation, the samples were subjected to an osteogenic PCR array containing selected markers related to cartilage/bone cell differentiation. Among affected molecules, Bmp7 and Gdf10 showed a significantly increased expression, while Itgam, Mmp9, Vdr, and Rankl decreased. Notably, Rankl is a key marker in bone remodeling/homeostasis and thus is a target in several treatment strategies, including a variety of fatty acids, and is balanced by its decoy receptor Opg (osteoprotegerin). To evaluate the effect of Cd36 downregulation on Rankl and Opg, Cd36 silencing was performed using micromass cultures. After Cd36 silencing, the expression of Rankl was downregulated and Opg upregulated, which was an inverse effect to caspase-1 inhibition (and Cd36 upregulation). These results demonstrate new functions of caspase-1 in chondrocyte differentiation and lipid metabolism-related pathways. The effect on the Rankl/Opg ratio, critical for bone maintenance and pathology, including osteoarthritis, is particularly important here as well.
Rapid Magneto-Sonoporation of Adipose-Derived Cells

By permeabilizing the cell membrane with ultrasound and facilitating the uptake of iron oxide nanoparticles, the magneto-sonoporation (MSP) technique can be used to instantaneously label transplantable cells (like stem cells) to be visualized via magnetic resonance imaging in vivo. However, the effects of MSP on cells are still largely unexplored. Here, we applied MSP to the widely applicable adipose-derived stem cells (ASCs) for the first time and investigated its effects on the biology of those cells. Upon optimization, MSP allowed us to achieve a consistent nanoparticle uptake (in the range of 10 pg/cell) and a complete membrane resealing in few minutes. Surprisingly, this treatment altered the metabolic activity of cells and induced their differentiation towards an osteoblastic profile, as demonstrated by an increased expression of osteogenic genes and morphological changes. Histological evidence of osteogenic tissue development was collected also in 3D hydrogel constructs. These results point to a novel role of MSP in remote biophysical stimulation of cells with focus application in bone tissue repair.
Subcellular architecture and metabolic connection in the planktonic photosymbiosis between Collodaria (radiolarians) and their microalgae

Photosymbiosis is widespread and ecologically important in the oceanic plankton but remains poorly studied. Here, we used multimodal subcellular imaging to investigate the photosymbiosis between colonial Collodaria and their microalga dinoflagellate (Brandtodinium) collected in surface seawaters. We showed that this symbiosis is a very dynamic system whereby symbionts interact with different host cells via extracellular vesicles within the “greenhouse-like” colony. 3D electron microscopy revealed that the volume of the photosynthetic apparatus (plastid and pyrenoid) of the microalgae increased in symbiosis compared to free-living while the mitochondria volume was similar. Stable isotope probing coupled with NanoSIMS showed that carbon and nitrogen were assimilated and stored in the symbiotic microalga in starch granules and purine crystals, respectively. Nitrogen was also allocated to the algal nucleus (nucleolus). After 3 hours, low 13C and 15N transfer was detected in the host Golgi. Metal mapping revealed that intracellular iron concentration was similar in free-living and symbiotic microalgae (ca 40 ppm) and two-fold higher in the host, whereas copper concentration increased in symbiotic microalgae (up to 6900 ppm) and was detected in the host cell and extracellular vesicles. Sulfur mapping also pinpointed the importance of this nutrient for the algal metabolism. This study, which revealed subcellular changes of the morphology and nutrient homeostasis in symbiotic microalgae, improves our understanding on the metabolism of this widespread and abundant oceanic symbiosis and paves the way for more studies to investigate the metabolites exchanged.
Utilization of Self-Consolidated Green Material for Sustainable Development: An Environment Friendly Waste Materials Application for Circular Economy

Self-Compacting Concrete (SCC) is a unique kind of concrete that tends to consolidate in terms of its weight. In this study, the prime target is to investigate the durability properties of SCC developed using eco-friendly economical waste binding materials as partial replacement to costly cement. This circular economy concept will not only help in the development of green concrete but will also help to improve the climatic condition by reducing the use and production of cement. An economical design methodology has been applied to produce environmentally friendly construction material. This research focuses on the application of Alum Sludge (AS) and Brick Dust (BD) in Self-Compacting Concrete (SCC). Both materials are waste materials containing binding properties. Performance of SCC developed using these two materials was tested considering mechanical properties of concrete using the destructive testing technique. Results showed that BD and AS can be utilized for up to 12% and 9% of replacement of cement, respectively, to achieve equal or higher compressive, tensile, and flexural strength. The application of BD and AS has demonstrated a subsequent improvement of SCC’s mechanical properties, i.e., compressive, tensile, and flexural strength. This study will help the production of composite green materials with the help of eco-friendly and economical waste materials for sustainable infrastructure development.