Miracle-dz/UniFAR-FTUs huggingface dataset:
The decellularized ovary as a potential scaffold for maturation of preantral ovarian follicles of prepubertal mice

ABSTRACT In the current study, a decellularized ovary scaffold was used for the encapsulation and development of preantral follicles. Maturation and the expression of the related genes were evaluated and compared against in vivo conditions. Mature rat ovaries were decellularized and decellularization was confirmed using hematoxylin/eosin and Hoechst stains. Collagen and glycosaminoglycan (GAG) preservation and the extracellular matrix (ECM) architecture were evaluated by Masson’s trichrome staining, Alcian blue staining, and scanning electron microscopy, respectively. Raman confocal microscopy and DNA quantification were performed to show DNA and cell debris depletion and ECM retention. Preantral follicles of mice were cultured for 12 days in the decellularized (3D) and two-dimensional (2D) conditions. Finally, the survival rate, antrum formation rate and diameters of follicles, levels of estradiol (E2) and progesterone (P4), and expression of the ZP2, Gdf9, Bmp6, and Bmp15 genes were evaluated in the 2D and 3D culture systems. On day 13 of culture, oocyte maturation was induced by hCG. Although histochemical tests showed partial retention of ECM, Raman confocal microscopy showed some extent of ECM washing out along with the depletion of DNA and cell debris. However, SEM showed the preservation of the ovarian ECM’s ultrastructure. The survival rate of follicles was similar, but the antrum formation rate, concentrations of E2 and P4, and oocyte maturation rate were significantly higher in 3D compared with 2D. The level of ZP2, Gdf9, Bmp6, and Bmp15 gene expression in follicles matured in 2D, 3D, and in vivo was statistically similar. In all matured follicles, their gene expression levels significantly declined relative to preantral follicles. Ovarian follicles that matured in the decellularized ovaries demonstrated the same follicular growth and maturation gene expression levels as those that grew in the natural ovary. This is consistent with using the decellularized ovary as a scaffold suitable for ovarian reconstruction. Abbreviations GAG: glycosaminoglycan; ECM: extracellular matrix; 2D: two-dimensional; E2: estradiol; P4: progesterone; BMP15: bone morphogenetic protein 15; GDF9: growth differentiation factor 9; ZP2: zona pellucida 2; Gdf9: growth/differentiation factor-9; Bmp6: bone morphogenetic protein 6; Bmp15: bone morphogenetic protein 15.
Skin Sensitization Potential and Cellular ROS-Induced Cytotoxicity of Silica Nanoparticles

Nowadays, various industries using nanomaterials are growing rapidly, and in particular, as the commercialization and use of nanomaterials increase in the cosmetic field, the possibility of exposure of nanomaterials to the skin of product producers and consumers is increasing. Due to the unique properties of nanomaterials with a very small size, they can act as hapten and induce immune responses and skin sensitization, so accurate identification of toxicity is required. Therefore, we selected silica nanomaterials used in various fields such as cosmetics and biomaterials and evaluated the skin sensitization potential step-by-step according to in-vitro and in-vivo alternative test methods. KeratinoSensTM cells of modified keratinocyte and THP-1 cells mimicking dendritic-cells were treated with silica nanoparticles, and their potential for skin sensitization and cytotoxicity were evaluated, respectively. We also confirmed the sensitizing ability of silica nanoparticles in the auricle-lymph nodes of BALB/C mice by in-vivo analysis. As a result, silica nanoparticles showed high protein binding and reactive oxygen species (ROS) mediated cytotoxicity, but no significant observation of skin sensitization indicators was observed. Although more studies are needed to elucidate the mechanism of skin sensitization by nanomaterials, the results of this study showed that silica nanoparticles did not induce skin sensitization.
Complete Assignment of the 1H and 13C NMR Spectra of Carthamin Potassium Salt Isolated from Carthamus tinctorius L.

Carthamin potassium salt isolated from Carthamus tinctorius L. was purified by an improved traditional Japanese method, without using column chromatography. The 1H and 13C nuclear magnetic resonance (NMR) signals of the pure product were fully assigned using one- and two-dimensional NMR spectroscopy, while the high purity of the potassium salt and deprotonation at the 3′ position of carthamin were confirmed by atomic adsorption spectroscopy and nano-electrospray ionization mass spectrometry.
The Synthesis and Evaluation of RGD−Conjugated Chitosan Gel as Daily Supplement for Body Weight Control

(1) Background: Obesity is one of the most widespread chronic diseases and increases the risk of several other chronic diseases, especially type 2 diabetes. (2) Methods: Endobarrier is a new medical device what is worn in the small intestines for the treatment of type 2 diabetes and obesity. However, given the invasive and other adverse effects of the Endobarrier, we propose the use of RGD peptide conjugated with chitosan (RC) as an alternative. (3) Results: The FTIR and NMR spectrum showed RGD peptide was successfully conjugated on chitosan and RGD−CT is retained in the small intestine even after digestion. In vitro of wst-1 and live and dead staining studies show that the RGD−CT gel is highly biocompatible and non-toxic. Rats treated with the RGD−CT gel for a short term showed significant decrease change more than 30% in body weight, while the blood and hematic biometrics were within normal values. (4) Conclusions: The RGD−CT gel is safe, suitable for the short-term, reducing visceral fat rate health food to control weight. In the future, it is expected to develop a safe, long-term effective, flexibility of use and low-side-effect anti-obesity therapy in the era of precision medicine by further modification.
Associations between Personality Traits, Intolerance of Uncertainty, Coping Strategies, and Stress in Italian Frontline and Non-Frontline HCWs during the COVID-19 Pandemic—A Multi-Group Path-Analysis

The COVID-19 pandemic represented a very difficult physical and psychological challenge for the general population and even more for healthcare workers (HCWs). The main aim of the present study is to test whether there were significant differences between frontline and non-frontline Italian HCWs concerning (a) personality traits, intolerance of uncertainty, coping strategies and perceived stress, and (b) the models of their associations. A total of 682 Italian HCWs completed a self-report questionnaire: 280 employed in COVID-19 wards and 402 in other wards. The analysis of variance omnibus test revealed significant differences between the two groups only for perceived stress, which was higher among the frontline. The multi-group path analysis revealed significant differences in the structure of the associations between the two groups of HCWs, specifically concerning the relations between: personality traits and intolerance of uncertainty; intolerance of uncertainty and coping strategies. Regarding the relation between coping strategies and stress no difference was identified between the two groups. In both of them, emotionally focused coping was negatively related with perceived stress, whereas dysfunctional coping was positively related with stress. These results could be useful in planning actions aiming to reduce stress and improve the effectiveness of HCWs’ interventions. Training programs aimed to provide HCWs with a skillset to tackle uncertain and stressful circumstances could represent an appropriate support to develop a preventive approach during outbreaks.
A Multi-Scale Model of Disease Transfer in Honey Bee Colonies

Simple Summary Inter-colony disease spread is a impediment to a healthy apiary. A multi-scale mathematical model is built to explore the effects of inter-colony behaviour on the spread of disease. We model different scenarios corresponding to different behaviours exhibited by honey bees. We show that a colony can use certain behaviours to lower the impact of disease on itself, and show that other behaviours are only relevant under specific conditions. The model can be extended to explore an entire apiary or modified to explore the evolutionary underpinnings of these behaviours. Abstract Inter-colony disease transfer poses a serious hurdle to successfully managing healthy honeybee colonies. In this study, we build a multi-scale model of two interacting honey bee colonies. The model considers the effects of forager and drone drift, guarding behaviour, and resource robbing of dying colonies on the spread of disease between colonies. Our results show that when drifting is high, disease can spread rapidly between colonies, that guarding behaviour needs to be particularly efficient to be effective, and that for dense apiaries drifting is of greater concern than robbing. We show that while disease can put an individual colony at greater risk, drifting can help less the burden of disease in a colony. We posit some evolutionary questions that come from this study that can be addressed with this model.
The Obscure Effect of Tribulus terrestris Saponins Plus Inulin on Liver Morphology, Liver Fatty Acids, Plasma Glucose, and Lipid Profile in SD Rats with and without Induced Type 2 Diabetes Mellitus

Diabetes is a predictor of nonalcoholic fatty liver disease (NAFLD). There are data suggesting that Tribulus terrestris (TT) saponins act as antidiabetic agents and protect against NAFLD. The effect of saponins may be increased by fermentable fibers such as inulin. The aim of the present study was to investigate the influence of TT saponins and TT saponins plus inulin on the plasma lipid profile and liver fatty acids of rats with induced diabetes mellitus type 2 (T2DM). The study was performed on 36 male Sprague–Dawley rats divided into two main groups: control and diabetic. Animals of the diabetic (DM) group were fed a high-fat diet and injected with streptozotocin (low doses). Animals of the control group (nDM) were on a regular diet and were injected with buffer. After the injections, the animals were split into subgroups: three non-diabetic (nDM): (i) control (c-C); (ii) saponin-treated rats (C-Sap); (iii) rats treated with saponins + inulin (C-Sap + IN), and three diabetic subgroups (DM): (iv) control (c-DM); (v) saponin-treated rats (DM-Sap); (vi) rats treated with saponins + inulin (DM-Sap + IN). Liver fatty acids were extracted and analyzed by gas chromatography, and plasma glucose and lipids were measured. The study showed significant changes in liver morphology, liver fatty acids, plasma lipid profile, and plasma glucose. In summary, supplementation with TT saponins or saponins with inulin for one month decreased the level of steatosis in rats with induced type 2 diabetes. Moreover, there were favorable effects on the plasma lipid profile in the rats. However, additional supplementation with inulin had a negative effect on liver morphology (with a microvesicular type of steatosis) in the non-diabetes group. Moreover, supplementation with inulin had a negative effect on plasma glucose in both diabetic and non-diabetic rats. These data show that a diet enriched with fermentable fibers reveals different effects in different organisms, and not all sources and forms of fiber are beneficial to health.
Increased Hypothalamic Anti-Inflammatory Mediators in Non-Diabetic Insulin Receptor Substrate 2-Deficient Mice

Insulin receptor substrate (IRS) 2 is a key mediator of insulin signaling and IRS-2 knockout (IRS2−/−) mice are a preclinical model to study the development of diabetes, as they develop peripheral insulin resistance and beta-cell failure. The differential inflammatory profile and insulin signaling in the hypothalamus of non-diabetic (ND) and diabetic (D) IRS2−/− mice might be implicated in the onset of diabetes. Because the lipid profile is related to changes in inflammation and insulin sensitivity, we analyzed whether ND IRS2−/− mice presented a different hypothalamic fatty acid metabolism and lipid pattern than D IRS2−/− mice and the relationship with inflammation and markers of insulin sensitivity. ND IRS2−/− mice showed elevated hypothalamic anti-inflammatory cytokines, while D IRS2−/− mice displayed a proinflammatory profile. The increased activity of enzymes related to the pentose-phosphate route and lipid anabolism and elevated polyunsaturated fatty acid levels were found in the hypothalamus of ND IRS2−/− mice. Conversely, D IRS2−/− mice have no changes in fatty acid composition, but hypothalamic energy balance and markers related to anti-inflammatory and insulin-sensitizing properties were reduced. The data suggest that the concurrence of an anti-inflammatory profile, increased insulin sensitivity and polyunsaturated fatty acids content in the hypothalamus may slow down or delay the onset of diabetes.
Silver Nanoparticles Biosynthesis, Characterization, Antimicrobial Activities, Applications, Cytotoxicity and Safety Issues: An Updated Review

Rapid advances in nanotechnology have led to its emergence as a tool for the development of green synthesized noble metal nanoparticles, especially silver nanoparticles (AgNPs), for applications in diverse fields such as human health, the environment and industry. The importance of AgNPs is because of their unique physicochemical and antimicrobial properties, with a myriad of activities that are applicable in various fields, including the pharmaceutical industry. Countries with high biodiversity require the collection and transformation of information about biological assets into processes, associations, methods and tools that must be combined with the sustainable utilization of biological diversity. Therefore, this review paper discusses the applicable studies of the biosynthesis of AgNPs and their antimicrobial activities towards microorganisms in different areas viz. medicine and agriculture. The confirmed antiviral properties of AgNPs promote their applicability for SARS-CoV-2 treatment, based on assimilating the virus’ activities with those of similar viruses via in vivo studies. In this review, an insight into the cytotoxicity and safety issues of AgNPs, along with their future prospects, is also provided.
Neuroprotective and Symptomatic Effects of Cannabidiol in an Animal Model of Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the Substantia Nigra pars compacta, leading to classical PD motor symptoms. Current therapies are purely symptomatic and do not modify disease progression. Cannabidiol (CBD), one of the main phytocannabinoids identified in Cannabis Sativa, which exhibits a large spectrum of therapeutic properties, including anti-inflammatory and antioxidant effects, suggesting its potential as disease-modifying agent for PD. The aim of this study was to evaluate the effects of chronic treatment with CBD (10 mg/kg, i.p.) on PD-associated neurodegenerative and neuroinflammatory processes, and motor deficits in the 6-hydroxydopamine model. Moreover, we investigated the potential mechanisms by which CBD exerted its effects in this model. CBD-treated animals showed a reduction of nigrostriatal degeneration accompanied by a damping of the neuroinflammatory response and an improvement of motor performance. In particular, CBD exhibits a preferential action on astrocytes and activates the astrocytic transient receptor potential vanilloid 1 (TRPV1), thus, enhancing the endogenous neuroprotective response of ciliary neurotrophic factor (CNTF). These results overall support the potential therapeutic utility of CBD in PD, as both neuroprotective and symptomatic agent.
Root-Associated Microbiomes, Growth and Health of Ornamental Geophytes Treated with Commercial Plant Growth-Promoting Products

The microbial community inhabiting a plant’s root zone plays a crucial role in plant health and protection. To assess the ability of commercial plant growth-promoting products to enhance the positive effects of this environment, two products containing beneficial soil bacteria and a product containing plant extracts were tested on Zantedeschia aethiopica and Ornithogalum dubium. The products were tested in two different growing media: a soil and a soilless medium. The effects of these products on Pectobacterium brasiliense, the causal agent of soft rot disease, were also evaluated in vitro, and on naturally occurring infections in the greenhouse. The growing medium was found to have the strongest effect on the microbial diversity of the root-associated microbiome, with the next-strongest effect due to plant type. These results demonstrate that either a single bacterial strain or a product will scarcely reach the level that is required to influence soil microbial communities. In addition, the microbes cultured from these products, could not directly inhibit Pectobacterium growth in vitro. We suggest density-based and functional analyses in the future, to study the specific interactions between plants, soil type, soil microbiota and relevant pathogens. This should increase the effectiveness of bio-supplements and soil disinfestation with natural products, leading to more sustainable, environmentally friendly solutions for the control of bacterial plant diseases.
Centrally Projecting Edinger-Westphal Nucleus in the Control of Sympathetic Outflow and Energy Homeostasis

The centrally projecting Edinger-Westphal nucleus (EWcp) is a midbrain neuronal group, adjacent but segregated from the preganglionic Edinger-Westphal nucleus that projects to the ciliary ganglion. The EWcp plays a crucial role in stress responses and in maintaining energy homeostasis under conditions that require an adjustment of energy expenditure, by virtue of modulating heart rate and blood pressure, thermogenesis, food intake, and fat and glucose metabolism. This modulation is ultimately mediated by changes in the sympathetic outflow to several effector organs, including the adrenal gland, heart, kidneys, brown and white adipose tissues and pancreas, in response to environmental conditions and the animal’s energy state, providing for appropriate energy utilization. Classic neuroanatomical studies have shown that the EWcp receives inputs from forebrain regions involved in these functions and projects to presympathetic neuronal populations in the brainstem. Transneuronal tracing with pseudorabies virus has demonstrated that the EWcp is connected polysynaptically with central circuits that provide sympathetic innervation to all these effector organs that are critical for stress responses and energy homeostasis. We propose that EWcp integrates multimodal signals (stress, thermal, metabolic, endocrine, etc.) and modulates the sympathetic output simultaneously to multiple effector organs to maintain energy homeostasis under different conditions that require adjustments of energy demands.
Present and Future of Parkinson’s Disease in Spain: PARKINSON-2030 Delphi Project

Parkinson’s disease (PD) is a chronic progressive and irreversible disease and the second most common neurodegenerative disease worldwide. In Spain, it affects around 120.000–150.000 individuals, and its prevalence is estimated to increase in the future. PD has a great impact on patients’ and caregivers’ lives and also entails a substantial socioeconomic burden. The aim of the present study was to examine the current situation and the 10-year PD forecast for Spain in order to optimize and design future management strategies. This study was performed using the modified Delphi method to try to obtain a consensus among a panel of movement disorders experts. According to the panel, future PD management will improve diagnostic capacity and follow-up, it will include multidisciplinary teams, and innovative treatments will be developed. The expansion of new technologies and studies on biomarkers will have an impact on future PD management, leading to more accurate diagnoses, prognoses, and individualized therapies. However, the socio-economic impact of the disease will continue to be significant by 2030, especially for patients in advanced stages. This study highlighted the unmet needs in diagnosis and treatment and how crucial it is to establish recommendations for future diagnostic and therapeutic management of PD.
The autoimmune signature of hyperinflammatory multisystem inflammatory syndrome in children.

Multisystem Inflammatory Syndrome in Children (MIS-C) manifests as a severe and uncontrolled inflammatory response with multiorgan involvement, occurring weeks after SARS-CoV-2 infection. Here we utilized proteomics, RNA sequencing, autoantibody arrays and B-cell receptor (BCR) repertoire analysis to characterize MIS-C immunopathogenesis and identify factors contributing to severe manifestations and intensive care unit admission. Inflammation markers, humoral immune responses, neutrophil activation, complement and coagulation pathways were highly enriched in MIS-C patient serum, with a more hyperinflammatory profile in severe than in mild MIS-C cases. We identified a strong autoimmune signature in MIS-C, with autoantibodies targeted to both ubiquitously expressed and tissue-specific antigens, suggesting autoantigen release and excessive antigenic drive may result from systemic tissue damage. We further identified a cluster of patients with enhanced neutrophil responses as well as high anti-spike IgG and autoantibody titers. BCR sequencing of these patients identified a strong imprint of antigenic drive with substantial BCR sequence connectivity and usage of autoimmunity-associated immunoglobulin heavy chain variable region (IGHV) genes. This cluster was linked to a TRBV11-2 expanded T cell receptor (TCR) repertoire, consistent with previous studies indicating a superantigen-driven pathogenic process. Overall, we identify a combination of pathogenic pathways that culminate in MIS-C and may inform treatment.
Adiponectin and Asthma: Knowns, Unknowns and Controversies

Adiponectin is an adipokine associated with the healthy obese phenotype. Adiponectin increases insulin sensitivity and has cardio and vascular protection actions. Studies related to adiponectin, a modulator of the innate and acquired immunity response, have suggested a role of this molecule in asthma. Studies based on various asthma animal models and on the key cells involved in the allergic response have provided important insights about this relation. Some of them indicated protection and others reversed the balance towards negative effects. Many of them described the cellular pathways activated by adiponectin, which are potentially beneficial for asthma prevention or for reduction in the risk of exacerbations. However, conclusive proofs about their efficiency still need to be provided. In this article, we will, briefly, present the general actions of adiponectin and the epidemiological studies supporting the relation with asthma. The main focus of the current review is on the mechanisms of adiponectin and the impact on the pathobiology of asthma. From this perspective, we will provide arguments for and against the positive influence of this molecule in asthma, also indicating the controversies and sketching out the potential directions of research to complete the picture.