Search Results (31)

Obesity is a condition of chronic low-grade inflammation affecting peripheral organs of the body, as well as the central nervous system. The adipose tissue dysfunction occurring under conditions of obesity is a key factor in the onset and progression of a variety of diseases, including neurodegenerative disorders. Mitochondria, key organelles in the production of cellular energy, play an important role in this tissue dysfunction. Numerous studies highlight the close link between obesity and adipocyte mitochondrial dysfunction, resulting in excessive ROS production and adipose tissue inflammation. This inflammation is transmitted systemically, leading to metabolic disorders that also impact the central nervous system, where pro-inflammatory cytokines impair mitochondrial and cellular functions in different areas of the brain, leading to neurodegenerative diseases. To date, several bioactive compounds are able to prevent and/or slow down neurogenerative processes by acting on mitochondrial functions. Among these, some molecules present in the Mediterranean diet, such as polyphenols, carotenoids, and omega-3 PUFAs, exert a protective action due to their antioxidant and anti-inflammatory ability. The aim of this review is to provide an overview of the involvement of adipose tissue dysfunction in the development of neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, emphasizing the central role played by mitochondria, the main actors in the cross-talk between adipose tissue and the central nervous system. Full article

(4Z,8Z)-Matricaria lactone (MAT) and (4Z)-lachnophyllum lactone (LAC) are natural acetylenic furanones with bioherbicidal potential. This study evaluates their possibilities and ecotoxicological impact on aquatic (Aliivibrio fischeri, Raphidocelis subcapitata, and Daphnia magna) and terrestrial (Caenorhabditis elegans, Lepidum sativum) model organisms. MAT exhibited rapid degradation, with 90% decomposition within 24 h and over 98% by day 16, while LAC was more stable, degrading by only 8.5% in 24 h and 67% by day 16. Despite its rapid breakdown, MAT exhibited higher acute toxicity to A. fischeri (EC₁₀ = 0.063 mg L⁻¹; EC₅₀ = 0.642 mg L⁻¹) compared to LAC (EC₁₀ = 0.524 mg L⁻¹; EC₅₀ = 8.078 mg L⁻¹). Toxicity patterns in R. subcapitata differed, with MAT promoting slightly higher growth compared to the control, suggesting hormetic effects (EC₁₀ = 3.417 mg L⁻¹; EC₅₀ = 4.520 mg L⁻¹), while LAC inhibited growth concentration (EC₁₀ = 0.304 mg L⁻¹; EC₅₀ = 9.880 mg L⁻¹). Both compounds immobilized D. magna, with LAC showing greater delayed toxicity (EC₅₀ = 1.728 mg L⁻¹ vs. MAT EC₅₀ = 2.239 mg L⁻¹). Furthermore, for L. sativum, there were no effects on the germination, but effects were observed in the lengths of the shoots (LAC EC₅₀ = 85.89 mg L⁻¹ vs. MAT EC₅₀ = 82.30 mg L⁻¹). In contrast, C. elegans showed no mortality, suggesting lower terrestrial toxicity. These findings suggest that MAT and LAC may pose risks to aquatic ecosystems through runoff or leaching, necessitating further studies on their degradation products, soil microbiota, and non-target terrestrial organisms. Comparative analyses with conventional herbicides highlight MAT and LAC as selective, lower-impact alternatives. Future research should focus on their effects on terrestrial organisms, the ecological safety of degradation products, and large-scale bioassays to ensure their sustainability in agriculture. Full article

Milk and its derivatives are included in a balanced diet of humans as excellent sources of proteins, vitamins, and essential minerals that are functional nutrients. Knowledge about the nutritional benefits or harms due to milk consumption has been expanding in recent years. We previously explored, in rodent models, the metabolic effects of isoenergetic intake of milk derived from cows, donkeys, or humans, while the impact of goat’s milk intake has remained unexplored. The aim of this work was to investigate, in an animal model, the effects of dietary supplementation with goat’s milk on energy homeostasis and inflammatory state, focusing on the modulation of mitochondrial functions in most metabolically active organs, such as skeletal muscle and the liver. In addition, we highlighted a link between nutrient intake, substrate metabolism, and the orexinergic system. Our results indicate that goat milk improves mitochondrial oxidative capacity and reduces inflammation and oxidative stress in both organs. Notably, goat milk lowers the circulating levels of Orexin-A, a neuropeptide that plays a crucial role in regulating peripheral energy balance and central nervous system mechanisms. These data provide the first evidence that the anti-inflammatory and antioxidant effects of goat milk are mediated by the modulation of mitochondrial functions and orexinergic signaling. Full article

Buffelgrass (Cenchrus ciliaris L.) is an invasive C4 perennial grass species that substantially reduces native plant diversity of the Sonoran Desert through fire promotion and resource competition. Broad-spectrum herbicides are essentially used for its control, but they have a negative environmental and ecological impact. Recently, phytotoxicity on C. ciliaris has been discovered for two metabolites produced in vitro by the phytopathogenic fungi Cochliobolus australiensis and Pyricularia grisea. They were identified as (10S,11S)-(—)-epi-pyriculol and radicinin and resulted in being potential candidates for the development of bioherbicides for buffelgrass biocontrol. They have already shown promising results, but their ecotoxicological profiles and degradability have been poorly investigated. In this study, ecotoxicological tests against representative organisms from aquatic ecosystems (Aliivibrio fischeri bacterium, Raphidocelis subcapitata alga, and Daphnia magna crustacean) revealed relatively low toxicity for these compounds, supporting further studies for their practical application. The stability of these metabolites in International Organization for Standardization (ISO) 8692:2012 culture medium under different temperatures and light conditions was also evaluated, revealing that 98.90% of radicinin degraded after 3 days in sunlight. Significant degradation percentages (59.51–73.82%) were also obtained at room temperature, 30 °C or under ultraviolet (254 nm) light exposure. On the other hand, (10S,11S)-epi-pyriculol showed more stability under all the aforementioned conditions (49.26–65.32%). The sunlight treatment was also shown to be most effective for the degradation of this metabolite. These results suggest that radicinin could provide rapid degradability when used in agrochemical formulations, whereas (10S,11S)-epi-pyriculol stands as a notably more stable compound. Full article

Orobanche cumana is an obligate holoparasitic plant with noxious effects in sunflower crops. Bellardia trixago is a facultative hemiparasitic plant that infects ruderal plants without noxious significance in agriculture and is known to produce a wide spectrum of bioactive metabolites. The objective of this study was to evaluate the allelopathic effects of B. trixago on the growth of O. cumana seedlings. Three different extracts using solvents of increasing polarity (n-hexane, dichloromethane and ethyl acetate) were prepared from the flowers, aerial green organs and roots of two populations, a white-flowered and a yellow-flowered population of B. trixago, both collected in southern Spain. Each extract was studied using allelopathic screenings on O. cumana which resulted in the identification of allelopathic activity of the ethyl acetate extracts against Orobanche radicles. Five iridoid glycosides were isolated together with benzoic acid from the ethyl acetate extract of aerial green organs by bio-guided purification. These compounds were identified as bartsioside, melampyroside, mussaenoside, gardoside methyl ester and aucubin. Among them, melampyroside was found to be the most abundant constituent in the extract (44.3% w/w), as well as the most phytotoxic iridoid on O. cumana radicle, showing a 72.6% inhibition of radicle growth. This activity of melampyroside was significantly high when compared with the inhibitory activity of benzoic acid (25.9%), a phenolic acid with known allelopathic activity against weeds. The ecotoxicological profile of melampyroside was evaluated using organisms representing different trophic levels of the aquatic and terrestrial ecosystems, namely producers (green freshwater algae Raphidocelis subcapitata and macrophyte Lepidium sativum), consumers (water flea Daphnia magna and nematode Caenorhabditis elegans) and decomposers (bacterium Aliivibrio fischeri). The ecotoxicity of melampyroside differed significantly depending on the test organism showing the highest toxicity to daphnia, nematodes and bacteria, and a lower toxicity to algae and macrophytes. The findings of the present study may provide useful information for the generation of green alternatives to synthetic herbicides for the control of O. cumana. Full article

Biocides based on chemical synthetic compounds have been commonly used to counteract damages caused by microorganisms on stone cultural heritage. However, in the last few years, the use of commercial and traditional biocides has been banned and/or limited due to their dangerous profile for the environment, as well as human and animal health. Natural products could be used as suitable alternatives for cultural heritage purposes, as they have low toxicity and stability compared with synthetic pesticides. Even if most of the investigated solutions have already shown promising results, their efficiency, ecotoxicological, and chemical features are poorly investigated. In this manuscript, we aimed to evaluate the ecotoxicological profile of four fungal metabolites—namely, cavoxin, epi-epoformin, seiridin, and sphaeropsidone—with potential antimicrobial properties for monumental artworks. A battery of ecotoxicological tests using Aliivibrio fischeri (bacterium), Raphidocelis subcapitata (alga), Raphanus sativus L. (macrophyte), Daphnia magna (crustacean), and Caenorhabditis elegans (nematode) revealed a relative lower toxicity of these compounds, especially when compared with Preventol^® and Rocima^®, commercial biocides mainly used for the conservation of cultural heritage. Full article

Background: balloon cell melanoma represents less than 1% of all histological forms of malignant melanoma and represents a diagnostic challenge for the dermatopathologist. Methods: in this paper we present our cases of BCM found in our daily practice from 1 January 2008 to 31 December 2021, and we conduct a review of the literature relating to this entity in the period from the first description, 1970, to early 2022. Results: four cases of melanoma balloon cell have been extrapolated from our electronic database, while in the review of the literature we have identified 115 cases of patients with primary and/or metastatic BCM. Conclusions: we believe that future studies with numerous case series are essential not only to increase the knowledge of the pathophysiology of this neoplasm but also to correctly evaluate the response of BCM patients to new oncological therapies. Full article

Background: Cutaneous squamous cell carcinoma (cSCC) is one of the most devastating complications of recessive dystrophic epidermolysis bullosa (RDEB). We recently demonstrated a reduction in immune cell peritumoral infiltration in RDEB patients with cSCC, together with a reduction in CD3+, CD4+, CD68+ and CD20 lymphocytes as compared to primary and secondary cSCC in patients without RDEB. Recently, new molecules, such as high mobility group box 1 (HMGB1), T cell immunoglobulin, mucin domain 3 (TIM-3) and Heme oxygenase-1 (HO-1), have been shown to play a role in antitumoral immunity. Objective: Patients with RDEB are known to be at increased risk of developing skin cancers, including the dreaded squamous cell carcinoma of the. Tendentially, cSCCs that arise in the context of EBDR are more aggressive and lead to statistically significant bad outcomes compared to cSCCs developed on the skin of patients without EBDR. In an attempt to study the microenvironment of these lesions, we conducted an immunohistochemical analysis study of proteins that could be actively involved in the genesis of this type of malignant neoplasms. Methods: In this retrospective study, the OH1-HMGB1-TIM3 activation axis, as correlated to the T lymphocytes cell count, was assessed in biopsy samples from 31 consecutive cases consisting of 12 RDEB patients with cSCC, 12 patients with primary cSCC and 7 RDEB patients with pseudoepitheliomatous cutaneous hyperplasia. Parametric Student’s t-test was applied for normally distributed values, such as CD4+ and CD8+, and non-parametric Mann–Whitney test for non-normally distributed values, such as HMGB-1, TIM-3 and HO-1. Results: In RDEB patients with cSCC and with pseudoepitheliomatous hyperplasia, the expression of CD4 T helper lymphocytes was lower than in the peritumoral infiltrate found in primary cSCC. CD8 cytotoxic T lymphocytes were increased in primary cSCC compared to the other two groups. An increased HMGB1 expression was evident in both primary and RDEB cSCC. TIM3 expression was higher in RDEB patients with cSCC compared to the other two groups. A significantly reduced immunohistochemical expression of HO-1 was evident in the tumoral microenvironment of cSCC-RDEB as compared to primary cSCC. Conclusions: These data suggest that a reduced immune cell peritumoral infiltration in RDEB patients could be responsible, in the complexity of the mechanisms of carcinogenesis and host response, of the particular aggressiveness of the cSCC of RDEB patients, creating a substrate for greater local immunosuppression, which, potentially, can “open the doors” to development and eventual metastasis by this malignant neoplasm. Full article

Background: SPARK nevus represents a little-known and characterized entity, with few case series available in the literature. Methods and results: we present a case series of 12 patients (6 F and 6 M) between January 2005 and December 2020 and conduct a review of the current literature. Ten articles were selected on the basis of the adopted inclusion criteria and the PRISMA guidelines. Conclusions: The definition of histopathological and dermoscopic criteria are important to allow for an agreement to be reached among dermopathologists, and for the development of a consensus on higher case studies. To our knowledge, there are not many case series in the literature, and ours is part of the attempt to increase the knowledge of an entity that remains little-known and characterized. Full article

Periprostatic adipose tissue (PPAT) has emerged as a key player in the prostate cancer (PCa) microenvironment. In this study, we evaluated the ability of PPAT to promote PCa cell migration, as well as the molecular mechanisms involved. Methods: We collected conditioned mediums from in vitro differentiated adipocytes isolated from PPAT taken from PCa patients during radical prostatectomy. Migration was studied by scratch assay. Results: Culture with CM of human PPAT (AdipoCM) promotes migration in two different human androgen-independent (AI) PCa cell lines (DU145 and PC3) and upregulated the expression of CTGF. SB431542, a well-known TGFβ receptor inhibitor, counteracts the increased migration observed in presence of AdipoCM and decreased CTGF expression, suggesting that a paracrine secretion of TGFβ by PPAT affects motility of PCa cells. Conclusions: Collectively, our study showed that factors secreted by PPAT enhanced migration through CTGF upregulation in AI PCa cell lines. These findings reveal the potential of novel therapeutic strategies targeting adipocyte-released factors and TGFβ/CTGF axis to fight advanced PCa dissemination. Full article

Background: Malignant melanoma is the most aggressive of skin cancers and the 19th most common cancer worldwide, with an estimated age-standardized incidence rate of 2.8–3.1 per 100,000; although there have been clear advances in therapeutic treatment, the prognosis of MM patients with Breslow thickness greater than 1 mm is still quite poor today. The study of how melanoma cells manage to survive and proliferate by consuming glucose has been partially addressed in the literature, but some rather interesting results are starting to be present. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and a search of PubMed and Web of Sciences (WoS) databases was performed until 27 September 2021 using the terms: glucose transporter 1 and 3 and GLUT1/3 in combination with each of the following: melanoma, neoplasm and immunohistochemistry. Results: In total, 46 records were initially identified in the literature search, of which six were duplicates. After screening for eligibility and inclusion criteria, 16 publications were ultimately included. Conclusions: the results discussed regarding the role and expression of GLUT are still far from definitive, but further steps toward understanding and stopping this mechanism have, at least in part, been taken. New studies and new discoveries should lead to further clarification of some aspects since the various mechanisms of glucose uptake by neoplastic cells are not limited to the transporters of the GLUT family alone. Full article

Mycetoma is an uncommon, chronic infective disease of the skin and subcutaneous tissues, characterized by the triad of tumefaction, draining sinuses, and the presence in the exudate of colonial grains. In cases of long-term disease, the presence of colonial grains together with the host’s derivative material can lead to the formation of real sinuses. Histological analysis is of fundamental importance to allow an accurate etiological diagnosis and to understand if the basic pathogen is an actinomycete (bacterium) or a real fungus (eumycetic mycetomas) and is also fundamental for therapy, which is quite different. Here, we present a case of Mycetoma in an 11-year-old patient who emigrated from Djibouti, Somalia, and showed the essential histopathological features of this rare and forgotten nosographic entity in the industrialized world and briefly discuss the major and most important differential diagnoses. Full article

Dedifferentiated melanoma is a particular form of malignant melanoma with a progressive worsening of the patient’s clinical outcome. It is well known that melanoma can assume different histo-morphological patterns, to which specific genetic signatures correspond, sometimes but not always. In this review we address the diagnostic difficulties in correctly recognizing this entity, discuss the major differential diagnoses of interest to the dermatopathologist, and conduct a review of the literature with particular attention and emphasis on the latest molecular discoveries regarding the dedifferentiation/undifferentiation mechanism and more advanced therapeutic approaches. Full article

Over the years, increasing information has been asked of the pathologist: we have moved from a purely morphological diagnosis to biomolecular and genetic studies, which have made it possible to implement the use of molecular targeted therapies, such as anti-epidermal growth factor receptor (EGFR) molecules in EGFR-mutated lung cancer, for example. Today, next generation sequencing (NGS) has changed the approach to neoplasms, to the extent that, in a short time, it has gained a place of absolute importance and diagnostic, prognostic and therapeutic utility. In this scenario, formaldehyde-fixed and paraffin-embedded (FFPE) biological tissue samples are a source of clinical and molecular information. However, problems can arise in the genetic material (DNA and RNA) for use in NGS due to fixation, and work is being devoted to possible strategies to reduce its effects. In this paper, we discuss the applications of FFPE tissue samples in the execution of NGS, we focus on the problems arising with the use of this type of material for nucleic acid extraction and, finally, we consider the most useful strategies to prevent and reduce single nucleotide polymorphisms (SNV) and other fixation artifacts. Full article

Meningioma is one of the most frequent neoplasms of all in the central nervous system. Different variants are known, and of these some have peculiar characteristics, both from a morphological point of view and from a biological point of view. Here, we present a rare case of relapsed papillary meningioma in a young patient, focusing on histological characteristics, medical-surgical therapy and focusing on the risk of progression and/or recurrence of the lesion if not completely eradicated. Finally, we provide detailed molecular characteristics of the case in question. Full article