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Synthesis, Structural Studies, and Biological Evaluation of Copper(I) and Copper(II) Complexes Supported by Bis(pyrazol-1-yl)acetate Ligand Functionalized with Amantadine for the Treatment of Glioblastoma
No full textThis paper reports the synthesis, structural characterization, and biological evaluation of a novel series of CuI and CuII complexes supported by an amantadine-functionalized bis(pyrazol-1-yl)acetate ligand (LAd) as potential anticancer agents for the treatment of glioblastoma (GBM). Comprehensive spectroscopic and structural investigations, including SR-XPS, XANES/EXAFS, and DFT modeling, confirmed the successful coordination of LAd to copper centers in both oxidation states, affording well-defined molecular architectures with distinct coordination geometries. Among the synthesized compounds, the CuI complexes bearing triphenylphosphine co-ligands (compounds 4 and 5) exhibited the strongest cytotoxicity against U87 MG and LN18 GBM cell lines, showing IC50 values lower than those of cisplatin. These complexes induced a pronounced redox imbalance through reactive oxygen species (ROS) overproduction and glutathione (GSH) depletion, leading to G2/M cell cycle arrest and cell death. Flow cytometry and Western blot analyses demonstrated that cell death occurs via caspase-dependent apoptosis in LN18 cells, as evidenced by PARP cleavage, downregulation of Bcl-xL, release of cytochrome c, and mitochondrial translocation of Bax. Altogether, these findings highlight the potential of lipophilic amantadine-functionalized CuI complexes as promising anticancer candidates targeting glioma cells through mitochondrial dysfunction and redox-mediated pathways
Evaluation of Systemic Injury in Calves with Rotavirus-Induced Diarrhea Using Sensitive Biomarkers and Immunopathology
No full textStudies in human medicine have demonstrated that rotavirus infection can also affect
extraintestinal sites due to its systemic effects. However, in veterinary medicine, the injury
caused by rotavirus diarrhea is limited to the intestines, and its effects on various systemic
structures remain poorly understood. In this observational case–control study, we aimed to
determine the effects of HSP-27, Caspase-3, IL-2, γ-H2AX, HMGB-1, SP-D, and GDH (or
GLDH) on the pathogenesis of rotavirus infection by using biomarkers for diagnostic purposes
in lung and liver injury in neonate diarrheic calves naturally infected with rotavirus,
both alive and post-mortem. Fifty-two Simmental calves (1–28 days old) of both sexes,
40 infected with rotavirus and 12 healthy, were studied. Twenty-eight out of 40 survived,
while the remainder underwent necropsy for histopathological and immunopathological
(HSP-27, Caspase-3, IL-2, γ-H2AX) examination of the lungs and livers. Lung and
liver-specific serum E-selectin, glutamate dehydrogenase, surfactant protein-D, and high
mobility group box-1 were analyzed by a bovine-specific ELISA kit (Shanghai Coon Koon
Biotech Co., Ltd., China). Histopathological and immunohistochemical analyses confirmed
lung and liver injury in naturally infected calves. HMGB-1, SP-D, and GDH concentrations
were significantly higher in naturally infected calves than in the control group (p < 0.001,
p < 0.001, and p < 0.05, respectively), showing an excellent diagnostic predictive capacity for
lung and liver injury. Also, IL-2, HSP-27, CASP-3, and γ-H2AX were significantly expressed
in the lungs (p < 0.001, p < 0.001, p < 0.001, and p < 0.05, respectively) and liver (p < 0.001,
p < 0.001, p < 0.01, and p < 0.01, respectively). All these observations led us to hypothesize
that oxidative stress, apoptosis, and DNA damage may underlie the pathogenesis of this
condition. Nevertheless, further studies on large populations of rotavirus-infected calves
are needed to confirm the data reported in the current study
Integrative Use of Cannabidiol, Melatonin, and Oxygen–Ozone Therapy in Triple-Negative Breast Cancer with Lung and Mediastinal Metastases. A Case Report
No full textBackground and Clinical Significance: Breast cancer is the most frequent malignancy in women. Metastatic breast cancer is considered a treatable but incurable condition, with a median overall survival of only 2–3 years. Among its subtypes, triple-negative breast cancer (TNBC) accounts for a high proportion of breast cancer-related deaths. It is characterized by an aggressive clinical course, early recurrence, and a strong propensity for visceral and brain metastases. Case Presentation: We report the case of a Caucasian woman who developed systemic disease recurrence with lung and mediastinal lymph node metastases, occurring two years after her primary diagnosis and treatment for TNBC. The patient received three months of chemotherapy combined with an adjuvant integrative protocol consisting of melatonin, cannabidiol, and oxygen–ozone therapy. This combined approach led to the complete disappearance of the lung nodules. Subsequently, stereotactic radiotherapy was performed and, in association with the ongoing integrative treatment, resulted in a significant reduction in mediastinal adenopathy. Introduction of immunotherapy, supported continuously by the same adjuvant strategy, achieved a complete and durable remission. Strikingly, the patient remained disease-free five years after the diagnosis of lung and mediastinal metastases. Conclusions: This clinical case highlights the potential benefit of using melatonin, cannabidiol, and oxygen–ozone therapy as part of an integrative approach in patients with aggressive metastatic TNBC. While it is not possible to establish causality from a single case, the sustained remission observed suggests that such unconventional adjuvant strategies could play a supportive role in enhancing the efficacy of standard oncologic therapies
Involvement of Keap1/Nrf2 and the antioxidant defence in cytoprotective effects induced by cannabis polyphenols in SH-SY5Y neuronal cells
No full textOxidative stress (OS) is widely recognized as a central promoter to the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). Cannabis sativa L. synthesizes a complex array of bioactive compounds that extends well beyond the well-known cannabinoids to include a diverse suite of polyphenols, terpenes, fatty acids, tocopherols, and proteins. The non-cannabinoid polyphenolic fraction is composed primarily of flavonoids, stilbenoids, lignans, and lignanamides, which contribute substantially to the plant’s antioxidant, anti-inflammatory, and neuroprotective properties. This study investigates the redox-modulating and cytoprotective properties of a polyphenolic fraction derived from Cannabis sativa L. in SH-SY5Y neuroblastoma cells. Neurons were treated with various concentrations of the aqueous polyphenolic cannabis extract and exposed to oxidative stress using hydrogen peroxide (100 μM). Protein and gene expression related to redox signalling were analyzed via Western blot and qPCR, and molecular docking studies were performed in silico. Furthermore, antioxidant enzymes activity was measured by spectrophotometry. Results revealed that the phenolic fraction significantly activated the Keap1/Nrf2 pathway, increased expression of PRDX1 and PRDX3, and enhanced endogenous antioxidant defences. Simultaneously, it reduced endoplasmic reticulum stress-induced apoptosis (via Bax/Bcl-2 modulation) and attenuated inflammatory markers, including NO, NF-κB2, IL-6, and IL-8. In silico docking studies identified Leu583 as a key residue in Nrf2-ligand interactions. These findings suggest that Cannabis sativa L. polyphenols are key bioactive compounds modulating redox homeostasis and inflammation, and offering neuroprotective benefits with potential relevance in diseases involving mitochondrial dysfunction and oxidative damage
Using deep learning to assess the toxicological effects of sublethal exposure of a novel green pesticide in a stored-product beetle
No full textBACKGROUND: Managing stored-grain pests requires new strategies to limit economic and health risks. This study analyses the sublethal effects of the natural compound carlina oxide on Prostephanus truncatus, providing new behavioural insights through a multidisciplinary approach. A fully automatic computer vision approach was developed to label two specific insect body parts, enabling the generation of an annotated dataset without manual intervention. This dataset was used to train a convolutional neural network (CNN) for pose estimation. A second dedicated CNN focused on the antennae to investigate neuroethological and sensory variations.
RESULTS: CNN for body parts detection achieved an average precision of 0.78, recall of 0.90, and F1 score of 0.84 on the test dataset. An additional CNN tracked key points for antennal pose estimation. Motor analysis showed that the LC30 of carlina oxide reduced average speed and distance, induced altered exploratory behaviour, and affected thigmotaxis. Statistically sig- nificant features were evaluated using machine learning classifiers: random forest, support vector machine, and K-nearest neighbours. The analysis comparing control and treated groups distinguishes LC30 and LC10 from the control group, while SHapley Additive exPlanation (SHAP) analysis explained the features contribution to predictions.
CONCLUSIONS: Metrics poorly distinguish individuals in the LC10 and LC30 classes, supporting the employment of lower suble- thal concentration for the control of P. truncatus. However, our findings indicate possible neuroethological effects of green pes- ticides on sensory systems, highlighting the need for an accurate risk assessment to minimize ecosystem impacts and supporting integrated pest management within One-Health and Eco-Health frameworks
Three ectomycorrhizal fungal inoculum modifies the growth performance and tolerance of Quercus nuttallii seedlings under salt stress
No full textSoil salinization constitutes a significant global environmental challenge, seriously threatening the health and stability of various ecosystems. Ectomycorrhizal fungi (EMF) may enhance the adaptability of plants to salt stress, thus selecting EMF-plant symbiosis with high salt tolerance is essential for ecological restoration of salinized land. In this study, three different EMF (Pisolithus tinctorius, Tuber pseudoexcavatum and Suillus grevillea) strains were inoculated to Quercus nuttallii seedlings subjected to different salinity levels (S0: no NaCl addition, S1: 1 ‰ NaCl per pot, S2: 2 ‰ NaCl per pot, S3: 3 ‰ NaCl per pot) in greenhouse condition, to explore the mechanism and efficacy of EMF inoculation in mitigating salt stress in plants. Our results indicated that the colonization rate of P. tinctorius and S. grevillea on Q. nuttallii seedlings increased at treatment S1 and declined with increasing salt stress, while the colonization rate of T. pseudoexcavatum significantly decreased with increasing salt stress. EMF inoculation improved the growth performance (height, basal diameter, dry biomass) of Q. nuttallii seedlings under salt stress, through enhancing the nutrient absorption (nitrogen and phosphorus) and the chlorophyll concentration. EMF facilitated the production of soluble sugars, thereby improving the tolerance of Q. nuttallii to osmotic stress. Moreover, EMF mitigated the oxidative damage of Q. nuttallii seedlings under salt stress, substantially decreased the contents of malondialdehyde, through bolstering plant protection antioxidant enzymes (superoxide dismutase, peroxidase, catalase). Comprehensive evaluation indicated that S. grevillea showed the strongest ability to modify the growth performance and tolerance of Q. nuttallii seedlings across all NaCl levels, suggesting that S. grevillea-Q. nuttallii associations is promising for the restoration and revegetation of the sites with soil salinization
Prime riflessioni sul concetto di sicurezza urbana attraverso la prospettiva di genere
No full textIl post integra l’intervento programmato all’Incontro del Gruppo di San Martino tenutosi all’Università di Cagliari il 16-17 maggio 2024
Production, chemical composition, nutraceutical potential and functional benefits of coconut oil in humans and animals: Advancing sustainable livestock production
No full textCoconut oil (CO) has recently gained increasing scientific and industrial attention owing to its rich profile of
medium-chain fatty acids (MCFAs) and diverse bioactive constituents. These unique components confer promising
nutraceutical and functional properties relevant to both human health and sustainable livestock production.
This review aims to provide an updated and integrative overview of the biological roles and mechanisms of
coconut oil, emphasizing its potential applications in animal nutrition and health promotion. Coconut oil exhibits
a wide spectrum of biological activities, including antimicrobial, antioxidant, anti-inflammatory, hepatoprotective,
neuroprotective, and metabolic regulatory effects. These functions are primarily mediated through
modulation of oxidative stress, lipid metabolism, and inflammatory signaling pathways. In animal production,
dietary inclusion of coconut oil has been shown to improve growth performance, immune responses, and product
quality, although some findings remain inconsistent and context dependent. Despite the increasing interest in its
health benefits, clinical validation of coconut oil's long-term effects in humans and animals remains limited.
Therefore, understanding its mechanisms of action and standardizing dosages are crucial to ensure safe and
effective utilization. In summary, coconut oil represents a promising natural ingredient that bridges human
nutrition and sustainable livestock production. However, further mechanistic and clinical investigations are
warranted to substantiate its long-term functional and health-promoting effects
Bayesian and Markovian classical feedforward for discriminating qubit channels
No full textWe address the issue of multi-shot discrimination between two qubit channels by
invoking a simple adaptive protocol that employs Helstrom measurement at each
step and classical information feedforward, beside separable inputs. We contrast the
performance of Bayesian and Markovian strategies. We show that the former is only
slightly advantageous and for a limited parameters’ region