Repurposing FDA-approved drugs to target G-quadruplexes in breast cancer.

Breast cancer, a leading cause of cancer-related mortality in women, is characterized by genomic instability and aberrant gene expression, often influenced by noncanonical nucleic acid structures such as G-quadruplexes (G4s). These structures, commonly found in the promoter regions and 5'-untranslated RNA sequences of several oncogenes, play crucial roles in regulating transcription and translation. Stabilizing these G4 structures offers a promising therapeutic strategy for targeting key oncogenic pathways.

Design, Synthesis, and Anticancer Activity of Drug-like Iron Chelators/G-Quadruplex Binders as Synergic Dual Targeting Agents.

Iron homeostasis is strictly related to numerous physiological pathways including cell cycle progression and cell growth. The newest anticancer strategies focus on either depleting the cells with a suitable chelator or increasing their loading by administering iron complexes to induce ferroptosis. Iron depletion inhibits cell proliferation, while iron overload induces the damage of guanine nucleobases in G-quadruplex structures via ROS generation, leading to genome instability.

The Medico-Legal and Social Aspects of the Eligibility Examination for Enrolment in the Seafarers Registry: A Single-Center Retrospective Study.

Background: Working on board presents unique healthcare challenges for maritime personnel. Italian Law mandates a medical fitness assessment for seafarers registry enrolment. The Port Health Officer assesses seaworthiness and, against this judgment, the applicants can appeal to the First-degree Medical Commission.

[Mortality due to mesothelioma and asbestosis in Campania Region (Southern Italy): perspectives for reducing asbestos exposure].

Objectives: to provide an overview of the geographical distribution of mesothelioma and asbestosis deaths in the Campania Region (Southern Italy) occurred from 2005 to 2018 and to identify areas at higher risk.

Design: for each municipality, Standardized Mortality Ratios (SMRs) for mesothelioma and asbestosis have been estimated from the mortality data provided by the Italian National Institute of Statistics (Istat). Deaths for which mesothelioma and asbestosis were identified as the underlying causes, according to the classification system ICD-10 codes (C45 and J61, respectively), were included.

Diet-induced impairment of skeletal muscle and adipose tissue metabolic homeostasis and its prevention by probiotic administration.

Western dietary pattern is one of the main contributors to the increased risk of obesity and chronic diseases, through oxidative stress and inflammation, that are the two key mechanisms targeting metabolic organs, such as skeletal muscle and adipose tissue. The chronic exposure to high levels of dietary fatty acids can increase the amount of intramyocellular lipids in skeletal muscle, altering glucose homeostasis and contributing to a reduction in mitochondrial oxidative capacity. Probiotic administration is a promising approach as preventive strategy to attenuate metabolic damage induced by Western diet.

Sensitization of melanoma cells to standard chemotherapy: G-quadruplex binders as synergistic agents.

The use of chemotherapeutics has achieved considerable success in cancer therapy; however, their toxicity can severely impact patients' health. In this study, aiming to reduce the doses and potential side effects of traditional chemotherapeutics, we systematically treated A375MM human melanoma cells with seven clinically approved antineoplastic drugs, in combination with three well-characterized G-quadruplex (G4) ligands, using either simultaneous or sequential dosing schedules. Interestingly, the G4 binders synergized with most of the investigated anticancer drugs, with the degree of synergism being strictly dependent on both the treatment schedule and the drug sequence employed.

Colorectal Cancer and Asbestos Exposure: A Women's Health Perspective.

Background: Colorectal cancer (CRC) is considered a "man's disease". However, emerging data show that females may have a higher prevalence of certain risk factors. A potential causal role of asbestos in CRC carcinogenesis has been suggested.

uL3 Regulates Redox Metabolism and Ferroptosis Sensitivity of p53-Deleted Colorectal Cancer Cells.

Despite advancements in therapeutic strategies, the development of drug resistance and metastasis remains a serious concern for the efficacy of chemotherapy against colorectal cancer (CRC). We have previously demonstrated that low expression of ribosomal protein uL3 positively correlates with chemoresistance in CRC patients. Here, we demonstrated that the loss of uL3 increased the metastatic capacity of CRC cells in chick embryos.

Protective role of cells and spores of Shouchella clausii SF174 against fructose-induced gut dysfunctions in small and large intestine.

The oral administration of probiotics is nowadays recognized as a strategy to treat or prevent the consequences of unhealthy dietary habits. Here we analyze and compare the effects of the oral administration of vegetative cells or spores of Shouchella clausii SF174 in counteracting gut dysfunctions induced by 6 weeks of high fructose intake in a rat model. Gut microbiota composition, tight junction proteins, markers of inflammation and redox homeostasis were evaluated in ileum and colon in rats fed fructose rich diet and supplemented with cells or spores of Shouchella clausii SF174.

Noise Level of a Ring Laser Gyroscope in the Femto-Rad/s Range.

Absolute angular rotation rate measurements with sensitivity better than prad/s would be beneficial for fundamental science investigations. In this regard, large frame Earth based ring laser gyroscopes are top instrumentation as far as bandwidth, long-term operation, and sensitivity are concerned. Here, we demonstrate that the GINGERINO active-ring laser upper limiting noise is close to 2×10^{-15}  rad/s for ∼2×10^{5}  s of integration time, as estimated by the Allan deviation evaluated in a differential measurement scheme.

Development of a multi-targeted chemotherapeutic approach based on G-quadruplex stabilisation and carbonic anhydrase inhibition.

A novel class of compounds designed to hit two anti-tumour targets, G-quadruplex structures and human carbonic anhydrases (hCAs) IX and XII is proposed. The induction/stabilisation of G-quadruplex structures by small molecules has emerged as an anticancer strategy, disrupting telomere maintenance and reducing oncogene expression. hCAs IX and XII are well-established anti-tumour targets, upregulated in many hypoxic tumours and contributing to metastasis.

Visible Light-promoted C(sp)-H α-Carbamoylation of Cyclic Ethers with Isocyanides.

A protocol exploiting isocyanides as carbamoylating agents for the α-C(sp)-H functionalization of cyclic ethers has been optimized via a combined visible light-driven hydrogen atom transfer/Lewis acid-catalyzed approach. The isocyanide substrate scope revealed an exquisite functional group compatibility (18 examples, with yields up to 99 %). Both radical and polar trapping, kinetic isotopic effect and real-time NMR studies support the mechanistic hypothesis and provide insightful details for the design of new chemical processes involving the generation of oxocarbenium ions.

Limosilactobacillus reuteri DSM 17938 relieves inflammation, endoplasmic reticulum stress, and autophagy in hippocampus of western diet-fed rats by modulation of systemic inflammation.

The consumption of western diets, high in fats and sugars, is a crucial contributor to brain molecular alterations, cognitive dysfunction and neurodegenerative diseases. Therefore, a mandatory challenge is the individuation of strategies capable of preventing diet-induced impairment of brain physiology. A promising strategy might consist in the administration of probiotics that are known to influence brain function via the gut-brain axis.

Atypical Postmortem "Incaprettamento" After an Honor Homicide.

Honor killing is a murder carried out to protect the family's reputation by actions that are perceived as shameful. Usually, honor killing occurs to preserve family's honor, which has been violated by adulteries, premarital pregnancies, or inappropriate relationships. In Southern Italy, the culture of honor is quite strong especially among the local criminal organizations.

Colorectal Cancer: 35 Cases in Asbestos-Exposed Workers.

Background: Asbestos is considered one of the major global work-related carcinogens. Some studies suggest a potential causal relationship between asbestos exposure and colorectal cancer (CRC). However, the role of asbestos in CRC carcinogenesis is still controversial.

DSM 17938 reverses gut metabolic dysfunction induced by Western diet in adult rats.

Introduction: Microencapsulation of probiotic bacteria is an efficient and innovative new technique aimed at preserving bacterial survival in the hostile conditions of the gastrointestinal tract. However, understanding whether a microcapsule preserves the effectiveness of the bacterium contained within it is of fundamental importance.

Methods: Male Wistar rats aged 90 days were fed a control diet or a Western diet for 8 weeks, with rats fed the Western diet divided into three groups: one receiving the diet only (W), the second group receiving the Western diet and free DSM 17938 (WR), and the third group receiving the Western diet and microencapsulated DSM 17938 (WRM).

G-quadruplexes in cancer-related gene promoters: from identification to therapeutic targeting.

Introduction: Guanine-rich DNA sequences can fold into four-stranded noncanonical secondary structures called G-quadruplexes (G4s) which are widely distributed in functional regions of the human genome, such as telomeres and gene promoter regions. Compelling evidence suggests their involvement in key genome functions such as gene expression and genome stability. Notably, the abundance of G4-forming sequences near transcription start sites suggests their potential involvement in regulating oncogenes.

Semi-computational approach for assessing the damage to human soft tissues: the case of FMJRN versus HP-XTP 9 mm bullet penetration in ballistic soap.

Ballistic soap blocks are used in wound ballistics to assess the potential damage of the ammunition employed, allowing observation of the energy transfer occurred along the wound channel. The density and viscosity of ballistic soap (also called tissue simulant) simulate, to a good degree of approximation, the effect resulting from the interaction of penetrating bullets with living human soft tissue. Ballistic soap has a "plastic reaction" to bullet penetration, and therefore, unlike ballistic gelatin, the expansion of temporary cavity remains imprinted in the tissue simulant.

Comparison of the biological effects of gadodiamide (Omniscan) and gadoteridol (ProHance) by means of multi-organ and plasma metabolomics.

Gadolinium-based contrast agents (GBCAs) are massively employed in radiology to increase the diagnostic power of MRI. However, investigations aiming at detecting possible metabolic perturbations or adverse health effects due to gadolinium deposition are still lacking. In this work, aqueous organs extract and plasma samples were analyzed by GC-MS and H-NMR, respectively, to investigate the effects of multiple administrations of one linear (Omniscan) and one macrocyclic (ProHance) GBCA, on the main metabolic pathways in healthy mice.

Gunshot injuries in Campania (Italy): A retrospective thirty-years (1981-2011) study.

From 1981 to 2011, 200 firearm deaths were autopsied in Naples, at the Institute of Legal Medicine of the University of Campania "Luigi Vanvitelli". 188 cases were homicides and most of them (116) were related to the local organized crime. The majority of victims were young Italian males in the 20-39 age fired in outdoor environments.

Age-Dependent Skeletal Muscle Mitochondrial Response to Short-Term Increased Dietary Fructose.

The harmful effect of a long-term high-fructose diet is well established, but the age-dependent physiological responses that can be triggered by a short-term high-fructose diet in skeletal muscles have not been deeply explored. Therefore, the aim of this work was to compare the alterations in mitochondrial energetic and insulin responsiveness in the skeletal muscle induced by a short-term (2 weeks) fructose feeding in rats of different ages. For this purpose, fructose and uric acid levels, insulin sensitivity, mitochondrial bioenergetics and oxidative status were evaluated in the skeletal muscles from young (30 days old) and adult (90 days old) rats.

Skeletal muscle insulin resistance and adipose tissue hypertrophy persist beyond the reshaping of gut microbiota in young rats fed a fructose-rich diet.

To investigate whether short term fructose-rich diet induces changes in the gut microbiota as well as in skeletal muscle and adipose tissue physiology and verify whether they persist even after fructose withdrawal, young rats of 30 d of age were fed for 3 weeks a fructose-rich or control diet. At the end of the 3-weeks period, half of the rats from each group were maintained for further 3 weeks on a control diet. Metagenomic analysis of gut microbiota and short chain fatty acids levels (faeces and plasma) were investigated.

Ligand-based drug repurposing strategy identified SARS-CoV-2 RNA G-quadruplex binders.

The single-stranded RNA genome of SARS-CoV-2 contains some G-quadruplex-forming G-rich elements which are putative drug targets. Here, we performed a ligand-based pharmacophore virtual screening of FDA approved drugs to find candidates targeting such RNA structures. Further and assays identified three drugs as emerging SARS-CoV-2 RNA G-quadruplex binders.