Faricimab efficacy in type 1 macular neovascularization: AI-assisted quantification of pigment epithelium detachment (PED) volume reduction over 12 months in Naïve and switch eyes.

Background: This study evaluates the efficacy of intravitreal Faricimab in reducing pigment epithelium detachment (PED) and fluid volumes in both treatment-naïve eyes and eyes unresponsive to anti-VEGF mono-therapies, all diagnosed with type 1 macular neovascularization (T1 MNV) over a period of 12-month.

Methods: A retrospective, single-center cohort study was conducted at the Jules Gonin Eye Hospital, Lausanne, Switzerland. Clinical records of treatment-naïve and non-responder switch patients presenting T1 MNV secondary to neovascular age-related macular degeneration (nAMD) from September 2022 to March 2023 were reviewed.

Trace Element Concentration in the Blood and Aqueous Humor of Subjects with Eye Cataract.

Cataract, characterized by the opacification of the lens, is the leading cause of reversible blindness and visual impairment globally. The study aims to investigate the role of trace elements such as Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Se, and Zn in the development and severity of cataract. Elements were quantified by inductively coupled plasma mass spectrometry in blood and aqueous humor of 32 cataract cases and 27 controls living in the Latium region, Italy.

Toxic Metal and Essential Element Concentrations in the Blood and Tissues of Pancreatic Ductal Adenocarcinoma Patients.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive lethal neoplasm, and it has an average 5-year survival rate of less than 10%. Although the factors that influence PDAC development remain unclear, exposure to toxic metals or the imbalance in essential elements may have a role in PDAC-associated metabolic pathways.

Methods: This study determined the concentrations of Cd, Cr, Cu, Fe, Mn, Ni, Pb, Se and Zn in whole blood, cancer and non-cancer tissues of patients affected by PDAC, and compared them with levels in healthy controls using inductively coupled plasma mass spectrometry.

Potentially harmful elements released by volcanic ash of the 2021 Tajogaite eruption (Cumbre Vieja, La Palma Island, Spain): Implications for human health.

This study assesses the potential impacts on human health of volcanic ash emitted during the 2021 Tajogaite eruption (La Palma Island, Spain). Ash samples were physically and chemically characterized and leaching tests (with deionized water and acidic solution) were performed according to the IVHHN protocols to elucidate i) the leachable elements that may affect water quality and represent a potential threat for livestock and humans through drinking water supply; and ii) the bioaccessible fraction of toxicants able to be solubilized from ash surfaces if ashes are incidentally ingested by children. The most abundant readily water-soluble compounds were SO, F, Cl, Na, Ca, Ba, Mg, and Zn.

Heavy Metal(loid) Accumulation in the Ovarian Tissue of Free-Ranging Queens and Bitches Inhabiting Highly Polluted Urban Environments.

There is strong scientific evidence that exposure to environmental contaminants, such as heavy metal(loid)s (HMs), can impair female reproductive function. Pets, such as cats and dogs, who share the same habitat as humans, may be particularly useful sentinel models for detecting HMs in the ovary. In the present study, we compared the concentration of essential (Ems; Cu, Fe, Mn, Se, and Zn) and non-essential metal(loid)s (NEMs; Al, As, Cd, and Pb) in the ovarian tissues of free-ranging queens and bitches of different ages living in industrialized/highly polluted (south group) and non-polluted (north group) urban areas of the island of Sardinia, Italy.

The effects of the exposure to neurotoxic elements on Italian schoolchildren behavior.

Neurodevelopmental disorders are constantly increasing on a global scale. Some elements like heavy metals are known to be neurotoxic. In this cross-sectional study we assessed the neurobehavioral effect of the exposure to trace elements including lead, mercury, cadmium, manganese, arsenic and selenium and their interactions among 299 schoolchildren residing in the heavily polluted Taranto area in Italy.

Hydrochemical, isotopic and microbiota characterization of telese mineral waters (Southern Italy).

The study deals with the analyses of springs and wells at the base of Montepugliano Hill that represents the SE edge of the wide carbonate Matese massif (Campania, southern Italy). At the base of the hill, from west to east and for almost one kilometre, cold springs HCO-Ca type (Grassano springs, ~ 4.5 m/s; TDS: about 0.

The levels of trace elements in sputum as biomarkers for idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a rare lung disease that quickly leads to death. This paper addressed the issue of whether the levels of trace elements in sputum samples are suitable biomarkers for IPF disease. The sputum Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn concentrations were measured by sector field inductively coupled plasma mass spectrometry in populations sampled in Sardinia Island (Italy) including 31 patients with IPF, 31 patients with other lung-related diseases and 30 age- and gender-matched healthy controls.

An overview on amyotrophic lateral sclerosis and cadmium.

The present review represents an update about the knowledge of the possible role of Cadmium (Cd) in amyotrophic lateral sclerosis (ALS) initiation and its progression. ALS is a neurodegenerative disease that occurs in adulthood; its etiology is unknown and leads to death within a few years from its appearance. Among the various possible causes that can favor the development of the disease, heavy metals cannot be excluded.

Amyotrophic lateral sclerosis and lead: A systematic update.

Heavy metals are considered to be among the leading environmental factors that trigger amyotrophic lateral sclerosis (ALS). However, no convincing biopathological mechanism and therapeutic clinical implication of such metals in ALS pathogenesis have been established. This is partly attributable to the technical and scientific difficulties in demonstrating a direct and causative role of heavy metals in the onset of ALS in patients.

A pilot study to evaluate the levels of aqueous humor trace elements in open-angle glaucoma.

Background: Primary open angle glaucoma (POAG) is the most common form of chronic, progressive optic neuropathies characterized by slow degeneration of the retinal ganglion cells and their axons, resulting in visual field loss. Risk factors for this disease are elevated intraocular pressure (IOP), increased age, European and African ethnicity, family history, myopia and decreased corneal thickness. In addition, studies indicated that levels of trace elements are also significantly related to the POAG.

Neurocognitive impact of metal exposure and social stressors among schoolchildren in Taranto, Italy.

Background: Metal exposure is a public health hazard due to neurocognitive effects starting in early life. Poor socio-economic status, adverse home and family environment can enhance the neurodevelopmental toxicity due to chemical exposure. Disadvantaged socio-economic conditions are generally higher in environmentally impacted areas although the combined effect of these two factors has not been sufficiently studied.

Tetra-substituted pyrrole derivatives act as potent activators of p53 in melanoma cells.

Cutaneous melanoma, the most aggressive form of skin cancer, is characterized by activating BRAF mutations. Despite the initial success of selective BRAF inhibitors, only few patients exhibited complete responses, whereas many showed disease progression. Melanoma is one of the few types of cancer in which p53 is not frequently mutated, but p53 inactivation can be indirectly achieved by a stable activation of MDM2 induced by a deletion in CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) locus, encoding for p16 and p14, two tumor suppressor genes.

Novosphingobium sp. PP1Y as a novel source of outer membrane vesicles.

Outer membrane vesicles (OMVs) are nanostructures of 20-200 nm diameter deriving from the surface of several Gram-negative bacteria. OMVs are emerging as shuttles involved in several mechanisms of communication and environmental adaptation. In this work, OMVs were isolated and characterized from Novosphingobium sp.

Identification of the 2-Benzoxazol-2-yl-phenol Scaffold as New Hit for JMJD3 Inhibition.

JMJD3 is a member of the KDM6 subfamily and catalyzes the demethylation of lysine 27 on histone H3 (H3K27). This protein was identified as a useful tool in understanding the role of epigenetics in inflammatory conditions and in cancer as well. Guided by a virtual fragment screening approach, we identified the benzoxazole scaffold as a new hit suitable for the development of tighter JMJD3 inhibitors.

Association Between Exposure to Heavy Metals and Systemic Sclerosis: the Levels of Al, Cd, Hg, and Pb in Blood and Urine of Patients.

Systemic sclerosis (SSc) is a multisystem connective tissue disease; exogenous factors-including heavy metals-may have a role in the disease pathogenesis. In this context, a study on the quantification of Al, Cd, Hg, and Pb in blood and urine of 27 SSc patients and 30 controls was carried out. Main findings were that Al was significantly depleted in blood and increased in urine of SSc patients respect to controls; and Pb was found slightly increased in blood and significantly decreased in SSc group.

Discovery of new erbB4 inhibitors: Repositioning an orphan chemical library by inverse virtual screening.

Inverse Virtual Screening (IVS) is a docking based approach aimed to the evaluation of the virtual ability of a single compound to interact with a library of proteins. For the first time, we applied this methodology to a library of synthetic compounds, which proved to be inactive towards the target they were initially designed for. Trifluoromethyl-benzenesulfonamides 3-21 were repositioned by means of IVS identifying new lead compounds (14-16, 19 and 20) for the inhibition of erbB4 in the low micromolar range.

Trace elements in ALS patients and their relationships with clinical severity.

An exploratory study of trace elements in ALS and their relationships with clinical severity was detected. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that causes irreversible damage in humans, with the consequent loss of function of motoneurons (MNs), with a prognosis up to 5 years after diagnosis. Except to genetic rare cases it is not known the etiology of the disorder.

Metals in bones of the middle-aged inhabitants of Sardinia island (Italy) to assess nutrition and environmental exposure.

Metals in bones of 72 subjects lived between the twelfth and eighteenth century AC and collected in four Sardinian (Italian insular region) burial sites (Alghero, Bisarcio, Geridu, and Sassari) were determined and used as biomarkers to evaluate diet and potential social-environmental differences. Concentrations of Ba, Ca, Cd, Cu, Hg, Pb, Sr, and Zn were quantified in different types of compact bone (femur, fibula, humerus, radius, tibia, ulna) by sector field inductively coupled plasma mass spectrometry previous acidic digestion and differences among the various burial sites, centuries, types of bone, gender, and age were explored by univariate and multivariate analyses. Results indicated differences between sites in terms of diet: Bisarcio (inland village) had increased ratios of Ba/Ca and Zn/Ca due to higher incidence of vegetables, cereals, and animal foods in the diet; Geridu (coastal village) showed increased Sr/Ca ratio indicating foods of plant and marine origin that were predominant; Alghero (coastal site) and Sassari (inland site) displayed prevalently a mixed diet reflecting a higher economy and food imports.

Essential trace elements in amyotrophic lateral sclerosis (ALS): Results in a population of a risk area of Italy.

Sardinian (Italy) island population has a uniquely high incidence of amyotrophic lateral sclerosis (ALS). Essential trace element levels in blood, hair, and urine of ALS Sardinian patients were investigated in search of valid biomarkers to recognize and predict ALS. Six elements (Ca, Cu, Fe, Mg, Se, and Zn) were measured in 34 patients compared to 30 age- and sex-matched healthy controls by a validated method.

Drug Affinity Responsive Target Stability (DARTS) Identifies Laurifolioside as a New Clathrin Heavy Chain Modulator.

Five new diterpenes (1-5) and a megastigmane derivative (6) were isolated from the aerial parts of Euphorbia laurifolia, along with several known compounds. Their structures were elucidated by NMR, MS, and ECD and by chemical methods. A chemical proteomics drug affinity responsive target stability (DARTS) approach to investigate the lathyrane diterpene 1, laurifolioside, on its putative cellular target(s) was performed.

Determination of mercury in hair: Comparison between gold amalgamation-atomic absorption spectrometry and mass spectrometry.

Mercury is a heavy metal that causes serious health problems in exposed subjects. The most toxic form, i.e.

Annexin A1 contributes to pancreatic cancer cell phenotype, behaviour and metastatic potential independently of Formyl Peptide Receptor pathway.

Annexin A1 (ANXA1) is a Ca(2+)-binding protein over-expressed in pancreatic cancer (PC). We recently reported that extracellular ANXA1 mediates PC cell motility acting on Formyl Peptide Receptors (FPRs). Here, we describe other mechanisms by which intracellular ANXA1 could mediate PC progression.

Level of neurotoxic metals in amyotrophic lateral sclerosis: A population-based case-control study.

The association between exposure to toxic metals and amyotrophic lateral sclerosis (ALS) was explored in a population-based case-control study in the Sardinia island (Italy), a region characterized by elevated rates of ALS cases. In 34 patients with ALS (mean age, 62 ± 10 years) and 30 controls (mean age, 65 ± 11 years), Al, Cd, Hg, Mn and Pb were determined in blood, hair and urine by sector field inductively coupled mass spectrometry. Results indicated that, in blood, concentrations of Al (p=0.

Identification and mechanism of action analysis of the new PARP-1 inhibitor 2″-hydroxygenkwanol A.

Background: Poly(ADP-ribose) polymerase 1 (PARP-1) activity has been implicated in the pathogenesis of numerous diseases as cancer, inflammation, diabetes and neurodegenerative disorders, therefore the research for new PARP-1 inhibitors is still an active area.

Methods: To identify new potential PARP-1 inhibitors, we performed a screening of a small-molecule library consisting of polyphenols isolated from plants used in the traditional medicine, by Surface Plasmon Resonance (SPR). Biochemical and cellular assays were performed to confirm SPR results and select the promising candidate(s).