Renata Esposito

BACKGROUND: Microplastics and nanoplastics (MNPs) are emerging as a potential risk factor for cardiovascular disease in preclinical studies. Direct evidence that this risk extends to humans is lacking. METHODS: We conducted a prospective, multicenter, observational study involving patients who were undergoing carotid endarterectomy for asymptomatic carotid artery disease. The excised carotid plaque specimens were analyzed for the presence of MNPs with the use of pyrolysis-gas chromatography-mass spectrometry, stable isotope analysis, and electron microscopy. Inflammatory biomarkers were assessed with enzyme-linked immunosorbent assay and immunohistochemical assay. The primary end point was a composite of myocardial infarction, stroke, or death from any cause among patients who had evidence of MNPs in plaque as compared with patients with plaque that showed no evidence of MNPs. RESULTS: A total of 304 patients were enrolled in the study, and 257 completed a mean (±SD) follow-up of 33.7±6.9 months. Polyethylene was detected in carotid artery plaque of 150 patients (58.4%), with a mean level of 21.7±24.5 μg per milligram of plaque; 31 patients (12.1%) also had measurable amounts of polyvinyl chloride, with a mean level of 5.2±2.4 μg per milligram of plaque. Electron microscopy revealed visible, jagged-edged foreign particles among plaque macrophages and scattered in the external debris. Radiographic examination showed that some of these particles included chlorine. Patients in whom MNPs were detected within the atheroma were at higher risk for a primary end-point event than those in whom these substances were not detected (hazard ratio, 4.53; 95% confidence interval, 2.00 to 10.27; P<0.001). CONCLUSIONS: In this study, patients with carotid artery plaque in which MNPs were detected had a higher risk of a composite of myocardial infarction, stroke, or death from any cause at 34 months of follow-up than those in whom MNPs were not detected. (Funded by Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale and others; ClinicalTrials.gov number, NCT05900947.).

The role of the gut microbiota in human health is one of the most important research topics. There is a strong relationship between the microbiota-gut-brain axis and cognitive functions. Since Alzheimer's disease (AD) is a disease characterized by cognitive impairment, the influence of the gut microbiota in the development and treatment of the disease attracts considerable attention. Gerobiotics is a new concept that includes probiotics or derived postbiotics involved in delaying the aging process. Increasing evidence in the literature suggests that gerobiotics has important roles in the pathogenesis and progression of AD, and even in its treatment, through various mechanisms of action. Several researchers have established the linkage between ingestion of gerobiotics and improved gut dysbiosis and cognitive functions, nevertheless the dose and duration of treatment differ based on strain. Furthermore, oxidative-inflammatory pathways are mainly involved in the neuroprotective effects caused by gerobiotics. This review provides the effects of gerobiotics on microbiota alteration and modulation in AD.

OBJECTIVE: To evaluate the feasibility and results of stenting of the arterial duct in newborns with duct-dependent pulmonary circulation using low-profile, high-flexibility premounted coronary stents. DESIGN: Prospective interventional and clinical follow-up study. SETTING: Tertiary referral centre. PATIENT POPULATION: Between April 2003 and December 2006, 26 neonates (mean (SD) age 15.2 (19.9) days, mean (SD) weight 3.3 (0.8) kg) underwent attempts at stenting of the arterial duct. MAIN OUTCOME MEASURES: Procedural success and complication rates. Early and mid-term follow-up results. RESULTS: The procedure was successfully completed in 24/26 (92.3%) cases. Minor complications occurred in 2/26 (7.7%) cases. No mortality occurred. After stenting, the ductal diameter increased from 1.2 (1.0) mm to 3.1 (0.4) mm (p<0.001) and the percutaneous O(2) saturation increased from 70 (14)% to 86 (10)% (p<0.001), respectively. Over a mid-term follow-up, 2/24 patients (8.3%) needed a systemic-to-pulmonary artery shunt because of inadequate ductal flow and 4/24 patients (16.7%) underwent stent redilatation after 6.0 (4.4) months, but before corrective surgery. Cardiac catheterisation before corrective surgery in 9 patients showed an increase of the Nakata index from 112 (49) mm/mm(2) to 226 (108) mm/mm(2) (p<0.001), without any left-to-right imbalance of the pulmonary artery size. In the subset of 11 patients who improved without needing an additional source of pulmonary blood supply, the stented arterial duct closed uneventfully in 45.5% of cases after 4.0 (2.2) months. CONCLUSIONS: Stenting of the arterial duct is a feasible, safe and effective palliation in newborns with duct-dependent pulmonary circulation, supporting the spontaneous improvement process or promoting significant and balanced pulmonary artery growth for subsequent corrective surgery.

Elevated plasma free radical concentration (expression of enhanced oxidative stress) is related to different pathophysiological conditions such as ageing, cancer and diabetes. Nevertheless, even in healthy subjects a rise in plasma free radicals is due to hyperglycaemia, elevated free fatty acids and hyperinsulinaemia. Once elevated oxidative stress occurs, accelerated atherosclerosis may be present. Thus, antioxidants might potentially be useful in preventing or delaying the development of atherosclerosis. Several epidemiological studies have provided conflicting results, whereas interventional studies have demonstrated that antioxidant administration at pharmacological doses is useful for secondary prevention of atherosclerosis. The role of antioxidants in diabetic patients is still debatable, and it is too early to suggest this means for the prevention of atherosclerosis. Concerning trace elements, several studies have indicated that iron, copper, zinc and selenium may play a role in the pathogenesis of atherosclerosis. Nevertheless, only future longitudinal studies can provide a final response. In conclusion, the whole body of studies to date clearly demonstrates that antioxidants may be useful for secondary prevention of coronary heart disease.

Abstract Programmed Death Ligand 1 (PD-L1) is crucial in regulating the immunological tolerance in non-small cell lung cancer (NSCLC). Alveolar macrophage (AM)-derived PD-L1 binds to its receptor, PD-1, on surveilling lymphocytes, leading to lymphocyte exhaustion. Increased PD-L1 expression is associated with cigarette smoke (CS)-exposure. However, the PD-L1 role in CS-associated lung diseases associated with NSCLC, such as chronic obstructive pulmonary disease (COPD), is still unclear. In two different cohorts of ever smokers with COPD or NSCLC, and ever and never smoker controls, we evaluated PD-L1 expression: (1) via cutting-edge digital spatial proteomic and transcriptomic profiling (Geomx) of formalin-fixed paraffin-embedded (FFPE) lung tissue sections (n = 19); and (2) via triple immunofluorescence staining of bronchoalveolar lavage (BAL) AMs (n = 83). PD-L1 mRNA expression was also quantified in BAL AMs exposed to CS extract. PD-L1 expression was increased in the bronchiolar wall, parenchyma, and vascular wall from mild-moderate (GOLD 1–2) COPD patients compared to severe-very severe (GOLD 3–4) COPD patients and controls. Within all the COPD patients, PD-L1 protein expression was associated with upregulation of genes involved in tumor progression and downregulation of oncosuppressive genes, and strongly directly correlated with the FEV 1 % predicted, indicating higher PD-L1 expression in the milder vs. more severe COPD stages. In bronchioles, PD-L1 levels were strongly directly correlated with the number of functionally active AMs. In BAL, we confirmed that AMs from patients with both GOLD 1–2 COPD and NSCLC had the highest and similar, PD-L1 expression levels versus all the other groups, independently from active cigarette smoking. Intriguingly, AMs from patients with more severe COPD had reduced AM PD-L1 expression compared to patients with mild COPD. Acute CS extract stimulation increased PD-L1 mRNA expression only in never-and not in ever-smoker AMs. Lungs from patients with mild COPD and NSCLC are characterized by a similar strong PD-L1 expression signature in bronchioles and functionally active AMs compared to patients with severe COPD and controls. Active smoking does not affect PD-L1 levels. These observations represent a new resource in understanding the innate immune mechanisms underlying the link between COPD and lung cancer onset and progression and pave the way to future studies focused on the mechanisms by which CS promotes tumorigenesis and COPD.