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Abstract Tirzepatide is a new drug targeting glucagon-like peptide 1(GLP1) and gastric inhibitory polypeptide (GIP) receptors. This drug has demonstrated great potential in improving the clinical outcomes of patients with type 2 diabetes. It can lead to weight loss, better glycemic control, and reduced cardiometabolic risk factors. GLP1 receptor agonists have been proven effective antidiabetic medications with possible cardiovascular benefits. Even though they have been proven to reduce the risk of major adverse cardiovascular events, their effectiveness in treating heart failure is unknown. Unlike traditional GLP1 receptor agonists, tirzepatide is more selective for the GIP receptor, resulting in a more balanced activation of these receptors. This review article discusses the possible mechanisms tirzepatide may use to improve cardiovascular health. That includes the anti-inflammatory effect, the ability to reduce cell death and promote autophagy, and also its indirect effects through blood pressure, obesity, and glucose/lipid metabolism. Additionally, tirzepatide may benefit atherosclerosis and lower the risk of major adverse cardiac events. Currently, clinical trials are underway to evaluate the safety and efficacy of tirzepatide in patients with heart failure. Overall, tirzepatide’s dual agonism of GLP1 and GIP receptors appears to provide encouraging cardiovascular benefits beyond glycemic control, offering a potential new therapeutic option for treating cardiovascular diseases and heart failure. Graphical abstract

Sex-specific differences in lifespan and ageing are observed in various species. In humans, women generally live longer but are frailer and suffer from different age-related diseases compared to men. The hallmarks of ageing, such as genomic instability, telomere attrition or loss of proteostasis, exhibit sex-specific patterns. Sex chromosomes and sex hormones, as well as the epigenetic regulation of the inactive X chromosome, have been shown to affect lifespan and age-related diseases. Here we review the current knowledge on the biological basis of sex-biased ageing. While our review is focused on humans, we also discuss examples of model organisms such as the mouse, fruit fly or the killifish. Understanding these molecular differences is crucial as the elderly population is expected to double worldwide by 2050, making sex-specific approaches in the diagnosis, treatment, therapeutic development and prevention of age-related diseases a pressing need.

Introduction Respiratory pathogens are frequently isolated from airway samples in primary ciliary dyskinesia (PCD) patients. Few studies have investigated associations between these pathogens and lung function, with current management based on evidence from cystic fibrosis. We investigated the association between commonly isolated respiratory pathogens and lung function in PCD patients. Methods Using a cross-sectional design, we prospectively collected clinical and concurrent microbiology data from 408 participants with probable or confirmed PCD, aged ≥5 years, from 12 countries. We used Global Lung Function Initiative 2012 references to calculate forced expiratory volume in 1 s (FEV1) z-scores. For 351 patients (86%) with complete data, we assessed the association of the four most frequently isolated pathogens with lung function by fitting multilevel linear models with country as random intercept, adjusted for age at diagnosis, age at lung function, use of antibiotic prophylaxis and body mass index z-scores. Results Individuals with Pseudomonas aeruginosa growth in culture had significantly lower FEV1 z-scores (β= −0.87, 95% CI −1.40– −0.34), adjusted for presence of Haemophilus influenzae, methicillin-sensitive Staphylococcus aureus and Streptococcus pneumoniae, and for covariates. When stratified by age, associations remained strong for adults but not for children. Results were similar when ciliary defects by transmission electron microscopy were included in the models and when restricting analysis to only confirmed PCD cases. Conclusions We found that P. aeruginosa was associated with worse lung function in individuals with PCD, particularly adults. These findings suggest that it is prudent to aim for P. aeruginosa eradication in the first instance, and to treat exacerbations promptly in colonised patients.

Abstract Background Early diagnosis of hepatocellular carcinoma (HCC) is essential towards the improvement of prognosis and patient survival. Circulating markers such as α-fetoprotein (AFP) and micro-RNAs represent useful tools but still have limitations. Identifying new markers can be fundamental to improve both diagnosis and prognosis. In this approach, we harness the potential of metabolomics and lipidomics to uncover potential signatures of HCC. Methods A combined untargeted metabolomics and lipidomics plasma profiling of 102 HCV-positive patients was performed by HILIC and RP-UHPLC coupled to Mass Spectrometry. Biochemical parameters of liver function (AST, ALT, GGT) and liver cancer biomarkers (AFP, CA19.9 e CEA) were evaluated by standard assays. Results HCC was characterized by an elevation of short and long-chain acylcarnitines, asymmetric dimethylarginine, methylguanine, isoleucylproline and a global reduction of lysophosphatidylcholines. A supervised PLS-DA model showed that the predictive accuracy for HCC class of metabolomics and lipidomics was superior to AFP for the test set (100.00% and 94.40% vs 55.00%). Additionally, the model was applied to HCC patients with AFP values

Abstract Many studies have explored the extraction of bioactive compounds from different onion solid wastes, such as bulb, skin, and peel. However, onion leaves have received limited attention despite their potential as a valuable source of nutraceutical compounds. This study aimed to valorise, for the first time, the agricultural waste in the form of spring onion leaves (CN, Cipollotto Nocerino) to obtain antioxidant-rich polyphenolic extracts. A Box–Behnken design (BBD) was used to assess the impact of microwave-assisted extraction (MAE) variables (temperature, time, extraction volume, and ethanol concentration) on total polyphenol content (TPC) measured by Folin–Ciocalteu method and the antioxidant power determined by FRAP assay. Response surface methodology (RSM) was applied, and regression equations, analysis of variance, and 3D response curves were developed. Our results highlighted that the TPC values range from 0.76 to 1.43 mg GAE g−1 dw, while the FRAP values range from 8.25 to 14.80 mmol Fe(II)E g−1 dw. The optimal extraction conditions predicted by the model were 60 °C, 22 min, ethanol concentration 51% (v/v), and solvent volume 11 mL. These conditions resulted in TPC and FRAP values of 1.35 mg GAE g−1 dw and 14.02 mmol Fe(II)E g−1 dw, respectively. Furthermore, the extract obtained under optimized conditions was characterized by UHPLC-ESI-Orbitrap-MS analysis. LC/MS–MS platform allowed us to tentatively identify various compounds belonging to the class of flavonoids, saponins, fatty acids, and lipids. Finally, the ability of CN optimal extract to inhibit the intracellular reactive oxygen species (ROS) release in a hepatocarcinoma cell line using an H2O2-induced oxidative stress model, was evaluated. The results highlighted the potential of CN extract as a valuable source of polyphenols with significant antioxidant properties, suitable for various applications in the food and pharmaceutical industries.

Abstract The last year saw intensive efforts to advance knowledge in pediatric medicine. This review highlights important publications that have been issued in the Italian Journal of Pediatrics in 2022. We have chosen papers in the fields of allergy, anesthesiology, cardiology, dermatology, endocrinology, gastroenterology, genetics, global health, infectious diseases, metabolism, neonatology, neurology, oncology, pulmonology. Novel valuable developments in epidemiology, pathophysiology, prevention, diagnosis and treatment that can rapidly change the approach to diseases in childhood have been included and discussed.

Abstract Background Sodium–glucose cotransporter 2 (SGLT2) inhibitors constitute the gold standard treatment for type 2 diabetes mellitus (T2DM). Among them, empagliflozin (EMPA) has shown beneficial effects against heart failure. Because cardiovascular diseases (mainly diabetic cardiomyopathy) are the leading cause of death in diabetic patients, the use of EMPA could be, simultaneously, cardioprotective and antidiabetic, reducing the risk of death from cardiovascular causes and decreasing the risk of hospitalization for heart failure in T2DM patients. Interestingly, recent studies have shown that EMPA has positive benefits for people with and without diabetes. This finding broadens the scope of EMPA function beyond glucose regulation alone to include a more intricate metabolic process that is, in part, still unknown. Similarly, this significantly increases the number of people with heart diseases who may be eligible for EMPA treatment. Methods This study aimed to clarify the metabolic effect of EMPA on the human myocardial cell model by using orthogonal metabolomics, lipidomics, and proteomics approaches. The untargeted and multivariate analysis mimicked the fasting blood sugar level of T2DM patients (hyperglycemia: HG) and in the average blood sugar range (normal glucose: NG), with and without the addition of EMPA. Results Results highlighted that EMPA was able to modulate and partially restore the levels of multiple metabolites associated with cellular stress, which were dysregulated in the HG conditions, such as nicotinamide mononucleotide, glucose-6-phosphate, lactic acid, FA 22:6 as well as nucleotide sugars and purine/pyrimidines. Additionally, EMPA regulated the levels of several lipid sub-classes, in particular dihydroceramide and triacylglycerols, which tend to accumulate in HG conditions resulting in lipotoxicity. Finally, EMPA counteracted the dysregulation of endoplasmic reticulum-derived proteins involved in cellular stress management. Conclusions These results could suggest an effect of EMPA on different metabolic routes, tending to rescue cardiomyocyte metabolic status towards a healthy phenotype. Graphical Abstract

Lycium barbarum, commonly recognized as goji berry or wolfberry, is highly appreciated not only for its organoleptic and nutritional properties but also as an important source of bioactive compounds such as polysaccharides, carotenoids, phenolics, and various other non-nutritive compounds. These constituents give it a multitude of health benefits, including antioxidant, anti-inflammatory, and anticancer properties. However, the precise biochemical mechanisms responsible for its anticancer effects remain unclear, and the comprehensive composition of goji berry extracts is often insufficiently explored. This study aimed to investigate the biochemical pathways modulated in breast cancer cells by an ethanolic extract of Lycium barbarum fruit (LBE). Following metabolomic profiling using UHPLC-HRMS/MS, we assessed the antitumoral properties of LBE on different breast cancer cell lines. This investigation revealed that LBE exhibited cytotoxic effects, inducing a pro-oxidant effect that triggered pyroptosis activation through endoplasmic reticulum (ER) stress and subsequent activation of the P-IRE1α/XBP1/NLRP3 axis in MCF-7 cells. In addition, LBE did not display cytotoxicity toward healthy human cells but demonstrated antioxidant properties by neutralizing ROS generated by doxorubicin. These findings underscore the potential of LBE as a highly promising natural extract in cancer therapy.

Abstract In this review, we report the developments across pediatric subspecialties that have been published in the Italian Journal of Pediatrics in 2021. We highlight advances in allergy and immunology, critical care, endocrinology, gastroenterology, genetics, hematology, infectious diseases, neonatology, neurology, nutrition, palliative care, respiratory tract illnesses and telemedicine.

Punica granatum L., commonly known as pomegranate, is a typical fruit of Asia, Mediterranean countries, the Middle East and the USA. While in ancient times pomegranate was considered an ornamental plant, nowadays numerous scientific studies have highlighted its antioxidant and anti-radical activities, making it a “superfood”. Pomegranate presents a high content of natural bioactive compounds (NBCs), and its consumption appears to exert numerous healthy effects, in particular, in several pathological conditions as metabolic syndrome, cancer, nephrolithiasis, urinary tract infections and neurodegenerative diseases. Moreover, recent studies have pointed out the possible beneficial action of pomegranate on oral health. For these reasons, the utility of pomegranate in internal medicine and dentistry represents a promising field, as it could enable the development of innovative natural adjuvant therapies and empower standard pharmaceutical therapies.

Background: A novel β-coronavirus infection (COVID-19) was first detected in Wuhan city, spreading rapidly to other countries and leading to a pandemic. Dental professionals and patients are exposed to a high risk of COVID-19 infection, particularly in the prosthodontic practice, because of the bio-aerosol produced during teeth preparation with dental handpieces and the strict contact with oral fluids during impression making. This paper aimed to provide an overview to limit the risk of transmission of COVID-19 infections during prosthetic procedures in dental offices. Methods: An electronic search was conducted on the electronic databases of PubMed/Medline, Google Scholar, Embase, Scopus, Dynamed, and Open Grey with the following queries: (COVID-19) AND/OR (SARS-CoV-2) AND/OR (Coronavirus) AND/OR (contaminated surface) AND/OR (cross-infection) AND/OR (Prosthodontics) AND/OR (dental ceramic) AND/OR (glass-ceramic). A manual search was performed as well. Results: From the 1023 collected records, 32 papers were included. Conclusions: Dental offices are at high risk of spreading SARS-CoV-2 infection due to the close contact with patients and continuous exposure to saliva during dental procedures. Therefore, pre-check triages via telephone, decontamination, the disinfection of impressions, the sterilization of scanner tips, and the use of specific personal protective equipment, dental high-speed handpieces with dedicated anti-retraction valves, and effective mouthwashes are strongly recommended.

Exogenous heavy metals or non-metallic waste products, for example lanthanide or iodinated contrast media for radiological procedures, may interfere with the biochemical pools in patients and in common food sources, creating an excess buildup of exogenous compounds which may reach toxic levels. Although the mechanisms are unknown, our experiments were designed to test if this toxicity can be attributed to “transmetallation” or “chelation” reactions freeing up lanthanides or chelated transition metals in acidic fruits used as phantoms representing the biologically active and mineral-rich carbohydrate matrix. The rapid breakdown of stable contrast agents have been reported at a lower pH. The interaction of such agents with native metals was examined by direct imaging of contrast infused fresh apples and sweet potatoes using low energy X-rays (40–44 kVp) and by magnetic resonance imaging at 1.5 and 3T. The stability of the exogenous agents seemed to depend on endogenous counterions and biometals in these fruits. Proton spin echo MR intensity is sensitive to paramagnetic minerals and low energy X-ray photons are sensitively absorbed by photoelectric effects in all abundant minerals and were compared before and after the infusion of radiologic contrasts. Endogenous iron and manganese are believed to accumulate due to interactions with exogenous iodine and gadolinium in and around the infusion spots. X-ray imaging had lower sensitivity (detection limit approximately 1 part in 104), while MRI sensitivity was two orders of magnitude higher (approximately 1 part in 106), but only for paramagnetic minerals like Mn and Fe in our samples. MRI evidence of such a release of metal ions from the native pool implicates transmetallation and chelation reactions that were triggered by infused contrast agents. Since Fe and Mn play significant roles in the function of metalloenzymes, our results suggest that transmetallation and chelation could be a plausible mechanism for contrast induced toxicity in vivo.

The aim of this study is to evaluate the effects of orthodontic traction, by means of light and controlled forces, on root length in impacted maxillary canines and physiologically erupted maxillary canines. Disinclusion of impacted maxillary canines is a frequent procedure in orthodontics due to their higher incidence of impaction. The effects of orthodontic traction, by means of light and controlled forces, can lead to a resorption of the root length in impacted and physiologically erupted teeth. Therefore, apical root resorption is a common phenomenon that must be taken into consideration. Apical root resorption measurements were taken using pre-treatment CBCTs and pre-treatment and post-treatment digital panoramic radiographs of 52 patients who underwent fixed-appliance treatment by using light and controlled orthodontic forces. The experimental group consisted of 26 patients with one impacted maxillary canine. The control group consisted of 26 patients without any impaction. Apical root resorption was calculated from root lengths before and after orthodontic treatment. In the experimental group, impacted canines with incomplete apical formation underwent root elongation, while impacted canines with completed root formation went through apical root resorption. The latter showed a slightly greater apical root resorption (0.2 mm) compared to the control group (95% confidence interval; p = 0.04). The extent of root resorption of impacted canines was significantly higher than that of physiologically erupted ones. However, this differential resorption did not compromise the structural and functional integrity of the involved teeth. The orthodontic treatment performed with light and controlled forces is, therefore, a procedure to be considered acceptable and safe.

Tomato by-products represent a good source of phytochemical compounds with health properties, such as the steroidal glycoalkaloid α-tomatine (α-TM) and its aglycone tomatidine (TD). Both molecules have numerous beneficial properties, such as potential anticancer activity. Unfortunately, their therapeutic application is limited due to stability and bioavailability issues. Therefore, a valid strategy seems to be their encapsulation into Solid Lipid Nanoparticles (SLN). The nanoformulations containing α-TM (α-TM-SLN) and TD (TD-SLN) were prepared by solvent-diffusion technique and subsequently characterized in terms of technological parameters (particle size, polydispersity index, zeta potential, microscopy, and calorimetric studies). To assess the effect of α-TM and TD on the percentage of cellular viability in Olfactory Ensheathing Cells (OECs), a peculiar glial cell type of the olfactory system used as normal cells, and in SH-SY5Y, a neuroblastoma cancer cell line, an MTT test was performed. In addition, the effects of empty, α-TM-SLN, and TD-SLN were tested. Our results show that the treatment of OECs with blank-SLN, free α-TM (0.25 µg/mL), and TD (0.50 µg/mL) did not induce any significant change in the percentage of cell viability when compared with the control. In contrast, in SH-SY5Y-treated cells, a significant decrease in the percentage of cell viability when compared with the control was found. In particular, the effect appeared more evident when SH-SY5Y cells were exposed to α-TM-SLN and TD-SLN. No significant effect in blank-SLN-treated SH-SY5T cells was observed. Therefore, SLN is a promising approach for the delivery of α-TM and TD.

This paper aims at illustrating the different diagnostic methods and compare the reliability of the Digital Imaging Fiber Optic Transillumination (DIAGNOcamTM, KaVo Kerr, Brea, California, US) with the use of intraoral radiographs. Since the discovery of radiography, various methods have been introduced in order to provide early diagnosis of caries. In this review, specific keywords have been chosen on different search engines and medical databases. Scientific papers published from 1990 to 2022 were included. Nine articles comparing two different methods for early detection of carious lesions were selected. An analysis of the existing literature seems to support the hypothesis that making diagnosis by using the Digital Imaging Fiber Optic Transillumination systems represents a safe and effective support for early diagnosis of interproximal carious lesions within enamel. However, it is still to be considered a complementary method to traditional bitewing and periapical radiographs.