Cardiovascular diseases (CVD), including heart and pathological circulatory conditions, are the world’s leading cause of mortality and morbidity. Endothelial dysfunction involved in CVD pathogenesis is a trigger, or consequence, of oxidative stress and inflammation. Endothelial dysfunction is defined as a diminished production/availability of nitric oxide, with or without an imbalance between endothelium-derived contracting, and relaxing factors associated with a pro-inflammatory and prothrombotic status. Endothelial dysfunction-induced phenotypic changes include up-regulated expression of adhesion molecules and increased chemokine secretion, leukocyte adherence, cell permeability, low-density lipoprotein oxidation, platelet activation, and vascular smooth muscle cell proliferation and migration. Inflammation-induced oxidative stress results in an increased accumulation of reactive oxygen species (ROS), mainly derived from mitochondria. Excessive ROS production causes oxidation of macromolecules inducing cell apoptosis mediated by cytochrome-c release. Oxidation of mitochondrial cardiolipin loosens cytochrome-c binding, thus, favoring its cytosolic release and activation of the apoptotic cascade. Oxidative stress increases vascular permeability, promotes leukocyte adhesion, and induces alterations in endothelial signal transduction and redox-regulated transcription factors. Identification of new endothelial dysfunction-related oxidative stress markers represents a research goal for better prevention and therapy of CVD. New-generation therapeutic approaches based on carriers, gene therapy, cardiolipin stabilizer, and enzyme inhibitors have proved useful in clinical practice to counteract endothelial dysfunction. Experimental studies are in continuous development to discover new personalized treatments. Gene regulatory mechanisms, implicated in endothelial dysfunction, represent potential new targets for developing drugs able to prevent and counteract CVD-related endothelial dysfunction. Nevertheless, many challenges remain to overcome before these technologies and personalized therapeutic strategies can be used in CVD management.

Breast cancer represents the main malignancy in women and autologous fat grafting is a diffuse procedure in the management of post-surgical breast defects causing patients’ psychosocial problems, with high costs for the public health. Recently, beneficial effects of fat grafting during post-surgical breast reconstruction have been amplified from the enrichment with human adipose-derived stem cells (ASCs) present in the stromal vascular fraction (SVF) of adult adipose tissue isolated during intraoperatory procedures. The major concern about the ASC enrichment during post-surgery breast reconstruction depends on their potential ability to release growth factors and hormones that can promote proliferation of residual or quiescent cancer cells, with the risk of de novo cancer development or recurrence. The recent description that adult stem cells primed in vitro may be vehicle for anti-cancer drug delivery offers a new vision concerning the role of ASCs in breast reconstruction after cancer surgery. Paclitaxel (PTX) is a chemotherapeutic agent acting as a microtubule-stabilizing drug inhibiting cancer cell mitotic activity. We optimized PTX loading and release in cultured ASCs and then analyzed the effects of PTX-loaded ASCs and their conditioned medium on CG5 breast cancer survival, proliferation and apoptosis in vitro, and inCG5 xenograft in vivo. We documented that ASCs can uptake and release PTX in vitro, with slight cytotoxic effects. Interestingly, PTX-loaded ASCs in co-culture, as well as conditioned medium alone, inhibited CG5 cell proliferation and survival in vitro and xenograft tumor growth in vivo. The antitumor effect of PTX-loaded ASCs may offer a new perspective concerning the use of ASCs during breast reconstruction becoming an additional local preventive chemotherapeutic agent against tumor recurrence. However, further experiments in vitro and in vivo are needed to collect more evidence confirming the efficacy and safety in cancer patients.

Marfan syndrome (MFS) is a connective tissue disease caused by mutations in the FBN1 gene, leading to alterations in the extracellular matrix microfibril assembly and the early formation of thoracic aorta aneurysms (TAAs). Non-genetic TAAs share many clinico-pathological aspects with MFS and deregulation of some microRNAs (miRNAs) has been demonstrated to be involved in the progression of TAA. In this study, 40 patients undergoing elective ascending aorta surgery were enrolled to compare TAA histomorphological features, miRNA profile and related target genes in order to find specific alterations that may explain the earlier and more severe clinical outcomes in MFS patients. Histomorphological, ultrastructural and in vitro studies were performed in order to compare aortic wall features of MFS and non-MFS TAA. MFS displayed greater glycosaminoglycan accumulation and loss/fragmentation of elastic fibers compared to non-MFS TAA. Immunohistochemistry revealed increased CD133⁺ angiogenic remodeling, greater MMP-2 expression, inflammation and smooth muscle cell (SMC) turnover in MFS TAA. Cultured SMCs from MFS confirmed higher turnover and α-smooth muscle actin expression compared with non-MFS TAA. Moreover, twenty-five miRNAs, including miR-26a, miR-29, miR-143 and miR-145, were found to be downregulated and only miR-632 was upregulated in MFS TAA in vivo. Bioinformatics analysis revealed that some deregulated miRNAs in MFS TAA are implicated in cell proliferation, extracellular matrix structure/function and TGFβ signaling. Finally, gene analysis showed 28 upregulated and seven downregulated genes in MFS TAA, some of them belonging to the CDH1/APC and CCNA2/TP53 signaling pathways. Specific miRNA and gene deregulation characterized the aortopathy of MFS and this was associated with increased angiogenic remodeling, likely favoring the early and more severe clinical outcomes, compared to non-MFS TAA. Our findings provide new insights concerning the pathogenetic mechanisms of MFS TAA; further investigation is needed to confirm if these newly identified specific deregulated miRNAs may represent potential therapeutic targets to counteract the rapid progression of MFS aortopathy.

Mpox is traditionally considered a zoonotic disease with endemic circulation in Africa, but the 2022–2023 outbreak reached an unprecedented high number of cases in non-endemic countries, so that it was declared a public health emergency of international concern. The reasons for this extensive global spread, characterized by sexual transmission amongst men who have sex with men (MSM), have not been fully clarified. The existence of asymptomatic carriers with viable viral shedding might be an explanation and is under-debated after retrospective studies suggested that infection without symptoms might have a prevalence of 6.5%. We aimed to prospectively assess the presence of mpox infection in asymptomatic high-risk MSM using HIV pre-exposure prophylaxis and living with HIV. We selected individuals with no signs of active infection nor suggestive symptoms in the previous 21 days. Eligible individuals collected oral and anal swabs to undergo point-of-care testing for mpox and completed a 21-days follow-up. Seventy-two individuals were enrolled, and none tested positive for mpox infection nor developed symptoms during follow-up. We selected a high-risk population with a significant history of sexual exposure, but we failed to detect any asymptomatic infection. This observation might have important consequences in terms of contact management and epidemic control.

Background: Italy has witnessed high levels of COVID-19 deaths, mainly at the elderly age. We assessed the comorbidity and the biochemical profiles of consecutive patients ≤65 years of age to identify a potential risk profile for death. Methods: We retrospectively analyzed clinical data from consecutive hospitalized-for-COVID-19 patients ≤65 years, who were died (593 patients) or discharged (912 patients) during February–December 2020. Multivariate logistic regression identified the mortality risk factors. Results: Overweight (adjusted odds ratio (adjOR) 5.53, 95% CI 2.07–14.76), obesity (adjOR 8.58, CI 3.30–22.29), dyslipidemia (adjOR 10.02, 95% CI 1.06–94.22), heart disease (adjOR 17.68, 95% CI 3.80–82.18), cancer (adjOR 13.28, 95% CI 4.25–41.51) and male sex (adjOR 5.24, 95% CI 2.30–11.94) were associated with death risk in the youngest population. In the older population (46-65 years of age), the overweight and obesity were also associated with the death risk, however at a lower extent: the adjORs varyied from 1.49 to 2.36 for overweight patients and from 3.00 to 4.07 for obese patients. Diabetes was independently associated with death only in these older patients. Conclusion: Overweight, obesity and dyslipidemia had a pivotal role in increasing young individuals’ death risk. Their presence should be carefully evaluated for prevention and/or prompt management of SARS-CoV2 infection in such high-risk patients to avoid the worst outcomes.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a worldwide non-fermenting Gram-negative bacillus responsible for potentially severe nosocomial infections, especially in critically ill patients. CRAB tends to colonize inert surfaces and epithelia, especially the respiratory tract of mechanically ventilated patients, and may then become responsible for lower respiratory tract infections, probably the more challenging infection due to the site and the multidrug-resistant phenotype which makes it difficult to establish an effective antimicrobial regimen. Despite its diffusion, data regarding the treatment of CRAB are mainly retrospective and usually heterogeneous. Current international consensus guidelines prefer the use of ampicillin/sulbactam, but the strength of recommendation and grade of evidence tend to be weak to moderate. Moreover, no specific recommendation is given for different sites of infections. The recently introduced cefiderocol still received a recommendation against its use due to the results of the first randomized clinical trial, though retrospective and observational experiences showed favourable outcomes in this setting. We reviewed the major antibacterial drugs active against CRAB and discussed their combination in lower respiratory tract infections.