MiR profile could be associated to CV risk, and also to prognosis/outcome in response to therapeutic approach. We aimed to evaluate if anti-hypertensive drugs enalapril, losartan or olmesartan have effects on monocyte miR profile in essential hypertensives without target organ involvement. For this purpose, 82 hypertensives and 49 controls were included; we evaluated SBP/DBP, lipid profile, glucose, CRP, fibrinogen, arterial stiffness indices (PWV; AIx), and cIMT at baseline (T0) and after 24 weeks of treatment (T1). Subjects with LDL-C ≥ 160 mg/dL, TG ≥ 200 mg/dL, BMI ≥ 30, and other additional CV risk factors were excluded. Patients who were prescribed to receive once-a-day enalapril 20 mg, losartan 100 mg or olmesartan 20 mg were eligible for the study. At T1, we found a significant improvement of SBP (−18.5%), DBP (−18%), HDL-C and LDL-C (+3% and −5.42%), glucose (−2.15%), BMI (−3.23%), fibrinogen (−11%), CRP (−17.5%,), AIx (−49.1%) PWV (−32.2%), and monocyte miR expression (miR-221: −28.4%; miR-222: −36%; miR-145: +41.7%) with respect to baseline. miR profile was compared to control subjects at baseline and at T1. We found some little difference in the behaviour of the three treatments on some variables: olmesartan was the most effective in reducing fibrinogen, DBP, CRP, and AIx (−13.1%, −19.3%, −21.4%, and −56.8%, respectively). Enalapril was the drug more significantly increasing the expression of miR-145. In conclusion, enalapril, losartan and olmesartan are effective in improving mechanical and humoral factors associated to AS and atherogenesis. These drugs appear to be able to modify miRs 221/222 and miR-145 expression in drug-naïve hypertensives, making it closer to that of control subjects; additionally, this provides a good blood pressure compensation, contributing to slow the progression of vascular damage.

Cadmium (Cd) is a potentially toxic element able to interfere with cellular functions and lead to disease or even death. Cd accumulation has been demonstrated in cartilage, where it can induce damage in joints. The aim of this study was to evaluate the effect of CdCl₂ on primary cultures of human chondrocytes and the possible protective effect of seleno-methionine (Se-Met). Human primary articular chondrocytes were cultured and treated as follows: control groups, cells challenged with 7.5 μM and 10 μM CdCl₂ alone, and cells pretreated with 10 and 20 μM Se-Met and then challenged with 7.5 μM and 10 μM CdCl₂. Twenty-four hours after incubation, cell viability, histological evaluation with hematoxylin–eosin stain, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were performed. Furthermore, reverse transcription-PCR was carried out to evaluate mRNA levels of BAX, BAK1, CASP-3, and CASP-9. After CdCl₂ challenge at both doses, a reduced cell viability and an overexpression of BAX, BAK1, CASP-3, and CASP-9 genes, as well as a high number of TUNEL-positive cells, were demonstrated, all parameters becoming higher as the dose of CdCl₂ was increased. The pretreatment with Se-Met lowered the expression of all considered genes, improved cell viability and morphological changes, and reduced the number of TUNEL-positive cells. It was concluded that Se-Met plays a protective role against CdCl₂-induced structural and functional changes in chondrocytes in vitro, as it improved cell viability and showed a positive role in the context of the apoptotic pathways. It is therefore suggested that a translational, multifaceted approach, with plant-based diets, bioactive functional foods, nutraceuticals, micronutrients, and drugs, is possibly advisable in situations of environmental pollution caused by potentially toxic elements.

Oxidative stress destabilizes microRNA homeostasis in the retinal pigment epithelium (RPE), driving apoptosis and the epithelial-to-mesenchymal transition, which contribute to age-related macular degeneration. We investigated whether Quantum Molecular Resonance (QMR^®) electrostimulation, alone or combined with Patient Blood-Derived (PBD) secretoma, can reprogram the RPE miRNome and mitigate stress-induced damage. Human ARPE-19 cells were exposed to tert-butyl-hydroperoxide and treated with QMR^®, PBD secretome, or their combination. The deep sequencing of small RNAs at 24 h and 72 h, followed by differential expression and pathway enrichment analyses, delineated treatment-driven miRNA signatures. Oxidative stress deregulated > 50 miRNAs, enriching pro-apoptotic, fibrotic, and inflammatory pathways. QMR^® restored roughly 40% of these miRNAs and upregulated additional cytoprotective species such as miR-590-3p, a known regulator of the NF-κB and NLRP3 pathways according to validated target databases. While these observations suggest the potential involvement of inflammatory and stress-related cascades, functional assays will be required to directly confirm such effects. Secretome treatment preferentially increased anti-inflammatory miR-146a-5p and regenerative miR-204-5p while suppressing pro-fibrotic let-7f-5p. Combined QMR^® + secretome triggered the broadest miRNA response, normalizing over two-thirds of stress-altered miRNAs. These changes are predicted to influence antioxidant, anti-apoptotic, and anti-fibrotic pathways, although they did not translate into additional short-term cytoprotection compared with QMR^® alone. These data indicate that QMR^® and PBD secretome modulate complementary miRNA programs that converge on stress response networks. This broader molecular reprogramming may reflect regulatory complementarity, but functional validation is needed to determine whether it provides benefits beyond those observed with QMR^® alone. These findings offer molecular insights into potential non-invasive, cell-free strategies for retinal degeneration, although in vivo validation will be required before any clinical translation to Age-Related Macular Degeneration (AMD) therapy.

Appendiceal mucinous neoplasms (AMNs) are a rare but clinically significant category of gastrointestinal tumors, ranging from low-grade appendiceal mucinous neoplasm (LAMN), the main precursor of pseudomyxoma peritonei (PMP), to high-grade appendiceal mucinous neoplasm (HAMN), poorly differentiated and signet-ring-cell adenocarcinomas, and goblet cell adenocarcinoma. Although current WHO and PSOGI classifications provide well established diagnostic criteria, controversies persist regarding the biological behavior and prognostic significance of the most aggressive subtypes and the relationship between HAMN and mucinous adenocarcinoma. While appendectomy is sufficient for localized LAMN, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is the treatment of choice for peritoneal dissemination This review integrates the histopathological and molecular classification of AMN and PMP with the evolution of intraperitoneal chemotherapy. Key findings indicate that KRAS and GNAS mutations are central drivers of mucin overproduction and peritoneal spread, that tumor grade and mucin cellularity remain the strongest prognostic determinants, and that the evidence supporting HIPEC and PIPAC derives largely from observational rather than randomized data. As a novel insight, we highlight the emerging role of patient-derived organoids as translational models for functional drug testing. Progress will depend on integrating molecular characterization, critical appraisal of intraperitoneal therapies, and organoid-based testing to advance individualized treatment for peritoneal surface malignancies.

Oxidative stress destabilizes microRNA homeostasis in retinal pigment epithelium (RPE), driving apoptosis and epithelial-to-mesenchymal transition that contribute to age-related macular degeneration. We investigated whether quantum molecular resonance (QMR^®) electrostimulation, alone or combined with Patient Blood-Derived (PBD) secretoma, can reprogram the RPE miRNome and mitigate stress-induced damage. Human ARPE-19 cells were exposed to tert-butyl-hydroperoxide and treated with QMR^®, PBD secretome, or their combination. Deep-sequencing of small RNAs at 24 h and 72 h, followed by differential expression and pathway enrichment analyses, delineated treatment-driven miRNA signatures. Oxidative stress deregulated >50 miRNAs, enriching pro-apoptotic, fibrotic, and inflammatory pathways. QMR^® restored roughly 40 % of these miRNAs and up-regulated additional cytoprotective species such as miR-590-3p, collectively dampening NF-κB and NLRP3 axes. Secretome treatment preferentially increased anti-inflammatory miR-146a-5p and regenerative miR-204-5p while suppressing pro-fibrotic let-7f-5p. Combined QMR^® + secretome triggered the broadest response, normalizing over two-thirds of stress-altered miRNAs and synergistically reinforcing antioxidant, anti-apoptotic, and anti-fibrotic gene networks. These data indicate that QMR^® and PBD secretome act through complementary miRNA programs that converge to preserve RPE viability under oxidative insult; their combination offers additive modulation of key survival pathways, supporting development of a non-invasive, cell-free therapeutic strategy for retinal degenerative disorders.