Obesity is a multidimensional condition characterized by autonomic imbalance, metabolic inflexibility, impaired physical resilience, and ectopic adiposity, pathophysiological alterations that arise long before overt cardiometabolic disease becomes clinically detectable. Despite this, current cardiometabolic risk scores continue to rely predominantly on biochemical and anthropometric variables, such as BMI, waist circumference, glucose, and lipid levels. While these markers are practical, inexpensive, and validated across large population cohorts, growing evidence shows that they offer limited incremental predictive value and fail to capture early functional and structural abnormalities. The recent literature highlights the prognostic importance of autonomic dysfunction, reduced metabolic flexibility, diminished cardiorespiratory fitness, impaired muscular strength, and ectopic fat depots including visceral and epicardial adiposity, independently of the traditional anthropometric indices. The domains remain absent from traditional algorithms such as the Metabolic Syndrome criteria, the Framingham Risk Score, and SCORE2. As a result, cardiometabolic risk is frequently underestimated in key subgroups, including young adults with obesity, individuals with high visceral adiposity but normal BMI, those with subclinical myocardial dysfunction, and metabolically unhealthy normal-weight phenotypes. This narrative review synthesizes current evidence on obesity-related cardiometabolic impairment, highlights major gaps in established risk scores, and supports the conceptual development of the C.O.R.E. (Cardio-Obesity Risk Evaluation) Indicator Model-a hypothesis-generating, non-validated multidomain framework integrating autonomic, metabolic, functional, and structural markers to enable earlier risk phenotyping in future studies.

Cardiometabolic diseases remain the leading cause of morbidity and mortality worldwide, despite major advances in pharmacological and lifestyle interventions. Exercise training is a cornerstone of prevention and treatment; however, adherence to traditional aerobic programs remains suboptimal. Isometric handgrip (IHG) training has emerged as a simple, time-efficient, and potentially effective strategy for improving cardiovascular and metabolic outcomes. This state-of-the-art review synthesizes current evidence on the physiological mechanisms underlying IHG training, including autonomic modulation, vascular function improvement, endothelial adaptation, and metabolic regulation. We summarize clinical data regarding its effects on blood pressure, arterial stiffness, endothelial function, insulin sensitivity, and inflammatory markers. Special attention is given to its applicability in specific populations, including hypertensive patients, individuals with metabolic syndrome, heart failure patients, and cancer survivors. We also discuss methodological heterogeneity across studies, safety considerations, and knowledge gaps. Finally, we outline future research directions needed to define optimal protocols and clarify long-term cardiometabolic benefits. IHG training represents a promising adjunctive strategy within cardiometabolic prevention and rehabilitation programs.

Cardiorenal disease reflects a tightly interconnected pathophysiological continuum driven by neurohormonal activation, inflammation, oxidative stress, and progressive fibrosis. Among these mechanisms, mineralocorticoid receptor (MR) overactivation has emerged as a central mediator of cardiac and renal injury independent of blood pressure effects. Finerenone, a non-steroidal selective MR antagonist, exhibits distinct pharmacological properties compared with steroidal MR antagonists, including enhanced receptor selectivity, balanced cardiac and renal tissue distribution, and differential cofactor modulation that translates into potent anti-inflammatory and antifibrotic activity with an improved safety profile. Large outcome trials have established finerenone as an effective cardiorenal protective therapy. The FIDELIO-DKD and FIGARO-DKD trials demonstrated significant reductions in kidney disease progression and cardiovascular events in patients with type 2 diabetes and chronic kidney disease, with consistent benefits confirmed in the pooled FIDELITY analysis. More recently, the FINEARTS-HF trial extended these benefits to patients with heart failure with mildly reduced or preserved ejection fraction regardless of diabetes status. Across trials, hyperkalemia was infrequent when structured monitoring strategies were applied. Beyond established indications, emerging data suggest potential systemic effects on retinal and hepatic outcomes, while ongoing studies are evaluating finerenone in non-diabetic chronic kidney disease. Subgroup analyses consistently demonstrate preserved efficacy and favorable safety when finerenone is combined with sodium–glucose cotransporter-2 inhibitors, supporting complementary disease-modifying strategies. This review integrates molecular mechanisms, clinical trial evidence, systemic effects, and therapeutic positioning of finerenone within contemporary cardiorenal care, highlighting its expanding role in multidrug approaches targeting the cardiovascular–renal–metabolic axis.

Traditional anthropometric indices reflect total body adiposity, whereas novel shape-based indices capture fat distribution and unfavorable adiposity. How these measures relate to hepatic steatosis and fibrosis risk across the spectrum of metabolic dysfunction–associated steatotic liver disease (MASLD) remains unclear. In this cross-sectional study, 222 patients with MASLD were included. Body mass index (BMI), waist circumference (WC), a body shape index (ABSI) and body roundness index (BRI) were evaluated. Hepatic steatosis was assessed by ultrasonography using the Bright Liver Echo Pattern (BLEP), while fibrosis risk was estimated using the Fibrosis-4 (FIB-4) index. BMI, WC, and BRI were higher in individuals with moderate-to-severe hepatic steatosis (BLEP ≥ 2), whereas ABSI did not differ according to steatosis severity. In multivariable logistic regression, BMI was independently associated with BLEP ≥ 2 (OR 1.19; 95

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent worldwide and represents the hepatic manifestation of a systemic cardiometabolic-inflammatory syndrome rather than an isolated organ disease. In parallel, anticancer therapies carry a well-recognised burden of cancer therapy-related cardiovascular toxicity (CTR-CVT). Evidence suggests that the metabolic-inflammatory cascade driving steatosis → steatohepatitis → fibrosis may also contribute to endothelial dysfunction, myocardial remodelling and cardiomyocyte vulnerability to chemotherapy-induced oxidative stress. This narrative review proposes a unifying conceptual framework in which MASLD may act as a potential amplifier of cardiotoxicity in oncology patients and examines whether lifestyle and dietary interventions could mitigate this cumulative risk. Methods: A structured literature search of PubMed, Scopus and Web of Science was performed, prioritising systematic reviews, meta-analyses, randomised controlled trials, large cohort studies and recent international guidelines on MASLD, cardio-oncology and nutritional interventions. Results: Four converging molecular axes were identified as plausible links between MASLD and cardiomyocyte susceptibility to anticancer therapy: mitochondrial dysfunction with reactive oxygen species overproduction, NLRP3 inflammasome activation and metaflammation, endothelial nitric oxide impairment, and pro-fibrotic TGF-β/hepatic stellate cell signalling. Mediterranean-style dietary patterns, selected micronutrients and emerging metabolic therapies modulate the same network and may offer translational opportunities. Conclusions: Reframing MASLD as a potentially modifiable amplifier of CTR-CVT supports the integration of hepatic phenotyping into baseline cardio-oncology risk stratification and the use of personalised nutrition as a precision tool acting on shared mitochondrial, inflammatory, endothelial and fibrotic pathways. Multidisciplinary framework and prospective interventional studies, adopting composite hepato-cardio-oncological endpoints, are warranted.

Background: Glucagon-like peptide-1 receptor agonists and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GIP/GLP-1) receptor agonists have substantially improved the management of obesity and cardiometabolic disease, providing significant benefits on weight reduction, glycemic control, and cardiovascular outcomes. Despite these advances, gastrointestinal (GI) adverse events remain a major cause of dose reduction, treatment interruption, and poor long-term adherence. Increasing evidence suggests that interactions between incretin-based therapies and the intestinal microenvironment may contribute to GI tolerability and influence treatment persistence. Methods: We conducted a narrative review of the literature examining the relationship between incretin-based therapies, gut microbiota, intestinal barrier function, and microbial metabolites. Evidence from randomized clinical trials, observational studies, systematic reviews, and mechanistic investigations was evaluated to explore potential gut-directed supportive strategies during incretin-based treatment. Results: Preclinical and mechanistic evidence suggests possible bidirectional interactions between incretin pharmacology and the intestinal microenvironment, whereas direct human evidence remains limited and inconsistent. Alterations in gastrointestinal motility induced by GLP-1 receptor agonists could theoretically influence microbial composition and fermentation dynamics, although human studies have not consistently demonstrated significant microbiota changes. Based on these observations, we propose the Incretin-Microbiota Tolerance Axis (IMTA) as a conceptual framework linking gut homeostasis, GI tolerability, and treatment adherence. Among potential supportive interventions, partially hydrolyzed guar gum (PHGG) may promote SCFA-producing microbiota and improve bowel function, whereas simethicone may provide symptomatic relief of gas-related discomfort during dose escalation. SCFA-supportive nutritional approaches may further contribute to maintenance of intestinal homeostasis. Conclusions: Optimization of the intestinal microenvironment may represent a complementary strategy to improve GI tolerability and support long-term adherence during incretin-based therapy. Although the IMTA framework is supported by biological plausibility and emerging evidence, prospective clinical studies are required to determine whether microbiota-targeted interventions improve treatment persistence and cardiometabolic outcomes in patients receiving GLP-1 receptor agonists or dual GIP/GLP-1 receptor agonists.

Background: Bruton’s tyrosine kinase inhibitors, particularly ibrutinib, have improved outcomes in patients with chronic lymphocytic leukemia but are associated with an increased risk of atrial fibrillation. The early identification of patients with increased susceptibility to atrial fibrillation remains a major challenge in cardio-oncology. Methods: This prospective pilot study included 45 patients with chronic lymphocytic leukemia treated with ibrutinib. All patients underwent comprehensive transthoracic echocardiography at baseline and after 6 months. Left atrial structure and function were assessed, with particular emphasis on speckle-tracking-derived left atrial strain parameters, including peak atrial longitudinal strain and peak atrial contraction strain. Results: At follow-up, a modest but significant increase in indexed left atrial volume was observed, while left atrial functional parameters remained stable. Patients who developed atrial fibrillation showed significantly lower baseline Peak Atrial Contraction Strain values compared with those who remained in sinus rhythm, whereas no significant differences in Peak Atrial Longitudinal Strain were detected. Conclusions: Ibrutinib-related atrial fibrillation appears to be driven primarily by pre-existing atrial vulnerability rather than early drug-induced atrial dysfunction. The baseline impairment of left atrial contractile function may represent a candidate echocardiographic marker of atrial functional vulnerability and may inform cardiovascular surveillance and monitoring strategies in patients treated with ibrutinib.

BACKGROUND:Paget's disease of the bone (PDB) is a metabolic bone disorder involving one or more skeletal sites. Cardiovascular diseases (CVDs) have been described in patients with PDB but have not been systematically analysed. OBJECTIVES:This study aimed to compare standard and advanced (speckle-tracking) echocardiographic parameters measured in patients with PDB and controls matched for age, weight, height and history of hypertension but without metabolic bone disorders. METHODS:This multicentre case-control study included all patients with PDB referred to the Federico II and Siena Universities, Italy, from March 2019 to October 2022. During the same time, we enrolled at least one control for each patient, matched for age, sex, body mass index (BMI) and history of hypertension. RESULTS:Sixty-nine patients with PDB and 115 healthy controls were enrolled in this study. All patients with PDB were treated with zoledronic acid at the time of diagnosis. Compared with controls, on standard echocardiography, patients with PDB showed a high prevalence of aortic and mitral valve calcifications and/or sclerosis, reduced left ventricular (LV) ejection fraction, stroke volume, cardiac output, increased interventricular septum thickness, posterior wall thickness, LV mass index, relative wall thickness, relative diastolic wall thickness, E/e' ratio and systemic vascular resistance. Using speckle-tracking echocardiography, patients with PDB showed a lower global longitudinal strain and global myocardial work efficiency than controls. There was no relationship between the PDB activity and extent and severity of cardiac abnormalities. CONCLUSION:Overall, the myocardial function and structure were impaired in patients with PDB. Additionally, PDB was associated with early subclinical myocardial damage.

Right ventricular (RV) involvement in cardio-oncology is primarily represented by RV dysfunction caused by chemotherapeutical agents and target therapies [1]. Several classes of tyrosine kinase inhibitors (TKIs) exhibit pathologic effects on pulmonary vasculature and cardiomyocytes, consequently increasing pulmonary artery pressure (PAPs) and causing right ventricular dysfunction [2].BCR-ABL inhibitors, among which dasatinib, are the most involved agents, exhibiting partially unknown alternative molecular pathways. Of note, possible off-target effects of other TKIs on pulmonary pressures and RV are not known, and no echocardiographic studies have ever been conducted. The aim of our study was to assess echocardiographic parameters of RV function, PAPs and ventricular-arterial coupling in patients administered with Bruton tyrosine kinase inhibitors (BTKIs) to demonstrate if there may be any subclinical changes and possible undiscovered effects on the right ventricle of this class of TKIs. We retrospectively evaluated 30 patients with chronic lymphocytic leukemia (CLL) undergoing therapy with a BTKI. Only patients with complete echocardiography reports and RV optimal images before initiation of therapy and after 6 months were included in the study. 17 patients were selected with a mean age of 73 +/- 8 years and a mean time at follow-up echocardiography of 5.7 months. Only 5 people out of 15 were females (33%). Also, none of them was presenting with any baseline heart dysfunction, either left ventricular or valve-related. Regarding therapy with BTKIs, 11 people (73%) were administered with ibrutinib whilst 4 people with acalabrutinib (27%). We proceeded to examine structural RV parameters including basal, medial and longitudinal diameters. Also, fractional area change (FAC), PAPS, tricuspid annular plane systolic excursion (TAPSE) and, when images were suitable, RV global longitudinal strain (GLS) and left ventricular systolic parameters were calculated and compared. All the structural and functional parameters followed a normal distribution according to the Shapiro-Wilk test. At the hypothesis testing, nearly any echocardiographic RV parameter remained stable in time (table 1), suggesting that, in absence of any other explanation, BTKIs were not causing any damage to the RV, neither acute nor chronic. A slightly significative reduction in RV GLS was noted but in a smaller cohort of patients, where the measure was feasible. Also, left ventricular systolic parameters did not differ. In our experience, BTKIs neither modify the PAPs, nor right ventricular function, nor its structure in a period of 6 months. Our patients were selected with no active pulmonary disease or any pathology predisposing per se to RV dysfunction. Further studies with larger populations need to be conducted to deeply understand eventual clinical occurrence of damage to the right heart chambers.Table depicting results.

IntroductionProspective studies have demonstrated the favorable prognosis of differentiated thyroid cancer, primarily due to its low risk of recurrence and mortality. Considering these favorable outcomes, the most recent ATA guidelines recommend individualizing the degree of TSH suppression to balance the risks and benefits of LT4 therapy based on the aggressiveness of the disease. However, no studies have evaluated the cardiovascular risk in disease-free patients receiving long-term replacement doses of LT4 following the 2016 ATA guidelines.Patients and methodsThis study aimed to evaluate cardiovascular risk in disease-free athyreotic patients with differentiated thyroid cancer according to the 2021 European Society of Cardiology (ESC) guidelines. Only patients without major CV events prior to DTC diagnosis and treated with long-term LT4 therapy after the 2016 ATA guidelines were included. From a larger cohort, 300 disease-free patients who underwent total thyroidectomy—with or without radioiodine (RAI)—were selected and 102 patients were included in this study. The cardiovascular risk was assessed using the ESC 2021 scoring systems: SCORE2, SCORE2-OP, and SCORE2-Diabetes.ResultsAmong the 102 patients analyzed in detail, 14 experienced major adverse cardiovascular events (MACE) over a mean follow-up of 12.79 ± 9.13 years post-DTC diagnosis. In patients without MACE, none were classified as having a very high CV risk. A high CV risk was observed in 6% (SCORE2), 38.5% (SCORE2-OP), and 50% (SCORE2-Diabetes) of patients. Moderate CV risk was found in 34% (SCORE2), 38.5% (SCORE2-OP), and 50% (SCORE2-Diabetes), while low risk was recorded in 60% (SCORE2) and 23% (SCORE2-OP).DiscussionThese findings highlight the need for careful cardiovascular monitoring during long-term follow-up in patients with differentiated thyroid cancer. Specific cardiovascular management guidelines are needed in DTC, similar to those available for other cancer populations, to balance the risks and benefits of LT4 therapy and to identify patients at higher cardiovascular risk who may need closer monitoring.

The right heart–pulmonary circulation unit (RH-PCU) constitutes an integrated anatomo-functional system characterized by high-volume blood flow, low intravascular pressure, and minimal pulmonary vascular resistance. The RH-PCU dysfunction is a challenge for clinicians, as it can result from numerous pathological conditions, each with different clinical presentations. The pathophysiological changes underlying the hemodynamic alterations in the pressure and volume affecting the right ventricle can lead the patient to present with the primary symptom: dyspnea. We review the clinical presentation, the laboratory test, and the role of multimodality imaging in the evaluation of the disfunction of the RHPCU, including echocardiography, stress echocardiography, computed tomography, magnetic resonance imaging, nuclear imaging, and invasive pressure measurement through catheterization. We therefore aimed to describe the various diagnostic options available to clinicians, evaluating their effectiveness and limitations of use.

Thymoma is a rare malignancy, with affected patients frequently exhibiting multiple risk factors for cardiovascular disease. These individuals may present with intracardiac tumoral masses but their intrinsic cardiovascular risk —specifically concerning subclinical systemic inflammation and previous chemotherapeutical regimens [1,2]—has not been investigated yet. To date, echocardiographic case-control studies in this population have never been performed and literature only offers reports on cardiac tissue invasion. The aim of this study was to compare echocardiographic parameters between patients with thymoma, predominantly in stage III to IV of the disease, and healthy controls, to determine whether significant differences in cardiac function exist. Echocardiographic data were retrospectively collected from 60 patients, comprising 30 individuals diagnosed with thymus cancer and 30 matched controls. The latter were selected to match the patient group for age, sex, and common cardiovascular risk factors, including hypertension, type 2 diabetes mellitus, coronary artery disease, and dyslipidemia. After reviewing the exams, 23 patients with thymoma and 20 controls were included for final analysis based on the quality of the images. Clinical, electrocardiographic, and echocardiographic data were gathered and analyzed to assess significant differences using hypothesis testing (Table 1). Subsequently, regression analyses were performed to account for relevant variables. Statistical analysis revealed significant differences between thymoma patients and controls in various echocardiographic parameters, particularly in systolic function of both the left and right ventricles. Specifically, ejection fraction (EF) (p < 0.001), global longitudinal strain (GLS) (p = 0.01), and tricuspid annular plane systolic excursion (TAPSE) (p = 0.001) were significantly reduced in patients with a previous diagnosis of thymoma. Linear regression analysis demonstrated that the strongest association was found with EF, which was significantly higher in the control group (B = 5.15, p < 0.001, R = 0.5, R² = 0.27). Similarly, GLS was found to be higher in the control group (B = 1.7, p = 0.03, R = 0.3, R² = 0.12), as was TAPSE (B = 2.4, p = 0.01, R = 0.38, R² = 0.15). Also, the incidence of myasthenia gravis was not associated with any anomaly, although considering all patients were on antimyasthenics. Our findings suggest that patients with thymoma exhibit significantly lower systolic function of both the left and right ventricles compared to controls. The reduction in systolic function could be attributed to several factors, including the effects of radiotherapy and chemotherapy, which a majority of these patients had undergone years prior to our assessment. Additionally, echocardiographic acoustic windows in thymoma patients were often suboptimal, likely as a consequence of prior mediastinal irradiation.Table depicting significant results.

BACKGROUND:A uniform definition distinguishing metabolically healthy obesity (MHO) from metabolically unhealthy obesity (MUO) is lacking. MUO is characterized by higher liver and visceral fat than MHO. Epicardial fat tissue (EFT) is an index of cardiac adiposity strongly associated with risk of cardiovascular events. This study aimed to further define the MHO/MUO status by evaluating EFT and hepatic steatosis/fibrosis indices in adults presenting visceral obesity. METHODS:In this monocentric, observational study, 56 patients (48 females; 43.8±13.1 years) were recruited. Clinical characteristics, anthropometric measurements, and metabolic parameters were evaluated. Hepatic fibrosis and steatosis were assessed by Fibroscan (502Touch, Echosense). EFT thickness was assessed by transthoracic echocardiography (GE Vivid E95 system). EFT thickness values of 9.5 mm in men and 7.5 mm in women were used as predictors of the metabolic syndrome (MetS). RESULTS:Patients with MUO had significantly higher steatosis/fibrosis indices and EFT values than the MHO group (P<0.001). EFT values above the cut-off were found in 82.1% of MUO, but also in 42.9% of MHO. At ROC analysis, the specificity and sensitivity of the EFT cut-off point to predict MUO phenotype combined with hypertension, 60-min post load plasma glucose, and adiponectin, were 98.6% and 92.0%, respectively. CONCLUSIONS:As EFT thickness values above the predictive threshold for MetS were found in about half of MHO, the MHO/MUO classification may not correctly identify the cardiovascular risk of MHO. Further clinical evidence is needed to confirm EFT thickness as potential additional marker for MHO/MUO phenotypic differentiation.

Marine sponges represent a good source of natural metabolites for biotechnological applications in the pharmacological, cosmeceutical, and nutraceutical fields. In the present work, we analyzed the biotechnological potential of the alien species Haliclona (Halichoclona) vansoesti de Weerdt, de Kluijver & Gomez, 1999, previously collected in the Mediterranean Sea (Faro Lake, Sicily). The bioactivity and chemical content of this species has never been investigated, and information in the literature on its Caribbean counterpart is scarce. We show that an enriched extract of H. vansoesti induced cell death in human melanoma cells with an IC50 value of 36.36 µg mL−1, by (i) triggering a pro-inflammatory response, (ii) activating extrinsic apoptosis mediated by tumor necrosis factor receptors triggering the mitochondrial apoptosis via the involvement of Bcl-2 proteins and caspase 9, and (iii) inducing a significant reduction in several proteins promoting human angiogenesis. Through orthogonal SPE fractionations, we identified two active sphingoid-based lipid classes, also characterized by nuclear magnetic resonance and mass spectrometry, as the main components of two active fractions. Overall, our findings provide the first evaluation of the anti-cancer potential of polar lipids isolated from the marine sponge H. (Halichoclona) vansoesti, which may lead to new lead compounds with biotechnological applications in the pharmaceutical field.

Background: Obesity is a public health problem which prevalence has increased worldwide and is associated with different degrees of hemodynamic alterations and structural cardiac changes. The aim of the study is to investigate the impact of body mass index (BMI) on left atrial function using standard and advanced echocardiography in a population of patients with non-valvular atrial fibrillation (AF). Methods: 395 adult patients suffering from non-valvular AF, divided into three tertiles based on BMI value, carry out a cardiological examination with standard and advanced echocardiography. Results: Peak atrial longitudinal strain (PALS), a measure of left atrial function, is lower in the tertile with highest BMI (14.3 ± 8.2%) compared to both the first (19 ± 11.5%) and the second tertile (17.7 ± 10.6%) in a statistically significant manner (p < 0.002). Furthermore, BMI is significantly associated independent with the PALS by multilinear regression analysis, even after correction of the data for CHA2DS2-VASc score, left ventricular mass index, left ventricular ejection fraction, E/E’ ratio and systolic pulmonary arterial pressure (coefficient standardized β = −0.127, p < 0.02; Cumulative R2 = 0.41, SEE = 0.8%, p < 0.0001). Conclusions: BMI could be considered an additional factor in assessing cardiovascular risk in patients with non-valvular atrial fibrillation, in addition to the well-known CHA2DS2-VASc score.

Plastic pollution is a notable environmental issue, being plastic widespread and characterized by long lifetime. Serious environmental problems are caused by the improper management of plastic end-of-life. In fact, plastic litter is currently detected in any environment. Biodegradable Polymers (BPs) are promising materials if correctly applied and managed at their end of life, to minimize environmental problems. However, poor data on the fate and toxicity of BPs on marine organisms still limit their applicability. In this work we tested the effects of five biodegradable polymers (polybutylene succinate, PBS; polybutylene succinate-co-butylene adipate, PBSA; polycaprolactone, PCL; poly (3-hydroxybutyrates, PHB; polylactic acid, PLA) widely used for several purposes. Adult individuals of the isopod Idotea balthica basteri were fed on these polymers for twenty-seven days by adding biodegradable microplastic polymers (BMPs) to formulated feeds at two concentrations, viz. 0.84 and 8.4 g/kg feed. The plastic fragments affected the mortality rates of the isopods, as well as the expression levels of eighteen genes (tested by Real Time qPCR) involved in stress response and detoxification processes. Our findings confirmed that I. balthica basteri is a convenient model organism to study the response to environmental pollution and emerging contaminants in the aquatic environment, and highlighted the need for the correct use of BMPs.

Long non-coding RNAs (lncRNAs) represent an emerging class of genes which play significant and diverse roles in human cancers. Nevertheless, the functional repertoires of lncRNAs in cancer cell subtypes remains unknown since most studies are focused on protein coding genes. Here, we explored the contribution of lncRNAs in Colorectal Cancer (CRC) heterogeneity. We analyzed 49436 single-cells from 29 CRC patients and showed that lncRNAs are significantly more cell type specific compared to protein-coding genes. We identified 996 lncRNAs strongly enriched in epithelial cells. Among these, 98 were found to be differentially expressed in tumor samples compared to normal controls, when integrating 270 bulk CRC profiles. We validated the upregulation of two of them (CASC19 and LINC00460) in CRC cell lines and showed their involvement in CRC proliferation by CRISPR-Cas9 knock down experiments. This study highlights a list of novel RNA targets for potential CRC therapeutics, substantiated through experimental validation.

The protandric shrimp Hippolyte inermis is the only known marine invertebrate whose sex determination is strongly influenced by the composition of its food. In H. inermis, a sex reversal is triggered by the ingestion of diatoms of the genus Cocconeis associated with leaves of the seagrass Posidonia oceanica. These diatoms contain compounds that promote programmed cell death (PCD) in H. inermis and also in human cancer cells. Transcriptomic analyses suggested that ferroptosis is the primary trigger of the shrimp’s sex reversal, leading to the rapid destruction of the androgen gland (AG) followed by a chain of apoptotic events transforming the testes into ovaries. Here, we propose a molecular approach to detect the effects of compounds stimulating the PCD. An RNA extraction method, suitable for young shrimp post-larvae (five days after metamorphosis; PL5 stage), was established. In addition, six genes involved in apoptosis, four involved in ferroptosis, and seven involved in the AG switch were mined from the transcriptome, and their expression levels were followed using real-time qPCR in PL5 fed on Cocconeis spp., compared to PL5 fed on a basic control feed. Our molecular approach, which detected early signals of sex reversal, represents a powerful instrument for investigating physiological progression and patterns of PCD in marine invertebrates. It exemplifies the physiological changes that may start a few days after the settlement of post-larvae and determine the life destiny of an individual.