The RANK–RANKL–OPG system is a complex signaling pathway that plays a critical role in bone metabolism, mammary epithelial cell development, immune function, and cancer. RANKL is a ligand that binds to RANK, a receptor expressed on osteoclasts, dendritic cells, T cells, and other cells. RANKL signaling promotes osteoclast differentiation and activation, which leads to bone resorption. OPG is a decoy receptor that binds to RANKL and inhibits its signaling. In cancer cells, RANKL expression is often increased, which can lead to increased bone resorption and the development of bone metastases. RANKL-neutralizing antibodies, such as denosumab, have been shown to be effective in the treatment of skeletal-related events, including osteoporosis or bone metastases, and cancer. This review will provide a comprehensive overview of the functions of the RANK–RANKL–OPG system in bone metabolism, mammary epithelial cells, immune function, and cancer, together with the potential therapeutic implications of the RANK–RANKL pathway for cancer management.

Calcification is a process of accumulation of calcium in tissues and deposition of calcium salts by the crystallization of PO₄³⁻ and ionized calcium (Ca²⁺). It is a crucial process in the development of bones and teeth. However, pathological calcification can occur in almost any soft tissue of the organism. The better studied is vascular calcification, where calcium salts can accumulate in the intima or medial layer or in aortic valves, and it is associated with higher mortality and cardiovascular events, including myocardial infarction, stroke, aortic and peripheral artery disease (PAD), and diabetes or chronic kidney disease (CKD), among others. The process involves an intricate interplay of different cellular components, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), fibroblasts, and pericytes, concurrent with the activation of several signaling pathways, calcium, Wnt, BMP/Smad, and Notch, and the regulation by different molecular mediators, growth factors (GFs), osteogenic factors and matrix vesicles (MVs). In the present review, we aim to explore the cellular players, molecular pathways, biomarkers, and clinical treatment strategies associated with vascular calcification to provide a current and comprehensive overview of the topic.

The growing impact of infections and the rapid emergence of antibiotic resistance represent a public health concern worldwide. The exponential development in the field of biomaterials and its multiple applications can offer a solution to the problems that derive from these situations. In this sense, antimicrobial hydrogels represent a promising opportunity with multiple translational expectations in the medical management of infectious diseases due to their unique physicochemical and biological properties as well as for drug delivery in specific areas. Hydrogels are three-dimensional cross-linked networks of hydrophilic polymers that can absorb and retain large amounts of water or biological fluids. Moreover, antimicrobial hydrogels (AMH) present good biocompatibility, low toxicity, availability, viscoelasticity, biodegradability, and antimicrobial properties. In the present review, we collect and discuss the most promising strategies in the development of AMH, which are divided into hydrogels with inherent antimicrobial activity and antimicrobial agent-loaded hydrogels based on their composition. Then, we present an overview of the main translational applications: wound healing, tissue engineering and regeneration, drug delivery systems, contact lenses, 3D printing, biosensing, and water purification.

Objectives: The aim of this study was to analyze the prognostic factors of survival in patients with peritoneal metastasis (PM) from colorectal cancer (CRC). The type of relationship between survival and the PM time of detection was used to determine whether it was synchronous with the primary tumor or metachronous. Patients and Methods: Retrospective observational study. It included patients treated for colorectal adenocarcinoma diagnosed between January 2005 and December 2019 who presented PM at the time of diagnosis or during follow-up. Variables, such as sex, age, differentiation grade, positive adenopathy (pN+), tumor size (pT), tumor location, mucinous component, peritoneal carcinomatosis index (PCI), and KRAS mutational status, were analyzed. Results: During the study period, 1882 patients were surgically treated for CRC in our hospital. Of these, 240 patients (12.8%) were included in the study after evidence of PM. The mean age was 67 ± 12 years (range: 32–92 years), and 114 patients were female (47.5%). The mean follow-up was 20 ± 13 months (median 12 months). The Kaplan–Meier survival at 36 months was higher in patients with metachronous PM (24% vs. 8%; p = 0.002), WT-KRAS tumors (31% vs. 15%; p < 0.001), N0 stage (30% vs. 19%; p < 0.001), T3 stage tumors (18% vs. 19% in T4A and 3% in T4B; p > 0.001), and tumors with classic adenocarcinoma histology (18% vs. 8%; p = 0.011). Patients with a PCI of 1–10 showed a likelihood of survival at 36 months of 56%, which was longer than that found in patients with a PCI of 11–20 (8%) or a PCI of >20 (0%) (p < 0.001). In the multiple regression analysis, the factors with an independent prognostic value were: poor grade of differentiation (HR 1.995; 95% CI: 1.294–3.077), KRAS mutation (HR 1.751; 95% CI: 1.188–2.581), PCI 11–20 (HR: 9.935; 95% CI: 5.204–18.966) and PCI > 20 (HR: 4.011; 95% CI: 2.291–7.023). Conclusions: PCI should continue as the as the most useful prognostic indicator in order to assess prognostic estimations as well as therapeutic and surgical decisions, but tumor grade and KRAS mutational status may help in the treatment decision process by providing complementary information. The time of PM detection did not achieve statistical significance in the multiple regression analysis.

Preeclampsia (PE) is a complex multisystem disease characterized by hypertension of sudden onset (>20 weeks’ gestation) coupled with the presence of at least one additional complication, such as proteinuria, maternal organ dysfunction, or uteroplacental dysfunction. Hypertensive states during pregnancy carry life-threatening risks for both mother and baby. The pathogenesis of PE develops due to a dysfunctional placenta with aberrant architecture that releases factors contributing to endothelial dysfunction, an antiangiogenic state, increased oxidative stress, and maternal inflammatory responses. Previous studies have shown a correlation between grade 3 placental calcifications and an elevated risk of developing PE at term. However, little is known about the molecular pathways leading to placental calcification. In this work, we studied the gene and protein expression of c-Jun N-terminal kinase (JNK), Runt-related transcription factor 2 (RUNX2), osteocalcin (OSC), osteopontin (OSP), pigment epithelium-derived factor (PEDF), MSX-2/HOX8, SOX-9, WNT-1, and β-catenin in placental tissue from women with late-onset PE (LO-PE). In addition, we employed von Kossa staining to detect mineral deposits in placental tissues. Our results show a significant increase of all these components in placentas from women with LO-PE. Therefore, our study suggests that LO-PE may be associated with the activation of molecular pathways of placental calcification. These results could be the starting point for future research to describe the molecular mechanisms that promote placental calcification in PE and the development of therapeutic strategies directed against it.

Klotho, initially identified as an anti-aging gene, has been shown to play significant roles in cancer biology. Alongside α-Klotho, the β-Klotho and γ-Klotho isoforms have also been studied; these studies showed that Klotho functions as a potential tumor suppressor in many different cancers by inhibiting cancer cell proliferation, inducing apoptosis and modulating critical signaling pathways such as the Wnt/β-catenin and PI3K/Akt pathways. In cancers such as breast cancer, colorectal cancer, hepatocellular carcinoma, ovarian cancer, and renal cell carcinoma, reduced Klotho expression often correlates with a poor prognosis. In addition, Klotho’s role in enhancing chemotherapy sensitivity and its epigenetic regulation further underscores its potential as a target for cancer treatments. This review details Klotho’s multifaceted contributions to cancer suppression and its potential as a therapeutic target, enhancing the understanding of its significance in cancer treatment and prognoses.