Post-translational modifications (PTMs) of proteins dynamically build the buffering and adapting interface between oncogenic mutations and environmental stressors, on the one hand, and cancer cell structure, functioning, and behavior. Aberrant PTMs can be considered as enabling characteristics of cancer as long as they orchestrate all malignant modifications and variability in the proteome of cancer cells, cancer-associated cells, and tumor microenvironment (TME). On the other hand, PTMs of proteins can enhance anticancer mechanisms in the tumoral ecosystem or sustain the beneficial effects of oncologic therapies through degradation or inactivation of carcinogenic proteins or/and activation of tumor-suppressor proteins. In this review, we summarized and analyzed a wide spectrum of PTMs of proteins involved in all regulatory mechanisms that drive tumorigenesis, genetic instability, epigenetic reprogramming, all events of the metastatic cascade, cytoskeleton and extracellular matrix (ECM) remodeling, angiogenesis, immune response, tumor-associated microbiome, and metabolism rewiring as the most important hallmarks of cancer. All cancer hallmarks develop due to PTMs of proteins, which modulate gene transcription, intracellular and extracellular signaling, protein size, activity, stability and localization, trafficking, secretion, intracellular protein degradation or half-life, and protein–protein interactions (PPIs). PTMs associated with cancer can be exploited to better understand the underlying molecular mechanisms of this heterogeneous and chameleonic disease, find new biomarkers of cancer progression and prognosis, personalize oncotherapies, and discover new targets for drug development.

Alzheimer’s disease (AD) is primarily recognized for progressive cognitive decline driven by beta-amyloid accumulation and tau pathology. However, many individuals with AD also experience chronic pain and depressive symptoms, which significantly impair daily functioning and quality of life and increase caregiver burden. These non-cognitive features are frequently underrecognized, despite evidence suggesting they share overlapping biological pathways with neurodegeneration. Emerging data highlight the role of neuroinflammation, oxidative stress, hypothalamic–pituitary–adrenal axis dysregulation, and endocannabinoid system alterations in linking AD pathology to disturbances in pain processing and mood regulation. Persistent microglial activation, cytokine imbalance, redox disruption, and chronic stress signaling may simultaneously promote neuronal vulnerability while shaping affective and nociceptive responses. This review synthesizes current preclinical and clinical evidence on the interplay between pain, depression, and AD, emphasizing their shared pathophysiological mechanisms and clinical relevance. Recognizing these symptoms as integral components of disease progression, rather than isolated comorbidities, can inform the development of integrated, multidimensional therapeutic strategies in AD care.

Background: Wound healing remains a major clinical challenge, often impaired by persistent inflammation, oxidative stress, and abnormal extracellular matrix remodeling. Electrospun nanofibers (NFs) have emerged as promising wound dressing platforms due to their biomimetic structure and capacity to incorporate multiple bioactive compounds (ACs) with synergistic therapeutic effects. Objectives: This study aimed to biologically assess novel chitosan/poly(vinyl alcohol) (CH/PVA) NFs functionalized with natural active compounds (L-arginine—ARG, allantoin—ALA, royal jelly—RJ, and curcumin—CUR) as multifunctional systems for wound healing and tissue remodeling. Methods: The nanofibrous systems performed the in vitro evaluation of antioxidant activity (DPPH, ABTS, FRAP, PRAP), anti-inflammatory potential (protein denaturation test), hemocompatibility, and cytocompatibility using dermal fibroblasts. In vivo healing performance was evaluated in an excisional wound model using macroscopic wound contraction analysis, histopathology, and immunohistochemical staining (MMP-9, CD31, VEGF-A, α-SMA). Results: The bioactive-enriched CH/PVA NFs exhibited strong antioxidant and anti-inflammatory activity, excellent hemocompatibility (hemolysis < 5%), and excellent cytocompatibility, with promoting fibroblast proliferation. In vivo experiments revealed that the treated groups exhibited accelerated wound closure, improved re-epithelialization, increased angiogenesis, and showed more efficient tissue remodeling compared to the controls, as validated by histological and immunohistochemical studies. Conclusions: The findings indicate that bioactive-enriched CH/PVA NFs serve as effective, biocompatible, and multifunctional matrices for wound healing, hence endorsing their potential for further translational advancement in skin regeneration applications.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by β-amyloid (Aβ) deposition, tau pathology and cognitive decline. Increasing evidence from genetic, transcriptomic, experimental and clinical studies has identified microglia as key regulators of AD pathogenesis. Under physiological conditions, microglia maintain central nervous system homeostasis through immune surveillance, phagocytosis and neurotrophic support. However, persistent exposure to pathological stimuli promotes a shift toward dysfunctional inflammatory states that contribute to neuroinflammation, synaptic impairment, tau propagation and neurodegeneration. Recent advances have revealed substantial microglial heterogeneity, highlighting the existence of dynamic and disease stage-dependent activation states rather than fixed phenotypes. In early disease stages, microglia can promote Aβ clearance and tissue repair, whereas chronic activation may exacerbate pathological processes. These findings have driven the development of microglia-targeted therapeutic strategies aimed at enhancing protective functions while limiting maladaptive inflammatory responses. This review summarizes current knowledge regarding microglial involvement in AD and discusses emerging therapeutic approaches, ranging from immunomodulation and metabolic reprogramming to gene-based and nanotechnology-driven interventions, with a focus on their translational potential.

Background: Intracerebral administration of amyloid-β (Aβ) peptides remains a widely used experimental approach for modeling key neurochemical features of Alzheimer's disease (AD), including neuroinflammation, oxidative stress, and synaptic dysfunction. Among these models, Aβ ₁₋₄₂ and Aβ ₁₋₄₀ are most frequently employed. However, their effects are often treated as interchangeable despite recognized differences in aggregation behavior and biological activity. Objective: This systematic review aimed to synthesize evidence on how peptide selection between Aβ ₁₋₄₂ and Aβ ₁₋₄₀ shapes neurochemical outcomes in intracerebral rat models of AD. Methods: The review was conducted in accordance with PRISMA guidelines and registered in PROSPERO. A structured search identified in vivo rat studies using Aβ ₁₋₄₂ or Aβ ₁₋₄₀ . Given methodological heterogeneity, findings were synthesized using a qualitative framework. To address potential structural confounding, stratified analyses were performed according to injection route and aggregation state. Results: Eighty-three studies met inclusion criteria (Aβ ₁₋₄₂ = 60; Aβ ₁₋₄₀ = 23). Across neurochemical domains, Aβ ₁₋₄₂ was more frequently associated with earlier and glial activation, increased pro-inflammatory mediators, oxidative imbalance, and synaptic alterations, often accompanied by behavioral deficits. In contrast, Aβ ₁₋₄₀ models showed a more variable and generally attenuated neurochemical response with greater dependence on experimental parameters. Structural analyses indicated clustering by injection route, whereas aggregation-state distribution was not statistically skewed between peptides. Conclusions: The available evidence suggests that Aβ ₁₋₄₂ and Aβ ₁₋₄₀ should not be assumed interchangeable without explicit methodological consideration. Observed differences appear context-dependent and influenced by experimental design variables. Peptide selection with defined mechanistic objectives may enhance interpretability and translational relevance in preclinical AD research.

Background: Standardized and ethically compliant animal models remain essential for improving translational research in Alzheimer’s disease. Although Aβ_1–42-induced rodent models are widely used, methodological variability continues to limit reproducibility. Methods: We explored the feasibility of a stereotactic intrahippocampal Aβ_1–42 rat model established by bilaterally injecting pre-aggregated peptide into the hippocampus of adult Sprague Dawley rats. Model feasibility and targeting accuracy were assessed intraoperatively. Cognitive performance was evaluated using the Y-maze for spatial recognition memory and the novel object recognition (NOR) test. Histological examination was performed using hematoxylin–eosin (H&E) and Congo red staining to assess cytoarchitecture and to provide supportive evidence of amyloid-like deposits. Results: The surgical procedure was well-tolerated, and the injected animals showed reduced performance in behavioural testing, including reduced spatial recognition memory in the Y-maze and decreased discrimination indices in the NOR test. The animals also showed histological changes, including Congo red-positive birefringent structures consistent with amyloid-like congophilic material. Conclusions: This study presents a feasible experimental framework for intrahippocampal Aβ_1–42 administration, showing behavioural and histological changes under the present experimental conditions. However, further validation, including sham-operated controls and molecular characterization, will be required before these findings can be interpreted as specific to Aβ-driven pathology.