Search Results (2,270)

Background/Objectives: Postoperative cognitive dysfunction (POCD) represents a significant and potentially preventable complication in elderly patients undergoing colorectal cancer surgery, with reported incidence ranging from 2.8% to 62.2% depending on perioperative management strategies and assessment methods. This narrative review synthesizes current evidence on the epidemiology, pathophysiology, risk factors, and prevention strategies for POCD in this vulnerable population. Methods: A comprehensive narrative review was conducted to examine the current literature on POCD in elderly colorectal cancer patients. Evidence was synthesized from published studies addressing epidemiology, assessment tools, risk factors, pathophysiological mechanisms, and prevention strategies, with a particular focus on Enhanced Recovery After Surgery (ERAS) protocols and multicomponent interventions. Results: Advanced age, pre-existing cognitive impairment, frailty, and surgical complexity emerge as key risk factors for POCD. ERAS protocols demonstrate substantial protective effects, reducing POCD incidence from 35% under conventional care to as low as 2.8% in optimized pathways. The pathophysiology involves multifactorial mechanisms, including neuroinflammation, blood–brain barrier disruption, neurotransmitter dysregulation, and oxidative stress, with surgical trauma triggering systemic inflammatory cascades that activate microglial responses within the central nervous system. Evidence-based prevention strategies include preoperative cognitive and frailty screening, minimally invasive surgical techniques, multimodal opioid-sparing analgesia, regional anesthesia, depth-of-anesthesia monitoring, and structured postoperative care bundles adapted from the Hospital Elder Life Program. Conclusions: The integration of comprehensive perioperative cognitive care protocols represents a critical priority as surgical volumes in elderly populations continue to expand globally. Emerging directions include biomarker development for early detection and risk stratification, precision medicine approaches targeting individual vulnerability profiles, and novel therapeutic interventions addressing neuroinflammatory pathways. Standardized assessment tools, multidisciplinary collaboration, and implementation of evidence-based preventive interventions offer substantial promise for preserving cognitive function and improving long-term quality of life in elderly colorectal cancer patients. Full article

Triple-negative breast cancer (TNBC) is an aggressive and clinically challenging subtype of breast cancer characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression. This molecular phenotype narrows the availability of targeted therapies and contributes to high rates of early relapse, therapeutic resistance, and poor clinical outcomes. Mounting evidence pinpoints the tumor microenvironment (TME) as a central driver of TNBC progression, immune evasion, and resistance to treatment. The TME encompasses a complex and dynamic network of immune and stromal cells, extracellular matrix components, and soluble mediators that collectively shape tumor behavior and influence therapeutic response. Notably, TNBC often displays an immunologically active microenvironment, marked by high levels of tumor-infiltrating lymphocytes and immune checkpoint expression, opening a window for immune-based therapeutic strategies. This narrative review summarizes current knowledge on the cellular, molecular, and structural features of the TNBC tumor microenvironment, with particular focus on immunosuppressive mechanisms mediated by tumor-associated macrophages, myeloid-derived suppressor cells, cancer-associated fibroblasts, and dysfunctional T cells. We describe the clinical development and therapeutic impact of monoclonal antibodies, including immune checkpoint inhibitors and antibody–drug conjugates. Additionally, we discuss strategies aimed at modulating the TME to enhance monoclonal antibody efficacy, including immune cell reprogramming, extracellular matrix remodeling, cytokine/chemokine blockade, and combination treatment strategies. Finally, we highlight the role of biomarker-driven patient stratification and personalized therapeutic strategies, addressing current challenges and future directions in TME-targeted drug development. Together, these insights underscore the potential of integrating immune modulation and monoclonal antibody-based therapies to improve outcomes for TNBC patients. Full article

Urothelial carcinoma represents one of the deadliest urological tumors, due to its biological aggressiveness and the ephemeral response to platinum-based chemotherapy of advanced-stage disease. The use of immune checkpoint inhibitors has positively impacted the prognosis of these patients, although only a proportion of them achieve long lasting disease control. As with other solid tumors, in the last decade, there has been a growing interest in the molecular characterization of urothelial carcinoma in order to identify new therapeutic targets and improve survival in these patients. The aim of this narrative review is to summarize the main evidence available in the literature concerning the role of targeted therapies in urothelial carcinoma, especially focusing on related molecular targets, published data on clinical efficacy, and on future perspectives. Specifically, the effort of this review aims to strengthen the clinical impact of well-known molecular patterns and relative target treatments (such as FGFR inhibitors and Nectin-4-directed antibody–drug conjugates) and to examine the role and preliminary data of drugs targeting biomarkers that are not yet commonly used in clinical practice (such as HER2). Full article

Parkinson’s disease (PD) has been associated with some types of food and drugs. Here, we query PubMed for the association of PD with foods and drugs, using a list of 217,776 compounds derived from the Human Metabolome Database (HMDB). To calculate associations, a Python script was developed to query PubMed for co-citations of PD with each compound, and adjust this count for compound abundance. Notably, PD is found to be associated with small-molecule drugs, adjunctive therapies, contraindicated drugs, diagnostic agents, biomarkers, conditional essential molecules, and inducers. Drugs include L-dopa (49%), carbidopa (63%), benserazide (50%), entacapone (74%), tolcapone (56%), rasagiline (76%), selegiline (46%), pargyline (4%), ropinirole (61%), pramipexole (56%), lisuride (27%), cabergoline (16%), bromocriptine (12%), and zonisamide (9%). Adjunctive therapies include droxidopa (33%), trihexyphenidyl (28%), biperiden (17%), amantadine (24%), memantine (7%), rivastigmine (13%), donepezil (6%), galantamine (4%), domperidone (6%), clonazepam (4%), tetrabenazine (16%), mazindol (13%), quetiapine (6%), and clozapine (4%). Contraindicated drugs include haloperidol (4%), sulpiride (3%), and methyldopa (6%). Diagnostic agents include FP-CIT (60%) and beta-CIT (43%). Biomarkers include 3-methoxytyrosine (48%) and homovanillic acid (12%). Endogenous cofactors include tetrahydrobiopterin (4%) and Coenzyme Q10 (4%). Chemical inducers of PD include 6-hydroxydopamine (40%), N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 78%), tetrahydropyridine (77%), probenecid (4%), quinolinic acid (4%), 1,2,3,4-tetrahydroisoquinoline (TIQ, 16%), salsolinol (32%), rotenone (25%), and β-Methylamino-L-alanine (BMAA, 29%). Notably, our study highlights conditional essential endogenous cofactors associated with PD and emphasizes rational directions for investigation in PD. Full article

Sarcopenia, defined as the progressive decline of muscle mass, strength, and function, severely compromises autonomy and quality of life in older adults. This systematic review evaluated synergistic effects of protein supplementation combined with resistance exercise on biochemical and functional biomarkers of sarcopenia. The search for scientific evidence was conducted in PubMed, Scopus, ScienceDirect, and Cochrane databases (2019–2025), applying explicit inclusion and exclusion criteria, like only randomized controlled trials in humans, published in English, Spanish, or French, were included to ensure high-quality evidence. After selection, the risk of bias of the articles was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions. Seven randomized controlled trials, with a total of 260 participants, met the eligibility criteria. Interventions combining resistance exercise three times per week at 60–80% of one-repetition maximum with daily protein supplementation of at least 15 g, mainly from dairy sources, showed synergistic effects. Improvements were observed in inflammatory and anabolic biomarkers, with reductions in myostatin, activin, and IL-6, and increases in IGF-1, follistatin, and IL-10. Functional outcomes included gains in muscle strength, fat-free mass, and muscle fiber cross-sectional area. Despite heterogeneity in duration and sample size, findings support this combined approach as a promising and clinically applicable strategy to prevent and treat sarcopenia. No external funding was received, and the review is registered in PROSPERO (CRD42025640989). Full article

Background: Melanoma outcomes have improved in recent years as a result of modern systemic therapies. A major molecular feature of melanoma is abnormal telomerase activation; this is most often caused by telomerase reverse transcriptase (TERT) promoter mutations, which occur in 50–82% of cases and are the most common noncoding alteration in this cancer. Telomerase maintains telomere length, allowing melanoma cells to avoid senescence and continue dividing. However, how telomerase activity influences melanoma cell doubling time remains unclear, and the pathways linking TERT expression to faster cell-cycle progression require further study. Although telomerase inhibitors show promise in preclinical models, their clinical use is limited by delayed cytotoxicity and resistance. Materials and Methods: A scoping review was conducted using Scopus, ScienceDirect, MEDLINE/PubMed, and CINAHL (Cumulative Index to Nursing and Allied Health Literature). Keywords included “telomerase,” “melanoma,” “cancer,” “cell proliferation,” and “doubling time,” using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Telomerase-related biomarkers were found to correlate with disease stage and survival. Suggested therapeutic strategies include enzyme inhibitors, cytotoxic nucleotide incorporation, telomere destabilization, and immunotherapies such as peptide or dendritic cell vaccines, etc. Conclusions: Understanding both telomere-dependent and -independent TERT functions is essential for developing effective biomarkers and therapies that overcome resistance and slow melanoma progression. Full article

Lung cancer remains a major public health challenge due to high incidence and mortality. The chemokine receptor CXCR4 and its ligand CXCL12 (SDF-1) constitute a critical axis in tumor biology, influencing tumor cell proliferation, invasion, angiogenesis, and immune evasion. Aberrant CXCR4 expression is frequently observed in lung cancer and is closely associated with adverse prognosis, enhanced metastatic potential, and therapeutic resistance. Mechanistically, CXCR4 activates signaling pathways including PI3K/AKT, MAPK/ERK, JAK/STAT, and FAK/Src, promoting epithelial–mesenchymal transition, stemness, and survival. The CXCL12/CXCR4 axis also orchestrates interactions with the tumor microenvironment, facilitating chemotaxis toward CXCL12-rich niches (e.g., bone marrow and brain) and modulating anti-tumor immunity via regulatory cells. Regulation of CXCR4 occurs at transcriptional, epigenetic, and post-transcriptional levels, with modulation by hypoxia, inflammatory signals, microRNAs, and post-translational modifications. Clinically, high CXCR4 expression correlates with metastasis, poor prognosis, and reduced response to certain therapies, underscoring its potential as a prognostic biomarker and therapeutic target. Therapeutic strategies targeting CXCR4 include small-molecule antagonists (e.g., AMD3100/plerixafor; balixafortide), anti-CXCR4 antibodies, and CXCL12 decoys, as well as imaging probes for patient selection and response monitoring (e.g., 68Ga-pentixafor PET). Preclinical and early clinical studies suggest that CXCR4 blockade can impair tumor growth, limit metastatic spread, and enhance chemotherapy and immunotherapy efficacy, although hematopoietic side effects and infection risk necessitate careful therapeutic design. This review synthesizes the molecular features, regulatory networks, and translational potential of CXCR4 in lung cancer and discusses future directions for precision therapy and biomarker-guided intervention. Full article

Tumor-associated glycosylation is a defining hallmark of cancer, exerting profound effects on multiple aspects of tumor biology. This phenomenon arises from the central role of glycosylation in a wide range of cellular processes and its inherently diverse structural complexity. In cancer cells, aberrant glycosylation often results in the modification of glycoconjugate structures, leading to alterations in cell surface architecture that disrupt cellular homeostasis and signaling pathways. These changes can enhance tumor cell proliferation, invasion, and metastasis by modulating cell adhesion, receptor activation, and intracellular communication. Beyond its direct impact on cancer cells, tumor-associated glycosylation plays a pivotal role in shaping the tumor microenvironment. Aberrant glycan structures influence immune cell infiltration by altering antigen presentation and immune checkpoint interactions, contributing to immune evasion. Additionally, these modifications regulate angiogenesis by affecting endothelial cell function and promoting the formation of aberrant vasculature, which supports tumor growth and metastasis. Glycosylation also mediates tumor–stroma interactions, influencing extracellular matrix remodeling and fibroblast activation, further enhancing cancer progression. This interplay between cancer-associated glycan modifications and their functional roles in tumorigenesis presents a promising therapeutic approach. Unlike conventional treatments, glycan-targeting therapies confer high tumor specificity, operate independently of canonical immune checkpoint targets, and help mitigate immune cell exhaustion. This review explores commonly dysregulated glycan motifs implicated in tumorigenesis and delves into their mechanistic contributions to cancer pathogenesis. We then highlight emerging opportunities for therapeutic intervention, including the development of glycan-targeted therapies and biomarker-driven strategies for cancer diagnosis and treatment. We also outline where glycan-targeted agents (e.g., desialylating biologics, glycomimetics, and anti-glycan mAbs) can complement checkpoint blockade and potentially overcome immune escape. Full article

Cardiac transplantation remains an important therapy for end-stage heart failure, although allograft rejection continues to pose significant clinical challenges. This review evaluates both established and emerging blood-based biomarkers for noninvasive monitoring of rejection in heart transplant recipients. Donor-derived cell-free DNA (ddcfDNA) and gene expression profiling (GEP) represent well-validated, commercially available molecular tools that demonstrate strong discriminative capacity for acute rejection episodes. Additionally, microRNAs (miRs) and extracellular vesicles (EVs) show considerable potential as novel biomarkers, although further validation is required. In contrast, conventional biomarkers such as B-type natriuretic peptide (BNP), cardiac troponins, and creatine kinase-MB (CK-MB) offer limited specificity in the context of rejection. This review synthesizes current evidence on the clinical utility, methodological challenges, and integration strategies of these biomarkers, highlighting a shift toward molecular-based approaches for improving post-transplant surveillance and patient outcomes. Full article

Field cancerization is a fundamental paradigm in tumorigenesis, emphasizing that carcinogenesis begins long before the appearance of clinically detectable lesions and often precedes recognizable premalignant changes. A direct manifestation of this process is the molecular dysregulation observed in the peritumoral mucosa—histologically normal-appearing tissue that nonetheless exhibits genetic and epigenetic alterations similar to those of the adjacent tumor. This review summarizes current evidence on the molecular alterations shared between tumor tissue and peritumoral mucosa in HNSCC and evaluates their potential as biomarkers for defining molecular margins and improving surgical precision. A literature search was conducted in PubMed using combinations of the keywords “peritumor,” “laryngeal”, “HNSCC,” and “field cancerization.” Studies were included if they directly compared tumor tissue with peritumoral mucosa and, preferably, a third set of distant normal control samples. Only nine studies met the inclusion criteria, highlighting the scarcity of focused research in this area. Reported biomarkers exhibiting comparable dysregulation in both tumor and peritumor tissues include MDM2, E2F2, CDKN2A/p16, ETS-1, MGMT, and multiple microRNAs (e.g., miR-21, miR-96-5p, miR-145-5p). These molecular signatures demonstrate the presence of a biologically altered field extending beyond histologically defined tumor margins. Peritumoral mucosal dysregulation, as a consequence of field cancerization, underscores the need to redefine surgical margins at the molecular level. The identification and validation of biomarkers reflecting this continuum could enable the establishment of molecular margins—improving risk assessment, reducing local recurrence, and advancing personalized oncologic surgery in HNSCC. Standardizing definitions and sampling protocols for “normal adjacent tissue” remains essential for future translational research. Full article

Diet plays a central role in shaping the composition and metabolic activity of the oral microbiota, thereby influencing both oral and systemic health. Disturbances in this delicate host–microbe balance, triggered by dietary factors, smoking, poor oral hygiene, or antibiotic use, can lead to microbial dysbiosis and increase the risk of oral diseases such as periodontitis, as well as chronic systemic disorders including diabetes, cardiovascular disease, Alzheimer’s disease, and certain cancers. Among dietary contaminants, exposure to toxic heavy metals such as cadmium (Cd), lead (Pb), mercury (Hg), nickel (Ni), and arsenic (As) represents an underrecognized modifier of the oral microbial ecosystem. Even at low concentrations, these elements can disrupt microbial diversity, promote inflammation, and impair metabolic homeostasis. Saliva has recently emerged as a promising, non-invasive biofluid for monitoring nutritional status and early metabolic alterations induced by diet and environmental exposures. Salivary biomarkers, including metabolites, trace elements, and microbial signatures, offer potential for assessing the combined effects of diet, microbiota, and toxicant exposure. This review synthesizes current evidence on how diet influences the oral microbiota and modulates susceptibility to heavy metal toxicity. It also examines the potential of salivary biomarkers as integrative indicators of nutritional status and metabolic health, highlights methodological challenges limiting their validation, and outlines future research directions for developing saliva-based tools in personalized nutrition and precision health. Full article

This study explores crude oil as a chemically and structurally heterogeneous system with potential pharmaceutical relevance beyond its established roles as an energy and feedstock resource. Recent advances in analytical technologies have enabled the detailed characterization of crude oil constituents at the molecular level, thereby linking structural features to physicochemical properties and possible biological activities. The presented analysis outlines the rationale, methodological considerations, and future research directions for integrating crude oil molecular motifs into the pharmaceutical chemical space. Beyond its conventional role as an industrial and energy resource, crude oil may also hold promise for drug discovery. This study seeks to provide a conceptual framework for reconsidering crude oil as a reservoir of pharmacologically relevant scaffolds and to outline methodological approaches for their systematic assessment. Its rigid sp³-rich frameworks, together with sterane/hopane biomarkers, porphyrins, and functional aromatics, structurally overlap with established therapeutic classes and are naturally present in crude oil in suitable abundance, offering opportunities to reduce synthetic effort and expand the chemical space accessible to drug discovery. Advances in petroleomics and in silico methodologies now enable petroleum-derived constituents to be characterized in terms of drug-likeness, bioactivity, and toxicity, providing a framework to reconsider crude oil as an unconventional but analytically and computationally tractable resource for pharmaceutical research. Full article

Background: Thymic epithelial tumors (TETs), including thymic carcinomas and thymomas, are rare malignancies originating in the mediastinum. Therapeutic options remain limited for patients experiencing disease progression following platinum-based chemotherapy. High tumor mutational burden (TMB) is uncommon in thymic malignancies but may predict response to immunotherapy. We report a patient with TMB-high TET who participated in the KOSMOS-II study in South Korea and achieved a durable response to atezolizumab without developing immune-related adverse events (irAEs). Case presentation: A 73-year-old woman who had been treated for thymoma 20 years ago presented with a left neck mass. A biopsy of the neck mass confirmed recurrent thymoma, type B3, and her disease progressed despite platinum-based chemotherapy and subsequent pemetrexed treatment. TMB-high thymoma is very rare, but based on the next-generation sequencing (NGS) results, she was diagnosed with TMB-high (20.3 mutations/Mb) thymoma. As TMB-based immunotherapy is not approved in Korea, she was enrolled in the KOSMOS-II study and initiated on atezolizumab following molecular tumor board review. She achieved stable disease after three cycles and has remained progression-free for 14 months, completing 20 cycles without significant irAEs. Notably, her underlying myasthenia gravis did not worsen during treatment. Conclusions: This case demonstrates a favorable outcome with biomarker-directed ICI treatment in recurrent thymoma with limited treatment options, highlighting the importance of appropriate molecular markers to predict drug response. Although TMB-based immunotherapy is FDA-approved in the U.S., it remains unavailable in Korea, underscoring the need to explore flexible access pathways, including the potential use of immunotherapy beyond current indications, to improve treatment options for patients with life-threatening conditions. Full article

Background/Objectives: Energy availability (EA), defined as the dietary energy remaining after exercise energy expenditure (EEE), is a central determinant of both health and performance in athletes. Chronic insufficient EA leads to low energy availability (LEA), which is an underlying mechanism of Relative Energy Deficiency in Sport (REDs). This narrative review critically explores the conceptual evolution of EA and LEA, summarizes current physiological evidence, and discusses methodological and practical challenges in their assessment and application in free-living athletes. Methods: Evidence from experimental and observational studies was reviewed to describe the hormonal, metabolic, and performance outcomes associated with LEA. Screening tools, including the Low Energy Availability in Females Questionnaire (LEAF-Q) and the Low Energy Availability in Males Questionnaire (LEAM-Q), were also evaluated for their validity and applicability in different sports contexts. Results: LEA is associated with alterations in thyroid and reproductive hormones, which, in turn, contribute to reduced resting metabolic rate, lower bone mineral density, and delayed recovery. While screening questionnaires can help identify athletes at risk, their accuracy varies by sport and individual characteristics. Incorporating hormonal and metabolic biomarkers provides a more direct and sensitive method for detecting physiological stress. Measuring dietary intake, EEE, endocrine balance and body composition in real-world settings remains a major methodological challenge. Combining hormonal, metabolic, and behavioral indicators may improve the identification of athletes experiencing LEA. Conclusions: EA plays a central role in the interaction between nutrition, exercise, and athlete health, but methodological limitations in its assessment may compromise accurate diagnosis. Improving measurement techniques and adopting integrated monitoring strategies are essential to improve early detection, guide individualized nutrition, and prevent RED-related health and performance impairments. Full article

Epilepsy remains an active and important area of research due to its complex etiology, significant global burden, and variable response to treatment. Current knowledge has provided valuable insights into the underlying molecular mechanisms of the disease and continues to guide the development of novel therapeutic strategies. This review presents a comprehensive overview of the etiologies of epilepsy, as well as traditional and modern medical and surgical treatment approaches, while highlighting future research directions. Peer-reviewed articles retrieved from PubMed and Google Scholar were analyzed and synthesized to produce this review. The etiological complexity of epilepsy arises from genetic, metabolic, structural, and inflammatory mechanisms, which often coexist rather than act independently. A wide range of anti-seizure drugs (ASDs) is currently available, with many new agents targeting novel mechanisms under development. Surgical approaches, including resection, disconnection, corpus callosotomy, and neuromodulation, are widely used for patients with drug-resistant epilepsy and result in variable seizure outcomes. In addition, minimally invasive techniques such as laser interstitial thermal therapy (LITT), stereoelectroencephalography-guided radiofrequency thermocoagulation, gamma knife radiosurgery, and high-intensity focused ultrasound have gained clinical relevance and continue to be explored. Emerging technologies, including artificial intelligence, machine learning, and precision medicine, offer promising directions for future research. Although several potential biomarkers have been identified, none are yet established for routine clinical use. Continued investigation is essential to improve understanding of epileptogenesis and to develop safer, more effective therapies. Full article