Search Results (2,649)

Metastases are responsible for the majority of cancer-related deaths and remain one of the most complex and therapeutically challenging hallmarks of cancer. The metastatic cascade involves a multistep process by which cancer cells invade local tissue, enter and survive in circulation, extravasate, and ultimately colonize distant organs. Increasingly, the tumor microenvironment (TME), particularly the extracellular matrix (ECM), has emerged as a central regulator of these steps. Far from being a passive scaffold, the ECM actively influences cancer progression through its biochemical signals, structural properties, and dynamic remodeling. Among ECM components, collagens play a particularly pivotal role by mediating tumor cell adhesion, migration, invasion, survival, immune evasion, and therapeutic resistance. This narrative review synthesizes current knowledge of the dual roles of collagen in the metastatic process, with a focus on the cellular and molecular mechanisms. We highlight how altered ECM architecture and signaling contribute to metastatic niche formation and explore the potential of targeting ECM components as a strategy to enhance cancer therapy and improve patient outcomes. Full article

This autoethnographic study examines my transformation as an educator teaching gender and sexuality to future helping professionals in South African higher education. Through systematic analysis of personal journals, teaching reflections, and pedagogical materials collected over 180 contact hours, I explore how innovative approaches can create collaborative learning environments in traditionally sensitive subject areas. Drawing on critical pedagogy, queer theory, and decolonizing methodologies, the research reveals three interconnected pedagogical innovations: structured vulnerability protocols that transcend traditional “safe space” models, progressive exposure pedagogy that challenges heteronormative assumptions by introducing diverse content early, and indigenous knowledge integration that positions students as knowledge co-creators. The findings demonstrate how my professional evolution from knowledge authority to learning facilitator enabled authentic engagement with diverse epistemologies while maintaining academic rigor. Students consistently contributed concepts absent from academic literature—from social media discourse about sexual identity hierarchies to traditional cultural practices—enriching collective understanding. This study addresses significant gaps in South African literature on tertiary-level sexuality education pedagogy, offering concrete strategies for implementing transformative approaches. The research contributes to autoethnographic scholarship by demonstrating how systematic reflection can generate theoretical insights about collaborative knowledge construction while acknowledging the ongoing challenges of teaching sensitive subjects within complex cultural contexts. Full article

Fusobacterium nucleatum (Fn) has been increasingly recognized as a crucial mediator of colorectal cancer (CRC) biology, particularly in microsatellite-stable (MSS) tumors, where immune checkpoint inhibitors (ICIs) have shown limited efficacy. Rather than representing a passive microbial passenger, Fn actively shapes tumor behavior by adhering to epithelial cells, activating oncogenic signaling, and promoting epithelial–mesenchymal transition (EMT). At the same time, it remodels the tumor microenvironment, driving immune suppression through inhibitory receptor engagement, accumulation of myeloid-derived cells, and metabolic reprogramming of tumor-associated macrophages. These mechanisms converge to impair cytotoxic immunity and contribute to both intrinsic and acquired resistance to ICIs. Beyond immune escape, Fn interferes with conventional chemotherapy by sustaining autophagy and blocking ferroptosis, thereby linking microbial colonization to multidrug resistance. Most of these mechanisms derive from preclinical in vitro and in vivo models, where causal relationships can be inferred. In contrast, human data are mainly observational and provide correlative evidence without proving causality. No interventional clinical studies directly targeting Fn have yet been conducted. Its enrichment across the adenoma–carcinoma sequence and consistent detection in both tumor and fecal samples highlight its potential as a biomarker for early detection and patient stratification. Importantly, multidimensional stool assays that integrate microbial, genetic, and epigenetic markers are emerging as promising non-invasive tools for CRC screening. Therapeutic strategies targeting Fn are also under exploration, ranging from antibiotics and bacteriophages to multifunctional nanodrugs, dietary modulation, and natural microbiota-derived products. These approaches may not only reduce microbial burden but also restore immune competence and enhance the efficacy of immunotherapy in MSS CRC. Altogether, current evidence positions Fn at the intersection of microbial dysbiosis, tumor progression, and therapy resistance. A deeper understanding of its pathogenic role may support the integration of microbial profiling into precision oncology frameworks, paving the way for innovative diagnostic and therapeutic strategies in CRC. Full article

Two-pore channel 2 (TPC2) is a member of the endolysosomal ion channel family, playing critical roles in intracellular calcium signaling and endomembrane dynamics. This review provides an in-depth analysis of TPC2, covering its structural and functional properties, physiological roles, and involvement in human diseases. We discuss current experimental approaches to studying TPC2, including heterologous expression in plant vacuoles and computational modeling strategies. Particular emphasis is placed on the structural determinants of ion permeation, with a focus on the selectivity filter and the central cavity’s influence on channel kinetics. Furthermore, we explore emerging roles of TPC2 in viral infections, particularly SARS-CoV-2, and in cancer, including melanoma progression and neoangiogenesis. The inhibitory potential of natural compounds, such as naringenin, is also examined. By offering a comprehensive overview of current knowledge and methodologies, this review underscores the potential of TPC2 as a promising pharmacological target in both infectious and neoplastic diseases. Full article

Oxidative stress and inflammation are deeply interconnected processes implicated in the onset and progression of numerous chronic diseases. Despite promising mechanistic insights, conventional antioxidant and anti-inflammatory therapies such as NSAIDs, corticosteroids, and dietary antioxidants have shown limited and inconsistent success in long-term clinical applications due to challenges with efficacy, safety, and bioavailability. This review explores the molecular interplay between redox imbalance and inflammatory signaling and highlights why conventional therapeutic translation has often been inconsistent. It further examines emerging strategies that aim to overcome these limitations, including mitochondrial-targeted antioxidants, Nrf2 activators, immunometabolic modulators, redox enzyme mimetics, and advanced delivery platforms such as nanoparticle-enabled delivery. Natural polyphenols, nutraceuticals, and regenerative approaches, including stem cell-derived exosomes, are also considered for their dual anti-inflammatory and antioxidant potential. By integrating recent preclinical and clinical evidence, this review underscores the need for multimodal, personalized interventions that target the redox-inflammatory axis more precisely. These advances offer renewed promise for addressing complex diseases rooted in chronic inflammation and oxidative stress. Full article

Background: Maple syrup urine disease (MSUD) is a genetic disorder caused by mutations in the branched-chain α-ketoacid dehydrogenase (BCKDH) complex, leading to toxic buildup of branched-chain amino acids (BCAAs) and their ketoacid derivatives. While newborn screening (NBS) and molecular testing are standard diagnostic tools, they face challenges such as delayed results and false positives. Untargeted metabolomics has emerged as a complementary approach, offering comprehensive metabolic profiling and potential for novel biomarker discovery. We previously applied untargeted metabolomics to neonates with MSUD, identifying distinct metabolic signatures. Objective: This follow-up study investigates metabolic changes and biomarkers in pediatric MSUD patients and explores shared dysregulated metabolites between neonatal and pediatric MSUD. Methods: Dried blood spot (DBS) samples from pediatric MSUD patients (n = 14) and matched healthy controls (n = 14) were analyzed using LC/MS-based untargeted metabolomics. Results: In pediatric MSUD, 3716 metabolites were upregulated and 4038 downregulated relative to controls. Among 1080 dysregulated endogenous metabolites, notable biomarkers included uric acid, hypoxanthine, and bilirubin diglucuronide. Affected pathways included sphingolipid, glycerophospholipid, purine, pyrimidine, nicotinate, and nicotinamide metabolism, and steroid hormone biosynthesis. Seventy-two metabolites overlapped with neonatal MSUD cases, some exhibiting inverse trends between age groups. Conclusion: Untargeted metabolomics reveals that the metabolic profiling of MCUD pediatric patients different from that of their controls. Also, there are valuable age-specific and shared metabolic alterations in MSUD, enhancing the understanding of disease progression in MSUD patients. This supports its utility in improving diagnostic precision and developing personalized treatment strategies across developmental stages. Full article

Chronic kidney disease (CKD) affects nearly 10% of the global population, ranks among the top ten causes of death, and often progresses silently to end-stage disease without timely intervention. Increasing evidence indicates that many adult-onset cases originate in early life through adverse influences on kidney development, a process termed kidney programming within the Developmental Origins of Health and Disease (DOHaD) framework. Environmental pollutants are now recognized as key drivers of kidney injury across the life course. Heavy metals, air pollutants, plastic contaminants such as bisphenol A, phthalates, and micro/nanoplastics—as well as biocontaminants like mycotoxins and aristolochic acid—and chronic light pollution can accumulate in kidney tissue or act systemically to impair function. These exposures promote oxidative stress, inflammation, and endothelial and circadian disruption, culminating in tubular injury, glomerular damage, and fibrosis. Notably, early-life exposures can induce epigenetic modifications that program lifelong susceptibility to CKD and related complications. Oxidative stress is central to these effects, mediating DNA, lipid, and protein damage while influencing developmental reprogramming during gestation. Preclinical studies demonstrate that antioxidant-based interventions may mitigate these processes, providing both renoprotective and reprogramming benefits. This review explores the mechanistic links between environmental pollutants, oxidative stress, and kidney disease and highlights antioxidant strategies as promising avenues for prevention and intervention in vulnerable populations. Full article

Diabetic retinopathy (DR) is a leading cause of vision loss globally and represents one of the most common microvascular complications of diabetes. In addition to metabolic disturbances associated with hyperglycemia, oxidative stress has emerged as a critical contributor to the onset and progression of DR. Oxidative stress, defined as an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense mechanisms, leads to cellular injury, inflammation, and increased vascular permeability. In the diabetic retina, excessive ROS production promotes endothelial cell apoptosis, breakdown of the blood-retinal barrier (BRB), and induction of angiogenic factors such as vascular endothelial growth factor (VEGF). This review provides a comprehensive overview of the pathophysiology of DR, focusing on the molecular mechanisms of oxidative stress. Relevant studies were identified through a structured search of PubMed, Web of Science, and Scopus (2000–2025) using terms such as ‘diabetic retinopathy’, ‘oxidative stress’, and ‘antioxidants’. We explore current knowledge on oxidative stress-related biomarkers and therapeutic strategies targeting oxidative damage, including antioxidant compounds and mitochondrial protective agents. Recent findings from both experimental and clinical studies are summarized, highlighting the translational potential of oxidative stress modulation in DR management. Finally, future research directions are discussed, including biomarker standardization, personalized medicine approaches, and long-term clinical validation of antioxidant-based therapies. A deeper understanding of oxidative stress may offer valuable insights into novel diagnostic and therapeutic strategies for DR. Full article

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder characterized by progressive cognitive decline and an impaired quality of life, for which no curative treatment is currently available. Recent research indicates that chronic pulmonary conditions—including chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA)—exhibit significant epidemiological associations with AD pathogenesis, suggesting that the lung–brain axis may contribute to AD development. Acupuncture, a core TCM intervention, shows promise for modulating multisystem functions and enhancing cognitive performance. This review synthesizes the current evidence regarding pulmonary diseases influencing AD through the lung–brain axis, elucidates potential mechanisms by which acupuncture may modulate pulmonary function and mitigate AD pathology, and explores future directions for lung–brain axis-targeted acupuncture interventions. Our overarching aim is to propose integrative, evidence-based strategies that combine Chinese and Western medicine for the prevention and management of AD. Full article

This review offers a comprehensive overview of mycotoxin research and related publications in Algeria, outlining key trends, existing challenges, and prospects for future advancement. Despite limited exploration of mycotoxins in Algeria, researchers have made significant progress in understanding mycotoxin contamination and its effects on food safety and public health. The review delves into both research achievements and the challenges encountered in resource-limited settings, while also exploring strategies employed to surmount these obstacles. Through an analysis of existing literature, key themes emerge regarding mycotoxin identification, detection methods, mitigation strategies, and their implications. The importance of collaborative efforts among academia and government agencies is underscored as pivotal in addressing mycotoxin-related challenges. Moreover, this review identified gaps in current research and offered recommendations for future investigations, aiming to advance mycotoxin research in Algeria and beyond. Full article

Breast cancer is a heterogeneous disease and a leading cause of cancer-related deaths worldwide, underscoring the urgent need for effective biomarkers to guide diagnosis, prognosis, and therapeutic decisions. Bioinformatics methodologies, including genomics, transcriptomics, proteomics, and metabolomics data analysis, are essential for deciphering the complex molecular landscape of breast cancer. Bioinformatics tools facilitate the identification of differentially expressed genes, non-coding RNAs, and proteins, unraveling crucial pathways involved in tumor initiation, progression, and metastasis. By constructing and analyzing protein–protein interaction networks and signaling pathways, bioinformatics approaches can identify potential diagnostic, prognostic, and predictive biomarkers. Herein, we explore the role of bioinformatics in breast cancer research and its potential application in identifying novel therapeutic targets and predicting drug response, ultimately enabling the development of tailored treatment strategies. We also address the challenges and future directions in utilizing bioinformatics for biomarker discovery and validation, emphasizing the need for robust statistical methods, standardized data analysis pipelines, and collaborative efforts to translate bioinformatics insights into improved clinical outcomes for breast cancer patients. Full article

Diabetic wounds, especially diabetic foot ulcers, pose a major global clinical challenge due to their slow healing and high infection susceptibility. Their typical pathological features include impaired angiogenesis, chronic hypoxia, persistent inflammation, oxidative stress, bacterial colonization, and neuropathy. Traditional treatment methods have limited efficacy, creating an urgent need for innovative therapeutic strategies. In recent years, biomaterials have emerged as a research focus in diabetic wound treatment, owing to their biocompatibility, versatility, and tissue regeneration potential. This article comprehensively reviews the pathological mechanisms of diabetic wounds. It also summarizes the application progress of biomaterials in diabetic wound healing. Over the past decade, researchers have explored the properties, mechanisms of action, and roles of various natural and synthetic biomaterials. These biomaterials include DNA nanomaterials, peptide hydrogels, cells, exosomes, and cytokines. These biomaterials play significant role in promoting angiogenesis, regulating inflammation, inhibiting bacteria, and enhancing cell proliferation and migration. Full article

Cancer has remained a major global health challenge, with around 20 million new cases and 9.7 million fatalities recorded each year. Even though there has been recent progress in therapies such as radiotherapy, chemotherapy, immunotherapy, and gene therapy, cancer remains a major treatment challenge due to late diagnosis and difficulties in therapeutic effectiveness. Flavonoids, a substantial category of naturally occurring polyphenols, have received considerable interest in recent years for their potential involvement in cancer management and prevention, especially concerning breast cancer. These bioactive compounds, abundant in vegetables, fruits, and herbs, exhibit various therapeutic actions, including antioxidant, anti-inflammatory, and antimutagenic effects. The advanced therapeutic potential of flavonoids, when combined with FDA-approved medicines, offers synergistic effects and enhanced clinical results. Additionally, flavonoid-loaded nano-formulations, involving co-delivery systems, are being explored to increase solubility, stability, and bioavailability, enabling targeted delivery to cancer cells while reducing off-target adverse effects. This review examines the role of flavonoids in the prevention and management of breast cancer, focusing on their dietary sources, metabolism, and pharmacokinetic properties. Furthermore, we explore novel strategies, such as combination therapies with FDA-approved drugs and the application of flavonoid-based nanoformulations, which have the potential to enhance therapeutic outcomes. The clinical application of these strategies has the potential to improve breast cancer treatment and create new opportunities for the advancement of flavonoid-based therapies. Full article

Twice-exceptional students, who are both gifted and present with characteristics of neurodiversity such as Autism Spectrum Disorder (ASD), possess distinctive academic and socio-emotional needs that necessitate individualized educational strategies. This qualitative case study explores the academic and socio-emotional experiences of Murat, an eighth-grade learner identified as gifted and diagnosed with ASD, from the perspectives of the student himself, his mother, and his teachers. Data were collected through semi-structured interviews and analyzed using Braun and Clarke’s six-phase reflexive thematic analysis. The findings revealed that Murat achieved success in mathematics and science, particularly within enriched, strength-oriented environments that accommodated his sensory sensitivities. Despite challenges in social skills and group participation, he benefited considerably from teacher scaffolding and interactive pedagogies. His mother’s active engagement and strong family–school collaboration emerged as pivotal factors in his developmental progress. This study extends beyond individual challenges to highlight the potential strengths that arise from by the intersection of neurodiversity and giftedness. Additionally, it contributes to the limited body of literature exploring how the notion of twice-exceptionality manifests within underrepresented educational contexts. Future research could investigate diverse socio-cultural contexts and develop strategies to enhance teacher preparation and family engagement in supporting gifted learners with ASD. Full article

Recent progress in tumor immunotherapy highlights the important role of the immune system in combating various cancers. Traditionally designed to protect against infectious diseases, vaccines are now being adapted to stimulate immune responses against tumor-specific neoantigens. Both preclinical studies and clinical trials have explored innovative approaches for identifying neoantigens and optimizing vaccine design, advancing the field of personalized oncology. Among these, DNA-based vaccines have become a particularly attractive approach for cancer immunotherapy. This evolution has been driven by improvements in molecular biology techniques, including more precise methods for detecting tumor-specific mutations, computational tools for predicting immunogenic antigens, and novel platforms for delivering nucleic acid vaccines. Personalized DNA vaccines are typically developed through a complex, multi-step process that involves sequencing a patient’s tumor, computational analysis to identify potential targets, and custom vaccine production. In this review, we examine the use of both shared tumor antigens and individualized neoantigens in cancer vaccine development. We outline strategies for neoantigen identification that provide insights into tumor-specific alterations. Furthermore, we highlight recent advances in DNA vaccine technologies, address the current limitations facing cancer vaccines, propose strategies to overcome these challenges, and consider key clinical and technical factors for successful implementation. Full article