Peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) is a master transcriptional coactivator responsible for regulating cellular energy metabolism and mitochondrial biogenesis across high-energy tissues such as the heart, skeletal muscle, and brown adipose tissue. To orchestrate its regulatory functions, PGC-1α interacts with a diverse array of transcription factors such as peroxisome proliferator-activated receptors (PPARs), estrogen-related receptors (ERRs), and nuclear respiratory factors (NRFs), which is facilitated by its dynamic three-dimensional structure, the presence of distinct functional domains, and the ability to be modulated via post-translational modifications. This review examines the protein's interactions with key nuclear receptors and the biological consequences of these complexes, including the regulation of thermogenesis, gluconeogenesis, and fatty acid oxidation. Furthermore, we discuss the extensive post-translational modifications-including phosphorylation, acetylation, methylation, O-GlcNAcylation, and ubiquitination-that tightly regulate PGC-1α stability and coactivation efficiency. Finally, this review highlights recent progress in the identification of small molecule modulators, such as the activator ZLN005 and the inhibitor SR18292, evaluating their physiological outcomes and potential as therapeutic agents for metabolic disorders and cancer, while addressing the challenges posed by the protein's structural disorder in drug discovery.
Morin (2',3,4',5,7-pentahydroxyflavone) is a polyphenolic dietary flavonoid found naturally in foods and has demonstrated anticancer effects in multiple preclinical models. This narrative review presents a comprehensive pharmacological analysis of morin's capacity to modulate apoptosis and autophagy, which are convergent pathways of programmed cell death (PCD) in both solid and hematological malignancies. Morin has been reported to influence intracellular reactive oxygen species (ROS) levels and disrupt the mitochondrial membrane potential (ΔΨm), thereby affecting the AMPK-mTOR-ULK1-Beclin-1 autophagic pathway. This review synthesizes preclinical data obtained from in vitro cancer cell line models, in vivo xenograft and chemical-induced tumor systems, and hypothesis-generating in silico molecular docking and network pharmacology studies. The significant crosstalk between apoptosis and autophagy appears to involve the Bcl-2/Beclin-1 pathway, cleavage of autophagy-related proteins by caspases, and shared redox stress. Mechanistic interpretation should be used with caution, as several studies have used associative molecular end points, and the accumulation of LC3-II does not equate to complete autophagic flux. Novel nanoformulation-based drug delivery strategies, the potential of chemo-sensitization in drug-resistant tumor models, and available preclinical safety and toxicology data are examined in the context of the pharmacokinetic limitations of morin, such as poor oral bioavailability, low aqueous solubility, intestinal metabolism, P-glycoprotein efflux, and limited clinical pharmacokinetic validation. Pharmacological studies suggest that morin may be classified as a multi-target phytopharmacological agent. However, more rigorous studies are required for target validation, including autophagy flux assays, clinically relevant tumor models, and pharmacokinetic optimization, before it can be translated into a therapeutic application.
Antigen escape and intratumoral heterogeneity remain major barriers to durable responses in chimeric antigen receptor (CAR)-based cancer immunotherapies. While single-antigen CAR-T cell therapies have achieved notable success in hematologic malignancies, relapse driven by antigen loss, lineage plasticity, and tumor evolution remains common, and efficacy in solid tumors is limited. Similar antigen-dependent limitations are also observed in other targeted immunotherapies, including bispecific antibodies, underscoring the broader challenge of achieving durable immune control. To address these challenges, bispecific and combinatorial CAR strategies have emerged to broaden antigen coverage, enhance tumor selectivity, and reduce immune evasion. This review examines the biological mechanisms underlying antigen escape and critically evaluates dual-targeting CAR architectures, including tandem CARs, dual-CAR systems, logic-gated designs, and inhibitory CARs. We distinguish between mechanistic rationale and clinically validated benefit, highlighting the heterogeneity of outcomes across studies and the limited evidence supporting consistent superiority over optimized monospecific approaches. We summarize preclinical and clinical evidence supporting bispecific CAR-T strategies, particularly in B-cell malignancies, while discussing challenges related to toxicity, manufacturing complexity, and translational scalability. We further evaluate CAR-engineered natural killer (CAR-NK) cells as a complementary platform. Their innate cytotoxicity, favorable safety profile, and compatibility with allogeneic manufacturing offer important translational advantages, although limitations in persistence, tumor infiltration, and clinical validation remain. Finally, we position CAR-based therapies within the evolving immunotherapy landscape, emphasizing therapeutic sequencing, combination strategies, potential cross-resistance, and the need to align CAR design and platform selection with tumor-specific patterns of antigen expression and immune escape.
Breast and cervical cancers remain significant causes of cancer-related deaths in women, necessitating the development of effective treatments. This study investigated the repositioning potential of procaterol as a chemosensitizer to increase the efficacy of cisplatin in HeLa and MCF-7 cells. On its own, procaterol showed limited cytotoxicity; however, it significantly inhibited cell viability when combined with low doses of cisplatin. Both colony formation and cell proliferation studies showed a strong inhibition of cell growth, especially in HeLa cells. Similarly, wound-healing studies showed greater inhibition of cell migration in the presence of both drugs than with either drug alone. Live/dead assays and elevated TNF-α (tumour necrosis factor-alpha) expression confirmed apoptosis. The increased generation of reactive oxygen species suggested that HeLa cells are under oxidative stress. Flow cytometric analyses showed that procaterol induced G0/G1 arrest, cisplatin induced G2/M arrest, and the combination induced both arrests while significantly decreasing S-phase populations. Procaterol sensitized cisplatin by increasing apoptosis and oxidative stress and inducing cell cycle arrest. As an FDA-approved compound, it can be used as a cost-effective adjuvant for treating breast and cervical cancer. Additional in vivo verification and clinical trials are required to establish the translational value of this new combination for the treatment of cervical and breast cancer.
Pulmonary arterial hypertension (PAH) is increasingly recognized as a metabolically dysregulated and inflammatory vascular disease rather than a purely haemodynamic disorder. Among emerging metabolic pathways, the bile acid-oxysterol axis has gained attention as a potential link between sterol imbalance, endothelial dysfunction, and pulmonary vascular remodeling. This narrative review examines current evidence linking selected bile acid and oxysterol species to PAH phenotypes and discusses their potential mechanistic and translational implications. Human lung tissue studies, circulating metabolomics, and experimental models suggest that selected bile acid intermediates and oxysterol species may carry biological information beyond nonspecific disease severity, although their effects are molecule-specific, receptor-specific, and context-dependent rather than uniform across the entire metabolite class. In particular, recent work implicates disturbed lysosomal sterol trafficking and impaired endothelial lysosomal acidification, including NCOA7-related mechanisms, in generating pro-inflammatory sterol signatures that promote endothelial immunoactivation and worsen experimental PAH. At the same time, the biological origin and interpretation of these metabolites are likely heterogeneous, involving lung-intrinsic sterol remodeling, systemic gut-liver signals, and potential confounding from right-heart failure or congestive hepatopathy. We argue that the bile acid-oxysterol axis should not be viewed as uniformly causal or purely biomarker-like across all patients, but rather as a compartment- and endotype-dependent framework whose interpretation depends on the level of evidence considered. This framework has important implications for biomarker development, therapeutic targeting, and precision trial design, and identifies sterol trafficking and lysosomal homeostasis as promising areas for future investigation.
To evaluate whether cumin (Cuminum cyminum) oil attenuates nandrolone decanoate (ND)-induced hepatic alterations in rats. Eighty male Sprague-Dawley rats were randomized into six groups: control, cumin oil alone, ND low dose (10 mg/kg/week), ND high dose (20 mg/kg/week), ND low dose + cumin oil, and ND high dose + cumin oil. Cumin oil was administered orally at 400 mg/kg/day for 4 weeks. Outcomes included relative liver weight index, serum ALT/AST, total bilirubin, lipid profile, and blinded histopathology. Both ND doses increased ALT/AST and bilirubin levels and worsened the lipid profile compared with controls, with more pronounced and significant alterations in the high-dose ND group. Co-administration of cumin oil attenuated ND-associated elevations in liver enzymes and bilirubin, improved lipid parameters, and was associated with reduced histological damage compared with ND alone. Interestingly, cumin oil alone increased ALT/AST and lipid parameters compared with controls, although liver architecture remained unremarkable on H&E. In this rat model, cumin oil co-administration partially attenuated ND-induced hepatic biochemical, lipid, and histological alterations. However, cumin oil alone increased ALT/AST and lipid parameters despite unremarkable H&E morphology. Therefore, the present findings should be interpreted as evidence of context-dependent attenuation during ND exposure, not as proof of an independent hepatoprotective or lipid-lowering effect of cumin oil in healthy rats. Dose-ranging, safety evaluation, batch-specific chemical profiling, preparation standardization, and mechanistic studies incorporating antioxidant/oxidative stress markers such as MDA, GSH, SOD, CAT, GPx, and molecular endpoints are needed to clarify pathways and translational relevance.
Self-amplifying RNA (saRNA) derived from alphavirus replicons enables robust intracellular RNA amplification and high-level protein expression at substantially lower doses than nonreplicating messenger RNA (mRNA) platforms. Venezuelan equine encephalitis virus (VEEV)-based replicons lacking the viral structural genes are among the most extensively characterized saRNA backbones, combining efficient cytoplasmic replication with a favorable safety profile. However, incorporating chemical nucleoside modifications such as N1-methylpseudouridine (m1ψ), now standard in conventional mRNA workflows, can directly impact replicase activity and hinder RNA amplification, necessitating backbone-specific optimization. Recent studies have shown that incorporation of 5-methylcytidine (m5C) preserves VEEV saRNA replication while reducing innate immune activation and improving expression durability. In an independent study, phosphatase treatment to remove residual 5'-triphosphates was shown to enhance saRNA functionality. Building on these findings, here we describe a streamlined protocol for generating m5C-modified VEEV-based saRNA using a single-step in vitro transcription (IVT) strategy. This protocol utilizes PCR-generated DNA templates with an encoded poly(A) tail, CleanCap AU for co-transcriptional capping, and post-transcriptional phosphatase treatment to minimize immunostimulatory RNA species. Finally, the RNA was purified using the phenol-chloroform-isoamyl alcohol method and functionally evaluated by transfection into HEK293T cells. This protocol provides a reproducible framework for producing capped, tailed, and chemically modified saRNA suitable for downstream functional and translational studies. © 2026 Wiley Periodicals LLC. Basic Protocol 1: IVT and purification of saRNA with modified nucleotides Basic Protocol 2: Functional assessment of IVT-generated saRNA in HEK293T Cells.
Ebola virus disease (EVD) is a severe and often fatal illness characterized by aggressive viral replication, dysregulated immunity, and multi-organ dysfunction. Emerging evidence demonstrates that microRNAs (miRNAs), both host-derived and virus-encoded, play essential regulatory roles throughout the course of Ebola virus (EBOV) infection. Host miRNAs are widely dysregulated across different tissues and cell types during infection and contribute to antiviral defense, viral persistence, immune suppression, endothelial dysfunction, and hemorrhagic pathology. In parallel, EBOV generates its own miRNA-like molecules that target key host signaling pathways, including nuclear transport, interferon responses, apoptosis regulation, and inflammatory cascades. These dual layers of miRNA crosstalk shape infection outcomes by modulating viral replication, immune evasion, cellular adhesion, and vascular leakage. Additionally, several host and viral miRNAs show strong potential as diagnostic and prognostic biomarkers, and recent work suggests that therapeutic modulation through miRNA mimics or inhibitors may offer new antiviral strategies. This review synthesizes current evidence on miRNA interactions during EBOV infection and outlines their implications for disease pathogenesis, clinical outcomes, and translational applications.
Explainable Artificial Intelligence (XAI) is gaining popularity in early diagnosis and monitoring of dementia. Herein, we recommend the incorporation of the National Institute of Mental Health's Research Domain Criteria (NIMH-RDoC) framework with XAI-informed diagnostic protocols to help establish diagnosis at early stages of Alzheimer's disease (AD). RDoC has a dimensional structure that extends across units of analysis from genes and molecules to circuits, physiology, behavior, and introspection. By restructuring diverse features as inputs including apolipoprotein E (APOE) genotype, amyloid and tau biomarkers, computational neuroimaging-informed cortical atrophy, Positron Emission Tomography (PET) hypometabolism, quantitative electroencephalography (qEEG) rhythms, cognitive tests, and digital behavioral markers), onto RDoC units provides more insightful and inclusive models. In this context, data-driven approaches such as XAI can achieve not only increased interpretability but also enhance their mechanistic validity. Such an innovative approach places data-driven model outputs within neurobiologically based domains such as Cognitive Systems, Negative Valence, and Arousal/Regulatory Systems. Our synthesis suggests that a 'converging RDoC and XAI' approach may help bolster the coherence of AD biomarkers, promote model exploration in clinical decision-making. This approach is also expected to provide a strategic roadmap for translational neuroscience and personalized medicine. Another major aim of this study is to critically analyze current XAI approaches used in dementia research, particularly the diagnostic and prognostic aspects. By explicitly grounding explanations in RDoC cognitive domains and paradigms, the framework also aims to make model outputs meaningful in terms of specific mental functions (e.g., episodic memory, cognitive control), thereby supporting neuropsychologically-informed diagnosis, categorization, and communication with patients and caregivers.
Parkinson's Disease (PD) represents the second most prevalent neurodegenerative condition which leads to the progressive destruction of dopaminergic neurons in the substantia nigra through oxidative stress mechanisms. The research evaluated Gallic Acid (GA) as a natural polyphenol with proven antioxidant properties for its ability to protect cells from 1-methyl-4-phenylpyridinium (MPP⁺)-induced neurotoxicity in SH-SY5Y dopaminergic cell models. The research used SH-SY5Y cells which received 1 mM MPP⁺ treatment alongside different GA concentrations (25, 50 and 100 µM) for 24 and 48 h. The CCK-8 assay measured cell viability while flow cytometry evaluated apoptosis and SOD and MDA levels determined oxidative status through SOD and Catalase and NO measurements. The addition of MPP⁺ resulted in a 32.74% decrease in cell viability at 48 h while simultaneously decreasing SOD and Catalase and NO levels and increasing MDA levels. The addition of 25 µM GA protected cells from damage by increasing their viability to 86.53% at 48 h and decreasing apoptotic cell numbers. Our results revealed that co-treatment with 25-50 µM GA effectively mitigated oxidative damage by preventing the depletion of catalase and NO levels. Furthermore, GA successfully reduced lipid peroxidation; specifically, 25 µM GA decreased MDA levels from 21.18 to 9.64 nM/mg protein at 48 h, thereby restoring the cellular antioxidant defense system against MPP+-induced oxidative stress. In conclusion, the present study demonstrates that GA exerts a significant neuroprotective effect in an in vitro PD model by modulating the endogenous antioxidant network and alleviating lipid peroxidation. By effectively reversing the depletion of crucial enzymes and reducing apoptosis, GA shows potential therapeutic efficacy against oxidative stress-associated neurodegeneration. These findings suggest that GA is a promising phytochemical candidate warranting further in vivo evaluation to clarify its long-term bioavailability and translational value.
The dynamics of surface carriers in conventional n-type semiconductors are generally restricted by the energy band bending at their interfaces, thereby severely limiting the extraction of photoelectrons for cathodic bioassays. Herein, we reported a nonconventional cathodic photoelectrochemical (PEC) immunoassay, utilizing an Ag-decorated Gd-doped BiFeO3 (Ag/BGFO) Schottky junction for fundamentally overriding the n-type depletion limitations. Despite its typical n-type nature confirmed by Mott-Schottky analysis, the BGFO photoelectrode generates a robust cathodic photocurrent of 23.5 μA at 0 V, which is more than four times higher than pure BFO. This counterintuitive phenomenon is governed by the powerful spontaneous depolarization field (Edp) of the ferroelectric BGFO, which forcefully pumps photoelectrons to the surface, overriding the conventional depletion layer. Subsequently, the upward-bent Ag/BGFO Schottky barrier acts as a unidirectional valve, efficiently extracting these electrons into the Ag electron sinks while strictly preventing interfacial backflow. Leveraging this exceptionally electron-rich cathodic platform, a split-type PEC immunosensor was constructed for α-fetoprotein (AFP) detection. By spatially isolating the target-triggered enzymatic generation of H2O2 from the photoelectric interface, the sensor thoroughly eliminates biofouling, achieving an ultralow limit of detection of 2.46 pg/mL and a remarkable 90-day storage stability (>97% retention). Furthermore, clinical validation using 50 human serum specimens demonstrated an excellent linear correlation (R2 = 0.9986) with the gold-standard ELISA. This work not only provides profound physical insights into ferroelectric-modulated charge dynamics but also establishes a highly robust paradigm for translational clinical diagnostics.
To evaluate whether GPT-4.1 and Llama 3.3 70B, large language models (LLMs) assessed in zero-shot, baseline configurations, detect and categorize clinically consequential errors across types that range from pattern-based to reasoning-dependent. Two hundred fifty-six radiology reports encompassing CT (n = 104), MRI (n = 104), and X-ray (n = 48) studies across multiple anatomical regions were retrospectively analyzed. For each original report, four variants (n = 1024) were generated, each incorporating one of four predefined error types: E1, anatomical mislabeling that could cause wrong-site actions; E2, physiologically impossible or nonsensical findings; E3, diagnostic inconsistencies that affect staging or diagnosis; E4, inappropriate recommendations. The evaluated models were GPT‑4.1 04-14) and Llama 3.3 70B, both used without domain-specific training or prompt optimization to assess baseline model performance. Model performance revealed a systematic hierarchy governed by error type and imaging modality. Physiologically impossible errors (E2) showed the lowest performance: 46.2% (CT) and 33.7% (MRI) for GPT-4.1, compared with 32.7% and 25.0% for Llama 3.3, respectively. Overall success for GPT-4.1 on E2 was 16.3% (CT), 8.7% (MRI), and 12.5% (X-ray). Mislabeling errors (E1) were detected in 49.0% by GPT‑4.1 and 33.7% by Llama 3.3 for MRI. Best performance occurred for inappropriate recommendations (E4), with GPT‑4.1 achieving 85.4% detection in X-ray with high classification accuracy. The evaluation framework and benchmark dataset provide a methodology for assessing LLM performance on clinically significant errors. Applied to GPT-4.1 and Llama 3.3 70B in zero-shot settings, the framework reveals a performance gap between pattern-based and reasoning-dependent error detection that warrants investigation across additional models and optimization strategies. Question LLMs are increasingly used for quality assurance of radiology reports, but whether their linguistic competence translates into the detection of clinically significant errors remains unclear. Findings Error detection was type-dependent, both GPT-4.1 and Llama 3.3 70B performed poorly on physiologic and anatomical errors, but better on inappropriate recommendations. Clinical relevance LLMs failed to detect most clinically consequential errors in radiology reports, especially physiologically impossible statements that trained radiologists would rapidly identify.
Intestinal transplantation requires high levels of long-term immunosuppression, putting recipients at high risk of developing malignancies. Factors influencing the incidence and outcomes of these malignancies remain poorly understood. We conducted a retrospective multicenter study surveying 11 of 15 intestinal transplantation (ITx) centers in the United States, including 336 of 451 transplants performed between 2020 and 2025. Forty-four patients developed de novo malignancies, including 34 posttransplant lymphoproliferative disorder, 5 skin carcinomas and 5 other carcinomas. Malignancy incidence was 13.1% at a mean follow-up time of 2.33 y. Overall survival did not significantly differ between all intestinal transplant recipients and those who developed malignancies. Malignancy incidence was significantly influenced by maintenance immunosuppression: tacrolimus + Steroids was associated with increased odds of malignancy and tacrolimus + mycophenolate mofetil + steroids with decreased odds. Subsequently reducing immunosuppression did not impact the incidence or severity of rejection. However, concurrent infection-especially opportunistic infection-was associated with higher mortality in the malignancy group. Malignancy after ITx is likely related to greater T-cell immunosuppression with increased incidence associated with tacrolimus-predominant maintenance regimens and improved outcomes with multimodal regimens and the absence of infections. Our results suggest that reduced T-cell suppression and maintenance of some level of immunocompetence may decrease the incidence, morbidity, and mortality of malignancy after ITx without increasing rejection rates.
Sport-related concussion injuries are common in community Rugby Union. Despite research advancements in SRC management in recent years, little is known about the translation of research to practice within community Rugby Union cohorts. To develop and evaluate a novel system to track comprehensive SRC history, symptoms, and treatment data within community Rugby Union players. The Three-Phase Rugby Concussion System (TPRCS) collected comprehensive SRC data from players throughout the 2024-25 community Rugby Union season at baseline, 0-5 days post-SRC, and 0-5 days post-unrestricted return to play. Semi-structured interviews were conducted for stakeholders (players and club medics, n = 10) involved post-season, to evaluate participation experience, alongside perceived research facilitators, barriers, and usefulness. Survey compliance ranged from 51% at baseline (n = 135), to 74% for post-SRC (n = 23), and post-clearance surveys (n = 23). The evaluation surveys received positive feedback for TPRCS's ease of use and communication pathways, with player enthusiasm levels for study participation being the lowest-scoring survey response. The main facilitators for TPRCS included club culture, incentives, and personal contact, whilst the main barriers were absence of injury reporting and lack of prioritisation from players. Stakeholders identified education, injury treatment, and policy change as potential areas of usefulness. Medics and players in community Rugby Union are enthusiastic to progress practice and behaviours in line with research. Overall, this stakeholder-evaluated comprehensive SRC data collection system can serve as a novel SRC research framework across Rugby Unions.
Parents of children with achondroplasia face sustained caregiving demands that may affect multiple dimensions of well-being. Despite growing recognition of these challenges, no validated, condition-specific instrument exists to assess the quality of life (QoL) of parents of children with achondroplasia. This study aimed to develop, and pilot test the Quality of Life of Parents of Children with Achondroplasia (QOLA) questionnaire. QOLA was developed using a multi-phase mixed-methods design in accordance with established standards for developing self-reported outcome measures for caregivers and parents. Phase 1 comprised semi-structured qualitative interviews with 17 parents of children with achondroplasia to identify relevant QoL domains and language. Interview data were analysed using qualitative content analysis and informed systematic item generation (Phase 2). Conceptual structure was examined through researcher-led card sorting (Phase 3) and two rounds of international card sorting following translation (Phase 4). The resulting 63-item questionnaire across eight domains was pilot-tested in a cross-sectional, multi-country study with embedded cognitive debriefing in Germany, Italy, and Portugal (total N = 50). The final pilot version of QOLA comprised 63 items across eight domains covering healthcare experiences, challenges and support, physical health, mental health, social life and relationships, coping, family and daily life, and worries and future concerns. Item-level missing data were minimal, and no pronounced floor or ceiling effects were observed. Internal consistency was acceptable to good for domains (α = 0.624-0.821) and good for the total scale (α = 0.798). Inter-domain correlations were generally moderate to strong. Cognitive debriefing was highly acceptable and relevant across countries, with some suggestions for further refinement. QOLA shows strong preliminary evidence of acceptability and internal consistency and addresses a key measurement gap in achondroplasia research. Further large-scale psychometric validation is warranted.
Despite major advances in prevention and treatment, cardiovascular disease remains a leading cause of death and disability worldwide. Cardiovascular genetic epidemiology has moved from family-based and candidate-gene studies to a genome-wide discipline supported by genome-wide association studies (GWAS), population-scale biobanks, whole-genome sequencing, and multi-omics resources. This narrative review examines how the field is shifting from locus discovery toward a continuous but still incomplete evidence chain that links variants to genes, cellular context, causal pathways, functional validation, and clinical use. We emphasize a central tension: cardiovascular genetics has been exceptionally successful at discovering associations, but robust mechanistic resolution and implementation-ready clinical translation remain uneven across diseases, populations, and use cases. We synthesize progress in coronary artery disease, blood pressure traits, atrial fibrillation, stroke, heart failure, inherited cardiovascular disorders, and intermediate phenotypes, and we distinguish established applications from promising but still emerging approaches such as polygenic risk scores, spatial omics, EHR-linked implementation, and genetically informed target prioritization. We also highlight persistent bottlenecks, including ancestry imbalance, noncoding locus interpretation, limited functional validation, imperfect polygenic score portability, data-governance constraints, and the need for privacy-preserving analytical frameworks. Overall, the next phase of cardiovascular genetic epidemiology will depend less on the mere accumulation of loci and more on rigorous evidence triangulation, context-specific functional testing, ancestry equity, and feasible clinical implementation pathways.
Global consumption of muscle foods (a tissue-based classification; eg, meat, fish, and poultry) is expected to rise in the coming decades, intensifying debates about the roles of these foods in health, disease, and environmental sustainability. From a nutritional perspective, foods, including muscle foods, are often discussed on the basis of their nutritional composition and expected medium- and long-term health effects, without considering the acute role of muscle foods in postprandial metabolism and how these effects can translate into long-term health outcomes. The present evidence-based narrative review synthesizes the current knowledge on how acute consumption of muscle foods influences postprandial metabolism and the implications for health and dietary recommendations. First, we analyzed global consumption trends and the environmental impacts of muscle foods using a nutrient density score (NDS) and greenhouse gas emission rates. Next, we reviewed human clinical studies examining postprandial responses, including glycemic, lipemic, aminoacidemic, and incretin responses to different muscle foods, considering the roles of digestibility, amino acid composition, and cooking methods. Evidence indicates that fish intake generally promotes more favorable postprandial metabolic profiles, including lower glycemic excursions and enhanced insulin sensitivity, whereas red meat intake tends to stimulate higher postprandial incretin secretion, likely reflecting differences in digestion kinetics and amino acid bioaccessibility. These findings highlight the importance of considering the impact of food systems on planetary health and the need to better understand the effects of muscle foods on postprandial metabolism as a crucial step towards dietary recommendations that considers environmental sustainability and human health.
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Head and neck squamous cell carcinoma (HNSCC) is a global malignancy characterised by extremely low survival rates, primarily contributed to by late diagnosis, tumour heterogeneity, and resistance to available therapies. Deciphering reliable biomarkers is crucial for early diagnosis, prognosis and personalized therapy. This review discusses the possibilities of clusterin (CLU) as an emerging biomarker in the field of HNSCC therapeutics by incorporating insights derived from preclinical, clinical and proteomic data. The expression of CLU in HNSCC cases has been found to be correlated with advanced stages of the tumour, metastatic potential higher histological grades and therapeutic resistance. Mechanistic studies demonstrate that CLU plays a dual role in enhancing tumour cell survival and facilitating apoptosis, contingent upon isoform and environmental context. Recent findings confirm the effectiveness of CLU as a biomarker for early diagnosis, risk evaluation, and forecasting therapeutic response. This review also focuses on the comparison of CLU to known HNSCC biomarkers and stresses the progress made in non-invasive screening and targeted therapies. In conclusion, CLU shows strong potential as a biomarker and therapeutic target, warranting further research for clinical application in HNSCC.
The contribution of fatty acid oxidation (FAO) to colorectal cancer (CRC) progression has been recognized. However, the detailed mechanisms underlying FAO remain obscure. This study explored the influence of ring finger protein 14 (RNF14) on FAO and its related mechanisms in CRC. We found that RNF14 was up-regulated in CRC, which was positively associated with FAO level. High expression of RNF14 promoted FAO to facilitate growth of CRC cells in vitro and in vivo. Mechanistically, RNA binding motif protein 15 (RBM15)/YTH N6-methyladenosine RNA binding protein 1 (YTHDF1)-mediated N6-methyladenosine (m6A) modification enhanced RNF14 translation. RNF14 reduced TATA-box binding protein associated factor 1 (TAF1) protein stability via promoting its ubiquitination. Moreover, TAF1 bound to PTEN-induced kinase 1 (PINK1) promoter to trigger its transcription. RNF14 knockdown or TAF1 overexpression repressed FAO of CRC cells, which was overturned by TAF1 or PINK1 silencing, respectively. In conclusion, RBM15/YTHDF1-mediated m6A modification of RNF14 mRNA contributed to FAO enhancement via ubiquitination of TAF1 to transcriptionally inhibit PINK1, thus promoting CRC progression.