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The International Union of Biochemistry and Molecular Biology Trainee Initiative supports early-career researchers globally. This overview covers what researchers gain from the initiative, such as funding pathways, science communication training, and strategies for building a professional network, thereby illustrating how the Trainee Initiative empowers trainees' career development.

Multiple myeloma (MM) remains an incurable hematologic malignancy, necessitating novel therapeutic strategies. This study investigates the clinical significance of adiponectin receptors and the anti-myeloma efficacy of their agonist, AdipoRon. Bioinformatic analysis of GEO datasets (GSE124489, GSE187009) revealed significant downregulation of ADIPOR1 and ADIPOR2 in MM patients. Low expression of ADIPOR1 correlated with poor prognosis. Functionally, AdipoRon exerted potent anti-proliferative effects on MM cell lines (U266, RPMI8226) in time- and dose-dependent manners. Mechanistic studies demonstrated that AdipoRon induced mitochondrial apoptosis, evidenced by increased cleavage of PARP and Caspase-9, and triggered G0/G1 cell cycle arrest. At the signaling level, AdipoRon activated the AMPK pathway while concurrently suppressing AKT phosphorylation. The critical role of AMPK was confirmed through pharmacological approaches: the AMPK activator AICAR mimicked AdipoRon's effects, whereas the AMPK inhibitor Compound C partially reversed them. Further investigation identified acetyl-CoA carboxylase (ACC) as a key downstream effector, with ACC inhibition (TOFA) recapitulating AdipoRon's anti-MM effects. Specifically, AdipoRon preferentially suppressed ACC1 expression and subsequently downregulated CPT1A, indicating disruption of fatty acid metabolism. These findings establish that AdipoRon suppresses MM progression through AMPK-driven metabolic reprogramming and apoptosis induction, positioning adiponectin receptor agonism as a promising therapeutic strategy for multiple myeloma.

Mitochondria, as the center of cellular energy metabolism, play multiple key roles in the progression of triple-negative breast cancer (TNBC). Mitochondrial fission regulator 1 (MTFR1) is a mitochondrial regulatory factor that plays a part in regulating mitochondrial fission and cell development. It is still unknown how MTFR1 functions in TNBC. We discovered MTFR1 to be a crucial gene in TNBC with clinical diagnostic value using database mining analysis. The effects of MTFR1 on TNBC cell proliferation, migration, invasion, and mitochondrial function were determined using the Cell Counting Kit-8, wound healing, and Transwell assays. Nude mouse models were established to explore the impact of MTFR1 on TNBC tumor growth and metastasis. Additionally, western blot and transcriptome sequencing (RNA-seq) were used to investigate the mechanism of MTFR1's involvement in TNBC progression. We used database extraction, WGCNA, Cox regression, and ROC (receiver operating characteristic) curve analysis to identify and confirm MTFR1 as a critical gene in TNBC. In TNBC patients, high MTFR1 expression is related to poor prognosis and diagnostic value. Knockdown of MTFR1 inhibits the proliferation and metastasis of TNBC cells and tumor bodies, affecting mitochondrial function. MTFR1 knockdown inhibits the growth, metastasis, and mitochondrial function of TNBC cells and tumors. Furthermore, transcriptome sequencing and western blot experiments confirmed that MTFR1 knockdown inhibits the activation of the NF-κB signaling pathway. In this study, we report for the first time that MTFR1 is a critical gene upregulated in TNBC. MTFR1 is an oncogene in TNBC and is involved in cell growth, migration, and mitochondrial function, and promotes TNBC progression through the NF-κB signaling pathway. Therefore, targeting MTFR1 may be a promising therapeutic target for TNBC patients.

Chemoresistance remains a significant hurdle in breast cancer treatment. To address this, we explored the therapeutic potential of combining epirubicin, an anthracycline commonly associated with the development of resistance in cancer cells and with known cytotoxic effects, with 4-methylumbelliferone, a plant-derived coumarin. Our results demonstrated a coactive enhancement of epirubicin efficacy when this combination was applied to 3D breast cancer models, irrespective of molecular subtype. Mechanistically, 4-methylumbelliferone inhibits synthesis of hyaluronan, a key component of the tumor microenvironment that promotes tumor growth and metastasis. By disrupting hyaluronan production, this compound facilitated drug penetration into tumor spheroids and reduced the expression of drug efflux pumps, thereby increasing intracellular drug accumulation. Consequently, the combined treatment led to a significant reduction in cell viability and promotion of cell death. Our findings suggest that targeting hyaluronan metabolism in conjunction with conventional chemotherapy offers a promising strategy to overcome drug resistance in breast cancer. This drug repositioning approach not only improves treatment efficacy but also highlights the potential of targeting the tumor microenvironment to enhance cancer therapy. Further studies are warranted to elucidate the underlying mechanisms and to evaluate the clinical translation of this combination therapy.

Gastric cancer represents the fifth most common malignancy globally and the third leading cause of cancer-related deaths. Due to its insidious early symptoms and frequent metastasis at diagnosis, the survival rate remains dismal. There is thus an urgent clinical need for novel therapeutic agents. Innovative strategies combining traditional chemotherapy with interventions that induce novel cell death pathways represent a promising translational direction for improving patient outcomes. Punicalagin (PUN), a natural polyphenol derived from pomegranate, exhibits potent antioxidant and broad-spectrum antitumor activities, yet its role in gastric cancer remains understudied. Three gastric cancer cell lines (AGS, HGC27, MFC) and one normal gastric mucosal epithelial cell line (GES-1) were initially selected for in vitro experiments. The effects of PUN on gastric cancer cells and normal gastric mucosal epithelial cells were assessed through MTT assay, propidium iodide (PI) staining, and cell colony formation assays, while cell migration ability was evaluated using a scratch wound healing assay. The inhibitory effect of PUN on gastric cancer was tested in a subcutaneous tumor model in nude mice, with pathological changes in vital tissues and organs observed via hematoxylin and eosin (H&E) staining. Subsequently, transcriptome sequencing was performed, and JC-1, H2DCFDA, and DHE staining methods were employed to measure mitochondrial function and reactive oxygen species (ROS) levels in PUN-treated cells. Western blotting was used to detect the expression of apoptosis- and cell cycle-related proteins. Next, two gastric cancer cell lines (AGS, HGC27) were selected for in vitro experiments to assess the combined effects of PUN and the copper ionophore elesclomol (ES) (hereafter referred to as ES-Cu, representing the combination of ES and Cu2+). Cell viability was assessed using the MTT assay, and morphological changes were observed under a microscope. Cell proliferation and migration abilities were assessed via colony formation and scratch wound healing assays, respectively. Fluorescence staining was used to examine mitochondrial function and ROS levels in cells co-treated with PUN and ES-Cu. Laser confocal microscopy and Western blotting were employed to determine the oligomerization level of DLAT protein by quantifying soluble and insoluble protein expression, along with the expression of ACO2, ETFDH, FDX1, and LIAS proteins. Molecular docking, molecular dynamics simulations, immunofluorescence staining, and transfection techniques were utilized to confirm the critical role of FDX1 in copper-induced cell death following co-treatment with PUN and ES-Cu. We found that PUN could suppress the viability, proliferation, and migration of gastric cancer cells in a concentration- and time-dependent manner. Subsequent in vivo experiments demonstrated that PUN inhibited tumor growth in nude mice at a safe dosage. Besides, transcriptome sequencing and Western blot analysis revealed that PUN induced cell cycle arrest and apoptosis. Secondly, the cell death mechanism triggered by PUN was closely associated with mitochondrial stress. PUN increased intracellular ROS levels and reduced mitochondrial membrane potential. Transcriptome sequencing and proteomic analysis further revealed molecular changes at both the mRNA and protein levels, with differential gene analysis identifying potential targets and pathways. Moreover, when PUN was combined with ES-Cu, cell viability, proliferation, and migration were all suppressed, while exacerbating mitochondrial dysfunction and elevated oxidative stress. Laser confocal microscopy and Western blotting were used to assess the expression of soluble and insoluble proteins, confirming the oligomerization of the DLAT protein. Western blot also showed that PUN could regulate the expression levels of ACO2, ETFDH, FDX1, and LIAS proteins. Molecular docking, molecular dynamics simulations, and siRNA transfection were performed to confirm the critical role of ferredoxin 1 (FDX1) in copper-induced cell death. Furthermore, when used in combination with chemotherapy drugs, PUN exhibited synergistic inhibitory effects on gastric cancer growth. PUN demonstrates significant antitumor activity both in vivo and in vitro by inducing mitochondrial dysfunction, which subsequently triggers apoptosis. In combination therapy strategies, PUN can work synergistically with chemotherapy drugs to suppress gastric cancer growth. Furthermore, PUN enhances its inhibitory effect on gastric cancer by working synergistically with cuproptosis through targeting FDX1.

Super-enhancers (SEs) are large clusters of enhancers that drive high-level expression of genes critical for normal development and tumorigenesis. However, their precise roles in high-grade serous ovarian carcinoma (HGSOC) remain unclear. This study integrated SE-derived regulatory networks with proteomic profiles to identify key pro-tumorigenic signaling in HGSOC progression. Weighted gene co-expression network analysis (WGCNA) and machine learning were used to screen SE-driven core oncoproteins. The influence on cell phenotypes was evaluated by detecting invasion, proliferation, apoptosis, glucose consumption, lactate generation, and tube formation. M2 macrophage polarization was assessed by detecting CD163+ cell proportion and TGF-β1 and IL-10 secretion. The MAZ/HDGF interaction was confirmed by luciferase and ChIP-qPCR assays. Xenograft studies were used to evaluate the in vivo function. HDGF was overexpressed and was identified as a core SE-driven oncoprotein in HGSOC. Silencing of HDGF inhibited the invasion, proliferation, and glycolysis of HGSOC cells, promoted their apoptosis, and attenuated HUVEC tube formation and M2 macrophage polarization. Mechanistically, MAZ transcriptionally activated HDGF through promoter binding. Moreover, HDGF re-expression counteracted the suppressive effects of MAZ knockdown on HGSOC cell malignant behaviors, HUVEC tube formation, M2 macrophage polarization, and the growth of xenograft tumors. In conclusion, our study unveils the MAZ/HDGF axis as a novel SE-mediated oncogenic pathway in HGSOC, providing previously unrecognized insights into SE-driven oncogenesis and highlighting potential targets for HGSOC treatment.

Hypoxia is associated with increased tumour aggressiveness and relapses in hepatocellular carcinoma (HCC) through HIF signalling. Tumour suppressor p53, its deacetylase SIRT1 and liver-specific miRNAs are deregulated in hypoxia, further driving HCC tumorigenesis. The role of HIFs-p53-SIRT1-miRNAs in tumorigenesis of HepG2 tumourspheres under hypoxic conditions remains unexplored, hence is the focus of this study. HepG2 tumourspheres cultured under hypoxic and serum-free conditions for 19 days showed reduced proliferation and apoptosis, and increased pro-survival autophagy, CSC features and resistance. HIF-1α and HIF-2α proteins were stabilised in HepG2 tumourspheres cultured in hypoxia for up to 15 days compared to only up to 24 h in monolayer cells. p53 was activated in hypoxia, evidenced by significant increase in Ace-p53 expression and Ace-p53/total-p53 ratio, which were negatively correlated with HIF-1α/HIF-2α throughout hypoxia. Concurrently, nuclear p53 localisation was reduced in hypoxia, suggesting HIFs-suppression of p53 transcriptional activity. SIRT1 however, showed no correlation with p53 acetylation and HIF-1α/HIF-2α, with no notable changes in its nuclear-cytoplasmic localisation. Among the six selected miRNAs, miR-145-5p, -26a-5p and -375-3p were upregulated, miR-22-3p was downregulated, while miR-29c-3p and miR-34a-5p remained unchanged. miR-145-5p showed a negative correlation with p53 expression in hypoxia. Pharmacological inhibition of HIFs resulted in significant upregulation of p53 and miR-375-3p, while SIRT1, miR-145-5p and miR-26a-5p were downregulated. miR-145-5p was negatively correlated with p53 protein when HIFs were stabilised but positively correlated when HIFs were inhibited. This study highlights the role of HIFs/p53/miR-145-5p-associated regulation under hypoxic conditions in HepG2 tumourspheres, providing insights for future therapeutic exploration in HCC.

Pulmonary arterial hypertension (PAH) is a severe, progressive disease characterized by elevated pulmonary arterial pressure and increased vascular resistance. This hemodynamic strain forces the right ventricle to pump against a high-pressure system, ultimately leading to right-sided heart failure and death. The pathogenesis of PAH involves a complex interplay of vasoconstriction, chronic inflammation, and pathological remodeling of the pulmonary vessel walls-specifically hypertrophy of the smooth muscle and intimal layers-driven by molecular imbalances and genetic predispositions. Current FDA-approved therapies primarily manage symptoms through vasodilation but fail to directly target the underlying vascular remodeling. Imatinib, a tyrosine kinase inhibitor originally developed for oncological indications, has emerged as a potential disease-modifying agent for PAH. By inhibiting platelet-derived growth factor receptors (PDGFR), imatinib targets the aberrant proliferation of smooth muscle cells, offering a mechanism to potentially reverse or arrest vascular remodeling. Clinical trials, including the IMPRES study, have demonstrated encouraging hemodynamic improvements in patients with severe PAH refractory to standard therapies. However, systemic safety concerns and dose-dependent adverse reactions have limited its clinical approval. This review examines the pharmacological rationale for imatinib, its impact on vascular structure, and the safety signals observed in long-term studies. Furthermore, it discusses emerging strategies, such as inhaled formulations and pharmacogenetic approaches (e.g., the PIPAH study), aimed at enhancing the efficacy-to-safety ratio of kinase inhibitors to improve long-term outcomes for patients with PAH.

To effectively combat atherosclerotic diseases, it is essential to identify novel biomarkers and therapeutic targets that can detect early-stage atherosclerosis before the development of high-risk, unstable plaques. Due to their distinct chemical and biological characteristics, long noncoding RNAs (lncRNAs) have emerged as promising biomarkers for various diseases. This review highlights the potential therapeutic intervention targeting lncRNAs in atherosclerosis. Recent research has pointed out the significant role of lncRNAs in the pathogenesis and progression of atherosclerosis, influencing endothelial dysfunction in both proliferation and migration, lipid metabolism, and plaque stability through diverse molecular mechanisms such as NEAT1, lincRNA-p21, MALAT1, H19, GAS5, MEG3, HOTAIR, and TUG1. This study also emphasizes the role of lncRNAs in the diagnosis and prognosis of atherosclerosis, such as APPAT, MALAT1, MIAT, SOX2-OT, HIF1A-AS1, lncRNA-ATB, PVT1, NORAD, HOTAIR, H19, LIPCAR, and DANCR. The research highlighted the therapeutic intervention targeting various lncRNAs in atherosclerosis via different signaling pathways, such as TNF-α, JAK/STAT, IFN-γ signaling, ROCK1, AP1, and NF-κB signaling, PI3K/AKT/mTOR, which holds a new class of RNA-based therapeutics. The research aims to elucidate the crucial roles of lncRNAs in regulating gene expression and cellular processes involved in atherosclerosis development, which could emerge as potential therapeutic targets for atherosclerosis.

Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous malignancy with poor prognosis and limited predictive biomarkers for therapy response. Characterizing malignant cell heterogeneity may improve prognostic and therapeutic stratification. We integrated single-cell RNA sequencing (scRNA-seq) data from 58 HNSCC patients (181,003 cells) to define malignant cell subpopulations, their differentiation states, developmental trajectories, cell-cell interactions, and spatial localization. Coexpression gene modules and meta-programs were identified using hdWGCNA and NMF. These programs were projected onto bulk RNA-seq datasets to classify HNSCC subtypes and examine associations with clinical outcomes, tumor microenvironment (TME), genomic instability, and predicted response to immune checkpoint inhibitors (ICIs). Twelve malignant clusters were identified with distinct clinical and molecular features. MC-5 exhibited a stem-like phenotype associated with poor prognosis, while MC-7 and MC-11 showed high TME communication and immune engagement. Coexpression analysis revealed 16 modules and eight meta-programs encompassing proliferation, differentiation, stress response, and immune activity. Translation to bulk RNA-seq defined three HNSCC subtypes (MS-1, MS-2, MS-3) with divergent survival, immune infiltration, stromal composition, and genomic features. MS-2, an immune-enriched subtype, demonstrated superior survival, high HPV positivity, and predicted ICI responsiveness. A 25-gene malignant cell score (MCScore) robustly predicted both prognosis and immunotherapy response. This study provides a comprehensive map of malignant cell heterogeneity in HNSCC, identifies key functional expression programs, and defines molecular subtypes with clinical and therapeutic relevance. Malignant cell-specific signatures, such as MCScore, offer promising tools for patient stratification and precision immunotherapy.

Phosphomannomutase-2 (PMM2) deficiency leads to the prominent Congenital Disorder of Glycosylation (CDG), a rare disease currently lacking effective treatment options. The complete absence of PMM2 activity is incompatible with life, and all patients carry at least one missense destabilising variant that allows residual enzymatic function. This makes PMM2-CDG amenable to pharmacological chaperone treatment. Glucose-1,6-bisphosphate (Glc-1,6-P2) is PMM2's natural activator and stabiliser, but its clinical application is severely limited due to its unfavourable physicochemical profile. Here, we applied the bioprecursor prodrug strategy to design and synthesise Lipo-Glc-1,6-P2, a novel prodrug with good stability and oral bioavailability. Its advantageous physicochemical profile was confirmed through metabolomics-based studies in fibroblasts derived from PMM2-CDG patient.

Curcumin exhibits strong anti-inflammatory, antioxidant, and anticancer activities. However, its clinical use is limited due to poor solubility, low gastrointestinal absorption, and rapid systemic metabolism. Nanocurcumin offers enhanced solubility, bioavailability, and targeted delivery through systems such as nanoparticles, liposomes, micelles, and nanoemulsions. In oral health, nanocurcumin has shown significant therapeutic promise. In periodontitis models, it attenuates pro-inflammatory cytokines and oxidative stress markers. In radiation- and chemotherapy-induced oral mucositis, randomized clinical trials report reduced lesion severity and pain scores with nanomicellar curcumin compared to placebo. Studies on oral lichen planus and aphthous ulcers have demonstrated superior symptom control and lesion resolution with nanocurcumin compared to conventional curcumin or corticosteroids. Preclinical data in oral squamous cell carcinoma reveal antiproliferative, pro-apoptotic, and anti-angiogenic effects mediated through the NF-κB, STAT3, and MAPK pathways. This review explores nanoformulation strategies, their physicochemical advantages, and therapeutic outcomes across in vitro, in vivo, and clinical studies. It also addresses translational challenges like stability, cost, and regulatory hurdles and discusses future perspectives including personalized nanomedicine and multifunctional nanocarriers. Nanocurcumin represents a promising advancement in oral therapeutics with potential to bridge current gaps in treatment efficacy and drug delivery.

Influenza viruses present an ongoing global health risk because they are always changing, which in turn results in the ineffectiveness of current strain-specific vaccines and leaves the world vulnerable to potential pandemics. The need for a universal influenza vaccine, designed to develop lasting broadly protective immunity against volatile influenza virus strains has led to advances in immunogen design. Nanotechnology, specifically self-assembled nanovaccines, offers a truly revolutionary "bottom-up" strategy to address this issue. Nanovaccines that spontaneously self-assemble into easily discernable pathogen-like nanoparticles, including protein cages (e.g., ferritin) and virus-like particles, provide densely displayed conserved influenza epitopes-such as hemagglutinin (HA) stalk, neuraminidase (NA), and M2 ectodomain (M2e)-in a multivalent array, greatly enhancing B-cell activation, initiated by extensive receptor crosslinking, and generating immune responses to a magnitude and breadth that is unattainable with soluble antigens. Moreover, self-assembled nanovaccines, often in adjuvant-free or self-adjuvanting formulations, not only induce durable and broad cross-protective humoral and cellular immunity but also offer protection from numerous heterosubtypic viral challenges. While significant hurdles remain in scaling the process to a manufacturing level and subsequently translating it into the clinic, self-assembling nanovaccines represent a paradigm shift in influenza prevention, providing a rational and promising pathway toward the development of a universal vaccine and a rapid response platform for future pandemics.

Endoplasmic reticulum glycosyltransferase ALG8 controls metabolic fate in autosomal dominant polycystic kidney disease (ADPKD). In this paper, we summarize human genetics, cell-based, and organ-based evidence to investigate whether ALG8 variants affect cyst initiation and metabolic states of ADPKD. Population screening showed ALG8 variant enrichment in ADPKD cohorts (OR = 9.75, P0.001); loss-of-function alleles interact with PKD1 mutations to accelerate cystogenesis. ALG8 deficiency leads to metabolic collapse by several mechanisms. Impaired polycystin-1 glycosylation disrupts ER-to-cilium trafficking, prevents PC1/PC2 complex assembly, and impedes calcium-dependent ATP production. Deficient LRP6 glycosylation activates Wnt/-catenin signaling. This shifts metabolism toward aerobic glycolysis, leading to Warburg-like reprogramming seen in malignancy. Single cell analysis showed ALG8 deficient cystic epithelium has tumor-like metabolic signatures, such as increased glucose uptake, suppressed oxidative phosphorylation, and glutamine dependence. Chemical chaperones that restore folding capacity or glycosylation inhibitors that lower anabolic demand both suppressed cyst formation in ALG8/PKD1-deficient organoids. The connection from ALG8 loss to "oncogenic-like" metabolism remains incomplete. Study-to-study variability in model system, genotype, and endpoint still limits cross-cohort comparison. This dual vulnerability-of protein folding and glycosylation-is due to the fragile metabolic balance in cystogenesis. These results recast ADPKD as a metabolic disorder where glycosylation defects link ciliary dysfunction to oncogenic transformation. We focus on three areas: (i) convergence with multiple lines of evidence, (ii) disagreement, and (iii) testable predictions for future studies and trials. The overlap between cystogenic and tumorigenic metabolic programs suggests cancer metabolic inhibitors may be reused for ADPKD in near-term translation. By defining ALG8 as a metabolic checkpoint in polycystic disease, we uncover targets at the glycosylation-metabolism interface.

The core pathogenesis of carotid atherosclerosis (CAS) lies in the rupture of vulnerable plaques, with macrophages (MC) playing a critical role in plaque progression and destabilization. However, the functional characteristics of MC subpopulations in CAS remain poorly understood. This study systematically investigates the cellular composition of CAS and the regulatory mechanisms of MC by integrating single-cell RNA sequencing (scRNA-seq), in vitro models, and spatial transcriptomics. Differentially expressed genes upregulated in MC were significantly enriched in multiple signaling pathways, including Lipid and Atherosclerosis, Lysosome, and Antigen Processing and Presentation. Gene Set Variation Analysis (GSVA) revealed higher MC scores for Angiogenesis and Lipid Metabolism in the atherosclerotic core (AC). A total of seven distinct MC subtypes were identified. Pseudotime analysis indicated that IGSF21+ MC constitute the initial cell population, while FABP4+ MC represent the terminal cells along the trajectory. An in vitro atherosclerosis model was established to validate the diagnostic value of SPP1, FTH1, and FTL. Spatial transcriptomics further revealed the spatial connection patterns of the SPP1 signaling pathway network across different cell types. This study provides novel molecular insights into the pathogenesis of CAS and lays the groundwork for developing diagnostic biomarkers and therapeutic targets.

Muscle wasting, characterized by loss of muscle mass and strength, severely impacts patient quality of life and is associated with numerous chronic diseases and aging. The molecular mechanisms are complex, involving protein synthesis/degradation imbalance. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) and ubiquitin-specific peptidase 7 (USP7) have diverse cellular roles, but their coordinated function in skeletal muscle homeostasis remains poorly understood. DYRK1A overexpression in vivo induced muscle atrophy phenotypes, including reduced muscle mass, grip strength, fiber cross-sectional area (CSA), altered fiber type composition, and neuromuscular junction integrity, accompanied by elevated atrophy markers: muscle atrophy F-box protein (Atrogin-1), muscle ring finger 1 (MuRF-1), myostatin and suppressed myogenic markers: myoblast determination protein 1 (MyoD), myogenin (MyoG), myocyte enhancer factor 2C (Mef2c), myogenic factor 5 (Myf5). Conversely, pharmacological inhibition of DYRK1A with Harmine ameliorated these atrophy phenotypes in transgenic DYRK1A overexpressing (TgD) mice. In vivo, USP7 deficiency resulted in similar muscle wasting phenotypes. In vitro, DYRK1A overexpression or USP7 overexpression inhibited C2C12 myoblast proliferation and differentiation, effects rescued by Wnt3a treatment or USP7 knockdown, respectively. Mechanistically, DYRK1A activity suppressed active β-catenin levels. USP7 was found to interact with and deubiquitinate axis inhibition protein 1 (Axin1), leading to its stabilization. Knockdown of USP7 increased Axin1 ubiquitination and degradation, thereby promoting β-catenin signaling and myogenesis, counteracting the effects of DYRK1A. Our findings reveal a novel signaling axis where DYRK1A and USP7 cooperatively suppress Wnt/β-catenin signaling to promote muscle wasting. DYRK1A likely acts upstream, potentially phosphorylating pathway components, whereas USP7 stabilizes the β-catenin destruction complex scaffold protein Axin1 through deubiquitination. This coordinated action inhibits myogenesis and activates atrophy pathways. Targeting DYRK1A or USP7 could represent promising therapeutic strategies for muscle wasting disorders.

Myocardial ischemia (MI), which is a key form of ischemic heart disease, is still the most common cause of morbidity and mortality in the world. While reperfusion therapy has changed clinical management, many of the unmet needs for the early diagnosis and treatment of MI remain. Two rapid advances, namely, extracellular vesicle biology and the field of non-coding RNA genomics, have combined to identify a class of potent signaling molecules, exosomal long non-coding RNAs (lncRNAs). In this review, we characterize the specific functions of prominent exosomal lncRNAs in the core biological pathophysiological elements of MI, including apoptosis, inflammation, angiogenesis, autophagy, and fibrosis. Exosomal lncRNAs can either be involved in damaging - transmitting signals of injury-or restorative-driving repair and regeneration-and often play such roles based on their source and recipient. In addition to their therapeutic advantage, exosomal lncRNAs have enormous diagnostic capacity as stable, sensitive, and early-stage "liquid biopsy" diagnostics. By integrating core biology into clinical possibilities, we hope this review represents the field's current viewpoint and where it is heading to change the diagnosis and treatment of myocardial ischemia.

The CYP17A1 gene encodes the P450 17α-hydroxylase/17,20-lyase protein, a key enzyme in steroidogenesis. In the past, it was associated with disorders such as congenital adrenal hyperplasia, disorders of sex development, and castration resistant prostate cancer. Recently, genome-wide association studies have revealed that the locus harboring the CYP17A1 gene is strongly associated with multiple other traits, including cardiovascular and metabolic characteristics. This review summarizes the current knowledge about the regulatory mechanisms and monogenic disease implications of the CYP17A1 gene, then attempts to link the locus to cardiovascular and metabolic diseases, using experimental evidence supporting these relationships. Additionally, the review also speculates that the research focus may have been placed solely on one gene of the locus, which could have obscured the effects of other neighboring ones. In summary, our review aimed to highlight this locus as a complex regulatory region with implications that extend beyond a single gene.