ABSTRACT This study aimed to reveal the relationship between experimental varicocele and melatonin levels. Forty adult Wistar albino rats were used in this study. Control (C), Melatonin (M), Varicocele (V), Varicocele+Melatonin (V + M) were planned. Varicocele was created on the first day of the experiment by opening the abdominal area, narrowing the left renal vein with a 0.85 mm metal wire and using a 4‐0 silk suture, after removing the metal wire, the animal was closed (with a 3‐0 silk suture) and kept for 60 days. Melatonin was administered at 10 mg/kg ip (intraperitoneal) on the 61st day, every 24 h for 7 days. Histological analysis and GADD34, GADD45g, GADD153 immunohistochemical staining were performed. Additionally, StAR and GDNF gene expressions were examined. ABP, FSH, LH, Testosterone, Melatonin hormones, TAS and TOS levels were evaluated from blood serum taken from experimental animals. According to our results, group V showed a decrease in testicular weights, seminiferous tubule diameter, and JTBS score, while GADD34, GADD45g and GADD153 proteins increased. In group V, testosterone and TAS levels decreased and TOS levels increased. In group V, testosterone, FSH, ABP, melatonin levels decreased and LH level increased. StAR and GDNF gene expression also decreased in group V. In the V + M group where melatonin was applied, an improvement was observed in biochemical parameters as well as histological, immunohistochemical and gene expression analyses. During varicocele, endogenous melatonin level decreases and activates various mechanisms and hormones in the tissue, including GADDs, causing loss of structure and function, while melatonin acts as a good therapeutic on varicocele.
ABSTRACT Cancer cells undergo metabolic reprogramming to sustain proliferation, resist apoptosis, and adapt to oxidative stress. In the present study, we comparatively evaluated the anticancer effects of four medicinal plant extracts ( Inula helenium, Hypericum alpestre, Rumex obtusifolius , and Alchemilla smirnovii ) on HeLa cervical cancer cells, with particular emphasis on oxidative stress, l ‐arginine metabolism, and cellular energy pathways. Cell viability was assessed using the MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay, while biochemical colorimetric methods were used to determine nitric oxide production, arginase and nitric oxide synthase activities, malondialdehyde levels, superoxide dismutase and catalase activities, proline content, and key glycolytic metabolites. Nuclear morphology changes consistent with apoptotic features were examined by Hoechst 33258 staining. All tested extracts exhibited cytotoxic effects in HeLa cells in a time‐ and concentration‐dependent manner, which were further enhanced when combined with the metabolic inhibitors l‐NAME (Nω‐nitro‐l‐arginine methyl ester) or nor‐NOHA (Nω‐hydroxy‐nor‐l‐arginine). Inula helenium showed the strongest potentiation in combination treatments. Several extracts significantly decreased arginase activity while increasing nitric oxide synthase activity and nitrite levels, indicating modulation of l‐arginine metabolism. Treatments also increased malondialdehyde levels and stimulated antioxidant enzyme activities, consistent with redox imbalance and oxidative stress–mediated cytotoxicity. In addition, Inula helenium and Alchemilla smirnovii reduced intracellular glucose, pyruvate, and lactate concentrations, suggesting partial modulation of glycolytic metabolism. Fluorescence microscopy revealed chromatin condensation, nuclear fragmentation, and apoptotic body formation, particularly after treatment with Hypericum alpestre and Rumex obtusifolius . These findings demonstrate that selected medicinal plant extracts exert cytotoxic effects by simultaneously modulating oxidative stress, amino acid metabolism, and energy pathways in cervical cancer cells. The investigated plants may represent promising sources of bioactive compounds for the development of complementary metabolic anticancer strategies.
ABSTRACT Breast cancer continues to pose a public health problem and is the second leading cause of cancer‐related mortality among women globally. Despite advances in our understanding of cancer biology and the development of treatment strategies, the therapeutic response is not often satisfactory as treatment efficacy is limited by severe side effects and drug resistance. Therefore, there is an urgent need for innovative approaches to improve diagnosis, prognosis, and treatment of breast cancer. Recent advances in bioinformatics and proteomics have enabled the discovery of a novel class of small proteins encoded from the small open reading frames, which were previously thought to be non‐coding. Emerging evidence has indicated that these microproteins play a pivotal role in modulating breast cancer progression. This article reviews the current understanding of microproteins, highlights the microproteins identified to date as key regulators in breast cancer, and explores their potential clinical applications in improving breast cancer management.
CD1d is a cell-surface expressed glycoprotein that presents a variety of lipid and glycolipid antigens to invariant natural killer T-cells (iNKT). We have examined the role of the N-linked glycans on the human CD1d (hCD1d) in modulating the responses of iNKT cells using a combination of cell-free, cell-based assays and in silico analyses. Deficiency of one or more glycans on hCD1d diminished the activation of iNKT cells. Soluble glycan mutants did not have significant differences in terms of binding to the nickel-coated 96-well plates. Our cell-free assay, together with docking and MM-GBSA analyses, confirms that Glycan 1 and Glycan 2 are critical determinants of optimal iNKT cell activation. Taken together, our data emphasized an essential role of the hCD1d N-linked glycans in modulating iNKT cell response.
Necroptosis has been demonstrated to play a role in the process of lung ischemia-reperfusion injury (LIRI) in a variety of clinical conditions, including cardiopulmonary bypass and pulmonary embolism. Melatonin has been reported to exert a protective role by reducing oxidative stress and acute inflammatory reactions in LIRI. However, the effect of melatonin on necroptosis in LIRI remains unclear. The aim of this study was to investigate whether the protective effects of melatonin against H/R-induced injury are associated with modulation of necroptosis and related changes in mitochondrial function and oxidative stress. The cells were exposed to H/R (16/4 h) or normoxia, in the absence or presence of 2.5 µM melatonin. Cell viability was determined by the MTT method, while morphological changes in BEAS-2B cells resulting from H/R exposure were evaluated by fluorescence microscopy using acridine orange/ethidium bromide (AO/EtBr) staining. Mechanistic analyses, including flow cytometry-based cell cycle assessment, apoptosis detection (Annexin V-FITC), mitochondrial membrane potential evaluation (JC-1), and reactive oxygen species (ROS) measurements, were performed on BEAS-2B cells. The level of the mixed lineage kinase domain-like pseudokinase (MLKL), a key component of the necroptosis complex, was also quantified using an enzyme-linked immunosorbent assay. In addition, the ATP, pH, and lactate levels were determined. The findings indicated that melatonin treatment reduced the H/R-induced increase in the percentage of necrotic cells and increased the percentage of viable cells (p < 0.05). In addition, melatonin treatment reduced the increase in MLKL, ROS, and lactate levels, preserved mitochondrial membrane integrity, and increased intracellular ATP levels in BEAS-2B cells exposed to H/R (p < 0.05). In conclusion, this study suggests that melatonin protects BEAS-2B cells against H/R-induced injury, and that this protective effect may be associated with reduced oxidative stress, preservation of mitochondrial function, and suppression of necroptosis-related signaling.
Previous transcriptomic analysis revealed that eicosapentaenoic acid (EPA) alters miRNA expression in HepG2 cells. Two key miRNA-mRNA axes mediating EPA's antioxidant effects were identified. EPA was found to downregulate let-7c-3p, which directly targets mitochondrial transcription factor A (TFAM). Inhibiting let-7c-3p or overexpressing TFAM enhanced antioxidant capacity, reduced reactive oxygen species, improved mitochondrial function, and promoted mitochondrial biogenesis. In parallel, EPA was found to upregulate miR-34c-5p, which directly targets NAD-Dependent Protein Deacetylase Sirtuin (SIRT1). This repression of SIRT1 is associated with increased activities of antioxidant enzymes, including catalase, superoxide dismutase, and glutathione peroxidase. These findings indicate a dual-miRNA mechanism through which EPA alleviates oxidative stress via coordinated enhancement of mitochondrial biogenesis and enzymatic defenses.
Ferroptosis is a form of programmed cell death characterized by iron-dependent phospholipid peroxidation and is implicated in a wide range of human diseases. Emerging evidence highlights the critical role of epigenetic regulation in this process. Dysregulation of histone post-translational modifications (HPTMs) is increasingly recognized as a pivotal mechanism linking metabolic reprogramming to various pathological conditions. HPTMs constitute one of the key epigenetic regulatory mechanisms and mediate ferroptosis by modulating the transcription of core ferroptosis-related genes. This review systematically summarizes site-specific HPTMs, including histone methylation, acetylation, ubiquitination, phosphorylation, lactylation, and β-hydroxybutyrylation. Furthermore, we elucidate how infectious diseases, tumors, and chronic non-infectious conditions drive disease progression via HPTMs-dependent regulation of ferroptosis. A comprehensive dissection of these epigenetic regulatory networks may facilitate the development of combinatorial therapeutic strategies targeting HPTMs and ferroptosis inducers, thereby providing new insights into the treatment of ferroptosis-associated disorders.
Breast cancer is the most frequently diagnosed malignancy among women worldwide, with 2.3 million new cases and approximately 670,000 deaths reported in 2022 alone. Despite advances in therapy, metastasis and acquired drug resistance remain major clinical challenges. Reactive oxygen species (ROS) play a dual role in breast cancer biology: physiological levels sustain normal cellular signaling, moderately elevated levels promote tumorigenesis through DNA damage, proto-oncogene activation, and tumor suppressor inactivation, while excessive accumulation can trigger cancer cell death. This review examines how redox dysregulation contributes to breast cancer initiation and progression through key signaling pathways, including phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), mitogen-activated protein kinase (MAPK), and Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2), as well as apoptotic cascades. We evaluate the evidence for dietary and synthetic antioxidants-melatonin, curcumin, vitamins C and E, and carotenoids-as chemopreventive and adjuvant agents, highlighting both their therapeutic promise and the conflicting data on their safety during cancer treatment. We further discuss emerging ROS-responsive nanoagents for targeted drug delivery and immunotherapy, and strategies to exploit redox vulnerabilities in multidrug-resistant breast cancer cells, including induction of ferroptosis, an iron-dependent cell death pathway driven by lipid peroxide accumulation that has emerged as a promising vulnerability in therapy-resistant and mesenchymal-phenotype tumors. Recent advances in machine learning and multi-omics integration, which have begun to identify redox-related gene signatures with prognostic and immunotherapy-predictive value, further point toward precision redox oncology as an emerging clinically actionable framework. By integrating molecular mechanisms with translational advances, this review identifies current gaps and future directions for ROS-targeted therapeutic strategies in breast cancer.
Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease of unknown cause, marked by excessive deposition of extracellular matrix (ECM) components such as collagen. This pathological accumulation results in progressive destruction of the lung architecture and ultimately leads to respiratory failure. Growing evidence indicates that dysfunction across multiple cell types is an important driver of IPF. Nevertheless, its underlying pathobiology remains incompletely understood. The normal integrity of organelles is critical for cellular function, and in different IPF lung cells, such as alveolar epithelial cells (AECs), fibroblasts, and macrophages, we found dysfunctional development of key organelles and metabolic reprogramming changes driving malignant progression of pulmonary fibrosis. This review summarizes the contributions of key organelles-mitochondria, the endoplasmic reticulum, lysosomes, and peroxisomes-and functional changes in metabolic reprogramming during IPF progression. We further clarify the core mechanisms of how inter-organelle network disruptions drive fibrosis, with the goal of identifying critical organelle nodes to disrupt pathogenic metabolic reprogramming and ultimately provide a rationale for developing new treatments.
NHE-1 is a Na+/H+ exchanger that receives phosphorylation signals, binds calmodulin and responds to neurohormonal input from angiotensin II, endothelin-1, and adrenergic pathways. In cardiac myocytes, NHE-1 maintains pH homeostasis and couples to Na+/Ca2+ exchange and mitochondrial ion handling. During heart disease sustained activation drives intracellular Na+ accumulation, promoting Ca2+ overload and mitochondrial dysfunction. Oxidative stress then creates amplifying cycles that activate signaling pathways resulting to arrhythmias and fibrosis. Clinical trials failed despite preclinical promise, due to a variety of false experimental factors. SGLT2 inhibitors appear to modulate NHE-1 indirectly through metabolic reprogramming and hemodynamic effects rather than direct blockade. Current approaches use structural data to target regulatory sites and phosphorylation-dependent conformational states instead of the transport pore. Translation to patients will require biomarkers identifying pathological hyperactivity and better patient stratification methods. Here, we try to review NHE-1 structure, regulation, and physiology that may influence research on future drug development.
The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway, as a key DNA sensor, plays a significant role in the regulation of innate immune responses. This pathway can be activated by sensing abnormal DNA, and is of great significance for resisting the invasion of pathogenic microorganisms and maintaining tissue homeostasis. In addition, the cGAS-STING pathway plays a dual role in cancer, and oncogenic viruses can cause cell carcinogenesis in the body through multiple mechanisms, thereby affecting human health. This manuscript reviews the vital role of cGAS-STING in the immune process, as well as the fact that viruses causing human tumor lesions can activate cGAS-STING, leading to virus inhibition and further preventing the occurrence and development of related cancers, and the paradoxically promoted progression of related cancers by viruses through cGAS-STING. And summarize the agonists and inhibitors that act in different ways based on the activation mechanism of cGAS-STING.
AKT (protein kinase B, PKB) coordinates the balance between anabolic and catabolic signaling in skeletal muscle through distinct ubiquitin chain types. Some E3 ubiquitin ligases (E3s) and deubiquitinases (DUBs) form stable binary complexes via non-catalytic interfaces, adding a regulatory layer unavailable to either enzyme alone. This mechanistic synthesis review presents a systematic literature analysis (inception to May 2026; 26 eligible studies). It identified four E3-DUB pairs proposed to regulate AKT in skeletal muscle. These are TRAF6-CYLD (plasma-membrane K63-ubiquitination), MUL1-USP9X (mitochondrial K48-ubiquitination of AKT2), CHIP-UCH37 (proteasome-proximal quality control), and SCF-Skp2-USP37 (PHLPP1/2-dependent control of AKT Ser473 phosphorylation). All four interfaces are structurally separate from the catalytic sites and are regulated by upstream kinase phosphorylation. Evidence for the four pairs is markedly uneven. TRAF6-CYLD is supported by endogenous co-immunoprecipitation and functional data in muscle models. CHIP and UCH37 each act on AKT-related substrates independently and are individually well documented, but a direct CHIP-UCH37 interaction has not itself been demonstrated. SCF-Skp2-USP37 interaction data rest on a real but non-muscle direct interaction, whereas MUL1-USP9X has no reported direct interaction at all; CHIP-UCH37, SCF-Skp2-USP37, and MUL1-USP9X are therefore all presented as testable hypotheses of varying strength. In chronic atrophy, available data are consistent with disruption of these complexes contributing to AKT suppression through parallel, largely independent mechanisms. However, simultaneous disruption of all four has not been demonstrated in a single system. Available gene expression and protein datasets from sarcopenic muscle broadly support these predictions, though direct experimental validation in human tissue remains pending. This complex-centric framework recasts AKT ubiquitination as an integrated regulatory framework. Each structurally autonomous interface may represent a potentially distinct target for muscle-wasting conditions that currently lack approved therapies.
Multiple myeloma (MM) is a malignant plasma cell disorder, and despite substantial improvements in prognosis achieved through chemotherapy, immunotherapy, and autologous stem cell transplantation, most patients ultimately develop relapsed or refractory disease. Drug resistance (DR) is increasingly recognized as a dynamically evolving ecosystem shaped by tumor-intrinsic plasticity and continuous remodeling of the bone marrow microenvironment (BMME), rather than as a single molecular lesion. This review summarizes the major mechanisms of resistance across key drug classes, including alterations in drug targets and signaling nodes, rewiring of apoptotic, proteostatic, and metabolic circuits, and BMME-dependent protection. We highlight how these processes converge on a limited set of survival hubs and collectively raise the apoptotic threshold under therapeutic pressure. The key to overcoming DR is to conceptualize it as an evolving ecosystem, thereby enabling rational, mechanism-based combination and sequencing strategies that may prolong progression-free survival and move MM closer to a functional cure.
Tuberculosis, caused by Mycobacterium tuberculosis (MTB), affects approximately 25% of people globally as latent infection (LTBI). Although macrophage CREB activation promotes MTB survival, the underlying mechanisms remain unclear. This study reveals, for the first time, how MTB modulates M2 macrophage polarization through the CREB1/TREM2 signaling pathway. Mononuclear macrophages were isolated from clinical sample. Flow cytometry was used to determine the M2 polarization ratio. The expression of TNF-α, IL-10, and IL-1β was determined by ELISA. The mRNA expression of iNOS, IL-1β, CD206, Arg-1, IL-10, CREB1, and TREM2 was assessed by qPCR. The protein expression of CREB1, CD206, Arg-1, IL-10, and TREM2 was evaluated by western blot. The colony-forming unit (CFU) assay was used to detect the survival of MTB. CHIP and Dual-luciferase reporter assays were used to confirm the binding of CREB1 and TREM2. Clinical sample analysis revealed that the expression levels of CREB1 and TREM2 in peripheral blood mononuclear macrophages (PBMCs) were significantly upregulated in tuberculosis patients. Following H37Rv infection, an increase in the M2 macrophage proportion was observed. Infection with MTB also elevated the protein level of IL-10, as well as CREB1 mRNA and protein expression. Transfecting sh-CREB1 into macrophages or adding CREB inhibitors 666-15 markedly reduced intracellular MTB CFU counts, implying a potential restrictive effect on viable MTB load within macrophages. Knockdown of TREM2 similarly decreased MTB CFU burden and restrained macrophage M2 polarization. Furthermore, transfecting sh-CREB1 into macrophages can suppress the proliferation of MTB within macrophages, and these effects could be further counteracted by the action of oe-TREM2. These results elucidated that MTB promoted M2 macrophage polarization through CREB1/TREM2.
Meningiomas exhibit marked biological heterogeneity that is not fully captured by current histopathological grading. Increasing evidence suggests that mitochondrial metabolism contributes to tumor aggressiveness; however, the molecular mechanisms regulating mitochondrial function in meningiomas remain poorly defined. Here, we investigated the role of mitochondrial transcription factor A (TFAM)-driven mitochondrial biogenesis and translation in meningioma progression. We performed integrative transcriptomic, immunohistochemical, and mitochondrial DNA analyses in a well-characterized cohort of 91 meningiomas, comprising World Health Organization grade 1 (G1) and grade 2 (G2) tumors with long-term clinical follow-up. RNA sequencing identified enrichment for mitochondrial metabolic pathways, including oxidative phosphorylation and ATP metabolism, that was preferentially activated in G2 meningiomas. TFAM and its upstream regulator PGC1α were significantly upregulated at both mRNA and protein levels in G2 tumors and exhibited a positive correlation, consistent with enhanced mitochondrial biogenesis. Although mitochondrial DNA copy number did not differ significantly between grades, G2 meningiomas showed a trend toward increased mitochondrial mass. Notably, G2 meningiomas demonstrated marked enrichment of mitoribosomal genes, including MRPL15, MRPL35, MRPL42 and MRPS22, whose expression correlated positively with TFAM and PGC1α expression levels. Network analysis identified TFAM as a central hub linking mitochondrial biogenesis, translation, and metabolic pathway activation. These findings were independently validated using a publicly available meningioma transcriptomic dataset. Together, our results reveal a TFAM-centered mitochondrial regulatory program that integrates mitochondrial biogenesis, translational capacity, and oxidative metabolism in higher-grade meningiomas. This mitochondrial translational axis represents a previously unrecognized mechanism underlying meningioma progression and highlights potential metabolic vulnerabilities for therapeutic intervention.
The role of microbes in cancer is gaining attention these days, especially in the context of tumor-associated biofilms and dysbiotic microbiota. Biofilm-producing microorganisms, such as Fusobacterium nucleatum and Helicobacter pylori, trigger oncogenic inflammation and immune evasion in tumor initiation and progression, and in the development of chemoresistance, through the activation of the NF-κB, STAT3, and β-catenin pathways. Dietary terpenoids are a structurally diverse group of antitumor and antibiofilm plant metabolites. Monoterpenoids, sesquiterpenoids, and triterpenoids are known to inhibit quorum sensing, the biosynthesis of extracellular polymeric substances (EPS), and the expression of biofilm-associated virulence factors, proposing an unexplored convergence among antibiofilm and anticancer mechanisms. Importantly, the biofilm structure (thickness, developmental stage, EPS density) affects the efficacy of terpenoids, affecting diffusion, microbial persistence, and therapeutic susceptibility. The quorum-sensing disruption is more effective in the early stages of biofilms, while high concentrations of EPS in mature, thick biofilms will require more penetration to disrupt quorum sensing. Innovative functional food matrices, including nano-enabled delivery systems, are emerging strategies to improve bioavailability and microbiome modulation of terpenoids. Furthermore, nano-formulations allow better penetration in dense biofilm matrices, protect terpenoids from early degradation, and allow prolonged and focused drug release in the tumor microenvironment associated with biofilms. Combining precision nutrition with microbiome-informed dietary strategies can be used to prevent and treat cancer. The present review combines studies linking biofilm-driven carcinogenesis with terpenoid-mediated antibiofilm-anticancer pathways and nano-mediated functional delivery and biofilm penetration, including highlighting the potential for microbiome modulation in cancer therapy.
Breast cancer is the most common malignancy in females internationally. Doxorubicin (DOX) has been well-thought-out as the most effective regimen for breast cancer treatment for several years. The chronic side effects of DOX obligate us to control the dosage that can be used, although its efficacy. Radiotherapy is a vigorous regimen in breast cancer treatment, but correlated side effects are determining factors for a successful recovery. Combined metronomic chemotherapy and radiotherapy, at low doses, can reduce the side effects of single-modality treatments. We have studied the dose 1.8 mg/kg twice per week for 8 weeks of DOX singly or with 0.5 Gy fractionated doses of gamma radiation on inducing cell death, cell cycle arrest, and apoptosis, and also P53, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), and caspase-3 gene expression in an animal breast cancer model. Treatment with DOX resulted in upregulation of apoptosis and downregulation of cell division at an accumulated dose of 0.5 Gy, as well as downregulation of Bcl-2 gene expression and upregulation of p53, Bax, and caspase-3 gene expression in animals bearing breast cancer. In addition, DOX in combination with radiation decreased the tumor size. A metronomic dose of DOX, when used with a low dose of gamma radiation, with the least side effects, could be a successful treatment for breast cancer in clinical trials.
Adipocyte hypertrophy poses an important mechanical challenge-adipocytes can increase in volume up to a thousand-fold while still maintaining their structural integrity. Although lipid metabolism is well studied, little is known about the cytoskeletal adaptations that are required to accommodate this expansion and the resulting pathological consequences. This review critically examines how the cytoskeletal remodelling is associated with insulin resistance. We explore how mechanotransduction pathways like YAP/TAZ, which inhibit the expression of adipogenic genes, are triggered when cortical actin transforms into stress fibres. This review also discusses the role of the microtubule network in lipid droplet fusion and the vimentin cage that regulates lipolysis. Further, we highlight the emerging role of the Septin family (SEPT), specifically the conflicting pro- and anti-adipogenic roles of SEPT7, where SEPTs might act as a molecular brake on adipocyte expansion. We conclude that obesity-induced insulin resistance is partially due to a failure of cytoskeletal mechanics, making cytoskeletal regulators potential therapeutic targets for metabolic disease.
Among 15-20 cases of breast cancer, triple-negative breast cancer (TNBC) is the deadliest form of the disease. The most effective form of treatment for this type of cancer is still targeted chemotherapy because it lacks hormone receptors. Myristicin, an active aromatic compound with anticancer properties, is mostly found in nutmeg. Antitumor, antioxidant, and antimicrobial activity are among few of the numerous properties of myristicin. On TNBC cells, the exact modes of action are mostly unidentified. This study shows that myristicin triggered the mitochondria-mediated apoptosis in MDA-MB-231 cells. The MTT assay assessed the anti-proliferative potential of myristicin on TNBC cells (IC50 0.65 mM ± 0.98). Flow cytometry analysis was used to evaluate the myristicin's effects on cell apoptosis using annexin V/PI (46.4 ± 2.31%). After evaluating the protein expression, myristicin significantly decreased the expression of Bcl2 and HSP60 while enhancing the expression of proteins such as caspase 9, caspase 3, bid, bad, caspase 7, P53, cytochrome c, and SDHA. Furthermore, our research confirmed that myristicin has a lower toxicological profile and greater in vivo therapeutic efficacy. In BALB/c mice, 4T1 cells were injected subcutaneously to develop breast tumors, and the mice subsequently received myristicin. According to in vivo results, myristicin treatment reduced tumor weight and volume when compared to the breast cancer control group. Besides, the enzyme analysis, gene, and protein expression showed significant apoptotic properties on myristicin treated group. According to these results, myristicin may be used as a therapeutic approach for the management of TNBC.
Cancer remains a major cause of global mortality, necessitating the identification of novel biomarkers to improve prognosis and guide therapy. ABCA1, an ATP-binding cassette transporter involved in cholesterol efflux, has been implicated in tumorigenesis, yet its pan-cancer roles and clinical relevance are not fully understood. We conducted a comprehensive multi-omics analysis of ABCA1 across diverse cancers, evaluating its expression, prognostic significance, genomic alterations, tumor immune microenvironment interactions, and regulatory mechanisms. ABCA1 expression was dysregulated in multiple malignancies and associated with poor prognosis in STAD, STES, and LGG, though favorable outcomes were observed in KIRC. It correlated with genomic instability markers (TMB, MSI, HRD), immune cell infiltration, and cancer stemness. Pathway analyses revealed enrichment in cholesterol metabolism and efferocytosis-related pathways. Among the cancer types examined, esophageal squamous cell carcinoma (ESCC) was selected for exploratory functional validation due to its prognostic relevance. In vitro, ABCA1 knockdown inhibited proliferation, invasion, and migration in ESCC cell lines. In silico drug sensitivity analysis suggested potential associations with dasatinib response and panobinostat resistance, warranting further experimental validation. Collectively, these findings highlight the context-dependent associations of ABCA1 with cancer progression, immune modulation, and genomic integrity, suggesting its potential utility as a prognostic biomarker that warrants further investigation for therapeutic targeting.
