Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03938-3
Background: Despite the pivotal role of fat grafting in plastic, reconstructive, and aesthetic surgery, inconsistent survival rates of transplanted adipose tissue, primarily due to early ischemic and hypoxic insults, remain a significant challenge. The infusion of healthy mitochondria has emerged as a promising intervention to support tissue recovery from ischemic, hypoxic, and other types of damages across various organ systems. Objectives: This study aims to evaluate the impact of supplementing human adipose tissue grafts with healthy exogenous mitochondria on their volume and mass retention rates when transplanted into the subcutaneous layers of nude mice. This approach seeks to improve and optimize fat grafting techniques. Methods: Human adipose tissues were preconditioned with exogenous mitochondria (10 µg/mL), a combination of exogenous mitochondria and the inhibitor Dyngo-4a, Dyngo-4a alone, or PBS, and then transplanted into the subcutaneous tissue of 24 nude mice. Samples were harvested at 1 and 3 months post-transplantation for analysis of mass and volume retention. The structural morphology and integrity of the adipose tissues were assessed using Hematoxylin and Eosin (H&E) staining. Results: Mitochondrial preconditioning significantly enhanced the retention of mass and volume in fat grafts, demonstrating superior structural morphology and integrity compared to the control group. Conclusions: This study highlights the potential of exogenous mitochondrial augmentation in fat transplantation to significantly improve fat graft survival, thereby optimizing the success of fat grafting procedures.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024004
SRP14 is a crucial protein subunit of the signal recognition particle (SRP), a ribonucleoprotein complex essential for co-translational translocation to the endoplasmic reticulum. During our investigation of SRP14 expression across diverse cell lines, we observe variations in its migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), with some cells exhibiting slower migration and others migrating faster. However, the cause of this phenomenon remains elusive. Our research rules out alternative splicing as the cause and, instead, identifies the presence of a P124A mutation in SRP14 (SRP14P124A) among the faster-migrating variants, while the slower-migrating variants lack this mutation. Subsequent ectopic expression of wild-type SRP14P124 or SRP14WT and SRP14P124A in various cell lines confirms that the P124A mutation indeed leads to faster migration of SRP14. Further mutagenesis analysis shows that the P117A and A121P mutations within the alanine-rich domain at the C-terminus of SRP14 are responsible for migration alterations on SDS-PAGE, whereas mutations outside this domain, such as P39A, Y27F, and T45A, have no such effect. Furthermore, the ectopic expression of SRP14WT and SRP14P124A yields similar outcomes in terms of SRP RNA stability, cell morphology, and cell growth, indicating that SRP14P124A represents a natural variant of SRP14 and retains comparable functionality. In conclusion, the substitution of proline for alanine in the alanine-rich tail of SRP14 results in faster migration on SDS-PAGE, but has little effect on its function.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024106
Acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) represents a primary cause of treatment failure in non-small cell lung cancer (NSCLC) patients. Chemokine (C-C motif) ligand 2 (CCL2) is recently found to play a pivotal role in determining anti-cancer treatment response. However, the role and mechanism of CCL2 in the development of EGFR-TKIs resistance have not been fully elucidated. In the present study, we focus on the function of CCL2 in the development of acquired resistance to EGFR-TKIs in NSCLC cells. Our results show that CCL2 is aberrantly upregulated in EGFR-TKIs-resistant NSCLC cells and that CCL2 overexpression significantly diminishes sensitivity to EGFR-TKIs. Conversely, CCL2 suppression by CCL2 synthesis inhibitor, bindarit, or CCL2 knockdown can reverse this resistance. CCL2 upregulation can also lead to enhanced migration and increased expressions of epithelial-mesenchymal transition (EMT) markers in EGFR-TKI-resistant NSCLC cells, which could also be rescued by CCL2 knockdown or inhibition. Furthermore, our findings suggest that CCL2-dependent EGFR-TKIs resistance involves the AKT-EMT signaling pathway; inhibition of this pathway effectively attenuates CCL2-induced cell migration and EMT marker expression. In summary, CCL2 promotes the development of acquired EGFR-TKIs resistance and EMT while activating AKT signaling in NSCLC. These insights suggest a promising avenue for the development of CCL2-targeted therapies that prevent EGFR-TKIs resistance in NSCLC.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024055
Acute rejection is an important factor affecting the survival of recipients after liver transplantation. Salidroside has various properties, including anti-inflammatory, antioxidant, and hepatoprotective properties. This study aims to investigate whether salidroside can prevent acute rejection after liver transplantation and to examine the underlying mechanisms involved. An in vivo acute rejection model is established in rats that are pretreated with tacrolimus (1 mg/kg/d) or salidroside (10 or 20 mg/kg/d) for seven days after liver transplantation. In addition, an in vitro experiment is performed using neutrophils incubated with salidroside (1, 10, 50 or 100 μM). Hematoxylin-eosin staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, immunosorbent assays, immunofluorescence analysis, Evans blue staining, and western blot analysis are performed to examine the impact of salidroside on NET formation and acute rejection in vitro and in vivo. We find that Salidroside treatment reduces pathological liver damage, serum aminotransferase level, and serum levels of IL-1β, IL-6, and TNF-α in vivo. The expressions of proteins associated with the HMGB1/TLR-4/MAPK signaling pathway (HMGB1, TLR-4, p-ERK1/2, p-JNK, p-P38, cleaved caspase-3, cleaved caspase-9, Bcl-2, Bax, IL-1β, TNF-α, and IL-6) are also decreased after salidroside treatment. In vitro experiments show that the release of HMGB1/TLR-4/MAPK signaling pathway-associated proteins from neutrophils treated with lipopolysaccharide is decreased by salidroside. Moreover, salidroside inhibits NETosis and protects against acute rejection by regulating the HMGB1/TLR-4/MAPK signaling pathway. Furthermore, salidroside combined with tacrolimus has a better effect than either of the other treatments alone. In summary, salidroside can prevent acute liver rejection after liver transplantation by reducing neutrophil extracellular trap development through the HMGB1/TLR-4/MAPK signaling pathway.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261614
Aging-related sarcopenia remains a clinical challenge due to limited effective interventions. This study systematically evaluated the therapeutic potential of the iridoid fraction from Morinda officinalis and elucidated its mechanism via the PI3K/Akt/mTOR pathway. Using monotropein and deacetylasperulosidic acid as markers, extraction was optimized with 60% ethanol under heated reflux, yielding the highest iridoid content. Purification employed H103 macroporous resin with water as eluent, achieving maximal recovery. In vitro, the fraction significantly ameliorated D-galactose-induced C2C12 myotube atrophy (P < 0.001) and promoted myotube differentiation (P < 0.05, 0.01, 0.001), as evidenced by MYHC expression. In vivo, D-galactose-accelerated aging mice treated with the fraction exhibited increased limb grip strength and hindlimb muscle mass-to-body weight ratio (P < 0.05, 0.01, 0.001), along with expanded cross-sectional area of tibialis anterior and gastrocnemius muscles (P < 0.01, 0.001). Transcriptomic and network pharmacology analyses implicated the PI3K/Akt pathway. Western blotting and qRT-PCR confirmed upregulation of key proteins and genes (PIK3CA, AKT1, mTOR) in the pathway (P < 0.05, 0.01, 0.001), while the PI3K inhibitor LY294002 reversed these effects (P < 0.05). These findings demonstrate that the iridoid fraction from M. officinalis mitigates aging-related sarcopenia through PI3K/Akt/mTOR signaling, providing a promising candidate for clinical translation.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21207
BACKGROUND: Hypoxia preconditioning can increase extracellular vesicles, growth factors, anti-inflammatory and immunosuppressive factors in the parasecretory secretions of mesenchymal stem cells. Exosomes derived from human amniotic mesenchymal stem cells preconditioned with hypoxia are expected to play a better therapeutic role in tissue damage repair. OBJECTIVE: To observe the repair effect of exosomes from human amniotic mesenchymal stem cells preconditioned with hypoxia on radiation-induced submandibular gland epithelial cell damage. METHODS: The passage 3 human amniotic mesenchymal stem cells were divided into two groups: hypoxia and normoxia. They were pretreated with hypoxia (1% O2 by volume) and normoxia (20% O2 by volume) for 48 hours, respectively. Then, normoxic and hypoxic human amniotic mesenchymal stem cell exosomes were extracted from the culture supernatant of human amniotic mesenchymal stem cells by modified ultrahigh-speed centrifugation. The submandibular gland epithelial cells of SD newborn rats were divided into blank control group, radiation control group, normoxia-treated group, and hypoxia-treated group. The submandibular gland epithelial cells were treated with 5 Gy radiation to construct a radiation-induced injury model. The normoxia-treated and hypoxia-treated groups were co-cultured with normoxic or hypoxic exosomes for 3 days. CCK-8 assay was used to detect the proliferation activity of rat submandibular gland epithelial cells; ELISA was used to measure the content of α-amylase in the supernatant; RT-qPCR was used to detect the expression of aquaporin 5 mRNA. RESULTS AND CONCLUSION: The cell proliferation activity in the radiation control group was significantly lower than that in the blank control group (P < 0.05). The cell proliferation activity in the normoxia-treated and hypoxia-treated groups on days 2 and 3 was significantly higher than that in the radiation control group (P < 0.05). The cell proliferation activity in the hypoxia-treated group on day 1 was higher than that in the normoxia-treated group, and showed an increasing trend on days 2 and 3, but there was no statistical difference compared with the normoxia-treated group (P > 0.05). The α-amylase content in the radiation control group was significantly lower than that in the blank control group (P < 0.05). The α-amylase content in the normoxia-treated and hypoxia-treated groups was significantly higher than that in the radiation control group (P < 0.05). Compared with the normoxia-treated group, the α-amylase content in the hypoxia-treated group showed an increasing trend, but there was no statistical difference (P > 0.05). The expression of aquaporin 5 mRNA in the radiation control group was significantly lower than that in the blank control group (P < 0.05). The expression of aquaporin 5 mRNA in the normoxia-treated and hypoxia-treated groups was significantly higher than that in the radiation control group (P < 0.05). The expression of aquaporin 5 mRNA in the hypoxia-treated group was slightly higher than that in the normoxia-treated group, but there was no statistical difference (P > 0.05). The results indicate that both normoxic and hypoxic preconditioned human amniotic mesenchymal stem cell exosomes have a repair effect on radiation-induced submandibular gland epithelial cell damage, but hypoxic exosomes have no obvious advantage.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21261
BACKGROUND: The glycocalyx serves as a selective permeability barrier that enables the controlled exchange of substances and maintains fluid balance between within and outside the blood vessels. It is also involved in various pathological processes, including inflammation, thrombus formation, and microcirculation disorders, and is significantly associated with the development and progression of diseases such as atherosclerosis, diabetes, and cancer. OBJECTIVE: To correlate glycocalyx with exercise and disease. METHODS: A literature search was conducted across international databases (MedReading, PubMed, and Web of Science) and Chinese databases (CNKI, WanFang, and VIP) to identify academic articles. The search terms used were “glycocalyx, physical exercise, disease” in Chinese and “glycocalyx, physical exercise, exercises, physical activity, acute exercise, isometric exercises, aerobic exercise, resistance training, exercise training, disease, diseases” in English. A total of 81 publications were included in the final analysis. RESULTS AND CONCLUSION: As a biological barrier of the vascular endothelium, the glycocalyx plays a key role in regulating vascular permeability, mediating inflammatory responses, sensing blood shear stress, and facilitating anticoagulation. The integrity of the glycocalyx is essential for maintaining stable normal blood circulation and ensuring the physiological functions of various organs in the body. Shedding of the glycocalyx can induce structural changes in the endothelial barrier, leading to an abnormal increase in endothelial permeability and accelerating the pathological processes associated with atherosclerosis. Research has confirmed that the extensive thickening and shedding of the glycocalyx on the surface of cancer cells promote tumor proliferation, metastasis, and disease progression. In traumatic diseases, the severity can be assessed by measuring the levels of debris resulting from glycocalyx injury. The glycocalyx is influenced by factors such as the duration of exercise, changes in exercise mode, and exercise intensity. Acute exercise can induce microvascular changes and increase glycocalyx thickness. Aerobic exercise-induced shedding sensitivity of glycocalyx components varies by sex, age, and body mass index. Resistance exercise has positive acute effects on endothelial glycocalyx. Long-term exercise training can protect the glycocalyx. The glycocalyx serves as an intervention target for atherosclerosis, sepsis, cancer, and other diseases, providing theoretical support for developing non-pharmacological therapeutic strategies. However, clinical application of glycocalyx damage markers is not yet standardized, and the mechanisms among glycocalyx, exercise, and disease require further investigation.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21302
BACKGROUND: The benefits of exercise as a classical intervention for aging have been widely recognized. The homeostatic balance of a wide range of microorganisms in the intestinal flora indirectly regulates aging, and the bidirectional association between exercise and the intestinal flora can collectively influence the process of aging. OBJECTIVE: To sort out the effects of exercise, intestinal flora and their interactions on aging, and to explore the specific physiological mechanisms involved. METHODS: A computer-based search in CNKI, WanFang, VIP, PubMed, MedReading, and Web of Science, with the time limit of 1976-01-01/2025-02-28, was conducted to collect the relevant studies on the effects of exercise and intestinal flora on aging. The search terms were “intestinal flora, gut microbiota, physical exercise, age, aerobic exercise, resistance exercise, low intensity exercise, moderate intensity exercise, high intensity exercise” in Chinese and English. RESULTS AND CONCLUSION: (1) Exercise and intestinal flora are both means to intervene in aging, and the combined benefits of exercise and gut microbiota in intervening in aging are even more pronounced. (2) Exercise changes the composition and function of intestinal flora, stimulates intestinal production of short-chain fatty acids, regulates host metabolism and immune function, reduces inflammatory response, and promotes the synthesis of vitamins and neurotransmitters. (3) The specific manifestations of aging, when the intestinal flora is regulated via different exercise modes, are different. (4) Different gut-organ axis regulated by exercise has different effects on aging.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21396
BACKGROUND: Current finite element models of the wrist joint predominantly focus on osseous and ligamentous structures, with insufficient incorporation of musculotendinous components, thereby limiting their fidelity and accuracy. OBJECTIVE: To establish a high-fidelity finite element model of the wrist joint, providing a reference for in-depth biomechanical investigations. METHODS: Upper limb CT and MRI data from a 33-year-old healthy male volunteer were imported into Mimics 20.0. Threshold-based selection, region growing, and image segmentation techniques were employed to reconstruct wrist-related bones and soft tissues (including muscles). The model underwent surface optimization, patch generation, and meshing in SolidWorks 2020 and HyperMesh 14.0. Material property assignment and ligament-cartilage contact interfaces were implemented in ABAQUS 6.13 to construct a three-dimensional finite element model of the wrist joint. Stress distribution across wrist structures under axial compression was analyzed. RESULTS AND CONCLUSION: (1) A three-dimensional finite element model encompassing the ulna, radius, distal humerus, carpal bones, metacarpals, pronator teres, pronator quadratus, supinator, lateral muscle group, volar muscle group, dorsal muscle group, interosseous membrane, major ligaments, and cartilage structures was successfully established, comprising 759 191 elements and 245 510 nodes. The stress distribution pattern at the radiocarpal joint under axial compression was obtained and compared with cadaveric studies from the literature, validating the model's authenticity and effectiveness. (2) In summary, based on human CT and MRI imaging data, a more complete wrist joint bone and soft tissue structure was reconstructed through computer software simulation, establishing the origin and insertion points of forearm muscles and their contact with bones during muscle course, resulting in a more realistic finite element model of the wrist joint.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21344
BACKGROUND: Neural stem cells located in the ventricular zone and subventricular zone are crucial for cortical neurodevelopment and the treatment of neurodegenerative diseases. However, their precise regulatory mechanisms remain incompletely understood. miRNA-9 is one of the most abundantly expressed miRNAs in the vertebrate embryonic and adult brain, playing diverse roles during development. Nevertheless, the role of miR-9 in neural stem cell differentiation remains unclear. OBJECTIVE: To investigate the role of miR-9 in regulating the differentiation of neural stem cells in the ventricular zone and subventricular zone. METHODS: Neural stem cells were isolated from the ventricular zone and subventricular zone of embryonic day 14.5 ICR mice and cultured in proliferation medium for 3-4 days to form neurospheres. Stemness was identified by Pax6/Nestin immunofluorescence double staining. The expression profile of miR-9 was detected by qRT-PCR in telencephalon tissues at embryonic days 12.5, 14.5, 16.5, 18.5 and postnatal days 0, 7, as well as in embryonic day 14.5 neural stem cells cultured in vitro. Neural stem cells were transfected with miR-9 inhibitor or mimic using transfection reagents. After 24 hours, cells were differentiated for 3-4 days (neurons) and 6-8 days (glial cells). The differentiation of each lineage was quantified by immunofluorescence staining for Tuj1 (neuronal marker), myelin basic protein (oligodendrocyte marker), and glial fibrillary acidic protein (astrocyte marker). RESULTS AND CONCLUSION: qRT-PCR results showed that miR-9 was highly expressed in early embryonic telencephalon (E12.5-E14.5) and gradually decreased with development (E16.5 to P7). In E14.5 neural stem cells, miR-9 expression level was close to 90% of the internal reference RNU6B. Functional experiments showed that compared with the control group, the miR-9 inhibition group had decreased proportions of Tuj1-positive neurons and myelin basic protein-positive oligodendrocytes, while the proportion of glial fibrillary acidic protein-positive astrocytes increased. Conversely, the miR-9 overexpression group had increased proportions of Tuj1-positive neurons and myelin basic protein-positive oligodendrocytes, and decreased proportion of glial fibrillary acidic protein-positive astrocytes, with significant differences (P < 0.001). These results indicate that miR-9 plays a bidirectional regulatory role in neural stem cell differentiation: (1) It participates in the temporal regulation of neurogenesis through developmental stage-specific expression patterns (high early, downregulated later); (2) It maintains the balance of trilineage differentiation by promoting neuronal and oligodendrocyte differentiation while inhibiting astrocyte generation.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21528
BACKGROUND: Modern research suggests that the “muscle-bone imbalance” in cervical spondylotic radiculopathy is associated with changes in the performance of cervical muscles due to biomechanical alterations of the head and neck. However, most studies have focused on static analysis of the cervical spine, lacking dynamic quantitative data on neck muscle strength and activation. OBJECTIVE: To investigate the differences in muscle strength and muscle activation during cervical spine movement between patients with cervical spondylotic radiculopathy and healthy individuals from a biomechanical perspective. METHODS: From October 1, 2023 to March 1, 2024, 10 volunteers were recruited from the orthopedic outpatient or inpatient department and health examination center of the First Affiliated Hospital of Guangxi University of Chinese Medicine, including 5 patients with cervical spondylotic radiculopathy (cervical spondylotic radiculopathy group) and 5 healthy individuals (healthy control group). Inertial motion capture sensors were used to capture the motion data of the neck in six degrees of freedom: flexion, extension, left lateral flexion, right lateral flexion, left rotation, and right rotation. Each movement was repeated three times, yielding 18 sets of data per subject. Based on MRI-derived muscle parameters of patients and healthy individuals, OpenSim head-neck musculoskeletal models were respectively established. After preprocessing, the captured neck motion data were imported into the OpenSim simulation model to calculate and compare the neck muscle strength and muscle activation levels between the two groups. RESULTS AND CONCLUSION: (1) The healthy control group showed orderly synergistic activation of muscle groups, while the cervical spondylotic radiculopathy group exhibited disordered synergistic activation patterns, characterized by insufficient activation of the affected side muscles, excessive compensation of the healthy side, and significantly reduced synergy of core muscles such as the sternocleidomastoid, middle and upper trapezius, and longus colli. In the cervical spondylotic radiculopathy group, during extension, the muscle strength of the sternocleidomastoid, middle trapezius, longus capitis, and upper trapezius was lower than that of the healthy control group (P < 0.05). During flexion, the muscle strength of the sternocleidomastoid, longus capitis, longus colli, levator scapulae, multifidus, splenius cervicis, splenius capitis, and middle/upper trapezius was lower than that of the healthy control group (P < 0.05). During left lateral flexion, the muscle strength of the sternocleidomastoid, longus capitis, longus colli, scalene, levator scapulae, multifidus, splenius cervicis, splenius capitis, and middle/upper trapezius was lower than that of the healthy control group (P < 0.05). During right lateral flexion, the muscle strength of the longus colli and upper trapezius was lower than that of the healthy control group (P < 0.05). During left rotation, the muscle strength of the levator scapulae was lower than that of the healthy control group (P < 0.05). During right rotation, the muscle strength of the longus colli was lower than that of the healthy control group (P < 0.05). (2) These findings indicate that patients with cervical spondylotic radiculopathy exhibit muscle synergy imbalance in all directions of cervical spine movement. The imbalance is characterized by degeneration of the affected side muscles and nerves, reduced muscle strength and coordination, while the healthy side muscles and nerves compensate for the functional insufficiency of the affected side, leading to over-control. Among the muscle groups involved in cervical spine movement, the degeneration of the sternocleidomastoid and middle/upper trapezius is the most significant, which is one of the important features causing cervical spondylotic radiculopathy.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21600
BACKGROUND: Combining exosomes with biomaterials such as hydrogels and biological scaffolds enables targeted delivery, providing effective support for damaged tissue and significantly enhancing the therapeutic efficiency of exosomes, thus positively impacting spinal cord injury repair. OBJECTIVE: To review the action mechanisms and research progress of exosomes combined with biomaterials in spinal cord injury. METHODS: Databases including CNKI, PubMed, and Web of Science were searched using the Chinese and English search terms “spinal cord injury, exosomes, hydrogel, biological scaffold, neuroinflammation, oxidative stress, axonal regeneration, angiogenesis.” Based on the inclusion criteria, 106 articles were finally included in this review. RESULTS AND CONCLUSION: Current research focuses on the repair of secondary injury after spinal cord injury, and how to better alleviate the damage caused by secondary injury is a key research question. Exosomes combined with biomaterials treat spinal cord injury mainly through regulating neuroinflammation, promoting axonal regeneration, and alleviating oxidative stress. This approach avoids immune rejection, solves the problem of low bioavailability of exosomes, and provides effective tissue support, thereby alleviating secondary symptoms after spinal cord injury. Most studies on exosome-loaded biomaterials for spinal cord injury are limited to cell and animal experiments, lacking clinical trial data. Future research should focus on further mechanistic studies, safety evaluations, and related clinical trials.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025113
Nasopharyngeal carcinoma (NPC) remains a prevalent malignancy in East Asia and Southeast Asia, with current radiotherapeutic and chemotherapeutic regimens yielding unsatisfactory 5-year survival rates and substantial acute and late toxicities. Nobiletin (NOB), a polymethoxyflavonoid exclusive to citrus peel, exhibits potent anticancer activity. This study evaluated the chemopreventive potential of NOB through comprehensive in vitro and in vivo assessments using subcutaneous tumor mouse models. NOB effectively hindered the migration and invasion capacities of CNE-2 and 5-8F NPC cells in a dose- and time-dependent manner. Mechanistically, NOB acts as a potent KEAP1 activator, significantly disrupting the NRF2/ARE signaling pathway by accelerating proteasomal degradation of NRF2 and suppressing its nuclear translocation. This cascade reduces the expression of ARE-driven genes and antioxidant enzymes, thereby increasing intracellular reactive oxygen species (ROS) levels and augmenting antitumor immunity. Notably, the sensitivity induced by NOB was markedly diminished in CNE-2 cells following KEAP1 gene silencing, underscoring the pivotal role of NOB in activating KEAP1. Overall, KEAP1 has emerged as a compelling target for potential malignancy treatment in NPC cell lines. These results suggest the promising application of NOB as a natural sensitizer in chemotherapy, opening avenues for therapeutic interventions.