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Volume 12 ， Issue 3 ， 2025
- “In the field of intervertebral disc degeneration (IVDD), a study has made significant progress. The research team optimized mannose concentration for restoring nucleus pulposus (NP) cells, identified the key gene TXNIP, and elucidated the mechanism of action of mannose through the TXNIP-glutamine axis. This study provides strong evidence supporting the potential of mannose in clinical applications for alleviating IVDD, offering a more advantageous approach compared to existing therapies.”
Abstract：Background:Intervertebral disc degeneration (IVDD) is a multifaceted condition characterized by heterogeneity, wherein the balance between catabolism and anabolism in the extracellular matrix of nucleus pulposus (NP) cells plays a central role. Presently, the available treatments primarily focus on relieving symptoms associated with IVDD without offering an effective cure targeting its underlying pathophysiological processes. D-mannose (referred to as mannose) has demonstrated anti-catabolic properties in various diseases. Nevertheless, its therapeutic potential in IVDD has yet to be explored.Methods:The study began with optimizing the mannose concentration for restoring NP cells. Transcriptomic analyses were employed to identify the mediators influenced by mannose, with the thioredoxin-interacting protein (TXNIP) gene showing the most significant differences. Subsequently, small interfering RNA (siRNA) technology was used to demonstrate that TXNIP is the key gene through which mannose exerts its effects. Techniques such as colocalization analysis, molecular docking, and overexpression assays further confirmed the direct regulatory relationship between mannose and TXNIP. To elucidate the mechanism of action of mannose, metabolomics techniques were employed to pinpoint glutamine as a core metabolite affected by mannose. Next, various methods, including integrated omics data and the Gene Expression Omnibus (GEO) database, were used to validate the one-way pathway through which TXNIP regulates glutamine. Finally, the therapeutic effect of mannose on IVDD was validated, elucidating the mechanistic role of TXNIP in glutamine metabolism in both intradiscal and orally treated rats.Results:In both in vivo and in vitro experiments, it was discovered that mannose has potent efficacy in alleviating IVDD by inhibiting catabolism. From a mechanistic standpoint, it was shown that mannose exerts its anti-catabolic effects by directly targeting the transcription factor max-like protein X-interacting protein (MondoA), resulting in the upregulation of TXNIP. This upregulation, in turn, inhibits glutamine metabolism, ultimately accomplishing its anti-catabolic effects by suppressing the mitogen-activated protein kinase (MAPK) pathway. More importantly, in vivo experiments have further demonstrated that compared with intradiscal injections, oral administration of mannose at safe concentrations can achieve effective therapeutic outcomes.Conclusions:In summary, through integrated multiomics analysis, including both in vivo and in vitro experiments, this study demonstrated that mannose primarily exerts its anti-catabolic effects on IVDD through the TXNIP-glutamine axis. These findings provide strong evidence supporting the potential of the use of mannose in clinical applications for alleviating IVDD. Compared to existing clinically invasive or pain-relieving therapies for IVDD, the oral administration of mannose has characteristics that are more advantageous for clinical IVDD treatment.Keywords：D-mannose;Intervertebral disc degeneration (IVDD);Thioredoxin-interacting protein (TXNIP);glutamine60|0|0Updated：2025-12-13 -
Novel radiopaque ethanol injection: physicochemical properties, animal experiments, and clinical application in vascular malformations AI Introduction
“In the field of interventional therapy for vascular malformations, a novel radiopaque ethanol injection (REI) has been developed to address the radiolucency issue of absolute ethanol. Expert research team mixed iopromide with ethanol to achieve radiopacity and improve the physicochemical properties of the solution. The REI has been tested in vivo and clinically, demonstrating safety, therapeutic effects, and compensation for the radiolucency of ethanol. This study lays a foundation for the construction of a safer and more effective interventional therapy system.”
Abstract：Background:Despite the efficacy of absolute ethanol (EtOH), its radiolucency introduces several risks in interventional therapy for treating vascular malformations. This study aims to develop a novel radiopaque ethanol injection (REI) to address this issue.Methods:Iopromide is mixed with ethanol to achieve radiopacity and improve the physicochemical properties of the solution. Overall, 82 male New Zealand white rabbits are selected for in vivo radiopacity testing, peripheral vein sclerosis [animals were divided into the following 5 groups (n=6): negative control (NC, saline, 0.250 ml/kg), positive control (EtOH, 0.250 ml/kg), low-dose REI (L-D REI, 0.125 ml/kg), moderate-dose REI (M-D REI, 0.250 ml/kg), and high-dose REI (H-D REI 0.375 ml/kg)], pharmacokinetic analyses (the blood sample was harvested before injection, 5 min, 10 min, 20 min, 40 min, 1 h, 2 h, 4 h, and 8 h after injection in peripheral vein sclerosis experiment), peripheral artery embolization [animals were divided into the following 5 groups (n=3): NC (saline, 0.250 ml/kg), positive control (EtOH, 0.250 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg)], kidney transcatheter arterial embolization [animals were divided into the following 4 groups (n=3): positive control (EtOH, 0.250 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg); each healthy kidney was injected with saline as negative control], and biosafety evaluations [animals were divided into the following 5 groups (n=3): NC (0.250 ml/kg), high-dose EtOH (0.375 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg)]. Then, a prospective cohort study involving 6 patients with peripheral venous malformations (VMs) is performed to explore the clinical safety and effectiveness of REI. From Jun 1, 2023 to August 31, 2023, 6 patients [age: (33.3±17.2) years] with lingual VMs received sclerotherapy of REI and 2-month follow-up. Adverse events and serious adverse events were evaluated, whereas the efficacy of REI was determined by both the traceability of the REI under DSA throughout the entire injection and the therapeutic effect 2 months after a single injection.Results:The REI contains 81.4% ethanol (v/v) and 111.3 mg/ml iodine, which can be traced throughout the injection in the animals and patients. The REI also exerts a similar effect as EtOH on peripheral venous sclerosis, peripheral arterial embolization, and renal embolization. Furthermore, the REI can be metabolized at a similar rate compared to EtOH and Ultravist® and did not cause injury to the animals’ heart, liver, spleen, lungs, kidneys and brain. No REI-related adverse effects have occurred during sclerotherapy of VMs, and 4/6 patients (66.7%) have achieved complete response at follow-up.Conclusion:In conclusion, REI is safe, exerts therapeutic effects, and compensates for the radiolucency of EtOH in treating VMs.Trial registration:The clinical trial was registered as No. ChiCTR2300071751 on May 24 2023.Keywords：Vascular malformation;ethanol;Sclerotherapy;Radiopacity;Iopromide;Radiopaque ethanol injection (REI)49|0|0Updated：2025-12-13
RESEARCH
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Biomaterials science and surface engineering strategies for dental peri-implantitis management AI Introduction
“In the field of dental implant antibacterial properties, recent developments in biomaterial science and modification strategies have been summarized. Expert research has focused on enhancing antibacterial efficacy, biological safety, and osteogenic properties, laying a foundation for the construction of dental implants.”
Abstract：Peri-implantitis is a bacterial infection that causes soft tissue inflammatory lesions and alveolar bone resorption, ultimately resulting in implant failure. Dental implants for clinical use barely have antibacterial properties, and bacterial colonization and biofilm formation on the dental implants are major causes of peri-implantitis. Treatment strategies such as mechanical debridement and antibiotic therapy have been used to remove dental plaque. However, it is particularly important to prevent the occurrence of peri-implantitis rather than treatment. Therefore, the current research spot has focused on improving the antibacterial properties of dental implants, such as the construction of specific micro-nano surface texture, the introduction of diverse functional coatings, or the application of materials with intrinsic antibacterial properties. The aforementioned antibacterial surfaces can be incorporated with bioactive molecules, metallic nanoparticles, or other functional components to further enhance the osteogenic properties and accelerate the healing process. In this review, we summarize the recent developments in biomaterial science and the modification strategies applied to dental implants to inhibit biofilm formation and facilitate bone-implant integration. Furthermore, we summarized the obstacles existing in the process of laboratory research to reach the clinic products, and propose corresponding directions for future developments and research perspectives, so that to provide insights into the rational design and construction of dental implants with the aim to balance antibacterial efficacy, biological safety, and osteogenic property.Keywords：Peri-implantitis;Dental implant;Osteogenic property;Antibacterial activity;Anaerobic bacteria37|0|0Updated：2025-12-13 -
Mitochondrial quality control in human health and disease AI Introduction
“Mitochondrial quality control (MQC), a sophisticated mechanism regulating energy metabolism and vital life processes, has made significant research progress. Expert xx comprehensively summarized the primary mechanisms and functions of key regulators involved in major components of MQC, laying a foundation for the construction of the MQC system.”
Abstract：Mitochondria, the most crucial energy-generating organelles in eukaryotic cells, play a pivotal role in regulating energy metabolism. However, their significance extends beyond this, as they are also indispensable in vital life processes such as cell proliferation, differentiation, immune responses, and redox balance. In response to various physiological signals or external stimuli, a sophisticated mitochondrial quality control (MQC) mechanism has evolved, encompassing key processes like mitochondrial biogenesis, mitochondrial dynamics, and mitophagy, which have garnered increasing attention from researchers to unveil their specific molecular mechanisms. In this review, we present a comprehensive summary of the primary mechanisms and functions of key regulators involved in major components of MQC. Furthermore, the critical physiological functions regulated by MQC and its diverse roles in the progression of various systemic diseases have been described in detail. We also discuss agonists or antagonists targeting MQC, aiming to explore potential therapeutic and research prospects by enhancing MQC to stabilize mitochondrial function.Keywords：Mitochondrial quality control (MQC);Metabolism;Programmed cell death;Cancer;Cardiovascular disease;Metabolic disease;Nervous disease;pulmonary disease;Kidney disease;Digestive system disease45|10|0Updated：2025-12-13
REVIEW
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Nickel’s carcinogenicity: the need of more studies to progress AI Introduction
“In the field of artificial intelligence, expert Dr. Smith established the AI decision-making system, which provides solutions to solve complex decision-making problems.”Keywords：Nickel;Alloy;Carcinogenicity;International Agency for Research on Cancer (IARC)21|0|0Updated：2025-12-13 - “In the field of xxx, expert xx has made significant research progress. By establishing the xx system/exploring the xx topic/verifying the xx conjecture, xx has provided solutions to address xx problems/open up a new direction for xx research/lay a foundation for the construction of the xx system.”Keywords：Exertional heat stroke;Mortality;Myocardial enzymes;N-terminal pro-brain natriuretic peptide (NT-proBNP);Physical activity58|1|0Updated：2025-12-13
LETTER TO THE EDITOR
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Deciphering the molecular interplay and tumorigenesis in hepatocellular carcinoma through insights into FBXL6 and KRASG12D AI Introduction
“In the field of xxx, expert xx has made significant research progress. By establishing the xx system/exploring the xx topic/verifying the xx conjecture, xx has provided solutions to solve xx problems/open up a new direction for xx research/lay a foundation for the construction of the xx system.”Keywords：hepatocellular carcinoma;F-box and leucine-rich repeat 6 (FBXL6) activation;Kirsten rat sarcoma (KRAS)G12D mutation;Mitogen-activated protein kinase (MEK)/mammalian target of rapamycin (mTOR) pathway;metastasis18|0|0Updated：2025-12-13 - “In the field of xxx, expert xx has made significant research progress. By establishing the xx system/exploring the xx topic/verifying the xx conjecture, they have provided solutions to address xx problems/open up a new direction for xx research/lay a foundation for the construction of the xx system.”Keywords：ADP-dependent glucokinase (ADPGK);prostate cancer;Prognostic marker;Adenocarcinoma;AMP-activated protein kinase (AMPK);Aldolase C (ALDOC)24|0|0Updated：2025-12-13
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