Discovery Medicine[JOURNAL]
Sun
200 papers
ACSL6-Mediated Cell Ferroptosis by Inhibiting AMPK Pathway in Periodontitis Stem Cells.
Chang Y, Chou L, Zeng C … +4 more , Li P, Allaf OS, Lu Y, Xu Y
Discov Med · 2025 Mar · PMID 40116099 · Publisher ↗
BACKGROUND: Periodontitis is an immunoinflammatory disease. Ferroptosis is a type of inflammation-associated cell death. The article aims to investigate the expression, role, and mechanism of the ferroptosis-related gene...
BACKGROUND: Periodontitis is an immunoinflammatory disease. Ferroptosis is a type of inflammation-associated cell death. The article aims to investigate the expression, role, and mechanism of the ferroptosis-related gene acyl-CoA synthetase long-chain family member 6 () in periodontitis Methods: Ferroptosis-related genes were identified using the Gene Expression Omnibus dataset and the Kyoto Encyclopedia of Genes and Genomes pathway. expression was validated using quantitative reverse-transcription polymerase chain reaction in patients with periodontitis. Human periodontal ligament fibroblasts (hPDLFs) were isolated and characterized. Following treatment, related experiments were performed to evaluate iron levels, reactive oxygen species (ROS) production, cell viability, expression, and ferroptosis-related proteins in hPDLFs. RESULTS: In this study, 185 genes were upregulated, and 102 were downregulated in the periodontitis group ( < 0.05). , a ferroptosis-related gene, exhibited high expression levels in periodontitis tissues ( < 0.05). lipopolysaccharide (-LPS) upregulated ( < 0.05), downregulated ferroptosis-related genes (glutathione peroxidase 4 ( < 0.001) and cystine/glutamate transporter (Solute Carrier Family 7 Member 11) ( < 0.01)) and phosphor (p)-AMP-activated protein kinase (AMPK) ( < 0.05), reduced cell viability ( < 0.001), and elevated iron ( < 0.001) and ROS levels ( < 0.001) in hPDLFs. silencing could counteract the effects of -LPS ( < 0.01). Furthermore, AMPK inhibitors lessen the effect of silencing ( < 0.01). CONCLUSIONS: The ferroptosis-related gene was highly expressed in periodontitis tissues, and silencing enhanced viability and inhibited ferroptosis in -LPS-mediated hPDLFs by upregulating the AMPK pathway.
Targeting HSF1-TLR9 Axis: Celastrol as a Potential Therapeutic for Liver Injury in Traumatic Hemorrhagic Shock.
Zhu J, Sun X, Zhan Y
Discov Med · 2025 Mar · PMID 40116098 · Publisher ↗
BACKGROUND: One of the pharmacological effects of celastrol (Cel) is the amelioration of acute liver injury. In this study, we explored the mechanism of Cel underlying the alleviation of liver injury induced by traumatic...
BACKGROUND: One of the pharmacological effects of celastrol (Cel) is the amelioration of acute liver injury. In this study, we explored the mechanism of Cel underlying the alleviation of liver injury induced by traumatic hemorrhagic shock (THS). METHODS: The THS model was developed from Sprague-Dawley rats through transverse fractures, blood loss and fluid infusion. Then, the THS rats were intraperitoneally injected with 0.5, 1, and 1.5 mg/kg Cel. The rats were injected in the tail vein with lentivirus-mediated small interfering RNA (siRNA) negative control (siNC), siRNA targeting heat shock transcription factor 1 (), and siRNA targeting toll-like receptor 9 () 72 hours before the establishment of THS model. Hematoxylin-eosin (HE) staining was performed to highlight the pathological alterations in the rat liver tissue. Enzyme-linked immunosorbent Assay (ELISA) was utilized to determine the expression levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and total bilirubin (TB). The expression levels of B-cell lymphoma 2 () and B-cell lymphoma 2 associated X protein () were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The expression levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were determined to assess the extent of oxidative stress. Western blotting was used to evaluate the expression levels of heat shock transcription factor 1 (HSF1), toll-like receptor 9 (TLR9) and myeloid differentiation factor 88 (MyD88). RESULTS: Cel was shown to therapeutically alleviate liver injury, decrease ALT and AST levels, and simultaneously downregulate inflammation factors levels (TNF-α, IL-1β), alleviated apoptosis, and decreased oxidative stress in the THS model in a concentration-dependent manner. Moreover, Cel increased the expression of and decreased the expression of and in the THS model. And silencing increased and expression. Further, the silencing of resulted in liver injury, inflammation and apoptosis, which could be reversed by silencing. CONCLUSIONS: This study demonstrates that Cel attenuates THS-induced liver injury by positively regulating so as to inhibit the expression of .
Machine Learning Models Based on Stretched-Exponential Diffusion Weighted Imaging to Predict TROP2 Expression in Nude Mouse Breast Cancer Models.
Deng Y, Han CG, Deng ZQ … +4 more , Yang SY, Wu ZH, Liu JL, Ma JM
Discov Med · 2025 Mar · PMID 40116097 · Publisher ↗
BACKGROUND: Trophoblast cell surface antigen 2 (TROP2) is a promising target for various cancers, including breast cancer. The development of noninvasive techniques for assessing TROP2 expression in tumors holds consider...
BACKGROUND: Trophoblast cell surface antigen 2 (TROP2) is a promising target for various cancers, including breast cancer. The development of noninvasive techniques for assessing TROP2 expression in tumors holds considerable importance. This study aims to explore the efficacy of machine learning models based on multi-b-value diffusion-weighted imaging (DWI) using the stretched-exponential model (SEM) for predicting TROP2 expression in breast cancer in nude mouse models. MATERIALS AND METHODS: Thirty-two nude mouse breast cancer models were subjected to 1.5T magnetic resonance imaging (MRI). Using the freely available software package FireVoxe, we extracted the distribution diffusion coefficient (DDC) and water molecule diffusion heterogeneity index (α) values from SEM, along with histogram parameters of DDC and α maps. TROP2 expression was identified by immunohistochemical staining, with integrated optical density (IOD) quantifying the expression levels. Mice were categorized into high and low TROP2 expression groups based on the median IOD. Key imaging parameters were selected to establish three machine learning models: extreme gradient boosting (XGBoost) classifier, logistic regression, and adaptive boosting (AdaBoost) classifier. We compared the models using the area under the curve (AUC) of the receiver operating characteristic (ROC) on a validation set to determine the superior model. The dataset was split into a training set (28 cases) and a test set (4 cases). The selected model was trained to optimize its performance. We evaluated the models' predictive accuracy in estimating TROP2 expression using AUC, calibration curve, and decision curve analysis (DCA). RESULTS: Thirty-eight imaging parameters, including DDC, α value, and 36 histogram parameters, were extracted per sample. Using these, we identified eight key imaging parameters for constructing the machine learning models. The validation set AUC values for the XGBoost, logistic regression, and AdaBoost models were 0.828, 0.639, and 0.728, respectively, with XGBoost demonstrating superior prediction performance. In the training set, XGBoost achieved an AUC of 1, sensitivity of 0.911, specificity of 1, and accuracy of 0.954; each of these values was 1 in the test set. Cross-validation yielded an AUC of 0.689, sensitivity of 0.567, specificity of 0.567, and accuracy of 0.580. The calibration curve's Brier score was 0.044, indicating proximity to the ideal curve. DCA indicated favorable net benefits within a risk threshold range of 20-90%. CONCLUSIONS: Machine learning models based on SEM show promise for predicting TROP2 expression in breast cancer in nude mouse models. Among the models, XGBoost demonstrated outstanding performance, suggesting its potential for clinical applications.
Notoginsenoside R1 Promotes Osteogenic Differentiation of Dental Pulp Stem Cells via MAPK Pathway.
Yang J, Weng X, Chen C … +1 more , Pan Y
Discov Med · 2025 Mar · PMID 40116096 · Publisher ↗
BACKGROUND: Notoginsenoside R1 (NGR1) is a bioactive compound of (Burk.) F.H. Chen (PNS), which possesses desirable properties in bone fracture healing and osteogenic differentiation of human periodontal ligament stem c...
BACKGROUND: Notoginsenoside R1 (NGR1) is a bioactive compound of (Burk.) F.H. Chen (PNS), which possesses desirable properties in bone fracture healing and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). Whether NGR1 can promote osteogenic differentiation of human dental pulp stem cells (DPSCs) is still unknown. This study aimed to assess the biocompatibility of NGR1 and its impact on DPSCs. METHODS: DPSCs were obtained from human wisdom teeth. Flow cytometry and multilineage differentiation were applied to determine stem cell properties. Then, the cells were treated with NGR1 for 1, 2 and 3 days, and its efficacy was detected by means of a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Alizarin red staining (ARS), alkaline phosphatase (ALP) activity, quantitative calcium node analysis, western blot and reverse-transcription-quantitative polymerase chain reaction (RT-qPCR) were executed to detect osteogenic differentiation-related proteins and genes. Western blot was also performed to assess the activation levels of the p38 mitogen-activated protein kinase (p-38 MAPK), c-Jun N-terminal kinase mitogen-activated protein kinase (JNK MAPK), and extracellular signal-regulated protein kinase mitogen-activated protein kinase (ERK MAPK) pathways in DPSCs following treatment with NGR1. RESULTS: DPSCs were positive for CD105 and CD166, while negative for CD34 and CD45. NGR1 at concentrations of 10 and 100 μg/mL did not exhibit cytotoxicity ( > 0.05), the group of cells receiving 200 μg/mL and 500 μg/mL NGR1 exhibited proliferation inhibition on the second day as well as on the third day ( < 0.05). Compared to the control group (no treatment), the cells treated with 100 μg/mL NGR1 exhibited significantly higher ALP expression and calcium deposition. The 100 μg/mL NGR1 group also showed higher expression of Osterix (OSX), Runt-related transcription factor 2 (RUNX2), Collagen Type I (COL-1), and Osteocalcin (OCN) at both protein and gene levels. Western blot analysis revealed that NGR1 activated the MAPK pathway by upregulating p38 and ERK, but not JNK, in DPSCs. When the p38 and ERK signaling pathways were inhibited by SB203580 and U0126, the gene expression levels of , , , and were significantly decreased ( < 0.05), but such alterations were not observed with the inhibition of the JNK pathway. CONCLUSION: At the concentration of 100 μg/mL, NGR1 enhances DPSC osteogenic differentiation by regulating the MAPK pathways.
Neuro-Immuno-Endocrine Regulation of Bone Homeostasis.
Banoriya GK, Singh VK, Maurya R … +1 more , Kharwar RK
Discov Med · 2025 Mar · PMID 40116095 · Publisher ↗
Bone is an important connective tissue involved in the movement and mechanical support of the body. Its homeostasis refers to the equilibrium between bone formation by osteoblasts and bone resorption by osteoclasts. Hema...
Bone is an important connective tissue involved in the movement and mechanical support of the body. Its homeostasis refers to the equilibrium between bone formation by osteoblasts and bone resorption by osteoclasts. Hematopoietic progenitor cells are shared by bone and immune cells, and the skeletal system is extensively innervated by an extensive nerve network. The immune, endocrine and nervous systems synthesize and secrete cytokines, hormones and neurotransmitters, respectively, which regulate physiological processes involved in bone homeostasis. Hormones such as gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen, testosterone, insulin, thyroxine, parathyroid hormone (PTH), calcitonin, etc., regulate bone formation and resorption. Tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin (interleukin (IL)-1,3,4,6,10,17,18,23,27) regulate the function of osteoblasts and osteoclasts as well as the bone microenvironment. The skeleton is innervated by sympathetic, parasympathetic and sensory nerve fibers that release neurotransmitters/factors such as serotonin, nerve growth factor, neuropeptide Y, substance P, norepinephrine and acetylcholine, which interact with various cells in the bone. Sclerostin, osteopontin, osteoprotegerin, osteocalcin, prostaglandin E2 and receptor activator of nuclear factor-kappa B ligand (RANKL)/receptor activator of nuclear factor-kappa B (RANK) are some of the important proteins released by osteoblasts, osteocytes and osteoclasts that regulate osteoblastogenesis, osteoclastogenesis and angiogenesis and are also involved in pathological conditions. Further research is needed to establish links between the skeleton and other tissues and to gain additional insights into the etiology of degenerative diseases and the drug development process. The aim of this minireview is therefore to understand the composition of bone and the maintenance of bone homeostasis through three coordinates, namely the endocrine, nervous and immune systems.
Research and Application of Methods for Improving Nail Permeation: A Review.
Ma H, Wang H
Discov Med · 2025 Mar · PMID 40116094 · Publisher ↗
This review aims to explore the current methods and advancements in nail permeation, with a focus on the potential of ultrashort pulse lasers to enhance drug delivery. The treatment of nail diseases, such as onychomycosi...
This review aims to explore the current methods and advancements in nail permeation, with a focus on the potential of ultrashort pulse lasers to enhance drug delivery. The treatment of nail diseases, such as onychomycosis, is particularly challenging due to the dense structure of nails, which hinders drug permeation. We reviewed traditional methods that are used to enhance drug penetration; however, these methods are often limited by discomfort, infection risks, and inadequate drug permeability. Laser therapy offers a novel perspective in enhancing transungual drug delivery by creating channels on the nail surface without damaging the nail root or bed, thus improving drug absorption. However, common lasers (such as CO lasers) may increase the target temperature beyond the thermal denaturation threshold, thus causing thermal damage to the nail bed and underlying tissues. This can also induce cracks and tissue debris, thus potentially spreading fungal pathogens in cases of onychomycosis. We specifically noted the potential of ultrashort pulsed lasers, which operate in the femtosecond range, to produce high peak power with minimal thermal damage to surrounding tissues. These lasers can create micropores on the nail plate via cold ablation, thus making them promising tools for improving the treatment of nail diseases. However, experimental data on this method are limited, and further studies, including histological research, are needed to validate its effectiveness in enhancing local drug permeability. This represents both a challenge and an opportunity for advancing nail disease treatments.
Biological Therapy and Oral Surgery: Safety Recommendations and Practices.
Dinkova AS, Petrov PG
Discov Med · 2025 Mar · PMID 40116093 · Publisher ↗
The integration of biological therapies, including biologics and biosimilars, into the medical practice has transformed the management of numerous chronic inflammatory, autoimmune, and oncological conditions. However, th...
The integration of biological therapies, including biologics and biosimilars, into the medical practice has transformed the management of numerous chronic inflammatory, autoimmune, and oncological conditions. However, these treatments can pose challenges in oral and maxillofacial surgery due to their potential effects on wound healing, infection risk, and immune responses. This article reviews the most commonly used biological agents and provides safety recommendations for managing patients on biological therapies undergoing oral surgical procedures, such as tooth extractions (including multiple and surgical extractions), implant placement, periodontal and soft tissue surgeries, and the removal of non-cancerous or cancerous growths in the oral cavity. Key considerations include the oral complications associated with biologic treatments, preoperative risk assessment, perioperative timing of biologic administration, and postoperative monitoring to minimize complications. While several professional organizations have issued recommendations on the perioperative management of biological agents, there is currently no specific guidance tailored to dental or oral surgical procedures. This paper aims to explore the existing literature and recommendations regarding the use of biologics in the perioperative period.
Exploring the Potentials: Therapeutic Uses of Mesenchymal Stem Cells in Treating Corneal Conditions.
Zeppieri M, Gagliano C, D'Esposito F … +6 more , Longo A, Bale BI, Suleman A, Chukwuyem E, Tognetto D, Musa M
Discov Med · 2025 Mar · PMID 40116092 · Publisher ↗
Corneal disorders, encompassing injuries, infections, and degenerative diseases, are major contributors to visual impairment globally. Conventional procedures, including corneal transplantation and pharmacological treatm...
Corneal disorders, encompassing injuries, infections, and degenerative diseases, are major contributors to visual impairment globally. Conventional procedures, including corneal transplantation and pharmacological treatments, encounter constraints such as donor shortages, rejection risks, and diminished effectiveness in extreme instances. Mesenchymal stem cells (MSCs) have emerged as viable therapeutic alternatives owing to their regeneration potential, immunomodulatory characteristics, and capacity to differentiate into corneal cell types. This study examines the therapeutic potential of MSCs in addressing various corneal illnesses through the analysis of preclinical studies, clinical trials, and current breakthroughs. MSCs facilitate corneal wound healing, diminish scarring, and reinstate transparency via processes including paracrine signaling, extracellular matrix remodeling, and anti-inflammatory actions. Although early-phase clinical trials indicate the safety and feasibility of MSC-based therapeutics, obstacles persist in optimizing delivery techniques, assuring cell viability, and creating uniform protocols. Additional research is necessary to address these issues and validate MSCs as a feasible clinical alternative. This review aims to summarize the therapeutic applications, challenges, and future prospects of mesenchymal stem cells in corneal treatments, emphasizing their importance as emerging alternatives to traditional therapies.
Unlocking the Potential of Immunomodulators as Synergistic Immune-Based Therapies in Cancer.
Tomar S, Siddiqui S, Pathak R … +1 more , Srivastava V
Discov Med · 2025 Mar · PMID 40116091 · Publisher ↗
Over the recent years, immunomodulators have opened a new avenue in cancer treatment by virtue of their ability to boost the immune system for neoplastic cell elimination. Improving treatment outcomes by leveraging the i...
Over the recent years, immunomodulators have opened a new avenue in cancer treatment by virtue of their ability to boost the immune system for neoplastic cell elimination. Improving treatment outcomes by leveraging the interaction of these agents with traditional cancer treatments is the main emphasis of this review. Checkpoint inhibitors, chemokine receptors, and pattern recognition receptors are the immunological targets of their interactive mechanisms. Immunomodulators are generally categorized as inhibitors of checkpoint, cytokines, agonists, or adjuvants. Despite their high efficacy and specificity, modern-day antibody-based therapies face several key limitations such as immunogenicity, insufficient tissue penetration, and restricted oral bioavailability. To address these shortcomings, researchers are crafting small molecules with the potential for oral administration and improved pharmacokinetic properties. These agents can augment antibody therapies for synergistic effects to enhance therapeutic efficacy for different types of cancers. This review explores the synergy between immunomodulators and traditional cancer treatments (chemotherapy, radiation, and targeted therapies) as well as newer strategies like adoptive cell therapies (chimeric antigen receptor therapies such as chimeric antigen receptor-T (CAR-T) cell therapy and chimeric antigen receptor-natural killer (CAR-NK)). These combinations improve treatment effectiveness in a number of ways: radiotherapy increases tumor antigen presentation and T-cell infiltration, chemotherapy-induced immunogenic cell death boosts immune responses and targeted therapies lessen immunosuppression in the tumor microenvironment. Despite the potential appeal as adjuvants, immunomodulators also pose challenges in maximizing their efficacy and minimizing adverse effects. In this paper, clinical trials proving the effectiveness of these combined techniques are reviewed, and innovative approaches including next-generation checkpoint inhibitors and delivery systems based on nanoparticles are also highlighted. Overall, this review evaluates the existing impact of immunomodulatory adjuvants and their prospective trends in cancer care. Further development of immunomodulators will pave the way for more accessible and effective therapies, marking a significant step towards personalized oncological interventions.
Renin-Angiotensin System Drives Leukemia Progression by Reprogramming the Niche.
Guffroy B, Miguet L, Lioure B … +2 more , Freund JN, Tavian M
Discov Med · 2025 Feb · PMID 39973563 · Publisher ↗
Abstract loading — click title to view on PubMed.
Immunity Holds the Key to Anti-Ageing Interventions.
Ahmed AU
Discov Med · 2025 Feb · PMID 39973562 · Publisher ↗
Abstract loading — click title to view on PubMed.
Angiotensin II and AGTR1 in ESCC Proliferation and Invasion: Insights from the JAK/STAT3 Pathway.
Xie B, Gu Y, Li J … +2 more , Wang H, Wang Y
Discov Med · 2025 Feb · PMID 39973561 · Publisher ↗
BACKGROUND: Angiotensin II (Ang II) and its receptor, Angiotensin II receptor type 1 (AGTR1), have been implicated in the proliferation of cancer cells across various tumor types. This study aims to examine the impact of...
BACKGROUND: Angiotensin II (Ang II) and its receptor, Angiotensin II receptor type 1 (AGTR1), have been implicated in the proliferation of cancer cells across various tumor types. This study aims to examine the impact of Ang II and AGTR1 on esophageal squamous cell carcinoma (ESCC) cells. METHODS: The clonogenicity and proliferation of tumor cells were evaluated through Clone Formation and Cell Counting Kit-8 (CCK-8) assays. Cell migration and invasion were determined utilizing Transwell assays. Flow cytometry was employed to analyze the cell cycle. Additionally, to investigate the expressions of genes associated with cell growth, migration, infiltration, and Janus kinase-signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathways, quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were utilized. RESULTS: In the current study, it was observed that increasing the concentration of Ang II significantly augmented the proliferation of ESCC cells. However, with the addition of its inhibitor losartan, the proliferative activity of ESCC cells was significantly reduced with the increase of losartan concentration ( < 0.05). The inhibition of AGTR1 also markedly reduced the proliferative activity of ESCC cells, counteracting the effect induced by Ang II treatment ( < 0.05). Additionally, Ang II was found to stimulate the migration and invasion of ESCC cells, facilitate the transition of these cells from the first gap (G1) to the synthesis (S) phase, and impede apoptosis ( < 0.05). However, treatment with losartan and AGTR1 inhibition significantly diminished the number of migratory and invasive cells, inhibited the transition from G1 to S phase, and promoted apoptosis in ESCC cells ( < 0.05). Regarding the mechanism, our research team found that Ang II and AGTR1 can enhance the proliferation and invasion of ESCC cells and inhibit their apoptosis via the JAK/STAT3 signaling pathway. Nevertheless, the AGTR1 blocker, losartan, effectively obstructed this process. CONCLUSION: The activation of the JAK/STAT3 signaling pathway by Ang II and AGTR1 promotes the advancement of ESCC tumors. Consequently, targeting Ang II and AGTR1 could potentially emerge as a promising strategy for ESCC treatment.
Development of a Radiomic Model to Detect the Retromolar Canal on Panoramic Radiographs.
Zhan D, Wang F, Zeng D … +4 more , Hao L, Ye L, Qi Y, Xu Q
Discov Med · 2025 Feb · PMID 39973560 · Publisher ↗
BACKGROUND: The retromolar canal (RMC) is an extension of the mandibular canal located in the distal region of the mandibular third molar. Accurately detecting the RMC using conventional two-dimensional images is challen...
BACKGROUND: The retromolar canal (RMC) is an extension of the mandibular canal located in the distal region of the mandibular third molar. Accurately detecting the RMC using conventional two-dimensional images is challenging, potentially leading to anesthetic failure and sensory disorders. This study aims to explore the clinical application of a radiomic model based on panoramic radiographs in detecting the RMC. METHODS: A retrospective collection of cone beam computed tomography (CBCT) and panoramic radiographs was conducted on 800 patients, covering 1555 hemimandibles. CBCT images served as the gold standard for confirming the presence of RMC. A dataset comprising 846 retromolar regions was established for model training and testing, with an 8:2 ratio. On the panoramic radiographs, the retromolar regions were delineated as the regions of interest, and radiomic features were extracted and selected. Support vector machine (SVM), logistic regression (LR), k-nearest neighbors (KNN), and multilayer perceptron (MLP) were employed to construct detection models for the RMC. The performance of these algorithms was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA), and the area under the receiver operating characteristics curve (AUC) values were compared with those of a dentist and a radiologist. RESULTS: The RMC was identified in 423 (27.2%) out of 1555 hemimandibles on CBCT images. The four algorithms, particularly SVM and MLP, demonstrated outstanding classification abilities in detecting the RMC, with AUC values ranging from 0.831 to 0.895 in the training set and from 0.719 to 0.808 in the testing set. These results significantly surpassed those of the dentist and radiologist ( < 0.05). CONCLUSION: Radiomics based on panoramic radiographs exhibit a high detection capability for the RMC, emphasizing its considerable clinical application value.
Effects of Four Main Active Flavonoids of Nutt. on Oleic Acid-Induced Lipid Metabolism and Oxidative Stress in HepG2 Cells.
Zhao LS, Liu RF, Kang YT … +4 more , Chen YY, Xiao YC, Zhang LL, Cheng XR
Discov Med · 2025 Feb · PMID 39973559 · Publisher ↗
BACKGROUND: Traditional Chinese medicines exhibit tremendous beneficial effects on the control of hyperlipidemia and hyperlipidemia-associated disorders. In the present study, we investigated the effects of four Nutt. e...
BACKGROUND: Traditional Chinese medicines exhibit tremendous beneficial effects on the control of hyperlipidemia and hyperlipidemia-associated disorders. In the present study, we investigated the effects of four Nutt. extracts, including luteolin, marein, naringenin (NGN) and chlorogenic acid (CQA), on lipid accumulation and oxidative stress induced by oleic acid (OA) in HepG2 cells. METHODS: Oleic acid was employed to create a high-lipid milieu in a cellular setting using HepG2 cells. After treatment by luteolin, marein, NGN, and CQA, cell counting kit-8 assay was used for measuring cell viability. Lipid accumulation, lipid metabolism and oxidative stress were examined by means of enzyme-linked immunosorbent assay, Oil red O staining, quantitative real-time polymerase chain reaction (qRT-PCR) and 2',7'-dichlorodihydro fluorescein diacetate assays. Western blot and qRT-PCR assays were applied to determine the expression of genes and proteins, respectively. RESULTS: In OA-treated HepG2 cells, the administration of the four active flavonoids of Nutt. (luteolin, marein, NGN and CQA) enhanced cell viability ( < 0.05 or < 0.01); reduced lactate dehydrogenase releasing, lipid deposition and production of triglyceride, total cholesterol and low-density lipoprotein-cholesterol ( < 0.05 or < 0.01); and elevated high-density lipoprotein-cholesterol production ( < 0.05 or < 0.01 or < 0.001). Moreover, after luteolin, marein, NGN or CQA treatment, the expression of lipid metabolism-related genes including 3-hydroxy-3-methylglutaryl-CoA reductase (), low-density lipoprotein receptor () and apical sodium-dependent bile acid transporter () was downregulated ( < 0.01 or < 0.001) but the expression of cytochrome P450 family 7 subfamily A member 1 () was upregulated ( < 0.05 or < 0.01 or < 0.001) in OA-treated HepG2 cells. Similarly, luteolin, marein, NGN or CQA treatment greatly enhanced the anti-oxidant activities ( < 0.05 or < 0.01 or < 0.001) and decreased reactive oxygen species production ( < 0.01 or < 0.001) in OA-treated HepG2 cells. Sterol regulatory element-binding protein, a major transcription factor that moderates the biosynthesis of fatty acid, cholesterol and triglyceride, was also inhibited after luteolin, marein, NGN or CQA treatment ( < 0.05 or < 0.01 or < 0.001). CONCLUSION: These findings demonstrated that luteolin, marein, NGN or CQA can effectively reduce OA-induced oxidative stress and lipid accumulation, corroborating their potential in hyperlipidemia treatment.
The Relationship between Hematocrit Levels and Major Adverse Cardiovascular Events in Patients with Acute Myocardial Infarction.
Shi Y, Xu B, Yang J … +5 more , Zhao X, Zhou H, Yang J, Ding Z, Wan H
Discov Med · 2025 Feb · PMID 39973558 · Publisher ↗
BACKGROUND: The relationship between hematocrit (HCT) levels and the occurrence of major adverse cardiovascular events (MACEs) in patients with acute myocardial infarction (AMI) remains unexplored. A better understanding...
BACKGROUND: The relationship between hematocrit (HCT) levels and the occurrence of major adverse cardiovascular events (MACEs) in patients with acute myocardial infarction (AMI) remains unexplored. A better understanding of this interplay may enhance the prognosis and management of AMI patients. METHODS: Between January 2021 and August 2022, clinical data were collected from patients diagnosed with AMI at 10 tertiary healthcare institutions in China. A total of 1946 eligible participants were included and divided into three groups based on sex-specific tertiles of HCT levels upon admission: 648 patients with low HCT levels, 649 patients with intermediate HCT levels, and 649 patients with high HCT levels. Follow-up approaches included hospital outpatient visits, inpatient stays, and telephone calls for 180 days. The primary endpoint was the occurrence of MACEs. Influential factors, including general information, admission status, and supplementary examination results that differed across the cohorts, were analyzed. Cox regression analysis was employed to evaluate the 180-day MACE rates and HCT levels in patients with AMI. To assess the reliability of the findings, three sensitivity analyses and subgroup analyses were performed. RESULTS: During this time, 136 individuals in the low HCT group, 77 in the intermediate HCT group, and 73 in the high HCT group experienced endpoint events. With all covariates controlled, the Cox regression analysis indicated that the low HCT group had a higher risk of MACEs compared to the intermediate HCT group [hazard ratio (HR) = 1.44, 95% confidence interval (CI) = 1.07-1.95, = 0.017]. The low HCT group also presented a higher risk of acute coronary syndrome (HR = 1.57, 95% CI = 1.06-2.32, = 0.024). However, the high and intermediate HCT groups exhibited comparable prognoses for AMI. The limited cubic spline plot revealed that HCT values between 41.58% and 45.36% implied a protective effect against MACEs. These results were further verified by sensitivity analysis, and the subgroup analysis showed no variable interaction. CONCLUSIONS: Our findings indicate that low HCT levels in patients with AMI increase the incidence of MACEs within 180 days, offering new insights into the prognosis and management of AMI patients. CLINICAL TRIAL REGISTRATION: ChiCTR2200066456.
Constructing a Multivariate Predictive Model for Postoperative 90-Day Depression Risk in Non-Small Cell Lung Cancer Based on Preoperative Peripheral Blood NLR, LMR, and PLR.
Wu X, Dai L, Guo H … +4 more , Peng C, Zhang P, Mo L, Zhang X
Discov Med · 2025 Feb · PMID 39973557 · Publisher ↗
BACKGROUND: Depression represents a significant clinical concern for individuals diagnosed with non-small cell lung cancer (NSCLC) following surgical resection. This study aimed to investigate the potential of preoperati...
BACKGROUND: Depression represents a significant clinical concern for individuals diagnosed with non-small cell lung cancer (NSCLC) following surgical resection. This study aimed to investigate the potential of preoperative peripheral blood parameters, including the neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), and platelet/lymphocyte ratio (PLR), as predictive indicators for the risk of developing depression within the initial 90-day postoperative period in NSCLC patients. METHODS: A prospective cohort study was conducted, enrolling 350 NSCLC patients, with 250 participants in the training set and 100 participants in the testing set. Participants were classified based on the presence or absence of depression 90 days after surgery. Preoperative blood parameters, including NLR, LMR, PLR, and inflammatory biomarkers, were measured. Statistical analyses, encompassing Logistics regression analysis and receiver operating characteristic (ROC) curve analysis, were performed to assess the significance and predictive value of these blood parameters. Multivariate predictive models were constructed based on the identified significant parameters. RESULTS: In the training set, statistically significant differences were observed between the non-depression and depression groups for NLR (4.35 ± 1.23 vs. 3.14 ± 0.82, t = 8.715, < 0.001), LMR (3.84 ± 1.58 vs. 5.58 ± 1.23, t = 8.849, < 0.001), PLR (187.46 ± 35.26 vs. 152.36 ± 32.46, t = 7.112, < 0.001), and various blood parameters. Logistics regression analysis showed significant associations between NLR, LMR, PLR, and postoperative depression. ROC curve analysis indicated the predictive value of NLR [area under the curve (AUC) = 0.794], LMR (AUC = 0.800), and PLR (AUC = 0.766), with the multivariate model yielding an AUC of 0.931. These results were consistent in the testing set, where significant differences were observed between the non-depression and depression groups for NLR (4.23 ± 1.24 vs. 3.13 ± 0.75, t = 5.417, < 0.001), LMR (3.17 ± 1.55 vs. 4.76 ± 1.22, t = 5.412, < 0.001), PLR (189.46 ± 46.58 vs. 151.48 ± 34.26, t = 4.481, < 0.001), and various blood parameters. The AUC values were 0.771, 0.791, and 0.755 for NLR, LMR, and PLR, respectively, while the multivariate model yielded an AUC of 0.928. CONCLUSIONS: The study highlights the potential of preoperative peripheral blood NLR, LMR, and PLR as predictive indicators for the risk of postoperative 90-day depression in patients with NSCLC. CLINICAL TRIAL REGISTRATION: Approval number: ChiCTR2300070375, https://www.chictr.org.cn/index.html.
Mechanisms of Age Differences in the Effectiveness of Phototherapy of Glioblastoma.
Shirokov A, Navolokin N, Bucharskaya A … +6 more , Blokhina I, Terskov A, Tzoy M, Dubrovsky A, Fedosov I, Semyachkina-Glushkovskaya O
Discov Med · 2025 Feb · PMID 39973556 · Publisher ↗
BACKGROUND: Glioblastoma is an incurable and aggressive oncological disease of the brain. Recent studies have shown that transcranial non-invasive photobiomodulation is a promising new alternative method for suppression...
BACKGROUND: Glioblastoma is an incurable and aggressive oncological disease of the brain. Recent studies have shown that transcranial non-invasive photobiomodulation is a promising new alternative method for suppression of glioblastoma growth. The lymphatic endothelium of the meningeal lymphatic vessels is an important target for the therapeutic effects of photobiomodulation. However, the functions of the meningeal lymphatic vessels decline with age. Therefore, it remains unknown whether photobiomodulation can be effective in adults and the elderly. To answer this question, this study examined the role of the meningeal lymphatic vessels and brain drainage in age-related differences in resistance to glioblastoma. METHODS: The studies were performed on 6- and 24-month-old rats using a model of fluorescent glioblastoma. Tumor progression was assessed using magnetic resonance imaging and the Fluor I fluorescence imaging system. Photobiomodulation was performed for 14 days for phototherapy of glioblastoma or once to study photoeffects on the brain's drainage. Brain drainage was studied by optical imaging of the lymphatic excretion of dye from the brain to the deep cervical lymph nodes, as well as by assessing the water content in brain tissues and the intracranial pressure. Histological and immunohistochemical methods were used to study apoptosis, proliferation and migration of CD8+ cells from the peripheral lymphatic system to glioblastoma. RESULTS: We clearly show that the network of the meningeal lymphatic vessels and brain drainage reduced in 24-month-old rats vs. 6-month-old animals ( < 0.001), which is accompanied by a decrease in resistance to the development of glioblastoma. Photobiomodulation significantly increases survival in 6-month-old ( < 0.001), but not in 24-month-old rats via an improvement of the functions of the meningeal lymphatic vessels, including a facilitating the traffic of protective CD8+ cells to glioblastoma ( < 0.001), reducing intracranial pressure and brain edema. The blockade of lymphatic communication between the peripheral and meningeal lymphatic systems completely suppresses the therapeutic effects of photobiomodulation in 6-month-old rats ( < 0.001). CONCLUSION: Thus, photobiomodulation is an effective method of stimulation of brain drainage and immunity increasing resistance to glioblastoma progression in early but not in late ontogenesis due to the age-related decline in the functions of the meningeal lymphatic vessels.
GNPNAT1 Regulation: A Key Role in Radioimmune Function and NK Cell Resistance in NSCLC.
Xiang F, Dai Y, Yao C … +3 more , Li Y, Zhao W, Wei J
Discov Med · 2025 Feb · PMID 39973555 · Publisher ↗
BACKGROUND: Glucosamine-6-phosphate N-acetyltransferase 1 (GNPNAT1) is an enzyme involved in the hexosamine biosynthetic pathway, which is critical for glycosylation processes. In the context of non-small cell lung cance...
BACKGROUND: Glucosamine-6-phosphate N-acetyltransferase 1 (GNPNAT1) is an enzyme involved in the hexosamine biosynthetic pathway, which is critical for glycosylation processes. In the context of non-small cell lung cancer (NSCLC), GNPNAT1 plays a significant role in modulating immune responses. The purpose of this study is to investigate the role of GNPNAT1 in regulating the efficacy of radiotherapy and resistance to natural killer (NK) cell-mediated cytotoxicity in patients with NSCLC. METHODS: To assess GNPNAT1's impact on radiotherapy efficacy, 122 lung cancer patients were categorized into radiosensitive and radioresistant groups. GNPNAT1 expression levels in cancerous tissues from both groups were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting. This analysis was extended to various lung cancer cell lines (BEAS-2B, A549, LTEP-2, SPCA1, and H157) using the same molecular techniques. To investigate GNPNAT1's functional role in radioresistance, radioresistant A549 cells (A549R26-1) were established, and GNPNAT1 expression was genetically manipulated. Experimental groups included control, si-NC, si-GNPNAT1, Oe-NC, and Oe-GNPNAT1. Post-treatment, GNPNAT1 levels were measured via qRT-PCR and Western blotting. Cells were exposed to varying doses of radiation, and subsequent assessments included cell proliferation (Cell Counting Kit-8 (CCK-8) assay), radiosensitivity (plate cloning assays), and apoptosis rates (flow cytometry). Isolated and purified primary NK cells were co-cultured with lung cancer cells from each experimental group. The cytotoxicity of NK cells against lung cancer cells was assessed through lactate dehydrogenase (LDH) release and colony formation assays. RESULTS: Compared to the radiosensitive group, the radioresistant group exhibited significantly elevated GNPNAT1 expression levels ( < 0.05). The radioresistant cell line A549R26-1 demonstrated higher proliferation ability and lower apoptosis levels compared to its parental cell line, A549P. Subsequently, down-regulation of GNPNAT1 expression in A549R26-1 cells resulted in reduced proliferation, increased apoptosis, and weakened resistance to NK cell cytotoxicity. Conversely, up-regulation of GNPNAT1 expression in A549R26-1 cells following co-culture with NK cells led to increased proliferation and survival rates, and enhanced resistance to NK cell cytotoxicity. Notably, GNPNAT1 knockdown effectively attenuated the radioresistance of A549R26-1 cells. CONCLUSION: Down-regulation of GNPNAT1 expression reduces the immune resistance of non-small cell lung cancer to radiotherapy and enhances susceptibility to NK cell cytotoxicity.
ELF1's Role in Colorectal Cancer: Up-Regulating DCLK1 Expression to Propel Malignant Progression and Stemness Features.
Zhou D, Tian X, Yang H … +3 more , Xiao S, Lu Y, Zeng F
Discov Med · 2025 Feb · PMID 39973554 · Publisher ↗
BACKGROUND: Exploring the pathological mechanism of colorectal cancer (CRC) onset and advancement is critical to clinical diagnosis and treatment. In this context, our study brings a novel perspective by investigating th...
BACKGROUND: Exploring the pathological mechanism of colorectal cancer (CRC) onset and advancement is critical to clinical diagnosis and treatment. In this context, our study brings a novel perspective by investigating the role and regulatory mechanism of E74 Like ETS Transcription Factor 1 () in CRC, a topic that has not been extensively explored. METHODS: Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting (WB) assays were used to detect the expression of ELF1 in CRC cells. Sh-ELF1, ELF1 overexpresses lentivirus (Oe-ELF1), and Oe-Doublecortin Like Kinase 1 (DCLK1) were constructed and transfected into CRC cells. Transfection efficiency and the expression of stemness, as well as epithelial-mesenchymal transition (EMT)-related proteins were detected using RT-qPCR and WB assays. Cell proliferation and sphere-forming ability were detected using Cell Counting Kit-8 (CCK-8) assay, 5-Ethynyl-2'-deoxyuridine (EdU) staining, and sphere formation assay. Cell migration and invasion were detected using wound healing and transwell assay. The tube-forming ability of human umbilical vein endothelial cells (HUVEC) cells was detected using tubular formation experiments. To investigate the regulatory mechanism of ELF1, the crosstalk between ELF1 and downstream DCLK1 was predicated and verified using the JASPAR database, luciferase reporter gene, and Chromatin Immunoprecipitation (ChIP) assay. RESULTS: Results of the present study demonstrated that ELF1 expression was upregulated in CRC cells ( < 0.001). ELF1 silence significantly inhibited CRC cell proliferation, stemness, invasion, migration, and angiogenesis ( < 0.001). ELF1 silence also suppressed the expressions of Nanog Homeobox (Nanog), SRY-Box Transcription Factor 2 (Sox2), Octamer-Binding Transcription Factor 4 (OCT4), N-cadherin, and Vimentin while increasing the expression of E-cadherin ( < 0.001). Besides, ELF1 could positively regulate DCLK1 expression. However, the results of subsequent experiments revealed that DCLK1 overexpression partially offset the inhibitory effects of ELF1 knockdown on CRC cell proliferation, stemness, invasion, migration, and angiogenesis ( < 0.01). CONCLUSION: In summary, our study provides compelling evidence that ELF1 up-regulates DCLK1 expression, thereby promoting the malignant progression and stemness of colorectal cancer. These findings significantly contribute to our understanding of the regulatory mechanisms in CRC and may have implications for future therapeutic strategies.
Prognostic Significance of a 9-Gene Signature Related to Tertiary Lymphoid Structures in Male Stomach Adenocarcinoma Patients.
Yuan Z, Huang S, Qin F … +7 more , Wang F, Wei H, Luo S, Zhang Y, Liang H, Jiang J, Ye L
Discov Med · 2025 Feb · PMID 39973553 · Publisher ↗
BACKGROUND: The role of tertiary lymphoid structures (TLSs) in stomach adenocarcinoma (STAD) remains unclear despite their known potential effects on tumor progression and prognosis. METHODS: Data were collected from 362...
BACKGROUND: The role of tertiary lymphoid structures (TLSs) in stomach adenocarcinoma (STAD) remains unclear despite their known potential effects on tumor progression and prognosis. METHODS: Data were collected from 362 patients with STAD from The Cancer Genome Atlas (TCGA) database. Using single-sample genomic enrichment analysis, TLSs were quantified based on a 9-gene signature, and the patients were categorized into TLS-signature high (TLS-high) and TLS-signature low (TLS-low) groups. The association of TLS signature with prognosis, tumor microenvironment (TME) immune status, tumor mutation burden, and gene mutation status was evaluated. The GSE26253 cohort served as an external dataset to validate the prognostic predictive effect of the TLS signature in patients with STAD. RESULTS: The TLS-high group exhibited notably lower overall survival (OS) among male patients with STAD from the TCGA cohort ( = 0.01). Multivariate analysis revealed that the TLS signature was a significant independent negative predictor of OS in male patients with stage I-III STAD (hazard ratio (HR): 2.68; 95% confidence interval (CI): 1.19-6.00; = 0.02). The TLS-high patients exhibited increased infiltration of immune cell subsets; however, cancer-immunity cycle analysis revealed both antitumor and protumor responses within the TME. Correlation analyses indicated that TLS was more strongly associated with immunosuppression-related cells than with antitumor immune cells. Furthermore, expressions of immunosuppressive cell-recruitment factors, immunosuppressive factors, and immune checkpoint receptors were higher in the TLS-high group than in the TLS-low group. Nonetheless, among male patients with stage I-III STAD who received adjuvant therapy, multivariate analysis identified TLS trait as a significant independent positive predictor of relapse-free survival in the GSE26253 cohort (HR: 0.61; 95% CI: 0.38-0.97; = 0.04). Interaction of the TLS signature with adjuvant therapy exerted a significant positive effect on OS in these patients (HR: 0.41; 95% CI: 0.17-0.97; = 0.04). CONCLUSION: In the TCGA cohort, the TLS signature acted as an independent adverse prognostic factor for male patients with stage I-III STAD and was associated with immunosuppressive TME, which interacted to affect patient prognosis. However, adjuvant therapy may affect the prognostic predictive effect of TLS in male patients with stage I-III STAD.
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