Discovery Medicine[JOURNAL]
Sun
200 papers
Urolithin B Promotes Meniscal Regeneration and Prevents the Development of Osteoarthritis in Mice.
Wang W, Wang H, Wang L … +3 more , Zhang Y, Liu H, Ci B
Discov Med · 2025 Feb · PMID 39973552 · Publisher ↗
BACKGROUND: Osteoarthritis (OA) is one of the most prevalent arthritis types globally, with the knee being particularly susceptible due to its frequent and strenuous use. Urolithin B (UB) exhibits various biological prop...
BACKGROUND: Osteoarthritis (OA) is one of the most prevalent arthritis types globally, with the knee being particularly susceptible due to its frequent and strenuous use. Urolithin B (UB) exhibits various biological properties, with meniscal repair playing an important role in preventing knee OA. This study aimed to explore the impact of UB on meniscal regeneration and OA progression. METHODS: Initially, we explored the effect of UB on meniscal cells. Utilizing the cell counting kit (CCK)-8 assay, we determined the optimum concentration of UB treatment. Enzyme-linked immunosorbent assay (ELISA) was used for detecting inflammation-related interleukin-1beta (IL-1β). Real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) was used for measuring the expression of extracellular matrix (ECM)-related proteins, ECM-degrading enzymes, and genes associated with joint formation in meniscal cells. Furthermore, 5-Bromo-2'-deoxyuridine (BrdU) staining was used to evaluate the proliferation of meniscal cells. Meniscal tissues were cultured , and western blot analysis was used to detect levels of proliferation-related markers such as proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF), as well as ECM protein collagen-1 (COL-1) and ECM degradation-related matrix metallopeptidase-13 (MMP-13). Mice were subjected to meniscus injury to establish a knee joint model of meniscus injury-induced osteoarthritis (MIOA) and to verify the effect of UB on meniscal cells . Pathological changes in knee joints were observed using hematoxylin-eosin (H&E) staining. Additionally, western blot was used to assess PCNA, VEGF, COL-1, and MMP-13 levels, while ELISA was used to detect inflammation-related tumor necrosis factor-alpha (TNF-α), IL-1β, IL-6, and interferon-gamma (IFN-γ) in mouse menisci. RESULTS: At concentrations up to 100 μM, UB exhibited non-toxicity and concomitantly decreased IL-1β in meniscal cells ( < 0.001). Moreover, UB increased the expression of ECM-related proteins ( < 0.001) and genes associated with joint formation ( < 0.001), while concurrently decreasing the expression of ECM-degrading enzymes ( < 0.001) in meniscal cells. UB promoted meniscal cell proliferation ( < 0.001). Additionally, UB increased PCNA, VEGF, and COL-1 while suppressing MMP-13 in menisci cultured ( < 0.001). Moreover, UB mitigated the pathological alterations observed in knee joints affected by meniscus injury. In murine models, MIOA led to decreased PCNA, VEGF, and COL-1 levels, alongside increased MMP-13, TNF-α, IL-1β, IL-6, and IFN-γ levels ( < 0.001), all of which were effectively reversed by UB treatment ( < 0.001). CONCLUSION: UB effectively promotes meniscal regeneration and repair, while protecting against knee OA in mice, suggesting its potential role in clinical OA treatment.
Silencing TGF-β3 Alleviates Recurrent Spontaneous Abortion Inflammation in Mice: the Importance of Treg/Th17 Cell Balance.
Peng L, Yang M, Luo X
Discov Med · 2025 Feb · PMID 39973551 · Publisher ↗
BACKGROUND: Recurrent spontaneous abortion (RSA), also known as repeated miscarriage, refers to the consecutive loss of pregnancy three times or more before the fetus reaches viability. In this study, we aimed to investi...
BACKGROUND: Recurrent spontaneous abortion (RSA), also known as repeated miscarriage, refers to the consecutive loss of pregnancy three times or more before the fetus reaches viability. In this study, we aimed to investigate the impact of transforming growth factor β3 (TGF-β3), which plays a crucial role in immune dysregulation, on the imbalance of regulatory T cell (Treg) and T helper 17 (Th17) cells. METHODS: First, we isolated T cells from an RSA mouse model we established in-house. Tregs and Th17 cells were labeled by targeting forkhead box protein P3 (Foxp3) and retinoic-acid-receptor-γt (RORγt), respectively, and the levels of Tregs and Th17 were determined by flow cytometry. The expression levels of Foxp3, RORγt, TGF-β3, interleukin (IL)-10, and IL-17 in T cells were measured by means of reverse-transcription quantitative polymerase chain reaction (qRT-PCR) and Western blotting. The levels of interferon-γ (IFN-γ), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-4 in mouse serum were quantified using enzyme-linked immunosorbent assay (ELISA). si-TGF-β3 was transfected into RSA mice, and the expression levels of IL-17 and CD25 were determined by flow cytometry, during which T cells were labeled with antibodies against IL-17 and CD25, respectively. Additionally, si-TGF-β3 or TGF-β3 interference therapy was administered to RSA mice, and the expression levels of IL-1β, tumor necrosis factor-α (TNF-α), IL-6, IFN-γ, GM-CSF, and IL-4 in mouse serum were measured using ELISA. RESULTS: In the RSA model, there was a significant decrease in the percentage of Treg cells, alongside an elevation of mRNA ( < 0.05). The percentage of Th17 cells in RSA mice significantly increased and correlated positively with TGF-β3 levels. In RSA, the levels of pro-inflammatory cytokines IL-1β, TNF-α, IL-6, IFN-γ, and GM-CSF increased, while those of anti-inflammatory cytokine IL-4 decreased ( < 0.05). Transfection of si-TGF-β3 into RSA mice reduced the percentage of Th17 cells and increased the percentage of Tregs and Treg/Th17 ( < 0.05). Increased levels of Th17-related markers and reduced levels of Tregs-related markers occurred following the administration of TGF-β3 to RSA mice ( < 0.05). Transfection of si-TGF-β3 into RSA mice also resulted in a decrease in pro-inflammatory cytokines and an increase in anti-inflammatory cytokines ( < 0.05), while TGF-β3 administration reversed these changes in RSA mice, indicating the role of TGF-β3 in modulating the inflammatory response during RSA. CONCLUSIONS: Knockdown of TGF-β3 enhanced Treg/Th17 balance in RSA, suggesting TGF-β3 as a potential therapeutic target for RSA.
Research Progress on Alzheimer's Disease Biomarkers Based on the ATX(N) Framework.
Cao H, Zhang W, Lin J … +1 more , Yu E
Discov Med · 2025 Feb · PMID 39973550 · Publisher ↗
Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Early diagnosis and treatment of AD are of paramount importance, with the concept of biomarkers being intrinsically linked to diagnosis and therapy. B...
Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Early diagnosis and treatment of AD are of paramount importance, with the concept of biomarkers being intrinsically linked to diagnosis and therapy. Biomarkers are indices that can be objectively measured to indicate normal biological processes, pathological conditions, or responses to therapeutic interventions. In 2023, the National Institute on Aging and Alzheimer's Association released updated clinical diagnostic guidelines, refining the 2018 research framework. These guidelines categorize AD biomarkers into three types: core AD biomarkers, non-specific biomarkers of tissue response related to AD pathophysiology, and biomarkers for non-AD comorbidities, thus enhancing the amyloid/tau/x/neurodegeneration (ATX(N)) framework. This article aimed to provide a comprehensive overview of the advancements within the ATX(N) framework and the progress in the study of various biomarkers under this framework. It analyzes how biomarkers can facilitate early disease diagnosis, discusses the challenges of translating biomarkers into effective treatments, and explores their therapeutic prospects.
Channels out of Order: A Review of Central and Peripheral Nervous System Channelopathies.
Verriello L, Belluzzo M, Pauletto G … +6 more , Torre CD, D'Esposito F, Gagliano C, Musa M, Bertolotti C, Zeppieri M
Discov Med · 2025 Feb · PMID 39973549 · Publisher ↗
A vast range of neurological conditions impacting the central and peripheral nervous system are caused by ion channel dysfunctions, which are collectively referred to as channelopathies. These disorders, which are freque...
A vast range of neurological conditions impacting the central and peripheral nervous system are caused by ion channel dysfunctions, which are collectively referred to as channelopathies. These disorders, which are frequently autoimmune or genetic in nature, present as a variety of clinical syndromes, such as migraine, epilepsy, ataxia, neuropathic pain, and intermittent paralysis. The pathogenic mechanisms underlying these illnesses have been uncovered by recent developments in molecular genetics and electrophysiological research, opening up new avenues for accurate diagnosis and specialized treatment approaches. With an emphasis on important genetic variations and clinical manifestations, this study offers a targeted synthesis of channelopathies of the central and peripheral nervous system. By providing the most recent information on these complex disorders, this review aims to help physicians identify and treat channelopathies.
Tailoring Pharmacological Treatment in Cardiogenic Shock: A Narrative Review.
Crispino SP, Segreti A, Nafisio V … +6 more , Ciancio M, Cavallari I, Giannone S, Melfi R, Ussia GP, Grigioni F
Discov Med · 2025 Feb · PMID 39973548 · Publisher ↗
Cardiogenic shock (CS) is a critical condition marked by end-organ hypoperfusion and sustained hypotension, necessitating the use of inotropic or vasoactive agents for hemodynamic support. It is the leading cause of mort...
Cardiogenic shock (CS) is a critical condition marked by end-organ hypoperfusion and sustained hypotension, necessitating the use of inotropic or vasoactive agents for hemodynamic support. It is the leading cause of mortality in patients with acute myocardial infarction (AMI), exhibiting in-hospital mortality rates of 40% to 50% despite advances in treatment. Treatment strategies aim to restore hemodynamic stability and address the underlying cause through pharmacological agents and mechanical circulatory support devices. However, the persistently high mortality rates underline the challenges of a timely diagnosis, the limitations of current treatments, and the lack of a standardized multidisciplinary network of care. This review critically examines the existing literature on CS management, focusing on the efficacy, safety, and practical application of pharmacological interventions. By synthesizing evidence from recent studies, clinical guidelines, and expert consensus, our objective is to provide a useful, comprehensive, evidence-based framework to guide clinicians in the use of pharmacologic therapies tailored to the diverse presentations and stages of CS.
The Ubiquitin Code in Disease Pathogenesis and Progression: Composition, Characteristics and its Potential as a Therapeutic Target.
Lee JS, Kim HY, Kwon YT … +3 more , Ji CH, Lee SJ, Kim SB
Discov Med · 2025 Feb · PMID 39973547 · Publisher ↗
Conjugation of substrate proteins with ubiquitin (Ub), a 76 amino acid protein, was discovered as the first major translational modification responsible for protein degradation. Ubiquitination occurs as a cascade among u...
Conjugation of substrate proteins with ubiquitin (Ub), a 76 amino acid protein, was discovered as the first major translational modification responsible for protein degradation. Ubiquitination occurs as a cascade among ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin ligases (E3) enzymes that transfer and covalently conjugate Ub to the lysine (Lys) residue and α-amino group in methionine (Met) residues of substrates. Following the initial conjugation, Ub itself then undergoes ubiquitination via its seven lysine residues (K6, K11, K27, K29, K33, K48, and K63) and N-terminal methionine (M1). These possible sites of Ub polymerization/assembly result in a significantly diverse and numerous set of linkage types and lengths, including homotypic, mixed and/or branched chains, which provoke distinct cellular responses via their proteolytic and non-proteolytic functions. We overview here the multiplicity of ubiquitin code with a particular focus on linkage-specific roles in biological processes, especially in the pathogenesis and progression of diseases such as cancer, neurodegeneration, and immune disorders. We will also discuss the possibility and ongoing efforts of modulating the ubiquitin code as a therapeutic strategy in drug development, including targeted protein degradation (TPD).
Correction: Chen . β-Sitosterol Enhances Lung Epithelial Cell Permeability by Suppressing the NF-κB Signaling Pathway. Discovery Medicine. 2023; 35(179): 946-955.
Chen X, Chen J, Ren Y … +7 more , Wang M, Yang Z, Zhang W, Li Q, Liu C, Sun Z, Nie S
Discov Med · 2025 Jan · PMID 39851235 · Publisher ↗
Correction of Discovery Medicine 2023, 35 (179) https://www.discovmed.com/EN/10.24976/Discov.Med.202335179.90 The authors wish to make the following correction to this paper [1]: The authors would like to correct the nam...
Correction of Discovery Medicine 2023, 35 (179) https://www.discovmed.com/EN/10.24976/Discov.Med.202335179.90 The authors wish to make the following correction to this paper [1]: The authors would like to correct the name of their affiliated institution, the corrected author's affiliation is provided below: 1Department of Emergency Medicine, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, 210002 Nanjing, Jiangsu, China.
Fruit Acid Inhibits UV-Induced Skin Aging via PI3K/Akt and NF-κB Pathway Inhibition.
Wang B, Dong J, Liu F
Discov Med · 2025 Jan · PMID 39851234 · Publisher ↗
BACKGROUNDS: Ultraviolet (UV) radiation-induced photoaging is a multifaceted biological process. Fruit acids have shown promise in combating photoaging. This study aims to investigate the mechanisms underlying the protec...
BACKGROUNDS: Ultraviolet (UV) radiation-induced photoaging is a multifaceted biological process. Fruit acids have shown promise in combating photoaging. This study aims to investigate the mechanisms underlying the protective effects of fruit acids on UV-induced skin photoaging. METHODS: Initially, we induced skin photoaging in rats through UV irradiation. Subsequently, the model group received glycolic acid treatment. The reparative effects of glycolic acid on skin tissue morphology and structure were assessed using Hematoxylin-eosin (HE) staining. The influence of glycolic acid on oxidative stress indicators (Superoxide Dismutase (SOD), Glutathione Peroxidase (GSH-Px), Malondialdehyde (MDA), Catalase (CAT)) and levels of cellular inflammatory factors (Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), IL-1β, Interferon-gamma (IFN-γ)) in photoaged skin was evaluated via Enzyme-Linked Immunosorbent Assay (ELISA). Additionally, alterations in collagen expression and levels of proteins associated with the Phosphoinositide 3-kinase/Protein Kinase B (PI3K/Akt) and Nuclear Factor kappa B (NF-κB) signaling pathways were determined through Western blot analysis. RESULTS: Compared to the model group, the fruit group exhibited a decrease in the thickness of the skin epidermal keratinization layer, an increase in dermal thickness, and more vigorous cortical secretion. Moreover, compared with the model group, the fruit group showed significant increases in SOD activity, CAT, GSH-Px, Collagen I, Collagen III, Collagen VII, and elastin. Conversely, levels of MDA, IL-6, IL-1β, IFN-γ, and TNF-α were lower in the fruit acid group than in the model group. Additionally, fruit acid treatment inhibited the phosphorylation levels of PI3K, Akt, and p65 induced by UV. CONCLUSION: Fruit acid demonstrates the ability to diminish the oxidative stress and inflammatory responses in skin photoaging rat models, thereby facilitating collagen recovery and ameliorating symptoms of skin photoaging. Its potential mechanism may entail the inhibition of the activation of the PI3K/Akt and NF-κB signaling pathways.
Plays a Pivotal Role in Colorectal Cancer Progression via the Dual Regulation of Cell Cycle and Epithelial-Mesenchymal Transition.
Luo Q, Zhu B, Wang C … +1 more , Wang Y
Discov Med · 2025 Jan · PMID 39851233 · Publisher ↗
BACKGROUND: Cytoskeleton-associated protein 2 like () has been demonstrated to mediate the cell cycle in cancer cells. However, it is unknown whether CKAP2L impacts colorectal cancer (CRC). The purpose of this study was...
BACKGROUND: Cytoskeleton-associated protein 2 like () has been demonstrated to mediate the cell cycle in cancer cells. However, it is unknown whether CKAP2L impacts colorectal cancer (CRC). The purpose of this study was to investigate the role of in CRC. METHODS: and regulatory factor X 5 () expression profiles in colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ) were analyzed in UALCAN. Human colorectal adenocarcinoma epithelial cells, DLD1, were transfected with small interfering RNA targeting and -overexpressing vectors (OE-CKAP2L). The interaction between and was identified by dual-luciferase assay and chromatin immunoprecipitation. Epithelial-mesenchymal transition (EMT)- and protein kinase B/mammalian target of the rapamycin (AKT/mTOR) pathway-associated proteins were evaluated by western blotting. RESULTS: and expression was increased in CRC based on the UALCAN database. downregulation inhibited proliferation, migration, invasion, and EMT while promoting G1/S phase arrest ( < 0.01). knockdown downregulated expression and mediated the inactivation of the AKT/mTOR pathway ( < 0.001). acted as an upstream transcription factor of . overexpression attenuated the restriction of downregulation on CRC cell malignant phenotypes ( < 0.01). CONCLUSION: transcriptionally activated by accelerates CRC proliferation and metastasis by promoting the cell cycle and EMT. This study provides potential molecular targets for treating CRC.
Glioblastoma Stem Cells: MAP17 as a Novel Predictive Biomarker and Therapeutic Target Associated with Quiescence and Immune Evasion.
Aghamiri SS, Amin R
Discov Med · 2025 Jan · PMID 39851232 · Publisher ↗
BACKGROUND: Glioblastoma multiforme (GBM) is one of the deadliest and most heterogeneous forms of brain cancer, characterized by its resistance to conventional therapies. Within GBM, a subpopulation of slow-cycling cells...
BACKGROUND: Glioblastoma multiforme (GBM) is one of the deadliest and most heterogeneous forms of brain cancer, characterized by its resistance to conventional therapies. Within GBM, a subpopulation of slow-cycling cells, often linked to quiescence and stemness, plays a crucial role in treatment resistance and tumor recurrence. This study aimed to identify novel biomarkers associated with these slow-cycling GBM cells. METHODS: We utilized The Cancer Genome Atlas (TCGA)-GBM dataset and presented the reproducible bioinformatics analysis for our results. RESULTS: Our analysis highlighted Membrane-Associated Protein 17 () as strongly associated with the slow-cycling phenotype. We found that the protein cargo expression is related to mesenchymal signatures and stem cell-related pathways. Also, was linked to a distinct metabolic profile, characterized by significant enrichment in pathways related to folate, zinc, and fatty acids. Moreover, the immune cell distribution analysis revealed that correlates with key molecular immune processes, including interferon-gamma () signaling and antigen presentation, as well as immunosuppressive cells like myeloid-derived suppressor cells (MDSCs) and macrophages. -high tumors also showed elevated expression of several immune checkpoint inhibitors, indicating an immunosuppressive microenvironment. CONCLUSION: These findings provide insight into the role of in quiescence, stemness, and immune evasion, positioning it as a promising therapeutic target.
Zinc Finger SWIM-Type Containing 3 Reprograms Lipid Metabolism and Drives Breast Cancer Progression.
Ma X, Wang A, Wang Y … +3 more , Ma J, Liu Y, Mei Y
Discov Med · 2025 Jan · PMID 39851231 · Publisher ↗
BACKGROUND: Zinc finger proteins (ZNFs) have been proved to play important roles in driving the progression of breast cancer (BC), one of the most common cancers among women. This study aimed to investigate the involveme...
BACKGROUND: Zinc finger proteins (ZNFs) have been proved to play important roles in driving the progression of breast cancer (BC), one of the most common cancers among women. This study aimed to investigate the involvement of zinc-finger SWIM domain-containing protein 3 () in promoting BC cell progression by regulating lipid metabolism. METHODS: Differential expression of in BC was confirmed by comparing its expression in normal human mammary epithelial cells and BC cells. MCF7 cells, a BC cell line, were subjected to knockdown/overexpression experiments. The lipid contents in MCF7 cells were measured by assay kits and immunofluorescence test. The lipogenic enzymes in the cells were detected by enzyme-linked immunosorbent assay (ELISA). The cells were also subjected to further transfection experiments to manipulate the expression of sterol regulatory element-binding transcription factor 1 ()/ in -regulated MCF7 cells to verify whether the targets . Subsequently, the lipid contents in the transfected cells were determined, and the cell viability, proliferation and metastasis were measured. RESULTS: was overexpressed in BC cells. knockdown/overexpression led to a significant decrease/increase of the lipid contents including triglyceride, free fatty acid, cholesterol, phospholipid and neutral lipid, and lipogenic enzymes ( < 0.01). The knockdown decreased the expression of and ( < 0.01). Our findings showed that lipid content reduction induced by knockdown was reversed by overexpression. MCF7 cell viability, proliferation and metastasis, which were all suppressed by knockdown ( < 0.001), were reversible through overexpression ( < 0.001). On the other hand, the overexpression increased and expression ( < 0.001). Lipid content elevation, as well as increased MCF7 cell viability, proliferation and metastasis, which were induced by overexpression, could be counteracted by downregulation ( < 0.001). CONCLUSION: promotes BC progression by enhancing lipid synthesis. This study reveals the malevolent effect of on BC, underpinned by the reprogramming of lipid metabolism, providing insights into potential therapeutic targets for BC treatments.
Analysis of Risk Factors Associated with Organic Erectile Dysfunction in Patients with Type 2 Diabetes Mellitus and Erectile Dysfunction.
Lu M, Ni D, Wu W … +2 more , Xu C, Zhang Y
Discov Med · 2025 Jan · PMID 39851230 · Publisher ↗
BACKGROUND: Diabetes mellitus is a common metabolic disorder, and diabetic erectile dysfunction (DMED) is one of its common complications. The differentiation of the types of erectile dysfunction (ED) is fundamental to t...
BACKGROUND: Diabetes mellitus is a common metabolic disorder, and diabetic erectile dysfunction (DMED) is one of its common complications. The differentiation of the types of erectile dysfunction (ED) is fundamental to treatment, yet there is a lack of simple and efficacious tools for this purpose in clinical practice. In this study, we endeavor to predict ED types using commonly available clinical data from diabetic patients, aiming to develop and assess a risk prediction model for organic erectile dysfunction in individuals with type 2 diabetes. METHODS: The study was a retrospective analysis. Data were obtained from the hospital's internal medical record system. We selected and analyzed the clinical data of 250 patients with type 2 diabetes. Lasso regression was used for risk factor selection, and the selected variables were included in a multivariate logistic regression analysis to establish the risk prediction model. Internal validation was performed using the bootstrap method, and the discrimination, calibration, and clinical effectiveness of the model were evaluated using the C-index, calibration curve, decision curve analysis (DCA), and receiver operating characteristic (ROC) curve. RESULTS: Among the 250 patients, 168 (67.2%) were diagnosed with organic ED. The risk factors included in the logistic regression analysis were the duration of diabetes, low-density lipoprotein cholesterol (LDL-C), red blood cell distribution width (RDW), intima-media thickness of the carotid artery, diabetic retinopathy, diabetic nephropathy, and peripheral neuropathy. The C-index was 0.827 (95% confidence interval (CI) = 0.772-0.882). The distribution curve of the predicted values and the calibration curve of the model were well fitted. The decision curve analysis (DCA) suggested that using the model could be clinically beneficial when the threshold probability was between 28% and 100%. CONCLUSION: By combining the duration of diabetes, carotid artery intima-media thickness, diabetic retinopathy, diabetic nephropathy, peripheral neuropathy, RDW, and LDL-C, this study preliminarily establishes a risk prediction model for organic ED in patients with type 2 diabetes mellitus. The model demonstrates good predictive performance.
Carbamazepine Inhibits Lung Cancer Metastasis by Suppressing Chemokine Receptor 4 Expression.
Zhang C, Ma X, Lv Z … +2 more , Lin D, Chen C
Discov Med · 2025 Jan · PMID 39851229 · Publisher ↗
BACKGROUND: Lung cancer is one of the leading causes of cancer-related deaths worldwide, with treatment failure resulting from metastasis. C-X-C chemokine receptor type 4 () plays a crucial role in tumor cell migration a...
BACKGROUND: Lung cancer is one of the leading causes of cancer-related deaths worldwide, with treatment failure resulting from metastasis. C-X-C chemokine receptor type 4 () plays a crucial role in tumor cell migration and metastasis. Recent studies have suggested that the commonly used antiepileptic drug, carbamazepine (CBZ), may impede tumor metastasis; however, its specific mechanism remains unclear. METHODS: In this study, we evaluated the effects of CBZ on the migration and invasion of lung cancer cells through cell cultures and animal models. The regulatory effect of CBZ on expression was analyzed using western blot and reverse transcription-quantitative polymerase chain reaction techniques. To further validate whether CBZ's anti-metastatic effect is mediated through , we used the agonist NUCC-390 and overexpression of the gene in lung cancer cell lines. RESULTS: The results demonstrated that CBZ significantly inhibited the migration and invasion of lung cancer cells (* < 0.001). In animal experiments, CBZ treatment significantly reduced the extent of metastasis in the lungs (* < 0.01). Moreover, CBZ downregulated the expression of (* < 0.001). When NUCC-390 was used or was overexpressed, the anticancer effect of CBZ was reversed, indicating the anti-metastatic effect of CBZ is closely associated with its inhibition of expression. CONCLUSION: This study reveals, for the first time, a novel mechanism by which CBZ inhibits lung cancer metastasis through the suppression of expression. These findings offer a new avenue for the treatment of lung cancer using CBZ as a potential agent against lung cancer metastasis. Further research is warranted to explore the clinical potential of CBZ and to offer more treatment options for lung cancer patients.
Knocking Down in Colorectal Cancer: Implications for Apoptosis and Cell Cycle Arrest via the p53 Signaling Pathway.
Hu M, Zhou H, Du X … +1 more , Zhang Y
Discov Med · 2025 Jan · PMID 39851228 · Publisher ↗
BACKGROUND: Preventing the progression and recurrence of colorectal cancer (CRC) remains a clinical challenge due to its heterogeneity and drug resistance. This underscores the need to discover new targets and elucidate...
BACKGROUND: Preventing the progression and recurrence of colorectal cancer (CRC) remains a clinical challenge due to its heterogeneity and drug resistance. This underscores the need to discover new targets and elucidate their cancer-promoting mechanisms. This study analyzed the cancer-promoting mechanisms of tryptophanyl-tRNA synthetase 1 () in CRC. METHODS: Clinical data and RNA expression profiles of CRC patients in public databases were analyzed using bioinformatics to determine the expression of . A knockdown assay was conducted with HCT116 and RKO cell lines to systematically assess the effects of on CRC cell proliferation, migration, cell cycle, and apoptosis. These assessments employed reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting, wound healing and transwell assays, flow cytometry, and xenograft tumor assays. Additionally, RNA sequencing and gene enrichment-based analysis were performed following knockdown to detect gene expression changes and related pathways. RESULTS: was overexpressed in CRC tissues ( < 0.05). Downregulation of inhibited the growth and migration of RKO and HCT116 cell lines ( < 0.05). This inhibitory effect on tumor growth was also observed in xenografts in nude mice after knockdown ( < 0.01). Flow cytometry revealed an increase in apoptosis and cell cycle arrest following knockdown ( < 0.05). Transcriptome sequencing analysis showed that reduced expression of activated the p53 signaling pathway and apoptosis while suppressing DNA replication and the cell cycle. The p53 transcriptional inhibitor pifithrin-α partially prevented the activation of caspase 3 and reduced the levels of c-poly-ADP-ribose polymerases 1 () and cyclin-dependent kinase inhibitor 1A (). CONCLUSION: was highly expressed in CRC, and its low expression was identified as a risk factor for CRC progression and recurrence. The current findings provide a theoretical basis for the development of therapeutic agents targeting and elucidate its mechanism in CRC progression.
Repeated Amphetamine Exposure Blunted Angiotensin II-Induced Responses Mediated by AT Receptors.
Casarsa BS, Occhieppo VB, Piermarini MJ … +3 more , Basmadjian OM, Baiardi G, Bregonzio C
Discov Med · 2025 Jan · PMID 39851227 · Publisher ↗
BACKGROUND: Angiotensin II, is critical in regulating the sympathetic and neuroendocrine systems through angiotensin II type 1 receptors (AT-R). Angiotensin II intracerebral administration increases water and sodium inta...
BACKGROUND: Angiotensin II, is critical in regulating the sympathetic and neuroendocrine systems through angiotensin II type 1 receptors (AT-R). Angiotensin II intracerebral administration increases water and sodium intake, as well as renal sodium excretion. Previously, our group has shown that AT-R is involved in behavioral and neurochemical sensitization induced by amphetamine. We aimed to assess the physiological output, behavioral, and neurochemical responses to intracerebral angiotensin II administration, via the AT-R, twenty-one days after amphetamine administration. MATERIAL AND METHODS: Male Wistar rats received daily vehicle or AT-R antagonist (oral) for 10 days, and amphetamine or saline intraperitoneal (i.p.) from day 6 to 10. On day 25 they were implanted with an intracerebral cannula. On day 32, the animals received intracerebral angiotensin II. First group: the animals were tested in a free choice paradigm for 2% NaCl and water intake, and sacrificed for neuronal activity assessment via c-Fos immunohistochemistry. Second group: urine samples were collected for electrolyte determination. Third group: the animals were tested in the plus maze or the hole board for anxiety and working memory evaluation, respectively, and sacrificed for c-Fos immunohistochemistry. RESULTS: Amphetamine exposure blunted the increase in sodium intake ( = 0.0022), and potentiated the natriuretic ( = 0.0043) and kaliuretic effect ( = 0.0002) induced by angiotensin II. Moreover, amphetamine exposure prevented the expression of the anxiogenic effect (drug effect < 0.0001) and the memory deficit ( = 0.1314) induced by cerebral angiotensin II administration. Amph decreased c-Fos immunoreactivity in nucleus tractus solitarii (NTS) = 0.0037; paraventricular nucleus (PVN) = 0.0047; Central amygdala (CeA) = 0.0008; Basolateral amygdala (BLA) = 0.0018; increased in hippocampus region CA1 = 0.0043; CA3 = 0.026; and dentate gyrus (DG) = 0.0057. The blockade of AT-R prevented these alterations (sodium intake = 0.0421 natriuresis = 0.019; kaliuresis = 0.196; working memory ( < 0.0001); but no the anxiogenic response to angiotensin II (drug effect < 0.0001); as well as the c-Fos changes (NTS = 0.0052; PVN = 0.029; CeA = 0.0002; BLA = 0.0021; CA1 = 0.0026; CA3 = 0.022; and DG = 0.0016). CONCLUSION: Most of the long-lasting AT-R altered responses to brain angiotensin II administration induced by repeated amphetamine exposure could be prevented by AT-R blockade.
LncRNA : A Promising Therapeutic Target for Colorectal Cancer by Regulating -Mediated Cell Proliferation, Invasion and Apoptosis.
Li H, Shen X, Li Y
Discov Med · 2025 Jan · PMID 39851226 · Publisher ↗
BACKGROUND: Long non-coding RNA (lncRNA) zinc finger protein 667-antisense RNA 1 () is closely related to the advancement of a variety of cancers, but its functional role in colorectal cancer remains unclear. This study...
BACKGROUND: Long non-coding RNA (lncRNA) zinc finger protein 667-antisense RNA 1 () is closely related to the advancement of a variety of cancers, but its functional role in colorectal cancer remains unclear. This study was designed to explore the function and molecular mechanisms of lncRNA in colorectal cancer. METHODS: Reverse transcriptase real-time quantitative polymerase chain reaction (RT-qPCR) was used for the detection of and proline-rich nuclear receptor co-activator protein 2 () expression level. Cell counting kit-8 (CCK-8), 5-Ethynyl-2'- deoxyuridine (EdU), and colony formation assays were conducted to assess cell proliferation; flow cytometry and transwell invasion assay were performed separately to measure cell apoptosis and invasion. RNA immunoprecipitation (RIP) assay was utilized to analyze the relationship between and . Western blot was to test the PNRC2 protein expression. The role of in the advancement of colorectal cancer was evaluated by tumor xenograft assay. RESULTS: LncRNA and were both decreased in colorectal cancer tissue samples and cells ( < 0.05). overexpression remarkably restrained proliferation and invasion in HCT-116 and LOVO cells, but enhanced cell apoptosis ( < 0.0001). Moreover, directly targeted , and positively regulated its expression. The influence of overexpression on invasion, apoptosis, and proliferation was suppressed by knockdown in HCT-116 and LOVO cells. Additionally, overexpression markedly inhibited tumor growth via upregulation of in mice ( < 0.05). CONCLUSION: LncRNA expressed low in colorectal cancer. LncRNA repressed proliferation and invasion, and enhanced apoptosis of colorectal cancer cells by targeting .
Construction of a Multi-View Deep Learning Model for the Severity Classification of Acute Pancreatitis.
Xiang K, Shang D
Discov Med · 2025 Jan · PMID 39851225 · Publisher ↗
BACKGROUND: Acute pancreatitis (AP) is a prevalent pathological condition of abdomen characterized by sudden onset, high incidence and complex progression. Timely assessment of AP severity is crucial for informing interv...
BACKGROUND: Acute pancreatitis (AP) is a prevalent pathological condition of abdomen characterized by sudden onset, high incidence and complex progression. Timely assessment of AP severity is crucial for informing intervention decisions so as to delay deterioration and reduce mortality rates. Existing AP-related scoring systems can only assess current condition of patients and utilize only a single type of clinical data, which is of great limitation. Therefore, it is imperative to establish more accurate and data-compatible methods for predicting the severity of AP. The artificial intelligence (AI) algorithm based on artificial neural network (ANN) allow for the adaptive feature extraction for objective task through its internal complex network, instead of the hand-crafted methods commonly used in traditional machine learning (ML) algorithms. In this study, we delve into the final severity classification prediction of newly admitted AP patients, using deep learning (DL) algorithm to develop multi-view models, incorporated with patients' demographic information, vital signs, AP-related laboratory indexes and admission computed tomography (CT) images. METHODS: The pancreatitis database in the platform of Clinical Data Research Center of Acute Abdominal Surgery at the First Affiliated Hospital of Dalian Medical University was used to gather AP cases. Deep neural network (DNN) and convolutional neural network (CNN) were utilized to construct models. The DNN prediction models with clinical data as input, the CNN prediction models with admission CT as input, and the multi-view models combining the two inputs were respectively established to predict the severity of AP. RESULTS: DL models for AP severity classification based on clinical indexes, imaging data and merged data were constructed. The multi-view model based on merged data offered more accurate prediction of the final severity classification of AP, with an overall accuracy rate of 80.26% (95% confidence interval (CI): 79.58%-80.94%). The constituent accuracy rates for mild acute pancreatitis, moderately severe acute pancreatitis, and severe acute pancreatitis were 91.69% (95% CI: 87.80%-95.57%), 64.90% (95% CI: 58.85%-70.95%), and 75.56% (95% CI: 68.58%-82.53%), respectively. CONCLUSION: The multi-view models using clinical indexes and imaging data as input outperform single-view models in AP severity prediction.
Regulation of Concanavalin A-induced Immune Hepatitis in Mice by Dihydromyricetin at the M1/M2 Type Macrophage Level.
Zhang X, Liu Y, Yang K … +3 more , Tang J, Zhao K, Li Y
Discov Med · 2025 Jan · PMID 39851224 · Publisher ↗
BACKGROUND: Autoimmune hepatitis (AIH) is an autoimmune disease accompanied by an autoimmune inflammatory response that often leads to severe liver damage. In addition, it may further lead to complications such as liver...
BACKGROUND: Autoimmune hepatitis (AIH) is an autoimmune disease accompanied by an autoimmune inflammatory response that often leads to severe liver damage. In addition, it may further lead to complications such as liver fibrosis, cirrhosis and liver failure. Dihydromyricetin (DHM) possesses various pharmacological properties, such as being anti-inflammatory, antioxidant, and antibacterial. In this experiment, we investigated the effect of DHM on autoimmune hepatitis mice based on the level of M1/M2 type macrophages. METHODS: An autoimmune hepatitis mouse model was established by the administration of DHM followed by tail vein injection of Concanavalin A (Con A). Liver tissues were examined for pathological and morphological changes. Interleukin-1β (IL-1β), interleukin-10 (IL-10), interleukin-6 (IL-6), and interleukin-4 (IL-4) levels in liver tissues were assessed. Serum hepatic function indexes were measured, including alanine aminotransferase (ALT), aspartate transaminase (AST), and lactatedehydrogenase (LDH). Oxidative stress indexes, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and Nitric oxide (NO), were quantified. Additionally, tumor necrosis factor-α () and nuclear factor kappa-B () mRNA and protein expression polarization were determined. The presence of M1/M2-type macrophages was also investigated. RESULTS: Compared to the model group, mice in the DHM group exhibited a significant reduction in serum hepatic function indexes ( < 0.05). Liver tissues from the DHM group showed a noteworthy decrease in MDA and NO levels, along with a significant increase in SOD and GSH-Px levels ( < 0.05). Furthermore, in the liver tissues of mice from the DHM group, there was a notable reduction in the count of M1-type macrophages and a considerable elevation in the M2-type macrophages ( < 0.05). IL-1β and IL-6 expression levels exhibited a significant decrease, whereas IL-10 and IL-4 levels displayed a significant increase ( < 0.05). Additionally, both and mRNA levels and protein expression experienced a noteworthy decrease ( < 0.05). CONCLUSION: DHM mitigates the inflammatory response in AIH mice by reducing oxidative stress and modulating macrophage polarization and the TNF-α/NF-κB pathway.
Clinical Application of a Big Data Machine Learning Analysis Model for Osteoporotic Fracture Risk Assessment Built on Multicenter Clinical Data in Qingdao City.
Li B, Yang Y, Shen F … +4 more , Wang Y, Wang T, Chen X, Lu C
Discov Med · 2025 Jan · PMID 39851223 · Publisher ↗
BACKGROUND: Osteoporotic fractures (OPF) pose a public health issue, imposing significant burdens on families and societies worldwide. Currently, there is a lack of comprehensive and validated risk assessment models for...
BACKGROUND: Osteoporotic fractures (OPF) pose a public health issue, imposing significant burdens on families and societies worldwide. Currently, there is a lack of comprehensive and validated risk assessment models for OPF. This study aims to develop a model to assess and predict the risk of OPF in Qingdao City, China. METHODS: From January 2021 to January 2023, we recruited 84 osteoporotic patients diagnosed with fractures from Qingdao University Affiliated Hospital, Qingdao Municipal Hospital, Qingdao Hiser Hospital Affiliated of Qingdao University, and Qingdao Central Hospital as the experimental group. In addition, 112 osteoporotic patients without fractures were recruited as the control group. In this study, we employed seven machine learning models, namely Adaboost, random forest (RF), K-Nearest Neighbors (KNN), Support Vector Machine (SVM), Logistic Regression (LR), Naive Bayes (NB), and Gradient Boosting Decision Trees (GBDT), to analyze the risk factors influencing the occurrence of OPF. Next, we plotted receiver operating characteristic (ROC), Precision-Recall (PR), and calibration curves to evaluate the predictive values of the different risk assessment models for OPF. RESULTS: Among the seven models built based on the training set data, the Adaboost model showed area under the curve (AUC), sensitivity, and specificity values close to 1, indicating the best classification performance. In the test set, the AUC values for the RF, SVM, LR, KNN, NB, AdaBoost, and GBDT models were 0.936, 0.905, 0.88, 0.93, 0.862, 0.939, and 0.859, respectively ( < 0.001). All sensitivity and specificity values for these models were higher than 0.8, with sensitivity and specificity values of the Adaboost model closest to 1. Additionally, six models had an area under the Precision-Recall curve (prAUC) values higher than 0.9, except KNN at 0.284 ( < 0.001). The calibration curves of the seven models did not significantly deviate from the ideal curve, indicating acceptable discriminative ability and predictive performance of the predictive model. All results showed that trabecular bone score (TBS) was the most important variable affecting the model, followed by osteocalcin (OST) and hunchback. CONCLUSIONS: Given the various clinical data from patients with OPF, we assessed and demonstrated the good predictive performance of our risk predictive models. This model will enable us to take timely intervention measures to reduce the incidence of OPF and improve patient prognosis.
Mechanism of Corylin Inhibiting the Development of Osteosarcoma: Regulating /p38 MAPK Signaling.
Yan R, Wang H, Cai Z … +1 more , Zeng Z
Discov Med · 2025 Jan · PMID 39851222 · Publisher ↗
BACKGROUND: High-mobility group box 1 () participates in the progression of osteosarcoma (OS) through the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Corylin, one of the active components of , has anti...
BACKGROUND: High-mobility group box 1 () participates in the progression of osteosarcoma (OS) through the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Corylin, one of the active components of , has anti-oxidant, anti-inflammatory, and anti-tumor effects. This study investigates the association between corylin and , and their impact and mechanism of action on OS. METHODS: OS cells and osteoblasts were transfected with/without overexpression plasmid and si. Cell viability was examined using the Cell Counting Kit-8 (CCK-8) assay after treatment with corylin (0, 2.5, 5, 10, 30 μM). The effects of corylin on cell malignant behaviors were examined by cell function assays. The mRNA expression level of high-mobility group box 1 () was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The protein levels of HMGB1, matrix metalloproteinase-2 (MMP-2), MMP-9, and alpha-smooth muscle actin (α-SMA) were measured by western blotting. The effects of corylin and on the expression of p38 MAPK signaling pathway-related proteins were also assessed. RESULTS: Corylin decreased OS cell viability, proliferation, migration, and invasion but increased apoptosis in a concentration-dependent manner. Corylin concentration-dependently suppressed the levels of , MMP-2, MMP-9, and α-SMA. Overexpression of was partially reversed, while knockdown of enhanced the above effects of corylin. CONCLUSION: Corylin inhibits OS cell migration and invasion through regulation of the -mediated p38 MAPK signaling pathway.
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