Objective: As global smoking rates decline, Lung Cancer in Never-Smokers (LCINS) has emerged as a distinct and increasingly important clinical entity. However, its underlying pathogenesis remains poorly understood, highlighting the need to identify circulating molecular determinants and candidate biomarkers. Methods: Genetic instruments for plasma proteins were obtained from pQTL datasets (Fenland study and UK Biobank Pharma Proteomics Project), while summary statistics for LCINS were sourced from TRICL-ILCCO. Two-sample Mendelian Randomization (MR) was performed using inverse-variance weighting as the primary approach, complemented by sensitivity analyses for heterogeneity (Cochran’s Q), horizontal pleiotropy (MR-Egger intercept), and outlier detection (MR-PRESSO). Tissue-level validation was conducted using CPTAC proteomic data. Further analyses, including Bayesian colocalization, Protein-Protein Interaction (PPI) network construction, Gene Ontology (GO) enrichment, and mediation analysis, were applied to investigate shared genetic architecture, functional pathways, and immune-mediated mechanisms. results: Analysis of 543 cis-acting plasma proteins identified 15 potential risk-increasing and 20 protective proteins for LCINS. Following multiple testing correction, genetically predicted RARRES1 emerged as the sole significant causal risk factor (OR = 1.17, P.adjust = 2.72 × 10-5), a finding replicated in an independent cohort. Bayesian colocalization supported a shared causal variant (PPH4 = 0.83). Functionally, RARRES1 was linked to T-cell suppression and exosomes. Mechanistically, elevated RARRES1 increased LCINS risk in part by reducing CD16-CD56 intensity on NKT cells, accounting for 11.8% of its total effect. Results: Among 543 cis-acting plasma proteins evaluated in the discovery phase, 35 exhibited evidence of association with LCINS risk, including 15 positively and 20 inversely associated proteins. After False Discovery Rate (FDR) correction, only genetically proxied plasma RARRES1 remained statistically significant (OR = 1.17, adjusted P = 2.72 × 10-5), and this finding was replicated in an independent cohort. Bayesian colocalization supported a shared causal variant (PPH4 = 0.83). Functional enrichment analyses implicated RARRES1-related networks in immune regulation and extracellular processes. Two-step MR mediation analysis nominated CD16-CD56 intensity on NKT cells as a potential immune-mediated pathway, accounting for an estimated 11.8% of the genetic effect. Discussion: This study prioritizes genetically proxied plasma RARRES1 as a candidate protein associated with LCINS risk and highlights CD16-CD56 intensity on NKT cells as a potential immune-related mechanism. These findings provide biologically plausible evidence supporting a role for RARRES1 in LCINS pathogenesis and its potential utility in biomarker development. Conclusion: Genetically proxied plasma RARRES1 is associated with increased LCINS risk and may contribute to disease susceptibility through immune-related alterations involving NKT-cell phenotypes. RARRES1 represents a promising candidate for future mechanistic studies and blood-based diagnostic biomarker development in LCINS.
INTRODUCTION/OBJECTIVE:Psoriasis is associated with an increased risk of Ischemic Stroke (IS), but the underlying mechanisms remain unclear. This study aims to identify shared associated genes and explore potential mechanisms underlying psoriasis and IS. METHODS:Gene expression datasets from the GEO database were analyzed to identify common Differentially Expressed Genes (co-DEGs). Integrative bioinformatics analyses, machine-learning algorithms, single-cell RNA sequencing, molecular docking, and molecular dynamics simulations were employed to identify candidate shared genes and investigate the potential molecular mechanisms. RESULTS:We identified 57 co-DEGs shared between psoriasis and IS. Enrichment analyses indicated that these genes were mainly associated with immune and inflammatory pathways, including NET formation, NF-κB, TLR, and IL-17 signaling pathways. TLR2 and TNFSF10 were identified as shared associated genes and remained significant across leave-one-out sensitivity analyses, demonstrating the robustness of their differential expression. Single-cell analysis revealed that TLR2 and TNFSF10 were mainly expressed in macrophages, NK cells, and smooth muscle cells. Epigallocatechin gallate was identified as a candidate compound for further investigation. DISCUSSION:Our integrative analysis highlights TLR2 and TNFSF10 as potential mechanistic candidates associated with persistent immune activation, endothelial dysfunction, and vascular injury. These genes may participate in interconnected inflammatory processes involving TLR, IL-17, NF-κB, and NET-related pathways, providing a potential molecular link between psoriasis and IS. CONCLUSION:Chronic inflammation and immune dysregulation may contribute to psoriasis and IS comorbidity. TLR2 and TNFSF10 were identified as shared associated genes. These findings provide exploratory insights into the immunoinflammatory mechanistic association between psoriasis and IS.
BACKGROUND:Rheumatoid Arthritis (RA) is a common autoimmune disease with complex pathogenesis and high prevalence, severely affecting patients' quality of life. Multi-omics analysis has emerged as a powerful tool in RA research, providing insights into cell heterogeneity, genetic mechanisms, and immune microenvironment characteristics. This research looks into important genes linked to rheumatoid arthritis(RA) using single-cell data and Mendelian randomization analysis, while also uncovering the characteristics of the immune microenvironment and its mechanisms linking to these key genes. METHODS:Gene expression, eQTL, and GWAS data were collected. Analyses included single-cell data processing (quality control, dimensionality reduction, clustering, cell annotation, and cell subset contribution assessment), subgroup non-negative matrix factorization, Mendelian randomization, co-localization analysis, immune infiltration analysis, and GSEA/GSVA. RESULTS:This study analyzed 95,036 single-cell samples and found that alterations in B cells are closely associated with disease progression. Further analysis identified seven distinct B cell subpopulations, with immune responses and the tumor microenvironment exerting significant influence on their dynamics. Mendelian randomization analysis revealed key genes, CD83 and CRIP2, that are linked to the risk of RA. Subsequent investigation demonstrated strong associations between these genes and immune cell populations. GSEA and GSVA analyses showed that CD83 is involved in pathways related to allograft rejection and antigen processing, while CRIP2 is associated with interactions of extracellular matrix receptors and the IL-17 signaling pathway. Additionally, immunometabolism pathway analysis highlighted potential therapeutic targets and underlying mechanisms. DISCUSSION:The findings suggest that B cells play a major role in the RA immune microenvironment and identify CD83 and CRIP2 as potential biomarkers and therapeutic targets. CD83 may contribute to RA through immune regulation, antigen presentation, and inflammatory signaling, whereas CRIP2 may be involved in metal ion homeostasis, cellular stress responses, and immune-related pathological processes. Immune infiltration analyses further indicate that these genes are closely associated with immune-cell activity in RA. Overall, the study provides new insight into RA pathogenesis and supports the potential clinical relevance of CD83 and CRIP2, although further experimental and clinical validation is required. CONCLUSION:This study offers valuable understanding about RA pathogenesis and identifies probable diagnostic biomarkers as well as therapeutic targets (CD83 and CRIP2), which could improve our awareness of the illness and help with formulating more successful care plans.
Objective: This study aimed to clarify the pan-cancer expression pattern, upstream regulatory mechanisms, prognostic relevance, and immune associations of CDC20B. Method: Using public databases (GTEx, GEO, and TCGA), we examined CDC20B expression and its associations with prognosis and tumor immunity across multiple cancers. Immunohistochemistry (IHC) on an independent clinical cohort was performed to validate CDC20B upregulation in tumor tissues. Promoter methylation, genetic alterations, and immune infiltration were analyzed using bioinformatics tools (cBioPortal, UALCAN, TIMER2.0, ESTIMATE). Functional enrichment was assessed by GSEA and single-cell state analysis (CancerSEA). Results: CDC20B was markedly upregulated in most tumor types (p <0.001), with strong diagnostic efficiency (AUC > 0.7 in 15 cancers) and potential regulation by promoter hypomethylation. IHC confirmed its overexpression in clinical tumor tissues. However, the prognostic impact of CDC20B was cancer-type-specific: high expression correlated with poor overall survival in UCS, LGG, KIRC, and OV, but with favorable survival in BRCA, LUAD, and PAAD. CDC20B expression was associated with immune infiltration patterns, showing negative correlations with ImmuneScore in most cancers but positive correlations with CD8+ T cells in PAAD. Functional analyses indicated involvement in EMT, KRAS/NF-κB signaling, and DNA damage response pathways. Discussion: The dual prognostic role of CDC20B suggests context-dependent functions, likely influenced by tumor microenvironment composition and underlying oncogenic programs. Promoter hypomethylation emerges as a potential epigenetic driver of overexpression. The associations with immune modulation and genomic instability suggest that CDC20B is a candidate biomarker, though causal relationships require experimental validation. Conclusion: CDC20B may contribute to tumor progression in a context-dependent manner, with its prognostic impact varying across cancer types. Its role in tumor immunity and oncogenic pathways warrants further investigation, particularly in stratified patient populations.
Graphene is a two-dimensional crystal formed by carbon atoms through sp2 hybridization, exhibiting exceptional physicochemical properties such as ultra-high strength, high specific surface area, and outstanding chemical stability. It has garnered extensive attention across multiple fields and emerged as a core focus in interdisciplinary research. This paper systematically reviews the fundamental information and key physicochemical properties of graphene and its derivatives, elucidating their differences in structure, performance, and functionality. It analyzes the research progress of graphene-based materials over the past decade, focusing on the latest achievements in the biomedical field. Based on graphene heating films, this study delves into the mechanism of far-infrared radiation. This study systematically addresses core issues in biomedical applications. It focuses particularly on variations in biocompatibility and safety, as well as potential influencing factors. Existing biomedical applications of graphene and its derivatives are enumerated, elucidating the biological activity of graphene's far-infrared radiation. Its antitumor mechanisms are analyzed at both in vitro and in vivo levels, though relevant clinical research data remains scarce. This underscores the immense application potential and translational value of graphene-based materials in biomedicine. Finally, it analyzes existing barriers in the graphene industry from three aspects: standard establishment, safety assessment, and mechanism clarification. It identifies priority development directions for graphene materials: improving the quality standards system, optimizing safety and biocompatibility, supplementing clinical data, and deepening research on therapeutic mechanisms. These are key prerequisites for graphene-based materials to break through laboratory research limitations and advance toward clinical application, which is crucial for accelerating their industrialization in the biomedical field.
Abstract: Ovarian cancer remains one of the most lethal gynecological malignancies due to late diagnosis, high recurrence rates, and resistance to conventional therapies. Emerging evidence underscores the therapeutic potential of natural compounds, among which ginsenosides, the principal bioactive components of ginseng, exhibit remarkable anticancer properties. This review summarizes current insights into the anti-ovarian cancer activities of ginsenosides, with particular focus on their regulatory effects on non-- coding RNAs, especially microRNAs. Ginsenosides modulate diverse molecular pathways, including apoptosis induction, autophagy regulation, epithelial-to-mesenchymal transition suppression, angiogenesis inhibition, and epigenetic reprogramming. Increasing evidence demonstrates that ginsenosides exert tumor-suppressive effects by restoring tumor-suppressor microRNAs and repressing oncogenic ones, thereby interfering with cancer stem cell maintenance, metabolic reprogramming, and metastatic progression. Furthermore, ginsenosides enhance the efficacy of chemotherapeutic agents such as paclitaxel and cisplatin while reducing associated toxicity. Despite promising preclinical findings, clinical translation remains limited due to challenges in bioavailability and pharmacokinetics. Collectively, ginsenosides represent a promising class of phytochemicals for ovarian cancer treatment, particularly through microRNA-centered mechanisms, warranting further investigation into optimized formulations, nanodelivery systems, and well-designed clinical trials.
Background: Mouse neuroblastoma cells (N2a) are spontaneously derived from mice and possess the characteristics of neural stem cells. The proliferation, differentiation, and protrusion growth of N2a cells in vitro are consistent with those in vivo. Flavonoids isolated from the aerial parts of Scutellaria barbata (SBFs) can improve learning and memory deficits and protect against neuronal injury in many in vivo AD-- like models. N2a cells exposed to Aβ25-35 for Alzheimer’s disease-related toxicity were subsequently used to observe the ameliorative effects of SBFs, and the effective mechanism through which SBFs promote the phosphorylation of CREB was further studied by using BI-D1870, an indirect inhibitor, and Rolipram, an activator of CREB phosphorylation. Methods: Immunofluorescence (IF) was used to detect the protein expression of the neuron-specific proteins NeuN, NeuroD1, and DCX. N2a cells were exposed to 100 μM Aβ25-35 and treated with SBFs at doses of 17.5, 35 and 75 mg·L-1 or 363 μM Rolipram. Cell morphology was observed under an inverted microscope, the cell survival rate was detected by the Cell Counting Kit-8 (CCK-8) method, and the release of lactate dehydrogenase (LDH) into the cell culture medium was determined by the pyruvate reduction method. The mRNA expression levels of ERK, RSK, CREB, and EGR-1 in cells were detected by real-time quantitative polymerase chain reaction (qPCR). IF and/or western blotting (WB) were used to measure the protein expression levels of BDNF, NGF, TrkB, Ras, ERK/p-ERK, Rsk/p90RSK, CREB/p-CREB-Ser133, and EGR-1 in N2a cells Results: NeuN, NeuroD1, and DCX expression in N2a cells was positive, as indicated by green fluorescence. Both Aβ25-35 and BI-D1870 resulted in abnormal morphological changes in N2a cells, reduced the cell survival rate (P<0.01), increased the release of LDH (P<0.01) into the culture medium, and decreased the mRNA expression levels of ERK, RSK, and CREB and the protein expression levels of p-ERK, TrkB, p90RSK, pCreb-SER133, BDNF, NGF and EGR-1 (P<0.01) in cells. However, SBFs, to varying degrees, reversed the aforementioned abnormal changes in N2a cells caused by Aβ25-35 or BI-D1870, and the effects of SBFs were consistent with those of Rolipram. Conclusion: SBFs protected against N2a cell damage induced by toxic Aβ25-35, and the effective mechanism by which SBFs promote the phosphorylation of CREB at the Ser133 site was confirmed through the application of the indirect CREB phosphorylation inhibitor BI-D1870 and the activator Rolipram. These findings suggest that SBFs may be helpful in the treatment of AD by intervening in CREB phosphorylation.
When inhaled, environmental toxins enter not only the respiratory system but also the olfactory system. Metallic compounds in the environment form various free radicals through Fenton reactions and Fenton-like reactions. These free radicals damage the olfactory system in various ways. Reactive oxygen species generated during Fenton and Fenton-like reactions damage olfactory G protein-coupled receptors, disrupting the receptor's coupling to GOₗf and cAMP- and IP3/Ca2+-dependent signaling. The cascade of reactions involves ion channels, mitochondria, enzymes, lipids, proteins, DNA, and antioxidant defense mechanisms, including Nrf2-dependent transcriptional programs, glutathione, and others. Essentially, Fenton and Fenton-like reactions both generate free radicals; however, the reactive hydroxyl radical (•OH) generated in the classical Fenton reaction rapidly and locally damages neuronal cell and receptor structural molecules, whereas Fenton-like reactions, through surface-mediated, prolonged ROS production, cause progressive, chronic damage that differentially alters GPCR-GOₗf signaling and neuronal function; the study of these mechanisms is essential for assessing oxidative neurotoxicity of the olfactory system. This review discusses damage to olfactory receptor structures by radicals generated during Fenton and Fenton-like reactions, the characteristics of these chemical reactions, and the corresponding behavioral clinical changes.
Background: Neurological disorders are a significant and increasing public health concern due to their multifactorial pathogenesis, progressive clinical course, and limited long-term effectiveness of current therapeutic strategies. Recent experimental and clinical studies have increasingly focused on bioactive natural compounds as potential modulators of neuroinflammation, oxidative stress and neuronal apoptosis — processes that play a central role in neurodegeneration. Of these, nobiletin (a polymethoxylated flavonoid found in citrus peels) has attracted particular attention thanks to its reported antioxidant, anti-inflammatory and neuroprotective properties in preclinical models. Objective: We discuss the potential therapeutic role of nobiletin in neurological diseases, examining the relevant molecular mechanisms, preclinical findings, and emerging clinical data. Methods: We searched the electronic databases PubMed, Scopus, and Embase to identify studies examining the therapeutic effects of nobiletin on neurological disorders published up to October 2025. Results: This review discusses the neuroprotective actions of nobiletin, with particular attention to its anti-inflammatory, anti-apoptotic, and antioxidant activities and their involvement in major intracellular signaling pathways. In addition, available preclinical findings and emerging clinical data are examined to assess the therapeutic relevance of nobiletin in experimental and clinical models of neurological disorders. Discussion: Experimental evidence suggests that nobiletin has neuroprotective properties that could reduce pathological processes associated with neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases. However, further well-designed studies are needed to clarify its mechanisms of action and determine whether these effects are beneficial in clinical practice, either as a standalone therapy or in combination with existing treatments. Conclusion: Overall, the available evidence indicates that nobiletin may have beneficial effects on a wide range of neurological conditions, such as Parkinson's disease, Alzheimer's disease, stroke, epilepsy, depression, schizophrenia, multiple sclerosis, glioma, and sciatic nerve injury.
Introduction: In-depth analysis of the biological status of Hematopoietic Stem Cells (HSCs) may reveal the intrinsic pathological mechanism of Chronic Myelomonocytic Leukemia (CMML). Materials and Methods: Single-cell dataset GSE211033 and bulk transcriptomic dataset GSE102312 were analyzed. Single-cell preprocessing was performed using the Seurat package, cell-cell communication was analyzed with CellChat, and HSC-associated co-- expression modules were identified via hdWGCNA. Pathway and candidate-compound analyses were conducted using Enrichr with the DSigDB database. Molecular docking and a 100 ns molecular dynamics simulation were performed with GROMACS 2025, and the function of ENO1 was preliminarily assessed in myeloid leukemia cell lines. Results: Ten major cell populations were identified, among which HSCs comprised 14,729 cells. Seven HSC co-expression modules were classified. Among 25 genes represented in the M1 hub-gene network, ENO1 was the only evaluated candidate that showed a distinct difference between CMML samples and healthy controls. ENO1 knockdown reduced the viability of HL-60 and MV-4-11 cells in a time-dependent manner. High ENO1 expression was associated with enrichment of cell-cycle, DNA damage- response, and energy-metabolism pathways. Naftopidil ranked first among the significant HL-60-associated candidates screened from the DSigDB. Molecular docking and 100 ns molecular dynamics simulation revealed that the ligand dynamically interacted with ENO1 following conformational rearrangement, although direct binding remains to be experimentally validated. Discussion: ENO1 emerged as an HSC-associated candidate gene with a potential role in supporting the metabolic and proliferative state of CMML-related hematopoietic cells. Naftopidil was computationally predicted as a candidate ENO1-binding compound, but its direct binding and therapeutic activity require experimental validation. Conclusion: These findings provide a hypothesis-generating basis for further investigation of ENO1 and naftopidil in CMML-specific models, primary samples, and in vivo studies.
Introduction: The tryptophan (TRP)-serotonin pathway is disrupted and redirected towards kynurenine by the action of indoleamine 2,3-dioxygenase 2 (IDO2) and kynureninase (KYNU). In ovarian cancer, concurrent kynurenine activation encourages tumor growth and immune evasion. The investigation of phytochemicals has focused on identifying therapeutic targets in ovarian cancer. Introduction: The tryptophan (TRP)-serotonin pathway is disrupted and redirected towards kynurenine by the action of indoleamine 2,3-dioxygenase 2 (IDO2) and kynureninase (KYNU). In ovarian cancer, concurrent kynurenine activation encourages tumor growth and immune evasion. The investigation of phytochemicals has focused on identifying therapeutic targets in ovarian cancer. Methods: Gene expression, survival plots, and comparisons of correlated genes were computed to obtain holistic insights into the identified targets. A Kaplan-Meier analysis was performed to examine the survival patterns of IDO1 and KYNU targets. Molecular docking was performed to determine the binding affinity of ligands, and the Desmond module of Schrodinger was used to confirm the docking scores through simulation. Physiochemical and ADMET properties were assessed using SwissADME and pkCSM. Electronic effects and stability were further confirmed using Gaussian software. Results: Protein-protein interactions of TRP metabolism revealed IDO2 and KYNU as potential targets involved in pathway diversion. The comparison of mutated and non-mutated targets showed no significant difference, reflecting the tumor’s heterogeneity and the limited number of mutated samples. Molecular docking studies of 368 phytochemicals from six sources, reported to have anti-ovarian cancer properties, revealed 11 phytochemicals with higher binding affinities of -9.7 kcal/mol for IDO2 and -9.4 kcal/mol for KYNU. The interaction between the target and ligand was confirmed by molecular dynamics simulation using the Desmond module V3 of Schrödinger software. The stability and reactivity of phytochemicals were assessed using HOMO-LUMO and energy gap calculations. The highest electron stability was shown in 24MC (6.95 eV) and C24β (6.93 eV) compared with controls. The identified phytochemicals were further evaluated for their ADMET properties to refine therapeutic hit compounds. Compounds, such as Hemanthidine (HAT), Ergometrine (ERG), Tazettine (TZT), Tenatoprazole (TU-199), Rucaparib (CO-338), and Nicotinylalanine (NAL), have been reported to improve drug absorption. Discussion: By altering the ovarian cancer microenvironment, targeting immunometabolism with a clinically relevant approach improves therapeutic efficacy. Target expression clarifies the immune-rich tumor microenvironment rather than the actual tumor growth. Higher-binding- affinity compounds demonstrate high electronic stability in energy estimates as well as improved drug availability in pharmacokinetic investigations. However, this finding remains a computational approach and requires experimental validation. Discussion: By altering the ovarian cancer microenvironment, targeting immunometabolism with a clinically relevant approach improves therapeutic efficacy. Target expression clarifies the immune-rich tumor microenvironment rather than the actual tumor growth. Higher-binding-affinity compounds demonstrate high electronic stability in energy estimates as well as improved drug availability in pharmacokinetic investigations. However, this finding remains a computational approach and requires experimental validation. Conclusion: This computational study identifies suitable hit compounds for targeting TRP depletion, expanding the scope for subsequent in vitro and in vivo exploration to expedite drug discovery. Conclusion: This computational study identifies suitable hit compounds for targeting TRP depletion, expanding the scope for subsequent in vitro and in vivo exploration to expedite drug discovery.
Background/Objectives: Colorectal cancer (CRC) is a major cause of cancer- related deaths worldwide and poses a significant global health challenge. Metabolic reprogramming, including transketolase (TKT) upregulation in the pentose phosphate pathway, is a hallmark of CRC. Drugs targeting TKT have shown promise in cancer treatments; however, their mechanisms are poorly understood. Methods: In this study, by integrating bioinformatics analysis of 494 cases from the TCGA database, we identified that transketolase (TKT) may be a potential key target for colorectal cancer. Furthermore, we systematically screened the Natural Product Library for HTS (L6000) TargetMol using molecular docking technology. Results: Anamorelin was identified, which exhibited optimal spatial matching with the ligand in the target protein crystal structure. As a selective growth hormone secretagogue receptor (GHS-R) agonist, anamorelin has been clinically demonstrated to significantly improve appetite and increase lean body mass in patients with CRC by activating the GHS-R signaling pathway and is currently used for treating cancer cachexia in patients with advanced CRC. However, existing research has primarily focused on its metabolic benefits, and its direct effects on tumor cell proliferation, migration, and related molecular mechanisms remain unclear. This study elucidated the regulatory relationship between anamorelin and TKT in CRC, thereby addressing a critical knowledge gap in this field (Fig. 1). Discussion: These findings reveal a previously unrecognized antitumor mechanism of anamorelin through TKT inhibition. These findings provide preliminary evidence of a TKT-associated mechanism of anamorelin in CRC, offering dual benefits in cachexia management and tumor suppression, and warrant further validation in advanced preclinical models. Further preclinical and clinical validation is warranted to translate these insights into practice. Conclusion: By integrating bioinformatics analysis with in vitro cellular experiments, we systematically validated the molecular mechanism whereby anamorelin inhibited tumor cell proliferation and migration via the targeted suppression of TKT. These findings provide a theoretical foundation for the development of novel metabolism-based therapeutic strategies for CRC, ultimately contributing to improved clinical outcomes.
INTRODUCTION:Although some studies have examined the relationship between serum calcium levels and Metabolic Syndrome (MetS), results remain inconsistent, and a quantitative synthesis is lacking. This meta-analysis aims to consolidate existing evidence and clarify the association between serum calcium levels and MetS risk. METHODS:We systematically searched seven databases up to May 1, 2025, for observational studies comparing serum calcium in MetS versus non-MetS groups. A random-effects model was applied to pool Odds Ratios (ORs) and Weighted Mean Differences (WMDs) with 95% Confidence Intervals (CIs). Subgroup analyses, sensitivity analyses, and publication bias assessments were also performed. RESULTS:Twenty-three studies (n=67,148) showed a positive association in categorical data analysis (OR=1.79, 95% CI: 1.37-2.34, P<0.0001, I2=82.3%), whereas continuous data did not reveal a significant difference (WMD=0.0107 mmol/L, 95% CI: -0.0078-0.0291, P=0.258, I2=89.4%). Subgroup analysis tentatively suggested a higher MetS risk in elderly (65 years old or older) populations (OR=2.44, 95% CI: 1.70-3.51), though this finding was based on a limited number of studies. Substantial heterogeneity was observed in both analyses. DISCUSSION:These findings suggest a potential association between elevated serum calcium and increased MetS risk, which may follow a nonlinear, threshold-like pattern. The observed age-related difference, while notable, should be interpreted with caution given the small number of studies in the elderly subgroup. The inconsistency between categorical and continuous results underscores the need for standardized protocols and further prospective investigations to clarify the nature of this relationship. CONCLUSION:Elevated serum calcium may be associated with an increased risk of MetS, with a possibly more pronounced effect suggested in older adults. However, these preliminary observations require validation in well-designed prospective studies with agespecific analyses.
Background: Enhanced recovery after lung surgery is important as it impacts patient outcomes. Among Traditional Chinese Medicine (TCM) herbs, Panax Notoginseng (PN) has been studied for its remarkable properties, making it a promising candidate for accelerating postoperative healing. However, the mechanisms of PN in enhancing recovery after lung surgery remain incompletely understood. Methods: First, animal experiments were conducted to validate the efficacy of PN in postoperative recovery following lung surgery. Then, herb-component-target network and Protein-Protein Interaction (PPI) network were constructed to identify the bioactive components of PN and key protein targets. Molecular docking was employed to validate the interactions between the active components and candidate recovery targets. Results: Animal experiments demonstrated that PN significantly improved postoperative recovery by enhancing collagen deposition and reducing pulmonary edema around the wound. Eight active components from PN and 251 targets associated with its therapeutic effects were revealed; 650 targets were linked to postoperative recovery after lung surgery. Key protein targets, including SRC, PIK3R1, and EGFR, were identified, with Quercetin, Liquiritigenin, and Mandenol emerging as the core active ingredients. Molecular docking demonstrated that the core components exhibited favorable binding energies with target proteins. KEGG and GO enrichment analyses highlighted the PI3KAKT signaling pathway and epithelial cell proliferation as critical pathways and biological processes underlying PN’s efficacy. Discussion: PN may offer a novel strategy to enhance postoperative lung repair, as it may activate the PI3K/AKT pathway, which links traditional Chinese medicine with postoperative recovery. In this work, PN contributes to ERAS protocols in thoracic surgery, bridging molecular insights with clinical outcomes. Conclusion: The active components of PN, including Quercetin, Liquiritigenin, and Mandenol, can accelerate postoperative recovery after lung surgery by potentially activating the PI3K-AKT pathway and promoting collagen deposition processes.
INTRODUCTION:Platinum-based drugs, including cisplatin, carboplatin, and oxaliplatin, are widely used in the treatment of various malignancies. However, the route-stratified adverse-event reporting patterns have not been fully characterized. This study aims to describe and characterize the patterns and time-to-onset distributions of adverse events (AEs) for platinum drugs across intravenous (IV), intraperitoneal (IP), and intraarterial (IA) routes. METHODS:Data covering the period from 2004Q1 to 2024Q4 were collected from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Disproportionality analyses were conducted to identify potential safety signals by platinum agent and route. The identified signals were then classified according to clinical priority, a categorization based on clinical relevance, reporting rate, fatality rate, and signal stability. Furthermore, time-to-onset profiles were analyzed using Kaplan-Meier analysis, the log-rank test, and Weibull shape parameter modeling. RESULTS:The study identified AE reports associated with cisplatin (5,783 IV, 193 IP, 135 IA), carboplatin (17,091 IV, 115 IP, 171 IA), and oxaliplatin (18,845 IV, 170 IP, 108 IA). IP reports were more frequently submitted for female patients, whereas IA reports were more frequently submitted for male patients, likely reflecting route-associated clinical indications. AE reporting profiles differed by platinum agent and route, with partial overlap. Among the identified AEs, twelve AEs were classified as high clinical priority. Of these, hepatic failure was the most frequently reported high-priority AE for both IV cisplatin and IV oxaliplatin. Notably, all IV platinum agents exhibited early failure- type patterns. The cumulative reporting distributions following IV administration differed significantly by drug. Patients treated with cisplatin showed shorter time to onset, with a median of 16 days (IQR: 7-46 days). DISCUSSION:Through a comprehensive analysis of FAERS data, this study has identified and characterized the AE signals for platinum drugs across IV, IP, and IA routes, assessed clinical priorities, and elucidated temporal characteristics. These findings should be interpreted as exploratory pharmacovigilance signals because FAERS does not support incidence estimation, comparative risk assessment, or causal inference. Therefore, large-scale prospective studies are warranted to validate and extend these results. CONCLUSION:This study identified differences in AE reporting profiles and time-to-onset patterns stratified by platinum agent and administration route. This underscores the importance of pharmacovigilance and the integration of safety monitoring systems to facilitate timely identification and management of AEs in clinical practice.
Background: Osteoarthritis (OA) is the most common degenerative joint disorder, affecting millions worldwide. It is characterized by progressive cartilage degradation and hypertrophic changes in the bone. Despite extensive research, no definitive cure exists, and understanding OA pathophysiology is crucial for developing novel therapies. Objective: This study aimed to investigate the effects of Pioglitazone and Bortezomib, individually and in combination, on OA progression in a rat model. Methods: Thirty-six male Sprague-Dawley rats underwent medial meniscectomy and anterior cruciate ligament transection to induce OA. Rats were randomly assigned to four groups: (1) intra-articular nano-Pioglitazone, (2) intra-articular Bortezomib, (3) combination of both drugs, and (4) control receiving normal saline. Histological assessment (Chambers score) and biochemical analyses of oxidative stress and inflammatory markers (MDA, IL-17, NF-κB) were performed. Results: No significant difference was observed in joint surface degeneration between the nano-Pioglitazone group and the control group (p = 0.09). Significant improvements were detected in the Bortezomib-treated group and combination therapy group compared to the control (p <0.000001). Combination therapy showed significant improvement over nano-Pioglitazone alone (p < 0.000001) but was not significantly superior to Bortezomib monotherapy (p = 0.61). Biochemical analysis demonstrated that MDA, IL-17, and NF-κB levels were significantly reduced in the combination therapy group compared with control and single-drug groups (p <0.0001). Discussion: These findings suggest that targeting oxidative stress and inflammatory signaling pathways, particularly NF-κB-mediated mechanisms, may play a critical role in mitigating OA progression. While combination therapy enhanced biochemical outcomes, its lack of additional structural benefit over bortezomib alone indicates that biochemical improvement does not necessarily translate into superior cartilage preservation within the studied timeframe. Conclusion: Combined administration of nano-pioglitazone and bortezomib reduced inflammatory and oxidative stress markers and improved antioxidant activity in the OA model. Histological evaluation indicated reduced synovial inflammation and cartilage damage; however, no significant structural superiority was observed compared with bortezomib monotherapy. These findings suggest that the primary benefit of the combination therapy may lie in its biochemical effects, warranting further investigation in future studies.
Background: Imatinib (IM) is a tyrosine kinase inhibitor that targets the growth factor receptors. IM has demonstrated remarkable clinical efficacy across multiple cancer types. IM abrogates the activity of the Bcr-Abl oncoprotein, leading to the inhibition of cell proliferation and induction of apoptosis. However, side effects may negatively affect its efficiency. Objective: This prompted us to incorporate IM into nanostructured Bovine Serum Albumin- Coated Mesoporous carbon carriers (BSA/CMK-3) and to evaluate the electrochemically controlled release of the IM@BSA/CMK-3 nanoformulation in an in vitro model. Methods: The physicochemical characteristics of the IM@BSA/CMK-3 nanocapsules were examined using Field-Emission Scanning Electron Microscopy (FE-SEM), Ultraviolet- Visible (UV-Vis), Fourier Transform Infrared (FT-IR), X-ray Diffraction (XRD), and cyclic voltammetry analyses. Results: It was found that BSA/CMK-3 is an efficient carrier with IM loading as much as 84.6% in 0.1 M phosphate-buffered solution (PBS, pH 7.0) for 3 hours. BSA/CMK-3, due to the presence of functional groups (amino and carboxyl) in BSA, forms strong hydrogen bonds with the IM drug. We demonstrated that BSA/CMK-3 is a sensitive and efficient platform, and that BSA increases the stability of the IM@BSA/CMK-3 interface-- modified Screen-Printed Carbon Electrode (SPCE) and controls the release of the IM drug from the IM@BSA/CMK-3 hybrid. Furthermore, 81.4% of IM could be released upon application of +0.9 V for 2 hours at the IM@BSA/CMK-3 interface into PBS (0.1 M, pH 4.0). Furthermore, kinetic models were evaluated, and it was found that the drug release was best fit to the Higuchi model. Discussion: The BSA/CMK-3 nanohybrid, due to the presence of functional groups-rich BSA, seemed to provide effective loading and controlled electrochemical release of the IM drug. Conclusion: The electrochemically released IM drug loaded onto BSA/CMK-3 offers substantial potential for drug delivery applications.
Ovarian cancer (OC) is an aggressive disease with nonspecific clinical manifestations that is frequently diagnosed at advanced stages, drastically reducing the 5- year survival rate, due in part to the absence of specific biomarkers. Owing to its high sensitivity and reproducibility, low cost, and minimal invasiveness, liquid biopsy is a promising technique for OC. Although proteins, ctDNA, and miRNAs have been widely studied as biomarkers, lncRNAs are more advantageous due to their cell- and tissue-specific expression and high stability. Several lncRNAs with potential as liquid biomarkers in OC have been characterized, but none are currently used clinically. The study has analysed 662 lncRNAs deregulated in OC to determine their ability to be detected in biofluids. Twenty-three have been identified in blood samples, four in ascites, and twenty- seven in extracellular vesicles isolated from biofluids. Most of these lncRNAs have an oncogenic role and have been associated with poor prognosis, primarily overall survival. Regarding their diagnostic value, some have even been positively associated with FIGO stages, but only one, included in the panel RP5-837J1.2/miR-361-3p/PELI3, allows differentiation between patients in early stages and healthy women. Information on lncRNAs detected in biofluids related to cancer hallmarks has also been included to identify gaps in the field and to serve as a guide for future research.
