Introduction Douyin is a leading short-video platform in China, widely used for sharing experiences and disseminating knowledge. Although many medical science videos exist, the quality of atherosclerosis-related content remains unclear. This study evaluates the sources, content, and quality of such videos to address this literature gap.Theory We retrieved 141 atherosclerosis-related videos from Douyin and selected 90 high-quality samples. Video sources and misinformation were recorded and categorized.Method Video content, understandability, actionability, and reliability were evaluated using hexagonal radar charts, the Patient Education Materials Assessment Tool for Audiovisual Materials, and the DISCERN instrument. Data were analyzed using SPSS, with p < 0.05 considered statistically significant.Results The number of atherosclerosis-related videos on Douyin has been increasing in recent years. The 90 videos provided more management information (1.31 points) and outcomes (1.20 points) but less on symptoms (0.67 points). Understandability was high (82%), but actionability was low (67%). Significant differences in understandability (p = 0.02), actionability (p = 0.01), and overall quality (p = 0.03) were found among videos from different uploaders. However, no significant difference in actionability was observed among videos from different sources (p = 0.11). Most videos (55/90, 61%) were created by healthcare professionals, demonstrating greater actionability. Approximately 33% (30/90) of videos contained misinformation.Discussion Atherosclerosis-related videos on Douyin are unbalanced, of poor quality, and riddled with misinformation, failing to meet public health needs. If video creators ensure more comprehensive and accurate content, Douyin could serve as an important channel for medical information dissemination.

Postoperative peritoneal adhesion (PPA) develops through TGF-β1-driven fibrotic remodeling, characterized by neutrophil extracellular trap (NETs)-induced aberrant epithelial-to-mesenchymal transition (EMT) deposition. Although aloe-emodin (AE) exhibits anti-fibrosis potential, its molecular mechanisms remain elusive. Forkhead box protein C2 (FOXC2) is a critical regulator of fibrotic tissue formation, yet its role in PPA is unknown. Here, it is demonstrated that FOXC2 expression is elevated in human ileostomy tissue, PPA rodent model, and TGF-β1-exposed peritoneal mesothelial cells (PMCs), where it orchestrates NETs formation and extracellular matrix (ECM) remodeling. Mechanically, CRISPR/Cas-based knockdown and overexpression of FOXC2 alter EMT changes in PMCs, which is achieved via TGF-β1-Smad2/3 signaling. FOXC2 functions as a dual mediator and amplifier through the TGF-β1-Smad2/3 pathway feedback loop to drive EMT alterations. Its overexpression further induces neutrophil recruitment and NETs formation, exacerbating EMT in PMCs. Notably, AE ameliorates FOXC2-driven peritoneal fibrosis by impeding NETs formation and EMT changes through the TGF-β1-Smad2/3 pathway. Moreover, AE binds directly to FOXC2, and the Ser125 residue is critical for the binding of FOXC2 to AE. These findings identify FOXC2 as a pivotal effector in fibrotic responses during PPA formation and reveal that AE targeting the Ser125 residue of FOXC2 may be a promising therapeutic approach to attenuate PPA.

Background : Postoperative intra-abdominal adhesion (IA), driven by hypoxia, remains a global surgical challenge due to the lack of effective therapeutic interventions. Although the herbal HuoXueTongFu Formula (HXTF) has positive effects on adhesion formation, its primary bioactive constituent and the underlying mechanism have not been fully elucidated. Purpose : This study aimed to identify the main bioactive constituents of HXTF, elucidate its therapeutic mechanism against IA, and provide a foundation for clinical application. Methods : Time-course RNA sequencing with Mfuzz analysis was employed to determine the hypoxic duration-dependent transcriptional modules. Molecular docking and dynamics simulations were used to identify the major constituent of HXTF that bound to HIF-1α. Then, magnetic beads pull-down, co-immunoprecipitation, immunofluorescence, extracellular acidification rate (ECAR) measurements, and lactate content analysis were performed to explore the critical roles of emodin (a bioactive constituent of HXTF) on hypoxia-induced HMrSV5 (human peritoneal mesothelial) cells. With IA rodent models, adhesion scoring, H&E with Masson staining, and western blotting were applied to validate the therapeutic effect of emodin on IA. Results : Mfuzz clustering analysis revealed time-dependent glycolytic reprogramming in hypoxic HMrSV5 cells, with HIF-1α activation peaking at 6 hours. Molecular docking and dynamics simulations identified that emodin exhibited the highest and stable binding affinity to HIF-1α. This effect was mediated by emodin’s inhibition of HIF-1α nuclear translocation and disruption of its dimerization with ARNT, as evidenced by magnetic beads pull-down, co-immunoprecipitation, and immunofluorescence assays. ECAR measurements and lactate content analysis in vitro showed that emodin effectively downregulated HIF-1α-mediated transcriptional activation of glycolysis gene expression (e.g., GLUT3 and PFKFB3) and decreased lactate content. Moreover, emodin alleviated the intra-abdominal adhesion formation in vivo by reducing the fibrous band formation and collagen deposition, which was achieved by suppression of the HIF-1α-mediated glycolytic reprogramming. Conclusion : Emodin could reduce IA formation by inhibiting HIF-1α-mediated glycolytic reprogramming. This effect was achieved through direct binding with HIF-1α, which subsequently inhibited its nuclear translocation and disrupted its dimerization with ARNT, thereby downregulating HIF-1α-mediated transcriptional activation of glycolytic gene expression (e.g., GLUT3 and PFKFB3) and reducing lactate content. These findings suggest that emodin may be a promising therapeutic candidate to attenuate IA.

To address the multifactorial pathology of Alzheimer's disease (AD), eighteen butyrylcholinesterase (BChE) and histone deacetylase 6 (HDAC6) dual inhibitors were designed, synthesized, and biologically evaluated. Through structure-activity relationship studies, compound 17 emerged as the most potent candidate, with IC50 value of 0.3 nM for human BChE and 56.7 nM for HDAC6. This compound demonstrated favorable safety profiles, drug-like properties, and significant neuroprotective effects in vitro. In a mouse model of scopolamine-induced cognitive impairment, 17 (10 mg/kg) exhibited excellent safety and markedly improved cognitive deficits. These findings highlight compound 17 as a promising BChE/HDAC6 dual inhibitor, supporting its further development as a potential therapeutic agent for AD.

Postoperative peritoneal adhesion (PPA) is pathological tissue hyperplasia between surgical wounds and nearby organs. Currently, traditional double-sided bioadhesives are limited in preventing PPA due to the indiscriminate adhesive properties and the poor interaction with wet tissues. Herein, we developed a Janus hydrogel, named PAA-Cos, by using the polycationic carbohydrate polymer of chitooligosaccharide (Cos) and the polyanionic polymer of polyacrylic acid (PAA). The adhesive layer of Janus hydrogels could adhere to wet tissue tightly due to surfaces composed of carboxyls, and the positively charged biomaterial (Cos) neutralized carboxyls on one side of PAA hydrogel to form Janus hydrogels. Moreover, PAA-Cos can further load with ligustrazine hydrochloride (Ligu), a pharmaceutical compound with anti-inflammatory and anti-fibrotic effects, finally obtaining PAA-Cos@Ligu. After the application of PAA-Cos@Ligu on the surgical trauma, the bottom surface can adhere to wet tissues robustly to restore the wound, while the top surface acts as a physical barrier with antiadhesive effects to avoid PPA. PAA-Cos@Ligu also exhibited anti-inflammatory effects by promoting M2 macrophage polarization, inhibiting the myofibroblast-like differentiation of peritoneal mesothelial cells, and blocking the TGF-β/Smad2/3 signaling pathway to hinder collagen deposition. Our findings suggest that PAA-Cos@Ligu has great potential as an anti-adhesion candidate with biocompatibility and ease of preparation.

BackgroundThe HuoXueTongFu Formula (HXTF) originates from the classic prescription “DaHuangMuDan Decoction” from the “Synopsis of the golden chamber”. Our previous study revealed that HXTF has a positive effect on postoperative peritoneal adhesion (PPA). However, the specific mechanism of HXTF on PPA formation within the time-to-treatment window has not been fully elucidated. This study aimed to determine the critical roles of HXTF as a result of its specific anti-inflammatory and antifibrinolytic activities for PPA treatment.MethodsThe eight main bioactive components of HXTF were subjected to high-performance liquid chromatography-mass spectrometry. The core targets, critical biological processes, and underlying pathways of HXTF and PPA were identified via a series of network pharmacological methods. The specific anti-inflammatory function in the initial step of PPA formation was validated in peritoneal macrophages (PMs) isolated from PPA mice on Day 3 postsurgery. The potential anti-fibrinolytic activity in the next stage of PPA formation was subsequently explored in PPA mice on Day 7 postsurgery.ResultsNetwork pharmacology revealed 160 common targets between HXTF and PPA. Several core targets, i.e., matrix metalloproteinase 9 (MMP9), tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor 1 (PAI-1), were annotated as important biological processes (extracellular matrix disassembly and the collagen catabolic process). Validation experiments revealed that HXTF could induce macrophage polarization-mediated anti-inflammatory reactions by increasing the phagocytic capacity of PMs and promoting the release of anti-inflammatory cytokines (IL-4 and IL-10). In addition, HXTF promoted fibrinogenolysis and improved fibrinolytic activity, thereby inhibiting collagen deposition and reducing adhesion development.ConclusionThe ameliorative effects of herbal HXTF on PPA formation are attributable to the induction of macrophage polarization-mediated anti-inflammatory reactions in the early stage of PPA formation and the promotion of fibrinogenolysis and fibrinolytic activity in the middle stage of PPA formation. HXTF may be a promising alternative agent for the prevention and treatment of PPA.

BACKGROUND:The incidence of insomnia is increasing annually worldwide. Most Western tranquilisers have side effects, such as strong dependence and notable withdrawal reactions. The sour jujube kernel and five-flavour berry can calm the mind and improve sleep, but the underlying mechanism is still unclear. OBJECTIVE:We investigated the active ingredients and mechanism of action of the sour jujube kernel-fiveflavour berry pair in treating insomnia. METHODS:The chemical compositions and targets of sour jujube kernels and five-flavour berries were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, PubChem, and PharmMapper. Insomnia disease targets were screened using the GeneCards, Online Mendelian Inheritance in Man, and Therapeutic Target Database. We constructed shared target data for topological analysis and network construction using the STRING database and the Cytoscape software. Gene Ontology functional and metabolic pathway analyses were performed using the DAVID database and validated through molecular docking using AutoDock and PyMOL software. RESULTS:This study demonstrated that the sour jujube kernel and five-flavour berry combination primarily addresses insomnia through the activity of eight hub genes: ALB, CASP3, DRD1, ESR1, MAOB, NOS3, SLC6A3, and SLC6A4. Molecular docking simulations showed that jujuboside A exhibited robust docking to these hub genes, whereas longikaurin A showed a strong binding affinity with ALB and ESR1. CONCLUSION:We establish a theoretical foundation for further experimental studies, which may lead to the application of sour jujube kernel and five-flavour berry in clinical practice.

BACKGROUND:With its high prevalence, frequent recurrence, and significant disability rates, depression has emerged as a major global health burden. Ginsenosides, the primary components of the herbal medicine ginseng, demonstrate antidepressant effects. METHODS:Drug affinity-responsive target stability (DARTS) and lipid chromatography-mass spectrometry were employed to identify the potential targets of ginsenosides. Active components were characterized through biolayer interferometry (BLI), molecular docking, and site-directed mutagenesis assays to assess binding affinity and interaction sites. RNAscope in situ hybridization and tissue clearing were used to visualize the expression pattern of kynurenine 3-monooxygenase (KMO) and the distribution of ginsenoside metabolite compound K (CK) in brain. In corticosterone-induced depressive mouse models, behavioral phenotyping, viral-mediated gene manipulations, and bulk RNA sequencing with Mfuzz clustering were performed to explore the roles of KMO and ginsenosides in vivo. RESULTS:DARTS-based screening identified KMO as a critical binding target of ginsenosides. Among the components, CK showed the strongest direct binding to KMO, as confirmed by BLI. Molecular docking and mutations of candidate residues (I309 and G316) validated the specificity of the KMO-CK interaction. Spatial visualization via tissue clearing revealed colocalization of KMO and CK in the brain, with notable enrichment of KMO in thalamic neurons. Importantly, CK exerts antidepressant effects in a KMO-dependent pattern: it alleviated corticosterone-induced depressive-like behaviors and counteracted the associated upregulation of KMO expression. Furthermore, CK restored the neuroactive kynurenine pathway balance by modulating the quinolinic acid/kynurenic acid ratio. CONCLUSIONS:KMO serves as a direct target of ginsenosides in the brain. CK acts as a novel brain-penetrant KMO inhibitor that confers antidepressant activity. The enrichment of KMO in thalamic neurons-as opposed to cortical microglia-offers new insights into the neuroanatomical basis of KMO function and the mechanism of antidepressant interventions.

Background: The healing process in diabetic wounds is an emerging challenge, emphasizing the development of new pharma-cologic strategies. Ferulic acid (FA) and astragaloside IV (AS-IV) have been recognized for their angiogenic potential, but how their combination impacts the angiogenesis under a high-glucose environment is yet to be explored. Therefore, this study was designed to assess the synergistic effects of FA and AS-IV and their underlying mechanisms on angiogenesis in a high-glucose environment.Methods: Network pharmacology was utilized to screen the common targets associated with diabetic wounds, as well as FA and AS-IV. Subsequently, the signal pathways involved in these common targets were enriched using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Furthermore, the angiogenesis-promoting effects of FA and AS-IV were validated using flow cytometry, scratch assay, and tube formation assay. Additionally, the molecular mechanism underlying the impacts of FA and AS-IV on angiogenesis was evaluated using si-RNA interference assay. Results: Using bioinformatics analysis, 101 common target genes linked to diseases were identified. These target genes were enriched in various signaling pathways such as hydroxylated hypoxia-inducible factor 1 (HIF-1) signaling pathway and vascular endothelial growth factors (VEGFs) signaling pathway. Furthermore, cytological experiments revealed that FA and AS-IV promoted angiogenesis under a high-glucose condition by activating the HIF-1 signaling pathway. The combination of these two drugs significantly reduced the apoptosis level, increased cell migration, and promoted tube formation. Additionally, they increased the expression levels of VEGFs, vascular endothelial growth factor receptor 2 (VEGFR2), and HIF-1 alpha proteins. Conversely, the protein expression level of the von Hippel-Lindau tumor-suppressor protein (VHL) significantly decreased. These effects were partially reversed when HIF-1 alpha was down-regulated using specific si-HIF-1 alpha. Conclusions: FA in combination with AS-IV promotes angiogenesis within a high-glucose environment by activating the HIF-1 signaling pathway. Hence, FA+AS-IV might be a promising option for treating diabetic wounds. These findings provide a novel experimental and theoretical basis for managing diabetic wounds.

Immunocheckpoint inhibitors have shown impressive efficacy in patients with colon cancer and other types of solid tumor that are mismatch repair-deficient (dMMR). Currently, PCR-capillary electrophoresis is one of the mainstream detection methods for dMMR, but its accuracy is still limited by germline mismatch repair (MMR) mutations, the functional redundancy of the MMR system, and abnormal methylation of MutL Homolog 1 promoter. Therefore, this study aimed to develop new biomarkers for dMMR based on artificial intelligence (AI) and pathologic images, which may help to improve the detection accuracy. To screen for the differential expression genes (DEGs) in dMMR patients and validate their diagnostic and prognostic efficiency, we used the expression profile data from the Cancer Genome Atlas (TCGA). The results showed that the expression of Immunoglobulin Lambda Joining 3 in dMMR patients was significantly downregulated and negatively correlated with the prognosis. Meanwhile, our diagnostic models based on pathologic image features showed good performance with area under the curves (AUCs) of 0.73, 0.86, and 0.81 in the training, test, and external validation sets (Jiangsu Traditional Chinese Medicine Hospital cohort). Based on gene expression and pathologic characteristics, we developed an effective prognosis model for dMMR patients through multiple Cox regression analysis (with AUC values of 0.88, 0.89, and 0.88 at 1-, 3-, and 5-year intervals, respectively). In conclusion, our results showed that Immunoglobulin Lambda Joining 3 and nucleus shape-related parameters (such as nuclear texture, nuclear eccentricity, nuclear size, and nuclear pixel intensity) were independent diagnostic and prognostic factors, suggesting that they could be used as new biomarkers for dMMR patients.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects the first and second motoneurons (MNs), associated with muscle weakness, paralysis and finally death. The exact etiology of the disease still remains unclear. Currently, efforts to develop novel ALS treatments which target specific pathomechanisms are being studied. The mechanisms of ALS pathogenesis involve multiple factors, such as protein aggregation, glutamate excitotoxicity, oxidative stress, mitochondrial dysfunction, apoptosis, inflammation etc.. Unfortunately, to date, there are only two FDA-approved drugs for ALS, riluzole and edavarone, without curative treatment for ALS. Herein, we give an overview of the many pathways and review the recent discovery and preclinical characterization of neuroprotective compounds. Meanwhile, drug combination and other therapeutic approaches are also reviewed. In the last part, we analyze the reasons of clinical failure and propose perspective on the treatment of ALS in the future.

INTRODUCTION:Inflammatory bowel disease (IBD) has become one of the public problems worldwide and its incidence rate is increasing year by year. Its concomitant disease i.e. diabetes mellitus (DM) has attracted more and more attention due to DM altering the progression of IBD and leading to long periods of intermittent recurrence and deterioration. The common mechanism and potential target drug of IBD with comorbid chronic conditions of DM were explored. METHODS:Gene expression profile data were downloaded from the Gene Expression Omnibus (GEO) public database. The differentially expressed genes (DEGs) were identified by R software. GO annotation and pathway enrichment were performed, a protein-protein interaction (PPI) network was constructed, associated lncRNAs were predicted and drug prediction targeting key genes was made. Additionally, the regulatory network among core genes, associated pathways, and predicted lncRNA in IBD with coexistent DM were visualized. RESULTS:We identified the critical gene MMP3 with lncRNA CDKN2BAS involved in the PPAR pathway, which uncovered the underlying regulatory mechanism of IBD with coexistent DM. We also predicted the potential therapeutic compound ZINC05905909 acting on MMP3. CONCLUSION:Our findings revealed the regulatory mechanism chain of critical gene MMP3, lncRNA CDKN2BAS, and PPAR pathway and provided potential therapeutic compound ZINC05905909 for drug therapy to treat comorbid IBD DM.

The pathogenesis of depression is complex, involving abnormalities in tryptophan (TRP) metabolism through the kynurenine pathway (KP). Moreover, depression is closely related to the hypothalamic-pituitary-adrenal (HPA) axis, the gut-brain axis, neuroinflammation, and stress. These factors collectively influence the multidimensional pathological mechanisms of depression. TRP, a fundamental amino acid, serves as a precursor for neuroactive metabolites vital to physiological functions. Central to TRP metabolism is the KP, and the imbalance between neurotoxic and neuroprotective metabolites is closely related to the onset and progression of depression. Therefore, maintaining the balance of KP metabolites is important. In this review, we have investigated the role of the KP in depression and explored the complexity of KP dysregulation and its therapeutic importance. Here, we highlight how a deeper understanding of the KP and its regulation can pave the way for new treatment strategies. Specifically, we have summarized the latest advances in elucidating the key mechanisms of rate-limiting enzyme inhibitors, providing insights into their potential therapeutic efficacy. In addition, we have explored the emerging field of Chinese herbal medicine, discussing its potential to regulate KP metabolites and alleviate depressive symptoms, thereby expanding the treatment options for depression. Our findings emphasize the multifaceted nature of depression and the necessity of interdisciplinary research to fully utilize KP regulation and Chinese herbal medicine as strategies to advance the treatment of depression.

BACKGROUND:Recent epidemic survey data have revealed a globally increasing prevalence of autism spectrum disorders (ASDs). Currently, while Western medicine mostly uses a combination of comprehensive intervention and rehabilitative treatment, patient outcomes remain unsatisfactory. Polygala-Acorus, used as a pair drug, positively affects the brain and kidneys, and can improve intelligence, wisdom, and awareness; however, the underlying mechanism of action is unclear. OBJECTIVES:We performed network pharmacology analysis of the mechanism of Polygala-Acorus in treating ASD and its potential therapeutic effects to provide a scientific basis for the pharmaceutical's clinical application. METHODS:The chemical compositions and targets corresponding to Polygala-Acorus were obtained using the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform, Chemical Source Website, and PharmMapper database. Disease targets in ASD were screened using the DisGeNET, DrugBank, and GeneCards databases. Gene Ontology functional analysis and metabolic pathway analysis (Kyoto Encyclopedia of Genes and Genomes) were performed using the Metascape database and validated via molecular docking using AutoDock Vina and PyMOL software. RESULTS:Molecular docking analysis showed that the key active components of Polygala- Acorus interacted with the following key targets: EGFR, SRC, MAPK1, and ALB. Thus, the key active components of Polygala-Acorus (sibiricaxanthone A, sibiricaxanthone B tenuifolin, polygalic acid, cycloartenol, and 8-isopentenyl-kaempferol) have been found to bind to EGFR, SRC, MAPK1, and ALB. CONCLUSION:This study has preliminarily revealed the active ingredients and underlying mechanism of Polygala-Acorus in the treatment of ASD, and our predictions need to be proven by further experimentation.

Traditionally, lactate has been considered a ‘waste product’ of cellular metabolism. Recent findings have shown that lactate is a substance that plays an indispensable role in various physiological cellular functions and contributes to energy metabolism and signal transduction during immune and inflammatory responses. The discovery of lactylation further revealed the role of lactate in regulating inflammatory processes. In this review, we comprehensively summarize the paradoxical characteristics of lactate metabolism in the inflammatory microenvironment and highlight the pivotal roles of lactate homeostasis, the lactate shuttle, and lactylation (‘lactate clock’) in acute and chronic inflammatory responses from a molecular perspective. We especially focused on lactate and lactate receptors with either proinflammatory or anti-inflammatory effects on complex molecular biological signalling pathways and investigated the dynamic changes in inflammatory immune cells in the lactate-related inflammatory microenvironment. Moreover, we reviewed progress on the use of lactate as a therapeutic target for regulating the inflammatory response, which may provide a new perspective for treating inflammation-related diseases.

Nuclear factor erythroid 2-related factor 2 (NRF2) is a crucial transcription factor involved in oxidative stress response, which controls the expression of various cytoprotective genes. Recent research has indicated that constitutively activated NRF2 can enhance patients' resistance to chemotherapy drugs, resulting in unfavorable prognosis. Therefore, the development of NRF2 inhibitors has emerged as a promising approach for overcoming drug resistance in cancer treatment. However, there are limited reports and reviews focusing on NRF2 inhibitors. This review aims to provide a comprehensive analysis of the structure and regulation of the NRF2 signaling pathway, followed by a comprehensive review of reported NRF2 inhibitors. Moreover, the current design strategies and future prospects of NRF2 inhibitors will be discussed, aiming to establish a foundation for the development of more effective NRF2 inhibitors.

Postoperative adhesion (PA) is currently one of the most unpleasant complications following surgical procedures. Researchers have developed several new strategies to alleviate the formation of PA to a great extent, but so far, no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention. Chinese medicine (CM) has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine. Therefore, this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments, including their pharmacological effects, therapeutic mechanisms and advantages in PA prevention. We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.

A series of tetrahydrothienopyridine derivatives have been designed, synthesized, and evaluated as selective BChE inhibitors. Compounds were analyzed via HRMS, 1H NMR, and 13C NMR. The inhibitory effects were evaluated according to the method of Ellman et al. 6n was the most potent and selective inhibitor against BChE (eeAChE IC50 = 686.4 ± 478.6 μM, eqBChE IC50 = 10.5 ± 5.0 nM, SI = 6.5*104, hBChE IC50 = 32.5 ± 6.5 nM). Cell-based assays have confirmed the low neurotoxicity of 6a and 6n and their moderate neuroprotective effects. Compounds 6a and 6n provide novel chemical entities for the treatment of Alzheimer's disease.