Wilson disease (WD) is an autosomal recessive disorder caused by pathogenic variants in the ATP7B gene, leading to toxic copper accumulation. The integration of computational genomics approaches is now essential for deciphering the complex genotype-phenotype relationships and advancing towards targeted therapies. This review synthesizes how multiscale computational strategies are transforming WD research. At the atomic level, molecular dynamics (MD) simulations reveal the conformational dynamics of the ATP7B protein, the functional impact of mutations, and the detailed copper transport cycle. At the systems level, machine learning (ML) models integrate genomic, epigenomic, transcriptomic, and clinical data to classify variant pathogenicity, predict disease subtypes, and forecast clinical outcomes such as cirrhosis or neurological deterioration. Furthermore, multi-omics network analyses uncover disease-associated regulatory modules, elucidate the role of epigenetic dysregulation, and implicate emerging pathways like cuproptosis in WD pathogenesis. Critically, these computational insights are increasingly guiding therapeutic innovation, including the in silico design of allosteric modulators (e.g., nanobodies) and pharmacological chaperones to correct ATP7B folding. By bridging scales from molecular structure to patient phenotypes, computational genomics provides a powerful, integrative framework that holds the potential to accelerate the development of dynamic, mechanism-based therapies and pave the way for personalized medicine in Wilson disease.

BACKGROUND: Adenosine-related RNA modifications, including N6-methyladenosine (m6A), N1-methyladenosine (m1A), alternative polyadenylation (APA), and adenosine-to-inosine (A-to-I) editing, critically regulate transcriptional programs in cancer. However, their coordinated contribution to bladder cancer biology and response to immunotherapy remains poorly understood. METHODS: We systematically characterized four classes of RNA modification “writer” genes in bladder cancer, assessing somatic mutations, copy-number variations, and mRNA expression patterns across seven independent cohorts, including TCGA-BLCA, E-MTAB-4321, and GEO datasets (GSE32894, GSE13507, GSE48276, GSE70691, and GSE69795). Unsupervised consensus clustering identified RNA modification-based molecular subtypes, which were used to construct an RNA modification-based prognostic and immunotherapy response score (RMP_Score). This score was validated across multiple external cohorts, including the IMvigor210 anti-PD-L1 dataset. Differentially expressed genes (DEGs) between subtypes were assessed and integrated through Kaplan-Meier survival analysis and Cox proportional hazards regression to construct the RMP_Score. Bulk and single-cell transcriptomic analyses, complemented by in vitro functional assays, were performed to investigate the role of carboxylesterase 1 (CES1), a key component of the RMP_Score. Tumor microenvironment (TME) composition was quantified using single-sample gene set enrichment analysis (ssGSEA). RESULTS: RNA modification “writer” genes exhibited frequent somatic mutations and copy-number amplifications, which were strongly associated with transcriptional dysregulation and inferior overall survival. Unsupervised clustering revealed two distinct subtypes: a metabolism-enriched cluster associated with favorable prognosis, and an immune- and stroma-enriched cluster characterized by abundant regulatory T-cell infiltration and adverse clinical outcomes. The RMP_Score robustly stratified patient survival across six independent cohorts, correlated with differential sensitivity to inhibitors targeting the JNK/p38, PI3K/mTOR, and WNT pathways, and accurately predicted clinical responses to anti-PD-L1 immunotherapy, with low RMP_Scores demonstrating superior responses. CES1 emerged as a robust predictor of poor survival and immunotherapy resistance, closely associated with tumor progression, extracellular matrix remodeling, and an immunosuppressive, fibroblast-rich TME. Functionally, CES1 silencing significantly attenuated bladder cancer cell viability, invasive capacity, and migratory potential in vitro. CONCLUSIONS: These findings established an RNA modification-based framework for molecular classification and risk stratification in bladder cancer, and identified CES1 as a metabolically driven regulator of the TME with potential utility as a prognostic and predictive biomarker for immune checkpoint blockade.

BackgroundOsteoporosis is a metabolic bone disease characterized by dysregulated osteoclast activity, resulting in increased bone degradation and compromised bone microarchitecture. While the interconnection between osteoclast differentiation and cellular energy metabolism has become increasingly recognized, the role of pyrimidine metabolism in this process remains largely undefined.MethodsIntegrative multi-omics analyses were performed to characterize transcriptional and metabolic alterations during receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. The effects of uridine (UD) on osteoclast development and resorptive function were assessed in vitro using RAW264.7 cells and bone marrow-derived macrophages (BMMs). In vivo effects of UD on bone loss were evaluated in an ovariectomized (OVX) mouse model.ResultsIntegrative analyses revealed distinct metabolic remodeling during osteoclast differentiation and identified UD as a pivotal metabolite that showed a significant decline upon RANKL stimulation. Experimental evidence indicated that exogenous UD supplementation significantly suppressed osteoclast development and resorptive function, along with a reduction in the expression of nuclear factor of activated T cells c1 (NFATc1) and cathepsin K (CTSK). In OVX mice, UD administration improved trabecular microarchitecture, reduced osteoclast burden, and mitigated bone loss. Mechanistically, UD inhibited phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) phosphorylation, facilitated Forkhead box O (FoxO) nuclear translocation, and suppressed reactive oxygen species (ROS) accumulation, thereby preventing NFATc1 activation and nuclear import.ConclusionCollectively, this research identifies a novel metabolic–signaling interplay linking pyrimidine metabolism with osteoclast differentiation and highlights UD as a promising metabolic regulator for the treatment and prevention of osteoporosis.

BACKGROUND:Hepatoblastoma (HB) is the most prevalent primary liver malignancy in children and is characterized by aggressive progression and suboptimal therapeutic outcomes. Despite advances in multimodal treatment strategies, the prognosis of high-risk or relapsed HB remains poor, highlighting an urgent need for novel and effective therapeutic approaches. Ganoderic acid A (GAA), a bioactive triterpenoid derived from Ganoderma lucidum, has demonstrated antitumor activity across multiple cancer types; however, its therapeutic potential and mechanistic role in HB have not yet been elucidated. METHODS:A comprehensive experimental framework integrating in vitro functional assays, in vivo xenograft models, and mechanistic investigations was employed to evaluate the antitumor effects of GAA in HB. Cellular proliferation, migration, apoptosis and senescence were systematically assessed. In vivo therapeutic efficacy was determined using bioluminescence imaging in xenograft models. Molecular docking, molecular dynamics simulations and genetic overexpression analyses were conducted to elucidate the molecular targets and mechanistic basis of GAA action. RESULTS:GAA exerted significant antitumor effects in HB cells by markedly inhibiting proliferation, migration and invasion, while simultaneously inducing apoptosis and cellular senescence. In vivo, GAA treatment resulted in a substantial reduction in tumor burden in HB xenograft models. Mechanistic studies revealed that GAA directly interacts with heat shock protein 90 alpha family class A member 1 (HSP90), leading to impairment of its chaperone function and promoting proteasome-mediated degradation. Importantly, enforced overexpression of HSP90 effectively attenuated the antitumor effects of GAA, establishing HSP90 as a critical functional mediator. Molecular dynamics simulations further substantiated the stable binding and atomic-level interactions between GAA and HSP90. CONCLUSIONS:This study identifies GAA as a previously unrecognized senescence-inducing agent in HB through targeted degradation of HSP90, thereby revealing a novel therapeutic vulnerability. Collectively, these findings position GAA as a promising candidate for targeted therapy in HB and provide a strong rationale for its further translational development.

BACKGROUND:Chemotherapy resistance remains a major clinical challenge in the treatment of gastrointestinal (GI) cancers. Mitochondrial remodeling contributes to chemoresistance through several interconnected functional modules, including metabolic reprogramming, elevation of the apoptotic threshold, adjustment of the reactive oxygen species setpoint, and mitophagy-mediated mitochondrial quality control. Polysaccharides and polysaccharide-based systems may represent promising candidates for modulating mitochondria-associated dysfunctions because of their structural diversity, biological activity, and generally favorable biocompatibility in specific experimental settings. PURPOSE:This review aimed to systematically summarize the molecular mechanisms by which mitochondrial remodeling contributes to chemotherapy resistance in GI tumors and to evaluate the potential of polysaccharides and polysaccharide-based systems as therapeutic candidates for modulating these mitochondrial abnormalities. METHODS:This PRISMA-guided systematic review with qualitative evidence synthesis searched PubMed and Web of Science from database inception to July 4, 2026. The search strategy covered terms related to polysaccharides and polysaccharide-based delivery systems, GI tumors, chemoresistance or chemosensitization, and mitochondria-related mechanisms. Records were deduplicated and screened according to predefined eligibility criteria. Core eligible studies were original experimental studies that investigated polysaccharide or polysaccharide-based interventions in GI tumor models, reported chemotherapy-related outcomes, and included endpoints related to mitochondria, redox regulation, apoptosis, autophagy, metabolism, or the tumor microenvironment. Because of substantial heterogeneity in polysaccharide sources, tumor models, chemotherapeutic agents, intervention formats, and mechanistic endpoints, the evidence was synthesized qualitatively rather than by meta-analysis. RESULTS:The search identified 652 records, including 322 from PubMed and 330 from Web of Science. After removal of 174 duplicate records, 478 records were screened. Full texts were sought for 75 reports, of which 20 could not be retrieved. Ultimately, 55 reports were assessed for eligibility; one retracted article and 34 reports that did not meet the core eligibility criteria were excluded. In total, 20 studies were included in the core evidence synthesis. These studies supported the involvement of polysaccharides or polysaccharide-based systems in modulating chemotherapy responses in GI tumors through several mitochondria-related mechanisms, including metabolic remodeling, regulation of the apoptotic threshold, modulation of redox status, and autophagy/mitophagy-associated adaptation. Additional mechanistic and contextual evidence suggested that polysaccharide-based delivery platforms and gut microenvironment modulation may influence drug accumulation, chemotherapy-related toxicity, and therapeutic sensitivity. CONCLUSIONS:Current evidence, mainly from preclinical studies, suggests that polysaccharides and polysaccharide-based systems may help modulate chemotherapy resistance in GI cancers by targeting mitochondria-related pathways. However, clinical translation remains limited by heterogeneity in polysaccharide structure, incomplete pharmacokinetic characterization, limited human evidence, and insufficient standardization of intervention models. Future studies should prioritize structural characterization, mechanism-guided validation, pharmacokinetic evaluation, and well-designed clinical studies to clarify their therapeutic value.

Abstract Wilson disease (WD) is a severe metabolic disorder caused by mutations in the copper-transporting ATPase ATP7B. The MBD5–6 tandem module serves as a critical regulatory hub for the protein, harboring several pathogenic missense mutations, including T587M, A595T, and R616Q within the MBD6 domain. However, the atomistic mechanisms by which these localized defects propagate across the MBD5–6 tandem module to disrupt interdomain organization remain unclear. In this study, we employed AlphaFold 3 to generate initial structures of the wild-type and variant ATP7B, followed by three independent 500 ns all-atom molecular dynamics (MD) simulations of the extracted apo MBD5–6 region. Our results reveal that these pathogenic mutations disrupt module-level structural stability through distinct microscopic physicochemical mechanisms. Specifically, T587 M triggers steric overpacking and abnormal rigidification; A595T induces hydrophobic core melting and water penetration; and R616Q abolishes critical electrostatic tethers. Crucially, we uncover a multiscale pathogenic mechanism, in which localized perturbations propagate via the flexible linker, allosterically disrupting the interdomain structural tethering to drive macroscopic conformational heterogeneity. This study delineates a multiscale pathway from local atomic defects to interdomain dysfunction within the apo MBD5–6 module and provides structural hypotheses for how these perturbations may affect the conformational regulation of full-length ATP7B.

Compound Shougong Powder (CSP) is composed of six Chinese herbal medicines and exerts effects in reducing swelling and relieving pain. It is mainly applied in clinical practice as an adjuvant therapy for various malignant tumors; however, its chemical constituents and the material basis of its efficacy have not been fully clarified. This study aimed to clarify the chemical constituents, their migration and distribution in vivo, and the pharmacodynamic material basis and anti-tumor mechanism of CSP. Ultrahigh-performance liquid chromatography (UHPLC) combined with high-resolution mass spectrometry (HRMS) was employed to identify the chemical constituents of CSP and their migration and distribution in mouse serum and tissues; network pharmacology was integrated to explore the potential anti-tumor mechanism of the stably distributed constituents. A total of 3645 chemical constituents were identified under both positive- and negative-ion modes. Following oral administration, 611 constituents derived from the formulation were detected in mouse serum. In tissues, 1187, 1020, 618, and 401 prototype constituents were identified in the stomach, esophagus, liver, and lungs, respectively. Systematic analysis of all identified constituents revealed 95 that were stably distributed across the original formulation, serum, and the liver, lung, esophagus, and stomach. These 95 constituents stably present in the formula, serum, and target tissues may act synergistically to contribute to the antitumor and analgesic efficacy of CSP. Furthermore, network pharmacology was integrated to explore the potential mechanism of these constituents. A total of 152 overlapping targets between CSP and cancer were identified by Venn diagram analysis. Protein-protein interaction (PPI) network analysis revealed hub genes such as ALB, PTGS2, EGFR, CXCL8, and GSK3B. Gene Ontology (GO) enrichment showed involvement in apoptotic regulation, cell proliferation, and kinase activity, while Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted key pathways including cancer, PI3K-Akt, TNF, and MAPK signaling pathways. These findings clarify the chemical constituents and in vivo distribution of CSP, confirm that the 95 stably distributed constituents are the potential pharmacodynamic material basis, and suggest that CSP exerts anti-tumor effects through a multicomponent, multi-target, and multi-pathway regulatory network, providing a basis for further investigation into the pharmacodynamic material foundation of CSP in the treatment of malignant tumors.

Parkinson’s disease (PD) has afflicted numerous patients and troubled countless families worldwide, but an effective therapeutic approach has not been discovered so far. Yet, emerging evidence suggested that photobiomodulation (PBM) can fundamentally delay and inhibit neuronal degeneration, and thus promisingly serve as a non-invasive alternative to conventional drug and surgical treatments. Nevertheless, the light wavelength and spectrum are crucial to PBM. To optimize the spectral formula of photomedicine and reveal photobiological effects, an acute PD model by injecting paraquat into mice abdomen was established in this study. Then, these mice were treated with the narrowband light-emitting diode (LED)-chip light peaked at 670 nm, the broadband phosphor-converted LED light peaked at 840 nm in 600−1000 nm region, and their combination. The results indicate that the PBM is safe, and the combined (narrow 670 + broad 840 nm) light exerted the most potent therapeutic effects. It significantly attenuated oxidative stress levels, enhanced axonal regeneration, protected dopaminergic neurons in the substantia nigra pars compacta (SNpc), preserved striatal neuronal integrity, and improved neuronal morphology and marker expression. Thereby, broadband wavelength through multitarget synergistic therapy helps to improving pathological features and facilitating neural function repair in acute PD mice. However, behavioral validation remains necessary in future studies and further richens the spectrum engineering to PBM.

IntroductionRadiation-induced oral mucositis (RIOM) manifests as mucosal ulceration, pain, and dysphagia, disrupting treatment and quality of life. Its pathogenesis involves inflammatory imbalance and immune dysregulation, driven by microbial infiltration and cytokine storms. Current therapies remain inadequate, necessitating deeper exploration of immune-microbial interactions for effective interventions.MethodsBioactive components of Huoshan Dendrobium Zengye Jiedu Formula (HDZJF) and RIOM-related targets were retrieved from public databases. Core therapeutic targets and pathways were systematically analyzed via protein-protein interaction (PPI) networks, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Molecular docking evaluated interactions between HDZJF components and key targets. A rat RIOM model validated HDZJF efficacy by assessing mucositis severity, inflammatory cytokines, and EGFR/PI3K/AKT pathway protein expression.ResultsA total of 102 bioactive components and 379 potential targets for RIOM were identified. GO and KEGG enrichment analyses suggest that HDZJF exerts therapeutic effects on RIOM by modulating processes such as angiogenesis, inflammation, and apoptosis through pathways like PI3K-AKT. Molecular docking confirmed strong binding affinities between HDZJF components and key targets. In vivo, HDZJF reduced inflammation, promoted mucosal healing, improved body weight, and modulated protein expression related to EGFR/PI3K/AKT.DiscussionThe findings highlight HDZJF's capacity to alleviate RIOM by targeting the EGFR/PI3K/AKT pathway, thereby suppressing inflammatory responses and apoptotic processes. These results underscore HDZJF's translational potential for RIOM treatment and justify further clinical investigation into its therapeutic utility.

Dopamine (DA) is one of the most important neurotransmitters in the human body, which is becoming a key breakthrough for addressing myopia, neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease, and mental diseases such as depression and schizophrenia. However, the activity of DA shows diurnal and seasonal variations, which may be due to the influence of solar activity time on the biological clock of the suprachiasmatic nucleus. By irradiating ARPE-19 cells with red and near-infrared light of different wavelengths, we studied and confirmed that the secretion and transformation of the light-induced neurotransmitter DA significantly depend on light wavelength and light dose. LED-chip light sources with emission peaks at 620, 680, 730, 800, and 850 nm and phosphor-converted LED light sources with emission peaks at 710 and 830 nm were used. It was confirmed that both the red and near-infrared light with variant wavelengths and doses can induce DA secretion to some extent. Yet, the concentrations of DA induced by the wideband spectral light of W710 and SW830 are higher than those induced by the narrowband single-LED-chip light and remain relatively stable under variant light doses. Among all the light sources, the model SW830 light source is the best one. This paper proposes a noninvasive way to induce the secretion of neurotransmitter DA and paves a reliable way to treat myopia, neurodegenerative diseases, and other diseases by using the neurotransmitter DA and the basic knowledge of photophysiology.

Photobiomodulation is promisingly used as a noninvasive new weapon against Sjogren's syndrome, which is a disorder of immune system with two main symptoms of dry eyes and a dry mouth. This work reports a new NIR LED device made from LiScO2:Cr3+ phosphor for the application. The absorbance, internal, and external quantum efficiency of the optimal Li(Sc0.98Cr0.02)O-2 phosphor reach 40.9%, 34.5%, and 14.1%, respectively; and the output power and energy conversion efficiency of the LED device packaged using the phosphor driven under 20 mA are 4.23 mW, respectively. The emission spectrum of the LED device can well cover the action spectrum of oxidized CuA in cytochrome c oxidase molecules. Both the pathological changes of mice submandibular gland and the expression of human submandibular gland epithelial cells (HSG) in AQP5, M3R andEGR1 confirm that the NIR light has great potential application for treating Sjogren's syndrome. Moreover, study with mice approved that the therapy using the NIR light is more efficient than the conventional medicine treatment using hydroxychloroquine sulfate.

The increasing incidence of cancer-related deaths highlights the pressing need for effective treatment modalities, particularly in the context of digestive tract cancers, such as gastric, hepatic, esophageal, intestinal, and pancreatic tumors. While conventional drug therapies play a critical role in managing these malignancies, their associated side effects often pose significant challenges to patient quality of life. Thus, there is a growing focus on traditional Chinese medicine (TCM) and its compounds, which are safe, non-toxic, and reliable. During anti-tumor therapy, TCM compounds, based on their multi-target, multi-pathway, and multi-level regulatory effects, fully mobilize multiple mechanisms of the body, presenting significant advantages in inhibiting tumor development, boosting patient welfare, and increasing their lifespan. This article reviews the mechanisms by which TCM inhibits tumor cell proliferation, promotes tumor cell death, suppresses tumor cell invasion and metastasis, regulates the tumor microenvironment, inhibits angiogenesis, and enhances anti-tumor drug resistance. This knowledge might provide a theoretical and scientific basis for preventing and treating tumors using TCM.

Objectives The study was aimed to investigate the effects of Xinfeng capsule (XFC) on tissue morphology, and gland function of the salivary gland (SG) in a primary Sj & ouml;gren's syndrome (pSS) mouse model. Methods An animal model of pSS was established by inducing SG protein in C57BL/6 mice. SG tissues were collected for tissue sequencing and subsequent experiments to detect the expression of cholinergic receptor muscarinic 3(M3R), early growth response factor 1 (EGR1) and target genes in the SG before and after XFC intervention, with in vitro validation. Results Downstream targets of the EGR1 gene were predicted and analyzed using data analysis. EGR1 showed high expression and was selected for subsequent experiments. Administration of XFC significantly increased saliva production (P < 0.001) and reduced the extent of lymphatic infiltration observed in SG. Furthermore, the expression of EGR1 was increased in the model group with statistical significance in contrast with the control group but decreased after administration of XFC (P < 0.05). Data analysis predicted the downstream target of EGR1 as signal transducer and activator of transcription 3 (STAT3), which was validated in SG tissues of mice (P < .05). Conclusions XFC demonstrated a significant improvement in the salivary secretion function of the SG in pSS mice. EGR1 can serve as a biomarker and therapeutic target for pSS.

The apelin receptor (APJ) is a key player in tumour angiogenesis, but its role in hepatocellular carcinoma (HCC) remains unclear. This study aims to elucidate the function of the apelin/APJ pathway in HCC using a multi-omics approach and identify potential therapeutic biomarkers. Differentially expressed genes related to the apelin/APJ axis were identified from bulk transcriptomics to reveal HCC-associated disparities. Single-cell and spatial transcriptomics were used to localize and analyse the function of these genes. Machine learning models were constructed to predict outcomes based on apelin/APJ expression, and experimental validation was conducted to explore the pathway's impact on HCC angiogenesis. Single cell analysis revealed an overexpression of APJ/Aplin in the endothelium. The stemness of endothelial cell (EC) with high apelin/APJ was enhanced, as well as the expression of TGFb, oxidative stresses and PI3K/AKT pathway genes. Spatial transcriptomics confirmed that EC populations with high APJ scores were enriched within the tumour. Machine learning models showed high prognostic accuracy. High APJ expression was linked to worse outcomes ( p  = 0.001), and AUC values were high (1 year, 3 year, 5 year) (0.95, 0.97, 0.98). Immune suppression and non-responsiveness of immune therapy were also seen in high-risk groups. The experimental validation showed that silencing apelin reduced angiogenesis ( p   < 0.05), endothelial proliferation, decreased expression of ANG2, KLF2, VEGFA and lower ERK1/2 phosphorylation. Apelin may serve as a potential therapeutic target in HCC, given its role in promoting tumour angiogenesis and poor patient outcomes.

CONTEXT:Our clinical observation found that JiJiaoLiHuang Pill (JJLH), a classic traditional Chinese medicine (TCM) formulation, can significantly reduce the abdominal circumference of patients with malignant ascites, increase urine output, and improve the quality of life of patients, with preliminary efficacy. But, the exact mechanism is not yet clear. OBJECTIVE:Based on the above observations, the potential mechanism of action of the treatment was preliminarily explored. METHODS:We identified active ingredients by constructing a "Chinese medicine ingredient-key target-target" network, and verified them by molecular docking using AutoDock tools and PyMOL. Finally, we conducted preliminary verification of the validated pathways and targets using a mouse model of liver cancer ascites. RESULTS:Network pharmacology analysis obtained the top five active ingredients were quercetin, EUPATIN, kaempferol, Obtucarbamate B, and isorhamnetin and the top five key genes were SRC, HSP90AA1, MAPK1, STAT3, and PIK3CA. Molecular docking showed that all 5 active compounds were closely bound to key target genes (binding energy <-6). The animal experiment results showed that JJLH can significantly reduce abdominal circumference, increase urine output, and exhibit dose-dependent inhibition of the AQP-3/JAK-STAT-3 signaling pathway and the expression of related inflammatory factors. CONCLUSIONS:The JJLH potentially inhibits the recurrence of liver cancer malignant ascites through the AQP-3/JAK-STAT-3 pathway and affects the prognosis of MA patients.

Objective To investigate the effect of Jianpi Huashi Tongluo Formula-containing serum on apoptosis and inflammation of synovial fibroblasts（FLSs） in rats with adjuvant arthritis. Methods The primary FLSs was isolated and cultured in the rat model of adjuvant arthritis by subcutaneous injection of Fredrich’s complete adjuvant. 10 times the clinical equivalent dose（3.24 mg/g） was given twice a day for 3 d by gavage to prepare the drug-containing serum. Cell CCK-8 was used to evaluate the effect of Jianpi Huashi Tongluo Formula on the proliferation of FLSs. Flow cytometry was used to detect the effect of Jianpi Huashi Tongluo Formula on the apoptosis of FLSs. ELISA was used to detect the levels of IL-1β, IL-4 and IL-10 inflammatory factors.Results The number of apoptotic cells in FLSs decreased. However, the proliferation rate of FLSs increased.The levels of IL-1β and IL-4 increased and the level of IL-10 decreased significantly. The serum containing Jianpi Huashi Tongluo Formula significantly increased the number of FLSs apoptotic cells, inhibited the proliferation rate of FLSs cells, decreased the expression levels of IL-1β and IL-4, and increased the expression level of IL-10.Conclusion Jianpi Huashi Tongluo Formula can effectively inhibit the proliferation of FLSs in adjuvant arthritis rats in vitro, promote apoptosis and enhance the expression of anti-inflammatory factors and reduce the level of inflammatory factors.

Background: Xinfeng capsule (XFC) is a well-known drug against rheumatoid arthritis (RA). However, the combination mechanisms of XFC on RA remain unclear. Objective: The purpose of this study is to explore the mechanisms of XFC against RA in terms of compounds, targets, and signaling pathways via network pharmacology. Methods: The bioactive compounds and potential targets of XFC were extracted from TCMSP and BATMAN-TCM database, and the putative RA-related targets were determined from the DisGeNET, PHGKB, PharmGKB, and CTD database. The approach of protein-protein interaction, gene ontology analysis, and kyoto encyclopedia of genes and genomes pathway enrichment analysis were constructed, respectively. In animal experiments, we evaluated the expression of core targets. Results: We found that XFC handled 30 active compounds and 131 common target genes. Among them, mairin, folic acid, cholesterol, and triptolide in XFC were selected as the central active compounds against RA. The mechanisms of XFC on RA which concerned critical targets were protein kinase B (AKT1) and tumor necrosis factor (TNF). In vivo, we found that the expression levels of AKT1 and TNF in the modeling group were significantly increased but reversed by XFC. Conclusion: The combination mechanisms of XFC were elucidated in terms of components and targets and signaling pathways, which may be related to inhibiting the proliferation of synovial cells and inflammation.

IntroductionMouse models are the basis for primary Sjögren’s syndrome (pSS) research. However, the depth of comparisons between mice and humans in salivary gland (SG) immune cells remains limited.MethodsThe gene expression profiles of SGs from normal subjects and pSS patients were downloaded from the Gene Expression Comprehensive Database. The proportion of infiltrating immune cell subsets was then assessed by cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT). An experimental Sjögren’s syndrome (ESS) mouse model was successfully constructed using SG protein. Based on mouse SG tissue RNA-Seq data, the seq-ImmuCC model was used to quantitatively analyze the compositional ratios of 10 immune cells in pSS patients and mouse model SG tissues.ResultsComputed and obtained 31 human data samples using the CIBERSORT deconvolution method. The immune cell infiltration results showed that, compared to normal human SG tissue, the content of gamma delta T cells was significantly different from naive CD4+ T cells and significantly increased, while the plasma cell content decreased. Principal component analysis indicated differences in immune cell infiltration between pSS patients and normal subjects. Meanwhile, for ESS model mouse data analysis, we found that the proportion of macrophages increased, while the proportion of CD4+ T cells, B cells, and monocytes decreased. Furthermore, we found that the proportion of monocytes was decreased, while the proportion of macrophages was increased in the SG tissues of pSS patients and model mice. The infiltration of CD4+ T, CD8+ T, and B cells also showed some differences.DiscussionWe comprehensively analyzed SG immune infiltration in pSS patients and model mice. We demonstrated conserved and nonconserved aspects of the immune system in mice and humans at the level of immune cells to help explain the primary regulation of immune mechanisms during the development of Sjögren’s syndrome.

Objective: Primary Sjogren's syndrome (pSS) is a intricate autoimmune disease mainly characterized of immunemediated destruction of exocrine tissues, such as salivary and lacrimal glands, occurring dry mouth and eyes. Although some breakthroughs in understanding pSS have been uncovered, many questions remain about its pathogenesis, especially the internal relations between exocrine glands and secretions. Method: Transcriptomic and proteomic analyses were conducted on salivary tissues and saliva in experimental Sjogren syndrome (ESS). The ESS model was established by immunization with salivary gland protein. The expression of mRNAs and proteins in salivary tissues and saliva were determined by high-throughput sequencing transcriptomic analysis and LC-MS/MS-based proteome, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to recognize dysregulated genes and proteins. The association between RNA and protein abundance was investigated to provides a comprehensive understanding of RNA-protein correlations in the pathogenesis of pSS. Results: As a result, we successfully established the ESS model. We recognized 3221 differentially expressed genes (DEGs) and 253 differentially expressed proteins (DEPs). The sample analysis showed that 61 proteins overlapped through the integrative analysis of transcriptomics and proteomics data. The enrichment pathway analysis of DEGs and DEPs in samples showed alterations in renin-angiotensin-system (RAS), lysosome, and apoptosis. Notably, we found that some genes, such as AGT, FN1, Klk1b26, Klk1, Klk1b5, Klk1b3 had a consistent trend in the regulation at the RNA and protein levels and might be potential diagnostic biomarkers of pSS. Conclusion: Herein, we found critical processes and potential biomakers that may contribute to pSS pathogenesis by analyzing dysregulated genes and pathways. Additionally, the integrative multi-omics datasets provided additional insight into understanding complicated disease mechanisms.

面诊属于中医学望诊的范畴,具备极大的临床意义.活用面诊,能够以无创、便捷、直观的方式从患者面部获得大量辨证资料,用于辅助诊断,发扬了中医"简便廉验"的优点.但是,传统的中医诊断通常是"定性的",容易受到医生"主观性"和外部环境的影响,因而产生诊断信息的遗漏或诊断结果的误判等;而通过面诊客观化可以实现"定量"诊断,扬长避短,有利于中医面诊的发展和推广,因此面诊客观化研究可行且必要.一直以来,恶性肿瘤疾病严重危害着人们的健康,而通过中医面诊及其客观化研究,有望在癌症的辅助诊断、疗效评价、三级预防等方面拓展新的思路和方向,这也是今后需要关注的研究方向.该文从中医面诊及其客观化研究的角度出发,查阅古代及近现代的相关文献,概括了近年来面诊及其客观化在肿瘤疾病诊疗及预防中的重要价值,为中医临床治疗恶性肿瘤及其面诊客观化的研究提供参考和建议.