Metabolic reprogramming is a hallmark of cancer, enabling tumor cells to meet the demands of rapid growth and survival. Within tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) influence tumor metabolism through metabolic crosstalk. However, role of CAF-derived factors in regulating glutamine metabolism in laryngeal squamous cell carcinoma (LSCC) remains unclear. Primary fibroblasts were isolated from LSCC tumors and adjacent tissues and classified as CAFs or normal fibroblasts (NFs). These were co‑cultured with LSCC cell lines to assess effects on proliferation, migration, invasion, stemness, and chemoresistance using assays such as CCK‑8, EdU, sphere formation, Transwell migration/invasion, and real‑time RTCA assays. Exosomes were harvested from fibroblast-conditioned media, characterized by TEM, NTA, and Western blotting, and used to treat LSCC cells. Metabolic profiling included Seahorse measurements, TCA metabolites, ATP content, glutamine uptake ([3H]-glutamine assay), glutamine consumption, as well as glucose consumption and lactate production assays. Mechanistic studies involved manipulating gene expression via transfection, and detection of targets by qRT‑PCR, Western blotting, and histological staining. Interaction of SFRP2, ELAVL1, and GID8 was assessed via Co‑IP and RIP assays. SFRP2 was increased in LSCC and linked to advanced stage, lymph node metastasis, and poor survival. It was mainly produced by a unique group of CAFs with myofibroblastic traits. Exosomal SFRP2 from these CAFs promoted glutamine uptake, mitochondrial activity, and aggressive tumor behaviors. Mechanistically, SFRP2 stabilized GID8 mRNA via ELAVL1 and promoted β-catenin nuclear translocation, activating canonical Wnt signaling. A novel CAF-driven SFRP2-ELAVL1-GID8 pathway promotes metabolic reprogramming involving in LSCC progression.

Mitochondria regulate energy metabolism, redox balance, cell survival, and innate immune signaling. Neutrophils, the most abundant circulating innate immune effector cells, play an essential role in reshaping the tumor microenvironment and can exhibit both anti-tumor and tumor-supporting behaviors. Although mitochondrial processes are increasingly recognized as key drivers of neutrophil functional diversity and neutrophil-tumor cell communication, a systematic synthesis centered on mitochondria remains limited. The review opens with an overview of defining features of mitochondrial biology, including fission and fusion dynamics, oxidative stress responses, calcium balance, apoptosis-related pathways, and mitochondrial damage signals that influence immune activation. Mitochondria-dependent programs supporting neutrophil survival, lifespan control, and physiological defense functions are then outlined to show how subcellular metabolism shapes innate effector activity. The focus subsequently shifts to mitochondrial contributions in tumor-supportive interactions between neutrophils and tumor cells, highlighting the capacity of mitochondrial signals from both sides to reinforce tumor-promoting neutrophil traits, tumor cell aggressiveness, and bidirectional crosstalk. Emerging strategies capable of redirecting neutrophil mitochondria toward anti-tumor phenotypes are finally summarized, including stimulation of mitochondrial biogenesis, delivery of mitochondrial-targeted proteins to enhance neutrophil-driven immunity, dual disruption of extracellular traps and tumor mitochondria to break tumor-supportive feedback, and modulation of mitochondrial quality-control and oxidative signaling to rebalance tumor-supportive neutrophils. A mitochondria-centered subcellular perspective provides a more cohesive framework for understanding neutrophil-tumor communication and may help inform the development of subcellularly targeted cancer therapies.

The incidence and mortality of lung cancer are among the highest in the world, involving a variety of complex pathological mechanisms and processes. Previous studies have demonstrated that the tumor immunosuppressive microenvironment (TIME) plays a key role in tumor progression, promoting tumor invasion and metastasis and leading to resistance to therapy. Tumor-associated macrophages (TAMs) are important cell components in TIME, and their phenotypes affect the prognosis of tumors. Tumor-derived exosomes carrying specific information as a medium of crosstalk between macrophages and tumor cells are considered to be an underexplored information transfer medium affecting tumor progression and tumor microenvironment remodeling. In the previous study, we found that Shuangshen granule (SSG) can reduce the formation of lung tumors in mouse models of spontaneous lung cancer, but the specific mechanism of SSG inhibiting lung cancer has not been solved. Starting from the exosomes of tumor cells, we established the M1-like TAMs overexpression mouse lung cancer transplantation tumor model and constructed MIF+/+ Lewis stable transfection cell line and shMIF Lewis stable transfection cell line to analyze the specific molecular biological mechanism of SSG inhibiting lung cancer. The experimental results showed that SSG significantly reduced the volume and mass of Lewis lung cancer xenografts in mice, and its inhibitory effect on Lewis lung cancer was related to the increase in the proportion of M1-like TAMs. Flow cytometry and western blot revealed that SSG can increase the proportion of CD8+ central memory T cells, reduce the proportion of CD8+ effector memory T cells, reduce the proportion of CD4+CD25+Foxp3+ Treg cells, and play a role in regulating the tumor microenvironment. In vitro experiments further showed that SSG drug-containing serum could inhibit the expression of MIF protein and RNA in MIF+/+ Lewis cells and increase the expression of miR-34a in MIF+/+ Lewis cell exosomes. Interestingly, we also found that MIF+/+ Lewis cell-derived exosomes after SSG-containing serum intervention can reverse the increase in the proportion of M2-like TAMs and increase the proportion of M1-like TAMs. Subsequent gene modification experiments showed that MIF+/+ Lewis cell exosomes can increase the expression of the KLF4 gene in macrophages in vitro. In conclusion, our study revealed that SSG can regulate the polarization of TAMs through lung cancer cell-derived exosomes, and its mechanism is related to the MIF-miR-34a-KLF4 pathway. Summary:•SSG can inhibit the proliferation of lung cancer, which is related to the antitumor mechanism involving macrophages.•The poor prognosis of lung cancer caused by macrophage migration inhibitory factor (MIF) is related to the TAM phenotype, and SSG can inhibit lung cancer by inhibiting MIF.•SSG regulates the tumor cell MIF-MiR-34a exosome pathway and regulates the polarization and function of TAMs.

Understanding aging and complex diseases requires diverse data, ranging from molecular profiles to imaging and routine clinical tests. However, most multi-omic datasets measure only a subset of modalities and are confounded by batch effects. Here, we present AURORA (AI unification and reconstruction of omics reassembly atlas), a generative deep-learning platform that integrates seven modalities (including transcriptomics, metabolomics, microbiome, 3D and thermal facial imaging, and clinical laboratory tests) across 581,763 samples from 425,258 individuals. AURORA harmonizes batch effects and reconstructs missing data across modalities, enabling highly accurate multimodal aging clocks and disease risk predictors. It also supports personalized in silico perturbation analyses to predict intervention and drug responses, validated using longitudinal cohorts. As a proof of concept, we provide a prototype AI agent that converts single-input modalities into a multimodal report for users and researchers. Together, AURORA links non-invasive inputs to comprehensive aging biomarkers and therapeutic discovery.

Objective This study aimed to comprehensively investigate the anti-ovarian cancer (OC) efficacy of Yiyi Fuzi Baijiang Powder (YFBP), identify its key chemical constituents, and elucidate the underlying mechanisms of action. Methods The chemical profile of YFBP was characterized using UHPLC-MS/MS. The potential mechanisms were predicted through integrated network pharmacology and bioinformatics analyses. The anti-tumor effects were validated in SK-OV-3 cells and a xenograft mouse model by performing CCK-8, flow cytometry, and TUNEL assays. The effects on the tumor inflammatory microenvironment and the JNK/c-Jun signaling pathway were assessed by ELISA, Western blotting, and qRT-PCR. Results UHPLC-MS/MS analysis identified 271 chemical constituents in YFBP. In vivo, YFBP significantly suppressed tumor growth (inhibition rate up to 52.4%) without systemic toxicity. It inhibited cell proliferation, induced apoptosis, and arrested the cell cycle in the S-phase. Mechanistically, YFBP ameliorated the inflammatory tumor microenvironment (TME) by reducing pro-inflammatory cytokine levels (TNF-α, IL-6, IL-1β) and concurrently activated the JNK/c-Jun signaling pathway. Rescue experiments confirmed that the JNK inhibitor SP600125 attenuated the anti-proliferative effects of YFBP. Conclusion This study demonstrates that YFBP exerts significant anti-OC therapeutic effects by modulating the inflammatory TME and activating the JNK/c-Jun pathway. Our findings provide a pharmacological basis for the traditional use of YFBP and highlight its potential as a promising candidate phytomedicine for OC therapy.

OBJECIVE:To explore the objective biological evidence for the classification and diagnosis of Traditional Chinese Medicine (TCM) syndromes in ankylosing spondylitis (AS) using multiomics analysis. METHODS:Patients with AS were categorized into kidney deficiency and blood stasis syndrome (SX group) and damp-heat stasis syndrome (SR group). Transcriptomic sequencing and quantitative plasma proteomics were performed on patients with AS and healthy volunteers. Multiomics integration was used to characterize the biological basis of AS with renal deficiency and blood stasis syndrome. Specific proteins were validated by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS:Transcriptomic sequencing identified 31 significantly upregulated genes in patients with AS compared to healthy controls. These genes were primarily involved in tumor necrosis factor, interleukin-17, and nuclear factor kappa-B signaling pathways, as well as osteoblast differentiation and various viral infection pathways. Differentially expressed genes, including intercellular adhesion molecule 1 (ICAM1), 6-phosphofructo-2-kinase, cyclin-dependent kinase inhibitor 1A, interleukin 1 receptor antagonist, integrin alpha IIb, and myosin light chain 9 were more upregulated in the SX group than in the SR group. Quantitative proteomics identified 723 differential proteins associated with the disease and 788 differential proteins between the SX and SR groups. Notable proteins such as myeloperoxidase, cluster of differentiation 14, macrophage simulating 1 (MST1), and Ras homolog enriched in brain may serve as characteristic proteins of the SX group. By integrating transcriptomic and proteomic data, 45 associated differential molecules involved in platelet activation, pathogenic intestinal flora infection, glycolysis/gluconeogenesis, and T-cell receptor signaling pathways were identified in patients with AS compared to healthy controls. Additionally, ICAM1, MST1, C-X-C motif chemokine ligand 8 (CXCL8), suppressor of cytokine signaling 3 (SOCS3), and insulin-like growth factor binding protein 1 (IGFBP1) were detected in TCM syndromes by RT-qPCR and ELISA, showing upregulation in AS renal deficiency and blood stasis syndromes, which is consistent with the proteomic and transcriptomic results. CONCLUSIONS:ICAM1, MST1, CXCL8, SOCS3, and IGFBP1 were identified as biomarkers of renal deficiency and blood stasis syndrome in AS. This study provides a biological basis for the differential diagnosis of TCM syndromes in AS, offering new insights into Chinese medicine evidence and more precise Chinese medicine treatments for AS.

ETHNOPHARMACOLOGICAL RELEVANCE:Pancreatic cancer presents a significant challenge in clinical treatment. Pi Ji Pills (PJP) is a compound formula made up of seven traditional Chinese medicinal herbs. It has demonstrated positive clinical outcomes in the treatment of pancreatic cancer, and its potential pharmacological mechanisms warrant further investigation. AIM OF THE STUDY:This study aimed to identify the possible mechanisms by which PJP inhibits pancreatic cancer, followed by experimental verification and more profound exploration. MATERIALS AND METHODS:An in vivo pancreatic cancer xenograft model was established to observe the effect and safety of PJP on tumor growth. The SW1990 cells were cultured to investigate the intervention effects of PJP-containing serum on the malignant biological behavior of pancreatic cancer cells. Subsequently, network pharmacology analysis was employed to explore the potential mechanisms. Furthermore, both in vivo and in vitro experiments were conducted to validate the core pathways and targets. An in-depth exploration was performed, with a focus on the role of neutrophil extracellular traps (NETs) in the inhibition of pancreatic cancer by PJP. RESULTS:PJP inhibits tumor growth, and its combination with gemcitabine exhibits enhanced inhibitory effects, partially alleviating immune suppression. PJP-containing serum was found to inhibit the malignant biological behavior of SW1990 cells. naringenin, atractylenolide I, isoalantolactone, curcumenol, parthenolide, and arglabin are the main active components of PJP. PJP inhibits PI3K/AKT pathway, key to its anti-pancreatic cancer effects. Additionally, PJP's treatment inhibited SW1990 cell proliferation indenpence of reducing IL-8 and downregulating NETs-related protein expression in the co-culture system. CONCLUSIONS:PJP combats pancreatic cancer and enhances gemcitabine efficacy by remodeling the immunosuppressive tumor microenvironment. This anticancer effect may be attributed to a dual-target mechanism involving suppression of the PI3K/AKT pathway and regulation of NETs formation in the tumor microenvironment.

Introduction: Ankylosing spondylitis (AS) is a systemic inflammatory disorder that predominantly involves the axial skeleton, often leading to irreversible structural damage and disability. Although several therapeutic measurements are available, limitations in efficacy and long-term outcomes remain significant. Therefore, identifying novel biomarkers and therapeutic targets is of critical importance for optimizing clinical management and prognostic evaluation in AS patients. Objectives: This study aims to elucidate the immune features and discover potential biomarkers for AS by the integration of deep plasma proteomics and deep learning strategies. Methods: The deep quantitative proteomics was applied to analyze the plasma samples from 104 participants of AS patients with active and stable stages, along with healthy controls. The immune and functional features of AS patients in different stages were assessed. By integrating random forest (RF) with orthogonal partial least squares discriminant analysis (OPLS-DA), a machine learning model-based score matrix was constructed to identify biomarkers. ELISA experiments were performed on an independent cohort of 79 participants to confirm the potential biomarkers for AS. Results: Patients with AS exhibit significant dysregulation in the distributions and characteristics of immune cells. Several key proteins involved in integrin signaling pathway were significantly differentially expressed in patients with AS, highlighting the pathway’s role in the pathogenesis of AS. Four proteins including SAA1, FERMT3, ILK, and TLN1, were identified as potential biomarkers for AS and further verified by ELISA experiments. Conclusions: By integrating the machine learning-based method with deep proteomics analysis, we explored the pathological mechanism and identified biomarkers for AS. Our study provides insights into the distinct protein expression patterns and pathogenesis of AS and may contribute to diagnosis, long-term monitoring, and therapy for this disease.

BACKGROUND:Coronavirus has caused high-mortality viral pneumonia worldwide. The pathogenesis is characterized by hyperinflammatory reactions resulting from immune homeostasis dysregulation. Verbenalin, an iridoid glucoside derived from Verbena officinalis L., is widely used in Traditional Chinese Medicine (TCM) clinical practice for its antioxidant, anti-inflammatory and antiviral properties. PURPOSE:This study aimed to investigate the pharmacological effects and underlying mechanisms of verbenalin on coronavirus pneumonia both in vivo and in vitro. METHODS:A coronavirus pneumonia mouse model and macrophage injury models, including mouse alveolar macrophage cell line (MH-S) cells and primary macrophages, were established to initially confirm the antiviral effects of verbenalin. Time-resolved proteomic were then employed to uncover proteomic changes and identify potential therapeutic targets for coronavirus treatment. Subsequently, flow cytometry and Western blot were employed to investigate verbenalin's effects on NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome pathway. Additionally, the targeting regulation of phosphatase and tensin homolog-induced putative kinase 1 (PINK1) / E3 ubiquitin ligase Parkin (Parkin) pathway by verbenalin was validated through molecular docking, surface plasmon resonance (SPR), immunofluorescent staining, RNA interference (RNAi), and mitophagy inhibition both in vivo and in vitro. RESULTS:Verbenalin reduced cell injury and inflammation in Human coronavirus 229E (HCoV-229E)-infected macrophages and improved lung inflammation in mice. Proteomics analysis highlighted the roles of nucleotide-binding oligomerization domain (NOD)-like receptor signaling and mitophagy pathways in coronavirus pneumonia. Verbenalin bound strongly to PINK1 and Parkin proteins, increased mitochondrial membrane potential (MMP), decreased mitochondrial reactive oxygen species (mtROS) levels, reduced the opening of mitochondrial permeability transition pore (MPTP), maintained mitochondrial mass, promoted mitophagy flux, upregulated the expression of PINK1, Parkin, and microtubule-associated protein 1A/1B-light chain 3BII (LC3BII). Additionally, verbenalin inhibited the activation of the NLRP3 inflammasome and downregulated the expression of Interleukin-1 beta (IL-1β), cysteine aspartate-specific protease 1 (caspase-1), and gasdermin D (GSDMD) both in vivo and in vitro. Furthermore, treatment with a mitophagy inhibitor and RNAi attenuated the inhibitory effects of verbenalin on NLRP3 activation, confirming the involvement of the PINK1/Parkin/NLRP3 pathway in verbenalin's protective effects. CONCLUSION:Verbenalin enhances PINK1/Parkin-mediated mitophagy to suppress NLRP3 activation, thereby promoting immune homeostasis and mitigating HCoV-229E-induced inflammation.

Background:Influenza A viruses(IAVs)are the major pathogens associated with respiratory infections which can result in extensive pathological damage in lungs and serious complications.Isorhamnetin,an abundant natural flavonoid in fruits and medicinal plants,has recently been shown to have strong antioxidative,anti-inflammatory,and antiviral effects. Objective:This study investigated the pharmacological effects of isorhamnetin on viral pneumonia and explored the underlying mech-anisms by in vivo and in vitro experiments. Materials and methods:In the present study,the protective effect of isorhamnetin against IAV was evaluated by the cytopathogenic effect assay,cell counting kit-8 assay,real-time polymerase chain reaction,and immunofluorescence assay in vitro.Then the pathological damage associated with pneumonia was examined by calculating the pulmonary index and performing micro-CT and hematoxylin-eosin staining in vivo.Thereafter,the related protein or gene levels of factors in the mitogen-activated protein kinase(MAPK)and nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathways were determined by Western blot and immunofluorescence staining. Results:Isorhamnetin exerted significant anti-influenza effects and inhibited the expression of viral RNA in A549 cells,counteracting ox-idative stress and apoptosis by suppressing the production of reactive oxygen species and caspase-3.The in vivo experiment results showed that isorhamnetin(20 and 40 mg/kg)caused a significant decrease in the pulmonary index,ameliorated pathological damage in the lung tissue,decreased viral load and NA activity,and reduced cytokines and nuclear factors.Furthermore,isorhamnetin could coun-teract the B cell lymphoma-2/B cell lymphoma-2-associated X protein(Bax)imbalance induced by PR8,suppress activation of the MAPK pathway,and upregulate the expression of Nrf2 and HO-1. Conclusions:Isorhamnetin can protect against viral pneumonia by activating the Nrf2/HO-1 pathway and suppressing the MAPK path-way.This study deciphers the pharmacological mechanism of isorhamnetin in alleviating pathological damage in viral pneumonia and provides rationale for the application of isorhamnetin in influenza treatment.

Telomeres and telomerase play crucial roles in the initiation and progression of cancer. As biomarkers, they aid in distinguishing benign from malignant tissues. Despite the promising therapeutic potential of targeting telomeres and telomerase for therapy, translating this concept from the laboratory to the clinic remains challenging. Many candidate drugs remain in the experimental stage, with only a few advancing to clinical trials. This review explores the relationship between telomeres, telomerase, and cancer, synthesizing their roles as biomarkers and reviewing the outcomes of completed trials. We propose that changes in telomere length and telomerase activity can be used to stratify cancer stages. Furthermore, we suggest that differential expression of telomere and telomerase components at the subcellular level holds promise as a biomarker. From a therapeutic standpoint, combining telomerase-targeted therapies with drugs that mitigate the adverse effects of telomerase inhibition may offer a viable strategy.

Metabolic reprogramming and epigenetic modification have been widely observed in cancer research. Based on accumulating experimental evidence in recent years, beginning with metabolic reprogramming driven by carcinogenic signals, the accumulation of key metabolites, represented by lactate, continuously affects cellular plasticity and alters the epigenetic landscape. As a new post-translational modification of histone, histone lactylation not only changes the nucleosome structure, but also regulates chromatin dynamics and gene expression, which is closely related to the poor prognosis of tumors, contributing to immune escape, immune monitoring and angiogenic events in tumor progression. Before the discovery of histone lactylation in 2019, there was a lack of systematic understanding of the lactate regulation of tumor metabolism, immune effects and microenvironmental homeostasis. From metabolic changes to stable gene expression, histone lactylation has become an important entry point in tumor research, connecting the relationship network of metabolic reprogramming, Tumor microenvironment (TME) and epigenetic modification. It represents an important conceptual link between metabolism and epigenetics, and emerging evidence suggests it may be a promising area for understanding tumor progression and developing targeted therapies. In this review, we focus on how tumor cell metabolic reprogramming reshapes the epigenetic landscape into histone lactylation. Besides, we discussed the plasticity of tumor metabolism regulated by histone lactylation in reverse, involving TME biological processes such as immunity and metabolism. Finally, we reviewed the new molecular targets and targeted therapeutic strategies of histone lactylation for cancer treatment. Elucidating these problems will provide theoretical basis for further research and clinical application in this field in the future.

OBJECTIVES:To investigate the neuroprotective effects of electroacupuncture (EA) preconditioning against cerebral ischemia-reperfusion injury (CIRI) mediated by gut microbiota modulation, Nrf2/HO-1 pathway activation, and ferroptosis suppression. METHODS:Adult male SD rats were divided into sham operation group, CIRI model group, and EA preconditioning group. In the latter two groups, rat models of CIRI were established by middle cerebral artery occlusion (MCAO), and in EA preconditioning group, EA was applied at Baihui (DU20) and Zusanli (ST36) for 3 days before modeling. Neurological deficits, cerebral infarction, and hippocampal pathology of the rats were evaluated using behavioral tests, TTC staining, and Nissl and HE staining, and the oxidative stress markers (MDA, ROS, and SOD), apoptosis/ferroptosis-related proteins (Bax, Bcl-2, GPX4, and SLC7A11), and changes in gut microbiota were analyzed. RESULTS:EA preconditioning significantly reduced neurological deficits, decreased infarct volume, promoted hippocampal neuronal survival, and improved structural integrity of the hippocampal neurons in MCAO rats. EA preconditioning also significantly lowered MDA and ROS and increased SOD levels, upregulated Bcl-2, GPX4, and SLC7A11 expressions, and downregulated Bax expression in the hippocampal tissue of the rats, causing also activation of Nrf2/HO-1 signaling and improvement of gut microbiota composition. CONCLUSIONS:EA preconditioning alleviates CIRI in rats by suppressing ferroptosis and apoptosis, enhancing antioxidant defenses via activating Nrf2/HO-1 signaling, and regulating the gut-brain axis.

Objective The aetiology of pancreatic cancer is complex, and there is limited research on its incidence. We aimed to investigate the incidence trends of pancreatic cancer in 43 countries and predict trends up to 2030.Methods The annual incidence of pancreatic cancer was obtained from the Cancer Incidence in Five Continents database, which comprises 108 cancer registries from 43 countries. Based on available data, we calculated age-standardized incidence rates (ASRs) per 100 000 people for 1988–2012. A Bayesian age-period-cohort model was used to predict the number of new cases and incidence rates up to 2030.Results From 1988 to 2012, the global incidence rate of pancreatic cancer showed a continuously increasing trend, with the ASR increasing from 5.89 in 1988 to 6.78 in 2012, representing an overall average annual percentage change of 8.45%. This increasing trend is expected to persist in most selected countries, whereas a few countries are projected to exhibit a declining trend by 2030.Conclusion It appears that the future global incidence of pancreatic cancer is on the rise, but the rate of increase varies among different countries, with some showing a declining trend.

Objective: We aimed to explore the influence of ferroptosis on an oxygen-glucose deprivation/reoxygenation (OGD/R) model in primary rat microglia. Methods: Primary microglia were extracted from rats and cultured in vitro. The cells were subjected to a hypoxic environment for 6 h in a glucose-free medium, and then re-oxygenated for 24 h in DMEM/F12. Rat microglia were pretreated with the ferroptosis activator erastin and the ferroptosis inhibitor ferrostatin 1 for 24 h, followed by detection of cell cycle progression and apoptosis by flow cytometry. Intracellular total iron levels were measured. In addition, the relative levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) were determined using enzyme-linked immunosorbent assay. The protein levels of 15-lox2, GPX4, SLC7A11, ACSL4, and TFR1 were examined by western blotting. Results: Compared with rat microglia subjected to OGD/R, pretreatment with erastin did not influence cell apoptosis but significantly enhanced total iron levels, MDA, and ROS levels, whereas it reduced SOD levels. Moreover, it upregulated ACSL4, TFR1, and 15-lox2 and downregulated GPX4 and SLC7A11. Pretreatment with ferrostatin 1 significantly inhibited cell apoptosis and cell cycle arrest in the G0/G1 phase. It significantly reduced total iron levels, MDA, and ROS levels and enhanced SOD levels, which also downregulated ACSL4, TFR1, and 15-lox2, and upregulated GPX4 and SLC7A11. Conclusion: Our study showed that inhibition of ferroptosis is favorable against potential OGD/R-induced damage in rat microglia.

Ethnopharmacological relevance: Maxing Shigan Decoction (MXSG) is a traditional Chinese Medicine effectively used in respiratory infections and bacterial pneumonia. However, the mechanism of MXSG treating acute Pseudomonas aeruginosa (P. aeruginosa) pneumonia is still unclear. Aim of the study: This study aimed to investigate the therapeutic effects of MXSG on acute P. aeruginosa pneumonia and explore its potential mechanisms. Materials and methods: HPLC-MS analysis was performed to analyze the chemical composition. Antibacterial effects in vitro were evaluated by minimum inhibitory concentration (MIC). Forty-five male BALB/c mice were divided into control group, model group, levofloxacin group, MXSG-L (7.7 g/kg/d), and MXSG-H group (15.4 g/ kg/d). Mice were intranasal instillation with P. aeruginosa to induce acute P. aeruginosa pneumonia model. Levofloxacin and MXSG were administered by oral gavage once a day. After 3 days of treatment, the lung index measurement, micro-CT, arterial blood gas analysis, bacteria load determination, and HE staining were performed. Network pharmacological analysis and transcriptome sequencing were employed to predict the potential mechanisms of MXSG on bacterial pneumonia. The expressions of relating genes were detected by immunofluorescence, Western blot, and RT-PCR. Results: In vitro, MIC of P. aeruginosa is greater than 500 mg/mL. In the treatment of acute P. aeruginosa pneumonia model, MXSG significantly improved body weight loss, lung index, and pulmonary lesions. MXSG treatment also reduced the bacterial load and ameliorated oxygen saturation significantly. Transcriptomes, immunofluorescence, Western blot, and RT-PCR analysis showed MXSG treating acute P. aeruginosa pneumonia through the IL-17 signaling pathway and HIF-1 alpha/IL-6/STAT3 signaling pathway. Conclusions: We demonstrated the efficacy and mechanism of MXSG in the treatment of acute P. aeruginosa pneumonia, which provides a scientific basis for its clinical application.

Background: Although many experiments and clinical studies have proved the link between the expression of CDKN3 and human tumors, we have not been able to identify any bioinformatics study in which the extensive tumor-promoting effect of CDKN3 was systematically analyzed. Objective: Explore the extensive tumor-promoting effects of CDKN3 and review the research progress of CDKN3 in cancer. Methods: We systematically reviewed the literature on CDKN3 and tumors. We explored the potential tumor-promoting effects of CDKN3 on different tumors in the TCGA database and the GTEx database using multiple platforms and websites. We studied the expression level of CDKN3, survival, prognosis, diagnosis, genetic variation, immune infiltration, and enrichment analysis using databases such as TIMER 2.0, GEPIA2, cBioPortal, and STRING. Results: We found that CDKN3 is highly expressed in most tumors. The expression of CDKN3 is closely related to the prognosis of some tumors. And CDKN3 may have diagnostic value. The conclusion of our literature review is roughly the same, but there are differences, which are worthy of further study. Moreover, CDKN3 may be related to immune cell infiltration in tumor tissues. The genetic alteration of LUAD, STAD, SARC, PCPG, and ESCA with ''Amplification'' as the main type. In addition, through enrichment analysis, we found that CDKN3 affects tumors mainly through the control of the cell cycle and mitosis. Conclusion: CDKN3 is highly expressed in most tumor tissues and has a statistical correlation with survival prognosis. It has extensive tumor-promoting effects that may be related to mechanisms such as immune infiltration.

Ankylosing spondylitis (AS) is a common chronic progressive inflammatory autoimmune disease. T helper 17 (Th17) cells are the major effector cells mediating AS inflammation. Histone 3 Lys 27 trimethylation (H3K27me3) is an inhibitory histone modification that silences gene transcription and plays an important role in Th17 differentiation. The objective of this study was to investigate the expression of H3K27me3 in patients with AS and to explore its epigenetic regulation mechanism of Th17 differentiation during AS inflammation. We collected serum samples from 45 patients with AS at various stages and 10 healthy controls to measure their Interleukin-17 (IL-17) levels using ELISA. A quantitative polymerase chain reaction was used to quantify the mRNA levels of RORc and the signaling molecules of the JAK2/STAT3 pathway, JMJD3, and EZH2. Additionally, Western blot analysis was performed to quantify the protein levels of H3K27me3, RORγt, JAK2, STAT3, JMJD3, and EZH2 in cell protein extracts. The results showed that H3K27me3 expression in peripheral blood mononuclear cells (PBMCs) was significantly lower in patients with active AS compared to both the normal control groups and those with stable AS. Moreover, a significant negative correlation was observed between H3K27me3 expression and the characteristic transcription factor of Th17 differentiation, RORγt. We also discovered that patients with active AS exhibited significantly higher levels of JMJD3, an inhibitor of H3K27 demethylase, compared to the normal control group and patients with stable AS, while the expression of H3K27 methyltransferase (EZH2) was significantly lower. These findings suggest that H3K27me3 may be a dynamic and important epigenetic modification in AS inflammation, and JMJD3/EZH2 regulates the methylation level of H3K27me3, which may be one of the key regulatory factors in the pathogenesis of AS. These findings contribute to our understanding of the role of epigenetics in AS and may have implications for the development of novel therapeutic strategies for AS.

Lipopolysaccharide (LPS)-triggered damage in human dental pulp cells (hDPCs) is associated with the progression of gingivitis, which is inflammation of the gingival tissue. Nesfatin-1 is a peptide secreted by neurons and peripheral tissues. Here, we report a novel property of Nesfatin-1 in ameliorating LPS-induced inflammatory response and senescence in hDPCs. First, we demonstrate that Nesfatin-1 repressed LPS-triggered expression of inflammatory factors. Secondly, Nesfatin-1 restored telomerase activity and the expression of human telomerase reverse transcriptase (hTERT) and telomeric repeat binding factor 2 (TERF2) against LPS. Senescence-associated β-galactosidase (SA-β-gal) staining assay revealed that Nesfatin-1 attenuated LPS-induced cellular senescence in hDPCs. We also found that Nesfatin-1 increased telomerase activity in LPS-challenged hDPCs. It is also shown that Nesfatin-1 reduced the expression of plasminogen activator inhibitor-1 (PAI-1) and p16. Additionally, LPS stimulation reduced the expression of SIRT1, which was rescued by Nesfatin-1. However, the silencing of sirtuin1 (SIRT1) abrogated the protective property of Nesfatin-1 in preventing cellular senescence, implying that the function of Nesfatin-1 is regulated by SIRT1. Taken together, our findings suggest that Nesfatin-1 might possess a protective effect against gingivitis.