There is a growing trend of applying traditional Chinese medicine (TCM) to treat immune diseases. This study reveals the possible mechanism of luteolin, an active ingredient in the core prescription of TCM, in alleviating systemic sclerosis (SSc) inflammation. Bibliometrics was performed to retrieve the core keywords of SSc inflammation. The key inflammatory indicators in the serum samples of 50 SSc patients were detected by ELISA. Data mining was applied for correlation analysis, association rule analysis, and binary logistic regression analysis on the clinical indicators and medication of 50 SSc patients before and after treatment to determine the core prescription. Network pharmacology was used for identifying candidate genes and pathways; molecular docking was conducted to determine the core monomer components of the prescription, providing a basis for subsequent in vitro molecular mechanism research. The effect of luteolin on SSc-human dermal fibroblasts (HDF) viability and inflammatory factors was evaluated by means of ELISA, RT-PCR, and Western blot. The role of TNF in inflammation was explored by using a TNF overexpression vector, NF-κB inhibitor (PKM2), and SSc-HDF. The involvement of TNF/NF-κB pathway was validated by RT-PCR, Western blot, and immunofluorescence. TCM treatment partially corrected the inflammatory changes in SSc patients, indicating its anti-inflammatory effects in the body. Atractylodes, Yam, Astragalus root, Poria cocos, Pinellia ternata, Salvia miltiorrhiza, Safflower, Cassia twig, and Angelica were identified as the core prescriptions for improving inflammatory indicators. Luteolin was the main active ingredient in the prescription and showed a strong binding energy with TNF and NF-κB. Luteolin exerted anti-inflammatory effects in vitro by reducing inflammatory cytokines in SSc-HDF and inhibiting the activation of TNF/NF-κB. Mechanistically, luteolin inhibited the activation of the TNF/NF-κB pathway in SSc-HDF, as manifested by an increase in extranuclear p-P65 and TNF but a decrease in intranuclear p-P65. Interestingly, the addition of PKM2 augmented the therapeutic function of luteolin against inflammation in SSc-HDF. Our study showed the TCM alleviates the inflammatory response of SSc by inhibiting the activation of the TNF/NF-κB pathway and is an effective therapeutic agent for the treatment of SSc.

There is a close relationship between immune-mediated inflammation and cancer, and there is still controversy over whether rheumatoid arthritis (RA) increases the risk of malignancy. We first used Mendelian randomization (MR) analysis to explore the potential causal relationship between RA and pan-cancer. And verify the effect of immune-mediated inflammation on cancer through intermediate MR analysis. Then we extracted the standardized incidence rate of malignancy in RA patients relative to the general population through large-scale meta-analysis. Finally, we performed pan-cancer analysis on the RA related genes obtained from MR analysis. And perform immune related analysis on key genes to reveal the association between RA and malignancy. The MR analysis demonstrated a negative correlation between RA and pan-cancer (p = 0.008). Autoimmune traits were the main mediating variable for the causal relationship between RA and pan-cancer. Based on the results of the meta-analysis, we validated that RA reduces the risk of developing colorectal cancer (SIR = 0.69, 95% CI 0.53-0.85). Pan-cancer analysis also showed that high expression of RA related genes was negatively correlated with colon adenocarcinoma. IL6R was the gene with the highest correlation among them, and its correlation with immune cells was higher in colorectal cancer than in other malignancy. Our MR study provides evidence that RA was associated with reduced risk of colorectal cancer. This effect is caused by immune-mediated inflammation, with IL6R being a key regulatory gene.

Lysosomes are highly dynamic organelles that maintain cellular homeostasis and regulate fundamental cellular processes by integrating multiple metabolic pathways. Lysosomal ion channels such as TRPML1-3, TPC1/2, ClC6/7, CLN7, and TMEM175 mediate the flux of Ca2+, Cl-, Na+, H+, and K+ across lysosomal membranes in response to osmotic stimulus, nutrient-dependent signals, and cellular stresses. These ion channels serve as the crucial transducers of cell signals and are essential for the regulation of lysosomal biogenesis, motility, membrane contact site formation, and lysosomal homeostasis. In terms of pathophysiology, genetic variations in these channel genes have been associated with the development of lysosomal storage diseases, neurodegenerative diseases, inflammation, and cancer. This review aims to discuss the current understanding of the role of these ion channels in the central nervous system and to assess their potential as drug targets.

Advanced in vivo imaging techniques have facilitated the comprehensive visual exploration of animal biological processes, leading to groundbreaking discoveries such as the glymphatic system. However, current limitations of macroscopic imaging techniques impede the precise investigation of physiological parameters regulating this specialized lymphatic transport system. While NIR-II fluorescence imaging has demonstrated advantages in peripheral lymphatic imaging, there are few reports regarding its utilization in the glymphatic system. To address this, a noninvasive transcranial macroscopic NIR-II fluorescence imaging model is developed using a cyanine dye-protein coupled nanoprobe. NIR-II imaging with high temporal and spatial resolution reveals that hypothermia can increase the glymphatic influx by reducing the flow rate of cerebrospinal fluid. In addition, respiratory rate, respiratory amplitude, and heart rate all play a role in regulating the glymphatic influx. Thus, targeting the glymphatic influx may alter the trajectory of immune inflammation following brain injury, providing therapeutic prospects for treating brain injury with mild hypothermia.

UNASSIGNED: Neutrophil-to-high-density lipoprotein cholesterol ratio (NHR), monocyte-to-high-density lipoprotein cholesterol ratio (MHR), lymphocyte-to-high-density lipoprotein cholesterol ratio (LHR), platelet-to-high-density lipoprotein cholesterol ratio (PHR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) have been identified as immune-inflammatory biomarkers associated with the prognosis of cardiovascular diseases. However, the relationship of these biomarkers with the prognosis of myocardial infarction with non-obstructive coronary arteries (MINOCA) remains unclear.
UNASSIGNED: Patients with MINOCA who underwent coronary angiography at the 920th Hospital of Joint Logistics Support Force were included in our study. Clinical baseline characteristics and laboratory testing data were collected from the hospital record system. The patients were divided into two groups on the basis of major adverse cardiovascular events (MACE) occurrence. Multiple logistic regression analysis was conducted to assess the relationship between NHR, MHR, LHR, PHR, SII, SIRI, AISI, and MACE. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive value of NHR, MHR, LHR, PHR, SII, SIRI, and AISI for MACE in patients with MINOCA. The accuracy of the prediction was indicated by the area under the curve (AUC) value.
UNASSIGNED: The study included 335 patients with MINOCA. (81 in the MACE group and 254 in the No-MACE group). The MACE group had higher levels of NHR, MHR, LHR, PHR, SII, SIRI, and AISI than the No-MACE group. Multiple logistic regression analysis adjusted for confounding factors indicated that the higher levels of NHR, MHR, PHR, SII, SIRI, and AISI were associated with the occurrence of MACE in patients with MINOCA (P < 0.001). The AUC values for NHR, MHR, PHR, SII, SIRI, and AISI were 0.695, 0.747, 0.674, 0.673, 0.688, and 0.676, respectively. The combination of NHR, MHR, PHR, SII, SIRI, and AISI improved the accuracy of predicting MACE in patients with MINOCA (AUC = 0.804).
UNASSIGNED: Higher levels of NHR, MHR, PHR, SII, SIRI, and AISI were associated with the occurrence of MACE, and the combination of NHR, MHR, PHR, SII, SIRI, and AISI improved the accuracy for predicting the incidence of MACE events in patients with MINOCA.

Insomnia is one of the most common accompanying symptoms of depression, with both sharing highly overlapping molecular pathways. The same pathological changes can trigger comorbidity of insomnia and depression, which further forms a vicious cycle with the involvement of more mechanisms and disease progression. Thus, understanding the potential interaction mechanisms between insomnia and depression is critical for clinical diagnosis and treatment. Comorbidity genetic factors, the hypothalamic-pituitary-adrenal axis, along with circadian rhythms of cortisol and the brain reward mechanism, are important ways in contributing to the comorbidity occurrence and development. However, owing to lack of pertinent investigational data, intricate molecular mechanisms necessitate further elaboration. Synaptic plasticity is a solid foundation for neural homeostasis. Pathological alterations of depression and insomnia may perturb the production and release of neurotransmitter, dendritic spine remodeling and elimination, which converges and reflects in aberrant synaptic dynamics. Hence, the introduction of synaptic plasticity research route and the construction of a comprehensive model of depression and insomnia comorbidity can provide new ideas for clinical depression insomnia comorbidity treatment plans.
失眠是抑郁症最常见的伴随症状之一，二者具有高度重合的分子机制。通过相似的病理学改变可以引发失眠和抑郁症的共病，随着病程进展可能形成恶性循环。因此，了解失眠、抑郁症二者潜在交互机制对于临床诊疗十分重要。共病基因、下丘脑-垂体-肾上腺轴与皮质醇昼夜节律、免疫炎症、大脑奖赏机制是参与共病发生、发展的重要途径，但由于缺乏相关研究数据，详细的分子机制有待进一步阐明。突触可塑性是神经功能稳定的坚实基础，抑郁症和失眠的病理改变都可能影响神经递质的产生和释放、树突棘剪切和消除等过程，表现为异常的突触活动。探究突触可塑性研究路径并构建抑郁症和失眠共病发生及影响的综合模型，可为临床抑郁症和失眠共病的治疗方案提供新思路。.

Arsenic can cause immune inflammation, which is the basis of arsenic-induced damage to multiple organs and systems. Forkhead box P3 (Foxp3)-labelled CD4+CD25+ regulatory T cells (Tregs) play an essential role in maintaining immune homeostasis. Nuclear factor-κb (NF-κB) and Interleukin-2 (IL-2) are critical regulators of Foxp3. Rosa roxburghii Tratt (RRT) is an edible medicinal plant with anti-inflammation effects. In this study, a control group (n = 41) and an arseniasis group (n = 209) were recruited, and screened subjects from the arseniasis patients for RRTJ (n = 46) or placebo (n = 43) to explore the possible mechanism by which RRT alleviates immune inflammation. The results indicated that RRTJ can inhibits NF-κB and increases IL-2, and alleviates the Foxp3-mediated Tregs imbalance in the peripheral blood of arseniasis patients. In summary, these findings suggest a novel intervention or therapeutic target for immune inflammation in arseniasis patients and provide new evidence that RRTJ inhibits immune inflammation.
UNASSIGNED:
UNASSIGNED: The online version contains supplementary material available at 10.1007/s10068-023-01384-0.

The prevalence of generalised anxiety disorder (GAD) is high. However, the underlying mechanisms remain elusive. Proteomics techniques can be employed to assess the pathological mechanisms involved in GAD.
Twenty-two drug-naive GAD patients were recruited, their serum samples were used for protein quantification and identified using Tandem Mass Tag and Multiple Reaction Monitoring (MRM). Machine learning models were employed to construct predictive models for disease occurrence by using clinical scores and target proteins as input variables.
A total of 991 proteins were differentially expressed between GAD and healthy participants. Gene Ontology analysis revealed that these proteins were significantly associated with stress response and biological regulation, suggesting a significant implication in anxiety disorders. MRM validation revealed evident disparities in 12 specific proteins. The machine learning model found a set of five proteins accurately predicting the occurrence of the disease at a rate of 87.5%, such as alpha 1B-glycoprotein, complement component 4 A, transferrin, V3-3, and defensin alpha 1. These proteins had a functional association with immune inflammation.
The development of generalised anxiety disorder might be closely linked to the immune inflammatory stress response.

Adhesion G protein-coupled receptor G2 (ADGRG2) is an orphan adhesion G protein-coupled receptor (GPCR), which performs a tumor-promoting role in certain cancers; however, it has not been systematically investigated in hepatocellular carcinoma (HCC). In the current study, we utilized multiple databases to analyze the expression and diagnostic and prognostic value of ADGRG2 in HCC and its correlation with immune infiltration and inflammatory factors. The function and upstream regulatory miRNA of ADGRG2 were validated through qPCR, Western blot, CCK8, wound healing, and dual luciferase assays. It turned out that ADGRG2 was significantly higher in HCC and had a poor survival rate, especially in AFP ≤ 400 ng/mL subgroups. Functional enrichment analysis suggested that ADGRG2 may be involved in cancer pathways and immune-related pathways. In vitro, siRNA-mediated ADGRG2 silencing could inhibit the proliferation and migration of Huh7 and HepG2 cells. There was a highly significant positive correlation between ADGRG2 and neutrophils. Moreover, NET-related genes were filtered and confirmed, such as ENO1 and S100A9. Meanwhile, the high expression of ADGRG2 was also accompanied by the highest number of inflammatory cytokines, chemokines, and chemokine receptors and good immunotherapy efficacy. Finally, AGDGR2 may be sensitive to two drugs (PIK-93 and NPK76-II-72-1) and can be targeted by miR-326. In conclusion, ADGRG2 may serve as a novel biomarker and drug target for HCC diagnosis, immunotherapy, and prognosis and was related to neutrophils and the inflammatory process of liver cancer development.

Posttraumatic epilepsy (PTE) is a severe complication arising from a traumatic brain injury caused by various violent actions on the brain. The underlying mechanisms for the pathogenesis of PTE are complex and have not been fully defined. Approximately, one-third of patients with PTE are resistant to antiepileptic therapy. Recent research evidence has shown that neuroinflammation is critical in the development of PTE. This article reviews the immune-inflammatory mechanisms regarding microglial activation, astrocyte proliferation, inflammatory signaling pathways, chronic neuroinflammation, and intestinal flora. These mechanisms offer novel insights into the pathophysiological mechanisms of PTE and have groundbreaking implications in the prevention and treatment of PTE. Immunoinflammatory cross-talk between glial cells and gut microbiota in posttraumatic epilepsy. This graphical abstract depicts the roles of microglia and astrocytes in posttraumatic epilepsy, highlighting the influence of the gut microbiota on their function. TBI traumatic brain injury, AQP4 aquaporin-4, Kir4.1 inward rectifying K channels.