Peri-implant diseases are characterized by the resorption of hard tissue and the inflammation of soft tissue. Epigenetics refers to alterations in the expression of genes that are not encoded in the DNA sequence, influencing diverse physiological activities, including immune response, inflammation, and bone metabolism. Epigenetic modifications can lead to tissue-specific gene expression variations among individuals and may initiate or exacerbate inflammation and disease predisposition. However, the impact of these factors on peri-implantitis remains inconclusive. To address this gap, we conducted a comprehensive review to investigate the associations between epigenetic mechanisms and peri-implantitis, specifically focusing on DNA methylation and microRNAs (miRNAs or miRs). We searched for relevant literature on PubMed, Web of Science, Scopus, and Google Scholar with keywords including "epigenetics," "peri-implantitis," "DNA methylation," and "microRNA." DNA methylation and miRNAs present a dynamic epigenetic mechanism operating around implants. Epigenetic modifications of genes related to inflammation and osteogenesis provide a new perspective for understanding how local and environmental factors influence the pathogenesis of peri-implantitis. In addition, we assessed the potential application of DNA methylation and miRNAs in the prevention, diagnosis, and treatment of peri-implantitis, aiming to provide a foundation for future studies to explore potential therapeutic targets and develop more effective management strategies for this condition. These findings also have broader implications for understanding the pathogenesis of other inflammation-related oral diseases like periodontitis.
Peri-Implantitis/genetics* ; Humans ; Epigenesis, Genetic ; DNA Methylation ; MicroRNAs/genetics*

OBJECTIVE To investigate the mechanism of anti-colorectal cancer growth and metastasis-related effects of Astraga-lus mongholicus Bunge-Curcuma aromatica-Paridis Rhizoma(Qi-Zhu-Zao)pairing through PERK/eIF2α/ATF4 signaling pathway mediating endoplasmic reticulum stress.METHODS Twenty-four BALB/c male mice were randomly divided into sham-operated group,model group,5-FU(5-fluorouracil)group(25 mg·kg-1),and Qi-Zhu-Zao high dose group(5.85 g·kg-1),Qi-Zhu-Zao low dose group(2.925 g·kg-1)(n=6)to construct a mouse model of colorectal cancer in situ transplantation tumor,and the inter-vention effect of Qi-Zhu-Zao combination on tumor growth was assessed by the change of tumor volume size after 15 days of administra-tion;the intervention effect of Qi-Zhu-Zao combination on tumor growth was assessed by H&E.Pathological staining was used to eval-uate the effect of Qi-Zhu-Zao combination on the liver and tumor tissues of mice.The changes of MDA,SOD and GSH-Px levels were detected by enzyme-linked immunosorbent assay(ELISA);the expression of PERK/eIF2α/ATF4 signaling pathway and EMT-related proteins were detected by protein immunoblotting(Western blot).RESULTS Compared with the model group,the tumor volume was significantly reduced(P＜0.000 1),liver and spleen metastases were less pronounced in the Qi-Zhu-Zao high-dose group,and his-topathological staining results of liver tissue and tumor produced changes in oxidative stress indicators SOD,MDA,and GSH-Px,up-regulation of ER stress-related proteins p-PERK,p-IF2α,and ATF4,etc.,upregulated the protein expression levels of E-Cadherin,downregulated N-Cadherin,Vimentin,and Snail,and inhibited the EMT process(P＜0.01 or P＜0.05).CONCLUSION In this paper,we investigated the regulatory mechanism related to the inhibition of colorectal cancer growth and metastasis by the combination of Qi-Zhu-Zao trigonal medicine,and demonstrated that it may inhibit the growth and metastasis of colorectal cancer by activating the PERK/eIF2α/ATF4 pathway to induce sustained ER stress and affect the EMT process of colorectal cancer.

Dysbiosis can cause microenvironmental dysregulation, which can further lead to local or systemic diseases, such as caries, inflammatory bowel disease, obesity, and diabetes. Dysbiosis is primarily manifested as the disturbance of metabolic processes and products. Arginine plays an important role in various metabolic processes and homeostasis of the microbial flora and the host. This study aims to explore the potential therapeutic value of arginine and its metabolism and homeostasis regulation in diseases associated with oral-intestinal dysbiosis. Host and microbial homeostasis can be restored by regulating the composition or function of host microbiota, and arginine has been found to exhibit significant clinical potential in restoring host microbiota composition and function. For example, arginine can reduce the risk of caries by regulating the relative abundance of Streptococcus mutans and Streptococcus sanguineus. Additionally, arginine metabolism may play a therapeutic role in inflammatory bowel disease and obesity by regulating the relative abundance of Firmicutes and Bacteroidetes. In addition, supplementation of arginine and its metabolite polyamine has clinical prospects in the treatment of diabetic patients with ketoacidosis. Although studies have demonstrated the therapeutic role of arginine in oral, intestinal, and metabolism-related diseases, the specific mechanism is yet to be explored. In addition, further research is required to determine the optimal clinical dosage of arginine that can maintain microbiota homeostasis without causing any side effects.

As an important concept in Chinese medicine theory， "qi sinking" is the inheritance and extension of the thought core of sinking of qi in whole body. This article explored the concept of sinking of pectoral qi， center qi， and kidney qi in the theory of qi sinking， and believed that sinking of pectoral qi， stagnation and sinking of center qi， deficiency and sinking of kidney qi were the core pathogenesis of postoperative injury in malignant tumours. Anchored to the method of reinforcing healthy qi and lifting the sunken， this article recommended to identify pattern and treat by guiding supplement and lifting the sunken. For lung gold impairment， heart yang depletion， and pectoral qi sinking， the treatment is to warm and supplement heart and lung， lift pectoral qi， and restore the respiratory function by modified Shengxian Decoction （升陷汤） plus Guizhi Decoction （桂枝汤）； for spleen depletion and pathways blockage， liver failing to act freely， and center qi stagnation and sinking， the treatment is to warm and supplement center qi， raise yang and lift the sunken， and restore the digestive function by modified Buzhong Yiqi Decoction （补中益气汤）； for source exhausted and essence deficiency， liver qi hiding， and kidney qi deficiency to inward invasion， the treatment is to nourish the kidney and astringe the liver， consolidate the original qi and lift qi， improve the pelvic floor dysfunction， and protect the kidney function by modified Liuwei Dihuang Pill （六味地黄丸） plus Shengma Chaihu Decoction （升麻柴胡汤）. Modification need base on different disease patterns and stages， and new ideas for postoperative traditional Chinese medicine treatment and rehabilitation of malignant tumours were provided.

Objectives:This study aims to explore the effects of pioglitazone on the attenuation of ventricular arrhythmias(VAs)induced by β1-adrenergic receptor autoantibodies(β1AAb)and its potential mechanisms. Methods:48 SD rats were uniformly randomly divided into four groups using number table:control group received vehicle injection,β1AAb group received back multi-point injection of β1AR-ECLⅡ antigen peptide with adjuvant,2 mg/(kg·time),pioglitazone group received pioglitazone gavage for 2 weeks after 8 weeks of immunization,4 mg/(kg·d),and GW9662 group received pioglitazone+GW9662 intraperitoneal injection for 2 weeks after 8 weeks of immunization,1 mg/(kg·d).Powerlab recorded electrocardiograms and blood collection every 2 weeks.Baseline and week 10 echocardiography were recorded,followed by electrophysiology,histopathology,immunohistochemical staining,and electron microscopy examination after 10 weeks. Results:Compared to control group,β1AAb group showed a higher incidence of ventricular arrhythmias,shorter ventricular effective refractory period(VERP),longer action-recovery interval(ARI),lower left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS),lower positive staining area ratio of glucose transporter 1(GLUT1)and carnitine palmitoyltransferase 1a(CPT1a),all P＜0.05.Mitochondrial morphology abnormalities and network damage were also significantly observed(P＜0.05).In contrast to β1AAb group,pioglitazone group showed a reduced incidence of ventricular arrhythmias,prolonged VERP,shortened ARI,recovered LVEF and LVFS,increased the positive staining area ratio of GLUT1 and CPT1a,all P＜0.05.Improvement was observed in mitochondrial morphology abnormalities and network damage(P＜0.05).Compared to pioglitazone group,GW9662 group exhibited a higher incidence of ventricular arrhythmias,shorter VERP,and longer ARI,lower LVEF and LVFS,lower positive staining area ratio of GLUT1 and CPT1a,all P＜0.05.Mitochondrial morphology abnormalities and network damage did not recover(P＜0.05). Conclusions:Pioglitazone can reduce VAs induced by β1AAb,improve ventricular electrical conduction and activation recovery time heterogeneity,and mitigate ventricular remodeling caused by β1AAb at the tissue pathology level,accompanied by upregulation of ventricular cardiomyocyte glucose and lipid transport channel proteins and repair of damaged mitochondrial networks.

Spinal cord injury (SCI) represents a complex pathophysiological process involving the interaction of multiple cell types. Conventional sequencing methods can only detect the average gene expression level of the damaged local cell populations, which is difficult to reflect its heterogeneity. Therefore, new technologies are needed to reveal the intercellular heterogeneity and the complex intercellular interactions of the damaged lesions. The single-cell RNA sequencing (scRNA-seq) technique facilitates high-resolution profiling of gene expression at the single-cell level, providing insights into cellular heterogeneity and function, potential molecular pathways, cell fate transitions, and the intercellular interactions pertinent to disease progression. This technology generates valuable gene expression data that support both basic and translational research efforts aiming at the identification of therapeutic targets for intervention. The scRNA-seq technique and its multifaceted application in the local immune microenvironment of injury after SCI were discussed, which will contribute to a more comprehensive understanding of the pathophysiological processes in the immune microenvironment of SCI.
Spinal Cord Injuries/genetics* ; Humans ; Single-Cell Analysis/methods* ; Sequence Analysis, RNA/methods* ; Animals ; Gene Expression Profiling/methods* ; Cellular Microenvironment/genetics*

An effective therapeutic regimen for hepatic fibrosis requires a deep understanding of the pathogenesis mechanism. Hepatic fibrosis is characterized by activated hepatic stellate cells (aHSCs) with an excessive production of extracellular matrix. Although promoted activation of HSCs by M2 macrophages has been demonstrated, the molecular mechanism involved remains ambiguous. Herein, we propose that the vitamin D receptor (VDR) involved in macrophage polarization may regulate the communication between macrophages and HSCs by changing the functions of exosomes. We confirm that activating the VDR can inhibit the effect of M2 macrophages on HSC activation. The exosomes derived from M2 macrophages can promote HSC activation, while stimulating VDR alters the protein profiles and reverses their roles in M2 macrophage exosomes. Smooth muscle cell-associated protein 5 (SMAP-5) was found to be the key effector protein in promoting HSC activation by regulating autophagy flux. Building on these results, we show that a combined treatment of a VDR agonist and a macrophage-targeted exosomal secretion inhibitor achieves an excellent anti-hepatic fibrosis effect. In this study, we aim to elucidate the association between VDR and macrophages in HSC activation. The results contribute to our understanding of the pathogenesis mechanism of hepatic fibrosis, and provide potential therapeutic targets for its treatment.
Humans ; Hepatic Stellate Cells/pathology* ; Receptors, Calcitriol ; Liver Cirrhosis/pathology* ; Macrophages/metabolism*

BACKGROUND: Intensive systolic blood pressure (SBP) control improved outcomes in the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Whether baseline serum lipid parameters influence the benefits of intensive SBP control is unclear. METHODS: The STEP trial was a randomized controlled trial that compared the effects of intensive (SBP target of 110 to <130 mmHg) and standard (SBP target of 130 to <150 mmHg) SBP control in Chinese patients aged 60 to 80 years with hypertension. The primary outcome was a composite of cardiovascular disease events. A total of 8283 participants from the STEP study were included in this post hoc analysis to examine whether the effects of the SBP intervention differed by baseline low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) concentrations. RESULTS: Regardless of the randomized SBP intervention, baseline LDL-C and non-HDL-C concentrations had a J-shaped association with the hazard of the primary outcome. However, the effects of the intensive SBP intervention on the primary outcome were not influenced by baseline LDL-C level ( P for interaction = 0.80) and non-HDL-C level ( P for interaction = 0.95). Adjusted subgroup analysis using tertiles in LDL-C1 (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.52-1.13; P = 0.18), LDL-C2 (HR, 0.81; 95% CI, 0.55-1.20; P = 0.29), and LDL-C3 (HR, 0.68; 95% CI, 0.47-0.98; P = 0.04) was provided, with an interaction P value of 0.49. Similar results were showed in non-HDL-C1 (HR, 0.87; 95% CI, 0.59-1.29; P = 0.49), non-HDL-C2 (HR, 0.70; 95% CI, 0.48-1.04; P = 0.08), and non-HDL-C3 (HR, 0.67; 95% CI, 0.47-0.95; P = 0.03), with an interaction P -value of 0.47. CONCLUSION: High baseline serum LDL-C and non-HDL-C concentrations were associated with increased risk of primary cardiovascular disease outcome, but there was no evidence that the benefit of the intensive SBP control differed by baseline LDL-C and non-HDL-C concentrations. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT03015311.
Aged ; Humans ; Cardiovascular Diseases ; Blood Pressure/physiology* ; Cholesterol, LDL ; Hypertension ; Cholesterol ; Risk Factors

BACKGROUND: Sarcopenia is an age-related progressive skeletal muscle disorder involving the loss of muscle mass or strength and physiological function. Efficient and precise AI algorithms may play a significant role in the diagnosis of sarcopenia. In this study, we aimed to develop a machine learning model for sarcopenia diagnosis using clinical characteristics and laboratory indicators of aging cohorts. METHODS: We developed models of sarcopenia using the baseline data from the West China Health and Aging Trend (WCHAT) study. For external validation, we used the Xiamen Aging Trend (XMAT) cohort. We compared the support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGB), and Wide and Deep (W&D) models. The area under the receiver operating curve (AUC) and accuracy (ACC) were used to evaluate the diagnostic efficiency of the models. RESULTS: The WCHAT cohort, which included a total of 4057 participants for the training and testing datasets, and the XMAT cohort, which consisted of 553 participants for the external validation dataset, were enrolled in this study. Among the four models, W&D had the best performance (AUC = 0.916 ± 0.006, ACC = 0.882 ± 0.006), followed by SVM (AUC =0.907 ± 0.004, ACC = 0.877 ± 0.006), XGB (AUC = 0.877 ± 0.005, ACC = 0.868 ± 0.005), and RF (AUC = 0.843 ± 0.031, ACC = 0.836 ± 0.024) in the training dataset. Meanwhile, in the testing dataset, the diagnostic efficiency of the models from large to small was W&D (AUC = 0.881, ACC = 0.862), XGB (AUC = 0.858, ACC = 0.861), RF (AUC = 0.843, ACC = 0.836), and SVM (AUC = 0.829, ACC = 0.857). In the external validation dataset, the performance of W&D (AUC = 0.970, ACC = 0.911) was the best among the four models, followed by RF (AUC = 0.830, ACC = 0.769), SVM (AUC = 0.766, ACC = 0.738), and XGB (AUC = 0.722, ACC = 0.749). CONCLUSIONS: The W&D model not only had excellent diagnostic performance for sarcopenia but also showed good economic efficiency and timeliness. It could be widely used in primary health care institutions or developing areas with an aging population. TRIAL REGISTRATION Chictr.org, ChiCTR 1800018895.
Humans ; Aged ; Sarcopenia/diagnosis* ; Deep Learning ; Aging ; Algorithms ; Biomarkers

Cell Cycle Checkpoints/genetics* ; Checkpoint Kinase 1/metabolism* ; Heterozygote ; Humans ; Mitosis/genetics* ; Mutation ; Zygote/metabolism*