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Background Previous studies have traditionally attributed the initiation of cancer cells to genetic mutations, considering them as the fundamental drivers of carcinogenesis. However, recent research has shed light on the crucial role of epigenomic alterations in various cell types present within the tumor microenvironment, suggesting their potential contribution to tumor formation and progression. Despite these significant findings, the progress in understanding the epigenetic mechanisms regulating tumor heterogeneity has been impeded over the past few years due to the lack of appropriate technical tools and methodologies. Results The emergence of single-cell sequencing has enhanced our understanding of the epigenetic mechanisms governing tumor heterogeneity by revealing the distinct epigenetic layers of individual cells (chromatin accessibility, DNA/RNA methylation, histone modifications, nucleosome localization) and the diverse omics (transcriptomics, genomics, multi-omics) at the single-cell level. These technologies provide us with new insights into the molecular basis of intratumoral heterogeneity and help uncover key molecular events and driving mechanisms in tumor development. Conclusion This paper provides a comprehensive review of the emerging analytical and experimental approaches of single-cell sequencing in various omics, focusing specifically on epigenomics. These approaches have the potential to capture and integrate multiple dimensions of individual cancer cells, thereby revealing tumor heterogeneity and epigenetic features. Additionally, this paper outlines the future trends of these technologies and their current technical limitations.

Background The age of glioma plays a unique role in prognosis. We hypothesized that age is not positively correlated with survival prognosis and explored its exact relationship. Methods Glioma was identified from the SEER database (between 2000 and 2018). A multivariate Cox proportional regression model and restricted cubic spline (RCS) plot were used to assess the relationship between age and prognosis. Results A total of 66465 patients with glioma were included. Hazard ratios (HR) for ten-year by age: 0–9 years, HR 1.06 (0.93–1.20); 10–19 years: reference; 20–29 years, HR 0.90 (0.82–1.00); 30–39 years, HR 1.14 (1.04–1.25); 40–49 years, HR 2.09 (1.91–2.28); 50–59 years, HR 3.48 (3.19–3.79); 60–69 years, HR 4.91 (4.51–5.35);70–79 years, HR 7.95 (7.29–8.66); 80–84 years, HR 12.85 (11.74–14.06). After adjusting for covariates, the prognosis was not positively correlated with age. The smooth curve of RCS revealed this non-linear relationship: HR increased to 10 years first, decreased to 23 years, reached its lowest point, and became J-shaped. Conclusion The relationship between age and glioma prognosis is non-linear. These results challenge the applicability of current age groupings for gliomas and advocate the consideration of individualized treatment guided by precise age.

Background Infective endocarditis (IE) involving prosthetic valves is a critical cardiac condition that can lead to complications such as structural heart damage, heart failure, and arterial embolism, with a high associated mortality rate. This report describes an uncommon instance of infective endocarditis of a prosthetic aortic valve leading to multiorgan embolism. Case presentation A 52-year-old male with a history of Bentall surgery and prosthetic aortic valve replacement presented with chest pain and dyspnea. Coronary angiography demonstrated blockage of the distal left anterior descending artery, which was addressed with balloon angioplasty. A transesophageal echocardiogram (TEE) detected vegetation on the prosthetic valve, and metagenomic next-generation sequencing of blood confirmed infection with Cardiobacterium hominis. During treatment, he experienced acute ischaemia in the right lower limb necessitating thrombectomy, and MRI disclosed numerous tiny infarct foci in the brain. Following a period of six weeks of antibiotic treatment, the patient was discharged in a better condition. However, the valve dysfunction persisted and regular follow-up was required in order to determine whether to perform a further operation. Conclusion This case underscores the risk of multi-organ embolic consequences in prosthetic valve infective endocarditis, highlighting the necessity for prompt identification, antimicrobial treatment, and surgical intervention where warranted.

Background Ameloblastoma (AM) is the most common benign odontogenic tumor, which is more often detected in the mandible than maxilla, especially the mandibular body and mandibular angle. Pediatric AM is a rare disease, especially in patients aged 10 and younger. Compared with the mainstream osteotomy and reconstructive surgery for adult ameloblastoma, there is more room for discussion in the treatment of pediatric ameloblastoma. The postoperative functional and psychological influence can not be ignored. Especially for children in the period of growth and development, an osteotomy is often challenging to be accepted by their parents. We report two patients with ameloblastoma under 10 years old who are treated with curettage and fenestration, which is a beneficial method for children with ameloblastoma. Case presentation We present two cases of classic ameloblastoma in children. We describe in detail the patients’ characteristics, treatment processes, and follow-up result. The bone formation and reconstruction in the lesion area after fenestration decompression and curettage are recorded at every clinic review. The surgical details and principles of curettage and decompression are also described and discussed. The two patients have good bone shape recovery and no recurrence. Conclusions Children are in the growth and development period and possess an extremely strong ability of bone formation and reconstruction. Based on the principles of minimally invasive and functional preservation, we believe that curettage combined with decompression can be the first choice for treating AM in children, especially for mandibular lesions.

Vascular smooth muscle cell (VSMC) phenotypic switching plays a critical role in the formation of abdominal aortic aneurysms (AAAs). FoxO3a is a key suppressor of VSMC homeostasis. We found that in human and animal AAA tissues, FoxO3a was upregulated, SM22α and α-smooth muscle actin (α-SMA) proteins were downregulated and synthetic phenotypic markers were upregulated, indicating that VSMC phenotypic switching occurred in these diseased tissues. In addition, in cultured VSMCs, significant enhancement of FoxO3a expression was found during angiotensin II (Ang II)-induced VSMC phenotypic switching. In vivo, FoxO3a overexpression in C57BL/6J mice treated with Ang II increased the formation of AAAs, whereas FoxO3a knockdown exerted an inhibitory effect on AAA formation in ApoE −/− mice infused with Ang II. Mechanistically, FoxO3a overexpression significantly inhibited the expression of differentiated smooth muscle cell (SMC) markers, activated autophagy, the essential repressor of VSMC homeostasis, and promoted AAA formation. Our study revealed that FoxO3a promotes VSMC phenotypic switching to accelerate AAA formation through the P62/LC3BII autophagy signaling pathway and that therapeutic approaches that decrease FoxO3a expression may prevent AAA formation.

Background Betel nut chewing plays a role in the pathogenesis of oral submucous fibrosis (OSF) and oral squamous cell carcinoma (OSCC). As the major active ingredient of the betel nut, the effect of arecoline and its underlying mechanism to OSF and OSCC pathogenesis remain unclear. Methods Next-generation sequencing-based transcriptome and dRRBS analysis were performed on OSF and OSCC cells under low-dose arecoline exposure. Functional analyses were performed to compare the different roles of arecoline during OSF and OSCC pathogenesis, and key genes were identified. Results In this study, we identified that low-dose arecoline promoted cell proliferation of both NFs and OSCC cells via the acceleration of cell cycle progression, while high-dose arecoline was cytotoxic to both NFs and OSCC cells. We performed for the first time the transcriptome and methylome landscapes of NFs and OSCC cells under low-dose arecoline exposure. We found distinct transcriptome and methylome profiles mediated by low-dose arecoline in OSF and OSCC cells, as well as specific genes and signaling pathways associated with metabolic disorders induced by low-dose arecoline exposure. Additionally, low-dose arecoline displayed different functions at different stages, participating in the modulation of the extracellular matrix via Wnt signaling in NFs and epigenetic regulation in OSCC cells. After exposure to low-dose arecoline, the node roles of FMOD in NFs and histone gene clusters in OSCC cells were found. Meanwhile, some key methylated genes induced by arecoline were also identified, like PTPRM and FOXD3 in NFs, SALL3 and IRF8 in OSCC cells, indicating early molecular events mediated by arecoline during OSF and OSCC pathogenesis. Conclusions This study elucidated the contribution of low-dose arecoline to OSF and OSCC pathogenesis and identified key molecular events that could be targeted for further functional studies and their potential as biomarkers.

Atrial fibrillation (AF) is a prevalent arrhythmia that requires effective biomarkers and therapeutic targets for clinical management. In recent years, non-coding RNAs (ncRNAs) have emerged as key players in the pathogenesis of AF, particularly through the ceRNA (competitive endogenous RNA) mechanism. By acting as ceRNAs, ncRNAs can competitively bind to miRNAs and modulate the expression of target mRNAs, thereby influencing the biological behavior of AF. The ceRNA axis has shown promise as a diagnostic and prognostic biomarker for AF. This review provides a comprehensive overview of the roles of ncRNAs in the development and progression of AF, highlighting the intricate crosstalk between different ncRNAs in AF pathophysiology. Furthermore, we discuss the potential implications of targeting the circRNA/lncRNA-miRNA-mRNA axis for the diagnosis, prognosis, and therapeutic intervention of AF.

Background The gut microbiome plays an important role in various cardiovascular diseases, such as atherosclerosis and hypertension, which are associated with abdominal aortic aneurysms (AAAs). Methods Here, we used 16S rRNA sequencing to explore gut microbiota in C57BL ApoE −/− mice with AAAs. A mouse model of abdominal aortic aneurysms was induced with angiotensin II (Ang II) (1000 ng/min per kg). On day 28 after the operation, fecal samples were collected and stored at − 80 °C until DNA extraction. We determined the relative abundances of bacterial taxonomic groups using 16S rRNA amplicon metabarcoding, and sequences were analyzed using a combination of mother software and UPARSE. Results We found that the gut microbiome was different between control and AAA mice. The results of correlation analysis between AAA diameter and the gut microbiome as well as LEfSe of the genera Akkermansia, Odoribacter, Helicobacter and Ruminococcus might be important in the progression of AAAs. Conclusions AAA mice is subjected to gut microbial dysbiosis, and gut microbiota might be a potential target for further investigation.

Glioma stem cell (GSC)-derived extracellular vesicles (EVs) can mediate the communication between GSCs and microglia. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression in GSCs, EVs, and supernatant was detected by real-time PCR. The direct targeting between MALAT1 and miR-129-5p, miR-129-5p, and HMGB1 were tested with luciferase reporter analysis. The expression and secretion of interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α were determined in lipopolysaccharide-stimulated microglia or miR-129-5p inhibitor transferred to microglia exposed to GSC EVs or EVs derived from siMALAT1 pre-transferred GSCs. MALAT1 was enriched in GSC EVs compared with GSCs, and up-regulated MALAT1 was also observed in microglia upon GSC EVs incubation. The relative expression and secretion of IL-6, IL-8, and TNF-α in lipopolysaccharide-stimulated microglia were up-regulated in the GSC supernatant group, which could be reversed by dimethyl amiloride (DMA) (EV secretion inhibitor) co-administration or si-MALAT1 pre-transfection of GSCs. Luciferase reporter assay testified the direct binding of MALAT1 and miR-129-5p, miR-129-5p, and HMGB1, and si-MALAT1 could up-regulate miR-129-5p expression and down-regulate HMGB1 expression in microglia cells. The concentration of IL-6, IL-8, and TNF-α in lipopolysaccharide-stimulated microglia exposed to EVs from siMALAT1 transfected GSCs could be up-regulated by miR-129-5p inhibition. EVs lncRNA MALAT1 released from GSCs could modulate the inflammatory response of microglia after lipopolysaccharide stimulation through regulating the miR-129-5p/HMGB1 axis.

The role of promoter methylation in the inactivation of E-cadherin (CDH1) in salivary carcinoma ex pleomorphic adenoma (CXPA) is unknown. The objective of this study was to determine the role and potential clinical implications of CDH1 promoter methylation in salivary CXPA. The CDH1 promoter methylation status was determined by bisulfite sequencing PCR in 37 primary CXPA tissues and 2 CXPA cell lines. E-cadherin expression levels were determined by immunohistochemical analysis of each tumor. E-cadherin protein levels and CDH1 mRNA levels were examined by immunoblotting and quantitative real-time PCR, respectively, in 2 CXPA cell lines. Cells were treated with 5-Aza-dC or TGF-β1 to test the influence of promoter methylation on CDH1 mRNA and protein expression. Associations between CDH1 molecular alterations and patients' clinicopathologic characteristics and prognosis were statistically evaluated. CDH1 promoter hypermethylation was detected in 21 of 37 tumors (56.76%). Of these 37 tumors, 13 tumors (35.14%) showed low E-cadherin expression. Tumors that had CDH1 promoter methylation had a histological tendency toward luminal differentiation (P=0.004), high tumor grade (P=0.005), high T stage (P=0.024) and high TNM stage (P=0.038) compared with tumors that did not. The two CXPA cell lines exhibited an inverse relationship between CDH1 promoter methylation status and CDH1 mRNA and protein expression. Treatment of the hypermethylated cell line with 5-Aza-dC restored CDH1 mRNA and E-cadherin protein expression. The induction of hypermethylation by TGF-β1 resulted in the repression of CDH1 mRNA and protein expression. CDH1 is commonly silenced in CXPA through promoter methylation. CDH1 methylation is closely related to tumor cell differentiation, histological grade, lymph node metastasis and advanced TNM stage, indicating that CDH1 methylation may play a role in the initiation and progression of CXPA.