The immunosuppressive tumor microenvironment (TME) remains a primary barrier to effective immunotherapy. Tumor-associated neutrophils (TANs) are key contributors to this immunosuppressive landscape; however, the mechanisms governing their recruitment and infiltration into tumor tissues remain poorly understood. In this study, we unravel a pro-tumorigenic role of thrombospondin-1 (THBS1) in gastric cancer (GC) mediated by TAN recruitment. By integrating single-cell RNA sequencing with immunohistochemical analyses, we demonstrated that THBS1 is predominantly expressed in vascular smooth muscle cell (VSMC)-like cancer-associated fibroblast (CAF), with lower expression observed in malignant epithelial cells. Notably, THBS1-expressing CAFs are significantly expanded in GC tissues. Accordingly, THBS1 is upregulated in GC, and its overexpression is clinically associated with malignant progression and poor prognosis. Genetic depletion of THBS1 in CAFs markedly suppressed GC progression both in vitro and in vivo. Furthermore, deconvolution analysis, patient-derived xenograft (PDX) models, and multiplex immunofluorescence (mIHC) revealed a pronounced spatial co-localization between THBS1-positive CAFs and TANs within GC tissues. TAN infiltration was significantly elevated in GC and positively correlated with THBS1 expression levels and adverse survival outcomes. Critically, neutralizing THBS1 with monoclonal antibodies or specifically knocking down THBS1 in CAFs dramatically reduced TAN infiltration in both PDX and nude mouse xenograft models. Mechanistically, THBS1 knockdown in CAFs impaired the autocrine production and secretion of key neutrophil-attracting chemokines, including CXCL1, CXCL5, and CXCL6. In summary, our findings underscore the significance of SMC-like CAF-derived THBS1 as a critical molecular mediator in the dynamic interplay between CAFs and TANs, ultimately driving GC progression.

Background Current evidence on the relationship between periodontitis and hypertension remains inconsistent. We performed a two-sample univariable and multivariable Mendelian randomization (MR) study to investigate the causal relationships between periodontitis and elevated blood pressure as well as hypertension. Methods We selected single nucleotide polymorphisms (SNPs) with strong (P < 5×10-8) or moderate (P < 5×10-6) evidence of association with periodontitis from genome-wide association studies. Summary-level genetic data for elevated blood pressure and hypertension were obtained from the International Consortium of Blood Pressure Genome-Wide Association Studies and the UK Biobank. Primary analyses used SNPs strongly associated with periodontitis, whereas secondary analyses extended this set to include SNPs with moderate association. Fixed- and random-effects inverse variance weighted (IVW) methods were employed to assess the causal associations, and multivariable MR was performed to verify the robustness of results. MR estimates were calculated as coefficients (β) with 95% confidence intervals (CIs) for continuous blood pressure outcomes, and as odds ratios (ORs) with 95% CIs for the binary hypertension outcome. Results In primary analyses, genetic liability to periodontitis showed a nominally significant association with a 0.105mmHg increase in systolic blood pressure (95% CI: 0.009, 0.200; P = 0.032), which indicated a potential association but does not reach the Bonferroni-corrected significance threshold (P < 0.008). No robust causal associations were observed for diastolic blood pressure (β = 0.049, 95% CI: –0.006, 0.104; P = 0.083) or pulse pressure (β = 0.058, 95% CI: –0.007, 0.123; P = 0.079). Secondary analyses incorporating both strongly and moderately associated SNPs yielded no evidence supporting a causal effect of genetic liability to periodontitis on elevated blood pressure risk. In addition, a genetic liability to periodontitis was not associated with increased risk of hypertension (including essential hypertension, secondary hypertension, and total hypertension) in both primary and secondary analyses. These null associations for elevated blood pressure and hypertension remained after adjustment for smoking, alcohol consumption and body mass index separately or together in the multivariable MR analysis. Conclusions The results suggested that genetic liability to periodontitis was not significantly associated with the risk of elevated blood pressure and hypertension after multiple testing corrections. Large-scale prospective observations and multi-omics studies are warranted to further clarify the associations between periodontitis and blood pressure-related disorders.

Objective To analyze the global disease burden and its changing trend of severe periodontitis from 1990 to 2021. Methods Data from the Global Burden of Disease Study 2021 (GBD 2021) database were obtained to analyze the incidence, prevalence, year lived with disability (YLD) of severe periodontitis by regional, socio-demographic index (SDI), age and sex group from 1990 to 2021. The change of age-standardized rate was estimated by calculating the estimated annual percentage change. Results In 2021, the global age-standardized incidence rate (ASIR) of severe periodontitis was 1,069.44 per 100,000, the age-standardized prevalence rate (ASPR) was 12,498.3 per 100,000, and the age-standardized YLD rate (ASYR) was 80.89 per 100,000 person years. From 1990 to 2021, there was no significant changing trend in the global ASIR [EAPC=0.03%, 95%CI (-0.04%, 0.09%)], ASPR [EAPC=0.08%, 95%CI (-0.02%, 0.18%)], and ASYR [EAPC=0.08%, 95%CI (-0.02%, 0.17%)] of severe periodontitis. The relatively high ASIR, ASPR, and ASYR were recorded in South-East Asia Region, Eastern Mediterranean Region, and Region of the Americas in 2021, respectively. ASIR, ASPR, and ASYR for severe periodontitis were higher in regions with lower SDI. In 2021, the global incidence, prevalence, and YLD rate of severe periodontitis increased with age in the 15-54 age group. The incidence rate was higher in men than in women in the 15-49 age group, and the prevalence and YLD rate were higher in men across all age groups. Conclusion The global burden of severe periodontitis varies across geographic regions, levels of socioeconomic development, sex and age. In the future, appropriate prevention and treatment strategies should be developed for low-income areas, young men and the elderly.

Helicobacter pylori (Hp.) infection is one of the high-risk factors for gastric carcinogenesis (GC). However, the underlying mechanism remains largely unclear. In this study, we uncover an essential role of Hp. infection in mediating tumor suppressor gene silencing in gastric epithelial cells through promoter DNA hypermethylation. Hepatocyte nuclear factor HNF4A was downregulated in GC and predicted poor survival. The in vitro and in vivo assays together confirmed that HNF4A plays a tumor suppressive role in GC. Single-cell analysis showed that HNF4A was selectively expressed in gastric epithelial cells. Besides, the reduced HNF4A expression in GC was due to promoter DNA hypermethylation. More importantly, we have provided strong evidence that Hp. infection causes HNF4A down-regulation by hypermethylation of its gene promoter. Meanwhile, silencing of HNF4A resulted in loss of epithelial polarity and activation of TGFβ-induced EMT signaling in gastric epithelial cells by transcriptionally regulating the expression of downstream target genes. In addition, the rescue assays indicated that Hp. infection activated EMT signaling of gastric epithelial cells in a HNF4A-dependent manner, thereby driving gastric tumorigenesis and metastasis. In conclusion, HNF4A is a tumor suppressor gene in GC. Hp. infection causes silence of the HNF4A gene by hypermethylation of its promoter, which then disrupts epithelial polarity and induces EMT signaling in gastric epithelial cells, thereby driving gastric tumorigenesis and metastasis.

A method for analyzing tumor evolution based on bulk RNA-sequencing data has not been reported yet. The epithelial–mesenchymal transition (EMT) is an evolutionarily conserved cellular program with high heterogeneity and plasticity. In this study, we proposed an EMT heterogeneity-based molecular typing (EHBMT) method to visualize cancer evolution and guide personalized medicine. Multiplex immunohistochemical assay and single-cell analysis were performed to confirm the feasibility of this method. EHBMT divided gastric (cancer) tissues into an epithelial phenotype cluster (EPC), hybrid epithelial–mesenchymal phenotype cluster (HPC) and mesenchymal phenotype cluster (MPC). Patients with gastric cancer with different EHBMT subtypes possessed distinct clinical features, molecular characteristics and prognostic outcomes. Furthermore, the proliferation ability of EPC, HPC and MPC subtypes decreases sequentially. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analysis showed that HPC subtypes are associated with inflammation and immune activation. More importantly, EHBMT discovered a sharp increase in the proportion of the HPC subtype during gastric cancer evolution. Traceability analysis indicated that the surge in HPC in gastric cancer was due to the transition from approximately 70–80 Cancer development is a complex process with many differences between patients and even within a single tumor. Here researchers focused on a process called the epithelial–mesenchymal transition (EMT), which helps cancer cells spread. They developed a method to classify stomach cancer based on EMT differences using data from various sources, including RNA sequencing. This method divides cancer into three types: epithelial, hybrid and mesenchymal, each with different characteristics and outcomes. The study found that the hybrid type is more common in cancerous tissues than in normal ones. This suggests that changes in EMT are linked to cancer progression. The researchers used advanced techniques such as single-cell analysis and immunohistochemistry (a method to visualize proteins in tissues) to confirm their findings. They concluded that understanding the EMT can help predict cancer behavior and guide treatment decisions. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.

The vast majority of lncRNAs have low expression abundance, which greatly limits their functional range and impact. As a high expression abundance lncRNA, FGD5-AS1’s non-ceRNA biological function in cancer is unclear. RNA-seq studies and chromatin immunoprecipitation (Chip) assays were performed to identify ZEB1-regulated lncRNAs. RNA sequencing, RNA pulldown, RNA Immunoprecipitation assays, and rescue assays were conducted to explore the molecular mechanisms of FGD5-AS1 in GC. As one of the most abundant lncRNAs in cells, FGD5-AS1 has been shown to be transcriptionally activated by ZEB1, thus closely related to epithelial-mesenchymal transition (EMT) signaling. Clinical analysis showed that FGD5-AS1 overexpression was clinically associated with lymph node metastasis, and predicted poor survival in GC. Loss-of-function studies confirmed that FGD5-AS1 knockdown inhibited GC proliferation and induced cisplatin chemosensibility, cell senescence, and DNA damage in GC cells. Mechanismically, FGD5-AS1 is a YBX1-binding lncRNA due to its mRNA contains three adjacent structural motifs (UAAUCCCA, ACCAGCCU, and CAGUGAGC) that can be recognized and bound by YBX1. And this RNA-protein interaction prolonged the half-life of the YBX1 protein in GC. Additionally, a rescue assay showed that FGD5-AS1 promotes GC by repressing cell senescence and ROS production via YBX1. FGD5-AS1 is a cellular high-abundant lncRNA that is transcriptionally regulated by ZEB1. FGD5-AS1 overexpression promoted GC progression by inhibiting cell senescence and ROS production through binding and stabilizing the YBX1 protein. FGD5-AS1 is an EMT-related, cellularly abundant lncRNA. The expression of FGD5-AS1 is directly regulated by the transcription factor ZEB1. FGD5-AS1 overexpression was clinically associated with lymph node metastasis and a poor prognosis in GC. Knockdown of FGD5-AS1 causes senescence-associated secretory phenotypes, DNA damage, cisplatin chemosensibility, and growth inhibition in GC cells. FGD5-AS1 prolongs the half-life of the YBX1 protein by RNA-protein interaction. The UAAUCCCA, ACCAGCCU, and CAGUGAGC linear 8-mer motifs in the FGD5-AS1 transcript mediate the interaction between YBX1 and FGD5-AS1. FGD5-AS1 promotes GC proliferation by inhibiting cell senescence and ROS production in a YBX1-dependent manner.

BackgroundCancer/testis antigens (CTAs), also known as tumor-specific antigens (TSAs) are specifically expressed in cancer cells and exhibit high immunogenicity, making them promising targets for immunotherapy and cancer vaccines.MethodsA new integrated high-throughput screening methodology for CTAs was proposed in this study through combining DNA methylation and RNA sequencing data. Briefly, the genes with increased transcript level and decreased DNA methylation were identified by multi-omics analysis. RNA sequencing studies in cell lines exposed to DNA methyltransferase (DNMT) inhibitors were performed to validate the inherent causal relationship between DNA hypomethylation and gene expression upregulation.ResultsWe proposed a new integrated high-throughput screening methodology for identification of CTAs using multi-omics analysis. In addition, we tested the feasibility of this method using gastric cancer (GC) as an example. In GC, we identified over 2000 primary candidate CTAs and ultimately identified 20 CTAs with significant tissue-specificity, including a testis-specific serine protease TESSP1/PRSS41. Integrated analysis confirmed that PRSS41 expression was reactivated in gastrointestinal cancers by promoter DNA hypomethylation at the CpG site (cg08104780). Additionally, DNA hypomethylation of PRSS41 predicted a poor prognosis in GC.ConclusionWe propose a new high-throughput screening method for the identification of CTAs in cancer and validate its effectiveness. Our work emphasizes that serine protease PRSS41 is a novel TSA that is reactivated in GC due to promoter DNA hypomethylation.

Transforming growth factor beta (TGFβ) signaling plays a critical role in tumorigenesis and metastasis. However, little is known about the biological function of TGFbeta-induced lncRNA in cancer. In this study, we discovered a novel TGFbeta-induced lncRNA, termed TGILR, whose function in cancer remains unknown to date. TGILR expression was directly activated by the canonical TGFbeta/SMAD3 signaling axis, and this activation is highly conserved in cancer. Clinical analysis showed that TGILR overexpression showed a significant correlation with lymph node metastasis and poor survival and was an independent prognostic factor in gastric cancer (GC). Depletion of TGILR caused an obvious inhibitory effect on GC cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) in vitro and in vivo. More importantly, we demonstrated that TGFbeta signaling in GC was overactivated due to cancer-associated fibroblast (CAF) infiltration. Mechanistically, increased level of CAF-secreted TGFbeta activates TGFbeta signaling, leading to TGILR overexpression in GC cells. Meanwhile, TGILR overexpression inhibited the microRNA biogenesis of miR-1306 and miR-33a by interacting with TARBP2 and reducing its protein stability, thereby promoting GC progression via TCF4-mediated EMT signaling. In conclusion, CAF infiltration drives GC metastasis and EMT signaling through activating TGFbeta/TGILR axis. Targeted blocking of CAF-derived TGFbeta should be a promising anticancer strategy in GC.

Background:We analysed the cancer burden among elderly Chinese people over the age of 55 years and compared them to USA and Western Europe to explore the cancer model in China. Methods:We retrieved data on 29 cancers with 34 risk factors from the 2019 Global Burden of Disease database to evaluate the cancer burden in Chinese elderly individuals aged 55 years and older. We then used the age-standardised incidence rate (ASIR), age-standardised death rate (ASDR), age-standardised disability-adjusted life year (DALY) rate, and average annual percentage change (AAPC) to compare the characteristics and change trend of cancers among China, USA, and Western Europe. Results:In 2019, the number of incident cases of 29 cancers among people aged 55 years and above in China increased more than 3-fold compared to 1990, while the number of deaths and DALYs approximately doubled. We also found that the cancer population in China was ageing; meanwhile, the cancer burden became significantly higher for men than for women, and the gap between men and women had widened. Cancers with the highest cancer DALYs were lung cancer (13 444 500; 95% uncertainty interval (UI) = 11 307 100, 15 853 700), stomach cancer (7 303 900; 95% UI = 6 094 600, 8 586 500), oesophageal cancer (4 633 500; 95% UI = 3 642 500, 5 601 200), colon and rectum cancer (4 386 500; 95% UI = 3 769 500, 5 067 200), liver cancer (2 915 100, 95% UI = 2 456 300, 3 463 900), and pancreatic cancer (2 028 400; 95% UI = 1 725 000, 2 354 900). Compared with 1990, the DALY rate and incidence rate of stomach cancer, oesophageal cancer, and liver cancer had markedly decreased. The DALY rate and incidence rate of lung, colon, rectum, and pancreatic cancer had increased significantly, as did the incidence rate of breast cancer in women. Smoking and diet were the top two cancer risk factors, and the impact of ambient particulate matter pollution on cancer increased each year. The overall 29 cancers age-standardised DALY rate and ASDR in China, USA, and Western Europe were similar, and all showed downward trend in the past 30 years. Compared with the USA and Western Europe, the age-standardised DALY rate of liver, nasopharyngeal, oesophageal, stomach, and cervical cancers in China was more prominent. The age-standardised DALY rate of lung cancer and colon and rectum cancer decreased annually in Western Europe and the USA, but increased in China. Conclusions:Over the past 30 years, China had made progress in controlling stomach, oesophageal, and liver cancer. However, lung, colon, rectum, pancreatic, and breast cancers had become more prevalent, having risen alongside economic development. The risks of smoking and dietary were major issues that need to be addressed urgently. The cancer situation in China remains serious; future cancer prevention efforts need to balance economic development with people's physical health, identify key groups, improve the health environment of residents and guide them to live a healthy life, and expand the scope of cancer screening.

Increasing evidence suggests a close association between endoplasmic-reticulum (ER) stress and ferroptosis. Receptor accessory protein 6 (REEP6) is known to play a crucial role in maintaining ER homeostasis. However, its involvement in ferroptosis remains unknown. In this study, we found that REEP6 was overexpressed, and its overexpression showed a significant association with tumor size and poor survival in OSCC patients. Besides, in vitro and in vivo assays together showed that REEP6 plays an oncogenic role in OSCC progression. The GO/KEGG, and GSEA analysis showed that REEP6 overexpression leads to the inactivation of ferroptosis signaling in OSCC. Moreover, REEP6 overexpression conferred resistance to RSL3, a ferroptosis inducer, whereas REEP6 knockdown sensitized OSCC cells to RSL3. Overexpression of REEP6 decrease the accumulation of iron ions, ROS production, but increase the number of mitochondrial cristae in OSCC cells. More importantly, we confirmed that REEP6 inhibited ferroptosis in OSCC cells by maintaining ER homeostasis via regulating ACSL4 expression. In addition, we identified promoter DNA hypomethylation as the underlying cause of REEP6 overexpression in OSCC. Taken together, REEP6 acts as a novel suppressor of ferroptosis, with its overexpression driven by promoter hypomethylation contributing to OSCC progression by ER stress-mediated ferroptosis via ACSL4.

PurposeThe primary cause of pulp and periapical diseases is the invasion of bacteria into the root canal, which results from the continuous destruction of dental hard tissues. Effective management of infections during root canal therapy necessitates effectively irrigation. This study aims to investigate the effects of two antimicrobial peptides (AMPs), buCaTHL4B and Im-4, on root canal biofilms in vitro.MethodsTwo-species biofilms (Enterococcus faecalis and Fusobacterium nucleatum) were selected and anaerobically cultivated. The following treatments were applied: 10 μg/mL buCaTHL4B, 10 μg/mL Im-4, 5 μg/mL buCaTHL4B, 5 μg/mL Im-4, 1 μg/mL buCaTHL4B, 1 μg/mL Im-4, 1% NaOCl, and sterile water. Each group was treated for 3 min. Subsequently, the two strains were co-cultured with 10 μg/mL buCaTHL4B, 10 μg/mL Im-4, 1% NaOCl, and sterile water for 24, 48, and 72 h. The biofilms were examined using confocal laser scanning microscopy (CLSM) with fluorescent staining, and the percentages of dead bacteria were calculated. Quantitative real-time PCR (qRT-PCR) was employed to assess the variations in bacterial proportions during biofilm formation.ResultsCompared to 1% NaOCl, 10 μg/mL buCaTHL4B or Im-4 exhibited significantly greater bactericidal effects on the two-species biofilms (p < 0.05), leading to their selection for subsequent experiments. Over a 48-hour period, 10 μg/mL Im-4 demonstrated a stronger antibiofilm effect than buCaTHL4B (p < 0.05). Following a 24-hour biofilm formation period, the proportion of F. nucleatum decreased while the proportion of E. faecalis increased in the sterile water group. In the buCaTHL4B and 1% NaOCl groups, the proportion of F. nucleatum was lower than that of E. faecalis (p < 0.05), whereas in the Im-4 group, the proportion of F. nucleatum was higher than that of E. faecalis (p < 0.05). The proportions of bacteria in the two AMPs groups gradually stabilized after 24 h of treatment.ConclusionbuCaTHL4B and Im-4 exhibited remarkable antibacterial and anti-biofilm capabilities against pathogenic root canal biofilms in vitro, indicating their potential as promising additives to optimize the effectiveness of root canal treatment as alternative irrigants.

The cancer-associated fibroblast (CAF)-derived secretome plays critical roles in tumor progression by remodelling tumor microenvironment. Tumorigenesis is accompanied by the transformation of normal fibroblasts (NF) into CAF, leading to significant changes in their secretome. This work aims to identify the differential components of secretome between NFs and CAFs and reveal their functions in gastric cancer (GC). Firstly, our molecular typing studies and immune infiltration analysis showed that CAF infiltration level was increased and showed a significant association with clinical characteristics and poor prognosis of GC patients. Secondly, RNA-seq analysis revealed that a total of 1531 genes showed significant expression changes between NF and CAF. According to the annotation of the Human Protein Atlas (HPA) database, 147 genes encode secreted proteins, including FGF2. Particularly, the cell co-culture and RNA sequencing studies confirmed that exogenous recombinant FGF2 protein treatment promoted GC cell proliferation by enhancing ribosome biogenesis. The rescue assay showed that CAF-secreted FGF2 protein promotes GC cell growth and proliferation in a FGFR1-dependent manner. Our finding provides evidence that targeting blockade of CAF-derived FGF2 protein might be a promising treatment for GC.

Epithelial-mesenchymal transition (EMT) or mesenchymal-epithelial transition (MET) plays critical roles in cancer metastasis. Recent studies, especially those based on single-cell sequencing, have revealed that EMT is not a binary process, but a heterogeneous and dynamic disposition with intermediary or partial EMT states. Multiple double-negative feedback loops involved by EMT-related transcription factors (EMT-TFs) have been identified. These feedback loops between EMT drivers and MET drivers finely regulate the EMT transition state of the cell. In this review, the general characteristics, biomarkers and molecular mechanisms of different EMT transition states were summarized. We additionally discussed the direct and indirect roles of EMT transition state in tumour metastasis. More importantly, this article provides direct evidence that the heterogeneity of EMT is closely related to the poor prognosis in gastric cancer. Notably, a seesaw model was proposed to explain how tumour cells regulate themselves to remain in specific EMT transition states, including epithelial state, hybrid/intermediate state and mesenchymal state. Additionally, this article also provides a review of the current status, limitations and future perspectives of EMT signalling in clinical applications.

Accumulating evidence has shown that fibromodulin (FMOD) plays a pivotal role in tumorigenesis and metastasis. However, the biological function of FMOD in oral squamous cell carcinoma (OSCC) remains largely unclear to date. In this study, we confirmed that FMOD was overexpressed and showed a significant association with malignant progression and lymph node metastasis in OSCC. Depletion of FMOD inhibited OSCC proliferation and metastasis in vitro and in vivo. RNA sequencing, western blotting, and rescue assays verified that FMOD exerted oncogenic roles in OSCC via activation of EGFR signaling. In addition, FMOD was proved to be a putative target gene of miR-338-3p. Taken together, FMOD overexpression due to the reduced level of miR-338-3p promotes OSCC by activating EGFR signaling. Our findings provide direct evidence that targeting FMOD could be a promising therapeutic strategy for OSCC patients.

We previously reported that IGFBP7 plays a role in maintaining mRNA stability of oncogenic lncRNA UBE2CP3 by RNA-RNA interaction in gastric cancer (GC). Clinical cohort studies had implied an oncogenic role of IGFBP7 in GC. However, the molecular mechanism of IGFBP7 in GC progression remains unknown. In this study, clinical analysis based on two independent cohorts showed that IGFBP7 was positively associated with poor prognosis and macrophage infiltration in GC. Loss-of-function studies confirmed the oncogenic properties of IGFBP7 in regulating GC cell proliferation and invasion. Mechanismly, IGFBP7 was highly expressed in cancer-associated fibroblasts (CAF) and mesenchymal cells, and was induced by epithelial-to-mesenchymal transition (EMT) signaling, since its expression was increased by TGF-beta treatment and reduced by overexpression of OVOL2 in GC. RNA sequencing, qRT-PCR, ELISA assay showed that IGFBP7 positively regulated FGF2 expression and secretion in GC. Transcriptome analysis revealed that FGFR1 was downregulated in M1 polarization but upregulated in M2 polarization. Exogenous recombinant IGFBP7 treatment in macrophages and GC cells further identified that IGFBP7 promotes tumor associated macrophage (TAM) polarization via FGF2/FGFR1/PI3K/AKT axis. Our finding here represented the first evidence that IGFBP7 promotes GC by enhancing TAM/M2 macrophage polarization through FGF2/FGFR1/PI3K/AKT axis.

BACKGROUND:Cancer/testis (CT) antigens/genes are usually overexpressed in cancers and exhibit high immunogenicity, making them promising targets for immunotherapy and cancer vaccines. The role of serine protease PRSS56 in cancers remains unknown to date.METHODS:RNA sequencing studies were performed to screen CT genes in gastric cancer (GC) and colorectal cancer (CRC) cells exposed to DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-AZA-CdR). Bioinformatics analysis was conducted to analyze the correlation between PRSS56 expression and DNA methylation. Functional experiments were performed to explore the biological function of PRSS56 in GC and CRC.RESULTS:In this study, we identified the testis-specific serine proteases PRSS56 as a novel CT antigen. PRSS56 was frequently overexpressed in various cancers, especially in gastrointestinal cancer. PRSS56 expression was negatively associated with promoter DNA methylation level, and positively associated with gene body methylation level. PRSS56 expression was significantly activated in colorectal and gastric cancer cells exposed to DNA methyltransferase inhibitors. Importantly, our finding highlights that the decreased methylation level of the CpG site cg10242318 in the PRSS56 promoter region resulted in its overexpression in GC and CRC. Additionally, functional assays verified that PRSS56 overexpression activated PI3K-AKT signaling in GC and CRC.CONCLUSION:Serine protease PRSS56 is a novel CT antigen that is reactivated in cancers by promoter DNA hypomethylation. PRSS56 functions oncogenic roles in GC and CRC by activating of PI3K/AKT axis. Our results presented here represent the first data on the function of the serine protease PRSS56 in cancers.

Purpose To characterize the bacterial community in the primarily infected root canals. Methods A total of 13 samples were collected from the primarily infected root canals. 16 S rDNA sequencing was performed to define bacterial community. Taxonomic annotation, bacterial hierarchical structures, community richness and diversity, and inter-subject variability of the bacterial community in the root canal samples were analyzed. Gender, age, and duration of the toothache-specific bacterial community associated with the patient groups were analyzed. Results A total of 359 Species were annotated and identified in the whole study cohort. The Alpha diversity analysis showed that the species diversity and detection rate of the 13 samples were high, which reflected the authenticity of sequencing results. The Beta diversity analysis was used to compare the degree of difference between different root canal samples. The 13 samples were divided into two groups according to the results, group A was samples I1-I12, and group B was samples I13. The bacterial species of group A samples were analyzed with the clinical characteristics of patients, and it was found that gender, and duration specific differences in bacterial species, and there was no significant difference in species types among different ages of patients. Conclusion There were a wide diversity and inter-subject variability in the bacterial community in the primary infected root canals. While Porphyromonas gingivalis was the most abundant species, Fusobacterium nucleatum was the most variable species in the bacterial community of the root canal. The bacterial community at different taxonomic levels varied from sample to sample, despite consistent disease diagnoses. There was gender, duration-specific differences in the bacterial species in the primary infected root canals.

BACKGROUND:To investigate the long-term and spatial patterns of incidence, prevalence, and disability-adjusted life year (DALY) rates of severe periodontitis in Asia from 1990 to 2019, and to estimate the associations between disease burden and socioeconomic development using the Socio-Demographic Index (SDI). METHODS:Data were obtained from the global burden of disease study 2019. The average annual percent change (AAPC) was calculated to reflect temporal trends, spatial autocorrelation analysis was conducted to estimate the spatial characteristics, and spatial panel models were used to investigate the association between SDI and severe periodontitis burden. RESULTS:For Asia as a whole, the crude rates increased by 1.10% per year for incidence, 1.42% per year for prevalence, and 1.41% per year for DALY from 1990 to 2019. The age-standardized incidence, prevalence and DALY rates increased by 0.18%, 0.22%, and 0.23% per year, respectively. Spatially, the hot spots of age-standardized incidence, prevalence and DALY rates were located in Southern Asia, besides, these rates all showed increasing trends in most countries, and the increases were clustered in Southeastern Asia. Further, SDI showed a negative association with incidence (coef = -14.44; 95% CI: -24.63, -4.25) and prevalence (coef = -40.09; -51.81, -28.36), and a positive association with DALY rates (coef = 0.31; 0.23; 0.38). CONCLUSIONS:Severe periodontitis poses a serious public health challenge in Asian countries with increasing temporal trends and substantial spatial inequalities. Effective geographically targeted public health interventions and strategies are needed to address the growing burden associated with severe periodontitis.

Background: Stanniocalcin-2 (STC2) is a secreted glycoprotein which plays an important role in regulating the homeostasis of calcium, glucose homeostasis, and phosphorus metastasis. Accumulating evidence suggests that STC2 is implicated in cancer mechanisms. However, the effects of STC2 on cancer development and progression across pan-cancer are not yet completely known. Methods: Data were downloaded from The Cancer Genome Atlas database to obtain differentially expressed genes significantly associated with prognosis (key genes). A gene was selected for subsequent correlation studies by integrating the significance of prognosis and the time-dependent ROC curve. Gene expression of different tumor types was analyzed based on the UCSC XENA website. Furthermore, our study investigated the correlation of STC2 expression between prognosis, immune cell infiltration, immune checkpoint genes (ICGs), mismatch repair genes (MMRs), tumor mutation burden (TMB), microsatellite instability (MSI), and drug sensitivity in various malignant tumors. Gene set enrichment analysis (GSEA) was conducted for correlated genes of STC2 to explore potential mechanisms. Results: A total of 3,429 differentially expressed genes and 397 prognosis-related genes were identified from the TCGA database. Twenty-six key genes were found by crossing the former and the latter, and the highest risk gene, STC2, was selected for subsequent correlation studies. STC2 had good diagnostic performance for HNSCC, and was closely related to the survival status and clinicopathological stage of HNSCC patients. In pan-cancer analysis, STC2 was upregulated in 20 cancers and downregulated in seven cancers. STC2 overexpression was overall negatively correlated with overall survival, disease-free survival, disease-specific survival, and progress-free survival. STC2 was profoundly correlated with the tumor immune microenvironment, including immune cell infiltration, ICGs, MMRs, TMB, and MSI. Moreover, STC2 was significantly negatively correlated with the sensitivity or resistance of multiple drugs. Conclusion: STC2 was a potential prognostic biomarker for pan-cancer and a new immunotherapy target.

Endothelial progenitor cells (EPCs) expressing vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) and bone marrow mesenchymal stem cells (BMSCs) expressing endogenous bone morphogenetic protein-2 (BMP-2) play the important role in new bone formation. This study investigated the effects of a porous hydroxyapatite (HA)/chitosan (CS)/polycaprolactone (PCL) composite scaffold-engrafted EPCs and BMSCs on the expression of BMP-2, VEGF, and PDGF in the calvarial defect rabbit model in vivo. It showed that a three-dimensional composite scaffold was successfully constructed by physical interaction with a pore size of 250 μm. The HA/CS/PCL scaffold degraded slowly within 10 weeks and showed non-cytotoxicity. By X-ray, micro-CT examination, and H&E staining, compared with the HA/CS/PCL group, HA/CS/PCL + EPCs, HA/CS/PCL + BMSCs, and HA/CS/PCL + EPCs + BMSCs groups performed a more obvious repair effect, and the dual factor group presented particularly significant improvement on the percentages of bone volume at week 4 and week 8, with evident bone growth. Osteogenesis marker (BMP-2) and vascularization marker (VEGF and PDGF) expression in the dual factor group were much better than those of the HA/CS/PCL control group and single factor groups. Collectively, the HA/CS/PCL composite scaffold-engrafting EPCs and BMSCs is effective to repair calvarial defects by regulating endogenous expression of BMP-2, VEGF, and PDGF. Thus, this study provides important implications for the potential clinical application of biomaterial composite scaffold-engrafted engineering cells.