lncRNA FGD5-AS1 is required for gastric cancer proliferation by inhibiting cell senescence and ROS production via stabilizing YBX1.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Association between periodontitis and dental caries: a systematic review and meta-analysis.

OBJECTIVES: Recent evidence suggested a link between periodontitis (PD) and dental caries, but the trends and nature of this association remained unclear. The overall aim of this study was to critically assess the correlation of two disorders. METHODS: A comprehensive search was conducted within the PUBMED and EMBASE databases including grey literatures up to July 5th, 2023. The Newcastle-Ottawa scale was used to qualitatively evaluate the risk of bias. RESULTS: Overall, 18 studies were included. In terms of caries risk in PD patients, the prevalence of caries was increased by PD (OR = 1.57, 95%CI:1.20-2.07), both in crown (OR = 1.03, 95%CI:1.01-1.05) and root caries (OR = 2.10, 95%CI:1.03-4.29). Odds of caries were also raised by PD severity (OR moderate = 1.38, 95%CI:1.15-1.66; OR severe = 2.14, 95%CI:1.74-2.64). Besides, patients with PD exhibited a higher mean number of decayed, missing and filled teeth (DMFT) and decayed and filled root teeth (DFR) [weighted mean difference (WMD)DMFT = 0.87, 95%CI: -0.03-1.76; WMDDFR = 1.13, 95%CI: 0.48-1.78]. Likewise, patients with caries had an elevated risk of PD (OR = 1.79, 95%CI:1.36-2.35). However, Streptococcus mutans, one of the main pathogens of caries, was negatively correlated with several main pathogens of periodontitis. CONCLUSIONS: This study indicated a positive correlation between dental caries and periodontitis clinically, while the two disease-associated pathogens were antagonistic. CLINICAL RELEVANCE: Further research, including clinical cohort studies and mechanisms of pathogens interaction is needed on this link for better prevention and treatment of PD and caries. In addition, innovative prevention strategies need to be developed and incorporated in dental practices to prevent these two highly prevalent oral diseases.

A novel TGFbeta/TGILR axis mediates crosstalk between cancer-associated fibroblasts and tumor cells to drive gastric cancer progression.

Transforming growth factor beta (TGFß) 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.

A new high-throughput screening methodology for the discovery of cancer-testis antigen using multi-omics data.

BACKGROUND: Cancer/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. METHODS: A 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. RESULTS: We 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. CONCLUSION: We 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.

Cancer-associated fibroblasts promote gastric cancer cell proliferation by paracrine FGF2-driven ribosome biogenesis.

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.

Cancer burden and risk in the Chinese population aged 55 years and above: A systematic analysis and comparison with the USA and Western Europe.

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.

Bacterial diversity in primary infected root canals of a Chinese cohort: analysis of 16 S rDNA sequencing.

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.

Fibromodulin overexpression drives oral squamous cell carcinoma via activating downstream EGFR signaling.

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.

Serine protease PRSS56, a novel cancer-testis antigen activated by DNA hypomethylation, promotes colorectal and gastric cancer progression via 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.

Heterogeneity and plasticity of epithelial-mesenchymal transition (EMT) in cancer metastasis: Focusing on partial EMT and regulatory mechanisms.

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.

Cancer-associated fibroblast-secreted IGFBP7 promotes gastric cancer by enhancing tumor associated macrophage infiltration via FGF2/FGFR1/PI3K/AKT axis.

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.

A Pan-Cancer Analysis Reveals the Prognostic and Immunotherapeutic Value of Stanniocalcin-2 (STC2).

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.

Improved repair of rabbit calvarial defects with hydroxyapatite/chitosan/polycaprolactone composite scaffold-engrafted EPCs and BMSCs.

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.

Periodontitis Is Associated With Heart Failure: A Population-Based Study (NHANES III).

Objectives: The aim of this study was to investigate the relationship between periodontitis and heart failure using the Third National Health and Nutrition Examination Survey (NHANES III). Methods: Participants who had received a periodontal examination were included and investigated for the occurrence of heart failure. The included participants were divided into no/mild periodontitis and moderate/severe periodontitis groups according to their periodontal status. Weighted prevalence of heart failure was calculated, and weighted logistic regressions models were used to explore the association between periodontitis and heart failure. Possible influencing factors were then explored through subgroup analysis. Results: Compared with that of the no/mild periodontitis group, the incidence of heart failure in participants with moderate/severe periodontitis was 5.72 times higher (95% CI: 3.76-8.72, p < 0.001). After adjusting for gender, age, race, body mass index, poverty income ratio, education, marital status, smoking status, drinking status, hypertension, diabetes, stroke, and asthma, the results showed that the incidence of heart failure in the moderate/severe group was 3.03 times higher (95% CI: 1.29-7.13, p = 0.012). Subgroup analysis showed that criteria, namely, male, 40-60 years old, non-Hispanic white, body mass index >30, poverty income ratio ≥1, not more than 12 years of education, currently drinking, stroke but no diabetes, or asthma supported moderate/severe periodontitis as a risk factor for heart failure (p < 0.05). Conclusion: According to data from this nationally representative sample from the United States, periodontitis is associated with an increased risk of heart failure.

The spatial and temporal trends of severe periodontitis burden in Asia, 1990-2019: A population-based epidemiological study.

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.

Genome-wide association studies identify miRNA-194 as a prognostic biomarker for gastrointestinal cancer by targeting ATP6V1F, PPP1R14B, BTF3L4 and SLC7A5.

Background: The dysregulated genes and miRNAs in tumor progression can be used as biomarkers for tumor diagnosis and prognosis. However, the biomarkers for predicting the clinical outcome of gastrointestinal cancer (GIC) are still scarce. Methods: Genome-wide association studies were performed to screen optimal prognostic miRNA biomarkers. RNA-seq, Ago-HITS-CLIP-seq, western blotting and qRT-PCR assays were conducted to identify target genes of miR-194. Genome-wide CRISPR-cas9 proliferation screening analysis were conducted to distinguish passenger gene and driver gene. Results: A total of 9 prognostic miRNAs for GIC were identified by global microRNA expression analysis. Among them, miR-194 was the only one miRNA that significantly associated with overall survival, disease-specific survival and progress-free interval in both gastric, colorectal and liver cancers, indicating miR-194 was an optimal prognostic biomarker for GIC. RNA-seq analysis confirmed 18 conservative target genes of miR-194. Four of them, including ATP6V1F, PPP1R14B, BTF3L4 and SLC7A5, were directly targeted by miR-194 and required for cell proliferation. Cell proliferation assay validated that miR-194 inhibits cell proliferation by targeting ATP6V1F, PPP1R14B, BTF3L4 and SLC7A5 in GIC. Conclusion: In summary, miR-194 is an optimal biomarker for predicting the outcome of GIC. Our finding highlights that miR-194 exerts a tumor-suppressive role in digestive system cancers by targeting ATP6V1F, PPP1R14B, BTF3L4 and SLC7A5.

Oral microbiota in the oral-genitourinary axis: identifying periodontitis as a potential risk of genitourinary cancers.

Periodontitis has been proposed as a novel risk factor of genitourinary cancers: although periodontitis and genitourinary cancers are two totally distinct types of disorders, epidemiological and clinical studies, have established associations between them. Dysbiosis of oral microbiota has already been established as a major factor contributing to periodontitis. Recent emerging epidemiological evidence and the detection of oral microbiota in genitourinary organs indicate the presence of an oral-genitourinary axis and oral microbiota may be involved in the pathogenesis of genitourinary cancers. Therefore, oral microbiota provides the bridge between periodontitis and genitourinary cancers. We have carried out this narrative review which summarizes epidemiological studies exploring the association between periodontitis and genitourinary cancers. We have also highlighted the current evidence demonstrating the capacity of oral microbiota to regulate almost all hallmarks of cancer, and proposed the potential mechanisms of oral microbiota in the development of genitourinary cancers.

Convalescent plasma is of limited clinical benefit in critically ill patients with coronavirus disease-2019: a cohort study.

BACKGROUND: Recently, convalescent plasma (CP) transfusion was employed for severe or critically ill patients with coronavirus disease-2019. However, the benefits of CP for patients with different conditions are still in debate. To contribute clinical evidence of CP on critically ill patients, we analyze the characteristics and outcomes of patients with or without CP transfusion. METHODS: In this cohort study, 14 patients received CP transfusion based on the standard treatments, whereas the other 10 patients received standard treatments as control. Clinical characteristics and outcomes were analyzed. The cumulative survival rate was calculated by Kaplan-Meier survival analysis. RESULTS: Data analysis was performed on 24 patients (male/female: 15/9) with a median age of 64.0 (44.5-74.5) years. Transient fever was reported in one patient. The cumulative mortality was 21% (3/14) in patients receiving CP transfusion during a 28-day observation, whereas one dead case (1/10) was reported in the control group. No significant difference was detected between groups in 28-day mortality (P = 0.615) and radiological alleviation of lung lesions (P = 0.085). CONCLUSION: In our current study, CP transfusion was clinically safe based on the safety profile; however, the clinical benefit was not significant in critically ill patients with more comorbidities at the late stage of disease during a 28-day observation.

Continuous exposure of isoprenaline inhibits myoblast differentiation and fusion through PKA/ERK1/2-FOXO1 signaling pathway.

AIM: The objective of this study is to determine if exuberant sympathetic nerve activity is involved in muscle satellite cell differentiation and myoblast fusion. METHODS AND RESULTS: By using immunoassaying and western blot analyses, we found that ß1 and ß2-adrenergic receptors (AdR) were expressed in C2C12 cells. The differentiated satellite cells exhibited an increased expression of ß2-AdR, as compared with the proliferating cells. Continuous exposure of isoprenaline (ISO), a ß-AdR agonist, delayed C2C12 cell differentiation, and myoblast fusion in time- and dose-dependent manner. ISO also increased short myotube numbers while decreasing long myotube numbers, consistent with the greater reduction in MyHC1, MyHC2a, and MyHC2x expression. Moreover, continuous exposure of ISO gradually decreased the ratio of PKA RI/RII, and PKA RI activator efficiently reversed the ISO effect on C2C12 cell differentiation and myoblast fusion while PKA inhibitor H-89 deteriorated the effects. Continuous single-dose ISO increased ß1-AdR expression in C2C12 cells. More importantly, the cells showed enhanced phospho-ERK1/2 levels, resulting in increasing phospho-ß2-AdR levels while decreasing ß2-AdR levels, and the specific effects could be abolished by ERK1/2 inhibitor. Furthermore, continuous exposure of ISO induced FOXO1 nuclear translocation and increased the levels of FOXO1 in nuclear extracts while reducing pAKT, p-p38MAPK, and pFOXO1 levels. Conversely, blockade of ERK1/2 signaling partially abrogated ISO effects on AKT, p38MAPK, and FOXO1signaling, which partially restored C2C12 cell differentiation and myoblast fusion, leading to an increase in the numbers of medium myotube along with the increased expression of MyHC1 and MyHC2a. CONCLUSION: Continuous exposure of ISO impedes satellite cell differentiation and myoblast fusion, at least in part, through PKA-ERK1/2-FOXO1 signaling pathways, which were associated with the reduced ß2-AdR and increased ß1-AdR levels.

Periodontal Disease and Risk of Bladder Cancer: A Meta-Analysis of 298476 Participants.

Objective: It has been reported that the periodontal disease is linked to a number of malignant tumors such as lung cancer and pancreatic cancer. In this study, we aimed to investigate the association of periodontal disease with risk of bladder cancer by a meta-analysis. Methods: PubMed, Scopus, ScienceDirect, and Chinese National Knowledge Infrastructure (CNKI) were searched for eligible publications up to December 15, 2017. Cohort and nested case-control studies on the association between periodontal disease and risk of bladder cancer were included. After study selection and data extraction, pooled hazard ratios (HRs) and their 95% confidence intervals (95%CIs) were calculated using a fixed-effect inverse-variance model. All analyses were performed using the RevMan 5.3 software. Results: Finally, five cohort studies were identified and included in this meta-analysis, involving 1,104 bladder cancer cases of 298,476 participants. Summary estimates based on adjusted data showed that periodontal disease was not significantly associated with the risk of bladder cancer (HR = 1.09, 95% CI = 0.95-1.25, I2 = 0%). A similar result was also observed after cumulative, subgroup and sensitivity analyses. Conclusions: Current evidence from cohort studies suggests that patients with periodontal disease may not be at an increased risk of developing bladder cancer.