Identification of the Neointimal Hyperplasia-Related LncRNA-mRNA-Immune Cell Regulatory Network in a Rat Carotid Artery Balloon Injury Model.

Excessive neointimal hyperplasia (NIH) of coronary vessels in patients is the main cause of restenosis (RS) after percutaneous coronary intervention (PCI). This study aimed to identify the regulatory genes related to NIH in a rat carotid artery balloon injury model.We established a rat model and performed RNA sequencing to identify differentially expressed long non-coding RNAs (DElncRNAs) and differentially expressed message RNAs (DEmRNAs). Immune cells were analyzed using a murine Microenvironment Cell Population counter. The Pearson correlation between DEmRNAs, DElncRNAs, and immune cells was analyzed, followed by function enrichment analysis. Core DEmRNA was identified using Cytoscape. Next, a core lncRNAs-mRNAs-immune cell regulatory network was constructed. NIH-related gene sets from the Gene Expression Omnibus and GeneCards databases were used for validation.A total of 2,165 DEmRNAs and 705 DElncRNAs were identified in rat carotid artery tissue. Four key immune cells were screened out, including mast cells, vessels, endothelial cells, and fibroblasts. Based on the Pearson correlation between DEmRNAs, DElncRNAs and 4 key immune cells, 246 DEmRNAs and 93 DElncRNAs were obtained. DEmRNAs that interact with lncRNAs were mainly involved in the cell cycle, MAPK signaling pathway, and PI3K-Akt signaling pathway. A core lncRNA-mRNA-immune cell regulatory network was constructed, including 9 mRNAs, 4 lncRNAs, and fibroblasts. External datasets validation confirmed the significant correlation of both these mRNAs and lncRNAs with NIH.In this study, an lncRNA-mRNA-immune cell regulatory network related to NIH was constructed, which provided clues for exploring the potential mechanism of RS in cardiovascular diseases.

Cholelithiasis increased prostate cancer risk: evidence from a case-control study and a meta-analysis.

INTRODUCTION: Cholelithiasis represents a known risk factor for digestive system neoplasm. Few studies reported the association between cholelithiasis and the risk of prostate cancer (PCa), and the results were controversial. METHODS: We reviewed the medical records of the Second Affiliated Hospital of Chongqing Medical University Hospital to perform a retrospective matched case-control study, which included newly diagnosed 221 PCa patients and 219 matched controls. Logistic regression was applied to compare cholelithiasis exposure and adjusted for confounding factors. Additionally, we conducted a meta-analysis pooling this and published studies further to evaluate the association between cholelithiasis and PCa risk. Related ratio (RR) and 95% confidence interval (95%CI) were used to assess the strength of associations. RESULTS: Our case-control study showed that cholelithiasis was associated with a higher incidence of PCa (OR = 1.87, 95% CI: 1.06-3.31) after multivariable adjustment for covariates. The incidence of PCa was increased in patients with gallstones but not cholecystectomy. 7 studies involving 80,403 individuals were included in the meta-analysis. Similarly, the results demonstrated that cholelithiasis was associated with an increased risk of PCa (RR = 1.35, 95%CI: 1.17-1.56) with moderate-quality evidence. Cholelithiasis patients with low BMI increased the PCa incidence. Moreover, Subgroup analysis based on region showed that cholelithiasis was associated with PCa in Europe (RR = 1.24, 95%CI 1.03-1.51) and Asia (RR = 1.32, 95%CI 1.24-1.41). CONCLUSIONS: The results suggested an association between cholelithiasis and the risk of PCa. There was no significant relationship between cholecystectomy therapy and PCa risk. Further cohort studies should be conducted to demonstrate the results better.

Association between male infertility and the risk of hypertension: A meta-analysis and literature review.

To explore the association between male infertility and hypertension risk, a meta-analysis and systematic review was conducted. Observational studies were sought in Medline, PubMed, EMBASE, Web of Science, and China National Knowledge Infrastructure up to April 30, 2021. Two independent reviewers selected available studies and extracted the data. The association between male infertility and hypertension risk was estimated by calculating the relative risk (RR) and 95% confidence interval (95% CI) using Stata12.0 statistical software. A total of seven studies were included in this meta-analysis, including 102,152 patients and 636,645 healthy individuals. The results demonstrated that male infertility was significantly associated with increased hypertension incidence (RR = 1.08; 95% CI 1.02-1.14; p = 0.004), with moderate-quality evidence. A subgroup analysis based on region showed that a positive association was observed in Europe but not the United States or Asia. This positive association was further confirmed in a cohort study, but not in a case-control study. After adjusting for potential confounders, male infertility was still significantly associated with hypertension risk (RR = 1.06, 95% CI 1.03-1.09). In conclusion, our findings suggest that male infertility increases the risk of hypertension incidence. However, further studies are needed to provide more conclusive evidence.

Development and validation of a model for predicting the risk of prostate cancer.

BACKGROUND: Abnormal hematologic parameters before patients undergoing prostate biopsy play a pivotal role in guiding the surgical management of prostate cancer (PCa) incidence. This study aims to establish the first nomogram for predicting PCa risk for better surgical management. METHODS: We retrospectively reviewed and analyzed the data including basic information, preoperative hematologic parameters, and imaging examination of 540 consecutive patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsy for elevated prostate-specific antigen (PSA) in our medical center between 2017 and 2021. Logistic regression analysis was used to determine the risk factors for PCa occurrence, and the nomogram was constructed to predict PCa occurrence. Finally, the data including 121 consecutive patients in 2022 were prospectively collected to further verify the results. RESULTS: In retrospective analyses, univariate and multivariate logistic analyses identified that three variables including age, diabetes, and De Ritis ratio (aspartate transaminase/alanine transaminase, AST/ALT) were determined to be significantly associated with PCa occurrence. A nomogram was constructed based on these variables for predicting the risk of PCa, and a satisfied predictive accuracy of the model was determined with a C-index of 0.765, supported by a prospective validation group with a C-index of 0.736. The Decision curve analysis showed promising clinical application. In addition, our results also showed that the De Ritis ratio was significantly correlated with the clinical stage of PCa patients, including T, N, and M stages, but insignificantly related to the Gleason score. CONCLUSIONS: The increased De Ritis ratio was significantly associated with the risk and clinical stage of PCa and this nomogram with good discrimination could effectively improve individualized surgical management for patient underdoing prostate biopsy.

Decorin-mediated inhibition of colorectal cancer growth and migration is associated with E-cadherin in vitro and in mice.

Previous studies have shown that decorin expression is significantly reduced in colorectal cancer tissues and cancer cells, and genetic deletion of the decorin gene is sufficient to cause intestinal tumor formation in mice, resulting from a downregulation of p21, p27(kip1) and E-cadherin and an upregulation of ß-catenin signaling [Bi,X. et al. (2008) Genetic deficiency of decorin causes intestinal tumor formation through disruption of intestinal cell maturation. Carcinogenesis, 29, 1435-1440]. However, the regulation of E-cadherin by decorin and its implication in cancer formation and metastasis is largely unknown. Using a decorin knockout mouse model (Dcn(-/-) mice) and manipulated expression of decorin in human colorectal cancer cells, we found that E-cadherin, a protein that regulates cell-cell adhesion, epithelial-mesenchymal transition and metastasis, was almost completely lost in Dcn(-/-) mouse intestine, and loss of decorin and E-cadherin accelerated colon cancer cell growth and invasion in Dcn(-/-) mice. However, increasing decorin expression in colorectal cancer cells attenuated cancer cell malignancy, including inhibition of cancer cell proliferation, promotion of apoptosis and importantly, attenuation of cancer cell migration. All these changes were linked to the regulation of E-cadherin by decorin. Moreover, overexpression of decorin upregulated E-cadherin through increasing of E-cadherin protein stability as E-cadherin messenger RNA and promoter activity were not affected. Co-immunoprecipitation assay showed a physical binding between decorin and E-cadherin proteins. Taken together, our results provide direct evidence that decorin-mediated inhibition of colorectal cancer growth and migration are through the interaction with and stabilization of E-cadherin.

Age of menarche and primary bladder cancer risk: A meta-analysis and systematic review.

INTRODUCTION: The incidence and outcomes of bladder cancer (BCa) have apparent sex differences. Various observational studies have demonstrated that the age of menarche might be associated with female BCa. To explore this relationship, a meta-analysis and systematic review were performed based on available studies. MATERIAL AND METHODS: A systematic search was performed in PubMed, Embase, and Web of Science for studies published up to October 1, 2021. Two reviewers independently extracted related data between age of menarche and BCa risk from the included studies. The Newcastle-Ottawa quality assessment scale was applied to evaluate the quality of the studies. The relative risk (RR) ratio and its 95% confidence interval (CI) were then calculated. RESULTS: A total of 12 studies containing 3,719 BCa cases and 1,350,207 women, were included in this meta-analysis. The pooled data showed that the age of menarche was not significantly associated with BCa risk (RR = 0.96, 95% CI: 0.85-1.08), although the evidence was of moderate quality. Similar results were observed in case-control (RR = 1.33, 95% CI = 0.77-2.21) and cohort studies (RR = 0.95, 95% CI = 0.84-1.07). Moreover, subgroup analyses based on study quality, population, exposure assessment, and several potential important confounders and risk factors revealed similar results. No evidence of publication bias and significant heterogeneity was found among these studies. Furthermore, a random-effects dose-response meta-regression model was established, which revealed negative results. CONCLUSIONS: Our findings suggested that the age of menarche was not associated with BCa risk in women. However, these findings needed to be further confirmed given the limitations and potential biases.

Debriding effect of bromelain on firearm wounds in pigs.

BACKGROUND: Wound excision is the standard treatment for firearm wounds. However, achieving a satisfactory curative effect is difficult because of the traumatic mechanism of high-velocity projectiles. We propose a new therapy by using topical bromelain as a supplement to wound incision for the debridement of firearm wounds. We clarified the debriding effect of bromelain on firearm wounds in pigs. METHODS: In vitro, muscle tissues around the wound track and normal muscle were incubated in bromelain solutions of different concentrations. Tissue hydrolization was estimated by measuring tissue weight and the release of total amino acids. In vivo, the hind limbs of 15 pigs were wounded with high-velocity projectiles. Five groups were classified as follows: wound excision (E), wound incision (I), bromelain (B), incision + bromelain (IB), and control (C). Debriding effectiveness was estimated using bacterial content, histopathologic examination, and wound healing time. RESULTS: In vitro, hydrolization of wound tissue was significantly more intensive than that of normal tissue. Bromelain solution (10 mg/mL) hydrolyzed wound tissue rapidly with minimal proteolysis of normal tissue. In vivo, the wound-track bacterial content of group IB was similar to that of group E and was significantly lower than that of groups I, B, and C. The wound healing time of group IB was also shorter. CONCLUSIONS: Bromelain is effective in the debridement of uncomplicated firearm wounds if used as a supplement to simple wound incision. This new therapy shows notable advantages over conventional surgical debridement as it greatly simplifies the procedures.

[The effect of hepatitis B virus X protein on the c-met promoter activity in HepG2 cells].

OBJECTIVE: To confirm the effect of hepatitis B virus X (HBx) protein on the c-met promoter activity in HepG2 cells. METHOD: The expression of c-met protein was detected by western blot in HBx-transfected HepG2 cells, the human c-met promote activity was checked by luciferase assay using five different constructs with deletion or point mutation. RESULTS: HBx protein stimulated the expression of the c-met in HepG2 cells. The enhanced expression of c-met in HBx-transfected cells was mediated by the activation of AP-2 and SP-1 transcriptional activity at the c-met promoter region (-183bp--100bp), HBx increased the invasiveness of HepG2 cells as determined by Matrigel invasion assay. CONCLUSION: These results suggests that HBx induces the expression of c-met through the activation of AP-2 and SP-1 activity at the promoter region; in addition, our data indicate that HBx stimulates the invasive potential of HepG2 cells.

[Hepatitis B virus X protein regulates c-met promoter via the ERKs singal pathway in HepG2 cells].

OBJECTIVE: To explore the signal pathway mediating the regulatory effect of Hepatitis B virus X protein (HBX) on c-met gene promoter in HepG2 cells. METHODS: The expression of c-met in HBX-transfected HepG2 cells treated with different signal pathway inhibitors was detected by western blot, the invasion capability of cells was determined by Matrigel invasion assay. RESULTS: ERK inhibitor U0126 inhibited the expression of the c-Met in HBx-transfected HepG2 cells. However, both p38MAPK inhibitor SB203580 and PI-3K inhibitor wortmanin had no effect on expression of the c-Met in HBx-transfected HepG2 cells. Furthermore, the ERK inhibitor U0126 also inhibited the invasiveness of HBX-transfected HepG2 cells. CONCLUSION: HBx induces invasion of HCC via activation of ERK pathway.

Effects of human ß-defensin-3 on biofilm formation­regulating genes dltB and icaA in Staphylococcus aureus.

An understanding of the regulatory mechanisms that drive Staphylococcus aureus biofilm formation may lead to the development of an effective strategy to control the increasing number of refractory clinical infections it causes. The present study examined the effects of the antimicrobial agent human ß­defensin 3 (hBD­3) and the antibiotics vancomycin and clindamycin on the expression of the S. aureus biofilm formation­regulating genes, icaA and dltB, during bacterial adhesion and biofilm formation. Transcription (mRNA) levels of dlt and ica genes were measured using quantitative polymerase chain reaction, and slimes of S. aureus biofilm were examined with confocal scanning laser microscopy during S. aureus adhesion and biofilm formation. Although hBD­3, vancomycin and clindamycin led to significantly attenuated biofilm formation, their treatment­associated effects on the mRNA expression of dlt and ica were not identical. Vancomycin and clindamycin induced sustained expression of the dlt and ica genes, which may be harnessed to induce biofilm formation. However, hBD­3 did not have a significant affect on the transcription level of dltB during either bacterial adhesion or biofilm formation. Therefore, the mechanism of hBD­3 that regulated the suppression of biofilm formation appears to differ from the mechanisms of vancomycin and clindamycin.