Quorum-quenching enzyme Est816 assisted antibiotics against periodontitis induced by Aggregatibacter actinomycetemcomitans in rats.

Introduction: Quorum-quenching enzyme Est816 hydrolyzes the lactone rings of N-acyl homoserine lactones, effectively blocking the biofilm formation and development of Gram-negative bacteria. However, its applications in the oral field is limited. This study aimed to evaluate the efficacy of enzyme Est816 in combination with antibiotics against periodontitis induced by Aggregatibacter actinomycetemcomitans in vitro and in vivo. Methods: The antimicrobial efficacy of enzyme Est816 in combination with minocycline, metronidazole, and amoxicillin was determined using the minimum inhibitory concentration test. The anti-biofilm effect of enzyme Est816 was assessed using scanning electron microscopy, live/dead bacterial staining, crystal violet staining, and real-time quantitative PCR. Biocompatibility of enzyme Est816 was assessed in human gingival fibroblasts (HGF) by staining. A rat model of periodontitis was established to evaluate the effect of enzyme Est816 combined with minocycline using micro-computed tomography and histological staining. Results: Compared to minocycline, metronidazole, and amoxicillin treatment alone, simultaneous treatment with enzyme Est816 increased the sensitivity of biofilm bacteria to antibiotics. Enzyme Est816 with minocycline exhibited the highest rate of biofilm clearance and high biocompatibility. Moreover, the combination of enzyme Est816 with antibiotics improved the antibiofilm effects of the antibiotics synergistically, reducing the expression of the virulence factor leukotoxin gene (ltxA) and fimbria-associated gene (rcpA). Likewise, the combination of enzyme Est816 with minocycline exhibited a remarkable inhibitory effect on bone resorption and inflammation damage in a rat model of periodontitis. Discussion: The combination of enzyme Est816 with antibiotics represents a prospective anti-biofilm strategy with the potential to treat periodontitis.

New prognostic factor for hepatitis B virus-related decompensated cirrhosis: Ratio of monocytes to HDL-cholesterol.

AIM: Hepatitis B virus-related decompensated cirrhosis (HBV-DeCi) has a high mortality rate, and it remains a challenge to predict its outcomes in clinical practice. We aimed to determine the association between monocyte-to-HDL-cholesterol ratio (MHR) and short-term prognosis in HBV-DeCi patients. METHODS: A total of 145 HBV-DeCi patients were enrolled. A multivariate analysis was performed to identify predictors of mortality. The findings were validated by a receiver operating characteristic analysis using the area under the curve (AUC). RESULTS: A total of 20 (13.8%) patients had died 30 days after admission. MHR was markedly increased in the non-survivors compared with the survivors. In the multivariate analysis, MHR was identified as an independent risk factor for mortality, with a significant predictive value (AUC = 0.825; sensitivity, 90.0%; specificity, 62.4%). CONCLUSIONS: Elevated MHR is associated with increased mortality rate in HBV-DeCi patients.

Identification of potential metabolite markers for colon cancer and rectal cancer using serum metabolomics.

BACKGROUND: To determine the metabolic characteristics of patients with colon cancer (CC) and rectal cancer (RC) using gas chromatography-mass spectrometry (GC-MS)-based metabolomics. METHODS: In this study, serum samples were collected from 22 CC patients and 23 RC patients preoperatively and postoperatively and 45 healthy volunteers (HVs), and subjected to metabolomics analysis by GC-MS. Differential metabolites in the preoperative RC and CC samples and HVs were identified as potential biomarkers and evaluated for their utilities by receiver operating characteristic analyses. RESULTS: The different metabolic markers between CC and RC patients were identified, which may assist in distinguishing the two types of cancers. The area under the curve (AUC) was 0.805 for combination of d-glucose and d-mannose for CC diagnosis, and 0.889 for combination of 2-aminobutanoic acid, 3-hydroxypyridine, d-glucose, d-mannose, isoleucine, l-tryptophan, urea, and uric acid for RC diagnosis. The combinations of metabolite markers showed a better predictability than CEA and CA199 two commonly used protein markers for CRC diagnosis in clinical practice. Combining the metabolite markers with these two protein markers effectively improved the diagnostic accuracy with the AUC reaching 0.936 and 0.937 for CC and RC diagnosis, respectively. CONCLUSIONS: Metabolic profiles are different in the blood samples between CC and RC patients. The study has established a panel of metabolic markers as a predictive and multiplexing signature for CC and RC diagnosis.

Development and validation of an immune-related gene pairs signature in colorectal cancer.

Although the outcome of colorectal cancer (CRC) patients has improved significantly with the recent implementation of annual screening programs, reliable prognostic biomarkers are still needed due to the disease heterogeneity. Increasing pieces of evidence revealed an association between immune signature and CRC prognosis. Thus, we aim to build a robust immune-related gene pairs (IRGPs) signature that can estimate prognosis for CRC. Gene expression profiles and clinical information of CRC patients were collected from six public cohorts, divided into training cohort (n = 565) and five independent validation cohorts (n = 572, 290, 90 177 and 68, respectively). Within 1534 immune genes, a 19 IRGPs signature consisting of 36 unique genes was constructed which was significantly associated with the survival. In the validation cohorts, the IRGPs signature significantly stratified patients into high- vs low-risk groups in terms of prognosis across and within subpopulations with early stages disease and was prognostic in univariate and multivariate analyses. Several biological processes, including response to bacterium, were enriched among genes in the IRGPs signature. Macrophage M2 and mast cells were significantly higher in the high-risk risk group compared with the low-risk group. The IRGPs signature achieved a higher accuracy than commercialized multigene signatures for estimation of survival. When integrated with clinical factors such as sex and stage, the composite clinical and IRGPs signature showed improved prognostic accuracy relative to IRGPs signatures alone. In short, we developed a robust IRGPs signature for estimating prognosis in CRC, including early-stage disease, providing new insights into the identification of CRC patients with a high risk of mortality.

Serum Cystatin C Predicts Mortality in HBV-Related Decompensated Cirrhosis.

BACKGROUND: Some studies have reported that renal dysfunction is associated with poor prognosis in cirrhotic patients. Serum cystatin C (CysC) is an accurate biomarker for early renal dysfunction. This study aimed to assess the prognostic value of serum CysC levels in patients with hepatitis B virus-related decompensated cirrhosis (HBV-DeCi). METHODS: This retrospective study included 75 subjects who had been diagnosed with HBV-DeCi. The association between serum CysC and prognosis was estimated by receiver operating characteristic curve analysis and a multivariable logistic regression model. RESULTS: Serum CysC levels were higher in nonsurvivors than in survivors and were positively correlated with model for end-stage liver disease (MELD) scores. In multivariate analysis, CysC and the MELD score were independent prognostic factors in all HBV-DeCi patients. However, only serum CysC was an independent factor predicting mortality in patients with normal creatinine levels. CONCLUSIONS: These data suggest that high serum CysC levels can be considered an independent biomarker of 3-month mortality in patients with HBV-DeCi.