Causal relationship between the gut microbiota, immune cells, and coronary heart disease: a mediated Mendelian randomization analysis.

Background: Recent studies have shown that the gut microbiota (GM), immune cells, and coronary heart disease (CHD) are closely related, but the causal nature of these relationships is largely unknown. This study aimed to investigate this causal relationship and reveal the effect of GM and immune cells on the risk of developing CHD using mediated Mendelian randomization (MR) analysis. Methods: First, we searched for data related to GM, immune cells, and CHD through published genome-wide association studies (GWAS). We filtered the single nucleotide polymorphisms (SNPs) associated with GM and immune cells and then performed the first MR analysis to identify disease-associated intestinal bacteria and disease-associated immune cells. Subsequently, three MR analyses were conducted: from disease-associated GM to disease-associated immune cells, from disease-associated immune cells to CHD, and from disease-associated GM to CHD. Each MR analysis was conducted using inverse variance weighting (IVW), MR-Egger regression, weighted median, weighted models, and simple models. Results: A total of six GM and 25 immune cells were found to be associated with CHD. In the MR analysis using the inverse variance weighting (IVW) method, g__Desulfovibrio.s__Desulfovibrio_piger was associated with EM DN (CD4-CD8-) %T cells (P < 0.05 and OR > 1), EM DN (CD4-CD8-) %T cells was associated with CHD (P < 0.05 and OR < 1), and g__Desulfovibrio.s__Desulfovibrio_piger was associated with CHD (P < 0.05 and OR < 1). Conclusion: An increase in the abundance of g__Desulfovibrio.s__Desulfovibrio_piger leads to an increase in the amount of EM DN (CD4-CD8-) %T cells, and an increase in the amount of EM DN (CD4-CD8-) %T cells reduces the risk of developing CHD. Our study provides some references for reducing the incidence of CHD by regulating GM and immune cells.

Five-Year Outcomes of Bioresorbable Stent Therapy for Coronary Heart Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: The efficacy of bioresorbable vascular scaffolds (BVS) compared to metallic stents for the treatment of coronary heart disease remains controversial. The analysis of clinical outcomes at five years following the initial treatment has yet to be reviewed. This study sought to assess the five-year outcomes in randomized controlled trials of BVS in the treatment of coronary heart disease using a systematic review and meta-analysis. Methods: A systematic database search was conducted from their inception to June 30th, 2023 using various Medical Subject Headings (MeSH) terms including: "Coronary Disease", "Bioresorbable stent", "Randomized controlled trials". Results: After a rigorous selection process, a total of five high-quality articles were finally included in this study. Each trial demonstrated a low risk of bias. After 5 years, bioresorbable stents showed outcomes similar to conventional metal stents in terms of cardiac mortality. However, they were inferior in terms of lesion revascularization rates, in-stent thrombosis rates, target lesion failure, target vessel failure, and myocardial infarction. Conclusions: While bioresorbable stents are comparable to metallic stents in terms of cardiac mortality rates, they exhibit significant drawbacks that warrant clinical consideration.

Circ_PABPC1 promotes the malignancy of gastric cancer through interacting with ILK to activate NF-κB pathway.

BACKGROUND: Gastric cancer (GC) is a common cancer type with both high incidence and mortality. Recent studies have revealed an important role of circRNA in the development of GC. However, more experiments are needed to reveal the precise molecular mechanisms of circRNA in GC development. METHODS: Bioinformatics analysis was conducted to predict the potential role of circ_PABPC1 in GC and the target proteins of circ_PABPC1. Quantitative RT-PCR, Western blot and immunohistochemistry assays were conducted to detect the levels of circ_PABPC1, NF-κB p65, NF-κB p65 (Ser536) and ILK. MTT, Edu staining, cell scratch-wound and trans-well assays were carried out to detect cell proliferation, migration and invasion. The interaction between ILK and circ_PABPC1 was confirmed by RNA immunoprecipitation (RIP), RNA pull-down and fluorescence in situ hybridization assays. Genetically modified GC cells were injected into mice to evaluate the tumor growth performance. RESULTS: This study found that the high expression of circ_PABPC1 was associated with a poor prognosis of GC. The up-regulation of circ_PABPC1 promoted the proliferation, migration and invasion of GC cells. Circ_PABPC1 bound to ILK protein, thereby preventing the degradation of ILK. ILK mediated the effect of circ_PABPC1 on GC cells through activating NF-κB. CONCLUSION: circ_PABPC1 promotes the malignancy of GC cells through binding to ILK to activate NF-κB signaling pathway.

An Integrated Analysis of Prognostic Signature and Immune Microenvironment in Tongue Squamous Cell Carcinoma.

Tongue squamous cell carcinoma (TSCC) is a prevalent cancer of the oral cavity. Survival metrics are usually unsatisfactory, even using combined treatment with surgery, radiation, and chemotherapy. Immune checkpoint inhibitors can prolong survival, especially in patients with recurrent or metastatic disease. However, there are few effective biomarkers to provide prognosis and guide immunotherapy. Here, we utilized weighted gene co-expression network analysis to identify the co-expression module and selected the turquoise module for further scrutiny. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed the innate pathways. The findings indicated that cell junction organization, response to topologically incorrect protein, and regulation of cell adhesion pathways may be essential. Eleven crucial predictive genes (PLXNB1, N4BP3, KDELR2, INTS8, PLAU, PPFIBP2, OAF, LMF1, IL34, ZFP3, and MAP7D3) were used to establish a risk model based on Cox and LASSO analyses of The Cancer Genome Atlas and GSE65858 databases (regarding overall survival). Kaplan-Meier analysis and receiver operating characteristic curve suggested that the risk model had better prognostic effectiveness than other clinical traits. Consensus clustering was used to classify TSCC samples into two groups with significantly different survival rates. ESTIMATE and CIBERSORT were used to display the immune landscape of TSCC and indicate the stromal score; specific types of immune cells, including naïve B cells, plasma cells, CD8 T cells, CD4 memory resting and memory activated T cells, follicular helper T cells, and T regulatory cells, may influence the heterogeneous immune microenvironment in TSCC. To further identify hub genes, we downloaded GEO datasets (GSE41613 and GSE31056) and successfully validated the risk model. Two hub genes (PLAU and PPFIBP2) were strongly associated with CD4+ and CD8+ T cells and programmed cell death protein 1 (PD1) and PD-ligand 1.

In vitro digestion and fermentation of released exopolysaccharides (r-EPS) from Lactobacillus delbrueckii ssp. bulgaricus SRFM-1.

The aim of this study was to investigate the in vitro digestion and fermentation prebiotic properties of three released-exopolysaccharide fractions (r-EPS1, r-EPS2 and r-EPS3) from Lactobacillus delbrueckii ssp. bulgaricus SRFM-1. There were no free oligosaccharides and/or monosaccharides for r-EPS1 before and after simulated buccal, gastric and small intestinal (GSI) digestion in vitro. In contrast, r-EPS2 (13.4 %) and r-EPS3 (10.6 %) generated a few monosaccharides after digestion. Additionally, r-EPS1 and r-EPS2 seemed to present a strong bifidogenic effect comparing to inulin, as they exhibited high values of selectivity index (13.17 and 12.84, respectively). Furthermore, the fermentation with r-EPS1 produced the highest contents of acetic acid and lactic acid (56.3 mM and 44.29 mM, respectively), which resulted in the highest amounts of total short chain fatty acid (145.51 mM) followed by r-EPS2 (135.57 mM) and inulin (99.28 mM). These results indicated that r-EPS from L. delbrueckii ssp. bulgaricus SRFM-1 could be a good potential candidate for new functional food prebiotic.

Structural characterization and antioxidant property of released exopolysaccharides from Lactobacillus delbrueckii ssp. bulgaricus SRFM-1.

Three released exopolysaccharide fractions (r-EPS1, r-EPS2 and r-EPS3) were isolated from the fermented milk of Lactobacillus delbrueckii ssp. bulgaricus SRFM-1 and purified by anion exchange chromatography, and characterizations of the structures were conducted. The r-EPS1 and r-EPS2 were homogenous with the average molecular weights of 3.97×105Da and 3.86×105Da, respectively. Three r-EPS fractions were composed of galactose and glucose with a molar ratio of 1.23: 1.00, 1.33: 1.00 and 1.00: 1.34, respectively. Structural characterization indicated that the r-EPS1 contained a backbone of →6-ß-d-Galp-(1→4)-ß-d-Glcp-(1→4)-α-d-Galp-(1→4)-ß-d-Galp-(1→6)-ß-d-Galp-(1→4)-ß-d-Glcp-(1→4)-α-d-Galp-(1→4)-ß-d-Galp-(1→4)-α-d-Glcp-(1→, and had three branching points which existed in terminal with D-Glcp residues with α/ß-d-(1→6) linkages. The r-EPS2 was composed of →6-ß-d-Galp-(1→4)-ß-d-Glcp-(1→6)-α-d-Galp-(1→ as the backbone chain with a branching point which also existed in terminal D-Glcp residue with ß-(1→6) linkage. In addition, three r-EPS fractions exhibited strong scavenging activities on superoxide radical, hydroxyl radical, DPPH radical and chelating activity on ferrous ion, and their antioxidant activities decreased in the order of r-EPS1>r-EPS2>r-EPS3.

Research progress in the treatment of small cell lung cancer.

Small cell lung cancer (SCLC) accounts for approximately 10-15% of all lung cancers. No significant improvement has been made for patients with SCLC in the past several decades. The main progresses were the thoracic radiation and prophylactic cranial irradiation (PCI) that improved the patient survival rate. For patients with limited disease and good performance status (PS), concurrent chemoradiotherapy (CCRT) followed by PCI should be considered. For extensive disease, the combination of etoposide and platinum-based chemotherapy remains the standard treatment and consolidative thoracic radiotherapy is beneficial for patients who have a significant respond to initial chemotherapy. However, the prognosis still remains poor. Recently, efforts have been focused on molecular targets and immunotherapy. But numerous molecular targets methods have failed to show a significant clinical benefit in patients with SCLC. It is anticipated that further development of research will depend on the on-going trials for molecular targeted therapy and immunotherapy which are promising and may improve the outcomes for SCLC in the next decade.

Characterization of a novel polysaccharide with anti-colon cancer activity from Lactobacillus helveticus MB2-1.

The present study aimed at investigating the potential anti-colon cancer activity of three purified exopolysaccharides fractions (LHEPS-1, LHEPS-2 and LHEPS-3) from the Lactobacillus helveticus MB2-1. The experimental evidence showed that LHEPS-1 significantly inhibited cell proliferation of human colon cancer Caco-2 cells in both time- and concentration-dependent manners. In contrast, no significant improvements of the inhibitory effects of LHEPS-2 and LHEPS-3 on Caco-2 cells were observed with increasing sample concentrations or prolonged incubation time. Furthermore, the structure of LHEPS-1 was elucidated using methylated analysis, gas chromatography-mass spectroscopy (GC-MS) and nuclear magnetic resonance spectroscopy (NMR), including one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR). Results indicated that the LHEPS-1 consisted of a decasaccharide repeating unit with the following structure (n ≈ 122)： Our results suggested that the LHEPS-1 produced by L. helveticus MB2-1 might be suitable for using as natural anti-colon cancer drugs and functional foods ingredients.

Structural characterization and anticancer activity of cell-bound exopolysaccharide from Lactobacillus helveticus MB2-1.

A novel cell-bound exopolysaccharide (c-EPS) was isolated from Lactobacillus helveticus MB2-1 by ultrasonic extraction, anion exchange, and gel filtration chromatography before being structurally characterized. The c-EPS is a heteropolysaccharide with an average molecular weight of 1.83 × 10(5) Da and is composed of glucose, mannose, galactose, rhamnose, and arabinose at a molar ratio of 3.12:1.01:1.00:0.18:0.16. Methylation analysis and nuclear magnetic resonance analysis revealed that the c-EPS is a linear glucomannogalactan containing repeating units of → 6)-ß-D-Manp-(1 → 3)-ß-D-Glcp-(1 → 3)-ß-D-Glcp-(1 → 3)-ß-D-Glcp-(1 → 4)-α-D-Galp-(1 → and trace amounts of Rhap-(1 → and (1 → 4)-Arap residues. Complex formation with Congo red demonstrated a triple-strand helical conformation for the c-EPS. Scanning electron microscopy of the c-EPS revealed many regular feather-like structural units. Topographical examination of c-EPS by atomic force microscopy revealed that the c-EPS formed rounded-to-spherical lumps with different sizes and chain formations. Furthermore, preliminary in vitro tests revealed that c-EPS significantly inhibited the proliferation of HepG-2, BGC-823, and especially HT-29 cancer cells.

Characterization of an antiproliferative exopolysaccharide (LHEPS-2) from Lactobacillus helveticus MB2-1.

In this study, we reported that three purified exopolysaccharides fractions (LHEPS-1, LHEPS-2 and LHEPS-3) and crude LHEPS from the Lactobacillus helveticus MB2-1 inhibited the proliferation potential of human gastric cancer BGC-823 cells. We found that all the LHEPS fractions and crude LHEPS exerted concentration and time dependent inhibitory activities in vitro on BGC-823 cells. LHEPS-2 exhibited higher antiproliferative activity against BGC-823 cells in vitro than LHEPS-1, LHEPS-3 and crude LHEPS. With the consideration of the outstanding antiproliferative effect of LHEPS-2 on BGC-823 cells, more fine structural characterization of LHEPS-2 was further identified. The structure of LHEPS-2 was elucidated by methylated analysis, GC-MS, (1)H NMR and (13)C NMR spectroscopy, together with two-dimensional (2D) COSY, TOCSY, HSQC, HMBC and NOESY spectroscopy. Results showed that the LHEPS-2 was consisted of the following repeating units: