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Nutrients May 2024Studies have suggested that alkalinized foods may reduce the effects of the acidogenic Western diet in promoting obesity, metabolic syndrome, type 2 diabetes, cancer,...
Studies have suggested that alkalinized foods may reduce the effects of the acidogenic Western diet in promoting obesity, metabolic syndrome, type 2 diabetes, cancer, and coronary heart disease. Indeed, a recent study in mice fed a high-fat diet containing dietary beef supplemented with ammonium hydroxide showed improvement in a suite of metabolic outcomes. However, the effects of dietary protein ammonium supplementation on the microbiome remain unknown. In this study, the effects of ammonium supplementation on beef protein towards microbiome taxa and function in a high-fat diet were analyzed. Fecal microbiomes were characterized using a shotgun metagenomic approach for 16-month-old male and female mice after long-term diet treatments. The results for ammoniated diets showed that several bacteria known to be associated with health benefits increased significantly, including , , and . The beneficial mucin-degrader was especially abundant, with a high prevalence (~86%) in females. Concurrently, the phyla Actinomycetota (Actinobacteria) and Bacteroidota (Bacteroidetes) were significantly reduced. While sex was a confounding factor affecting microbiome responses to ammonium supplementation in dietary protein, it is worth noting that several putatively beneficial microbiome functions increased with ammonium supplementation, such as glycine betaine transport, xenobiotic detoxification, enhanced defense, and others. Conversely, many disease-associated microbiome functions reduced. Importantly, modifying protein pH alone via ammonium supplementation induced beneficial microbiota changes. Taken together, these results suggest that ammonium-supplemented proteins may mediate some negative microbiome-associated effects of high-fat/Western diets.
Topics: Animals; Diet, High-Fat; Female; Male; Gastrointestinal Microbiome; Mice; Dietary Supplements; Ammonium Hydroxide; Feces; Red Meat; Dietary Proteins; Bacteria; Cattle
PubMed: 38892546
DOI: 10.3390/nu16111613 -
International Journal of Molecular... Jun 2024Ovarian cancer (OC) has an unfavorable prognosis. Due to the lack of effective screening tests, new diagnostic methods are being sought to detect OC earlier. The aim of...
Ovarian cancer (OC) has an unfavorable prognosis. Due to the lack of effective screening tests, new diagnostic methods are being sought to detect OC earlier. The aim of this study was to evaluate the concentration and diagnostic utility of selected matrix metalloproteinases (MMPs) as OC markers in comparison with HE4, CA125 and the ROMA algorithm. The study group consisted of 120 patients with OC; the comparison group consisted of 70 patients with benign lesions and 50 healthy women. MMPs were determined via the ELISA method, HE4 and CA125 by CMIA. Patients with OC had elevated levels of MMP-3 and MMP-11, similar to HE4, CA125 and ROMA values. The highest SE, SP, NPV and PPV values were found for MMP-26, CA125 and ROMA in OC patients. Performing combined analyses of ROMA with selected MMPs increased the values of diagnostic parameters. The topmost diagnostic power of the test was obtained for MMP-26, CA125, HE4 and ROMA and performing combined analyses of MMPs and ROMA enhanced the diagnostic power of the test. The obtained results indicate that the tested MMPs do not show potential as stand-alone OC biomarkers, but can be considered as additional tests to raise the diagnostic utility of the ROMA algorithm.
Topics: Humans; Female; Ovarian Neoplasms; CA-125 Antigen; WAP Four-Disulfide Core Domain Protein 2; Middle Aged; Algorithms; Biomarkers, Tumor; Adult; Aged; Matrix Metalloproteinase 2; Proteins; Matrix Metalloproteinases; Matrix Metalloproteinase 3; Membrane Proteins; Case-Control Studies; ROC Curve; Matrix Metalloproteinase 11
PubMed: 38892452
DOI: 10.3390/ijms25116265 -
International Journal of Molecular... May 2024N-acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties. The respiratory syncytial virus (RSV) is one of the most important... (Review)
Review
N-acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties. The respiratory syncytial virus (RSV) is one of the most important etiological factors of lower respiratory tract infections, and exposure to air pollution appears to be additionally associated with higher RSV incidence and disease severity. We aimed to systematically review the existing literature to determine which molecular mechanisms mediate the effects of NAC in an RSV infection and air pollution, and to identify the knowledge gaps in this field. A search for original studies was carried out in three databases and a calibrated extraction grid was used to extract data on the NAC treatment (dose, timing), the air pollutant type, and the most significant mechanisms. We identified only 28 studies conducted in human cellular models ( = 18), animal models ( = 7), and mixed models ( = 3). NAC treatment improves the barrier function of the epithelium damaged by RSV and air pollution, and reduces the epithelial permeability, protecting against viral entry. NAC may also block RSV-activated phosphorylation of the epidermal growth factor receptor (EGFR), which promotes endocytosis and facilitates cell entry. EGFR also enhances the release of a mucin gene, MUC5AC, which increases mucus viscosity and causes goblet cell metaplasia; the effects are abrogated by NAC. NAC blocks virus release from the infected cells, attenuates the cigarette smoke-induced shift from necrosis to apoptosis, and reverses the block in IFN-γ-induced antiviral gene expression caused by the inhibited Stat1 phosphorylation. Increased synthesis of pro-inflammatory cytokines and chemokines is induced by both RSV and air pollutants and is mediated by the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways that are activated in response to oxidative stress. MCP-1 (monocyte chemoattractant protein-1) and RANTES (regulated upon activation, expressed and secreted by normal T cells) partially mediate airway hyperresponsiveness (AHR), and therapeutic (but not preventive) NAC administration reduces the inflammatory response and has been shown to reduce ozone-induced AHR. Oxidative stress-induced DNA damage and cellular senescence, observed during RSV infection and exposure to air pollution, can be partially reversed by NAC administration, while data on the emphysema formation are disputed. The review identified potential common molecular mechanisms of interest that are affected by NAC and may alleviate both the RSV infection and the effects of air pollution. Data are limited and gaps in knowledge include the optimal timing or dosage of NAC administration, therefore future studies should clarify these uncertainties and verify its practical use.
Topics: Humans; Acetylcysteine; Respiratory Syncytial Virus Infections; Animals; Air Pollution; ErbB Receptors
PubMed: 38892239
DOI: 10.3390/ijms25116051 -
Cells May 2024Plasma gelsolin (pGSN) overexpression in ovarian cancer (OVCA) disarms immune function, contributing to chemoresistance. The aim of this study was to investigate the...
Plasma gelsolin (pGSN) overexpression in ovarian cancer (OVCA) disarms immune function, contributing to chemoresistance. The aim of this study was to investigate the immunoregulatory effects of pGSN expression on natural killer (NK) cell function in OVCA. OVCA tissues from primary surgeries underwent immunofluorescent staining of pGSN and the activated NK cell marker natural cytotoxicity triggering receptor 1 to analyze the prognostic impact of pGSN expression and activated NK cell infiltration. The immunoregulatory effects of pGSN on NK cells were assessed using apoptosis assay, cytokine secretion, immune checkpoint-receptor expression, and phosphorylation of STAT3. In OVCA tissue analyses, activated NK cell infiltration provided survival advantages to patients. However, high pGSN expression attenuated the survival benefits of activated NK cell infiltration. In the in vitro experiment, pGSN in OVCA cells induced NK cell death through cell-to-cell contact. pGSN increased T-cell immunoglobulin and mucin-domain-containing-3 expression (TIM-3) on activated NK cells. Further, it decreased interferon-γ production in activated TIM-3+ NK cells, attenuating their anti-tumor effects. Thus, increased pGSN expression suppresses the anti-tumor functions of NK cells. The study provides insights into why immunotherapy is rarely effective in patients with OVCA and suggests novel treatment strategies.
Topics: Humans; Killer Cells, Natural; Female; Gelsolin; Carcinoma, Ovarian Epithelial; Drug Resistance, Neoplasm; Ovarian Neoplasms; Cell Line, Tumor; Middle Aged; Hepatitis A Virus Cellular Receptor 2; Apoptosis; STAT3 Transcription Factor; Interferon-gamma
PubMed: 38891037
DOI: 10.3390/cells13110905 -
Journal of Microbiological Methods Jun 2024The mucin-degrading gut commensal Akkermansia muciniphila (A. muciniphila) negatively correlates with various diseases, including metabolic disorders, neurodegenerative...
The mucin-degrading gut commensal Akkermansia muciniphila (A. muciniphila) negatively correlates with various diseases, including metabolic disorders, neurodegenerative disorders, and cancers, through interacting with host receptors by diverse molecules. Still, their exact metabolic capability within the nutrient-rich environment (such as in the human gut) is not fully characterized. Therefore, in the present study, we investigated the comprehensive metabolome and lipidome of A. muciniphila after supplementation of four major gut microbial nutrients: mucin, inorganic salts, bile salts, and short-chain fatty acids (SCFAs). Our results showed that mucin is the predominant driver of the different lipidomic and metabolomic profiles of A. muciniphila, and it promotes the overall growth of this bacteria. While the addition of inorganic salts, bile salts, and SCFAs was found to inhibit the growth of A. muciniphila. Interestingly, inorganic salts affected the purine metabolism in A. muciniphila cultures, while adding bile salts significantly increased the production of other bile acids and N-acyl amides. Lastly, SCFAs were identified to alter the A. muciniphila energy utilization of triglycerides, fatty acyls, and phosphatidylethanolamines. To our knowledge, this is the first study to examine the comprehensive lipidome and metabolome of A. muciniphila, which highlights the importance of nutritional impacts on the lipidome and metabolome of A. muciniphila and hence providing foundational knowledge to unveil the potential effects of A. muciniphila on host health.
PubMed: 38889842
DOI: 10.1016/j.mimet.2024.106975 -
JCI Insight Jun 2024Mucus plugs occlude airways to obstruct airflow in asthma. Studies in patients and in mouse models show that mucus plugs occur in the context of type 2 inflammation, and...
Mucus plugs occlude airways to obstruct airflow in asthma. Studies in patients and in mouse models show that mucus plugs occur in the context of type 2 inflammation, and studies in human airway epithelial cells (HAECs) show that interleukin 13 (IL-13) activated cells generate pathologic mucus independently of immune cells. To determine how HAECs autonomously generate pathologic mucus, we used a magnetic microwire rheometer to characterize the viscoelastic properties of mucus secreted under varying conditions. We found that normal HAEC mucus exhibits viscoelastic liquid behavior and that mucus secreted by IL-13 activated HAECs exhibits solid-like behavior caused by mucin cross-linking. In addition, IL-13 activated HAECs show increased peroxidase activity in apical secretions, and an overlaid thiolated polymer (thiomer) solution shows an increase in solid behavior that is prevented by peroxidase inhibition. Furthermore, gene expression for thyroid peroxidase (TPO), but not lactoperoxidase (LPO), is increased in IL-13 activated HAECs and both TPO and LPO catalyze the formation of oxidant acids that cross-link thiomer solutions. Finally, gene expression for TPO in airway epithelial brushings is increased in asthma patients with high airway mucus plug scores. Together, our results show that IL-13 activated HAECs autonomously generate pathologic mucus via peroxidase-mediated cross-linking of mucin polymers.
PubMed: 38889046
DOI: 10.1172/jci.insight.181024 -
VideoGIE : An Official Video Journal of... Jun 2024Video 1A case characterizing the extent and morphology of an intraductal mucinous biliary neoplasm using a novel cholangioscope and treatment with ampullectomy.
Video 1A case characterizing the extent and morphology of an intraductal mucinous biliary neoplasm using a novel cholangioscope and treatment with ampullectomy.
PubMed: 38887736
DOI: 10.1016/j.vgie.2024.02.009 -
BMC Gastroenterology Jun 2024B3GNT7, a glycosyltransferase of significant importance that is highly expressed in intestinal epithelial cells, plays a pivotal role in intestinal physiological...
BACKGROUND
B3GNT7, a glycosyltransferase of significant importance that is highly expressed in intestinal epithelial cells, plays a pivotal role in intestinal physiological processes. This study elucidates novel insights into the potential role and underlying mechanisms of B3GNT7 in ulcerative colitis (UC).
METHODS
An experimental colitis model was induced using DSS in mice to investigate B3GNT7 expression in the colon via transcriptomics and immunohistochemistry. Bioinformatics analysis was employed to delineate the biological functions of B3GNT7. Additionally, the correlation between the transcription levels of B3GNT7 in colonic tissues from patients with UC, sourced from the IBDMDB database, and the severity of colonic inflammation was analyzed to elucidate potential mechanisms.
RESULTS
The DSS-induced colitis model was successfully established, and transcriptomic analysis identified a marked downregulation of B3GNT7 expression in the colonic tissues compared to the controls. Functional enrichment analysis indicated B3GNT7's predominant role in mucin O-glycosylation. Protein interaction analysis revealed that B3GNT7 predominantly interacts with members of the mucin MUC family, including MUC2, MUC3, and MUC6. In patients with UC, B3GNT7 transcription levels were significantly reduced, particularly in those with moderate to severe disease activity. The expression level of B3GNT7 exhibited a negative correlation with the endoscopic severity of UC. Gene set enrichment analysis (GSEA) further demonstrated significant enrichment of B3GNT7 in the mucin O-glycosylation synthesis pathway.
CONCLUSION
The downregulation of B3GNT7 expression in the colonic tissues of UC patients may contribute to the compromised mucin barrier function and the exacerbation of colitis.
Topics: Animals; Humans; Male; Mice; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Down-Regulation; Glycosylation; Intestinal Mucosa; Mice, Inbred C57BL; Mucins; N-Acetylglucosaminyltransferases
PubMed: 38886669
DOI: 10.1186/s12876-024-03287-8 -
BMC Gastroenterology Jun 2024Dilatation of common bile duct (CBD) is mostly pathological and mainly occurs secondary to mechanical causes. We aimed to explore the prevalence of CBD dilatation in...
BACKGROUND
Dilatation of common bile duct (CBD) is mostly pathological and mainly occurs secondary to mechanical causes. We aimed to explore the prevalence of CBD dilatation in Intraductal Papillary Mucinous Neoplasms of the pancreas (IPMN) among patients referred to EUS.
METHODS
A retrospective study of all patients who had an EUS diagnosis of IPMN from 2011 to 2019 at Galilee Medical Center were extracted. Control group including patients with other types of pancreatic cysts.
RESULTS
Overall, 2400 patients were included in the study, of them 158 patients were diagnosed with pancreatic cysts, 117 patients (74%) diagnosed with IPMN (group A), and 41 patients (26%) diagnosed with other pancreatic cysts (group B). Univariate analysis showed significant association of IPMN (OR 3.8, 95% CI 1.3-11.5), resected gallbladder (GB) (OR 7.75, 95% CI 3.19-18.84), and age (OR 1, 95% CI 1.01-1.08) with CBD dilatation. Classifying IPMN to sub-groups using adjusted multivariate logistic regression analysis, only main duct-IPMN (MD-IPMN) significantly correlated with CBD dilatation compared to branch duct (BD)-IPMN and mixed type-IPMN (OR 19.6, 95% CI 4.57-83.33, OR 16.3, 95% CI 3.02-88.08).
CONCLUSION
MD-IPMN was significantly correlated with dilated CBD. Assessment of the pancreas is warranted in encountered cases of dilated CBD without obvious mechanical cause.
Topics: Humans; Male; Female; Retrospective Studies; Middle Aged; Dilatation, Pathologic; Aged; Common Bile Duct; Pancreatic Intraductal Neoplasms; Endosonography; Pancreatic Cyst; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Adenocarcinoma, Mucinous
PubMed: 38886637
DOI: 10.1186/s12876-024-03291-y -
Journal of Clinical Pathology Jun 2024Colorectal cancer (CRC) is the third most common malignancy worldwide. Accurate pathological diagnosis and predictive abilities for treatment response and prognosis are...
AIMS
Colorectal cancer (CRC) is the third most common malignancy worldwide. Accurate pathological diagnosis and predictive abilities for treatment response and prognosis are crucial for patients with CRC. This study aims to analyse the expressions of p21 and EGFR in CRC and their relationships with clinicopathological characteristics and prognosis to enhance diagnostic and prognostic evaluations.
METHODS
This study conducted a retrospective analysis of p21 and EGFR expressions in 12 319 Chinese patients with CRC using immunohistochemistry. The relationships between these expressions and clinicopathological characteristics and survival outcomes were explored through statistical and survival analyses.
RESULTS
Differential expressions of p21 and EGFR in CRC were closely related to clinicopathological characteristics and significantly impacted overall survival (OS). p21 expression was associated with the primary tumour site, mucinous subtype, lymphovascular invasion, perineural invasion, circumferential resection margin, T stage, N stage, tumour, node, metastases (TNM) stage, and mismatch repair status. EGFR expression was related to mucinous subtype, tumour differentiation, lymphovascular invasion, perineural invasion, tumour size, T stage, N stage, TNM stage and gene mutation. p21 and EGFR expressions were positively correlated (r=0.11). High p21 expression correlated with favourable OS, whereas high EGFR expression predicted poorer OS. A prognostic nomogram incorporating these biomarkers and clinical variables demonstrated robust predictive power for patient survival rates.
CONCLUSION
p21 and EGFR serve as potential indicators for pathological diagnosis, risk stratification, and predicting treatment efficacy and prognosis in patients with CRC. The study's findings provide valuable references for personalised treatment and prognosis evaluation in clinical practice.
PubMed: 38886043
DOI: 10.1136/jcp-2024-209450