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Scientific Reports Sep 2019Pepsin represents a potential biomarker for extraesophageal reflux disease when detected in airways, however a direct role for pepsin in lung dysfunction has not been...
Pepsin represents a potential biomarker for extraesophageal reflux disease when detected in airways, however a direct role for pepsin in lung dysfunction has not been clearly established. Children experiencing gastroesophageal and extraesophageal reflux are often prescribed proton pump inhibitors (PPIs) to reduce gastric acid associated damage to esophageal and airway mucosa. The potential of pepsin and gastric fluid, from children that were either on or off PPI therapy, to cause inflammation and damage using a human in vitro co-culture model of the airway mucosa was evaluated herein. Exposure of the airway model to acidic solutions caused cellular damage and loss of viability, however, acid alone did not disrupt barrier integrity or instigate neutrophil trans-epithelial migration without pepsin. Gastric fluid from patients on PPI therapy exhibited only a slightly higher pH yet had significantly higher concentrations of pepsin and elicited more barrier disruption and neutrophil trans-epithelial migration compared to gastric fluid from patients off PPIs. Inflammatory and damaging responses observed with gastric fluid from patients on PPIs were largely driven by pepsin. These results indicate the potential for PPI usage to raise concentrations of pepsin in gastric fluid, which may enhance the pathological impact of micro-aspirations in children with extraesophageal reflux.
Topics: Adolescent; Adult; Bile Acids and Salts; Cell Line; Cell Movement; Child; Epithelium; Esophageal pH Monitoring; Esophagus; Female; Gastric Acid; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Inflammation; Male; Neutrophils; Pepsin A; Proton Pump Inhibitors; Young Adult
PubMed: 31551494
DOI: 10.1038/s41598-019-50360-4 -
Environment International Sep 2023Microplastics residues in natural waters can adsorb organic contaminants owing to their rough surface morphology and high specific surface area, potentially harming...
Microplastics residues in natural waters can adsorb organic contaminants owing to their rough surface morphology and high specific surface area, potentially harming human health when ingested. Although humans inevitably ingest microplastics, the bioaccessibility of microplastic-associated chemicals in the human gastric and intestinal fluids remains unresolved. This study investigated the mechanism and primary factor controlling the bioaccessibility of polypropylene (PP) microplastic fiber-associated tetracycline (TC) and ciprofloxacin (CIP) in simulated human gastrointestinal fluids. After mixing 0.1 g of PP microfiber with 10 mg/L of TC (or CIP) for 96 h and exposure to simulated human gastrointestinal fluids, the TC concentrations were 0.440, 0.678, and 1.840 mg/L and the CIP concentrations were 0.700, 1.367, and 3.281 mg/L CIP in the simulated human saliva, gastric, and intestinal fluids after incubation for 60 s, 4 h, and 8 h, respectively. This indicated that the antibiotics TC and CIP adsorbed onto microfiber surface are readily released into human gastrointestinal fluids upon ingestion. Gastric and intestinal fluids showed enhanced bioaccessibility to TC/CIP adhered to PP microfiber. The primary factors affecting the bioaccessibility to TC/CIP adhered to PP microfiber surfaces were found to be pepsin in human gastric fluid and trypsin in human intestinal fluid. Molecular docking and simulated molecular dynamic analyses results showed that pepsin and trypsin stablish connections with TC via hydrogen bonds (reaction sites: pepsin TC: T, T, S, D, D and Y; trypsin TC: S, H, K, G, and G) and CIP via hydrophobic interactions (reaction sites: pepsin CIP: Y, T, T, F, I, V, and I; trypsin CIP: W, I, C, and C). Our findings highlight that microplastic ingestion increases the risk of microplastics and the co-contaminants adsorbed to human health; thus, these findings are helpful to assess the risk of microplastics and co-contaminants to human health.
Topics: Humans; Ciprofloxacin; Microplastics; Plastics; Polypropylenes; Molecular Docking Simulation; Pepsin A; Trypsin; Anti-Bacterial Agents; Tetracycline
PubMed: 37703772
DOI: 10.1016/j.envint.2023.108193 -
EFSA Journal. European Food Safety... Jun 2023The food enzyme containing chymosin (EC 3.4.23.4) and pepsin A (EC 3.4.23.1) is prepared from the abomasum of calves and cows () by Chr. Hansen. The food enzyme is...
The food enzyme containing chymosin (EC 3.4.23.4) and pepsin A (EC 3.4.23.1) is prepared from the abomasum of calves and cows () by Chr. Hansen. The food enzyme is intended to be used in milk processing for cheese production and in milk processing for the production of fermented milk products. As no concerns arise from the animal source of the food enzyme, from its manufacture, and based on the history of safe use and consumption, the Panel considered that toxicological data were unnecessary and an estimation of dietary exposure was not required. A search for the similarity of the amino acid sequences of the two proteins (chymosin and pepsin A) to those of known allergens was made and one match with pig pepsin, a respiratory allergen, was found. The Panel considered that, under the intended conditions of use, the risk of allergic reactions upon dietary exposure cannot be excluded, but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.
PubMed: 37396876
DOI: 10.2903/j.efsa.2023.8084 -
BioMed Research International 2021Elderly patients receiving nasal feeding have weaker physiological function, and placement of a nasogastric tube weakens the natural barrier of the cardia-esophageal...
BACKGROUND
Elderly patients receiving nasal feeding have weaker physiological function, and placement of a nasogastric tube weakens the natural barrier of the cardia-esophageal sphincter; therefore, the risk of gastroesophageal reflux (GER) is higher. Many studies have shown that pepsin is extremely sensitive in predicting GERD, so this study intends to investigate the level of pepsin in saliva of elderly patients with nasal feeding and analyze its influencing factors.
METHODS
This was a cross-sectional study. Patients admitted to the Chinese PLA General Hospital from April 2018 to October 2018 who received nasal feeding were included. One ml of saliva was collected from each patient in while sitting during fasting in the morning and 1 hour after lunch for 3 consecutive days. Pepsin was quantified by enzyme-linked immunosorbent assay (ELISA). The patients were predivided into two groups (≥7.75g/ml or <7.75g/ml) based on the median pepsin. Baseline and clinical factors were compared.
RESULTS
The mean age of the patients was 91.09 ± 4.91 years. There were statistical differences in diabetes and feeding methods between the two groups. There was a positive correlation between the morning and postprandial pepsin levels ( = 0.442, < 0.001), and has no statistical difference ( = 0.175). Multivariate analysis showed that the risk factors for higher pepsin levels were diabetes (odds ratio (OR): 2.67; 95% CI: 1.225-5.819, = 0.013) and nasal feeding methods (OR: 2.475; 95% CI: 1.183-5.180, =0.016).
CONCLUSIONS
For patients undergoing nasal feeding who are older than 80 years, the fasting and 1-hour postprandial pepsin concentration were consistent. Diabetes and feeding methods are risk factors for high pepsin levels. For the elderly over 80 years old, age has no influence on pepsin concentration.
Topics: Administration, Intranasal; Aged; Aged, 80 and over; Eating; Electric Impedance; Esophageal pH Monitoring; Esophagus; Feeding Methods; Female; Gastroesophageal Reflux; Humans; Male; Pepsin A; Saliva
PubMed: 33564676
DOI: 10.1155/2021/4721812 -
American Journal of Otolaryngology 2020This study aimed to evaluate if laryngopharyngeal reflux (LPR) plays a role as a risk factor for vocal fold polyps (VFPs), and if pepsin is associated with higher...
PURPOSE
This study aimed to evaluate if laryngopharyngeal reflux (LPR) plays a role as a risk factor for vocal fold polyps (VFPs), and if pepsin is associated with higher oxidative DNA damage of VFPs in the presence of LPR.
METHODS
Thirty patients with VFPs were recruited between 2017 and 2018. Prior to surgery, a laryngoscopy was performed on all subjects to evaluate VFPs. Polyp tissue and saliva samples were obtained scrupulously. Hematoxylin-eosin staining was performed for pathologic analysis. Immunohistochemistry and ELISA were used to detect pepsin in tissue and saliva of VFP patients. 8-OHdG and p-H2AX expression was detected to measure oxidative DNA damage in tissue. DNA damage was investigated in human immortalized laryngeal epithelial cells exposed to pepsin.
RESULTS
The pepsin concentration in saliva was significantly higher (t = 2.38, P = .024) in the pepsin positive group. There was no significant difference in pepsin expression at different sites and pathological subtypes of VFPs. The levels of 8-OHdG and p-H2AX were significantly higher in the pepsin positive group and positively correlated with the tissue expression of pepsin. The concentration of pepsin in saliva also showed a significant correlation with 8-OHdG levels. Expression of 8-OHdG and p-H2AX, and tail moment of the comet assay were elevated in human immortalized laryngeal epithelial cells following treatment with pepsin.
CONCLUSION
Patients with VFPs have higher levels of oxidative DNA damage in the presence of pepsin reflux. Pepsin may induce DNA damage in laryngeal epithelial cells and participate in the pathogenesis of VFPs.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Female; Gene Expression; Histones; Humans; Laryngeal Diseases; Laryngopharyngeal Reflux; Male; Oxidative Stress; Pepsin A; Polyps; Vocal Cords
PubMed: 32889371
DOI: 10.1016/j.amjoto.2020.102681 -
Medical Science Monitor : International... Dec 2018BACKGROUND Gastroesophageal reflux disease (GERD) is very common. Salivary pepsin detection has previously been considered as a method for GERD diagnosis. We performed a... (Meta-Analysis)
Meta-Analysis
BACKGROUND Gastroesophageal reflux disease (GERD) is very common. Salivary pepsin detection has previously been considered as a method for GERD diagnosis. We performed a meta-analysis to investigate the utility of salivary pepsin assay as a diagnostic tool of GERD. MATERIAL AND METHODS PubMed, Web of Science, the Cochran Library, and EMBASE (from January 1980 to 23 October 2018) were searched for pepsin in saliva for GERD diagnosis. We summarized the retrieved specificity, sensitivity, negative likelihood ratio (NLR), positive likelihood ratio (PLR), diagnostic odds ratio (DOR), and receiver operating characteristic (ROC) curves data in the meta-analysis. RESULTS In final analysis, a total of 5 studies were included. The summary sensitivity, specificity, NLR, and PLR were 0.60 (95% CI 0.41-0.76), 0.71 (95% CI 0.51-0.86), 0.56 (95% CI 0.34-0.93), and 2.1 (95% CI 1.1-4.1), respectively. The pooled DOR was 4 (95% CI 1.0-11.0) and area under the ROC was 0.70 (95% CI 0.66-0.74). CONCLUSIONS The meta-analysis showed that pepsin in saliva has moderate diagnostic value for GERD, and is not as helpful as previously thought.
Topics: Adult; Biomarkers; Gastroesophageal Reflux; Humans; Odds Ratio; Pepsin A; ROC Curve; Saliva; Sensitivity and Specificity
PubMed: 30596632
DOI: 10.12659/MSM.913978 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Feb 2023To analyze the consistency of pepsin assay kit, pepsin IHC, reflux symptom index(RSI) and reflux finding score(RFS) in the diagnosis of laryngopharyngeal reflux...
To analyze the consistency of pepsin assay kit, pepsin IHC, reflux symptom index(RSI) and reflux finding score(RFS) in the diagnosis of laryngopharyngeal reflux disease(LPRD). The clinical data of 61 inpatients with laryngeal diseases who were admitted to the Department of Otolaryngology, the First Affiliated Hospital of Kunming Medical University from May 2020 to December 2021 were retrospectively analyzed. The RSI and RFS scores, the Formwitz score of pepsin immunohistochemistry, and the results of pepsin detection kit were recorded. ICC group correlation coefficient and Kappa consistency analysis was used for three detection methods. Among 61 patients, 30 cases were positive and 31 cases were negative for the pepsin test kit, with a positive rate of 49.18%. The positive rate of pepsin immunohistochemistry was 45.90%(28/61), and the diagnostic agreement rate between the two was 70.49%. The consistency between them was high(=0.409). The positive rate of RSI and RFS in diagnosing LPRD was 62.30%(38/61), and the consistency rate was 73.77% with pepsin detection kit. The consistency between them was high(=0.486). Taking pepsin IHC as the reference standard, the sensitivity, specificity, positive predictive value and negative predictive value of pepsin detection kit were 71.43%(20/28), 69.70%(23/33), 66.67%(20/30) and 74.19%(23/31), respectively. Using RSI and RFS scales as reference criteria, the sensitivity, specificity, positive predictive value and negative predictive value of pepsin detection kit were 89.29%(25/28), 60.61%(20/33), 65.79%(25/38) and 86.96%(20/23), respectively. Analysis of correlation coefficient within ICC group: ICC value was 0.628, 95% confidence interval(0.497-0.741), the three methods have good consistency. The RSI and RFS scale scores were in good agreement with the pepsin test kit, and the pepsin test kit was also in good agreement with pepsin immunohistochemistry. As a non-invasive diagnostic technique, the pepsin test kit can be widely used in the diagnosis of pharyngeal reflux in combination with pepsin immunohistochemistry and RSI and RFS scale.
Topics: Humans; Laryngopharyngeal Reflux; Pepsin A; Retrospective Studies; Immunohistochemistry; Pharynx
PubMed: 36756822
DOI: 10.13201/j.issn.2096-7993.2023.02.004 -
BMC Pulmonary Medicine Sep 2023Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lung infection has represented a global challenge. Intriguingly, it has been shown that the alveolar lung...
BACKGROUND
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lung infection has represented a global challenge. Intriguingly, it has been shown that the alveolar lung epithelium expresses little Angiotensin Converting Enzyme receptor protein (ACE2), the entry receptor for SARS-CoV-2. Upper airway establishment of infection and translocation to the lung is well documented but other anatomical niches may be relevant to potentially serious lung infection. ACE2 is heavily expressed in the gastrointestinal tract and gastrointestinal symptoms support a clinical diagnosis of Coronavirus disease 2019 (COVID-19). This suggests a research question and the need to gather patient data exploring potential aerodigestive links in SARS-CoV-2 tranlocation and infection which may be relevant in the peripheral lung. This recognizes anatomical proximity and concepts of bi-directional movement between the Gastrointestinal and lung systems in normal physiology and disease. We have therefore explored the potential for gastro oesophageal reflux disease (GORD) micro aspiration and aeorodigestive pathophysiology in a novel prospective investigation of patients hospitalized with COVID-19.
METHODS
This is a prospective descriptive cohort study of 210 patients who were hospitalized with a confirmed diagnosis of COVID-19. The cohort was divided into three groups of patients based on symptom severity and radiological results. The Reflux Symptom Index (RSI) was used to evaluate the presence and severity of GOR. An RSI greater than 13 is considered to be abnormal. Patients' saliva samples were tested using enzyme-linked immunosorbent assay (ELISA) to determine the level of salivary pepsin among the cohort of patients.
RESULTS
A total of 210 patients with COVID-19 were enrolled in the study with 55.2% (116/210) classified as mildly ill, 31.9% (67/210) moderately ill and 12.9% (27/210) as severely ill. 34% (72/210) of the patients had an RSI score of over 13 and a median salivary pepsin value of 54 ± 29 ng/ml which suggested an incidence of extraesophageal reflux (EOR) in around a third of patients. The presence of respiratory comorbid conditions, an RSI score of over 13 and a salivary pepsin level of > 76ng/ml increased the risk of developing a more severe COVID-19 infection.
CONCLUSION
The study showed a high prevalence of EOR among the study cohort and provide the first prospective evidence suggesting the potential for aerodigestive pathophysiology including microaspiration in COVID-19 disease. We believe that the results of our study support the need for more extensive research.
Topics: Humans; COVID-19; Prospective Studies; SARS-CoV-2; Jordan; Angiotensin-Converting Enzyme 2; Cohort Studies; Pepsin A; Gastroesophageal Reflux
PubMed: 37697259
DOI: 10.1186/s12890-023-02638-7 -
Histochemistry and Cell Biology Jun 2023This study compares three different pretreatment protocols for the immunohistochemical detection of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in...
This study compares three different pretreatment protocols for the immunohistochemical detection of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in nuclear DNA. The human biological samples analyzed included formalin-fixed and paraffin-embedded (FFPE) normal squamous epithelium, ethanol-fixed cultured cells, and metaphase chromosomes. The antigen retrieval methods included low pH Citrate and high pH Tris-ethylenediaminetetraacetic acid (EDTA) protocols, as well as a method using Pepsin pretreatment combined with HCl for DNA denaturation. A gradual increase in the detection levels of 5-mC and 5-hmC was observed when going from Citrate via Tris/EDTA to Pepsin/HCl retrieval. While the Citrate retrieval protocol was the least efficient for the detection of 5-mC and 5-hmC, it did preserve nuclear morphology and enabled visualization of differences in intra- and internuclear distribution patterns in tissue and cell culture samples by single- and double-fluorescence detection. Quantification of (hydroxy)methylation levels in FFPE material demonstrated a significant heterogeneity and differences in 5-mC and 5-hmC levels within and between nuclei in the different compartments of normal squamous epithelium. It was concluded that immunohistochemical detection of 5-mC and 5-hmC enables the correlation of these DNA modifications with histomorphological features in heterogeneous tissues, but this is influenced by different pretreatment protocols that must be carefully chosen to allow an appropriate interpretation of these epigenetic switches.
Topics: Humans; Edetic Acid; Pepsin A; 5-Methylcytosine; Epigenesis, Genetic; DNA; DNA Methylation; Antigens; Carcinoma, Squamous Cell; Citrates; Cytosine
PubMed: 37010548
DOI: 10.1007/s00418-023-02187-4 -
International Journal of Molecular... Apr 2021Pepsin refluxate is considered a risk factor for laryngopharyngeal carcinogenesis. Non-acidic pepsin was previously linked to an inflammatory and tumorigenic effect on...
Pepsin refluxate is considered a risk factor for laryngopharyngeal carcinogenesis. Non-acidic pepsin was previously linked to an inflammatory and tumorigenic effect on laryngopharyngeal cells in vitro. Yet there is no clear evidence of the pepsin-effect on a specific oncogenic pathway and the importance of pH in this process. We hypothesized that less acidic pepsin triggers the activation of a specific oncogenic factor and related-signalling pathway. To explore the pepsin-effect in vitro, we performed intermittent exposure of 15 min, once per day, for a 5-day period, of human hypopharyngeal primary cells (HCs) to pepsin (1 mg/mL), at a weakly acidic pH of 5.0, a slightly acidic pH of 6.0, and a neutral pH of 7.0. We have documented that the extracellular environment at pH 6.0, and particularly pH 7.0, vs. pH 5.0, promotes the pepsin-effect on HCs, causing increased internalized pepsin and cell viability, a pronounced activation of EGFR accompanied by NF-B and STAT3 activation, and a significant upregulation of , , , , , , , and . We herein provide new evidence of the pepsin-effect on oncogenic EGFR activation and its related-signaling pathway at neutral and slightly acidic pH in HCs, opening a window to further explore the prevention and therapeutic approach of laryngopharyngeal reflux disease.
Topics: Cell Survival; Cell Transformation, Neoplastic; Cells, Cultured; ErbB Receptors; Humans; Hydrogen-Ion Concentration; Hypopharynx; NF-kappa B; Pepsin A; Proto-Oncogene Proteins c-bcl-2; STAT3 Transcription Factor; Signal Transduction
PubMed: 33924087
DOI: 10.3390/ijms22084275