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The Annals of Otology, Rhinology, and... Mar 2020Laryngomalacia is a common cause of stridor in infants and is associated with laryngopharyngeal reflux (LPR). Although pepsin in operative supraglottic lavage specimens...
OBJECTIVES
Laryngomalacia is a common cause of stridor in infants and is associated with laryngopharyngeal reflux (LPR). Although pepsin in operative supraglottic lavage specimens is associated with severe laryngomalacia, detection of pepsin in oral secretions has not been demonstrated in an outpatient setting.
METHODS
Children <2 years old with laryngomalacia diagnosed by flexible laryngoscopy and children without stridor were selected. Oral secretion samples were obtained in clinic from all subjects. Pepsin, IL-1β, and IL-8 enzyme-linked immunosorbent assays were performed to determine presence of LPR.
RESULTS
Sixteen laryngomalacia and sixteen controls were enrolled. Pepsin was detected more frequently in oral secretions of patients with laryngomalacia (13/16) than in controls (2/16; < .001). Four patients with laryngomalacia developed symptoms requiring supraglottoplasty. Presence and level of salivary pepsin was not significantly associated with need for surgical management, nor were the levels or presence of IL-1β or IL-8 significantly associated with presence or level of pepsin, diagnosis of laryngomalacia, or need for operative management.
CONCLUSION
Pepsin in saliva appears to be associated with laryngomalacia, suggesting a role for salivary pepsin as a noninvasive marker of LPR in patients with laryngomalacia. Future studies will determine the utility of this test in laryngomalacia.
Topics: Biomarkers; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infant; Interleukin-1beta; Interleukin-8; Laryngomalacia; Laryngopharyngeal Reflux; Laryngoscopy; Male; Pepsin A; Respiratory Sounds; Saliva
PubMed: 31631681
DOI: 10.1177/0003489419884332 -
Bioscience Reports Nov 2020The current study was performed to determine the presence of pepsin in saliva and laryngeal tissue among participants with benign and malignant laryngeal neoplasms. (Comparative Study)
Comparative Study
OBJECTIVES
The current study was performed to determine the presence of pepsin in saliva and laryngeal tissue among participants with benign and malignant laryngeal neoplasms.
STUDY DESIGN
Case-control study included three groups of patients with: (1) benign laryngeal neoplasms, (2) malignant laryngeal neoplasms and (3) control subjects without symptoms or signs of laryngopharyngeal reflux (LPR).
METHODS
Eighty-one voluntary participants were included into study. They were recruited from a group of patients with histologically proven benign and malignant laryngeal neoplasms and in case of control subjects among patients with nasal septum deformation without symptoms of LPR. Morning saliva samples were collected preoperatively. Tumor biopsies were collected by directoscopy of larynx and the control samples from interarytenoid unit of larynx. All samples were analyzed by Enzyme-Linked Immunosorbent Assay (ELISA) and Immunohistochemistry.
RESULTS
Pepsin was found in all samples of saliva and tissue biopsies in groups with malignant and benign neoplasms. The highest concentration of pepsin was found in a group of patients with malignant laryngeal neoplasms. Patients with benign laryngeal neoplasms had lower concentrations and the control subjects presented with the lowest concentration of pepsin measured from their saliva. Differences were not statistically significant. Immunohistochemical (IHC) analysis showed the largest number of high positive samples in the group of malignant lesions.
CONCLUSION
These results suggest that pepsin and LPR can contribute to the development of benign and malignant laryngeal neoplasms. Further prospective studies, with far more patients, are necessary to prove the role of pepsin in multifactorial etiology of laryngeal neoplasms.
Topics: Adult; Aged; Biomarkers, Tumor; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunohistochemistry; Laryngeal Neoplasms; Laryngopharyngeal Reflux; Larynx; Male; Middle Aged; Pepsin A; Saliva; Young Adult
PubMed: 33103719
DOI: 10.1042/BSR20200216 -
The Laryngoscope Jan 2023At the conclusion of this presentation, participants should better understand the carcinogenic potential of pepsin and proton pump expression in Barrett's esophagus.
EDUCATIONAL OBJECTIVE
At the conclusion of this presentation, participants should better understand the carcinogenic potential of pepsin and proton pump expression in Barrett's esophagus.
OBJECTIVE
Barrett's esophagus (BE) is a well-known risk factor for esophageal adenocarcinoma (EAC). Gastric H /K ATPase proton pump and pepsin expression has been demonstrated in some cases of BE; however, the contribution of local pepsin and proton pump expression to carcinogenesis is unknown. In this study, RNA sequencing was used to examine global transcriptomic changes in a BE cell line ectopically expressing pepsinogen and/or gastric H /K ATPase proton pumps.
STUDY DESIGN
In vitro translational.
METHODS
BAR-T, a human BE cell line devoid of expression of pepsinogen or proton pumps, was transduced by lentivirus-encoding pepsinogen (PGA5) and/or gastric proton pump subunits (ATP4A, ATP4B). Changes relative to the parental line were assessed by RNA sequencing.
RESULTS
Top canonical pathways associated with protein-coding genes differentially expressed in pepsinogen and/or proton pump expressing BAR-T cells included those involved in the tumor microenvironment and epithelial-mesenchymal transition. Top upstream regulators of coding transcripts included TGFB1 and ERBB2, which are associated with the pathogenesis and prognosis of BE and EAC. Top upstream regulators of noncoding transcripts included p300-CBP, I-BET-151, and CD93, which have previously described associations with EAC or carcinogenesis. The top associated disease of both coding and noncoding transcripts was cancer.
CONCLUSIONS
These data support the carcinogenic potential of pepsin and proton pump expression in BE and reveal molecular pathways affected by their expression. Further study is warranted to investigate the role of these pathways in carcinogenesis associated with BE.
LEVEL OF EVIDENCE
NA Laryngoscope, 133:59-69, 2023.
Topics: Humans; Proton Pumps; Pepsinogen A; Proton Pump Inhibitors; Barrett Esophagus; Esophageal Neoplasms; Pepsin A; Carcinogenesis; Adenosine Triphosphatases; Tumor Microenvironment
PubMed: 35315085
DOI: 10.1002/lary.30109 -
Food & Function May 2021Enzyme-catalysed hydrolysis is important in protein digestion. Protein hydrolysis is initiated by pepsin at low pH in the stomach. However, pepsin action and...
Enzyme-catalysed hydrolysis is important in protein digestion. Protein hydrolysis is initiated by pepsin at low pH in the stomach. However, pepsin action and acidification happen simultaneously to gastric emptying, especially for liquid meals. Therefore, different extents of exposure to the gastric environment change the composition of the chyme that is emptied from the stomach into the small intestine over time. We assessed the susceptibility of a protein to trypsin-catalysed hydrolysis in the small intestine, depending on its pH and hydrolysis history, simulating chyme at different times after the onset of gastric emptying. Isothermal titration calorimetry was used to study the kinetics of pepsin and trypsin-catalysed hydrolysis. Bovine serum albumin (BSA) that was acidified and hydrolysed with pepsin, showed the highest extent and most efficient hydrolysis by trypsin. BSA in the chyme that would be first emptied from the stomach, virtually bypassing gastric acidity and peptic action, reduced trypsin-catalysed hydrolysis by up to 58% compared to the acidified, intact protein, and 77% less than the acidified, pepsin-hydrolysate. The least efficient substrate for trypsin-catalysed hydrolysis was the acidified, intact protein with a specificity constant (k/K) nearly five times lower than that of the acidified, pepsin-hydrolysate. Our results illustrate the synergy between pepsin and trypsin hydrolysis, and indicate that gastric hydrolysis increases the efficiency of the subsequent trypsin-catalysed hydrolysis of a model protein in the small intestine.
Topics: Calorimetry; Catalysis; Digestion; Gastric Emptying; Hydrogen-Ion Concentration; Hydrolysis; Pepsin A; Protein Conformation; Serum Albumin, Bovine; Stomach; Trypsin
PubMed: 33908536
DOI: 10.1039/d1fo00413a -
Journal of Chemical Information and... Feb 2022The flexibility of β hairpin structure known as the flap plays a key role in catalytic activity and substrate intake in pepsin-like aspartic proteases. Most of these...
The flexibility of β hairpin structure known as the flap plays a key role in catalytic activity and substrate intake in pepsin-like aspartic proteases. Most of these enzymes share structural and sequential similarity. In this study, we have used apo Plm-II and BACE-1 as model systems. In the apo form of the proteases, a conserved tyrosine residue in the flap region remains in a dynamic equilibrium between the normal and flipped states through rotation of the χ and χ angles. Independent MD simulations of Plm-II and BACE-1 remained stuck either in the normal or flipped state. Metadynamics simulations using side-chain torsion angles (χ and χ of tyrosine) as collective variables sampled the transition between the normal and flipped states. Qualitatively, the two states were predicted to be equally populated. The normal and flipped states were stabilized by H-bond interactions to a tryptophan residue and to the catalytic aspartate, respectively. Further, mutation of tyrosine to an amino-acid with smaller side-chain, such as alanine, reduced the flexibility of the flap and resulted in a flap collapse (flap loses flexibility and remains stuck in a particular state). This is in accordance with previous experimental studies, which showed that mutation to alanine resulted in loss of activity in pepsin-like aspartic proteases. Our results suggest that the ring flipping associated with the tyrosine side-chain is the key order parameter that governs flap dynamics and opening of the binding pocket in most pepsin-like aspartic proteases.
Topics: Aspartic Acid Endopeptidases; Catalysis; Pepsin A
PubMed: 35138093
DOI: 10.1021/acs.jcim.1c00840 -
American Journal of Respiratory and... Dec 2022
Topics: Humans; Pepsin A; Primary Graft Dysfunction; Lung Transplantation; Lung; Inflammation; Allografts; Microbiota
PubMed: 36222878
DOI: 10.1164/rccm.202210-1873ED -
Journal of Trace Elements in Medicine... Jul 2021The paper presents a study on the influence of different lithium carbonate and lithium citrate concentration on proteolytic enzymes, namely pepsin and trypsin, in vitro....
BACKGROUND
The paper presents a study on the influence of different lithium carbonate and lithium citrate concentration on proteolytic enzymes, namely pepsin and trypsin, in vitro. Lithium can directly affect enzyme activity. Its influence on many bodily functions in both ill and healthy people has been proven.
METHODS
To assess the influence of Li ions concentration and the substrate/enzyme ratio on pepsin and trypsin activity in vitro, 60 factorial experiments were conducted (each repeated 30 times).
MAIN FINDINGS
For both enzymes, statistically significant changes in their activity under the influence of lihium carbonate and lithium citrate were observed. The biggest increase in enzyme activity reached even 198.6 % and the largest decrease in enzyme activity reached about 50 %.
CONCLUSIONS
The study shows that both organic and inorganic forms of lithium salts cause changes in the activity of digestive enzymes. Different concentrations of lithium carbonate and lithium citrate stimulate or inhibit the activity of trypsin and pepsin.
Topics: Citrates; Dose-Response Relationship, Drug; Enzyme Inhibitors; Humans; Ions; Lithium Carbonate; Pepsin A; Trypsin
PubMed: 33915410
DOI: 10.1016/j.jtemb.2021.126763 -
Molecules (Basel, Switzerland) Apr 2023Skin aging represents a health and aesthetic problem that could result in infections and skin diseases. Bioactive peptides can potentially be used in skin aging...
Skin aging represents a health and aesthetic problem that could result in infections and skin diseases. Bioactive peptides can potentially be used in skin aging regulation. Chickpea ( L.) selenoproteins were obtained from germination with 2 mg NaSeO/100 g of seeds for 2 days. Alcalase, pepsin, and trypsin were used as hydrolyzers, and a membrane < 10 kDa was used to fractionate the hydrolysate. Se content, antioxidant capacity, elastase and collagen inhibition, functional stability, and preventative capacity were analyzed. Significant increases in Se content were found in germinated chickpea flour and protein related to the control. An increase of 38% in protein was observed in the selenized flour related to the control. A band (600-550 cm) observed in the selenized hydrolysates suggested the insertion of Se into the protein. Hydrolysates from pepsin and trypsin had the highest antioxidant potential. Se enhanced the stability of total protein and protein hydrolysates through time and increased their antioxidant capacity. Hydrolysates > 10 kDa had higher elastase and collagenase inhibition than the total protein and hydrolysates < 10 kDa. Protein hydrolysates < 10 kDa 6 h before UVA radiation had the highest inhibition of collagen degradation. Selenized protein hydrolysates showed promising antioxidant effects that could be related to skin anti-aging effects.
Topics: Antioxidants; Cicer; Protein Hydrolysates; Pepsin A; Trypsin; Pancreatic Elastase
PubMed: 37110634
DOI: 10.3390/molecules28083402 -
The Laryngoscope Feb 2022Otitis media (OM) is a common inflammatory disease spectrum. Cytokine signaling, neutrophil activity, and mucin hypersecretion during recurrent and chronic OM contribute...
OBJECTIVE
Otitis media (OM) is a common inflammatory disease spectrum. Cytokine signaling, neutrophil activity, and mucin hypersecretion during recurrent and chronic OM contribute to persistent, viscous middle ear (ME) effusions, hearing loss, and potential for developmental delay. Extraesophageal reflux (EER), specifically pepsin, triggers inflammatory signaling in respiratory mucosa and is associated with OM. The objective of this study was to investigate the association of pepsin with ME inflammatory signaling and the outcomes and examine causality in vitro.
STUDY DESIGN
Cross-sectional study.
METHODS
ME fluid (MEF) and preoperative audiometric data were collected from 30 pediatric subjects undergoing tympanostomy tube placement for recurrent OM or OM with effusion. MEF viscosity was characterized by the surgeon. Pepsin, inflammatory molecules, and mucin were assayed by enzyme-linked immunosorbent assay (ELISA). ME epithelial primary culture was exposed to 0.1 to 1 mg/ml pepsin at pH 5, 6, and 7 for 30 minutes, and cytokine expression was assayed via qPCR.
RESULTS
Pepsin was observed in the MEF of 77% of patients (range 71-2,734 ng/ml). Pepsin correlated with effusion viscosity, interleukins -6 and -8, neutrophil elastase, and mucin 5B (P < .05). Pepsin-negative MEF was more frequently absent of interleukin 8 or mucin 5B (P < .05). Weak acid was generally insufficient to elicit cytokine expression in ME cells in vitro, however, pepsin induced IL6, IL8, and TNF at pH 7 (P < .05) and weak acid (pH 6) facilitated a response at lower pepsin concentration.
CONCLUSIONS
Pepsin may contribute to inflammatory signaling, persistent viscous effusion, and poorer OM outcomes.
LEVEL OF EVIDENCE
4 Laryngoscope, 132:470-477, 2022.
Topics: Child; Child, Preschool; Cross-Sectional Studies; Female; Humans; Infant; Male; Otitis Media with Effusion; Pepsin A; Viscosity
PubMed: 34272879
DOI: 10.1002/lary.29749 -
Journal of Otolaryngology - Head & Neck... Oct 2023To study the variability and diagnostic value of multiple salivary pepsin measurements in the detection of laryngopharyngeal reflux (LPR).
OBJECTIVE
To study the variability and diagnostic value of multiple salivary pepsin measurements in the detection of laryngopharyngeal reflux (LPR).
METHODS
Patients with LPR symptoms were consecutively recruited from December 2019 to Augustus 2022. Twenty-one asymptomatic individuals completed the study. The diagnostic was confirmed with hypopharyngeal-esophageal impedance-pH monitoring (HEMII-pH). Patients collected three saliva samples during the 24-h testing period. Symptoms and findings were studied with reflux symptom score-12 and reflux sign assessment. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values of pepsin measurements were calculated considering morning, post-lunch and post-dinner samples. The consistency and relationship between HEMII-pH, pepsin measurements, and clinical features were investigated.
RESULTS
Morning, post-lunch and post-dinner saliva pepsin concentrations were measured in 42 patients. Pepsin measurements were 64.9%, 59.5%, and 59.0% sensitive for morning, post-lunch and post-dinner collections at cutoff ≥ 16 ng/mL. Considering the highest concentration of the three pepsin saliva collections, the accuracy, sensitivity, specificity and PPV were 70.5%, 73.0%; 66.7% and 78.9%, respectively. Morning pepsin measurements reported higher consistency, sensitivity, and specificity than post-dinner and post-lunch pepsin measurements.
CONCLUSION
The collection of several saliva pepsin samples improves the detection rate of LPR. In case of high clinical LPR suspicion and negative pepsin test, a HEMII-pH study could provide further diagnostic information.
Topics: Humans; Laryngopharyngeal Reflux; Saliva; Pepsin A; Prospective Studies; Esophageal pH Monitoring
PubMed: 37794462
DOI: 10.1186/s40463-023-00670-5