Role of acid-sensing ion channel 3 in sub-acute-phase inflammation

<p>Abstract</p> <p>Background</p> <p>Inflammation-mediated hyperalgesia involves tissue acidosis and sensitization of nociceptors. Many studies have reported increased expression of acid-sensing ion channel 3 (ASIC3) in inflammation and enhanced ASIC3 channel activity with pro-inflammatory mediators. However, the role of ASIC3 in inflammation remains inconclusive because of conflicting results generated from studies of <it>ASIC3 </it>knockout (<it>ASIC3</it>^-/-) or dominant-negative mutant mice, which have shown normal, decreased or increased hyperalgesia during inflammation.</p> <p>Results</p> <p>Here, we tested whether ASIC3 plays an important role in inflammation of subcutaneous tissue of paw and muscle in <it>ASIC3</it>^-/-mice induced by complete Freund's adjuvant (CFA) or carrageenan by investigating behavioral and pathological responses, as well as the expression profile of ion channels. Compared with the <it>ASIC3</it>^+/+controls, <it>ASIC3</it>^-/-mice showed normal thermal and mechanical hyperalgesia with acute (4-h) intraplantar CFA- or carrageenan-induced inflammation, but the hyperalgesic effects in the sub-acute phase (1–2 days) were milder in all paradigms except for thermal hyperalgesia with CFA-induced inflammation. Interestingly, carrageenan-induced primary hyperalgesia was accompanied by an <it>ASIC3</it>-dependent <it>Nav1.9 </it>up-regulation and increase of tetrodotoxin (TTX)-resistant sodium currents. CFA-inflamed muscle did not evoke hyperalgesia in <it>ASIC3</it>^-/-or <it>ASIC3</it>^+/+mice, whereas carrageenan-induced inflammation in muscle abolished mechanical hyperalgesia in <it>ASIC3</it>^-/-mice, as previously described. However, <it>ASIC3</it>^-/-mice showed attenuated pathological features such as less CFA-induced granulomas and milder carrageenan-evoked vasculitis as compared with <it>ASIC3</it>^+/+mice.</p> <p>Conclusion</p> <p>We provide a novel finding that ASIC3 participates in the maintenance of sub-acute-phase primary hyperalgesia in subcutaneous inflammation and mediates the process of granuloma formation and vasculitis in intramuscular inflammation.</p

Acute kidney injury in patients with COVID-19 compared to those with influenza: a systematic review and meta-analysis

BackgroundCOVID-19 and influenza can both lead to acute kidney injury (AKI) as a common complication. However, no meta-analysis has been conducted to directly compare the incidence of AKI between hospitalized patients with COVID-19 and influenza. The objective of our study aims to investigate the incidence and outcomes of AKI among hospitalized patients between these two groups.Materials and methodsA systematic search of PubMed, Embase, and Cochrane databases was conducted from December 2019 to August 2023 to identify studies examining AKI and clinical outcomes among hospitalized patients with COVID-19 and influenza. The primary outcome of interest was the incidence of AKI, while secondary outcomes included in-hospital mortality, recovery from AKI, hospital and ICU stay duration. The quality of evidence was evaluated using Cochrane and GRADE methods.ResultsTwelve retrospective cohort studies, involving 17,618 hospitalized patients with COVID-19 and influenza, were analyzed. COVID-19 patients showed higher AKI incidence (29.37% vs. 20.98%, OR: 1.67, 95% CI 1.56–1.80, p &lt; 0.01, I2 = 92.42%), and in-hospital mortality (30.95% vs. 5.51%, OR: 8.16, 95% CI 6.17–10.80, p &lt; 0.01, I2 = 84.92%) compared to influenza patients with AKI. Recovery from AKI was lower in COVID-19 patients (57.02% vs., 80.23%, OR: 0.33, 95% CI 0.27–0.40, p &lt; 0.01, I2 = 85.17%). COVID-19 patients also had a longer hospital stay (SMD: 0.69, 95% CI 0.65–0.72, p &lt; 0.01, I2 = 98.94%) and longer ICU stay (SMD: 0.61, 95% CI 0.50–0.73, p &lt; 0.01, I2 = 94.80%) than influenza patients. In our study, evidence quality was high (NOS score 7–9), with low certainty for AKI incidence and moderate certainty for recovery form AKI by GRADE assessment.ConclusionCOVID-19 patients had higher risk of developing AKI, experiencing in-hospital mortality, and enduring prolonged hospital/ICU stays in comparison to influenza patients. Additionally, the likelihood of AKI recovery was lower among COVID-19 patients

Prevalence and risk factors of erosive esophagitis in Taiwan

Background: Erosive esophagitis is a common condition in the western population. However, the prevalence and risk factors of this disorder in Taiwan remain unclear. This study investigated the current prevalence of erosive esophagitis in Taiwan and attempted to identify the risk factors for this disease. Methods: From January 2008 to May 2009, 2040 consecutive subjects who underwent upper gastrointestinal endoscopy during their annual health check-up were enrolled. The severity of erosive esophagitis was evaluated according to the Los Angeles classification, and the independent risk factors of erosive esophagitis were analyzed using the logistic regression method. Results: The prevalence of erosive esophagitis was 17.3% (352/2040), with 71.6%, 27.8%, 0.5% and 0% cases of grades A, B, C and D, respectively, according to the Los Angeles classification. Univariate analysis revealed that male sex, smoking, alcohol consumption, betel nut chewing habit, body mass index ≥ 27 kg/m2, hypertension, use of calcium channel blockers, diabetes, hyperglycemia, hypertriglyceridemia, and hiatus hernia were associated with the development of erosive esophagitis. Multivariate analysis revealed that male sex [odds ratio (OR) = 2.013, 95% confidence interval (CI) = 1.439–2.815; p < 0.001), smoking (OR = 1.301, 95% CI = 1.089–1.555; p = 0.004), body mass index > 27 (OR = 1.348, 95% CI = 1.138–1.598; p = 0.001), and hiatus hernia (OR = 4.331, 95% CI = 3.304–5.784; p < 0.001) were independent risk factors for the development of erosive esophagitis. Conclusion: The current prevalence of erosive esophagitis in Taiwan is 17.3%. Male sex, smoking, obesity, and hiatus hernia are four independent risk factors for the development of erosive esophagitis in the Taiwanese population

Meta-Analysis for Correlating Structure of Bioactive Peptides in Foods of Animal Origin with Regard to Effect and Stability

Amino acid (AA) sequences of 807 bioactive peptides from foods of animal origin were examined in order to correlate peptide structure with activity (antihypertensive, antioxidative, immunomodulatory, antimicrobial, hypolipidemic, antithrombotic, and opioid) and stability in vivo. Food sources, such as milk, meat, eggs, and marine products, show different frequencies of bioactive peptides exhibiting specific effects. There is a correlation of peptide structure and effect, depending on type and position of AA. Opioid peptides contain a high percentage of aromatic AA residues, while antimicrobial peptides show an excess of positively charged AAs. AA residue position is significant, with those in the first and penultimate positions having the biggest effects on peptide activity. Peptides that have activity in vivo contain a high percentage (67%) of proline residues, but the positions of proline in the sequence depend on the length of the peptide. We also discuss the influence of processing on activity of these peptides, as well as methods for predicting release from the source protein and activity of peptides