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Background: Gastroesophageal reflux disease (GERD) is a chronic condition of the digestive tract with limited therapeutic options. Bitter taste receptors (TAS2Rs) and transient receptor potential vanilloid-1 (TRPV1) are implicated in modulating inflammatory responses. Berberine (BBR) and evodiamine (EVO) are known to activate TAS2Rs and TRPV1, respectively. However, whether BBR and EVO can ameliorate GERD by targeting TAS2Rs and TRPV1 remains uncertain., Purpose: This study aims to determine whether BBR and EVO mitigate esophageal injury by targeting TAS2R38 and TRPV1 and to elucidate their underlying molecular mechanisms., Methods: A GERD rat model was developed using esophagogastric anastomosis, while GERD in human esophageal epithelial cells (HEECs) was induced via bile acid (BA) exposure. Esophageal pathology was analyzed through hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). mRNA and protein levels were measured via qRT-PCR, immunofluorescence, immunohistochemistry and Western blot analysis. Small interfering RNA was used to silence TAS2R38 and TRPV1 in HEECs. The activation of TAS2R38 and TRPV1 by BBR and EVO was assessed through Ca 2+ mobilization assays. Finally, in vivo validation was conducted using U73122 to inhibit TAS2Rs and resiniferatoxin (RTX) to ablate TRPV1., Results: BBR and EVO treatments significantly improved esophageal pathology in GERD rats and reduced BA-induced inflammation in HEECs. Additionally, BBR and EVO suppressed proinflammatory factors expression, upregulated barrier proteins such as E-cadherin and claudin-1, and inhibited the phosphorylation of p65, JNK, and ERK in the MAPK/NF-κB signaling pathways in both in vivo and in vitro models. Furthermore, BBR and EVO, whether individually or in combination, reduced dilated intercellular spaces (DIS), increased desmosome numbers, and modulated macrophage polarization in GERD rats. Knockdown of TAS2R38 and TRPV1 in HEECs notably diminished the stimulatory effects of BBR and EVO. Moreover, the regulation of barrier function and MAPK/NF-κB pathway proteins by BBR and EVO in BA-induced HEECs was abrogated upon TAS2R38 and TRPV1 knockdown. Similarly, U73122 and RTX reversed the effects of BBR and EVO on macrophage polarization and MAPK/NF-κB signaling pathways in vivo., Conclusion: We firstly demonstrate that BBR and EVO alleviate GERD, with enhanced synergistic efficacy observed when used in combination. Mechanistically, BBR and EVO activate the TAS2R38 and TRPV1, respectively, leading to downregulation of phosphorylation in MAPK/NF-κB signaling pathways and modulation of macrophage polarization. These findings offer a novel foundation for the clinical application of BBR and EVO in GERD treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Obesity has become a global public health problem, and its relationship with gastrointestinal diseases has become a major concern. The visceral adiposity index (VAI) is a novel index to assess the distribution and content of visceral fat, and this study aimed to investigate the association between VAI and bowel habits (chronic diarrhea, chronic constipation) and inflammatory bowel disease (IBD). The 2005-2010 National Health and Nutrition Examination Survey (NHANES) dataset was used for the cross-sectional survey. Bowel habits and IBD were defined by self-report. Multiple logistic regression models were used to test the linear association of VAI with bowel habits and IBD. Fitted smoothed curves and threshold effects analyses were used to characterize nonlinear relationships. This cross-sectional study included 10,391 adults (≥ 20 years). After adjusting for covariates, there was a significant negative association between VAI and chronic constipation (OR [95% CI]: 0.97 [0.95, 1.00]) but no significant association with IBD (OR [95% CI]: 0.97 [0.87, 1.07]). Additionally, there was a nonlinear association between VAI and chronic diarrhea with a breakpoint of 3.08, with a positive correlation between the two on the left side of the breakpoint and no statistical significance on the right side. Subgroup analyses and interaction tests showed that maintaining sleep health was associated with a low risk of chronic constipation. Elevated VAI levels were negatively associated with chronic constipation, and elevated levels were positively associated with chronic diarrhea at VAI < 3.08. This reminds us that maintaining moderate levels of visceral fat may prevent the onset of chronic constipation and circumvent the risk of chronic diarrhea. Notably, maintaining healthy sleep may play a positive role in reducing chronic constipation., (© 2024. The Author(s).)

Background: Coronavirus disease 2019 (COVID-19) has led to severe pneumonia and mortality worldwide, however, clinical outcomes in end-stage renal disease patients remain unclear. This study evaluates the prognostic value of chest computed tomography (CT) findings in predicting COVID-19-related outcomes in prevalent hemodialysis patients., Methods: We retrospectively analyzed 326 prevalent hemodialysis patients diagnosed with COVID-19 who underwent chest CT scans. Characteristics assessed included pleural effusion, lung involvement volume, nodular consolidation, patchy infiltration, and ground-glass opacity. Artificial intelligence (AI)-assisted CT analysis quantified lung involvement. The primary endpoint was in-hospital mortality. Clinical data were collected, and logistic regression analysis assessed the association between CT findings and mortality., Results: The mean age of the patients was 66.7 ± 12.6 years, 61.0% were male, and 58.6% were diabetic. Chest CT showed that 18.1% had lung involvement >10%, 32.5% had pleural effusion, 68.7% had nodular consolidation, 57.1% had patchy infiltration, and 58.0% had ground-glass opacity. Seventy patients (21.5%) died. Multivariate logistic regression analysis identified lung involvement >2.7% (odds ratio [OR], 16.70; 95% confidence interval [CI], 4.35-65.63), pleural effusion (OR, 3.28; 95% CI, 1.15-9.35), nodular consolidation (OR, 4.08; 95% CI, 1.12-14.82), and patchy infiltration (OR, 3.75; 95% CI, 1.17-12.03) as significant mortality risk factors., Conclusion: Chest CT findings, including lung involvement >2.7% and the presence of pleural effusion, nodular consolidation, and patchy infiltrates, significantly indicated mortality in COVID-19 pneumonia among prevalent hemodialysis patients. AI-assisted CT analysis proved useful in assessing lung involvement extent, showing that even minimal lung involvement can be associated with increased mortality.

Background: Natural products exhibit structural complexity, diversity, and historical therapeutic significance, boasting attractive functions and biological activities that have significantly influenced drug discovery endeavors. The identification of target proteins of active natural compounds is crucial for advancing novel drug innovation. Currently, methods for identifying targets of natural products can be categorized into labeling and label-free approaches based on whether the natural bioactive constituents are modified into active probes. In addition, there is a new avenue for rapidly exploring the targets of natural products based on their innate functions., Aim: This review aimed to summarize recent advancements in both labeling and label-free approaches to the identification of targets for natural products, as well as the novel target identification method based on the natural functions of natural products., Methods: We systematically collected relevant articles published in recent years from PubMed, Web of Science, and ScienceDirect, focusing on methods employed for identifying protein targets of bioactive natural products. Furthermore, we systematically summarized the principles, procedures, and successful cases, as well as the advantages and limitations of each method., Results: Labeling methods allow for the direct labeling of target proteins and the exclusion of indirectly targeted proteins. However, these methods are not suitable for studying post-modified compounds with abolished activity, chemically challenging synthesis, or trace amounts of natural active compounds. Label-free methods can be employed to identify targets of any natural active compounds, including trace amounts and multicomponent mixtures, but their reliability is not as high as labeling methods. The structural complementarity between natural products and their innate receptors significantly increase the opportunities for finding more promising structural analogues of the natural products, and natural products may interact with several structural analogues of receptors in humans., Conclusion: Each approach presents benefits and drawbacks. In practice, a combination of methods is employed to identify targets of natural products. And natural products' innate functions-based approach is a rapid and selective strategy for target identification. This review provides valuable references for future research in this field, offering insights into techniques and methodologies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Teres minor denervation (TMD) has gained increasing attention in recent years, particularly with the advent of magnetic resonance imaging (MRI). The potential association between TMD and shoulder instability or rotator cuff tear remains a subject of interest in the orthopedic community. In this retrospective and cross-sectional study, authors aim to investigate the potential association between TMD and shoulder instability or rotator cuff tears. Authors retrospectively analyzed MRI findings from 105 patients with TMD, focusing on rotator cuff pathologies, posterior labrocapsular complex (PLCC) tears, and posteroinferior glenohumeral joint capsule alterations. Authors assessed the association between TMD and rotator cuff and PLCC tears. For the multivariate analysis, partial proportional odds models were constructed for subscapularis (SSC) and SSP tears. Rotator cuff tears were present in 82.9% of subjects, with subscapularis (SSC) tears being the most frequent (77.1%). A significant association was observed between TMD and rotator cuff pathology (P = .002). PLCC tears were found in 82.3% of patients, and humeral position relative to the osseous glenoid was noted in 60% of patients with TMD. A significant association was identified between TMD and shoulder instability or labral/capsular abnormalities (P < .001). More than half of the cases exhibited a long tethering appearance toward the axillary neurovascular bundle on T1-weighted sagittal images. Our findings suggest that TMD is significantly associated with rotator cuff tears and shoulder instability. This study highlights the importance of identifying and treating PLCC tears in patients with TMD to address shoulder instability. Further research is needed to elucidate the role of TMD in the pathogenesis of shoulder instability and rotator cuff pathology., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To investigate longitudinal changes in the anterior segment (AS) using serial optical coherence tomography (OCT) images and determine the impact of these changes on the anterior chamber angle (ACA) in eyes with primary angle closure disease (PACD) treated with laser peripheral iridotomy (LPI)., Design: Retrospective clinical cohort study., Methods: This study included 103 patients with PACD who underwent LPI and were followed up by a mean 6.7 ± 1.7 AS-OCT examinations for a mean 6.5 ± 2.9 years. Temporal changes in AS-OCT parameters, including anterior chamber depth (ACD), angle opening distance (AOD750), angle recess area (ARA750), iris thickness (IT750), lens vault (LV), and pupil diameter (PD), were analyzed by multivariate linear mixed effects models (LMEMs)., Results: Multivariate LMEMs showed that decrease in AOD750 was not significant (-1.59 µm/y, P = .222); however, ARA750 decreased over time (-2.3 × 10 3 µm 2 /y, P = .033) and SSA showed marginal significance (-0.20°/y, P = .098), and LV increased significantly (11.6 µm/y, P < .001) after LPI. Mean LV change was negatively associated with AOD750, ARA750, and SSA, whereas PD was negatively associated with ARA750 (P < .001 each). PD decreased with aging (-13.7 µm/y, P = .036), accompanied by thinning of IT750 (-1.7 µm/y, P = .063)., Conclusions: LV tends to increase with aging, which contributes to the shallowing of the anterior chamber and narrowing of ACA in PACD eyes treated with LPI. In the meantime, pupillary constriction and subsequent peripheral iris thinning associated with aging could possibly offset the effect of ACA narrowing., (Copyright © 2023 Elsevier Inc. All rights reserved.)