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Models of kidney injury have classically concentrated on glomeruli as the primary site of injury leading to glomerulosclerosis or on tubules as the primary site of injury leading to tubulointerstitial fibrosis. However, current evidence on the mechanisms of progression of chronic kidney disease indicates that a complex interplay between glomeruli and tubules underlies progressive kidney injury. Primary glomerular injury can clearly lead to subsequent tubule injury. For example, damage to the glomerular filtration barrier can expose tubular cells to serum proteins, including complement and cytokines, that would not be present in physiological conditions and can promote the development of tubulointerstitial fibrosis and progressive decline in kidney function. In addition, although less well-studied, increasing evidence suggests that tubule injury, whether primary or secondary, can also promote glomerular damage. This feedback from the tubule to the glomerulus might be mediated by changes in the reabsorptive capacity of the tubule, which can affect the glomerular filtration rate, or by mediators released by injured proximal tubular cells that can induce damage in both podocytes and parietal epithelial cells. Examining the crosstalk between the various compartments of the kidney is important for understanding the mechanisms underlying kidney pathology and identifying potential therapeutic interventions. Glomerular injury and damage to the glomerular filtration barrier can promote the development of tubulointerstitial fibrosis. Here, the authors discuss potential mechanisms underlying this effect, as well as the emerging evidence of the tubule–glomerulus crosstalk that promotes glomerular damage following tubular injury. Key points: Primary glomerular injury can lead to the development of subsequent tubule injury that promotes the development of tubulointerstitial fibrosis and a progressive decline in kidney function. Serum factors — for example, immunoglobulins, complement proteins and lipids — rather than albumin itself seem to be key mediators of proximal tubule dysfunction associated with high proteinuria. Increasing evidence suggests that injurious factors released from injured tubules, or loss of protective factors, can feedback to the glomerulus, where they promote or exacerbate glomerular injury. In models of acute kidney injury, glomerulosclerosis is attenuated in atubular glomeruli. This effect might be related to reduced filtration in the atubular glomeruli and less oxidative stress in podocytes. [ABSTRACT FROM AUTHOR]

Knowledge of how novel antigens or dietary stimuli affect stomach development and function in pigs remains limited. This study aimed to investigate stomach characteristics, parietal cell numbers, and the expression of genes essential to the functioning of the fundic and pyloric gland regions at weaning compared to seven days post-weaning and to examine whether maternal probiotic supplementation or piglet dietary tryptophan (Trp) levels influence these stomach parameters. This study has a 2 × 3 factorial design, with 48 sows assigned to one of two diets: basal or basal supplemented with Bacillus subtilis and Bacillus amyloliquefaciens. Their litters received creep diets containing 0.22, 0.27, or 0.33% standardized ileal digestible (SID) Trp. In total, 96 pigs were sacrificed for gastric sampling, 48 on the day of weaning and 48 on day 7 post-weaning. At 7 days post-weaning, pigs had an increased number of parietal cells and expression of parietal cell activity and digestive enzyme (PGA5 and CHIA) genes in the fundic gland region (p < 0.05), although the expression of signaling molecules involved in the regulation of acid secretion was unchanged in the fundic gland region (p > 0.05) and reduced in the pyloric gland region (p < 0.05), compared to the day of weaning. Overall, maternal probiotic supplementation had a significant impact on gene expression in the fundic gland region of the offspring, elevating several genes related to parietal cell activity (CLIC6, HRH2, KCNE1, KCNQ1, CHRM3, CCKBR, and SSTR2) (p < 0.05). Additionally, there were time × maternal interactions, where certain acid secretion pathway (ATP4A and HDC), chitinase enzyme (CHIA), and ghrelin (GHRL) genes were increased in offspring from probiotic sows compared to control sows at weaning (p < 0.05), but not at 7 days post-weaning (p > 0.05). Maternal probiotic supplementation did not influence growth performance pre-weaning or during the 7-day post-weaning period. There was a limited effect of creep Trp level or maternal × creep interactions on performance, gene expression, or parietal cell counts. Low pre-weaning creep intake may have confounded this analysis. In conclusion, maternal probiotic supplementation accelerated the maturation of the offspring's stomach, particularly in terms of the expression of genes linked to acid secretion from parietal cells. [ABSTRACT FROM AUTHOR]

Gastrin is secreted following a rise in gastric pH, leading to gastric acid secretion. Sleeve gastrectomy (SG), a bariatric surgery where 80% of the gastric corpus is excised, presents a challenge for gastric pH homeostasis. Using histology, and single-cell RNA sequencing of the gastric epithelium in 12 women, we observed that SG is associated with an increase in a sub-population of acid-secreting parietal cells that overexpress respiratory enzymes and an increase in histamine-secreting enterochromaffin-like cells (ECLs). ECLs of SG-operated patients overexpressed genes coding for biosynthesis of neuropeptides and serotonin. Mathematical modeling showed that pH homeostasis by gastrin is analogous to non-linear proportional and integral control, that drives adaptation of the epithelium to acid-secretion demand. Quantitative model predictions were validated in patients. The results demonstrate human gastric epithelium remodeling following SG at the molecular and cellular levels, and more generally how trophic hormones enable robust adaptation of tissue function to meet physiological demand. Sleeve gastrectomy is a common bariatric surgery in which most of the gastric corpus is removed. Here, the authors show the adaptation of the gastric mucosa to surgery in patients, and how it facilitates maintenance of gastric pH homeostasis through a proportional-integral feedback control. [ABSTRACT FROM AUTHOR]

Parietal Epithelial Cells (PECs) activation and proliferation are common to several distinct forms of glomerulopathies. Due to several stimuli, PECs can change to a progenitor (CD24+ and CD133/2+) or a pro-sclerotic (CD44+) phenotype. In addition, PECs, which are constantly exposed to filtered albumin, are known to be involved in albumin internalization, but how this mechanism occurs is unknown. We hypothesized that PECs can transport albumin via receptor-mediated endocytosis and that albumin overload may affect the state of PECs. Conditionally immortalized human PECs (hPECs) were incubated with different albumin concentrations at different times. Albumin internalization studies were performed. Protein expression was assessed using In-Cell Western and immunofluorescence. Cell morphology was analyzed by phase-contrast microscopy and F-actin staining. We demonstrate that hPECs internalize albumin via receptor-mediated mechanisms. Under albumin stimulation, megalin, cubilin, ClC-5, CD133/2, CD24, and CD44 were upregulated. The increase of pERK1/2, the upregulation of ROCK1, ROCK2, caspase -3, -6, and -7, and the morphological changes associated with loss of F-actin fibers indicated that inflammation, proliferation and apoptosis mechanisms had been activated. Our results demonstrate that long-term exposure to high doses of albumin induces up-regulation of molecules involved in the tubular protein uptake machinery and suggest that albumin overload is able to trigger a regenerative process as well as an activation state which might lead in vivo to glomerular crescent formation. [ABSTRACT FROM AUTHOR]

Introduction: Proton pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are widely used to manage gastric acid-related disorders by inhibiting hydrochloric acid (HCl) secretion from parietal cells in the stomach. Although PPIs are known to have anti-inflammatory properties beyond their role in inhibiting gastric acid secretion, research on P-CABs is lacking. In this study, we aimed to investigate whether all available P-CABs exhibit anti-inflammatory effects in gastroesophageal reflux-induced esophagitis and to elucidate the underlying mechanisms. Methods: Het-1A cells, normal esophageal epithelial cells, were treated with HCl (pH 4) for 30 min. Esomeprazole, a representative PPI, and three currently marketed P-CABs (vonoprazan, tegoprazan, and fexuprazan) were used for pretreatment. Total RNA sequencing was performed using Het-1A cells pretreated with 1% DMSO or fexuprazan, followed by exposure to HCl. Pyroptosis was measured using lactate dehydrogenase (LDH) release and Annexin V-FITC/PI staining. Western blotting, qRT-PCR, and ELISA were used to determine the expression of the related genes. Results: Pretreatment with esomeprazole, vonoprazan, tegoprazan, and fexuprazan significantly inhibited the HCl-induced pro-inflammatory cytokines, including IL-6, IL-8, IL-1β, and TNF-α. Fexuprazan and vonoprazan significantly attenuated the HCl-induced pyroptosis rate, as assessed by elevated LDH release and Annexin V-FITC/PI staining, whereas esomeprazole and tegoprazan did not. RNA sequencing revealed that NOD-like receptor (NLR) family pyrin domain-containing 1 (NLRP1) was significantly reduced in Het-1A cells pretreated with fexuprazan compared to those treated with DMSO. Fexuprazan and vonoprazan markedly reduced the HCl-induced transcriptional and translational expression of genes involved in the pyroptosis pathway, including NLRP1, Caspase-1, gasdermin D, and IL-1β. Notably, fexuprazan reduced the HCl-induced increase in pyroptosis and IL-1β using siRNA, even in the presence of NLRP1 knockdown. Fexuprazan, tested on inflammatory THP-1 macrophage cells, significantly reduced NLRP1 expression and inhibited lipopolysaccharide-induced pyroptosis. Conclusion: Our findings reveal that all p-CABs exhibit anti-inflammatory properties, while fexuprazan inhibits inflammation and pyroptosis of esophageal cells caused by the gastric acid. Therefore, it is presumed to have additional benefits in gastroesophageal reflux disease in addition to suppressing gastric acid secretion. [ABSTRACT FROM AUTHOR]

INTRODUCTION: To describe the clinical features and the risk of developing gastric tumors in patients with autoimmune gastritis (AIG). METHODS: This was a retrospective, longitudinal, multicenter study conducted at 8 Italian tertiary referral centers. We retrieved clinical data from all histologically proven patients with AIG. Differences between Helicobacter pylori-exposed vs H. pylori-naive and anti-parietal cell antibody (PCA)-positive vs PCA- negative patients were investigated. The rate of gastric adenocarcinoma and type 1 gastric neuroendocrine neoplasm (gNEN) was assessed. A multivariable model for factors associated with gNEN was fitted. RESULTS: A total of 1,598 patients with AIG (median age 58 years, interquartile range 46–68; F:M ratio 2.7:1) were included. H. pylori-naive patients were more likely to have a first-degree family history of AIG (14.7% vs 8.9%; P 5 0.012), type 1 diabetes mellitus (4.9% vs 2.3%; P 5 0.025), and pernicious anemia (30.9% vs 21.1%; P 5 0.003). PCA-positive patients had significantly more associated autoimmune diseases (59.0% vs 42.9%; P < 0.001) and were more likely to have been diagnosed by a case-finding strategy (15.3% vs 2.6%; P < 0.001). Overall, 15 cases (0.9%) of gastric adenocarcinoma and 153 cases (9.6%) of gNEN occurred, with a global rate of 0.12 (95% confidence interval [CI] 0.07–0.20) and 1.22 (95% CI 1.03–1.42) per 100 person/year, respectively. Having a vitamin B12/ iron deficiency manifestation at AIG diagnosis was associated with a 16.44 (95% CI 9.94–27.20 P < 0.001) hazard ratio of gNEN. DISCUSSION: The “pure” AIG pattern has typical features of an autoimmune disease and seems to be unrelated to H. pylori. In a tertiary referral setting, the risk of developing overt gastric adenocarcinoma is low, while patients with vitamin B12 deficiency complications at onset may benefit from a more intense endoscopic follow-up for early gNEN detection. [ABSTRACT FROM AUTHOR]

Tapetal cells, like other parietal layer cells were small and oblong in the beginning. Shortly afterwards they incvcased in size and became binucleate, their cytoplasm being densely staincd with haematoxylin. Not a fow cells of the tapetum showed chromatin qranules in their nuclei. At the pollen tetrad stage, the tapetal cells had attained their maximum growth. The submicroscopic structure of the tapetal cells of the barley anthers has been investigated at the stages of a late tetrad and uninucleate pollen qrain before and after vacuolization. The tapetal cells of the barley as regards their structure and functions at these stages of development may be characterized as secretary ones. Their cytoplasm is abundant with cell organells. Numerous mitochondria and a Golgi apparatus are in close vicini ty with the cisterns of an endoplasmic reticulum. The presence of ribosomes on the onter cisternae of the stack relates the entire structure to the endoplasmic reticulum. Ocmiophilic substances apper in several places with respect to the tapetal cells. At the stage of an uninucleate pollen grain instead of the degenerated pr imary walls, surrounding every tapetal cell, a new wall is formed, which consists mainly of sporopollenin. [ABSTRACT FROM AUTHOR]

Mesothelial cells, in the outermost layer of internal organs, are essential for both organ development and homeostasis. Although the parietal mesothelial cell is the primary origin of mesothelioma that may highjack developmental signaling, the signaling pathways that orchestrate developing parietal mesothelial progenitor cell (MPC) behaviors, such as MPC pool expansion, maturation, and differentiation, are poorly understood. To address it, we established a robust protocol for culturing WT1+ MPCs isolated from developing pig and mouse parietal thorax. Quantitative qPCR and immunostaining analyses revealed that BMP4 facilitated MPC differentiation into smooth muscle cells (SMCs). In contrast, FGF2 significantly promoted MPC progenitor pool expansion but blocked the SMC differentiation. BMP4 and FGF2 counterbalanced these effects, but FGF2 had the dominant impact in the long-term culture. A Wnt activator, CHIR99021, was pivotal in MPC maturation to CALB2+ mesothelial cells, while BMP4 or FGF2 was limited. Our results demonstrated central pathways critical for mesothelial cell behaviors. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) are broadly used in the remedy of gastric acid-related diseases along with peptic ulcer disease, erosive esophagitis and gastroesophageal reflux disease, and so on. Proton pump inhibitors (PPIs) are recognized as a type of pharmaceutical agents that target H+/ K-ATPase, which is positioned in gastric parietal cells. These drugs existing a great safety profile and have become one of the most frequently prescribed drugs in primary and specialty care. The pharmaceutical analysis of drugs requires advantageous and efficient analytical techniques for quality control, as well as pharmacodynamics and pharmacokinetic studies. In this review article, a great survey in analytical chemistry journals had been performed and different analytical techniques developed so far and used for the estimation of some proton pump inhibitors in bulk drugs and its pharmaceutical formulations have been reviewed. This review covers over near about sixty reported analytical techniques which include electrochemical methods, Spectral method and different chromatographic technique. The article will assist analysts while choosing the essential parameters in the development of new technique for the estimation of proton pump inhibitors. The proposed review integrally addresses the analytical reports of esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole. [ABSTRACT FROM AUTHOR]

SUMMARY: Morphology, phylogeny and azaspiracid (AZA) production of a strain of Amphidoma languida isolated from the subtropical Mexican Pacific were examined. Scanning electron microscopy showed the thecal plate arrangement of Am. languida from Mexico as Po, cp, X, 6′, 6′′, 6C, 5S, 6′′′, 2′′′′, with the prominent apical pore complex, the ventral pore on the anterior of the 1′ plate near the suture to the 6′ plate, and the antapical pore on the 2′′′′ plate, which are congruent with those of Am. languida reported from the Atlantic. The ventral depression was occasionally observed on the anterior end of Sa plate. Cells had a dinokaryotic nucleus positioned in the posterior part of the cell and parietal yellowish chloroplasts with a spherical pyrenoid in the episome. Transmission electron microscopy showed crystalline vesicles and tubular cytoplasmic invaginations in the pyrenoid, which resembled those reported from the most related non‐toxigenic species Amphidoma fulgens. The intracellular components, different from Am. fulgens, were oil droplets and lipid‐associated membranous structures. AZA‐2 was detected from the strain by liquid chromatography‐tandem mass spectrometry with a cell quota of 30.9 fg cell−1. Three other AZA‐related compounds were also detected. This is the first report of AZA‐producing Am. languida in the Pacific Ocean. [ABSTRACT FROM AUTHOR]

Our understanding of the use of acid-suppressant drugs (ASDs) in companion animals is largely centered around the treatment of acid-related disorders including gastroesophageal reflux and gastrointestinal ulceration. The companion article by Grady et al, JAVMA, October 2024, summarizes our current knowledge of the efficacy of and indications for ASDs for the treatment of acid-related disorders. Far less is understood about both the benefits of and potential for adverse effects of ASDs outside of the parietal cell including those directed toward inflammation and immunomodulation, tumorigenesis, fibrosis, and oxidative stress. In this Currents in One Health article, we summarize the pH-independent properties of ASDs as demonstrated in studies conducted largely in humans and rodents. The objective of this review is to highlight and increase awareness of the pH-independent effects of ASDs to elucidate the need for further veterinary research in this area. [ABSTRACT FROM AUTHOR]

Autoimmune gastritis (AIG) is a chronic condition in which the body's immune system mistakenly attacks the stomach lining, specifically targeting parietal cells that produce stomach acid and intrinsic factors. After the H. pylori infection was eradicated, AIG developed in an elderly woman with symptoms of the disease. 1.5 years after eradication, esophagogastroduodenoscopy revealed remnants of the oxyntic mucosa sticky adherent dense mucus and scattered minute whitish protrusions at the greater curvature of the gastric corpus. Biopsy specimens from the greater curvature site of the gastric corpus before H. pylori eradication revealed neutrophilic cells in the superficial mucosa of the stomach that were mildly inflammatory and infiltrating. With the removal of H. pylori , the number of infiltrating inflammatory neutrophilic cells in the superficial mucosa decreased, whereas that of infiltrating lymphocytes increased in the sub-superficial mucosa. This case suggests that further studies regarding the detailed time course of AIG are required. [ABSTRACT FROM AUTHOR]

Identifying effective drugs for focal segmental glomerulosclerosis (FSGS) treatment holds significant importance. Our high-content drug screening on zebrafish larvae relies on nitroreductase/metronidazole (NTR/MTZ)-induced podocyte ablation to generate FSGS-like injury. A crucial factor for successful drug screenings is minimizing variability in injury induction. For this, we introduce nifurpirinol (NFP) as a more reliable prodrug for targeted podocyte depletion. NFP showed a 2.3-fold increase in efficiency at concentrations 1,600-fold lower compared with MTZ-mediated injury induction. Integration into the screening workflow validated its suitability for the high-content drug screening. The presence of crucial FSGS hallmarks, such as podocyte foot process effacement, proteinuria, and activation of parietal epithelial cells, was observed. After the isolation of the glomeruli from the larvae, we identified essential pathways by proteomic analysis. This study shows that NFP serves as a highly effective prodrug to induce the FSGS-like disease in zebrafish larvae and is well-suited for a high-content drug screening to identify new candidates for the treatment of FSGS. NEW & NOTEWORTHY: This research investigated the use of nifurpirinol in nanomolar amounts as a prodrug to reliably induce focal segmental glomerulosclerosis (FSGS)-like damage in transgenic zebrafish larvae. Through proteomic analysis of isolated zebrafish glomeruli, we were further able to identify proteins that are significantly regulated after the manifestation of FSGS. These results are expected to expand our knowledge of the pathomechanism of FSGS. [ABSTRACT FROM AUTHOR]

Introduction: Parietal cell antibody (PCA)-mediated auto-immune gastritis is known to increase the risk of iron-deficiency and pernicious anaemia in adults with type 1 diabetes mellitus. However, in children and young adults with type 1 diabetes, these data are scarce. We aimed to study the prevalence of parietal cell antibodies (PCAs) and its clinical associations in people with type 1 diabetes with onset below 30 years. Methods: In a cross-sectional study, 224 children and young adults with type 1 diabetes and 171 healthy controls were enrolled. We measured haemoglobin, serum ferritin, vitamin B12, PCA, thyroid peroxidase, and anti-tissue transglutaminase antibodies in all patients. Mann–Whitney U test for continuous data and Chi square test for categorical data were used. Linear regression analysis was performed with haemoglobin as a dependent variable. Results: The prevalence of PCA was significantly higher in patients than in controls (22% vs 10.2%; P = 0.002). Patients with PCA had a higher frequency of anaemia (60% vs 30%, P < 0.001), lower haemoglobin [7.3 (1.6) vs 7.8 (1.1) mmol/L; P = 0.002], and lower serum ferritin [46.9 (70.8) pmol/L vs 66.0 (105.3) pmol/L; P = 0.04], as compared to those without PCA. On multivariate analysis, haemoglobin was associated with PCA (β = -0.174, P = 0.005) and serum ferritin (β =0.247, P < 0.001). Conclusion: Presence of PCA was an independent risk factor for iron deficiency and anaemia in children and young adults with type 1 diabetes. [ABSTRACT FROM AUTHOR]

The KCNE2 protein is encoded by the kcne2 gene and is a member of the KCNE protein family, also known as the MinK-related protein 1 (MiRP1). It is mostly present in the epicardium of the heart and gastric mucosa, and it is also found in the thyroid, pancreatic islets, liver and lung, among other locations, to a lesser extent. It is involved in numerous physiological processes because of its ubiquitous expression and partnering promiscuity, including the modulation of voltage-dependent potassium and calcium channels involved in cardiac action potential repolarization, and regulation of secretory processes in multiple epithelia, such as gastric acid secretion, thyroid hormone synthesis, generation and secretion of cerebrospinal fluid. Mutations in the KCNE2 gene or aberrant expression of the protein may play a critical role in cardiovascular, neurological, metabolic and multisystem disorders. This article provides an overview of the advancements made in understanding the physiological functions in organismal homeostasis and the pathophysiological consequences of KCNE2 in multisystem diseases. [ABSTRACT FROM AUTHOR]

The lysosomal Ca2+ channel TRPML1 was found to be responsible for gastric acid secretion in murine gastric parietal cells by inducing the trafficking of H+/K+-ATPase containing tubulovesicles to the apical membrane. Therefore, we hypothesized a similar role of TRPML1 in regulating proton secretion in the immortalized human parietal cell line HGT-1. The primary focus was to investigate the involvement of TRPML1 in proton secretion using the known synthetic agonists ML-SA1 and ML-SA5 and the antagonist ML-SI3 and, furthermore, to identify food-derived compounds that target the channel. Proton secretion stimulated by ML-SA1 was reduced by 122.2 ± 22.7% by the antagonist ML-SI3. The steroid hormone 17β-estradiol, present in animal-derived foods, diminished the proton secretory effect of ML-SA1 by 63.4 ± 14.5%. We also demonstrated a reduction in the proton secretory effects of ML-SA1 and ML-SA5 on TRPML1 knock-down cells. The food-derived compounds sulforaphane and trehalose promoted proton secretion in HGT-1 cells but may act independently of TRPML1. Also, histamine- and caffeine-induced proton secretion were affected by neither the TRPML1 antagonist ML-SI3 nor the TRPML1 knock-down. In summary, the results obtained suggest that the activation of TRPML1 promotes proton secretion in HGT-1 cells, but the channel may not participate in canonical signaling pathways. [ABSTRACT FROM AUTHOR]

Parietal cell autoantibodies (PCAs), which recognize the enzyme H+/K+-ATPase as a target, are considered to be a diagnostic marker of autoimmune gastritis and pernicious anemia; these conditions are characterized by the presence of corpus atrophic gastritis. Circulating PCAs can be detected using several analytical methods that are commonly available in the clinical laboratory. Traditionally, indirect immunofluorescence (IIF) on rodent or primate stomach tissue is used as a screening test for the detection of PCAs. However, IIF suffers from a high inter-observer variability and lacks standardization. In addition, like immunoblotting, results are expressed only in a qualitative or semi-quantitative manner. Based on the few available studies that are reviewed herein, quantitative enzyme-linked immunosorbent assays (ELISAs) and fluorescence enzyme immunoassays (FEIAs) using purified H+/K+-ATPase perform better than IIF in the detection of PCAs, displaying higher sensitivity and utility in monitoring the disease. In light of their higher diagnostic accuracy, these solid-phase methods should be preferred to IIF in the screening of autoimmune atrophic gastritis. The use of methods to detect antibodies versus a specific subunit of H+/K+-ATPase (α or β) is currently confined to the world of research. Further investigation is required to define the clinical utility of H+/K+-ATPase subunit detection. [ABSTRACT FROM AUTHOR]

Background and Aim: Since the first report of gastric adenocarcinoma of the fundic‐gland type in 2010, the clinicopathological characteristics of gastric neoplasm of the fundic‐gland type (GNFG) have become clearer; however, their risk factors remain unclear. This exploratory study aimed to identify the risk factors for GNFG. Methods: We conducted a single‐center, retrospective, matched case–control study using medical information recorded at our health management center from January 2014 to July 2023. During this period, 39 240 people underwent upper gastrointestinal endoscopy. GNFG were extracted as cases and matched to controls, according to age and sex, in a 1:8 ratio, excluding those with a history of gastrointestinal surgery and those with a history or comorbidity of cancer. Univariate analysis was used to compare patient background and endoscopic findings. Multivariable analysis was performed, adjusting for factors with P values < 0.1 and antacid use. Results: A total of 20 GNFG cases and 160 matched healthy controls were included. In the univariate analysis, only reflux esophagitis was significantly more common in GNFG (40.0% vs 18.1%; P = 0.036). Factors antacids and duodenitis had P values < 0.1. Logistic regression analysis was performed, adjusting for antacids, reflux esophagitis, and duodenitis. Antacids and reflux esophagitis were the independent risk factors for GNFG (odds ratio = 3.68 [95% confidence interval: 1.04–11.91] and 3.25 [95% confidence interval: 1.11–9.35]). Conclusions: Although the sample of patients with GNFG was small, antacids and reflux esophagitis were identified as a risk factor. The pathogenesis of antacids and reflux esophagitis may be involved in the development of GNFG. [ABSTRACT FROM AUTHOR]

This study investigates the dynamic fluctuations of pH caused by gastric acid secretion, a process of both biological and clinical significance, with microrobots. Abnormal patterns of acidity often indicate gastrointestinal diseases, underlying the importance of precise intragastric pH monitoring. Traditional methods using fluorescent probes face challenges due to their faint solid‐state fluorescence, limited target specificity, and accuracy. To overcome these obstacles, pH‐responsive fluorescent organic microparticles decorated with magnetite (Fe3O4) nanoparticles are engineered. These microrobots exhibit a unique fluorescence switching capability at a critical pH, enabling the monitoring of gastric acidity. The magnetic part of these microrobots ensures magnetic maneuverability to enable targeted navigation. The microrobots' fluorescence switching mechanism is elucidated through comprehensive spectroscopy, microscopy, and X‐ray diffraction analyses, revealing molecular‐level structural transformations upon interaction with gastric acid and antacids. These transformations, specifically protonation and deprotonation of the microrobots' fluorescent components, prompt a distinct fluorescence response correlating with pH shifts. In vitro and ex vivo experiments, simulating stomach conditions, confirm the microrobots' efficacy in pH‐responsive imaging. The results showcase the promising diagnostic potential of microrobots for gastrointestinal tract diseases, marking a significant advancement in imaging‐based medical diagnostics at targeted locations. [ABSTRACT FROM AUTHOR]

Cardiotrophin‐1 (CT‐1), a member of the interleukin (IL)‐6 cytokine family, has renoprotective effects in mouse models of acute kidney disease and tubulointerstitial fibrosis, but its role in glomerular disease is unknown. To address this, we used the mouse model of nephrotoxic nephritis to test the hypothesis that CT‐1 also has a protective role in immune‐mediated glomerular disease. Using immunohistochemistry and analysis of single‐cell RNA‐sequencing data of isolated glomeruli, we demonstrate that CT‐1 is expressed in the glomerulus in male mice, predominantly in parietal epithelial cells and is downregulated in mice with nephrotoxic nephritis. Furthermore, analysis of data from patients revealed that human glomerular disease is also associated with reduced glomerular CT‐1 transcript levels. In male mice with nephrotoxic nephritis and established proteinuria, administration of CT‐1 resulted in reduced albuminuria, prevented podocyte loss, and sustained plasma creatinine, compared with mice administered saline. CT‐1 treatment also reduced fibrosis in the kidney cortex, peri‐glomerular macrophage accumulation and the kidney levels of the pro‐inflammatory mediator complement component 5a. In conclusion, CT‐1 intervention therapy delays the progression of glomerular disease in mice by preserving kidney function and inhibiting renal inflammation and fibrosis. [ABSTRACT FROM AUTHOR]

Since the introduction of vonoprazan, a potassium-competitive acid blocker (P-CAB), it has been demonstrated to reversibly inhibit gastric acid secretion by engaging in potassium-competitive ionic binding to H+/K+-ATPase. In contrast, proton pump inhibitors (PPIs) achieve H+/K+-ATPase inhibition through covalent binding to cysteine residues of the proton pump. Reported cases have indicated an emerging trend of P-CAB-related gastropathies, similar to those associated with PPIs, as well as unique gastropathies specific to P-CAB use, such as the identification of web-like mucus. Pathologically, parietal cell profusions, which show a positively correlated with hypergastrinemia, have a higher incidence in P-CAB users compared to PPI users. Thus, this review aims to summarize the endoscopic and pathological findings reported to date concerning P-CAB-related gastric mucosal lesions. Additionally, it seeks to discuss the differences between the PPIs and P-CABs in terms of the formation and frequency of associated gastropathies. This review highlights the evident differences in the mechanism of action and potency of acid inhibition between P-CABs and PPIs, notably contributing to differences in the formation and frequency of associated gastropathies. It emphasizes the necessity to distinguish between P-CAB-related and PPI-related gastropathies in the clinical setting. [ABSTRACT FROM AUTHOR]

The predominant characteristic of autoimmune gastritis (AIG) is corpusdominant advanced atrophy, which is mostly observed in the middle to late stages. More reports are needed on the endoscopic features of the early stage. In this report, we present two cases of early-stage AIG in which endoscopic examinations showed no atrophy of the gastric mucosa but displayed a transition of collecting venules from a regular to an irregular arrangement. In addition, yellowish-white cobblestone-like elevations were observed in the fundic gland region. Histologically, the observed manifestations included pseudohypertrophy and protrusion of parietal cells into the lumen, possibly along with hyperplasia of G cells, lymphocytic infiltration and potentially pseudopyloric gland metaplasia. Serologically, the anti-parietal cell antibody returned positive results, whereas the anti-intrinsic factor antibody yielded negative results. In this study, we summarized some endoscopic features of two patients, aiming to provide clues for endoscopists to detect early-stage AIG. [ABSTRACT FROM AUTHOR]

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Knowledge of how novel antigens or dietary stimuli affect stomach development and function in pigs remains limited. This study aimed to investigate stomach characteristics, parietal cell numbers, and the expression of genes essential to the functioning of the fundic and pyloric gland regions at weaning compared to seven days post-weaning and to examine whether maternal probiotic supplementation or piglet dietary tryptophan (Trp) levels influence these stomach parameters. This study has a 2 × 3 factorial design, with 48 sows assigned to one of two diets: basal or basal supplemented with Bacillus subtilis and Bacillus amyloliquefaciens. Their litters received creep diets containing 0.22, 0.27, or 0.33% standardized ileal digestible (SID) Trp. In total, 96 pigs were sacrificed for gastric sampling, 48 on the day of weaning and 48 on day 7 post-weaning. At 7 days post-weaning, pigs had an increased number of parietal cells and expression of parietal cell activity and digestive enzyme (PGA5 and CHIA) genes in the fundic gland region (p < 0.05), although the expression of signaling molecules involved in the regulation of acid secretion was unchanged in the fundic gland region (p > 0.05) and reduced in the pyloric gland region (p < 0.05), compared to the day of weaning. Overall, maternal probiotic supplementation had a significant impact on gene expression in the fundic gland region of the offspring, elevating several genes related to parietal cell activity (CLIC6, HRH2, KCNE1, KCNQ1, CHRM3, CCKBR, and SSTR2) (p < 0.05). Additionally, there were time × maternal interactions, where certain acid secretion pathway (ATP4A and HDC), chitinase enzyme (CHIA), and ghrelin (GHRL) genes were increased in offspring from probiotic sows compared to control sows at weaning (p < 0.05), but not at 7 days post-weaning (p > 0.05). Maternal probiotic supplementation did not influence growth performance pre-weaning or during the 7-day post-weaning period. There was a limited effect of creep Trp level or maternal × creep interactions on performance, gene expression, or parietal cell counts. Low pre-weaning creep intake may have confounded this analysis. In conclusion, maternal probiotic supplementation accelerated the maturation of the offspring’s stomach, particularly in terms of the expression of genes linked to acid secretion from parietal cells.

Background: Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs. Methods: Sprague‒Dawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and omeprazole once every other day (qod), and daily aspirin and omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers. Results: Both the omeprazole qd and omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However, omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy. Conclusions: Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment. [ABSTRACT FROM AUTHOR]

Uncovering the function of understudied G protein-coupled receptors (GPCRs) provides a wealth of untapped therapeutic potential. The poorly understood adhesion GPCR Gpr126 (Adgrg6) is widely expressed in developing kidneys. In adulthood, Gpr126 expression is enriched in parietal epithelial cells (PECs) and epithelial cells of the collecting duct and urothelium. Whether Gpr126 plays a role in kidney disease remains unclear. Here, we characterized Gpr126 expression in diseased kidneys in mice, rats, and humans. RT-PCR data show that Gpr126 expression is altered in kidney disease. A quantitative RNAscope® analysis utilizing cell type-specific markers revealed that Gpr126 expression upon tubular damage is mainly increased in cell types expressing Gpr126 under healthy conditions as well as in cells of the distal and proximal tubules. Upon glomerular damage, an increase was mainly detected in PECs. Notably, Gpr126 expression was upregulated in an ischemia/reperfusion model within hours, while upregulation in a glomerular damage model was only detected after weeks. An analysis of kidney microarray data from patients with lupus nephritis, IgA nephropathy, focal segmental glomerulosclerosis (FSGS), hypertension, and diabetes as well as single-cell RNA-seq data from kidneys of patients with acute kidney injury and chronic kidney disease indicates that GPR126 expression is also altered in human kidney disease. In patients with FSGS, an RNAscope® analysis showed that GPR126 mRNA is upregulated in PECs belonging to FSGS lesions and proximal tubules. Collectively, we provide detailed insights into Gpr126 expression in kidney disease, indicating that GPR126 is a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Background: In previous investigations, we explored the regulation of gastric function by hydrogen sulfide (H2S) and L-glutamate (L-Glu) injections in the nucleus ambiguus (NA). We also determined that both H2S and L-Glu have roles to play in the physiological activities of the body, and that NA is an important nucleus for receiving visceral sensations. The purpose of this study was to explore the potential pathway link between L-Glu and H2S, resulting in the regulation of gastric function. Methods: Physiological saline (PS), L-glutamate (L-Glu, 2 nmol), NaHS (2 nmol), D-2-amino-5-phopho-novalerate (D-AP5, 2 nmol) + L-Glu (2 nmol), aminooxyacetic acid (AOAA, 2 nmol) + L-Glu (2 nmol), D-AP5 (2 nmol) + NaHS (2 nmol) were injected into the NA. A balloon was inserted into the stomach to observe gastric pressure and for recording the changes of gastric smooth muscle contraction curve. The gastric fluid was collected by esophageal perfusion and for recording the change of gastric pH value. Results: Injecting L-Glu in NA was found to significantly inhibit gastric motility and promote gastric acid secretion in rats (p < 0.01). On the other hand, injecting the PS, pre-injection N-methyl-D-aspartate (NMDA) receptor blocker D-AP5, cystathionine beta-synthase (CBS) inhibitor AOAA and re-injection L-Glu did not result in significant changes (p > 0.05). The same injection NaHS significantly inhibit gastric motility and promote gastric acid secretion in rats (p < 0.01), but is eliminated by injection D-AP5 (p > 0.05). Conclusion: The results indicate that both exogenous L-Glu and H2S injected in NA regulate gastric motility and gastric acid secretion through NMDA receptors. This suggests that NA has an L-Glu-NMDA receptor-CBS-H2S pathway that regulates gastric function. [ABSTRACT FROM AUTHOR]

PAX2 regulates kidney development, and its expression persists in parietal epithelial cells (PECs), potentially serving as a podocyte reserve. We hypothesized that mice with a Pax2 pathogenic missense variant (Pax2A220G/þ) have impaired PEC-mediated podocyte regeneration. Embryonic wild-type mouse kidneys showed overlapping expression of PAX2/Wilms' tumor-1 (WT-1) until PEC and podocyte differentiation, reflecting a close lineage relationship. Embryonic and adult Pax2A220G/þ mice have reduced nephron number but demonstrated no glomerular disease under baseline conditions. Pax2A220G/þ mice compared with wildtype mice were more susceptible to glomerular disease after adriamycin (ADR)-induced podocyte injury, as demonstrated by worsened glomerular scarring, increased podocyte foot process effacement, and podocyte loss. There was a decrease in PAX2- expressing PECs in wild-type mice after adriamycin injury accompanied by the occurrence of PAX2/WT-1-coexpressing glomerular tuft cells. In contrast, Pax2A220G/þ mice showed no changes in the numbers of PAX2-expressing PECs after adriamycin injury, associated with fewer PAX2/WT-1-coexpressing glomerular tuft cells compared with injured wild-type mice. A subset of PAX2- expressing glomerular tuft cells after adriamycin injury was increased in Pax2A220G/þ mice, suggesting a pathological process given the worse outcomes observed in this group. Finally, Pax2A220G/þ mice have increased numbers of glomerular tuft cells expressing Ki-67 and cleaved caspase-3 compared with wild-type mice after adriamycin injury, consistent with maladaptive responses to podocyte loss. Collectively, our results suggest that decreased glomerular numbers in Pax2A220G/þ mice are likely compounded with the inability of their mutated PECs to regenerate podocyte loss, and together these two mechanisms drive the worsened focal segmental glomerular sclerosis phenotype in these mice. [ABSTRACT FROM AUTHOR]

In one of the most important non-photic mechanisms of the circadian biological clock synchronization of the hypothalamus suprachiasmatic nucleus with environmental geophysical 24 h rhythm, information on feeding schedule, composition and calorie content of food is used. Hormone ghrelin, a product of the neuroendocrine oxyntic cells of the gastric mucosa to be a signal molecule within this mechanism. In experiments on sagittal hypothalamic slices of male Wistar rats, the effects of 25 nM ghrelin on spike activity and parameters of spike information coding were investigated. Application of ghrelin induced an increase in spike frequency and a decrease in entropy of interspike interval distribution in 32.1% of the neurones recorded. In 29.6% of the cells, opposite responses in the form of a reduction of activity and an increase in the entropy of interspike interval distribution were observed. Parameters of spike activity of the reminder 38.3% neurones of the suprachiasmatic nucleus did not change. The observed responses of the entropy of interspike interval distribution indicate the appropriate changes in a degree of irregularity of interspike interval induced by ghrelin. Application of selective high-affinity antagonist of GHS-R1a receptor, JMV 2959 (100 nM) did not induce responses of the investigated parameters of spike activity but completely prevented changes of both, spike frequency and entropy of interspike interval distribution observed in the presence of ghrelin. The obtained data show that hormone ghrelin by a direct influence on the suprachiasmatic nucleus in vitro modulates the activity level and spike code of relatively numerous population of neurones of the nucleus, wherein the effects of ghrelin are mediated by GHS-R1a receptors. The results of the current study provide additional evidence in favour of the hypothesis on the involvement of ghrelin in mechanisms of non-photic entrainment of the circadian biological clock in accordance with severity of food motivation and level of metabolism. [ABSTRACT FROM AUTHOR]

Most gastric cancers arise in the setting of chronic inflammation which alters gland organization, such that acid-pumping parietal cells are lost, and remaining cells undergo metaplastic change in differentiation patterns. From a basic science perspective, recent progress has been made in understanding how atrophy and initial pyloric metaplasia occur. However, pathologists and cancer biologists have long been focused on the development of intestinal metaplasia patterns in this setting. Arguably, much less progress has been made in understanding the mechanisms that lead to the intestinalization seen in chronic atrophic gastritis and pyloric metaplasia. One plausible explanation for this disparity lies in the notable absence of reliable and reproducible small animal models within the field, which would facilitate the investigation of the mechanisms underlying the development of gastric intestinal metaplasia (GIM). This review offers an in-depth exploration of the current state of research in GIM, shedding light on its pivotal role in tumorigenesis. We delve into the histological subtypes of GIM and explore their respective associations with tumor formation. We present the current repertoire of biomarkers utilized to delineate the origins and progression of GIM and provide a comprehensive survey of the available, albeit limited, mouse lines employed for modeling GIM and engage in a discussion regarding potential cell lineages that serve as the origins of GIM. Finally, we expound upon the myriad signaling pathways recognized for their activity in GIM and posit on their potential overlap and interactions that contribute to the ultimate manifestation of the disease phenotype. Through our exhaustive review of the progression from gastric disease to GIM, we aim to establish the groundwork for future research endeavors dedicated to elucidating the etiology of GIM and developing strategies for its prevention and treatment, considering its potential precancerous nature. [ABSTRACT FROM AUTHOR]

The gastric H+,K+-ATPase is an integral membrane protein which derives energy from the hydrolysis of ATP to transport H+ ions from the parietal cells of the gastric mucosa into the stomach in exchange for K+ ions. It is responsible for the acidic environment of the stomach, which is essential for digestion. Acid secretion is regulated by the recruitment of the H+,K+-ATPase from intracellular stores into the plasma membrane on the ingestion of food. The similar amino acid sequences of the lysine-rich N-termini α-subunits of the H+,K+- and Na+,K+-ATPases, suggests similar acute regulation mechanisms, specifically, an electrostatic switch mechanism involving an interaction of the N-terminal tail with the surface of the surrounding membrane and a modulation of the interaction via regulatory phosphorylation by protein kinases. From a consideration of sequence alignment of the H+,K+-ATPase and an analysis of its coevolution with protein kinase C and kinases of the Src family, the evidence points towards a phosphorylation of tyrosine-7 of the N-terminus by either Lck or Yes in all vertebrates except cartilaginous fish. The results obtained will guide and focus future experimental research. [ABSTRACT FROM AUTHOR]

Introduction: Marginal ulcers are the most prevalent endoscopic abnormality after RYGB. The etiology is still poorly understood; however, an increase in acid secretion has been strongly implicated as a causal agent. Although gastrin is the greatest stimulant of acid secretion, to date, the presence of gastrin producing G cells retained in the gastric pouch, related to the occurrence of marginal ulcers, has not been evaluated. Objective: Evaluate the density of G cells and parietal cells in the gastric pouch of RYGB patients with a diagnosis of marginal ulcer on the post-op EGD. Method: We retrospectively evaluated 1104 gastric bypasses performed between 2010 and 2020. Patients with marginal ulcer who met the inclusion criteria and controls were selected from this same population. Endoscopic gastric pouch biopsies were evaluated using immunohistochemical study and HE staining to assess G cell and parietal cell density. Results: In total, 572 (51.8%) of the patients performed endoscopic follow-up after RYGB. The incidence of marginal ulcer was 23/572 (4%), and 3 patients required revision surgery due to a recalcitrant ulcer. The mean time for ulcer identification was 24.3 months (2–62). G cell count per high-power field (× 400) was statistically higher in the ulcer group (p < 0.05). There was no statistical difference in parietal cell density between groups (p 0.251). Conclusion: Patients with a marginal ulcer after gastric bypass present a higher density of gastrin-producing G cells retained in the gastric pouch. [ABSTRACT FROM AUTHOR]

This article presents a study on the long-term effects of vonoprazan, a potassium-competitive acid blocker, on gastric mucosal lesions. The study reports two cases where patients developed gastric cracked mucosa, white spots, and gastric polyps after starting vonoprazan treatment. However, these lesions improved or disappeared when the patients switched to proton pump inhibitors. The article emphasizes the need for further research to understand the underlying mechanisms and suggests that long-term monitoring is necessary to track changes in the lesions' appearance. The document also includes microscopic evidence from a tissue biopsy, showing a mucus pool within a dilated duct, and provides images of the two cases for reference. This information may be valuable for researchers studying gastropathies in patients undergoing P-CAB treatment. [Extracted from the article]

Background and aimsStomach cells can be converted to insulin-producing cells by Neurog3, MafA, and Pdxl over-expression. Enteroendocrine cells can be similarly made to produce insulin by the deletion of FOXO1. Characteristics and functional properties of FOXO1-expressing stomach cells are not known.MethodsUsing mice bearing a FOXO1-GFP knock-in allele and primary cell cultures, we examined the identity of FOXO1-expressing stomach cells and analyzed their features through loss-of-function studies with red-to-green fluorescent reporters.ResultsFOXO1 localizes to a subset of Neurog3 and parietal cells. FOXO1 deletion ex vivo or in vivo using Neurog3-cre or Atp4b-cre increased numbers of parietal cells, generated insulin- and C-peptide-immunoreactive cells, and raised Neurog3 messenger RNA. Gene expression and ChIP- seq experiments identified the cell cycle regulator cyclin E1 (CCNE1) as a FOXO1 target.ConclusionFOXO1 is expressed in a subset of stomach cells. Its ablation increases parietal cells and yields insulin-immunoreactive cells, consistent with a role in lineage determination.

Introduction: Senescence is a normal succession in time and cell maturity with progressive structural and functional cellular changes. Its influence predisposes numerous non-communicable diseases such as neurodegenerative, metabolic and cardiovascular diseases, as well as cancers with subsequent high morbidities and mortalities. Gastrointestinal tract (GIT) manifestations are commonly associated with ageing starting from stomatitis to maldigestion and malabsorption. Nicotinamide adenine dinucleotide [NAD+], a co-enzyme in oxidative-phosphorylation and redox reactions in metabolism and energy production, is decreased in multiple ageing-associated pathological conditions and its replenishment reveals marked improvement in these conditions. Aim of the Work: This study aimed at evaluating the senescence sequelae on gastric parietal cells of male albino rats, the probable role of NAD+ and the potential protecting influence of nicotinamide riboside (NR) [a NAD+ precursor]. Materials and Methods: 18 male albino rats were grouped equally into the non-aged group [~3 months, group I], aged group [~24 months, group II] and aged/NR group [~24 months, group III] that received daily single oral dose of 200mg/kg NR for 3 weeks. Just before sacrifice, serum NAD+, gastrin and pepsinogen-I levels were assessed for all animals. Then, biochemical, histological, immunohistochemical [for H+/K+ ATPase & B-cell lymphoma-2 (Bcl-2)] and morphometric studies were done. Results: The senescence features demonstrated in the parietal cells of the aged rats were markedly ameliorated with 3 weeks oral intake of NR [a NAD+ precursor]. Conclusion: Ageing is a systemic process of NAD+ reduction and consequent oxidative stress, inflammageing, DNA damage and altered apoptosis. Parietal cells ageing results in GIT disturbances that may exacerbate ageing sequelae through induction of anaemia, and continuous NAD+ reduction. Most manifestations can be blocked by oral supplementation of a NAD+ precursor, especially NR as it has many advantages over the others. [ABSTRACT FROM AUTHOR]

Citrobacter braakii (C. braakii) is an anaerobic, gram‐negative bacterium that has been isolated from the environment, food, and humans. Infection by C. braakii has been associated with acute mucosal inflammation in the intestine, respiratory tract, and urinary tract. However, the pathogenesis of C. braakii in the gastric mucosa has not yet been clarified. In this study, the bacterium was detected in 35.5% (61/172) of patients with chronic gastritis (CG) and was closely associated with the severity of mucosal inflammation. Citrobacter braakii P1 isolated from a patient with CG exhibited urease activity and acid resistance. It contained multiple secretion systems, including a complete type I secretion system (T1SS), T5aSS and T6SS. We then predicted the potential pilus‐related adhesins. Citrobacter braakii P1 diffusely adhered to AGS cells and significantly increased lactate dehydrogenase (LDH) release; the adhesion rate and LDH release were much lower in HEp‐2 cells. Strain P1 also induced markedly increased mRNA and protein expression of IL‐8 and TNF‐α in AGS cells, and the fold increase was much higher than that in HEp‐2 cells. Our results demonstrate proinflammatory and cytotoxic role of C. braakii in gastric epithelial cells, indicating the bacterium is potentially involved in inducing gastric mucosa inflammation. [ABSTRACT FROM AUTHOR]

The study was aimed to validate and optimize high performance liquid chromatographic (HPLC) method for the determination of coumarin-3-carboxylic acid (C3A) in the heart and liver issue of Sprague-Dawley (SD) rats after intragastric administration of extractive of leaves of Ficus virens var sublanceolata. And simple ADME and target prediction analyses were performed for C3A. Ethyl acetate was employed to precipitate protein with appropriate sensitivity and acceptable matrix effects. The satisfactory separation was developed on an ODS2 column (4.6 mm × 250 mm, 5 μm) by gradient elution with a methanol-acetic acid solution (pH = 3.0) as the mobile phase. The flow rate was 1.0 mL min−1, the column temperature was maintained at 30 ± 2 °C, the injection volume was 20 μL, and the detection wavelength was set as 309 nm. The method was fully validated in terms of selectivity, linearity, accuracy, precision, extraction recovery and stability. The results of the ADME analysis found that C3A has excellent characteristics of drug-likeness, consistent with good bio-absorption. And the predicted 12 target protein belongs to the amine oxidoreductase and carbonic anhydrase target class. This method is simple, rapid, sensitive, and accurate for the determination of coumarin-3-carboxylic acid in the heart and liver tissue of SD rats. [ABSTRACT FROM AUTHOR]

Estrogen, well known as a female hormone, is synthesized primarily by ovarian aromatase. However, extra-glandular tissues also express aromatase and produce estrogen. It is noteworthy that aromatase in gastric parietal cells begins expression around 20 days after birth and continues secreting considerable amounts of estrogen into the portal vein throughout life, supplying it to the liver. Estrogen, which is secreted from the stomach, is speculated to play a monitoring role in blood triglyceride, and its importance is expected to increase. Nevertheless, the regulatory mechanisms of the aromatase expression remain unclear. This study investigated the influence of transforming growth factor α (TGFα) on gastric aromatase expression during postnatal development. The administration of TGFα (50 μg/kg BW) to male Wistar rats in the weaning period resulted in enhanced aromatase expression and increased phosphorylated ERK1+2 in the gastric mucosa. By contrast, administration of AG1478 (5 mg/kg BW), a protein tyrosine kinase inhibitor with high selectivity for the epidermal growth factor receptor and acting as an antagonist of TGFα, led to the suppression of aromatase expression. In fact, TGFα expression in the gastric fundic gland isthmus began around 20 days after birth in normal rats as did that of aromatase, which indicates that TGFα might induce the expression of aromatase in the parietal cells concomitantly. [ABSTRACT FROM AUTHOR]

Ascariasis (roundworm) is the most common parasitic helminth infection globally and can lead to significant morbidity in children including chronic lung disease. Children become infected with Ascaris spp. via oral ingestion of eggs. It has long been assumed that Ascaris egg hatching and larval translocation across the gastrointestinal mucosa to initiate infection occurs in the small intestine. Here, we show that A. suum larvae hatched in the host stomach in a murine model. Larvae utilize acidic mammalian chitinase (AMCase; acid chitinase; Chia) from chief cells and acid pumped by parietal cells to emerge from eggs on the surface of gastric epithelium. Furthermore, antagonizing AMCase and gastric acid in the stomach decreases parasitic burden in the liver and lungs and attenuates lung disease. Given Ascaris eggs are chitin-coated, the gastric corpus would logically be the most likely organ for egg hatching, though this is the first study directly evincing the essential role of the host gastric corpus microenvironment. These findings point towards potential novel mechanisms for therapeutic targets to prevent ascariasis and identify a new biomedical significance of AMCase in mammals. Author summary: Ascariasis is the most common helminth infection and leads to significant global morbidity. Current therapies specifically target intraluminal adult intestinal worms and do not provide sufficient protection against the Ascaris larva. To reduce Ascaris-induced morbidity, novel interventions are needed that target Ascaris larval migration which calls for a better understanding of the Ascaris larval migration cycle. After oral ingestion of Ascaris eggs, previous studies have indicated that Ascaris larval migration initiates in the small intestine. However, our study demonstrates that Ascaris larva begin the migration cycle by hatching in the stomach by using the host's acidic mammalian chitinase and stomach acid to help degrade the chitinous egg shell. The larvae subsequently translocate across the stomach mucosa in this mouse model. Our study provides the first insight that the gastric corpus microenvironment plays a critical role in Ascaris egg hatching and initiation of infection, and will aid in the identification of novel drug targets. [ABSTRACT FROM AUTHOR]

Background The Banff Classification may not adequately address protocol transplant biopsies categorized as normal in patients experiencing unexplained graft function deterioration. This study seeks to employ convolutional neural networks to automate the segmentation of glomerular cells and capillaries and assess their correlation with transplant function. Methods A total of 215 patients were categorized into three groups. In the Training cohort, glomerular cells and capillaries from 37 patients were manually annotated to train the networks. The Test cohort (24 patients) compared manual annotations vs automated predictions, while the Application cohort (154 protocol transplant biopsies) examined predicted factors in relation to kidney function and prognosis. Results In the Test cohort, the networks recognized histological structures with Precision, Recall, F-score and Intersection Over Union exceeding 0.92, 0.85, 0.89 and 0.74, respectively. Univariate analysis revealed associations between the estimated glomerular filtration rate (eGFR) at biopsy and relative endothelial area (r = 0.19, P  = .027), endothelial cell density (r = 0.20, P  = .017), mean parietal epithelial cell area (r = –0.38, P  < .001), parietal epithelial cell density (r = 0.29, P  < .001) and mesangial cell density (r = 0.22, P  = .010). Multivariate analysis retained only endothelial cell density as associated with eGFR (Beta = 0.13, P  = .040). Endothelial cell density (r = –0.22, P  = .010) and mean podocyte area (r = 0.21, P  = .016) were linked to proteinuria at biopsy. Over 44 ± 29 months, 25 patients (16%) reached the primary composite endpoint (dialysis initiation, or 30% eGFR sustained decline), with relative endothelial area, mean endothelial cell area and parietal epithelial cell density below medians linked to this endpoint [hazard ratios, respectively, of 2.63 (P  = .048), 2.60 (P  = .039) and 3.23 (P  = .019)]. Conclusion This study automated the measurement of intraglomerular cells and capillaries. Our results suggest that the precise segmentation of endothelial and epithelial cells may serve as a potential future marker for the risk of graft loss. [ABSTRACT FROM AUTHOR]

(1) Background: An early mesothelial reaction of the pleura, leading to fibrosis, has been reported in animals after chemical or heavy metal exposure. However, the visual monitoring of early time-sequential mesothelial reaction-associated cryoinjury has not been fully investigated. Therefore, this study aimed to evaluate and visualize the early mesothelial reactions seen following cryoinjury using rabbit pleura. (2) Methods: We monitored the early mesothelial reaction in rabbit pleurae after cryoinjury using optical coherence tomography (OCT), in real-time, which was then compared with pathological images. Due to the penetration limit of OCT, we made a thoracic window to image the parietal and visceral pleurae in vivo. We also used an innovative technique for capturing the microstructure in vivo, employing a computer-controlled intermittent iso-pressure breath hold to reduce respiratory motion, increasing the resolution of OCT. We organized three sample groups: the normal group, the sham group with just a thoracic window, and the experimental group with a thoracic window and cryotherapy. In the experimental group, localized cryoinjury was performed. The mesothelial cells at the level of pleura of the cryotherapy-injured site were visualized by OCT within the first 30 min and then again after 2 days at the same site. (3) Results: In the experimental group, focal thickening of the parietal pleura was observed at the site of cryoinjury using OCT after the first injury, and it was then confirmed pathologically as focal mesothelial cell proliferation. Two days after cryoinjury, diffuse mesothelial cell proliferation in the parietal pleura was noted on the reverse side around the cryoinjured site in the same rabbit. In the sham group, no pleural reaction was found. The OCT and pathological examinations revealed different patterns of mesothelial cell reactions between the parietal and visceral pleurae: the focal proliferation of mesothelial cells was found in the parietal pleura, while only a morphological change from flat cells to cuboidal cells and a thickened monolayer without proliferation of mesothelial cells were found in the visceral pleural. (4) Conclusions: An early mesothelial reaction occurs following cryoinjury to the parietal and visceral pleurae. [ABSTRACT FROM AUTHOR]

The lesser bamboo rat (Cannomys badius), a fossorial rodent distributed in Indochina, has the ability to feed on cyanogenic plants that normally induce cyanide poisoning and lead to cell death. Immunohistochemical staining was used for localizing 3-mercaptopyruvate sulfurtransferase (MST), a cyanide-detoxifying enzyme, in the digestive organs of C. badius. The results revealed MST-positive staining in gastric parietal cells, columnar epithelial cells in the large intestine, hepatocytes, and some endocrine cells in the pancreatic islets. Specifically, cecal and colonic epithelial cells and pericentral hepatocytes were relatively strongly stained. The present study suggests that MST in the parietal cells and the endocrine pancreas is not involved in cyanide detoxification but in the regulation of acid and hormone secretion. It is also postulated that cyanide produced by microbial fermentation of food in the cecum is primarily detoxified by MST in cecal epithelial cells and subsequently neutralized further by MST in the colon and liver. The digestive system of C. badius reflects a protective mechanism against cyanide toxicity allowing it to survive a diet of cyanogenic plants. [ABSTRACT FROM AUTHOR]

This review comprehensively examines the diverse spectrum of gastric cancers, focusing on unusual or uncommon histology that presents significant diagnostic and therapeutic challenges. While the predominant form, tubular adenocarcinoma, is well-characterized, this review focuses on lesser-known variants, including papillary adenocarcinoma, micropapillary carcinoma, adenosquamous carcinoma, squamous cell carcinoma (SCC), hepatoid adenocarcinoma, gastric choriocarcinoma, gastric carcinoma with lymphoid stroma, carcinosarcoma, gastroblastoma, parietal cell carcinoma, oncocytic adenocarcinoma, Paneth cell carcinoma, gastric adenocarcinoma of the fundic gland type, undifferentiated carcinoma, and extremely well-differentiated adenocarcinoma. Although these diseases have different nomenclatures characterized by distinct histopathological features, these phenotypes often overlap, making it difficult to draw clear boundaries. Furthermore, the number of cases was limited, and the unique histopathological nature and potential pathogenic mechanisms were not well defined. This review highlights the importance of understanding these rare variants for accurate diagnosis, effective treatment planning, and improving patient outcomes. This review emphasizes the need for ongoing research and case studies to enhance our knowledge of these uncommon forms of gastric cancer, which will ultimately contribute to more effective treatments and better prognostic assessments. This review aimed to broaden the pathological narrative by acknowledging and addressing the intricacies of all cancer types, regardless of their rarity, to advance patient care and improve prognosis. [ABSTRACT FROM AUTHOR]

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A whole exome sequencing (WES)‐driven approach to uncover the etiology of unexplained inflammatory gastritides has been underutilized by surgical pathologists. Here, we discovered the pathobiology of an unusual chronic atrophic gastritis in two unrelated patients using this approach. The gastric biopsies were notable for an unusual pattern of gastritis with persistent dense inflammation, loss of both parietal and neuroendocrine cells in the oxyntic mucosa, and sparing of the antral mucosa. The patients were found to harbor pathogenic variants in telomeropathic genes (POT1 and DCLRE1B). Clonality testing for one of the patients showed evidence of evolving clonality of TCR‐gene rearrangement. Both patients showed significantly decreased numbers of stem/progenitor cells by immunohistochemistry, which appears to be responsible for the development of mucosal atrophy. No such cases of unusual chronic atrophic gastritis in the setting of telomeropathy have been previously reported. The loss of stem/progenitor cells suggests that stem/progenitor cell exhaustion in the setting of telomere dysfunction is the likely mechanism for development of this unusual chronic atrophic gastritis. The results underscore the need for close monitoring of these gastric lesions, with special regard to their neoplastic potential. This combined WES‐driven approach has promise to identify the cause and mechanism of other uncharacterized gastrointestinal inflammatory disorders. [ABSTRACT FROM AUTHOR]

This article explores the brain's control over vital organs and homeostatic mechanisms, focusing on the bladder and kidney. The author discusses recent advances in neuroscience that allow for more detailed study of brain-body control pathways. The methods used in these studies include the use of specific gene promoters and adeno-associated viruses to express proteins in specific neuron subpopulations, as well as the measurement of physiological functions. The results reveal complex neural circuits involved in bladder and kidney function, with potential implications for understanding and treating bladder diseases and brain degenerative diseases. The researchers also discuss experiments conducted on neurons to understand their role in regulating renal function and cardiac function, with the goal of identifying and mapping out the neural circuits responsible for regulating renal function. The approach used in this study can be applied to studying other organs and their neural control, providing insights into the physiology and pathophysiology of major organs. [Extracted from the article]

The article presents a case study of a 74-year-old woman with chronic cough and progressive shortness of breath. It is reported that pulmonary function tests showed a severe obstructive ventilatory disorder, and imaging revealed bilateral micronodules and nodules. It underscores the importance of considering pleural involvement in the differential diagnosis of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH).