Atractylenolide I Alleviates Indomethacin-Induced Gastric Ulcers in Rats by Inhibiting NLRP3 Inflammasome Activation.

Atractylodes macrocephala Koidz, a traditional Chinese medicine, contains atractylenolide I (ATR-I), which has potential anticancer, anti-inflammatory, and immune-modulating properties. This study evaluated the therapeutic potential of ATR-I for indomethacin (IND)-induced gastric mucosal lesions and its underlying mechanisms. Noticeable improvements were observed in the histological morphology and ultrastructures of the rat gastric mucosa after ATR-I treatment. There was improved blood flow, a significant decrease in the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1ß, and IL-18, and a marked increase in prostaglandin E2 (PGE2) expression in ATR-I-treated rats. Furthermore, there was a significant decrease in the mRNA and protein expression levels of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), and nuclear factor-κB (NF-κB) in rats treated with ATR-I. The results show that ATR-I inhibits the NLRP3 inflammasome signaling pathway and effectively alleviates local inflammation, thereby improving the therapeutic outcomes against IND-induced gastric ulcers in rats.

Global trends in oxidative stress in the Retina: A bibliometric analysis of 2013-2023.

Background: Oxidative stress plays a significant role in the pathogenesis of many retinal diseases. However, only a few systematic bibliometric studies have been conducted. This study aims to visualize research hotspots and developmental trends in oxidative stress in the retina from 2013 to 2023 by analyzing bibliometric data. Methods: We retrieved papers on oxidative stress in the retina published between 2013 and 2023 from the Web of Science Core Collection. The data were visually analyzed using CiteSpace and VOSviewer software. Results: The total number of 2100 publications were included in the analysis. An overall increasing trend in the number of publications is observed between 2013 and 2023. Chinese publications were the most contributive, but United States publications were the most influential. Shanghai Jiao Tong University was the most active and prolific institution. Antioxidants was the most productive journal, while Oxidative Medicine and Cellular Longevity were the journals with the most-cited articles. Kaarniranta K, from Finland, was the most productive and influential author. Examination of co-cited references revealed that researchers in the field are primarily focused on investigating the molecular mechanisms, preventive strategies, and utilization of antioxidants to address retinal oxidative damage. Diabetic retinopathy, endothelial growth factor, retinitis pigmentosa, retinal degeneration, antioxidant response, retinal ganglion cells, and genes are the research hotspots in this field. Metabolism, sodium iodate, and system are at the forefront of research in this field. Conclusion: Attention toward retinal oxidative stress has increased over the past decade. Current research focuses on the mechanisms of retinal diseases related to oxidative stress and the experimental study of antioxidants in retinal diseases, which may continue to be a trend in the future.

Astragaloside IV ameliorates indomethacin-induced intestinal inflammation in rats through inhibiting the activation of NLRP3 inflammasome.

The administration of nonsteroidal anti-inflammatory drugs (NSAIDs) may cause significant intestinal alteration and inflammation and lead to the occurrence of inflammatory diseases resembling duodenal ulcers. Astragaloside IV (AS-IV) is a glycoside of cycloartane-type triterpene isolated from the dried root of Astragalus membranaceus (Fisch.) Bge. (family Fabaceae), and has been used for ameliorating the NSAID-induced inflammation in the small intestine. The present study aimed to investigate the effects of AS-IV on indomethacin (IND)-induced inflammation in the small intestine of rats and its underlying mechanisms. Hematoxylin-eosin (H&E) staining, transmission and scanning electron microscopy were carried out to observe the surface morphology and ultrastructure of the small intestinal mucosa. Immunofluorescence and ELISA tests were employed to detect the expressions of NLRP3, ASC, caspase-1, and NF-κB proteins, as well as inflammatory factors IL-1ß and IL-18, to uncover potential molecular mechanisms responsible for mitigating small intestinal inflammation. The results demonstrated that AS-IV significantly decreased the ulcer index, improved the surface morphology and microstructure of the small intestinal mucosa, and increased mucosal blood flow. Molecular docking revealed a strong and stable binding capacity of AS-IV to NLRP3, ASC, caspase-1, and NF-κB proteins. Further experimental validation exhibited that AS-IV markedly decreased levels of IL-1ß and IL-18, and inhibited the protein expression of NLRP3, ASC, caspase-1, and NF-κB. Our data demonstrate that AS-IV ameliorates IND-induced intestinal inflammation in rats by inhibiting the activation of NLRP3 inflammasome and reducing the release of IL-1ß and IL-18, thereby representing a promising therapy for IND-induced intestinal inflammation.

Global knowledge mapping and emerging trends in Helicobacter pylori-related precancerous lesions of gastric cancer research: A bibliometric analysis from 2013 to 2023.

Helicobacter pylori (H pylori) infection is a crucial element in chronic gastritis progression towards precancerous lesions of gastric cancer (PLGC) formation and, potentially, gastric cancer; however, screening for and eliminating H pylori has several challenges. This study aimed to assess the present research status, prominent themes, and frontiers of H pylori-related PLGC and to provide impartial evaluations of the developmental trends in this domain. This study extracted articles and review papers concerning H pylori-related PLGC published from 2013 to 2023 from the Web of Science Core Collection. The data was analyzed and visualized using VOSviewer and CiteSpace. The study encompassed 1426 papers, with a discernible upward trend in publications between 2013 and 2023. China emerged as the most productive country, whereas the United States exerted the greatest influence. Baylor College of Medicine was the most prolific institution. World Journal of Gastroenterology featured the highest number of published papers, whereas Gastroenterology was the most frequently cited journal. Kim N. from South Korea was the most prolific author. Co-cited literature pertained to various aspects such as gastritis classification, H pylori infection management, gastric cancer prevention, and managing patients with PLGC. Future research will focus on the Kyoto classification, cancer incidence, and gastric intestinal metaplasia. The results of this study indicate a persistent increase in attention directed toward H pylori-associated PLGC. The research emphasis has transitioned from molecular mechanisms, epidemiology, monitoring, and diagnosis to clinical prevention and treatment methodologies. The forthcoming research direction in this area will concentrate on controlling and preventing malignant PLGC transformation.

Helicobacter pylori infection: a dynamic process from diagnosis to treatment.

Helicobacter pylori, a gram-negative microaerophilic pathogen, causes several upper gastrointestinal diseases, such as chronic gastritis, peptic ulcer disease, and gastric cancer. For the diseases listed above, H. pylori has different pathogenic mechanisms, including colonization and virulence factor expression. It is essential to make accurate diagnoses and provide patients with effective treatment to achieve positive clinical outcomes. Detection of H. pylori can be accomplished invasively and noninvasively, with both having advantages and limitations. To enhance therapeutic outcomes, novel therapeutic regimens, as well as adjunctive therapies with probiotics and traditional Chinese medicine, have been attempted along with traditional empiric treatments, such as triple and bismuth quadruple therapies. An H. pylori infection, however, is difficult to eradicate during treatment owing to bacterial resistance, and there is no commonly available preventive vaccine. The purpose of this review is to provide an overview of our understanding of H. pylori infections and to highlight current treatment and diagnostic options.

Qi-Shen-Tang alleviates retinitis pigmentosa by inhibiting ferroptotic features via the NRF2/GPX4 signaling pathway.

Ferroptosis has been observed during retinal photoreceptor cell death, suggesting that it plays a role in retinitis pigmentosa (RP) pathogenesis. Qi-Shen-Tang (QST) is a combination of two traditional Chinese medicines used for the treatment of ophthalmic diseases; however, its mechanism of action in RP and ferroptosis remains unclear. Therefore, this study aimed to explore the effect and potential molecular mechanisms of QST on RP. QST significantly improved tissue morphology and function of the retina in the RP model mice. A significant increase in retinal blood flow and normalization of the fundus structure were observed in mice in the treatment group. After QST treatment, the level of iron and the production of malondialdehyde decreased significantly; the levels of superoxide dismutase and glutathione increased significantly; and the protein expression of glutathione peroxidase 4 (GPX4), glutathione synthetase, solute carrier family 7 member 11, and nuclear factor erythroid 2-related factor 2 (NRF2) increased significantly. The molecular docking results demonstrated potential interactions between the small molecules of QST and the key proteins of NRF2/GPX4 signaling pathway. Our results indicate that QST may inhibit ferroptosis by inhibiting the NRF2/GPX4 signaling pathway, thereby reducing RP-induced damage to retinal tissue.

Research on antibiotic resistance in Helicobacter pylori: a bibliometric analysis of the past decade.

Resistance of Helicobacter pylori (H. pylori) to antibiotics has reached alarming levels worldwide, and the efficacy of the H. pylori eradication treatment has decreased dramatically because of antibiotic resistance. To gain a more comprehensive understanding of the development status, research hotspots, and future trends related to H. pylori antibiotic resistance, we conducted a thorough retrospective analysis via the bibliometrics method. We searched the Science Citation Index Expanded of the Web of Science Core Collection for all pertinent articles on H. pylori antibiotic resistance from 2013 to 2022. R-bibliometrix, CiteSpace, and VOSviewer tools were utilized to depict statistical evaluations in order to provide an unbiased presentation and forecasts in the field. We incorporated a total of 3,509 articles related to H. pylori antibiotic resistance. Publications were inconsistent prior to 2017, but steadily increased after 2017. China generated the most papers and the United States of America received the most citations and the highest H-index. Baylor College of Medicine was the most influential institution in this field, with the highest number of publications and citations, as well as the highest H-index. Helicobacter was the most productive journal, followed by the World Journal of Gastroenterology and Frontiers in Microbiology. The World Journal of Gastroenterology had the highest citation. Graham, David Y was the most productive and cited author. Clarithromycin resistance, prevalence, gastric cancer, quadruple therapy, sequential therapy, 23S rRNA, whole genome sequencing, bismuth, and probiotics appeared with a high frequency in the keywords. The top keywords with the highest citation bursts were vonoprazan, RdxA, biofilm formation, and fatty acid chain. Our research illustrated a multi-dimensional facet and a holistic knowledge structure for H. pylori antibiotic resistance research over the past decade, which can serve as a guide for the H. pylori research community to conduct in-depth investigations in the future.

Trends in Helicobacter pylori-related gastric ulcer research from 2012 to 2022: A bibliometric and visual analysis.

Background: Helicobacter pylori-related gastric ulcer (H. pylori-related GU) is one of the most common digestive system diseases that have received widespread attention from researchers. The purpose of this article was to analyze the research status and hotspots of H. pylori-related GU and to predict its future research directions. Methods: The article and review papers associated with H. pylori-related GU published from 2012 to 2022 were retrieved from the Web of Science Core Collection (WoSCC). The analysis of knowledge maps and bibliometrics was done with CiteSpace 6.1.R2 Basic and VOSviewer 1.6.18. Results: A total of 2,971 articles were included in the study. Between 2012 and 2022, the number of papers published showed an increasing trend. China was the most prolific country, and the United States was the most influential country. Baylor College of Medicine had the largest number of publications and citations among publishing agencies. World Journal of Gastroenterology published the most articles on the H. pylori-related GU field, and GUT was the journal with the most cited articles. Yamaoka Y from Japan was the most productive author, and Graham DY from the USA was the most influential author. A keyword and reference analysis showed that the hot topics of research were the mechanism of H. pylori and the treatment of H. pylori-related GU. The keywords that emerged in the recent 5 years were oxidative stress, probiotics, competitive acid blocker, vonoprazan, gut microbiota, and neutrophil-activating protein. Conclusion: Over the recent 10 years, research on H. pylori-related GU has generally shown an increasing trend. The treatment and pathogenesis of H. pylori-related GU remain a hot topic of research. The treatment of H. pylori by oxidative stress and competitive acid inhibitor mechanisms, the influence of gastrointestinal flora on H. pylori, probiotic adjuvant therapy of H. pylori-related GU, and the immunoprotective effect of neutrophil activator protein could be popular research directions and trends in the future.

Traditional Chinese Medicine prescription Huang-Qi-Jian-Zhong-Tang ameliorates indomethacin-induced duodenal ulcers in rats by affecting NF-κB and STAT signaling pathways.

Huang-Qi-Jian-Zhong-Tang (HQJZT) is a well-known traditional Chinese herbal formulation. This study aimed to investigate the duodenoprotective properties of HQJZT against Indomethacin (IND)-induced duodenal ulceration in rats, and the mechanisms involved, particularly through NF-κB and STAT signaling pathways. Our results showed that HQJZT completely protected the duodenal mucosa from ulceration caused by IND, as indicated by improved macroscopic and histological appearances. There was a significant decrease in ulcer index and microscopic score, an increase in villus height and crypt depth, and a normalization of the tissue architecture of the duodenum in rats following HQJZT treatment. Blood flow into the duodenal mucosa was significantly increased after HQJZT administration. HQJZT significantly increased PGE2 and NO levels in the duodenal mucosa. A significant reduction in the production of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α was observed in the duodenal mucosa under treatment with HQJZT. Mechanistically, the administration of HQJZT significantly lowered the duodenal protein expression of inflammation-related genes, including p-NF-κB and p-IκBß, compared with the ulcer control group. Furthermore, the STAT signaling pathway-related protein markers p-JAK and p-STAT were significantly reduced in the HQJZT (1.30 and 2.60 g/kg) groups. As a result of these findings, HQJZT alleviates duodenal mucosal ulcers caused by IND. A protective effect of HQJZT on duodenal ulcers is attributed to its ability to improve mucosal blood flow, stimulate the production of cytoprotective mediators, minimize proinflammatory cytokines, and block the activation of NF-κB and STAT signaling pathways.

Characteristics and functions of glyceraldehyde 3-phosphate dehydrogenase S-nitrosylation during controlled aging of elm and Arabidopsis seeds.

Seed aging is the gradual decline in seed vigor, during which programmed cell death (PCD) occurs. The functions of nitric oxide (NO) are exerted through protein S-nitrosylation, a reversible post-translational modification. During seed aging, more than 80 proteins are S-nitrosylated, but the particular role of individual proteins is unknown. Here, we showed that the S-nitrosylation level of glyceraldehyde 3-phosphate dehydrogenase (UpGAPDH) in elm (Ulmus pumila L.) seeds increased after controlled deterioration treatment. UpGAPDH was S-nitrosylated at Cys154 during S-nitrosoglutathione (GSNO) treatment, and its oligomerization was triggered both in vitro and in elm seeds. Interestingly, UpGAPDH interacted with the mitochondrial voltage-dependent anion channel in an S-nitrosylation-dependent way. Some UpGAPDH-green fluorescent protein in Arabidopsis protoplasts co-localized with mitochondria during the GSNO treatment, while the S-nitrosylation-defective UpGAPDH C154S-GFP protein did not. Seeds of oxUpGAPDH lines showed cell death and lost seed vigor rapidly during controlled deterioration treatment-triggered seed aging, while those overexpressing S-nitrosylation-defective UpGAPDH-Cys154 did not. Our results suggest that S-nitrosylation of UpGAPDH may accelerate cell death and seed deterioration during controlled deterioration treatment. These results provide new insights into the effects of UpGAPDH S-nitrosylation on protein interactions and seed aging.

Fructus Lycii and Salvia miltiorrhiza Bunge extract alleviate retinitis pigmentosa through Nrf2/HO-1 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Lycii and Salvia miltiorrhiza Bunge (FS) are popular Chinese herbs for the treatment of retinitis pigmentosa (RP). AIM OF THE STUDY: This study was to evaluate protective effects of FS extract on RP and to explore whether FS extract exerts its protective effects via oxidative stress by regulating Nrf2/HO-1 signaling pathway. MATERIAL AND METHODS: FS extract were identified by UPLC chromatographic analysis. Rd10 mice as the model of RP, followed by a 4-week FS extract treatment by intragastric administration. After the animal sacrifice, histopathological examination and Scotopic electroretinography (ERG) analysis were assessed. The oxidative stress markers were determined and the expression levels of Nrf2 and HO-1 mRNA were evaluated by qRT-PCR. The expression and distribution of Nrf2 and HO-1 protein were determined by Western blot and immunohistochemistry. RESULTS: The morphological changes of Outer nuclear layer (ONL) thickness and number of the ONL were observed with a significant increased, and the functional changes of a-amplitude and b-wave amplitude were measured with a markedly increased. Treatment with FS extract remarkably increased levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and decreased level of malondialdehyde (MDA). Moreover, FS extract up-regulated mRNA and protein expression of Nrf2 and HO-1. CONCLUSIONS: This study indicated that FS extract can improve retinal morphology and function, which may have occurred through the regulation of the Nrf2/HO-1 pathway to inhibit the oxidative reaction.

Functional characterization of an unobtrusive protein, CkMT4, in re-establishing desiccation tolerance in germinating seeds.

Desiccation tolerance (DT) is gradually lost during seed germination, while it can be re-established by pre-treatment with polyethylene glycol (PEG) and/or abscisic acid (ABA). Increasing knowledge is available on several stress-related proteins in DT re-establishment in herb seeds, but limited information exists on novel proteins in wood seeds. This study aimed to investigate the role of metallothionein CkMT4, a protein species with the highest fold increase in abundance in Caragana korshinskii seeds on PEG treatment. The fluctuation in mRNA levels of CkMT4 during seed development was consistent with the changes in DT, and the expression of CkMT4 could be up-regulated by ABA. Besides metal-binding capacity, CkMT4 might supply Cu2+/Zn2+ to superoxide dismutase (SOD) under high redox potential provided by PEG treatment for excess reactive oxygen species (ROS) scavenging. The overexpression of CkMT4 in yeast results in enhanced oxidation resistance. Experimentally, this study demonstrated the overexpression of CkMT4 in Arabidopsis seeds benefited the re-establishment of DT and enhanced the activity of SOD. On the whole, these findings suggested that CkMT4 facilitated the re-establishment of DT in C. korshinskii seeds mainly through diminishing excess ROS, which put the mechanism underlying the re-establishment of DT in xerophytic wood seeds into a new perspective.

Traditional Chinese Medicine Li-Zhong-Tang accelerates the healing of indomethacin-induced gastric ulcers in rats by affecting TLR-2/MyD88 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Li-Zhong-Tang (LZT) is a well-known Chinese herbal formulation first described in one of traditional Chinese medicine (TCM) scriptures, Treatise on Febrile Diseases. LZT has been commonly prescribed for the treatment of various gastrointestinal diseases for over 1800 years, and has demonstrated pronounced therapeutic effects on patients with gastric ulcers. AIM OF THE STUDY: The present study aimed to scientifically evaluate protective effects of LZT on indomethacin (IND)-induced gastric injury in rats and to elucidate whether LZT exerts its gastro-protective effects via enhancing mucosal immunity by regulating TLR-2/MyD88 signaling pathway. MATERIAL AND METHODS: Gastric ulcers were induced in male Sprague-Dawley (SD) rats with a single oral dose of 150 mg/kg IND. Ulcer index (UI) and curative index (CI) were evaluated. Histopathological examinations were performed and microscopic score (MS) was macroscopically calculated. The volume of gastric juice, free acidity, total acidity, and gastric pH was measured. The gastroprotective and inflammatory biomarkers including levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), and malondialdehyde (MDA) were determined. Expression levels of TLR-2 and MyD88 mRNA were assessed by qRT-PCR. The expression, distribution, and co-localization of TLR-2 and MyD88 protein were determined by Western blot, immunohistochemistry, and immunofluorescence, respectively. RESULTS: Induction of gastric ulcers in rats resulted in very significantly increased UI and elevated volume and acidity of gastric juice, which were markedly attenuated by LZT treatment. Microscopic examinations of the IND-induced gastric ulcers revealed severe gastric hemorrhagic necrosis, submucosal edema, and destruction of epithelial cells, which were significantly attenuated in LZT-treated rats. Moreover, treatment with LZT remarkably increased gastric mucosal levels of PGE2 and NO, and lowered highly elevated levels of TNF-α and MDA in gastric ulcerative rats. Mechanistically, LZT inhibited mRNA and protein expression of TLR-2 and MyD88 and enhanced immune function in gastric mucosa. Immunohistochemical analyses and immunofluorescent detection further confirmed a markedly decreased co-localization of TLR-2 and MyD88 protein in the gastric mucosa of LZT-treated rats as compared to that of gastric ulcerative rats. CONCLUSIONS: These findings indicate that LZT alleviates serious gastric mucosal ulcerations induced by IND. Protective effects of LZT on gastric ulcers are believed to be associated with the intensification of the anti-oxidative defense system, mitigation of proinflammatory cytokines, stimulation of the production of cytoprotective mediators, and improvement of the mucosal immunity through TLR-2/MyD88 signaling pathway.

Antiulcerogenic Activity of Li-Zhong Decoction on Duodenal Ulcers Induced by Indomethacin in Rats: Involvement of TLR-2/MyD88 Signaling Pathway.

BACKGROUND: Administration of nonsteroidal anti-inflammatory drugs (NSAIDs) often causes small intestinal ulcers in patients, but few effective drugs are currently available to manage such serious adverse events of NSAIDs. Li-Zhong decoction (LZD), a well-known traditional Chinese medicine (TCM) formula, is commonly prescribed for treatment of gastrointestinal diseases. The present study aimed to investigate the anti-ulcerogenic activity of LZD on indomethacin- (IND-) induced duodenal ulcer in rats. Mechanistic studies of action of LZD were focused on involvement of TLR-2/MyD88 signaling pathway. METHODS: Fifty male Sprague-Dawley (SD) rats were randomly and evenly divided into five groups: normal control, ulcer control (IND, 25 mg/kg), IND + esomeprazole (ESO, 4.17 mg/kg), and IND + low and high doses of LZD (3.75 and 7.50 g/kg). Macroscopic and histopathological examinations were performed for evaluation of ulcer index (UI), curative index (CI), and microscopic score (MS). Levels of duodenal inflammatory biomarkers and cytoprotective mediators including interleukin-4 (IL-4), IL-10, tumor necrosis factor-α (TNF-α (TNF. RESULTS: Gross and microscopic examinations of the IND-treated rats revealed severe duodenal hemorrhagic necrosis, inflammatory infiltration, villus destruction, and crypt abscess, while LZD-treated rats manifested these pathological events to a markedly lesser degree. LZD significantly decreased UI and MS, increased CI, preserved the integrity of the villus and crypt, and normalized the tissue architecture of the duodenum of rats. The elevated TNF-α (TNF. CONCLUSIONS: Our data demonstrate that LZD protects the duodenal mucosa from IND-caused lesions, which is at least partially attributable to the interaction of its potential cytoprotective and anti-inflammatory mechanisms together with enhancement of the mucosal immunity through TLR-2/MyD88 signaling pathway.