Caffeic Acid Reduces Ferroptosis to Dampen Inflammation of Keratinocytes in Psoriasis by Inhibiting EGR1-induced Transcription Activation of CHAC1.

BACKGROUND: Ferroptosis of keratinocytes is closely associated with amplification of skin inflammation in psoriasis. This study focuses on unlocking the role of caffeic acid (CA), a polyphenol compound, in keratinocyte ferroptosis and understanding the underlying mechanistic basis. METHODS: The interaction between early growth response protein 1 (EGR1) and chac glutathione specific γ­glutamylcyclotransferase 1 (CHAC1) was predicted by bioinformatics and validated via chromatin immunoprecipitation and dual-luciferase reported assays. Their expressions in primary human epidermal keratinocytes were altered by transfection of EGR1/CHAC1 overexpression or knockdown plasmids, and then keratinocytes were followed by CA treatment and Erastin (ferroptosis inducer). Keratinocyte viability was determined by CCK-8 assay, and the ferroptotic effect was evaluated using colorimetric assay and flow cytometry. Proinflammatory cytokine secretion by keratinocytes was detected via ELISA. Expressions of EGR1 and CHAC1 in keratinocytes were analyzed by qRT-PCR or Western blot. RESULTS: Increased expressions of EGR1 and CHAC1 were detected in keratinocytes with Erastin treatment. CA (100 µM) antagonized Erastin (10 µM)-induced decrease in viability, increases in EGR1 and CHAC1 expressions, upregulation of MDA, ROS, and Fe2+, downregulation of GSH and SOD, and secretion of proinflammatory cytokines from keratinocytes. EGR1 overexpression potentiated Erastin-induced effects. Moreover, EGR1 overexpression and CA mutually counteracted their effects on Erastin-induced keratinocytes. EGR1 transcriptionally activated and positively regulated CHAC1. The above Erastin-induced effects were neutralized by EGR1 knockdown but potentiated by CHAC1 overexpression. Moreover, EGR1 knockdown and CHAC1 overexpression reversed each other's effects. CONCLUSION: CA reduces ferroptosis by inhibiting EGR1-induced activation of CHAC1 to dampen inflammation of keratinocytes in psoriasis. This study providing new compounds and candidate targets for the clinical treatment of psoriasis.

Main chemical constituents and mechanism of anti-tumor action of Solanum nigrum L.

OBJECTIVE: Solanum nigrum L. (SNL) is a natural drugwith diverse bioactive components and multi-targeted anti-tumor effects, gaining increasing attention in clinical application. METHOD AND RESULTS: This paper reviews the studies on SNL by searching academic databases (Google Scholar, PubMed, Science Direct,and Web of Science, among others), analyzing its chemical compositions (alkaloids, saponins, polysaccharides, and polyphenols, among others), andbriefly describes the anti-tumor mechanisms of the main components. DISCUSSION: This paper discusses the shortcomings of the current research on SNL and proposes corresponding solutions, providing theoretical support for further research on its biological functions and clinical efficacy.

Monocyte/macrophage-mediated venous thrombus resolution.

Venous thromboembolism (VTE) poses a notable risk of morbidity and mortality. The natural resolution of the venous thrombus might be a potential alternative treatment strategy for VTE. Monocytes/macrophages merge as pivotal cell types in the gradual resolution of the thrombus. In this review, the vital role of macrophages in inducing inflammatory response, augmenting neovascularization, and facilitating the degradation of fibrin and collagen during thrombus resolution was described. The two phenotypes of macrophages involved in thrombus resolution and their dual functions were discussed. Macrophages expressing various factors, including cytokines and their receptors, adhesion molecules, chemokine receptors, vascular endothelial growth factor receptors, profibrinolytic- or antifibrinolytic-related enzymes, and other elements, are explored for their potential to promote or attenuate thrombus resolution. Furthermore, this review provides a comprehensive summary of new and promising therapeutic candidate drugs associated with monocytes/macrophages that have been demonstrated to promote or impair thrombus resolution. However, further clinical trials are essential to validate their efficacy in VTE therapy.

Pancreatic fistula after pancreaticoduodenectomy - Alternative therapy of endoscopic ultrasound guided pancreatic duct puncture drainage.

Pancreatic fistula is a very difficult complication after pancreatic surgery(1). Endoscopic ultrasound guided drainage of pancreatic duct (EUS-PD)was a challenging endoscopic procedure that can solve the problem of postoperative pancreatic fistula. However, EUS-PD cannot be completed in patients with undilated pancreatic ducts. Here, we present a case of fistula-digestive anastomosis in the treatment of postoperative pancreatic fistula.

Human Strongyloides stercoralis infection.

Strongyloides stercoralis is an important soil-transmitted helminth occurring world-wide and affecting 30-100 million people. Because many cases are asymptomatic and sensitive diagnostic methods are lacking, S. stercoralis infection is frequently underdiagnosed. The increasing incidence of autoimmune and wasting diseases and increased use of immunosuppressive agents, as well as the increased use of immunosuppressants and cytotoxic drugs, have increased S. stercoralis infection and their mortality. This review provides information about S. stercoralis epidemiology, life cycle, aetiology, pathology, comorbidities, immunology, vaccines, diagnosis, treatment, prevention, control and makes some recommendations for future prevention and control of this important parasite.

ERCP-Related adverse events in pediatric patients: a 10-years single-site review.

PURPOSE: This retrospective analysis aimed to assess the feasibility and safety of endoscopic retrograde cholangiopancreatography (ERCP) in pediatric patients by examining ERCP-related adverse events (AEs) occurring over a decade at a single center. METHODS: Pediatric patients under 18 years old who underwent ERCP at the Second Hospital of Hebei Medical University from 1/2013 to 11/2023 were included. ERCP-related AEs were defined according to ERCP-related adverse events: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Clinical data of patients experiencing ERCP-related AEs were obtained from electronic medical records for analysis. RESULTS: Over the past decade, a total of 76 pediatric patients underwent 113 ERCP procedures, including 26 patients who underwent repeat ERCP, totaling 63 procedures. There were 32 males and 44 females, with a median age of 13 years (range 3 years and 5 months-17 years and 9 months). Among all ERCP procedures, 14 (12.4%) were diagnostic and 99 (87.6%) were therapeutic, with a 100% success rate. 16 cases (14.2%) of ERCP-related AEs, all post-ERCP pancreatitis (PEP), were observed, while no other AEs defined by ESGE such as bleeding, perforation, cholangitis, cholecystitis, or sedation-related events were noted. Additionally, 23 cases (20.4%) of ERCP-related AEs not included in the ESGE definition were observed, including post-ERCP abdominal pain in 20 cases (17.7%), post-ERCP nausea and vomiting in 2 cases (1.8%), and unplanned reoperation in 1 case (0.9%). In the 26 cases of pediatric patients who underwent repeat ERCP, we observed that AEs occurred in 15 cases (57.7%) during their initial ERCP, which was much higher than the overall average level. CONCLUSIONS: Post-ERCP abdominal pain and PEP are the most common ERCP-related AEs in pediatric patients, while severe AEs such as bleeding and perforation are rare. The incidence of AEs after initial ERCP in pediatric patients who received repeat ERCP is higher than the overall average level. Based on our center's experience, we believe that ERCP can be safely performed in children over 3 years old with biliary and pancreatic diseases and obtain reliable clinical benefits. However, active monitoring and management of ERCP-related AEs are essential to improve the clinical outcomes of pediatric ERCP.

Endoscopic management of recurrent obstructive jaundice after EUS-guided biliary drainage.

EUS-GUIDED biliary drainage (EUS-BD) has recently gained widespread acceptance as a minimally invasive alternative method for biliary drainage. However, the risks of encountering recurrent biliary obstruction (RBO) after EUS-BD have increased due to the growing clinical experience of EUS-BD and prolonged prognosis of the underlying disease. Previous studies have shown that the incidence of RBO following EUS-BD ranges from 11% to 25%. Nevertheless, literature on the efficacy of reintervention of RBO after EUS-GUIDED hepaticogastrostomy (EUS-HGS) and case reports describing the procedural details of endoscopic reintervention following EUS-HGS are lacking.

External fistula internalization - Endoscopic ultrasound guided stent implantation between stomach and fistula in the treatment of refractory pancreatic cutaneous fistula.

Pancreatic cutaneous fistula is a complex condition, making it challenging to achieve favorable outcomes with conservative medical treatment. Surgical interventions often entail surgical risks and postoperative complications. Here, we present a case involving endoscopically guided stent placement between the stomach and the fistula. By internalizing the fistula, patients can potentially remove the external drainage tube, offering a novel endoscopic treatment approach for such cases.

QPH-FR: A Novel Quinoa Peptide Enhances Chemosensitivity by Targeting Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 5 in Colorectal Cancer.

Chemoresistance is one of the difficulties in the treatment of colorectal cancer (CRC), and the enhanced stemness of tumor cells is the underlying contributing factor. Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a classical marker of CRC stem cells and can be an important potential target for CRC chemotherapy. Quinoa, a protein-rich plant, offers potential as a source of high-quality active peptides. Novelly, the study obtained quinoa protein hydrolysate (QPH) from whole quinoa grains by simulated digestion. In vivo experiments revealed that the tumor volume in the 5-FU+QPH group decreased from 145.90 ± 13.35 to 94.49 ± 13.05 mm3 in the 5-FU group, suggesting that QPH enhances the chemosensitivity of CRC. Further, the most effective peptide QPH-FR from 631 peptides in QPH was screened by activity prediction, molecular docking, and experimental validation. Mechanistically, QPH-FR competitively suppressed the formation of the LGR5/RSPO1 complex by binding to LGR5, causing RNF43/ZNRF3 to ubiquitinate the FZD receptor, thereby suppressing the Wnt/ß-catenin signaling pathway and exerting stemness inhibition. In summary, the study proposes that a novel peptide QPH-FR from quinoa elucidates the mechanism by which QPH-FR targets LGR5 to enhance chemosensitivity, providing theoretical support for the development of chemotherapeutic adjuvant drugs based on plant peptides.

Unexpected finding: a patient with choledocholithiasis found mass at the lower end of common bile duct.

.

Simplified single-session EUS-guided transhepatic antegrade stone removal for management of choledocholithiasis in patients with surgically altered anatomy.

Background: Endoscopic ultrasound (EUS)-guided transhepatic antegrade stone removal (TASR) has been reserved for choledocholithiasis after failed endoscopic retrograde cholangiopancreatography (ERCP) in recent years. The aim of this study was to evaluate the techniques, feasibility, and safety of simplified single-session EUS-TASR for choledocholithiasis in patients with surgically altered anatomy (SAA). Methods: A retrospective database of patients with SAA and choledocholithiasis from the Second Hospital of Hebei Medical University (Shijiazhuang, China) between August 2020 and February 2023 was performed. They all underwent single-session EUS-TASR after ERCP failure. Basic characteristics of the patients and details of the procedures were collected. The success rates and adverse events were evaluated and discussed. Results: During the study period, 13 patients underwent simplified single-session EUS-TASR as a rescue procedure (8 males, median age, 64.0 [IQR, 48.5-69.5] years). SAA consisted of four Whipple procedures, one Billroth II gastrectomy, four gastrectomy with Roux-en-Y anastomoses, and four hepaticojejunostomy with Roux-en-Y anastomoses. The technical success rate was 100% and successful bile duct stone removal was achieved in 12 of the patients (92.3%). Adverse events occurred in two patients (15.4%), while one turned to laparoscopic surgery and the other was managed conservatively. Conclusions: Simplified single-session EUS-TASR as a rescue procedure after ERCP failure appeared to be effective and safe in the management of choledocholithiasis in patients with SAA. But further evaluation of this technique is still needed, preferably through prospective multicenter trials.

Characterization of physical and chemical properties of dietary fiber from grain bran and its regulation of gut microbiota and metabolite to prevent colitis.

Grain bran dietary fiber (DF) has the effect of promoting intestinal health and is worth being studied. In the present study, the physicochemical properties and prevention effect of DF on ulcerative colitis (UC) were investigated. The results showed that the optimal extraction conditions were determined as α-amylase (350 U/g, 70 °C, pH 7.0, 2.5 h) and papain (100 U/g, 60 °C, pH 7.0, 1.5 h), resulting in a yield of 83.81% for DF. Moreover, DF exhibited unique physicochemical properties contributing to its preventive effects, as evidenced by its ability to mitigate symptoms such as hematochezia, immune inflammation, and impaired intestinal barrier in UC mice. The underlying mechanism can be attributed to the regulation of phenylalanine, tyrosine and tryptophan biosynthesis pathway and maintenance of intestinal microbial homeostasis. Therefore, our study suggests that grain bran DF holds potential for the prevention of UC, providing a basis for the development and utilization of grain bran.

Rheological characterization of chia seed gum as a thickening agent used for dysphagia management.

Dysphagia has emerged as a serious health issue facing contemporary society. Consuming thickened liquids is an effective approach for improving the swallowing safety for dysphagia patients. The thickening effect of chia seed gum (CSG), a novel thickener, in different dispersing media (water, orange juice, and skim milk) was investigated. Moreover, the potential application of CSG for dysphagia management was evaluated by comparison with xanthan gum (XG) and guar gum (GG). The thickened liquids prepared with 0.4 %-1.2 % (w/v) CSG, XG, and GG could be classified into levels 1-4, 2-4, and 1-3, respectively, according to the International Dysphagia Diet Standardization Initiative (IDDSI) framework. All the thickened liquids displayed shear-thinning characteristics that facilitated safe swallowing. The viscosities (η50) of CSG dissolved in water (0.202-1.027 Pa·s) were significantly greater than those of CSG dissolved in orange juice (0.070-0.690 Pa·s) and skim milk (0.081-0.739 Pa·s), indicating that CSG had a greater thickening effect in water than in orange juice and skim milk. Compared with those prepared with GG, the thickened liquids prepared with CSG and XG exhibited greater viscoelasticity, better water-holding capacity, and more compact networks. The findings suggested that CSG can be used as a potential thickener for thickening liquid foods to manage dysphagia.

TaMYB72 directly activates the expression of TaFT to promote heading and enhance grain yield traits in wheat (Triticum aestivum L.).

Heading date, grain number per spike, and grain weight are crucial traits affecting yield and adaptability in wheat. The transcription factor TaMYB72 is an important regulator of wheat grain yield and its knock-out mutants can be used as germplasm resources for wheat improvement.

Construction and characterization of alginate/calcium ß-hydroxy-ß-methylbutyrate hydrogels: Effect of M/G ratios and calcium ion concentration.

Calcium ß-hydroxy-ß-methylbutyrate (CaHMB), a functional calcium salt, is used to maintain and improve muscle health. Here, a new hydrogel material prepared from alginate (ALG) with three M/G ratios (1:1, 2:1, and 1:2) and CaHMB (0-2 mg/mL) was investigated. CaHMB regulates the formation and properties of ALG hydrogels through chelation and hydrogen bonding. When the M/G ratio was 2:1, the anionic groups of CaHMB containing carboxyl and hydroxyl groups formed hydrogen bonds with the polysaccharide chains, hindering the capture of Ca2+ by the G-residue fragments of ALG, which in turn retarded the gelation process. The noncalcium cross-linked polysaccharide chain structure of ALG and the anionic group of CaHMB also affected the water distribution in the hydrogel, especially when M residue content ≥G residue content. Lower M/G ratios and higher CaHMB concentrations could increase the number of "egg box" crosslinking junctions of calcium alginate, and the microstructure was denser in the gel pores, resulting in a stronger gel strength and more free water bound in the gel matrix. This study provides a theoretical and methodological basis for the design of novel hydrogels by studying the crosslinking features of ALG/CaHMB.

Effective identification and differential analysis of anticancer peptides.

Anticancer peptides (ACPs) have recently emerged as promising cancer therapeutics due to their selectivity and lower toxicity. However, the number of experimentally validated ACPs is limited, and identifying ACPs from large-scale sequence data is time-consuming and expensive. Therefore, it is critical to develop and improve upon existing computational models for identifying ACPs. In this study, a computational method named ACP_DA was proposed based on peptide residue composition and physiochemical properties information. To curtail overfitting and reduce computational costs, a sequential forward selection method was utilized to construct the optimal feature groups. Subsequently, the feature vectors were fed into light gradient boosting machine classifier for model construction. It was observed by an independent set test that ACP_DA achieved the highest Matthew's correlation coefficient of 0.63 and accuracy of 0.8129, displaying at least a 2% enhancement compared to state-of-the-art methods. The satisfactory results demonstrate the effectiveness of ACP_DA as a powerful tool for identifying ACPs, with the potential to significantly contribute to the development and optimization of promising therapies. The data and resource codes are available at https://github.com/Zlclab/ACP_DA.

Comparison between Endoscopic Ultrasound-Guided Antegrade and Transluminal Stent Implantation in Distal Malignant Biliary Obstruction after Failed ERCP.

Background: Distal malignant biliary obstruction (DMBO) can result in obstructive jaundice. Endoscopic ultrasound- (EUS-) guided biliary drainage (EUS-BD) has been an alternative for DMBO after failed ERCP. Aim: To compare the efficacy and safety between antegrade and transluminal approaches in patients with unresectable DMBO when ERCP failed. Methods: Patients with DMBO leading to obstructive jaundice after failed ERCP were enrolled in this study. We retrospectively evaluated the safety and efficacy between EUS-guided transluminal stenting (TLS group) and antegrade stenting (AGS group). Results: 82 patients were enrolled, of which 45 patients were in TLS group and 37 in AGS group. There were no statistical differences in the malignancy type, baseline common bile duct diameter, total bilirubin level, reason for EUS-BD, and history of biliary drainage between TLS and AGS groups. The technical success rate was statistically higher in TLS group than in AGS group (97.8 vs. 81.1%, P = 0.031). There were no statistical differences in clinical success rate, procedure-related adverse events, stent migration rate, stent dysfunction rate, reintervention rate, and overall patient survival time between TLS and AGS groups. The median time to stent dysfunction or patient death in TLS and AGS groups was 53 and 81 days, respectively (P = 0.017). Conclusions: Although AGS had a lower technical success rate than TLS, it was superior to TLS in stent patency in patients with DMBO.

Facet-Dependent Fe2O3/BiVO4(110)/BiVO4(010)/Fe2O3 Dual S-Scheme Photocatalyst as an Efficient Visible-Light-Driven Peroxymonosulfate Activator for Norfloxacin Degradation.

A lack of eco-friendly, highly active photocatalyst for peroxymonosulfate (PMS) activation and unclear environmental risks are significant challenges. Herein, we developed a double S-scheme Fe2O3/BiVO4(110)/BiVO4(010)/Fe2O3 photocatalyst to activate PMS and investigated its impact on wheat seed germination. We observed an improvement in charge separation by depositing Fe2O3 on the (010) and (110) surfaces of BiVO4. This enhancement is attributed to the formation of a dual S-scheme charge transfer mechanism at the interfaces of Fe2O3/BiVO4(110) and BiVO4(010)/Fe2O3. By introducing PMS into the system, photogenerated electrons effectively activate PMS, generating reactive oxygen species (ROS) such as hydroxyl radicals (·OH) and sulfate radicals (SO4·-). Among the tested systems, the 20% Fe2O3/BiVO4/Vis/PMS system exhibits the highest catalytic efficiency for norfloxacin (NOR) removal, reaching 95% in 40 min. This is twice the catalytic efficiency of the Fe2O3/BiVO4/PMS system, 1.8 times that of the Fe2O3/BiVO4 system, and 5 times that of the BiVO4 system. Seed germination experiments revealed that Fe2O3/BiVO4 heterojunction was beneficial for wheat seed germination, while PMS had a significant negative effect. This study provides valuable insights into the development of efficient and sustainable photocatalytic systems for the removal of organic pollutants from wastewater.