Search Results (134)

Helicobacter pylori (Hp), a Class I carcinogen infecting over 50% of the global population, is increasingly resistant to conventional antibiotics. This study presents an AI-engineered probiotic strategy targeting urease, a key Hp virulence factor. A humanized single-domain antibody (UreBAb), previously identified and selected in our laboratory, was synthesized commercially and modeled using AlphaFold2, with structural validation conducted via SAVES 6.0. Molecular docking (PyMOL/ClusPro2) and binding energy analysis (InterProSurf) identified critical urease-active residues: K40, P41, K43, E82, F84, T86, K104, I107, K108, and R109. Machine learning-guided optimization using mCSA-AB, I-Mutant, and FoldX prioritized four mutational hotspots (K43, E82, I107, R109), leading to the generation of nine antibody variants. Among them, the I107W mutant exhibited the highest activity, achieving 65.6% urease inhibition—a 24.95% improvement over the wild-type antibody (p < 0.001). Engineered Escherichia coli Nissle 1917 (EcN) expressing the I107W antibody significantly reduced gastric HP colonization by 4.42 log10 CFU in the treatment group and 3.30 log10 CFU in the prevention group (p < 0.001 and p < 0.05, respectively), while also suppressing pro-inflammatory cytokine levels. Histopathological (H&E) analysis confirmed that the I107W antibody group showed significantly enhanced mucosal repair compared to wild-type probiotic-treated mice. Notably, 16S rRNA sequencing revealed that intestinal microbiota diversity and the abundance of core microbial species remained stable across different ethnic backgrounds. By integrating AI-guided antibody engineering with targeted probiotic delivery, this platform provides a transformative and microbiota-friendly strategy to combat antibiotic-resistant Hp infections. Full article

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed the management of type 2 diabetes mellitus and obesity. However, their sustained effect on delaying gastric emptying raises new challenges in gastrointestinal endoscopy performed under sedation. This narrative review aims to summarize current evidence on the impact of GLP-1 RAs on gastric motility and to propose clinical strategies to mitigate associated procedural risks. Methods: A narrative review was conducted integrating findings from scintigraphy, capsule endoscopy, gastric ultrasound, and existing clinical guidelines. Emphasis was placed on studies reporting residual gastric content (RGC), anesthetic safety outcomes, and procedural feasibility in patients undergoing endoscopy while treated with GLP-1 RAs. Results: GLP-1 RAs significantly increase the prevalence of clinically relevant RGC, despite prolonged fasting, with potential implications for airway protection and sedation safety. Although the risk of pulmonary aspiration remains low (≤0.15%), procedural delays, modifications, or cancellations can occur in up to 30% of cases without adapted protocols. Several professional societies (AGA, ASGE, AASLD) advocate for individualized management based on procedure type, symptomatology, treatment phase, and point-of-care gastric ultrasound (POCUS), in contrast to the systematic discontinuation recommended by the ASA. Conclusions: Effective management requires personalized fasting protocols, risk-based stratification, tailored anesthetic approaches, and interprofessional coordination. We propose a clinical decision algorithm and highlight the need for training in gastrointestinal pharmacology, POCUS, and airway management for endoscopists. Future priorities include prospective validation of clinical algorithms, safety outcome studies, and the development of intersocietal consensus guidelines. Full article

Background: Anti-programmed death 1 receptor (PD-1) therapy is a promising treatment strategy for patients with unresectable advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer. However, its response rate and survival benefits are still limited; an immunological analysis of the residual tumor after anti-PD-1 therapy would be important. Methods: We evaluated the clinical efficacy of tumor resection (TR) after chemotherapy or anti-PD-1 therapy in patients with unresectable advanced or recurrent G/GEJ cancer and analyzed the immune status of tumor microenvironment (TME) by immunohistochemistry using their surgically resected specimens. Results: Patients treated with TR after anti-PD-1 therapy had significantly longer survival compared to those treated with chemotherapy and anti-PD-1 therapy alone. Expression of human leukocyte antigen (HLA) class I and major histocompatibility complex (MHC) class II on tumor cells was markedly downregulated after anti-PD-1 therapy compared to chemotherapy. Furthermore, the downregulation of HLA class I may be associated with the activation of transforming growth factor-β signaling pathway in the TME. Conclusions: Immune escape from cytotoxic T lymphocytes may be induced in the TME in patients with unresectable advanced or recurrent G/GEJ cancer after anti-PD-1 therapy due to the downregulation of HLA class I and MHC class II expression on tumor cells. TR may be a promising treatment strategy for these patients when TR is feasible after anti-PD-1 therapy. Full article

Background/Objectives: Delayed gastric emptying (DGE) is a well-known complication of laparoscopic pylorus-preserving gastrectomy (LPPG). Patients who underwent LPPG in the KLASS-04 trial, which was a multicenter prospective randomized control trial comparing LPPG and laparoscopic distal gastrectomy (LDG), showed an unneglectable incidence of long-term DGE compared to patients who underwent LDG. This study aimed to identify the multifactorial risk factors associated with DGE and to analyze the quality of life (QoL) of patients with DGE following LPPG. Methods: DGE was defined as “nearly normal diet residue” at least once in the endoscopic follow-up at 1, 2, and 3 years after the surgery. Clinicopathological features, surgical outcomes, and QoL were compared between the DGE and non-DGE groups. Results: DGE was observed in 21/124 patients (16.3%) who underwent LPPG. Patients without previous abdominal surgery had a higher incidence of DGE in the univariate (32% vs. 4.8%, p = 0.011) and logistic regression analyses (odds ratio: 0.106, 95% confidence interval: 0.014–0.824, p = 0.032). Patients with DGE reported more symptoms of nausea and vomiting (p = 0.004), constipation (p = 0.04), and a dry mouth (p = 0.005). Conclusions: Despite the strict protocol used to avoid well-known risk factors for DGE, such as damage to the hepatic branch of the vagus nerve, infrapyloric artery and vein, and short antral cuff, the LPPG group of the KLASS-04 trial exhibited a considerable incidence of DGE. No clinicopathological or surgical factors, other than the absence of a previous surgical history, were identified as multifactorial risk factors for DGE. However, DGE had a negative impact on the QoL of patients. Full article

This study developed phospholipid-based liposomes loaded with extract from wild thyme (Thymus serpyllum L.) tea processing residues to enhance polyphenol stability and delivery. Liposomes were prepared with phospholipids alone or combined with 10–30 mol% cholesterol or β-sitosterol. The effect of different lipid compositions on encapsulation efficiency (EE), particle size, polydispersity index (PDI), zeta potential, stability, thermal properties, diffusion coefficient, and diffusion resistance of the liposomes was investigated. Liposomes with 10 mol% sterols (either cholesterol or β-sitosterol) exhibited the highest EE of polyphenols, while increasing sterol content to 30 mol% resulted in decreased EE. Particle size and PDI increased with sterol content, while liposomes prepared without sterols showed the smallest vesicle size. Encapsulation of the extract led to smaller liposomal diameters and slight increases in PDI values. Zeta potential measurements revealed that sterol incorporation enhanced the surface charge and stability of liposomes, with β-sitosterol showing the most pronounced effect. Stability testing demonstrated minimal changes in size, PDI, and zeta potential during storage. UV irradiation and lyophilization processes did not cause significant polyphenol leakage, although lyophilization slightly increased particle size and PDI. Differential scanning calorimetry revealed that polyphenols and sterols modified the lipid membrane transitions, indicating interactions between extract components and the liposomal bilayer. FT-IR spectra confirmed successful integration of the extract into the liposomes, while UV exposure did not significantly alter the spectral features. Thiobarbituric acid reactive substances (TBARS) assay demonstrated the extract’s efficacy in mitigating lipid peroxidation under UV-induced oxidative stress. In contrast, liposomes enriched with sterols showed enhanced peroxidation. Polyphenol diffusion studies showed that encapsulation significantly delayed release, particularly in sterol-containing liposomes. Release assays in simulated gastric and intestinal fluids confirmed controlled, pH-dependent polyphenol delivery, with slightly better retention in β-sitosterol-enriched systems. These findings support the use of β-sitosterol- and cholesterol-enriched liposomes as stable carriers for polyphenolic compounds from wild thyme extract, as bioactive antioxidants, for food and nutraceutical applications. Full article

Secreted Frizzled-related protein 4 (SFRP4) has been identified as a patient-level biomarker of the stem-like subtype of gastric cancer (GC), which is associated with poor prognosis and resistance to chemotherapy. Although multiple studies have documented the clinical significance of SFRP4 in GC, its mechanistic role in the stem-like subtype remains incompletely understood. In this study, we elucidate how phosphorylation of SFRP4 by protein kinase A (PKA) converts it into a Wnt signaling agonist. We began with a phosphoproteomic database search to identify candidate kinases that phosphorylate SFRP4. Co-immunoprecipitation assays revealed a direct interaction between PKA and SFRP4, and in vitro kinase assays confirmed that PKA phosphorylates SFRP4 at key threonine residues. Phosphorylated SFRP4 then associates with β-catenin, augmenting Wnt-driven transcriptional activity. Importantly, pharmacological inhibition of PKA significantly reduced SFRP4 phosphorylation and suppressed stemness-associated phenotypes, such as sphere formation, migratory capacity, and chemoresistance, in gastric cancer cells. Collectively, our data demonstrate that PKA-mediated phosphorylation of SFRP4 enhances cancer stemness-related properties in GC through Wnt signaling. Furthermore, these results highlight the PKA–SFRP4 axis as a promising therapeutic target in the stem-like subtype of GC. Full article

Egg protein gels have relatively poor water-holding capacity, hardness, and freeze–thaw properties. Jujube juicing residue dietary fiber (JJRDF) is available, but it is rarely used in the food industry because of its poor hydration properties. Versions of JJRDF modified via cellulase and xylanase hydrolysis separately coupled with carboxymethylation (JJRDF-CXHC), phosphate crosslinking (JJRDF-CXHPC), and acetylation (JJRDF-CXHA) were prepared, and their effects on heat-induced and alkaline-induced egg protein gels (HA-EPGs) were studied. Smaller particle sizes and higher solubility, viscosity, expansion volume, and ability to retain water were observed in JJRDF-CXHC, JJRDF-CXHPC, and JJRDF-CXHA compared to JJRDF (p < 0.05). JJRDF-CXHC showed the highest viscosity (18.46 cP) and expansion volume (10.40 mL/g). Higher random coil and β-sheet contents resulted in an increase in pH, adhesiveness, hardness, and chewiness, and a decrease in the water-losing rate in freeze–thaw cycles, and gastric digestion was observed in the HA-EPGs as a consequence of adding JJRDF, JJRDF-CXHC, JJRDF-CXHPC, and JJRDF-CXHA at 3–5 g/100 g. Moreover, JJRDF-CXHC and JJRDF-CXHPC were better at improving the textural quality of the unmodified HA-EPG compared to JJRDF-CXHA and JJRDF (p < 0.05). Therefore, to improve egg protein gel quality, JJRDF modified with cellulase and xylanase hydrolysis separately coupled with carboxymethylation and crosslinking is a good choice. However, the functionalities of these modified JJRDFs should be studied. Full article

Background/Objectives: Premature infants frequently experience feeding difficulties due to the disrupted coordination of sucking, swallowing, and breathing, increasing the risk of airway compromise. In adults with dysphagia, cold liquids can enhance swallowing by stimulating sensory receptors in the pharyngeal mucosa. We previously demonstrated that short-duration feeding with cold liquid significantly reduces dysphagia in preterm infants; however, the impact of an entire feeding with cold milk remains unexplored. This study aimed to evaluate the safety of cold milk feedings in preterm infants with uncoordinated feeding patterns and their impact on their feeding performance. Methods: Preterm infants with uncoordinated feeding patterns (n = 26) were randomized to be fed milk at either room temperature (RT) or cold temperature (CT) using an experimental, randomized crossover design. We monitored axillary and gastric content temperatures, mesenteric blood flow, and feeding performance. Results: There were no significant differences in mesenteric blood flow Doppler measurements or axillary body temperatures between the CT and RT feeding conditions. However, a reduction in gastric content temperatures of 3.6 °F and 2.7 °F was observed at one and thirty minutes following CT feeding, respectively. No evidence of cold stress, increased episodes of apnea or bradycardia, gastric residuals, or emesis was noted in infants during or after the CT feeding condition. Feeding performance outcomes did not differ significantly regarding milk transfer rate (p = 0.781) or proficiency (p = 0.425). However, the quality score on the Infant-Driven Feeding Scale (IDFS) showed a significant improvement following CT feeding (p = 0.001). Conclusions: Cold milk feeding can be a safe therapeutic option for preterm infants. This underscores the potential for further comprehensive investigations to evaluate cold milk feeding as an effective therapeutic strategy for managing feeding and swallowing difficulties in preterm infants. The study was registered at clinicaltrials.org under #NCT04421482. Full article

Background: Controversy exists about the usefulness of gastric residual (GR) evaluation in preterm infants, and different results have been obtained in studies addressing this practice. Therefore, this meta-analysis aimed to evaluate the efficacy and safety of the practice of routine monitoring of GR compared to avoiding routine aspiration or alternative interventions. Methods: An online database search was conducted for relevant randomized trials from 2017 to 2023. The efficacy of the intervention was assessed from the incidence of necrotizing enterocolitis (NEC) and the time taken for full enteral feeds. The safety was assessed from the duration of hospitalization, incidence of late-onset sepsis, and days of total parenteral nutrition. Results: Only six studies were deemed eligible, fit the inclusion criteria, and were included in the quantitative synthesis. There was no significant difference between the groups in the incidence of NEC, with a mean difference of 0.95 (95% CI: 0.52, 1.75), while the intervention practice showed the early achievement of full enteral feeds (−2.21; 95% CI: −2.58, −1.84), a shorter duration of hospitalization (−0.65; 95% CI: −1.33, 0.02), a lower incidence of late-onset sepsis (0.70; 95% CI: 0.45, 1.09), and less days of total parenteral nutrition −1.65 (95% CI: −1.90, −1.40). Conclusions: For preterm infants with no signs of feeling intolerance, the results from this study stress the omission of the practice of routine gastric residual aspiration. Full article

Endoscopic submucosal dissection (ESD) is very effective for the treatment of digestive tract neoplasia. However, it is very demanding, with a long learning curve, and, therefore, a significant rate of non-curative resections is expected, considering lesion characteristics, location, and endoscopist experience. The management of patients after a non-curative ESD is not definitely established. It must consider patients’ comorbidities and expected survival, as well as the morbidity and mortality of complementary treatments such as surgery, chemotherapy, or radiotherapy. On the other hand, there is a window of opportunity to offer those additional treatments to complete neoplastic treatment and give patients an oncological cure. This decision is sometimes difficult, since the diverse histological criteria that define a non-curative ESD do not have the same weight regarding residual risk and oncological progression. The prediction of residual lesion would be paramount to decide whether to refer patients to surgery; nowadays, this prediction is far from perfect, since most of the patients that undergo surgery due to a non-curative ESD do not have residual neoplasia in the surgical specimen. In this review, ESD curativeness and the management of non-curative ESDs performed for esophageal, gastric, and colorectal lesions will be addressed. Full article

Background/Objectives: Glucagon-like peptide-1 receptor agonists are increasingly used worldwide for weight and hyperglycemia management. There is an ongoing debate on the presence of increased gastric residue, leading to complications such as aspiration and overall safety in patients receiving upper gastrointestinal endoscopy. We aimed to study the effect of GLP-RAs on endoscopy outcomes. Methods: We conducted a detailed search of online databases to select the studies which provided details of the effects of GLP-RAs on patients undergoing endoscopy. The outcomes of interest were odds of retained gastric content (RGC), aspiration risk, and aborted and repeated procedures. A random effect model was used to calculate the pooled odds of outcomes with a 95% CI. We further calculated the pooled odds of predictive factors associated with an increased rate of retained gastric residues in the study population. Results: We included 12 studies with a total of 105,515 patients, of which 32,144 were on GLP-1 RAs and 73,273 were in the control group. A total of 234 (0.73%) aspiration events in GLP-RA users were noted compared to 257 (0.35%) events in the control group. No increased odds (1.26, 95% CI 0.86–1.87, I² 34%) of aspiration were found in GLP-1 users compared to the non-GLP-1 group. Patients on GLP-1 RA had increased RGC compared to the control group (OR 6.30, 95% CI 5.30–7.49, I² 0%). The pooled odds of aborted (OR 5.50, 95% CI 3.25–9.32, I² 0%) and repeated procedures (OR 2.19, 95% CI 1.42–3.38, I² 0%) were significantly higher in GLP-1 RA users. Patients taking Tirazepatide had the highest percentage of RGC (18.9%), while exenatide users had the lowest rate (6.2%) of food retention. Patients undergoing concomitant colonoscopy were found to have significantly low pooled odds of RGC (OR 0.26, 95% CI 0.04–0.48). GLP-1 RAs use was independently associated with increased odds of RGC (3.91, 95% CI 3.21–4.62, I² 0%). The results were homogenous and stayed consistent in the sensitivity analysis. Conclusions: Although the odds of RGC and aborted procedures are high in the GLP-1 RAs group compared to the control, no significant difference in the odds of aspiration was found between the two groups. Simple measures such as a clear liquid diet for 24 h, as routinely set for patients undergoing colonoscopy, may reduce the risk of retaining gastric residue in these patient populations. Full article

Wheat bran dietary fiber (WBDF) is a potential functional additive to enrich products used for relieving constipation. The purpose of this study was to understand the effects of different particle size ranges (mean sizes of 84.14, 61.74, 37.39, and 22.33 μm) of WBDF on constipation. With the decrease in particle size, its morphology exhibited an increase in fiber fragmentation, larger pore sizes, and the formation of structural faults. The oil-holding capacity (OHC) and swelling capacity (SC) of WBDF were found to change with particle size, with the highest OHC observed at 37.39 μm and the greatest SC at 84.14 μm. Animal experiments demonstrated that the WBDF of smaller particle sizes significantly alleviated loperamide-induced constipation with an increased intestinal propulsion rate, decreased first melanin excretion time, and reduced gastric residual rate. Meanwhile, WBDF samples markedly increased serum MTL and serum AChE levels. Notably, compared with the constipation model (CMNC) group, the small intestinal propulsion rate in the MPS40 group increased by 41.21%, and the gastric residue rate significantly decreased by 19.69%. The improvement in constipation symptoms was most pronounced. Additionally, the abundance of Lactobacillus in the MPS40 group increased by 52.52%, while the relative abundance of Prevotella decreased by 83.55%, and the diversity of the gut microbiota was altered. These findings provide valuable insights into the potential commercial applications of WBDF in fiber-enriched functional foods to support intestinal health. Full article

The genes that encode the universal stress protein (USP) family domain (pfam00582) aid the survival of bacteria in specific host or habitat-induced stress conditions. Genome sequencing revealed that the genome of Helicobacter pylori, a gastric cancer pathogen, typically contains one USP gene, while related helicobacters have one or two distinct USP genes. However, insights into the functions of Helicobacteraceae (Helicobacter and Wolinella) USP genes are still limited to inferences from large-scale genome sequencing. Thus, we have combined bioinformatics and visual analytics approaches to conduct a more comprehensive data investigation of a set of 1045 universal stress protein sequences encoded in 1014 genomes including 785 Helicobacter pylori genomes. The study generated a representative set of 183 USP sequences consisting of 180 Helicobacter sequences, two Wolinella succinogenes sequences, and a sequence from a related campylobacteria. We used the amino acid residues and positions of the 12 possible functional sites in 1030 sequences to identify 25 functional sites patterns for guiding studies on functional interactions of Helicobacteraceae USPs with ATP and other molecules. Genomic context searches and analysis identified USP genes of gastric and enterohepatic helicobacters that are adjacent or in operons with genes for proteins responsive to DNA-damaging oxidative stress (ATP-dependent proteases: ClpS and ClpA); and DNA uptake proteins (natural competence for transformation proteins: ComB6, ComB7, ComB8, ComB9, ComB10, ComBE, and conjugative transfer signal peptidase TraF). Since transcriptomic evidence indicates that oxidative stress and the presence of virulence-associated genes regulate the transcription of H. pylori USP gene, we recommend further research on Helicobacter USP genes and their neighboring genes in oxidative stress response and virulence of helicobacters. To facilitate the reuse of data and research, we produced interactive analytics resources of a dataset composed of values for variables including phylogeography of H. pylori strains, protein sequence features, and gene neighborhood. Full article

Antibiotic resistance in Helicobacter pylori is increasing rapidly and emerging as a major factor in treatment failure. We aimed to identify genetic mutations associated with resistance to clarithromycin (23S rRNA peptidyl transferase), fluoroquinolones (gyrA), and metronidazole (rdxA), and to explore their mechanisms of action through molecular modeling. H. pylori detection and the molecular characterization of genes were conducted directly on gastric biopsies by real-time PCR followed by nucleotide sequencing. A 3D model was used to evaluate molecular interactions between the antibiotics and respective target proteins. H. pylori was identified in 66.7% of 33 patients. An analysis of 23SrRNA revealed novel mutations that, by in silico analysis, do not appear to contribute to clarithromycin resistance. In gyrA, mutations in amino acid residues 87 and 91 had an incidence of 27%, and the in silico analysis revealed that these positions are relevant in the binding and resistance to fluoroquinolones. It is also reported for other mutations, some of which are never described. All rdxA mutations were missense, with R16H, M56V, H97T, G98S, A118T, V123T, and R131K predicted by in silico analysis to impact metronidazole resistance. Monitoring H. pylori gene mutations is crucial for tailoring effective antibiotic therapies. Our study advances personalized medicine by introducing novel methods to detect resistance-related mutations and uncovering the molecular mechanisms driving this resistance. Full article

Background/Objectives: Premature neonates are at risk for retinopathy of prematurity (ROP) and routinely undergo screening exams that involve substantial physical manipulation, often causing significant signs of pain, despite pain-relieving interventions. It remains unclear whether these exams affect energy utilization, cellular hypoxia, and clinically significant events, and whether receiving supplemental oxygen affects these relationships. This work examines the effects of ROP screening on (1) urinary uric acid-to-creatinine concentration ratios ([UA]/[Cr]), a known marker of ATP degradation, hypoxia, and oxidative stress; and (2) clinically significant events (apnea, bradycardia, gastric residuals, and oxygen desaturations) in premature neonates on room air or oxygen support. Methods: This prospective pilot study included premature neonates requiring ROP screening examinations at Loma Linda University’s NICU. Urinary [UA]/[Cr], measured by high-performance liquid chromatography, and clinical events, documented by prospective medical chart review, were analyzed pre- and post-exam in subjects on room air (n = 18) or on oxygen support (n = 20). Statistical analyses included a generalized linear mixed model for urinary [UA]/[Cr] and Wilcoxon signed rank tests for clinical events. Results: A significant time effect (p = 0.010) was observed for urinary [UA]/[Cr], with higher levels at 0–12 (p = 0.023) and 12–24 (p = 0.023) hours post-exam. Subjects receiving oxygen support had more total (p = 0.028) and more severe (p = 0.026) oxygen desaturations. Conclusions: ROP examinations may increase energy utilization in premature neonates, with those receiving oxygen support being particularly susceptible to oxygen desaturations post-exam. Further research is needed to clarify the full impact of the procedure and to identify strategies to minimize stress associated with these screening examinations. Full article