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Gastric cancer is one of the most malignant tumors worldwide and remains a major health threat in Asia-Pacific regions, while its pathological mechanism is generally unknown. Recent research has advanced the understanding of the relationship between metabolic reprogramming and carcinogenesis. In particular, metabolic regulation and cancer research are being further brought into sharp focus with the emergence of metabolomics. Not only can metabolomics provide global information on metabolic profiles of specific tumors, but it can also act as a promising tool to discover biomarkers regarding diagnosis, metastatic surveillance and chemotherapeutic sensitivity prediction. Meanwhile, metabolism-based anticancer therapies will be further discovered. Up to now, accumulative studies have highlighted the application of metabolomics in gastric cancer research regarding different aspects; therefore we summarized the current available results of how metabolic changes are linked to gastric carcinogenesis, and how metabolomics holds promise for the diagnosis, metastatic surveillance, treatment and prognosis prediction of gastric cancer.

Helicobacter pylori ( H. pylori ) infection is an infectious disease with a prevalence rate of up to 50% worldwide. It can cause indigestion, gastritis, peptic ulcer, and gastric cancer. H. pylori eradication treatment can effectively control disease progression and reduce the risk of the above conditions. However, the escalating trend of antibiotic resistance presents a global challenge for H. pylori eradication. We aim to provide guidance on pharmacological treatment of H. pylori infection. This clinical practice guideline is developed following the World Health Organization's recommended process, adopting Grading of Recommendations Assessment, Development and Evaluation in assessing evidence quality, and utilizing Evidence to Decision framework to formulate clinical recommendations, minimizing bias and increasing transparency of the clinical practice guideline development process. We used the Reporting Items for practice Guidelines in HealThcare (RIGHT) statement and The Appraisal of Guidelines for Research and Evaluation II (AGREE II) as reporting and conduct guides to ensure the guideline's completeness and transparency. Though decreasing in developed countries, the prevalence of H. pylori remains high in developing countries, causing a major public health burden. This clinical practice guideline contains 12 recommendations concerning pharmacological treatment for H. pylori eradication. Among them, it is worth highlighting that bismuth preparations are inexpensive, safe, and effective, consequently making bismuth quadruple therapy a preferred choice for initial and rescue treatment. In empirical treatment, high-dose dual therapy is equally effective compared with bismuth quadruple therapy. The 12 recommendations in this clinical practice guideline are formed with consideration for stakeholders' values and preferences, resource use, feasibility, and acceptability. Recommendations are generalizable to resource limited settings with similar antibiotic resistance pattern as China, and lower middle-income countries facing comparable sociological and technical challenges. Guidelines International Network (GIN) website, https://guidelines.ebmportal.com/node/69996 .

Gastric epithelium operates in a hazardous environment that curtails the lifespan of the constituent cells, imposing a requirement for continuous epithelial renewal. Stem cells that reside in the stomach are thus essential for regulating physiological tissue renewal and injury repair because of their self-renewal, high proliferation capacity and multiple differentiation potentials. Recent investigations using lineage tracing models have identified diverse populations of gastric stem cells and even fully differentiated cells that can regain stem cell capacity, so enriching our understanding on the identity and plasticity of gastric stem cells. These cell populations include the Villin promotor, Lgr5+, CCKR2+, Axin2+ and AQP5+ stem cells in the antrum, TFF2 mRNA, Mist1+ cells and Troy+ mature chief cells in the corpus, as well as Sox2, eR1, Lrig1, Bmi1-marked cell in both the antrum and the corpus. Establishment of gastric organoids derived from primary gastric tissues and pluripotent stem cells or embryonic stem cells characterizes niche factors required by the gastric stem cell populations, and further provides new insights into stomach development, host-Helicobacter pylori interactions and malignant transformation. Furthermore, focus on the gastric stem cells and their niches uncovers the initiation of stomach precancerous lesions and origin of gastric cancer, providing options for cancer prevention and intervention. In summary, with the development of stem cell research, gastric stem cells give us more opportunities to prevent and treat stomach diseases.

Transferrin (Tf), widely known for its role as an iron-binding protein, exemplifies multitasking in biological processes. The role of Tf in iron metabolism involves both the uptake of iron from Tf by various cells, as well as the endocytosis mediated by the complex of Tf and the transferrin receptor (TfR). The direct conjugation of the therapeutic compound and immunotoxin studies using Tf peptide or anti-Tf receptor antibodies as targeting moieties aims to prolong drug circulation time and augment efficient cellular drug uptake, diminish systemic toxicity, traverse the blood-brain barrier, restrict systemic exposure, overcome multidrug resistance, and enhance therapeutic efficacy with disease specificity. This review primarily discusses the various biological actions of Tf, as well as the development of Tf-targeted nano-based drug delivery systems. The goal is to establish the use of Tf as a disease-targeting component, accentuating the potential therapeutic applications of this protein.

A nano-form composite of MXenes (Ti3C2Tx, Tx = -O, -OH, -F) was synthesized through depositing bismuth-nanoparticle (BiNPs) onto Ti3C2Tx sheets. Because of the preventive effect of the two-dimensional layered structure of Ti3C2Tx, the nanoparticles of Bi were uniform and well attached on the Ti3C2Tx. The obtained BiNPs/Ti3C2Tx nano-composite was applied for sensors construction of electrochemical detecting of Pb2+ and Cd2+ heavy metal ions. The produced BiNPs@Ti3C2Tx-based sensor showed high effective surface area and excellent conductivity. Also, the BiNPs were efficient for anodic-stripping voltammetric to detect heavy metal ions. After conditions optimization, the BiNPs@Ti3C2Tx nano-sensor could detect Pb2+ and Cd2+ simultaneously and the detection limits were 10.8 nM for Pb2+ and 12.4 nM for Cd2+. The BiNPs@Ti3C2Tx was promising for detecting heavy metal ions due to their high surface area, fast electron-transfer ability, environmental friendliness, and facial preparation.

The impact of different Helicobacter pylori (H. pylori) status (H. pylori negative, H. pylori eradication and H. pylori persistence) on the development of metachronous gastric lesions after endoscopic resection of early gastric cancer is not well defined. Thus, a systematic review and meta-analysis was performed to investigate this relationship. Two authors independently searched the electronic databases (Pubmed, Embase, the Cochrane Library and Web of Science) through March 2018, without language restriction. Pooled risk ratio for metachronous gastric lesions with regard to H. pylori status was calculated using fixed- or random-effects models, and heterogeneity and publication bias were also measured. 20 eligible studies were finally identified in systematic review, and 17 out of 20 studies were further included in meta-analysis. H. pylori eradication was associated with overall 50% lower odds of metachronous events (RR = 0.50; 95 % CI 0.41–0.61). Pooled risk ratios for metachronous gastric neoplasm were 0.85 (95 % CI 0.43–1.68) between H. pylori-eradicated and -negative patients, and 0.63 (95 % CI 0.35–1.12) between H. pylori-negative and -persistent patients, respectively. In conclusion, based on the best available evidence, eradication of H. pylori can provide protection against secondary gastric neoplasm, and this quantitative benefit seemed greater than among asymptomatic individuals. Metachronous risk seems comparable between H. pylori-eradicated and -negative population, or between H. pylori-negative and -persistent patients.

Chemoenzymatic cascade catalysis has emerged as a revolutionary tool for streamlining traditional retrosynthetic disconnections, creating new possibilities for the asymmetric synthesis of valuable chiral compounds. Here we construct a one-pot concurrent chemoenzymatic cascade by integrating organobismuth-catalyzed aldol condensation with ene-reductase (ER)-catalyzed enantioselective reduction, enabling the formal asymmetric α-benzylation of cyclic ketones. To achieve this, we develop a pair of enantiocomplementary ERs capable of reducing α-arylidene cyclic ketones, lactams, and lactones. Our engineered mutants exhibit significantly higher activity, up to 37-fold, and broader substrate specificity compared to the parent enzyme. The key to success is due to the well-tuned hydride attack distance/angle and, more importantly, to the synergistic proton-delivery triade of Tyr28-Tyr69-Tyr169. Molecular docking and density functional theory (DFT) studies provide important insights into the bioreduction mechanisms. Furthermore, we demonstrate the synthetic utility of the best mutants in the asymmetric synthesis of several key chiral synthons. Given the importance of the chiral α-benzyl cyclic carbonyl motif in pharmaceutically active compounds, various transformations have been developed to access chiral compounds containing this motif but they often include harsh reaction conditions. Here the authors develop a one-pot concurrent chemoenzymatic cascade reaction and demonstrate the synthesis of α-benzylcyclic ketones with high enantioselectivity.

Given the general unavailability, common adverse effects, and complicated administration of tetracycline, the clinical application of classic bismuth quadruple therapy (BQT) is greatly limited. Whether minocycline can replace tetracycline for Helicobacter pylori ( H . pylori ) eradication is unknown. We aimed to compare the eradication rate, safety, and compliance between minocycline- and tetracycline-containing BQT as first-line regimens. This randomized controlled trial was conducted on 434 naïve patients with H . pylori infection. The participants were randomly assigned to 14-day minocycline-containing BQT group (bismuth potassium citrate 110 mg q.i.d., esomeprazole 20 mg b.i.d., metronidazole 400 mg q.i.d., and minocycline 100 mg b.i.d.) and tetracycline-containing BQT group (bismuth potassium citrate/esomeprazole/metronidazole with doses same as above and tetracycline 500 mg q.i.d.). Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed at 4-8 weeks after eradication to evaluate outcome. We used a noninferiority test to compare the eradication rates of the two groups. The intergroup differences were evaluated using Pearson chi-squared or Fisher's exact test for categorical variables and Student's t -test for continuous variables. As for the eradication rates of minocycline- and tetracycline-containing BQT, the results of both intention-to-treat (ITT) and per-protocol (PP) analyses showed that the difference rate of lower limit of 95% confidence interval (CI) was >-10.0% (ITT analysis: 181/217 [83.4%] vs . 180/217 [82.9%], with a rate difference of 0.5% [-6.9% to 7.9%]; PP analysis: 177/193 [91.7%] vs . 176/191 [92.1%], with a rate difference of -0.4% [-5.6% to 6.4%]). Except for dizziness more common (35/215 [16.3%] vs . 13/214 [6.1%], P = 0.001) in minocycline-containing therapy groups, the incidences of adverse events (75/215 [34.9%] vs . 88/214 [41.1%]) and compliance (195/215 [90.7%] vs . 192/214 [89.7%]) were similar between the two groups. The eradication efficacy of minocycline-containing BQT was noninferior to tetracycline-containing BQT as first-line regimen for H . pylori eradication with similar safety and compliance. ClinicalTrials.gov, ChiCTR 1900023646.

Background Eradicating Helicobacter pylori infection is clinically challenging, notably in cases with penicillin allergy. Cephalosporin could be used in lieu of amoxicillin to eradicate Helicobacter pylori . The current work aimed to assess therapeutic efficacy and safety of a cefuroxime-based quadruple regimen in treatment-naïve individuals with penicillin allergy, as well as patient compliance. Methods In the present prospective single-center cohort study, 152 Helicobacter pylori infected individuals with penicillin allergy received eradication therapy with cefuroxime (500 mg twice/day), levofloxacin (500 mg once/day), esomeprazole (20 mg twice/day) and bismuth potassium citrate (220 mg twice/day; 14 days). Safety and compliance were evaluated 1 to 3 days upon eradication. The urea breath test was carried out 8 to 12 weeks upon eradication for efficacy assessment. Results This quadruple antimicrobial regimen eradicated the pathogen at 85.5% (95% confidence interval (CI) 79.6–90.8%), 88.4% (95% CI 83.0–93.2%) and 90.1% (95% CI 85.2–94.4%) in intention-to-treat, modified intention-to-treat and per-protocol analyses, respectively, with resistance rates of 4.6 and 40.0% in the background of cefuroxime and levofloxacin, respectively. Meanwhile, 21.3% of patients had adverse reactions, but none was serious. A total of 95.3% of patients showed good compliance. Poor compliance and cefuroxime resistance were detected by uni- or multivariate analyses as independent factors predicting therapeutic failure. Eradication rates in patients with dual levofloxacin and cefuroxime susceptibility, isolated levofloxacin resistance, isolated cefuroxime resistance and dual resistance were 97.2, 84.0, 50.0, and 0%, respectively ( P  = 0.002). Conclusions Cefuroxime, levofloxacin, esomeprazole, and bismuth achieved decent efficacy, safety and compliance as first-line antimicrobial regimen in patients with Helicobacter pylori and penicillin allergy.

Austocystin D is a natural compound that induces cytochrome P450 (CYP) monooxygenase‐dependent DNA damage and growth inhibition in certain cancer cell lines. Cancer cells exhibiting higher sensitivity to austocystin D often display elevated CYP2J2 expression. However, the essentiality and the role of CYP2J2 for the cytotoxicity of this compound remain unclear. In this study, we demonstrate that CYP2J2 depletion alleviates austocystin D sensitivity and DNA damage induction, while CYP2J2 overexpression enhances them. Moreover, the investigation into genes involved in austocystin D cytotoxicity identified POR and PGRMC1, positive regulators for CYP activity, and KAT7, a histone acetyltransferase. Through genetic manipulation and analysis of multiomics data, we elucidated a role for KAT7 in CYP2J2 transcriptional regulation. These findings strongly suggest that CYP2J2 is crucial for austocystin D metabolism and its subsequent cytotoxic effects. The potential use of austocystin D as a therapeutic prodrug is underscored, particularly in cancers where elevated CYP2J2 expression serves as a biomarker. CYP2J2 is crucial for austocystin D metabolism and its subsequent cytotoxic effects. The investigation into genes involved in austocystin D cytotoxicity identified POR and PGRMC1, positive regulators for CYP activity, and KAT7, a histone acetyltransferase. Austocystin D holds potential as a therapeutic drug for cancers wherein upregulated CYP2J2 serves as a biomarker.