The Effects of HP0044 and HP1275 Knockout Mutations on the Structure and Function of Lipopolysaccharide in Helicobacter pylori Strain 26695

Helicobacter pylori infection is associated with several gastric diseases, including gastritis, peptic ulcer, gastric adenocarcinoma and mucosa-associated lymphatic tissue (MALT) lymphoma. Due to the prevalence and severeness of H. pylori infection, a thorough understanding of this pathogen is necessary. Lipopolysaccharide, one of the major virulence factors of H. pylori, can exert immunomodulating and immunostimulating functions on the host. In this study, the HP0044 and HP1275 genes were under investigation. These two genes potentially encode GDP-D-mannose dehydratase (GMD) and phosphomannomutase (PMM)/phosphoglucomutase (PGM), respectively, and are involved in the biosynthesis of fucose. HP0044 and HP1275 knockout mutants were generated; both mutants displayed a truncated LPS, suggesting that the encoded enzymes are not only involved in fucose production but are also important for LPS construction. In addition, these two gene knockout mutants exhibited retarded growth, increased surface hydrophobicity and autoaggregation as well as being more sensitive to the detergent SDS and the antibiotic novobiocin. Furthermore, the LPS-defective mutants also had significantly reduced bacterial infection, adhesion and internalization in the in vitro cell line model. Moreover, disruptions of the HP0044 and HP1275 genes in H. pylori altered protein sorting into outer membrane vesicles. The critical roles of HP0044 and HP1275 in LPS biosynthesis, bacterial fitness and pathogenesis make them attractive candidates for drug inventions against H. pylori infection.

Development and Application of Magnetically Controlled Capsule Endoscopy in Detecting Gastric Lesions

In the past 20 years, several magnetically controlled capsule endoscopes (MCCE) have been developed for the evaluation of gastric lesions, including NaviCam (ANKON), MiroCam-Navi (Intromedic), Endocapsule MGCE (Olympus and Siemens), SMCE (JIFU), and FAMCE (Jinshan). Although limited to observing esophageal and duodenal lesions and lacking the ability of biopsy, MCCE has the advantages of comfort, safety, no anesthesia, no risk of cross-infection, and high acceptability. Several high-quality RCTs showed that the diagnostic accuracy of MCCE is comparable to the traditional gastroscopy. Due to the nonnecessity of anesthesia, MCCE may be more suitable for the elderly with obvious comorbidities as well as children. With more evidences accumulated and more innovative technologies developed, MCCE is expected to be an important tool for screening of early gastric cancer or the diagnosis of gastric diseases.

In Silico Screening and In Vitro Assessment of Natural Products with Anti-Virulence Activity against Helicobacter pylori

Helicobacter pylori is one of the most frequent human pathogens and a leading etiological agent of various gastric diseases. As stringent response, coordinated by a SpoT protein, seems to be crucial for the survivability of H. pylori, the main goal of this article was to use in silico computational studies to find phytochemical compounds capable of binding to the active site of SpoT from H. pylori and confirm the ability of the most active candidates to interfere with the virulence of this bacterium through in vitro experiments. From 791 natural substances submitted for the virtual screening procedure, 10 were chosen and followed for further in vitro examinations. Among these, dioscin showed the most interesting parameters (the lowest MIC, the highest anti-biofilm activity in static conditions, and a relatively low stimulation of morphological transition into coccoids). Therefore, in the last part, we extended the research with a number of further experiments and observed the ability of dioscin to significantly reduce the formation of H. pylori biofilm under Bioflux-generated flow conditions and its capacity for additive enhancement of the antibacterial activity of all three commonly used antibiotics (clarithromycin, metronidazole, and levofloxacin). Based on these results, we suggest that dioscin may be an interesting candidate for new therapies targeting H. pylori survivability and virulence.

The Involvement of TRIB3 and FABP1 and Their Potential Functions in the Dynamic Process of Gastric Cancer

Background: Dysregulated expression of TRIB3 and FABP1 have been previously observed in human cancer tissues. However, there are little information as to their expression change in dynamic gastric diseases and the functional roles.Methods: Tissues from a total of 479 patients, including 89 GS, 102 IM-GA, 144 EGC, and 144 AGC were collected. The protein expressions of TRIB3 and FABP1 were detected by immunohistochemical staining. Meanwhile, the potential functions of TRIB3 and FABP1 in GC were further analyzed by R software and some internet public databases, such as TCGA and DAVID.Results: During this multi-stage process that go through GS to EGC, the expression trend of TRIB3 and FABP1 protein was GS > IM-GA > EGC. Besides, the expression of TRIB3 protein continued to decrease in AGC, while the expression of FABP1 was abnormally increased. Hp infection was significantly associated with the decreased expression of TRIB3 and FABP1. In addition, the diagnostic efficiency of the combination of these two indicators to diagnose EGC was higher than that of a single indicator. Survival analysis showed that higher expression of TRIB3 or FABP1 could indicate a better prognosis of GC. The protein expressions of TRIB3 and FABP1 were significantly positively correlated. Moreover, CEACAM5 and PRAP1 were positively correlated with both TRIB3 and FABP1 expressions, while GABRP and THBS4 were negatively correlated. The macrophages M0 infiltration was positively correlated with both TRIB3 and FABP1 expressions.Conclusion: The protein expressions of TRIB3 and FABP1 gradually decreased with the gastric disease progress, and was positively correlated. Hp infection may reduce the protein expression of TRIB3 and FABP1. Combing TRIB3 and FABP1 expressions can improve the diagnostic efficiency for EGC. Either a high expression of TRIB3 or FABP1 indicates a better prognosis for GC. TRIB3 and FABP1 may interact with CEACAM5, PRAP1, GABRP and THBS4, and affect tumor immune microenvironment by regulating immune cells, and participate in the development and progression of GC.

Detrimental relevance of Helicobacter pylori infection with sarcopenia

Background Helicobacter pylori (H. pylori), Gram negative microaerophilic bacteria, is a well-known pathogen of many gastrointestinal diseases. But several emerging evidences suggest it role in numerous other extra-gastric diseases. The current study investigates the relationship between H. pylori infection and sarcopenia, a clinical condition characterized by the loss of mass and function of skeletal muscle. A total of 3453 eligible participants from the Third National Health and Nutrition Examination Survey (NHANES III), the United States, were enrolled. Based on the serum laboratory results, subjects were categorized into three groups: normal (without evidence of any H. pylori infection), anti-H. pylori IgG positive [H. pylori (+)], and concurrent anti-H. pylori IgG and anti-cytotoxin-associated gene A IgG positive [CagA (+)]. Sarcopenia was determined as having a skeletal muscle index (SMI) value that is more than 1 standard deviation away from the mean value of sex-specific, healthy young adults between 20 and 39 years old. Risk of sarcopenia and its components are compared between subgroups. Results Odds ratios (OR) for confirmed diagnosis of sarcopenia were higher in H. pylori (+) (OR = 2.052, 95% CI 1.697–2.481, p < 0.001) and CagA (+) (OR = 1.585, 95% CI 1.278–1.965, p < 0.001) groups. Moreover, negative beta regression coefficient of SMI were shown in H. pylori (+) (β: − 0.023, p < 0.001) and CagA (+) (β: − 0.017, p < 0.001). Sub-analyses which categorized participants by gender revealed that absolute value of beta regression coefficient for SMI were higher in female in H. pylori (+) subgroup (β: − 1.745 in male and − 2.942 in female, p were both < 0.001), and the CagA (+) subgroup (β: − 1.407 in male and − 2.159 in female, p were both < 0.001). Conclusions Positive serum H. pylori infectious markers including anti-H. pylori antibody and CagA seropositivity are correlated with sarcopenia and low muscle quantity. Therefore, H. pylori eradication therapy may bring benefits to sarcopenia patients with concurrent active H. pylori infection.

Antimicrobial Resistance and Genetic Characteristics that Might be Related to Antibiotic Resistance of 112 Helicobacter Pylori Shanghai Isolates

Background Shanghai, east China has one of the world’s highest burdens of Helicobacter pylori infection. While multidrug regimens can effectively eradicate H. pylori, antibiotic-resistant (AR) H. pylori has been recognized by the WHO as ‘high priority’ for urgent need of new therapies. Moreover, the genetic characteristics of H. pylori AR in Shanghai is under-reported. The purpose of this study was to determine the resistance prevalence, re-substantiate resistance-conferring mutations, and investigate novel genetic elements might be related to H. pylori AR. Results We performed a whole-genomic and phenotypic analysis of 112 H. pylori isolated from gastric biopsy specimens from a population with different gastric diseases and residing in Shanghai. No strains were resistant to amoxicillin. Levofloxacin, metronidazole and clarithromycin resistance was observed in 39, 73 and 18 isolates, respectively. There was no association between gastroscopy diagnosis and resistance phenotypes. We reported the presence or absence of several subsystem proteins including hopE, hofF, spaB, cagY and pflA, and a combination of CRISPRs, which were potentially correlated with resistance phenotypes. The H. pylori isolates were also annotated for AR genes to define a resistome containing 80 genes. A resistome-wide association study (RWAS) was performed for the three antibiotics by correlating the phenotypes with the variation data. The RWAS correctly identified the well-known intrinsic resistance associated mutations for levofloxacin (N87T/I and/or D91G/Y mutations in gyrA), metronidazole (I38V mutation in fdxB), and clarithromycin (A2143G and/or A2142G mutations in 23S rRNA), and added 174 novel variations, with 23 nsSNPs and 48 fsIndels significantly enriched in resistant or susceptible populations. The variant-level linkage disequilibrium analysis demonstrated a series of variations with strong co-occurring correlation with known mutations, and highlighted the underlying role of a protease Lon. Conclusion Our study indicated H. pylori isolates from Shanghai exhibit multidrug antibiotic resistance, and identified specific genomic characteristics in relation to H. pylori AR in Shanghai. Continued surveillance of H. pylori AR in Shanghai is warranted in order to establish appropriate eradication treatment regimens for this population.

Fatigue and fracture resistance and survival of occlusal veneers of composite resin and ceramics blocks in posterior teeth with occlusal wear: A protocol for a systematic review

Review question / Objective: The aim of this systematic review is to synthesize the scientific evidence that evaluates fatigue and fracture resistance, survival, and stress distribution, of composite resin CAD/CAM and ceramic CAD/CAM occlusal veneers in posterior teeth with severe occlusal wear. Condition being studied: Currently there is an increase in cases of dental wear, due to several factors such as: excessive consumption of carbonated drinks, a diet high in acids, gastric diseases, anorexia, bulimia, dental grinding, use of highly abrasive toothpastes, or a combination of these(9) (10) (11) (12); which affect the patient in several aspects: loss of vertical dimension, sensitivity due to the exposure of dentin, esthetics, affectation of the neuromuscular system(11) (13) (14). With the advent of minimally invasive dentistry, occlusal veneers have been found to be a valid option to rehabilitate this type of cases and thus avoid greater wear of the dental structure with full coverage restorations. Sometimes when performing a tabletop it is not necessary to perform any preparation, thus preserving the maximum amount of dental tissue(3) (6) (15). Due to the masticatory load either in patients without parafunction where the maximum masticatory force is approximately 424 N for women and 630 N for men or in those who present parafunction where the maximum bite force can vary from 780 to 1120N(7), it is necessary that the occlusal veneers support that load which makes indispensable a compilation of studies investigating both fatigue and fracture resistance and the survival rate of occlusal veneers in different materials and thicknesses.

Helicobacter pylori and Respiratory Diseases: 2021 Update

Helicobacter pylori (H. pylori) is a Gram-negative bacterium involved in the development of gastritis, peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue. Unexplained iron deficiency anemia, idiopathic thrombocytopenic purpura and vitamin B12 deficiency have also been related to H. pylori infection, whereas for other extra-gastric diseases, the debate is still open. In this review, we evaluate and discuss the potential involvement of H. pylori infection in the pathogenesis of several respiratory diseases. A MEDLINE search of all studies published in English from 1965 to 2021 was carried out. Controversial findings have been reported in patients with bronchial asthma, chronic obstructive pulmonary disease, bronchiectasis, lung cancer, tuberculosis, cystic fibrosis, and sarcoidosis. Most of the available literature is concerned with case-control studies based on seroprevalence, with a small sample size and low consideration of confounders, which represents a potential issue. So far, there is no clear evidence of a causal association between H. pylori infection and respiratory diseases, and larger studies with appropriate epidemiological design are required.

Comparative evaluation of research methods for patients with gastric ulcer

It can be said without exaggeration that gastric diseases in our country and in the Union have occupied a particularly prominent place among other diseases in recent years. Each internist, and partly a surgeon, in his daily practical work has to devote a significant part of his working time to the analysis of patients with various gastric diseases.

Glycosaminoglycan biosynthesis pathway in host genome is associated with Helicobacter pylori infection

Helicobacter pylori is a causative pathogen of many gastric and extra-gastric diseases. It has infected about half of the global population. There were no genome-wide association studies (GWAS) for H. pylori infection conducted in Chinese population, who carried different and relatively homogenous strain of H. pylori. In this work, we performed SNP (single nucleotide polymorphism)-based, gene-based and pathway-based genome-wide association analyses to investigate the genetic basis of host susceptibility to H. pylori infection in 480 Chinese individuals. We also profiled the composition and function of the gut microbiota between H. pylori infection cases and controls. We found several genes and pathways associated with H. pylori infection (P < 0.05), replicated one previously reported SNP rs10004195 in TLR1 gene region (P = 0.02). We also found that glycosaminoglycan biosynthesis related pathway was associated with both onset and progression of H. pylori infection. In the gut microbiome association study, we identified 2 species, 3 genera and several pathways had differential abundance between H. pylori infected cases and controls. This paper is the first GWAS for H. pylori infection in Chinese population, and we combined the genetic and microbial data to comprehensively discuss the basis of host susceptibility to H. pylori infection.