The prevalence of Helicobacter pylori (H. pylori) infection increases with age. However, the relationship between H. pylori infection and anemia in the elderly population remains to be identified. The aim of this study is to explore whether H. pylori infection is associated with anemia in a male elderly cohort. A cross-sectional study was designed using data collected from asymptomatic male senior citizens (≥ 65 years old) who received an assessment of their health status at the General Hospital of Chinese PLA from January 2015 to December 2015. H. pylori infection was confirmed by the 13C-urea breath test. Blood samples from the participants were taken to assay for hemoglobin and other erythroid-related indices - serum iron, ferritin, and C-reactive protein (CRP). Anemia was defined as hemoglobin values lower than 120.0 g/L. Charlson Comorbidity Index (CCI) was applied to establish baseline comorbidities. Data from 646 subjects were analyzed. The mean age of the study cohort was 79.4 ± 8.9 years. The overall prevalence of H. pylori infection was 35.3%. The prevalence of anemia in the H. pylori positive group was higher than that in the negative group (5.3% vs. 2.2%, P = .033). Among the patients who had higher CCI scores (> 2), the prevalence of anemia in the H. pylori positive and negative groups were 10.3 and 1.4%, respectively (P = .009). Compared to the H. pylori negative group, the odds ratio for anemia of the H. pylori positive group was 2.53 (P = .033). No correlation between H. pylori infection and serum iron and ferritin levels was found. The mean corpuscular volume of the H. pylori positive and negative group was 91.17 ± 3.94 fl and 91.17 ± 4.09 fl (mean ± SD), respectively (P = .986). The CRP level in the H. pylori positive group was higher than that in the H. pylori negative group (Median: 0.17 mg/dL vs. 0.10 mg/dL, P < .001). H. pylori infection seems to be associated with normocytic and normochromic anemia in elderly males, especially in those with more comorbidities. Further clinical studies are needed to verify the association.
Efficacy of Helicobacter pylori (H. pylori) eradication therapy has declined due to rapid rises in antibiotic resistance. We investigated how increased temperature affected H. pylori (NCTC 11637) growth and its sensitivity to metronidazole in vitro. We performed transcriptomic profiling using RNA-sequencing to identify differentially expressed genes (DEGs) associated with increased temperature. Transcriptional pathways involved in temperature-driven metronidazole resistance changes were analyzed through bioinformatic and literature curation approaches. We showed that H. pylori growth was inhibited at 41°C and inhibition was more apparent with prolonged incubation. Resistance to metronidazole was also reduced—minimum inhibitory concentration for metronidazole decreased from > 256 μg/ml at 37°C to 8 μg/ml at 41°C after culturing for 3 days. RNA-sequencing results, which were highly concordant within treatment conditions, revealed more than one third of genes (583/1,552) to be differentially expressed at increased temperatures with similar proportions up and down-regulated. Quantitative real-time PCR validation for 8 out of 10 DEGs tested gave consistent direction in gene expression changes. We found enrichment for redox and oxygen radical pathways, highlighting a mechanistic pathway driving temperature-related metronidazole resistance. Independent literature review of published genes associated with metronidazole resistance revealed 46 gene candidates, 21 of which showed differential expression and 7 out of 9 DEGs associated with “redox” resistance pathways. Sanger sequencing did not detect any changes in genetic sequences for known resistance genes rdxA, frxA nor fdxB. Our findings suggest that temperature increase can inhibit the growth and reduce H. pylori resistance to metronidazole. Redox pathways are possible potential drivers in metronidazole resistance change induced by temperature. Our study provides insight into potential novel approaches in treating antibiotic resistant H. pylori.
The diagnostic value ofHelicobacter pyloristool antigen (HpSA) tests in elderly subjects remains unclear. The objective of this study was to assess the diagnostic accuracy of the immunochromatographic assay‐based HpSA test in a male elderly cohort and identify factors affecting the accuracy. Data for asymptomatic elderly male citizens (≥65 years old) who received health checkups at the Chinese PLA General Hospital between July 2007 and November 2018 were collected. The diagnostic accuracy of the HpSA test was determined using the13C‐urea breath test as a reference standard. Associations between baseline comorbidities and the accuracy of the HpSA test were analyzed. In total, 316 participants were enrolled, including 193 in the pre‐treatment group (77.2 ± 7.8 years old) and 123 in the post‐treatment group (78.7 ± 8.3 years old). The accuracy (91.5%, 91.2%, and 91.9%) and specificity (97.6%, 98.7%, and 96.0%) were high in all participants, pre‐ and post‐treatment groups, respectively. However, sensitivities were only 68.7%, 65.1%, and 75.0%, respectively. In the pre‐treatment group, constipation was associated with decreased sensitivity (p = 0.039), while colorectal polyps were associated with increased sensitivity (p = 0.010). Multivariate analysis indicated that constipation and colorectal polyps are independent factors for the sensitivity of HpSA in the pre‐treatment group. The immunochromatographic assay‐based HpSA test achieved high accuracy with high specificity but suboptimal sensitivity in the elderly male cohort. Constipation and colorectal polyps were negatively and positively associated with HpSA sensitivity, respectively, in the pre‐treatment group.
Background: Helicobacter pylori (H. pylori) eradication plays a crucial role in gastric cancer prevention, but the antimicrobial resistance of H. pylori is obstructing this elimination process. In this study, we developed nanoclusters (NCs) from Zn0.3Fe2.7O4 nanoparticles using a poly(ethylene glycol)-b-poly(ε-caprolactone)-based nanocarrier as an innovative antibiotic-independent H. pylori management. Results: The nanocluster showed minimal toxicity and maximal biocompatibility. With a low concentration (50 µg/mL) of NCs under a short time period (~ 2 min) of near-infrared (808 nm) irradiation, we kept the culture medium temperature to 41 °C for 20 min with continuous irradiation. The heated NCs exhibited efficient photothermal effects and resulted in an excellent inhibition of H. pylori growth, adhesion and ability to induce vacuolization in eukaryotic cells in in vitro investigation. Transmission electron microscopy showed a dramatic morphologic change after NCs photothermia on H. pylori, including cell wall and membrane rupture, as well as ribosome damage. Besides, levofloxacin and clarithromycin resistance was decreased after photothermal treatment in H. pylori NCTC 11637 and/or clinical strains, however metronidazole resistance was unchanged. We also discovered a significant decrease in the biofilm formation of H. pylori under the NCs-based photothermal application, while efflux pump function was unchanged. Conclusions: Based on this novel NCs-based photothermal approach, we were able to demonstrate in vitro a significant inhibition of both H. pylori growth and molecular toxicity, and its improvement in antibiotic sensitivity alone with the eradication of H. pylori biofilms previously believed to be tolerant to conventional antibiotics.
Long interspersed nuclear element-1 (LINE-1 or L1), the most abundant and only autonomously active family of non-LTR retrotransposons in the human genome, expressed not only in the germ lines but also in somatic tissues. It contributes to genetic instability, aging, and age-related diseases, such as cancer. Our previous study identified in human gastric adenocarcinoma an upregulated transcript GCRG213, which shared 88% homology with human L1 sequence and contained a putative conserved apurinic/apyrimidinic endonucleas1 domain. Immunohistochemistry was carried out by using a monoclonal mouse anti-human GCRG213 protein (GCRG213p) antibody produced in our laboratory, on tissue microarray constructed with specimens from 175 gastric adenocarcinoma patients. The correlation between GCRG213p expression and patient clinicopathological parameters was evaluated. GCRG213p expression in gastric cancer cell lines were studied using Western blotting analysis. L1 promoter methylation status of gastric cancer cells was tested using methylation-specific PCR. BLASTP was used at the NCBI Blast server to identify GCRG213p sequence to any alignments in the Protein Data Bank databases. Most primary gastric cancer, lymph node metastases and gastric intestinal metaplasia glands showed positive GCRG213p immunoreactivity. High GCRG213p immunostaining score in the primary gastric cancer was positively correlated with tumor differentiation (well differentiated, p = 0.001), Lauren’s classification (intestinal type, p < 0.05) and a late age onset of gastric adenocarcinoma (≥65 yrs; p < 0.05). GCRG213p expression has no association with other clinicopathological parameters, including survival. Western blotting analysis of GCRG213p expression in gastric cancer cells indicated that GCRG213p level was higher in gastric cancer cell lines than in human normal gastric epithelium immortalized cell line GES-1. Partial methylation of L1 in gastric cancer cells was confirmed by methylation-specific PCR. BLASTP program analysis revealed that GCRG213p peptide shared 83.0% alignment with the C-terminal region of L1 endonuclease (L1-EN). GCRG213p sequence possesses the important residues that compose the conserved features of L1-EN. GCRG213p could be a variant of L1-EN, a functional member of L1-EN family. Overexpression of GCRG213p is common in both primary gastric cancer and lymph node metastasis. These findings provide evidence of somatic L1 expression in gastric cancer, and its potential consequences in the form of tumor.