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Search Results (938)

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Keywords = H. pylori

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10 pages, 485 KiB  
Article
Clinicopathologic Features of Early Gastric Cancer after Heli-cobacter pylori Eradication in Japanese Patients: Comparative Study between Early (<10 Years) and Late (>10 Years) Onset
by Hajime Teshima, Takahiro Kotachi, Toshio Kuwai, Akiyoshi Tsuboi, Hidenori Tanaka, Ken Yamashita, Hidehiko Takigawa, Yoshihiro Kishida, Yuji Urabe and Shiro Oka
Cancers 2024, 16(18), 3154; https://doi.org/10.3390/cancers16183154 (registering DOI) - 14 Sep 2024
Viewed by 162
Abstract
Background/Objectives: Eradication therapy for Helicobacter pylori gastritis was approved for insurance coverage by the Japanese government in 2013. Since then, the incidence of gastric cancer discovered after eradication (GCAE) has increased. However, there are only a few reports of GCAE diagnosed more than [...] Read more.
Background/Objectives: Eradication therapy for Helicobacter pylori gastritis was approved for insurance coverage by the Japanese government in 2013. Since then, the incidence of gastric cancer discovered after eradication (GCAE) has increased. However, there are only a few reports of GCAE diagnosed more than 10 years after eradication. We investigated the clinicopathological characteristics of early-stage GCAE, including histological types and the interval from eradication to diagnosis. Methods: Overall, 379 patients with a total of 448 GCAE lesions treated with endoscopic resection or surgery at our hospital between January 2015 and December 2021 were assessed, and 315 patients with a known interval from eradication to diagnosis of GCAE with a total of 354 lesions were included. We classified the cases into two groups: differentiated-type GCAE (D-GCAE; 279 patients, 318 lesions) and undifferentiated-type GCAE (UD-GCAE; 36 patients, 36 lesions). Results: Smoking and a mild-to-moderate degree of atrophy were risk factors associated with differentiated-type gastric cancer occurring more than 10 years after H. pylori eradication. Additionally, the rate of a mixture of histological types with relatively high malignant potential was significantly higher in UD-GCAE presenting more than 10 years after eradication group than those presenting within 10 years after eradication. Full article
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<p>Flowchart showing data of patients enrolled in this study.</p>
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12 pages, 7302 KiB  
Article
Type 2 Diabetes Mellitus and Helicobacter pylori Gastritis in Patients Referred for Endoscopy—A Single-Center Romanian Study
by Sabrina-Nicoleta Munteanu, Dragoș Huțanu, Ana-Maria Filip, Andreea Raluca Cozac-Szőke, Simona Mocan and Anca Negovan
Life 2024, 14(9), 1160; https://doi.org/10.3390/life14091160 - 13 Sep 2024
Viewed by 249
Abstract
Background: Type 2 diabetes mellitus (T2DM) affects up to 10% of adults globally, and its complications can mask the risk of gastrointestinal bleeding or malignancy. Methods: Our study enrolled 633 endoscopic patients stratified according to T2DM presence (4:1 ratio in favor of the [...] Read more.
Background: Type 2 diabetes mellitus (T2DM) affects up to 10% of adults globally, and its complications can mask the risk of gastrointestinal bleeding or malignancy. Methods: Our study enrolled 633 endoscopic patients stratified according to T2DM presence (4:1 ratio in favor of the control group). Results: T2DM patients referred for endoscopy experienced lower prevalence of epigastric pain and heartburn (OR = 0.637/OR = 0.346, p < 0.05). Often being anemic (OR = 2.23, p < 0.001), they had significantly lower hemoglobin (p = 0.001) and serum iron (p = 0.02), but serum cholesterol was higher in non-diabetics. Ulcers, erosions and mucosal hemorrhages were comparable between groups (p < 0.05), although low-dose aspirin use was more prevalent in diabetics (p = 0.000, OR = 2.34). T2DM was associated with the increased frequency of antro-corporal active gastritis (OR = 1.451/OR 1.501), with smokers presenting a higher frequency of active H. pylori infection (OR = 3.37). T2DM predicted anemia (adjusted OR = 1.70) and the absence of gastroesophageal reflux symptoms (adjusted OR = 0.37), but not active H. pylori gastritis or premalignant lesions. Conclusion: In an endoscopic population, patients with T2DM had lower hemoglobin and serum iron levels. There was an inverse correlation between T2DM and heartburn. H. pylori gastritis and premalignant lesions occurred more frequently in diabetic patients (predominantly pangastritis) before adjusting for age or associated comorbidities, with smoking increasing the risk for active infection. Full article
(This article belongs to the Special Issue Helicobacter pylori)
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<p>Patient selection process. Final included groups were composed of 119 patients with T2DM and 514 patients with no history of T2DM. EGD—esophagogastroduodenoscopy; T2DM—type 2 diabetes mellitus.</p>
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<p>Antral reactive gastropathy.</p>
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<p>Antral active chronic gastritis.</p>
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<p>Corporeal active chronic gastritis.</p>
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18 pages, 18776 KiB  
Article
Optimization of Helicobacter pylori Biofilm Formation in In Vitro Conditions Mimicking Stomach
by Paweł Krzyżek, Paweł Migdał, Barbara Krzyżanowska and Anna Duda-Madej
Int. J. Mol. Sci. 2024, 25(18), 9839; https://doi.org/10.3390/ijms25189839 - 11 Sep 2024
Viewed by 283
Abstract
Helicobacter pylori is one of the most common bacterial pathogens worldwide and the main etiological agent of numerous gastric diseases. The frequency of multidrug resistance of H. pylori is growing and the leading factor related to this phenomenon is its ability to form [...] Read more.
Helicobacter pylori is one of the most common bacterial pathogens worldwide and the main etiological agent of numerous gastric diseases. The frequency of multidrug resistance of H. pylori is growing and the leading factor related to this phenomenon is its ability to form biofilm. Therefore, the establishment of a proper model to study this structure is of critical need. In response to this, the aim of this original article is to validate conditions of the optimal biofilm development of H. pylori in monoculture and co-culture with a gastric cell line in media simulating human fluids. Using a set of culture-based and microscopic techniques, we proved that simulated transcellular fluid and simulated gastric fluid, when applied in appropriate concentrations, stimulate autoaggregation and biofilm formation of H. pylori. Additionally, using a co-culture system on semi-permeable membranes in media imitating the stomach environment, we were able to obtain a monolayer of a gastric cell line with H. pylori biofilm on its surface. We believe that the current model for H. pylori biofilm formation in monoculture and co-culture with gastric cells in media containing host-mimicking fluids will constitute a platform for the intensification of research on H. pylori biofilms in in vitro conditions that simulate the human body. Full article
(This article belongs to the Special Issue Pathogenicity and Antibiotic Resistance of Helicobacter pylori)
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<p>Assessment of the impact of a one-week culture on the physiological parameters of <span class="html-italic">H. pylori</span> 2CML in BHI + 5% FCS and the concentration gradient of STF (0–10%, with 1% intervals). An increasing concentration of STF is marked by the intensified gray of bars. (<b>A</b>) Autoaggregation measured microscopically by estimating the degree of the observation field coverage, <span class="html-italic">n</span> = 3. (<b>B</b>) Biofilm formation determined by a crystal violet staining method and spectrophotometric measurements, <span class="html-italic">n</span> = 9. (<b>C</b>) Viability of bacterial cells determined by fluorescent staining with a LIVE/DEAD kit and a ratio of green/red fluorescence, <span class="html-italic">n</span> = 3. (<b>D</b>) Density of planktonic cells assessed by spectrophotometry, <span class="html-italic">n</span> = 9. (<b>E</b>) A set of images showing the growth of <span class="html-italic">H. pylori</span> 2CML under the most optimal conditions of the current model—BHI + 5% FCS + 5% STF (marked with red bars). Scale bars, 20 µm. * indicates statistical difference (<span class="html-italic">p</span> &lt; 0.05) with the control—0%.</p>
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<p>Assessment of the impact of a one-week culture on the physiological parameters of <span class="html-italic">H. pylori</span> 2CML in STF and the concentration gradient of FCS (0–10%, with 1% intervals). An increasing concentration of FCS is marked by the intensified gray of bars. (<b>A</b>) Autoaggregation measured microscopically by estimating the degree of the observation field coverage, <span class="html-italic">n</span> = 3. (<b>B</b>) Biofilm formation determined by a crystal violet staining method and spectrophotometric measurements, <span class="html-italic">n</span> = 9. (<b>C</b>) Viability of bacterial cells determined by fluorescent staining with a LIVE/DEAD kit and the ratio of green/red fluorescence, <span class="html-italic">n</span> = 3. (<b>D</b>) Density of planktonic cells assessed by spectrophotometry, <span class="html-italic">n</span> = 9. (<b>E</b>) A set of images showing growth of <span class="html-italic">H. pylori</span> 2CML under the most optimal conditions of the current model—STF + 8% FCS (marked with red bars). Scale bars, 20 µm. * indicates statistical difference (<span class="html-italic">p</span> &lt; 0.05) with the control—0%. Because of the low values for all the physiological parameters during 1- and 2-day cultures, these data were not recorded.</p>
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<p>Assessment of the impact of a one-week culture on the physiological parameters of <span class="html-italic">H. pylori</span> 2CML in BHI + 5% FCS and the concentration gradient of SGF (0–2%, with 0.2% intervals). An increasing concentration of SGF is marked by the intensified gray of bars. (<b>A</b>) Autoaggregation measured microscopically by estimating the degree of the observation field coverage, <span class="html-italic">n</span> = 3. (<b>B</b>) Biofilm formation determined by a crystal violet staining method and spectrophotometric measurements, <span class="html-italic">n</span> = 9. (<b>C</b>) Viability of bacterial cells determined by fluorescent staining with a LIVE/DEAD kit and a ratio of green/red fluorescence, <span class="html-italic">n</span> = 3. (<b>D</b>) Density of planktonic cells assessed by spectrophotometry, <span class="html-italic">n</span> = 9. (<b>E</b>) A set of images showing the growth of <span class="html-italic">H. pylori</span> 2CML under the most optimal conditions of the current model—BHI + 5% FCS + 1% SGF (marked with red bars). Scale bars, 20 µm. * indicates statistical difference (<span class="html-italic">p</span> &lt; 0.05) with the control—0%.</p>
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<p>Assessment of the impact of a one-week culture on the physiological parameters of <span class="html-italic">H. pylori</span> 2CML in STF and the concentration gradient of SGF (0–2%, with 0.2% intervals). An increasing concentration of SGF is marked by the intensified gray of bars. (<b>A</b>) Autoaggregation measured microscopically by estimating the degree of the observation field coverage, <span class="html-italic">n</span> = 3. (<b>B</b>) Biofilm formation determined by a crystal violet staining method and spectrophotometric measurements, <span class="html-italic">n</span> = 9. (<b>C</b>) Viability of bacterial cells determined by fluorescent staining with a LIVE/DEAD kit and a ratio of green/red fluorescence, <span class="html-italic">n</span> = 3. (<b>D</b>) Density of planktonic cells assessed by spectrophotometry, <span class="html-italic">n</span> = 9. (<b>E</b>) A set of images showing the growth of <span class="html-italic">H. pylori</span> 2CML under the most optimal conditions of the current model—STF + 1% SGF (marked with red bars). Scale bars, 20 µm. * indicates statistical difference (<span class="html-italic">p</span> &lt; 0.05) with the control—0%. Because of the low values for all the physiological parameters during 1- and 2-day cultures, these data were not recorded.</p>
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<p>Representative images showing a co-culture between <span class="html-italic">H. pylori</span> 2CML and KATO III cells growing on semi-permeable membranes in host-mimicking fluids. (<b>A</b>) A set of images obtained by fluorescence microscopy with different components of the co-culture model being stained (FM 1–43 to visualize bacterial biomass (biofilm), DAPI to show cell nuclei of eukaryotic cells, and WGA-conjugated Texas Red to indicate the presence of mucus glycoproteins (mucins)). Scale bars, 20 µm. (<b>B</b>) A set of images obtained by scanning electron microscopy. On the top, a control constituting non-infected KATO III cells; on the bottom, a co-infection of KATO III with <span class="html-italic">H. pylori</span> 2CML, where red arrows indicate areas of biofilm development. Scale bars, 20 µm.</p>
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<p>Representative images showing a co-culture between <span class="html-italic">H. pylori</span> 2CML and KATO III cells growing in microfluidic conditions in host-mimicking fluids. (<b>A</b>) Time-dependent development of <span class="html-italic">H. pylori</span> biofilm attached to KATO III cells. (<b>B</b>) An image showing a one-day co-culture with a marking of specific components of this model, where red circles indicate KATO III cells and yellow dashed lines highlight areas of the development of <span class="html-italic">H. pylori</span> biofilm, being in close contact with these cells. Scale bars, 20 µm. To see stacked time-lapse sequences from the above experiments, please see <a href="#app1-ijms-25-09839" class="html-app">Videos S1 and S2</a>.</p>
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14 pages, 3598 KiB  
Article
Genotypes and Phylogenetic Analysis of Helicobacter pylori Clinical Bacterial Isolates
by Marcela Ríos-Sandoval, Evangelina Esmeralda Quiñones-Aguilar, Guillermo Alejandro Solís-Sánchez, Jorge Bravo-Madrigal, Norma Velázquez-Guadarrama and Gabriel Rincón-Enríquez
Microbiol. Res. 2024, 15(3), 1845-1858; https://doi.org/10.3390/microbiolres15030123 - 10 Sep 2024
Viewed by 437
Abstract
Helicobacter pylori is a human pathogen bacterium associated with gastritis, peptic ulcer, and gastric cancer. It can be identified through the 16S rRNA gene and characterized through cagA and vacA virulence genes. Clinical cultures of H. pylori were isolated and identified from human [...] Read more.
Helicobacter pylori is a human pathogen bacterium associated with gastritis, peptic ulcer, and gastric cancer. It can be identified through the 16S rRNA gene and characterized through cagA and vacA virulence genes. Clinical cultures of H. pylori were isolated and identified from human stomach biopsies. The isolates were characterized according to their colonial and microscopic morphology, and molecular genotyping was conducted to determine the bacterial virulence. A phylogenetic analysis of the 16S rRNA gene sequencing was performed. In addition, multilocus sequence typing analysis was performed to determine the phylogeographic nature of the isolated strains. Three bacterial isolates were selected from 22 gastric biopsies, identified as H. pylori through colonial morphology, Gram staining, urease, catalase, and oxidase tests and identification of the ureC gene through end-point PCR. Amplification of 16S rRNA, urea, and tonB genes was performed, as well. Differences between the cagA and vacA genotypes were determined among the isolates. The phylogenetic analysis confirmed the identity of the three isolates as the specie Helicobacter pylori. Different genotypes were obtained for each H. pylori strain, and all the clinical isolates showed the vacA s2/m2 genotype, indicating an absence of the VacA cytotoxin. Only HCGDL-MR01 is a cagA gene carrier with a greater risk to develop a serious disease, such as stomach cancer and peptic ulcer. The multilocus sequence typing placed all the strains within the hpEurope population structure. Full article
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<p>Typical <span class="html-italic">Helicobacter pylori</span> colonial morphology of the HCGDL-MR17 isolate at 72 h growth. Cultured in Remel Casman agar base supplemented with 5% goat blood and incubated at 37 °C and 5% CO<sub>2</sub>. Left image = 40×, right image = 50×. Observations were performed with Nikon SMZ745T stereo microscope, Lumenera Infinity 1 CMOS digital camera, and Infinity Capture Application (version 6.5.4, Lumenera Corporation, Ottawa, ON, Canada).</p>
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<p>Microscopic morphological characterization of Gram staining bacterial isolates of patients from Antiguo Hospital Civil de Guadalajara. (<b>A</b>) HCGDL-MR01; (<b>B</b>) HCGDL-MR13; (<b>C</b>) HCGDL-MR17. (<b>D</b>) ATCC 43504 <span class="html-italic">H. pylori</span> reference strain. Micrographs were taken at 100×. Observations were performed with Olympus BH2-RFCA microscope, Leica digital camera DFC450C, and software (Application Suite LAS v.4.1.0, Wetzlar, Germany). Arrows indicate typical <span class="html-italic">H. pylori</span> morphology in culture with “seagull wing” in “C” or “S” curved–shaped. The boxes show an amplification of this typical morphology.</p>
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<p>Genotyping of the <span class="html-italic">H. pylori</span> study isolates obtained from patients of Antiguo Hospital Civil de Guadalajara. (<b>A</b>) <span class="html-italic">ureC</span> gene, 1: MW (1 kb-Plus, Invitrogen<sup>TM</sup>); 2: ATCC 43504; 3: HCGDL-MR01; 4: HCGDL-MR13; 5: HCGDL-MR17; (<b>B</b>) <span class="html-italic">tonB</span> gene, 1: MW; 2: HCGDL-MR17; 3: HCGDL-MR13; 4: HCGDL-MR01; 5: ATCC 43504; (<b>C</b>) <span class="html-italic">ureA</span> gene, 1: MW; 2: ATCC 43504; 3: HCGDL-MR01; 4: HCGDL-MR13; 5: HCGDL-MR17; (<b>D</b>) <span class="html-italic">cagA</span> gene, 1: MW; 2: ATCC 43504; 3: HCGDL-MR01; 4: HCGDL-MR13; 5: HCGDL-MR17; (<b>E</b>) <span class="html-italic">vacA</span> gene <span class="html-italic">m1</span> allele, 1: MW; 2: ATCC 43504; 3: HCGDL-MR01; 4: HCGDL-MR13.; 5: HCGDL-MR17; (<b>F</b>) <span class="html-italic">vacA</span> gene <span class="html-italic">m2</span> allele, 6: ATCC 43504; 7: HCGDL-MR01; 8: HCGDL-MR13; 9: HCGDL-MR17; 10: MW; (<b>G</b>) <span class="html-italic">vacA</span> gene <span class="html-italic">s1a</span> allele, 1: MW; 2: ATCC 43504; 3: HCGDL-MR01; 4: HCGDL-MR13; 5: HCGDL-MR17; (<b>H</b>) <span class="html-italic">vacA</span> gene <span class="html-italic">s1b</span> allele; 6: MW; 7: HCGDL-MR17; 8: HCGDL-MR13; 9: HCGDL-MR01; 10: ATCC 43504; (<b>I</b>) <span class="html-italic">vacA</span> gene <span class="html-italic">s2</span> allele; 11: MW; 12: ATCC 43504; 13: HCGDL-MR01; 14: HCGDL-MR13; 15: HCGDL-MR17. Electrophoresis conditions: 1% agarose, dehydrogenated disodium borate buffer (pH 8.5), 80 V.</p>
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<p>Relationship of bacterial isolates from Antiguo Hospital Civil de Guadalajara according to <span class="html-italic">H. pylori</span> genotypes. Construction of a distance tree using clustering with the unweighted pair group method with the arithmetic mean (UPGMA) method.</p>
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<p>16S rRNA phylogenetic analysis of the bacterial isolates of study from Antiguo Hospital Civil de Guadalajara against bacterial sequences of <span class="html-italic">Helicobacter</span> genus. Bacterial isolates highlighted in the bold square. Alignment performed in MUSCLE [<a href="#B22-microbiolres-15-00123" class="html-bibr">22</a>]. Parameters MEGA: maximum likelihood method with 1000 bootstrap replicates, 5 gamma distribution, Kimura 2-parameter model. <span class="html-italic">H. pylori</span> ATCC 43504 reference strain.</p>
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<p>Phylogenetic analysis of the bacterial isolates against 198 STs of <span class="html-italic">H. pylori</span> bacterial strains obtained from the PubMLST database (<a href="https://pubmlst.org/" target="_blank">https://pubmlst.org/</a>), performed with DNA sequences of the seven housekeeping (<span class="html-italic">atpA</span>, <span class="html-italic">efp</span>, <span class="html-italic">mutY</span>, <span class="html-italic">ppa</span>, <span class="html-italic">trpC</span>, <span class="html-italic">ureI</span>, <span class="html-italic">yphC</span>) genes. Alignment was performed with ClustalW. MEGA parameters: maximum likelihood method with 1000 bootstrap replicates, gamma distribution of 5, kimura 2-parameter method. <span class="html-italic">H. pylori</span> ATCC 43504 reference strain. Image edited in iTOL [<a href="#B28-microbiolres-15-00123" class="html-bibr">28</a>].</p>
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21 pages, 3689 KiB  
Article
Introducing HeliEns: A Novel Hybrid Ensemble Learning Algorithm for Early Diagnosis of Helicobacter pylori Infection
by Sultan Noman Qasem
Computers 2024, 13(9), 217; https://doi.org/10.3390/computers13090217 - 2 Sep 2024
Viewed by 415
Abstract
The Gram-negative bacterium Helicobacter pylori (H. infection) infects the human stomach and is a major cause of gastritis, peptic ulcers, and gastric cancer. With over 50% of the global population affected, early and accurate diagnosis of H. infection infection is crucial for effective [...] Read more.
The Gram-negative bacterium Helicobacter pylori (H. infection) infects the human stomach and is a major cause of gastritis, peptic ulcers, and gastric cancer. With over 50% of the global population affected, early and accurate diagnosis of H. infection infection is crucial for effective treatment and prevention of severe complications. Traditional diagnostic methods, such as endoscopy with biopsy, serology, urea breath tests, and stool antigen tests, are often invasive, costly, and can lack precision. Recent advancements in machine learning (ML) and quantum machine learning (QML) offer promising non-invasive alternatives capable of analyzing complex datasets to identify patterns not easily discernible by human analysis. This research aims to develop and evaluate HeliEns, a novel quantum hybrid ensemble learning algorithm designed for the early and accurate diagnosis of H. infection infection. HeliEns combines the strengths of multiple quantum machine learning models, specifically Quantum K-Nearest Neighbors (QKNN), Quantum Naive Bayes (QNB), and Quantum Logistic Regression (QLR), to enhance diagnostic accuracy and reliability. The development of HeliEns involved rigorous data preprocessing steps, including data cleaning, encoding of categorical variables, and feature scaling, to ensure the dataset’s suitability for quantum machine learning algorithms. Individual models (QKNN, QNB, and QLR) were trained and evaluated using metrics such as accuracy, precision, recall, and F1-score. The ensemble model was then constructed by integrating these quantum models using a hybrid approach that leverages their diverse strengths. The HeliEns model demonstrated superior performance compared to individual models, achieving an accuracy of 94%, precision of 97%, recall of 92%, and an F1-score of 94% in detecting H. infection infection. The quantum ensemble approach effectively mitigated the limitations of individual models, providing a robust and reliable diagnostic tool. HeliEns significantly improved diagnostic accuracy and reliability for early H. infection detection. The integration of multiple quantum ML algorithms within the HeliEns framework enhanced overall model performance. The non-invasive nature of the HeliEns model offers a cost-effective and user-friendly alternative to traditional diagnostic methods. This research underscores the transformative potential of quantum machine learning in healthcare, particularly in enhancing diagnostic efficiency and patient outcomes. HeliEns represents a significant advancement in the early diagnosis of H. infection infection, leveraging quantum machine learning to provide a non-invasive, accurate, and reliable diagnostic tool. This research highlights the importance of QML-driven solutions in healthcare and sets the stage for future research to further refine and validate the HeliEns model in real-world clinical settings. Full article
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<p>Architecture of H. infection detection.</p>
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<p>Model architecture.</p>
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<p>Mathematical visualization of proposed model.</p>
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<p>Pairwise scatter plot of encoded features.</p>
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<p>KNN decision boundary.</p>
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<p>LR decision boundary.</p>
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<p>NB decision boundary.</p>
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<p>Ensemble model decision boundary.</p>
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31 pages, 893 KiB  
Review
Protein Biomarkers of Gastric Preneoplasia and Cancer Lesions in Blood: A Comprehensive Review
by Thomas Bazin, Karine Nozeret, Catherine Julié, Dominique Lamarque and Eliette Touati
Cancers 2024, 16(17), 3019; https://doi.org/10.3390/cancers16173019 - 29 Aug 2024
Viewed by 510
Abstract
Gastric cancer (GC) is a major cause of cancer-related mortality worldwide. It is often associated with a bad prognosis because of its asymptomatic phenotype until advanced stages, highlighting the need for its prevention and early detection. GC development is preceded by the emergence [...] Read more.
Gastric cancer (GC) is a major cause of cancer-related mortality worldwide. It is often associated with a bad prognosis because of its asymptomatic phenotype until advanced stages, highlighting the need for its prevention and early detection. GC development is preceded by the emergence of gastric preneoplasia lesions (GPNLs), namely atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia (DYS). GC is currently diagnosed by endoscopy, which is invasive and costly and has limited effectiveness for the detection of GPNLs. Therefore, the discovery of non-invasive biomarkers in liquid biopsies, such as blood samples, in order to identify the presence of gastric preneoplasia and/or cancer lesions at asymptomatic stages is of paramount interest. This comprehensive review provides an overview of recently identified plasma/serum proteins and their diagnostic performance for the prediction of GPNLs and early cancer lesions. Autoantibodies appear to be promising biomarkers for AG, IM and early gastric cancer detection, along with inflammation and immunity-related proteins and antibodies against H. pylori virulence factors. There is a lack of specific protein biomarkers with which to detect DYS. Despite the need for further investigation and validation, some emerging candidates could pave the way for the development of reliable, non-invasive diagnostic tests for the detection and prevention of GC. Full article
(This article belongs to the Special Issue The Biomarkers for the Diagnosis and Prognosis in Cancer)
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<p>(<b>A</b>) Histologic and endoscopic characteristics of gastric lesions during gastric carcinogenesis. Gastric histologic lesions obtained from gastric biopsies, H&amp;E staining (a,c,e,f,h) and examination in NBI (b,d,g) and White Light. (i) Olympus endoscopy without optical zoom. Lesions of gastric atrophy (a,b). a (17.4×): chronic follicular atrophic non-metaplastic gastritis (complete atrophy). b: glandular atrophy shows pale appearance of gastric mucosa (green arrow), increased visibility of vasculature due to thinning of the gastric mucosa (red arrows), and loss of gastric folds. Lesions of intestinal metaplasia (c,d). c (9.4×): chronic atrophic and metaplastic gastritis (severe atrophy, severe intestinal metaplasia). d: intestinal metaplasia (red arrows) in gastric corpus. Rounded to branched pit pattern, with mucosa slightly darker than adjacent mucosa. Green arrows show normal gastric corpus mucosa, with round pit pattern. Lesions of dysplasia (e,f,g). e (31.5×): low-grade dysplasia. f (31.3×): high-grade dysplasia. g: endoscopically visible low-grade dysplasia with central ulcer. Vessel disorganization (red arrows) and glandular disorganization (green arrows) are observed. Glandular atrophy (yellow arrows) surrounds the lesion. Lesions of early gastric cancer (h,i). h (3.8×): early gastric cancer (intramucosal, red arrow). i: early gastric cancer centered on an ulcer. Absent glands with complete architectural loss of the mucosal and vascular pattern. (<b>B</b>) Plasma biomarkers identified at each step of the gastric cancer cascade. * detailed in <a href="#cancers-16-03019-t001" class="html-table">Table 1</a>.</p>
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18 pages, 6377 KiB  
Article
Helicobacter pylori HP0018 Has a Potential Role in the Maintenance of the Cell Envelope
by Kyle Rosinke, Vincent J. Starai and Timothy R. Hoover
Cells 2024, 13(17), 1438; https://doi.org/10.3390/cells13171438 - 27 Aug 2024
Viewed by 524
Abstract
Helicobacter pylori is a bacterial pathogen that colonizes the human stomach, where it can cause a variety of diseases. H. pylori uses a cluster of sheathed flagella for motility, which is required for host colonization in animal models. The flagellar sheath is continuous [...] Read more.
Helicobacter pylori is a bacterial pathogen that colonizes the human stomach, where it can cause a variety of diseases. H. pylori uses a cluster of sheathed flagella for motility, which is required for host colonization in animal models. The flagellar sheath is continuous with the outer membrane and is found in most Helicobacter species identified to date. HP0018 is a predicted lipoprotein of unknown function that is conserved in Helicobacter species that have flagellar sheaths but is absent in Helicobacter species that have sheath-less flagella. Deletion of hp0018 in H. pylori B128 resulted in the formation of long chains of outer membrane vesicles, which were most evident in an aflagellated variant of the Δhp0018 mutant that had a frameshift mutation in fliP. Flagellated cells of the Δhp0018 mutant possessed what appeared to be a normal flagellar sheath, suggesting that HP0018 is not required for sheath formation. Cells of the Δhp0018 mutant were also less helical in shape compared to wild-type cells. A HP0018-superfolder green fluorescent fusion protein expressed in the H. pylori Δhp0018 mutant formed fluorescent foci at the cell poles and lateral sites. Co-immunoprecipitation assays with HP0018 identified two enzymes involved in the modification of the cell wall peptidoglycan, AmiA and MltD, as potential HP0018 interaction partners. HP0018 may modulate the activity of AmiA or MltD, and in the absence of HP0018, the unregulated activity of these enzymes may alter the peptidoglycan layer in a manner that results in an altered cell shape and hypervesiculation. Full article
(This article belongs to the Section Cell Motility and Adhesion)
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<p>TEM and SEM images of wild-type <span class="html-italic">H. pylori</span> B128, the non-motile Δ<span class="html-italic">hp0018</span> mutant (H19), and the motile Δ<span class="html-italic">hp0018</span> isolate (H23). (<b>A</b>,<b>D</b>) TEM and SEM images, respectively, of wild-type <span class="html-italic">H. pylori</span> B128 cells. Note that the cells in the panel are flagellated. (<b>B</b>,<b>E</b>) TEM and SEM images, respectively, of H19. Note the chains of OMVs near the cell poles for many of the cells, which are indicated by the black arrows. Material that we infer to be free OMVs are indicated by the white arrows in (<b>E</b>). (<b>C</b>,<b>F</b>) TEM and SEM images, respectively, of strain H23. Note that the majority of the cells are flagellated and some of the cells appear to have OMVs on the cell surface (black arrows). (<b>G</b>–<b>I</b>) Close-up TEM images of chains of OMVs attached to cells (<b>G</b>,<b>H</b>) or detached from cells (<b>I</b>). Images shown in (<b>G</b>–<b>I</b>) are of strain H19. The magnification for the SEM images was 15,000×.</p>
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<p>Motility of <span class="html-italic">H. pylori</span> strains in soft agar medium. <span class="html-italic">H. pylori</span> strains were stab inoculated into soft agar medium and incubated under microaerobic conditions for 7 d. Strains shown on the plate are wild-type <span class="html-italic">H. pylori</span> B128 (WT), H19 (non-motile Δ<span class="html-italic">hp0018</span> mutant), H23 (motile Δ<span class="html-italic">hp0018</span> isolate), and H23 carrying a derivative of plasmid pHel3 bearing a copy of <span class="html-italic">hp0018</span> (H23/pKR66).</p>
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<p>Flagella of strains H19 and H23. (<b>A</b>) TEM image of a flagellated cell and an aflagelleted cell of strain H19. Note that the flagellated cell has several OMVs on the cell surface, but lacks the chain of OMVs at the cell pole, while the aflagellated cell has a chain of OMVs at the cell pole. (<b>B</b>) TEM image of cells of strain H23. In both strains, note that some of the flagella had the characteristic bulb at the end of the filament (indicated by arrows). (<b>C</b>) Close-up image of flagella shown in panel A, where the bulb-like structures are clearly seen.</p>
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<p>TEM images of OMVs isolated from wild-type, H19, and H23 strains. (<b>A</b>) OMV preparation from wild-type <span class="html-italic">H. pylori</span> B128. (<b>B</b>) OMV preparation from strain H19. (<b>C</b>) OMV preparation from strain H23. OMV preparations from H19 and H23 displayed tubular structures (indicated by arrows).</p>
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<p>Localization of a HP0018-sfGFP fusion protein in <span class="html-italic">H. pylori</span> by fluorescent microscopy. (<b>A</b>,<b>B</b>) Identical X- and Y-planes and a slightly different Z-plane of a section of a slide with HP0018-sfGFP. (<b>A</b>) Red channel showing membrane staining with FM4-64, and (<b>B</b>) green channel showing the localization of HP0018-sfGFP. White arrows indicate the lateral localization of HP0018-sfGFP, red arrows a polar localization, and blue arrows multiple foci. (<b>C</b>–<b>E</b>) Merged channels of red (FM4-64) and green (HP0018-sfGFP) showing (<b>C</b>) lateral, (<b>D</b>) polar, and (<b>E</b>) multiple foci. For panels (<b>C</b>–<b>E</b>), all of the scale bars correspond to 2 µm. (<b>F</b>) The frequency of fluorescent foci at the cell pole (polar) and lateral sites was determined, as well as the frequency of cells with four or more fluorescent foci (multiple) (<span class="html-italic">n</span> = 133).</p>
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<p>AlphaFold2 predictions of protein–protein interactions between HP0018 and AmiA or MltD. (<b>A</b>) Most energetically favorable model for interactions between HP0018 (shown in red) and the catalytic domain of AmiA (shown in blue). (<b>B</b>) Most energetically favorable model for interactions between HP0018 (shown in red) and MltD (shown in green).</p>
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18 pages, 3978 KiB  
Article
Liposomal Drug Delivery against Helicobacter pylori Using Furazolidone and N-Acetyl Cysteine in Augmented Therapy
by Muhammad Irfan Alam, Timothy Paget, Najla Yussuf Moosa, Husein Alghurairy and Amal Ali Elkordy
Pharmaceutics 2024, 16(9), 1123; https://doi.org/10.3390/pharmaceutics16091123 - 26 Aug 2024
Viewed by 613
Abstract
Helicobacter pylori (H. pylori) infection is a significant global health concern, affecting approximately 50% of the world’s population and leading to gastric ulcers, gastritis, and gastric cancer. The increase in antibiotic resistance has compromised the efficacy of existing therapeutic regimens, necessitating [...] Read more.
Helicobacter pylori (H. pylori) infection is a significant global health concern, affecting approximately 50% of the world’s population and leading to gastric ulcers, gastritis, and gastric cancer. The increase in antibiotic resistance has compromised the efficacy of existing therapeutic regimens, necessitating novel approaches for effective eradication. This study aimed to develop a targeted liposomal drug delivery system incorporating furazolidone and N-acetylcysteine (NAC) to enhance mucopenetration and improve Helicobacter pylori eradication. Liposomes were formulated with furazolidone, NAC, and Pluronic F-127 using a modified reverse-phase evaporation technique. The formulations were categorized based on charge as neutral, negative, and positive and tested for mucopenetration using a modified silicon tube method with coumarin-6 as a fluorescent marker. The encapsulation efficiency and particle size were analyzed using HPLC and an Izon q-nano particle size analyzer. The results indicated that charged liposomes showed a higher encapsulation efficiency than neutral liposomes with Pluronic F-127. Notably, combining furazolidone with 1% NAC achieved complete eradication of H. pylori in 2.5 h, compared to six hours without NAC. The findings of this study suggest that incorporating NAC and Pluronic F-127 into liposomal formulations significantly enhances mucopenetration and antimicrobial efficacy. Full article
(This article belongs to the Topic Personalized Drug Formulations)
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<p>Spot plating technique for different dilutions from (<b>A</b>). 10<sup>−1</sup> through 10<sup>−3</sup> and (<b>B</b>). from 10<sup>−1</sup> to 10<sup>−6</sup>.</p>
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<p>Transmission electron microscopic, TEM, images of mucopenetrative liposomes (<b>A</b>). MP3, cationic liposomes with Pluronic F-127 (<b>B</b>). MP1, neutral liposomes with Pluronic F-127. For formulations’ composition, refer to <a href="#pharmaceutics-16-01123-t001" class="html-table">Table 1</a>.</p>
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<p>Diffusion of mucopenetrative liposomal particles from MP1 to MP6 through 1 mm thick sigma mucin type I in a silicon tube maintained at pH 6.0 at 37 °C at 1, 2, and 3 hours’ time (n = 3, mean ± SD shown). Abbreviations: MP1 (neutral with Pluronic F-127), MP4 (neutral without Pluronic F-127), MP2 (negative with Pluronic F-127), MP5 (negative without Pluronic F-127), MP3 (positive with Pluronic F-127), MP6 (positive without Pluronic F-127). For formulations’ composition, refer to <a href="#pharmaceutics-16-01123-t001" class="html-table">Table 1</a>.</p>
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<p>(<b>A</b>). In vitro drug release of furazolidone from the mucopenetrative formulation MP1 and MP4 up to a 4 h time at pH 6.0 (n = 3, mean ± SD shown). Abbreviations: MP1 (neutral with Pluronic F-127), MP4 (neutral without Pluronic F-127). (<b>B</b>). In vitro drug release of furazolidone from the mucopenetrative formulation MP3 and MP6 up to a 4 h time at pH 6.0 (n = 3, mean ± SD shown). Abbreviations: MP3 (positive with Pluronic F-127), MP6 (positive without Pluronic F-127). (<b>C</b>). In vitro drug release of furazolidone from the mucopenetrative formulation MP2 and MP5 for up to a 4 h time at pH 6.0 (n = 3, mean ± SD shown). Abbreviations: MP2 (negative with Pluronic F-127), MP5 (negative without Pluronic F-127).</p>
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<p>(<b>A</b>). In vitro drug release of furazolidone from the mucopenetrative formulation MP1 and MP4 up to a 4 h time at pH 6.0 (n = 3, mean ± SD shown). Abbreviations: MP1 (neutral with Pluronic F-127), MP4 (neutral without Pluronic F-127). (<b>B</b>). In vitro drug release of furazolidone from the mucopenetrative formulation MP3 and MP6 up to a 4 h time at pH 6.0 (n = 3, mean ± SD shown). Abbreviations: MP3 (positive with Pluronic F-127), MP6 (positive without Pluronic F-127). (<b>C</b>). In vitro drug release of furazolidone from the mucopenetrative formulation MP2 and MP5 for up to a 4 h time at pH 6.0 (n = 3, mean ± SD shown). Abbreviations: MP2 (negative with Pluronic F-127), MP5 (negative without Pluronic F-127).</p>
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<p>(<b>A</b>). In vitro drug release of NAC from the mucopenetrative formulation from MP1 and MP4 for up to 4 h time at pH 6.0 (n = 3, mean ± SD shown). Abbreviations: MP1 (neutral with Pluronic F-127), MP4 (neutral without Pluronic F-127). (<b>B</b>). In vitro drug release of NAC from the mucopenetrative formulation from MP2 and MP5 for up to 4 h time at pH 6.0 (n = 3, mean ± SD shown). Abbreviations: MP2 (negative with Pluronic F-127), MP5 (negative without Pluronic F-127). (<b>C</b>). In vitro drug release of NAC from the mucopenetrative formulation from MP3 and MP6 for up to 4 h time at pH 6.0 (n = 3, mean ± SD shown). Abbreviations: MP3 (positive with Pluronic F-127), MP6 (positive without Pluronic F-127).</p>
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<p>(<b>A</b>). In vitro drug release of NAC from the mucopenetrative formulation from MP1 and MP4 for up to 4 h time at pH 6.0 (n = 3, mean ± SD shown). Abbreviations: MP1 (neutral with Pluronic F-127), MP4 (neutral without Pluronic F-127). (<b>B</b>). In vitro drug release of NAC from the mucopenetrative formulation from MP2 and MP5 for up to 4 h time at pH 6.0 (n = 3, mean ± SD shown). Abbreviations: MP2 (negative with Pluronic F-127), MP5 (negative without Pluronic F-127). (<b>C</b>). In vitro drug release of NAC from the mucopenetrative formulation from MP3 and MP6 for up to 4 h time at pH 6.0 (n = 3, mean ± SD shown). Abbreviations: MP3 (positive with Pluronic F-127), MP6 (positive without Pluronic F-127).</p>
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<p>A time–kill curve experiment of furazolidone augmented with NAC at a concentration of 1% of its minimum inhibitory concentration (MIC) against <span class="html-italic">H. pylori</span> inoculated on a blood agar plate and incubated at 37 °C for 24 h in an anaerobic jar with CampyGen gas packs before counting the colonies. The mean value of the log number of cfu per milliliter was plotted against time (n = 6, mean ± SD).</p>
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<p>The coding for mucopenetrative liposomal formulation compositions (MP1-MP6).</p>
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11 pages, 5478 KiB  
Review
Epidemiology of Gastric Cancer—Changing Trends and Global Disparities
by Manami Inoue
Cancers 2024, 16(17), 2948; https://doi.org/10.3390/cancers16172948 - 24 Aug 2024
Viewed by 514
Abstract
Overall, the past century has seen a substantial decline in gastric cancer, attributable to decreases in risk factors such as H. pylori infection, tobacco smoking, and the intake of salt-preserved food. One potential preventive strategy for those at high risk is H. pylori [...] Read more.
Overall, the past century has seen a substantial decline in gastric cancer, attributable to decreases in risk factors such as H. pylori infection, tobacco smoking, and the intake of salt-preserved food. One potential preventive strategy for those at high risk is H. pylori eradication for infected subjects, but confirmation of this effect awaits longer follow-up. Obesity continues to advance and may cause increases in cardia cancer, particularly in Western populations, and careful monitoring of this outcome is warranted in both Western and Asian populations. These changes in gastric cancer epidemiology foreshadow a new era in gastric cancer control and warrant further monitoring of descriptive patterns and risk factors. Full article
(This article belongs to the Special Issue Gastric Cancer: Evolving Landscape and Emerging Therapies)
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<p>Most frequent cancers worldwide by incidence and mortality in both sexes in 1990 and 2022 [<a href="#B1-cancers-16-02948" class="html-bibr">1</a>,<a href="#B2-cancers-16-02948" class="html-bibr">2</a>].</p>
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<p>Age-standardized rate (world) of cancers per 100,000 by incidence and mortality in both sexes in 2022 [<a href="#B1-cancers-16-02948" class="html-bibr">1</a>].</p>
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<p>Age-standardized incidence rate (world) of gastric cancer per 100,000 in both sexes in 2022 [<a href="#B1-cancers-16-02948" class="html-bibr">1</a>]. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization/International Agency for Research on Cancer concerning the legal status of any country, territory, city, or area or of its authorities or concerning the delimitation of its frontiers or boundaries. Dotted and dashed lines on maps represent approximate borderlines for which there may not yet be full agreement.</p>
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<p>Age-standardized (world) incidence rate of gastric cancer by UN Region in both sexes in 2022 [<a href="#B1-cancers-16-02948" class="html-bibr">1</a>].</p>
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<p>Age-standardized incidence rate (world) of gastric cancer by country ranking in both sexes in 2022 [<a href="#B1-cancers-16-02948" class="html-bibr">1</a>].</p>
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<p>Distribution of gastric cancer by UN region by absolute numbers in both sexes in 2022 [<a href="#B1-cancers-16-02948" class="html-bibr">1</a>].</p>
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<p>Global distribution of age-standardized 5-year net survival for adults (15–99 years old) diagnosed with gastric cancer in 2010–2014 (both sexes) [<a href="#B3-cancers-16-02948" class="html-bibr">3</a>].</p>
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<p>Subsite distribution of gastric cancer in males in 2013–2017 [<a href="#B4-cancers-16-02948" class="html-bibr">4</a>].</p>
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<p>Declining trend in prevalence of <span class="html-italic">Helicobacter pylori</span> infection by birth year (1908–2003) in a Japanese population. Meta-analysis of 170,752 Japanese [<a href="#B10-cancers-16-02948" class="html-bibr">10</a>].</p>
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<p>Estimated number of new cases of gastric cancer from 2022 to 2045 in both sexes by UN Region [<a href="#B33-cancers-16-02948" class="html-bibr">33</a>].</p>
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<p>Age-standardized gastric cancer incidence rates (ASR) in 2010 and predicted rates in 2035 in both sexes combined [<a href="#B34-cancers-16-02948" class="html-bibr">34</a>].</p>
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16 pages, 2048 KiB  
Article
Castanea sativa Mill. By-Products: Investigation of Potential Anti-Inflammatory Effects in Human Intestinal Epithelial Cells
by Carola Pozzoli, Giulia Martinelli, Marco Fumagalli, Chiara Di Lorenzo, Nicole Maranta, Luca Colombo, Stefano Piazza, Mario Dell’Agli and Enrico Sangiovanni
Molecules 2024, 29(16), 3951; https://doi.org/10.3390/molecules29163951 - 21 Aug 2024
Viewed by 483
Abstract
Castanea sativa Mill. (C. sativa) processing and pruning generate several by-products, including leaves, burs, and shells (inner and outer teguments), which are considered an important source of high-value phytochemicals. Ellagitannins from C. sativa leaf extracts have been described to impair H. [...] Read more.
Castanea sativa Mill. (C. sativa) processing and pruning generate several by-products, including leaves, burs, and shells (inner and outer teguments), which are considered an important source of high-value phytochemicals. Ellagitannins from C. sativa leaf extracts have been described to impair H. pylori viability and inflammation in gastric cells. Furthermore, chestnut shells showed an important anti-inflammatory effect in gastric epithelial cells. Dietary polyphenols, including tannins, have been reported to interfere with targets of inflammation, including the nuclear factor κB (NF-κB). A promising role as a further therapeutical target for gut disorders has been recently proposed for the regulatory subunit of hypoxia-inducible factor (HIF-1α), as a potential stabilizer of intestinal barrier integrity. Therefore, the main objective of this work is the chemical characterization of several chestnut by-products (bud, spiny bur, wood, pericarp and episperm), together with the exploitation of their anti-inflammatory properties in intestinal cells, scavenging capacity, and stability following gastrointestinal digestion. The chemical characterization confirmed the presence of bioactive polyphenols in the extracts, including ellagitannins. In CaCo-2 cells stimulated by an IL-1β-IFN-γ cocktail, nearly all chestnut by-products (50 µg/mL) inhibited the release of proinflammatory mediators (CXCL-10, IL-8, MCP-1, ICAM), along with the NF-κB-driven transcription, and induced the HRE-driven transcription. The stability of the most promising extracts, identified through PCA and cluster analysis, was addressed by in vitro gastrointestinal digestion. Despite the significant reduction in total polyphenol index of chestnut bud and wood after gastric and intestinal digestion, the activity of these extracts on both scavenging and anti-inflammatory parameters remained promising. These data contribute to exploit the potential of chestnut by-products as sources of dietary polyphenols with anti-inflammatory properties at the intestinal level. Moreover, this study could represent an important step to encourage the recycling and valorization of chestnut by-products, promoting the circular economy and reducing the environmental impact related to the management of agriculture waste. Full article
(This article belongs to the Special Issue Advances in Functional Foods)
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<p>Effect of hydroalcoholic extracts from <span class="html-italic">C. sativa</span> by-products (50 µg/mL) on CXCL-10 (<b>A</b>), IL-8 (<b>B</b>), MCP-1 (<b>C</b>), ICAM-1 (<b>D</b>) release, measured by ELISA assay. Epigallocatechin-3-O-gallate (20 μM) was used as a reference inhibitor (positive control). Data (<span class="html-italic">n</span> = 3) are expressed as mean (%) ± SEM relative to IL-1β-IFN-γ, which was arbitrarily assigned the value of 100%. *** <span class="html-italic">p</span> &lt; 0.001 vs. IL-1β-IFN-γ.</p>
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<p>Effect of hydroalcoholic extracts from <span class="html-italic">C. sativa</span> by-products (50 µg/mL) on NF-κB- (<b>A</b>) and HRE (<b>B</b>)-driven transcriptions, measured by luciferase assay and reporter plasmids. DMOG (250 μM) was used as a reference compound for HIF induction (positive control) (<b>A</b>). Apigenin (20 μM) was used as reference inhibitor of the NF-κB activity (positive control). Data (<span class="html-italic">n</span> = 3) are expressed as mean (%) ± SEM relative to IL-1β -IFN-γ (<b>A</b>) or to control (<b>B</b>), which was arbitrarily assigned the value of 100%. * <span class="html-italic">p</span> &lt; 0.05, *** <span class="html-italic">p</span> &lt; 0.001 vs. IL-1β -IFN-γ (<b>A</b>) or Control (<b>B</b>).</p>
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<p>Classification of chestnut by-products for inflammation (MCP-1, ICAM-1, CXCL-10, IL-8 release vs. stimulus; NF-κB-driven transcription vs. stimulus), antioxidant activity (ORAC and DPPH), total polyphenol index, ellagitannin content (vescalagin and castalagin), HRE-driven transcription (induction % vs. CTRL), based on PCA (<b>A</b>) and cluster analysis (<b>B</b>).</p>
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<p>Effect of gastric or gastrointestinal digestion on total polyphenol index (mg gallic acid equivalent/g ± SE) and antioxidant activity (mmol Trolox equivalent/g ± SE) measured by DPPH assay on <span class="html-italic">C. sativa</span> bud and dry wood extract. Data (<span class="html-italic">n</span> = 3) are expressed as mean ± SEM. *** <span class="html-italic">p</span> &lt; 0.001 vs. undigested extracts.</p>
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<p>Effect of <span class="html-italic">C. sativa</span> bud (<b>A</b>) and dry wood (<b>B</b>) extracts after in vitro gastrointestinal digestion on CXCL-10 release, measured by ELISA assay. Epigallocatechin-3-O-gallate (20 μM) was used as reference inhibitor (positive control, in yellow). Data (<span class="html-italic">n</span> = 3) are expressed as mean (%) ± SEM related to IL-1β-IFN-γ, which was arbitrarily assigned the value of 100%. *** <span class="html-italic">p</span> &lt; 0.001 vs. IL-1β-IFN-γ.</p>
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<p>MTT assay performed on <span class="html-italic">C. sativa</span> by-product extracts (50 µg/mL) in CaCo-2 cells. Data (<span class="html-italic">n</span> = 3) are expressed as mean (%) ± SEM relative to control, which was arbitrarily assigned the value of 100%.</p>
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<p>NRU assay performed on <span class="html-italic">C. sativa</span> by-product extracts (50 µg/mL) in CaCo-2. Data (<span class="html-italic">n</span> = 3) are expressed as mean (%) ± SEM relative to control, which was arbitrarily assigned the value of 100%.</p>
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29 pages, 1182 KiB  
Review
Cardiovascular and Neurological Diseases and Association with Helicobacter Pylori Infection—An Overview
by Vlad Pădureanu, Dalia Dop, Daniel Cosmin Caragea, Dumitru Rădulescu, Rodica Pădureanu and Mircea-Cătălin Forțofoiu
Diagnostics 2024, 14(16), 1781; https://doi.org/10.3390/diagnostics14161781 - 15 Aug 2024
Viewed by 713
Abstract
This article investigates the link between Helicobacter pylori (H. pylori) infection and cardiovascular and neurological disorders. Recent research suggests that H. pylori may play a role in cardiovascular diseases like atherosclerosis, myocardial infarction, and stroke, as well as neurological diseases including [...] Read more.
This article investigates the link between Helicobacter pylori (H. pylori) infection and cardiovascular and neurological disorders. Recent research suggests that H. pylori may play a role in cardiovascular diseases like atherosclerosis, myocardial infarction, and stroke, as well as neurological diseases including Alzheimer’s disease, multiple sclerosis, and Parkinson’s disease. Cardiovascular Diseases: H. pylori induces endothelial dysfunction and chronic inflammation, promoting atherosclerotic plaque formation and other cardiac complications. High infection prevalence in cardiovascular patients implies that systemic inflammation from H. pylori accelerates disease progression. Eradication therapies combined with anti-inflammatory and lipid-lowering treatments may reduce cardiovascular risk. Neurological Diseases: H. pylori may contribute to Alzheimer’s, multiple sclerosis, and Parkinson’s through systemic inflammation, neuroinflammation, and autoimmune responses. Increased infection prevalence in these patients suggests bacterial involvement in disease pathogenesis. The eradication of H. pylori could reduce neuroinflammation and improve outcomes. Discussions and Future Research: Managing H. pylori infection in clinical practice could impact public health and treatment approaches. Further research is needed to clarify these relationships. Longitudinal and mechanistic studies are essential to fully understand H. pylori’s role in these conditions. Conclusions: H. pylori infection is a potential risk factor for various cardiovascular and neurological conditions. Additional research is critical for developing effective prevention and treatment strategies. Targeted therapies, including H. pylori eradication combined with anti-inflammatory treatments, could improve clinical outcomes. These findings highlight the need for an integrated clinical approach to include H. pylori evaluation and treatment. Full article
(This article belongs to the Special Issue Advances in the Diagnosis of Nervous System Diseases—2nd Edition)
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<p>Relationship between <span class="html-italic">H. pylori</span> infection and neurological diseases—created with BioRender.com.</p>
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<p>Relationship between <span class="html-italic">H. pylori</span> infection and cardiovascular diseases—created with BioRender.com.</p>
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13 pages, 2207 KiB  
Article
Insights into Probiotic Prescription among Gastroenterologists and Other Healthcare Professionals: Evidence from an Italian Survey
by Giovanni Marasco, Angelo Bruni, Olga Maria Nardone and Loris Riccardo Lopetuso
J. Clin. Med. 2024, 13(16), 4749; https://doi.org/10.3390/jcm13164749 - 13 Aug 2024
Viewed by 534
Abstract
Background: Probiotics, which are live microorganisms that provide health benefits, have been extensively studied for their various clinical applications. However, despite their potential, high-quality data supporting their use in several gastrointestinal diseases are often lacking, and prescription behaviors can widely differ. This [...] Read more.
Background: Probiotics, which are live microorganisms that provide health benefits, have been extensively studied for their various clinical applications. However, despite their potential, high-quality data supporting their use in several gastrointestinal diseases are often lacking, and prescription behaviors can widely differ. This study aimed to assess different behaviors in probiotics knowledge and prescriptions among Italian gastroenterologists and healthcare professionals (HPs). Methods: A web-based electronic survey was distributed to all participants at the National Meeting of the Italian Young Gastroenterologist and Endoscopist Association (AGGEI) held in 2023. The survey investigated probiotic prescription practices for several gastrointestinal conditions, such as acute diarrhea, irritable bowel syndrome, inflammatory bowel disease, and diverticular disease. Results: Among 200 participants, 142 completed the survey, of whom 59 were gastroenterologists and 83 were HPs (surgeons, nutrition biologists, and other physicians). Significant differences were observed in the prescription of probiotics for the treatment of acute diarrhea and H. pylori. Both groups prescribed probiotics in monthly cycles for patients with IBS, although the majority prescribed multistrain formulations. Gastroenterologists were more likely to prescribe cyclic courses for IBS, while HPs tended to continue therapy by changing the probiotic strain in case of inefficacy. For ulcerative colitis, gastroenterologists prescribed probiotics more but for shorter durations. In Crohn’s disease, gastroenterologists prescribed probiotics less and were less likely to prescribe multistrain formulations. Regarding SUDD, gastroenterologists tended to prescribe probiotics less frequently, although without a significant difference, with similar rates of preference for multistrain formulations. Conclusions: This survey highlights heterogeneous behaviors in probiotic prescription between gastroenterologists and HPs, with gastroenterologists more aligned with guidelines and available scientific evidence. Hence, enhancing probiotic education among healthcare professionals and gastroenterologists is crucial. Further studies are needed to better understand probiotics’ role in gastrointestinal disorders through large-scale randomized controlled trials. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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<p>Use and prescription of probiotics for acute diarrhea, antibiotic-associated diarrhea, and <span class="html-italic">C. difficile</span> infection and treatment of <span class="html-italic">H. pylori</span> eradication (percentage): (<b>A</b>) Use of probiotics for acute diarrhea, (<b>B</b>) type of probiotic prescribed for acute Diarrhea, (<b>C</b>) use of probiotics to prevent antibiotic-associated diarrhea and <span class="html-italic">C. difficile</span> infection, (<b>D</b>) type of probiotic prescribed to prevent antibiotic-associated diarrhea and <span class="html-italic">C. difficile</span> infection, (<b>E</b>) use of probiotics as adjuncts in the treatment of <span class="html-italic">H. pylori</span> eradication, (<b>F</b>) type of probiotic prescribed as adjuncts in the treatment of <span class="html-italic">H. pylori</span> eradication.</p>
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<p>Prescription of probiotics for IBS and IBD (percentage): (<b>A</b>) Do you prescribe probiotics for patients with IBS? (<b>B</b>) What type of probiotic do you prescribe for IBS? (<b>C</b>) Do you prescribe probiotics for patients with Ulcerative Colitis? (<b>D</b>) Do you prescribe probiotics for patients with Crohn’s Disease? (<b>E</b>) What type of probiotic do you prescribe for ulcerative colitis and Crohn’s disease?</p>
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<p>Prescription of probiotics for diverticulosis, SUDD, and acute diverticulitis (percentage): (<b>A</b>) In patients with a history of diverticulosis do you prescribe probiotics? (<b>B</b>) What type of probiotic do you prescribe for patients with diverticulosis? (<b>C</b>) Do you prescribe probiotics for patients with SUDD? (<b>D</b>) What type of probiotic do you prescribe for SUDD? (<b>E</b>) In patients with a history of acute diverticulitis, do you prescribe probiotics? (<b>F</b>) What type of probiotic do you prescribe in patients with a history of acute diverticulitis?</p>
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11 pages, 2304 KiB  
Article
Trends in Upper Gastrointestinal Bleeding in Children: The Impact of Helicobacter pylori Infection and Non-Steroidal Anti-Inflammatory Drug Use
by Felicia Galos, Mara Ioana Ionescu, Mihai Daniel Luca Mirea, Anca Andreea Boboc, Andreea Ioan and Catalin Boboc
Antibiotics 2024, 13(8), 752; https://doi.org/10.3390/antibiotics13080752 - 10 Aug 2024
Viewed by 619
Abstract
Upper gastrointestinal bleeding (UGIB) is a significant concern in children, contributing to 6–20% of cases in pediatric intensive care units. This study evaluates the roles of Helicobacter pylori (H. pylori) infection and non-steroidal anti-inflammatory drug (NSAID) usage in the etiology of [...] Read more.
Upper gastrointestinal bleeding (UGIB) is a significant concern in children, contributing to 6–20% of cases in pediatric intensive care units. This study evaluates the roles of Helicobacter pylori (H. pylori) infection and non-steroidal anti-inflammatory drug (NSAID) usage in the etiology of UGIB in children, with a particular focus on trends observed during the COVID-19 pandemic. We conducted a retrospective analysis of 103 pediatric patients who underwent esophagogastroduodenoscopy (EGD) for UGIB between January 2015 and December 2023. Of these, 88 patients were included in the final analysis, where the source of bleeding was successfully identified. Hematemesis was the most common presentation, and the source of bleeding was identified in 85.43% of cases. The prevalence of H. pylori infection remained stable across the pre-pandemic (39.7%) and post-pandemic (36.7%) periods. However, NSAID usage increased nearly threefold during the pandemic, with 36.7% of post-pandemic UGIB cases associated with NSAID use, compared to 12.1% pre-pandemic. These findings underscore the significant roles of H. pylori and NSAID use in pediatric UGIB, with a notable increase in NSAID-related cases during the pandemic. Full article
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<p>Endoscopic image of the gastric mucosa from a 17-year-old male patient included in this cohort. This image shows a gastric ulcer located in the prepyloric region on the right and a rare finding of a pediatric gastric diverticulum on the left. The detailed visualization of the mucosal texture and vascular patterns aids in the diagnosis and management of these gastrointestinal abnormalities. Image taken from our personal collection.</p>
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<p>Microscopic image showing <span class="html-italic">Helicobacter pylori</span> bacilli in a gastric biopsy from a pediatric patient included in this cohort, using Giemsa stain at 400x magnification. The bacilli appear as short, curved, or spiral-shaped organisms adhering to the gastric epithelial surface. Panel (<b>A</b>) shows a mild infiltration of inflammatory cells with presence of <span class="html-italic">H. pylori</span> bacilli on the surface of the epithelial cells. Panel (<b>B</b>) exhibits a more severe inflammatory response with denser infiltration of inflammatory cells, also showing <span class="html-italic">H. pylori</span> bacilli. Images taken from our personal collection.</p>
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13 pages, 1985 KiB  
Article
Galectin-2 Agglutinates Helicobacter pylori via Lipopolysaccharide Containing H Type I Under Weakly Acidic Conditions
by Takaharu Sasaki, Midori Oyama, Mao Kubota, Yasunori Isshiki, Tomoharu Takeuchi, Toru Tanaka, Takashi Tanikawa, Mayumi Tamura, Yoichiro Arata and Tomomi Hatanaka
Int. J. Mol. Sci. 2024, 25(16), 8725; https://doi.org/10.3390/ijms25168725 - 10 Aug 2024
Viewed by 533
Abstract
Galectins are β-galactoside-binding animal lectins involved in various biological functions, such as host defense. Galectin-2 and -3 are members of the galectin family that are expressed in the stomach, including the gastric mucosa and surface mucous cells. Galectin-3 exhibits aggregation and bactericidal activity [...] Read more.
Galectins are β-galactoside-binding animal lectins involved in various biological functions, such as host defense. Galectin-2 and -3 are members of the galectin family that are expressed in the stomach, including the gastric mucosa and surface mucous cells. Galectin-3 exhibits aggregation and bactericidal activity against Helicobacter pylori in a β-galactoside-dependent manner. We previously reported that galectin-2 has the same activity under neutral pH conditions. In this study, the H. pylori aggregation activity of galectin-2 was examined under weakly acidic conditions, in which H. pylori survived. Galectin-2 agglutinated H. pylori even at pH 6.0, but not at pH 5.0, correlating with its structural stability, as determined using circular dichroism. Additionally, galectin-2 binding to the lipopolysaccharide (LPS) of H. pylori cultured under weakly acidic conditions was investigated using affinity chromatography and Western blotting. Galectin-2 could bind to H. pylori LPS containing H type I, a Lewis antigen, in a β-galactoside-dependent manner. In contrast, galectin-3 was structurally more stable than galectin-2 under acidic conditions and bound to H. pylori LPS containing H type I and Lewis X. In conclusion, galectin-2 and -3 might function cooperatively in the defense against H. pylori in the stomach under different pH conditions. Full article
(This article belongs to the Special Issue Galectins (Gals))
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<p>The aggregation of <span class="html-italic">Helicobacter pylori</span> induced by Gal-2 at various pH. The number of nonaggregated bacteria with (gray bar) or without (black bar) rGal-2 (93.9 µg/mL) under pH 7.4, 6.0, and 5.0 conditions is shown. Each bar represents the mean ± standard deviation (SD) from five samples. **, <span class="html-italic">p</span> &lt; 0.01, ***, <span class="html-italic">p</span> &lt; 0.001 by Student’s <span class="html-italic">t</span>-test (vs. without rGal-2).</p>
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<p>The structure and circular dichroism (CD) spectra of Gal-2 at various pH. (<b>a</b>) The structure of the hGal-2 dimer with lactose (PDB: 1HLC) shown using a ribbon diagram. The β-sheet is colored in blue. (<b>b</b>) CD spectra of rGal-2 (0.5 mg/mL) at pH 7.4, 6.0, and 5.0.</p>
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<p>Lipopolysaccharide (LPS) from <span class="html-italic">Helicobacter pylori</span> contains a Lewis antigen. (<b>a</b>) A schematic representation of the Lewis antigen contained in <span class="html-italic">H. pylori</span> LPS and <span class="html-italic">N</span>-acetyllactosamine (LacNAc). The β-galactoside structures are surrounded by red dotted lines. (<b>b</b>) The silver staining of LPS extracted from <span class="html-italic">H. pylori</span> (ATCC43504) using the hot aqueous phenol extraction method. The lyophilized LPS extract was applied to the lanes of a sodium dodecyl sulfate–polyacrylamide gel and electrophoresed. The gel was silver-stained after treatment with periodic acid. (<b>c</b>) Western blotting of LPS extract from <span class="html-italic">H. pylori</span> using anti-lacto-<span class="html-italic">N</span>-fucopentaose I (H type I) and anti-SSEA1 (Lewis X) antibodies. (<b>d</b>) Western blotting of LPS extract from <span class="html-italic">H. pylori</span> after affinity chromatography using an hGal-2-immobilized column. After washing with phosphate-buffered saline containing 1 mM EDTA (E-PBS) (Fraction Nos. 1–6), the bound materials were specifically eluted with 0.1 M lactose (Fraction No. 7, 8).</p>
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<p>The structural stability of Gal-3 and its interacting Lewis antigens. (<b>a</b>) The structure of the galectin domain of hGal-3 with lactose (PDB: 1KJL) shown using a ribbon diagram. The β-sheet is colored in blue. (<b>b</b>) Circular dichroism (CD) spectra of hGal-3 (0.2 mg/mL) at various pH. (<b>c</b>) Western blotting of lipopolysaccharide (LPS) extract from <span class="html-italic">Helicobacter pylori</span> after affinity chromatography using an hGal-3-immobilized column. After washing with E-PBS (Fraction Nos. 1–6), the bound materials were specifically eluted with 0.1 M of lactose (Fraction Nos. 7, 8).</p>
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<p>A schematic diagram of the potential biological defense mechanisms against <span class="html-italic">Helicobacter pylori</span> infection by Gal-2 and Gal-3 in the stomach. The aggregation effects of Gal-2 and Gal-3 against <span class="html-italic">H. pylori</span> in the stomach are shown.</p>
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13 pages, 1635 KiB  
Article
Optical Biosensor Based on Porous Silicon and Tamm Plasmon Polariton for Detection of CagA Antigen of Helicobacter pylori
by Guoguang Rong, Alexey Kavokin and Mohamad Sawan
Sensors 2024, 24(16), 5153; https://doi.org/10.3390/s24165153 - 9 Aug 2024
Viewed by 574
Abstract
Helicobacter pylori (H. pylori) is a common pathogen with a high prevalence of infection in human populations. The diagnosis of H. pylori infection is critical for its treatment, eradication, and prognosis. Biosensors have been demonstrated to be powerful for the rapid [...] Read more.
Helicobacter pylori (H. pylori) is a common pathogen with a high prevalence of infection in human populations. The diagnosis of H. pylori infection is critical for its treatment, eradication, and prognosis. Biosensors have been demonstrated to be powerful for the rapid onsite detection of pathogens, particularly for point-of-care test (POCT) scenarios. In this work, we propose a novel optical biosensor, based on nanomaterial porous silicon (PSi) and photonic surface state Tamm Plasmon Polariton (TPP), for the detection of cytotoxin-associated antigen A (CagA) of H. pylori bacterium. We fabricated the PSi TPP biosensor, analyzed its optical characteristics, and demonstrated through experiments, with the sensing of the CagA antigen, that the TPP biosensor has a sensitivity of 100 pm/(ng/mL), a limit of detection of 0.05 ng/mL, and specificity in terms of positive-to-negative ratio that is greater than six. From these performance factors, it can be concluded that the TPP biosensor can serve as an effective tool for the diagnosis of H. pylori infection, either in analytical labs or in POCT applications. Full article
(This article belongs to the Special Issue Optical Biosensors and Applications)
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<p>The PSi TPP biosensor structure and its optical measurement configuration. The Au NPs embedded in the first LP PSi layer means that Au NP can infiltrate into the nanopores of porous silicon. The picture on the bottom left shows the setup of the 12 × 8 biosensor array and its sequential measurement by an in-house developed equipment mainly consisting of a two-dimensional moving stage to carry and position the sensor array and a fiber spectrometer to take the optical measurement.</p>
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<p>(<b>a</b>) Cross-sectional scanning electron microscopy image of the TPP biosensor structure. The periodic layered structure of the porous silicon DBR is clearly visible. The gold thin film is the bright layer on top of the porous silicon DBR with the thickness not to scale due to a focusing issue; (<b>b</b>) atomic force microscopy image of a Au thin film surface morphology, showing the nanoporous structure of Au due to conformal deposition onto porous silicon; (<b>c</b>) Color map of electrical field strength distribution profile of TPP biosensor simulated by COMSOL V5.5. The field peak resides in the first (or top) PSi layer close to the thin metal film. Light is incident from the left side of the TPP device in air with a power of 1 W/m; (<b>d</b>) An example of the reflection spectrum of the TPP device is that of where the resonant state manifests as the reflection minimum at a wavelength of around 730 nm; (<b>e</b>) Example of the redshift of the TPP resonance wavelength upon the specific biomolecular binding of 3 ng/mL CagA antigen with the CagA antibody immobilized on the biosensor surface beforehand. The spectrum of the TPP biosensor both before (solid curve) and after (dashed curve) binding is shown. The redshift of the resonance minimum, indicated as arrows, is around 360 pm. (<b>f</b>) Example TPP resonance spectra upon exposure to PBS buffer with CagA antibody immobilized on the biosensor surface beforehand. The spectrum of the TPP biosensor both before (solid curve) and after (dashed curve) PBS is shown. The shift of resonance minimum, indicated as arrows, is 0 pm.</p>
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<p>Response characterization of CagA antigen detection for detecting varying concentrations of CagA antigen in the PBS buffer, with both PSi TPP (black circles) and PSi DBR (grey circles) biosensors. Error bars on the experimental data points (solid circle) show a standard error from five experiments, with each experiment using a different biosensor. The linear fittings (dashed curves) are performed to match the data points. The linear equations go through the origin and the quality of the fitting is also given in the figure.</p>
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<p>Specificity test and competitivity test of the PSi TPP biosensor with the objective of CagA antigen detection. CagA has a concentration of 1 ng/mL and all other nonspecific species concentrations of 5 ng/mL. Error bars on the experimental data bars (solid rectangle) show the standard error from five experiments, with each experiment using a different biosensor.</p>
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