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Children with cerebral palsy (CP) frequently have associated disorders and complications, including gastrointestinal problems. Helicobacter pylori is a common infection worldwide, frequently associated with gastrointestinal manifestations. To estimate the prevalence of H. pylori infection in children with CP , a cross-sectional study over an eight-month period was performed in the pediatric neurology outpatient clinic of Tanta University Hospital. The study included 100 patients with CP aged two to 17 years. All patients were tested for H. pylori antigen in stool by enzyme-linked immunosorbent assay. The mean age of studied children with CP was 7.03 ± 4.1 years; there were 57 males and 43 females. Spastic quadriplegic CP was the most common type of CP (34%). Forty-five children with CP were positive for H. pylori antigen in stool. Intellectual disability (ID), low sociodemographic scoring system, semisolid diet, and Eating and Drinking Ability Classification System (EDACS) levels 4 and 5 were significant predictors of H. pylori infection (odds ratio of 1.86, 2.63, 12, and 1.77, respectively, P < 0.05). Vomiting, abdominal pain, and gastrointestinal tract bleeding were significantly more frequent in H. pylori -infected children with CP than noninfected children with CP (P value < 0.05) H. pylori is a relatively common infection among children with CP. The main risk factors for H. pylori infection were low socioeconomic level, ID, semisolid diet, and EDACS levels 4 and 5. [ABSTRACT FROM AUTHOR]

Toll-like receptor (TLR)-mediated sensing of microbial molecular patterns and corresponding signaling is one of the major innate immune mechanisms against intruding pathogens. TLRs also play a major role in innate and adaptive immune responses against Helicobacter pylori. Understanding of molecular masking by H. pylori for manipulating or diverting the TLR signaling and effector mechanisms is a key element to pinpoint survival and persistence strategies by this bacterium. Masking of canonical TLR4 and TLR5 agonists with structures of advantageous characteristics gives more flexibility to H. pylori in modulating host immune responses and thereby reducing the challenges from the host and other environmental factors. Immune responses against H. pylori are balanced between pro- and anti-inflammatory reactions, an equilibrium that is affected by both the bacteria and the host. The available data on this balance can at least partially explain the clinical outcome of infection, inhibition of bacterial clearance, and resolution of inflammation. Helicobacter pylori is a paradigm of chronic bacterial infection and is associated with peptic ulceration and malignancies. H. pylori uses specific masking mechanisms to avoid canonical ligands from activating Toll-like receptors (TLRs), such as lipopolysaccharide (LPS) modification and specific flagellin sequences that are not detected by TLR4 and TLR5, respectively. Thus, it was believed for a long time that H. pylori evades TLR recognition as a crucial strategy for immune escape and bacterial persistence. However, recent data indicate that multiple TLRs are activated by H. pylori and play a role in the pathology. Remarkably, H. pylori LPS, modified through changes in acylation and phosphorylation, is mainly sensed by other TLRs (TLR2 and TLR10) and induces both pro- and anti-inflammatory responses. In addition, two structural components of the cag pathogenicity island-encoded type IV secretion system (T4SS), CagL and CagY, were shown to contain TLR5-activating domains. These domains stimulate TLR5 and enhance immunity, while LPS-driven TLR10 signaling predominantly activates anti-inflammatory reactions. Here, we discuss the specific roles of these TLRs and masking mechanisms during infection. Masking of typical TLR ligands combined with evolutionary shifting to other TLRs is unique for H. pylori and has not yet been described for any other species in the bacterial kingdom. Finally, we highlight the unmasked T4SS-driven activation of TLR9 by H. pylori , which mainly triggers anti-inflammatory responses. [ABSTRACT FROM AUTHOR]

A novel MIP-based electrochemical sensing platform was developed for the ultrasensitive detection of vacuolating cytotoxin A (VacA) toxin of H. pylori bacteria. VacA virulence factor is majorly involved in H. pylori -associated pathogenesis and plays a vital role in the establishment of bacteria inside host gastric cells. Herein, we have developed a SiO 2 nanoparticle decorated imprinting polymer-based sensing platform on a screen printed electrode (SPE) that is attributed as a receptor of VacA protein. The molecularly imprinted polymer has been developed by a polymerization process directly over the screen-printed electrode using template VacA antigen and the performance of the fabricated electrode was studied electrochemically. Under the optimized experimental conditions the fabricated VacA-MIP/SiO 2 @SPE sensor exhibits high sensitivity (0.304 mA ng−1 ml−1) and a very low limit of detection (0.01 ng ml−1) in a 0.01–100 ng ml−1 linear range. The influence of various other possible interferents in analytical response has also been observed with the successful determination of VacA antigen. [Display omitted] • Molecular imprinting based electrochemical sensor was designed to detect VacA. • H. pylori -specific VacA toxin used as a template to develop imprinted polymers. • The SiO 2 nanoparticles coated screen printed electrode used as sensing platform. • The performance of biosensor was investigated by electrochemical characterization. • Developed biosensor exhibits high sensitivity with 0.01 ng/ml detection limit. [ABSTRACT FROM AUTHOR]

Laryngopharyngeal reflux-associated symptoms embrace a wide variety of head and neck manifestations. Its participation in eye disorders has recently been postulated, and there is currently no consensus in this regard. The aim of this manuscript is to review the role of reflux in the development of ocular signs and symptoms, and its physio-pathological mechanisms. A systematic approach based on the preferred reporting Items for a systematic review and meta-analysis checklist with a modified population, intervention, comparison, and outcome framework was used to structure the review process of studies that evaluated the possible association, with clear diagnostic methods, of laryngopharyngeal reflux and ocular signs and symptoms. Search was conducted in different indexed databases (PubMed/MEDLINE, the Cochrane Library, Scielo and Web of Science) and through the meta-searcher Trip Database with the keywords: reflux, laryngitis, laryngopharyngeal, gastroesophageal, ocular, eye, symptoms, signs, conjunctivitis, keratitis, dacryocystitis, dry eye. Seven studies met the inclusion criteria, in which the primary acquired nasolacrimal duct obstruction and the ocular surface disease were evaluated. The local increase of eye pepsin concentration (>2.5 ng/mL) may affect ocular surface though its direct proteolytic activity and the local expression of proinflammatory cytokines. The H. Pylori , with a similar mechanism to reach the lacrimonasal duct, would be associated with the release of proinflammatory and vasoactive substances that would lead to a mucosa injury and chronic inflammation. Ocular Surface Disease Index seems to correlate directly with the reflux severity, with cut-off of 41.67 score as predictor for disease. The role of laryngopharyngeal reflux in the development of ocular disorders has not yet been demonstrated and data are limited and heterogeneous. It seems theoretically conceivable that pepsin may reach lachrymal duct area through hypopharyngeal-nasal gaseous reflux events. Future studies using objective testing for diagnosis and pepsin detection into the tear and nasal mucosa are needed in order to explore this potential relationship. [ABSTRACT FROM AUTHOR]

H. pylori infection is a common bacterial infection worldwide, but its prevalence varies widely between different regions and populations. The objective of this study was to determine the prevalence of H. pylori infection and associated risk factors among HIV-positive and HIV-negative individuals in northern Ethiopia. A cross-sectional study was conducted from June to September 2020 in four randomly selected health facilities located in the Tigray region of Ethiopia. A total of 463 study participants were enrolled, of whom 288 were HIV-positive and 175 were HIV-negative individuals. H. pylori stool antigen tests were performed to detect H. pylori infection. Additionally, CD4+ T cell counts were measured from only a certain number of participants. The overall prevalence of H. pylori infection among enrolled study participants was 39.7 %. Notably, the H. pylori infection rate was significantly higher in HIV-positive patients (43.4 %) compared to HIV-negative individuals (33.7 %); χ2 = 4.27, p = 0.039. Higher H. pylori prevalence was observed in participants with higher CD4+ T cell counts in both HIV-positive and HIV-negative individuals. Khat chewing habit, education, and monthly income levels were significantly associated with H. pylori infection in HIV-negative individuals, while the association between Body mass index (BMI) and H. pylori infection was observed in HIV-positive patients, but not HIV-negative individuals. This study demonstrates a higher prevalence of H. pylori infection in HIV-positive patients compared to HIV-negative individuals, emphasizing the importance of comprehensive diagnostics, patient care, and management of H. pylori infection in HIV-positive individuals. [ABSTRACT FROM AUTHOR]

1-(2-((4-Bromophenyl)amino)-2-oxoethyl)pyridin-1-ium chloride Schiff base (CH-Py) was prepared via reacting (CH) with pyridine-3-carboxaldehyde, followed by reacting the product with N -(4-bromophenyl)-2-chloroacetamide. The structure of the resulting CH derivative was determined via 1HNMR and FTIR. The CH-Py derivative was converted into nanoparticles (CH-Py-Cl NPs) using sodium tripolyphosphate (TPP). Additionally, the nanocomposites (CH-Py-Cl NPs) were prepared discretely by dispersion of 3.0 % Se and 3.0 % Fe 2 O 3 nanoparticles into the CH-Py-Cl NPs matrix to derive the products denoted as CH-Py-Cl/Se and CH-Py-Cl/Fe, respectively aiming to develop innovative effective chitosan Schiff base nanocomposites towards H. pylori. Anti- H. pylori activity of CH-Py-Cl NPs, CH-Py-Cl/Fe, and CH-Py-Cl/Se were found to be at a minimal inhibitory concentrations MIC value of 62.5, 31.25, and 15.62 μg/mL, indicating that CH-Py-Cl/Se possessed the highest biological activity in our investigation. Finally, the CH-Py-Se-NPs nanocomposite was examined for its in vitro cytotoxicity against colon cancer cell lines (Caco-2). The results obtained indicated that the developed CH-Py-Cl/Se showed toxic effects on Caco-2 cells, with an IC 50 value of 124.52 ± 1.15 μg/mL. [ABSTRACT FROM AUTHOR]

Previous studies have linked Helicobacter pylori infection with pancreatic diseases, including cancer. To explore the influence of pomegranate exocarp extract (PEE) on epithelial-mesenchymal transition (EMT) in H. pylori -induced pancreatic rat tissue and to uncover the underlying molecular mechanisms. Twenty-eight rats were divided into six groups: group 1 (negative control), group 2 (H. pylori- infected), group 3 (infected + PEE pretreatment), group 4 (infected + PEE treatment), group 5 (infected + metronidazole treatment), and group 6 (infected + metronidazole/PEE co-treatment). This study aimed to assess the effectiveness of pomegranate exocarp extract (PEE) in treating Helicobacter pylori infection and its associated pancreatic tissue changes in Wistar rats. The study involved Forty-eight male rats divided into six groups: H. pylori -infected control, PEE-preventive, PEE treatment, metronidazole treatment, PEE combined with metronidazole treatment, and negative control. The results showed a significant reduction in H. pylori concentration in the antrum in the PEE-treated groups (27.08 %) compared to that in the positive control group (p < 0.05). The group receiving the combined treatment exhibited the highest reduction (55.8 %) in H. pylori concentration (p < 0.005), with no significant difference observed between the PEE-preventive and metronidazole-treated groups. The ELISA results showed that the groups treated with PEE, PEE-preventive, and PEE combined with metronidazole experienced a significant increase in pancreatic E-cadherin levels by 47.7 %, 73.8 %, and 118.06 % respectively, and a substantial decrease in vimentin levels by 16.6 %, 31.6 %, and 43.5 % respectively, compared to the positive control group (p < 0.05). The results of the RT-qPCR analysis showed that the PEE treatment group, as well as the PEE preventive and PEE combined with metronidazole treatment groups, displayed significant downregulation of vimentin, sirtuin1, and lncRNA MALAT-1, and upregulation of E-cadherin compared to the positive control group. However, there was no significant difference between the PEE-preventive and metronidazole-treated groups (p < 0.05). Histopathological analysis showed considerable improvement in pancreatic tissue morphology in the PEE-treated groups. The inflammation score was significantly lower in these groups (p < 0.05), and the combined treatment group exhibited minimal signs of metaplasia and mononuclear cell infiltration. A computational study identified 54 human target genes of bioactive compounds in PEE. These findings shed light on the crucial interactions and pathways in treating pancreatic tumors. Additionally, GO enrichment and KEGG pathway analyses revealed significant pathways, such as the MAPK signaling and RTK pathway, enriched with genes targeted by PEE. Furthermore, evaluation of drug-likeness and ADME properties indicated that ellagic acid possesses drug-like properties and has a high potential for oral absorption. In conclusion, PEE has shown significant therapeutic potential in reducing H. pylori load and improving pancreatic tissue health while influencing key molecular markers and pathways associated with pancreatic tumors. [Display omitted] • The study aimed to investigate the impact of pomegranate exocarp extract (PEE) on epithelial-mesenchymal transition (EMT) in H. pylori -induced pancreatic rat tissue and elucidate the underlying molecular mechanisms. • PEE administration, alone or with metronidazole, significantly reduced H. pylori concentration in the antrum of infected rats. • E-cadherin expression and concentration significantly increased with PEE treatment, alone or combined with metronidazole. • PEE inhibits EMT in H. pylori -induced pancreatic rat tissue, possibly through sirtuin1 inhibition and lncRNA MALAT-1 downregulation. [ABSTRACT FROM AUTHOR]

Helicobacter pylori infection is very common and affects more than one-third of adults in Italy. Helicobacter pylori causes several gastro-duodenal diseases, such as gastritis, peptic ulcer and gastric malignancy, and extra-gastric diseases. The eradication of the bacteria is becoming complex to achieve due to increasing antimicrobial resistance. To address clinical questions related to the diagnosis and treatment of Helicobacter pylori infection, three working groups examined the following topics: (1) non-invasive and invasive diagnostic tests, (2) first-line treatment, and (3) rescue therapies for Helicobacter pylori infection. Recommendations are based on the best available evidence to help physicians manage Helicobacter pylori infection in Italy, and have been endorsed by the Italian Society of Gastroenterology and the Italian Society of Digestive Endoscopy. [ABSTRACT FROM AUTHOR]

Cag type IV secretion system (CagT4SS) translocates oncoprotein cytotoxin-associated gene A (CagA) into host cells and plays a key role in the pathogenesis of Helicobacter pylori. The structure of the outer membrane core complex (OMCC) in CagT4SS consists of CagX, CagY, CagM, CagT, and Cag3 in a stoichiometric ratio of 1:1:2:2:5 with 14-fold symmetry. However, the assembly pathway of OMCC remains elusive. Here, we report the crystal structures of CagT and Cag3-CagT complex, and the structural dynamics of Cag3 and CagT using hydrogen deuterium exchange-mass spectrometry (HDX-MS). The interwoven interaction of Cag3 and CagT involves conformational changes of CagT and β strand swapping. In conjunction with biochemical and biophysical assays, we further demonstrate the different oligomerization states of Cag3 and Cag3-CagT complex. Additionally, the association with CagM requires the pre-formation of Cag3-CagT complex. These results demonstrate the generation of different intermediate sub-assemblies and their structural flexibility, potentially representing different building blocks for OMCC assembly. [Display omitted] • Cag3-CagT complex formation involves a CagT conformational change and β strand swapping • Multiple oligomerization equilibria are observed for Cag3 and Cag3-CagT complex • An assembly model of OMCC peripheral components is proposed The Cag type IV secretion system (CagT4SS) is critical for the virulence of Helicobacter pylori. Mok et al. report a conformational change of CagT upon Cag3 binding and the formation of different sub-assemblies of the outer membrane core complex. These findings provide insights into the assembly and dynamics of CagT4SS. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) infection is highly prevalent worldwide, affecting more than 43% of world population. The infection can be transmitted through different routes, like oral-oral, fecal-oral, and gastric-oral. Electrochemical sensors play a crucial role in the early detection of various substances, including biomolecules. In this study, the development of nanobody (Nb)-based immunosensor for the detection of H. pylori antigens in saliva samples was investigated. The D2_Nb was isolated and characterized using Western blot and ELISA and employed in the fabrication of the immunosensor. The sensor was prepared using gold screen-printed electrodes, with the immobilization of Nb achieved through chemical linkage using cysteamine-glutaraldehyde. The surface of the electrode was characterized using EIS, FTIR and SEM. Initially, the Nb-based immunosensor's performance was evaluated through cyclic voltammetry (CV), differential pulse voltammetry (DPV), and square wave voltammetry (SWV). The sensor exhibited excellent linearity with an R2 value of 0.96. However, further assessment with the DPV technique revealed both a low limit of detection (5.9 ng/mL, <1 cfu/mL) and high selectivity when exposed to a mixture of similar antigens. Moreover, the immunosensor demonstrated robust recovery rates (96.2%–103.4%) when spiked into artificial saliva and maintained its functionality when stored at room temperature for 24 days. [ABSTRACT FROM AUTHOR]

Mycobacterium bovis (M. bovis) Bacillus Calmette-Guerin (BCG) strain used in immunotherapy of bladder cancer (onco-BCG) due to its acid tolerance can be a candidate for prevention or reversion of deleterious effects towards gastric cell barrier initiated by gastric pathogen Helicobacter pylori (Hp) with high resistance to commonly used antibiotics. Colonization of gastric mucosa by Hp promotes oxidative stress, apoptosis resulting in the gastric barrier damage. The aim of this study was to examine the ability of onco-BCG bacilli to control the Hp driven gastric damage using the model of Cavia porcellus primary gastric epithelial cells or fibroblasts in vitro. These cells were treated with Hp surface antigens (glycine acid extract-GE or lipopolysaccharide-LPS) alone or with onco-BCG bacilli and evaluated for cell apoptosis and proliferation in conjunction with the level of soluble lipid peroxidation marker (s4HNE). The cell migration was determined by "wound healing assay", while cytokine response of cells, including interleukin (IL)-33, IL-1β, IL-8 and tumor necrosis factor alpha (TNF-α), by the ELISA. The apoptosis of cells pulsed in vitro with Hp surface components present in GE or with LPS was reduced after exposure of cells to mycobacteria. Similarly, the cell regeneration which was diminished by Hp LPS has been improved in response to mycobacteria. This study reveals that vaccine mycobacteria may reduce gastric barrier damage induced by Hp infection. [ABSTRACT FROM AUTHOR]

With the apparent stagnation in the antibiotic discovery and the propagation of multidrug resistance, Helicobacter pylori associated gastric infections are hard to eradicate. In pursuance of alternative medicines, in this study, covalent modification of chitosan (CS) polymer with curcumin (Cur) was accomplished. Proton Nuclear Magnetic Resonance and Fourier Transform Infrared spectroscopy elucidated the covalent interaction between Cur and CS with characteristic peak of imine functional group (C=N). Scanning Electron Microscopy provided visual proof for surface topology, while size and zeta potential values further affirmed the development of curcumin functionalized chitosan nanosystems (Cur-FCNS). The complexation efficiency of CS with Cur was found as 70 ± 3% at an optimal ratio of 5:1 for CS and Cur, respectively. Cur-FCNS developed with ionic gelation and ultrasonication method demonstrated synergistic anti- H. pylori activity in growth-kinetics and anti-biofilm assays, which was superior to free Cur and even chitosan nanosystems. Under simulated gastric conditions, Cur-FCNS revealed cumulative-release of only 16 ± 0.8% till 40 h, which indicated its improved stability to interact with H. pylori. In silico findings affirmed high binding affinity of Cur-FCNS with multiple bacterial virulence factors. Thus, our results affirmed the exceptional potential of Cur-FCNS as next-generation alternative-medicine to treat resistant H. pylori. • Covalent modification of chitosan polymer with curcumin (Cur) was accomplished. • NMR and FTIR data revealed the successful conjugation of curcumin and chitosan. • Cur-FCNS inhibited the growth of gastric pathogens in planktonic state. • Effective antibiofilm activity of Cur-FCNS: Preventive and therapeutic potential. [ABSTRACT FROM AUTHOR]

Two chitosan Schiff bases were synthesized by condensation of chitosan with 2-(4-formylphenoxy)- N -phenylacetamide and N -(4-bromophenyl)-2-(4-formylphenoxy) acetamide denoted as Cs-SBA and Cs-SBBr, respectively. The molecular structures of the resulting chitosan derivatives were characterized using FTIR and 1HNMR and their thermal properties were investigated by TGA. These derivatives were treated with sodium tripolyphosphate (TPP) to produce Cs Schiff base nanoparticles. The nanoparticles physicochemical properties were determined by FTIR, XRD, TEM, and zeta potential analysis. The antimicrobial action against Helicobacter pylori (H. pylori) was evaluated and the results indicated that the anti- H. pylori activity had minimal inhibitory concentration MIC values of 15.62 ± 0.05 and 3.9 ± 0.03 μg/mL for Cs-SBA and Cs-SBBr nanoparticles (Cs-SBA NPs and Cs-SBBr NPs), respectively. The better biologically active nanoparticles, Cs-SBBr NPs, were tested for their cyclooxygenases (COX-1 and COX-2) inhibitory potential. Cs-SBBr NPs demonstrated COX enzyme inhibition activity against COX-2 (IC 50 4.5 ± 0.165 μg/mL) higher than the conventional Indomethacin (IC 50 0.08 ± 0.003 μg/mL), and Celecoxib (IC 50 0.79 ± 0.029 μg/mL). Additionally, the cytotoxicity test of Cs-SBBr NPs showed cytotoxic effect on Vero cells (CCL-81) with IC 50 = 17.95 ± 0.12 μg/mL which is regarded as a safe compound. Therefore, Cs-SBBr NPs may become an alternative to cure H. pylori and prevent gastric cancer. [ABSTRACT FROM AUTHOR]

Peptic ulcer is a sore on the stomach lining that results from the erosion of the gastrointestinal tract mucosa due to various influencing factors. Of these, Helicobacter pylori infection and non-steroidal anti-inflammatory drugs (NSAIDs) stand out as the most prominent causes. This condition poses a significant global health concern due to its widespread impact on individuals worldwide. While various treatment strategies have been employed, including proton pump inhibitors and histamine-2 receptor antagonists, these have notable side effects and limitations. Thus, there is a pressing need for new treatments to address this global health issue. Rutin, a natural flavonoid, exhibits a range of biological activities, including anti-inflammatory, anticancer, and antioxidant properties. This review explores the potential anti-ulcer effect of rutin in experimental models and how rutin can be a better alternative for treating peptic ulcers. We used published literature from different online databases such as PubMed, Google Scholar, and Scopus. This work highlights the abundance of rutin in various natural sources and its potential as a promising option for peptic ulcer treatment. Notably, the anti-inflammatory properties of rutin, which involve inhibiting inflammatory mediators and the COX-2 enzyme, are emphasized. While acknowledging the potential of rutin, it is important to underscore the necessity for further research to fully delineate its therapeutic potential and clinical applicability in managing peptic ulcers and ultimately improving patient outcomes. This review on the anti-ulcer potential of rutin opened a new door for further study in the field of alternative medicine in peptic ulcer management. [Display omitted] • Rutin, a natural flavonoid, exhibits anti-inflammatory, anticancer, and antioxidant properties. • Rutin may attenuate peptic ulcers by inhibiting inflammation, suppressing oxidative stress, and eliminating H. pylori. • Further research is needed to confirm rutin's therapeutic efficacy for peptic ulcers in humans. [ABSTRACT FROM AUTHOR]

Helicobacter pylori and intestinal parasites cause gastrointestinal diseases with a high prevalence in children in resource limited developing countries. There is paucity of information in Nigeria on co-infection of H. pylori and intestinal parasites. The study was conducted to determine the prevalence of H. pylori and parasite co-infection in children from selected low-income communities in Lagos, Nigeria. Fecal samples were collected from 151 healthy children aged ≤11 years across six low-income communities in Lagos. H. pylori was detected using stool antigen test and conventional PCR assay, intestinal parasites were detected using formol-ether concentration and nested PCR assay. Structured questionnaires were administered to parents and legal guardians of the children by an interviewer to collect relevant data on demographic and lifestyle factors. The prevalence of H. pylori was 31.79% (48), with a higher prevalence in children aged 2–3 years. The prevalence of intestinal parasites was 21.19% (32) with the lowest frequency found in children aged 8–9 years. The parasites detected include: A. lumbricoides (10.6%), G. intestinalis (7.3%), hookworm (1.99%), E. histolytica (0.66%), S. mansoni (0.66%). There was co-infection prevalence of 10.6% (16) which was associated with the parasites: G. intestinalis (7.3%) and A. lumbricoides (3.97%). Polyparasitism with G. intestinalis and A. lumbricoides was reported in 2 children infected with H. pylori. This study which is the first reported in Lagos established a low prevalence of H. pylori and intestinal parasite co-infection in children and provides better understanding of the epidemiology of H. pylori infection associated with intestinal parasites in Nigeria. [Display omitted] • This is the first study on H. pylori and parasite co-infection in children in Lagos. • H. pylori co-infection more with Giardia intestinalis and Ascaris lumbricoides. • Polyparasitism (G. intestinalis and A. lumbricoides) with H. pylori was found. [ABSTRACT FROM AUTHOR]

• Synthesis of ten new hydrazone derivatives and the structures were confirmed by 1H NMR, 13C NMR and elemental analysis. • All compounds were evaluated for in vitro urease inhibitory and anti- H. pylori activities. • The effects of the synthesized compounds against two different gastric cancer cell lines (SNU1 and AGS) were also evaluated. • Compounds 3c and 3f proved to be most active urease inhibitors and anticancer activity. • Compounds 3c and 3d were found to be the most active in the series against H. pylori with MIC values 4 µg/mL and 5 µg/mL. In this study, new hydrazone derivatives were synthesized by taking into account the virulence factor of the urease in the urease-positive microorganism H. pylori. The structure of synthesized compounds 3a-3j was confirmed using 1H NMR, 13C NMR and elemental analyses. After structure confirmations all compounds were evaluated for in vitro urease inhibitory and anti- H. pylori activities. Furthermore, since H. pylori infection is associated with gastric cancer, the effects of the synthesized compounds against two different gastric cancer cell lines (SNU1 and AGS) were also evaluated. Amongst the series, two compounds 3c and 3j were found to be excellent inhibitors of urease, having IC 50 values of 9.813 ± 0.403 µM and 11.407 ± 0.393 µM, better than the standard thiourea (IC 50 = 13.428 ± 0.587 µM), whereas the remaining compounds displayed moderate activity. Compounds 3c and 3d were found to be the most active in the series against H. pylori with MIC values 4 µg/mL and 5 µg/mL. Next, compounds were evaluated as anti-gastric cancer activity and the compounds 3c and 3j were more potent than reference drug cisplatin against SNU1 and AGS. The docking study was executed to analyzed the interaction between the active site of the urease and the compounds 3c and 3j. When the all activities (anti- H. pylori , anti-urease and anti-gastric cancer activities) examined, it was found that the presence of the nitro group, which is an electron withdrawing group, in the 5th position of the thiophene ring (compound 3c) increased all activities. From the structure-activity relationship, it has been observed that the compound 3c showed excellent potential for anti- H. pylori , anti-gastric cancer and can be alternative therapy in the future. [Display omitted] [ABSTRACT FROM AUTHOR]

• A 3D-printed gastric model developed in this research combines biomimetic properties, including fold structures, flexibility, and fluid dynamics. • The rugae structure of the 3D model was effective in shielding bacteria and cancer cells from fluid stress and drugs. • This gastric model, crafted through our study, is a promising platform for drug development due to its biomimetic properties. The in vitro biomimetic digestive system simulating the digestive tract environment of animals and humans is necessary for research on drug development, food ingestion, and digestion processes. However, most current digestive models do not present the surface structures of a human stomach, the mechanical properties and fluid dynamics at the same time. In this study, a gastric model was fabricated by photo-curing 3D printing, where the mechanical strength, topographical cues, surface chemistry, and fluid dynamics were biocompatible. A gastric simulation system was assembled with soft and flexible photoresin having biomimetic mechanical strength. The gastric rugae were then replicated by 3D printing on the surface of gastric models, followed by designing the fluid dynamic based on the flow of in vivo gastric juice. Due to the combination of gastric flexibility, rugae morphology, fluid dynamics, and gastric juice emptying behavior, a highly biomimetic gastric model was created. The model was examined with antibiotic and anticancer drugs, where H. pylori and gastric cancer cells, MKN-45, were cultured on model surfaces. The survival rates of H. pylori and MKN-45 on 2D/3D models were systematically evaluated. The cultured bacteria and cells presented more biomimetic responses to drugs, compared to conventional in vitro tests for gastric diseases. The overestimated therapeutic activity in convectional 2D models was modified using the gastric model developed in this research. [Display omitted] [ABSTRACT FROM AUTHOR]

• H. pylori may trigger aneurysm by inducing miR-155 and apoptosis in ECs. • Upregulated miR-21 in ECs by L. acidophilus may prevent initiation of AAA. • H. pylori increased the level of miR-326 and 663 in ECs, co-cultured with PBMCs. • The effect of L. acidophilus on ECs was different in the presence or absence of PBMCs. • H. pylori and L. acidophilus seems to be comparable to enhance the late stages of aneurysm. Regarding the role of micro RNAs (miRNA) in the proliferation and differentiation of T cells as well as the controversy around the role of bacteria in the pathogenesis of abdominal aortic aneurysm (AAA), the effects of Helicobacter pylori (Hp) and Lactobacillus acidophilus (La) were investigated in the induction of miRNAs and apoptosis in CD4+ memory T (Tem) cells of AAA patients and controls. Signature atherosclerosis miRNAs 21, 92a, 146a, 155, 326 and 663 were measured in the sera and tissues of AAA patients and control. PBMCs separately and in co-culture with HUVEC were treated with Hp -water-extract (HpWE) and La-conditioned-medium (LaCM). Apoptosis and miRNA levels were assessed in the isolated Tem by flowcytometry and real-time-PCR. In single-culture, HpWE increased apoptosis and miR-155 and LaCM decreased apoptosis and increased miR-21. In co-culture, apoptosis decreased in both groups in response to CagA+HpWE. Also, all miRNAs increased in patients Tem but in controls, only miR- 146a and 21 showed changes. Although, apoptosis was similar in Tem of patients and controls, the effects of Hp and La were different on the induction of apoptosis and miRNAs and also these bacteria showed different impacts in single and co-culture conditions. Beyond the direct effects of these bacteria on the pathogenesis of diseases, their effects on miRNAs expression may shed light on their roles in the development and the prevention of AAA. [ABSTRACT FROM AUTHOR]

• A decreasing trend in the efficacy of rifabutin-based therapy was detected, particularly when clarithromycin resistance was present. • Our data confirm Pylera® regimen as a reliable option to successfully treat eradication failure patients. Indeed, the eradication rates are steadily high (90%) until the fourth-line attempt. • These findings would suggest that the role of rifabutin-based regimen as rescue therapy should be at least reconsidered, and its use reserved to selected patients. • Unfortunately, Pylera® regimen is really complex and causes side-effects more frequently than other therapies. H. pylori treatment remains a challenge for clinicians, and a definite quote of patients require two or more treatments. We evaluated the efficacy of rifabutin-based therapy and Pylera® regimen as rescue therapies. Between January 2016 and December 2019, dyspeptic patients with at least one therapeutic failure observed in clinical practice received either a 12-day rifabutin-based triple therapy (esomeprazole 40 mg and amoxicillin 1 g, both twice daily, and rifabutin 150 mg once daily) or 10-day quadruple therapy with Pylera® (three in one capsule containing 140 mg bismuth subcitrate potassium, 125 mg metronidazole and 125 mg tetracycline). The eradication rates according to previous number of eradication failure therapies were calculated. The role antibiotic resistance pattern in H. pylori isolates was also investigated. Data of 423 patients were available. A total of 270 patients were treated with rifabutin-based therapy, and the overall eradication rate was 61.9%. Pylera® therapy was administered to 153 patients and the cure rate was 88.3%. According to the number of previous therapeutic failures, the eradication rate for the rifabutin-based therapy was 68.3% as second-line and further decreased to 63.1% in fourth-line therapy. Following Pylera® regimen, the cure rate was 94.8% in second-line, and remained 89.6% in fourth-line therapy. Efficacy of rifabutin-based and Pylera® therapies significantly decreased when clarithromycin and levofloxacin resistance, respectively, were present. Our data documented a decreasing trend for rifabutin-based therapy efficacy according to previous therapy failures, whilst this did not occur for Pylera®. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer in women worldwide and is associated with substantial medical and economic burden. We report the development of a hybrid immunotherapeutic system based on recombinant Nap protein from Helicobacter pylori (HP-Nap) for the treatment of breast tumors. Chitosan nanoparticles with pseudo-spherical morphology and positive zeta potential were synthesized as carriers for HP-Nap. In vitro study was performed on mouse breast cancer cell line (4T1) and human breast cancer cell lines (MCF7). In vivo study was done on 4T1 tomural mice. TUNEL assay and real time PCR test were performed on tumor mice receiving the nanoparticle treatment. The nanoparticle-protein complex induced apoptosis in vitro in cultured breast cancer cells. In-vivo studies on inbred, female BALB/c mice confirmed the shrinkage of tumor mass after administration of the nanoparticle complex containing HP-Nap. The TUNEL assay further confirmed apoptosis in extracted mouse breast cancer cells. A decrease in the expression of VEGF and MMP9 genes was observed in 4T1 cells as shown by real time PCR. Our data suggesting that the therapeutic nanocomplex may have led to decreased tumor growth in mice through changing the production rate of cytokines and increasing tumoricidal activities of the immune system. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) is classified as a class I carcinogen that colonizes the human gastrointestinal (GI) tract. The detection at low concentrations is crucial in combatting H. pylori. HopQ protein is located on H. pylori's outer membrane and is expressed at an early stage of contamination, which signifies it as an ideal biomarker. In this study, we presented the development of an electrochemical impedimetric immunosensor for the ultra-sensitive detection of HopQ at low concentrations. The sensor employed polypyrrole nanotubes (PPy-NTs) and carboxylated multi-walled carbon nanotubes (MWCNT-COOH) nanocomposite. PPy-NTs were chosen for their excellent conductivity, biocompatibility, and redox capabilities, simplifying sample preparation by eliminating the need to add redox probes upon measurement. MWCNT-COOH provided covalent binding sites for HopQ antibodies (HopQ-Ab) on the biosensor surface. Characterization of the biosensor was performed using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), contact angle measurements, and electrochemical impedance spectroscopy (EIS), complemented by numerical semiempirical quantum calculations. The results demonstrated a dynamic linear range of 5 pg/mL to 1.063 ng/mL and an excellent selectivity, with the possibility of excluding interference using EIS data, specifically charge transfer resistance and double-layer capacitance as multivariants for the calibration curve. Using two EIS components, the limit of detection is calculated to be 2.06 pg/mL. The biosensor was tested with a spiked drinking water sample and showed a signal recovery of 105.5% when detecting 300 pg/mL of HopQ. This novel H. pylori biosensor offers reliable, simple, portable, and rapid screening of the bacteria. [Display omitted] [ABSTRACT FROM AUTHOR]

H. pylori infection shows an inverse relationship with allergies. Dendritic cells regulate mucosal immune responses including the induction of T regulatory cells which are fundamental in Helicobacter pylori -induced dampening of allergies. In this respect expression of high-affinity IgE receptor (FcεRI) has been associated with a regulatory dendritic cell profile. Therefore we aimed to evaluate possible mechanisms by which H. pylori infection might modify atopy in pediatric patients. Here we show that H. pylori- infected children exhibited both increased expression of FcεRI on peripheral myeloid and plasmacytoid dendritic cells and higher levels of Foxp3 and Latency Associated Peptide on T regulatory cells. Moreover, exposure to H. pylori drove increased FcεRI expression and IL-10 secretion by both pediatric H. pylori -exposed monocyte derived dendritic cells and T cells. Finally, we show a positive correlation between expression of FcεRI in circulating myeloid DCs and total Treg cells, suggesting that in children, H. pylori infection may have a modulating role in atopy, mediated by both altered surface expression of FcεRI on children's DC and an increased T regulatory cell profile. [ABSTRACT FROM AUTHOR]

Chronic atrophic gastritis (CAG) is an underdiagnosed condition characterised by translational features going beyond the strict field of gastroenterology as it may manifest itself by a variable spectrum of gastric and extra-gastric symptoms and signs. It is relatively common among older adults in different parts of the world, but large variations exist. Helicobacter pylori -related CAG [multifocal] and autoimmune CAG (corpus-restricted) are apparently two different diseases, but they display overlapping features. Patients with cobalamin and/or iron deficiency anaemia or autoimmune disorders, including autoimmune thyroiditis and type 1 diabetes mellitus, should be offered screening for CAG. Pepsinogens, gastrin-17, and anti- H. pylori antibodies serum assays seem to be reliable non-invasive screening tools for the presence of CAG, helpful to identify individuals to refer to gastroscopy with five standard gastric biopsies in order to obtain histological confirmation of diagnosis. Patients with CAG are at increased risk of developing gastric cancer, and they should be estimated with histological staging systems (OLGA or OLGIM). H. pylori eradication may be beneficial by modifying the natural history of atrophy, but not that of intestinal metaplasia. Patients with advanced stages of CAG (Stage III/IV OLGA or OLGIM) should undergo endoscopic surveillance every three years, those with autoimmune CAG every three-five years. In patients with CAG, a screening for autoimmune thyroid disease and micronutrient deficiencies, including iron and vitamin B 12 , should be performed. The optimal treatment for dyspeptic symptoms in patients with CAG remains to be defined. Proton pump inhibitors are not indicated in hypochlorhydric CAG patients. [ABSTRACT FROM AUTHOR]

A myriad of drug-resistant strains of Helicobacter pylori and adverse drug-reactions create a big-barrier in the treatment, thereby demanding novel proof-of-concept inhibitors and breakthrough medicines. Hence, an affinity-centric protocol was devised to implement scaffold-design for 3-dehydroquinate dehydratase-II (AroQ) as a follow-up of our study against beaucoup strains. Herein, the study focuses on preferred the attractive-target methodically due to its salient features include conserving, essential and specific for H. pylori , not present in humans and gut-flora. Structural refinement, energy minimization and optimization of the developed best-model were employed with confirming active site residues around substrate. Published AroQ-inhibitors and substrate were utilized to probe an in-house library of molecules. The prepared dataset was allowed to lead-optimization campaign includes rigid-receptor docking through high-throughput virtual, standard-precision, extra-precision screening filters, quantum-polarized-ligand (quantum mechanical and molecular mechanical (QM/MM)) and induced-fit docking experiments. Convergence threshold (0.05) and Truncated Newton Conjugate Gradient (TNCG) were set in ConfGen's algorithm to produce high-quality bioactive conformations by thoroughly narrowing the conformational space accessible to the leads. ADME/Tox predictions and long-range molecular dynamics simulations were executed after post-docking evaluations. The approach provided seven ranked compounds with better scoring functions, bioactive-conformers and pharmacokinetics profiles than published ligands and substrate. Simulations revealed more consistency of lead1–AroQ complex throughout chemical time than controls in the formulated physiological milieu. The study outcomes showing the good competitive binding propensity for active-tunnel over the substrate and previous ligands, thereby these leads could be ideal for proposing as selective cutting-edge inhibitors to target AroQ specific for H. pylori strains. Image 1 • Data-mining of complete genomes of H. pylori strains resulted H. pylori specific target DHQase –II. • In lead-optimization campaign, modelling, energy-minimization, dataset and library screening were performed. • Physics based-ADME/Tox, energy-functions and bioactive-conformations were investigated for better lead-scaffolds. • Binding potencies and MD simulations revealed novel residue hotspots, bond patterns, and sustained stability of leads with target. • Through that, proposed scaffolds act as a barrier in substrate binding and leads fatal consequences in pathogen. [ABSTRACT FROM AUTHOR]

Functional dyspepsia is an exclusion diagnosis requiring different tests, including endoscopy, often repeated over time. Duodenal biopsies are frequently resorted to, not rarely revealing duodenal microscopic inflammation. Aim of the study is to confirm a previously supposed role of antro-duodenal low-grade inflammation in functional dyspepsia, evaluating the frequency of duodenal lymphocytosis, H. pylori infection and their association in a group of patients with functional dyspepsia compared to asymptomatic control subjects. A cross-sectional, observational study has been conducted screening all the patients who underwent duodenal biopsies during upper endoscopy, in a 30 months period. All the patients without endoscopic lesions were analysed. The study group consisted of patients compatible with the diagnosis of functional dyspepsia (Rome III criteria). The control group consisted of healthy asymptomatic subjects in the population subjected to endoscopy. The presence of duodenal lymphocytosis and of H. pylori infection in the two groups was evaluated. 216 patients were enrolled: 161 in the functional dyspepsia group and 55 as asymptomatic control group. The frequency of duodenal lymphocytosis was similar between cases and control groups (25.47% vs 25.45%; p = 0.99), as well as H. pylori infection (26.71% vs 23.64%; p = 0.78). Duodenal lymphocytosis was significantly associated with functional dyspepsia only in H. pylori positive dyspeptic patients (p = 0.047). 94% of the subjects with both lymphocytosis and H. pylori infection suffer from dyspepsia. Duodenal intraepithelial lymphocytosis is significantly associated with bloating (p = 0.0082). In our cohort of dyspeptic patients, duodenal lymphocytosis is significantly associated with bloating and the simultaneous presence of duodenal lymphocytosis and H. pylori infection is significantly more prevalent than in control subjects. [ABSTRACT FROM AUTHOR]

Naphthalene diimide (NDI) derivatives have been shown to exhibit promising antineoplastic properties. In the current study, we assessed the anticancer and anti-bacterial properties of di-substituted NDI derivative. The naphthalene-bis-hydrazimide, 1 , negatively affected the cell viability of three cancer cell lines (AGS, HeLa and PC3) and induced S phase cell cycle arrest along with SubG0/G1 accumulation. Amongst three cell lines, gastric cancer cell line, AGS, showed the highest sensitivity towards the NDI derivative 1. Compound 1 induced extensive DNA double strand breaks causing p53 activation leading to transcription of p53 target gene p21 in AGS cells. Reduction in protein levels of p21 and BRCA1 suggested that 1 treated AGS cells underwent cell death due to accumulation of DNA damage as a result of impaired DNA damage repair. β-catenin downregulation and consequently decrease in levels of c-Myc may have led to 1 induced AGS cell proliferation inhibition. 1 induced AGS cell S phase arrest was mediated through CylinA/CDK2 downregulation. The possible mechanisms involved in anticancer activity of 1 includes ROS upregulation, induction of DNA damage, disruption of mitochondrial membrane potential causing ATP depletion, inhibition of cell proliferation and downregulation of antiapoptotic factors ultimately leading to mitochondria mediated apoptosis. Further compound 1 also inhibited H. pylori proliferation as well as H. pylori induced morphological changes in AGS cells. These findings suggest that NDI derivative 1 exhibits two-pronged anticancer activity, one by directly inhibiting cancer cell growth and inducing apoptosis and the other by inhibiting H. pylori. Image 1 • Naphthalene diimide (NDI) derivative 1 induced S Phase arrest and Sub G0/G1 population accumulation. • DNA dsbreaks and p53 activation but downregulation of p21 and BRCA1 protein levels were mediated by NDI derivative 1. • NDI derivative 1 downregulated c-Myc levels, upregulated ROS and induced mitochondrial apoptosis. • H. pylori growth and H. pylori induced AGS cell morphological changes were inhibited by NDI derivative 1. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Because T 2 (OH)B showed large stokes shift through ESIPT process, it can be useful for fluorescent probe. • Owing to turn-on fluorescence emission behavior of T 2 (OH)B above physiological pHs, it was successfully applied for mitochondria of mammalian cells, as well as detected H. pylori adhered to mammalian cells. • Also, T 2 (OH)B displayed faster staining rates than commercially available MitoTracker red. Abstract An hydroxythiophene-conjugated benzothiazole (T 2 (OH)B) was synthesized as a pH sensitive fluorescent probe. T 2 (OH)B displayed dual emission behavior due to the excited state intramolecular proton transfer (ESIPT) process, while the methoxy analogs, T 2 (OMe)B , did not. T 2 (OH)B showed strong fluorescence enhancement above physiological pHs. The applicability of T 2 (OH)B as a biological pH indicator was demonstrated by its use for staining mitochondrial compartment and H. pylori. Owing to its strong fluorescence emission with a large stokes shift and its effective response to pH, T 2 (OH)B serves as a platform for the design of new types of fluorescent probes. [ABSTRACT FROM AUTHOR]

Abstract Anaemia is a common pathologic condition, present in almost 5% of the adult population. Iron deficiency is the most common cause; other mechanisms can be involved, making anaemia a multi-factorial disorder in most cases. Anaemia being a frequent manifestation in the diseases of the gastrointestinal tract, patients are often referred to gastroenterologists. Furthermore, upper and lower endoscopy and enteroscopy are pivotal to the diagnostic roadmap of anaemia. In spite of its relevance in the daily clinical practice, there is a limited number of gastroenterological guidelines dedicated to the diagnosis of anaemia. For this reason, the Italian Association of Hospital Gastroenterologists and Endoscopists and the Italian Society of Paediatric Gastroenterology, Hepatology and Nutrition commissioned a panel of experts to prepare a specific guideline on anaemia and its diagnostic roadmap in the gastroenterological scenario. The panel also discussed about the potential involvement of gastroenterologists and endoscopists in the management of patients with anaemia, with particular attention to the correct use of investigations. The panel paid particular attention to practical issues with the aim to support gastroenterologists in their clinical practice when dealing with patients with anaemia. [ABSTRACT FROM AUTHOR]

Abstract Neutrophil infiltration typically occurs in Helicobacter pylori (H. pylori)-induced acute gastritis; however, this immune response fails to eradicate H. pylori in vivo. Moreover, reactive oxygen species (ROS), which are generated by neutrophils, cause severe damage to gastric mucosa. Patchouli alcohol (PA) has been reported to have effective anti-oxidative and anti- H. pylori activities, and we investigated its effects on H. pylori -induced neutrophil recruitment and activation in this research. In neutrophil recruitment experiment, H. pylori was injected into rat air pouch to explore the effects of PA (10, 20 and 40 mg/kg) on acute inflammatory response. The results revealed that PA significantly reduced the weight of exudate and the number of neutrophils in the air pouch. Meanwhile, remarkable decrements in TNF-α and IL-8 levels in exudates were observed. In neutrophil activation experiment, rat neutrophils were isolated and activated by using 50 μg/mL H. pylori water-soluble surface protein with or without the treatment of PA (5, 10 or 20 μmol/L). Results indicated that PA not only significantly inhibited the production of ROS, but also reduced the gene and protein expressions of p22/p47-phoxes, and the binding of p22/p47-phoxes. Furthermore, the influence of PA on the neutrophil activation genes of H. pylori (h - nap and sabA) was investigated, and the results showed that expressions of h - nap and sabA were remarkably decreased after PA treatment. In conclusion, PA reduced the recruitment and activation of neutrophils induced by H. pylori , as shown by its inhibition of pro-inflammatory factor generation, p22/p47-phoxes function and H. pylori neutrophil activation-related gene expression. Highlights • Patchouli alcohol (PA) inhibited helicobacter pylori -induced neutrophils recruitment in rat air pouch model. • PA reduced the reactive oxygen species (ROS) generation from activated neutrophils induced by helicobacter pylori. • PA inhibited the p22phox/p47phox mRNA and protein expression and weaken the assemblage of p22phox and p47phox. [ABSTRACT FROM AUTHOR]

The production of novel natural medicines for the treatment of Helicobacter pylori (H. pylori) has lately attracted a lot of interest. Some bacterial infections have traditionally been alleviated by terpenes. The present work intended to examine the impact of several chitosan menthone Schiff base nanocomposites on the treatment of H. pylori infection as well as on its anti-inflammatory capacity. Chitosan (Cs) was condensed with menthone with different molar ratios of Cs:menthone (1:0.5, 1:1, and 1:2) to produce chitosan Schiff bases namely; Cs-SB1, Cs-SB2, and Cs-SB3, respectively. Cs-SB3 Schiff base nanocomposites were prepared individually by adding 2%Ag, 2%Se, (1%Ag + 1%Se), and 2%Fe 2 O 3 nanoparticles to produce compounds denoted as Cs-SB-Ag, Cs-SB-Se, Cs-SB-Ag/ Se, and Cs-SB-Fe, respectively. The anti- H. pylori activity of Cs-SB-Se was detected at a minimal inhibitory concentration MIC of 1.9 μg/mL making it the most biologically active compound in our study. Cs-SB-Se nanocomposite was tested for its cyclooxygenases (COX-1 and COX-2) inhibitory potential which demonstrated inhibitory efficacy towards COX enzymes with inhibition value against COX-1 (IC 50 = 49.86 ± 1.784 μg/mL) and COX-2 (IC 50 = 12.64 ± 0.463 μg/mL) which were less than the well-known Celecoxib (22.65 ± 0.081 and 0.789 ± 0.029 μg/mL) and Indomethacin (0.035 ± 0.001 and 0.08 ± 0.003 μg/mL) inhibitors. The selectivity index SI = 3.94 for tested nanocomposites indicated higher selectivity for COX-1. The cytotoxicity of the Cs-SB-Se nanocomposite was evaluated in Vero cells (CCL-81) and it showed that at a concentration of 62.5 μg/mL, cell viability was 85.43 %. [ABSTRACT FROM AUTHOR]

This study aim to investigate the diagnostic potential of Raman spectroscopy in comparison with rapid urease test and histopathology in diagnosis of H. pylori infection. A comparative study was conducted at Pathology Laboratory and a total of 94 samples were collected from patients based on Rome IV criteria. Sensitivity, specificity and accuracy of histopathology, rapid urease test and for Raman spectroscopy were investigated. Rapid urease test showed 23 false negative results of H. pylori as compared to Raman spectroscopy and histopathology. We concluded that Raman spectroscopy showed sensitivity (94.5%), accuracy (94.0%) and specificity of (87.5%) in the diagnosis of H. pylori infection. However rapid urease test showed specificity of 92.5% while low sensitivity 75%, and 78% accuracy as compared to Raman spectroscopy and histopathology. This study illustrates the applicability of Raman spectroscopy as a potent innovative detection tool for the molecular detection of H. pylori infection in gastritis. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) infection can cause gastritis, gastric ulcer and even gastric cancer. It was therefore listed as a class Ⅰ carcinogen in 2007. H. pylori infection is also widespread in the world but is easy to be eradicated. Therefore, the timely diagnosis of H. pylori infection is significantly important. In this study, a visual detection assay for H. pylori in saliva based on recombinase-aided amplification (RAA) and peptide nucleic acid-assisted split DNAzyme probes was developed. The sampling was easy and the whole detection could be finished in 100 min with low dependence on incubation equipment. The detection results could be qualitatively identified by naked eyes and visual analysis based on ImageJ software, and quantitatively analyzed by spectrophotometry in the range of 0 – 10^5 CFU/mL H. pylori and the limit of detection is low to 0.105 CFU/mL. Thus, with the advantages of easy sampling, low equipment dependence and high sensitivity, the visual detection assay for H. pylori in saliva developed in this study could help control H. pylori infection. • The assay could be used to detect saliva samples. • The reaction temperature of the assay was as low as the body temperature. • The results could be identified by the naked eyes and a visual analysis method. • The detection limit was as low as 0.105 CFU/mL with the introduction of PNA probe. [ABSTRACT FROM AUTHOR]

Abstract An Italian certified Neem seed oil was characterized through the color analysis, the HPLC phenolic fingerprint and the preliminary evaluation of the cytotoxicity profile against the human macrophage (THP-1) cell line. Moreover, a wide screening of its enzyme inhibitory profile, antimicrobial activity towards Helicobacter pylori , several Candida spp. and Malassezia furfur strains and antiprotozoal activity against Plasmodium falciparum , Leishmania infantum and Leishmania tropica were performed. Neem seed oil demonstrated low toxicity and a great inhibitory efficacy against tyrosinase and lipase enzymes. Antimalarial and anti-leishmanial activities were also demonstrated, but weak or no activity was evidenced against Helicobacter pylori , Candida and Malassezia strains. Overall, these findings encourage the potential use of this natural product in some disease treatments and justify its use in traditional medicine. Highlights • Neem oil was analyzed by HPLC-PDA and color parameters. • Neem oil was inactive against Candida spp. and Malassezia furfur. • Neem oil displayed a discrete antimalaria and anti- Leishmania activity. • Lipase and tyrosinase were strongly inhibited by Neem oil. • Cytotoxicity against THP-1 cell line was assessed by MTT assay. [ABSTRACT FROM AUTHOR]

Abstract Melatonin has important immuno-regulatory effects in inflammatory disorders but its specific role in Helicobacter pylori induced gastritis remains unclear. The aim of our study was to analyze the activity of melatonin against H. pylori induced gastritis in vivo, and explore the underlying mechanisms. The H. pylori infected mice showed extensive inflammatory cell infiltration in the gastric mucosa and submucosa, along with significantly reduced spleen and thymus weight. However, 2 and 6 weeks of treatment with 25 and 50 mg/kg melatonin restored the thymus weights relative to that of the untreated mice. TLR2 was upregulated in the gastric mucosa of the infected mice, which was restored to normal levels after 2 and 6 weeks of melatonin treatment. In contrast, TLR4 levels were similar between the treated and untreated mice. Furthermore, melatonin treatment restored spleen Foxp3 and serum TGF-β1 levels that were respectively increased and decreased in the infected mice. H. pylori infected mice also showed a decrease in the serum levels of IL-2, IL-6, IL-10, IL-17, IFN-γ and TFN-α following 2 and 6 weeks of melatonin treatment compared to the untreated mice. Melatonin treatment also resulted in decreased CD4+CD25+Foxp3+ Treg cell count in the spleen. The expression of TLR2, MyD88, p-ERK, p-p38, p65, p50 and Foxp3 in the gastric tissues were lower in the untreated mice compared to mice treated with melatonin for 2 weeks. However, the expression levels evened out after 6 weeks of treatment. Taken together, melatonin alleviates H. pylori induced gastritis by regulating TGF-β1 and Foxp3 expression via the TLR2 and TLR4 pathways. Highlights • (1) We showed for the first time that the activity of melatonin against H. pylori induced gastritis; • (2) Melatonin decreased H. pylori infected mice Foxp3 and cytokines expression; • (3) Melatonin exert its immunomodulatory effect via the TLR2 or TLR4 pathway. [ABSTRACT FROM AUTHOR]

Abstract HpaA is considered to be an effective protective antigen for vaccination against Helicobacter pylori (H. pylori) infection. Oral immunization with HpaA significantly decreases bacterial colonization in H. pylori infected mice. In this study, we investigated whether subcutaneous or intranasal immunization with HpaA could protect against H. pylori infection. Mice immunized subcutaneously with HpaA in Complete Freund's adjuvant, but not mice intranasally immunized with HpaA in CpG adjuvant acquired protection against H. pylori infection. However, intranasal immunization with immunodominant epitope peptides in CpG adjuvant protected mice against H. pylori infection, and immunodominant epitope peptides stimulated stronger Th1 responses and mediated more robust protection against H. pylori infection than subdominant ones. Our results suggest that the length of a candidate antigen is critical for particular vaccination routes, and that immunodominant epitope peptides are promising candidates for protection against H. pylori infection through nasal vaccination. [ABSTRACT FROM AUTHOR]

Gut microbiota dysfunction is associated with multiple gastrointestinal and extra-gastrointestinal diseases, thus the possibility of its modulation with prebiotics, probiotics and symbiotics has gained interest in the last years. Many probiotics are available on the market and products characterized by combination of multiple strains have been proposed as particularly effective. However, evidences supporting their efficacy are often inadequate and not homogenous. We reviewed available data on clinical efficacy of multistrain probiotics and symbiotics in gastrointestinal diseases in adults, focusing on data from randomised, double-blind, placebo-controlled clinical trials. Twenty-nine multistrain products satisfied inclusion criteria. The principal areas of application are irritable bowel syndrome, Helicobacter pylori eradication and antibiotic-associated diarrhoea. The most represented probiotic species in the different probiotic formulations was L. acidophilus . The combination of L. paracasei, L. plantarum, L. acidophilus, L. delbrueckii subsp. bulgaricus, B. longum, B. infantis , B. breve and S. thermophilus (VSL#3) showed the highest number of RCTs. [ABSTRACT FROM AUTHOR]

Helicobacter pylori is a major infective etiological agent of the upper gastrointestinal tract diseases. The bacterium exhibits resistance to various conventional antibiotics, being usually challenging for eradication. Since there is an urge to consider alternative therapeutic strategies, the aim of the study was to examine selected essential oils of plants belonging to families Cupressaceae ( Juniperus communis ) and Lamiaceae ( Hyssopus officinalis, Salvia officinalis, Melissa officinalis, Lavandula angustifolia, Ocimum basilicum and Thymus serpyllum ) against H. pylori , using an improved microdilution broth method. The oils were examined in concentration range from 0.03 to 4 μL/mL. The method comprises Brain-heart infusion broth supplemented with yeast extract, horse serum and IsoVitaleX. After 3 day incubation, an equal volume of double strengthen Christensen’s urea was added into each well and incubated for additional 4 h. In wells with present H. pylori , the medium changed color from yellow to purple, allowing MIC determination even without a microtitre plate reader. The microtitre format method is convenient as it is less expensive, easier to perform and requires less amount of an anti- H. pylori agent. The improved method enhances specificity to H. pylori , as fast urease activity is almost an exclusive property of this bacterium. The application of the second step incubation with Christensen’s urea decreases the possibility of false positive/negative results due to contaminant growth or commonly poor H. pylori growth. Among the examined oils, J. communis, H. officinalis and O. basilicum were not active with the highest applied concentrations, while the most active was T. serpyllum , with MIC 2.0–4.0 μL/mL. This is the first report on essential oils activity of T. serpyllum and H. officinalis against H. pylori. [ABSTRACT FROM AUTHOR]

Purpose Attachment of Helicobacter pylori to the mucous epithelial cells and the mucous layer is said to be a crucial step for infection development. Sugar antigens of gastric mucins (MUC5AC, MUC1) can act as receptors for bacterial adhesins. The aim of the study was to investigate if Lotus tetragonolobus and Maackia amurensis lectins influence the level of MUC1, MUC5AC, Lewis b, H type 1, sialyl Lewis x, phospho-IκBα and interleukin 8 in Helicobacter pylori infected gastric cancer cells. Materials and methods The study was performed with one clinical H. pylori strain and CRL-1739 gastric cancer cells. To assess the levels of mentioned factors immunosorbent ELISA assays were used. Results Coculture of cells with bacteria had no clear effect on almost all examined structures. After coculture with H. pylori and lectins, a decrease of the level of both mucins, Lewis b and H type 1 antigens was observed. Lectins addition had no effect on sialyl Lewis x. Maackia amurensis caused slight increase of phospho-IκBα while interleukin 8 level was decreased. Conclusions Lotus tetragonolobus and Maackia amurensis lectins can mediate in binding of Helicobacter pylori to gastric epithelium. [ABSTRACT FROM AUTHOR]

The main objective of this study is to analyze the relationship of H. pylori vacuolating gene in gastric cancer. H. pyroli strains were isolated from the biopsy specimens collected from 50 patients suspected of gastritis, gastric carcinoma and peptic ulcer disease. H. pylori JK was identified and the virulence gene was determined. The presence of vacuolating cytotoxin A gene was amplified using a polymerase chain reaction. The growth kinetics of the strain JK were evaluated up to 96 h at 37 °C and the culture was used for the determination of VacA gene expression. The screened H. pylori JK was positive for vacA gene and showed heterogeneity among H. pylori. Bacterial growth increased up to 48 h incubation and declined after 48 h. The isolated strain showed maximum growth after 72 h incubation, whereas, the toxic protein reached maximum yield after 96 h incubation and was not associated with growth. It was resistant to antibiotics such as ceftriaxone, cefuroxime, cefalexin, and co-trimoxazole. The intracellular H. pylori culture extracts induced vacuolation in HeLa cell lines in vitro. The isolated H. pylori strain showed more than 43% vacuolating activity after 24 h incubation. Immunoblotting assay revealed the presence of an immuno-reactive protein band in the culture supernatant of H. pylori JK. These results indicated the pathogenic activity of the VacA gene and toxin production. Generally, H. pylori persists for the lifetime of the individual, revealing the significance of eradication from the host. [ABSTRACT FROM AUTHOR]

Recently, nanotechnology has been considered one of most frontiers in scientific sector, which increasingly attracts researchers' interest due to its variable and valuable applications in all areas. The synthesis of nanoparticles represents a promising era in therapeutic research that may lead to the development of new approaches in pharmaceutical studies. Selenium nanoparticles (SeNPs) share a status of high repute owing to their remarkable therapeutic potential. Biological synthesis of environment-friendly SeNPs using plant extracts has emerged as a beneficial alternative approach to chemical synthesis. In this regard, we have synthesized biogenic PG-SeNPs using pomegranate peels aqueous extract (PPAE) as a stabilizing and reducing agent. The PG-SeNPs were evaluated for their anti- Helicobacter pylori and anti-stomach cancer potential. The PG-SeNPs were efficacious against H. pylori. The PG-SeNPs showed dose-dependent restriction of the growth of H. pylori. The anti-stomach cancer ability of the PG-SeNPs was evaluated against SNU-16 stomach cancer. As evident from the MTT results, PG-SeNPs reduced cell viability in a dose-dependent manner. Briefly, the PG-SeNPs evolved with synergistically emerging attributes that were effective against H. pylori ; Moreover, the PG-SeNPs and SeNPs@CuO embody intriguing anticancer potential against stomach cancer cells. [ABSTRACT FROM AUTHOR]

Helicobacter pylori is a species of bacteria that can colonize the human stomach mucosa. It is closely associated with gastric diseases. The restrictions of traditional methods have encouraged the development of innovative methods for rapid, reliable, and cost-effective diagnosis of H. pylori infection. In recent years, the concept of biosensor and microfluidic-based devices has opened new horizons in high-precision detection. Once combined with nanomaterials, nano-scale biosensors and microfluidic systems provide powerful analytical platforms for point of care (POC) diagnosing of H. pylori . In this article, a brief overview of general aspects of H. pylori infection and current diagnostic methods are firstly discussed. In addition, a clear and concise review of recent advances of biosensors, paper-based and microfluidic systems based on nanomaterials for the detection of H. pylori are discussed herein. Subsequently, the latest development of integrated and miniaturized microfluidic biosensing technologies for POC detection of H. pylori is explained. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between H. pylori infection and risk of incident diabetes in adults at high risk for diabetes who participated in the Diabetes Prevention Program (DPP) study.Methods: In a nested case-control study conducted among 421 adults with newly diagnosed diabetes and 421 matched controls, we examined the association between serological status of H. pylori at baseline and risk of incident diabetes over a mean follow-up period of 2.6years. Using data from the baseline visit of the DPP, we also examined the cross-sectional association between presence of H. pylori antibodies and insulin sensitivity, insulin secretion and the disposition index-like measure after a 75-g oral glucose tolerance test (OGTT).Results: At baseline, H. pylori antibodies were present in 40% of participants who developed diabetes and 39% of controls. After adjusting for matching factors, there was no association between exposure to H. pylori and incident diabetes (odds ratio [OR] of 1.04 (95% CI, 0.77 to 1.40). In cross-sectional analyses, H. pylori status was not significantly associated with insulin sensitivity and disposition index-like measure from OGTT.Conclusions: In adults at high risk for diabetes, H. pylori seropositivity was not associated with risk of developing diabetes. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor binding protein-1 (IGFBP-1), a secreted protein, implicated of various cells in mediating the proliferation, migration, invasion, adhesion, survival and so on. In this study, we assessed the expression and release of IGFBP-1 from gastric cancer cells with H. pylori 2669 5 infection and the biological functions of IGFBP-1 in gastric cancer cells. The results showed that the expression and release of IGFBP-1 were increased in gastric cancer cells (MGC-803, BGC-823, SGC-7901) infected with H. pylori 26695. In addition, the upregulation of IGFBP-1 was dose-dependent in BGC-823 cells infected with H. pylori 26695 but not time-dependent. The upregulation of IGFBP-1 got to peak at 12 h after H. pylori 26695 infection and then decreased over time. Subsequently, we measured its functions by silencing and overexpressing IGFBP1 which suggested that overexpression of IGFBP-1 could inhibit the migration of BGC-823 and SGC-7901 cells. However, knocking down the IGFBP-1 could increase the migration of BGC-823 and SGC-7901 cells. Functional findings illustrated that IGFBP-1 was implicated in H. pylori 26695-induced MMP-9 expression in BGC-823 cells. In addition, overexpressing IGFBP1 reduce the promoting effect of MMP-9 on the BGC-823 cells migration. In summary, we demonstrated that IGFBP-1 suppress the migration of BGC-823 cells and play a protective role in the process of H. pylori -induced gastric cancer. [ABSTRACT FROM AUTHOR]

Toll like receptors (TLRs) are an essential subset of pathogen recognition receptors (PRRs) which identify the microbial components and contribute in the regulation of innate and adaptive immune responses against the infectious agents. The TLRs, especially TLR2, TLR4, TLR5 and TLR9, participate in the induction of immune response against H. pylori . TLR2 is expressed on a number of immune and non-immune cells and recognizes a vast broad of microbial components due to its potential to form heterodimers with other TLRs, including TLR1, TLR6 and TLR10. A number of H. pylori –related molecules may contribute to TLR2-dependent responses, including HP-LPS, HP-HSP60 and HP-NAP. TLR2 plays a pivotal role in regulation of immune response to H. pylori through activation of NF-κB and induction of cytokine expression in epithelial cells, monocytes/macrophages, dendritic cells, neutrophils and B cells. The TLR2-related immune response that is induced by H. pylori -derived components may play an important role regarding the outcome of the infection toward bacterial elimination, persistence or pathological reactions. The immunomodulatory and immunoregulatory roles of TLR2 during H. pylori infection were considered in this review. TLR2 could be considered as an interesting therapeutic target for treatment of H. pylori -related diseases. [ABSTRACT FROM AUTHOR]

• Yogurt was manufactured and deliberately contaminated with H. pylori at 106 cfu/g. • Eugenol and cinnamaldehyde nanoemulsions were fabricated. • Two probiotic strains with high anti- H. pylori activity were selected. • The previous combination significantly inhibits H. pylori in yogurt. • The combination did not affect the activity of the non-pathogenic bacteria in yogurt. Different strains of probiotics were screened in vitro to select the one with the highest anti- H. pylori activity. Three nanoemulsions of eugenol, cinnamaldehyde and their mixture were fabricated and tested also in vitro against the same pathogen. The selected probiotic strains, the nanoemulsion mixture and their combination were imbedded in a lab-manufactured yogurt which is deliberately contaminated with 6.0 log cfu/g H. pylori during manufacture. The inhibitory activity of all treatments on the growth of H. pylori and the other microorganisms in yogurt was evaluated during 21 days. Combining the selected probiotic strains with the nanoemulsion mixture in the contaminated yogurt reduced the count of H. pylori by 3.9 log cycle. The nanoemulsion showed lower inhibitory effect against the other microorganisms like probiotics, starter culture and total bacterial count in the tested yogurt, where their enumeration did not fall below 106 cfu/g at the end of yogurt storage period. [ABSTRACT FROM AUTHOR]

• Is the prevalence of clarithromycin resistance correlated with macrolide consumption? • At a country level, these two are significantly associated. • At a world region level these two are positively correlated (not statistically significant). Bystander selection has been shown to result in strong population-level correlations between the level of antimicrobial consumption in the general population and resistance to that antimicrobial or similar antimicrobials in a range of bacteria. The prevalence of clarithromycin resistance in Helicobacter pylori has been increasing rapidly resulting in increased difficulty to eradicate this infection. Using country- and WHO-world-region-level macrolide resistance data from a systematic review and macrolide consumption data from the MIDAS Quantum data base, we tested the hypothesis that the prevalence of clarithromycin resistance was correlated with macrolide consumption. At a country level, we found these variables to be positively correlated (Spearman's rho = 0.49; P = 0.007). Whilst positive, the correlation between macrolide consumption and primary resistance was not statistically significant at world region level (Spearman's rho = 0.95; P = 0.05). [ABSTRACT FROM AUTHOR]

Objetive: H. pylori infection is acquired early in life, but symptoms occur mainly in adults. The mode of transmission remains unclear, but several studies have demonstrated that the microorganism may be transmitted orally. H. pylori has been detected in the oral cavity of children, and some authors have studied infection prevalence due to the importance of the bacteria in gastric and extragastric pathology. In México, little is known about H. pylori prevalence in the oral cavity of asymptomatic children, so the aims of this study were to estimate the prevalence of H. pylori in asymptomatic children and evaluate factors associated with the infection. Desing: We studied 162 asymptomatic children of 3.025 ± 1.474 years of age from a kindergarten in México City. Oral swabs, rotating around to cheeks inside of oral cavity were obtained to determine H. pylori, using the polymerase chain reaction for 16S rRNA and glmM genes. Results: We detected a 13% prevalence of H. pylori infection by PCR, and the results were confirmed by sequencing and showed a >97% identity with H. pylori. We observed increased infection with age. No association between H. pylori infection and variables such as sex, family history of gastric diseases, crowding or pets in the home were found. Conclusion: H. pylori infection in the oral cavity is frequent among asymptomatic children in México, which represents a risk of infection for other family members and for other children in educational facilities. Early diagnosis is essential for control of the infection and for the development of preventive strategies in childhood. [ABSTRACT FROM AUTHOR]