scholarly journals Structural Analysis of Variability and Interaction of the N-terminal of the Oncogenic Effector CagA of Helicobacter pylori with Phosphatidylserine

2018 ◽  
Vol 19 (10) ◽  
pp. 3273 ◽  
Author(s):  
Cindy Ulloa-Guerrero ◽  
Maria Delgado ◽  
Carlos Jaramillo
Keyword(s):  
Crystal Structure ◽  
Helicobacter Pylori ◽  
Conservation Score ◽  
Intermolecular Forces ◽  
P Value ◽  
Cytotoxin Associated Gene A ◽  
Molecular Forces ◽  
Severe Pathology ◽  
Risk Of Cancer ◽  
Bulk Effect

Helicobacter pylori cytotoxin-associated gene A protein (CagA) has been associated with the increase in virulence and risk of cancer. It has been demonstrated that CagA’s translocation is dependent on its interaction with phosphatidylserine. We evaluated the variability of the N-terminal CagA in 127 sequences reported in NCBI, by referring to molecular interaction forces with the phosphatidylserine and the docking of three mutations chosen from variations in specific positions. The major sites of conservation of the residues involved in CagA–Phosphatidylserine interaction were 617, 621 and 626 which had no amino acid variation. Position 636 had the lowest conservation score; mutations in this position were evaluated to observe the differences in intermolecular forces for the CagA–Phosphatidylserine complex. We evaluated the docking of three mutations: K636A, K636R and K636N. The crystal and mutation models presented a ΔG of −8.919907, −8.665261, −8.701923, −8.515097 Kcal/mol, respectively, while mutations K636A, K636R, K636N and the crystal structure presented 0, 3, 4 and 1 H-bonds, respectively. Likewise, the bulk effect of the ΔG and amount of H-bonds was estimated in all of the docking models. The type of mutation affected both the ΔG ( χ 2 ( 1 ) = 93.82 , p-value < 2.2 × 10 − 16 ) and the H-bonds ( χ 2 ( 1 ) = 91.93 , p-value < 2.2 × 10 − 16 ). Overall, 76.9% of the strains that exhibit the K636N mutation produced a severe pathology. The average H-bond count diminished when comparing the mutations with the crystal structure of all the docking models, which means that other molecular forces are involved in the CagA–Phosphatidylserine complex interaction.

scholarly journals Structural Analysis of Variability and Interaction of the N-Terminal of the Oncogenic Effector CagA of Helicobacter pylori with Phosphatidylserine

2018 ◽  
Author(s):  
Cindy P. Ulloa Guerrero ◽  
Maria del Pilar Delgado ◽  
Carlos A. Jaramillo
Keyword(s):  
Crystal Structure ◽  
Helicobacter Pylori ◽  
Conservation Score ◽  
Intermolecular Forces ◽  
P Value ◽  
Cytotoxin Associated Gene A ◽  
Molecular Forces ◽  
Severe Pathology ◽  
Delta G ◽  
Risk Of Cancer

Helicobacter pylori cytotoxin-associated gene A protein (CagA) has been associated with the increase in virulence and risk of cancer. It has been demonstrated that CagA's translocation is dependent on its interaction with phosphatidylserine. We evaluated the variability of the N-terminal CagA in 127 sequences reported in NCBI, by referring to molecular interaction forces with the Phosphatidylserine and the docking of 3 mutations chosen from variations in specific positions. The major sites of conservation of the residues involved in CagA-Phosphatidylserine interaction were 617, 621 and 626 which had no amino acid variation. Position 636 had the lowest conservation score, so mutations in this position were evaluated to observe the differences in intermolecular forces of the CagA-Phosphatidylserine complex. We evaluated the docking of 3 mutations: K636A, K636R and K636N. The models of the crystal and mutations presented a &Delta;G of &minus;8.919907, &minus;8.665261, &minus;8.701923, &minus;8.515097 Kcal/mol, respectively, while mutations K636A, K636R, K636N and the crystal structure presented 0, 3, 4 and 1 H-bonds, respectively. Likewise, the bulk effect of the &Delta;G and amount of H-bonds was estimated in all of the docking models. The type of mutation affected both the &Delta;G (&chi;2(1) = 93.82, p-value &lt; 2.2 &times; 10&minus;16) and the H-bonds (&chi;2(1) = 91.93, p-value &lt; 2.2 &times; 10&minus;16). In all the data, 76.9% of the strains that exhibit the K636N mutation produced a severe pathology. The average H-bond count diminished when comparing the mutations with the crystal structure of all the docking models, which means that other molecular forces are involved in the CagA-Phosphatidylserine complex interaction.

Helicobacter Pylori Infection in Sjögren’s Syndrome: Co-incidence or Causality?

2019 ◽  
Vol 15 (3) ◽  
pp. 238-241
Author(s):  
Massoud Saghafi ◽  
Nafiseh Abdolahi ◽  
Reza Orang ◽  
Mohammad Reza Hatef ◽  
Mohammad Hadi Molseghi
Keyword(s):  
Helicobacter Pylori ◽  
Serum Level ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Control Group ◽  
P Value ◽  
H Pylori ◽  
Sjögren‘S Syndrome

Background and Aim: Lymphoid cell infiltration and destruction of exocrine glands, specifically lacrimal and salivary glands are characteristics of Sjogren’s syndrome (SS). An etiological role has been proposed for Helicobacter pylori (H. pylori), interacting in the clinical course and complications of SS (including gastric cancer and lymphoma). The aim of this study was to identify the probable correlation between H. pylori infection and Sjogren’s syndrome (SS). Methods: In this case-control study, ELISA method was used to determine serum level of IgA and IgM anti H. pylori antibody in 43 subjects with SS according to the international criteria and 95 healthy subjects as control. SPSS-17 was used to analyze data with t-test. P value <.05 were considered significant. Results: Serum level of IgM (34.9% vs. 10.5%, p-value= 0.001) and IgA (67.4% vs. 46.3% p value= 0.021) anti H. pylori antibody were significantly higher in SS patients compared to the control group. There was a positive correlation between age and H. pylori infection (r=0.2, Pvalue= 0.05). Conclusion: Patients with SS had a higher prevalence of H. pylori infection compared to the normal population. Eradication of H. pylori is recommended particularly in older patients with SS.

scholarly journals Investigation of Solubility Behavior of Canagliflozin Hydrate Crystals Combining Crystallographic and Hirshfeld Surface Calculations

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 298
Author(s):  
Yefen Zhu ◽  
Yanlei Kang ◽  
Ling Zhu ◽  
Kaxi Yu ◽  
Shuai Chen ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Intermolecular Forces ◽  
Hirshfeld Surface ◽  
Reversible Inhibitor ◽  
Solubility Behavior ◽  
Hydrogen Bond Networks ◽  
Solvent Molecules ◽  
First Time ◽  
Better Than

Canagliflozin (CG) was a highly effective, selective and reversible inhibitor of sodium-dependent glucose co-transporter 2 developed for the treatment of type 2 diabetes mellitus. The crystal structure of CG monohydrate (CG-H2O) was reported for the first time while CG hemihydrate (CG-Hemi) had been reported in our previous research. Solubility and dissolution rate results showed that the solubility of CG-Hemi was 1.4 times higher than that of CG-H2O in water and hydrochloric acid solution, and the dissolution rates of CG-Hemi were more than 3 folds than CG-H2O in both solutions. Hirshfeld surface analysis showed that CG-H2O had stronger intermolecular forces than CG-Hemi, and water molecules in CG-H2O participated three hydrogen bonds, forming hydrogen bond networks. These crystal structure features might make it more difficult for solvent molecules to dissolve CG-H2O than CG-Hemi. All these analyses might explain why the dissolution performance of CG-Hemi was better than CG-H2O. This work provided an approach to predict the dissolution performance of the drug based on its crystal structure.

scholarly journals Helicobacter pylori eradication in patients with type 2 diabetes mellitus: Multicenter prospective observational study

2019 ◽  
Vol 7 ◽  
pp. 205031211983209 ◽  
Author(s):  
Seung-Joo Nam ◽  
Sung Chul Park ◽  
Sang Hoon Lee ◽  
Dong Wook Choi ◽  
Sung Joon Lee ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Observational Study ◽  
Prospective Observational Study ◽  
Eradication Rate ◽  
Laboratory Data ◽  
P Value ◽  
Diabetic Patients ◽  
Multicenter Prospective Observational Study ◽  
H Pylori

Objective: To compare Helicobacter pylori ( H. pylori) eradication rate of type 2 diabetic patients with non-diabetic subjects. Methods: In this multicenter prospective observational study, H. pylori-infected subjects were enrolled from three university-affiliated hospitals. Eradication regimen was triple therapy with standard dose of proton pump inhibitors (b.i.d), amoxicillin (1.0 g b.i.d), and clarithromycin (500 mg b.i.d) for 7 days. Urea breath test was performed 4 weeks after treatment. Various clinical and laboratory data were collected for identification of factors associated with successful eradication. Results: Totally, 144 subjects were enrolled and 119 (85 non-diabetic and 34 diabetic patients) were finally analyzed. Eradication rate was 75.6% and there was no difference between diabetic patients and non-diabetic subjects (73.5% vs 76.5%, p value: 0.814). Adverse drug reactions were reported in 44.5% of patients. In multivariate analysis for predicting H. pylori eradication in diabetic patients, HbA1c (⩾7.5%) was a significant factor affecting eradication rate (adjusted odds ratio: 0.100, 95% confidence interval: 0.011–0.909, p value: 0.041). Conclusion: Diabetes itself is not a major factor affecting H. pylori eradication. However, poor glucose control may harmfully affect H. pylori eradication.

scholarly journals Genotyping pattern of the vacuolating cytotoxin A and cytotoxin associated gene A of the Helicobacter pylori strains detected in fecal samples of household dogs

2017 ◽  
Vol 8 (2) ◽  
Author(s):  
Asieh Bolandi ◽  
Saam Torkan ◽  
Iman Alavi
Keyword(s):  
Helicobacter Pylori ◽  
16S Rrna ◽  
16S Rrna Gene ◽  
Pcr Amplification ◽  
Rrna Gene ◽  
Fecal Samples ◽  
The Status ◽  
Cytotoxin Associated Gene A ◽  
H Pylori

In despite of the high clinical impact of Helicobacter pylori, its exact sources and routes of transmission are unknown. Dogs may play an imperative role in the transmission of H. pylori to humans. The current investigation was done to study the status of vacA and cagA genotypes in the H. pylori strains of dogs. One-hundred and fifty fecal samples were collected from healthy and complicated household dogs. Genomic DNA was extracted from fecal samples and presence of 16S rRNA gene was studied using the PCR amplification. Distribution of vacA and cagA genotypes were studied by the multiplex PCR. Thirteen out of 150 fecal samples (8.66%) were positive for H. pylori 16S rRNA gene. Prevalence of H. pylori in healthy and complicated dogs were 5.55% and 8.57%, respectively. Male had the higher prevalence of H. pylori (P=0.038). The most commonly detected genotypes among the H. pylori strains were vacAs1A (61.53%), cagA (38.46%), vacAm1a (38.46%), vacAs2 (30.76%) and vacAm2 (30.76%). The most commonly detected combined genotypes were s1aCagA (30.76%), s1am1a (23.07%), s2m1a (23.07%) and s2CagA (23.07%). Iranian household dogs harbor H. pylori in their fecal samples similar in genotypes of the vacA and cagA alleles which suggest that complicated and even healthy dogs may be the latent host of the H. pylori and its genotypes. However, supplementary studies are required to found the exact role of dogs as a definitive host of the H. pylori.

scholarly journals Histopathological Changes in Helicobacter pylori Associated Gastritis and Scope of Special Stain and Immunohistochemistry as Diagnostic Aids

2020 ◽  
Vol 7 (50) ◽  
pp. 3027-3032
Author(s):  
Ruby Elizabeth Elias ◽  
Bindiya Gisuthan ◽  
Sreeganesh A.S
Keyword(s):  
Helicobacter Pylori ◽  
Positive Predictive Value ◽  
Negative Predictive Value ◽  
Chronic Gastritis ◽  
Predictive Value ◽  
Diagnostic Methods ◽  
P Value ◽  
Special Stain ◽  
Frequent Finding ◽  
H Pylori

BACKGROUND Helicobacter pylori associated chronic gastritis plays a vital role in the development of majority of gastric adenocarcinomas and most gastric MALT (Mucosa Associated Lymphoid Tissue) lymphomas. Many diagnostic methods are available for the identification of this organism. However, in gastroenterology practice, histopathological examination of biopsy samples provides visual identification of the pathogen and the associated mucosal changes with special stains like Giemsa. The aim of this study was to evaluate the efficacy of three stains H & E- (Haematoxylin and Eosin), Giemsa and IHC (Immunohistochemistry) in the identification of H. pylori. Associated histologic changes were noted and the relationship between the degree of colonisation and the activity and chronicity of gastritis were analysed. METHODS 585 gastric biopsies taken from dyspeptic patients were evaluated for gastritis, based on updated Sydney System. In 250 randomly selected cases, three staining methods were used. RESULTS Out of 585 cases, 413 (70.60 %) had features of chronic gastritis. Mild chronic gastritis was the commonest finding and is seen in most cases of mild H. pylori colonisation. When activity was monitored, mild activity was the most frequent finding [225 (38.46 %)]. Majority of the severe activity cases showed severe H. pylori colonisation. 13.16 %, 4.79 % and 7.35 % showed intestinal metaplasia, atrophy and dysplastic changes respectively. Out of 250 cases, H & E and Giemsa stains showed 45.6 % and 57.2 % positivity while IHC demonstrated maximum number of positivity (156 cases - 62.4 %). Sensitivity and specificity of H & E was found to be 77.90 % and 98.95 %, positive predictive value was 99.13 % and negative predictive value was 69.18 %. For Giemsa stain, sensitivity was 91.67 %, specificity was 100 %, positive predictive value was 100 % and negative predictive value was 87.85 %. DISCUSSION H. pylori gastritis was a frequent finding in dyspeptic patients in southern part of India. When chi-square test was done, a significant statistical relationship between the severity of H. pylori colonisation, activity and chronicity of gastritis was noted. P value was < 0.001. With the use of special stain, Giemsa and ancillary techniques like IHC, the detection rate of H. pylori was enhanced considerably. CONCLUSIONS With increasing number of H. pylori in the mucosa, there was increase in the chronicity and activity of gastritis. Although immunohistochemistry revealed more cases of H. pylori, Giemsa can be a cost-effective substitute, because of its high specificity and positive predictive value. KEYWORDS H. pylori Gastritis, Giemsa, Haematoxylin and Eosin Stain, Immunohistochemistry

scholarly journals Prevalence of Helicobacter Pylori Infection and Associated Factors Among Gastritis Patents in Yekatit 12 Teaching Hospital Addis Ababa Ethiopia

2020 ◽  
Author(s):  
Awraris Hailu ◽  
Bekureamanuel Sileshi ◽  
Hazaratali Panari
Keyword(s):  
Helicobacter Pylori ◽  
Teaching Hospital ◽  
Rural Areas ◽  
Associated Factors ◽  
Addis Ababa ◽  
Helicobacter Pylori Infection ◽  
Work Place ◽  
P Value ◽  
Hand Wash ◽  
H Pylori

Abstract Introduction: Helicobacter pylori colonize the stomach of about ~50% of the world’s human population and infection is more in clients with dyspeptic conditions and its associated with the severity of gastritis. The present study revealed that the magnitude of H. Pylori and burden of the bacterial infection as well as the contribution of H. Pylori for gastritis and also assesses the current prevalence of H. Pylori infection.Objective: To evaluate the prevalence of Helicobacter Pylori infection and associated factors among gastritis patents in Yekatit 12 Hospital.Methodology: An institutional based cross-sectional study was conducted in Yekatit 12 teaching hospital Addis Ababa city, Ethiopia. The participants were those patients come to the hospital for treatment of gastritis and send to the laboratory to confirm Helicobacter pylori infection in the data collection period. A total of 394 participants were interviewed by using a structured pre tested questionnaire. The data were coded and entered into Epi Data 3.1 version , cleaned and exported to version 20, SPSS. Multiple Logistic regression was used to estimate Adjusted (AORs) with a 95% confidence interval (CI) of positive responses to the different risk factors. P-value < 0.05 was considered as significant.Result: The total occurrence of H. Pylori in observers was 25.9%. Regarding income of family, those participants who have less income and living in rural areas were extra prone to be infected with H. Pylori (AOR=5.857, CI 95% = 1.389-24.686, P = 0.016 and AOR=3.663, CI 95% = 1.068-12.557, P =0.039) respectively. Further, the prevalence of study was significant association with participants who had experience of gastrointestinal illness, mouth to mouth kissing, unable to hand wash regularly before meal and after latrine used (AOR=4.270, 95%CI=1.785-10.21, P=0.01, AOR=53.085, 95%CI=16.185-174.114, P=0.000, AOR=7.316, 95%CI=1.944-27.536, P=0.003, AOR=3.374, 95%CI=1.024-11.114, P=0.046) respectively.Conclusion and recommendation: The finding shows that H. Pylori infection was significantly associated with occupational status,gender, smoking tobacco and hand washing regularly before meal and after toilet. I recommend making clean and saving the work place; regular hand wash, before food preparation, before feeding and after latrine. A health professional should give health education by using different media about the transition and health biro also should give emphases.

scholarly journals Helicobacter Pylori Induce Gastric Upset

2021 ◽  
pp. 1-1
Author(s):  
Hazim Abdul Rahman Alhit
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Serum Antibody ◽  
Endoscopic Biopsy ◽  
Helicobacter Pylori Infection ◽  
Gastric Epithelium ◽  
Gastric Diseases ◽  
Heterogeneous Distribution ◽  
Cytotoxin Associated Gene A ◽  
H Pylori

Editorial: Helicobacter pylori is a micro-aerophilic, helical-form gramnegative aggressive bacteria. Accordingly, the idiom “Helico” intimates its helical appearance, “bacter” symbolizes bacteria, while “pylori” denotes stomach due to the first and common site of this bacteria living. Further, Marshall B. and Warren R. observed and described it in 1982. Then, the followed investigators studied this bacterium in detail with its consequences and complexities [1]. Gastric upset (Indigestion), dyspepsia: means impaired gastric digestion. Accordingly, the patient complains of upper abdominal pain, heartburn, belching, nausea, even feeling earlier gastric fullness than expected while eating. Furthermore, there are many causes of indigestion like gastroesophageal reflux disease, ulcer disease, gastritis, and even gastric cancer. Hence, unexplained recent onset dyspepsia in older people may need additional examinations. Moreover, one of the common causes is Helicobacter pylori infection, which needs laboratory and endoscopic examination [2]. Argument Many theories investigated the etiology and pathogenesis of Helicobacter pylori infection, concerning chronic or acute gastritis. Hence, gastric upset is the main presentation of both types of gastritis. Evidences The genotype is valuable in determining the dominant Helicobacter pylori strains as the isolates were different genetically plus heterogeneous distribution. Accordingly, the vac and cag markers operate a significant function in defining clinical consequences. These virulence agents are present in a subset of Helicobacter pylori strains isolates like cagA, iceA, vacA, and ureC. Moreover, the cagA causes cytotoxins induction by the gastric epithelial cell as Interleukin 8 [3]. The molecular intercommunication researches exhibit that the act of acarus calamus in hindering biofilm formation in Helicobacter pylori is due to the inhibitory impact of phytobio-active component, β-sitosterol, on the quorum sensing molecules-ToxB, PhnB, DnaA, plus Sip. Consequently, this opinion may suggest the molecular mechanism of Helicobacter pylori in producing the acidrelated complaints and gives a clue to a new therapy [4]. Helicobacter pylori infection causes lncRNA risk impression linked to H. pylori in gastric cancer patients and can prognosticate the prediction of these patients [5]. There was a close relationship between raised serum IgE levels in Helicobacter pylori infected patients [6]. Counterargument The laboratory investigations of Helicobacter pylori infection depend on several factors like the fluctuations of serum antibody titers in a time series, the antigene detection in stool tests, the false-positive results of lab tests, or the manner of endoscopic biopsy collection. Furthermore, other factors like the variations in Cytotoxin-Associated Gene A (CagA) in East Asian patients. Moreover, the gastric nodularity or atrophy, the patient’s age, the severity of the gastric mucosal infection are causes of variations in Helicobacter pylori detection at the time of the investigation [7]. Refutation The significant markers of H. pylori, the presence of the vacuolating cytotoxin (vacA), the cytotoxin-associated gene A (cagA), which induced by the direct communication with gastric epithelium factor antigen (iceA gene), and the presence of urease C gene (ureC). Consequently, all these factors play the principal factors in deciding the gastric consequences of Helicobacter infections. Conclusion Helicobacter pylori induce gastric upset by several mechanisms to form numerous Gastric diseases.

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