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Objectives: Although color information is important in gastrointestinal endoscopy, there are limited studies on how endoscopic images are viewed by people with color vision deficiency. We aimed to investigate the differences in the visibility of blood vessels during endoscopic submucosal dissection (ESD) among people with different color vision characteristics and to examine the effect of red dichromatic imaging (RDI) on blood vessel visibility. Methods: Seventy-seven pairs of endoscopic images of white light imaging (WLI) and RDI of the same site were obtained during colorectal ESD. The original images were set as type C (WLI-C and RDI-C), a common color vision. These images were computationally converted to simulate images perceived by people with color vision deficiency protanope (Type P) or deutanope (Type D) and denoted as WLI-P and RDI-P or WLI-D and RDI-D. Blood vessels and background submucosa that needed to be identified during ESD were selected in each image, and the color differences between these two objects were measured using the color difference (ΔE 00) to assess the visibility of blood vessels. Results: ΔE 00 between a blood vessel and the submucosa was greater under RDI (RDI-C/P/D: 24.05 ± 0.64/22.85 ± 0.66/22.61 ± 0.64) than under WLI (WLI-C/P/D: 22.26 ± 0.60/5.19 ± 0.30/8.62 ± 0.42), regardless of color vision characteristics. This improvement was more pronounced in Type P and Type D and approached Type C in RDI. Conclusions: Color vision characteristics affect the visibility of blood vessels during ESD, and RDI improves blood vessel visibility regardless of color vision characteristics.
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With the expansion of nanomaterials (NMs) usage, concerns about their toxicity are increasing, and the wide variety of NMs makes it difficult to assess their toxicity. Therefore, the development of a high-throughput, accurate, and certified method to evaluate the immunotoxicity of NMs is required. In this study, we assessed the immunotoxicity potential of various NMs, such as nanoparticles of silver, silica, and titanium dioxide, using the human Cell Line Activation Test (h-CLAT) at the cellular level. After exposure to silver nanoparticle dispersions, the expression levels of CD86 and CD54 increased, suggesting the activation of antigen-presenting cells (APCs) by silver nanoparticles. Quantification of silver ions eluted from silver nanoparticles and the activation of APCs by silver ions suggested that it was due to the release of silver ions. Silica nanoparticles also increased the expression of CD86 and/or CD54, and their activation ability correlated with the synthesis methods and hydrodynamic diameters. The ability of titanium dioxide to activate APCs differed depending on the crystal type and hydrodynamic diameter. These results suggest a potential method to evaluate the immunotoxicity potential of various NMs based on their ability to activate APCs using human monocytic THP-1 cells. This method will be valuable in assessing the immunotoxicity potential and elucidating the immunotoxic mechanisms of NMs.
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Objective: Although cervical conization is considered a standard treatment for cervical intraepithelial neoplasia (CIN) 2/3, laser ablation can compensate for the disadvantages of the former. CO2, semiconductor, and holmium yttrium-aluminum-garnet (Ho:YAG) lasers are applied in ablation, but no previous studies have shown the effectiveness of any of these techniques. Here, we retrospectively analyzed the application of the Ho:YAG laser in our hospital to verify its efficacy, and discussed the methods for optimal recurrence detection. Methods: We evaluated the recurrence rates of the pathological condition in patients who underwent laser ablation with a Ho:YAG laser for CIN2/3 at our institution from June 2012 to November 2021. We defined the recurrence as histologically confirmed CIN2 or more advanced stage. Age, preoperative diagnosis, human papillomavirus (HPV) genotype, and postoperative high-risk HPV status were recorded to establish their association with recurrence rates. Results: We performed surgery in 607 patients and the 2-year recurrence rate after interventions was 5.6%. Five patients were diagnosed with invasive cancer at the time of recurrence. Older age significantly correlated with higher risk of recurrence, but preoperative CIN grade and preoperative HPV 16/18 status did not significantly affect it. The postoperative high-risk HPV test was 100% sensitive for detecting recurrence. Conclusions: Laser ablation with the Ho:YAG laser yields promising results. Together with postinterventional management, high-risk HPV test after laser ablation should be conducted after diagnostic conization.This study received the approval from the Ethics Committee of the NHO Tokyo Medical Center (Ethics Committee approval number: R22-067).
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BACKGROUND AND AIMS: Resection of colorectal polyps has been shown to decrease the incidence and mortality of colorectal cancer. Large nonpedunculated colorectal polyps are often referred to expert centers for endoscopic resection, which requires relevant information to be conveyed to the therapeutic endoscopist to allow for triage and planning of resection technique. The primary objective of this study was to establish minimum expected standards for the referral of large non-pedunculated colonic polyps for potential endoscopic resection. METHODS: A Delphi method was used to establish consensus on minimum expected standards for the referral of large colorectal polyps among a panel of international endoscopy experts. The expert panel was recruited through purposive sampling, and 3 rounds of surveys were conducted to achieve consensus. Quantitative and qualitative data were analyzed for each round. RESULTS: A total of 24 international experts from diverse continents participated in the Delphi study, resulting in consensus on 19 statements related to the referral of large colorectal polyps. The identified factors, including patient demographic characteristics, relevant medications, lesion factors, photodocumentation, and the presence of a tattoo, were deemed important for conveying the necessary information to therapeutic endoscopists. The mean scores for the statements, which were scored on a scale of 1 to 10, ranged from 7.04 to 9.29, with high percentages of experts considering most statements as a very high priority. Subgroup analysis according to continent revealed some variations in consensus rates among experts from different regions. CONCLUSIONS: The identified consensus statements can aid in improving the triage and planning of resection techniques for large colorectal polyps, ultimately contributing to the reduction of colorectal cancer incidence and mortality.
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Background and study aims Endoscopic treatment strategies for small superficial duodenal epithelial neoplasia (SDET) have not been established, and the R0 resection rates of all previously reported endoscopic techniques are somewhat low. Furthermore, no reports of cap-assisted endoscopic mucosal resection (EMRC), which is reportedly associated with a relatively high R0 resection rate, have been evaluated in sufficient numbers of patients. Therefore, we assessed the efficacy and safety of EMRC for SDETs ≤ 10 mm in a retrospective cohort study. Patients and methods We examined a prospectively maintained database and identified 248 consecutive patients (248 lesions) who had undergone endoscopic resection for SDETs ≤ 10 mm between January 2017 and June 2022. Our treatment strategy was consistent, with EMRC indicated for all SDETs ≤ 10 mm without non-lifting signs. The primary endpoint was the R0 resection rate. Results Overall, 20 lesions had non-lifting signs and were selected for endoscopic submucosal dissection, while the remaining 228 lesions were treated with EMRC. As a result of EMRC, the median tumor size was 5 mm, and the mean procedure time was 5 minutes. Most of the lesions (89.2%) were located in the descending part. The R0 resection rate was 97.4% (222/228 cases), and the en bloc resection rate was 99.6%. Only seven patients(3.1%) experienced adverse events (6 patients, delayed bleeding; 1 patient, acute pancreatitis), which were successfully managed without surgical intervention. Furthermore, no recurrences were observed. Conclusions We have demonstrated that EMRC is an effective and safe treatment for SDETs ≤ 10 mm that do not have non-lifting signs.
Subject(s)
Adenocarcinoma , Adenoma , Endoscopic Mucosal Resection , Stomach Neoplasms , Humans , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/surgery , Adenocarcinoma/pathology , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Adenoma/diagnostic imaging , Adenoma/surgery , Adenoma/pathology , Gastric Mucosa/surgery , Gastric Mucosa/pathology , GastroscopyABSTRACT
BACKGROUND AND AIMS: Patients with ulcerative colitis (UC) are at risk of developing colorectal cancer. The feasibility of endoscopic resection (ER) for UC-associated neoplasia has been suggested, but its efficacy and safety remain unclear. We aimed to assess the efficacy and safety of ER for colorectal neoplasms in patients with UC. METHODS: This was a retrospective, multicenter cohort study of patients with UC who initially underwent ER or surgery for colorectal neoplasms between April 2015 and March 2021. Patients who had prior colorectal neoplastic lesions were excluded. RESULTS: Among 213 men and 123 women analyzed, the mean age at UC onset was 41.6 years, and the mean age at neoplasia diagnosis was 56.1 years for 240 cases of total colitis, 59 cases of left-sided colitis, 31 cases of proctitis, and 6 cases of segmental colitis. EMR was performed for 142 lesions, and endoscopic submucosal dissection (ESD) was performed for 96 lesions. The perforation rate was 2.5% for all 238 lesions removed by ER and 6.3% for the 96 lesions removed by ESD. Among 146 ER lesions followed up with endoscopy, the local recurrence rate was 2.7%. The incidence of metachronous neoplasia after ER was 6.1%. All patients were followed a median of 34.7 months after initial treatment, and 5 died (all surgical cases). Overall survival was significantly higher in the ER group than in the surgery group (P = .0085). CONCLUSIONS: ER for colorectal neoplasms in UC may be acceptable in selected cases, although follow-up for metachronous lesions is necessary.
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In diseases related to oxidative stress, accumulation of metal ions at the site of pathogenesis results in the generation of reactive oxygen species (ROS) through the reductive activation of oxygen molecules catalyzed by the metal ions. If these metals can be removed and the generated ROS can be strongly scavenged, such diseases can be prevented and treated. Planar catechins exhibit stronger radical scavenging activity than natural catechins and can efficiently scavenge hydroxyl radicals generated by the Fenton reaction without showing pro-oxidant effects, even in the presence of iron ions. Hence, in the current study, we designed a compound in which diethylenetriaminepentaacetic acid (DTPA), a metal chelator, was bound to a planar catechin with enhanced radical scavenging activity by immobilizing the steric structure of a natural catechin to be planar. This compound showed almost no radical scavenging activity due to intramolecular hydrogen bonding of DTPA with the planar catechins; however, when coordinated with Fe3+, it showed more potent radical scavenging activity than planar catechins. Owing to its potent antioxidant activity triggered by metal coordination and its inhibition of ROS generation by trapping metal ions, this compound might exert excellent preventive and therapeutic effects against oxidative stress-related diseases.
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BACKGROUND: Vonoprazan, a potassium-competitive acid blocker (VPZ), significantly reduces postoperative bleeding after gastric ESD; however, there is no consensus on the appropriate treatment duration. We conducted a randomized controlled study to demonstrate that the 3-week administration of VPZ is not inferior to the 8-week administration for ulcer healing. METHODS: This is a prospective, open-label multicenter randomized controlled trial. Patients aged 20-85 years undergoing gastric ESD were included in this study. The key exclusion criteria were patients with bleeding tendencies and those taking NSAIDs, steroids, PPIs, or VPZ medications. Eligible patients were randomly assigned to the VPZ 3w or 8w treatment group. The primary endpoint was the proportion of patients with complete closure of the post-ESD wound at 24 weeks after ESD. The key secondary endpoints included the proportion of patients with complete closure of the post-ESD wound at 8 weeks and the proportion of bleeding or perforation more than 3 weeks after ESD. RESULTS: From May 2018 to October 2020, 234 patients were included. The proportion of patients with complete ulcer closure was significantly lower in the 3w group than in the 8w group (70.8% vs. 90.6%) at 8 weeks post-treatment. The complete closure rates at 24 weeks in the 3w and 8w groups were 99.1% and 99.2%, respectively. The absolute difference in the closure rate at 24 weeks was - 0.059% [95% confidence interval (CI) -3.4% to 3.2], and the lower limit of the 95% CI exceeded -10%, the preset threshold. None of the patients developed delayed bleeding 3 weeks after ESD. CONCLUSION: This multicenter randomized study demonstrated that 3 weeks of treatment with VPZ is sufficient for ulcer healing. Trial registry number. UMIN000031564.
Subject(s)
Endoscopic Mucosal Resection , Stomach Neoplasms , Stomach Ulcer , Humans , Ulcer , Proton Pump Inhibitors/therapeutic use , Stomach Ulcer/drug therapy , Stomach Ulcer/etiology , Prospective Studies , Stomach Neoplasms/drug therapy , Endoscopic Mucosal Resection/adverse effects , Treatment OutcomeABSTRACT
Several studies have suggested that the gut microbiota affect the health of the host. For example, the Firmicutes/Bacteroidetes (F/B) ratio and the proportion of Akkermansia muciniphila in the microbiota have been closely linked to obesity. In this study, we evaluated the effects of an anti-obesity lignan compound, arctigenin (AG), and burdock sprout extract (GSE), which contains AG, on the gut microbiota of an obese mouse model. C57BL/6J mice were fed high-fat, high-sucrose (HFHS) diets containing AG, GSE, or metformin (MF) for 8 weeks. The composition of the gut microbiota and the cecal content of short-chain fatty acids (SCFAs) were determined using 16S rRNA gene sequencing and high-performance liquid chromatography, respectively. Body weight gain was significantly suppressed in mice treated with AG, GSE, and MF. Analysis of the gut microbiota revealed that the F/B ratio was significantly reduced in the AG- and GSE-treated groups. Furthermore, the copy number of A. muciniphila in the feces was significantly increased in obese mice treated with AG and GSE. In addition, the amount of SCFAs (acetic, propionic, and butyric acids) in the cecal content and their fecal excretions were also significantly increased following AG and GSE treatment. Taken together, these results suggest that AG and GSE prevent obesity by improving the composition of the gut microbiota. Moreover, AG promoted the growth of A. muciniphila in vitro. Thus, AG and GSE may function as novel prebiotic supplements to ameliorate obesity, constipation, and intestinal disorders.
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The ease with which a nitrated polyaromatic hydrocarbon (NO2PAH) is activated by reductive metabolism is an important factor in determining mutagenicity. However, the mutagenicity of 3-nitrobenzo[a]pyrene (3-NO2BaP) is stronger than that of 1-NO2BaP despite similar reduction properties, and the more potent mutagenicity of 3,6-diNO2BaP relative to that of 1,6-diNO2BaP cannot be explained by relative reducibility. Here, we investigated structural factors leading to the mutagenicity of these compounds by synthesizing 1- and 3-NO2BaP derivatives with C6-position substituents that affect reduction properties and testing the mutagenicity of the compounds and their derivatives against Salmonella typhimurium TA98 and TA98NR. The LUMO and LUMO+1 energies of 6-substituted 3-NO2BaPs were found to correlate with mutagenicity, but such correlations were much weaker with 6-substituted 1-NO2BaPs, indicating that the mutagenicity of 3-NO2BaPs is influenced by the ease of reductive metabolic activation. In silico structural analyses demonstrated that the distances between the nitrogen of the N-acetoxyamino group in reductive metabolites and a DNA alkylation target were longer for 1-NO2BaPs than for 3-NO2BaPs. Therefore, the active metabolites of 6-substituted 3-NO2BaPs intercalate with DNA at a distance where they can readily form adducts with guanine. Conversely, the unfavorable position of intercalated active metabolites of 1-NO2BaPs relative to guanine leads to difficult adduct formation despite the facile formation of the active metabolite due to a low LUMO energy. Therefore, the chemical reducibility of the nitro group and, more importantly, the ease of adduct formation between an active metabolite and DNA are essential for the prediction of the mutagenicity of NO2PAHs.
Subject(s)
Guanine , Mutagens , DNA , Mutagenesis , Mutagenicity Tests , Mutagens/toxicity , Nitro Compounds/toxicity , Structure-Activity RelationshipABSTRACT
BACKGROUND AND AIM: Although the frequency of endoscopic diagnosis of superficial non-ampullary duodenal epithelial tumors (SNADETs) has been increasing in recent years, no criteria for the endoscopic diagnosis of these tumors have been established yet. The aim of this study was to assess the usefulness of endocytoscopy for diagnosis SNADETs and to establish new criteria. METHODS: This prospective study was conducted at the NTT Medical Center Tokyo from May 2019 to July 2020, and a total of 100 consecutive SNADETs were enrolled. All the endocytoscopic images of the lesions and surrounding normal mucosa were classified into three groups according to the degree of structural atypia and the nuclear morphology and size. The endocytoscopic diagnoses using endocytoscopic classification was compared with the final histopathological diagnoses. RESULTS: Data of 93 patients with 98 lesions were included in the analysis. The preoperative diagnosis by endocytoscopy coincided with the final histopathological diagnosis in 85 (86.7%) of 98 SNADETs. In addition, the sensitivity and specificity for VCL 4/5 were 87.7% and 85.4%, respectively. In contrast, the accuracy, sensitivity, and specificity of preoperative diagnosis by biopsy were 64.3%, 50.9%, and 82.9%, respectively. Preoperative diagnosis by endocytoscopy showed significantly superior accuracy and sensitivity as compared with preoperative biopsy diagnosis (P < 0.001, respectively). CONCLUSIONS: This new classification (endocytoscopic classification) allows prediction of the tumor histopathology in real time, during endocytoscopy without biopsy, and is expected to be of help in determining the appropriate therapeutic strategies for individual cases of SNADETs. (Clinical trial registration number: UMIN000038643.).
Subject(s)
Duodenal Neoplasms , Neoplasms, Glandular and Epithelial , Duodenal Neoplasms/classification , Duodenal Neoplasms/diagnostic imaging , Endoscopy , Humans , Neoplasms, Glandular and Epithelial/classification , Neoplasms, Glandular and Epithelial/diagnostic imaging , Prospective StudiesABSTRACT
OBJECTIVE: With increased screening, more patients with precancerous or early cervical cancer are now being identified. Age at pregnancy, and thus number of patients requiring fertility preservation, have also increased, resulting in more diagnostic and therapeutic cervical conization (conization) procedures. We here investigated the pathological and clinical characteristics of patients undergoing conization, with a focus on age. The objectives of our study were to identify the risk factors potentially involved in cervical intraepithelial neoplasia (CIN) recurrence or persistence, additional treatment after conization, the effects of conization on pregnancy, and the actual status of conization in Japan. STUDY DESIGN: A "Subcommittee for Investigation of Cervical Conization" within the Gynecologic Oncology Committee in the Japan Society of Obstetrics and Gynecology investigated pathological and clinical characteristics of conization at 205 institutions in Japan. We analyzed pathological and clinical characteristics according to age ≤50 and >50 years. RESULTS: Patients aged 20-40 years accounted for 12904 (87%) of the 14,832 study patients (median: 37 years, range: 16-88 years). However, 1838 (12.4%) were aged >50 years. The commonest post-operative diagnosis was CIN grade 3 in all age groups. Rates of invasive cancer, post-operative detection of more advanced lesions, positive surgical margins, additional treatment, and recurrence were significantly higher in patients aged ≥50 years than those aged <50 years (all p < 0.01), whereas rates of post-operative complications did not differ significantly between age groups. The relationship between cerclage and the incidence of amniorrhexis or premature birth did not differ significantly in any age group. CONCLUSION: Post-conization management of patients aged ≥50 years requires considering the high rates of detection of more advanced lesions post-operatively, positive surgical margins, and recurrence. Cerclage should not be performed post-conization without careful consideration.
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BACKGROUND: With the recent increased use of lanthanum carbonate, several cases of lanthanum phosphate deposition to gastric mucosa in dialysis patients have been reported. However, the endoscopic appearance of the early-stage lesion and the over-time alterations of endoscopic findings due to the progression of lanthanum phosphate deposition remain unclear. CASE PRESENTATION: An 80-year-old man receiving dialysis and taking lanthanum carbonate as a phosphate binder over a 4-year period underwent upper gastrointestinal endoscopy four times beginning 1 year after initiation of treatment. The first endoscopic examination (after 1 year of exposure to lanthanum carbonate) revealed rough mucosa with a few areas of white granular mucosa. Over the 3 years of endoscopic follow-up, the white granular mucosa spread and multiple erosions appeared. Histopathological findings of biopsy specimens from an erosion showed extensive infiltration by histiocytes containing deposits. Scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) revealed that the presence of the deposits containing phosphorus and lanthanum in the gastric mucosa. On the basis of these results, the patient was diagnosed with gastropathy associated with lanthanum phosphate deposition. CONCLUSIONS: Over a 3-year period, endoscopic findings associated with lanthanum deposition gradually changed and expanded from the early stage.
Subject(s)
Kidney Failure, Chronic , Stomach Diseases , Aged, 80 and over , Gastric Mucosa , Humans , Lanthanum/adverse effects , Male , Phosphates , Renal DialysisABSTRACT
OBJECTIVES: To (i) identify correlations between selected immunogenic factors and clinicopathological characteristics, (ii) determine whether intratumoral abundance of various specific tumor-infiltrating lymphocytes (TILs) is a prognostic indicator in women with Stage II and III cervical cancer who undergo treatment with cisplatin-based concurrent chemoradiotherapy (CCRT), and (iii) investigate subtypes of FOXP3+ T cells in 15 fresh samples of cervical cancer. METHODS: In this retrospective study, intratumoral lesions in colposcopic biopsies from 55 women with advanced cervical cancer who subsequently underwent CCRT at our institution were subjected to automatic immunological staining using the following six mouse monoclonal antibodies: anti-CD3, anti-CD4, anti-CD8, anti-CD20, anti-CD206, and anti-FOXP3. Associations between the findings on automatic scoring of the number of each type of TIL in each specimen and various clinicopathological characteristics were analyzed, as were associations between the abundance of various specific types of TIL and survival. Subtypes of FOXP3+ TILs in 15 additional fresh tumor samples were also investigated using flow cytometry. RESULTS: Infiltration with CD8+ TILs was associated with pelvic lymph node metastasis. Abundant infiltration by CD3+, CD4+, CD8+, CD206+, and FOXP3+ TILs were statistically significant indicators of better progression-free and overall survival. Regarding subtypes of FOXP3+ TILs, non-Tregs (Fr-III) were found in all samples tested for this. CONCLUSIONS: The abundance of various specific intratumoral TILs may be prognostic indicators in patients with advanced cervical cancer undergoing CCRT.
Subject(s)
Carcinoma, Squamous Cell/therapy , Chemoradiotherapy/methods , Lymphocytes, Tumor-Infiltrating/metabolism , Uterine Cervical Neoplasms/therapy , Adult , CD8-Positive T-Lymphocytes , Carcinoma, Squamous Cell/pathology , Female , Humans , Middle Aged , Retrospective Studies , Tumor Microenvironment , Uterine Cervical Neoplasms/pathologyABSTRACT
BACKGROUND: Gastric cancer after Helicobacter pylori (HP) eradication is a crucial clinical challenge today as HP eradication therapy is widely performed. Detecting gastric cancer after HP eradication tends to be difficult with normal white-light endoscopy. In the present study, we aimed to identify easily-evaluated endoscopic findings that indicate the presence of gastric cancer after HP eradication so that endoscopists can consider additional detailed examinations at the site. METHODS: We analyzed the endoscopic images of 43 patients who underwent endoscopic submucosal dissection for early gastric cancer after HP eradication and 119 patients with an HP eradication history who underwent esophagogastroduodenoscopy for a medical checkup. Endoscopic findings were evaluated according to the Kyoto classification of gastritis (atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness) and map-like redness. RESULTS: Patients with gastric cancer had significantly higher total Kyoto risk scores; more atrophy, intestinal metaplasia, and diffuse redness; and a significantly higher prevalence of map-like redness compared with those without gastric cancer, in the univariate analyses. We used logistic regression analysis with forward selection based on the likelihood ratio to develop a model using atrophy and diffuse redness. Receiver operating characteristic analysis showed that a score of A2 in the Kyoto classification of gastritis (open-type atrophic pattern in the Kimura-Takemoto classification) was an endoscopic marker for the presence of post-HP-eradication gastric cancer. CONCLUSIONS: Endoscopic severe gastric mucosal atrophy is useful to screen patients for gastric cancer after HP eradication.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Stomach Neoplasms , Atrophy/pathology , Gastric Mucosa/pathology , Helicobacter Infections/complications , Helicobacter Infections/drug therapy , Helicobacter Infections/pathology , Humans , Metaplasia/pathology , Stomach Neoplasms/pathology , Stomach Neoplasms/surgeryABSTRACT
The radical-scavenging reaction of fisetin, a natural antioxidant found in strawberries, is known to proceed via hydrogen transfer to produce a fisetin radical intermediate. Thus, introduction of an electron-donating group into the fisetin molecule is expected to stabilize the radical, leading to enhanced radical-scavenging activity. In this study, fisetin derivatives in which methyl substituents were introduced at the ortho positions relative to the catechol hydroxyl groups were synthesized and their radical scavenging activities were evaluated and compared with that of the parent fisetin molecule. Among the methyl derivatives, 5'-methyl fisetin, in which the inherent planar structure of fisetin was retained, exhibited the strongest radical scavenging activity. Introduction of methyl substituents may be effective for the enhancement of various biological activities of antioxidants, particularly radical-scavenging activity.