Effects of Vonoprazan Compared with Esomeprazole on the Healing of Artificial Postendoscopic Submucosal Dissection Ulcers: A Prospective, Multicenter, Two-Arm, Randomized Controlled Trial.

BACKGROUND: Vonoprazan affords more clinical benefits than proton pump inhibitors (PPIs) during the healing of gastroduodenal ulcers. However, it remains controversial whether vonoprazan is more effective than PPIs when used to heal artificial ulcers arising after endoscopic submucosal dissection (ESD). AIM: This study investigated the effects of vonoprazan compared with esomeprazole on the healing of post-ESD artificial ulcers. METHODS: Sixty patients who underwent gastric ESD between May 2015 and May 2017 were randomized to treatment with vonoprazan (V group) or esomeprazole (E group) for 8 weeks. Upper endoscopy was performed at 4 and 8 weeks after ESD, and drug effects were estimated based on the ulcer healing rates and shrinkage rates. RESULTS: Fifty-three patients were analyzed. The respective 4- and 8-week ulcer healing rates did not differ significantly between V and E groups (8.0 versus 11.5%, P = 0.669; 88.9 versus 84.6%, P = 0.420). Similarly, the respective 4- and 8-week ulcer shrinkage rates did not differ significantly between V and E groups (96.8 versus 97.5%, P = 0.656; 100 versus 100%, P = 0.257). CONCLUSION: The healing of artificial ulcers after ESD did not differ using vonoprazan or esomeprazole. Both vonoprazan and esomeprazole were effective when used to promote artificial ulcer healing after ESD.

Correction to: Helicobacter-induced gastric inflammation alters the properties of gastric tissue stem/progenitor cells.

CORRECTION: Unfortunately, the original article [1] contained an error incorporated during production. A duplicated version of Table 1 was published in place of Table 2. Table 2 has been corrected in the original article and is also included correctly below.

Vonoprazan- vs proton-pump inhibitor-based first-line 7-day triple therapy for clarithromycin-susceptible Helicobacter pylori: A multicenter, prospective, randomized trial.

BACKGROUND: The eradication rate of vonoprazan-based first-line triple therapy (combined with clarithromycin and amoxicillin) (V-AC) was reported to be 97.6% in patients with clarithromycin (CAM)-susceptible Helicobacter pylori in a phase III study, whereas our real-world, prospective, multicenter cohort study yielded an eradication rate <90%. OBJECTIVE: To validate the eradication rate of V-AC using CAM-susceptible testing in a multicenter, prospective, randomized trial. METHODS: We included 147 treatment-naïve H. pylori-positive patients [41 with CAM-resistant infections and 106 with CAM-susceptible infections]. The CAM-susceptible group patients were randomized to either the V-AC group (vonoprazan 20 mg bid, amoxicillin 750 mg bid, and clarithromycin 200 or 400 mg bid) or PPI-AC group (lansoprazole 30 mg, rabeprazole 10 mg, or esomeprazole 20 mg bid; amoxicillin 750 mg bid; and clarithromycin 200 or 400 mg bid). All CAM-resistant H. pylori were eradicated by V-AC, as measured by the urea breath test around 8 weeks after eradication. Safety was evaluated by patient questionnaires. RESULTS: The intention-to-treat and per-protocol eradication rates of V-AC in the CAM-susceptible H. pylori-infected patients were 87.3% (95% confidence interval 75.5%-94.7%) and 88.9% (77.4%-95.8%). The respective eradication rates of PPI-AC were 76.5% (62.5%-87.2%) and 86.7% (73.2%-94.9%). No significant difference was observed between the V-AC and PPI-AC regimes in terms of the intention-to-treat (P = .21) or per-protocol (P = .77) analyses. The questionnaire scores did not differ significantly between the groups. Both the intention-to-treat and per-protocol eradication rates of V-AC in the CAM-resistant patients were 82.9% (67.9%-92.8%). CONCLUSION: The eradication rate of V-AC treatment in the CAM-susceptible H. pylori-infected patients was <90%, as was that by PPI-AC, thus V-AC is not ideal regimen in CAM-susceptible H. pylori. However, the 82.9% eradication rate of V-AC in the CAM-resistant infections may indicate the potential of V-AC with modified dose, dosing interval, and treatment duration. (UMIN000016337).

Helicobacter-induced gastric inflammation alters the properties of gastric tissue stem/progenitor cells.

BACKGROUND: Although Helicobacter-induced gastric inflammation is the major predisposing factor for gastric carcinogenesis, the precise mechanism by which chronic gastritis causes gastric cancer remains unclear. Intestinal and spasmolytic polypeptide-expressing metaplasia (SPEM) is considered as precancerous lesions, changes in epithelial tissue stem/progenitor cells after chronic inflammation has not been clarified yet. In this study, we utilized three-dimensional gastric epithelial cell culture systems that could form organoids, mimicking gastric epithelial layer, and characterized the changes in epithelial cells after chronic Helicobacter felis infection. METHODS: We used three mice model; 1) long-term H. felis infection, 2) H. felis eradication, and 3) MNU chemical carcinogenesis model. We performed cRNA microarray analysis after organoid culture, and analyzed the effects of chronic gastric inflammation on tissue stem cells, by the size of organoid, mRNA expression profile and immunohistochemical analysis. RESULTS: The number of organoids cultured from gastric epithelial cells was significantly higher in organoids isolated from H. felis-infected mice compared with those from uninfected gastric mucosa. Based on the mRNA expression profile, we found that possible stem cell markers such as Cd44, Dclk1, and genes associated with the intestinal phenotype, such as Villin, were increased in organoids isolated from H. felis-infected mucosa compared with the control. The upregulation of these genes were cancelled after H. felis eradication. In a xenograft model, tumors were generated only from organoids cultured from carcinogen-treated gastric mucosa, not from H. felis infected mucosa or control organoids. CONCLUSIONS: Our results suggested that, as a possible mechanism of gastric carcinogenesis, chronic inflammation induced by H. felis infection increased the number of tissue stem/progenitor cells and the expression of stem cell markers. These findings suggest that chronic inflammation may alter the direction of differentiation toward undifferentiated state and that drawbacks may enable cells to redifferentiate to intestinal metaplasia or neoplasia.

First-Line Helicobacter pylori Eradication with Vonoprazan, Clarithromycin, and Metronidazole in Patients Allergic to Penicillin.

AIM: To assess the efficacy of 7-day first-line Helicobacter pylori eradication with vonoprazan (VPZ), clarithromycin (CAM), and metronidazole (MNZ) in patients with penicillin allergy. METHODS: Patients with penicillin allergy, diagnosed with Helicobacter pylori infection and did not have history of Helicobacter pylori eradication, were eligible for the study. Twenty patients were prospectively treated with 20 mg VPZ twice daily, 200 or 400 mg CAM twice daily, and 250 mg MNZ twice daily for 7 days. We also collected the data from 30 patients retrospectively treated with proton pump inhibitor (PPI), CAM, and MNZ. Safety was evaluated in patients completing an adverse effect questionnaire. RESULTS: Both the intention-to-treat and per-protocol effectiveness of VPZ-based eradication were 100% (95% CI: 86.1-100%; n = 20). The eradication rates of PPI-based regimen were 83.3% (95% CI: 65.3-94.4%) in the ITT and 82.7% (95% CI: 64.2-94.2%) in the PP analyses. Abdominal fullness was more frequent in VCM compared to PCM. However, all patients with VCM regimen had taken 100% of their course of medication. CONCLUSION: Triple therapy with VPZ, CAM, and MNZ is well tolerated and effective for eradicating Helicobacter pylori in patients allergic to penicillin. This study was registered in the UMIN Clinical Trials Registry as UMIN000016335.

c-Jun N-terminal kinase in pancreatic tumor stroma augments tumor development in mice.

Pancreatic ductal adenocarcinoma (PDAC) is a life-threatening disease and there is an urgent need to develop improved therapeutic approaches. The role of c-Jun N-terminal kinase (JNK) in PDAC stroma is not well defined even though dense desmoplastic reactions are characteristic of PDAC histology. We aimed to explore the role of JNK in PDAC stroma in mice. We crossed Ptf1aCre/+ ;KrasG12D/+ mice with JNK1-/- mice to generate Ptf1aCre/+ ;KrasG12D/+ ;JNK1-/- (Kras;JNK1-/- ) mice. Tumor weight was significantly lower in Kras;JNK1-/- mice than in Kras;JNK1+/- mice, whereas histopathological features were similar. We also transplanted a murine PDAC cell line (mPC) with intact JNK1 s.c. into WT and JNK1-/- mice. Tumor diameters were significantly smaller in JNK1-/- mice. Phosphorylated JNK (p-JNK) was activated in α-smooth muscle actin (SMA)-positive cells in tumor stroma, and mPC-conditioned medium activated p-JNK in tumor-associated fibroblasts (TAF) in vitro. Relative expression of Ccl20 was downregulated in stimulated TAF. Ccl20 is an important chemokine that promotes CD8+ T-cell infiltration by recruitment of dendritic cells, and the number of CD8+ T cells was decreased in Kras;JNK1+/- mice compared with Kras;JNK1-/- mice. These results suggest that the cancer secretome decreases Ccl20 secretion from TAF by activation of JNK, and downregulation of Ccl20 secretion might be correlated with reduction of infiltrating CD8+ T cells. Therefore, we concluded that inhibition of activated JNK in pancreatic tumor stroma could be a potential therapeutic target to increase Ccl20 secretion from TAF and induce accumulation of CD8+ T cells, which would be expected to enhance antitumor immunity.

The Superiority of Vonoprazan-based First-line Triple Therapy with Clarithromycin: A Prospective Multi-center Cohort Study on Helicobacter pylori Eradication.

Objective We evaluated the safety and efficacy of vonoprazan-based amoxicillin and clarithromycin 7-day triple therapy (VAC) in comparison to proton pump inhibitor (PPI)-based (PAC) as a first-line treatment and vonoprazan-based amoxicillin and metronidazole 7-day triple therapy (VAM) in comparison to PPI-based (PAM) as a second-line treatment for the eradication of Helicobacter pylori in Japan. Methods We performed a non-randomized, multi-center, parallel-group study to compare first-line VAC to PAC and second-line VAM to PAM. A pre-planned subgroup analysis on CAM resistance was also performed. Safety was evaluated with an adverse effects questionnaire (AEQ), which was completed by patients during therapy. Results The first-line eradication rates (ER) in the intention-to-treat (ITT) and per protocol (PP) analyses were 84.9% (95% CI: 81.9-87.6%, n=623) and 86.4% (83.5-89.1%, n=612), respectively, for VAC and 78.8% (75.3-82.0%, n=608) and 79.4% (76.0-82.6%, n=603), respectively, for PAC. The ER of VAC was higher than that of PAC in the ITT (p=0.0061) and PP analyses (p=0.0013). The ERs for VAC in patients with CAM-resistant and CAM-susceptible bacteria were 73.2% (59.7-84.2%, n=56) and 88.9% (83.4-93.1%, n=180), respectively. PAC was associated with higher AEQ scores for diarrhea, nausea, headache, and general malaise. In the second-line ITT and PP analyses VAM achieved ERs of 80.5% (74.6-85.6%, n=216) and 82.4% (76.6-87.3%, n=211), respectively, while PAM achieved ERs of 81.5% (74.2-87.4%, n=146) and 82.1% (74.8-87.9%, n=145), respectively. No significant differences were observed in the ITT (p=0.89) or PP (p=1.0) analyses. Conclusion The ER of first-line VAC was higher than that of PAC, but still <90%. No difference was observed between second-line VAM and PAM. Vonoprazan-based triple therapy was safe and well tolerated.

Case of a tumor comprising gastric cancer and duodenal neuroendocrine tumor.

The present report describes a rare case of a tumor composed of early gastric cancer and a duodenal neuroendocrine tumor (NET). A 78-year-old woman underwent esophagogastroduodenoscopy at a local institution for screening of the upper gastrointestinal tract which revealed a protruded tumor through the pyloric ring from the pyloric antrum. The tumor was too large to treat at the facility; consequently, she was referred to our hospital for further management. Esophagogastroduodenoscopy with tumor biopsy of the lesion revealed the diagnosis of early gastric cancer. Endoscopic submucosal dissection was performed with sufficient free margins in both vertical and horizontal directions. Histopathological findings showed NET confined to the submucosal layer and covered by well-differentiated adenocarcinoma. Immunohistochemical stainings showed that the two lesions existed continuously. While the possibility of a collision cancer was considered, it was suggested that the two lesions existed continuously. Finally, the tumor was diagnosed as gastric cancer composed of duodenal NET G1, with a lymphatic invasion of NET component.

Intestine-specific homeobox (ISX) induces intestinal metaplasia and cell proliferation to contribute to gastric carcinogenesis.

BACKGROUND: Helicobacter pylori induces chronic inflammation and intestinal metaplasia (IM) through genetic and epigenetic changes and activation of intracellular signaling pathways that contribute to gastric carcinogenesis. However, the precise mechanism of IM in gastric carcinogenesis has not been fully elucidated. We previously found that intestine-specific homeobox (ISX) mRNA expression increased in organoids cultured from Helicobacter-infected mouse mucosa. In this study, we elucidate the role of ISX in the development of IM and gastric carcinogenesis. METHODS: ISX expression was assessed in Helicobacter-infected mouse and human gastric mucosa. MKN45 gastric cancer cells were co-cultured with H. pylori to determine whether Helicobacter infection induced ISX expression. We established stable MKN45 transfected cells expressing ISX (Stable-ISX MKN45) and performed a spheroid colony formation assay and a xenograft model. We performed ISX immunohistochemistry in cancer and adjacent gastric tissues. RESULTS: ISX expression was increased in mouse and human gastric mucosa infected with Helicobacter. The presence of IM and H. pylori infection in human stomach was correlated with ISX expression. H. pylori induced ISX mRNA and protein expression. CDX1/2, cyclinD1, and MUC2 were upregulated in Stable-ISX MKN45, whereas MUC5AC was downregulated. Stable-ISX MKN45 cells formed more spheroid colonies, and had high tumorigenic ability. ISX expression in gastric cancer and adjacent mucosa were correlated. CONCLUSIONS: ISX expression induced by H. pylori infection may lead to IM and hyperproliferation of gastric mucosa through CDX1/2 and cyclinD1 expression, contributing to gastric carcinogenesis.

Effectiveness and clinical results of endoscopic management of sigmoid volvulus using unsedated water-immersion colonoscopy.

BACKGROUND AND AIM: Although intestinal obstruction as a result of sigmoid volvulus (SV) may be successfully resolved using endoscopic detorsion, surgical treatment remains the main therapeutic strategy. We evaluated the endoscopic detorsion procedure using unsedated water-immersion colonoscopy for the treatment of SV. METHODS: A retrospective chart review was conducted on the clinical background and prognosis of 21 SV patients who underwent 71 endoscopic detorsion procedures using unsedated, water-immersion colonoscopy. RESULTS: In all, 14 (67%) male and seven (33%) female patients, with a mean age of 73 years (range, 54-95 years) were enrolled; 86% were >70 years of age. Among these patients, 90% had a background of key predisposing factors. In the 21 patients, endoscopic detorsion was successfully done using unsedated water-immersion colonoscopy. SV recurred in 10 patients at a median of 180 days. Endoscopic detorsion for recurrent SV was successfully achieved in all cases, and none of the secondary cases became severe. Only male patients were observed to experience three or more recurrent episodes of SV. CONCLUSIONS: SV occurred most commonly in elderly patients with a surgical risk. Our experience suggests that conservative endoscopic treatment using unsedated water-immersion colonoscopy is a safe, reasonable, conservative endoscopic approach for elderly patients in the absence of necrotic findings. We currently use this procedure in most of our cases.

[A case of gastric carcinosarcoma treated with surgical resection and irinotecan and mitomycin C combination therapy].

A 59-year-old man was admitted following episodes of melena. Upper gastrointestinal endoscopy revealed a type 2 carcinoid-like tumor in the cardium of the stomach. Histopathological analysis of a biopsy specimen revealed adenocarcinoma. Although hepatic metastases were detected, total gastrectomy was initially performed for hemorrhage control. The final histopathological diagnosis of the resected primary tumor was gastric carcinosarcoma with an osteosarcoma component. After ineffective first-line combination therapy with S-1 (tegafur, gimeracil, and oteracil) and cisplatin, irinotecan and mitomycin C chemotherapy was introduced. Although the hepatic metastases showed shrinkage after three courses of the chemotherapy, the patient succumbed seven months after surgery. This case report suggests that systemic chemotherapy using irinotecan and mitomycin C may be effective in the treatment of gastric carcinosarcoma with an osteosarcoma component and distant metastases.

A case of acute hepatitis B related to previous gynecological surgery in Japan.

A 41-year-old woman became ill with acute hepatitis B after gynecological surgery performed by a surgeon who was hepatitis B surface antigen positive. The surgeon was positive for hepatitis B e antigen, and HBV DNA concentrations in the serum, saliva, and sweat of the surgeon were very high. HBV genotype and partial HBV DNA sequences from the HBV-infected surgeon were identical to those in the HBV-infected patient. Extensive research by the committee including infection control and prevention specialists judged the source of infection to be a surgeon infected with HBV. Transmission of HBV from a healthcare worker to patients who are not immune to HBV can actually happen. This case report illustrates the importance of a stringent policy of a nationwide HBV universal vaccination program.

The first example of metallocene-like coordination mode of THBQ(4-): a mixed-valence heptanucler palladium complex [Pd7(THBQ)2(tben)6](PF6)4.

The title compound adopts a structure reminiscent of metallocene analogues, in which two disk-like units [Pd(II)(3)(THBQ)(tben)(3)](2+) bind to one naked Pd(0) metal in a sandwich form through each C(6)O(6)(4-) (THBQ(4-)) ring with an eta(6)-binding fashion.

Evidence of immunostimulating lipoprotein existing in the natural lipoteichoic acid fraction.

Lipoteichoic acid (LTA) is a cell surface glycoconjugate of gram-positive bacteria and is reported to activate the innate immune system. We previously reported that purified LTA obtained from Enterococcus hirae has no immunostimulating activity, but a subfraction (Eh-AF) in an LTA fraction possesses activity. In this study, we established a mouse monoclonal antibody neutralizing the activity of Eh-AF and investigated its inhibitory effects. Monoclonal antibody (MAbEh1) was established by the immunization of BALB/c mice with Eh-AF, followed by hybridoma screening based on its inhibitory effect for the production of interleukin-6 (IL-6) induced by Eh-AF. MAbEh1 neutralized the production of IL-6 by LTA fraction from not only E. hirae but also Staphylococcus aureus, while it failed to block that of lipopolysaccharide, suggesting that the antibody recognized a common active structure(s) in LTA fractions. Synthetic glycolipids in these LTAs did not induce cytokine production, at least in our system. Interestingly, the antibody was found to inhibit the activity of immunostimulating synthetic lipopeptides, Pam(3)CSK(4) and FSL-1. These results suggest that MAbEh1 neutralizes the activity of lipoprotein-like compounds which is responsible for the activity of the LTA fraction of E. hirae and S. aureus.

Lipoprotein is a predominant Toll-like receptor 2 ligand in Staphylococcus aureus cell wall components.

Lipoteichoic acid (LTA) derived from Staphylococcus aureus is reported to be a ligand of Toll-like receptor 2 (TLR2). In this study, we demonstrated that lipoproteins obtained from S. aureus are potent activators of TLR2. A fraction obtained by Triton X-114 phase partitioning activated cells through TLR2. The fraction contained proteins and LTA. The activity was detected in compounds in a mass range of 12-40 kDa. Proteinase K digested the active compounds into lower molecular weight active materials <10 kDa. In contrast, hydrofluoric acid treatment, which decomposes LTA, did not alter the molecular mass of the active compounds. Further, most of the activity was abrogated by lipoprotein lipase digestion. These results suggested that lipoproteins are predominant TLR2 ligands in S. aureus cell wall components.

Oxygen tension regulates reactive oxygen generation and mutation of Helicobacter pylori.

Although both bacillary and coccoid forms of Helicobacter pylori reside in human stomach, the pathophysiological significance of the two forms remains obscure. The present work describes the effect of oxygen tension on the transformation and reactive oxygen species (ROS) metabolism of this pathogen. Most H. pylori cultured under an optimum O2 concentration (7%) were the bacillary form, whereas about 80% of cells cultured under aerobic or anaerobic conditions were the coccoid form. The colony-forming unit of H. pylori decreased significantly under both aerobic and anaerobic culture conditions. The bacillary form of H. pylori generated predominantly superoxide radical, whereas the coccoid form generated preferentially hydroxyl radical. Specific activities of cellular respiration, urease, and superoxide dismatase decreased markedly after transformation of the bacillary form to the coccoid form, with concomitant generation of protein carbonyls and 8-hydroxyguanine. The frequency of mutation of cells increased significantly during culture under nonoptimum O2 conditions. These results indicate that ROS generated by H. pylori catalyze the oxidative modification of cellular DNA, thereby enhancing the transformation from the bacillary to the coccoid form. The enhanced generation of mutagenic hydroxyl radicals in the coccoid form might accelerate mutation and increase the genetic diversity of H. pylori.

Serum nutritional status of tocopherol and retinol normalized to lipids of persons living in the southern rural Terai region in Nepal.

OBJECTIVE: The present study examined the levels of serum α-Tocopherol (Toc), retinol (Ret), cholesterol (Chol) and triglycerides (TG), and their correlations in the sera of people in Nepal. METHODS: The survey was conducted on the general populace in the agricultural Terai region in southern Nepal. The study population consisted of 93 males and 83 females aged 10-68 years. Serum Toc and Ret were measured by high-performance liquid chromatography. RESULTS: No significant differences were observed between the genders for the average of total Chol (T-Chol) (140 and 145 mg/100 ml, respectively), HDL-C (45 and 47 mg/100 ml), LDL-C (94 and 97 mg/100 ml), and TG (106 and 110 mg/100 ml), and the ratio of LDL/HDL (2.16). The levels of mean Toc (4.32 and 4.27 µg/ml) were about the same for both genders, while the mean Ret levels were significantly higher for males (624 ng/ml) than for females (535 ng/ml) (p<0.001). A direct relationship was found between the levels of Toc and Ret (r=0.46, p<0.001 and r=0.28, p<0.05 for males and females, respectively). Serum levels of Toc and Ret were positively related to the levels of Chol (r=0.48 and r=0.58, p<0.001 for males and r=0.49, p<0.01 and r-0.28, p<0.05 for females, respectively). The ratio of Toc/TG normalized to serum TG was directly correlated to the ratio of Ret/TG (r=0.79 for males, and r=0.72 for females, p<0.001, respectively) and the ratios of Toc/TG and Ret/TG were negatively related to the LDL/HDL levels (r=-0.49 and r=-0.43, for males, and r=-0.46 and r=-0.57 for females, p<0.001, respectively). CONCLUSION: The levels of Toc and Ret were low in the sera of people living in the southern rural Terai region in Nepal, and it was found that lower levels of Toc and Ret normalized to TG increased the ratio of LDL/HDL. These results suggest that greater intake of foods rich in Toc and Ret should be encouraged to reduce the erisk of coronary heart disease.

L-Serine, D- and L-proline and alanine as respiratory substrates of Helicobacter pylori: correlation between in vitro and in vivo amino acid levels.

Helicobacter pylori whole cells showed high rates of oxygen uptake with L-serine and L-proline as respiratory substrates, and somewhat lower rates with D-alanine and D-proline. These respiratory activities were inhibited by rotenone and antimycin A at low concentrations. Since pyruvate was produced from L-serine and D- and L-alanine in whole cells, the respiratory activities with these amino acids as substrates occurred via pyruvate. Whole cells showed 2,6-dichlorophenolindophenol (DCIP)-reducing activities with D- and L-proline and D-alanine as substrates, suggesting that hydrogen removed from these amino acids also participated in oxygen uptake by the whole cells. High amounts of L-proline, D- and L-alanine, and L-serine were present in H. pylori cells, and these amino acids also predominated in samples of human gastric juice. H. pylori seems to utilize D- and L-proline, D-alanine and L-serine as important energy sources in its habitat of the mucous layer of the stomach.

Endotoxic and immunobiological activities of a chemically synthesized lipid A of Helicobacter pylori strain 206-1.

A synthetic lipid A of Helicobacter pylori strain 206-1 (compound HP206-1), which is similar to its natural lipid A, exhibited no or very low endotoxic activities as compared to Escherichia coli-type synthetic lipid A (compound 506). Furthermore, compound HP206-1 as well as its natural lipid A demonstrated no or very low mitogenic responses in murine spleen cell. On the other hand, compound HP206-1 showed a weaker but significant production of interleukin-8 in a gastric cancer cell line, MKN-1, in comparison with compound 506. Furthermore, compound HP206-1 exhibited induction of tumor necrosis factor-alpha production in human peripheral blood mononuclear cells and the cytokine production was clearly inhibited by mouse anti-human Toll-like receptor (TLR) 4 monoclonal antibody HTA125. Our findings indicate that the chemically synthesized lipid A, mimicking the natural lipid A portion of lipopolysaccharide from H. pylori strain 206-1, has a low endotoxic potency and immunobiological activities, and is recognized by TLR4.