The photothermal therapy using nanomaterials has been recently attracted as an efficient strategy for the next generation of cancer treatments. Single walled carbon nanotube (SWNT) is an upcoming ...potent candidate for the photothermal therapeutic agent since it generates significant amounts of heat upon excitation with near-infrared light (NIR, lambda = 700-1100 nm) which is transparent to biological systems including skins. Such a photothermal effect can be employed to induce thermal cell death in a noninvasive manner. Here, we demonstrate in vivo obliteration of solid malignant tumors by the combined treatments of SWNTs and NIR irradiation. The photothermally treated mice displayed complete destruction of the tumors without harmful side effects or recurrence of tumors over 6 months, while the tumors treated in other control groups were continuously grown until the death of the mice. Most of the injected SWNTs were almost completely excreted from mice bodies in about 2 months through biliary or urinary pathway. These results suggest that SWNTs may potentially serve as an effective photothermal agent and pave the way to future cancer therapeutics.
Lactobacillus paracasei is a major probiotic and is well known for its anti-inflammatory properties. Thus, we investigated the effects of L. paracasei-derived extracellular vesicles (LpEVs) on ...LPS-induced inflammation in HT29 human colorectal cancer cells and dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice. ER stress inhibitors (salubrinal or 4-PBA) or CHOP siRNA were utilized to investigate the relationship between LpEV-induced endoplasmic reticulum (ER) stress and the inhibitory effect of LpEVs against LPS-induced inflammation. DSS (2%) was administered to male C57BL/6 mice to induce inflammatory bowel disease, and disease activity was measured by determining colon length, disease activity index, and survival ratio. In in vitro experiments, LpEVs reduced the expression of the LPS-induced pro-inflammatory cytokines IL-1α, IL-1β, IL-2, and TNFα and increased the expression of the anti-inflammatory cytokines IL-10 and TGFβ. LpEVs reduced LPS-induced inflammation in HT29 cells and decreased the activation of inflammation-associated proteins, such as COX-2, iNOS and NFκB, as well as nitric oxide. In in vivo mouse experiments, the oral administration of LpEVs also protected against DSS-induced colitis by reducing weight loss, maintaining colon length, and decreasing the disease activity index (DAI). In addition, LpEVs induced the expression of endoplasmic reticulum (ER) stress-associated proteins, while the inhibition of these proteins blocked the anti-inflammatory effects of LpEVs in LPS-treated HT29 cells, restoring the pro-inflammatory effects of LPS. This study found that LpEVs attenuate LPS-induced inflammation in the intestine through ER stress activation. Our results suggest that LpEVs have a significant effect in maintaining colorectal homeostasis in inflammation-mediated pathogenesis.
SUMMARY
Background
Tegoprazan is a novel potassium‐competitive acid blocker used to treat acid‐related disorders.
Aim
To compare tegoprazan 25 mg with lansoprazole 15 mg as maintenance therapy in ...healed erosive oesophagitis (EE)
Methods
In this phase 3, double‐blind, multi‐centre study, patients with endoscopically confirmed healed EE were randomised 1:1 to receive tegoprazan 25 mg or lansoprazole 15 mg once daily for up to 24 weeks. The primary efficacy endpoint was the endoscopic remission rate after 24 weeks. The secondary efficacy endpoint was the endoscopic remission rate after 12 weeks. Safety endpoints included adverse events, clinical laboratory results and serum gastrin and pepsinogen I/II levels.
Results
We randomised patients to tegoprazan 25 mg (n = 174) or lansoprazole 15 mg (n = 177). Most had mild EE (Los Angeles (LA) grade A: 57.3%, LA grade B: 37.3%). The endoscopic remission rate after 24 weeks was 90.6% with tegoprazan and 89.5% with lansoprazole. Tegoprazan was not inferior to lansoprazole for maintaining endoscopic remission at 24 weeks and 12 weeks. In subgroup analysis, tegoprazan 25 mg showed no significant difference in maintenance rate according to LA grade (p = 0.47). The maintenance effect of tegoprazan was consistent in CYP2C19 extensive metabolisers (p = 0.76). Increases in serum gastrin were not higher in tegoprazan‐treated than lansoprazole‐treated patients.
Conclusions
Tegoprazan 25 mg was non‐inferior to lansoprazole 15 mg in maintenance of healing of mild EE. In this study, tegoprazan had a similar safety profile to lansoprazole.
In this phase 3, double‐blind, multi‐centre study, patients with endoscopically confirmed healederosive oesophagitis were randomised 1:1 to receive tegoprazan 25 mg or lansoprazole 15 mg once daily for up to 24 weeks. The endoscopic remission rate after 24 weeks was 90.6% for the tegoprazan group and 89.5% for the lansoprazole group. Overall, tegoprazan was not inferior to lansoprazole for maintaining endoscopic remission rates at 24 weeks and 12 weeks, and was well tolerated during the maintenance period.
Summary
Background
Tegoprazan is a novel potassium‐competitive acid blocker for the treatment of acid‐related disorders.
Aims
To assess whether tegoprazan is non‐inferior to lansoprazole in terms of ...efficacy and safety in patients with gastric ulcers.
Methods
In this phase 3, double‐blind, active control, multicentre study, 306 gastric ulcer patients were randomised to one of three treatment groups: tegoprazan 50 mg, tegoprazan 100 mg and lansoprazole 30 mg once daily for 4 or 8 weeks. The primary endpoint was the cumulative proportion of patients with healed ulcers confirmed by endoscopy up to 8 weeks from treatment initiation. Symptoms and safety were assessed.
Results
In the full analysis set, the cumulative healing rates at week 8 were 94.8% (91/96) for the tegoprazan 50 mg, 95.0% (94/99) for the tegoprazan 100 mg and 95.7% (89/93) for the lansoprazole 30 mg groups. At week 4, the respective healing rates were 90.6% (87/96), 91.9% (91/99), and 89.2% (83/93). In per protocol analysis, 4‐week healing rates were 95.4% (84/88), 94.6% (88/93) and 92.9% (79/85) for tegoprazan 50 mg, tegoprazan 100 mg and lansoprazole 30 mg, respectively. Both doses of tegoprazan were non‐inferior to lansoprazole in ulcer healing at 4 and 8 weeks. The incidence of drug‐related treatment‐emergent adverse events did not differ among groups. The increase in serum gastrin concentration was not higher in tegoprazan‐treated patients than in lansoprazole‐treated patients.
Conclusions
Tegoprazan 50 or 100 mg were not inferior to lansoprazole 30 mg once daily in the treatment of gastric ulcers.
•Yuzu, wasabi, and rosemary were selected to inhibit the growth of microorganisms.•In optimal mixing conditions using RSM, yuzu juice was 3.92% (v/w).•Wasabi and rosemary extracts were 23.41% (v/w) ...and 3.93% (v/w), respectively.•The application of mixing antimicrobial agents was more effective than alone.
This study aimed to determine the antimicrobial effectiveness of natural antimicrobial agents (NAAs) (yuzu juice, wasabi extract, and rosemary extract) against three target microorganisms (TMs) (Escherichia coli, Staphylococcus aureus, and Salmonella Typhimurium) and to determine the optimal concentration of these agents using response surface methodology (RSM) to ensure the safety of meal kits manufactured using marinade sauce. The three NAAs added to marinade sauce effectively inactivated TMs (P<0.05), in particular, yuzu juice had the greatest antimicrobial effect against TMs, followed by wasabi and rosemary extracts. To determine the optimal concentration of NAAs using RSM, 17 concentrations were tested with three TMs as dependent variables and three NAAs as independent variables. The results showed that E. coli was not present under any of the conditions tested, whereas S. aureus and S. Typhimurium exhibited different characteristics depending on the conditions. Through response surface analysis of the TMs except for E. coli, which was not detected, it was determined that S. aureus had a coefficient of determination (R2) of 0.928 and a lack of fit of 0.074, and the linear regression of yuzu juice (X1) and quadratic regression of yuzu juice2 (X12) were both significant (P<0.05). S. Typhimurium had an R2 of 0.8955 and a lack of fit of 0.051, and only the quadratic regression of yuzu juice2 (X12) was significant (P<0.05). Based on RSM and ridge analysis, the optimal mixed conditions were determined to be 3.92% (v/w) yuzu juice, 23.41% (v/w) wasabi extract, and 3.93% (v/w) rosemary extract. After investigating the antimicrobial effect under the optimal conditions, E. coli and S. Typhimurium were absent, and S. aureus was reduced to 2.50 ± 0.09 log colony-forming units/g after 24 h. The results indicated that mixed treatment with the three NAAs had a more significant antimicrobial effect due to their synergistic properties compared to when used in isolation.
Mitochondrial defects and antimitochondrial cardiolipin (CL) antibodies are frequently detected in autoimmune disease patients. CL from dysregulated mitochondria activates various pattern recognition ...receptors, such as NLRP3. However, the mechanism by which mitochondrial CL activates APCs as a damage‐associated molecular pattern to prime antigen‐specific naïve T cells, which is crucial for T‐cell‐dependent anticardiolipin IgG antibody production in autoimmune diseases is unelucidated. Here, we show that CL increases the expression of costimulatory molecules in CD11c+ APCs both in vitro and in vivo. CL activates CD11c+ APCs via TLR2‐PI3K‐PKN1‐AKT/p38MAPK‐NF‐κB signaling. CD11c+ APCs that have been activated by CL are sufficient to prime H‐Y peptide‐specific naïve CD4+ T cells and OVA‐specific naïve CD8+ T cells. TLR2 is necessary for anti‐CL IgG antibody responses in vivo. Intraperitoneal injection of CL does not activate CD11c+ APCs in CD14 KO mice to the same extent as in wild‐type mice. CL binds to CD14 (Kd = 7 × 10−7 M). CD14, but not MD2, plays a role in NF‐kB activation by CL, suggesting that CD14+ macrophages contribute to recognizing CL. In summary, CL activates signaling pathways in CD11c+ APCs through a mechanism similar to gram (+) bacteria and plays a crucial role in priming antigen‐specific naïve T cells.
Cardiolipin induce cytoskeletal rearrangement and upregulate expression of costimulatory molecules of CD11c+ APCs via TLR2‐PI3K‐PKN1‐AKT/p38MAPK‐NF‐κB signaling pathway. CL induces proliferation and IFN‐γ production of antigen‐specific T cells when OVA or H‐Y peptide was administered together. CD14 also plays a role in activation of CD11c+ APCs in response to CL.
The relationship between fasting blood glucose (FBG) variability and colorectal cancer (CRC) remains ill-defined. This study aimed to evaluate the association of FBG variability with CRC risk in the ...healthy population without overt diabetes.
In the data from the Korean National Health Insurance Service-Health Screening Cohort, we included individuals examined by FBG testing at least 3 times between 2002 and 2007. FBG variability was calculated using standard deviation (SD) and coefficient of variation (CV).
Regarding FBG variability, an increase in the quintile of SD or CV was independently associated with CRC risk (all p for trend <0.01). When the change in FBG was classified into six trajectory patterns, unfavorable trajectory patterns (high stable and upward) were significantly associated with increased CRC risk (hazard ratio HR 2.30, p=0.003; HR 1.19, p=0.007, respectively). In subgroup analyses according to the sex, a significant association between FBG variability (SD or CV) and CRC risk was observed in men but not in women. The high stable and upward pattern were also associated with CRC risk in men (HR 2.47, p=0.002; HR 1.21, p=0.012) but not in women.
This study identified that FBG variability and unfavorable trajectory patterns were significantly associated with increased CRC risk in the healthy population without overt diabetes. Our findings suggest that FBG variability as well as FBG itself may be a predictive factor for the development of CRC.
Background/AimsWe examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication. MethodsA randomized, double-blind, controlled, multicenter ...study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)- based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases. ResultsIn total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences. ConclusionsTPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea (ClinicalTrials.gov identifier NCT03317223).
Although both per-oral endoscopic myotomy (POEM) and Heller myotomy (HM) have been used for the treatment of achalasia, the comparative efficacy of POEM and HM has yet to be fully evaluated.
We ...searched all relevant studies published up to September 2018 examining the comparative efficacy between POEM and HM. Study quality was assessed using the Newcastle-Ottawa scale. Meta-analyses for Eckardt scores, perioperative outcomes, and reflux-related outcomes were performed based on a random-effects model.
Fifteen studies with a total of 1213 patients were evaluated. The follow-up duration ranged from 2 to 46.2 months and from 2 to 54.2 months in the POEM and HM groups, respectively. Postoperative Eckardt scores were lower (better) in the POEM group than in the HM group (pooled standardized mean difference SMD, −0.58; 95% confidence interval CI, −1.03 to −0.13). Length of myotomy was greater in the POEM group than in the HM group (pooled SMD, 0.63; 95% CI, 0.42-0.84). There was no difference in reflux symptoms and pathologic reflux on pH monitoring between the groups (pooled risk ratio RR, 1.03; 95% CI, 0.61-1.73; and pooled RR, 1.22; 95% CI, 0.67-2.25, respectively). Erosive esophagitis on endoscopy tended to be less common in the HM group (pooled RR, 1.88; 95% CI, 0.98-3.62).
Although long-term follow-up data are insufficient, the short-term efficacy of POEM was superior to that of HM. Erosive esophagitis tended to be more common in the POEM group; however, there was no difference in reflux symptoms and pathologic reflux on pH monitoring between the groups.
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Tonsil-derived mesenchymal stem cells (TMSCs) showed therapeutic effects on acute and chronic murine colitis models, owing to their immunomodulatory properties; therefore, we evaluated enhanced ...therapeutic effects of TMSCs on a murine colitis model using three-dimensional (3D) culture method. The expression of angiogenic factors, VEGF, and anti-inflammatory cytokines, IL-10, TSG-6, TGF-β, and IDO-1, was significantly higher in the 3D-TMSC-treated group than in the 2D-TMSC-treated group (P < 0.05). At days 18 and 30 after inducing chronic colitis, disease activity index scores were estimated to be significantly lower in the 3D-TMSC-treated group than in the colitis control (P < 0.001 and P < 0.001, respectively) and 2D-TMSC-treated groups (P = 0.022 and P = 0.004, respectively). Body weight loss was significantly lower in the 3D-TMSC-treated group than in the colitis control (P < 0.001) and 2D-TMSC-treated groups (P = 0.005). Colon length shortening was significantly recovered in the 3D-TMSC-treated group compared to that in the 2D-TMSC-treated group (P = 0.001). Histological scoring index was significantly lower in the 3D-TMSC-treated group than in the 2D-TMSC-treated group (P = 0.002). These results indicate that 3D-cultured TMSCs showed considerably higher therapeutic effects in a chronic murine colitis model than those of 2D-cultured TMSCs via increased anti-inflammatory cytokine expression.
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