Background and Objectives: We evaluated the effect of adipose-derived stem cell-derived conditioned medium (ADSC-CM) on the renal function of rats with renal ischemia-reperfusion injury (IRI)-induced acute kidney injury. Methods: and Results: Forty male Sprague‐Dawley rats were randomly divided into four groups: sham, nephrectomy control, IRI control, ADSC-CM. The ADSC-CM was prepared using the three-dimensional spheroid culture system and injected into renal parenchyme. The renal function of the rats was evaluated 28 days before and 1, 2, 3, 4, 7, and 14 days after surgical procedures. The rats were sacrificed 14 days after surgical procedures, and kidney tissues were collected for histological examination. The renal parenchymal injection of ADSC-CM significantly reduced the serum blood urea nitrogen and creatinine levels compared with the IRI control group on days 1, 2, 3, and 4 after IRI. The renal parenchymal injection of ADSC-CM significantly increased the level of creatinine clearance compared with the IRI control group 1 day after IRI. Collagen content was significantly lower in the ADSC-CM group than in the IRI control group in the cortex and medulla. Apoptosis was significantly decreased, and proliferation was significantly increased in the ADSC-CM group compared to the IRI control group in the cortex and medulla. The expressions of anti-oxidative makers were higher in the ADSC-CM group than in the IRI control group in the cortex and medulla. Conclusions The renal function was effectively rescued through the renal parenchymal injection of ADSC-CM prepared using a three-dimensional spheroid culture system.

BACKGROUND: Physicians should try to achieve an optimal cure rate with their initial Helicobacter pylori (H. pylori) eradication therapy. Most physicians tend to use the same combination of drugs. There have been several reports that H. pylori infection in patients with peptic ulcer disease (PUD) is more likely to be cured than that in patients with non-ulcer dyspepsia (NUD). However, there is no report in Korea about that issue. The aim of this study was to evaluate the difference of eradication rates of H. pylori between patients with PUD and patients with NUD in Korea. METHODS: 297 patients who underwent upper gastrointestinal endoscopy, treated with seven-day triple therapy (proton pump inhibitor+amoxicillin+clarithromycin), and then performed follow-up urea breath test were reviewed retrospectively. RESULTS: 237 of 297 patients were PUD (98 gastric ulcers, 167 duodenal ulcers, 28 both ulcers), and 60 of 297 patients were NUD. The eradication rates were 85.7% (95% CI 80.6~89.6%) and 73.3% (95% CI 61.0~82.9%), respectively. The eradication rate of NUD group was lower than that of PUD group (p=0.032). CONCLUSIONS: Seven-day triple therapy showed lower eradication rate in patients with NUD than patients with PUD. Therefore, extention of treatment duration or use of more potent regimen may be needed for eradication of H. pylori in patients with NUD.
Breath Tests ; Duodenal Ulcer ; Dyspepsia* ; Endoscopy, Gastrointestinal ; Follow-Up Studies ; Helicobacter pylori* ; Helicobacter* ; Humans ; Korea ; Peptic Ulcer* ; Retrospective Studies ; Stomach Ulcer ; Urea

BACKGROUND: The aim of this study was to evaluate the anti-inflammatory and anti-tumorigenic effect of açai berry after chronic Helicobacter felis colonization in the stomachs of C57BL/6 mice. METHODS: A total of 57 four-week-old female C57BL/6 mice (18 control mice and 39 experimental mice) were used. The mice were administered orogastrically with vehicle only or vehicle containing H. felis, 5 times every other day. After inoculation of H. felis, mice were fed either a standard or an açai-containing diet and then sacrificed at 4, 24, and 52 weeks. The infection status and degree of inflammation were determined by culture and histopathology. The level of gastric mucosal myeloperoxidase (MPO), TNF-α, and interleukin-1β (IL-1β) were measured by ELISA. RESULTS: At 24 weeks after inoculation, mucosal atrophy and mucous metaplasia appeared in all infected mice. At 52 weeks after inoculation, dysplastic change was noted in 10%, 25%, and 50% of mice in the H. felis-control, H. felis-açai 5%, and H. felis-açai 10% groups, respectively. The neutrophil, monocyte, atrophy, and metaplasia grades of infected mice showed no significant difference among the H. felis-infected groups. H. felis-infected mice fed with açai berry showed no significant difference compared with H. felis-infected control mice in gastric mucosal MPO, TNF-α, and IL-1β levels. CONCLUSIONS: H. felis that colonized the stomachs of C57BL/6 mice provoked inflammation, and induced mucosal atrophy, metaplasia, and dysplasia. However, açai berry did not effectively prohibit the gastric carcinogenesis which was induced by chronic H. felis infection.
Animals ; Atrophy ; Carcinogenesis ; Cats ; Colon ; Diet ; Enzyme-Linked Immunosorbent Assay ; Felis ; Female ; Fruit* ; Helicobacter felis ; Helicobacter* ; Humans ; Inflammation ; Metaplasia ; Mice* ; Monocytes ; Neutrophils ; Peroxidase ; Stomach

Background: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease mediated by T helper type 2 (Th2) cells in acute phase. Group 2 innate lymphoid cells (ILCs) play a role in the initiation of the Th2 response. Although mold exposure is associated with the development of AD, studies on the underlying mechanisms are lacking. This study investigated whether group 2 ILCs are involved in inflammation in AD-like skin induced by Aspergillus fumigatus (Af). Methods: We investigated changes of group 2 ILCs population in Af-induced AD-like skin lesions. To induce AD-like skin lesions, Af extracts were applied to the dorsal skin of BALB/c and Rag1−/− mice five times per week, with repeat exposures at 2-week intervals. Results: The clinical parameters were higher in the Af-treated group than in the control group. Histologic findings revealed epiderrmal and dermal thickening as well as eosinophil and mast cell infiltration into the skin of Af-treated mice. Populations of group 2 ILCs in the skin were also significantly higher in the Af-treated group. In addition, interleukin-33 mRNA expression was significantly higher in the skin lesions of the Af-treated mice. In the Rag1−/− mice lacking mature lymphocytes, AD-like skin lesions were still induced by Af and ILCs depletion using an anti-CD90.2 mAb lowered the Af-induced inflammatory response. Conclusions Group 2 ILCs may play a role in a murine model of Af-induced AD-like skin lesions.

Background: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease mediated by T helper type 2 (Th2) cells in acute phase. Group 2 innate lymphoid cells (ILCs) play a role in the initiation of the Th2 response. Although mold exposure is associated with the development of AD, studies on the underlying mechanisms are lacking. This study investigated whether group 2 ILCs are involved in inflammation in AD-like skin induced by Aspergillus fumigatus (Af). Methods: We investigated changes of group 2 ILCs population in Af-induced AD-like skin lesions. To induce AD-like skin lesions, Af extracts were applied to the dorsal skin of BALB/c and Rag1−/− mice five times per week, with repeat exposures at 2-week intervals. Results: The clinical parameters were higher in the Af-treated group than in the control group. Histologic findings revealed epiderrmal and dermal thickening as well as eosinophil and mast cell infiltration into the skin of Af-treated mice. Populations of group 2 ILCs in the skin were also significantly higher in the Af-treated group. In addition, interleukin-33 mRNA expression was significantly higher in the skin lesions of the Af-treated mice. In the Rag1−/− mice lacking mature lymphocytes, AD-like skin lesions were still induced by Af and ILCs depletion using an anti-CD90.2 mAb lowered the Af-induced inflammatory response. Conclusions Group 2 ILCs may play a role in a murine model of Af-induced AD-like skin lesions.

Although previous and ongoing clinical studies have used stromal cells during renal ischemia-reperfusion injury (IRI), there is little consensus regarding the optimal protocol. We aimed to optimize the protocol for hypoxic preconditioned human bone marrow-derived mesenchymal stromal cell (HP-hBMSC) therapy in a rat model of renal IRI. We determined the optimal injection route (renal arterial, renal parenchymal, and tail venous injection), dose (low-dose: 1×10⁶, moderate-dose: 2×10⁶, and high-dose: 4×10⁶), and injection period (pre-, concurrent-, and post-IRI). During optimal injection route study, renal arterial injections significantly reduced the decreasing glomerular filtration rate (GFR), as compared to GFRs for the IRI control group, 2 and 4 days after IRI. Therapeutic effects and histological recoveries were the greatest in the group receiving renal arterial injections. During the dose finding study, high-dose injections significantly reduced the decreasing GFR, as compared to GFRs for the IRI control group, 3 days after IRI. Therapeutic effects and histological recoveries were the greatest in the high-dose injection group. While determining the optimal injection timing study, concurrent-IRI injection reduced elevated serum creatinine levels, as compared to those of the IRI control group, 1 day after IRI. Pre-IRI injection significantly reduced the decreasing GFR, as compared with GFRs for the IRI control group, 1 day after IRI. Therapeutic effects and histological recoveries were the greatest in the concurrent-IRI group. In conclusion, the concurrent-IRI administration of a high dose of HP-hBMSC via the renal artery leads to an optimal recovery of renal function after renal IRI.
Acute Kidney Injury ; Animals ; Cell- and Tissue-Based Therapy ; Consensus ; Creatinine ; Glomerular Filtration Rate ; Humans ; Mesenchymal Stromal Cells ; Models, Animal ; Rats ; Renal Artery ; Reperfusion Injury ; Stromal Cells ; Tail ; Therapeutic Uses

Background/Aims: Less invasive surgical treatment is performed in East Asia to preserve postoperative digestive function and reduce complications such as postgastrectomy syndromes, but there is an issue of metachronous gastric cancer (GC) in the remaining stomach. This study aimed to analyze the incidence of metachronous GC and its risk factors in patients who had undergone partial gastrectomy. Methods: A total of 3,045 GC patients who had undergone curative gastric partial resection at Seoul National University Bundang Hospital were enrolled and analyzed retrospectively for risk factors, including age, sex, smoking, alcohol, Helicobacter pylori status, family history of GC, histological type, and surgical method. Results: Metachronous GC in the remaining stomach occurred in 35 of the 3,045 patients (1.1%): 23 in the distal gastrectomy group (18 with Billroth-I anastomosis, five with Billroth-II anastomosis), seven in the proximal gastrectomy (PG) group, and five in the pylorus-preserving gastrectomy (PPG) group. Univariate and multivariate Cox regression analyses showed that age ≥60 years (p=0.005) and surgical method used (PG or PPG, p<0.001) were related risk factors for metachronous GC, while male sex and intestinal type histology were potential risk factors. Conclusions Metachronous GC was shown to be related to older age and the surgical method used (PG or PPG). Regular and careful follow-up with endoscopy should be performed in the case of gastric partial resection, especially in patients with male sex and intestinal type histology as well as those aged ≥60 years undergoing the PG or PPG surgical method.

BACKGROUND/AIMS: The aim of this study was to evaluate the effect of the synthetic S-allyl-l-cysteine (SAC) PMK-S005 on gastric acid secretion, inflammation, and antioxidant enzymes in aging rats. METHODS: The rats were divided into four groups at 31 weeks of age and were continuously fed a diet containing a vehicle control, PMK-S005 (5 or 10 mg/kg), or lansoprazole (5 mg/kg). Gastric acid secretion and connective tissue thickness of the lamina propria were evaluated at 74 weeks and 2 years of age. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and COX-2 levels were measured by using enzyme-linked immunosorbent assays (ELISAs) or Western blot assays. Levels of antioxidant enzymes, including heme oxyganase 1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1), were also measured. RESULTS: As the rats aged, gastric acid secretion significantly decreased, and the connective tissue of the lamina propria increased. However, 74-week-old rats in the PMK-S005 group exhibited greater levels of gastric acid secretion than those of the control and lansoprazole groups. The increase of TNF-α, IL-1β, and COX-2 expression in 74-week and 2-year-old control rats were inhibited by PMK-S005. In addition, the decrease in HO-1 and NQO-1 protein expression that occurred with aging was inhibited by PMK-S005 in the 74-week-old rats. CONCLUSIONS: These results suggest that PMK-S005 has therapeutic potential as an antiaging agent to ameliorate age-related gastric acid secretion, inflammation, and oxidative stress in the stomach.
Aging ; Animals ; Antioxidants ; Blotting, Western ; Child, Preschool ; Connective Tissue ; Diet ; Enzyme-Linked Immunosorbent Assay ; Gastric Acid* ; Heme ; Humans ; Inflammation* ; Interleukins ; Lansoprazole ; Mucous Membrane ; Oxidative Stress ; Rats* ; Stomach* ; Tumor Necrosis Factor-alpha

BACKGROUND/AIMS: Proton-pump inhibitor (PPI)-based triple therapy for Helicobacter pylori eradication is widely used with considerable failure rate. Bismuth-based, second-line therapy is also associated with failures in more than 20% of cases in Korea. Our aim was to evaluate the efficacy and tolerability of third-line therapy containing moxifloxacin as a rescue in Korea. METHODS: The subjects consisted of 201 patients infected with H. pylori, who were treated with PPI-based therapy, 42 patients treated with bismuth-based after failure of initial PPI triple therapy, and 10 patients treated with moxifloxacin-containing triple therapy after failure of successive initial and second-line therapy. Eradication rate, compliance and side effect rates were compared. RESULTS: The eradication rates of initial, second-line, and third-line therapy were as follows: 67.2%/83.3%, 54.8%/76.7%, 80.0%/88.9% by intention-to-treat and per protocol analysis, respectively. The compliance of patients for each treatment was 98.2%, 90.9%, 100%, respectively. The side effect rate was significantly higher in the bismuth triple therapy than in the PPI- or moxifloxacin-containing triple therapy (p<0.05). CONCLUSIONS: Moxifloxacin-containing triple therapy shows high eradication rate with fewer side effects and good compliance. Thus, this regimen could be used as a rescue therapy.
Adult ; Aged ; Antacids/administration & dosage ; Anti-Bacterial Agents/administration & dosage ; Aza Compounds/*administration & dosage ; Bismuth/administration & dosage ; Drug Therapy, Combination ; Female ; Helicobacter Infections/*drug therapy ; *Helicobacter pylori ; Humans ; Male ; Middle Aged ; Proton Pumps/antagonists & inhibitors ; Quinolines/*administration & dosage

BACKGROUND: Dextran sodium sulfate (DSS)-induced colitis mouse model is used for research of inflammatory bowel disease. The aim of this study was to establish the adequate conditions for DSS mice model, and to find useful tool to measure inflammation. METHODS: The 2.5% DSS was administered to six male C57BL/6 mice and 4% DSS to eight mice at 5 or 9 weeks of age. Each group was consisted of 6 mice with control group in which vehicle was administered instead of DSS. The mice were sacrificed on the 7th day after DSS or vehicle administration. Body weight, diarrhea, and hematochezia were recorded daily. Disease activity index (DAI) score which was composed of body weight change, diarrhea, and hematochezia was measured every day. Colon length was measured after sacrifice and colon mucosal level of interleukin 1 beta (IL-1beta) was measured by ELISA assay. Histological score was compared between ascending and descending colon in the DSS group. RESULTS: Colon length of five- and nine-week DSS group was significantly shorter than each control group but there was no statistical significance depending on DSS concentration or age. DAI score of 4% DSS group in nine-week was significantly higher than that five-week (P = 0.012) but there was no difference between 2.5% and 4% DSS group. The level of IL-1beta in DSS mice was much higher than control group (P < 0.01), but there was no difference among several DSS groups. The histological score was higher in the descending colon than in the ascending colon but there was no statistical difference between each pair of DSS groups. CONCLUSIONS: The 4% DSS mice in nine-week was adequate for DSS-induced colitis model. DAI score was useful tool and descending colon was more appropriate site for histological evaluation of colitis than ascending colon.
Animals ; Body Weight ; Body Weight Changes ; Colitis* ; Colon ; Colon, Ascending ; Colon, Descending ; Dextran Sulfate ; Dextrans* ; Diarrhea ; Enzyme-Linked Immunosorbent Assay ; Gastrointestinal Hemorrhage ; Humans ; Inflammation ; Inflammatory Bowel Diseases ; Interleukin-1beta ; Male ; Mice* ; Sodium*