RÉSUMÉ
Background@#Hepatic steatosis, which involves the excessive accumulation of lipid droplets in hepatocytes, presents a significant global health concern due to its association with obesity and metabolic disorders. Inflammation plays a crucial role in the progression of hepatic steatosis; however, the precise molecular mechanisms responsible for this process remain unknown. @*Methods@#This study investigated the involvement of the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) inflammasome and the forkhead box O6 (FoxO6) transcription factor in the pathogenesis of hepatic steatosis. We monitored the NLRP3 inflammasome and lipogenesis in mice overexpressing the constitutively active (CA)-FoxO6 allele and FoxO6-null mice. In an in vitro study, we administered palmitate to liver cells overexpressing CA-FoxO6 and measured changes in lipid metabolism. @*Results@#We administered palmitate treatment to clarify the mechanisms through which FoxO6 activates cytokine interleukin (IL)-1β through the NLRP3 inflammasome. The initial experiments revealed that dephosphorylation led to palmitate-induced FoxO6 transcriptional activity. Further palmitate experiments showed increased expression of IL-1β and the hepatic NLRP3 inflammasome complex, including adaptor protein apoptotic speck protein containing a caspase recruitment domain (ASC) and pro-caspase-1. Furthermore, thioredoxin-interacting protein (TXNIP), a key regulator of cellular redox conditions upstream of the NLRP3 inflammasome, was induced by FoxO6 in the liver and HepG2 cells. @*Conclusion@#The findings of this study shed light on the molecular mechanisms underpinning the FoxO6-NLRP3 inflammasome axis in promoting inflammation and lipid accumulation in the liver.
RÉSUMÉ
Strategies for efficient osteogenic differentiation and bone formation from stem cells would have clinical applications in treating nonunion fracture healing. Many researchers have attempted to develop adjuvants as specific stimulators of bone formation for therapeutic use in patients with bone resorption. Therefore, development of specific stimulators of bone formation has therapeutic significance in the treatment of osteoporosis. To date, investigations of the mature forms of bone morphogenetic proteins (BMPs) have focused on regulation of bone generation. However, we previously identified new peptides from the immature precursor of BMP, and further analysis of these proteins should be performed. In this study, we identified a new peptide called bone-forming peptide-2 (BFP-2), which has stronger osteogenic differentiation-promoting activity than BMP-7. BFP-2 treatment of multipotent bone marrow stromal cells (BMSCs) induced expression of active alkaline phosphatase. In addition, BFP-2 enhanced CD44 and CD51 expression levels and increased Ca2+ content in BMSCs. Moreover, radiography at 8 weeks revealed that animals that had received transplants of BFP-2-treated BMSCs showed substantially increased bone formation compared with animals that had received BMSCs treated with BMP-7. Our findings indicate that BFP-2 may be useful in the development of adjuvant therapies for bone-related diseases.
Sujet(s)
Animaux , Humains , Phosphatase alcaline , Protéine morphogénétique osseuse de type 7 , Protéines morphogénétiques osseuses , Résorption osseuse , Consolidation de fracture , Cellules souches mésenchymateuses , Ostéoblastes , Ostéogenèse , Ostéoporose , Peptides , Radiographie , Cellules souchesRÉSUMÉ
PURPOSE: To evaluate the long-term effectiveness of inferior retractor tightening combined with lateral tarsal strip surgery and anterior lamellar resection for simultaneously correcting the 3 main causes of involutional entropion. METHODS: In this retrospective study we reviewed 80 patients diagnosed with involutional entropion between April 2004 and February 2014 at the Korea University Guro Hospital and Cheonan Chungmu Hospital. The patients were evaluated for the 3 major causes of involutional entropion and were confirmed to have all components. Lateral canthal tendon laxity test and anterior lamellar redundancy test were performed to grade the involutional entropion patients. The patients received inferior retractor tightening, lateral tarsal strip operation and anterior lamellar resection procedure simultaneously. RESULTS: Eighty involutional entropion patients were included in the present study. The patients consisted of 35 males and 45 females with an average age of 71.1 ± 9.3 years. In the lateral canthal tendon laxity test, 52 (61.2%) eyes were grade II, 33 (38.8%) eyes were grade III. In the anterior lamellar redundancy test, 17 (20%) eyes were grade I, 57 (67.1%) eyes were grade II and; 11 (12.9%) eyes were grade III. Among the 80 patients, 85 eyelids received combined surgery, 84 had successful outcomes and 1 case recurred at 5 months following the primary surgery with an average follow up of 26.5 ± 4.6 months. Lateral canthal deformity was observed in 2 eyelids which were corrected successfully. CONCLUSIONS: Simultaneous correction of the 3 main causes of involutional entropion through inferior retractor tightening, lateral tarsal strip surgery and anterior lamellar resection procedure is effective in correcting involutional entropion and safe in avoiding overcorrection.
Sujet(s)
Femelle , Humains , Mâle , Malformations , Entropion , Paupières , Études de suivi , Corée , Études rétrospectives , TendonsRÉSUMÉ
Esophageal carcinoid tumors remain some of the rarest of all carcinoid tumors, with only several cases previously reported in the literature. The endoscopic mucosal resection of selected carcinoid tumors has been shown to be a valid, safe, and effective method of treatment. Endoscopic ultrasonography is the technique of choice to select patients eligible for endoscopic resection. Here, we report successful endoscopic mucosal resection of a low esophageal carcinoid tumor and review the relevant literature. The present case is the first reported case of esophageal carcinoid tumor in Korea.
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Humains , Tumeur carcinoïde , Endosonographie , CoréeRÉSUMÉ
Mucinous gastric carcinoma (MGC) is an unusual histologic subtype, and early detection of MGC is very rare. Early-stage MGC appears as an elevated lesion resembling a submucosal tumor (SMT) due to abundant mucin pools in the submucosa or mucosa. We report a rare case of SMT-like early-stage MGC. Tumor type was predicted preoperatively based on characteristic endoscopic findings, in which an SMT-like mass was observed at the gastric fundus. The tumor was covered by nearly normal mucosa, but with an opening allowing for the passage of copious mucus discharge. A total gastrectomy with Roux-en-Y esophagojejunostomy was subsequently performed. Histopathology of the tumor revealed early-stage (lamina propria) mucinous adenocarcinoma.
Sujet(s)
Adulte , Femelle , Humains , Adénocarcinome mucineux/diagnostic , Dépistage précoce du cancer , Endoscopie digestive , Muqueuse/anatomopathologie , Stadification tumorale , Tumeurs de l'estomac/diagnostic , TomodensitométrieRÉSUMÉ
BACKGROUND/AIMS: Although general guidelines have suggested weight-based dosing of azathioprine (AZA, 2.5 mg/kg/day) for Crohn's disease (CD), a substantial number of patients develop bone marrow suppression. The aim of this study was to evaluate the maximum dose of AZA not based on weight but titrated according to the lower limit of leukocyte count for maintaining remission in patients with CD. METHODS: Among a total of seventy-eight patients with CD, who had been followed-up at Kosin University Gospel Hospital (Busan, Korea) from 2010 to 2011, those treated with the maximum dose of AZA meeting both drug-tolerability and leukocytes count of more than 4,000/mm3 for steroid-free maintaining remission were enrolled. The titrated maximum AZA dose and its relationship with weight were evaluated. RESULTS: A total of 42 patients (male, 32 patients; mean age, 31 years) were enrolled. The maximum dose of AZA was 49.1 mg/day. The dose per weight was 0.87 mg/kg/day and negatively correlated with body weight (gamma=-0.51, p=0.01) and BMI (gamma=-0.33, p=0.034). AZA dose per weight in the below 40 years old group was significantly higher than that in the above 40 years old group (p=0.039). CONCLUSIONS: Dose decision of AZA based only on weight could put the patients to inappropriately low or high dose resulting in need of additional therapy or serious side effect, respectively. Therefore, the maximum dose-titration based on the lower limit of leukocyte count and tolerability is a novel and a valuable strategy in deciding the dose of thiopurines.
Sujet(s)
Adolescent , Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Jeune adulte , Azathioprine/usage thérapeutique , Maladie de Crohn/traitement médicamenteux , Relation dose-effet des médicaments , Calcul des posologies , Tolérance aux médicaments , Études de suivi , Immunosuppresseurs/usage thérapeutique , Numération des leucocytes , Leucocytes/cytologieRÉSUMÉ
BACKGROUND: Dendritic cell (DC)-based vaccines are currently being evaluated as a novel strategy for tumor vaccination and immunotherapy. However, inducing long-term regression in established tumor-implanted mice is difficult. Here, we show that deoxypohophyllotoxin (DPT) induces maturation and activation of bone marrow-derived DCs via Toll-like receptor (TLR) 4 activation of MAPK and NF-kappaB. METHODS: The phenotypic and functional maturation of DPT-treated DCs was assessed by flow cytometric analysis and cytokine production, respectively. DPT-treated DCs was also used for mixed leukocyte reaction to evaluate T cell-priming capacity and for tumor regression against melanoma. RESULTS: DPT promoted the activation of CD8+ T cells and the Th1 immune response by inducing IL-12 production in DCs. In a B16F10 melanoma-implanted mouse model, we demonstrated that DPT-treated DCs (DPT-DCs) enhance immune priming and regression of an established tumor in vivo. Furthermore, migration of DPT-DCs to the draining lymph nodes was induced via CCR7 upregulation. Mice that received DPT-DCs displayed enhanced antitumor therapeutic efficacy, which was associated with increased IFN-gamma production and induction of cytotoxic T lymphocyte activity. CONCLUSION: These findings strongly suggest that the adjuvant effect of DPT in DC vaccination is associated with the polarization of T effector cells toward a Th1 phenotype and provides a potential therapeutic antitumor immunity.
Sujet(s)
Animaux , Souris , Cellules dendritiques , Immunothérapie , Interleukine-12 , Noeuds lymphatiques , Test de culture lymphocytaire mixte , Lymphocytes , Phénotype , Podophyllotoxine , Lymphocytes T , Récepteurs de type Toll , Régulation positive , Vaccination , VaccinsRÉSUMÉ
BACKGROUND: Contrast induced nephropathy (CIN) is an important cause of acute renal failure in patients with renal dysfunction. We investigated whether oral NAC alone was sufficient to prevent CIN to the same extent as hydration in patients with renal dysfunction, and whether these treatments resulted in diffierences in the urinary excretion of nitric oxide, a vasodilator. METHODS: A total of 27 patients with renal dysfunction, who underwent radiographic examination with nonionic and low osmolar contrast, were randomly assigned to receive either NAC (600 mg orally twice daily; N=11) or 0.45% saline hydration (1 mL/kg/Hr; N=16) 12 hours prior to and 12 hours after the contrast procedure. We measured serum creatinine (sCr), fractional excretion of sodium (FENa), creatinine clearance (CCr), and urinary nitrite before and after contrast administration. RESULTS: The mean volume of contrast used was similar in the two groups (100.9+/-54.8 mL vs 114.7+/-38 mL; p=0.43), as was baseline sCr in the two groups (2.31+/-1.59 mg/dL vs 2.18+/-1.41 mg/dL; p=0.98). Treatment did not significantly affect the incidence of CIN, with 18.2% and 12.5% in the NAC group and hydration group, respectively (p=1.0). The urinary nitrite/creatinine ratio (micro mol/mg) was 1.26+/-0.57 and 1.43+/-0.64 at baseline and 48 hours after contrast exposure in the NAC group, respectively, and 0.80+/-0.40 and 1.18+/-0.60 in the hydration group, respectively, which were not significantly different. FENa increased significantly after contrast exposure in the NAC group compared with hydration group (p=0.04) CONCLUSIONS: NAC alone may prevent CIN. When bolus hydration is contraindicated in patients with renal dysfunction, administration of NAC alone may be sufficient.
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Humains , Acétylcystéine , Atteinte rénale aigüe , Créatinine , Incidence , Monoxyde d'azote , SodiumRÉSUMÉ
Castleman's disease is a rare lymphoproliferative disorder of uncertain etiology which most commonly occurs in the mediastinum. We describe a case of a benign Castleman 's disease of the hyaline vascular type affecting the upper extremity, an extremely rare site of the disease.
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Hyperplasie lymphoïde angiofolliculaire , Hamartomes , Substance hyaline , Syndromes lymphoprolifératifs , Médiastin , Membre supérieurRÉSUMÉ
Torsion of the accessory spleen is a rare entity that can have variable clinical presentations. We report case involving an 11-year-old boy with severe abdominal pain and a mass that was found to be due to infarction of the accessory spleen, which was twisted on its pedicle. CT revealed a low-attenuating mass with peripheral inflammatory changes in the left upper abdomen. The mass was pathologically confirmed as torsion of the ac-cessory spleen with infarction.
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Enfant , Humains , Mâle , Abdomen , Douleur abdominale , Infarctus , RateRÉSUMÉ
The distal thigh atrophy is a frequently associated sigh in the presence of knee pathology, and it is usually proved by the difference of the distal thigh circumference using tapeline measurement. But the proper position of measurement is known at this moment. From January of 1988 to December of 1991, we have 320 patients who had knee problems. Among them, 50 patients were selected as a sample of this study. We measured distal thigh circumference of normal and abnormal side by patella and also real circumference and area by taking cross sectional C-T image at each point of measurement. The obtained data are analysed by SPSS for statistical treatment. And the results are as follows: 1) We notice the largest difference on the point of 10cm above superior pole of patella. 2) The vastus medialis is the most conspicuously atrophied muscle among quadriceps and the atrophy of hamstring is minimal. 3) We have experienced the largest difference in cruciate ligament injury but a little difference in meniscus pathology. 4) There is no significantly difference between tapeline measurement and real circumference. As a conclusion of study, The position of 10cm above from the patella upper pole is the best site of clinical measurement of distal thigh circumference, and the muscle mainly associated with artophy is vastus medialis.