Background: Renal function declines with age as the kidneys become more vulnerable to inflammation and cellular senescence. This study examined gene expression changes linked to renal aging and assessed whether short-term calorie restriction (CR), a known anti-aging intervention, could reverse these alterations. Methods: Using RNA-seq data, we applied bioinformatics, systems biology, and molecular biology approaches to identify differentially expressed genes during aging and under CR. Gene Ontology and pathway analyses revealed that both aging and CR altered the expression of key senescence-associated secretory phenotype (SASP) genes, including cytokines and chemokines (Il1b, Ccl3, Ccl5, Il19, and Il24) and growth factors (Timp1 and Mmp12). Results: Renal aging is also associated with an increased expression of cell cycle arrest markers (p15INK4B (Cdkn2b), p16INK4A (Cdkn2a), and p21 (Cdkn1a)), which are suppressed by CR, suggesting a link to cellular senescence. Quantitative analysis of renal tissue samples confirmed the age-associated upregulation of these genes at the transcriptional level, and CR effectively attenuated these changes. Among these genes, we focused on the members of the interleukin 20 (IL-20) family, particularly Il19 and Il24. Furthermore, experimental induction of cellular senescence using H2O2 resulted in elevated Il19 and Il24 expression alongside other senescence markers. These findings suggest that aging and short-term CR regulate the IL-20 family expression, potentially influencing cellular senescence. Conclusion Our study suggests that Il19 and Il24 are associated with age-related renal decline and may represent hypothesis-generating candidates, highlighting potential molecular targets for future mechanistic and therapeutic investigations.

Background: Protease-activated protein-2 (PAR2) has been reported to regulate hepatic insulin resistance condition in type 2 diabetes mice. However, the mechanism of lipid metabolism through PAR2 in obesity mice have not yet been examined. In liver, Forkhead box O1 (FoxO1) activity induces peroxisome proliferator-activated receptor γ (PPARγ), leading to accumulation of lipids and hyperlipidemia. Hyperlipidemia significantly influence hepatic steatoses, but the mechanisms underlying PAR2 signaling are complex and have not yet been elucidated. Methods: To examine the modulatory action of FoxO1 and its altered interaction with PPARγ, we utilized db/db mice and PAR2-knockout (KO) mice administered with high-fat diet (HFD). Results: Here, we demonstrated that PAR2 was overexpressed and regulated downstream gene expressions in db/db but not in db+ mice. The interaction between PAR2/β-arrestin and Akt was also greater in db/db mice. The Akt inhibition increased FoxO1 activity and subsequently PPARγ gene in the livers that led to hepatic lipid accumulation. Our data showed that FoxO1 was negatively controlled by Akt signaling and consequently, the activity of a major lipogenesis-associated transcription factors such as PPARγ increased, leading to hepatic lipid accumulation through the PAR2 pathway under hyperglycemic conditions in mice. Furthermore, the association between PPARγ and FoxO1 was increased in hepatic steatosis condition in db/db mice. However, HFD-fed PAR2-KO mice showed suppressed FoxO1-induced hepatic lipid accumulation compared with HFD-fed control groups. Conclusion Collectively, our results provide evidence that the interaction of FoxO1 with PPARγ promotes hepatic steatosis in mice. This might be due to defects in PAR2/β-arrestin-mediated Akt signaling in diabetic and HFD-fed mice.

BACKGROUND: This study aimed to investigate the association between physical fitness and cardiometabolic health of Korean children and adolescents. METHODS: In total, 168 participants (89 boys and 79 girls) aged 10–16 years were recruited for the Intervention for Childhood and Adolescent Obesity via Activity and Nutrition Study in 2016. The subjects were categorized into two groups using the definition of metabolic syndrome by the International Diabetes Federation: metabolically unhealthy (with at least two of the five criteria) and healthy groups (with less than one criterion). Correlation analysis of the participants' general characteristics was performed. Odds ratios (ORs) of physical fitness for cardiometabolic risk were evaluated via logistic regression. RESULTS: Metabolically unhealthy children showed greater weight, height, and body mass index, higher Children's Depression Inventory score, and longer screen time than did the metabolically healthy children. Metabolically healthy children showed greater upper and lower extremity muscular strength than did the metabolically unhealthy children (P=0.04 and P<0.001, respectively). In the multiple logistic regression analysis, lower extremity muscle strength was inversely related to the clustered cardiometabolic risk of the children and adolescents with or without adjustment for confounders (OR, 4.32; 95% confidence interval [CI], 1.87–9.97; OR, 7.64; 95% CI, 1.55–37.74, respectively). CONCLUSION: Physical fitness, especially lower extremity muscle strength, is significantly inversely associated with individual and clustered cardiometabolic risks in Korean children and adolescents.
Adolescent ; Body Mass Index ; Child ; Depression ; Humans ; Korea ; Logistic Models ; Lower Extremity ; Muscle Strength ; Odds Ratio ; Pediatric Obesity ; Physical Fitness

PURPOSE: To analyze the prognostic factors for survivals and to evaluate the impact of postoperative whole pelvic radiotherapy (WPRT) on pelvic failure in patients with uterine sarcoma treated with radical surgery. MATERIALS AND METHODS: We retrospectively analyzed 75 patients with uterine sarcoma who underwent radical surgery with (n = 22) or without (n = 53) radiotherapy between 1990 and 2010. There were 23 and 52 patients with carcinosarcoma and non-carcinosarcoma (leiomyosarcoma, 22; endometrial stromal sarcoma, 25; others, 5), respectively. The median follow-up period was 64 months (range, 17 to 269 months). RESULTS: The 5-year overall survival (OS) and pelvic failure-free survival (PFFS) of total patients was 64.2% and 83.4%, respectively. Multivariate analysis revealed that mitotic count (p = 0.006) was a significant predictor of OS. However, factors were not found to be associated with PFFS. On analyzing each of the histologic subtypes separately, postoperative WPRT significantly reduced pelvic failure in patients with carcinosarcoma (10.0% vs. 53.7%; p = 0.046), but not in patients with non-carcinosarcoma (12.5% vs. 9.9%; p = 0.866). Among the patients with carcinosarcoma, 4 patients (17%) had recurrence within the pelvis and 3 patients (13%) had recurrence in other sites as an initial failure, whereas among the patients with non-carcinosarcoma, 3 patients (6%) experienced pelvic failure and 13 patients (25%) experienced distant failure. CONCLUSION: The most significant predictor of OS was mitotic count. Based on the improved PFFS after postoperative WPRT only in patients with carcinosarcoma and the difference in patterns of failure between histologic subtypes, optimal adjuvant treatment options should be offered to patients based on the risk of recurrence patterns.
Carcinosarcoma ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Pelvis ; Radiotherapy ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies ; Sarcoma* ; Sarcoma, Endometrial Stromal ; Uterus

PURPOSE: To evaluate the impact of postoperative radiotherapy (PORT) on patterns of failure and survivals in uterine carcinosarcoma patients treated with radical surgery. MATERIALS AND METHODS: Between October 1998 and August 2010, 19 patients with stage I-III uterine carcinosarcoma received curative hysterectomy and bilateral salpingo-oophorectomy with or without PORT at Seoul National University Hospital. Their hospital medical records were retrospectively reviewed. PORT and non-PORT groups included 11 and 8 patients, respectively. They were followed for a mean of 22.7 months (range, 7.8 to 126.6 months). RESULTS: At 5 years, the overall survival rates were 51.9% for entire, 61.4% for PORT, and 41.7% for non-PORT groups, respectively. There was no statistical difference between PORT and non-PORT groups with regard to overall survival (p = 0.682). Seven out of 19 (36.8%) patients showed treatment failures, which all happened within 12 months. Although the predominant failures were distant metastasis in PORT group and loco-regional recurrence in non-PORT group, there was no statistically significant difference in loco-regional recurrence-free survival (LRRFS) (p = 0.362) or distant metastasis-free survival (DMFS) (p = 0.548). Lymph node metastasis was found to be a significant prognostic factor in predicting poor LRRFS (p = 0.013) and DMFS (p = 0.021), while the International Federation Gynecology and Obstetrics (FIGO) stage (p = 0.043) was associated with LRRFS. CONCLUSION: Considering that adjuvant radiotherapy after surgical resection was effective to decrease loco-regional recurrence and most treatment failures were distant metastasis, multimodal therapy including surgery, radiotherapy, and chemotherapy might be an optimal treatment for uterine carcinosarcoma patients.
Carcinosarcoma ; Gynecology ; Humans ; Hysterectomy ; Lymph Nodes ; Medical Records ; Neoplasm Metastasis ; Obstetrics ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies ; Survival Rate ; Treatment Failure ; Uterus

Vitiligo, which is characterized by depigmentation of skin and mucosa is a common skin disease, affecting 1-4% of population. Although the pathogenesis is not clear, the basic defect lies in a decrease or absence of melanocytes. Vitiligo causes cosmetic disfiguration and exerts negative effects on quality of life. Phototherapy and topical agents such as corticosteroids, calcineurin inhibitors, and vitamin-D derivatives are basic treatment modalities. Recently, prostaglandin analogues have been reported to be effective on pigmentation of vitiligo lesions. We present three patients with periorbital vitiligo, who did not respond to established treatments such as tacrolimus and excimer laser, responding to application of latanoprost, a prostaglandin F2alpha analogue.

PURPOSE: To retrospectively assess the advantages and side effects of prophylactic Paraaortic irradiation in cervical cancer patients with common iliac nodal involvement, the results for survival, patterns of failure, and treatment-related toxicity. MATERIALS AND METHODS: From May 1985 to October 2004, 909 patients with cervical carcinoma received postoperative radiotherapy at the Seoul National University Hospital. Among them, 54 patients with positive common iliac nodes on pathology and negative Paraaortic node were included in the study. In addition, 44 patients received standard pelvic irradiation delivered 50.4 Gy per 28 fractions (standard irradiation group), and chemotherapy was combined in 16 of them. The other 10 patients received pelvic irradiation at a dose of 50.4 Gy per 28 fractions in addition to Paraaortic irradiation at 45 Gy per 25 fractions (extended irradiation group). In addition, all of them received chemotherapy in combination with radiation. Follow-up times for pelvic and Paraaortic irradiation ranged from 6 to 201 months (median follow-up time, 58 months) and 21 to 58 months (median follow-up time, 47 months), respectively. RESULTS: The 4-year overall survival, disease free survival, and distant metastasis free survival in the standard irradiation group and extended irradiation group were 67.2% vs. 90.0% (p=0.291), 59.0% vs. 70.0% (p=0.568) and 67.5% vs. 90.0% (p=0.196), respectively. The most common site of first failure for the standard irradiation group was the paraaortic lymph node, while no paraaortic failure was observed in the extended irradiation group. Relatively, hematologic toxicity grade 3 or greater was common in the extended irradiation group (2/10 extended vs. 2/44 standard), while gastrointestinal toxicity of grade 3 or greater was lower (2/10 extended vs. 6/44 standard), and urologic toxicity of grade 3 or greater was observed in the standard irradition group only (0/10 vs. 3/44). CONCLUSION: Concurrent chemotherapy and prophylactic Paraaortic irradiation in patients with common iliac nodal involvement showed slightly improved clinical outcomes aside from increased hematologic toxicity, which was statistically insignificant. Considering the relatively small number of patients and short follow-up times, additional studies are needed to obtain more conclusive outcomes.
Disease-Free Survival ; Follow-Up Studies ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Retrospective Studies ; Uterine Cervical Neoplasms

OBJECTIVE: The International Study of Unruptured Intracranial Aneurysms (ISUIA) reported that the 5-year cumulative rupture rate of small unruptured aneurysms less than 7 mm in diameter is very low depending on the aneurysm's location. However, we have seen a large number of ruptured aneurysms less than 7 mm in clinical practice. The purpose of this study was to review our experience and to measure the size and location at which aneurysms ruptured in our patient population. METHODS: We reviewed the characteristics of aneurysms, such as size and location, from the original angiograms of patients who were admitted to our hospital between January 2004 and December 2007. All aneurysms were treated surgically or through endovascular procedures. RESULTS: Interventional or surgical treatment was given to a total of 889 patients, including 568 females and 321 males. At the time of our study, 627 cases were ruptured aneurysms and 262 cases were unruptured aneurysms. Of the ruptured cases, the mean diameter of the aneurysm was 6.28 mm. We found that 71.8% of ruptured aneurysms were smaller than 7 mm in diameter, and 87.9%, were smaller than 10 mm. Based on location, the data show that anterior communicating artery aneurysms most often presented with rupture sizes less than 7 mm (76.8%) and 10 mm (92.1%) in diameter. Most ruptured aneurysms were less than 7 mm in size, although recent studies have noted that small aneurysms are less likely to rupture. CONCLUSION: Although the natural history of unruptured intracranial aneurysms remains controversial, the aneurysm size and location play a signigicant role in determining the risk of rupture. Larger sample sizes and a long term study are needed to reveal the natural history and the rupture risk of unruptured intracranial aneurysms because the size of most ruptured aneurysms was less than 7 mm in diameter in our series.
Aneurysm ; Aneurysm, Ruptured ; Endovascular Procedures ; Female ; Humans ; Intracranial Aneurysm ; Male ; Natural History ; Rupture ; Sample Size

BACKGROUND: In ESRD patients, malnutrition and atherosclerosis are strongly associated with inflammation resulting in MIA (Malnutrition-Inflammation-Atherosclerosis) syndrome. As compared with atherosclerosis, arteriosclerosis or arterial stiffening is another important cardiovascular risk factor. Therefore, we speculated on the presence of new MIA syndrome, which is composed of malnutrition, inflammation and arteriosclerosis, and evaluated causal relations among them in 70 chronic hemodialysis patients (age 53+/-13 years, male 53%, diabetes 40%). METHODS: As an indicator of arterial stiffness, brachial-ankle pulse wave velocity (PWV) was measured using a plethysmography. PWV index (measured PWV/nomogram based theoretical PWV) was then calculated to adjust confounding effects of age, blood pressure, and gender by using the PWV nomogram obtained in nonuremic population with same age, blood pressure, and gender. Nutritional status was assessed by serum albumin level, subjective global assessment (SGA) and normalized protein catabolic rate (nPCR). Extracellular fluid and intracellular fluid volume ratio (ECF/ICF) were determined using bioimpedance analysis. The presence of an inflammation was assessed by serum high sensitivity C-reactive protein (CRP) level. RESULTS: PWV index correlated positively with log transformed CRP (LnCRP) level, ECF/ICF and negatively with SGA, nPCR and serum albumin level. Serum albumin level correlated positively with nPCR, BUN, hemoglobin level and negatively with LnCRP level, age and ECF/ICF. Diabetic patients had higher PWV index and lower albumin level than non-diabetic patients. In multiple regression analysis, only LnCRP level was a significant common determinant of the both PWV index (R2=0.419; p >0.001) and serum albumin level (R2=0.543; p<0.001). CONCLUSION: Increased CRP levels are independently associated with arterial stiffening and hypoalbuminemia. Inflammation might be a linking mechanism of arterial stiffening and malnutrition in chronic hemodialysis patients.
Arteriosclerosis ; Atherosclerosis ; Blood Pressure ; C-Reactive Protein ; Extracellular Fluid ; Humans ; Hypoalbuminemia ; Inflammation* ; Intracellular Fluid ; Kidney Failure, Chronic ; Male ; Malnutrition* ; Nomograms ; Nutritional Status ; Plethysmography ; Pulse Wave Analysis ; Renal Dialysis* ; Risk Factors ; Serum Albumin ; Vascular Stiffness*

PURPOSE: We tried to investigate the outcome and patterns of failure of endometrial cancer patients who were treated with surgery and postoperative radiation therapy (RT). MATERIALS AND METHODS: Eighty-three patients with endometrial cancer who received postoperative RT between May 1979 and August 2000 were included in this retrospective study. Forty-one patients received total abdominal hysterectomy, 41 patients received Wertheim's operation and 1 underwent vaginal hysterectomy. Pelvic lymph node dissection or pelvic lymph node sampling was done in 56 patients and peritoneal cytology was done in 35. All the patients were staged according to 1988 FIGO (International Federation of Gynecology and Obstetrics) staging system; 2 were stage IA, 23 were stage IB, 20 were stage IC, 4 were stage IIA, 5 were stage IIB, 9 were stage IIIA, 2 were stage IIIB and 18 were stage IIIC. The histologic diagnoses were adenocarcinoma in seventy-four patients (89%). The histologic grades were Grade 1, 2 and 3 in 21 (25%), 43 (52%) and 10 (12%) patients, respectively. All the patients received external beam RT (EBRT) with a median dose of 5,040 cGy (range: 4,500~5,075 cGy) to the whole pelvis. Five patients with pathologically confirmed paraaortic lymph node metastasis received 4500 cGy to the paraaortic lymph nodes. Fifteen patients received low-dose intracavitary brachytherapy after their EBRT. A total dose of 7,500~9,540 cGy (median dose: 8511) was prescribed to the vaginal surface. RESULTS: Overall, 11 patients (13%) experienced disease relapse: 4 with initial stage I or II disease and 7 with initial stage III disease. Among the 54 stage I or II patients, 1 (2%) relapsed in the pelvis only, 2 (4%) relapsed in the vagina and distant organs, and 1 (2%) relapsed in the paraaortic lymph nodes (PANs). Among the 29 stage III patients, 1 (3%) relapsed in the vagina. The most common sites of failure for the stage III patients were the peritoneum (3 patients, 10%), PANs (2 patients, 7%), and lung (2 patients, 7%). With a median follow-up period of 86 months, the overall survival (OS) and disease-free survival (DFS) rates at 5 years were 87% for both. The five-year DFS rate was 93%, 100% and 74% for the stage I, II and III patients, respectively. Three patients experienced severe radiation-related late complications: RTOG (Radiation Therapy Oncology Group) grade 3 radiation cystitis was seen in one patient, and grade 3 bowel obstruction was seen in two patients. CONCLUSIONS: Postoperative RT was useful for controlling pelvic disease. The major patterns of failure for stage III patients were peritoneal seeding and distant metastasis. Selective use of whole abdominal radiotherapy or adjuvant chemotherapy may improve the therapeutic outcome of these patients.
Adenocarcinoma ; Brachytherapy ; Chemotherapy, Adjuvant ; Cystitis ; Diagnosis ; Disease-Free Survival ; Endometrial Neoplasms* ; Female ; Follow-Up Studies ; Gynecology ; Humans ; Hysterectomy ; Hysterectomy, Vaginal ; Lung ; Lymph Node Excision ; Lymph Nodes ; Neoplasm Metastasis ; Pelvis ; Peritoneum ; Radiotherapy ; Recurrence ; Retrospective Studies ; Vagina