The Catholic University of Korea Yeouido St. Mary's Hospital

OBJECTIVE: To determine the safety of laparoscopy-assisted distal gastrectomy (LADG) compared with open distal gastrectomy (ODG) in patients with clinical stage I gastric cancer in Korea. BACKGROUND: There is still a lack of large-scale, multicenter randomized trials regarding the safety of LADG. METHODS: A large-scale, phase 3, multicenter, prospective randomized controlled trial was conducted. The primary end point was 5-year overall survival. Morbidity within 30 postoperative days and surgical mortality were compared to evaluate the safety of LADG as a secondary end point RESULTS: : A total of 1416 patients were randomly assigned to the LADG group (n = 705) or the ODG group (n = 711) between February 1, 2006, and August 31, 2010, and 1384 patients were analyzed for modified intention-to-treat analysis (ITT) and 1256 were eligible for per protocol (PP) analysis (644 and 612, respectively). In the PP analysis, 6 patients (0.9%) needed open conversion in the LADG group. The overall complication rate was significantly lower in the LADG group (LADG vs ODG; 13.0% vs 19.9%, P = 0.001). In detail, the wound complication rate of the LADG group was significantly lower than that of the ODG group (3.1% vs 7.7%, P < 0.001). The major intra-abdominal complication (7.6% vs 10.3%, P = 0.095) and mortality rates (0.6% vs 0.3%, P = 0.687) were similar between the 2 groups. Modified ITT analysis showed similar results with PP analysis. CONCLUSIONS: LADG for patients with clinical stage I gastric cancer is safe and has a benefit of lower occurrence of wound complication compared with conventional ODG.

IMPORTANCE: Laparoscopic distal gastrectomy is gaining popularity over open distal gastrectomy for gastric cancer because of better early postoperative outcomes. However, to our knowledge, no studies have proved whether laparoscopic distal gastrectomy is oncologically equivalent to open distal gastrectomy. OBJECTIVE: To examine whether the long-term survival among patients with stage I gastric cancer undergoing laparoscopic distal gastrectomy is noninferior to that among patients undergoing open distal gastrectomy. DESIGN: The Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS) group, which includes 15 surgeons from 13 institutes, conducted a phase 3, multicenter, open-label, noninferiority, prospective randomized clinical trial (KLASS-01) of patients with histologically proven, preoperative clinical stage I gastric adenocarcinoma from January 5, 2006, to August 23, 2010. Survival and recurrence status of the patients was determined in December 2016. INTERVENTIONS: Patients were randomly assigned (1:1) to laparoscopic distal gastrectomy (n = 705) or open distal gastrectomy (n = 711). Of these patients, 85 received a surgical approach opposite the one to which they were randomized (63 randomized to the open surgery group and 22 to the laparoscopic group). MAIN OUTCOMES AND MEASURES: Difference in 5-year overall survival between the laparoscopic and open distal gastrectomy groups. The noninferiority margin was prespecified as -5% (corresponding hazard ratio of 1.54), with an assumed survival of 90% after 5 years in the open surgery group. RESULTS: Among the 1416 patients (mean [SD] age, 57.3 [11.1] years; 940 [66.4%] male) included in the study, the 5-year overall survival rates were 94.2% in the laparoscopic group and 93.3% in the open surgery group (log-rank P = .64). Intention-to-treat analysis confirmed the noninferiority of the laparoscopic approach compared with the open approach (difference, 0.9 percentage points; 1-sided 97.5% CI, -1.6 to infinity). The 5-year cancer-specific survival rates were similar between the 2 groups (97.1% in the laparoscopic group and 97.2% in the open surgery group, log-rank P = .91; difference, -0.03 percentage points; 1-sided 97.5% CI, -1.8 to infinity). Per-protocol analysis results were consistent with the intention-to-treat results for overall and cancer-specific survival rates. CONCLUSIONS AND RELEVANCE: The KLASS-01 trial revealed similar overall and cancer-specific survival rates between patients receiving laparoscopic and open distal gastrectomy. Laparoscopic distal gastrectomy is an oncologically safe alternative to open surgery for stage I gastric cancer. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00452751.

OBJECTIVE: The aim of the study was to evaluate the short-term outcomes of KLASS-02-RCT, a multicenter randomized controlled trial comparing laparoscopic distal gastrectomy (LDG) with D2 lymphadenectomy with open distal gastrectomy (ODG). SUMMARY BACKGROUND DATA: Although several benefits of laparoscopic gastric cancer surgery have been reported, strong evidence is still limited, especially in locally advanced gastric cancer which requires extensive lymph node dissection. METHODS: Enrollment criteria included histologically confirmed cT2-4a and N0-1 gastric adenocarcinoma. Thirty-day morbidity, 90-day mortality, postoperative pain, and recovery were compared between LDG and ODG groups. RESULTS: A total of 1050 patients were randomly assigned to LDG (n = 526) or ODG group (n = 524) between November 2011 and April 2015. After excluding patients who received bypass or no surgery, 1011 patients were analyzed as actual treatment group. Mean number of totally retrieved lymph nodes was similar in both groups (LDG = 46.6 vs ODG = 47.4, P = 0.451). Early morbidity rate was significantly lower after LDG (16.6%) than after ODG (24.1%; P = 0.003). Postoperative analgesics use and patients' reported pain score were significantly lower after LDG. First day of flatus was earlier after LDG (3.5 vs 3.7 d, P = 0.025) and postoperative hospital stay was shorter in LDG group (8.1 vs 9.3 d, P = 0.005). Ninety days' mortality rate was similar in both groups (LDG = 0.4% vs ODG = 0.6%, P = 0.682). CONCLUSIONS: Laparoscopic distal gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer shows benefits in terms of lower complication rate, faster recovery, and less pain compared with open surgery.

OBJECTIVE: As aging progresses, clinical characteristics of elderly patients in the emergency department (ED) vary by age. We aimed to study differences among elderly patients in the ED by age group. METHODS: For 2 years, patients aged 65 and older were enrolled in the study and classified into three groups: youngest-old, ages 65 to 74 years; middle-old, 75 to 84 years; and oldest-old, ≥85 years. Participants' sex, reason for ED visit, transfer from another hospital, results of treatment, type of admission, admission department and length of stay were recorded. RESULTS: During the study period, a total 64,287 patients visited the ED; 11,236 (17.5%) were aged 65 and older, of whom 14.4% were 85 and older. With increased age, the female ratio (51.5% vs. 54.9% vs. 69.1%, P<0.001), medical causes (79.5% vs. 81.3% vs. 81.7%, P=0.045), and admission rate (35.3% vs. 42.8% vs. 48.5%, P<0.001) increased. Admissions to internal medicine (57.5% vs. 59.3% vs. 64.7%, P<0.001) and orthopedic surgery (8.5% vs. 11.6% vs. 13.8%, P< 0.001) also increased. The ratio of admission to intensive care unit showed no statistical significance (P=0.545). Patients over age 85 years had longer stays in the ED (330.9 vs. 378.9 vs. 407.2 minutes, P<0.001), were discharged home less (84.4% vs. 78.9% vs. 71.5%, P<0.001), and died more frequently (6.3% vs. 10.4% vs. 13.0%, P<0.001). CONCLUSION: With increased age, the proportion of female patients and medical causes increased. Rates of admission and death increased with age and older patients had longer ED and hospital stays.

PURPOSE It is unclear whether laparoscopic distal gastrectomy for locally advanced gastric cancer is oncologically equivalent to open distal gastrectomy. The noninferiority of laparoscopic subtotal gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer compared with open surgery in terms of 3-year relapse-free survival rate was evaluated. PATIENTS AND METHODS A phase III, open-label, randomized controlled trial was conducted for patients with histologically proven locally advanced gastric adenocarcinoma suitable for distal subtotal gastrectomy. The primary end point was the 3-year relapse-free survival rate; the upper limit of the hazard ratio (HR) for noninferiority was 1.43 between the laparoscopic and open distal gastrectomy groups. RESULTS From November 2011 to April 2015, 1,050 patients were randomly assigned to laparoscopy (n = 524) or open surgery (n = 526). After exclusions, 492 patients underwent laparoscopic surgery and 482 underwent open surgery and were included in the analysis. The laparoscopy group, compared with the open surgery group, suffered fewer early complications (15.7% v 23.4%, respectively; P = .0027) and late complications (4.7% v 9.5%, respectively; P = .0038), particularly intestinal obstruction (2.0% v 4.4%, respectively; P = .0447). The 3-year relapse-free survival rate was 80.3% (95% CI, 76.0% to 85.0%) for the laparoscopy group and 81.3% (95% CI, 77.0% to 85.0%; log-rank P = .726) for the open group. Cox regression analysis after stratification by the surgeon revealed an HR of 1.035 (95% CI, 0.762 to 1.406; log-rank P = .827; P for noninferiority = .039). When stratified by pathologic stage, the HR was 1.020 (95% CI, 0.751 to 1.385; log-rank P = .900; P for noninferiority = .030). CONCLUSION Laparoscopic distal gastrectomy with D2 lymphadenectomy was comparable to open surgery in terms of relapse-free survival for patients with locally advanced gastric cancer. Laparoscopic distal gastrectomy with D2 lymphadenectomy could be a potential standard treatment option for locally advanced gastric cancer.

BACKGROUND: Asthma and atopic dermatitis (AD) are chronic allergic conditions, along with allergic rhinitis and food allergy and cause high morbidity and mortality both in children and adults. This study aims to evaluate the global, regional, national, and temporal trends of the burden of asthma and AD from 1990 to 2019 and analyze their associations with geographic, demographic, social, and clinical factors. METHODS: Using data from the Global Burden of Diseases (GBD), Injuries, and Risk Factors Study 2019, we assessed the age-standardized prevalence, incidence, mortality, and disability-adjusted life years (DALYs) of both asthma and AD from 1990 to 2019, stratified by geographic region, age, sex, and socio-demographic index (SDI). DALYs were calculated as the sum of years lived with disability and years of life lost to premature mortality. Additionally, the disease burden of asthma attributable to high body mass index, occupational asthmagens, and smoking was described. RESULTS: In 2019, there were a total of 262 million [95% uncertainty interval (UI): 224-309 million] cases of asthma and 171 million [95% UI: 165-178 million] total cases of AD globally; age-standardized prevalence rates were 3416 [95% UI: 2899-4066] and 2277 [95% UI: 2192-2369] per 100,000 population for asthma and AD, respectively, a 24.1% [95% UI: -27.2 to -20.8] decrease for asthma and a 4.3% [95% UI: 3.8-4.8] decrease for AD compared to baseline in 1990. Both asthma and AD had similar trends according to age, with age-specific prevalence rates peaking at age 5-9 years and rising again in adulthood. The prevalence and incidence of asthma and AD were both higher for individuals with higher SDI; however, mortality and DALYs rates of individuals with asthma had a reverse trend, with higher mortality and DALYs rates in those in the lower SDI quintiles. Of the three risk factors, high body mass index contributed to the highest DALYs and deaths due to asthma, accounting for a total of 3.65 million [95% UI: 2.14-5.60 million] asthma DALYs and 75,377 [95% UI: 40,615-122,841] asthma deaths. CONCLUSIONS: Asthma and AD continue to cause significant morbidity worldwide, having increased in total prevalence and incidence cases worldwide, but having decreased in age-standardized prevalence rates from 1990 to 2019. Although both are more frequent at younger ages and more prevalent in high-SDI countries, each condition has distinct temporal and regional characteristics. Understanding the temporospatial trends in the disease burden of asthma and AD could guide future policies and interventions to better manage these diseases worldwide and achieve equity in prevention, diagnosis, and treatment.

BACKGROUND: This study aimed to investigate the prevalence and management of diabetes mellitus, risk-factor control, and comorbidities among Korean adults. METHODS: We conducted a cross-sectional analysis of data from the Korea National Health and Nutrition Examination Survey to assess the prevalence, treatment, risk factors, comorbidities, and self-management behaviors of diabetes mellitus from 2019 to 2020. We also analyzed data from the Korean National Health Insurance Service to evaluate the use of antidiabetic medications in people with diabetes mellitus from 2002 through 2018. RESULTS: Among Korean adults aged 30 years or older, the estimated prevalence of diabetes mellitus was 16.7% in 2020. From 2019 through 2020, 65.8% of adults with diabetes mellitus were aware of the disease and treated with antidiabetic medications. The percentage of adults with diabetes mellitus who achieved glycosylated hemoglobin (HbA1c) <6.5% was 24.5% despite the increased use of new antidiabetic medications. We found that adults with diabetes mellitus who achieved all three goals of HbA1c <6.5%, blood pressure (BP) <140/85 mm Hg, and low-density lipoprotein cholesterol <100 mg/dL were 9.7%. The percentage of self-management behaviors was lower in men than women. Excess energy intake was observed in 16.7% of adults with diabetes mellitus. CONCLUSION: The prevalence of diabetes mellitus among Korean adults remained high. Only 9.7% of adults with diabetes mellitus achieved all glycemic, BP, and lipid controls from 2019 to 2020. Continuous evaluation of national diabetes statistics and a national effort to increase awareness of diabetes mellitus and improve comprehensive diabetes care are needed.

BACKGROUND: To determine whether the TyG index, a product of the levels of triglycerides and fasting plasma glucose (FPG) might be a valuable marker for predicting future diabetes. METHODS: A total of 5,354 nondiabetic subjects who had completed their follow-up visit for evaluating diabetes status were selected from a large cohort of middle-aged Koreans in the Chungju Metabolic Disease Cohort study. The risk of diabetes was assessed according to the baseline TyG index, calculated as ln[fasting triglycerides (mg/dL) × FPG (mg/dL)/2]. The median follow-up period was 4.6 years. RESULTS: During the follow-up period, 420 subjects (7.8%) developed diabetes. The baseline values of the TyG index were significantly higher in these subjects compared with nondiabetic subjects (8.9 ± 0.6 vs. 8.6 ± 0.6; P<0.0001) and the incidence of diabetes increased in proportion to TyG index quartiles. After adjusting for age, gender, body mass index, waist circumference, systolic blood pressure, high-density lipoprotein (HDL)-cholesterol level, a family history of diabetes, smoking, alcohol drinking, education level and serum insulin level, the risk of diabetes onset was more than fourfold higher in the highest vs. the lowest quartile of the TyG index (relative risk, 4.095; 95% CI, 2.701-6.207). The predictive power of the TyG index was better than the triglyceride/HDL-cholesterol ratio or the homeostasis model assessment of insulin resistance. CONCLUSIONS: The TyG index, a simple measure reflecting insulin resistance, might be useful in identifying individuals at high risk of developing diabetes.

Psoriasis is a chronic inflammatory skin disorder, and current treatments include topical therapies, phototherapy, systemic immune modulators, and biologics, aiming to alleviate symptoms and improve quality of life. However, challenges persist, such as adverse effects, treatment resistance, high costs, and variability in response among individuals. The future of psoriasis treatment shows promising emerging trends. New biologic agents targeting novel pathways, such as interleukin 23 inhibitors like mirikizumab, offer enhanced efficacy. Small molecule inhibitors like RORγt inhibitors and ROCK2 inhibitors provide additional treatment options. Combination therapies, including biologics with methotrexate, may improve treatment response. Advancements in topical treatments utilizing microneedles and nanoparticle-based carriers can enhance drug delivery and improve therapeutic outcomes. Biomarkers and multi-omics technologies hold potential for personalized treatment approaches, thus aiding in diagnosis, predicting treatment response, and guiding therapeutic decisions. Collaboration among researchers, clinicians, and industry stakeholders is crucial to translating these scientific breakthroughs into clinical practice. By addressing current challenges and exploring these promising trends, we can optimize psoriasis management and improve the lives of those affected by this chronic condition.

Human skin is the largest organ and serves as the first line of defense against environmental factors. The human microbiota is defined as the total microbial community that coexists in the human body, while the microbiome refers to the collective genome of these microorganisms. Skin microbes do not simply reside on the skin but interact with the skin in a variety of ways, significantly affecting the skin barrier function. Here, we discuss recent insights into the symbiotic relationships between the microbiome and the skin barrier in physical, chemical, and innate/adaptive immunological ways. We discuss the gut-skin axis that affects skin barrier function. Finally, we examine the effects of microbiome dysbiosis on skin barrier function and the role of these effects in inflammatory skin diseases, such as acne, atopic dermatitis, and psoriasis. Microbiome cosmetics can help restore skin barrier function and improve these diseases.

Aims: A high visit-to-visit variability in cholesterol levels has been suggested to be an independent predictor of major adverse cardiovascular events in patients with coronary artery disease (CAD). Because whether this notion applies to general population is not known, we aimed to investigate the associations between total cholesterol (TC) variability and the risk of all-cause mortality, myocardial infarction (MI), and stroke. Methods and results: We identified 3 656 648 subjects without a history of MI and stroke who underwent ≥3 health examinations from 2002 to 2007 in the Korean National Health Insurance System cohort. Total cholesterol variability was measured using the coefficient of variation (CV), standard deviation (SD), and variability independent of the mean (VIM). There were 84 625 deaths (2.3%), 40 991 cases of MI (1.1%), and 42 861 cases of stroke (1.2%) during the median follow-up of 8.3 years. There was a linear association between higher TC variability and outcome measures. In the multivariable adjusted model, the hazard ratios and 95% confidence intervals comparing the highest vs. lowest quartiles of CV of TC were 1.26 (1.24-1.28) for all-cause mortality, 1.08 (1.05-1.11) for MI, and 1.11 (1.08-1.14) for stroke, which was independent of mean TC levels and the use of lipid-lowering agents. The results were consistent when modelling variability of TC using SD and VIM, and in various sensitivity analyses. Conclusion: High variability in lipid levels is associated with adverse health-related outcomes. These findings suggest that lipid variability is an important risk factor in the general population.

Incidental thyroid nodules are commonly detected on ultrasonography (US). This has contributed to the rapidly rising incidence of low-risk papillary thyroid carcinoma over the last 20 years. The appropriate diagnosis and management of these patients is based on the risk factors related to the patients as well as the thyroid nodules. The Korean Society of Thyroid Radiology (KSThR) published consensus recommendations for US-based management of thyroid nodules in 2011 and revised them in 2016. These guidelines have been used as the standard guidelines in Korea. However, recent advances in the diagnosis and management of thyroid nodules have necessitated the revision of the original recommendations. The task force of the KSThR has revised the Korean Thyroid Imaging Reporting and Data System and recommendations for US lexicon, biopsy criteria, US criteria of extrathyroidal extension, optimal thyroid computed tomography protocol, and US follow-up of thyroid nodules before and after biopsy. The biopsy criteria were revised to reduce unnecessary biopsies for benign nodules while maintaining an appropriate sensitivity for the detection of malignant tumors in small (1-2 cm) thyroid nodules. The goal of these recommendations is to provide the optimal scientific evidence and expert opinion consensus regarding US-based diagnosis and management of thyroid nodules.

BACKGROUND: Variability in metabolic parameters, such as fasting blood glucose and cholesterol concentrations, blood pressure, and body weight can affect health outcomes. We investigated whether variability in these metabolic parameters has additive effects on the risk of mortality and cardiovascular outcomes in the general population. METHODS: Using nationally representative data from the Korean National Health Insurance System, 6 748 773 people who were free of diabetes mellitus, hypertension, and dyslipidemia and who underwent ≥3 health examinations from 2005 to 2012 were followed to the end of 2015. Variability in fasting blood glucose and total cholesterol concentrations, systolic blood pressure, and body mass index was measured using the coefficient of variation, SD, variability independent of the mean, and average real variability. High variability was defined as the highest quartile of variability. Participants were classified numerically according to the number of high-variability parameters (eg, a score of 4 indicated high variability in all 4 metabolic parameters). Cox proportional hazards models adjusting for age, sex, smoking, alcohol, regular exercise, income, and baseline levels of fasting blood glucose, systolic blood pressure, total cholesterol, and body mass index were used. RESULTS: There were 54 785 deaths (0.8%), 22 498 cases of stroke (0.3%), and 21 452 myocardial infarctions (0.3%) during a median follow-up of 5.5 years. High variability in each metabolic parameter was associated with a higher risk for all-cause mortality, myocardial infarction, and stroke. Furthermore, the risk of outcomes increased significantly with the number of high-variability metabolic parameters. In the multivariable-adjusted model comparing a score of 0 versus 4, the hazard ratios (95% CIs) were 2.27 (2.13-2.42) for all-cause mortality, 1.43 (1.25-1.64) for myocardial infarction, and 1.41 (1.25-1.60) for stroke. Similar results were obtained when modeling the variability using the SD, variability independent of the mean, and average real variability, and in various sensitivity analyses. CONCLUSIONS: High variability of fasting blood glucose and total cholesterol levels, systolic blood pressure, and body mass index was an independent predictor of mortality and cardiovascular events. There was a graded association between the number of high-variability parameters and cardiovascular outcomes.

Adiponectin exerts renoprotective effects against diabetic nephropathy (DN) by activating the AMP-activated protein kinase (AMPK)/peroxisome proliferative-activated receptor– α (PPAR α ) pathway through adiponectin receptors (AdipoRs). AdipoRon is an orally active synthetic adiponectin receptor agonist. We investigated the expression of AdipoRs and the associated intracellular pathways in 27 patients with type 2 diabetes and examined the effects of AdipoRon on DN development in male C57BLKS/J db/db mice, glomerular endothelial cells (GECs), and podocytes. The extent of glomerulosclerosis and tubulointerstitial fibrosis correlated with renal function deterioration in human kidneys. Expression of AdipoR1, AdipoR2, and Ca 2+ /calmodulin-dependent protein kinase kinase– β (CaMKK β ) and numbers of phosphorylated liver kinase B1 (LKB1)– and AMPK-positive cells significantly decreased in the glomeruli of early stage human DN. AdipoRon treatment restored diabetes-induced renal alterations in db/db mice. AdipoRon exerted renoprotective effects by directly activating intrarenal AdipoR1 and AdipoR2, which increased CaMKK β , phosphorylated Ser 431 LKB1, phosphorylated Thr 172 AMPK, and PPAR α expression independently of the systemic effects of adiponectin. AdipoRon-induced improvement in diabetes-induced oxidative stress and inhibition of apoptosis in the kidneys ameliorated relevant intracellular pathways associated with lipid accumulation and endothelial dysfunction. In high-glucose–treated human GECs and murine podocytes, AdipoRon increased intracellular Ca 2+ levels that activated a CaMKK β /phosphorylated Ser 431 LKB1/phosphorylated Thr 172 AMPK/PPAR α pathway and downstream signaling, thus decreasing high-glucose–induced oxidative stress and apoptosis and improving endothelial dysfunction. AdipoRon further produced cardioprotective effects through the same pathway demonstrated in the kidney. Our results show that AdipoRon ameliorates GEC and podocyte injury by activating the intracellular Ca 2+ /LKB1-AMPK/PPAR α pathway, suggesting its efficacy for treating type 2 diabetes–associated DN.

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association revised and updated the 6th Clinical Practice Guidelines in 2019. Targets of glycemic, blood pressure, and lipid control in type 2 diabetes mellitus (T2DM) were updated. The obese and overweight population is increasing steadily in Korea, and half of the Koreans with diabetes are obese. Evidence-based recommendations for weight-loss therapy for obesity management as treatment for hyperglycemia in T2DM were provided. In addition, evidence from large clinical studies assessing cardiovascular outcomes following the use of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM were incorporated into the recommendations.

Skin aging is a complex process influenced by intrinsic and extrinsic factors. Together, these factors affect the structure and function of the epidermis and dermis. Histologically, aging skin typically shows epidermal atrophy due to decreased cell numbers. The dermis of aged skin shows decreased numbers of mast cells and fibroblasts. Fibroblast senescence contributes to skin aging by secreting a senescence-associated secretory phenotype, which decreases proliferation by impairing the release of essential growth factors and enhancing degradation of the extracellular matrix through activation of matrix metalloproteinases (MMPs). Several molecular mechanisms affect skin aging including telomere shortening, oxidative stress and MMP, cytokines, autophagic control, microRNAs, and the microbiome. Accumulating evidence on the molecular mechanisms of skin aging has provided clinicians with a wide range of therapeutic targets for treating aging skin.

Background.Two important issues in the aging kidney are mitochondrial dysfunction and oxidative stress.An Nrf2 activator, resveratrol, is known to have various effects.Resveratrol may prevent inflammation and oxidative stress by activating Nrf2 and SIRT1 signaling.We examined whether resveratrol could potentially ameliorate the cellular condition, such as renal injury due to cellular oxidative stress and mitochondrial dysfunction caused by aging.Methods.Male 18-month-old C57BL/6 mice were used.Resveratrol (40 mg/kg) was administered to aged mice for 6 months.We compared histological changes, oxidative stress, and aging-related protein expression in the kidney between the resveratrol-treated group (RSV) and the control group (cont).We performed experiments using small-interfering RNAs (siRNAs) for Nrf2 and SIRT1 in cultured HK2 cells. Results. Resveratrol improved renal function, proteinuria, histological changes and inflammation in aging mice. Also, expression ofNrf2-HO-1-NOQ-1 signaling and SIRT1-AMPK-PGC-1α signaling was increased in the RSV group.Transfection with Nrf2 and SIRT1 siRNA prevented resveratrol-induced anti-oxidative effect in HK2 cells in media treated with H 2 O 2 .Conclusions.Activation of the Nrf2 and SIRT1 signaling pathways ameliorated oxidative stress and mitochondrial dysfunction.Pharmacological targeting of Nrf2 signaling molecules may reduce the pathologic changes of aging in the kidney.

Angiogenesis, the growth of new blood vessels from preexisting vessels, is associated with inflammation in various pathological conditions. Well-known angiogenetic factors include vascular endothelial growth factor (VEGF), angiopoietins, platelet-derived growth factor, transforming growth factor-β, and basic fibroblast growth factor. Yes-associated protein 1 (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) have recently been added to an important angiogenic factor. Accumulating evidence indicates associations between angiogenesis and chronic inflammatory skin diseases. Angiogenesis is deeply involved in the pathogenesis of psoriasis. VEGF, angiopoietins, tumor necrosis factor-a, interleukin-8, and interleukin-17 are unregulated in psoriasis and induce angiogenesis. Angiogenesis may be involved in the pathogenesis of atopic dermatitis, and in particular, mast cells are a major source of VEGF expression. Angiogenesis is an essential process in rosacea, which is induced by LL-37 from a signal cascade by microorganisms, VEGF, and MMP-3 from mast cells. In addition, angiogenesis by increased VEGF has been reported in chronic urticaria and hidradenitis suppurativa. The finding that VEGF is expressed in inflammatory skin lesions indicates that inhibition of angiogenesis is a useful strategy for treatment of chronic, inflammatory skin disorders.

Rosacea is a chronic cutaneous inflammatory disease that affects the facial skin. Clinically, rosacea can be categorized into papulopustular, erythematotelangiectatic, ocular, and phymatous rosacea. However, the phenotypic presentations of rosacea are more heterogeneous. Although the pathophysiology of rosacea remains to be elucidated, immunologic alterations and neurovascular dysregulation are thought to have important roles in initiating and strengthening the clinical manifestations of rosacea. In this article, we present the possible molecular mechanisms of rosacea based on recent laboratory and clinical studies. We describe the genetic predisposition for rosacea along with its associated diseases, triggering factors, and suggested management options in detail based on the underlying molecular biology. Understanding the molecular pathomechanisms of rosacea will likely aid toward better comprehending its complex pathogenesis.

When large engineered tissue structures are used to achieve tissue regeneration, formation of vasculature is an essential process. We report a technique that combines 3D printing with spatial and temporal control of dual growth factors to prevascularize bone tissue. Human dental pulp stem cells (DPSCs) that have both osteogenic and vasculogenic potential were printed with bone morphogenetic protein-2 (BMP-2) in the peripheral zone of the 3D printed construct, and with the vascular endothelial growth factor (VEGF) in the central zone, in which a hypoxic area forms. The structure was implanted in the back of a mouse and tissue regeneration was assessed after 28 d. Microvessels were newly formed in the hypoxic area of the printed large volume structure, and angiogenesis from the host tissue was also observed. Bone regeneration was faster in prevascularized structures than in nonvascularized structures. The 3D-printed prevascularized structure could be a promising approach to overcome the size limitation of tissue implants and to enhance bone regeneration.