Topical Clonidine Accelerates Cutaneous Wound Healing in Diabetic Rats by Regulating the Expression of Related Cytokine Signaling.

Based on the analgesic and anti-inflammatory effects of clonidine in previous studies, we hypothesized that clonidine could accelerate wound healing in rats by regulating the expression of related cytokines. In this study, the wound healing effect of clonidine was evaluated using an excision wound model in diabetic rats and a HaCaT cell model. The wounds were treated daily with topical clonidine. The results analyzed by ImageJ2 software show that the wounds of the rats that were treated with 15 ng/mL clonidine recovered faster, and the wound size was also significantly reduced compared to the control group. Western blot assays determined that clonidine induced an increase in the expression of vascular growth factors, namely, Ang-1, Ang-2, and VEGF. Moreover, clonidine demonstrated a rescuing effect on JAK2 within the JAK/STAT pathway by inhibiting SOCS3 expression, leading to decreased SOCS3 levels and increased expression of JAK2 and phospho-STAT3. Histopathological analysis revealed that clonidine promoted complete epithelial repair and minimized inflammation in skin tissue. Additionally, clonidine stimulated HaCaT cell proliferation in vitro and enhanced cellular energy levels in the presence of AGEs. In conclusion, clonidine promoted vascular growth and wound healing by stimulating the expression of cytokines that are beneficial for wound healing.

Predictors of abnormality in thallium myocardial perfusion scans for type 2 diabetes.

Type 2 diabetes mellitus (T2DM) increases coronary artery disease (CAD) risk. In this study, we used T2DM clinical variables to predict abnormality in thallium-201 myocardial perfusion scans (Th-201 scans). These clinical variables were summed stress score (SSS), summed rest score, and summed difference score (SDS), with data obtained from 368 male and 428 female participants with T2DM. Multiple linear regression results were as follows. In male participants, body mass index (BMI) and creatinine (Cr) were associated with SSS (ß = 0.224, p < 0.001; ß = 0.140, p = 0.022, respectively), and only BMI was associated with SDS (ß = 0.174, p = 0.004). In female participants, BMI and high-density lipoprotein cholesterol level were associated with SSS (ß = 0.240, p < 0.001; ß = - 0.120, p = 0.048, respectively), and only BMI was correlated with SDS (ß = 0.123, p = 0.031). Our multivariate logistic regression indicated that in male and female participants, BMI was the only independent indicator of high SSS (SSS ≥ 9). In this study, we demonstrated that male patients have a higher SSS and SDS than female patients do in Th-201 scans for T2DM in a Chinese population. For male and female patients, BMI was the strongest predictor of abnormality in Th-201 scans. Our results can help clinicians identify patients with T2DM at high risk of CAD.

Comprehensive analysis in mucin-producing urothelial-type adenocarcinoma of the prostate: case study with literature review.

It is critical to distinguish the rare neoplasm of mucin-producing urothelial-type adenocarcinoma of the prostate (MPUAP) from either prostate origin or metastatic adenocarcinoma. This is mainly because they have different tumor staging, clinical behavior and treatment plans. In the current study, we try to fulfill the lack of knowledge in this field. There were totally 24 MPUAP cases including previous reported 23 cases and adding one new MPUAP case in the current study. We performed IHC and 78 genes panel analysis in two cases of ours. Most of the cases had urinary obstruction symptoms and normal PSA level. Pathological features showed dissection of the stroma by mucin pools and glands lined by pseudostratified columnar mucinous epithelium with varying degrees of cytological atypia. The IHC results showed positive for CK20, CEA, CDX-2, ß-catenin, p53, MUC2 and MUC5AC, negative for PSA, AMACR, GATA3, MUC6, AR and NKX3.1 and variable expression for HMWCK and CK7. Genetic analysis revealed concurrent mutations of FAT1 (c.10001 T>C) and HNF1A in both cases. The similar morphology features of MPUAP and colorectal adenocarcinoma were seen. Membranous staining pattern of ß-catenin and genetic mutation of FAT1 and HNF1A are two distinct features in MPUAP.

Adenine decreases hypertrophic effects through interleukin-18 receptor.

Cardiac hypertrophy is the main cause of heart failure. Levels of circulating interleukin-18 (IL-18) have been reported to increase in congestive heart disease and cardiac hypertrophy. Relationships among IL-18 levels, IL-18 receptor (IL-18R) expression, and cardiac hypertrophy remain unclear. IL-18 can induce cardiac hypertrophy in cardiomyoblasts. We also studied IL-18R messenger RNA (mRNA) and protein expression through quantitative-polymerase chain reaction and Western blotting. Furthermore, we treated cardiomyoblasts with adenine, gold nanoparticles (AuNPs), and inhibitors to analyze the morphology and identify signaling pathways involved in cardiac hypertrophy. Moreover, we studied the effects of IL-18R small interfering RNA (siRNA) on signaling pathways through Western blotting. The mRNA expression of IL-18R in H9c2 cardiomyoblasts, which was induced by IL-18, increased significantly after 8 h, and the protein level increased significantly after 15 h. Morphological examination of H9c2 cardiomyoblasts showed that cell volume and cell diameter decreased after adenine pretreatment. Both p38 MAPK and PI3 kinase are biomarkers in the pathway correlated with cardiac hypertrophy. After treatment with inhibitors SB203580 and LY294002, the levels of p38 MAPK and PI3 kinase, respectively, decreased along with cell size and IL-18R expression. Treatment with adenine, but not AuNPs, reduced the levels of phosphorylated p38 and PI3 kinase expression more effectively than did treatment with the respective inhibitors alone. IL-18R siRNA significantly reduced cell size but not PI3 kinase expression and phosphorylation of p38 MAPK. However, adenine treatment reduced PI3 kinase expression after treatment with IL-18R siRNA. In this study, IL-18 induced cardiomyoblast hypertrophy through IL-18R upregulation, which was found to be related to p38 MAPK and PI3 kinase signaling. Adenine, but not AuNPs, showed antihypertrophic effects possibly because of decreased levels of signaling.

The neuroprotective role of metformin in advanced glycation end product treated human neural stem cells is AMPK-dependent.

Diabetic neuronal damage results from hyperglycemia followed by increased formation of advanced glycosylation end products (AGEs), which leads to neurodegeneration, although the molecular mechanisms are still not well understood. Metformin, one of the most widely used anti-diabetic drugs, exerts its effects in part by activation of AMP-activated protein kinase (AMPK). AMPK is a critical evolutionarily conserved enzyme expressed in the liver, skeletal muscle and brain, and promotes cellular energy homeostasis and biogenesis by regulating several metabolic processes. While the mechanisms of AMPK as a metabolic regulator are well established, the neuronal role for AMPK is still unknown. In the present study, human neural stem cells (hNSCs) exposed to AGEs had significantly reduced cell viability, which correlated with decreased AMPK and mitochondria associated gene/protein (PGC1α, NRF-1 and Tfam) expressions, as well as increased activation of caspase 3 and 9 activities. Metformin prevented AGEs induced cytochrome c release from mitochondria into cytosol in the hNSCs. Co-treatment with metformin significantly abrogated the AGE-mediated effects in hNSCs. Metformin also significantly rescued hNSCs from AGE-mediated mitochondrial deficiency (lower ATP, D-loop level, mitochondrial mass, maximal respiratory function, COX activity, and mitochondrial membrane potential). Furthermore, co-treatment of hNSCs with metformin significantly blocked AGE-mediated reductions in the expression levels of several neuroprotective genes (PPARγ, Bcl-2 and CREB). These findings extend our understanding of the molecular mechanisms of both AGE-induced neuronal toxicity, and AMPK-dependent neuroprotection by metformin. This study further suggests that AMPK may be a potential therapeutic target for treating diabetic neurodegeneration.

Mean arterial pressure is better at predicting future metabolic syndrome in the normotensive elderly: a prospective cohort study in Taiwan.

OBJECTIVE: To compare four different blood pressure (BP) measurements-systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP)-in predicting future metabolic syndrome (MetS) among the normotensive elderly population, and to estimate the optimal cutoff value of the best single measurement for clinical practice. METHODS: A total of 2782 non-medicated participants aged ≥ 60 years were enrolled in a standard health examination program in Taiwan from January 2004 to December 2013. Two thirds of the participants were randomly designated as the training group (n=1855) and the other one third as the validation group (n=927). The mean follow-up time was 3.60 years for both the training and validation groups. MAP and PP were calculated from SBP and DBP. RESULTS: SBP, DBP, and MAP were associated with future MetS, whereas PP was not. MAP had the largest hazard ratio in Cox regression (men 1.342 [95% CI 1.158-1.555] and women 1.348 [95% CI 1.185-1.534] in the training group; men 1.640 [95% CI 1.317-2.041] and women 1.485 [95% CI 1.230-1.794] in the validation group) and the largest area under the receiver operating characteristic curve (men 0.598 ± 0.021 and women 0.602 ± 0.021 in the training group). Multivariable Cox regression further indicated that a higher MAP level was independently associated with the future occurrence of MetS. Participants with MAP above the cutoff value (84.0mm Hg for men, 83.3mm Hg for women) had a higher cumulative incidence of MetS than did their counterparts after four years' follow-up in both the training and validation groups. The results derived from the training data could be replicated in the validation data, indicating that the results were generalizable across distinct samples. CONCLUSIONS: MAP is more accurate than SBP, DBP, and PP in predicting future MetS among the normotensive geriatric population. Calculation of MAP is recommended when dealing with normotensive patients aged ≥ 60 years in clinical practice.

Using hematogram model to predict future metabolic syndrome in elderly: a 4-year longitudinal study.

OBJECTIVES: The metabolic syndrome (MetS) is proposed to predict future occurrence of cardiovascular diseases and diabetes. There are some other "non-traditional" risk factors such as hematogram components that are also related to the same endpoints as MetS. In this four-year longitudinal study, we used hematogram components to build models for predicting future occurrence of MetS in older men and women separately. METHODS: Subjects above 65 years without MetS and related diseases were enrolled. All subjects were followed up until they developed MetS or until up to four years from the day of entry, whichever was earlier. RESULTS: Among the 4539 study participants, 1327 developed MetS. Models were built for men and women separately and the areas under the receiver operation curves were significant. The Kaplan-Meier plot showed that the models could predict future MetS. Finally, Cox regression analysis showed that the hematogram model was correlated to future MetS with hazard ratios of 1.567 and 1.738 in men and women, respectively. CONCLUSION: Our hematogram models could significantly predict future MetS in elderly and might be more practical and convenient for daily clinical practice.

Astaxanthin protects steroidogenesis from hydrogen peroxide-induced oxidative stress in mouse Leydig cells.

Androgens, especially testosterone produced in Leydig cells, play an essential role in development of the male reproductive phenotype and fertility. However, testicular oxidative stress may cause a decline in testosterone production. Many antioxidants have been used as reactive oxygen species (ROS) scavengers to eliminate oxidative stress to protect steroidogenesis. Astaxanthin (AST), a natural extract from algae and plants ubiquitous in the marine environment, has been shown to have antioxidant activity in many previous studies. In this study, we treated primary mouse Leydig cells or MA-10 cells with hydrogen peroxide (H2O2) to cause oxidative stress. Testosterone and progesterone production was suppressed and the expression of the mature (30 kDa) form of StAR protein was down-regulated in MA-10 cells by H2O2 and cAMP co-treatment. However, progesterone production and expression of mature StAR protein were restored in MA-10 cells by a one-hour pretreatment with AST. AST also reduced ROS levels in cells so that they were lower than the levels in untreated controls. These results provide additional evidence of the potential health benefits of AST as a potential food additive to ease oxidative stress.

Use of white blood cell counts to predict metabolic syndrome in the elderly: a 4 year longitudinal study.

BACKGROUND: The white blood cell (WBC) count was one of the first inflammatory markers associated with metabolic syndrome (MetS). Recently, two longitudinal studies have demonstrated a cause and effect relationship between MetS and WBC counts among middle-aged adults. However, no study has used WBC cutoff values to predict MetS in the elderly. METHODS: Subjects who underwent routine health checkups, and were above 60 years of age, were enrolled. All subjects were followed-up until they developed MetS or until 4 years from the date of entry, whichever came earlier. Of the 4539 subjects eligible for enrollment, 3428 subjects comprised the study group and 1111 subjects comprised the validation group. RESULTS: WBC counts were significantly different between subjects with and without MetS in both genders. Using the ROC curve, WBC cutoff values of 5.7 × 10(3)/µl in males and 5.0 × 10(3)/µl in females were associated with the increased risk of developing MetS (all p values <0.001). Using these WBC cutoff values, the hazard ratio (HR) for females was significant in both the study group and validation group. However, the HR for males failed significance in the validation group. Kaplan-Meier plots and κ coefficients confirmed that the WBC cutoff value could predict development of MetS in women but not in men. CONCLUSIONS: The association between WBC count and MetS was gender specific. A WBC cutoff value greater than 5.0 10(3)/µl may predict the development of MetS in elderly women.

The expected changes with different periods of home-based resistance exercise in patients with chronic kidney disease.

BACKGROUND: The comprehensive impact of prolonged home-based resistance training on individuals grappling with chronic kidney disease (CKD) have yet to be fully elucidated. This study aimed to explore the outcomes of varying exercise durations on physical performance, nutritional status, and kidney function within this specific population, encompassing patients undergoing dialysis and those affected by severe sarcopenia. METHODS: This was a 1-year observational double cohort study following a 52-week longitudinal design, we enrolled 101 adult CKD outpatients. These participants were divided into two groups: the continuous group, comprising individuals who consistently exercised for over 6 months, and the interrupted group, which included those who did not sustain regular exercise for the same duration. The exercise regimen involved resistance exercises conducted at least 3 to 5 days per week, involving activities like lifting dumbbells and executing weighted wall squats. Physical activity assessments and biochemical blood tests were conducted at weeks 0, 4, 16, 28, 40, and 52 for all participants. RESULTS: The continuous exercise group exhibited better handgrip strength and sit-to-stand movement compared to the interrupted group. Their estimated glomerular filtration rate stayed steady while the interrupted group was declined. Additionally, those who exercised consistently had better metabolism: higher carbon dioxide levels, increased albumin, better nutritional scores, and lower levels of blood urea nitrogen, creatinine, fasting blood glucose, and body weight. Subsequent adjustments for potential confounding factors continued to show improved physical performance and kidney function over time. CONCLUSION: Our findings indicate the advantageous impact of extended resistance exercise training on overall health of CKD patients, even those on dialysis or with severe sarcopenia. Dedication to this exercise routine could improve kidney function, metabolism, and physical abilities in these patients.

Epigallocatechin-3-gallate combined with alpha lipoic acid attenuates high glucose-induced receptor for advanced glycation end products (RAGE) expression in human embryonic kidney cells.

The anti-oxidant effects of epigallocatechin gallate (EGCG) and alpha lipoic acid (ALA) have been demonstrated in previous studies. The kidney protection effects of EGCG and ALA in patients with kidney injury are still under investigation. The purpose of this study is to investigate the anti-inflammatory and anti-oxidant effects of EGCG and ALA on high glucose-induced human kidney cell damage. EGCG inhibited high glucose(HG)-induced TNF-α and IL-6 production in human embryonic kidney (HEK) cells. Both EGCG and ALA decreased HG-induced receptor of advanced glycation end products (RAGE) mRNA and protein expressions in HEK cells. EGCG and ALA also recovered HG-inhibited superoxide dismutase production and decreased ROS expressions in HEK cells. The synergism of EGCG and ALA was also studied. The effect of EGCG combined with ALA is greater than the effect of EGCG alone in all anti-inflammation and anti-oxidant experiments. Our studies provide a potential therapeutic application of EGCG and ALA in preventing progression of diabetic nephropathy.

Glucagon-like peptide-1 receptor regulates receptor of advanced glycation end products in high glucose-treated rat mesangial cells.

BACKGROUND: Hyperglycemia-induced advanced glycation end products (AGEs) and receptor for AGEs (RAGEs) play major roles in diabetic nephropathy progression. In previous study, both glucagon-like peptide-1 (GLP-1) and peroxisome proliferator-activated receptors delta (PPARδ) agonists were shown to have anti-inflammatory effect on AGE-treated rat mesangial cells (RMCs). The interaction among PPARδ agonists, GLP-1, and AGE-RAGE axis is, however, still unclear. METHODS: In this study, the individual and synergic effect of PPARδ agonist (L-165 041) and siRNA of GLP-1 receptor (GLP-1R) on the expression of GLP-1, GLP-1R, RAGE, and cell viability in AGE-treated RMCs were investigated. RESULTS: L-165 041 enhanced GLP-1R mRNA and protein expression only in the presence of AGE. The expression of RAGE mRNA and protein was enhanced by AGE, attenuated by L-165 041, and siRNA of GLP-1R reversed L-165 041-induced inhibition. Cell viability was also inhibited by AGE. L-165 041 attenuated AGE-induced inhibition and siRNA GLP-1R diminished L-165 041 effect. CONCLUSION: PPARδ agonists increase GLP-1R expression on RMC in the presence of AGE. PPARδ agonists also attenuate AGE-induced upregulated RAGE expression and downregulated cell viability. The effect of PPARδ agonists needs the cooperation of GLP-1R activation.

Using Machine Learning to Identify the Relationships between Demographic, Biochemical, and Lifestyle Parameters and Plasma Vitamin D Concentration in Healthy Premenopausal Chinese Women.

INTRODUCTION: Vitamin D plays a vital role in maintaining homeostasis and enhancing the absorption of calcium, an essential component for strengthening bones and preventing osteoporosis. There are many factors known to relate to plasma vitamin D concentration (PVDC). However, most of these studies were performed with traditional statistical methods. Nowadays, machine learning methods (Mach-L) have become new tools in medical research. In the present study, we used four Mach-L methods to explore the relationships between PVDC and demographic, biochemical, and lifestyle factors in a group of healthy premenopausal Chinese women. Our goals were as follows: (1) to evaluate and compare the predictive accuracy of Mach-L and MLR, and (2) to establish a hierarchy of the significance of the aforementioned factors related to PVDC. METHODS: Five hundred ninety-three healthy Chinese women were enrolled. In total, there were 35 variables recorded, including demographic, biochemical, and lifestyle information. The dependent variable was 25-OH vitamin D (PVDC), and all other variables were the independent variables. Multiple linear regression (MLR) was regarded as the benchmark for comparison. Four Mach-L methods were applied (random forest (RF), stochastic gradient boosting (SGB), extreme gradient boosting (XGBoost), and elastic net). Each method would produce several estimation errors. The smaller these errors were, the better the model was. RESULTS: Pearson's correlation, age, glycated hemoglobin, HDL-cholesterol, LDL-cholesterol, and hemoglobin were positively correlated to PVDC, whereas eGFR was negatively correlated to PVDC. The Mach-L methods yielded smaller estimation errors for all five parameters, which indicated that they were better methods than the MLR model. After averaging the importance percentage from the four Mach-L methods, a rank of importance could be obtained. Age was the most important factor, followed by plasma insulin level, TSH, spouse status, LDH, and ALP. CONCLUSIONS: In a healthy Chinese premenopausal cohort using four different Mach-L methods, age was found to be the most important factor related to PVDC, followed by plasma insulin level, TSH, spouse status, LDH, and ALP.

Oral Bioavailability and Pharmacokinetics of Sildenafil Orally Disintegrating Tablets under Various Gastric pH Levels Following Administration of Omeprazole in Rats.

Sildenafil citrate, an oral drug used to treat erectile dysfunction, has low water solubility and oral bioavailability. The solubility is greatly influenced by the pH, changing from 37.25 mg/mL to 0.22 mg/mL with a change in pH from 1.2 to 8.0. This indicates that the absorption may decrease in patients who use drugs, such as proton pump inhibitors (PPIs), for gastroesophageal reflux disease. To improve the absorption of sildenafil citrate at various gastric pH levels, a sildenafil citrate orally disintegrating tablet (ODT), which has a rapid disintegration feature, was produced by a 3D printing technique. Our study investigated the pharmacokinetic parameters of the sildenafil citrate ODT in rats after oral administration and compared the absorption of the sildenafil citrate ODT and sildenafil citrate commercial tablet (RLD), with and without PPI treatment. The LC/MS/MS analysis of the plasma sildenafil concentration revealed that the area under curve from time 0 to infinity (AUC0-∞) of sildenafil in the sildenafil citrate ODT group was significantly higher than in the sildenafil citrate RLD group whether it was in combination with the PPI or not (274.8% and 144%, respectively; p < 0.05). The relative systemic bioavailability of sildenafil citrate RLD significantly decreased with the PPI, but that of sildenafil citrate ODT was not affected by the PPI. These results indicate that the relative systemic bioavailability of sildenafil citrate ODT was increased when it was prepared using the 3D printing technique and the absorption of this formulation was not affected by the PPI.

Asymptomatic bacteriuria among the elderly residents of long-term care facilities in Taiwan.

BACKGROUND: asymptomatic bacteriuria (ASB) is common among the institutionalised elderly (IE). The cytokine levels and factors associated with ASB are unknown. OBJECTIVE: to analyse cytokines and factors associated with ASB among the IE living in long-term care facilities (LTCFs) in Taiwan. METHODS: this case-control study included residents ≥65 years in two LTCFs. The demographics, functional status, serum and urine levels of cytokines and proteins were compared between IE with ASB and those with sterile urine. Logistic regression was used to determine the factors associated with ASB. RESULTS: the IE with ASB had elevated IL-8 in blood and urine compared with the IE with sterile urine. The Barthel index score, serum creatinine, blood IL-8 and tumour necrosis factor-α levels were significant factors associated with ASB among the IE [odds ratio (OR) 0.957, 95% CI: 0.936-0.979, P < 0.0001; OR: 0.264, 95% CI: 0.076-0.912, P = 0.035 and OR: 1.088, 95% CI: 1.022-1.158, P = 0.009; OR: 0.828, 95% CI: 0.711-0.965, P = 0.016, respectively). CONCLUSION: functional status, renal function and blood cytokine levels were factors significantly associated with ASB among the IE living in Taiwan.

The effects of gold nanoparticles in wound healing with antioxidant epigallocatechin gallate and α-lipoic acid.

Topical applications of antioxidant agents in cutaneous wounds have attracted much attention. Gold nanoparticles (AuNPs), epigallocatechin gallate (EGCG), and α-lipoic acid (ALA) were shown to have antioxidative effects and could be helpful in wound healing. Their effects in Hs68 and HaCaT cell proliferation and in mouse cutaneous wound healing were studied. Both the mixture of EGCG + ALA (EA) and AuNPs + EGCG + ALA (AuEA) significantly increased Hs68 and HaCaT proliferation and migration. Topical AuEA application accelerated wound healing on mouse skin. Immunoblotting of wound tissue showed significant increase of vascular endothelial cell growth factor and angiopoietin-1 protein expression, but no change of angiopoietin-2 or CD31 after 7 days. After AuEA treatment, CD68 protein expression decreased and Cu/Zn superoxide dismutase increased significantly in the wound area. In conclusion, AuEA significantly accelerated mouse cutaneous wound healing through anti-inflammatory and antioxidation effects. This study may support future studies using other antioxidant agents in the treatment of cutaneous wounds. FROM THE CLINICAL EDITOR: In this study, topically applied gold nanoparticles with epigallocatechin gallate and alpha-lipoic acid were studied regarding their effects in wound healing in cell cultures. Significant acceleration was demonstrated in wound healing in a murine model.

The Role of Lifestyle Intervention, in Addition to Drugs, for Diabetic Kidney Disease with Sarcopenic Obesity.

Diabetic kidney disease is the leading cause of end-stage renal disease in developing and developed countries. The growing prevalence and clinical challenges of sarcopenic obesity have been associated with the frailty and disability of diabetic kidney disease. It has been reported that insulin resistance, chronic inflammation, enhanced oxidative stress and lipotoxicity contribute to the pathophysiology of muscle loss and visceral fat accumulation. Sarcopenic obesity, which is diagnosed with dual-energy X-ray absorptiometry, is associated with worse outcomes in kidney disease. Growing evidence indicates that adherence to healthy lifestyles, including low protein diet, proper carbohydrate control, vitamin D supplement, and regular physical training, has been shown to improve clinical prognosis. Based on the higher risk of sarcopenic-obesity-related renal function decline, it has led to the exploration and investigation of the pathophysiology, clinical aspects, and novel approach of these controversial issues in daily practice.

High Mobility Group A 1 Expression as a Poor Prognostic Marker Associated with Tumor Invasiveness in Gastric Cancer.

The prognosis of advanced gastric cancer remains poor. Overexpression of high mobility group A 1 (HMGA1) in breast cancer and neuroblastoma indicates a poor prognosis. However, the relationship between HMGA1 expression and gastric cancer development remains unclear. Treatment strategies can be developed by identifying potential markers associated with gastric cancer. We used a constructed tissue array and performed hematoxylin and eosin and immunohistochemical staining. We quantified the staining results and performed statistical analysis to evaluate the relationship between HMGA1 expression and prognosis. HMGA1 expression was related to the expression of Ki-67, caspase3, CD31, N-cadherin, fibronectin, pAkt, and pErk. In the Kaplan-Meier graph, higher HMGA1 expression levels were associated with a relatively poor survival rate (p = 0.04). High expression of HMGA1 leads to a low survival rate, which is associated with HMGA1, proliferation, apoptosis, angiogenesis, epithelial-mesenchymal transition, and tyrosine kinase.

The Association between Human Epididymis Secretory Protein 4 and Metabolic Syndrome.

Individuals with metabolic syndrome (MetS) are known to have an increased risk of carcinogenesis. Human epididymis protein 4 (HE4) is a tumor marker and prognostic factor for epithelial ovarian carcinoma (EOC) patients. However, no studies have evaluated the association between MetS and HE4 levels. This study aimed to evaluate the relationship between HE4 levels and MetS in the National Health and Nutrition Examination Survey (NHANES 2001−2002). This cross-sectional analysis assessed all five components of MetS and HE4 levels in 2104 females (age ≥20 years) from the NHANES dataset. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) criteria. The analysis indicated MetS in 593 individuals, and the ß coefficient of their HE4 levels was 0.097 (95% CIs, 0.028−0.166, p = 0.006). Specifically, the ß coefficients of the HE4 levels of participants with 1, 2, 3, and ≥4 features of MetS were 0.072 (95% confidence interval (CI): −0.015−0.159), 0.125 (95% CI: 0.030−0.220), 0.161 (95% CI: 0.053−0.270), and 0.242 (95% CI: 0.117−0.368), respectively, and all p values were <0.001. The p-value for the trend was <0.001. There was a significant association between the presence of MetS and HE4 levels. There were positive relationships between HE4 levels and an increased number of MetS components (with 1, 2, 3, and ≥4 features of MetS, all p values <0.001). Among the MetS components, low high-density lipoprotein levels and high triglyceride levels were independently associated with HE4 levels.

Serotonin receptor subtype-2B signaling is associated with interleukin-18-induced cardiomyoblast hypertrophy in vitro.

Background: In patients with heart failure, interleukin-18 (IL-18) levels increase in the circulatory system and injured myocardial tissue. Serotonin (5-hydroxytryptamine) receptors subtype 2B (HTR2B) play an essential role in cardiac function and development, and their overexpression in rats leads to myocardial hypertrophy. Epigallocatechin gallate (EGCG) is cardioprotective in myocardial ischemia-reperfusion injury in rats and can prevent pressure overload-mediated cardiac hypertrophy in vivo. Mice deficient in peroxisome proliferator-activated receptor delta (PPARδ) can have cardiac dysfunction, myocardial hypertrophy, and heart failure. Matrix metalloproteinases (MMPs) are possibly involved in cardiac remodeling. However, the relationship between IL-18 signaling, cardiac hypertrophy, and the molecular mechanisms involved remain to be fully elucidated. Objectives: To elucidate the relationship between HTR2B and IL-18-induced myocardial hypertrophy and examine the antihypertrophic effects of EGCG and PPARδ. Methods: We induced H9c2 cardiomyoblast hypertrophy with IL-18 in vitro and investigated the downstream signaling by real-time polymerase chain reaction (PCR) and western blotting. Hypertrophy was assessed by flow cytometry. We determined the effects of EGCG and PPARδ on IL-18-induced hypertrophic signaling via HTR2B-dependent mechanisms. Results: IL-18-induced H9c2 hypertrophy upregulated brain natriuretic peptide (BNP) protein and mRNA expression by inducing the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and the hypertrophy was attenuated by pretreatment with EGCG (20 µM) and L-165,041 (2 µM), a PPARδ agonist. IL-18 upregulated the expression of HTR2B, which was inhibited by pretreatment with EGCG and L-165,041. SB215505 (0.1 µM), a HTR2B antagonist and siRNA for HTR2B, attenuated H9c2 hypertrophy significantly. Inhibition of HTR2B also downregulated the expression of MMP-3 and MMP-9. Conclusions: IL-18 and HTR2B play critical roles in cardiomyoblast hypertrophy. EGCG and L-165,041 inhibit the expression of HTR2B and augment remodeling of H9c2 cardiomyoblasts, possibly mediated by MMP-3 and MMP-9.