Aquaporin-8 promotes human dermal fibroblasts to counteract hydrogen peroxide-induced oxidative damage: A novel target for management of skin aging.

The skin is subjected to various external factors that contribute to aging including oxidative stress from hydrogen peroxide (H2O2). This study investigated the distribution of aquaporin-8 (AQP8), a protein that transports H2O2 across biological membranes, in skin cells, and its effects in mitigating H2O2-induced oxidative damage. Human dermal fibroblasts were treated with increasing concentrations of H2O2 to evaluate oxidative damage. Cell viability, reactive oxygen species (ROS) generation, and the expression of specific genes associated with skin aging (IL-10, FPR2, COL1A1, KRT19, and Aggrecan) were evaluated and AQP8 expression was assessed via quantitative polymerase chain reaction and western blotting. Small-interfering RNA was used to silence the AQP8 gene and evaluate its significance. The results show that H2O2 treatment reduces cell viability and increases ROS generation, leading to oxidative damage that affects the expression of target molecules. Interestingly, H2O2-treated cells exhibit high levels of AQP8 expression and gene silencing of AQP8 reverses high levels of ROS and low levels of COL1A1, KRT19, and Aggrecan expression in stressed cells, indicating that AQP8 plays a vital role in preventing oxidative damage and consequent aging. In conclusion, AQP8 is upregulated in human dermal fibroblasts during H2O2-induced oxidative stress and may help prevent oxidative damage and aging. These findings suggest that AQP8 could be a potential therapeutic target for skin aging. Further research is necessary to explore the feasibility of using AQP8 as a preventive or therapeutic strategy for maintaining skin health.

Gamma-Glutamyltransferase Is a Predictor for Future Changes of Diabetogenic Factors in Aged Chinese-A Four-Year Follow-Up Study.

Glucose homeostasis in the body is determined by four diabetes factors (DFs): insulin resistance (IR), glucose effectiveness (GE), and the two phases of insulin secretion-first phase (FPIS) and second phase (SPIS). Previous research points to a correlation between elevated levels of gamma-glutamyl transferase (γGT) and an increased risk of type 2 diabetes. This study investigates the relationship between γGT and the four DFs in older Chinese individuals. This study involved 2644 men and 2598 women, all of whom were relatively healthy Chinese individuals aged 60 years or more. The DFs were calculated using formulas developed by our research, based on demographic data and factors related to metabolic syndrome. Pearson's correlation was utilized to assess the relationship between γGT and the four DFs. The findings suggested a positive correlation between γGT and IR, FPIS, and SPIS, but a negative correlation with GE in men. Among women, only SPIS and GE were significantly correlated with γGT. The factors showed varying degrees of correlation, listed in descending order as follows: GE, SPIS, FPIS, and IR. This study confirms a significant correlation between γGT and DFs in this population, highlighting the noteworthy role of GE.

Changes in insulin resistance, glucose effectiveness, and first and second phases of insulin secretion in women aged 45-60 years old in Taiwan.

BACKGROUND: In women after menopause, the incidence of diabetes mellitus increases. Increased insulin resistance (IR), decreased glucose effectiveness (GE), and the first and second phases of insulin secretion (FPIS and SPIS), are the four most important factors that trigger glucose intolerance and diabetes (diabetogenic factor [DF]). In the cross-sectional study, we enrolled nondiabetic women between the ages of 45 and 60 years to observe the changes in DFs during the perimenopausal period and to elucidate the underlying mechanisms of diabetes in menopausal women. METHODS: We randomly enrolled 4194 women who underwent health checkups. Using demographic and biochemical data, IR, FPIS, SPIS, and GE were calculated using previously published equations. The relationship between the DFs and age was evaluated using a simple correlation. RESULTS: Body mass index, blood pressure, fasting plasma glucose, low-density lipoprotein cholesterol, triglyceride, and SPIS were higher, and GE was lower in older women (≥52 years old). A significant decrease in GE and increased SPIS were observed with age. However, no changes were observed in IR or FPIS. CONCLUSION: The IR and FPIS did not change during perimenopause. Increased SPIS may compensate for the decrease in GE, which is probably one of the reasons for the higher incidence of diabetes in menopausal women.

Visfatin and Retinol Binding Protein-4 in Young-Onset Type 2 Diabetes Mellitus.

Background and Objectives: The prevalence of type 2 diabetes mellitus in adolescents has increased rapidly in recent decades. However, the role of adipokines on pathophysiology in young-onset type 2 diabetes mellitus (YDM) is not clear. In this article, we explored the relationships between the adipokines (visfatin and retinol binding protein 4 (RBP4)) and metabolic syndrome (MetS) components in both YDM and late-onset type 2 diabetes mellitus (ODM). Materials and Methods: There were 36 patients with YDM (23.6 ± 4.8 years) and 36 patients with ODM (54.3 ± 10.1 years) enrolled. Visfatin, RBP4, and MetS components were measured. The relationships between visfatin, RBP4 and MetS components were assessed in YDM and ODM. Results: The visfatin, but not the RPB4 level, was significantly higher in YDM than in ODM. After adjusting for age and body mass index, visfatin was not related to any MetS components except that there was a negative correlation with fasting plasma glucose (FPG). As for RPB4, triglyceride was found to be positively and FPG negatively related to RBP4 in YDM. However, in ODM, the only positive relationship that existed was between RBP4 and diastolic blood pressure. Conclusions: In conclusion, both visfatin and RBP4 had certain roles in diabetes and MetS although their relationships were different in YDM and ODM. Further studies are needed to explore their physiological and pathological effects in glucose metabolism.

Predictors associated with prefrailty in older Taiwanese individuals with type 2 diabetes.

Type 2 diabetes (T2DM) is one of the most well-studied and important factors that increase the risk of prefrailty in older people in Taiwan. This study was conducted to examine whether metabolic biomarkers, lifestyle behaviors, body composition, and chronic diseases are associated with frailty in older people with T2DM. We also observed how people manage their T2DM related to prefrailty. This study investigated a total of 201 participants diagnosed with T2DM who received care in our hospital from September 2018 to February 2019. Patients were divided into 3 groups (not frail, prefrail, and frail), and frailty was measured with the 5-item FRAIL scale. Socioeconomic characteristics, metabolic biomarkers, lifestyle behaviors, body composition, and chronic diseases were assessed at enrollment. No participants who we tested met the criteria for frailty. Based on the results of chi-square tests, prefrailty was associated with female sex, middle school education, unemployment, alcohol use, high body fat percentage, above-normal waist circumference, obesity, cardiovascular disease, and hypertension. Logistic regression analyses identified a significant correlation of prefrailty with the type of job from which they retired, cardiovascular disease, and hypertension. An important and surprising finding of this study was that the unemployed group was at high risk for prefrailty, which was not observed in previous research. The groups engaged in manual and professional jobs had better hand grip strength, a slower walking speed, and less risk of prefrailty than the unemployed group.

Elevated alanine aminotransferase is associated with biphasic insulin secretion in the healthy elderly Han Chinese population.

OBJECTIVE: To evaluate the relationship between alanine transaminase (ALT) level and biphasic insulin secretion (BPIS) in healthy elderly Han Chinese individuals. METHODS: This cross-sectional study enrolled healthy elderly participants aged ≥60 years that were part of a health examination programme. In order to explore the correlation and severity of the clinical condition, those with any possible confounding factors known to affect insulin secretion or liver function were excluded from the study. BPIS was calculated using an equation developed previously by this research team. RESULTS: This study enrolled 39 845 healthy elderly individuals (19 058 males and 20 787 females). Participants were stratified into four quartile groups according to their ALT level. In both males and females, the increasing ALT quartiles (ordinal variable) were associated with greater values of log-transformed first-phase insulin secretion (FPIS) and second-phase insulin secretion (SPIS). The correlation and the linear regression model showed that increasing ALT level was significantly correlated with higher log-transformed FPIS and SPIS. CONCLUSIONS: ALT was positively correlated with BPIS in a healthy elderly population in both men and women. Elevated ALT may serve as an indicating factor for developing metabolic syndrome and type 2 diabetes mellitus in healthy elderly individuals.

Comparison between Machine Learning and Multiple Linear Regression to Identify Abnormal Thallium Myocardial Perfusion Scan in Chinese Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) patients have a high risk of coronary artery disease (CAD). Thallium-201 myocardial perfusion scan (Th-201 scan) is a non-invasive and extensively used tool in recognizing CAD in clinical settings. In this study, we attempted to compare the predictive accuracy of evaluating abnormal Th-201 scans using traditional multiple linear regression (MLR) with four machine learning (ML) methods. From the study, we can determine whether ML surpasses traditional MLR and rank the clinical variables and compare them with previous reports.In total, 796 T2DM, including 368 men and 528 women, were enrolled. In addition to traditional MLR, classification and regression tree (CART), random forest (RF), stochastic gradient boosting (SGB) and eXtreme gradient boosting (XGBoost) were also used to analyze abnormal Th-201 scans. Stress sum score was used as the endpoint (dependent variable). Our findings show that all four root mean square errors of ML are smaller than with MLR, which implies that ML is more precise than MLR in determining abnormal Th-201 scans by using clinical parameters. The first seven factors, from the most important to the least are:body mass index, hemoglobin, age, glycated hemoglobin, Creatinine, systolic and diastolic blood pressure. In conclusion, ML is not inferior to traditional MLR in predicting abnormal Th-201 scans, and the most important factors are body mass index, hemoglobin, age, glycated hemoglobin, creatinine, systolic and diastolic blood pressure. ML methods are superior in these kinds of studies.

Comparing Multiple Linear Regression and Machine Learning in Predicting Diabetic Urine Albumin-Creatinine Ratio in a 4-Year Follow-Up Study.

The urine albumin-creatinine ratio (uACR) is a warning for the deterioration of renal function in type 2 diabetes (T2D). The early detection of ACR has become an important issue. Multiple linear regression (MLR) has traditionally been used to explore the relationships between risk factors and endpoints. Recently, machine learning (ML) methods have been widely applied in medicine. In the present study, four ML methods were used to predict the uACR in a T2D cohort. We hypothesized that (1) ML outperforms traditional MLR and (2) different ranks of the importance of the risk factors will be obtained. A total of 1147 patients with T2D were followed up for four years. MLR, classification and regression tree, random forest, stochastic gradient boosting, and eXtreme gradient boosting methods were used. Our findings show that the prediction errors of the ML methods are smaller than those of MLR, which indicates that ML is more accurate. The first six most important factors were baseline creatinine level, systolic and diastolic blood pressure, glycated hemoglobin, and fasting plasma glucose. In conclusion, ML might be more accurate in predicting uACR in a T2D cohort than the traditional MLR, and the baseline creatinine level is the most important predictor, which is followed by systolic and diastolic blood pressure, glycated hemoglobin, and fasting plasma glucose in Chinese patients with T2D.

MCRS1 Expression Regulates Tumor Activity and Affects Survival Probability of Patients with Gastric Cancer.

Gastric cancer is the fifth most common cancer worldwide and the third most common cause of cancer-related deaths. Surgery remains the first-choice treatment. Chemotherapy is considered in the middle and advanced stages, but has limited success. Microspherule protein 1 (MCRS1, also known as MSP58) is a protein originally identified in the nucleus and cytoplasm that is involved in the cell cycle. High expression of MCRS1 increases tumor growth, invasiveness, and metastasis. The mechanistic relationships between MCSR1 and proliferation, apoptosis, angiogenesis, and epithelial-mesenchymal transition (EMT) remain to be elucidated. We clarified these relationships using immunostaining of tumor tissues and normal tissues from patients with gastric cancer. High MCRS1 expression in gastric cancer positively correlated with Ki-67, Caspase3, CD31, Fibronectin, pAKT, and pAMPK. The hazard ratio of high MCRS1 expression was 2.44 times that of low MCRS1 expression, negatively impacting patient survival.

Investigation of Psychological Stress and Sleep Quality of Emergency Medical Technicians in Taiwan Fire Department during the COVID-19 Pandemic.

When the coronavirus disease 2019 (COVID-19) began to ravage the world in 2019, the World Health Organization became concerned. The epidemic has a high mortality and contagion rate, with severe health and psychological impacts on frontline emergency medical service system practitioners. There are many hospital staff surveys, but few have covered the stress among emergency medical technicians. DASS-21, PSQI, and AUDIT questionnaires were used to evaluate the sources of psychological stress factors of firefighters in Taiwan. Multiple logistic regression was used to analyze the questionnaire content. We conducted questionnaire surveys from May 2022 to July 2022. Our sample comprised 688 participants. The odds ratios of increased depression, anxiety, and stress levels due to reduced family or peer understanding and support were 2.72 (95% CI: 1.50−4.92), p = 0.001; 2.03 (95% CI: 1.11−3.68), p = 0.021; and 3.27 (95% CI: 1.83−5.86), p < 0.001, respectively. The odds ratios of poor sleep quality due to depression, anxiety, and increased stress levels were 5.04 (3.18−7.99), p < 0.001; 2.44 (95% CI: 1.57−3.81), p < 0.001; and 4.34 (95% CI: 2.76−6.82), p-value < 0.001, respectively. During the COVID-19 pandemic, poor sleep quality and a lack of understanding and support from the Taiwan firefighting agency staff, family, or peers resulted in increased depression, anxiety, and stress levels.

Reduced Expression of Urokinase Plasminogen Activator in Brown Adipose Tissue of Obese Mouse Models.

In recent decades, the obesity epidemic has resulted in morbidity and mortality rates increasing globally. In this study, using obese mouse models, we investigated the relationship among urokinase plasminogen activator (uPA), metabolic disorders, glomerular filtration rate, and adipose tissues. Two groups, each comprised of C57BL/6J and BALB/c male mice, were fed a chow diet (CD) and a high fat diet (HFD), respectively. Within the two HFD groups, half of each group were euthanized at 8 weeks (W8) or 16 weeks (W16). Blood, urine and adipose tissues were collected and harvested for evaluation of the effects of obesity. In both mouse models, triglyceride with insulin resistance and body weight increased with duration when fed a HFD in comparison to those in the groups on a CD. In both C57BL/6J and BALB/c HFD mice, levels of serum uPA initially increased significantly in the W8 group, and then the increment decreased in the W16 group. The glomerular filtration rate declined in both HFD groups. The expression of uPA significantly decreased in brown adipose tissue (BAT), but not in white adipose tissue, when compared with that in the CD group. The results suggest a decline in the expression of uPA in BAT in obese m models as the serum uPA increases. There is possibly an association with BAT fibrosis and dysfunction, which may need further study.

The relationship of irisin with metabolic syndrome components and insulin secretion and resistance in schoolchildren.

ABSTRACT: Irisin, a novel myokine, is believed to be the crucial factor in converting white adipose tissue to beige adipose tissue. For this paper, we studied the relationship among irisin and components of metabolic syndrome (MetS), and insulin secretion and resistance in schoolchildren of Taiwan.Subjects receiving routine annual health examination at elementary school were enrolled. Demographic data, anthropometry, MetS components, irisin, and insulin secretion and resistance were collected. Subjects were divided into normal, overweight, and obese groups for evaluation of irisin in obesity. Finally, the relationship between irisin and MetS was analyzed.There were 376 children (179 boys and 197 girls), aged 10.3 ±â€Š1.5 years, were enrolled. In boys, irisin levels were not associated with body mass index percentile, body fat, blood pressure, lipid profiles, insulin secretion or resistance. After adjusting for age, the irisin level in boys was negatively related to fasting plasma glucose (FPG) (r = -0.21, P = .006). In girls, after adjusting for age, the irisin levels were positively related only to FPG (r = 1.49, P = .038). In both genders, irisin levels were similar among normal, overweight, and obese groups, and between subjects with and without MetS.The irisin levels were not associated with MetS in either boys or girls. In girls, circulating irisin levels have a nonsignificant declining trend in overweight and obese girls. However, irisin levels were negatively related to FPG in boys and positively related to FPG in girls. The contrary relationship between irisin and FPG in boys and girls needs further exploration.

First-phase insulin secretion is positively correlated with alanine aminotransferase in young adults.

BACKGROUND: Type 2 diabetes (T2D) is known to be one of the most prevalent diseases, and its prevalence is significantly associated with age and metabolic syndrome (MetS). Few studies have been conducted on liver function, MetS and insulin secretion among young adults. OBJECTIVES: In the present study, we explored the relationship between the liver function enzyme - alanine aminotransferase (ALT) - and first-phase insulin secretion (FPIS) among young adults. MATERIAL AND METHODS: There were 22,971 men and 28,740 women, aged 18-27 years, assigned to subgroups according to the presence of MetS and quartiles of ALT values. Simple correlation was applied to evaluate their relationship. The difference between the slopes of these relationships and FPIS were statistically analyzed with Chris's calculator. RESULTS: Most values for metabolic parameters, including ALT and FPIS, were determined to be relatively high in individuals with MetS. By contrast, individuals with MetS had lower high-density-lipoprotein cholesterol (HDL-C) counts and FPIS. Similar results were observed in the quartiles of ALT. Significant positive results were also found in the linear model. Depending on the ALT level, the slope change of FPIS still demonstrated a positive correlation between ALT and FPIS. This correlation was stronger for men than for women. CONCLUSIONS: A positive correlation between ALT and FPIS exists among young adults. Moreover, this correlation was stronger for men than for women. Both the cause and the effect require further investigation.

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.

Relationships between white blood cell count and insulin resistance, glucose effectiveness, and first- and second-phase insulin secretion in young adults.

The Increasing prevalence of type 2 diabetes mellitus (T2DM) has been observed in younger adults. Insulin resistance [IR], decreased first-, second-phase insulin secretion, and glucose effectiveness (GE) (IR, first phase insulin secretion [FPIS], second phase insulin secretion [SPIS], and GE), denoted as diabetes factors (DF), are core for developing T2DM. A body of evidence has shown that inflammation contributes to the development of diabetes. In the present study, our goals were first, evaluate the relationships between white blood cell (WBC) count and, second, examine the relative tightness between the 4 DFs to WBC count. Thus, the pathophysiology of T2DM in Chinese young men could be more understood.21112 non-obese males between 18 to 27 years old were recruited (mean age: 24.3 ±â€Š0.017), including 1745 subjects with metabolic syndrome. DFs were calculated by the published equations by our groups as follows:The association between DFs and WBC count was analyzed using a simple correlation. The r-values of the simple correlation are regarded as the tightness of the relationships.Higher WBC, FPIS, SPIS, IR, age, BMI, blood pressure, FPG, TG, Cholesterol, low-density lipoprotein cholesterol and lower HDL-C and GE were observed in subjects with metabolic syndrome. A similar trend was seen across the quartiles of WBC levels. Among the 4 DFs, GE has the highest r-value (r = -0.093, P < .001), followed by IR (r = 0.067, P < .001), SPIS (r = 0.029, P < .001) and FPIS (r = 0.027, P < .001).Elevated WBC count is significantly associated with all the 4 DFs and the relative order of the tightness, from the highest to the lowest, are GE, IR, SPIS, and FPIS in Chinese young men.

The roles of first phase, second phase insulin secretion, insulin resistance, and glucose effectiveness of having prediabetes in nonobese old Chinese women.

It has been established that prediabetes can causes significant comorbidities, particularly in the elderly. The deterioration of glucose metabolism are generally considered to be results of the impairment of the 4 factors: first, second insulin secretion (FPIS, SPIS, respectively), glucose effectiveness (GE), and insulin resistance. In this study, we enrolled older women to investigate their relationships with prediabetes.Five thousand four hundred eighty-two nonobese, nondiabetic women were included. They were divided into normal glucose tolerance and prediabetes groups. Receiver operating characteristic curve was performed to investigate the effects on whether to have prediabetes for each factors. Two models were built: Model 1: FPIS + SPIS, and Model 2: model 1 + GE. The area under the receiver operating characteristic (aROC) curve was used to determine the predictive power of these models.The aROC curve of GE was significantly higher than the diagonal line followed by SPIS and FPIS accordingly. The aROC curve of Model 1 (0.611) was not different from GE. However, Model 2 improved significantly up to 0.663. Based on this model, an equation was built (-0.003 × GE - 212.6 × SPIS - 17.9 × insulin resistance + 4.8). If the calculated value is equal or higher than 0 (≥0), then the subject has higher chance to have prediabetes (sensitivity = 0.607, specificity = 0.635).Among the 4 factors, GE is the most important contributor for prediabetes in older women. By building a model composed of FPIS, SPIS, and GE, the aROC curve increased significantly. The equation built from this model could predict prediabetes precisely.