Hsi-Hsien Chen

• Taipei Medical University

Background and Aims Billions of people have obesity induced diabetic nephropathy. Promoting the browning of white adipose tissue has been suggested as a potential strategy for, but a drug still needs to be identified. Method First, WT and ATF3 knockout mice fed a high-fat diet were treated with STZ to determine that ATF3 plays an important role in...

Long interspersed nuclear element-1 (LINE-1) methylation serves as an indicator of global DNA methylation. This study explored the correlation between LINE-1 methylation and chronic kidney disease (CKD). We also evaluated whether LINE-1 methylation could modify the association between CKD and metal exposure. A total of 213 patients with clinically...

Introduction Prior studies indicate that exposure to metals may alter DNA methylation. Evidence also shows that global DNA methylation is associated with chronic kidney disease (CKD). This study aimed to examine the association between CKD and 5-methyl-2-deoxycytidine (5mdC, %), a marker of global DNA methylation, and to evaluate the interaction be...

Obesity is an emerging concern globally with increasing prevalence. Obesity is associated with many diseases, such as cardiovascular disease, dyslipidemia, and cancer. Thus, effective new antiobesity drugs should be urgently developed. We synthesized SW20.1, a compound that induces activating transcription factor 3 (ATF3) expression. The results of...

Adiponectin is an adipokine multipeptide hormone with insulin-sensitizing; anti-atherosclerotic; and anti-inflammatory properties. Chronic kidney disease (CKD) may be associated with low adiponectin. The adiponectin gene ADIPOQ is thought to be the only major gene responsible for plasma adiponectin levels; which are associated with diabetes and dia...

Background: Hemodialysis patients are at high risk of muscle loss as a result of aging and disease, and combined with inadequate dietary intake. The Healthy Eating Index for HemoDialysis patients (HEI-HD) was developed to assess the dietary quality of hemodialysis patients. The purposes of this study were to examine the effects of different nutrit...

The induction of activating transcription factor 3 (ATF3) was identified as a promising therapeutic mechanism to overcome metabolic syndrome. Hence, a structure-activity relationship campaign on the chiral lead (1b) was conducted with a scaffold-hopping approach, whereby achiral 7-methoxy-3-methyl-1H-chromeno[4,3-c]pyrazol-4-one (16c) was recognize...

Immunoglobulin A nephropathy (IgAN) is a highly prevalent autoimmune renal disease. Human IgA1 with galactose deficiency in the hinge region (HR) has been identified as an autoantigen for this disease. Therefore, analyzing IgA1 HR glycoforms in biofluids is important for biomarker discovery. Herein, an analytical method that includes one-pot sample...

Cardiovascular disease (CVD) is the most common complication in hemodialysis patients. Nutritional education provided by dietitians could improve overall dietary quality and dietary fat quality to reduce the risk of CVD. However, no studies have investigated the relationship between dietary fat quality (using the hypocholesterolemic/hypercholestero...

Objective Plasma dipeptidyl peptidase-4 (DPP4) levels were significantly lower in patients with colorectal and liver cancers, and animal studies also showed DPP4 inhibitors (DPP4is) have procarcinogenic effects in colorectal cancer. Until now, whether DPP4is therapy affects the progression of liver cancer and colorectal cancer in patients with T2DM...

Chronic inflammation is the cause of chronic kidney disease (CKD). The nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome plays a vital role in the inflammation process and is associated with the regulatory effects of NLRP3 gene polymorphisms. This study evaluated the association between NLRP3 gene polymorphisms and CKD, and fur...

Pharmacological studies indicate that Salvia miltiorrhiza extract (SME) can improve cardiac and blood vessel function. However, there is limited knowledge regarding the effects (exerted through epigenetic regulation) of SME and newly derived single compounds, with the exception of tanshinone IIA and IB, on obesity-induced metabolic disorders. In th...

This study hypothesized that plasma folate and vitamin B12 levels modified the association between blood lead and cadmium and total urinary arsenic levels and bone loss. A total of 447 study subjects who received a physical examination at the Wanfang Hospital Medical Center were recruited. Bone loss was defined as a calcaneus bone mineral density T...

Purpose of the study The risk of bone fracture is high in patients with chronic kidney disease (CKD), and aggressive treatment to reduce fragility fracture risk is the major strategy. However, the outcomes of osteoporosis medications in patients with CKD remain unclear. Study design Patients with stage 3–5 CKD during 2011–2019 were enrolled. Patie...

Purpose of the study: The risk of bone fracture is high in patients with chronic kidney disease (CKD), and aggressive treatment to reduce fragility fracture risk is the major strategy. However, the outcomes of osteoporosis medications in patients with CKD remain unclear. Study design: Patients with stage 3-5 CKD during 2011-2019 were enrolled. P...

Circular RNAs (circRNAs) are an emerging group of long non-coding RNAs (lncRNAs) and have attracted attention again according to the progress in high-throughput sequencing in recent years. circRNAs are genome transcripts produced from pre-messenger (m)RNA regions in a specific process called “back-splicing,” which forms covalently closed continuous...

Metal exposure and lifestyle are important risk factors for osteoporosis. Our study aimed to investigate the association between red blood cell lead and cadmium, total urinary arsenic, and plasma selenium levels and bone mineral density (BMD). In addition, we explored whether alcohol and coffee consumption modified the association between BMD and m...

Heavy metals causing chronic nephrotoxicity may play a key role in the pathogenesis of chronic kidney disease (CKD). This study hypothesized that plasma folate and vitamin B12 would modify the association of CKD with total urinary arsenic and blood lead and cadmium levels. We recruited 220 patients with CKD who had an estimated glomerular filtratio...

Nucleotide-binding domain-like receptors protein 3 (NLRP3) inflammasomes are associated with neuroinflammation and multiple NLRP3 genes regulate NLRP3 expression. Our study aimed to investigate the association of NLRP3 polymorphisms with developmental delay in preschool children. We also explored whether NLRP3 modified the effects of total urinary...

Introduction: The characteristics in dialyzer is associated with mortality in patients with end-stage renal disease (ESRD) receiving hemodialysis (HD). This study is to investigate the effects of dialyzer membranes on 3-year mortality in ESRD patients. Methods: From the long-term nationwide population database database. Prevalent HD patient duri...

Sepsis-induced lung injury is a lethal complication with no effective treatment options, affecting millions of people worldwide. Oroxylin A (OroA) is a natural flavonoid with potent anticancer effects, but its modulating effect on inflammation through microRNAs (miRs) is not apparent. In this report, we investigated the target genes of the miR path...

Acute kidney injury (AKI), caused mainly by ischemia-reperfusion, sepsis, or nephrotoxins (such as contrast medium), is identified by an abrupt decline in kidney function and is associated with high morbidity and mortality. Despite decades of efforts, the pathogenesis of AKI remains poorly understood, and effective therapies are lacking. MicroRNAs...

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for patients with end-stage renal disease (ESRD) despite clinical guideline recommendations that the use of NSAIDs be avoided in this population. However, the relationship between NSAID use and adverse cardiovascular events remains unclear. Thus, this study investigated the...

An integrated transmission surface plasmon resonance platform with microfluidic sensor has a high potential to be a medical diagnostic tool. There has been extensive research into the potential use of transmission surface plasmon resonance, but here we demonstrate the practical application of transmission surface plasmon resonance to monitor and co...

Background and aim Several studies showed plasma dipeptidyl peptidase-4 (DPP4) levels were significantly lower in patients with colorectal and liver cancers, and animal studies also showed DPP4 inhibitors (DPP4is) have procarcinogenic effects in colorectal cancer. The aims of this study were to investigate the association between cumulative defined...

Background: Energy requirements must be estimated before nutritional care can be provided for patients undergoing hemodialysis (HD). However, the recommended caloric intake for patients has not been conclusively determined because of insufficiently large sample sizes. Method: This cross-sectional observational study recruited patients undergoing...

Billions of people have obesity-related metabolic syndromes such as diabetes and hyperlipidemia. Promoting the browning of white adipose tissue has been suggested as a potential strategy, but a drug still needs to be identified. Here, genetic deletion of activating transcription factor 3 (ATF3 -/- ) in mice under a high-fat diet (HFD) resulted in o...

A valid diet quality assessment scale has not been investigated in hemodialysis patients. We aimed to adapt and validate the alternative healthy eating index in hemodialysis patients (AHEI-HD), and investigate its associations with all-cause mortality. A prospective study was conducted on 370 hemodialysis patients from seven hospital-based dialysis...

Background: To investigate the association between insulin resistance (IR) and cardiovascular disease (CVD) risks among hemodialysis patients. Methods: We conducted a cross-sectional study between 2013 and 2017, on 384 hemodialysis patients from seven hospital-based-dialysis centers. HOMA-IR is classified according to median value. The CVD risks...

The association between body fat and mortality in hemodialysis patients remains controversial. We examined the effect of percent body fat (PBF) on all-cause mortality among adequate hemodialysis patients with and without insulin resistance (IR). A prospective cohort study was conducted on 365 adequate hemodialysis patients (equilibrated Kt/V ≥ 1.2)...

Background: The hyperhomocysteinemia was with high prevalence and has been considered as a risk factor for cardiovascular disease in hemodialysis patients. These patients also experienced a high risk of muscle wasting caused by the comorbidity, malnutrition, and low physical activity. We investigated the associations of homocysteinemia with muscle...

Background: Pain is one of the most common symptoms experienced by patients with end-stage renal disease. Although NSAIDs may lead to adverse events, NSAID use appears to be considerably high in patients with end-stage renal disease. However, whether NSAID use is associated with an increased risk of mortality in this population remains unknown. Aim...

This study aimed to determine the interaction of red blood cell cadmium and lead, total urinary arsenic, and plasma selenium in chronic kidney disease (CKD). We recruited 220 CKD patients as well as 438 gender- and age-matched controls, and we defined CKD as <60 mL/min/1.73 m ² estimated glomerular filtration rate (eGFR)for three or more consecutiv...

Objectives: The total medical (economic) costs of haemodialysis (HD) and peritoneal dialysis (PD), including direct medical costs, out-of-pocket (OOP) costs and productivity losses, have become an important issue. This study aims to compare the direct non-medical costs and indirect medical costs of both modalities in Taiwan. Design and setting:...

Hemodialysis patients are at the high risk for morbidity and mortality. Evaluation and management of body composition and biochemical values are important to improve dialysis outcomes. We aimed to examine the effects of the mid-arm circumference, body fat, nutritional and inflammatory biomarkers, blood glucose, and dialysis adequacy on the mortalit...

Introduction: Muscle wasting (cachexia) is common in hemodialysis patients and links to several adverse outcomes. We examined the association between cachexia indicators and metabolic syndrome (MetS) and its components. Methods: A cross-sectional study was conducted between September 2013 and April 2017 on 391 hemodialysis patients from seven hospi...

Altering the balance between lipogenesis/lipolysis or altered white fat remodeling is a potential strategy for treating obesity and metabolic syndrome. Here, we demonstrate that genetic deletion of Transcriptional factor‐X (TFX) decreased energy expenditure but increased body weight, insulin resistance and hepatic steatosis during high‐fat diet reg...

Abstract Background Metabolic syndrome (MetS) has been established as a risk for cardiovascular diseases and mortality in hemodialysis patients. Energy intake (EI) is an important nutritional therapy for preventing MetS. We examined the association of self-reported dietary EI with metabolic abnormalities and MetS among hemodialysis patients. Method...

Clinical assessment of short-stranded nucleic acid biomarkers such as miRNAs could potentially provide useful information for monitoring disease progression, prompting definitive treatment decisions. In the past decade, advancement in biosensing technology have shifted towards rapid, real-time and label-free detection systems, in such surface plasm...

Objective: To modify the hemodialysis eating index (m-HDEI) aligning with the Healthy Eating Index released by the US Department of Agriculture (USDA); and to investigate the associations of the m-HDEI with cardiovascular disease (CVD) risks in hemodialysis (HD) patients. Methods: In a clinical cross-sectional study, we recruited 492 HD patients,...

The current study was to examine the association of adequate intake of macronutrients and micronutrients with traditional and nontraditional cardiovascular risk factors in hemodialysis patients. A clinical cross-sectional study was conducted between September 2013 and April 2017 on 492 hemodialysis patients aged 20 years and above, received thrice-...

Dietary energy intake strongly linked to dialysis outcomes. We aimed to explore the optimal cut-off point of energy intake (EI) for identification of metabolic syndrome (MetS) in hemodialysis patients. The cross-sectional data of 243 hemodialysis patients from multi-dialysis centers in Taiwan was used. The dietary intake was assessed by using the t...

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The effect of dyslipidemia on peritoneal dialysis (PD) patients based on the presence of residual renal function (RRF; renal creatinine clearance >2 mL/min/1.73 m 2) is unknown. Data from the Taiwan Renal Registry Data System between 2005 and 2012 were analyzed to estimate the association between dyslipidemia and mortality in PD patients. Long-term...

Background: Insulin resistance (IR) is an independent predictor of cardiovascular morbidity and mortality in end-stage renal disease (ESRD) patients. This study was to investigate the association between IR and cardiovascular disease (CVD) risk factors among ESRD patients undergoing hemodialysis. Methods: A clinical cross-sectional study was conduc...

Biomarkers of chronic kidney disease-mineral and bone disorder (CKD-MBD) correlate with morbidity and mortality in dialysis patients. However, the comparative roles of each CKD-MBD biomarker remained undetermined on long-term peritoneal dialysis (PD) patients. This retrospective study, employing a population-based database, aimed to evaluate the pe...

Objective Adverse neurological effects may be common following acute kidney injury (AKI). The purpose of our study was to investigate the long-term risk of dementia following AKI and temporary dialysis during hospitalization. Materials and Methods The study was based on data from the National Health Insurance Research Database of Taiwan. Patients...

Background and aims: Previous studies show that serum bilirubin has potent antioxidant effect and is associated with protection from kidney damage and reduce cardiovascular events. The aim of this study was to examine the association of serum total bilirubin level and mortality in uremia patients who underwent hemodialysis. Methods: This is a na...

Objectives Taiwan succeeded in raising the proportion of peritoneal dialysis (PD) usage after the National Health Insurance (NHI) payment scheme introduced financial incentives in 2005. This study aims to compare the economic costs between automated PD (APD) and continuous ambulatory PD (CAPD) modalities from a societal perspective. Design and set...

Background Goblet cell carcinoid is a rare variant of appendiceal carcinoid with mixed endocrine and exocrine features. The most common symptom and signs are abdominal pain, acute appendicitis and palpable mass. Additionally, abdominal pain is common in patient on peritoneal dialysis, which may confound the diagnosis in such patient. Case presentat...

Objectives In Taiwan, peritoneal dialysis (PD) and haemodialysis are fully accessible to patients with end-stage renal disease. However, the usage of PD is considered low in Taiwan. Since 2005, 4 major policies have been implemented by Taiwan's Ministry of Health and Welfare, namely a multidisciplinary predialysis care programme and usage increasin...

Background Studies on the association of total cholesterol (TC) levels and mortality in hemodialysis (HD) patients demonstrated conflicting results. The differenct effect of Hypercholesterolemia on HD patients based on the presence of myocardial infarction (MI) or coronary artery disease (CAD) is unknown. Methods We analyzed data from the Taiwan Re...

Recent studies have indicated that the ratio of C-reactive protein to albumin (CRP–Alb ratio) is associated with clinical outcomes in patients with disease. We examined the predictive value of this ratio in patients undergoing hemodialysis (HD). In this cross-sectional study, 91 eligible adult HD patients were analyzed, and the correlation between...

The certification of Taipei Medical University Joint Institutional Review Board. (PDF)

Diabetic kidney disease is an increasingly frequent cause of end-stage renal disease. However, mixed results were shown between glycated hemoglobin and mortality. Methods: We used the average fasting plasma glucose (FPG) levels to predict mortality rates in long-term hemodialysis patients. We enrolled 46,332 hemodialysis patients with diabetes mell...

Chronic kidney disease (CKD) is inflammation-related. Patients with chronic renal failure who undergo hemodialysis (HD) have some acute adverse effects caused by dialysis-induced oxidative stress, protein adsorption, platelet adhesion, and activation of coagulation and inflammation. Here, resonantly illuminated gold nanoparticles-modified artificia...

Ischemia-reperfusion (I/R) induced acute kidney injury (AKI) is regulated by transcriptional factors and microRNAs (miRs). However, modulation of miRs by transcriptional factors has not been characterized in AKI. Here, we found that urinary miR-16 was 100-fold higher in AKI patients. MiR-16 was detected earlier than creatinine in mouse after I/R. U...

Objective: n-3 and n-6 polyunsaturated fatty acids (PUFAs) are essential nutrients in the human diet and possibly affect muscle mass. We evaluated the association between the dietary ratios of n-3 and n-6 PUFAs and muscle mass, indicated as skeletal muscle mass (SMM) and appendicular skeletal muscle mass (ASM), in patients with diabetes undergoing...

Although α-glucosidase inhibitors (AGIs) are commonly used for controlling postprandial blood glucose, AGIs-induced liver injuries have been reported. However, the relationship between AGIs and liver injuries in advanced chronic kidney disease (CKD) patients remains unexplored. In this nationwide case-control study, we recruited 1765 advanced diabe...

Background n-3 polyunsaturated fatty acids (PUFAs) might be useful nutritional strategy for treating patients with sarcopenia. We evaluated the effect of the intake of dietary n-3 PUFAs on the skeletal muscle mass (SMM), appendicular skeletal muscle mass (ASM), and its determinants in patients receiving standard hemodialysis (HD) treatment for the...

Predicting mortality in dialysis patients based on low intact parathyroid hormone levels is difficult, because aluminum intoxication, malnutrition, older age, race, diabetes, or peritoneal dialysis may influence these levels. We investigated the clinical implications of low parathyroid hormone levels in relation to the mortality of dialysis patient...

Successful diagnosis and treatment of many diseases depends on the availability of sensitive, reliable and low cost tools for the detection of the biomarkers associated with the diseases. Simple methods that use non-invasive biological samples are especially suitable for the deployment in the clinical environment. In this paper we demonstrate the a...

Transcriptional repressor activating transcription factor 3 (ATF3) is induced by various stress stimuli, including inflammation-induced renal injury. In addition, ATF3 also down-regulates adhesion molecules like intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), and monocyte chemotactic protein-1 (MCP-1). However, the r...

Background: Continuous renal replacement therapy (CRRT) may benefit patients requiring extracorporeal membrane oxygenation (ECMO). However, the clinical benefits and timing of CRRT have not been fully elucidated for these patients. Methods: This study was conducted retrospectively at the Taipei Medical University Hospital between January 2008 and D...

Objective In this study, a Hemodialysis Eating Index (HDEI) suitable for hemodialysis (HD) patients in Taiwan was developed based on the dietary recommendations of the U.S. National Kidney Foundation for HD patients and the Taiwanese 2011 Daily Food Guide. The HDEI was used to explore HD-associated cardiovascular disease (CVD) risk factors. Method...

Uremic toxins are mainly represented by blood urine nitrogen (BUN) and creatinine (Crea) whose removal is critically important in hemodialysis (HD) for kidney disease. Patients undergoing HD have a complex illness, resulting from: inadequate removal of organic waste, dialysis-induced oxidative stress and membrane-induced inflammation. Here we repor...

Activating transcription factor 3 (ATF3), a CREB/ATF family transcription factors member, has been implicated in cardiovascular and inflammatory system and is rapidly induced by ischemic-reperfusion injuries. We performed transverse aortic banding (TAB) experiments using ATF3 gene-deleted mice (ATF3(-/-)) and wild-type (WT) mice to find out what ef...

Background: Recent studies demonstrated that iron overload could enhance the production of arachidonic acid and prostanoid, suggesting a causal connection between these signals and iron-overload cardiomyopathy. However, information regarding the downstream signaling is limited. Because thromboxane A2 (TXA2) and prostacyclin are the 2 major prostan...

Adiponectin is a circulating adipose-derived cytokine that may act as an anti-oxidative and anti-inflammatory protein. Although adiponectin has been reported to exert cytoprotective effects in acute cardiac diseases, its effects on chronic heart failure are less clear. Therefore, we aimed to investigate whether adiponectin would have a beneficial e...

Objective To evaluate the effect of more vegetable intake on cardiovascular disease risk factors in hemodialysis (HD) patients. Methods This is a cross‐sectional study. All subjects were outpatients from Taipei Medical University Hospital. Fifty‐four HD patients and thirty‐five subjects with eGFR more than 60 ml/min/1.73m ² from department of Fami...

Lipopolysaccharide (LPS) triggers innate immunity mainly via TLR4 signaling. ATF3 is a negative regulator of TLR4 signaling. HMGB1 plays a critical role in the final step of sepsis. However, the mechanisms of ATF3 and the role of HMGB1 in regulating innate immunity-induced sepsis are incompletely understood. In this study, we found that serum HMGB1...

Background Sitagliptin, a dipeptidyl peptidase-IV inhibitor, is widely used as an oral hypoglycemic agent. It may induce hemodynamic effects when interacting with angiotensin II receptor blockers. Methods The study was conducted in an outpatient setting at Taipei Medical University Hospital. Diabetic patients who had already received angiotensin I...

MicroRNA-494 mediates apoptosis and necrosis in several types of cells, but its renal target and potential role in AKI are unknown. Here, we found that microRNA-494 binds to the 3'UTR of activating transcription factor 3 (ATF3) and decreases its transcription. In mice, overexpression of microRNA-494 significantly attenuated the level of ATF3 and in...