LncRNA HOTAIR impairs the prognosis of papillary thyroid cancer via regulating cellular malignancy and epigenetically suppressing DLX1.

PURPOSE: Papillary thyroid cancer (PTC) is the most common endocrine malignancy with a fast-growing incidence in recent decades. HOTAIR as a long non-coding RNA has been shown to be highly expressed in papillary thyroid cancer tissues with only a limited understanding of its functional roles and downstream regulatory mechanisms in papillary thyroid cancer cells. METHODS: We applied three thyroid cancer cell lines (MDA-T32, MDA-T41 and K1) to investigate the phenotypic influence after gain or loss of HOTAIR. The Cancer Genome Atlas (TCGA) database were utilised to select candidate genes possibly regulated by HOTAIR with validation in the cellular system and immunohistochemical (IHC) staining of PTC tissues. RESULTS: We observed HOTAIR was highly expressed in MDA-T32 cells but presents significantly decreased levels in MDA-T41 and K1 cells. HOTAIR knockdown in MDA-T32 cells significantly suppressed proliferation, colony formation, migration with cell cycle retardation at G1 phase. On the contrary, HOTAIR overexpression in MDA-T41 cells dramatically enhanced proliferation, colony formation, migration with cell cycle driven toward S and G2/M phases. Similar phenotypic effects were also observed as overexpressing HOTAIR in K1 cells. To explore novel HOTAIR downstream mechanisms, we analyzed TCGA transcriptome in PTC tissues and found DLX1 negatively correlated to HOTAIR, and its lower expression associated with reduced progression free survival. We further validated DLX1 gene was epigenetically suppressed by HOTAIR via performing chromatin immunoprecipitation. Moreover, IHC staining shows a significantly stepwise decrease of DLX1 protein from normal thyroid tissues to stage III PTC tissues. CONCLUSIONS: Our study pointed out that HOTAIR is a key regulator of cellular malignancy and its epigenetic suppression on DLX1 serves as a novel biomarker to evaluate the PTC disease progression.

Takotsubo Syndrome Occurring after mRNA COVID-19 Vaccination in a Patient with Graves' Disease.

Cardiovascular events such as myocarditis following mRNA COVID-19 vaccination are increasing. We present a 67-year-old postmenopausal woman with Takotsubo Syndrome and Graves' disease after mRNA COVID-19 vaccination. She developed chest pain and shortness of breath one week after vaccination. An electrocardiogram revealed ST elevation in the precordial leads. Coronary angiography revealed the absence of obstructive coronary artery disease, and the left ventriculography showed a typical feature with apical ballooning. Laboratory workup showed the elevation of free T4 and thyrotropin receptor antibodies. It was presumed that Takotsubo Syndrome and Graves' disease were probably related to the COVID-19 mRNA vaccination. The patient was treated with low-dose bisoprolol, diuretics, carbimazole, and steroid and discharged uneventfully. The mRNA COVID-19 vaccination is still safe and effective to defend against COVID-19 pandemic. However, clinicians should be aware of the possible cardiovascular adverse events other than myocarditis following vaccination.

High-Molecular-Weight Hyaluronic Acid Inhibits IL-1ß-Induced Synovial Inflammation and Macrophage Polarization through the GRP78-NF-κB Signaling Pathway.

Recent evidence has suggested that synovial inflammation and macrophage polarization were involved in the pathogenesis of osteoarthritis (OA). Additionally, high-molecular-weight hyaluronic acid (HMW-HA) was often used clinically to treat OA. GRP78, an endoplasmic reticulum (ER) stress chaperone, was suggested to contribute to the hyperplasia of synovial cells in OA. However, it was still unclear whether HMW-HA affected macrophage polarization through GRP78. Therefore, we aimed to identify the effect of HMW-HA in primary synovial cells and macrophage polarization and to investigate the role of GRP78 signaling. We used IL-1ß to treat primary synoviocytes to mimic OA, and then treated them with HMW-HA. We also collected conditioned medium (CM) to culture THP-1 macrophages and examine the changes in the phenotype. IL-1ß increased the expression of GRP78, NF-κB (p65 phosphorylation), IL-6, and PGE2 in primary synoviocytes, accompanied by an increased macrophage M1/M2 polarization. GRP78 knockdown significantly reversed the expression of IL-1ß-induced GRP78-related downstream molecules and macrophage polarization. HMW-HA with GRP78 knockdown had additive effects in an IL-1ß culture. Finally, the synovial fluid from OA patients revealed significantly decreased IL-6 and PGE2 levels after the HMW-HA treatment. Our study elucidated a new form of signal transduction for HMW-HA-mediated protection against synovial inflammation and macrophage polarization and highlighted the involvement of the GRP78-NF-κB signaling pathway.

Cilostazol inhibits hyperglucose-induced vascular smooth muscle cell dysfunction by modulating the RAGE/ERK/NF-κB signaling pathways.

BACKGROUND: Increasing evidence suggests that high glucose (HG) causes abnormalities in endothelial and vascular smooth muscle cell function (VSMC) and contributes to atherosclerosis. Receptor for advanced glycation end-products (RAGE) has been linked to the pathogenesis of both the macrovascular and microvascular complications of diabetes. Cilostazol is used to treat diabetic vasculopathy by ameliorating HG-induced vascular dysfunction. OBJECTIVES: In this study, we investigated whether the cilostazol suppression of HG-induced VSMC dysfunction is through RAGE signaling and its possible regulation mechanism. METHOD: We investigated the effect of HG and cilostazol on RAGE signaling in A7r5 rat VSMCs. Aortic tissues of streptozotocin (STZ) diabetic mice were also collected. RESULTS: Aortic tissue samples from the diabetic mice exhibited a significantly decreased RAGE expression after cilostazol treatment. HG increased RAGE, focal adhesion kinase (FAK), matrix metalloproteinase-2 (MMP-2), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions, and was accompanied with increased reactive oxygen species (ROS), cell proliferation, adhesion and migration. Cilostazol significantly reversed HG-induced RAGE, ROS, downstream gene expressions and cell functions. RAGE knockdown significantly reversed the expressions of HG-induced vasculopathy related gene expressions and cell functions. Cilostazol with RAGE knockdown had additive effects on downstream ERK/NF-κB signaling pathways, gene expressions and cell functions of A7r5 rat VSMCs in HG culture. CONCLUSIONS: Both in vitro and in vivo experimental diabetes models showed novel signal transduction of cilostazol-mediated protection against HG-related VSMC dysfunction, and highlighted the involvement of RAGE signaling and downstream pathways.

Cilostazol inhibits uremic toxin-induced vascular smooth muscle cell dysfunction: role of Axl signaling.

Chronic kidney disease (CKD) is associated with increased cardiovascular mortality, and vascular smooth muscle cell (VSMC) dysfunction plays a pivotal role in uremic atherosclerosis. Axl signaling is involved in vascular injury and is highly expressed in VSMCs. Recent reports have shown that cilostazol, a phosphodiesterase type 3 inhibitor (PDE3), can regulate various stages of the atherosclerotic process. However, the role of cilostazol in uremic vasculopathy remains unclear. This study aimed to identify the effect of cilostazol in VSMCs in the experimental CKD and to investigate whether the regulatory mechanism occurs through Axl signaling. We investigated the effect of P-cresol and cilostazol on Axl signaling in A7r5 rat VSMCs and the rat and human CKD models. From the in vivo CKD rats and patients, aortic tissue exhibited significantly decreased Axl expression after cilostazol treatment. P-cresol increased Axl, proliferating of cell nuclear antigen (PCNA), focal adhesion kinase (FAK), and matrix metalloproteinase-2 (MMP-2) expressions, decreased caspase-3 expression, and was accompanied by increased cell viability and migration. Cilostazol significantly reversed P-cresol-induced Axl, downstream gene expressions, and cell functions. Along with the increased Axl expression, P-cresol activated PLCγ, Akt, and ERK phosphorylation and cilostazol significantly suppressed the effect of P-cresol. Axl knockdown significantly reversed the expressions of P-cresol-induced Axl-related gene expression and cell functions. Cilostazol with Axl knockdown have additive changes in downstream gene expression and cell functions in P-cresol culture. Both in vitro and in vivo experimental CKD models elucidate a new signal transduction of cilostazol-mediated protection against uremic toxin-related VSMCs dysfunction and highlight the involvement of the Axl signaling and downstream pathways.

Association of complete blood cell counts with metabolic syndrome in an elderly population.

BACKGROUND: Metabolic syndrome's (MetS) role in predicting cardiovascular diseases and diabetes has been confirmed in many large cohort studies. Nontraditionally, hematogram components are significantly related to MetS in many different age groups. However, little is known about its role among the elderly. METHODS: We enrolled 18,907 subjects over the age of 65 years who underwent regular health examinations. They were divided into three groups according to age: young old (YO: ≥ 65 and < 74 years old), old old (OO: ≥ 75 and < 84 years old), and oldest old (ODO: ≥ 85 years old). The MetS components were determined, and correlations between MetS and hematogram components were evaluated using Pearson and multivariate linear regression analyses. The hematogram components were the independent variables evaluated separately against the dependent variable (MetS components). RESULTS: While SBP and HDL-C increased, most other MetS and hematogram parameters decreased in men with age. Fewer significant differences were noted among the women. In the YO and OO groups for both genders, the subjects with MetS had higher WBC and Hb. None of the hematogram components were different for subjects with or without MetS in the ODO group. Multiple regression results show that most of the relationships between hematogram and MetS components disappeared in the ODO groups. The WBC levels were mainly correlated with WC and TG. At the same time, Hb was associated with BP, FPG, and LDL-C. Compared to WBC and Hb, PLT was least related to MetS, except in the cases of LDL-C and TG. Among the MetS components, BMI, LDL-C, and TG were consistently related to all the hematogram components in YO and OO men. However, only TG had the same consistency among YO and OO women. CONCLUSIONS: This study's three major findings are as follows: WBC and Hb are associated with MetS, even among the YO and OO groups, regardless of gender; among the three hematogram components, Hb had the strongest and PLT had the weakest correlation with MetS; and TG is not the only component with relatively higher r values, and it is related to all hematogram components.

The role of traditional Chinese medicine on fracture surgery, hospitalization, and total mortality risks in diabetic patients with osteoporosis.

BACKGROUND: Studies have confirmed that osteoporosis has been considered as one of the complications of diabetes, and the health hazards to patients are more obvious. This study is mainly based on the Taiwan National Health Insurance Database (TNHID). Through the analysis of TNHID, it is shown that the combined treatment of traditional Chinese medicine (TCM) medicine in patients of diabetes with osteoporosis (T2DOP) with lower related risks. METHODS: According to the study design, 3131 patients selected from TNHID who received TCM treatment were matched by 1-fold propensity score according to gender, age, and inclusion date as the control group. Cox proportional hazards analyzes were performed to compare fracture surgery, hospitalization, and all-cause mortality during a mean follow-up from 2000 to 2015. RESULTS: A total of 1055/1469/715 subjects (16.85%/23.46%/11.42%) had fracture surgery/inpatient/all-cause mortality of which 433/624/318 (13.83%/19.93%/10.16%) were in the TCM group) and 622/845/397 (19.87%/26.99%/12.68%) in the control group. Cox proportional hazards regression analysis showed that subjects in the TCM group had lower rates of fracture surgery, inpatient and all-cause mortality (adjusted HR = 0.467; 95% CI = 0.225-0.680, P<0.001; adjusted HR = 0.556; 95% CI = 0.330-0.751, P<0.001; adjusted HR = 0.704; 95% CI = 0.476-0.923, P = 0.012). Kaplan-Meier analysis showed that the cumulative risk of fracture surgery, inpatient and all-cause mortality was significantly different between the case and control groups (all log-rank p<0.001). CONCLUSION: This study provides longitudinal evidence through a cohort study of the value of integrated TCM for T2DOP. More research is needed to fully understand the clinical significance of these results.

The efficacy and safety of combined GLP-1RA and basal insulin therapy among inadequately controlled T2D with premixed insulin therapy.

This study investigated the effect of a combination of glucagon-like peptide-1 receptor agonist (GLP-1 RA) and basal insulin (BI) in poorly controlled type 2 diabetes mellitus previously treated with premixed insulin. The possible therapeutic benefit of the subject is mainly hoped to provide a direction for optimizing treatment options to reduce the risk of hypoglycemia and weight gain. A single-arm, open-label study was conducted. The antidiabetic regimen was switched to GLP-1 RA plus BI to replace previous treatment with premixed insulin in type 2 diabetes mellitus subjects. After 3 months of treatment modification, GLP-1 RA plus BI was compared for superior outcomes by continuous glucose monitoring system. There were 34 subjects at the beginning, 4 withdrew due to gastrointestinal discomfort, and finally 30 subjects completed the trial, of which 43% were male; the average age was 58 ± 9 years old, and the average duration of diabetes was 12 ± 6 years, the baseline glycated hemoglobin level was 8.6 ± 0.9 %. The initial insulin dose of premixed insulin was 61 ± 18 units, and the final insulin dose of GLP-1 RA + BI was 32 ± 12 units (P < .001). Time out of range (from 59%-42%), time-in-range (from 39%-56%) as well as glucose variability index including standard deviation also improved, mean magnitude of glycemic excursions, mean daily difference and continuous population in continuous glucose monitoring system, continuous overall net glycemic action (CONGA). Also noted was a decrease in body weight (from 70.9 kg-68.6 kg) and body mass index (all P values < .05). It provided important information for physicians to decide to modify therapeutic strategy as individualized needs.

Gender-specific impacts of thigh skinfold thickness and grip strength for predicting osteoporosis in type 2 diabetes.

BACKGROUND: Diabetes with co-existing bone fragility or osteoporosis is common in elderly patients, whereas is frequently underestimated. METHODS: We conducted dual-energy x-ray absorptiometry (DXA) with 7-site skinfold (SF) and dominant hand grip strength measurements among patients with type 2 diabetes (T2DM) to assess their gender-specific associations. A total of 103 patients with T2DM (60 females and 43 males), aged between 50 and 80 years (median 68.0 years) were enrolled and 45 non-DM females were also included to compare with T2DM females. RESULTS: Our results revealed osteoporosis was negatively correlated with grip strength in both genders, negatively correlated with lean mass solely in males and negatively correlated with fat mass (particular the gynoid fat mass and thigh SF thickness) in females. Via performing multivariable stepwise logistic regression, we identified grip strength in both genders and thigh SF thickness in females as predictors for osteoporosis. Receiver operating characteristic curve analysis further disclosed 20.5 mm female thigh skinfold thickness, 18.1 kg female grip strength and 29.0 kg male grip strength as reasonable cutoff levels for predicting osteoporosis in the Taiwanese patients with T2DM. CONCLUSIONS: Patients with T2DM presented gender-specific associations between osteoporosis, body composition and grip strength. Grip strength and thigh SF thickness might serve as predictors for detection of osteoporosis in patients with T2DM.

DFATs derived from infrapatellar fat pad hold advantage on chondrogenesis and adipogenesis to evade age mediated influence.

Background: Dedifferentiated fat cells (DFATs) are highly homogeneous and multipotent compared with adipose-derived stromal cells (SCs). Infrapatellar fat pad (IFP)-SCs have advanced chondrogenic potency; however, whether IFP-DFATs could serve as better cell material remains unclear. Here, we aimed to examine the influence of age and body mass index (BMI) on the features of IFPs and IFP-derived cells (IFP-SCs and IFP-DFATs) with exploration of the clinical utilization of IFP-DFATs. Methods: We collected IFPs with isolation of paired IFP-SCs and IFP-DFATs from individuals aged 65 years and older with distinct body weights who underwent total knee replacement for osteoarthritis (OA). Flow cytometry was used to characterize the cellular immunophenotypes. Adipogenesis and chondrogenesis were performed in vitro. Real-time qPCR, western blotting, and Oil Red O or Alcian blue staining were performed to evaluate inflammation, adipogenesis, and chondrogenesis. RNA sequencing and Seahorse analyses were conducted to explore the underlying mechanisms. Results: We found that IFPs from old or normal-weight individuals with knee OA were pro-inflammatory, and that interleukin-6 (IL-6) signaling was associated with multiple immune-related molecules, whereas IFP-derived cells could escape the inflammatory properties. Aging plays an important role in diminishing the chondrogenic and adipogenic abilities of IFP-SCs; however, this effect was avoided in IFP-DFATs. Generally, IFP-DFATs presented a steady state of chondrogenesis (less influenced by age) and consistently enhanced adipogenesis compared to paired IFP-SCs in different age or BMI groups. RNA sequencing and Seahorse analysis suggested that the downregulation of eukaryotic initiation factor 2 (EIF2) signaling and enhanced mitochondrial function may contribute to the improved cellular biology of IFP-DFATs. Conclusions: Our data indicate that IFP-DFATs are superior cell material compared to IFP-SCs for cartilage differentiation and adipogenesis, particularly in advanced aging patients with knee OA. The translational potential of this article: These results provide a novel concept and supportive evidence for the use of IFP-DFATs for cell therapy or tissue engineering in patients with knee OA. Using Ingenuity Pathway Analysis (IPA) of RNA-seq data and Seahorse analysis of mitochondrial metabolic parameters, we highlighted that some molecules, signaling pathways, and mitochondrial functions are likely to be jointly coordinated to determine the enhanced biological function in IFP-DFATs.

PDIA4, a new endoplasmic reticulum stress protein, modulates insulin resistance and inflammation in skeletal muscle.

Introduction: Endoplasmic reticulum (ER) stress has emerged as a key player in insulin resistance (IR) progression in skeletal muscle. Recent reports revealed that ER stress-induced the expression of protein disulfide isomerase family a member 4 (PDIA4), which may be involved in IR-related diseases. A previous study showed that metformin modulated ER stress-induced IR. However, it remained unclear whether metformin alleviated IR by regulating PDIA4 expression in skeletal muscle. Methods: Herein, we used palmitate-induced IR in C2C12 cells and a high-fat diet-induced IR mouse model to document the relations between metformin, IR, and PDIA4. Results: In C2C12 cells, palmitate-induced IR increased inflammatory cytokines and PDIA4 expression. Besides, knocking down PDIA4 decreased palmitate-induced IR and inflammation in C2C12 cells. Furthermore, metformin modulated PDIA4 expression and alleviated IR both in vitro and in vivo. In addition, serum PDIA4 concentrations are associated with IR and inflammatory cytokines levels in human subjects. Discussion: Thus, this study is the first to demonstrate that PDIA4 participates in the metformin-induced effects on skeletal muscle IR and indicates that PDIA4 is a potential novel therapeutic target for directly alleviating IR.

PDIA4, a novel ER stress chaperone, modulates adiponectin expression and inflammation in adipose tissue.

Increasing evidence supporting a causal link between obesity and endoplasmic reticulum (ER) stress in adipose tissue is being reported. Protein disulfide isomerase 4 (PDIA4) is a novel ER chaperone involved in the pancreatic ß-cells pathogenesis in diabetes. However, the role of PDIA4 in obesity progression remains poorly understood. To assess the relationship between PDIA4, adiponectin, and metformin, we used the palmitate-induced inflammation in hypertrophic adipocytes and the high-fat diet-induced obesity mouse model. Our results revealed that palmitate-induced hypertrophic adipocytes exhibit obesity-associated conditions such as increased lipid accumulation, inflammation, and reduced glucose uptake. Pharmacological and genetic inhibition of PDIA4 significantly reverses these obesity-associated conditions in adipocytes. PDIA4 mechanistically promotes obesity progression via adiponectin downregulation. Furthermore, metformin modulates PDIA4 and adiponectin expression and improves obesity-associated conditions in both in vitro adipocytes and in vivo mouse models. Serum PDIA4 concentrations are also associated with body mass index, adiponectin, triglycerides, and inflammatory cytokines in humans. This is the first study demonstrating that PDIA4 modulates adipocytes by downregulating adiponectin. Moreover, metformin may serve as a potential therapeutic for preventing obesity via PDIA4-targeting.

Dipeptidyl peptidase-4 inhibitors attenuates osteoporosis in patients with diabetes: A nationwide, retrospective, matched-cohort study in Taiwan.

BACKGROUND: Patients with diabetes have a relatively high risk of fracture due to osteoporosis. However, the risk of osteoporosis associated with the use of oral hypoglycemic drugs and dipeptidyl peptidase-4 inhibitor (DPP-4i) by patients with diabetes is unclear. This study aimed to explore the effect of DPP-4i on the risk of osteoporosis in Taiwanese patients with type 2 diabetes mellitus (T2DM). METHODS: This study enrolled 6339 patients on DPP-4i (DPP-4i group) and 25 356 patients without DPP-4i (non-DPP-4i group). They were matched by 1:4 propensity score matching, using confounding variables including sex, age, comorbidities, medication, and index year. Cox proportional hazards analysis was used to compare hospitalization and mortality during an average follow-up period of 7 years. RESULTS: The mean age of patients in the two groups was 66 years. Men were slightly higher in number (51.79%) than women. At the end of the follow-up period, 113 (0.36%) patients had osteoporosis, of which 15 (0.24%) were in the case group and 98 (0.39%) in the control group. The risk of all-cause osteoporosis was significantly lower in the DPP-4i group than in the non-DPP-4i group (adjusted hazard ratio [HR] 0.616; 95% confidence interval [CI] 0.358-0.961; p = 0.011). Kaplan-Meier analysis showed that the preventive effect on osteoporosis was positively correlated with the cumulative dose of DPP-4i (log-rank, p = 0.039) with the class effect. CONCLUSION: Compared with not using DPP-4i, the use of DPP-4i in Taiwanese T2DM patients was associated with a lower risk of osteoporosis due to the class effect, and the preventive effect was dose-dependent. However, larger prospective studies are needed to validate this finding and to explore the possible mechanism of the preventive effect of DPP-4i.

Gout as a risk factor for acute myocardial infarction: evidence from competing risk model analysis.

Chronic inflammation, a hallmark of gout, is implicated in the pathogenesis of atherosclerosis. Thus, in theory, gout can be expected to increase the risk of acute myocardial infarction (AMI). Yet, results from several epidemiological studies have been inconclusive. A retrospective cohort study was conducted using the National Health Insurance Research Database of Taiwan dated from 2000 to 2013. The study cohort comprised 3581 patients with gout (the gout cohort) and 14,324 patients without gout (the non-gout cohort). The primary outcome was the incidence of AMI. To estimate the effect of gout on the risk of AMI, the Lunn-McNeil competing risk model was fitted to estimate cause-specific hazard ratios (HRs) and their 95% confidence intervals (CIs). The cumulative incidence of AMI was significantly higher in the gout cohort than in the non-gout cohort, resulting in an adjusted HR of 1.36 (95% CI 1.04 to 2.76). Further, HRs of gout with incident AMI were higher in patients without hypertension, diabetes mellitus, or hyperlipidemia (ranging from 1.63 to 2.09) than in those with each of these comorbidities (ranging from 0.95 to 1.13). The results of this study suggest that patients with gout have an increased risk of AMI. The AMI risk associated with gout was conditional on patients' cardiovascular risk profile. Future work is needed to confirm these findings.

Circulating Soluble IL-6 Receptor Concentration and Visceral Adipocyte Size Are Related to Insulin Resistance in Taiwanese Adults with Morbid Obesity.

BACKGROUND: Morbid obesity is related to chronic inflammation and many metabolic complications. Interleukin (IL)-6 plays a pivotal pathophysiological role in obesity, and IL-6 trans-signaling through the soluble IL-6 receptor (sIL-6R) has a major proinflammatory effect. The aim of this study was to investigate the association between sIL-6R, adipocyte size, and insulin resistance in morbidly obese individuals. METHODS: We measured concentrations of sIL-6R, high-sensitivity C-reactive protein, and lipid parameters and estimated homeostasis model assessment of insulin resistance (HOMA-IR) before the patients underwent bariatric surgery. Mesenteric adipose tissue was collected during surgery, and adipocyte size and concentrations of membrane-bound IL-6 receptor (mIL-6R) were evaluated. In total, 35 adults (20 men and 15 women) were recruited. RESULTS: The subjects with high HOMA-IR (≥2.4) had higher fasting glucose/insulin, triglycerides, sIL-6R, and adipocyte size and lower high-density lipoprotein cholesterol and mIL-6R than those with low HOMA-IR (<2.4). Adipocyte size positively correlated with sIL-6R (r = 0.559, P = 0.001) and HOMA-IR (r = 0.773, P ≤ 0.001) independent of age, gender, body mass index (BMI), waist, and use of diabetic drugs. In addition, every 1 ng/mL increase in sIL-6R concentration corresponded to a 10.2% decrease in the likelihood of maintaining lower insulin resistance. Furthermore, an sIL-6R level of 77.45 ng/mL was a reasonable cutoff level to propose lower insulin resistance in morbidly obese subjects. CONCLUSIONS: Circulating sIL-6R is more closely associated with insulin resistance status than waist-to-hip ratio or BMI in morbidly obese Taiwanese adults. sIL-6R may be a useful biomarker to assess insulin resistance among morbidly obese subjects.

Association of salivary alpha 2-macroglobulin levels and clinical characteristics in type 2 diabetes.

AIMS/INTRODUCTION: Studies suggest that salivary proteins can be used as potential non-invasive markers for clinical diagnosis and screening for diabetes. Previous reports showed that plasma alpha 2-macroglobulin (A2MG) levels were higher in diabetic patients, especially with diabetic complications. We investigated the relationship between salivary A2MG values and clinical characteristics in patients with type 2 diabetes. MATERIALS AND METHODS: A total of 91 adults were recruited from our outpatient clinics. The study the patients' collected general and biochemical data, and blood glucose (fasting glucose, glycated hemoglobin [HbA1c]) data. Plasma and salivary A2MG levels were examined by enzyme-linked immunosorbent assay. RESULTS: The salivary A2MG levels were significantly positively correlated with plasma A2MG levels, fasting glucose HbA1c and periodontitis status. After 3 months of follow up, the net change of salivary A2MG values positively correlated with the net change of fasting glucose, HbA1c and triglyceride levels, but negatively correlated with high-density lipoprotein cholesterol changes. Furthermore, the correlations between salivary A2MG and fasting glucose HbA1c were better than plasma A2MG, respectively. CONCLUSIONS: Our data show that salivary A2MG levels have better correlation with fasting glucose HbA1c and periodontitis status than plasma A2MG in diabetic patients. Salivary A2MG concentration might serve as a non-invasive marker for clinical diabetic control.

The differences of metabolic syndrome in elderly subgroups: A special focus on young-old, old-old and oldest old.

BACKGROUND: Metabolic syndrome (MetS) is known to be correlated to future diabetes and cardiovascular disease. Due to the aging society, the increasing prevalence of MetS in the elderly is an important health issue. However, there were few studies focusing in this field. We investigated the changes of MetS components in the subgroups of the elderly. METHODS: Subjects aged above 65 years old who underwent routine health checkups in Taiwan (N=18916) were divided into three groups (young-old: ≧65 and <75, old-old: ≧75 and <85 and oldest-old ≧85). By using multiple logistic regressions, the odds ratio (OR) of subjects with abnormal MetS components to have MetS were evaluated. RESULTS: For men, the systolic blood pressure (SBP) and high-density lipoprotein cholesterol increased as the age got older. On the contrary, the diastolic blood pressure and triglycerides (TG) decreased. In women, the waist circumference and SBP increased significantly from the young-old to the oldest-old groups. The highest percentage having MetS was 35% in old-old men and 62% in oldest-old women. Finally, subjects with high TG had the highest and BP had the lowest ORs for having MetS in both genders except oldest-old women. CONCLUSIONS: In the elderly, the MetS and its components have different patterns not only in young-, old- and oldest-old groups but also in men and women. Moreover, among the five components, hypertension was always the most prevalent one. Finally, subjects had high TG had the highest ORs to have MetS compared to other components.

Association Between a Glucokinase Regulator Genetic Variant and Metabolic Syndrome in Taiwanese Adolescents.

AIMS: Variants of the glucokinase regulator (GCKR) gene are associated with metabolic syndrome (MetS). The present study explored the association between a common variant of this gene and MetS and its related traits in Taiwanese adolescents. METHODS: The frequency of MetS and its features were compared between subjects (n = 962; 468 male, 494 female) with different genotypes or alleles of the GCKR rs780094 single-nucleotide polymorphism. Logistic regression analysis was carried out to explore the interdependence of MetS and metabolic traits. RESULTS: Low high-density lipoprotein cholesterol (HDL-C) levels and MetS were more prevalent in subjects with the T compared to the C allele of rs780094 (p = 0.009 and 0.044, respectively). T-genotype carriers also exhibited a higher frequency of low HDL-C levels (p = 0.028) than noncarriers, although MetS frequency was similar between the two groups. After adjusting for confounding factors, the odds ratios for low HDL-C levels and MetS incidence in T-genotype carriers were 1.64 (95% confidence interval [CI]: 1.07-2.53) and 2.79 (95% CI: 1.09-7.11), respectively. CONCLUSIONS: The GCKR rs780094 polymorphism is associated with low HDL-C levels and MetS incidence in Taiwanese adolescents.

Gefitinib leads to complete resolution of postoperative cervical chyloma and chylothorax in a lung cancer patient.

Cervical chyloma is a not uncommon complication after neck surgery, especially following diagnostic excision of supraclavicular lymph nodes. Conservative treatment remains the standard approach but is inevitably distressful. We describe the case of a 60-year-old Asian woman who was diagnosed as having adenocarcinoma of the lung with cervical and supraclavicular node involvement. She developed persistent cervical chyle leak after excisional biopsy of the supraclavicular nodes and proved refractory to all management. Subsequent gefitinib therapy led to rapid resolution of chyloma and tumor regression. This case provided a unique experience of managing intractable postoperative chyloma in a cancer patient.