Search

Rare copy number variations have been linked to an important source of mutation in many psychopathological traits and neurodevelopmental disorders. In this study, we describe a Taiwanese girl with mental retardation and mild macrocephaly who underwent a childhood psychological evaluation for several years first. When she was 5 years old, she came to our hospital for further diagnosis. We conducted molecular cytogenetic tests and confirmed she actually has Sotos syndrome. We compared our case with two others with very similar deletion regions, but their phenotypes were heterogeneous. Sotos syndrome is very rare in Taiwan, and it is suggested that genetic analysis should be considered early if symptoms of this case are observed.

Patients with chronic spontaneous urticaria (CSU) have a higher risk of developing hypertension. This study aimed to determine whether acupuncture could decrease the risk of hypertension in patients with CSU. We enrolled patients newly diagnosed with CSU between 1 January 2008, and 31 December 2018, from the Taiwanese National Health Insurance Research Database. The claims data were assessed from the index date to 31 December 2019. A Cox regression model was used to compare the hazard ratios (HRs) of the two cohorts. The cumulative incidence of hypertension was estimated using the Kaplan–Meier method. After propensity score matching with a 1:1 ratio, 43,547 patients with CSU who received acupuncture were matched with 43,547 patients with CSU who did not receive acupuncture in this study. After considering potential confounding factors, patients who received acupuncture had a significantly lower risk of hypertension than those in the control group (adjusted hazard ratio = 0.56, 95% confidence interval = 0.54–0.58). Patients who received medications combined with acupuncture tended to have the lowest risk of hypertension. This study revealed that acupuncture decreases the risk of hypertension in patients with CSU in Taiwan. The detailed mechanisms can be further clarified through prospective studies.

Background: Previous epidemiological investigations examining the association between Kawasaki disease (KD) and cerebrovascular disease have had conflicting results. We analyzed the association between KD and cerebrovascular disease by conducting a population-based retrospective cohort study designed to investigate the hypothesis that KD could be a risk factor for subsequent cerebrovascular disease. Methods: From the National Health Insurance Research Database of Taiwan, the data of children (aged 0–18 years old) with KD (n=8467) were collected. Starting with the first year of study observation (referred to as the baseline year), data was collected for each child with KD, and 4 non-KD patients matched for sex, urbanization level of residence, and parental occupation were randomly selected to form the non-KD cohort (n=33 868) for our analysis. For the period from January 1, 2000, to December 31, 2012, we calculated the follow-up person-years for each patient, which is the time from the index date to the diagnosis of cerebrovascular disease, death, or the end of 2012. Furthermore, we compared the incidence, the incidence rate ratio, and the 95% CI of cerebrovascular disease between the KD and non-KD cohorts. Results: The overall cerebrovascular disease incidence rate was found to be 3.19-fold higher, which is significantly higher, in the KD cohort than in the non-KD cohort (14.73 versus 4.62 per 100 000 person-years), and the overall risk of cerebrovascular disease remained higher in the KD cohort (adjusted hazard ratio, 3.16 [95% CI, 1.46–6.85]). Furthermore, children aged Conclusions: This nationwide retrospective cohort study shows that KD may increase the risk of subsequent cerebrovascular disease, especially in those with KD aged

Objective, To investigate the genetic characteristics of idiopathic central precocious puberty (ICPP) and validate its polygenic risk for early puberty. Design and methods A bootstrap subsampling and genome-wide association study were performed on Taiwanese Han Chinese girls comprising 321 ICPP patients and 148 controls. Using previous GWAS data on pubertal timing, a replication study was performed. A validation group was also investigated for the weighted polygenic risk score (wPRS) of the risk of early puberty. Results A total of 105 SNPs for the risk of ICPP were identified, of which 22 yielded an area under the receiver operating characteristic curve of 0.713 for the risk of early puberty in the validation group. A replication study showed that 33 SNPs from previous GWAS data of pubertal timing were associated with the risk of ICPP (training group: P-value < 0.05). In the validation group, a cumulative effect was observed between the wPRS and the risk of early puberty in a dose-dependent manner (validation group: Cochran–Armitage trend test: P-value < 1.00E−04; wPRS quartile 2 (Q2) (odds ratio (OR) = 5.00, 95% CI: 1.55–16.16), and wPRS Q3 (OR = 11.67, 95% CI: 2.44–55.83)). Conclusions This study reveals the ICPP genetic characteristics with 22 independent and 33 reported SNPs in the Han Chinese population from Taiwan. This study may contribute to understand the genetic features and underlying biological pathways that control pubertal timing and pathogenesis of ICPP and also to the identification of individuals with a potential genetic risk of early puberty.

Background/Aim: The T cell’s flexibility of the immune system to be regulated affects the onset of type 1 diabetes (T1D). However, the mechanisms of endoplasmic reticulum (ER) stress and inflammasome activation in the circulating CD3(+)CD56(+) T cells of patients with T1D remain unclear. This study evaluated the role of CD3(+)CD56(+) T cells in T1D and their correlations with ER stress, inflammasome activation and disease characteristics. Materials and Methods: The frequency of circulating CD3(+)CD56(+) T cells was determined using flow cytometry in healthy individuals and patients with T1D. Calnexin, NLR family pyrin domain containing 3 (NLRP3), ASC, caspase-1 (Casp1), cleaved caspase-3 (C-Casp3), and annexin V (AnnV) expression and propidium iodide staining in CD3(+)/CD56(+) T cells were analyzed using flow cytometry. Results: The frequency of CD3(+)CD56(+) T cells was reduced in patients with T1D relative to that in healthy individuals. In addition, high calnexin, NLRP3, ASC and Casp1 expression in CD3(+)CD56(+) T cells was negatively correlated with the percentage of CD3(+)CD56(+) T cells in patients with T1D. Conclusion: ER stress, inflammasome activation, and a lower peripheral frequency of circulating CD3(+)CD56(+) T cells might indicate disease progression and necessitate clinical T1D immunological self-tolerance monitoring.

Epigenetics alternation of non-genetic variation and genome-wide association study proven allelic variants may associate with insulin secretion in type 2 diabetes (T2D) development. We analyzed promoter DNA methylation array to evaluate the associated with increased susceptibility to T2D (30 cases, 10 controls) and found 1,091 gene hypermethylated in promoter regions. We performed the association study of T2D and found 698 single nucleotide polymorphisms in exon and promoter sites by using 2,270 subjects (560 cases, 1,710 controls). A comparison of DNA hypermethylation and gene silencing of mouse T2D results in our T2D patients' results showed that the 5'-nucleotidase, cytosolic II (NT5C2) and fucosyltransferase 8 (FUT8) genes were strongly associated with increased susceptibility to T2D. DNA hypermethylation in promoter regions reduced NT5C2 gene expression, but not FUT8 in T2D patients. NT5C2 protein expression was decreased in pancreatic β-cells from T2D mice. Transient transfection NT5C2 into RIN-m5F cells down-regulated DNA methyltransferase I (DNMT1) expression and up-regulation of the insulin receptor. Moreover, NT5C2 knockdown induced in DNMT1 overexpression and insulin receptor inhibition. Taken together, these results showed that NT5C2 epigenetically regulated insulin receptor in patients and mice with T2D, and maybe provide for T2D therapy strategy.

Epigenetics alternation of non-genetic variation and genome-wide association study proven allelic variants may associate with insulin secretion in type 2 diabetes (T2D) development. We analyzed promoter DNA methylation array to evaluate the associated with increased susceptibility to T2D (30 cases, 10 controls) and found 1,091 gene hypermethylated in promoter regions. We performed the association study of T2D and found 698 single nucleotide polymorphisms in exon and promoter sites by using 2,270 subjects (560 cases, 1,710 controls). A comparison of DNA hypermethylation and gene silencing of mouse T2D results in our T2D patients’ results showed that the 5′-nucleotidase, cytosolic II (NT5C2) and fucosyltransferase 8 (FUT8) genes were strongly associated with increased susceptibility to T2D. DNA hypermethylation in promoter regions reduced NT5C2 gene expression, but not FUT8 in T2D patients. NT5C2 protein expression was decreased in pancreatic β-cells from T2D mice. Transient transfection NT5C2 into RIN-m5F cells down-regulated DNA methyltransferase I (DNMT1) expression and up-regulation of the insulin receptor. Moreover, NT5C2 knockdown induced in DNMT1 overexpression and insulin receptor inhibition. Taken together, these results showed that NT5C2 epigenetically regulated insulin receptor in patients and mice with T2D, and maybe provide for T2D therapy strategy.

Background Gut microbiota may induce obesity, diabetes, and metabolic syndrome. Different weight reduction programs may induce different changes in gut microbiota. Objectives To assess the changes in gut microbiota between obese adults who participated in 2 different weight reduction programs, the dietary counseling (DC) group and sleeve gastrectomy (SG) group, for 3 months. Setting A University Hospital. Methods Ten obese participants from each group were matched according to sex, age, and body mass index. Gut microbiota compositions were determined by metagenomics using next-generation sequencing before and after treatment. Anthropometric indices, metabolic factors, and gut microbiota were compared between and within groups. Results After 3 months of treatment, compared with subjects in DC group, subjects in SG group experienced a greater reduction in body weight, body mass index, body fat, waist and hip circumference, diastolic blood pressure, hemoglobin, insulin, insulin resistance, glutamate pyruvate transaminase, blood urine nitrogen, and glycated hemoglobin (HbA1C). A total of 8, 17, and 46 species experienced significant abundance changes in DC, in SG, and between the 2 groups, respectively. Diversity of the gut flora increased in SG and between the 2 groups after treatment. The weight change over the course of the weight loss program was further adjusted and only 4 species, including Peptoniphilus lacrimalis 315 B, Selenomonas 4 sp., Prevotella 2 sp., and Pseudobutyrivibrio sp., were found to be significantly different between the 2 weight loss programs. These 4 species may be the different gut microbiota change between internal and surgical weight reduction programs. Conclusions There are significant differences not only in anthropometric indices and metabolic factors but also in gut microbiota change between the 2 programs.

Background: Congenital generalized lipodystrophy (CGL) is a rare disorder characterized by scarce adipose tissue. This disease is distributed worldwide, but little is known about these patients in the Chinese population. Here, we delineate the phenotype and prognosis of CGL in our cohort. Methods: Patients diagnosed with CGL from 8 medical centers were reviewed. The initial presentation, laboratory findings, and molecular testing were retrospectively analyzed. Results: A total of 16 patients were analyzed, and the current median age was 3.5 years (range, 9 months-17.5 years). In all patients, molecular results confirmed BSCL2 mutation. c.782dupG (p.Ile262Hisfs*12) was the most common genotype identified. All patients had triangular faces and muscular hypertrophy. In addition, 75% presented with hepatomegaly, 19% had cardiomegaly, and 44% exhibited acanthosis nigricans. Developmental delay was noted in 5 out of 9 patients (56%) with a median developmental quotient (DQ)/intelligence quotient (IQ) of 61. Thirteen patients (81.3%) had high triglyceride levels. Eight patients received leptin analysis, and 7 of them (88%) had low leptin levels. One patient exclusively received a lipid-lowering drug, 4 patients were exclusively placed on a fat-restricted diet, 5 patients were administered combination therapy, and 5 patients received no treatment. Three patients (19%) who developed diabetes mellitus received both oral hypoglycemic agents and insulin. Three patients (19%) experienced loss of ambulation and died prematurely. Conclusion: Our findings highlight the uniqueness of the genotype and phenotype in our cohort. Further long-term surveillance for comorbidities is necessary for early detection and management of these patients. Keywords: Congenital generalized lipodystrophy, Outcome, Morbidity

Acrylamide (ACR), which is formed during the Maillard reaction, is used in various industrial processes. ACR accumulation in humans and laboratory animals results in genotoxicity, carcinogenicity, neurotoxicity, and reproductive toxicity. In this study, we investigated the mechanisms by which ACR may induce vasorelaxation and neuromuscular toxicity. Vasorelaxation was studied using an isolated rat aortic ring model. The aortic rings were divided into the following groups: with or without endothelium, with nitric oxide synthase (NOS) inhibition, with acetylcholine receptor inhibition, and with extracellular calcium inhibition. Changes in tension were used to indicate vasorelaxation. Neuromuscular toxicity was assessed using a phrenic nerve–diaphragm model. Changes in muscle contraction stimulated by the phrenic nerve were used to indicate neuromuscular toxicity. ACR induced the vasorelaxation of phenylephrine-precontracted aortic rings, which could be significantly attenuated by NOS inhibitors. The results of the phrenic nerve–diaphragm experiments revealed that ACR reduced muscle stimulation and contraction through nicotinic acetylcholine receptor (AChR). ACR-induced vasotoxicity was regulated by NOS through the aortic endothelium. Nicotinic AChR regulated ACR-induced neuromuscular blockage.

Introduction: Multiple myeloma (MM) is an incurable, biologically heterogeneous disease of the plasma cells, associated with older age and is more common in men. Gaucher disease, caused by mutation in acid β-glucosidase (glucocerebrosidase, GBA) gene, has been linked to multiple cancers, especially MM. Pathological accumulation of glucosylceramide and complex glycosphingolipids coupled with chronic inflammation may be the cause of cancer in patients with Gaucher disease. In this study, we hypothesized patients with MM have mutations in the GBA gene and analyzed patients with MM to determine whether they have a higher frequency of GBA variants. Methods: Twenty-four MM samples were acquired from the Human Biobank, China Medical University Hospital, Taichung, Taiwan. GBA mutations were detected by polymerase chain reaction-directed DNA sequencing. Results: We found no mutations in the coding regions of GBA in any of the 24 study subjects. However, two single-nucleotide polymorphisms, rs2070679 and rs2361534, were identified. A significant difference was observed between the study and control groups (p = 0.0028) in rs2361534 allele distribution, with the C allele frequency being higher in patients (1/48, 2.1%) than in the control group (5/3030, 0.16%, Taiwan Biobank). Conclusion: In this study, the sample size was limited and GBA enzyme activity was not measured; therefore, we could not establish a direct correlation between MM and GBA mutations. However, the association of rs2361534 suggests that regions around this single-nucleotide polymorphism may be involved in MM. The relationship between MM and GBA mutations remains unclear. A large sample is required for a detailed analysis of this potential relationship.

Chronic inflammation caused by Helicobacter pylori infection increases the risk of developing gastric cancer. Even though the prevalence of H. pylori infection has been decreased in many regions, the development of antibiotic resistance strains has increased the difficulty of eradicating H. pylori. Therefore, exploring alternative approaches to combat H. pylori infection is required. It is well-known that probiotic therapy can improve H. pylori clearance. In this study, H. pylori-infected mice were treated with Lactobacillus fermentum P2 (P2), L. casei L21 (L21), L. rhamnosus JB3 (JB3), or a mixture including the aforementioned three (multi-LAB) for three days. All the lactic acid producing bacteria (LAB) treatments decreased H. pylori loads in the stomach and vacA gene expression, H. pylori specific immunoglobulin (Ig) A, and IgM levels in stomach homogenates, as well as serum levels of interferon-gamma and interleukin-1 beta. The multi-LAB and JB3 treatments further restored the superoxide dismutase and catalase activities suppressed by H. pylori infection. Furthermore, H. pylori infection decreased serum concentrations of 15 kinds of amino acids as well as palmitic acid. The multi-LAB treatment was able to recover the serum levels of alanine, arginine, aspartate, glycine, and tryptophan, which are all important in modulating immune functions. In addition, butyric acid, valeric acid, palmitic acid, palmitoleic acid, stearic acid, and oleic acid levels were increased. In this study, multi-LAB revealed its ability to adjust the composition of metabolites to improve health. To date, the mechanisms underlying how LAB strains crosstalk with the host are not fully understood. Identifying the mechanisms which are regulated by LABs will facilitate the development of effective therapies for infection in the future.

Chronic inflammation caused by Helicobacter pylori infection increases the risk of developing gastric cancer. Even though the prevalence of H. pylori infection has been decreased in many regions, the development of antibiotic resistance strains has increased the difficulty of eradicating H. pylori. Therefore, exploring alternative approaches to combat H. pylori infection is required. It is well-known that probiotic therapy can improve H. pylori clearance. In this study, H. pylori-infected mice were treated with Lactobacillus fermentum P2 (P2), L. casei L21 (L21), L. rhamnosus JB3 (JB3), or a mixture including the aforementioned three (multi-LAB) for three days. All the lactic acid producing bacteria (LAB) treatments decreased H. pylori loads in the stomach and vacA gene expression, H. pylori specific immunoglobulin (Ig) A, and IgM levels in stomach homogenates, as well as serum levels of interferon-gamma and interleukin-1 beta. The multi-LAB and JB3 treatments further restored the superoxide dismutase and catalase activities suppressed by H. pylori infection. Furthermore, H. pylori infection decreased serum concentrations of 15 kinds of amino acids as well as palmitic acid. The multi-LAB treatment was able to recover the serum levels of alanine, arginine, aspartate, glycine, and tryptophan, which are all important in modulating immune functions. In addition, butyric acid, valeric acid, palmitic acid, palmitoleic acid, stearic acid, and oleic acid levels were increased. In this study, multi-LAB revealed its ability to adjust the composition of metabolites to improve health. To date, the mechanisms underlying how LAB strains crosstalk with the host are not fully understood. Identifying the mechanisms which are regulated by LABs will facilitate the development of effective therapies for infection in the future.

In this study, a combined whole-cell biotransformation process was used for efficient synthesis of optically pure (1 R, 2 S )-norephedrine [(1 R, 2 S )-NE]. The genes encoding R -selective acetohydroxyacid synthase I (AHAS I) from Escherichia coli and S -selective ω-transaminase (ω-TA) from Chromobacterium violaceum BCRC10636 were cloned and over-expressed in E. coli NovaBlue cells. In the first biosynthetic step, l -phenylacetylcarbinol ( l -PAC) was produced from benzaldehyde and pyruvate by using recombinant E. coli (pQE- AHAS I) cells, with almost 100% conversion yield and 71.8% purification yield. The purified l -PAC was coupled to l -alanine by using recombinant E. coli (pQE- CvTA ) cells to produce (1 R, 2 S )-NE. This biocatalytic process was optimal at pH 6.5 to 8.0 and 37 °C, with a 1:10 ratio of l -PAC to l -alanine. Under the optimal conditions, the highest conversion yield of (1 R, 2 S )-NE was 62.2% and the enantiomeric excess value of (1 R, 2 S )-NE was more than 99%. The recombinant E. coli (pQE- CvTA ) cells could be reused for at least 20 cycles, with only a modest reduction in the conversion yield to 76.3% relative to the first cycle. Our results indicate that the combination of AHAS I- and ω-TA-expressing E. coli cells might be a potential biocatalyst for (1 R, 2 S )-NE production.

Background Noonan syndrome-like disorder with loose anagen hair-2 (NSLH2) is an extremely rare disease caused by a heterozygous mutation in the PPP1CB gene on chromosome 2p23. The syndrome causes not only numerous dysmorphic features but also hypotonia, developmental delay, and even intellectual disability. We report the first case of NSLH2 in Asia and the 16th in the world. Moreover, the first case of PPP1CB-related infantile spasms. The clinical and therapeutic significance is outlined in this paper. Case presentation We found a male infant presented with severe intractable epileptic spasms. Although certain clinical features of somatic dysmorphism were noted, numerous laboratory and neuroimaging studies failed to identify the cause. To determine the underlying etiology, whole-exome sequencing was conducted. We identified a de novo heterozygous mutation, NM_206876.1: c.548A > C (p.Glu183Ala), in the PPP1CB gene. His seizures were almost refractory to conventional antiepileptic drugs but relative seizure control was eventually achieved with a ketogenic diet. Conclusion This result expands the clinical spectrum of NSLH2 and strengthens the association between the PPP1CB gene and epileptic seizures. Furthermore, we suggest that the ketogenic diet can offer seizure reduction in particular drug-resistant epilepsy syndromes. Additional studies are warranted to clarify the pathogenic mechanisms underlying this PPP1CB mutation in epileptic seizures.

Febrile seizure (FS) is the most prevalent childhood seizure, it is significantly related to subsequent epilepsy and has possible links to childhood neurodevelopmental disorders. Separately, premature births are believed to increase the risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Therefore, this study investigated whether preterm birth is a risk factor for subsequent epilepsy, ASD, and ADHD in children with FS. We retrospectively collected data for children aged &lt, 5 years with FS from 1 January 2005, to 31 December 2013. We divided these children into two groups—the premature birth group and the full-term group—and compared their incidence rates of epilepsy, ASD and ADHD. The data of 426 patients with history of febrile convulsion were retrospectively collected. The premature birth group (FS+/preterm+) had 108 patients and the full-term group (FS+/preterm−) had 318 patients. The overall epilepsy risk in the FS+/preterm+ group was higher than in the FS+/preterm− group (odds ratio [OR], 2.52, 95% confidence interval [CI], 1.14–5.58, p = 0.02). The overall risk of ADHD in the FS+/preterm+ group was higher than that in the FS+/preterm− group (OR, 6.41, 95% CI, 3.39–12.09, p = 0.0001). In addition, children with FS+/preterm+ had 16.9 times (95% CI, 4.79–59.7, p = 0.0001) higher odds of having ASD compared with those with FS+/preterm−. Preterm birth may be a risk factor for subsequent epilepsy, ASD and ADHD in children with FS.

Purpose We report the first family with PIGA- associated epileptic encephalopathy in Taiwan and hope to elucidate its special phenotype and inheritance pattern. Method We found a Taiwanese family with several members suffered from severe epileptic encephalopathy (ZY07, ZY01, ZY04). To determine the underlying etiology, whole exome sequencing was conducted. Results A single novel variant, NM_002641: c.356G > A, p.Arg119Gln, was identified in the X chromosome PIGA gene in our proband patient (ZY07). The patient's mother (ZY02) and aunt (ZY03) were confirmed as carriers of the hemizygous variant. Conclusions This paper highlights the highly transmitted features of PIGA and other X-linked EIEEs, raising awareness of rare forms of epileptic encephalopathy.

Background Kawasaki disease (KD) is a common vasculitis of childhood in East Asia. The complications of KD ascribed to long-term cardiovascular sequelae are considerably diverse. Although studies have investigated neurodevelopmental problems following KD in the past few decades, they have reported inconsistent conclusions. This study investigated potential epilepsy and associated neurodevelopmental disorders (NDDs) following KD in Taiwanese children. Methods We retrospectively analyzed the data of children aged Results A total of 612 patients with an average age of 1.6 years were included. The prevalence of associated NDDs was 16.8% (n = 103/612) in the study group, which consisted of epilepsy, intellectual disability (ID), autism spectrum disorders, Tourette syndrome (TS), attention deficit hyperactivity disorder, (ADHD), and others. Moreover, children with KD had a higher prevalence of epilepsy and TS in both Taiwan and worldwide (epilepsy: 2.61% in the KD group vs 0.33% in Taiwan and 0.05–0.8% in worldwide, p p Conclusions Results revealed a higher prevalence rate of NDDs, especially epilepsy and TS, in Taiwanese children with KD than in the general pediatric population in Taiwan. However, these NDDs could be heterogeneous. Children diagnosed with KD were followed up because they had a higher risk of heterogeneous NDDs.

PURPOSE: Type-2 diabetes mellitus (T2D) is a metabolic disorder that can progress to a serious chronic disease and frequently develops in obese individuals in association with various pathogenic complications that shorten the lifespan of these patients. The liver is an important organ regulating lipid metabolism, which is damaged in both obesity and T2D; however, the specific pathways involved in these pathogenic effects remain unclear. Establishing a suitable animal model that effectively mimics the human biological condition is a critical factor to allow for precise identification of T2D-related genes. METHODS: The KK.Cg-A(y) mouse strain is one such model that has offered insight into obesity-related T2D pathogenesis. To comprehensively assess the association between obesity and T2D, in the present study, we performed microarray analysis on liver tissue samples of KK.Cg-A(y) and KK-α/α wild-type mice to examine differences in gene expression and methylation patterns and their related biological processes and pathways. RESULTS: We found that inflammation accompanied by abnormal lipid metabolism led to the spontaneous mechanism of obesity-induced diabetes, resulting in differential expression of some genes related to the terms of insulin resistance and glucose tolerance. Surprisingly, disruption of steroid biosynthesis strongly facilitated the diabetic pathogenesis. To support these findings, we highlighted some candidate genes and determined their relationships in biological networks of obesity-induced T2D. CONCLUSION: These findings provide valuable reference data that can facilitate further detailed investigations to elucidate the pathogenic mechanism of obesity-induced diabetes in mice, which can be associated with the human condition to inform new prevention and treatment strategies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40200-019-00453-8) contains supplementary material, which is available to authorized users.

Aims/hypothesis Type 1 diabetes mellitus is a major public health problem of increasing global concern, with potential neurological complications. A possible association exists between type 1 diabetes and subsequent epilepsy. This study evaluated the relationship between type 1 diabetes and epilepsy in Taiwan.

Genome-wide association study (GWAS) data showed that the protein tyrosine phosphatase receptor type delta (PTPRD) is associated with increased susceptibility to type 2 diabetes (T2D) in Han Chinese. A replication study indicated that PTPRD is involved in the insulin signaling pathway; however, the underlying mechanism remains unclear. We evaluated PTPRD expression in patients with T2D and controls. PTPRD expression levels were lower in patients and were correlated with the duration of the disease. Overexpression of the human insulin receptor PPARγ2 in HepG2 cells induced overexpression of PTPRD and the insulin receptor. PTPRD knockdown, using a shRNA, resulted in down-regulation of the insulin receptor. These results indicate that PTPRD activates PPARγ2 in the insulin signaling pathway. Similar results for PTPRD expression were found using a T2D mouse model. Silencing of PTPRD was caused by DNA methylation in T2D mice and patients, and correlated with DNMT1 expression. Furthermore, we showed that a DNMT1 SNP (rs78789647) was correlated with susceptibility to T2D. This study shows for the first time that DNMT1 caused PTPRD DNA hypermethylation and induced insulin signaling silencing in T2D patients. Our findings contribute to a better understanding of the crucial roles of these regulatory elements in human T2D.

Autophagy, a double-edged sword for cell survival, is the research object on 2016 Nobel Prize in Physiology or Medicine. Autophagy is a molecular mechanism for maintaining cellular physiology and promoting survival. Defects in autophagy lead to the etiology of many diseases, including diabetes mellitus (DM), cancer, neurodegeneration, infection disease and aging. DM is a metabolic and chronic disorder and has a higher prevalence in the world as well as in Taiwan. The character of diabetes mellitus is hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and failure of producing insulin on pancreatic beta cells. In T2DM, autophagy is not only providing nutrients to maintain cellular energy during fasting, but also removes damaged organelles, lipids and miss-folded proteins. In addition, autophagy plays an important role in pancreatic beta cell dysfunction and insulin resistance. In this review, we summarize the roles of autophagy in T2DM.

Background Obesity is one of the main causes of preventable death. Complications of childhood obesity include cardiovascular risk, impaired glucose tolerance, type 2 diabetes mellitus, and acanthosis nigricans (AN; associated with obesity as a manifestation of cutaneous insulin resistance). An interaction between AN and obesity as well as a detailed mechanism for the pre- and co-obesity appearance of AN in children are still to be revealed. Purposes This research tries to assess involvement of the insulin/insulin-like growth factor (IGF) receptor pathway in childhood pre- and co-obesity AN via a study of the association of polymorphisms of the INSR, IRS1, and IGF1R genes with pre- and co-obesity AN. Methods In total, 99 children with pre- and co-obesity AN and 100 healthy controls were genotyped and analyzed by the polymerase chain reaction-restriction fragment length polymorphism method. Results Intergroup frequency differed starkly for INSR His1085His and IGF1R IVS7-20, but not in the IRS1 Ala804Ala or IGF1R Thr766Thr genotypes. The T allele of INSR His1085His and C allele of IGF1R IVS7-20 both conferred a starkly( p=0.04 and 2.84E-6 = 2.84 x 10 −6 , respectively)higher risk for AN. Conclusion The above findings suggest that certain genetic variants in insulin/insulin-like growth factor (IGF) receptor pathway might be correlated with the appearance of AN prior to or concurrent with obesity, and also reveal the insulin/IGF receptor pathway as crucial in pre- and co-obesity AN.