Cellular apoptosis susceptibility (CSE1L/CAS) protein in cancer metastasis and chemotherapeutic drug-induced apoptosis

The cellular apoptosis susceptibility (CSE1L/CAS) protein is highly expressed in cancer, and its expression is positively correlated with high cancer stage, high cancer grade, and worse outcomes of patients. CSE1L (or CAS) regulates chemotherapeutic drug-induced cancer cell apoptosis and may play important roles in mediating the cytotoxicities of chemotherapeutic drugs against cancer cells in cancer chemotherapy. CSE1L was originally regarded as a proliferation-associated protein and was thought to regulate the proliferation of cancer cells in cancer progression. However, the results of experimental studies showed that enhanced CSE1L expression is unable to increase proliferation of cancer cells and CSE1L regulates invasion and metastasis but not proliferation of cancer cells. Recent studies revealed that CSE1L is a secretory protein, and there is a higher prevalence of secretory CSE1L in the sera of patients with metastatic cancer. Therefore, CSE1L may be a useful serological marker for screening, diagnosis and prognosis, assessment of therapeutic responses, and monitoring for recurrence of cancer. In this paper, we review the expression of CSE1L in cancer and discuss why CSE1L regulates the invasion and metastasis rather than the proliferation of cancer

A lack of association between genetic polymorphisms in beta-defensins and susceptibility of psoriasis in Taiwanese: A case–control study

AbstractBackgroundGenetic predisposition of the inflammatory-host response may affect the development of psoriasis. Previous studies have shown that copy number variations (CNVs) of β-defensin genes (DEFB) are associated with the susceptibility of psoriasis in Caucasian populations.ObjectivesThis study aimed to assess the role of the CNVs of the DEFB4 gene and functional variants in the DEFB1 gene in Taiwanese patients with psoriasis.MethodsIn total, 196 patients with psoriasis and 196 control individuals were analyzed for the presence of the DEFB4 CNVs using the paralogue ratio test, and also for the DEFB1 polymorphisms rs11362, rs1800972, and rs1799946, using a polymerase chain reaction.ResultsNone of the polymorphisms were found to be associated with psoriasis. The distribution of DEFB4 genomic CNVs did not significantly differ between the control group and psoriasis group. The frequencies of patients who carried a greater than the median (≥ 5) number of copies did not significantly differ in patients with psoriasis and controls. The multivariate analysis similarly revealed that the DEFB4 CNVs were not associated with psoriasis (odds ratio = 1.03, 95% confidence interval = 0.89–1.19, p = 0.720). No significant difference was detected in the genotype and allele distribution for any of the individual DEFB1 polymorphisms between the cases and the controls. Finally, the overall haplotype frequency profiles derived from the three polymorphisms did not significantly differ between the cases and the controls.ConclusionOur results do not suggest that these genetic variants of the β-defensin genes contribute to the genetic background of psoriasis in Taiwanese patients

Adiponectin gene (ADIPOQ) polymorphisms correlate with the progression of nephropathy in Taiwanese male patients with type 2 diabetes

Aims: Polymorphisms of the ADIPOQ gene were associated with diabetic nephropathy (DN) in case-control studies predominantly among European populations. Gender may modify the ADIPOQ associated risk for DN. We investigated the association of 18 ADIPOQ polymorphisms with DN in a prospective Taiwanese cohort of type 2 diabetes (T2D) and explored whether gender plays a role in this genetic association. Methods: Selected single nucleotide polymorphisms (SNPs) of ADIPOQ were genotyped in 566 T2D patients with normoalbuminuria at baseline. DN was defined based on urinary albumin-to-creatinine ratio (ACR). The Cox proportional hazard model was used to explore the association of individual SNP to DN events under different genetic models over a 6-year follow-up period. Analyses were further stratified by gender. Results: In male patients, the adjusted hazard ratios under the recessive models were 1.81 for rs2241766 TT (vs. GT+GG, 95% CI=1.10-2.96, p=0.019) and 1.89 for rs1063537 CC (vs. CT+TT, 95% CI=1.15-3.11, p=0.013). In the Kaplan-Meier survival curve, males carrying rs2241766 TT (vs. GT+GG, p=0.050) and rs1063537 CC (vs. CT+TT, p=0.037) recessive homozygotes also had a reduced nephropathy-free survival rate. SNPs rs2241767 and rs2082940, both in strong correlation with tag SNP rs1063537 (r≥0.96), were also associated with DN progression in males. In females, ADIPOQ polymorphisms were not associated with the progression of DN. Conclusions: ADIPOQ genetic polymorphisms rs2241766 (+45T>G), rs1063537, rs2241767 and rs2082940 were correlated with the progression of DN in Taiwanese male patients with T2D. The role of gender in this ADIPOQ genetic association needs to be further investigated in other populations

Sitagliptin and Fractures in Type 2 Diabetes: A Nationwide Population-Based Propensity-Matching Study

Background: Sitagliptin, a dipeptidyl peptidase-4 inhibitor possibly affects bone turnover. We conducted this cohort study to determine whether sitagliptin is associated with an increased risk of fracture.Methods: The sitagliptin cohort included 1,578 patients aged 20 years and above. The nonsitagliptin cohort comprised propensity-score matched patients at a ratio of 1:1. The primary outcome was the incidence of fractures, which was evaluated using Kaplan–Meier survival analysis and proportional hazards modeling.Results: The mean age of patients in the sitagliptin and nonsitagliptin cohorts was 63.1 and 63.3 years, respectively. The incidence of fractures in the sitagliptin cohort was 46 per 1,000 person-years and that in the nonsitagliptin cohort was 40.8 per 1,000 person-years. Compared with patients in the nonsitagliptin cohort, those in the sitagliptin cohort who received sitagliptin for ≥250 days had a higher risk of fracture (aHR = 1.32, 95% CI = 1.06–1.64).Conclusion: Using sitaglipin ≥250 days was associated with an increased risk of fracture

Is the level of serum lactate dehydrogenase a potential biomarker for glucose monitoring with type 2 diabetes mellitus?

IntroductionType 2 diabetes mellitus (T2DM) is a metabolic disorder due to defects in insulin secretion or insulin resistance leading to the dysfunction and damage of various organs. To improve the clinical evaluation of short-term blood glycemic variability monitoring, it is critical to identify another blood cell status and nutritional status biomarker that is less susceptible to interference. This study identifies the significance of serum lactate dehydrogenase (LDH) level among T2DM patients treated in outpatient clinics and investigates the relationship of LDH level with other variables.MethodsThis study comprised 72 outpatients with T2DM over 20 years of age. Blood samples were collected followed by a hematological analysis of serum glycated albumin (GA), LDH, fasting blood glucose, glycosylated hemoglobin, C-peptide, and insulin antibodies (insulin Ab).ResultsSerum LDH level was significantly correlated with GA (p < 0.001), C-peptide (p = 0.04), insulin Ab (p = 0.03), and thyroid-stimulating hormone (TSH) levels (p = 0.04). Hence, we performed a linear regression analysis of hematological markers. GA (p < 0.001, r2 = 0.45) and insulin Ab (p < 0.001, r2 = 0.40) were significantly associated with LDH level. Then, we classified patients into low (<200 U/L) and high (≥200 U/L) serum LDH level groups, respectively. GA (p < 0.001), C-peptide (p = 0.001), and TSH (p = 0.03) showed significant differences in patients with high LDH levels compared with those in patients with low LDH levels.ConclusionIn conclusion, we suggested that LDH level was independent of long-term but associated with short-term blood glucose monitoring. The results indicated that changes in serum GA induced cell damage and the abnormal elevation of the serum level of LDH may occur simultaneously with glycemic variability. It has been reported that many biomarkers are being used to observe glucose variability in T2DM. However, LDH could provide a more convenient and faster evaluation of glycemic variability in T2DM