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Background/Aims: Taiwan has the highest incidence of end-stage renal disease, which requires renal replacement therapy. Chronic kidney disease (CKD) contributes to this burden. However, the current data on the epidemiologic features of CKD in Taiwan are incomplete. Therefore, we aimed to investigate the prevalence and incidence of CKD in a population-based study and then estimate the average dwelling time (ADT) in the main clinical burden of CKD (stages 3–5). Methods: A prospective cohort study was designed with an integrated community-based multiple screening program of 106,094 individuals aged ≥20 years in Keelung, Taiwan, in 1999–2009. Prevalence was estimated as the percentage of CKD stages among individuals attending the first screening, and incidence was expressed as the ratio of total desired events in the following period to the total observational time. Finally, ADT was estimated from the ratio of prevalence to incidence. Results: The participants’ mean age was 47.7 ± 15.4 years. The estimated prevalence was 15.46% for total CKD and 9.06% for CKD stages 3–5. The incidence was 27.21/1,000 person-years (PY) for total CKD and 16.89/1,000-PY for CKD stages 3–5. Older patients, males, and those patients with comorbidities of diabetes mellitus (DM), hypertension, and metabolic syndrome (MetS) exhibited higher prevalence and incidence rates than their opposing counterparts. Moreover, the ADT of CKD stages 3–5 was 5.37 years (95% CI 5.17–5.57). Males and those with comorbidities of DM or MetS had shorter ADTs in CKD stages 3–5 than their opposing counterparts. Interestingly, the ADT of participants with hypertension was longer than those without. Conclusions: The prevalence and incidence of CKD in Taiwan are high. Moreover, ADT in CKD stages 3–5 varied according to sex, age, and comorbidity. Further exploration of the factors associated with the shifting of this duration will shed light on effective CKD management.

In chronic kidney disease (CKD), decreased erythropoietin production, low serum active vitamin D levels, and high renin-angiotensin-aldosterone activities had been regarded as major causes of renal anemia. At present, no clinical data are available to elucidate the association between renal anemia and fibroblast growth factor 23 (FGF23) levels in CKD. This study aimed to access whether FGF23 is involved in the pathogenesis of renal anemia.This cross-sectional observational study included 53 stable outpatients with CKD stages 3 and 4. Our primary predictor was serum FGF23 levels and outcome was hemoglobin levels. Measurements contained hemoglobin, FGF23, 25-hydroxyvitamin D, intact parathyroid hormone, plasma renin, serum aldosterone, HbA1C levels, lipid and iron profiles, and serum and urine electrolytes.Mean age of our patients was 66.4 ± 12.8 (SD) years, mean estimated glomerular filtration rate 33.5 ± 13.9 mL/min/1.73 m2, median FGF23 level 200 (25th–75th percentile, 124–303) pg/mL, vitamin D level 19.5 (25th–75th percentile, 14.0–25.9) ng/mL, and hemoglobin level 12.7 (25th–75th percentile, 10.7–13.75) g/dL. Even after adjusting multiple variables, lower hemoglobin levels correlated significantly with FGF23 levels that were higher than the median value (>200 pg/mL). Moreover, after adjusting for aldosterone, but not 25-hydroxyvitamin D, it decreased the association with FGF23 that higher than median level and hemoglobin levels. We also observed a significant decrease of hemoglobin level in the higher FGF23 group who had a diabetes history.High FGF23 levels were observed to be associated with low hemoglobin levels, which may be partially mediated through the effects of serum aldosterone levels in our patients with CKD stages 3 and 4. Furthermore, we also presumed that diabetes itself may have an impact on the loop among FGF23, hemoglobin, and aldosterone levels in these CKD patients.

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Dipeptidyl peptidase IV (DPP IV) is a surface glycoprotein that can degrade glucagon like pepetide-1 (GLP-1) by decreasing blood sugar. Herbal medicines for diabetic therapy are widely used with acceptable efficacy but unsatisfied in advances. DPP IV was chosen as a template to employ molecular docking via Discovery Studio to search for natural phenolic compounds whether they have the inhibitory function of DPP IV. Then, docking candidates were validated and further performed signal pathway via Caco-2, C2C12, and AR42J cells. Lastly, a diet-induced diabetes in mice were applied to examine the efficacy and toxicity of hit natural phenolic products in long-term use (in vivo). After screening, curcumin, syringic acid, and resveratrol were found in high affinity with DPP IV enzymes. In enzymatic tests, curcumin and resveratrol showed potential inhibition of DPP IV. In vitro assays, curcumin inhibited of DPP IV activity in Caco-2 cells and ERK phosphorylation in C2C12 cells. Additionally, curcumin attenuated blood sugar in S961-treated C57BL/6 mice and in diet-induced diabetic ICR mice and long-term regulate HbA1c in diabetic mice. Curcumin targeted to DPP IV for reducing blood glucose, it possesses potential and alternative substitution of synthetic clinical drugs for the medication of diabetes.

The inhibition of α-glucosidase and α-amylase is a clinical strategy for the treatment of type II diabetes, and herbal medicines have been reported to credibly alleviate hyperglycemia. Our previous study has reported some constituents from plant or herbal sources targeted to α-glucosidase and α-amylase via molecular docking and enzymatic measurement, but the hypoglycemic potencies in cell system and mice have not been validated yet. This study was aimed to elucidate the hypoglycemic efficacy of docking selected compounds in cell assay and oral glucose and starch tolerance tests of mice. All test compounds showed the inhibition of α-glucosidase activity in Caco-2 cells. The decrease of blood sugar levels of test compounds in 30 min and 60 min of mice after OGTT and OSTT, respectively and the decreased glucose levels of test compounds were significantly varied in acarbose. Taken altogether, in vitro and in vivo experiments suggest that selected natural compounds (curcumin, antroquinonol, HCD, docosanol, tetracosanol, rutin, and actinodaphnine) via molecular docking were confirmed as potential candidates of α-glucosidase and α-amylase inhibitors for treating diabetes.

Prodigiosin (PG) belongs to a family of prodiginines isolated from gram-negative bacteria. It is a water insoluble red pigment and a potent proapoptotic compound. This study elucidates the anti-tumor activity and underlying mechanism of PG in doxorubicin-sensitive (Dox-S) and doxorubicin-resistant (Dox-R) lung cancer cells. The cytotoxicity and cell death characteristics of PG in two cells were measured by MTT assay, cell cycle analysis, and apoptosis/autophagic marker analysis. Then, the potential mechanism of PG-induced cell death was evaluated through the phosphatidylinositol-4,5-bisphosphate 3-kinase-p85/Protein kinase B /mammalian target of rapamycin (PI3K-p85/Akt/mTOR) and Beclin-1/phosphatidylinositol-4,5-bisphosphate 3-kinase-Class III (Beclin-1/PI3K-Class III) signaling. Finally, in vivo efficacy was examined by intratracheal inoculation and treatment. There was similar cytotoxicity with PG in both Dox-S and Dox-R cells, where the half maximal inhibitory concentrations (IC50) were all in 10 μM. Based on a non-significant increase in the sub-G1 phase with an increase of microtubule-associated proteins 1A/1B light chain 3B-phosphatidylethanolamine conjugate (LC3-II), the cell death of both cells was categorized to achieve autophagy. Interestingly, an increase in cleaved-poly ADP ribose polymerase (cleaved-PARP) also showed the existence of an apoptosis-sensitive subpopulation. In both Dox-S and Dox-R cells, PI3K-p85/Akt/mTOR signaling pathways were reduced, which inhibited autophagy initiation. However, Beclin-1/PI3K-Class III downregulation implicated non-canonical autophagy pathways were involved in PG-induced autophagy. At completion of the PG regimen, tumors accumulated in the mice trachea and were attenuated by PG treatment, which indicated the efficacy of PG for both Dox-S and Dox-R lung cancer. All the above results concluded that PG is a potential chemotherapeutic agent for lung cancer regimens regardless of doxorubicin resistance.

BackgroundThe ankle—brachial blood pressure (BP) index (ABI) not only indicates the presence of peripheral artery occlusive disease (PAOD) but predicts mortality in patients undergoing hemodialysis (HD). However, whether the site of PAOD can provide additional contribution to predicting mortality have not been investigated yet. Our primary objective was to determine the associations between the site of PAOD and all-cause and cardiovascular mortality in chronic HD (CHD) patients.MethodsA retrospective cohort study was conducted to evaluate 444 Taiwanese CHD patients between December 2006 and June 2013. The site of PAOD together with other explanatory variables such as demographic data, body mass index, a history of cardiovascular diseases, HD vintage, biochemical data, and cardiothoracic ratio (CTR) were assessed by the Cox proportional hazards regression model.ResultsThe frequency of PAOD was 14.6% in both legs, 4.9% in the right side only, and 5.1% in the left side only. During the study period, 127 all-cause and 93 cardiovascular deaths occurred. PAOD site was found to have significant predictive power for all-cause mortality with the order of 3.04 (95% CI: 1.56–5.90) hazard ratio on the right side, 2.48 (95% CI: 1.27–4.82) on the left side, and 4.11 (95% CI: 2.76–6.13) on both sides. The corresponding figures for cardiovascular mortality were 3.81 (95% CI: 1.87–7.76) on the right side, 2.76 (95% CI: 1.30–5.82) on the left side, and 3.95 (95% CI: 2.45–6.36) on both sides. After adjustment for other explanatory variables, only right-sided PAOD still remained to have significant predictive power for all-cause and cardiovascular mortality and bilateral PAOD kept the significant association with all-cause mortality.ConclusionsThe site of PAOD revealed various predictive powers for all-cause and cardiovascular mortality in CHD patients and only right-sided PAOD remained an independent predictor for both types of mortality making allowance for relevant confounding factors.