Jiaan-Der Wang - Academia.edu (original) (raw)

Papers by Jiaan-Der Wang

Pediatrics & Neonatology, 2020

Turkish Journal of Hematology, 2019

American journal of hematology, Jan 11, 2016

to infliximab therapy in luminal and fistulizing Crohn’s disease. Aliment Pharmacol Ther 2005;22:... more to infliximab therapy in luminal and fistulizing Crohn’s disease. Aliment Pharmacol Ther 2005;22:613–626. 4. Vega MI, Huerta-Yepez S, Jazirehi AR, et al. Rituximab (chimeric anti-CD20) sensitizes BNHL cell lines to Fas-induced apoptosis. Oncogene 2005;24:8114–8127. 5. Villa-Morales M, Gonz alez-Gugel E, Shahbazi MN, et al. Modulation of the FAS-apoptosissignalling pathway by functional polymorphisms at Fas, FasL and Fadd and their implication in T-cell lymphoblastic lymphoma susceptibility. Carcinogenesis 2010;31:2165–2171. 6. Heredia-Galvez B, Ruiz-Cosano J, Torres-Moreno D, et al. Association of polymorphisms in TRAIL1 and TRAILR1 genes with susceptibility to lymphomas. Ann Hematol 2014;93: 243–247.

New England Journal of Medicine, 2020

BACKGROUND Up-regulation of hepatic delta-aminolevulinic acid synthase 1 (ALAS1), with resultant ... more BACKGROUND Up-regulation of hepatic delta-aminolevulinic acid synthase 1 (ALAS1), with resultant accumulation of delta-aminolevulinic acid (ALA) and porphobilinogen, is central to the pathogenesis of acute attacks and chronic symptoms in acute hepatic porphyria. Givosiran, an RNA interference therapy, inhibits ALAS1 expression. METHODS In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned symptomatic patients with acute hepatic porphyria to receive either subcutaneous givosiran (2.5 mg per kilogram of body weight) or placebo monthly for 6 months. The primary end point was the annualized rate of composite porphyria attacks among patients with acute intermittent porphyria, the most common subtype of acute hepatic porphyria. (Composite porphyria attacks resulted in hospitalization, an urgent health care visit, or intravenous administration of hemin at home.) Key secondary end points were levels of ALA and porphobilinogen and the annualized attack rate among patients with acute hepatic porphyria, along with hemin use and daily worst pain scores in patients with acute intermittent porphyria. RESULTS A total of 94 patients underwent randomization (48 in the givosiran group and 46 in the placebo group). Among the 89 patients with acute intermittent porphyria, the mean annualized attack rate was 3.2 in the givosiran group and 12.5 in the placebo group, representing a 74% lower rate in the givosiran group (P<0.001); the results were similar among the 94 patients with acute hepatic porphyria. Among the patients with acute intermittent porphyria, givosiran led to lower levels of urinary ALA and porphobilinogen, fewer days of hemin use, and better daily scores for pain than placebo. Key adverse events that were observed more frequently in the givosiran group were elevations in serum aminotransferase levels, changes in serum creatinine levels and the estimated glomerular filtration rate, and injection-site reactions. CONCLUSIONS Among patients with acute intermittent porphyria, those who received givosiran had a significantly lower rate of porphyria attacks and better results for multiple other disease manifestations than those who received placebo. The increased efficacy was accompanied by a higher frequency of hepatic and renal adverse events.

American Journal of Gastroenterology

International Journal of Molecular Sciences

Protein-bound uremic toxins, such as p-cresol sulfate (PCS), can be accumulated with declined ren... more Protein-bound uremic toxins, such as p-cresol sulfate (PCS), can be accumulated with declined renal function and aging and is closely linked with central nervous system (CNS) diseases. In the periphery, PCS has effects on oxidative stress and inflammation. Since oxidative stress and inflammation have substantial roles in the pathogenesis of neurological disorders, the CNS effects of PCS were investigated in unilateral nephrectomized C57/BL/6 mice. Unlike intact mice, unilateral nephrectomized mice showed increased circulating levels of PCS after exogenous administration. Upon PCS exposure, the unilateral nephrectomized mice developed depression-like, anxiety-like, and cognitive impairment behaviors with brain PCS accumulation in comparison with the nephrectomy-only group. In the prefrontal cortical tissues, neuronal cell survival and neurogenesis were impaired along with increased apoptosis, oxidative stress, and neuroinflammation. Circulating brain-derived neurotrophic factors (BDN...

International Journal of Molecular Sciences

Clinically, high cyclooxygenase-2 expression in malignant glioma correlates well with poor progno... more Clinically, high cyclooxygenase-2 expression in malignant glioma correlates well with poor prognosis and the use of aspirin is associated with a reduced risk of glioma. To extend the current understanding of the apoptotic potential of aspirin in most cell types, this study provides evidence showing that aspirin induced glioma cell apoptosis and inhibited tumor growth, in vitro and in vivo. We found that the human H4 glioma cell-killing effects of aspirin involved mitochondria-mediated apoptosis accompanied by endoplasmic reticulum (ER) stress, Noxa upregulation, Mcl-1 downregulation, Bax mitochondrial distribution and oligomerization, and caspase 3/caspase 8/caspase 9 activation. Genetic silencing of Noxa or Bax attenuated aspirin-induced viability loss and apoptosis, while silencing Mcl-1 augmented the effects of aspirin. Data from genetic and pharmacological studies revealed that the axis of ER stress comprised an apoptotic cascade leading to Noxa upregulation and apoptosis. The a...

Cells

Obesity is associated with a wide range of chronic diseases, including cancer. It has been noted ... more Obesity is associated with a wide range of chronic diseases, including cancer. It has been noted that the integration of metabolic mechanisms in obese patients may predispose them to suffer from cancer incidence and its progression. Thus, a better understanding of metabolic alterations in obesity, along with the development of feasible therapeutic approaches for intervention, are theoretically relevant to the prevention and treatment of cancer malignancy. Using a syngeneic tumor model involving Lewis Lung Carcinoma (LLC) cells and C57BL/6 mice fed with a high fat diet, obesity was found to be associated with dysregulated glucose and glutamine metabolism, inflammation, along with platelet activation and the promotion of tumor growth. Tumor-bearing lowered glucose levels while moderately increasing inflammation, platelet activation, and glutamine levels. The antiplatelet drug aspirin, mitigated tumor growth in obese mice, paralleled by a decrease in systemic glucose, insulin, inflamma...

Clinical and Applied Thrombosis/Hemostasis

There has been an ongoing debate as to whether hemophilia A (HA) is more severe than hemophilia B... more There has been an ongoing debate as to whether hemophilia A (HA) is more severe than hemophilia B (HB), and there are studies supporting each side of the argument. The study aimed to investigate whether any differences in major bleeding events exist between patients with severe HA and HB. A nationwide, population-based retrospective cohort study using the National Health Insurance Research Database was conducted. We compared 658 patients with severe HA and 137 patients with severe HB without inhibitors from 1997 to 2013, during the period when adult patients older than 18 years old were treated with the on-demand therapy since birth. There was no significant difference between patients with severe HA and HB in the rate of major bleeding events, with an adjusted relative ratio of 0.79 (95% confidence interval [CI]: 0.36-1.71, P = .548). There was also no significant difference in the incidence rate of major bleeding events between adult patients with HA and HB with the on-demand ther...

American Journal of Gastroenterology

Blood Coagulation & Fibrinolysis

The Journal of Pediatrics

A 5.5-year-old boy was brought to the outpatient clinic for assessment of a progressively dilated... more A 5.5-year-old boy was brought to the outpatient clinic for assessment of a progressively dilated vein over the lower abdomen since infancy. The vein became larger when he was standing up. In addition, he complained of swelling and pain in the right lower limb while walking for a long distance or standing for a long time. Physical examination revealed an engorged superficial vein crossing suprapubic area approximately 7 cm in length. A purple stain with irregular borders was noted in his right thigh, which was 2 cm larger in girth than the opposite thigh (Figure 1). No macrocephaly, digital anomalies, or epidermal nevi was noticed. The patient's growth and development were appropriate for his age. A multipledetector computed tomography showed deep venous malformation with absent right femoral vein (Figure 2; available at www.jpeds.com). Klippel-Trenaunay syndrome (KTS) was diagnosed. A compression stocking was applied, and reduced swelling and pain of the right leg was noted during follow-up. The clinical features of KTS are port-wine stain, venous malformation, and limb hypertrophy, with or without lymphatic anomalies. 1 A port-wine stain is a pink to reddish-purple birthmark caused by the capillary malformation in the skin. It occurs from birth, and is mostly observed on the lower extremities. Venous malformation refers to superficial or deep venous system affected, such as femoral vein aplasia in this patient. Limb hypertrophy is caused by soft tissue and/or bony overgrowth. Pain of affected limb is one of the common complications of KTS. 2 Conservative management with compression stocking can be applied to most of these patients. 3 n

Journal of the Chinese Medical Association

Clinical and Applied Thrombosis/Hemostasis

Recurrent hemarthrosis in patients with hemophilia (PWH) results in chronic arthropathy requiring... more Recurrent hemarthrosis in patients with hemophilia (PWH) results in chronic arthropathy requiring total joint replacement (TJR). This study aimed to compare the difference in TJR rate between patients with hemophilia A (HA) and hemophilia B (HB). A final total of 935 PWH (782 HA and 153 HB) without inhibitors were collected from the Taiwan's National Health Insurance Research Database between 1997 and 2013. Demographics, clinical characteristics, and TJR rate were compared between the 2 groups. The annual use of clotting factor concentrate was not different between HA and HB groups (P ¼ .116). The rate of comorbidities except for 29 PWH having HIV who were all in the HA group was also not different between the 2 groups. A total of 99 (10.6%) PWH had undergone 142 TJR procedures during the study period. All of them had received on-demand therapy. No difference was found in the cumulative incidence of TJR between HA and HB (P ¼ .787). After adjusting for various confounders including age, pyogenic arthritis, and HIV infection, no increased risk of TJR was found in patients with HA versus Patients with HB (hazard ratio: 0.92, 95% confidence interval 0.54-1.58). This finding suggests that the rate of TJR between patients with HA and HB is not significantly different.

PeerJ

Background Dry eye disease (DED), a chronic ocular disease, is associated with numerous medical i... more Background Dry eye disease (DED), a chronic ocular disease, is associated with numerous medical issues, including asthma. However, studies on these associations are limited. In this study, we investigated the incidence of DED among patients with asthma and its correlation with other allergic comorbidities. Methods We retrospectively analyzed data from the National Health Insurance Research Database of Taiwan. We compared the data of 41,229 patients with asthma with those of 164,916 sex- and age-matched non-asthma controls. We followed up the patient and control groups from 1998 to 2010, and compared the rate of DED in these two groups. We further analyzed the allergic comorbidities and asthma-related medication use among the patients with asthma to verify whether these factors were associated with DED. Results The patients in the asthma group were more likely to have DED than were the controls (6.35% vs. 4.92%, p < 0.0001). In the asthma group, female had a higher risk of DED (od...

IUBMB Life

Renal ischemia/reperfusion (I/R) is an alternation of renal hemodynamics, which results in divers... more Renal ischemia/reperfusion (I/R) is an alternation of renal hemodynamics, which results in diverse postischemic responses and eventually acute kidney injury. Although renal ischemic preconditioning (IPC) is known to protect the kidney from I/R injury, the precise renoprotective mechanisms are not completely understood. The multiple renoprotective effects of IPC underscore the importance in understanding molecular mechanisms and the targets of action involved. This study aimed to identify the biochemical changes in renal I/R injury and investigate the renoprotective mechanisms of IPC. Herein, renal I/R was produced in adult male Sprague-Dawley rats through the bilateral ligation of renal pedicles for 45 min, followed by reperfusion for 24 h. For the IPC group, rats were subjected to three cycles of 2-min ischemia, followed by a 5-min reperfusion, 15 min prior to renal I/R. Our data confirmed the beneficial effects that IPC has on renal I/R injury. IPC-mediated renoprotection was associated with the resolution of oxidative stress, inflammation, apoptosis, and hyperglycemia. Among the numerous signaling molecules involved in the renoprotective mechanisms of IPC, an elevated protein expression of Nrf2, HO-1, LC3 II conversion, along with Atg12 and protein phosphorylation of AMPK, as well as a decreased protein phosphorylation of ERK, p38 MAPK, and Akt and NF-κB DNA binding activity were identified. Importantly, the post renal I/R overproduction of counter-regulatory hormones, impaired hepatic insulin action, and augmented hepatic gluconeogenesis were improved through IPC. As counter-regulatory hormones have been implicated in the induction of oxidative stress, inflammation, apoptosis, impaired insulin action, hyperglycemia, and tissue destruction, our findings suggest that counter-regulatory hormones may well be valuable targets of IPC for combatting renal I/R injury. © 2018 IUBMB Life, 2018.

Biochemical and biophysical research communications, Jan 12, 2018

Aspirin is a novel chemopreventive agent against malignancy. However, outcomes of aspirin monothe... more Aspirin is a novel chemopreventive agent against malignancy. However, outcomes of aspirin monotherapy of renal cell carcinoma (RCC) are inconsistent across studies. ABT-737, an BH3 mimetic inhibitor, is also a promising antitumor drug. Cancer cells including those from RCC, that have high levels of Mcl-1, are refractory to ABT-737-induced apoptosis. We here investigated how aspirin treatment modulates the ABT-737-induced apoptosis. Using the in vitro model of human 786-O cells, we showed that aspirin had sensitized cells to ABT-737 induced apoptosis. Such aspirin-induced changes of ABT-737 resistance was accompanied by a host of biochemical events like protein phosphatase 2A (PP2A) activation, AKT dephosphorylation, Mcl-1/FLICE inhibiting protein (FLIP)/XIAP downregulation, and Bax mitochondrial redistribution. The PP2A inhibitor, okadaic acid, was able to reverse the apirin-induced apoptotic changes. Apart from the aspirin treatment, Mcl-1 silencing also rendered cells vulnerable t...

BMC pediatrics, Jan 2, 2018

Cholangitis may affect liver failure of biliary atresia (BA) patients after Kasai portoenterostom... more Cholangitis may affect liver failure of biliary atresia (BA) patients after Kasai portoenterostomy (KP). We examined whether the number of cholangitis episodes could be a prognostic marker for liver transplant (LT) in children with BA after Kasai portoenterostomy (KP). Data for BA patients born after 1998 and undergoing KP were obtained from National Health Insurance Research Database (NHIRD), Taiwan. Patients were followed up until the end of 2011. Incidence and the number of cholangitis episodes were recorded and compared between patients based on LT status. Ninety-six (26.8%) of the 366 BA patients underwent LT. More patients who underwent KP at < 60 days of age survived with their native liver (P = 0.007). The mean age at first cholangitis was 0.9 years and 0.8 years in the LT and non-LT groups, respectively (P = 0.868). The cumulative incidence of cholangitis within 2 years after KP did not differ between the groups (hazard ratio 1.2; 95% CI 0.9-1.6). However, the total numb...

Pediatrics & Neonatology, 2020

Turkish Journal of Hematology, 2019

American journal of hematology, Jan 11, 2016

to infliximab therapy in luminal and fistulizing Crohn’s disease. Aliment Pharmacol Ther 2005;22:... more to infliximab therapy in luminal and fistulizing Crohn’s disease. Aliment Pharmacol Ther 2005;22:613–626. 4. Vega MI, Huerta-Yepez S, Jazirehi AR, et al. Rituximab (chimeric anti-CD20) sensitizes BNHL cell lines to Fas-induced apoptosis. Oncogene 2005;24:8114–8127. 5. Villa-Morales M, Gonz alez-Gugel E, Shahbazi MN, et al. Modulation of the FAS-apoptosissignalling pathway by functional polymorphisms at Fas, FasL and Fadd and their implication in T-cell lymphoblastic lymphoma susceptibility. Carcinogenesis 2010;31:2165–2171. 6. Heredia-Galvez B, Ruiz-Cosano J, Torres-Moreno D, et al. Association of polymorphisms in TRAIL1 and TRAILR1 genes with susceptibility to lymphomas. Ann Hematol 2014;93: 243–247.

New England Journal of Medicine, 2020

BACKGROUND Up-regulation of hepatic delta-aminolevulinic acid synthase 1 (ALAS1), with resultant ... more BACKGROUND Up-regulation of hepatic delta-aminolevulinic acid synthase 1 (ALAS1), with resultant accumulation of delta-aminolevulinic acid (ALA) and porphobilinogen, is central to the pathogenesis of acute attacks and chronic symptoms in acute hepatic porphyria. Givosiran, an RNA interference therapy, inhibits ALAS1 expression. METHODS In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned symptomatic patients with acute hepatic porphyria to receive either subcutaneous givosiran (2.5 mg per kilogram of body weight) or placebo monthly for 6 months. The primary end point was the annualized rate of composite porphyria attacks among patients with acute intermittent porphyria, the most common subtype of acute hepatic porphyria. (Composite porphyria attacks resulted in hospitalization, an urgent health care visit, or intravenous administration of hemin at home.) Key secondary end points were levels of ALA and porphobilinogen and the annualized attack rate among patients with acute hepatic porphyria, along with hemin use and daily worst pain scores in patients with acute intermittent porphyria. RESULTS A total of 94 patients underwent randomization (48 in the givosiran group and 46 in the placebo group). Among the 89 patients with acute intermittent porphyria, the mean annualized attack rate was 3.2 in the givosiran group and 12.5 in the placebo group, representing a 74% lower rate in the givosiran group (P<0.001); the results were similar among the 94 patients with acute hepatic porphyria. Among the patients with acute intermittent porphyria, givosiran led to lower levels of urinary ALA and porphobilinogen, fewer days of hemin use, and better daily scores for pain than placebo. Key adverse events that were observed more frequently in the givosiran group were elevations in serum aminotransferase levels, changes in serum creatinine levels and the estimated glomerular filtration rate, and injection-site reactions. CONCLUSIONS Among patients with acute intermittent porphyria, those who received givosiran had a significantly lower rate of porphyria attacks and better results for multiple other disease manifestations than those who received placebo. The increased efficacy was accompanied by a higher frequency of hepatic and renal adverse events.

American Journal of Gastroenterology

International Journal of Molecular Sciences

Protein-bound uremic toxins, such as p-cresol sulfate (PCS), can be accumulated with declined ren... more Protein-bound uremic toxins, such as p-cresol sulfate (PCS), can be accumulated with declined renal function and aging and is closely linked with central nervous system (CNS) diseases. In the periphery, PCS has effects on oxidative stress and inflammation. Since oxidative stress and inflammation have substantial roles in the pathogenesis of neurological disorders, the CNS effects of PCS were investigated in unilateral nephrectomized C57/BL/6 mice. Unlike intact mice, unilateral nephrectomized mice showed increased circulating levels of PCS after exogenous administration. Upon PCS exposure, the unilateral nephrectomized mice developed depression-like, anxiety-like, and cognitive impairment behaviors with brain PCS accumulation in comparison with the nephrectomy-only group. In the prefrontal cortical tissues, neuronal cell survival and neurogenesis were impaired along with increased apoptosis, oxidative stress, and neuroinflammation. Circulating brain-derived neurotrophic factors (BDN...

International Journal of Molecular Sciences

Clinically, high cyclooxygenase-2 expression in malignant glioma correlates well with poor progno... more Clinically, high cyclooxygenase-2 expression in malignant glioma correlates well with poor prognosis and the use of aspirin is associated with a reduced risk of glioma. To extend the current understanding of the apoptotic potential of aspirin in most cell types, this study provides evidence showing that aspirin induced glioma cell apoptosis and inhibited tumor growth, in vitro and in vivo. We found that the human H4 glioma cell-killing effects of aspirin involved mitochondria-mediated apoptosis accompanied by endoplasmic reticulum (ER) stress, Noxa upregulation, Mcl-1 downregulation, Bax mitochondrial distribution and oligomerization, and caspase 3/caspase 8/caspase 9 activation. Genetic silencing of Noxa or Bax attenuated aspirin-induced viability loss and apoptosis, while silencing Mcl-1 augmented the effects of aspirin. Data from genetic and pharmacological studies revealed that the axis of ER stress comprised an apoptotic cascade leading to Noxa upregulation and apoptosis. The a...

Cells

Obesity is associated with a wide range of chronic diseases, including cancer. It has been noted ... more Obesity is associated with a wide range of chronic diseases, including cancer. It has been noted that the integration of metabolic mechanisms in obese patients may predispose them to suffer from cancer incidence and its progression. Thus, a better understanding of metabolic alterations in obesity, along with the development of feasible therapeutic approaches for intervention, are theoretically relevant to the prevention and treatment of cancer malignancy. Using a syngeneic tumor model involving Lewis Lung Carcinoma (LLC) cells and C57BL/6 mice fed with a high fat diet, obesity was found to be associated with dysregulated glucose and glutamine metabolism, inflammation, along with platelet activation and the promotion of tumor growth. Tumor-bearing lowered glucose levels while moderately increasing inflammation, platelet activation, and glutamine levels. The antiplatelet drug aspirin, mitigated tumor growth in obese mice, paralleled by a decrease in systemic glucose, insulin, inflamma...

Clinical and Applied Thrombosis/Hemostasis

There has been an ongoing debate as to whether hemophilia A (HA) is more severe than hemophilia B... more There has been an ongoing debate as to whether hemophilia A (HA) is more severe than hemophilia B (HB), and there are studies supporting each side of the argument. The study aimed to investigate whether any differences in major bleeding events exist between patients with severe HA and HB. A nationwide, population-based retrospective cohort study using the National Health Insurance Research Database was conducted. We compared 658 patients with severe HA and 137 patients with severe HB without inhibitors from 1997 to 2013, during the period when adult patients older than 18 years old were treated with the on-demand therapy since birth. There was no significant difference between patients with severe HA and HB in the rate of major bleeding events, with an adjusted relative ratio of 0.79 (95% confidence interval [CI]: 0.36-1.71, P = .548). There was also no significant difference in the incidence rate of major bleeding events between adult patients with HA and HB with the on-demand ther...

American Journal of Gastroenterology

Blood Coagulation & Fibrinolysis

The Journal of Pediatrics

A 5.5-year-old boy was brought to the outpatient clinic for assessment of a progressively dilated... more A 5.5-year-old boy was brought to the outpatient clinic for assessment of a progressively dilated vein over the lower abdomen since infancy. The vein became larger when he was standing up. In addition, he complained of swelling and pain in the right lower limb while walking for a long distance or standing for a long time. Physical examination revealed an engorged superficial vein crossing suprapubic area approximately 7 cm in length. A purple stain with irregular borders was noted in his right thigh, which was 2 cm larger in girth than the opposite thigh (Figure 1). No macrocephaly, digital anomalies, or epidermal nevi was noticed. The patient's growth and development were appropriate for his age. A multipledetector computed tomography showed deep venous malformation with absent right femoral vein (Figure 2; available at www.jpeds.com). Klippel-Trenaunay syndrome (KTS) was diagnosed. A compression stocking was applied, and reduced swelling and pain of the right leg was noted during follow-up. The clinical features of KTS are port-wine stain, venous malformation, and limb hypertrophy, with or without lymphatic anomalies. 1 A port-wine stain is a pink to reddish-purple birthmark caused by the capillary malformation in the skin. It occurs from birth, and is mostly observed on the lower extremities. Venous malformation refers to superficial or deep venous system affected, such as femoral vein aplasia in this patient. Limb hypertrophy is caused by soft tissue and/or bony overgrowth. Pain of affected limb is one of the common complications of KTS. 2 Conservative management with compression stocking can be applied to most of these patients. 3 n

Journal of the Chinese Medical Association

Clinical and Applied Thrombosis/Hemostasis

Recurrent hemarthrosis in patients with hemophilia (PWH) results in chronic arthropathy requiring... more Recurrent hemarthrosis in patients with hemophilia (PWH) results in chronic arthropathy requiring total joint replacement (TJR). This study aimed to compare the difference in TJR rate between patients with hemophilia A (HA) and hemophilia B (HB). A final total of 935 PWH (782 HA and 153 HB) without inhibitors were collected from the Taiwan's National Health Insurance Research Database between 1997 and 2013. Demographics, clinical characteristics, and TJR rate were compared between the 2 groups. The annual use of clotting factor concentrate was not different between HA and HB groups (P ¼ .116). The rate of comorbidities except for 29 PWH having HIV who were all in the HA group was also not different between the 2 groups. A total of 99 (10.6%) PWH had undergone 142 TJR procedures during the study period. All of them had received on-demand therapy. No difference was found in the cumulative incidence of TJR between HA and HB (P ¼ .787). After adjusting for various confounders including age, pyogenic arthritis, and HIV infection, no increased risk of TJR was found in patients with HA versus Patients with HB (hazard ratio: 0.92, 95% confidence interval 0.54-1.58). This finding suggests that the rate of TJR between patients with HA and HB is not significantly different.

PeerJ

Background Dry eye disease (DED), a chronic ocular disease, is associated with numerous medical i... more Background Dry eye disease (DED), a chronic ocular disease, is associated with numerous medical issues, including asthma. However, studies on these associations are limited. In this study, we investigated the incidence of DED among patients with asthma and its correlation with other allergic comorbidities. Methods We retrospectively analyzed data from the National Health Insurance Research Database of Taiwan. We compared the data of 41,229 patients with asthma with those of 164,916 sex- and age-matched non-asthma controls. We followed up the patient and control groups from 1998 to 2010, and compared the rate of DED in these two groups. We further analyzed the allergic comorbidities and asthma-related medication use among the patients with asthma to verify whether these factors were associated with DED. Results The patients in the asthma group were more likely to have DED than were the controls (6.35% vs. 4.92%, p < 0.0001). In the asthma group, female had a higher risk of DED (od...

IUBMB Life

Renal ischemia/reperfusion (I/R) is an alternation of renal hemodynamics, which results in divers... more Renal ischemia/reperfusion (I/R) is an alternation of renal hemodynamics, which results in diverse postischemic responses and eventually acute kidney injury. Although renal ischemic preconditioning (IPC) is known to protect the kidney from I/R injury, the precise renoprotective mechanisms are not completely understood. The multiple renoprotective effects of IPC underscore the importance in understanding molecular mechanisms and the targets of action involved. This study aimed to identify the biochemical changes in renal I/R injury and investigate the renoprotective mechanisms of IPC. Herein, renal I/R was produced in adult male Sprague-Dawley rats through the bilateral ligation of renal pedicles for 45 min, followed by reperfusion for 24 h. For the IPC group, rats were subjected to three cycles of 2-min ischemia, followed by a 5-min reperfusion, 15 min prior to renal I/R. Our data confirmed the beneficial effects that IPC has on renal I/R injury. IPC-mediated renoprotection was associated with the resolution of oxidative stress, inflammation, apoptosis, and hyperglycemia. Among the numerous signaling molecules involved in the renoprotective mechanisms of IPC, an elevated protein expression of Nrf2, HO-1, LC3 II conversion, along with Atg12 and protein phosphorylation of AMPK, as well as a decreased protein phosphorylation of ERK, p38 MAPK, and Akt and NF-κB DNA binding activity were identified. Importantly, the post renal I/R overproduction of counter-regulatory hormones, impaired hepatic insulin action, and augmented hepatic gluconeogenesis were improved through IPC. As counter-regulatory hormones have been implicated in the induction of oxidative stress, inflammation, apoptosis, impaired insulin action, hyperglycemia, and tissue destruction, our findings suggest that counter-regulatory hormones may well be valuable targets of IPC for combatting renal I/R injury. © 2018 IUBMB Life, 2018.

Biochemical and biophysical research communications, Jan 12, 2018

Aspirin is a novel chemopreventive agent against malignancy. However, outcomes of aspirin monothe... more Aspirin is a novel chemopreventive agent against malignancy. However, outcomes of aspirin monotherapy of renal cell carcinoma (RCC) are inconsistent across studies. ABT-737, an BH3 mimetic inhibitor, is also a promising antitumor drug. Cancer cells including those from RCC, that have high levels of Mcl-1, are refractory to ABT-737-induced apoptosis. We here investigated how aspirin treatment modulates the ABT-737-induced apoptosis. Using the in vitro model of human 786-O cells, we showed that aspirin had sensitized cells to ABT-737 induced apoptosis. Such aspirin-induced changes of ABT-737 resistance was accompanied by a host of biochemical events like protein phosphatase 2A (PP2A) activation, AKT dephosphorylation, Mcl-1/FLICE inhibiting protein (FLIP)/XIAP downregulation, and Bax mitochondrial redistribution. The PP2A inhibitor, okadaic acid, was able to reverse the apirin-induced apoptotic changes. Apart from the aspirin treatment, Mcl-1 silencing also rendered cells vulnerable t...

BMC pediatrics, Jan 2, 2018

Cholangitis may affect liver failure of biliary atresia (BA) patients after Kasai portoenterostom... more Cholangitis may affect liver failure of biliary atresia (BA) patients after Kasai portoenterostomy (KP). We examined whether the number of cholangitis episodes could be a prognostic marker for liver transplant (LT) in children with BA after Kasai portoenterostomy (KP). Data for BA patients born after 1998 and undergoing KP were obtained from National Health Insurance Research Database (NHIRD), Taiwan. Patients were followed up until the end of 2011. Incidence and the number of cholangitis episodes were recorded and compared between patients based on LT status. Ninety-six (26.8%) of the 366 BA patients underwent LT. More patients who underwent KP at < 60 days of age survived with their native liver (P = 0.007). The mean age at first cholangitis was 0.9 years and 0.8 years in the LT and non-LT groups, respectively (P = 0.868). The cumulative incidence of cholangitis within 2 years after KP did not differ between the groups (hazard ratio 1.2; 95% CI 0.9-1.6). However, the total numb...