Huei-Jane Lee

Polyphenols extracted from Hibiscus sabdariffa L. inhibited lipopolysaccharide-induced inflammation by improving antioxidative conditions and regulating cyclooxygenase-2 expression.

Oxidative stress and inflammation are related to several chronic diseases including cancer and atherosclerosis. Hibiscus sabdariffa Linnaeus has been found to possess antioxidant effects. In this study, polyphenols extracted from Hibiscus sabdariffa L. (HPE) were used to detect anti-inflammatory effects on nitrite and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS) treated RAW264.7 cells. Sequentially, an animal model examination was performed to confirm the effects of HPE on LPS-induced hepatic inflammation. The results showed that HPE reduced 94.6% of xanthine oxidase activity in vitro, and decreased nitrite and PGE2 secretions in LPS-induced cells. In LPS-treated rats, HPE significantly decreased the serum levels of alanine and aspartate aminotransferase. In the liver, lipid peroxidation and liver lesions decreased, and catalase activity and glutathione increased. The study also revealed that down-regulation of cyclooxygenase-2 (COX-2), p-c-Jun N-terminal kinase (p-JNK) and p-P38 might have been involved. In sum, this study found an anti-inflammatory potency of HPE both in vitro and in vivo.

Polyphenol extracts from Hibiscus sabdariffa linnaeus attenuate nephropathy in experimental type 1 diabetes.

Diabetic nephropathy progressed to end-stage renal disease (ESRD) is found in type 1 or type 2 diabetes. Oxidative stress is one of the precipitation factors in diabetic nephropathy. Previously, Hibiscus sabdariffa Linnaeus and its polyphenol extracts were found to possess antioxidative effects. This study is aimed to investigate the effect of Hibiscus sabdariffa L. polyphenol extract (HPE) in streptozotocin (STZ) induced diabetic nephropathy. The results show that HPE reduced kidney mass induced by STZ significantly, as well as improving hydropic change of renal proximal convoluted tubules in the rats. HPE also significantly reduced serum triglyceride, total cholesterol and LDL in STZ induced rats. Treatment with HPE significantly increased the activity of catalase and glutathione and reduced lipid peroxidation (thiobarbituric acid-reactive substances, TBARS). The findings of this research show the beneficial effects of HPE on STZ induced diabetic nephropathy including pathology, serum lipid profile and oxidative marker in kidney.

Leigh Syndrome: Clinical and Neuroimaging Follow-Up

Leigh syndrome, caused by dysfunction in mitochondrial energy metabolism, is an inherited, heterogeneous, and progressive neurodegenerative disorder of infancy and childhood. From 1983 to August 2006, 14 cases diagnosed with Leigh syndrome were studied in terms of characteristic neuroimaging findings and abnormal mitochondrial configurations under electron microscopy, as well as molecular analysis. Of the 14 cases, 11 presented clinical features before age 1 (79%). All 14 presented with variable symptoms of central nervous system involvement. The three most common symptoms were developmental delay (12/14; 86%), seizures (11/14; 79%), and altered consciousness (8/14; 57%). Extra-central nervous system manifestations were observed in 10 of the 14 cases, the most common symptoms being failure to thrive (5/14; 36%), pericardial effusion and dilated cardiomyopathy (3/14; 21%), and liver function impairment (3/14; 21%). In all 14 cases, neuroimaging revealed abnormal findings over the basal ganglion, brainstem, or both. The putamen was the most common lesion site in the basal ganglia (11/12; 92%). Cranial magnetic resonance imaging was used for follow-up in 6 cases because of changes in clinical features; in all 6 cases the imaging revealed evolution in the brain. Cranial magnetic resonance spectroscopy was performed in 3 cases and in 2 of them revealed lactate peaks during deterioration of the disease course. The prognosis for Leigh syndrome was poor during long-term follow-up. Seven cases were early fatalities, before 1 year and 6 months of age. Follow-up cranial magnetic resonance imaging together with magnetic resonance spectroscopy in cases with clinical evolution is helpful for monitoring this disease.

Aromatic l-amino acid decarboxylase deficiency in Taiwan

BACKGROUND Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive disorder of neurotransmitter synthesis. It has unique clinical presentations. AIMS The purpose of this study is to delineate the clinical features and molecular spectrum of AADC deficiency in Taiwanese infants and children. METHODS We report eight patients with characteristic clinical manifestations of AADC deficiency. Clinical presentations, treatment response, outcome and mutations of DOPA decarboxylase (DDC) gene were analyzed. RESULTS The clinical manifestations were similar to those previously reported, including symptoms onset before age 1 year with features of severe floppiness, oculogyric crises, athetoid movement, prominent startle response, tongue thrusting, ptosis, paroxysmal diaphoresis, nasal congestion, diarrhea, irritability and sleep disorders. In addition, we observed that all patients (100.0%) had small hands and feet. During the period of follow-up, all of them (100.0%) presented severe floppiness in spite of therapeutic trials with vitamin B6, dopamine agonist, MAO inhibitor and/or anticholinergics. Three different mutations were identified in the DDC gene, including two novel mutations 1303 C>T and 1367ins A and one IVS 6+4 A>T mutation. The IVS 6+4 A>T was a splicing mutation, which inserted an additional 37nt of intron 6 into the DDC mRNA. Thirteen out of 16 alleles (81.3%) carried IVS 6+4 A>T mutation and the IVS 6+4 A>T alleles shared a conserved haplotype. CONCLUSIONS Patients with AADC deficiency in Taiwan have particular clinical manifestations of small hands and feet, which have rarely been mentioned in the literature. The prevalence of IVS 6+4 A>T splicing mutation is high in our study group and the IVS 6+4 A>T mutation might have a founder effect.

Gallic acid induces G2/M phase cell cycle arrest via regulating 14-3-3β release from Cdc25C and Chk2 activation in human bladder transitional carcinoma cells

SCOPE Cell cycle regulation is a critical issue in cancer treatment. Previously, gallic acid (GA) has been reported to possess anticancer ability. Here, we have evaluated the molecular mechanism of GA on cell cycle modulation in a human bladder transitional carcinoma cell line (TSGH-8301 cell). METHODS AND RESULTS Using flow cytometer analysis, exposure of the cells to 40 μM GA resulted in a statistically significant increase in G2/M phase cells, which was accompanied by a decrease in G0/G1 phase cells. GA-treated cells resulted in significant growth inhibition in a dose-dependent manner accompanied by a decrease in cyclin-dependent kinases (Cdk1), Cyclin B1, and Cdc25C, but significant increases in p-cdc2 (Tyr-15) and Cip1/p21 by western blotting. Additional mechanistic studies showed that GA induces phosphorylation of Cdc25C at Ser-216. This mechanism leads to its translocation from the nucleus to the cytoplasm resulting in an increased binding with 14-3-3β. When treated with GA, phosphorylated Cdc25C can be activated by ataxia telangiectasia-mutated checkpoint kinase 2 (Chk2). This might be a DNA damage response as indicated by Ser-139 phosphorylation of histine H2A.X. Furthermore, treatment of the cells with a Chk2 inhibitor significantly attenuated GA-induced G2/M phase arrest. CONCLUSION These results indicate that GA can induce cell cycle arrest at G2/M phase via Chk2-mediated phosphorylation of Cdc25C in a bladder transitional carcinoma cell line.

Aqueous extract of hibiscus sabdariffa L. decelerates acetaminophen-induced acute liver damage by reducing cell death and oxidative stress in mouse experimental models

BACKGROUND Acetaminophen (AAP)-induced oxidative stress can cause cell death to induce liver damage. The antioxidant effect of Hibiscus sabdariffa L. (HS) was shown in previous studies. In this study the effect of HS extract (HSE) on AAP-induced liver injury in BALB/c mice was investigated. RESULTS In vivo, BALB/c mice were fed orally with 200, 400 or 600 mg kg(-1) HSE for 2 weeks and then injected with 1000 mg kg(-1) AAP. Pretreatment with HSE decreased lipid peroxidation and increased catalase activity and glutathione level. It also decreased AAP-induced liver injury, accompanied by decreased expression of pJNK, Bax and tBid in the liver. Additionally, HSE protected BALB/c normal liver cells from AAP-induced damage in vitro. CONCLUSION It has been demonstrated that HSE can protect the mouse liver from AAP-induced injury and that the protective mechanism might involve decreasing oxidative stress and reducing cell death.

A Polyphenol Extract of Hibiscus sabdariffa L. Ameliorates Acetaminophen-Induced Hepatic Steatosis by Attenuating the Mitochondrial Dysfunction in Vivo and in Vitro

Oxidative stress is the major contributor to acetaminophen (AAP)-caused liver damage. It promotes mitochondrial oxidative stress and collapses the mitochondrial membrane potential to cause cell death. We have previously shown that a polyphenol extract of Hibiscus sabdariffa L. (HPE) potentiated the antioxidative effect. We further examined in this study the possible mechanism of HPE against AAP-caused liver damage. BABL/c mice were orally fed with HPE (100, 200 or 300 mg/kg) for two weeks prior to an i.p. injection of 1000 mg/kg of AAP. The mice were decapitated 6 h after the AAP injection to collect the blood and liver for further determination. The results show that pretreating with HPE increased the level of glutathione (GSH), decreased the level of lipid peroxidation, and increased catalase activity in the liver. A histopathological evaluation shows that HPE could decrease AAP-induced liver sterosis accompanied by a decreased expression of AIF, Bax, Bid, and p-JNK in the liver. An in vitro assay revealed that HPE could reduce AAP-induced death of BABL/c normal liver cells (BNLs), reverse the lost mitochondrial potency and improve the antioxidative status, similarly to the results of the in vivo assay. We show in this study that HPE possessed the ability to protect the liver from AAP-caused injury. The protective mechanism might be regulated by decreasing oxidative stress and attenuating the mitochondrial dysfunction.

Cilostazol Ameliorates Nephropathy in Type 1 Diabetic Rats Involving Improvement in Oxidative Stress and Regulation of TGF-β and NF-κB

Diabetic nephropathy is characterized as the progressive development of renal insufficiency in a setting of hyperglycemia. Previous studies indicate that reactive oxygen species (ROS) play an important role in high glucose-induced renal injury. Cilostazol was reported to lower the production of superoxide significantly in situ. We hypothesized that cilostazol administration in streptozotocin-induced diabetic rats exerts effects via improving oxidative stress. Male Sprague–Dawley rats were fed with cilostazol (5 mg/kg or 25 mg/kg) for 12 weeks after streptozotocin-induced diabetes mellitus. The results showed that cilostazol decreased reactive oxygen species activity significantly in the kidneys of diabetic rats and improved the urine albumin/creatinine ratio. Cilostazol can also improve the levels of serum cholesterol, triglyceride, and LDL-cholesterol. Additionally, diabetes-caused increased glomerular size, TGF-β, and NF-κB decreased under treatment with cilostazol in diabetic rats. Our results indicate that cilostazol has beneficial effects in early diabetic nephropathy.

Aqueous Extract of Shi-Liu-Wei-Liu-Qi-Yin Induces G2/M Phase Arrest and Apoptosis in Human Bladder Carcinoma Cells via Fas and Mitochondrial Pathway

Shi-Liu-Wei-Liu-Qi-Yin (SLWLQY) was traditionally used to treat cancers. However, scientific evidence of the anticancer effects still remains undefined. In this study, we aimed to clarify the possible mechanisms of SLWLQY in treating cancer. We evaluated the effects of SLWLQY on apoptosis-related experiments inducing in TSGH-8301 cells by (i) 3-(4,5-dimethylthiazol-zyl)-2,5-diphenylterazolium bromide (MTT) for cytotoxicity; (ii) cell-cycle analysis and (iii) western blot analysis of the G2/M-phase and apoptosis regulatory proteins. Human bladder carcinoma TSGH-8301 cells were transplanted into BALB/c nude mice as a tumor model for evaluating the antitumor effect of SLWLQY. Treatment of SLWLQY resulted in the G2/M phase arrest and apoptotic death in a dose-dependent manner, accompanied by a decrease in cyclin-dependent kinases (cdc2) and cyclins (cyclin B1). SLWLQY stimulated increases in the protein expression of Fas and FasL, and induced the cleavage of caspase-3, caspase-9 and caspase-8. The ratio of Bax/Bcl2 was increased by SLWLQY treatment. SLWLQY markedly reduced tumor size in TSGH-8301 cells-xenografted tumor tissues. In the tissue specimen, SLWLQY up-regulated the expression of Fas, FasL and Bax proteins, and down-regulated Bcl2 as well as in in vitro assay. Our results showed that SLWLQY reduced tumor growth, caused cell-cycle arrest and apoptosis in TSGH-8301 cells via the Fas and mitochondrial pathway.

Reduced expression of transforming growth factor‐β1 and correlated elevation of interleukin‐17 and interferon‐γ in pediatric patients with chronic primary immune thrombocytopenia (ITP)

Dysregulated T helper (Th) cells are considered important in the pathophysiology of chronic primary immune thrombocytopenia (ITP). The present study investigated whether levels of Th cytokines in pediatric patients with chronic ITP were different compared with healthy controls.