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Biomedical subjects

C Y Chu

Publications and source records attributed to C Y Chu.

At least 19 recordsLinked to original sources

Induction of apoptosis by hibiscus protocatechuic acid in human leukemia cells via reduction of retinoblastoma (RB) phosphorylation and Bcl-2 expression.

Hibiscus protocatechuic acid (PCA), a phenolic compound isolated from the dried flower of Hibiscus sabdariffa L. (Malvaceae), demonstrated antioxidant and antitumor promotion effects in our previous study. In the present study, Hibiscus PCA was found to inhibit the survival of human promyelocytic leukemia HL-60 cells in a concentration- and time-dependent manner. The study revealed that HL-60 cells underwent internucleosomal DNA fragmentation and morphological changes characteristic of apoptosis after a 9-hr treatment with Hibiscus PCA (2 mM). Flow cytometric analysis of the DNA content of cells treated with PCA for 12 hr showed that the cells were distributed mainly in the hypodiploid phase (apoptotic peak, 46.7%), less in the G(1) (34.2%) and S phase (14.0%), and few in the G(2)/M phase (5.1%). Moreover, PCA treatment caused an increase in the level of hypophosphorylated retinoblastoma (RB; 180% of control at the 6-hr time point) and, on the contrary, a decline in hyperphosphorylated RB. A rapid loss of RB was observed when the treatment period was extended. Further studies showed that Hibiscus PCA application reduced Bcl-2 protein expression to 47%, and increased Bax protein expression to 181% after 1.5 hr as compared with time 0. Overexpression of Bcl-2 in HL-60 cells delayed the occurrence of Hibiscus PCA-induced apoptosis. These data suggest that Hibiscus PCA is an apoptosis inducer in human leukemia cells, and that RB phosphorylation and Bcl-2 protein may play a crucial role in the early stage.

Antineoplastic Agents↗

Protective effect of Hibiscus anthocyanins against tert-butyl hydroperoxide-induced hepatic toxicity in rats.

Hibiscus anthocyanins (HAs), a group of natural pigments occurring in the dried flowers of Hibiscus sabdariffa L., which is a local soft drink material and medical herb, were studied for antioxidant bioactivity. The preliminary study showed that HAs were able to quench the free radicals of 1,1-diphenyl-2-picrylhydrazyl. This antioxidant bioactivitiy was further evaluated using the model of tert-butyl hydroperoxide (t-BHP)-induced cytotoxicity in rat primary hepatocytes and hepatotoxicity in rats. The results demonstrated that HAs, at the concentrations of 0.10 and 0.20 mg/ml, significantly decreased the leakage of lactate dehydrogenase and the formation of malondialdehyde induced by a 30-min treatment of t-BHP (1.5 mM). The in vivo investigation showed that the oral pretreatment of HAs (100 and 200 mg/kg) for 5 days before a single dose of t-BHP (0.2 mmol/kg, ip) significantly lowered the serum levels of hepatic enzyme markers (alanine and aspartate aminotransferase) and reduced oxidative liver damage. The histopathological evaluation of the liver revealed that Hibiscus pigments reduced the incidence of liver lesions including inflammatory, leucocyte infiltration, and necrosis induced by t-BHP in rats. Based on the results described above, we speculate that Hibiscus pigments may play a role in the prevention of oxidative damage in living systems.

Alanine Transaminase↗

Fixed erythrodysaesthesia plaque due to intravenous injection of docetaxel.

Docetaxel (Taxotere), a semisynthetic taxoid, acts as an antimicrotubule agent and is considered to have great potential in the treatment of non-small cell lung cancer, advanced breast cancer, ovarian cancer and some other tumours. Well-recognized side-effects include dose-limiting neutropenia, fluid retention, myalgia, neuropathy, hypersensitivity reaction, alopecia, mucositis, nail changes and cutaneous reactions such as acral erythema. We describe a unique docetaxel-induced cutaneous reaction presenting as fixed erythematous plaque(s) unrelated to extravasation or previous skin injury; histopathological studies were performed in three of the four cases.

Adult↗

The SCFbeta-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro.

Ubiquitin-mediated proteolysis has a central role in controlling the intracellular levels of several important regulatory molecules such as cyclins, CKIs, p53, and IkappaBalpha. Many diverse proinflammatory signals lead to the specific phosphorylation and subsequent ubiquitin-mediated destruction of the NF-kappaB inhibitor protein IkappaBalpha. Substrate specificity in ubiquitination reactions is, in large part, mediated by the specific association of the E3-ubiquitin ligases with their substrates. One class of E3 ligases is defined by the recently described SCF complexes, the archetype of which was first described in budding yeast and contains Skp1, Cdc53, and the F-box protein Cdc4. These complexes recognize their substrates through modular F-box proteins in a phosphorylation-dependent manner. Here we describe a biochemical dissection of a novel mammalian SCF complex, SCFbeta-TRCP, that specifically recognizes a 19-amino-acid destruction motif in IkappaBalpha (residues 21-41) in a phosphorylation-dependent manner. This SCF complex also recognizes a conserved destruction motif in beta-catenin, a protein with levels also regulated by phosphorylation-dependent ubiquitination. Endogenous IkappaBalpha-ubiquitin ligase activity cofractionates with SCFbeta-TRCP. Furthermore, recombinant SCFbeta-TRCP assembled in mammalian cells contains phospho-IkappaBalpha-specific ubiquitin ligase activity. Our results suggest that an SCFbeta-TRCP complex functions in multiple transcriptional programs by activating the NF-kappaB pathway and inhibiting the beta-catenin pathway.

Amino Acid Sequence↗

Inhibitory effect of 12-O-tetradecanoylphorbol-13-acetate-caused tumor promotion in benzo[a]pyrene-initiated CD-1 mouse skin by baicalein.

The effects of topical application of baicalein on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced promotion of skin tumors, hyperplasia, ornithine decarboxylase activity, and inflammation were evaluated in female CD-1 mice. Topical application of baicalein (0.08, 0.16, or 0.2 mumol) with TPA (5 nmol) twice weekly for 24 weeks to mice previously initiated with benzo[a]pyrene inhibited the number of TPA-induced tumors per mouse significantly. Preapplication of the same amount of baicalein also afforded significant protection against TPA-induced hyperplasia in the ear skin. Topical application of baicalein inhibited tumor promoter-caused induction of epidermal ornithine decarboxylase activity by TPA (5 nmol). The topical application of baicalein (0.008, 0.016, or 0.02 mumol) inhibited TPA-induced edema of mouse ears by 88%, 96%, or 97%, respectively. Pretreatment of mouse skin with various amounts of baicalein caused inhibition of H2O2 and myeloperoxidase formation by TPA. These results indicate that baicalein can be a potential cancer-chemopreventive agent against tumor promotion.

Animals↗

Individual sex preferences and the population sex ratio of newborns.

This paper proposes the hypothesis that countries with stronger sex preferences are more likely to have a negative relationship between crude birth rates and male/female ratios of newborn babies. Conversely, the existence of a significantly negative relationship in any country may also be a supportive evidence of its preferences for sons. Our hypothesis is both behavioral and biological: on the behavioral side, parents with strong sex preferences are inclined to continue to bear children if the existing sex ratio of children is less than desirable. On the biological side, parents with many girls are more likely to be "girl producers", who with individual-specific biological characteristics tend to generate higher female births. We use the macro data in the United Nations Demographic Yearbook to verify and test our hypothesis. For developing countries which do not have reliable micro data on fertility, our approach using macro data is a useful and interesting alternative.

Female↗

Inhibitory effect of Hibiscus protocatechuic acid on tumor promotion in mouse skin.

Hibiscus protocatechuic acid (PCA), a phenolic acid isolated from Hibiscus sabdariffa L., was evaluated for its ability to inhibit the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced promotion in skin tumors of female CD-1 mice. Topical application of PCA (5, 10 or 20 micromol) 5 min prior to TPA (15 nmol) treatment twice weekly for 20 weeks to mice which were initiated with benzo[a]pyrene (B[a]P) inhibited the incidence of tumors in mice to 81.3, 62.5 and 56.3%, respectively, while all mice in the TPA-treated group developed tumors. The average number of tumors in mice pretreated with PCA was 2-4 and that of mice treated only with TPA was 6.6. The protection effects of PCA were also presented by its significant suppression on the TPA-induced hyperplasia in the skin and edema of mouse ears by 65 and 73% at doses of 10 and 20 micromol, respectively. When it was applied to the dorsal surface of CD-1 mice before TPA application, PCA (5, 10 or 20 micromol) inhibited the induction of epidermal ornithine decarboxylase (ODC) activity by 5 nmol TPA and myeloperoxidase (MPO) activity by 6.5 nmol TPA. The same doses of PCA also reduced the formation of hydrogen peroxide in the mouse skin to an inhibition of 61, 84 and 89%, respectively, when compared with that of the TPA-treated group. These results indicate that PCA possesses potential as a cancer chemopreventive agent against tumor promotion.

Animals↗

Protective effects of dried flower extracts of Hibiscus sabdariffa L. against oxidative stress in rat primary hepatocytes.

Dried flower extracts of Hibiscus sabdariffa L., a local soft drink material and medical herb, was found to possess antioxidant activity in the present study. In the preliminary studies, antioxidant potential of three fractions of the ethanol crude extract (HS-C: chloroform-soluble fraction; HS-E: ethyl acetate soluble fraction; HS-R: residual fraction) obtained from the dried flowers of Hibiscus sabdariffa L. were evaluated by their capacity of quenching 1,1 -diphenyl-2-picrylhydrazyl (DPPH) free radical and inhibiting xanthine oxidase (XO) activity. HS-E showed the greatest capacity of scavenging free radical (EC50=0.017mg/ml), and HS-C showed the strongest inhibitory effect on XO activity (EC5o=0.742 mg/ml). Furthermore, antioxidant bioactivities of these crude extracts were investigated using a model of tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in rat primary hepatocytes. All fractions were found to inhibit significantly the unscheduled DNA synthesis (UDS) induced by t-BHP at a concentration of 0.20 mg/ml. HS-C and HS-E also decreased the leakage of lactate dehydrogenase (LDH) and the formation of malondialdehyde (MDA) induced by t-BHP (1.5 mM) considerably at a concentration of 0.10 and 0.20 mg/ml in the rat primary hepatocyte cultures. These results indicated that the dried flower extracts (HS-C and HS-E) of H. sabdariffa L. protect rat hepatocytes from t-BHP-induced cytotoxicity and genotoxicity by different mechanisms.

Animals↗

Nucleus accumbens dopaminergic mediation of protection against gastric mucosal ulcerations by cold-restraint stress in the male hyperprolactinemic rats.

An investigation was undertaken to study the relationship between change in gastric lesion induced by cold-restraint stress and brain dopamine (DA) activity in male rat with chronic hyperprolactinemia. Male rats of Wistar strain were divided into two groups: one received extra two pieces of anterior pituitary (AP) from its littermates, the other grafted with several pieces of muscle served as control. Experiment I: From the 5th day to 40th day after transplantation, the levels of serum prolactin (PRL) in the AP-grafted group were higher than those of control (p < 0.05 or p < 0.01). Experiment II: On the 40th day after transplantation, AP-grafted and control rats were restrained and placed supine in a ventilated refrigerator with an ambient temperature of 5 degrees C for 3 hrs. Although gastric mucosal ulceration was observed in both groups, the ulcer index (including total number and length of gastric mucosal ulceration) was lower in AP-grafted group than that in control group (p < 0.05 or p < 0.01). Experiment III: On the 40th day after transplantation, all rats were divided into AP-grafted and muscle-grafted rats. Subsequently, they were allowed to expose to cold-plus-restraint stress and unstress (room temperature: 24 +/- 1 degrees C) respectively. After stress and unstress, all animals were immediately sacrificed by decapitation, the brains were dissected with Palkovits' micropunch technique. DA and its metabolites, DOPAC content in Nucleus accumbens (NAc) area of brain were assayed by HPLC with electrochemical detection. These results showed that concentrations of DA, DOPAC and their ratios (DOPAC/DA) in the NAc area of brain, were not statistically different under room temperature condition between muscle-grafted and AP-grafted rats. The DOPAC/DA ratio in both groups showed significant increase in the brain's NAc area under cold-restraint stress condition as compared with unstress condition. But AP-grafted rats exhibited significantly higher DOPAC content in the brain's NAc area when compared with muscle-grafted rats under cold-restraint stress condition (171.7 +/- 22.1 versus 101.5 +/- 14.2 ng/mg protein, p < 0.05). According to these findings, we suggest that reduced effect of chronic high serum PRL level from extra pituitary grafts on gastric mucosal ulceration produced by cold-restraint stress is probably mediated via Nucleus accumbens dopaminergic neuronal mechanism.

Animals↗

Age-distribution dynamics and aging indexes.

I analyze the dynamics of the age distribution as some vital rates change. When the fertility or mortality rate declines, the age distribution often manifests a dynamic stochastic-dominance relationship. I also propose some alternative indexes for measuring population aging. These indexes are closely connected with the age-distribution dynamics and contain more refined information about the distribution of age among the old.

Adult↗

Hepatotoxicity of 1,3,5-trinitro-2-acetyl pyrrole derived from nitrosation of Maillard reaction product in BALB/C mouse.

1,3,5-Trinitro-2-acetyl pyrrole (TNAP) is a product derived from the reaction of 2-acetyl pyrrole with nitrite in the model of Maillard browning systems. This compound is moderately mutagenic to the Salmonella strains TA98 and TA100 and is markedly cytotoxic to mouse C3H10T1/2 cells. Experiments are performed to investigate the effects of TNAP on the hepatic toxicity in mouse. Male BALB/C mice were subjected to a dose of 7.2 mg/kg body weight twice a week by i.p. injection for 24 weeks, then followed by a feeding diet for 21 weeks. TNAP-treated mice showed an increase in mortality and time-dependent appearance of lesions in the liver. TNAP is hepatotoxic as demonstrated by a marked increase in the activities of serum alanine transaminase (ALT) and aspartic transaminase (AST). TNAP-related lesions observed histologically in mice, included hapatic atrophy, mild fatty metamorphosis with multilocular cysts in the liver. In conclusion, TNAP was considered to be a toxic compound in mice as evidenced by increased incidences of mortality, and lesions of liver.

Alanine Transaminase↗

Promotion of colon carcinogenesis through increasing lipid peroxidation induced in rats by a high cholesterol diet.

To examine the influence of hypercholesteremia on 1,2-dimethylhydrazine (DMH)-induced rat colon cancer, Sprague-Dawley rats received dietary cholesterol (CH, 0-2%) and cholic acid (CA, 0.25%) with or without DMH (20 mg/kg, s.c. injection) for 18 weeks. The rats receiving dietary cholesterol and cholic acid all significantly increased total serum cholesterol and lipids but only a high cholesterol diet (2% CH plus 0.25% CA) decreased the activity of glutathione peroxidase (GSH-Px) and increased the formation of peroxides in the colon (P < 0.01). The rats that received the combination of DMH and high cholesterol diet enhanced these effects. At the end of the experiment, the diet group administered DMH and high cholesterol (2% CH plus 0.25% CA) developed colon adenoma at 50% of incidence in pathological examination, but no colon adenoma formed in the rats treated with high cholesterol alone. It is supposed that a non-carcinogenic agent like cholesterol may potentiate the carcinogenicity of DMH in rats via an increase of lipid peroxidation and decrease in the activity of peroxidase in the target organ.

1,2-Dimethylhydrazine↗

Inhibitory effect of atractylon on tert-butyl hydroperoxide induced DNA damage and hepatic toxicity in rat hepatocytes.

Atractylon, a main sesquiterpenic constituent of Atractylodes rhizomes, was studied for the mechanism of its inhibitory effects on the tert-butyl hydroperoxide (t-BHP)-induced cytotoxicity and lipid peroxidation in primary culture of rat hepatocytes. In the preliminary study, atractylon showed an effective antioxidant property tested by its capacity for quenching 1,1-diphenyl-2-picrylhydrazyl radical (DPPH). Further investigations showed that atractylon at the concentrations of 0.01, 0.1 and 1.0 mg/ml decreased the formation of malondialdehyde (MDA), leakage of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) and repair synthesis of DNA induced by 30-min treatment of t-BHP (1.5 mM) in primary cultured rat hepatocytes. Addition of atractylon also attenuated the genotoxicity of t-BHP evaluated by unscheduled DNA synthesis. The sum of the results suggested that the protective effect of atractylon against oxidative stress induced by t-BHP is via its ability to quench free radicals.

Animals↗

The effect of fissure morphology and pretreatment of the enamel surface on penetration and adhesion of fissure sealants.

Fissure sealants have been used successfully as a means of preventing fissure caries. This effectiveness is directly related to sealant retention and retention is dependent upon a meticulous method of application. The aims of this study were to determine if sealant adhesion and penetration were affected by the variation in preparation of the enamel surface, or by pretreatment of the enamel surface with dentine adhesive systems, in fissures of varying morphology. Non-carious posterior teeth were visually examined and sorted according to fissure type, classified as shallow, deep or intermediate. Occlusal fissures were sealed using one of six methods, thermocycled for 200 cycles between 5 and 55 degrees C, in artificial saliva, then placed in a 1.5% procion orange dye for 3 min. Teeth were sectioned bucco-lingually and examined with a light microscope for (i) penetration of the sealant into the fissure pattern and (ii) adhesion of the sealant. All sealant techniques employed in this study adapted well to the enamel surface as the 1.5% procion Reactive orange dye failed to penetrate any of the sealed tooth sections. Shallow fissures were well obturated in both lateral and vertical dimensions. Sealants adapted well to the vertical walls at the orifice of deep fissures but generally failed to penetrate into the deeper aspects. Reducing the etching period with 37% phosphoric acid resulted in increased voids between the sealant and enamel surface and poorer adaptation to the vertical walls. The addition of dentine adhesive systems, Scotchbond Multi-Purpose and All-Bond 2, enhanced the vertical penetration of the sealant, particularly in deep fissures. It is proposed that the dentine adhesive systems may improve the retention rate of sealants in deep fissures particularly if the fissure is not completely dry prior to resin placement.

Acid Etching, Dental↗

Terbutaline nebulization and epinephrine injection in treating acute asthmatic children.

Ninety children with acute asthma, equally divided into two study groups, were studied to compare the efficacy and safety of nebulized terbutaline with injected epinephrine in the treatment of acute exacerbation. The terbutaline group received 2 ml (5,0 mg) terbutaline solution diluted with 2 ml 0.9% saline for inhalation over 10 minutes; the epinephrine group received 0.01 ml/kg of 1:1000 epinephrine (maximum 0,3 ml) through subcutaneous injection at deltoid area. Spirometry, pulse oximetry, and clinical severity scoring system were evaluated at baseline and again 15 minutes after treatment. The baseline data of the two groups were not significantly different. The clinical severity score and spirometry of both groups were significantly improved after treatment. Compared with the terbutaline group, the epinephrine group had better mean oxygen saturation (SaO2; p < 0.001), frequency of oxygen desaturation (p = 0.0028) and forced expiratory flow 25-75% (FEF25-75%, p = 0.027). For those patients with initial forced expiratory volume in one second (FEV1) lower than 60% of predicted value, epinephrine treatment was more effective in the improvement of FEV1, FEF25-75%, and oxygen saturation (SaO2) (p = 0.011, 0.012, and 0.006, respectively). A Significantly higher rate of adverse effects occurred in patients given epinephrine (47% vs 11%, p = 0.0002); these included pallor, tremor, dizziness, headache, palpitation, soreness of legs, numbness of extremities, cold sweating, general weakness and nausea. Considering the general trend to noninvasive therapy in children and the more frequent adverse effects after epinephrine injection, such nebulized beta-2 agonists as terbutaline appear preferable for initial therapy of acute asthma if oxygen is supplemented to prevent possible hypoxemia. However, parenteral epinephrine still is worth trying, particularly in any severe, life-threatening attack.

Administration, Inhalation↗

Crocetin protects against oxidative damage in rat primary hepatocytes.

Crocetin is a major component in the fruit of Gardenia jaminoides Ellis, a Chinese herbal medicine. Its protective action and mechanism against oxidative damage were investigated and mechanism against oxidative damage were investigated. Reactive oxygen species (ROS) were generated enzymatically in the xanthine-xanthine oxidase (X/XO 5 microM/0.01 u/ml) system and non-enzymatically in the paraquat (PQ 5 mM) system. Both systems increased leakage of lactate dehydrogenase (LDH) and alanine transaminase (ALT) in rat primary hepatocytes, but the hepatotoxicity was significantly suppressed on pretreatment with crocetin (10, 20 microM). Crocetin decreased formation of malondialdehyde (MDA) as an index of lipid peroxidation induced by ROS. The oxyradical generation by X/XO or PQ caused DNA damage evaluated with unscheduled DNA synthesis (UDS) in rat primary hepatocytes. The addition of crocetin decreased genotoxicity evaluated with UDS in both systems. The data showed that crocetin also inhibited the formation of superoxide anion in the X/XO system and bleached the free radical 1, 1-diphenyl-2- picrylhydrazyl (DPPH). The protective action of crocetin operated via quenching of the superoxide anion and/or free radical.

Animals↗

Modulatory effect of piperine on benzo[a]pyrene cytotoxicity and DNA adduct formation in V-79 lung fibroblast cells.

Piperine, a major component of black pepper and long peppers, has been reported previously to have an effect on the activation and deactivation of some exogenous substances. In the present study, piperine was found to promote DNA damage and cytotoxicity induced by benzo[a]pyrene (B[a]P) in cultured V-79 lung fibroblast cells. The V-79 cells were treated with a non-toxic dose of piperine (1-20 microM) plus 10 microM B[a]P, or pretreated with piperine for 30 min or 2 hr prior to the administration of 10 microM B[a]P. B[a]P cytotoxicity was potentiated significantly by piperine under each experimental condition. The relative plating efficiency (RPE) was 71% when V-79 cells were exposed to 10 microM B[a]P alone. When the culture was exposed to B[a]P plus piperine or pretreated with piperine for 30 min prior to the administration of B[a]P, the RPE values were 63 and 44% (P < 0.001), respectively. Pretreatment with piperine for 2 hr had no significant effect (P > 0.05). Furthermore, the lowest activities (P < 0.05) of glutathione S-transferase (GST) and uridine diphosphate glucuronyl transferase (UDP-GTase) of piperine-treated V-79 cells occurred 30 min to 1 hr after the piperine pretreatment. Pretreatment of V-79 cells with piperine also caused an increase in the covalent binding of B[a]P-diol-epoxide to DNA, 2.3 times greater than that of the V-79 cells without piperine treatment. These results suggest that the promotion by piperine of B[a]P-induced cytotoxicity in V-79 lung fibroblast cells is due to mechanisms that decrease the activities of GST and UDP-GTase and increase the formation of a B[a]P-DNA adduct.

Alkaloids↗