Download Atherosclerosis is the leading cause of death in the cardiovascular

Atherosclerosis is the leading cause of death in the cardiovascular disease. It is a
systemic disease, a huge number of studies have revealed several risk factors involving in the
progression of atherosclerosis. In early atherogenesis, oxidative modification hypothesis of
atherosclerosis proposes that LDL oxidation and proliferation of vascular smooth muscle cell
(VSMC) in the intima plays a causative role. If agents that can prevent LDL oxidation and
proliferation of VSMC, it could possibly attenuate the development of atherosclerosis.
Flavonoids are a group of naturally occurring polyphenolic compounds ubiquitously
found in plants, fruits and vegetables. It has shown potential antioxidative effects. In this
study, we evaluated the effects of mulberry leaf extracts (MLE) to inbibit LDL oxidation and
VSMC proliferation.
In the Cu2+-induced LDL oxidation model, we observed that MLE were able to
apparently reduce the Apo B fragmentation, relative electrophoretic mobility (EM) and the
products of lipid peroxide-MDA formation. MLE possessed the best ability of DPPH radical
scavenging. Taken together, MLE showed a strong potency to inhibit the LDL oxidation
induced by Cu2+. In our previous studies, in cultured cells experiments, have demonstrated
that MLE could induce VSMC apoptosis. Nevertheless, does the lower dose of MLE effect ?
In this study, we focus on that is MLE able to inhibit VSMC on cell cycle progression and
migration? First, MLE effectively inhibit VSMC growth on the dose of 1~1.5 mg/ml MLE
which can’t induce cell apoptosis. In the experiments of flow cytometry assay, we also
evaluated the proportion of S and G2/M phase of cell cycle were decreased, but G1 phase
were increased abundantly on treatment VSMC with 1.0 mg/ml MLE. The western blot have
revealed that cyclinD1, CDK4, p-p53, p27, p21, p16 were increased and cyclinA, cyclinE,
CDK2, p-Rb were reduced. In the experiments of immunoprecipitation, we analyzed
attenuation of cyclinD/CDK4 complexes following the advancement of MLE dose. It means
MLE inhibited cell proliferation by interferencing the mechanism of VSMC cell cycle
progress to S phase. In addition, the best ability of MLE inhibited VSMC migration by wound
healing assay and Boyden chamber assay. The expression of MMP-9, MMP-2, small GTPase,
p-FAK and NF-κB were decrease progressively by gelatin zymography assay and westerb
blotting.
In conclusion, mulberry leaf extracts (MLE) possess ability to inhibit LDL oxidation and
abnormal proliferation of vascular smooth muscle cell. Therefore, it is suggestive the
mulberry leaves that may have multiple benefical effects on cardiovascular health, and the
potential clinical application of these fascinating natural substance.
Abstract
Cardiovascular disease has been a major cause of mortality in human and
hyperlipidemia plays an important role contributing to atherosclerosis. Oxidated
LDL (oxLDL) has known to damage the endothelial cells and cause endothelial
dysfunction. And oxLDL-mediated foam cell formation by macrophage initiates
the cascade of atherosclerosis.
This study was to evaluate the anti-oxidative and anti-atherosclerotic effects
of the MLE by a model of in vitro antioxdation and cell culture.
As shown in previous studies Morus alba L. leaves extract is a nature plant
containing a lot of pigments that was found to possess antioxidative activity. In
this study, we evaluated the antioxidative activity of the Morus alba L. leaves
extract
(MLE)
by
measuring
their effects
on
LDL oxidation
and
anti-atherosclerotic abilities. MLE possessed the ability of DPPH radical
scavenging. The antioxidative activity of the MLE on LDL oxidation was
defined by apoB fragmentation, relative electrophoretic mobility (REM) and
thiobarbituric acid-relative substances (TBARS) assay. Our results showed that
MLE was able to protect the apoB, to reduce REM and to inhibit TBARS assay
in the Cu2+-mediated oxidative LDL. Taken together, low concentration of MLE
could reduce marked the cellular cholesterol and triglycerides accumulation in
macrophage and inhibit the formation of foam cells. MLE inhibits
oxLDL-induced CD36 and SR-A expression. We found MLE also recovered
oxLDL-mediated NF-κB activity loss. MLE reduces macrophage phagocytosis
by latex beads.
Our study demonstrates the MLE can inhibit the oxidation of LDL and has
the anti-oxidatic and anti-atherosclerotic properties.
Abstract
It’s a popular topic of discussing how to prevent the formation of cancer. The development of
new drugs are both safe and effective will be important for the future of cancer
chemoprevention. Many studies demonstrate that Anthocyanins and Polyphenol widely in
many plants have the effects of antioxidation, hypolipidemic, anti-atherosclerotic and
anti-carcinogenesis, such as the Anthocyanins in the Hibiscus sabdariffa L. Our previous
reports demonstrated that anthocyanins extracted from Hibiscus sabdariffa Linne, Hibiscus
anthocyanins (HAs) and Hibiscus polyphenol（HPE）induced apoptosis effect on human
cancer cells. In this study, we explored the anti-cancer effect and the particularly mechanism
of HAs on human colon cancer cell. The Chinese herbal medicine has already been continued
to use for many years at many disease, has also included directing against the treatment of the
cancer. On the other hand, the research in recent years shows the cancer cell grows and
spreads because of being unable to wither and die normally. It’s an important subject to detect
the cancer cells with specially mechanism in cancer therapy. We used MTT assay, DAPI
staining, flow cytometery, mitochondria membrane potential analysis and western blot to
detect and found that HAs treatment markedly induced apoptosis in LoVo cells in a dose- and
time-dependent manner. The results also reveal inhibited NF-kB, induced by members of the
death receptor such as Fas/FasL that leads to the formation of pro-caspase-8, increased
cytochrome C release, and expression of Bcl-2 family protein via mitochondrial death
pathway. Followed, the mechanism of apoptosis is associated with activation of the caspase
cascade in the HAs-treated LoVo cells. We suggested that HAs could promote colon cancer
cell apoptosis and prevent or delay cancer cell progression. According to these results, HAs
has a potential in anticancer effect that could be developed as chemopreventive materials.
ABSTRACT
Chondrocyte is the sole cell type of the cartilage. At the joint, cartilage covers the end of
the bone. The extracellular matrix (ECM), a structure of highly hydrated matrix, is consisted
of collagen, and glycosaminoglycan (GAG) which is made of hyauronic acid back bone with
many other chondroitin sulfate, keratan sulfate and protein components. Chondrocytes are
embedded in this ECM structure and produce new collagen and GAGs in cartilage. When
chondrocytes are serially expanded, they progressively lose their original phenotype, this
process typically described as dedifferentiation. According to previous studies in our
laboratory, exogenous type II collagen promoted re-expression of type II collagen mRNA and
GAG accumulation in near quiescent rabbit chondrocytes. In this study, we treat human
chondrocytes with various exogenous extracellular matrix components (i.e. type II collagen,
hyaluronic acid, or chondroitin sulfate). The results demonstrated that exogenous type II
collagen indeed induced the re-expression of type II collagen and aggrecan mRNAs, and
glycosaminoglycan (GAG) levels. Since exogenous type II collagen indeed make near
quiescent chondrocytes re-differentiate, therefore, its preparations maybe be applied to
osteoarthritis therapy in the future. In addition, integrins are the principal receptors on animal
cells for the most of extracellular matrix proteins ― including collagens, fibronectin, and
laminins. Consequently, this study also examined the related signal pathway of integrin. We
found that the extracellular signal-regulared protein kinase (ERK) was activated during the
induction of the differentiation of dedifferentiated chondrocytes.
英文摘要
Recent advances in molecular genetics have revealed that multiple genetic
alterations including activation of oncogenes and inactivation of tumor
suppressor genes are required for tumor development and progression. K-ras is
frequently mutated in colorectal cancer. Previous studies have shown that
prostaglandin E2 (PGE2) is involved in intestinal carcinogenesis through its
binding to the PGE2 receptor subtypes EP1 and EP4 and activation of
downstream pathways. But the molecular mechanisms that link K-ras and PGE2
receptor are currently undefined.
The aim of the present work was to study the association between K-ras and
PGE2 receptor .We transfer pcDNA3.1 and pcDNA-K-ras in to HT29 colon
cancer cells. The transfected cells and the control cells (empty vector) were
analyzed by MTT assay and Western blot. Our data showed overexpression Ras
protein led to cell proliferation with activation of the phosphatidylinosotol-3
Kinase (PI3K)/Akt pathway, an effect likely to be due to inhibits
GSK3β(Glycogen synthase kinase 3β)activity. Inhibition of GSK3 stabilizes
β-catenin (decrease its degradation) and promotes β-catenin nuclear
translocation and transcriptional activation of TCF-regulated gene further
induction of COX-2 and activation EP1/EP4. We also used COX-2 inhibitor
(NS398) and EP4 inhibitor (AH23848) to confirm this pathway. At the same
time, we collected colorectal tumor tissues as well as to confirm tumor tissues
were overexpression Ras, pAkt and EP1/EP4 protein. Our result provided
colorectal cancer causes K-ras mutation which one newly thinks in the treatment.
In addition, EP1/EP4 inhibitor use regarding the colorectal cancer prevention
also is the choice which may consider.
英文摘要：
Atherosclerosis, a disease occurring in arteries, is one of the primary causes of heart
diseases, stroke and often cause of death in the cardiovascular disease. The oxidative
modification hypothesis of atherosclerosis proposes that LDL oxidation or proliferation and
migration of vascular smooth muscle cell (VSMC) in the intima plays a causative role in early
stage. Mulberry is a nature fruit containing a lot of pigments that was found to possess
antioxidative activity. The mulberry water extracts (MWEs) can effectively inhibit LDL
oxidation, may prevent atherosclerosis via reducing early atherogenesis, and slowing down
the progression to advance stages.In these experiments, mulberry water extracts (MWEs) and
polyphenol extracts (MPEs) were able to inhibit the Apo B fragmentation, MDA formation
(TBARS assay) and possessed the ability of DPPH radical scavenging. We demonstrated
that MWEs and MPEs could inhibit ASMC (A7r5 cell) migration cause apoptosis by down
regulation of Ras/PI3K/Akt and anti-apoptosis pathway strongly , and cell cycle arrest by
attenuating of cyclinD/CDK4, cyclin A、E/CDK2 , p53/Mdm2 complexes. In conclusion, we
not only evaluated the antioxidative activity of the mulberry extracts, but also observed the
mulberry water extracts (MWEs) and mulberry polyphenol extracts (MPEs) can inhibit
proliferation and migration of vascular smooth muscle cell by inhibite NFκB transcription
activity. FAK, RhoA , Rac-1, Cdc42, and Ras protein ,which facilitates integrin signaling,
regulating cell cycle progression, cell survival and cell migration , also can be inhibit by
treatment of mulberry extracts. Therefore, it is suggested that mulberry could be a healthy
food to prevent individuals from atherosclerosis .
Abstract:
Background: Diabetic patients have a higher propensity for in-stent restenosis after
percutaneous coronary intervention (PCI) as compared with normal subjects. Beyond
lipid-lowering effects, statins were reported to reduce intimal hyperplasia by inhibiting
smooth muscle cells (SMC) proliferation and migration and may improve outcomes after PCI.
We will investigate the mechanism of simvastatin to inhibit vascular SMC at high glucose
status mimicking diabetes.
Methods: A7r5, a rat smooth muscle of thoracic aorta, were used. Before simvastatin
treatment, the cells were pre-culture in starvation medium for 48 hours. Simvastatin were
added to the cells which were cultured in high glucose（25 mM）medium to achieve the
indicated concentrations (0-60 μM) for 48 hours. We used MTT assay to evaluate the cell
viability, flow cytometric analysis to analyze the cell cycle. We also used western blot,
immunoblotting, and immunoprecipitation analyses to evaluate the effect of simastatin on the
cyclin dependent kinase activity and cell cycle regulatory proteins (Rb, p53, p16, p21, p27).
Results: Following a 48 hr incubation with 0.5-60.0 μM of simvastatin treatment in the cells
at high glucose level, the percentage of survival cells was around 10~50％. Furthermore, a
time-dependent increase in simvastatin-induced cytotoxicity was also detected at dose of 40.0
μM. Simvastatin induced accumulation of significant numbers of cells around 8~18% in the
G0/G1 phase of the cell cycle in a concentration-dependent manner, while the cell numbers
was significantly decreased in the S and G2/M phases after simvastatin treatment. We also
found that simvastatin can inhibit phosphorylation of Rb and promote expression of p53,
increase the CDK inhibitory protein (p16, p21, p27) levels, and decrease the CDK2/4
activities.
Conclusions: Simvatatin inhibits vascular SMC proliferation at high glucose status
mimicking diabetes, which induces a G0/G1 phase growth arrest of the cell cycle by acting on
multiple steps upstream of pRb, inhibition of CDK2/4 expression and upregulation of p53 and
other CDK inhibitory proteins (p21, p16, p27). Hence, statins should be used in diabetic
patients even without dyslipidemia.
英文摘要：
Glutathione S-transferase (GST), an important detoxification dimeric enzyme in
mammalian cells, includes six isoforms: alpha, pi, mu, theta, zeta and sigma classes. Previous
investigations showed that GST would conjugate xenobiotics with the sulfhydry group of
GSH (glutathione) to increase the solubility of these xenobiotics. On the other hand, GST has
anti-oxidation function, which protect lipid or nucleic acid from the attack of toxins.
Therefore, GST plays an important role in the mechanism of detoxification and
anti-carcinogenesis. Among the isoforms, GST mu is thought to be related to cancer
susceptibility. It is also suggested that GSTM1 could serve as a predictive marker for invasive
bladder cancer. After the treatment of carcinogens, the expression of GST mu would increase
in the hepatocytes. In order to clarify the role of GST mu, a transient expression system of
GST mu was set up to study how the overexpression of GST mu affects the hepatotoxicity and
genotoxicity of carcinogen.
We used the primary cultured hepatocytes of SD rat to establish the transient transfection
system of rGST mu (Yb1), and challenged the cells with Aflatoxin B1. We found that the
transfected rGST mu would attenuate the damage of hepatocytes caused by Aflatoxin B1. The
treatment of Aflatoxin B1 for 12hr increased the cytosolic GST activity in both GST and
control vector-transfected cells in a dose-dependent manner. The GST activity in the cells
transfected with rGST mu was higher than those transfected with pcDNA3. The releases of
AST and LDH activity, from the Aflatoxin B1-treated cells were inhibited by the transfection
of rGST mu as compared to the control.
Abstract
Colorectal cancer arises through the stepwise, progressive disruption of
cellular signaling cascades which control cell proliferation, survival and
differentiation. A number of genes have been implicated in tumorigenesis.
However, the mechanisms for controlling cancer progression have not been
elucidated.In order to further understand whether disease progression is
associated with altered gene expression, we collected tumor tissues as well as
their surrounding normal tissues resected from patients with different stages of
colorectal cancer. Tumor tissues were firstly graded into B, C or D stage
according to Duke classification, and the expression of several proteins involved
in anti-apoptosis and proliferation, including Mcl-1, Bcl-2, IAP, NF-κB, PI3-K,
phospho-Bad, p38, cpp32 and p21, were examined by Western blotting.
Expression levels in tumors were normalized to those in normal tissues of the
same patients and then compared to other tumor samples derived from different
stages of disease.
We found that expression levels of PI3-K, Bcl-2 and phospho-Bad were
elevated as cancer progressed, suggesting that anti-apoptotic proteins were
involved in the regulation of colorectal cancer progression.
英文摘要：
Polyphenols are widely distributed antioxidant agents in plants, and they
have antitumor effects. Anthocyanins, one of the biofalvonols, also have strong
antioxidant effects. In previous studies, Hibiscus protocatechuic acid (HPCA), a
phenolic compound extracted from Hibiscus sabdariffa L., was found to protect
rat primary hepatocytes from oxidative damage by scavenging free radicals.
HPCA is also able to inhibit tumor promotion in mouse skin. In addition,
Hibiscus Anthocyanins (HACs) were also shown to protect rats from tert-butyl
hydroperoxide-induced hepatic toxicity. In this study, we used Hibiscus
polyphenolic acid (HPAs) to evalute the molecular mechanism by which the
phenolic extracts and the flavonid extracts of Hibiscus sabdariffa inbibit the
growth of cancer cells. Moreover the effects of the mutant mitochondrial DNA
(mtDNA) on the mechanism were also investigated. The results revealed that
HPAs have the capacity of scavenging reactive oxygen species. Moreover, they
inhibited the growth of cancer cells, even induced cell death. The cells harboring
high proportions of the 4977 bp-deleted mtDNA were more sensitive to HPAs,
and in a dose- dependent manner. In addition, after treatment of cybrids with
HPAs for 24 hrs, the cells were arrested at G2/M phase through a p53independent pathway. Furthermore, HPAs can respectively activate caspase 8,
caspase 9 and caspase 3 in the cybrids haboring only wild-type mtDNA, but the
activations of caspase 8 and caspase 3 induced by HPAs were repressed in the
cybrids harboring high proportions of the 4977 bp-deleted mtDNA. On the other
hand, HACs was also shown to inhibit the growth of cancer cells, but the effects
are lower than those of HPAs. Taken together, the results suggest that HPAs and
HACs can respectively prevent the growth and activation of the caspases in
cancer cells, and that the 4977 bp-deleted mtDNA in cancer cells can affect the
mechanism.
英文摘要：
Human hepatocellular carcinoma（HCC） is one of the most common cancers in
Asia﹒Our recent data had also showed that the decreased levels of membrane-bound
PKC activity and PKCα protein in HCC were correlated with tumor stage and tumor
size﹒To verify the role of PKC in HCC﹐this study was further determined the
mRNA level of PKC isoforms and cell proliferation markers in HCC by use RT-PCR﹒
The total mRNA was isolated from the surgical specimens of 43 patients of HCC
and adjacent normal tissues﹒The product of RT-PCR was also checked by DNA
sequence analysis﹒The result showed that the level PKCα mRNA in the cancer
tissue were significantly higher than that in the adjacent normal tissue﹐
specifying that the alteraions in the PKCα may signify their activation in liver
cancer﹒Inaddition﹐the level of PKCδ、PKCε、PKCμ and PKCζ mRNA in the cancer
tissue were also significantly higher than that in the adjacent normal tissue﹒
Moreover﹐the protein expressions of the PKC down-stream gene（c-raf、MEK、
MAPK ） and the mRNA expression of the cell proliferation markers were also
increased in cancer tissues. Thus , we suggested that the over-expression of
PKC isoforms may be involved in the malignant progression of HCC.
進階科技英文寫作測驗
1. estrogen receptor alpha 或 the estrogen receptor alpha
2. tumor suppressor protein p53 或 the tumor suppressor protein p53
3. They exert opposing effect on cellular proliferation. 或 They exert opposing effects on
cellular proliferation. 或 They exert opposing effects on the cellular proliferation.
4. As a transcriptional regulator, p53 is ... 或 As transcriptional regulator, p53 is ...
5. P53 is capable of activating various target genes. 或 P53 is capable of the activating
various target genes. 或 P53 is capable of the activating of various target genes. P53 is
capable of activation various target genes. P53 is capable of activation of various target
genes. 或 P53 is capable of the activation of various target genes.
6. P53 is capable of activating or repressing various target genes. 或 P53 is capable of
activating or repressing the various target genes. 或 P53 is able to activate or repress
various target genes.
7. We have previously reported that ... 或 We previously reported that ... 或 We have
previous reported that ... 或 We have a previous report that ...
8. ERalpha binds directly to p53. 或 ERalpha is bound directly to p53.
9. ERalpha binds directly to p53, leading to ... 或 ERalpha binds directly to p53, leads to ...
10. ERalpha binds directly to p53, leading to down-regulation of transcriptional activation by
p53. 或 ERalpha binds directly to p53, leading to the down-regulation of the
transcriptional activation of p53.
11. In addition to transcriptional activation, transcriptional repression plays important role in
diverse biological process. 或 In addition to transcriptional activation, transcriptional
repression plays important roles in diverse biological processes.
12. Transcriptional repression of a subset of target genes by p53 plays ... 或 Transcriptional
repression by a subset of target genes of p53 play ...
13. ... in diverse biological processes, such as apoptosis. 或 ... in diverse biological processes
such as the apoptosis.
14. Here, we report that ... 或 Here, we reported that ...
15. Here, we report that ERalpha inhibited p53-mediating transcriptional repression. 或 Here,
we report that ERalpha inhibits p53-mediated transcriptional repression.
16. Chromatin immunoprecipitation assays reveal that ... 或 Chromatin immunoprecipitation
assay revealed that ...
17. ... assays reveal that ERalpha interacts in vivo with p53 bound to promoters of Survivin.
或 ... assays reveal that ERalpha interacted in vivo with p53 binding to promoters of
Survivin.
18. ERalpha interacts in vivo with p53 bound to promoters of Survivin and multidrug
resistance gene 1. 或 ERalpha interacts in vivo with p53 bound to promoters of Survivin
and of multidrug resistance gene 1.
19. ... Survivin and multidrug resistance gene 1, both targets for transcriptional repression by
p53. 或 ... Survivin and multidrug resistance gene 1, both being targets for transcriptional
repression by p53.
20. ERalpha binding to p53 leads to inhibition of p53-mediated transcriptional regulation of
these genes in human cancer cells. 或 ERalpha binds to p53 leading to inhibition of
p53-mediated transcriptional regulation of these gene in human cancer cell.
Writing test
1. Transcriptional derepression of Survivin by ERalpha is depend on the p53-binding site on
Survivin promoter. 或 Transcriptional derepression of Survivin by ERalpha is dependent
on the p53-binding site on the Survivin promoter.
2. A is dependent on B, consistent with our observation that … 或 A is dependent on B,
which is consistent with our observation that …
3. … our observation that p53 is necessary for ERalpha to access the romoters. 或 … our
observation that p53 is necessary to ERalpha for access the promoters.
4. Important, mutagenic conversion of this site for an activation element enabled ERalpha
for repress p53-mediated transcriptional activation. 或 Importantly, mutagenic conversion
of this site to an activation element enabled ERalpha to repress p53-mediated
transcriptional activation.
5. Further, RNA interference-mediated knockdown of ERalpha resulted in reduced Survivin
expression and enhanced the propensity of MCF-7 cells to undergo apoptosis in response
to staurosporine treatment. 或 Furthermore, RNA interference-mediated knockdown of
ERalpha resulted reduced Survivin expression and enhanced in the propensity of MCF-7
cells for undergoing apoptosis in response to staurosporine treatment.
6. A resulted in B, an effect that was blocked by exogenous expression of Survivin. 或 A
resulted in B, that was an effect blocked by exogenous expression of Survivin.
7. These results unravel a novel mechanism which ERalpha opposes to p53-mediated
apoptosis in breast cancer cell. 或 These results unravel a novel mechanism by which
ERalpha opposes p53-mediated apoptosis in breast cancer cells.
8. The findings could have translational implications in developing new therapeutic and
prevention strategies. 或 The findings can have translational implication in developing
new therapeutic and prevention strategy.
9. Studies on retinoblastoma have been at the heart of many of the landmark discoveries in
cancer genetics over the past 35 years. 或 Studies of retinoblastoma have been in the
heart of many of the landmark discoveries on cancer genetics for the past 35 years.
10. However, these advances in the laboratory have had a little effect in the treatment of
children with retinoblastoma. 或 However, these advances in the laboratory have had
little effect on the treatment of children with retinoblastoma.
11. One of the reasons for this has been the lack of preclinical models that recapitulated the
genetic and histopathologic features of human retinoblastoma. 或 One of the reasons of
this have been the lack of preclinical models which recapitulated genetic and
histopathologic features of human retinoblastoma.
進階英文科技寫作練習
Class (
)
Number (
)
模仿造句：
1. The opium-induced sleep is unnatural and harmful.
Name (
)
2. Good luck is coupled to kindness.
3. The mechanisms by which the ants defend their territories are not yet fully understood.
4. His behavior is associated with his childhood traumatic experience.
5. She rejected him again and again, suggesting that she felt no pity for him.
6. Our results show that this is indeed a good therapy.
7. Jogging is considered to be health-promoting exercise.
8. This disease has been linked to excessive drinking.
9. To understand its side effect, we did a thorough study of this new drug.
10. We assayed using the new method to analyze the data.
11. When compared with John’s weaknesses, Peter’s strengths are even more noteworthy.
12. The effect was most marked among aged patients.
13. They are enjoying their power-derived profits.
14. He delivered a speech in response to the ruling party’s questioning and the opposition
party’s attack respectively.
15. When he found the majority of people were on his side, his boldness and his confidence
were enhanced.