My seminar subject: CXC chemokine ligand 4 (CXCL4) is a platelet-derived mediator of experimental liver fibrosis

My seminar presentation was finished, and I did very terribly. Anyway, here, I am going to talk about my seminar topic. As the title, my topic is "CXC chemokine ligand 4 (CXCL4) is a platelet-derived mediator of experimental liver fibrosis." First, I would like to introduce CXCL4 and liver fibrosis.

I think I would start with liver fibrosis. Liver fibrosis is cause by chronic liver disease and would lead to liver cirrhosis, end stage of liver failure, or even hepatocellular carcinoma. According to statistics of United States and Europe, the main reasons to cause liver fibrosis are HCV infection and steotohepatitis. The most important thing is that how does liver become fibrosis. The fact is that there are many myofibroblasts in the liver, and the main reason of liver fibrosis is that myofibroblasts secrete type I collagen which accumulates in the liver tissues and leads to liver fibrosis. However, there are many kinds of precursor of myofibroblast. They could be the cells derived from bone marrow, such as fibrocytes, or fibroblasts which are in the tissues originally, or sometimes hepatocytes could be changed into myofibroblast by stimulation of specific chemokines, but the main precursor is activated stellate cells. Hepatic stellate cells (HSCs) are in quiescent state in usual time, and they contain abundant lipid droplets which can store vitamin A. Quiescent HSCs could be activated by some conditions which could be liver injury, stimulation of lipopolysaccharide which is in the cell walls of gram-negative bacterium, or stimulation of specific chemokines. After HSCs being activated, they might have extra abilities such as proliferation, contractility, fibrogenesis, altered matrix degradation, chemotaxis, or releasing inflammatory signals. In addition, infiltration of immune cells could also lead to liver fibrosis.Fortunately, these mechanism of liver fibrosis could be regulated by some proteins like Timp-1, Tgf-beta, Mmp9, and IL-10.

Recently, the relation between coagulation cascade and liver fibrogenesis has been found. When coagulation cascade is activated, thrombins will be formed and platelets aggregation will be caused in the same time. If platelets aggregation occurs in liver, it will lead to HSCs proliferation. However, the key molecules of this mechanism are still unknown. One thing we know for sure is that platelets aggregation is caused by platelets activation. When tissues were injured, the collagen in the tissue may contact with blood stream, and the Von willebrand factor (vWF) in the blood stream would bind to collagen. The GPIIb-IIIa receptor on platelets membrane could bind to vWF and be activated after that. The activated platelets would release some coagulation factors, stored in platelets granules, to blood stream and caused clot formation, and one of the coagulation factors called fibrinogen could also bind to GPIIb-IIIa receptor. This would also make platelets to be activated and have the ability to link with each others and cause platelets aggregation. Interestingly, there are not only coagulation factors but also chemokines that are stored in platelet granules, and these chemokines would also be released to blood stream when platelets are activated. CXCL4 is an abundant chemokine in platelets. Actually, CXCL4 is both a chemokine and a coagulation factor. It is also called platelet factor 4 and it cause the formation of thrombus as a coagulation factor and it could activate monocytes as a chemokine. Recent studies show that CXCL4 mRNA was detected at elevated levels in the livers of patients with alcoholic liver disease ,and CXCL4 serum levels were elevated in patients with viral hepatitis. These evidences indirectly imply the potential of CXCL4 in liver disease. Therefore, the aim of this paper is to investigate the role of the platelet-derived CXCL4 in human experimental liver fibrosis.

In this experiment, both serum concentrations and intrahepatic CXCL4 mRNA were measured in patients with chronic liver disease and in mouse models. Electron microscopy and immunohistochemistry were utilized to determine platelet aggregation. Wild-type and CXCL4-/- mice were treated with CCl4 and thioacetamide (TAA) which are used to induce chronic liver damage. Intrahepatic infiltration of immune cells was investigated by fluorescence-activated cell sorting, and hepatic stellate cells were treated with recombinant murine CXCL4 in vitro. The results showed that CXCL4 serum levels and intrahepatic CXCL4 mRNA concentrations were increased in patients with advanced hepatitis C virus-induced liver fibrosis or nonalcoholic steatohepatisis. Platelets aggregation was obviously near collagen fibrils in the liver tissue. The treatment of CCl4 and TAA caused an increase of hepatic CXCL4 levels, platelet activation and aggregation in mice. Deletion of CXCL4 could reduce liver fibrosis significantly which is proved by histological and biochemical examinations. The results showed that the expression of fibrosis-related genes (tissue inhibitor of matrix metalloproteinase 1 [Timp-1], matrix metalloproteinase 9 [Mmp9], transforming growth factor beta [Tgf-β], interleukin 10 [IL-10]) were changed significantly in CXCL4-/- mice. In addition, infiltration of immune cells (neutrophils and CD8-positive T cells) into the liver was decreased in CXCL4-/- mice. In vitro results showed that hepatic stellate cells were activated after treating recombinant murine CXCL4 and showed the abilities of proliferation, chemotaxis, and chemokine expression.

In conclusion, when liver injury occur, platelets could be recruited to the injured site and be activated. Then activated platelets secrete CXCL4 which activates quiescent HSCs, and activated HSCs start to proliferate. This might cause the increasing of myofibroblasts since activated HSCs are the main precursor cells of myofibroblasts. Thus, increasing of myofibroblasts accelerate the accumulation of type I collagen. The collagen was accumulated in liver tissue not only cause liver fibrosis but also recruit much more platelets aggregate in liver and be activated at the same time. Then activated platelets secrete CXCL4 again. This mechanism speeds up the progress of liver fibrosis. However, when we knock out CXCL4 gene, activated platelets could not secrete CXCL4, so HSCs could not be activated. Which means that there are no more myofibroblasts increasing and no more accumulation of type I collagen in tissue. Therefore, the progress of liver fibrosis will be slow down.

That is pretty much it about my seminar subject. Honestly, it takes me about a week to finish this article. Maybe this article doesn't make any sense because of my unsuitable description in English. Let me know when it does happen.

Welcome Arjunan to join this blog!

The main reason that I set this blog is to practice my English writing, and my dream is that there are many people who join my blog and practice English together. I am very glad that Arjunan join my blog, and also shared some very useful information of how to improve English. I have to say thank god that I made a great step to my goal, even I don't believe god.

I was so happy that I couldnt' wait to write a welcome article for Arjunan on this blog. Therefore, I wrote this while I was preparing my presentation for the next day. Honestly, I planned at first to write this article in the next next week because I would be a little bit freer in those days. I am sure that the more people there are in this blog, the more motivation I will get to practice English writing.

Arjunan's joining really encouraged me a lot. Now, I am very sure that there is at least one person who will read my articles, or share good experiences, or even discuss things with me. I am so excited about it.

In the end, I would like to thanks Arjunan for the two wonderful articles and I hope he will write more and more great articles on this blog. Anyway, welcome to join this blog, Arjunan!

Good Sites - English

Hi Friends

The following sites are really helpful for Esl students.I Have learnt a lot of things from these sites.

1.www.phrasemix.com
    It is a very good site where you can learn many English phrases which helps in our day to day life.They are updating the informations everyday.Just take a look!!

2.www.talkenglish.com
     This site is Awesome where you can find many phrases.You can improve your listening practice as well.

3.www.voanews.com
No words to express about this web site.it is really helpful for non native speakers.You can improve your listening practice tremendously.The way they pronouncing the word is really good.we can improve our listening skills.

4.www.speakspeak.com
 Good site For grammar.grammar is very important in English which will help you to sharpen your grammar skills.

5.www.manythings.org
 It is heaven for ESL students where you can find many good stories in English and you can improve your listening skills and many English tests Etc.

Steps to improve English language skills

Hi Friends...I am very happy to talk with you by using this blog..Let me introduce myself first before moving to subject..I am Arjunan from Tamilnadu .I had finished my Engineering.This is My life few years back..Till 10th Standard i don't know even a single sentence to write or talk in English.

When i was joining the college,I came to know how the English communication plays a very important role.Many of my friends used to tease me a lot because i was from Tamil medium(local Language).From that day itself i have started to improve my skills.I have been improving my skills since 2005.I had a lot of obstacles when i was improving my skills.Many students are suffering a lot to improve Communication skills.

Follow these steps given below(It is from my experience).I am sure ,one day you will become master in that language.

1.Try to be very patience to improve your language skills.It is not a over night process.It is STEP BY STEP process.

2.Vocabulary is very important for any language.So take steps to improve Your vocabulary.Try to watch BBC, CNN IBN,NDTV,Times Now which helps a lot to improve your skills.Try to listen a news minimum for 30 minutes.you can improve your listening skills.you will find many unknown words.Try to put a separate Notebook and write down those words.

Example:-
```````````
Compile - Select ,Collect

Ex - The police have compiled a list of suspects.
It is the easiest way to remember the words.Read minimum 5 words.Try to use that word in Conversations.
If you cultivate the following habits,You can find many new words.

*Reading News papers

*Watching News or English movies.

3.Pronunciation is very important in English.Many softwares are available in net,Download it.

* Wordweb(it is a dictionary which helps to know the meanings and gives a pronunciation)

*Speech(you can find this in your system(control panel).

4.Grammar.Don't Read too much grammar,Try to know the basics which is more than enough to talk.

*Tenses

*Voices(active voice & passive voice)

*Conditional Sentence

5. Don't be Shy...Practice is the key to Enhance your skills..Practice Practice Practice as much as possible..

I am sure,One day you will post your experience like me in your Blog..

Bye Friends..

Arjunan.S

Backup files automatically!

When we use a computer, our files will store in the computer. Of course, all of us have known that we should backup our files frequently. Otherwise, when the hard disk is broken, our priceless files would be gone at the same time. If we use laptop, there will be another risk of loosing it or be stolen. In addition, I think that laptops are much easier to be broken, and when laptops are broken, they should be sent back to the service center to be fixed. There will be no chance for us to backup our files after laptops are broken. Unlike desktops, we can try to save our files after the desktop is crashed.

As I mention before, we should backup our files frequently. You may ask how frequently should we do? There is no standard answer for this question, honestly. It depends on how often we use computers. Take me as an example, I am postgraduate now, I have many important files every day, so I backup important files every day, and backup less important files once a month. The followings are some method I used to backup my files.

Dropbox
http://www.dropbox.com/

Dropbox is a web storage space which provides 2GB after we register an account. We can earn more spaces by inviting friends signing up in this website. The maximum space we can use free is 8GB. This website also provides a synchronized software. After we installing this software, there will be a new folder named "my dropbox" in the "my document" folder. When we put files in "my dropbox" folder, the files we put will be uploaded to web immediately. Last but not least,  we can install this software in many computers of ours even in iphone or android phone, and then all files we put in "my dropbox" folder can be accessed in these devices. Therefore, if one of our computer is broken, we can still use the synchronized files from other devices or from the website directly.

 There is an official video of introducing dropbox:




If you are interested in dropbox, and want to give it a try. Then sign up with this link:http://www.dropbox.com/referrals/NTMxOTk3MjI5, and you will get extra 250MB after you register an account.


Windows batch files and a 500GB external hard drive

Dropbox is a very ideal tool to backup our files, but unfortunately, there is only 2GB for us to use. That is not enough for me, so I bought a 500GB external hard drive to backup some files which is less important. My less important files are the files which I don't use very often such as the projects I have done, or the photos I took. I would backup these files in the external hard disk. However, these files are not in the same folder, so it would be very troublesome if I copy and paste these files manually, and plus, these files are really large. Therefore, I use 7zip and write a batch file with xcopy command and 7zip command to backup my files automatically.

Here is my batch files:

@echo off
@echo Backup Files
@echo.

@echo The following files will be backup:
@echo d:\software
@echo d:\chw
@echo d:\research tools
@echo.
@echo.


@pause

cls


@echo Backing up files please wait................
@echo.
@echo.



rem set date value
@For /f "tokens=1-3 delims=/ " %%a in ('date /t') do (set date=%%a-%%b-%%c)

rem @echo date is %date%


@echo Copying software files
xcopy d:\software d:\backup\"backup files"\backup-%date%\software /e /i /h /q
@echo.
@echo.


@echo Copying chw files
xcopy d:\chw d:\backup\"backup files"\backup-%date%\chw /e /i /h /q
@echo.
@echo.



@echo Copying research tools files
xcopy d:\"research tools" d:\backup\"backup files"\backup-%date%\"research tools" /e /i /h /q
@echo.
@echo.


@echo Creating log file in backup-%date%
cd d:\backup\"backup files"\backup-%date%\
@echo ==================================================== > "backup log".txt
@echo Files location: >> "backup log".txt
@echo ==================================================== >> "backup log".txt
@echo software        d:\software >> "backup log".txt
@echo chw            d:\chw >> "backup log".txt
@echo research tools        d:\ research tools >> "backup log".txt
@echo. >> "backup log".txt
@echo. >> "backup log".txt
@echo ==================================================== >> "backup log".txt
@echo Files informations: >> "backup log".txt
@echo ==================================================== >> "backup log".txt
dir d:\software /a >> "backup log".txt
@echo ------------- >> "backup log".txt
dir d:\chw /a >> "backup log".txt
@echo ------------- >> "backup log".txt
dir d:\"research tools" /a >> "backup log".txt
@echo. >> "backup log".txt
@echo. >> "backup log".txt
@echo ==================================================== >> "backup log".txt
@echo These files were backup on %date% >> "backup log".txt
@echo ==================================================== >> "backup log".txt
@echo Log file has been created

@echo.
@echo.

rem compress files to 7-zip
cd d:\backup\
7za a -scsUTF-8 -mx=9 d:\backup\"backup files"\backup-%date%.7z  d:\backup\"backup files"\backup-%date%\

@echo.
@echo.


@echo done!
@echo Files has been backuped in d:\backup\backup files\backup-%date%.7z
@echo.
@echo.


@pause

rem delete the folders
del /S /Q d:\backup\"backup files"\backup-%date%\
rd /S /Q d:\backup\"backup files"\backup-%date%\

I have to say it is not easy for me to write this file. I spent two hours finishing this files. If you want to try this method, you should download 7-Zip Command Line Version, and refer to the xcopy read me file. Other commands I used are echo, del and rd in the batch file. You can learn how to write a batch file in here, or just google it. I am sorry that I don't know how to write because I am not familiar with batch files, and I finished this batch files with google. Wish you enjoy it!

PS.
This is my first time to write a how to article. I hope all of you can know what I was writing.