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Ditemukan 15 dokumen yang sesuai dengan query
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Nissa Thoyyiba Oktavia
"Salah satu penyebab tingginya angka kematian ibu di Indonesia adalah adanya hipertensi pada kehamilan yang disebabkan oleh preeklampsia. Hingga saat ini, penyebab preeklampsia masih belum diketahui secara pasti, namun teori yang berkembang menyebutkan adanya iskemia plasenta. Iskemia plasenta disebabkan adanya kegagalan pada proses angiogenesis. Penelitian yang menggunakan desain potong lintang ini bertujuan untuk melihat perbedaan protein yang mempengaruhi proses angiogenesis pada plasenta normal dan preeklampsia serta melihat interaksinya. Sampel yang digunakan adalah 34 plasenta kehamilan normal dan 34 plasenta kehamilan preeklampsia. Kadar protein TGF- , TGF- Reseptor dan SMAD2 diperiksa menggunakan metode ELISA dan ekspresi relatif mRNA SMAD2 dan TSP-1 diperiksa menggunakan metode RT-qPCR.Kadar protein TGF- , TGF- Reseptor 1, TGF- Reseptor 2 dan protein SMAD2 meningkat pada preeklampsia p=0,0001, p=0,004, p=0,0001, p=0,0001 . Ekspresi mRNA SMAD2 dan TSP-1 pada preeklampsia juga mengalami peningkatan p=0,033, p=0,002 . Didapatkan korelasi positif kuat antara kadar protein TGF- Reseptor 1 dan TGF- Reseptor 2 pada plasenta normal p=0,0001 R=0,799 dan preeklampsia p=0,0001 R=0,783 . Korelasi positif sedang pada korelasi TGF- dan protein SMAD2 pada plasenta normal p=0,0001 R=0,672 dan korelasi positif ringan pada plasenta preeklampsia p=0,028 R=0,331 . Ada korelasi positif kuat antara TGF- Reseptor 1 dan protein SMAD2 0,0001 R=0,704 pada plasenta normal dan korelasi positif sedang pada plasenta preeklampsia p=0,0001 R=0,675 . Pada korelasi antara TGF- Reseptor 2 dengan protein SMAD2 plasenta normal diperoleh korelasi sedang p=0,0001 R=0,650 begitu juga pada plasenta preeklampsia 0,0001 R=0,675 . Kemudian pada uji korelasi antara protein TGF- dengan mRNA SMAD2 diperoleh korelasi positif ringan pada plasenta normal p=0,022 R=0,347 dan tidak ada korelasi pada plasenta preeklampsia. Pada uji korelasi antara protein TGF- Reseptor 1 dengan mRNA SMAD2 diperoleh korelasi positif ringan pada plasenta normal p=0,016 R=0,370 dan tidak ada korelasi pada plasenta preeklampsia. Tidak ditemukan korelasi antara TGF- Reseptor 2 dengan mRNA SMAD2 pada kedua kelompok. Kemudian tidak ditemukan korelasi protein SMAD2 dengan mRNA TSP-1 pada plasenta normal namun terdapat korelasi positif kuat pada plasenta preeklampsia p=0,0001 R=0,774 . Dari penelitian ini disimpulkan bahwa ada pengaruh peningkatan kadar TGF- , TGF- Reseptor, dan protein SMAD2 dengan ekspresi relatif TSP-1 pada proses angiogenesis.
One of the causes of high maternal mortality in Indonesia is the presence of hypertension in pregnancy caused by preeclampsia. Until now, the cause of preeclampsia is still not known, but the theory suggests the presence of placental ischemia. Placental ischemia is caused by failure of angiogenesis. This cross sectional study aims to examine the differences in proteins that affect angiogenesis in normal placenta and preeclampsia and see their interactions. The sample used was 34 placentas of normal pregnancy and 34 placental preeclampsia pregnancy. TGF protein levels, TGF receptors and SMAD2 were examined using the ELISA method and the relative expression of SMAD2 and TSP 1 mRNA was examined using the RT qPCR method.Levels of TGF protein, TGF Receptor 1, TGF Receptor 2 and protein SMAD2 increased in preeclampsia p 0.0001, p 0.004, p 0.0001, p 0.0001 . SMAD2 and TSP 1 mRNA expression in preeclampsia also increased p 0.033, p 0.002 . There was a strong positive correlation between protein content of TGF receptor 1 and TGF receptor 2 in normal placenta p 0.0001 R 0,799 and preeclampsia p 0.0001 R 0,783 . Moderate positive correlations in TGF and SMAD2 protein correla tion on normal placenta p 0.0001 R 0.672 and mild positive correlation of placenta preeclampsia p 0.028 R 0.331 . There was a strong positive correlation between TGF receptor 1 and the SMAD2 protein 0.0001 R 0.704 in normal placenta and moderately positive correlation in the preeclampsia placenta p 0.0001 R 0.675 . In the correlation between TGF Receptor 2 with normal placental SMAD2 protein obtained moderate correlation p 0.0001 R 0.650 as well as on preeclampsia placenta 0.0001 R 0.675 . Then the correlation test between TGF protein and SMAD2 mRNA obtained a mild positive correlation on normal placenta p 0,022 R 0,347 and no correlation on placenta preeclampsia. In the correlation test between TGF protein Receptor 1 and SMAD2 mRNA obtained a mild positive correlation on normal placenta p 0.016 R 0.370 and no correlation in placenta preeclampsia. No correlation was found between TGF receptor 2 and SMAD2 mRNA in both groups. Then there was no correlation of SMAD2 protein with TSP 1 mRNA in normal placenta but there was a strong positive correlation in placenta preeclampsia p 0.0001 R 0.774 . From this study it was concluded that there was an effect of increased levels of TGF , TGF receptor, and SMAD2 protein with relative expression of TSP 1 in angiogenesis process."
2018
T-Pdf
UI - Tesis Membership  Universitas Indonesia Library
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Dyah Suci Handayani
"ABSTRAK
Latar Belakang: Mangiferin merupakan senyawa bioaktif yang diketahui dapat menghambat fibrosis, yaitu proses reversibel akibat jejas pada hati. Penelitian ini bertujuan untuk membuktikan efek mangiferin dalam menghambat fibrogenesis melalui hambatan terhadap ekspresi mRNA TGF-?, yaitu sitokin profibrogenik utama. Metode: Penelitian eksperimental ini menggunakan RNA yang diisolasi untuk mendapatkan cDNA, di mana kelompok perlakuan diberikan tioasetamid 200 mg/kg BB sebanyak 3 kali/minggu selama 5 minggu oleh Arozal W, dkk. Perlakuan dibagi menjadi kelompok kontrol, tioasetamid 200 mg/kg BB, tioasetamid 200 mg/kg BB mangiferin 50 mg/kg BB/hari, dan tioasetamid 200 mg/kg BB mangiferin 100 mg/kg BB/hari. Tingkat ekspresi mRNA TGF-? diukur dengan RT-PCR dan dihitung dengan metode Livak. Hasil: Terdapat peningkatan ekspresi mRNA TGF-? pada kelompok yang hanya diberikan tioasetamid terhadap kelompok kontrol. Pada kelompok yang diberikan mangiferin, terdapat penurunan ekspresi mRNA TGF-? terhadap kelompok yang hanya diberikan mangiferin, dengan penurunan ekspresi mRNA pada kelompok yang diberikan mangiferin 50 mg/kg BB/hari lebih besar. Kesimpulan: Mangiferin dapat menurunkan tingkat ekspresi mRNA TGF-? pada hati tikus yang diinduksi oleh tioasetamid, namun efeknya tidak linear antara dosis mangiferin dengan respon yang diberikan.

ABSTRACT
Background Mangiferin is a bioactive compound that is known to inhibit fibrosis, a reversible process that occurs as a result of liver injury. This study aims to prove the antifibrotic effect of mangiferin through inhibition of mRNA expression of TGF , which is the main profibrogenic cytokine. Method This experimental design uses isolated RNA to get cDNA, which treatment groups are given thioacetamid with dose of 200 mg kg BW, three times a week for five weeks consecutively, in study from Arozal W, et al. The treatment groups are control group, thioacetamid 200 mg kg BW, thioacetamid 200 mg kg BW mangiferin 50 mg kg BW day, and thioacetamid 200 mg kg BW mangiferin 100 mg kg BW day. The expression of TGF mRNA is measured with RT PCR and quantified with Livak method. Result There is an increase mRNA expression of TGF in group that was given thioacetamide only compare to the control group. In the groups that were on treatment of mangiferin, the mRNA expressions of TGF are lower than the thioacetamid only group. The mRNA expression of TGF of the group that was given mangiferin of dose 50 mg kg BW day is also lower compare to the group that was given higher dose of mangiferin. Conclusion Mangiferin can lower the expression of TGF in rats liver induced by thioacetamide. However, mangiferin does not give linear effect between dose and response.
"
2017
S-Pdf
UI - Skripsi Membership  Universitas Indonesia Library
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Muhammad Zaal Haq
"ABSTRAK
Latar Belakang: Transforming growth factor-β1 (TGF-β1) adalah sitokin multifungsi yang mempunyai peran penting dalam menginisiasi diferensiasi hDPSCs menjadi sel seperti odontoblas. Proses tersebut memerlukan media kultur seperti Lysate-PRF untuk meningkatkan jumlah growth factor yang diperlukan agar proses diferensiasi tersebut bisa terjadi.
Tujuan: Membandingkan berbagai konsentrasi media kultur lysate PRF terhadap ekspresi TGF β1 pada proses diferensiasi hDPSCs.
Metode: Evaluasi ekspresi TGF β1 lysate PRF 1%, 5%, 10%, dan 25% serta FBS 10% (kontrol) pada diferensiasi hDPSCs menggunakan ELISA pada hari ke-7.
Hasil: Terdapat perbedaan bermakna antar kelompok uji yaitu lysate PRF 1%, 5%, 10%, 25% dan kelompok kontrol (FBS 10%).
Kesimpulan: Lysate PRF konsentrasi 25% memiliki ekspresi TGF β1yang lebih tinggi dibandingkan dengan kelompok konsentrasi lainnya maupun kelompok kontrol FBS 10% pada proses diferensiasi hDPSCs hari ke-7.

ABSTRACT
Background: Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine that has an important role in initiating differentiation of hDPSCs into cells such as the odontoblasts. The process requires culture media such as Lysate-PRF to increase the number of growth factors needed so that the differentiation process can occur.
Purpose: Comparing the various concentrations of PRF lysate culture media to TGF β1 expression in the differentiation process of hDPSCs. Methods: Evaluation of TGF β1 lysate PRF expression 1%, 5%, 10%, 25% and FBS 10% (control) on differentiation of hDPSCs using ELISA on day 7.
Result: There were significant differences between PRF lysate 1%, 5%, 10% and 25% and the control group (FBS 10%).
Conclusion: 25% PRF lysate has the highest TGF β1 expression compared to other concentration groups and 10% FBS control group in 7th day hDPSCs differentiation."
2018
SP-Pdf
UI - Tugas Akhir  Universitas Indonesia Library
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Harahap, Pony Purnamasari
"Penyakit crohn merupakan peradangan saluran cerna kronik yang berpotensi mempengaruhi setiap bagian dari saluran pencernaan. Hal ini menyebabkan akumulasi abnormal dari matriks ekstraselular dan pembentukan fibrosis yang berkaitan dengan meningkatnya jumlah Transforming Growth Factor-β dan dapat menyebabkan penyempitan usus hingga kegagalan organ. Tujuan penelitian ini adalah identifikasi situs pentargetan yang sensitif Transforming Growth Factor-β sebagai informasi untuk penghantaran obat terapi fibrosis pada usus hewan dan manusia. Dalam penelitian ini, identifikasi situs pentargetan sensitif TGF-β dapat dilakukan dengan menggunakan PCIS Precision-Cut Intestinal Slices yang merupakan suatu model ex vivo untuk mensimulasikan terjadinya fibrosis usus. Hasil penelitian menunjukkan bahwa TGF-β tidak mempengaruhi kelangsungan hidup irisan usus dan adanya pengaruh TGF-β terhadap perubahan fenotip yang berperan dalam penyempitan usus. Oleh karena itu, dapat ditentukan terapi farmakologis atau terapi gen terkait TGF-β yang berpotensi untuk mencegah penyempitan usus pada penyakit crohn.

Crohn's disease is a crohnic relapsing inflammatory bowel disease potentially affecting any portion of the gastrointestinal tract. It causes abnormal accumulation of extracellular matrix and formation of fibrosis which associated with the increasing amount of Transforming Growt Factor and can leads to intestinal stricture or organ failure. Aim of this research is to identification of targeting site which sensitive Transforming Growth Factor as information for drug delivery of fibrosis therapy in animal and human intestine. In this research, the identification of targeting site which sensitive to TGF can be done by using PCIS Precision Cut Intestinal Slices . It is an ex vivo models to simulate the occurrence of intestinal fibrosis. Results showed that TGF did not affect the viability of the slices and there was implication of TGF in the phenotypic transition which played a role in intestinal strictures. So that, it can be applicable for pharmacologic or targeted gene therapies related TGF which are potentially to prevent stricture of crohn's disease in the near future.
"
Depok: Fakultas Farmasi Universitas Indonesia, 2017
T47539
UI - Tesis Membership  Universitas Indonesia Library
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Wachid Putranto
"[ABSTRAK
Latar Belakang : Continous ambulatory peritoneal dialysis (CAPD) telah menjadi
alternatif selain hemodialisis untuk pengobatan penyakit ginjal tahap akhir. Fibrosis
peritoneum merupakan penyebab utama terjadinya kerusakan membran peritoneum.
Mekanisme fibrosis peritoneum belum diketahui secara pasti, namun ditengarai
transforming growth factor ? β (TGF ?β) berhubungan erat terhadap terjadinya fibrosis
peritoneum.
Tujuan : Tujuan penelitian ini adalah untuk mengetahui pengaruh kombinasi ACE
inhibitor (ACEI) dan calcium channel Blocker (CCB) terhadap penurunan ekspresi TGF
? β dan fibrosis peritoneum tikus jantan yang telah dilakukan CAPD.
Metode Penelitian : Penelitian eksperimental, post test only control group design. Tiga
puluh tikus Dawley spraque dibagi menjadi lima kelompok yaitu kelompok kontrol
(kelompok 1) dan kelompok perlakuan dengan pemberian masing-masing cairan CAPD
4,25% (kelompok2) lisinopril 1,44 mg oral dan CAPD (kelompok 3) diltiazem CD 6,48
mg oral dan CAPD (kelompok 4) lisinopril 1,44 mg dan diltiazem CD 6,48 mg oral dan
CAPD (kelompok 5). Setelah 4 minggu tikus dikorbankan dengan cara dislokasi cervical
kemudian diperiksa ekspresi TGF ? β dan terjadinya fibrosis pada peritoneum tikus,
selanjutnya dibuat sediaan histopatologi dan diwarnai dengan hematoksilin eosin serta
imunohistokimia menggunakan antihuman TGF-ß.
Hasil : Dua puluh peritoneum tikus berhasil diperiksa. Rerata skor TGF-β kelompok
kontrol 1,8, kelompok CAPD 2, kelompok lisinopril dan CAPD 1,8, kelompok diltiazem
CD dan CAPD 1,8, kelompok lisinopril dan diltiazem CD dan CAPD 1,7 (p=0,959).
Rerata skor fibrosis peritoneum kelompok kontrol 1,1, kelompok CAPD 2,6, kelompok
lisinopril dan CAPD 1,2, kelompok diltiazem CD dan CAPD 1,3, kelompok lisinopril dan
diltiazem CD dan CAPD1,5 (p=0,268)
Simpulan : Kombinasi lisinopril dan diltiazem mempunyai kecenderungan menurunkan
ekspresi TGF ? β lebih baik dibandingkan lisinopril maupun diltiazem yang diberikan
secara terpisah tetapi tidak bermakna secara statistik. Kombinasi lisinopril dan diltiazem
mempunyai kecenderungan mengurangi fibrosis peritoneum tetapi tidak bermakna secara
statistik dan tidak lebih baik dibandingkan lisinopril maupun diltiazem bila diberikan
secara terpisah.

ABSTRACT
Background : Continuous ambulatory peritoneal dialysis (CAPD) has been an
alternative other than hemodialysis for end stage kidney disease treatment.
Peritoneal fibrosis is the most serious cause of the damage in membrane
peritoneum. Mechanism of fibrosis peritoneum is not exactly known yet,
transforming growth factor ? β(TGF ? β) is closely related with the existence of
fibrosis peritoneum.
Purposes : The purpose of this study is to evaluate the effect of combination
between ACE inhibitor (ACEI) dan Calcium channel blocker (CCB) in reducing
expression of TGF ? β and fibrosis peritoneum in a male rat treated with CAPD.
Research Method : Experimental study, post test only control group design.
Thirsty Dawley spraque rats are divided into five groups control group ( Group
1), CAPD liquid 4,25% (group 2), lisinopril 1,44 mg oral and CAPD (group 3)
diltiazem CD 6,48 mg oral and CAPD (group 4) lisinopril 1,44mg + diltiazem CD
6,48 mg oral and CAPD (group 5). After 4 weeks, rats sacrificed. Expression of
TGF ? β and peritoneal fibrosis are conducted by histopatology with hematoxillineosin
staining and immunology with anti human-TGF-β.
Result : Twenty peritoneal of rats can be examined. Mean score TGF-β control
group is 1,8, CAPD group is 2, lisinopril and CAPD group is 1,8,diltiazem CD
and CAPD group is 1,8, lisinopril and diltiazem CD and CAPD group is 1,7
(p=0,959) .Mean score peritoneal fibrosis control group is 1,1, CAPD group is
2,6, lisinopril and CAPD group is 1,2, diltiazem CD and CAPD group is 1,3,
lisinopril and diltiazem CD and CAPD group is 1,5 (p=0,268)
Summary : Combination of lisinopril and diltiazem lower the expression of TGF
? β and fibrosis peritoneum better than lisinopril or diltiazem but statistically not
significant. Combination of lisinopril and diltiazem lower the peritoneal fibrosis
but statistically not significant and it doesn?t better than lisinopril or diltiazem.
Key words: ACE inhibitor, calcium channel blocker, TGF-β, peritoneal fibrosis.;Background : Continuous ambulatory peritoneal dialysis (CAPD) has been an
alternative other than hemodialysis for end stage kidney disease treatment.
Peritoneal fibrosis is the most serious cause of the damage in membrane
peritoneum. Mechanism of fibrosis peritoneum is not exactly known yet,
transforming growth factor ? β(TGF ? β) is closely related with the existence of
fibrosis peritoneum.
Purposes : The purpose of this study is to evaluate the effect of combination
between ACE inhibitor (ACEI) dan Calcium channel blocker (CCB) in reducing
expression of TGF ? β and fibrosis peritoneum in a male rat treated with CAPD.
Research Method : Experimental study, post test only control group design.
Thirsty Dawley spraque rats are divided into five groups control group ( Group
1), CAPD liquid 4,25% (group 2), lisinopril 1,44 mg oral and CAPD (group 3)
diltiazem CD 6,48 mg oral and CAPD (group 4) lisinopril 1,44mg + diltiazem CD
6,48 mg oral and CAPD (group 5). After 4 weeks, rats sacrificed. Expression of
TGF ? β and peritoneal fibrosis are conducted by histopatology with hematoxillineosin
staining and immunology with anti human-TGF-β.
Result : Twenty peritoneal of rats can be examined. Mean score TGF-β control
group is 1,8, CAPD group is 2, lisinopril and CAPD group is 1,8,diltiazem CD
and CAPD group is 1,8, lisinopril and diltiazem CD and CAPD group is 1,7
(p=0,959) .Mean score peritoneal fibrosis control group is 1,1, CAPD group is
2,6, lisinopril and CAPD group is 1,2, diltiazem CD and CAPD group is 1,3,
lisinopril and diltiazem CD and CAPD group is 1,5 (p=0,268)
Summary : Combination of lisinopril and diltiazem lower the expression of TGF
? β and fibrosis peritoneum better than lisinopril or diltiazem but statistically not
significant. Combination of lisinopril and diltiazem lower the peritoneal fibrosis
but statistically not significant and it doesn?t better than lisinopril or diltiazem.
Key words: ACE inhibitor, calcium channel blocker, TGF-β, peritoneal fibrosis.;Background : Continuous ambulatory peritoneal dialysis (CAPD) has been an
alternative other than hemodialysis for end stage kidney disease treatment.
Peritoneal fibrosis is the most serious cause of the damage in membrane
peritoneum. Mechanism of fibrosis peritoneum is not exactly known yet,
transforming growth factor ? β(TGF ? β) is closely related with the existence of
fibrosis peritoneum.
Purposes : The purpose of this study is to evaluate the effect of combination
between ACE inhibitor (ACEI) dan Calcium channel blocker (CCB) in reducing
expression of TGF ? β and fibrosis peritoneum in a male rat treated with CAPD.
Research Method : Experimental study, post test only control group design.
Thirsty Dawley spraque rats are divided into five groups control group ( Group
1), CAPD liquid 4,25% (group 2), lisinopril 1,44 mg oral and CAPD (group 3)
diltiazem CD 6,48 mg oral and CAPD (group 4) lisinopril 1,44mg + diltiazem CD
6,48 mg oral and CAPD (group 5). After 4 weeks, rats sacrificed. Expression of
TGF ? β and peritoneal fibrosis are conducted by histopatology with hematoxillineosin
staining and immunology with anti human-TGF-β.
Result : Twenty peritoneal of rats can be examined. Mean score TGF-β control
group is 1,8, CAPD group is 2, lisinopril and CAPD group is 1,8,diltiazem CD
and CAPD group is 1,8, lisinopril and diltiazem CD and CAPD group is 1,7
(p=0,959) .Mean score peritoneal fibrosis control group is 1,1, CAPD group is
2,6, lisinopril and CAPD group is 1,2, diltiazem CD and CAPD group is 1,3,
lisinopril and diltiazem CD and CAPD group is 1,5 (p=0,268)
Summary : Combination of lisinopril and diltiazem lower the expression of TGF
? β and fibrosis peritoneum better than lisinopril or diltiazem but statistically not
significant. Combination of lisinopril and diltiazem lower the peritoneal fibrosis
but statistically not significant and it doesn?t better than lisinopril or diltiazem.
Key words: ACE inhibitor, calcium channel blocker, TGF-β, peritoneal fibrosis.;Background : Continuous ambulatory peritoneal dialysis (CAPD) has been an
alternative other than hemodialysis for end stage kidney disease treatment.
Peritoneal fibrosis is the most serious cause of the damage in membrane
peritoneum. Mechanism of fibrosis peritoneum is not exactly known yet,
transforming growth factor ? β(TGF ? β) is closely related with the existence of
fibrosis peritoneum.
Purposes : The purpose of this study is to evaluate the effect of combination
between ACE inhibitor (ACEI) dan Calcium channel blocker (CCB) in reducing
expression of TGF ? β and fibrosis peritoneum in a male rat treated with CAPD.
Research Method : Experimental study, post test only control group design.
Thirsty Dawley spraque rats are divided into five groups control group ( Group
1), CAPD liquid 4,25% (group 2), lisinopril 1,44 mg oral and CAPD (group 3)
diltiazem CD 6,48 mg oral and CAPD (group 4) lisinopril 1,44mg + diltiazem CD
6,48 mg oral and CAPD (group 5). After 4 weeks, rats sacrificed. Expression of
TGF ? β and peritoneal fibrosis are conducted by histopatology with hematoxillineosin
staining and immunology with anti human-TGF-β.
Result : Twenty peritoneal of rats can be examined. Mean score TGF-β control
group is 1,8, CAPD group is 2, lisinopril and CAPD group is 1,8,diltiazem CD
and CAPD group is 1,8, lisinopril and diltiazem CD and CAPD group is 1,7
(p=0,959) .Mean score peritoneal fibrosis control group is 1,1, CAPD group is
2,6, lisinopril and CAPD group is 1,2, diltiazem CD and CAPD group is 1,3,
lisinopril and diltiazem CD and CAPD group is 1,5 (p=0,268)
Summary : Combination of lisinopril and diltiazem lower the expression of TGF
? β and fibrosis peritoneum better than lisinopril or diltiazem but statistically not
significant. Combination of lisinopril and diltiazem lower the peritoneal fibrosis
but statistically not significant and it doesn?t better than lisinopril or diltiazem.
Key words: ACE inhibitor, calcium channel blocker, TGF-β, peritoneal fibrosis.;Background : Continuous ambulatory peritoneal dialysis (CAPD) has been an
alternative other than hemodialysis for end stage kidney disease treatment.
Peritoneal fibrosis is the most serious cause of the damage in membrane
peritoneum. Mechanism of fibrosis peritoneum is not exactly known yet,
transforming growth factor ? β(TGF ? β) is closely related with the existence of
fibrosis peritoneum.
Purposes : The purpose of this study is to evaluate the effect of combination
between ACE inhibitor (ACEI) dan Calcium channel blocker (CCB) in reducing
expression of TGF ? β and fibrosis peritoneum in a male rat treated with CAPD.
Research Method : Experimental study, post test only control group design.
Thirsty Dawley spraque rats are divided into five groups control group ( Group
1), CAPD liquid 4,25% (group 2), lisinopril 1,44 mg oral and CAPD (group 3)
diltiazem CD 6,48 mg oral and CAPD (group 4) lisinopril 1,44mg + diltiazem CD
6,48 mg oral and CAPD (group 5). After 4 weeks, rats sacrificed. Expression of
TGF ? β and peritoneal fibrosis are conducted by histopatology with hematoxillineosin
staining and immunology with anti human-TGF-β.
Result : Twenty peritoneal of rats can be examined. Mean score TGF-β control
group is 1,8, CAPD group is 2, lisinopril and CAPD group is 1,8,diltiazem CD
and CAPD group is 1,8, lisinopril and diltiazem CD and CAPD group is 1,7
(p=0,959) .Mean score peritoneal fibrosis control group is 1,1, CAPD group is
2,6, lisinopril and CAPD group is 1,2, diltiazem CD and CAPD group is 1,3,
lisinopril and diltiazem CD and CAPD group is 1,5 (p=0,268)
Summary : Combination of lisinopril and diltiazem lower the expression of TGF
? β and fibrosis peritoneum better than lisinopril or diltiazem but statistically not
significant. Combination of lisinopril and diltiazem lower the peritoneal fibrosis
but statistically not significant and it doesn?t better than lisinopril or diltiazem.
Key words: ACE inhibitor, calcium channel blocker, TGF-β, peritoneal fibrosis., Background : Continuous ambulatory peritoneal dialysis (CAPD) has been an
alternative other than hemodialysis for end stage kidney disease treatment.
Peritoneal fibrosis is the most serious cause of the damage in membrane
peritoneum. Mechanism of fibrosis peritoneum is not exactly known yet,
transforming growth factor – β(TGF – β) is closely related with the existence of
fibrosis peritoneum.
Purposes : The purpose of this study is to evaluate the effect of combination
between ACE inhibitor (ACEI) dan Calcium channel blocker (CCB) in reducing
expression of TGF – β and fibrosis peritoneum in a male rat treated with CAPD.
Research Method : Experimental study, post test only control group design.
Thirsty Dawley spraque rats are divided into five groups control group ( Group
1), CAPD liquid 4,25% (group 2), lisinopril 1,44 mg oral and CAPD (group 3)
diltiazem CD 6,48 mg oral and CAPD (group 4) lisinopril 1,44mg + diltiazem CD
6,48 mg oral and CAPD (group 5). After 4 weeks, rats sacrificed. Expression of
TGF – β and peritoneal fibrosis are conducted by histopatology with hematoxillineosin
staining and immunology with anti human-TGF-β.
Result : Twenty peritoneal of rats can be examined. Mean score TGF-β control
group is 1,8, CAPD group is 2, lisinopril and CAPD group is 1,8,diltiazem CD
and CAPD group is 1,8, lisinopril and diltiazem CD and CAPD group is 1,7
(p=0,959) .Mean score peritoneal fibrosis control group is 1,1, CAPD group is
2,6, lisinopril and CAPD group is 1,2, diltiazem CD and CAPD group is 1,3,
lisinopril and diltiazem CD and CAPD group is 1,5 (p=0,268)
Summary : Combination of lisinopril and diltiazem lower the expression of TGF
– β and fibrosis peritoneum better than lisinopril or diltiazem but statistically not
significant. Combination of lisinopril and diltiazem lower the peritoneal fibrosis
but statistically not significant and it doesn’t better than lisinopril or diltiazem.
Key words: ACE inhibitor, calcium channel blocker, TGF-β, peritoneal fibrosis.]"
2016
T-Pdf
UI - Tesis Membership  Universitas Indonesia Library
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Gita Wideani
"Pertumbuhan kanker tidak hanya ditentukan oleh adanya sel kanker itu sendiri akan tetapi ditentukan juga oleh lingkungan mikro disekitarnya. Lingkungan mikro tersebut merupakan jaringan yang heterogen dengan adanya interaksi sel termasuk sel punca mesenkim. Sekretom mengandung faktor-faktor biologis terlarut yang dapat mempengaruhi pertumbuhan sel kanker. Stem cell from Human Exfoliated Deciduous SHED diketahui merupakan sumber sel punca yang memiliki banyak potensi. Sampai saat ini belum diketahui bagaimana dampak pemberian CM dari SHED terhadap sel punca kanker payudara. Oleh karena itu, penelitian ini bertujuan untuk menganalisis pemberian conditioned medium kultur SHED pada sel punca kanker payudara terhadap viablitas, proliferasi dan tumorigenitas serta kepuncaan dari sel punca kanker payudaraALDH dan sel punca kanker MCF7. Conditioned medium SHED SHED-CM adalah medium kultur bebas serum sel SHED yang dikumpulkan dalam 24 jam dan 48 jam. ALDH dan MCF7diberikan 50 v/v SHED-CM 24 jam dan 48 jam dan di inkubasi selama 72 jam. Hal yang sama dilakukan untukperlakuan aktivasi CM dengan suhu. CM sebelum digunakan terlebih dahulu dipanaskan dalam suhu 80 C selama 10 menit. Kontrol adalah sel yang diberikan 50 v/v a-MEM. Perhitungan viabilitas sel dilakukan dengan menggunakan metode Trypan Blue Exclusion Assay dan ekspresi relatif mRNA dari TGF-b1, TGF-b1 receptor TBRI, ALDH1A1 dan OCT4 menggunakan qRT-PCR dan analisis menggunakan perhitungan livak. Hasil penelitian menunjukkan bahwa ekspresi relatif dari TGF-b1, TGF-b1 reseptor TBRI, ALDH1A1 dan OCT4 pada sel ALDH dan MCF7 pasca induksi dengan CM SHED mengalami peningkatan yang signifikan dibandingkan dengan kontrol. Selain itu, peningkatan yang lebih signifikan ditunjukkan pada perlakuan aktivasi dibandingkan yang tidak diaktivasi. Hal yang berbeda pada hasil uji viabilitas sel. Viabilitas sel mengalami penurunan pasca induksi dengan CM SHED sedangkan setelah diinduksi dengan CM SHED yang telah diaktivasi, viabilitas sel mengalami peningkatan yang signifikan pada sel ALDH dan MCF7. Dengan demikian sekretom SHED dapat meningkatkan viabilitas dan proliferasi serta kemampuan kepuncaan dari ALDH dan MCF7.

Cancer development is not only determined by corresponding of cancer cells but also by the microenvironment. This includes a heterogen network of interacting cell include mesenchymal stem cells. Conditioned medium of MSC culture containing soluble factor hes been identified to affect intercellular communicating between MSC and cancer cells which could affect the stemness of cancer cells. Many studies reported that Stem cells from human exfoliated deciduous teeth SHED as a novel stem cell source with multipotent potential. However, the effect of MSC interaction with cancer cells can not be clearly understood so that the effects of safety in its utilization are not yet known for certain. This study is to confirm the relation between secretom of MSC from SHED with the stemness and agresiveness of ALDH and MCF7. SHED conditioned medium SHED CM, SHED were grown in serum free a MEM for 24 and 48 hours, consist of two groups, non heated and heated at 80 C for 10 min. Human BCSCs ALDH cultured in DMEM F12 were supplemented with 50 v v CM SHED 24 h and 48 h, as well as with heated by 72 h incubation. Control was BCSCs supplemented with 50 v v a MEM. We measured the viability with trypan blue assay and mRNA expression of TGF b1, TGF b1 receptor TBRI, as well as stemness genes ALDH1A1 and OCT4 using qRT PCR. The relative mRNA expression levels of TGF b1, T RI, OCT4 and ALDH1A1 in BCSCs supplemented with non heated SHED CM were increased compared to their control and also after TGF b1 heat activation was significantly higher than in non heated SHED CM. In the other hand, the viability cell was significantly reduced after supplemented with non heated SHED CM, but increased higher than control when treated with heated SHED CM, there are may be a role of the TGF b1 signaling involvement of other factors in SHED CM affect cell proliferation and increase the stemness. We found that secretomes SHED can increase proliferation of breast cancer stem cells ALDH and also expression of stemness gene OCT4 and ALDH1A1. the activation with heated can enhance the increase of proliferation and stemness. We assumed that signalling of TGF can affect tumor proggresion of ALDH and MCF7
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2018
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UI - Tesis Membership  Universitas Indonesia Library
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Farah Khalida Salsabila
"ABSTRAK
Pelipatan protein merupakan hal penting dalam pembentukan struktur native protein dan fungsi biologisnya. Kesalahan pelipatan protein dapat menyebabkan penyakit seperti Alzheimers dan fibrosis kistik. Struktur native protein Transforming growth factor b3 (TGF-b3) berbentuk dimer yang diperoleh dari hasil pelipatan monomer identik. Struktur native TGF-b3 dapat diperoleh dari rekombinan TGF-b3 dari E.coli dengan beberapa perlakuan kimia, namun proses ini cenderung membentuk badan iklusi yang mengandung protein non-aktif. Pada umumnya, protein yang terlipat dengan benar menjadi bentuk native merupakan protein yang aktif. Oleh karena itu diperlukan simulasi dinamika molekuler untuk mengetahui mampukah monomer protein TGF-b3 melakukan selffolding. Simulasi dinamika molekuler protein menggunakan perangkat Amber dilakukan pada rantai asam amino struktur monomer protein TGF-b3 dengan identitas PDB 1TGJ. Proses simulasi dilakukan selama 9 μs menggunakan parameter gabungan Amber forcefield ff14SBonlysc, GBNeck2, dan mbondi3 dalam sistem yang tidak menghitung interaksi atom dengan air. Hasil simulasi diperoleh struktur yang berbeda dari struktur monomer kristal protein pada PDB. Rata-rata RMSD dari perbandingan kedua struktur didapatkan kurang lebih 15-16 Å dengan RMSD terendah yakni 14,0479 Å. Dari simulasidinamika molekuler yang dilakukan dengan pendekatan all atom dalam implisit solven, diperoleh struktur monomer non-native protein TGF-b3

ABSTRACT
Protein folding has an important role in the formation of native structure and their biological functions. Incorrect folding can cause diseases such as Alzheimer's and cystic fibrosis. The structure of Transforming growth factor b3 (TGF-b3), in the form of dimers, obtained from folded monomer. Its native structure can be obtained from recombinant TGF-b3 from E. coli when given several chemical treatments, but prone to be misfolded therefore a molecular dynamics simulation is needed to determine whether self-folding of monomer TGF-b3 can be done. Molecular dynamics simulations of protein using Amber software were performed on amino acid chains of monomer TGF-b3 from PDB, the identity is 1TGJ. The simulation process is carried out for 9 μs using a combined parameter of Amber forcefield ff14SBonlysc, GBNeck2, and mbondi3 at an implicit water environment. Unfortunately, the structure obtained from the simulation was different from its monomer crystal structure. The average RMSD we got in the comparison between result structure and monomer crystal structures was approximately 15-16 Å with the lowest RMSD was 14,0479 Å. From the molecular dynamics simulation carried out with the approach of all atoms in implicit water, the non-native structure of monomer TGF-b3 protein was obtained."
2019
S-Pdf
UI - Skripsi Membership  Universitas Indonesia Library
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Bantari Wisynu Kusuma Wardhani
"Latar belakang: Terapi farmakologi kanker payudara triple negative (KPTN)
terbatas pada obat sitostatika seperti doksorubisin. Namun, resistensi doksorubisin
sulit dihindari. Salah satu jalur pensinyalan yang penting pada resistensi
KPTN terhadap doksorubisn adalah TGF-β. TMEPAI (transmembran prostat
androgen-induced protein), regulator negatif sekaligus gen target pada jalur TGF-
β diduga merupakan salah satu kunci dalam resistensi KPTN terhadap
doksorubisin.
Metode: Teknik CRISPR-Cas9 digunakan untuk menghilangkan TMEPAI pada
galur sel KPTN, BT549. Sel diberi perlakuan TGF-β 2 ng / mL dan doksorubisin
selama 24 jam. Pengukuran konsentrasi sitotoksik doksorubisin pada 50%
populasi sel (CC50) dilakukan terhadap sel KPTN wildtype (WT) dan knock out
(KO). Setelah itu, sel dipanen dan dihitung. Rantai Polimerase Waktu Nyata
Reaction (RT-PCR) dan western blot (WB) digunakan untuk mengukur tingkat
ekspresi penande proliferasi, apoptosis, EMT, dan transporter. Selain itu, SMAD
yang terfosforilasi dan aktivitas PI3K / Akt juga belajar.
Hasil: Galur sel yang tidak memiliki TMEPAI (KO) berhasil diperoleh dari sel
KPTN, BT549. Sel WT terbukti lebih resistan terhadap doksorubisin
dibandingkan sel KO yang ditunjukkan dengan peningkatan CC50 dan Ki-67.
TMEPAI menurunkan efek apoptosis doksorubisin dengan memodulasi ekspresi
bcl-2 dan kaspase-3, namun tidak kaspase-9 dan bax. Efek TMEPAI mengurangi
doksorubisin dengan menekan fosforilasi SMAD. Namun TMEPAI meningkatkan
penghambatan PI3K / Akt oleh doksorubisin. TMEPAI juga meningkatkan EMT
dan transporter efluks yang diinduksi oleh doksorubisin.
Kesimpulan: TMEPAI terhadap pertarungan dalam resistensi sel KPTN
doksorubisin melalui aktivasi jalur sinyal TGF-β non-canonical beserta protein
dan gen targetnya.
Background: Triple negative breast cancer (KPTN) pharmacological therapy
limited to cytostatic drugs such as doxorubicin. However, doxorubicin resistance
hard to avoid. One of the important signaling pathways of resistance
KPTN against doxorubisn is TGF-β. TMEPAI (transmembrane prostate
androgen-induced protein), a negative regulator as well as a target gene in the TGF-
β is thought to be one of the keys in the resistance of KPTN to
doxorubicin.
Method: The CRISPR-Cas9 technique was used to remove TMEPAI on
KPTN cell lines, BT549. Cells were treated with TGF-β 2 ng / mL and doxorubicin
for 24 hours. Measurement of the cytotoxic concentration of doxorubicin at 50%
cell population (CC50) was carried out against wildtype KPTN (WT) cells and knockout
(KO). After that, cells are harvested and counted. Real Time Polymerase Chain
Reaction (RT-PCR) and western blot (WB) were used to measure levels
expression markers of proliferation, apoptosis, EMT, and transporters. Apart from that, SMAD
the phosphorylated and PI3K / Akt activities also learn.
Results: Cell lines that did not have TMEPAI (KO) were obtained from the cells
KPTN, BT549. WT cells have been shown to be more resistant to doxorubicin
compared to cell knockout shown with increased CC50 and Ki-67.
TMEPAI decreases the apoptotic effect of doxorubicin by modulating expression
bcl-2 and caspase-3, but not caspase-9 and bax. TMEPAI reducing effects
doxorubicin by suppressing SMAD phosphorylation. However TMEPAI is improving
PI3K / Akt inhibition by doxorubicin. TMEPAI also increases EMT
and doxorubicin-induced efflux transporters.
Conclusion: TMEPAI against the fight against KPTN cell resistance
doxorubicin via activation of the non-canonical TGF-β signaling pathway along with proteins
and its target genes."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2019
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UI - Disertasi Membership  Universitas Indonesia Library
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Ari Rahman Iskandar
"Latar belakang: Atresia bilier merupakan penyebab paling umum fibrosis hati pada anak, dan menjadi indikasi terbanyak transplantasi hati. Fibrosis hati dapat dinilai dengan pemeriksaan histopatologis dan kuantifikasi skor Laennec. Pemeriksaan biomarker dari darah dan metode pencitraan radiologis merupakan upaya lain untuk menilai derajat fibrosis hati. Penelitian ini dimaksudkan untuk meneliti perbandingan biomarker penanda fibrosis transforming growth factor (TFG-β), matrix metalloproteinase (MMP)-7, dan ultrasonografi (USG) Acoustic Radiation Force Impulse (ARFI) dengan derajat fibrosis berdasarkan pemeriksaan histopatologi. Metode penelitian: Penelitian ini merupakan penelitian desain cross sectional pada pasien anak dengan kolestasis yang dicurigai akibat atresia bilier di ruang rawat anak RSUPN Cipto Mangunkusumo. Data penelitian ini adalah data primer dari anamnesis, pemeriksaan fisik, serta data sekunder dari rekam medis untuk melihat riwayat penyakit pasien. Dilakukan pemeriksan serum biomarker TGF-β dan MMP-7, dan USG ARFI oleh operator yang telah ditentukan. Dibandingkan hasil pemeriksaan TGF-β, MMP-7, USG ARFI dengan hasil skoring fibrosis biopsi hati.
Hasil penelitian: Dari total 15 pasien dengan AB, terdapat 6 pasien F2-F3, dan 9 pasien F4 berdasarkan derajat fibrosis biopsi hati. Terdapat peningkatan kadar TGF-β dengan adanya peningkatan derajat fibrosis biopsi hati, namun tidak terdapat hubungan bermakna antara derajat fibrosis hati dengan kadar TGF-β (uji Mann-Whitney, p=0.768). Pada penelitian ini, rerata kadar MMP-7 pada kelompok F2-3 dan F4 menunjukan peningkatan, namun tidak terdapat hubungan yang bermakna (Uji Mann-Whitney, p=0.409). Terdapat hubungan bermakna antara derajat fibrosis hati F2-F3 dengan derajat F4 yang diperoleh berdasarkan hasil USG ARFI dan hasil biopsi hati (p<0,01). Kesimpulan: TGF-β dan MMP-7 merupakan biomarker yang cukup efektif namun memiliki keterbatasan tidak spesifik untuk AB. USG ARFI merupakan pemeriksaan minimal invasive yang efektif untuk menentukan derajat fibrosis.

Background: Biliary atresia is the most common cause of liver fibrosis and the highest indication for liver transplantation in pediatrics. Liver fibrosis is quantified through Laennec score based on histopathology of liver biopsy. Blood serum biomarkers and radiological examinations are alternative methods that could determine liver fibrosis. This study aimed to compare the significance of serum biomarkers transforming growth factor (TFG-β), matrix metalloproteinase (MMP)-7, and Acoustic Radiation Force Impulse (ARFI) ultrasonography (USG) in determining the degree of liver fibrosis compared to histopathology score from liver biopsy. Method: This was a cross-sectional study, on patients in the pediatric ward at dr. Cipto Mangunkusumo National Hospital, that were admitted with cholestasis with biliary atresia as the suspected etiology. Primary data was obtained through anamnesis, and physical examination, and secondary data was obtained through patients’ medical records. Serum biomarkers TGF-β and MMP-7, and USG ARFI were examined by related experts and results were obtained through medical records. Results of TGF-β, MMP-7, and USG ARFI were compared with fibrosis scores based on liver biopsy.
Result: From a total of 15 patients with AB, there were 6 F2-F3 patients, and 9 F4 patients according to the biopsy results. TGF-β levels showed and increasing trend alongside increase in liver biopsy fibrosis score, however it was not statistically significant (Mann- Whitney test, p=0.768). In this study, there was an increase in MMP-7 levels in F2-3 group compared to f4 group, however there was no statically significant difference (Mann-Whitney test, p=0.409). The ARFI USG results showed significant difference between F2-F3 group and F4 group based on ARFI USG compared to liver biopsy (p<0.01). Conclusion: TGF-β and MMP-7 are effective serum biomarkers, however, lacked specificity to determine fibrosis levels in biliary atresia. A minimally invasive test that is effective in determining the degree of fibrosis can be done through ARFI USG.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2023
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UI - Tugas Akhir  Universitas Indonesia Library
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Wahyunia Likhayati Septiana
"ABSTRAK
Penggunaan sel punca sebagai anti fibrosis hati cukup menjanjikan. Sel punca CD34 asal darah tali pusat sudah banyak digunakan dalam studi anti fibrosis hati. Penelitian ini menjelaskan efek ko-kultur antara sel stelata hepatik HSC LX-2 dan sel punca CD34 asal darah tali pusat dalam morfologi sel dan ekspresi TGF-?, tenascin-C dan kolagen tipe 1A1. Metode : Sel CD34 diisolasi dari sel darah tali pusat manusia yang dikriopreservasi menggunakan separasi magnet. Sel HSC LX-2 dikultur sebagai kontrol monokultur. Sebagian dipanen dan dihitung untuk dilakukan ko-kultur dengan sel CD34 dalam rasio 1:1. Ko-kultur CD34 dan LX-2 dilakukan dengan metode kultur konvensional 2D dan 3D hanging drop. Hasil monokultur dan ko-kultur dipanen pada hari ke1, 2 dan 3 dan dilakukan pewarnaan imunositokimia tenascin-C ekstraksi RNA untuk analisis kuantitatif dengan real time PCR ekspresi TGF-? dan kolagen tipe 1A1.Hasil : Hasil menunjukkan perbedaan morfologi ko-kultur 2D dan 3D hanging drop dibandingkan kontrol monokultur. Pada ko-kultur 2D terdapat mikromassa, sedangkan pada monokultur 2D tidak ada mikromassa yang terbentuk. Pada ko-kultur 3D hanging drop, terdapat spheroid yang lebih kecil hambatan pembentukan spheroid dibandingkan monokultur 3D hanging drop. Sel CD34 memiliki efek direk terhadap aktivitas sinyal sel stelata hepatik dengan adanya kecenderungan penurunan ekspresi TGF-?. Analisis imunositokimia tenascin-C dalam mikromassa dan spheroid masih perlu dioptimasi. Ko-kultur 2D dan 3D hanging drop method sel punca CD34 asal darah tali pusat dan sel stelata hepatik memiliki efek terhadap penurunan ekspresi kolagen tipe 1A1.Kesimpulan : Sel punca CD34 asal darah tali pusat memiliki efek direk terhadap morfologi sel, inhibisi aktivitas sel stelata hepatik LX-2 yang ditandai dengan penurunan ekspresi TGF-beta dan inhibisi deposisi matriks ekstrasel yang ditandai penurunan ekspresi kolagen tipe 1A1.Kata kunci: sel punca asal darah tali pusat CD34 , sel stelata hepatik, liver fibrosis, TGF-beta, tenascin-C, kolagen 1A1.

ABSTRACT
Background The development of stem cell therapy antifibrotik placing as one of the promising therapy. Umbilical cord blood CD34 stem cells has been widely used in the study antifibrosis. This study describes the effect of co culture between hepatic stellate cells HSC LX 2 and umbilical cord blood CD34 stem cells on cell morphology and expression of TGF , tenascin C and collagen type 1A1.Method CD34 cells were isolated from thawed cryopreserved human umbilical cord blood cells using magnetic separation. LX 2 cells culture were harvested and counted. CD34 and LX 2 cells were mixed in suspension with 1 1 ratio v v . Cell suspension divided into 2 sets 2D co culture plated in standard well plate and 3D co culture as hanging drops. LX 2 monoculture, CD34 dan LX 2 coculture were harvested on day 1, 2 and 3 as sample for further analysis. Tenascin C expression was analysed by imunocytochemistry techniques. TGF Beta and collagen type 1A1 expression was analysed by qPCR.Result The result showed different morphology between co culture and monoculture on 2D and 3D hanging drop. The 2D co culture showed micromass formation, instead of no micromass formation on monoculture. The 3D hanging drop showed smaller spheroid formation spheroid formation inhibition compared with monoculture. CD34 cells showed direct effect on hepatic stellate cell signalling activity represented by the decrease in TGF beta expression, inhibition of extracellular matrix deposition represented by a decrease in Collagen type 1A1 expression.Conclusion UCB CD34 cells showed direct effect on cell morphology, inhibition of hepatic stellate cell LX 2 activity represented by a decrease in TGF beta expression, inhibition of extracellular matrix deposition represented by a decrease in collagen type 1A1 expression. "
2016
T-Pdf
UI - Tesis Membership  Universitas Indonesia Library
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