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"Fenomena utama pada pasien MDS adalah sitopenia di darah tepi, namun disertai kondisi hiperselular di sumsum tulang. sCD40L dianggap sebagai sitokin yang dapat memicu sintesis TNFα sebagai sitokin proapoptosis dan memicu sintesis VEGF sebagai sitokin proangiogenesis pada MDS. Oleh sebab itu sCD40L dianggap berpotensi sebagai biopenanda untuk memperkirakan perburukan pada MDS. Penelitian ini bertujuan untuk membuktikan peran pajanan rh-sCD40L dalam menginduksi sintesis TNFα dan VEGF pada sel progenitor hematopoesis, serta membuktikan peran pajanan TNFα dalam memicu apoptosis pada sel progenitor hematopoesis dan sel mesenkim MDS. Penelitian ini merupakan penelitian eksperimental in vitro komparatif. Subjek penelitian adalah pasien MDS yang didiagnosis dan diklasifikasikan berdasarkan kriteria WHO 2008. Pada bone marrow mononuclear cells (BMMC) dipajankan dengan rh-sCD40L dan antiCD40L, kemudian dilakukan pemeriksaan ekspresi mRNA TNFα dan mRNA VEGF yang dikuantifikasi dengan qRT-PCR, serta pemeriksaan kadar TNFα dan VEGF yang diperiksa dengan metode ELISA. Pada sel CD34+, CD33+, CD41+, dan CD73+ dipajankan rhTNFα kemudian dilakukan pemeriksaan aktivitas kaspase-3 dengan imunoflowsitometri.Terdapat 15 sampel MDS terdiri dari 4 dengan diagnosis RCUD, 7 RCMD, dan 4 RAEB1, serta 7 sampel kontrol. Pajanan rh-sCD40L meningkatkan ekspresi mRNA TNFα secara bermakna dibandingkan pajanan antiCD40L. Pajanan rh-sCD40L meningkatkan kadar TNFα secara bermakna dibandingkan kontrol. Namun pajanan rh-sCD40L tidak meningkatkan mRNA VEGF dan kadar protein VEGF. Pajanan rhTNFα meningkatkan aktivitas kaspase-3 pada sel progenitor MDS terutama yang berdiferensiasi menjadi mieloid (CD33+) dan megakariosit-trombosit (CD41+). Pajanan rhTNFα meningkatkan aktivitas kaspase-3 pada sel mesenkim (CD73+) MDS Simpulan: sCD40L berperan dalam meningkatkan sintesis sitokin proapoptosis TNFα di level mRNA dan protein, namun tidak terbukti berperan dalam meningkatkan sintesis proangiogenesis VEGF. TNFα berperan dalam meningkatkan apoptosis terutama pada sel hematopoesis yang telah berdiferensiasi menjadi seri mieloid dan seri megakariosit-trombosit, dan berperan dalam meningkatkan apoptosis pada sel mesenkim.

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Cytopenia is the primary phenomenon in Myelodysplastic Syndrome (MDS) patients, amidst hypercellular bone marrow. The soluble CD40 ligand (sCD40L) is considered as a cytokine that can trigger synthesis of TNFα and VEGF. The former is known as a cytokine that promotes apoptosis while the latter promotes angiogenesis in MDS patients. Therefore, the sCD40L may serve as a potential biomarker to predict worsening of MDS. This study aims to prove the role of rh-sCD40L exposure in inducing the synthesis of TNFα and VEGF in hematopoietic progenitor cells, as well as to establish the role of TNFα exposure in triggering apoptotic activity in hematopoietic progenitor and mesenchymal cells of MDS. The study was a comparative in vitro experimental study. Subjects were MDS patients diagnosed and classified using the WHO 2008 criteria. Bone marrow mononuclear cells (BMMC) were exposed to rh-sCD40L and antiCD40L. The expressions of TNFα and VEGF mRNAs were then quantified by qRT-PCR, and the level of TNFα and VEGF were measured using the ELISA method. The CD34+, CD33+, CD41+, and CD73+ cells were exposed to rhTNFα, then the activity of enzyme caspase-3 was measured using the immunoflowcytometry.There were 7 control and 15 MDS samples with the following diagnoses: 4 RCUD, 7 RCMD, and 4 RAEB1. Compared to antiCD40L, it is found that exposure of rh-sCD40L significantly increased the expression of TNFα mRNA. The similar exposure also significantly increased the level of TNFα compared to controls. However, the exposure of rh-sCD40L did not increase the expression of VEGF mRNA as well as the level of VEGF. The exposure of rhTNFα was found to increase the activity of caspase-3 in MDS progenitor cells, particularly those differentiated into myeloid cells (CD33+) and megakaryocyte-thrombocyte cells (CD41+). The exposure of rhTNFα was found to increase the activity of caspase-3 in MDS mesenchymal (CD73+) cells.Conclusion: The sCD40L plays a role in increasing the synthesis of TNFα which favors apoptotic activity in mRNA and protein level, but not in improving the synthesis of VEGF that promotes angiogenesis. Furthermore, TNFα plays a role in increasing apoptotic activity of hematopoietic cells, particularly those that have differentiated into myeloid series and megakaryocyte-thrombocyte series cells. Also TNFα plays a role in increasing apoptotic activity of mesenchymal cells."

"Sindrom mielodisplasia (Myelodysplastic Syndrome, MDS) adalah sejumlah gangguan yang terjadi akibat sumsum tulang tidak mampu menghasilkan sel-sel darah yang sehat.1 Diferensiasi sel prekursor darahterganggu, 2 dan apoptosis meningkat dengan signifikan sehingga sel-sel darah menjadi abnormal yang tidak sepenuhnya berkembang. 3 Gen PI-PLCß1 terlibat dalam proliferasi dan diferensiasi. Mutasi gen PI-PLCß1 dapat memengaruhi peningkatan proliferasi sel blast pada MDS dan cenderung bertransformasi menjadi Leukemia Mieloblastik Akut (Acute Myeloblastic Leukemia, AML). Diketahui PI-PLCβ1 berperan dalam kontrol siklus sel pada transisi G1/S dan perkembangan G2/M. Disregulasi ekspresi gen PI-PLCß1 menyebabkan gangguan pada jalur pensinyalan yang melibatkan proses diferensiasi sel, sehingga terjadi perubahan diferensiasi sel prekursor darah yang menyimpang. Banyak faktor yang menyulitkan pengamatan dalam pemeriksaan sitogenetika pada pasien MDS. Sehingga pemeriksaan ekspresi gen PI-PLCß1 diharapkan akan menjadi pengkajian awal dalam menilai prognostik MDS. Desain penelitian deskriptif dan analitik pada 4 subjek penelitian (3 pasien MDS-MLD, 1 pasien MDS yang telah menjadi AML), dan kontrol pasien dengan kelainan hematologi lain (Multiple Mieloma) sebanyak 1 pasien, serta 1 kontrol sehat. Sebanyak 3/5 (80%) memiliki kelainan kariotip kompleks, dan 1/5 (20%) memiliki kelainan kariotip ganda, dan 1/5 (20%) memiliki kelainan kariotip tunggal. Ekspresi gen PI-PLCß1 lebih rendah pada 4 pasien (MDS dan AML). Sedangkan pada 1 kontrol pasien dengan kelainan hematologi lainnya memiliki ekspresi gen PI-PLCß1 lebih tinggi dibandingkan dengan kontrol sehat. Ekspresi gen PI-PLCß1 lebih rendah pada pasien MDS dengan prognosis yang lebih buruk menurut skoring IPSS-R.

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Myelodysplastic syndrome (MDS) is a number of disorders that occur due to the bone marrow is not able to produce healthy blood cells. 1 The differentiation of blood precursor cells is impaired, 2 and apoptosis increases significantly that the blood cells become abnormal and do not fully develop. 3 The PI-PLCß1 gene is involved in proliferation and differentiation. PI-PLCß1 gene mutations can affect the increase in blast cell proliferation in MDS and tend to transform into Acute Myeloid Leukemia (AML). It is known that PI-PLCβ1 plays a role in cell cycle control in the G1/S transition and G2/M development. Dysregulation of PI-PLCß1 gene expression causes disruption of signaling pathways that involve the process of cell differentiation, resulting in aberrant changes in blood precursor cell differentiation. Many factors complicate observations in the cytogenetic studies of MDS patients. Therefore, it is hoped that the examination of PI-PLCß1 gene expression will be an initial assessment in assessing the prognostic value of MDS. The study design was descriptive and analytic in 5 study subjects (3 MDS-MLD patients, 1 AML patient, and 1 MM patient). Most of the patients had complex karyotype abnormalities, the rest had multiple karyotype abnormalities and single karyotype abnormalities. PI-PLCß1 gene expression was decreased in all MDS and AML patients. Meanwhile, MM patients had normal PI-PLCß1 gene expression. However, the increase in IPSS-R scores in patients was not significantly associated with a decrease in the expression of the PI-PLCß1 gene."

"ABSTRAKWalaupun publikasi mengenai endometriosis meningkat dalam lima tahun terakhir, penanganan dan terapi definitif untuk endometriosis masih belum ditemukan, menyebabkan 20 penurunan kualitas hidup pada pasien endometriosis. Asam galat telah digunakan pada sel kanker sehingga mendorong peneliti untuk menyelidiki potensi asam galat sebagai pemicu apoptosis pada sel endometriosis. Kultur primer didapatkan dengan teknik enzimatik dari pasien yang telah menjalani laparoskopi. Sel endometriosis in vitro diberi perlakukan dengan asam galat, heptil galat, dan oktil galat dengan dosis 25.6, 51.2, dan 102.4 selama 48 jam. Kuantifikasi dan penentuan kualitas sel dilakukan menggunakan mikroskop konfocal fluoresens dan pewarnaan Acridine Orange/Ethidium Bromide (AO/EB) dengan observasi sel yang mengalami apoptosis awal, apoptosis akhir,nekrosis, dan sel hidup. Sampel kontrol menunjukkan 63.8 sel mengalamiapoptosis. Apoptosis setelah pemberian asam galat menurun dari 90,1 menjadi 79,2 dengan peningkatan dosis. Sebaliknya, 51,2 6 heptyl meningkatkan apoptosis menjadi 92.5, sedangkan oktil 51,2 6 menunjukkan apoptosis terbesar dengan 93.1 Penelitian ini menunjukkan efek apoptosis oktil galat diikuti oleh heptil galat dan asam galat dan potensi penggunaan oktil galat sebagai terapi endometriosis

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ABSTRACTResearch into endometriosis falls behind despite increasing publication for the last five years, contributing to lack of non-invasive treatments and 20% decrease in quality of life. Since gallic acid usage as anti-inflammatory agent has been elucidated in cancer cells, this study serves to investigate the potential of gallic acid as an apoptotic inducer in endometriosis cells. Primary culture of endometriosis was derived from patients who had laparascopy via enzymatic technique. In vitro endometriosis cells were treated with three dosages of 25.6, 51.2 and 102.4 of gallic acid, heptyl gallate, and octyl gallate for 48 hours. Determination of quality and quantification of early, late, viable, and necrotic cells was done using confocal fluorescence with acridine orange/ethidium bromide staining of at least 100 cells per sample. Control samples showed 63.8 cell underwent apoptosis. Gallic acid, heptyl gallate, and octyl gallate showed differentinhibition pattern. Apoptosis after gallic acid treatment decreased from 90.1 to 79.2 as the dose is increased. On the contrary, 51.2 heptyl induce 92.5apoptosis, while octyl showed most apoptosis at 93.1 This study exhibitedapoptotic inductor effect of octyl gallate, followed by heptyl gallate and gallic acid and their potency as treatment for endometriosis."

"[ABSTRAKLatar Belakang: Kanker prostat adalah kanker yang paling umum pada pria. Kanker terjadi karena hilangnya kontrol atas proliferasi sel dan apoptosis sehingga sel berproliferasi terus menerus tanpa ada kematian sel. Apoptosis diregulasi oleh beberapa protein tertentu diantaranya protein keluarga Bcl-2 dan protein kanal. Perkembangan kanker prostat memerlukan transformasi dari sel epitel yang normal menjadi sel ganas yang kehilangan kemampuan untuk mengakumulasi zinc. Salah satu efek utama zinc adalah mencegah pertumbuhan sel kanker prostat dengan menginduksi apoptosis dengan memfasilitasi proses pembentukan pori Bax yang memulai apoptogenesis mitokondria. Selain keluarga Bcl-2, VDAC1 juga berperan penting dalam proses apoptosis. Beberapa penelitian menyatakan Bcl-2 mempunyai kaitan erat dengan VDAC1 terkait proses apoptosis dan protein pro-apoptotik Bax juga secara langsung berinteraksi dengan VDAC yang kemudian menginduksi keluarnya sitokrom c dari membran mitokondria.Tujuan: Mengevaluasi ekspresi mRNA dari gen mengkode keluarga protein Bcl-2 (Bax dan Bcl-2) dalam proses apoptogenesis pada galur sel kanker prostat yg diinduksi oleh zinc; Mengevaluasi ekspresi mRNA dari gen VDAC1 dalam proses apoptogenesis pada galur sel kanker prostat yang diinduksi oleh zinc; Menganalisis hubungan antara ekspresi VDAC1 dengan protein keluarga Bcl-2 pada apoptogenesis galur sel kanker prostat.Desain: Penelitian ini menggunakan eksperimental in vitro dan analisis statistikMetode: Untuk memperbanyak galur sel kanker prostat (PC3) dilakukan kultur sel, kemudian diberi perlakuan dengan tiga kelompok (kontrol, zinc 20 μM dan staurosporin 0,16 μM). Selanjutnya dilakukan isolasi RNA dan elektroforesis RNA untuk mengetahui keutuhan RNA. Terakhir dilakukan qRT PCR yang kemudian datanya dianalisis secara statistika.Hasil: Ekspresi Bax, Bcl-2 dan VDAC1 pada galur sel kanker prostat (PC-3) yang diberi perlakuan zinc mengalami penurunan dibandingkan dengan kontrol (tidak diberi perlakuan). Akan tetapi penurunan ekspresi tersebut tidak bernilai signifikan karena nilai p > 0,05 (nilai signifikansi Bax = 0,309; nilai signifikansi Bcl-2 = 0,236; nilai signifikansi VDAC1 = 0,437). VDAC1 mempunyai korelasi yang signifikan (p < 0,05) dengan Bax (p = 0,01) dibandingkan dengan Bcl-2 (p = 0,118).Kesimpulan: Terjadi perubahan ekspresi pada setiap gen (Bax, Bcl-2 dan VDAC1) pada galur sel kanker prostat yang diberi perlakuan zinc dengan yang tidak diberi perlakuan, akan tetapi tidak bernilai signifikan. VDAC1 mempunyai korelasi yang bermakna dengan Bax dan mempunyai korelasi yang tidak bermakna dengan Bcl-2.

ABSTRACT

Background: Prostate cancer is the most common cancer in men. Cancer occurs due to loss control of cell proliferation and apoptosis thus continuously proliferating cells without cell death. Apoptosis is regulated by specific proteins including Bcl-2 family proteins and channel proteins. The development of prostate cancer requires the transformation of normal epithelial cells into malignant cells that lose the ability to accumulate zinc. One of the main effects of zinc is to prevent the growth of prostate cancer cells by inducing apoptosis by facilitating the process of pore formation Bax that started apoptogenesis mitochondrial. In addition to Bcl-2 family, VDAC1 also plays an important role in the process of apoptosis. Some studies suggest Bcl-2 has close links with related VDAC1 apoptosis and pro-apoptotic protein Bax also directly interact with VDAC which then induces the release of cytochrome c from the mitochondrial membrane.

Objective: To evaluate the expression of mRNA of the gene encoding the Bcl-2 family proteins (Bax and Bcl-2) in the process apoptogenesis on prostate cancer cell line that is induced by zinc; Evaluate the mRNA expression of genes in the process VDAC1 apoptogenesis on prostate cancer cell line induced by zinc; Analyzing the relationship between the expression of VDAC1 with Bcl-2 family proteins in prostate cancer cell lines apoptogenesis.

Design: This study used an experimental in vitro and statistical analysis

Methods: To reproduce the prostate cancer cell lines (PC3) performed cell culture, then treated with three groups (control, zinc 20 μM and staurosporin 0,16 μM). Furthermore, the isolation of RNA and RNA electrophoresis to determine the integrity of the RNA. Recently performed qRT PCR and the data were analyzed statistically.

Results: The expression of Bax, Bcl-2 and VDAC1 on prostate cancer cell line (PC-3) were treated with zinc decreased than the control (untreated). However, a decrease in the expression of no significant value because the value of p > 0.05 (Bax significant value = 0.309; the value of the significance of Bcl-2 = 0.236; VDAC1 significant value = 0.437). VDAC1 has a significant correlation (p < 0.05) with Bax (p = 0.01) than Bcl-2 (p = 0.118).

Conclusion: There is a change in the expression of each gene (Bax, Bcl-2 and VDAC1) in prostate cancer cell lines that treated with zinc than untreated, but no significant value. VDAC1 has a significant correlation with Bax and had no significant correlation with Bcl-2.;Background: Prostate cancer is the most common cancer in men. Cancer occurs due to loss control of cell proliferation and apoptosis thus continuously proliferating cells without cell death. Apoptosis is regulated by specific proteins including Bcl-2 family proteins and channel proteins. The development of prostate cancer requires the transformation of normal epithelial cells into malignant cells that lose the ability to accumulate zinc. One of the main effects of zinc is to prevent the growth of prostate cancer cells by inducing apoptosis by facilitating the process of pore formation Bax that started apoptogenesis mitochondrial. In addition to Bcl-2 family, VDAC1 also plays an important role in the process of apoptosis. Some studies suggest Bcl-2 has close links with related VDAC1 apoptosis and pro-apoptotic protein Bax also directly interact with VDAC which then induces the release of cytochrome c from the mitochondrial membrane.

Objective: To evaluate the expression of mRNA of the gene encoding the Bcl-2 family proteins (Bax and Bcl-2) in the process apoptogenesis on prostate cancer cell line that is induced by zinc; Evaluate the mRNA expression of genes in the process VDAC1 apoptogenesis on prostate cancer cell line induced by zinc; Analyzing the relationship between the expression of VDAC1 with Bcl-2 family proteins in prostate cancer cell lines apoptogenesis.

Design: This study used an experimental in vitro and statistical analysis

Methods: To reproduce the prostate cancer cell lines (PC3) performed cell culture, then treated with three groups (control, zinc 20 μM and staurosporin 0,16 μM). Furthermore, the isolation of RNA and RNA electrophoresis to determine the integrity of the RNA. Recently performed qRT PCR and the data were analyzed statistically.

Results: The expression of Bax, Bcl-2 and VDAC1 on prostate cancer cell line (PC-3) were treated with zinc decreased than the control (untreated). However, a decrease in the expression of no significant value because the value of p > 0.05 (Bax significant value = 0.309; the value of the significance of Bcl-2 = 0.236; VDAC1 significant value = 0.437). VDAC1 has a significant correlation (p < 0.05) with Bax (p = 0.01) than Bcl-2 (p = 0.118).

Conclusion: There is a change in the expression of each gene (Bax, Bcl-2 and VDAC1) in prostate cancer cell lines that treated with zinc than untreated, but no significant value. VDAC1 has a significant correlation with Bax and had no significant correlation with Bcl-2., Background: Prostate cancer is the most common cancer in men. Cancer occurs due to loss control of cell proliferation and apoptosis thus continuously proliferating cells without cell death. Apoptosis is regulated by specific proteins including Bcl-2 family proteins and channel proteins. The development of prostate cancer requires the transformation of normal epithelial cells into malignant cells that lose the ability to accumulate zinc. One of the main effects of zinc is to prevent the growth of prostate cancer cells by inducing apoptosis by facilitating the process of pore formation Bax that started apoptogenesis mitochondrial. In addition to Bcl-2 family, VDAC1 also plays an important role in the process of apoptosis. Some studies suggest Bcl-2 has close links with related VDAC1 apoptosis and pro-apoptotic protein Bax also directly interact with VDAC which then induces the release of cytochrome c from the mitochondrial membrane.

Objective: To evaluate the expression of mRNA of the gene encoding the Bcl-2 family proteins (Bax and Bcl-2) in the process apoptogenesis on prostate cancer cell line that is induced by zinc; Evaluate the mRNA expression of genes in the process VDAC1 apoptogenesis on prostate cancer cell line induced by zinc; Analyzing the relationship between the expression of VDAC1 with Bcl-2 family proteins in prostate cancer cell lines apoptogenesis.

Design: This study used an experimental in vitro and statistical analysis

Methods: To reproduce the prostate cancer cell lines (PC3) performed cell culture, then treated with three groups (control, zinc 20 μM and staurosporin 0,16 μM). Furthermore, the isolation of RNA and RNA electrophoresis to determine the integrity of the RNA. Recently performed qRT PCR and the data were analyzed statistically.

Results: The expression of Bax, Bcl-2 and VDAC1 on prostate cancer cell line (PC-3) were treated with zinc decreased than the control (untreated). However, a decrease in the expression of no significant value because the value of p > 0.05 (Bax significant value = 0.309; the value of the significance of Bcl-2 = 0.236; VDAC1 significant value = 0.437). VDAC1 has a significant correlation (p < 0.05) with Bax (p = 0.01) than Bcl-2 (p = 0.118).

Conclusion: There is a change in the expression of each gene (Bax, Bcl-2 and VDAC1) in prostate cancer cell lines that treated with zinc than untreated, but no significant value. VDAC1 has a significant correlation with Bax and had no significant correlation with Bcl-2.]"

"Kanker kolorektal merupakan masalah kesehatan masyarakat global dengan prevalensi tinggi yang pengobatannya masih memiliki keterbatasan. Senyawa flavonoid terutama kuersetin dinilai memiliki aktivitas biologis sebagai antikanker, sehingga beberapa senyawa flavonoid lainnya diharapkan juga memiliki aktivitas serupa. Tujuan dari studi ini adalah melakukan analisis secara in-silico dan in-vitro terhadap beberapa senyawa flavonoid terutama kuersetin dan turunannya sebagai agen apoptosis sel kanker kolorektal HT-29. Metode yang dilakukan secara in-silico meliputi jejaring farmakologi dan simulasi molekuler. Senyawa terbaik berdasarkan analisis in-silico diuji secara in-vitro dengan menilai aktivitas sitotoksisitasnya pada sel HT-29 menggunakan metode MTT Assay dan apoptosisnya dianalisis menggunakan flow cytometry. Protein target yang memiliki interaksi dengan kuersetin dan senyawa turunannya yaitu AKT1, APAF1, BCL2, CASP3, MAPK1 dan CASP9. Berdasarkan analisis prediksi ADMET, kuersetin dan turunannya masuk dalam kategori aman sebagai kandidat obat. Dua senyawa terbaik berdasarkan analisis in-silico yakni isoramnetin dan isokuersitrin dipilih untuk diuji secara in-vitro. Aktivitas sitotoksik kuersetin, isoramnetin dan isokuersitrin terhadap sel HT-29 dinyatakan dengan nilai CC50 berturut-turut 158,92mm + 5,4, 65,52mm + 5,0 dan 47,59mm + 2,5. Aktivitas apoptosis mencapai 16,7% hingga 62,4% jika dibandingkan dengan kontrol sel. Isoramnetin dan Isokuersitrin sebagai senyawa flavonoid turunan kuersetin berpotensi sebagai agen apoptosis sel kanker kolorektal HT-29.Kanker kolorektal merupakan masalah kesehatan masyarakat global dengan prevalensi tinggi yang pengobatannya masih memiliki keterbatasan. Senyawa flavonoid terutama kuersetin dinilai memiliki aktivitas biologis sebagai antikanker, sehingga beberapa senyawa flavonoid lainnya diharapkan juga memiliki aktivitas serupa. Tujuan dari studi ini adalah melakukan analisis secara in-silico dan in-vitro terhadap beberapa senyawa flavonoid terutama kuersetin dan turunannya sebagai agen apoptosis sel kanker kolorektal HT-29. Metode yang dilakukan secara in-silico meliputi jejaring farmakologi dan simulasi molekuler. Senyawa terbaik berdasarkan analisis in-silico diuji secara in-vitro dengan menilai aktivitas sitotoksisitasnya pada sel HT-29 menggunakan metode MTT Assay dan apoptosisnya dianalisis menggunakan flow cytometry. Protein target yang memiliki interaksi dengan kuersetin dan senyawa turunannya yaitu AKT1, APAF1, BCL2, CASP3, MAPK1 dan CASP9. Berdasarkan analisis prediksi ADMET, kuersetin dan turunannya masuk dalam kategori aman sebagai kandidat obat. Dua senyawa terbaik berdasarkan analisis in-silico yakni isoramnetin dan isokuersitrin dipilih untuk diuji secara in-vitro. Aktivitas sitotoksik kuersetin, isoramnetin dan isokuersitrin terhadap sel HT-29 dinyatakan dengan nilai CC50 berturut-turut 158,92mm + 5,4, 65,52mm + 5,0 dan 47,59mm + 2,5. Aktivitas apoptosis mencapai 16,7% hingga 62,4% jika dibandingkan dengan kontrol sel. Isoramnetin dan Isokuersitrin sebagai senyawa flavonoid turunan kuersetin berpotensi sebagai agen apoptosis sel kanker kolorektal HT-29.

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Colorectal cancer is a global public health problem with a high prevalence, and its treatment still has limitations. Flavonoid compounds, especially quercetin, are considered to have biological activity as an anticancer, so several other flavonoid compounds are also expected to have similar activity. This study aimed to perform in-silico and in-vitro analysis of several flavonoid compounds, especially quercetin and its derivatives as apoptotic agents for colorectal cancer cells HT-29. The in silico method includes network pharmacology and molecular simulations. The best compounds based on in silico analysis were tested in-vitro by assessing their cytotoxic activity in HT-29 cells using the MTT Assay method. Their apoptosis was analyzed using flow cytometry. Target proteins interacting with quercetin and its derivatives are AKT1, APAF1, BCL2, CASP3, MAPK1 and CASP9. Based on ADMET prediction analysis, quercetin and its derivatives are included in the safe category as drug candidates. The best compounds based on in-silico analysis, isorhamnetin and isoquercitrin, were selected to be tested in-vitro. The cytotoxic activity of quercetin, isorhamnetin and isoquercitrin against HT-29 cells was expressed by CC50 values of 158.92 mm + 5.4, 65.52 mm + 5.0 and 47.59 mm + 2.5, respectively. Apoptotic activity reached 16.7% to 62.4% when compared to control cells. Isoramnetin and isoquercitrin, flavonoid compounds derived from quercetin, have potential apoptotic agents for HT-29 colorectal cancer cells."

"ABSTRAKNama : Elvira YunitaProgram Studi : Program Magister Ilmu BiomedikJudul : Efek In Vitro Andrografolida terhadap Apoptosis Jalur Intrinsik pada Sel Punca Kanker Payudara Manusia yang Dipaparkan Rotenon: Tinjauan Ekspresi Caspase-9, Caspase-3 dan Survivin. Latar belakang: Andrografolida ANDRO merupakan senyawa bioaktif utama yang berasal dari sambiloto, Andrographis paniculata. Penelitian in silico yang telah dilakukan menunjukan ANDRO mempengaruhi apoptosis intrinsik dengan berinteraksi dengan survivin, caspase-9 dan caspase-3. Penelitian lain menunjukkan bahwa Breast Cancer Stem Cell BCSC memiliki survival rate yang lebih tinggi setelah dipaparkan dengan rotenon jika dibandingkan dengan non-BCSC. Oleh karena itu penelitian ini bertujuan untuk menganalisis apoptosis jalur intrinsik pada BCSC yang telah dipaparkan rotenon dan ANDRO.Metode: BCSC dipaparkan dengan 50 ?M rotenon selama 6 jam dan kemudian sel dipaparkan dengan ANDRO 0.075 mM, 0.15 mM, 0.3 mM dan 0.6 mM selama 24 jam. RNA sel diisolasi dan diikuti dengan pengukuran ekspresi mRNA caspase-9 dan 3 dengan qRT-PCR. Protein sel akan digunakan untuk pengukuran ekspresi protein survivin total dan survivin terfosforilasi. Selain itu, Apoptosis sel juga diukur dengan flowcytomety.Hasil: Perlakuan dengan rotenon dan ANDRO dapat meningkatkan ekspresi mRNA caspase-9 dan caspase-3 yang juga disertai dengan penurunan viabilitas. Paparan ANDRO dengan konsentrasi rendah hingga 0.015 mM pada BCSC yang telah diberikan rotenon dapat menurunkan ekspresi mRNA survivin. Dosis yang lebih tinggi dapat meningkatkan ekspresi mRNA survivin. Ekspresi protein survivin mengalami peningkatan yang disertai dengan penurunan rasio survivin yang teraktivasi. Selain itu, persentase apoptosis setelah paparan rotenon dan ANDRO hingga 0.3 mM ANDRO juga mengalami peningkatan seiring dengan bertambahnya konsentrasi ANDRO yang dipaparkan dose dependent manner .Kesimpulan: Paparan rotenon dan ANDRO dapat menginduksi kematian sel melalui apoptosis jalur intrinsik pada BCSC. Selain itu, ANDRO juga diusulkan sebagai senyawa yang potensial menjadi agen terapi pendamping bagi pasien-pasien yang menjalani kemoterapi maupun radioterapi.

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ABSTRACTABSTRACT Name Elvira YunitaStudy Program Biomedical ScienceTitle In Vitro Effect of Andrographolide on the intrinsic pathway of apoptosis in rotenone induced human breast cancer stem cells Focus on caspase 9, caspase 3 and survivin expression Background Andrographolide ANDRO is an active compound of Andrographis paniculata, has been suggested to have an anti cancer property. Our in silico study has shown that ANDRO could interact with survivin, caspase 9 and caspase 3 which influence the intrinsic apoptotic pathway. We have also demonstrated that human breast cancer stem cells BCSCs could survive better than their counterpart non BCSCs after rotenone treatment. In this study, we aimed to investigate whether andrographolide could induced apoptotic of rotenone induced BCSCs.Method Human BCSCs ALDH cells were first induced by 50 M rotenone for 6 hours and treated with 0.075 mM, 0.15 mM, 0.3 mM dan 0.6 mM of ANDRO for 24 hours. Total RNA from the cells was isolated, followed by determination of survivin, caspase 9 and caspase 3 m RNA expression level using Real Time RT PCR technique. Protein from the cells used to examine expression of survivin and phosphorylated survivin. Besides, examining of apoptotic cell also measured by flowcytometry.Result Treatment of rotenone and ANDRO drastically increase caspase 9 and caspase 3 expression, leading to the decrease of cell viability. Low concentration of ANDRO treatment until 0.15 mM could supress survivin expression, but gradually increased higher than the control in line with the increasing of ANDRO concentration. Survivin protein expression was increased following by decreasing ratio of activated survivin. Besides, percentage of apoptosis after rotenone and ANDRO treatment until 0.3 mM of ANDRO treatment also increased in line with increasing ANDRO concentration dose dependent manner .Conclusion Rotenone and ANDRO treatment could induced apoptotic intrinsic in BCSCs. Thus, we propose that andrographolide as potential compound that could be used as a novel co chemoradiation therapy and radiotherapy targeted to BCSCs."

"Latar Belakang. Endometriosis ditandai dengan pertumbuhan jaringan endometrium di luar uterus, salah satunya disebabkan oleh disregulasi apoptosis sel yang memicu ketahanan sel ektopik. Asam galat dan turunannya pada beberapa penelitian mampu menghambat karsinogenesis pada beberapa cell line kanker. Penelitian kami terdahulu membuktikan asam galat dan turunannya dapat menekan proliferasi sel dan meningkatkan apoptosis sel endometriosis in vitro, namun efeknya terhadap mekanisme jalur apoptosis instrinsik belum di buktikan. Metode. Sel endometriosis berasal dari jaringan endometrium pasien laparaskopi, diisolasi secara enzimatis dan dikultur primer. Sel kultur diberi perlakuan asam galat, heptil galat, oktil galat dengan dosis 51,2 μg/ml, 102,4 μg/ml dan 153,6 μg/ml selama 48 jam, dilanjutkan induksi 10 ng/ml LPS selama 24 jam . Kelompok kontrol hanya di induksi LPS tanpa perlakuan. Ekspresi relatif mRNA Bax, Bcl-2, dan Caspase-3 dinilai dengan qRT-PCR. Hasil. Peningkatan tertinggi ekspresi mRNA Bax dan penekanan tertinggi ekspresi mRNA Bcl-2 pada oktil galat dosis 153,6 μg/ml. Peningkatan ekspresi mRNA Bax, dan penurunan ekspresi mRNA Bcl-2 akan di ikuti dengan peningkatan ekspresi mRNA Caspase-3. Secara statistik tidak terdapat perbedaan bermakna antara kelompok perlakuan dengan ekspresi mRNA Bax, Bcl-2, dan Caspase-3 (p > 0,05). Kesimpulan. Oktil galat, asam galat, dan heptil galat memiliki efek potensial pada mekanisme apoptosis intrinsik.

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Background. Endomeriosis characterized by the presence of extrauterine endometrial tissue, one of which caused by disregulation of apoptosis that contribute of endometrial ectopic survival. Our previous research has proven that gallic acid and its derivatives can suppress proliferation and induce apoptosis endometriosis cell in vitro. However, the effect of gallic acid and its derivatives on apoptosis intrinsic pathway mechanism is not proven yet. Method. Endometriosis cell from endometriosis patiens who had undergone laparascopy surgery were isolated by enzimatic reaction and primary cultured. Cultured cells treated by gallic acid, heptyl gallate and octyl gallate each with dosage 51.2 μg/ml, 102.4 μg/ml, 153.6μg/ml for 48 hours, than induced by LPS 10 ng/ml for 24 hours. Parameter research was assessed by qRT-PCR for mRNA expression of Bax, Bcl-2, Caspase-3. Result. Octyl gallate showed more effect to induce apoptosis intrinsic . Endometriosis cell were treated with octyl gallate shown increases of Bax and Caspase3 mRNA expression than decrease of Bcl-2 mRNA expression. Statistically, mean differences are not significant between treatment groups and mRNA expression (p > 0.05). Conclusion. This study exhibited that octyl gallate has a more potential effect on apoptosis intrinsic in endometriosis cell cultures followed by gallic acid and heptyl gallate and their potency as treatment for endometriosis."

"ABSTRAKLatar Belakang: Kanker ovarium merupakan salah satu kanker yang menyebabkan kematian paling tinggi pada wanita. Tujuh puluh persen saat didiagnosis ditemukan pada stadium lanjut, dengan angka kesintsan dalam 5 tahun hanya 46 . Modalitas terapi saat ini adalah sitoreduksi dengan kemotterapi adjuvant platinum based sebagai lini pertama. Efektivitas kemoterapi hanya 60 pada stadium lanjut, untuk selanjutnya berkembang menjadi rekuren. Oleh karena itu dibutuhkan jenis terapi tambahan berdasarkan jenis atau agen yang bekerja spesifik di sel kanker dan dapat bersinergi dengan pengobatan standar saat ini. Kurkumin sebagai salah satu agen yang banyak diuji memiliki efek anti-kanker. Kurkumin berpotensi sebagai anti kanker dan bekerja pada semua multistep karsinogenesis. Kurkumin dapat bekerja sebagai antiproliferasi dan meningkatkan apoptosis.Tujuan: untuk mengetahui antiproliferasi ekspresi Ki67 dan apoptosis caspase 3 dan caspase 8 kombinasi cisplatin dengan nanokurkumin pada sel hayati SKOV3.Metode: Penelitian ini dilakukan uji eksperimental in vitro dengan menggunakan sel hayati SKOV3 untuk mengetahui antiproliferasi ekspresi Ki67 dan apoptosis caspase 3 dan caspase 8 kombinasi cisplatin dengan nanokurkumin pada sel tersebut. Uji analisis data dengan T tidak berpasangan bila sebaran normal / uji Mann Whitney bila sebaran tidak normal serta menggunakan Graph Pad Prism.Hasil: Berdasarkan penelitian ini, didapatkan cc50 nanokurkumin 67 m dan cc50 cisplatin 54 m dengan menggunakan metode MTT Assay. Viabilitas sel pada penelitian ini menurun sesuai dengan dose dependent, dimana pada dosis kombinasi nanokurkumin 134 m dengan cisplatin 108 m ditemukan sel hidup yang paling rendah 24.3 p

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ABSTRACTBackground Ovarian cancer is one of the most leading cancers in women. Seventy percent at the time of diagnosis are found at an advanced stage, with a 5 year survival rate of only 46 . The current treatment modality is cytoreduction with platinum based adjuvant chemotherapy as first line. The effectiveness of chemotherapy is only 60 at an advanced stage, to further develop into recurrent. Therefore, additional types of therapy are required based on types or agents that work specifically in cancer cells and can synergize with current standard treatments. Curcumin as one of the many tested agents has anti cancer effects. Curcumin has the potential effect as an anti cancer and works on all multisteps of carcinogenesis. Curcumin can work as an antiproliferation and increase apoptosis.Objective to know antiproliferation effect expression Ki67 and apoptosis effect caspase 3 and caspase 8 of combination cisplatin with nanokurkumin on cell SKOV3.Methods This experimental study was conducted in vitro by using biological cell line SKOV3 to know antiproliferation effect expression Ki67 and apoptosis effect caspase 3 and caspase 8 of combination cisplatin with nanokurkumin on the cell. The data was analysed with unpaired T when normal distribution Mann Whitney test when distribution is not normal and also using Graph Pad Prism.Result Based on this result, cc50 of nanokurkumin is 67 m and cc50 of cisplatin is 54 m by using MTT Assay method. The viability of the cells in this study decreased according to the dose dependent, whereas in the combined dose of 134 m nanocurcumin with 108 m cisplatin found the lowest life cell 24.3 p "

"Sampai saat ini, belum ada obat untuk menyembuhkan infeksi HIV tetapi ada pengobatan yang bisa memperlambat perkembangan HIV dalam tubuh yang disebut Antiretroviral Treatment. Perkembangan HIV secara in vivo dapat dimodelkan ke dalam sistem persamaan diferensial biasa menggunakan pendekatan deterministik. Pada tesis ini dibentuklah model matematika untuk dinamika virus HIV di dalam tubuh dengan adanya intervensi Antiretroviral Treatment dan memperhitungkan pengaruh Apoptosis pada sel-T. Analisis sistem dinamik pada model untuk menentukan kestabilan dari titik keseimbangan bebas infeksi dan titik keseimbangan endemik menggunakan kriteria Routh-Hurwitz. Simulasi numerik menunjukkan bahwa penurunan jumlah sel-T sehat (T) dan perkembangan jumlah virus HIV (V) di dalam tubuh dapat dihambat dengan signifikan jika pengobatan ART diberikan setiap hari secara teratur dan pemilihan nilai parameter Apoptosis (A) berada pada interval [0,1 ; 0,5].

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Until now, there is no medicine to cure HIV infection, but there is a treatment that can slow the progression of HIV in the body called Antiretroviral Treatment. The development of HIV, when evaluated in vivo can be modeled into a system of ordinary differential equations using a deterministic approach. In this paper, be formed a mathematical model for the dynamics of HIV in the body with the intervention of Antiretroviral Treatment and take into account the influence of Apoptosis on T-cells. The dynamic system analysis of the model to determine the stability of the infectious free equilibrium point and the endemic equilibrium point uses the Routh-Hurwitz criterion. Numerical simulations show that a decrease in the number of healthy T-cells (T) and the proliferation of HIV virus (V) in the body can be significantly impeded if ART treatment is administered daily on a regular basis and the selection of Apoptosis (A) parameter values is at interval [0.1 ; 0.5]."