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"Endometriosis merupakan penyakit ginekologi yang ditandai dengan pertumbuhan jaringan mirip endometrium di luar rongga uterus. Inflamasi kronik pada endometriosis memiliki peranan penting dalam memfasilitasi perkembangan kista endometriosis. Penelitian ini bertujuan untuk menganalisis efektivitas oktil galat dalam menurunkan inflamasi pada tikus Wistar model endometriosis. Sejumlah 30 ekor tikus wistar betina dibagi secara acak ke dalam tiga kelompok. Kelompok pertama dan kedua direkayasa membentuk jaringan endometriosis, sedangkan kelompok ketiga dilaparatomi sebagai kelompok kontrol negatif. Setelah dua bulan, dilakukan laparatomi kedua pada kelompok satu dan dua untuk mengevaluasi pembentukan jaringan endometriosis. Induksi oktil galat diberikan pada kelompok pertama selama satu bulan. Seluruh tikus kemudian dieuthanasia dan jaringan endometriosis kelompok pertama dan kedua, serta jaringan endometrium kelompok ketiga, diambil untuk dianalisis. Pengukuran kadar sitokin TNF-α dan IL-10 dilakukan menggunakan Luminex Multiplex Assay, sedangkan kadar COX-2 dan PGE₂ diukur menggunakan metode ELISA. Analisis beda proporsi menunjukkan bahwa pemberian oktil galat pada kelompok pertama tidak memberikan perubahan kadar TNF-α kategori tinggi yang signifikan, sedangkan kadar COX-2, PGE₂, dan IL-10 kategori tinggi teramati mengalami penurunan signifikan sebesar 22,3%, 55,6%, dan 44,5%, dibandingkan dengan kelompok kedua (p<0,05). Oktil galat diketahui efektif dalam menurunkan mediator inflamasi COX-2 dan PGE₂, serta anti-inflamasi IL-10, yang memicu perbaikan gejala klinis berupa regresi ukuran kista endometriosis.

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Endometriosis is a gynecological disease, characterized by the growth of endometrial-like tissue outside the uterine cavity. Chronic inflammation in endometriosis has an important role in facilitating the development of endometriosis cysts. The present study aimed to analyze the anti inflammatory effect of octyl gallate in endometriosis Wistar rat model. 30 female Wistar rats were divided randomly into three groups. Endometriosis induction was performed in the first and second group, while a sham operation was performed in the third group. Two months later, a second laparotomy was performed in the first and second groups to evaluate endometriosis tissue formation. Octyl gallate was administered via oral gavage to the first group for one month. All rats were sacrificed and endometriosis tissue samples were collected for further analysis. TNF-α and IL-10 levels were measured using Luminex Multiplex Assay, while COX-2 and PGE₂ levels were measured using the ELISA method. The administration of octyl gallate in the first group did not significantly effect TNF-α levels, whereas the high category of COX-2, PGE₂, and IL-10 levels were observed to experience a significant decrease up to 22.3%, 55.6%, and 44.5% compared to the second group (p<0.05). In conclusion, octyl gallate was able to supress the inflammatory mediators, COX-2 and PGE₂, along the anti-inflammatory mediators IL-10, which induced the regression of endometriosis cysts size as an improvement of clinical symptoms."

"ABSTRAKEndometriosis merupakan penyakit ginekologi ditandai dengan implantasi jaringan endometrium di luar rongga uterus, berhubungan erat dengan proses inflamasi kronis. Stres oksidatif menjadi aktivator terjadinya proses inflamasi kronis di endometriosis. Oktil galat terbukti lebih efektif menekan proses inflamasi dibandingkan asam galat dan heptil galat pada sel kultur primer endometriosis. Penelitian ini bertujuan menganalisis pengaruh oktil galat pada proses inflamasi dan stres oksidatif pada tikus Wistar model endometriosis. Tiga puluh ekor tikus Wistar dibagi menjadi tiga kelompok, yaitu kelompok uji, kontrol endometriosis dan kelompok normal. Kelompok uji dilakukan autotransplantasi lalu diberikan suspensi oktil galat dan CMC selama satu bulan. Kelompok endometriosis dilakukan autotransplantasi lalu diberikan larutan CMC selama satu bulan, sedangkan kelompok normal hanya dilakukan laparotomi. Seluruh tikus kemudian dieuthanasia, dari kelompok uji dan kontrol endometriosis diambil jaringan endometriosisnya sedangkan dari kelompok sehat diambil jaringan endometriumnya untuk dianalisis. Analisis MDA (Malondialdhyde) dan SOD (Superoxide Dismutase) dilakukan secara spektofotometri, kadar NF-ĸB dengan ELISA dan IL-1β (Interleukin-1 Beta) dengan LUMINEX. Pemberian oktil galat pada kelompok uji tidak menurunkan kadar MDA namun berpotensi menekan kondisi stres oksidatif dengan meningkatkan kadar SOD. Oktil galat terbukti menekan aktivasi NF-ĸB secara signifikan, namun tidak menekan kadar IL-1β. Oktil galat berperan sebagai antiinflamasi pada tikus Wistar model endometriosis dengan cara induksi peningkatan SOD dan hambatan langsung pada translokasi nuklear NF-ĸB.

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ABSTRACTEndometriosis is a gynecological disease characterized by the implantation of endometrial tissue outside the uterine cavity, related to the chronic inflammatory process. Oxidative stress activates the occurrence of chronic inflammatory in endometriosis. Octyl gallate is more effective in suppressing the inflammatory process than gallic acid and heptil gallate in primary endometriosis culture cells. This study aimed to analyze the effect of octyl gallate on the inflammatory process and oxidative stress in endometriosis Wistar rat models. 30 Wistar rats were divided into three groups, the test group, endometriosis control and normal groups. The test group was autotransplantated and then given a suspension of octyl galate and CMC for one month. The endometriosis group was autotransplanted and then given a CMC solution for one month, while the normal group only underwent laparotomy. All rats were then euthanized, from the test and endometriosis group the endometriosis tissue was taken while from the normal group endometrial tissue was taken for analysis. MDA and SOD were measured using spectrophotometry, NF-ĸB with ELISA and IL-1β with LUMINEX. Induction of octyl gallate in the test group did not reduce MDA levels but could potentially suppress oxidative stress conditions by increasing SOD levels. Octyl gallate significantly inhibit the NF-ĸB activation, but not suppressing IL-1β levels significantly. Octyl gallate act as anti-inflammatory agent in endometriosis Wistar rat model through the enhancement of SOD and direct inhibition to nuclear translocation of NF-ĸB."

"ABSTRAKLatar belakang. Potensi terjadinya kekambuhan paska pengobatan endometriosisdengan terapi hormonal dan pembedahan konservatif masih terjadi sekitar 11-32dalam waktu 1-5 tahun. Salah satu faktor pemicunya adalah proses inflamasi kronikyang merangsang peningkatan sitokin proinflamasi dalam rongga peritoneum, sehinggaperlu pengembangan terapi baru. Heptil galat dan oktil galat merupakan senyawaturunan asam galat yang berpotensi menekan proliferasi beberapa jenis sel kanker.Penelitian kami sebelumnya membuktikan oktil galat dapat menekan ekspresi mRNANFkB yang merupakan faktor transkripsi aktivasi jalur proinflamasi, serta dapatmenekan proliferasi sel endometriosis in vitro. Saat ini kami ingin menganalisisaktivitas heptil galat dan oktil galat terhadap protein target NFkB melalui teknik insilicodocking dan efeknya terhadap regulasi sitokin proinflamasi IL-1, COX-2, TGF-1 dan IL-10 pada kultur primer sel endometriosis.Metode. In silico docking heptil galat dan oktil galat terhadap protein target NFkBmelalui teknik bioinformatika. Sel endometriosis dari jaringan primer pasien diisolasisecara enzimatis dan dikultur, kemudian diberi perlakuan heptil dan oktil galat dengan 2macam dosis (51,2 μg/mL dan 102,4 μg/mL) selama 48 jam, dilanjutkan induksi LPS 10ng/mL selama 24 jam. Kelompok kontrol positif hanya diinduksi LPS tanpa perlakuan,dan kontrol negatif tanpa perlakuan dan LPS. Regulasi inflamasi dinilai dari tingkatkadar sitokin IL-1, COX-2, TGF-1 dan IL-10 dengan teknik ELISA.Hasil. Analisis in-silico docking protein NFkB menunjukan nilai ikatan energi oktilgalat lebih tinggi (-7,98 kkal/mol) dibandingkan heptil galat (-7,68 kkal/mol) dan asamgalat (-7,66 kkal/mol). Terjadi penurunan kadar sitokin COX-2 secara signifikan(p<0,03) pada kelompok perlakuan dibandingkan dengan kontrol positif, begitu jugadengan sitokin IL-1 dan IL-10 cenderung menurun (p>0,05). Sedangkan kadar sitokinTGF-1 mengalami kenaikan pada kelompok perlakuan dibandingkan kontrol positifmeskipun kurang bermakna secara statistik (p>0,05).Kesimpulan. Melalui jalur NF-kB sebagai regulator inflamasi, baik oktil galat danheptil galat terbukti dapat menekan produksi sitokin proinflamasi COX2 dan IL-1serta meningkatkan sitokin TGF-1 dan menurunkan sitokin IL-10 sehingga berpotensisebagai bahan terapi tambahan pada endometriosis.

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ABSTRACTBackground: The potential for relapse post endometriosis treatment with hormonaltherapy and conservative surgery still occurs around 11-32 within 1-5 years. One ofthe trigger factors is a chronic inflammatory process that stimulates an increaseproinflammatory cytokines in the peritoneal cavity, so needed the development of newtherapies. Heptyl galate and octyl galate are gallic acid derivatives which have thepotential to suppress the proliferation of several types cancer cells. Our previousresearch proved that octyl galate can suppress the expression of NFkB mRNA which isa proinflammatory activation transcription factor, and can suppress endometriosis cellproliferation in vitro. We currently want to analyze the activity of heptyl galates andoctyl galates against the NFκB target protein through in-silico docking techniques andtheir effects on the regulation of proinflammatory cytokines IL-1, COX-2, TGF-1 andIL-10 in primary cultures of endometriosis cells.Method: In silico docking heptyl and octyl galates against the NFkB target proteinsthrough bioinformatics techniques. Endometriosis cells from primary tissue wereenzymatically isolated and cultured, then given heptyl and octyl gallate treatment with 2doses (51.2 μg/mL and 102,4 μg/mL) for 48 hours, continued induction of 10 ng / mLLPS for 24 hours. The positive control group only induced LPS without treatment, andnegative treatment without treatment and LPS. Inflammatory regulation was assessedfrom levels of cytokines IL-1, COX-2, TGF-1 dan IL-10 with ELISA techniques.Results: In-silico docking analysis of the NFkB gene showed higher energy bondingvalues in octyl galate (-7,98 kcal / mol) than heptyl galate (-7,68 kcal / mol) and gallicacid (-7,66 kcal / mol). Significantly decreased levels of COX-2 cytokine (p <0,03) inthe treatment group compared with positive controls, so also the cytokines of IL-1 andIL-10 tended to decrease (p> 0,05). Whereas the levels of cytokine TGF-1 experiencedan increase in the treatment group compared to the positive control although it was lessstatistically significant (p> 0,05).Conclusion: Through the NFkB pathway as an inflammatory regulator, both octylgalates and heptyl galates have been shown to suppress the production ofproinflammatory cytokines COX2 and IL-1, as well as increase TGF-1 cytokines andreduce IL-10 cytokines so that they have the potential to be additional therapeuticagents in endometriosis."

"Kondisi hipoksia hipobarik dapat mengganggu kesehatan manusia dan menjadi risiko keselamatan di dunia penerbangan. Berbagai jalur pensinyalan sensitif oksigen pada tingkat seluler, dapat diaktifkan selama paparan hipoksia hipobarik intermiten (HHI). HSP sebagai chaperokine berperan dalam transduksi sinyal dan modulasi sistem imun serta terkait dengan produksi sitokin pro-inflamasi atau anti-inflamasi. Penelitian ini bertujuan menganalisis efek HHI terhadap HSP70 dan produksi sitokin pro dan anti-inflamasi. Penelitian ini merupakan penelitian eksperimental dengan menggunakan jaringan hepar tikus Sprague-Dawley yang disimpan pada suhu -20°C. Tikus dibagi menjadi 5 kelompok yaitu kontrol (C), HHA, HHI1, HHI2, dan HHI3 dan diberikan paparan HHI pada ketinggian 25.000 kaki selama 5 menit. Analisis konsentrasi protein dan sitokin ditentukan dengan metode sandwich ELISA. Hasil penelitian menunjukkan terdapat perbedaan bermakna ekspresi protein HSP70 pada hepar tikus pada kelompok HHA dan HHI terhadap kontrol (p<0.05), terdapat perbedaan bermakna konsentrasi IL-10 antara kelompok HHI3 terhadap kontrol (p = 0,018), dan adanya korelasi positif dengan kekuatan korelasi sedang antara HSP70 dengan TNF-α dan IL-1β, serta korelasi positif sedang HSP70 dengan IL-10. HHI menginduksi peningkatan HSP70 sebagai mekanisme adaptasi dan memodulasi sistem imun tubuh untuk meningkatkan konsentrasi IL-10.

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Hypobaric hypoxic conditions can disrupt human health and become a risk for safety of aviation. Various signaling oxygen-sensitive pathways at the cellular level can be activated during intermittent hypobaric hypoxia (IHH) exposure. HSP as a chaperokine plays a role in signal transduction and modulation of the immune system and it is associated with the production of pro-inflammatory or anti-inflammatory cytokines. This study aims to analyze the effect of IHH on HSP70 and the production of pro- and anti-inflammatory cytokines. This study was an experimental study using Sprague-Dawley rat liver tissue stored at -20°C. Rats were divided into 5 groups, they are control (C), AHH, IHH1, IHH2, and IHH3. They were exposed to IHH at altitude of 25,000 feet for 5 minutes. Analysis of protein and cytokines concentrations was determined by the sandwich ELISA method. The results showed that there was a significant difference in HSP70 protein expression in the liver of rats in the HHA and IHH groups compared to the control (p<0.05), there was a significant difference in IL-10 concentration between the IHH3 group compared to the control (p = 0.018), a positive correlation with moderate correlation strength between HSP70 with TNF-α and IL-1β, and a moderate positive correlation between HSP70 with IL-10. HHI produces an increase in HSP70 as an adaptive mechanism and modifies the immune system to raise the levels of IL-10."

"Endometriosis merupakan penyakit ginekologi umum yang dipicu terjadinya peradangan kronis yang ditandai dengan produksi beberapa sitokin pro-inflamasi, salah satu yang terbanyak yaitu TNF-α. Di sisi lain, sitokin anti-inflamasi, seperti IL-10, dapat mengakhiri proses inflamasi berlanjut ini. Propolis adalah bahan bioaktif alami produk lebah, sebagai imunomodulator dan efek anti-inflamasi yang dapat menekan proliferasi sel-sel patologis. Penelitian ini bertujuan untuk menentukan pengaruh pemberian propolis terhadap tumor necrosis factor alpha dan interleukin 10. Penelitian ini menggunakan desain uji klinis dengan alokasi acak dan double-blinded. 24 wanita dengan terapi Levonorgestrel (LNG) karena endometriosis secara acak ditugaskan untuk menerima propolis yang mengandung 17,5 mg flavonoid per tetes atau plasebo. Intervensi diberikan dua kali sehari, pada pagi dan malam hari, dengan dosis 1 tetes/10 kg berat badan (kgBB) per kali. Sampel darah dan penilaian gizi diambil pada kunjungan pertama dan 30 hari setelahnya. Hasil penelitian menunjukkan bahwa kadar tumor necrosis factor alpha dan interleukin 10 tidak memiliki perbedaan yang signifikan antara kedua kelompok (p>0,05). Kadar tumor necrosis factor alpha mengalami penurunan yang lebih besar pada kelompok propolis sebesar 4,17 (44,36-50,05) pg/mL dibandingkan dengan kelompok plasebo. Kadar IL-10 menunjukkan peningkatan sebesar 344,94 setelah 30 hari diberikan intervensi. Pemberian flavonoid dalam propolis tidak menghasilkan perubahan yang signifikan dalam kadar Tumor Necrosis Factor Αlpha dan Interleukin 10 selama periode intervensi 30 hari.

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Endometriosis is a common gynecological disease triggered by chronic inflammation characterized by the production of several pro-inflammatory cytokines, one of which is TNF-α. On the other hand, anti-inflammatory cytokines, such as IL-10, can end this ongoing inflammatory process. Propolis are natural bioactive ingredients contained in bee products, as immunomodulators and anti-inflammatory effects that can suppress the proliferation of pathological cells. This study aimed to determine the effect of propolis supplementation on tumor necrosis factor alpha and interleukin 10. This study used clinical trial design with random allocation and double- blinded. 24 women with Levonorgestrel (LNG) therapy due to endometriosis were randomly assigned to receive propolis-contained 17.5 mg of flavonoids per drop or placebo. The intervention given two times a day,in the morning and at night, with a dose of 1 drop /10 kg body weight (kgBW) per time. Blood samples and nutritional assessment were taken at the first time of visit and 30 days thereafter. The results showed that the levels of tumor necrosis factor alpha and interleukin 10 did not differ significantly between the two groups (p>0.05). Tumor necrosis factor alpha levels experienced a greater decrease in the propolis group by 4.17 (44.36-50.05) pg/mL compared to the placebo group. IL-10 levels showed an increase of 344.94 after 30 days of intervention. The administration of propolis supplementation did not result in significant changes in the levels of Tumor Necrosis Factor Αlpha and Interleukin 10 during the 30- day intervention period."

"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. Proses inflamasi kronik dan persisten mempengaruhi tingginya rekurensi dan survival endometriosis pasca pembedahan. Hal ini menjadi permasalahan endometriosis, sehingga perlu pengembangan terapi target salah satunya yaitu asam galat. Asam galat terbukti efektif sebagai antikanker, anti tumor, anti inflamasi dan antibakterial pada beberapa cell line, namun efektifitasnya pada sel endometriosis harus dibuktikan. Tujuan. membuktikan efek asam galat dan senyawa turunannya terhadap regulasi inflamasi pada kultur primer endometriosis ditinjau dari ekspresi mRNA NF-kB, serta sekresi TNF-? dan IL-6. Metode. Sel endometriosis berasal dari jaringan endometriosis pasien yang menjalani laparaskopi, diisolasi secara enzimatis dan dikultur primer. Sel kultur diberi perlakuan asam galat, heptil dan oktil galat dengan dosis 25,6 g/mL, 51,2 g/mL dan 102,4 g/mL selama 48 jam, kemudian diinduksi dengan LPS 500 ng/mL selama 24 jam. Regulasi inflamasi dinilai dari ekspresi mRNA NF-kB dengan qRT-PCR, kadar sekresi TNF-? dan IL-6 dengan ELISA, serta inhibisi viabilitas sel dengan MTS Assay. Hasil. Setelah data dirasiokan dengan kontrol, ketiga zat signifikan menghambat viabilitas sel endometriosis p value 0,000 dengan inhibisi tertinggi pada dosis 102,4 g/mL. Terjadi penurunan ekspresi relatif NF-kB yang dirasiokan dengan kontrol dan IL-6 meskipun secara statistik tidak bermakna. Konsentrasi TNF? tidak berbeda secara bermakna p value 0,340 . Kesimpulan. Asam galat dan senyawa turunannya berpengaruh terhadap inhibisi viabilitas sel, penurunan ekspresi relatif NF-kB dan IL-6, namun tidak bermakna terhadap penekanan sitokin TNF-?. Perlu dilakukan studi lanjut untuk menilai efektifitas asam galat sebagai kandidat obat antiinflamasi pada endometriosis ditinjau aspek lain.

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ABSTRACTBackground. Endometriosis is a benign gynecological disorder characterized by the growth of the lining of the endometrium like tissue outside the uterus. The cause of the growth of endometriosis is not known well, chronic and persistent inflammatory process is suspected to be one of the pathogenesis that contributes to the high recurrence and survival endometriosis. One of the potential therapeutic agents is a gallic acid which proved effective in earlier studies as an anti cancer, anti tumor, anti inflammatory and antibacterial in several cell line. The Effectiveness of gallic acid to the endometriosis cell is a preliminary study and have not found evidence of publication yet. Object. Proving the effect of gallic acid and its derivatives on the inflammatory regulation of endometriosis primary culture study on mRNA expression of NF kB, TNF , and IL 6 secretion. Method. Endometriosis cells from Indonesian endometriosis patients tissues who had undergone laparoscopy surgery were isolated by the enzymatic reaction and primary cultured. Cultured cells treated by gallic acid and alkyl ester synthetic derivatives of the gallic acids heptyl gallate and octyl gallate each with the dosage of 25,6 g mL, 51,2 g mL, and 102.4 g mL for 48 hours and then induced by LPS 500 ng mL for 24 hours. Parameter research was assessed by qRT PCR for mRNA expression of NF kB, ELISA for the quantification of TNF and interleukin 6, and MTS assay was used to observe endometriosis cell viability. Results. After the data was rationalized with the control, three substances showed significant inhibition of endometriosis cell viability. The highest inhibition for all treatment was at doses 102,4 g mL. Overall there was an inhibition of relative expression of mRNA NF kB were rationalized to controls and suppression of IL 6 in octyl gallate groups. The concentration of TNF among the groups did not differ significantly p value 0.340 . Conclusion. Gallic acid and its derivatives have significantly inhibition effect toward cell viability, mRNA expression of NF kB, and IL 6 but have not significantly effect toward cytokine TNF . Further studies need to be conducted to assess the effectiveness of gallic acid as an anti inflammatory drug candidate toward to any pathway."

"ABSTRAKPrevalensi kolitis ulseratif semakin meningkat dari tahun ketahun. Penelitian ini bertujuan untuk melihat efek Ekstrak Etanol Daun Mahkota Dewa (EEDMD) terhadap gambaran histopatologi dan  ekspresi TNF-α, COX-2, dan NF-κβ pada jaringan kolon mencit Swiss berusia 20 minggu yang diinduksi dengan Dextran Sodium Sulfat (DSS) 2% melalui air minum. EEDMD dosis 100 mg, 200 mg, 300 mg, aspirin 0,21 mg, diberikan per oral selama 2 minggu. Pemeriksaan kandungan EEDMD menunjukan kadar total fenol sebesar 4,4103% atau 44,103 mgGAE/g ekstrak, kadar flavonoid sebesar 0,3429% atau 3,429 mgQE/g ekstrak, dan memiliki aktivitas antioksidan sedang (IC₅₀ sebesar 219,716 µg/mL). Pemeriksaan histopatologi pada jaringan kolon mencit dinilai dengan mengkuantifikasi jumlah radang dan rerata sel goblet pada jaringan kolon yang diwarnai hematoksilin-eosin. Pemberian EEDMD pada semua dosis menunjukan perbedaan bermakna pada jumlah radang (p<0,00) dan rerata sel goblet (p<0,00). Pemeriksaan imunohistokimia dilakukan untuk melihat ekspresi TNF-α, COX-2. NF-κβ. Sel positif mengekspresikan TNF-α, COX-2, dan NF-κβ dihitung/1000 sel epitel. Hasil menunjukan EEDMD mampu menurunkan ekspresi TNF-α secara signifikan dibandingkan dengan kontrol negatif. Sedangkan pada COX-2 (p<0,80) dan NF-κβ (p<0,90) tidak terdapat perbedaan yang signifikan.

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ABSTRACT

Ulcerative colitis prevalence increases from year to year. The purpose of this research to see the effect of Ethanol Extract of Mahkota Dewa Leaves (EEDMD) on histopathology and expression of TNF-α, COX-2, and NF-κβ on 20-week Swiss mice tissue induced with 2% Dextran Sodium Sulfate (DSS) through drinking water. EEDMD dose 100 mg, 200 mg, 300 mg, aspirin 0.21 mg, given orally for 2 weeks. Examination of EEDMD content showed total phenol levels of 4.4103% or 44.103 mgGAE / g extract, flavonoid levels of 0.3429% or 3.429 mgQE / g extract, and had moderate antioxidant activity (IC50 of 219.716 µg / mL). Histopathological examination of mice colon tissue was assessed by quantifying the amount of inflammation and the mean of goblet cells in colon tissue stained by hematoxylin-eosin. Giving EEDMD at all doses showed a significant difference in the number of inflammation (p <0.00) and mean goblet cells (p <0.00). Immunohistochemical examination was performed to see the expression of TNF-α, COX-2. NF-κβ. Positive cells express TNF-α, COX-2, and NF-κβ counts / 1000 epithelial cells. The results showed that EEDMD significantly reduced TNF-α expression compared to negative controls. Whereas in COX-2 (p <0.80) and NF-κβ (p <0.90) there were no significant differences."

"Latar Belakang: Acute Kidney Injury pada COVID-19 merupakan komplikasi penting dan dikaitkan dengan peningkatan risiko kematian diduga diperantarai kondisi inflamasi dan disregulasi imun, baik di awal maupun selama perawatan. Tujuan: Untuk mengetahui hubungan antara IL-6, IL-10, TNF-" dengan AKI dan memprediksi perburukan hematuria, dan kejadian AKI Metode: Studi potong lintang dan prospektif kohort melibatkan 43 pasien COVID-19 derajad sedang dan berat yang dirawat di Rumah Sakit Pertamina Pusat di Jakarta, Indonesia dari bulan November 2020 hingga Januari 2021. Selama observasi dilakukan pemeriksaan darah lengkap, serum kreatinin, urinalisis, kadar IL-6, IL-10, TNF-" pada hari pertama dan hari ketujuh pengobatan atau sebelum hari ketujuh jika pasien meninggal atau dipulangkan, dan perubahannya di analisis. Insiden AKI ditentukan ketika perubahan serum kreatinin dan urin output memenuhi kriteria pedoman Kidney Disease Improving Global Outcomes. Uji korelasi dilakukan terhadap peningkatan sitokin dengan perubahan hematuria dan kreatinin. Uji Wilcoxon dilakukan untuk mengetahui perbedaan kadar sitokin diantara status albuminuria. Selanjutnya dilakukan uji Receiver Operator Characteristic untuk melihat kemampuan prediksi IL-6, IL-10, TNF-" terhadap perburukan hematuria dan kejadian AKI, menggunakan AUC minimal 0,7 dengan batas bawah IK 95% lebih dari 0,5 dan nilai p <0,05 Hasil: Terdapat korelasi antara peningkatan kadar serum IL-10 dengan perubahan serum kreatinin (r= -0,343; p 0,024) tetapi tidak pada perubahan IL-6 dan TNF-a. Perubahan hematuria tidak berkorelasi dengan peningkatan ketiga kadar sitokin. Juga tidak ada perbedaan dalam kadar sitokin di antara kelompok albuminuria. Kadar serum TNF-" dihari pertama perawatan dapat memprediksi AKI pada hari ke tujuh, AUC 85%; p=0,045 (IK 0,737-0,963), tetapi tidak dapat memprediksi perburukan hematuria Kesimpulan: Terdapat korelasi antara peningkatan IL-10 dengan perubahan serum kreatinin. TNF-! pada hari pertama perawatan dapat memprediksi kejadian AKI di hari ketujuh perawatan pasien COVID-19 derajat sedang dan berat.

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Background: Acute Kidney Injury is an important complication and is associated with increased risk of death in COVID-19 due to inflammatory conditions and immune dysregulation, both at the beginning and during treatment. Aim: To determine the relationship between IL-6, IL-10, TNF-α with AKI and their ability to predict the worsening of hematuria, and the incidence of AKI. Methods: 43 moderate and severe COVID-19 patients treated from November 2020 to January 2021 at Pertamina Central Hospital in Jakarta, Indonesia were included in this cross-sectional and prospective cohort study. During observation, tests including complete blood count, serum creatinine, urinalysis, levels of IL-6, IL-10 and TNF-α were performed on the first and seventh day of treatment, or before day 7 if the patient died or was discharged, and the changes were analyzed. The incidence of AKI is determined when changes in serum creatinine and urine output meet the criteria in the Kidney Disease Improving Global Outcomes guidelines. Correlation test was performed on increased cytokines with changes in hematuria and creatinine. Wilcoxon test was performed to obtain differences in cytokine levels among albuminuria status. Receiver Operator Characteristic test was then carried out to see the predictive ability of IL-6, IL-10, TNF- α on the worsening of hematuria and the incidence of AKI. Results: There was a correlation between increased serum IL-10 levels with changes in serum creatinine (r= -0.343; p 0.024), but not in IL-6 and TNF-a levels. On the other hand, changes in hematuria did not correlate with an increase in the levels of the three cytokines. There was also no significant difference in the levels of cytokines among albuminuria groups. Serum TNF-! levels on the first day of treatment were able to predict AKI on the seventh day (AUC 85%; p=0.045; 95%CI 0.737-0.963), but did not predict the worsening of hematuria. Conclusion: There was a correlation between increased serum IL-10 with changes in serum creatinine. TNF-! on the first day of treatment can predict the incidence of AKI on the seventh day of treatment for moderate and severe COVID-19 patients."

"Psoriasis merupakan penyakit autoimun yang disebabkan kelainan genetik dan dipicu faktor lingkungan, penyakit ini menyerang kulit dan sistemik seperti sendi dan kuku. Sel punca mesenkim (SPM) asal tali pusat manusia memiliki kapasitas proliferasi yang tinggi, imunomodulator yang luas dan imunogenitas yang rendah. Penelitian ini menggunakan model tikus psoriasis yang diinduksi dengan krim imiquimod 5% selama 6 hari. Tikus dibagi menjadi kelompok 5 kelompok yang diberi SPM atau Phosphate Nuffer Saline (PBS) secara intradermal atau subkutan serta kontrol normal. Pemberian SPM dan PBS dilakukan sebelum pengolesan krim. Penilaian harian kulit tikus dilakukan dengan skoring modified Psoriasis Area and Severity Index (mPASI). Setelah pembedahan, kulit tikus dianalisa terhadap ekspresi relatif gen Interleukin (IL)-17 dan IL-10. Sebagian kulit difiksasi dengan formalin dan dilakukan pemeriksaan histologi dan imunohistokimia dengan antibodi Anti-CD11b. Analisa statistik memperlihatkan skor mPASI kelompok SPM mengalami penurunan bermakna dibanding kelompok PBS. Ekspresi relatif gen IL-17 menurun dan gen IL-10 meningkat pada kelompok SPM dibandingkan PBS. Pewarnaan Hematoksilin dan Eosin memperlihatkan rerata tebal epidermis dan jumlah kapiler mengalami penurunan pada kelompok SPM dibanding PBS. Rerata jumlah infiltrasi sel CD11b+ kelompok SPM menurun secara bermakna dibandingkan PBS. Penyuntikan SPM terutama intradermal mampu menyebabkan remisi pada lesi lokal kulit psoriasis pada model tikus Wistar.

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Psoriasis is a chronic inflammatory disease affecting mainly the skin and other parts such as nails and joints. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are highly proliferative immunomodulator cells with low immunogenicity. The Psoriasis rat model was induced with 5% imiquimod cream for 6 days. The rats were divided into 5 groups receiving intradermal or subcutaneous injections of hUC-MSCs or Phosphate Buffer Saline (PBS), and a normal control group. MSCs and PBS were administered before cream application. Daily skin assessments were performed using a modified Psoriasis Area and Severity Index (mPASI) scoring system. After harvest, rat skin was analyzed for relative expression of Interleukin (IL)-17 and IL-10 genes. Some skin samples were fixed with formalin for histological examination and immunohistochemistry with Anti-CD11b antibodies. Statistical analysis showed a significant reduction in mPASI scores in the hUC-MSCs group compared to the PBS group. Histology staining revealed a decrease in epidermal thickness and capillary in the hUC-MSCs group. The infiltration of CD11b+ cells significantly decreased in the hUC-MSCs group.  The relative gen expression of IL-17 decreased, while IL-10 gene increased in the hUC-MSCs group. Particularly, intradermal injection of hUC-MSCs induced remission of local psoriasis skin lesions in the rat model."