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"ABSTRACTBackground: MiR-21 is known to play a role in osteoclast proliferation and differentiation, but the role of serum miR-21 expression in osteoporosis remains unclear. Previous research found that serum miR-21 expression was positively correlated with bone mineral density in postmenopausal osteoporosis patients, but other factors involved in postmenopausal osteoporosis still unknown. This study aimed to determine the role of serum miR-21 expression, concentration of RANKL, OPG, TGF-β1, sclerostin and serum calcium, RANKL/OPG ratio, and physical activity on bone mineral density of spine in hypoestrogenic postmenopausal women with osteoporosis (PMOP) compared with no osteoporosis (PMNOP), with point of interest on the expression of serum miR-21. Methods: this study was conducted by comparative cross-sectional design. The subjects were divided into 2 groups of PMOP and PMNOP. We used an absolute quantification real-time PCR method to determine serum miR-21 expressions level. Results: Median of serum miR-21 expression at the PMOP group was significantly higher compared to PMNOP group (p = 0,001). Serum miR-21 expression, RANKL, RANKL/OPG ratio, and physical activity were significantly correlated with BMD values in the PMOP group. Moderate physical activity was significantly negatively correlated with serum miR-21 expression. We also obtained a linear regression equation BMD = 1,373-0,085*Ln.miR-21-0,176*Log10.RANKL (R2 = 52,5%). Conclusion: serum miR-21 expression in PMOP was higher compared with PMNOP. Serum miR-21 expression proved to have a negative effect on spinal BMD values in hypoestrogenic postmenopausal women with osteoporosis of 8,5%. Obtained equation of BMD = 1,373-0,085*Ln.miR-21-0,176*Log10.RANKL can explain the value of spinal BMD by 52,5%."

"ABSTRAKMiR-21 diketahui berperan dalam proliferasi dan diferensiasi osteoklas, namun peran ekspresi miR-21 serum pada osteoporosis masih belum jelas. Penelitian sebelumnya mendapatkan bahwa ekspresi miR-21 serum berkorelasi positif dengan densitas mineral tulang pada penderita osteoporosis pascamenopause, tetapi penelitian tersebut tidak menganalisis faktor-faktor lainnya yang terlibat dalam osteoporosis pascamenopause.Penelitian ini bertujuan untuk mengetahui peran ekspresi miR-21 serum, konsentrasi RANKL, OPG, TGF- ? 1, sklerostin, rasio RANKL/OPG, kalsium serum dan aktivitas fisis terhadap densitas mineral tulang belakang pada perempuan pascamenopause hipoestrogenik dengan osteoporosis dibandingkan dengan tanpa osteoporosis, dengan point of interest pada ekspresi miR-21 serum.Penelitian ini dilakukan dengan disain uji potong lintang komparatif, di RSUD Ulin Banjarmasin, pada bulan Agustus 2015 sampai Juli 2016. Subjek dibagi menjadi 2 kelompok yaitu perempuan pascamenopause hipoestrogenik dengan osteoporosis dan tanpa osteoporosis. Pengambilan sampel dilakukan dengan metode consecutive. Pemeriksaan ekspresi miR-21 serum menggunakan metode absolute quantification real-time PCR. Analisis statistik menggunakan uji korelasi Spearman, Mann-Whitney U test dan regresi linear berganda.Subjek dibagi menjadi 2 kelompok yaitu perempuan pascamenopause hipoestrogenik dengan osteoporosis PMOP dan tanpa osteoporosis PMNOP masing-masing sebanyak 60 subjek. Median ekspresi miR-21 serum pada PMOP lebih tinggi secara bermakna dibandingkan dan PMNOP p = 0,001 . Ekspresi miR-21 serum, RANKL, rasio RANKL/OPG dan aktivitas fisis berkorelasi bermakna dengan nilai BMD pada PMOP. Aktivitas fisis sedang berkorelasi negatif bermakna dengan ekspresi miR-21 serum pada PMOP dan PMNOP. Analisis regresi linear berganda menggunakan metode backward stepwise mendapatkan persamaan regresi linear: BMD = 1,373 - 0,085 Ln.miR-21 - 0,176 Log 10.RANKL R2 = 52,5 .Simpulan. Ekspresi miR-21 serum pada perempuan pascamenopsuse hipoestrogenik dengan osteoporosis terbukti lebih tinggi dibandingkan dengan tanpa osteoporosis. Ekspresi miR-21 serum terbukti memberikan pengaruh negatif terhadap nilai BMD tulang belakang pada perempuan pascamenopause hipoestrogenik dengan osteoporosis sebesar 8,5 , dengan persamaan regresi linear BMD = 1,373 - 0,085 Ln.miR-21 - 0,176 Log10.RANKL. Persamaan ini dapat menjelaskan nilai BMD tulang belakang sebesar 52,5 . Kata kunci: BMD, miR-21 serum, Osteoporosis, Pascamenopause

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ABSTRACTMiR-21 is known to play a role in osteoclast proliferation and differentiation, but the role of serum miR-21 expression in osteoporosis remains unclear. Previous research found that serum miR-21 expression was positively correlated with bone mineral density in postmenopausal osteoporosis patients, but the study did not analyze other factors involved in postmenopausal osteoporosis.This study aimed to determine the role of serum miR-21 expression, concentration of RANKL, OPG, TGF- ? 1, sclerostin and serum calcium, RANKL/OPG ratio, and physical activity on bone mineral density of spine in hypoestrogenic postmenopausal women with osteoporosis compared to no osteoporosis, with point of interest on the expression of serum miR-21.This study was conducted by comparative cross sectional design, conducted at Ulin General Hospital Banjarmasin, from August 2015 until July 2016. The subjects were divided into 2 groups of hypoestrogenic postmenopausal women with osteoporosis and without osteoporosis. Sampling was done by consecutive method. Examination of serum miR-21 expression using absolute quantification real-time PCR method. Statistical analysis using Spearman correlation test, Mann-Whitney U test and multiple linear regression.The subjects were divided into 2 groups of hypoestrogenic postmenopausal women with osteoporosis PMOP and without osteoporosis PMNOP each as many as 60 people. Median of serum miR-21 expression at PMOP group was significantly higher compared to PMNOP group p = 0.001 . Serum miR-21 expression, RANKL, RANKL/OPG ratio and physical activity were significantly correlated with BMD values ? ? ? ?in PMOP group. Moderate physical activity was significantly negative correlated with serum miR-21 expression. Multiple linear regression multivariate analysis using backward stepwise method obtained linear regression equation BMD = 1,373 - 0,085 Ln.miR-21 - 0,176 Log10.RANKL R2 = 52,5 .Conclusion. Serum miR-21 expression in hypoestrogenic postmenopausal women with osteoporosis has been shown to be higher compared with no osteoporosis. Serum miR-21 expression proved to have a negative effect on spinal BMD values in hypoestrogenic postmenopausal women with osteoporosis of 8.5 , with linear regression equation BMD = 1.373 - 0.085 Ln.miR-21 - 0.176 Log10.RANKL. This equation can explain the value of spinal BMD by 52.5 . Keywords: BMD, Osteoporosis, postmenopausal, serum miR-21 "

"Kanker serviks merupakan salah satu kanker terbanyak pada perempuan dengan jumlah kasus dan kematian yang bermakna, terutama di negara-negara berkembang seperti Indonesia. Penelitian terbaru menyoroti peran mikroRNA (miRNA) dalam karsinogenesis, terutama miR-21 yang terlibat dalam berbagai jenis kanker pada perempuan, termasuk kanker serviks. Selain itu, miR-145, LATS1, dan NF-κB dipercaya memiliki peran dalam radioresistensi. Penelitian ini bertujuan untuk membuktikan pengaruh konsentrasi miR-21, miR-145, Large Tumor Suppressor 1 (LATS1), dan Nuclear Factor Kappa B (NF-kB) serta usia terhadap respons kemoradiasi pada pasien kanker serviks stadium lanjut lokal. Penelitian ini menggunakan desain potong lintang analitik yang dilakukan di Rumah Sakit Cipto Mangunkusumo dari bulan Juli 2017 sampai Juni 2023. Sampel jaringan dari biopsi serviks diambil dan diperiksa menggunakan real-time reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) untuk mendeteksi miR-21 dan miR-145, serta ELISA untuk mendeteksi konsentrasi LATS1 dan NF-kB sebelum pasien menerima terapi kemoradiasi. Pemeriksaan ultrasonografi kemudian dilakukan kembali untuk menilai respons radiasi dengan menggunakan kriteria RECIST 1.1. Dari 140 subjek, ditemukan gambaran histopatologi karsinoma sel skuamosa pada 119 (85%) sampel, dengan distribusi kanker serviks stadium IIIB pada 102 (72,9%) subjek dan stadium IVA pada 38 (27,1%) subjek. Ekspresi miR- 21 di atas cut-off lebih banyak ditemukan pada subjek yang radioresisten (p = 0,010; AUC = 67,6%). Ekspresi miR-145 dan LATS1 di atas cut-off lebih banyak ditemukan pada kelompok radioresisten, masing-masing dengan p = 0,132 (AUC = 38,8%) dan p = <0,001 (AUC = 32,7%). Ekspresi NF-kB di bawah cut-off ditemukan lebih banyak pada kelompok radioresisten (p = 0,009; AUC = 61%), dan usia di bawah cut-off juga lebih banyak ditemukan pada kelompok radioresisten (p = 0,138; AUC = 39,2%). Penelitian ini menunjukkan bahwa ekspresi miR-21 dan LATS1 pra-kemoradiasi yang tinggi serta ekspresi NF-κB yang rendah berhubungan dengan terjadinya radioresistensi. Sebaliknya, konsentrasi miR-145 dan usia tidak berhubungan dengan radioresistensi, sehingga dapat disimpulkan bahwa miR-21 memiliki potensi sebagai biomarker radioresisten pada pasien kanker serviks stadium lanjut lokal dan pemeriksaan kombinasi tidak disarankan.

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Cervical cancer is one of the most common cancers in women with a significant number of cases and deaths, especially in developing countries such as Indonesia. Recent research highlights the role of microRNAs (miRNAs) in carcinogenesis, particularly miR-21, which is involved in various types of cancer in women, including cervical cancer. In addition, miR-145, LATS1 and NF-κB also considered to play a role in radioresistance. This study aims to determine the influence of miR- 21, miR-145, Large Tumor Suppressor 1 (LATS1), Nuclear Factor Kappa B (NF- κB), and age on chemoradiation response in locally advanced cervical cancer patients. This study used an analytical cross-sectional design conducted at Cipto Mangunkusumo Hospital from July 2017 to June 2023. Cervical biopsy tissue samples were collected and examined using real-time reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) to detect miR-21 and miR-145, and ELISA to measure LATS1 and NF-κB concentrations before patients underwent chemoradiation therapy. Ultrasound examination was then re-performed to assess radiation response using RECIST 1.1 criteria. This research obtained a total of 140 samples with histopathological subtype of squamous cell carcinoma found in 119 (85%) samples, with cervical cancer stage IIIB in 102 (72.9%) subjects and stage IVA in 38 (27.1%) subjects. Expression of miR-21 above the cut-off was more prevalent in radioresistant patients (p = 0.010; AUC = 67.6%). Expression of miR-145 and LATS1 above the cut-off were found to be higher in the radioresistant group with p = 0.132 (AUC = 38.8%) and p = <0.001 (AUC = 32.7%), respectively. NF-κB expression below the cut-off were found to be higher in the radioresistant group (p = 0.009; AUC = 61%), and age below the cut-off were also found to be higher in the radioresistant group (p = 0.138; AUC = 39.2%). This study showed that high expression of miR-21 and LATS1 pre-chemoradiation and low expression of NF-κB pre-chemoradiation were all associated with radioresistance, while miR- 145 concentration and age were not associated with radioresistance. This study concluded that miR-21 had the potential to be used as a radioresistant biomarker in patients with local advanced-stage cervical cancer and combination testing was not suggested."

"ABSTRAKKanker paru berkaitan dengan prognosis yang buruk. Oleh karenanya, diperlukan penanda sirkulasi untuk memprediksi respons terapi dan prognosis. Ekspresi mikroRNA 10b miR-10b dan aktivitas fibrinolitik, sebagaimana dicerminkan oleh soluble urokinase-type plasminogen activator receptor suPAR dan plasminogen activator inhibitor 1 PAI-1 , merupakan kandidat biomarker yang menjanjikan.Penelitian ini bertujuan mengevaluasi peran ekspresi miR-21, miR-10b, kadar suPAR dan PAI-1 plasma sebagai prediktor progresi dan respons terapi pada pasien kanker paru stadium lanjut.Penelitian ini merupakan studi kohort dan kesintasan di RS Kanker Dharmais RSKD , Jakarta. Subjek penelitian adalah pasien kanker paru karsinoma bukan sel kecil KPBBSK yang didiagnosis antara bulan Maret 2015 dan September 2016. Ekspresi miR-21 dan miR-10b dikuantifikasi dengan metode real-time polymerase chain reaction RT-PCR . Kadar suPAR dan PAI-1 diperiksa dengan metode enzyme-linked immunosorbent assay ELISA . Respons terapi dievaluasi berdasarkan kriteria RECIST 1.1. Pasien ditindaklanjuti sampai meninggal atau satu tahun setelah terapi.Terdapat 40 pasien yang dilibatkan dalam studi; 25 orang menyelesaikan sedikitnya4 siklus kemoterapi dan 15 lainnya meninggal selama terapi. Ekspresi miR-21 tidak berhubungan dengan progresi atau respons terapi. Kadar absolut miR-10b >592,145 copies/mL atau FC miR-10b > 0.066 bersifat protektif terhadap progresi dan respons buruk, sedangkan kadar suPAR > 4,237 pg/mL merupakan faktor risiko progresi dan respons buruk. Oleh karena dianggap penting, FC miR-10b juga dimasukkan dalam model prediksi progresi. Kadar PAI-1 > 4,6 ng/mL merupakan faktor protektif untuk respons buruk. Kadar suPAR merupakan faktor risiko independen untuk progresi dan respons buruk, sedangkan kadar PAI-1 merupakan faktor protektif independen untuk respons buruk.Simpulan: Model prediksi untuk progresi dapat dibuat dari ekspresi relatif miR-10b dan kadar suPAR, sedangkan respons terapi dapat diprediksi dari kadar suPARdan PAI-1. Dibutuhkan studi lebih lanjut untuk validiasi model-model prediksi ini.Kata kunci: kanker paru karsinoma bukan sel kecil KPKBSK , miR-10b, miR-21, overall survival, plasminogen activator inhibitor 1 PAI-1 , respons terapi, soluble urokinase-type plasminogen activator receptor suPAR

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ABSTRACTLung cancer is associated with poor prognosis. Circulating markers to predict treatment response and prognosis is needed. Expression of microRNA10b miR 10b and fibrinolytic activity, as reflected by soluble urokinase type plasminogen activator receptor suPAR and the plasminogen activator inhibitor 1 PAI 1 , were promising as biomarker candidates.This study aimed to evaluate the role of miR 21, miR 10b expression, suPAR and PAI 1 levels as predictors of progression during treatment and treatment response in advanced lung cancer patients.This was cohort and survival study in Dharmais Cancer Hospital DCH . The subjects were non small cell lung cancer NSCLC patients diagnosed between March 2015 and September 2016. Expression of miRNAs were quantified using real time polymerase chain reaction RT PCR method. Levels of suPAR and PAI 1 were assayed using the enzyme linked immunosorbent assay ELISA method. Treatment response was evaluated based on RECIST 1.1. Patients were followed up until death or one year after treatment.Forty patients were enrolled 25 completed at least 4 cycles of chemotherapy and15 patients died during treatment. Absolute and FC miR 21 were not associated with progression or treatment response. Absolute MiR 10b expression 592,145 copies mL or FC miR 10b 0.066 were protective for progressive disease and poor treatment response, while suPAR levels 4,237 pg mL was a risk factor for progressive disease and poor responders. Since FC miR 10b was an important predictive factor, it was included in the prediction model of progression. PAI 1 levels 4.6 ng mL was a protective factor for poor response group of patients. suPAR level was an independent risk factors for progression and poor response, while PAI 1 level was an independent protective factor of poor response.Conclusion A model to predict progression can be developed using miR 10b expression and suPAR levels, while treatment response can be predicted by suPAR and PAI 1 levels. Further studies are needed to validate this model.Key words miR 10b, miR 21, non small cell lung cancer NSCLC , overall survival, plasminogen activator inhibitor 1 PAI 1 , soluble urokinase type plasminogen activator receptor suPAR , treatment response"

"ABSTRAKLatar Belakang. Striktur usus merupakan suatu bentuk komplikasi dari hernia stangulata, yang menyebabkan obstruksi usus setelah beberapa bulan pascaoperasi. Kejadian striktur usus sangat berkaitan dengan fibrosis. Namun tidak semua fibrosis usus akan menjadi striktur. Penelitian ini bertujuan untuk melihat peran TGF-β, sitoglobin, miR-21, miR-29b sebagai faktor dalam memprediksi striktur usus pada tikus dengan studi eksperimental penjepitan usus.Metode. Studi dilakuakn di Fakultas Kedokteran Universitas Indonesia pada 2018-2019. Hewan coba yang digunakan di dalam penelitian adalah galur Sprague-Dawley dewasa muda berusia 6-8 minggu dengan berat 150-200gram. Tikus di anestesi menggunakan ketamin dan dilakukan laparotomi untuk melakukan tindakan penjepitan pada usus tikus. Penjepitan menggunakan cable tie dengan ukuran diameter lilitan 6 mm dan terlebih dahulu lindungi plastik rigid, pada bagian ileum terminal. Spesimen yang diperoleh berupa bagian usus di antara jepitan sepanjang 1 cm serta darah dari jantung pada jam ke-6 dan ke-24. Untuk pemeriksaan histopatologi diberikan pulasan hematoksilin-eosin dan Masson trichrome. Analisa serum biokimia menggunakan RT-PCR dan ELISA.Hasil. Serat kolagen ditemukan bermakna pada perlakuan jam ke-6 vs kontrol (10.66±4.66; p<0.05) dan jam ke-24 vs kontrol (17.98±6.93; p<0.01) serta deposit serat kolagen paling banyak terdapat pada lapisan submukosa. Deposisi kolagen usus diikuti peningkatan konsentrasi miR-21 baik pada serum (med.6jam=54.25; p>0.05&med.24jam=37 ;p>0.05) maupun jaringan (med.6jam=21.9; p<0.05&med.24jam=144 ;p>0.05) Deposisi kolagen usus diikuti peningkatan miR-29b baik serum (med.6jam=631.5; p>0.05 & med.24jam=863.5 ; p>0.05) maupun jaringan (med.6jam = 675; p>0.05& med.24jam=759.5 ; p>0.05). Deposisi kolagen usus diikuti dengan peningkatan yang bermakna pada TGF-β serum (medp.6jam= 32.85; p<0.05&med.24jam = 24.87; p<0.05) maupun jaringan (medp.6jam=14.8; p<0.05&med.24jam=58.32; p<0.05). Deposisi kolagen usus diikuti dengan peningkatan bermakna sitoglobin serum (medp.6jam=162.9; p<0.05&medp.24jam=263.72; p<0.05) dan jaringan (medp.6jam=2712.61; p<0.01&medp.24jam=1308.38; p>0.05). Terdapat korelasi yang bermakna antara serat kolagen dengan TGF-β jaringan (r= 0.436; p=0.033). Uji diagnostik menunjukkan TGF-β serum yang tinggi dan sitoglobin yang tinggi yang diperiksa pada jam ke 24 setelah jepitan memiliki sensitivitas yang tinggi untuk mendeteksi serat kolagen (fisher<0.01; sensitivitas 100%; spesifisitas 63%).Simpulan. Pemeriksaan serum TGF-B dan sitoglobin yang dilakukan secara bersamaan pada waktu 24 jam mempunyai hubungan dengan peningkatan serat kolagen yang berpotensi menjadi fibrosis sehingga dapat digunakan sebagai prediktor kejadian striktur usus.

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ABSTARCTBackground. Intestinal stricture has been a troublesome complication following strangulated hernia, which may result in intestinal obstruction after several months postsurgery. The occurrence of intestinal stricture is closely related to fibrosis. Not all of the fibrotic lesions, however, lead to stricture. The present study is aimed to investigate the role of TGF-β, cytoglobin, miR-21, miR-29b and collagen deposition as factors in predicting the occurrence of intestinal stricture in the rats underwent experimental intestinal strangulation.Methods. The study was conducted in Animal Cluster and Laboratories at Faculty of Medicine, University of Indonesia during 2018-2019. Adult, male Sprague-Dawley rats of 6-8 weeks old, 150-200 g were used in the study. Following anesthesia with ketamine, the rats were laparotomized and intestinal strangulation was conducted bymeans of a cable tie. Intestinal tissues and blood samples were collected at 6 and 24 hours of strangulation. Tissue samples were stained with Hematoxylin-eosin and Massons trichrome to visualize collagen and pathological alteration. TGF-β, cytoglobin, miR21 and miR29b were determined in blood sera and tissue samples and analyzed using RT-PCR and ELISA.Results. Collagen fiber was found to be significant at the 6th hour vs. control (10.66 ±4.66; p <0.05) and 24th hour vs control (17.98 ± 6.93; p <0.01), most collagen fibers deposit were found in the submucosal layer. Increase in intestinal collagen deposition was followed by an increase in the concentration of miR-21 both in serum (med.t.6 hours = 54.25; p> 0.05 & med. t.24 hours = 37; p> 0.05) and tissue (med.t.6 hours = 21.9; p <0.05 & med.t.24 hours = 144; p> 0.05) Increase in deposition of intestinal collagen followed by an increase in miR-29b both serum (med. t.6 hours = 631.5; p> 0.05 & med. t.24 hours = 863.5; p> 0.05) and tissue (med. t.6 hours = 675; p> 0.05 & med. t.24 hours = 759.5; p> 0.05). Increase in intestinal collagen deposition was followed by a significant increase in serum TGF-β (med.t.6 hours = 32.85; p <0.05 & med.t.24 hours = 24.87; p <0.05) and tissue (med.t.6 hours = 14.8; p <0.05 & med t.24 hours = 58.32 hours); p <0.05). Increase in intestinal collagen deposition was followed by a significant increase in serum cytoglobin (med.t.6 hours = 162.9; p <0.05 & med. t.24 hours = 263.72; p <0.05) and tissue (med.t.6 hours = 2712.61; p <0.01 & med.t.24 hours = 1308.38; p> 0.05). There was a significant correlation between collagen fiber and TGF-β tissue (r= 0.436; p = 0.033). Diagnostically, high serum TGF-β and cytoglobin that were examined at 24 hours after strangulation occur have high sensitivity to detect collagen fiber (fisher <0.01; sensitivity 100%; specificity 63%).Conclusions. Simultaneous increase of serum TGF-β and cytoglobin at 24 hours of strangulation associated with increased collagen fibers may become potential factors in predicting intestinal stricture in the rat underwent experimental strangulated intestines"