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"Prevalensi pre-frail tinggi pada usia lanjut dan kondisi tersebut dapat berubah menjadi frail. Kolekalsiferol diduga memiliki potensi untuk memperbaiki sindrom frailty pada usia lanjut. Penelitian ini bertujuan mengkaji pengaruh kolekalsiferol terhadap kekuatan genggam tangan, kecepatan berjalan serta reseptor vitamin D (vitamin D receptor/VDR), interleukin-6 (IL-6), dan insulin-like growth factor-1 (IGF-1) monosit pada usia lanjut dengan pre-frail. Uji klinis acak tersamar ganda dilakukan di Poliklinik Geriatri RSCM pada bulan April–Desember 2021. Sebanyak 120 subjek dirandomisasi menjadi kelompok yang mendapat kolekalsiferol 4.000 IU/hari (60 subjek) serta kelompok yang mendapat plasebo/hari (60 subjek). Seluruh subjek mendapat suplementasi kalsium laktat 500 mg /hari. Pengamatan dilakukan selama 12 minggu. Terdapat 57 subjek pada kelompok kolekalsiferol dan 56 subjek pada kelompok plasebo yang menjalani penelitian hingga selesai. Analisis intention to treat dilakukan untuk mengevaluasi luaran kekuatan genggam tangan dan kecepatan berjalan, sedangkan analisis per protokol untuk mengevaluasi VDR, IL-6 dan IGF-1 monosit. Pada akhir pengamatan, tidak terdapat perbedaan bermakna pada kekuatan genggam tangan (p = 0,228), kecepatan berjalan (p = 0,734), VDR monosit (p = 0,45), IL-6 monosit (p = 0,57) dan IGF-1 monosit (p = 0,72) antara kedua kelompok perlakuan. Tidak ada korelasi antara perubahan VDR, IL-6 dan IGF-1 monosit dengan kekuatan genggam tangan dan kecepatan berjalan. Terdapat peningkatan kadar 25(OH)D yang bermakna pada masing-masing kelompok perlakuan dan peningkatan bermakna pada kelompok kolekalsiferol dibandingkan plasebo. Pemberian kolekalsiferol 4.000 IU pada usia lanjut pre-frail 12 minggu meningkatkan kadar 25(OH)D secara bermakna, namun belum terbukti dapat memperbaiki kekuatan genggam tangan, kecepatan berjalan, meningkatkan VDR dan IGF-1 monosit serta menurunkan IL-6 monosit. Fungsi ginjal memiliki pengaruh terhadap efek kolekalsiferol pada IGF-1 monosit. Kolekalsiferol meningkatkan jumlah monosit dengan IGF-1+ pada eGFR > 90, namun tidak pada eGFR 30–59.

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Pre-frail prevalence is higher in the elderly. Frailty status is a dynamic condition. Pre-frail can fall into a frail condition. Cholecalciferol is regarded to have potential effect to improve frailty syndrome in the elderly. This study aimed to determine the effect of cholecalciferol on hand grip strength, walking speed, vitamin D receptors, IL-6, and IGF-1 monocyte in pre-frail elderly. A randomized double-blind clinical trial study at the RSCM Geriatric Polyclinic was conducted from April to December 2021. A total of 120 subjects were randomized into groups receiving 4000 IU cholecalciferol/day (60 subjects) and groups receiving placebo/day (60 subjects). All subjects received calcium lactate supplementation 500 mg/day. Observations were made for 12 weeks. There were 57 subjects in the cholecalciferol group and 56 subjects in the placebo group who completed the study. An intention to treat analysis was performed to evaluate the output of hand grip strength and walking speed, while a per protocol analysis was performed to evaluate monocyte VDR, IL-6 and IGF-1.There were no significant differences in hand grip strength (p = 0,228), walking speed (p = 0,734), VDR monocyte (p = 0,45), IL-6 monocyte (p = 0,57) and IGF-1 monocyte (p = 0,72) between treatment groups. There were no correlation between changes in the VDR, IL-6 and IGF-1 monocytes with changes in hand grip strength and walking speed. There was a significant increase in 25(OH)D levels in each group and a significant difference between groups. Supplementation of cholecalciferol 4.000 IU daily for 12 weeks increased serum 25(OH)D level significantly, however it did not improve hand grip strength and walking speed, and did not affect VDR, IL-6 and IGF-1 monocytes in pre-frail elderly. Kidney function had an influence on the effect of cholecalciferol on monocyte IGF-1. Cholecalciferol increased the number of monocytes with IGF-1+ at eGFR > 90, but not at eGFR 30–59."

"Latar belakang: Peningkatan suhu tubuh ekstrim menyebabkan denaturasi protein,terhentinya reaksi enzimatik, hilangnya aktivitas dan integritas membran, sertamemicu terjadinya kerusakan sel. Peningkatan suhu tubuh juga mempengaruhiterjadinya efek inotropik dan kronotropik positif pada jantung. Diperkirakan bahwapajanan panas dapat meningkatkan ekspresi protein Transient Receptor PotentialVanilloid 1 (TRPV1), Heat Shock Factor 1 (HSF1) dan Heat Shock Protein 70(Hsp70) pada kardiomiosit berperan penting dalam proses termotoleran danaklimatisasi terhadap panas serta berguna sebagai mekanisme adaptasi secara sistemikdan seluler. Tujuan dari penelitian adalah untuk menganalisis ekspresi TRPV1, HSF1,dan Hsp70 pada jantung sebagai respons protektif terhadap pajanan panas.Metode: Penelitian bersifat eksperimental in vivo menggunakan hewan coba tikusjenis Sprague Dawley (SD) berumur 12 minggu dengan berat badan 200-300 gram dilaboratorium hewan Balitbangkes Kemenkes RI, pada Oktober-Desember 2014.Sebanyak 28 ekor tikus jantan dengan n=4 pada tiap kelompoknya, dibagi dalamkelompok Kontrol (K) dan kelompok Perlakuan (P). Kelompok perlakuan terdiri dari6 subkelompok (kelompok hari ke-1,3,7,10,14 dan 21) mendapatkan pajanan panas didalam hyperthermic chamber bersuhu (45oC ± 0.3oC) dan kelembaban relatif (70% ±3%) selama 60 menit. Dilakukan pengukuran berat badan, suhu kulit, suhu rektal danfrekuensi denyut jantung. Perubahan morfologi kardiomiosit diamati menggunakanpewarnaan Hematoksilin-Eosin. Ekspresi TRPV1, HSF1 dan Hsp70 diperiksamenggunakan metode imunohistokimia dan ELISA.Hasil: Penelitian menunjukan pajanan panas 45oC; kelembaban relative 70% selama60 menit menyebabkan penurunan berat badan sejak hari ke-1 hingga hari ke-21perlakuan. Terjadi peningkatan suhu kulit, suhu rektal dan heart rate yang puncaknyaterjadi pada hari ke-7, dan menurun mulai pada hari ke-10 sampai pada hari ke-21meskipun intensitas pajanan panas tetap sama. Hal tersebut menandakan mekanismeaklimatisasi dan proses termotoleransi telah terjadi pada hari ke-7 perlakuan. Terjadipenambahan ukuran lebar kardiomiosit dan peningkatan berat pada jantung seiringlamanya pajanan panas, Hasil ini menunjukkan terjadinya hipertrofi jantung namuntidak disertai adanya fibrosis. Secara molekuler melalui pemeriksaan Imunohistokimiadan ELISA pada kardiomiosit menunjukkan ekspresi TRPV1, HSF1 dan Hsp70 yangbersifat sebagai protein protektif dan kardioprotektor cenderung mengalamipeningkatan sejak hari ke-1 sampai pada hari ke-7 perlakuan dan cenderung menurunpada hari ke-10 sampai dengan hari ke-21. Perubahan kadar ekspresi TRPV1, HSF1dan Hsp70 sejalan dengan perubahan yang terjadi pada suhu kulit, suhu rektal danheart rate.Kesimpulan: Pajanan panas pada tubuh memberikan pengaruh pada jantung berupaterjadinya hipertrofi konsentris disertai adanya peningkatan ekspresi TRPV1, HSF1dan Hsp70 yang berperan penting sebagai protein protektif dan kardioprotektorBackground: Increased extreme body temperature causes protein denaturation,cessation of enzymatic reactions, loss of membrane activity and integrity, and triggerscellular damage. Increased body temperature also affects the occurrence of positiveinotropic and chronotropic effects on the heart. It is postulated that increase inexpression Transient Receptor Potential Vanilloid 1 (TRPV1), Heat Shock Factor 1(HSF1), Heat Shock Protein 70 (Hsp70) in cardiomyocytes is activated by extremetemperatures and has an important role in thermotolerance and heat acclimatizationprocesses -and as a mechanism of systemic and cellular adaptation. The aim of thestudy was to analyze the expression of TRPV1, HSF1, and Hsp70 on cardiac muscleas a protective response to heat exposure.Methods: This in vivo experimental research was conducted using Sprague-Dawley(SD) rats (age 12 weeks, 200-300 gram) in animal laboratory National Institute ofHealth Research and Development, Indonesian Ministry of Health, October-December2014. A total of 28 male rats with n = 4 in each group, divided into Control group (K)and Treatment group (P). The treatment group consisted of 6 sub-groups (i.e.1,3,7,10,14 and 21 days) received heat exposure in hyperthermic chamber at (45oC ±0.3oC) and (70% ± 3%) with relative humidity of 60 minutes. Body weight, skintemperature, rectal temperature and heart rate were measured. Changes incardiomyocyte morphology were observed using Hematoxylin-Eosin staining.Expressions of TRPV1, HSF1 and Hsp70 were examined using immunohistochemicaland ELISA methods.Results: The results of this study showed that heat exposure at 45oC;70% RH for 60minutes resulted in weight loss from day 1st to day 21st of the treatment. Peakselevation in skin temperature, rectal temperature and heart rate were reached at day7th, and decreased gradually from day 10th to day 21st even though the intensity ofheat exposure was unchanged. This indicated the mechanism of acclimatization andthermotolerance process had occurred on the 7th day of heat treatment. There wasincreased in the size of the cardiomyocyte width and heart weight along with theduration of heat exposure. These results indicated the occurrence of heart hypertrophybut not accompanied by fibrosis. Molecular aspects on cardiomyocytes throughImmunohistochemistry and ELISA showed TRPV1, HSF1 and Hsp70 expression asprotective proteins and cardioprotectors, which tended to increase from day 1st to 7thday of treatment and decrease gradually on day 10th to day 21st. Changes inexpression levels of TRPV1, HSF1 and Hsp70 coincided with changes in skintemperature, rectal temperature and heart rate.Conclusion: Heat exposure to the body induced the development of heart hypertrophyand coincided with the increased expression of TRPV1, HSF1 and Hsp70 which act asa protective protein and cardioprotector."

"Latar belakang: Semaphorin-3B (SEMA3B) sebagai faktor antiangiogenik dan Cullin-1 (CUL1) sebagai faktor proangiogenik merupakan contoh dua protein yang bekerja secara antagonis dalam invasi trofoblas, yang bila terjadi ketidakseimbangan akan menyebabkan preeklamsia (PE). VEGF, MMP9, E-cadherin, p21, dan CASP3 merupakan kandidat protein terkait kaskade hantaran sinyal SEMA3B dan CUL1. Tujuan umum penelitian ini adalah untuk menganalisis kadar SEMA3B dan CUL1, serta kandidat protein terkait kaskade hantaran sinyalnya pada patologi PE berdasarkan perbedaan usia kehamilan saat persalinan. Metode: Penelitian diadakan di RS Cipto Mangunkusumo dan RS Budi Kemuliaan dari April 2017-April 2018. Studi potong lintang dengan observasi analitik dilakukan untuk mengukur kadar SEMA3B dan CUL1 dan kandidat protein terkait kaskade hantaran sinyalnya dalam plasenta, serta kadar SEMA3B dan CUL1 dalam serum ibu pada 70 pasien PE berdasarkan dua kelompok usia kehamilan saat persalinan: <34 minggu dan ≥34 minggu. Pemeriksaan dilakukan di Laboratorium Terpadu Fakultas Kedokteran Universitas Indonesia. Hasil: Kadar SEMA3B, CUL1, VEGF, dan E-cadherin secara bermakna lebih rendah pada kelompok usia kehamilan <34 minggu. Pada kelompok usia kehamilan <34 minggu: terdapat korelasi positif antara usia kehamilan dengan SEMA3B, CUL1, dan protein terkait kaskade hantaran sinyalnya; terdapat korelasi positif antara SEMA3B dengan VEGF dan p21; terdapat korelasi positif antara CUL1 dengan VEGF, MMP9, E-cadherin, p21, dan CASP3; dan korelasi negatif antara rasio p21/CUL1 dengan usia kehamilan. Pada kelompok usia kehamilan ≥34 minggu: terdapat korelasi positif antara SEMA3B dalam plasenta dengan SEMA3B dalam serum ibu; tidak ada korelasi SEMA3B dengan kandidat protein terkait kaskade hantaran sinyalnya; terdapat korelasi positif antara CUL1 dengan MMP9, E-cadherin, p21, dan CASP3. Kadar proangiogenik CUL1 dan VEGF yang rendah rendah dan ratio p21/CUL1 yang tinggi secara bermakna berhubungan dengan usia kehamilan <34 minggu saat persalinan. Analisis multivariat menunjukkan kadar CUL1 yang rendah meningkatkan risiko melahirkan sebesar empat kali lebih besar pada usia kehamilan <34 minggu dibandingkan usia kehamilan ≥34 minggu. Kesimpulan: Pada PE usia kehamilan <34 minggu saat persalinan, gambaran patologi PE lebih berat, kadar SEMA3B yang lebih rendah, serta kadar CUL1 yang lebih rendah memiliki risiko empat kali lebih besar terjadi persalinan dibandingkan usia kehamilan ≥34 minggu saat persalinan.

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Background: Semaphorin-3B (SEMA3B) as an antiangiogenic factor and Cullin-1 (CUL1) as a proangiogenic factor are examples of two proteins that work antagonistically in trophoblast invasion, which will cause preeclampsia (PE) if an imbalance occurs. VEGF, MMP9, E-cadherin, p21, and CASP3 are protein candidates related to the signal transduction cascade of SEMA3B and CUL1. The aim of this study was to analyze SEMA3B and CUL1 levels, as well as protein candidates related to the signal transduction cascade in pathology of PE based on differences in gestational age at delivery.

Methods: The study was conducted at Cipto Mangunkusumo Hospital and Budi Kemuliaan Hospital during April 2017 until April 2018. In this cross-sectional study SEMA3B, CUL1, and protein candidates related to the signal transduction cascade (VEGF, MMP9, E-cadherin, p21, CASP3) were measured in the placenta, as well as SEMA3B and CUL1 levels in maternal serum in 70 PE patients in two gestational age at delivery groups: <34 weeks and ≥34 weeks. Measurements were conducted at Integrated Laboratory of Faculty of Medicine Universitas Indonesia.

Results: Levels of SEMA3B, CUL1, VEGF, and E-cadherin were significantly lower in the gestational age group of <34 weeks compared to ≥34 weeks. In the gestational age group of <34 weeks: there were positive correlation between age gestational age and SEMA3B, CUL1, protein candidates related to their signal transduction cascade; there were positive correlations between SEMA3B and VEGF, p21; there were positive correlations between CUL1 and MMP9, E-cadherin, p21, CASP3; there were negative correlation between p21/CUL1 ratio and gestational age. In the gestational age group of ≥34 weeks: there were positive correlation between SEMA3B in placenta and SEMA3B in maternal serum; there were positive correlations between CUL1 and MMP9, Ecadherin, p21, CASP3; there were no correlation between SEMA3B and candidate protein related to the signal transduction cascade. Significantly, low level of proangiogenic CUL1 and VEGF, and high ratio p21/CUL1 were associated with <34 weeks of gestational age at delivery. Multivariate analysis showed that at <34 weeks of gestational age, low levels of CUL1 increased the risk of giving birth by four times greater than at ≥34 weeks of gestational age.

Conclusions: In PE at <34 weeks of gestation age at delivery, pathology of PE was worse, level of SEMA3B was lower, and lower level of CUL1 had four times greater risk of labor than at ≥34 weeks of gestational age at delivery. "

"Pendahuluan : Infertilitas merupakan masalah yang dialami pasangan suami istri, dimana faktor laki-laki berkontribusi sebesar 40%. Salah satu penyebab infertilitas dari faktor laki-laki adalah gangguan remodelling kromatin yang terjadi selama proses spermiogenesis. Pada proses ini histon akan digantikan oleh protein protamin yang menyebabkan DNA lebih padat dan kompak. Regulasi protamin dipengaruhi oleh kerja protein CREM yang merupakan faktor transkripsi pada gen protamin. Pada tahapan ini dibutuhkan peran androgen yang akan aktif setelah berikatan dengan reseptor androgen (AR), sehingga aktivitas AR sangat menentukan keberhasilan remodeling kromatin. Penelitian ini bertujuan menganalisis ekspresi protein CREM, Protamin 1 dan Protamin 2 pada spermatozoa laki-laki infertil dan kaitannya dengan variasi pengulangan CAG gen reseptor androgen. Metode: Desain penelitian cross sectional. Sampel spermatozoa berasal dari 30 pasien infertil OA/OAT dan 10 pria fertil sebagai kontrol. Protein dan DNA spermatozoa diekstraksi dari tiap-tiap individu. Analisis ekspresi protein CREM, protamin 1 dan protamin 2 dilakukan dengan teknik western immunoblotting. Distribusi protein CREM, protamin 1 dan protamin 2 dianalisis dengan teknik imunositokimia. Pemeriksaan jumlah pengulangan (CAG) dilakukan dengan sekuensing DNA spermatozoa. Hasil: Analisis protein CREM, protamin 1 dan 2 pada laki-laki infertil menunjukan ekspresi yang menurun dibandingkan dengan pria fertil. Penurunan ekspresi protein terlihat pada frekuensi keberadaan pita lebih rendah pada laki-laki infertil secara signifikan. Ekspresi protein CREM berhubungan dengan Protamin 1. Tidak terdapat hubungan ekspresi protein CREM dengan protamin 2, dan ekspresi protamine 1 dengan protamin 2. Analisis imunositokimia menunjukkan bahwa Protein CREM, Protamin 1 dan 2 diekspresikan pada daerah kepala spermatozoa laki-laki fertil dan infertil. Rerata jumlah pengulangan CAG pada laki-laki infertil 29,6 sedangkan pada laki-laki fertil 28,9. Hasil analisis statistik menunjukan tidak ada hubungan signifikan antara jumlah pengulangan CAG gen reseptor androgen dengan tingkat ekspresi CREM, Protamin 1 dan Protamin 2. Kesimpulan: Protein CREM, Protamine 1 dan protamin 2 diekspresikan lebih rendah pada spermatozoa laki-laki infertil dan tidak ada hubungan dengan pengulangan jumlah CAG gen reseptor androgen. Ekspresi protein CREM berhubungan dengan protein protamin 1.

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Introduction : Infertility is a problem experienced by married couples, and causes originated from male factors contribute around 40% of total cases. One of those factor is disturbance in chromatin remodeling during spermiogenesis. During this process, an important event in which histone protein is replaced by protamine takes place. As a result, DNA becomes more compact in size, bond by protamines protein. The expression of protamines is influenced by CREM which is a transcription factor regulating protamine genes. Protamine is transcripted in round spermatid, and translated in elongated spermatid, a process which is dependent on Androgen action. The aims of this study was to analyze CREM and protamine expression in spermatozoa from infertile patients and its correlation with CAG repeats variation of androgen receptor gene.

Method: This cross sectional study was conducted from December 2012 through March 2015. Protein and DNA sperm were extracted from spermatozoa of infertile men. CREM, and protamines expressions were analyzed by using western immunobloting. Localization and distribution of CREM and protamines expression were analyzed by immunocytochemistry. Examination of CAG repeat was performed by DNA sequencing.

Result: CREM and protamines were found to be down-regulated in infertile men compared to fertile individuals. A significant association was found between CREM and protamine 1 expression, but not with protamine 2. No significant association was found between protamine 1 and protamine 2. Analyses using immunocytochemistry showed reduced expression in CREM and Protamine from infertile patient compared to normal individuals. The average CAG repeat of infertile men was 29.6 compared to 28,9 of fertile donors. Statistical analysis showed no significant association between expression level of CREM and Protamine towards the number of CAG repeats variation androgen receptor gene.

Conclusion: CREM, protamine 1 and protamine 2 expression are lower in spermatozoa of infertile male and no association with CAG repeats variation of androgen receptor gene. CREM expression is associated with protamine 1."

"ABSTRAKDefisiensi vitamin B12 merupakan masalah kesehatan di negara maju dan berkembang. Penelitian ini menganalisis hubungan restriksi vitamin B12 dengan perubahan struktur dan fungsi ginjal. Tikus Sprague-Dawley 18 ekor dibagi menjadi tiga kelompok: 1 kontrol yang diberi pakan standar hewan coba AIN-93M selama 12 minggu; 2 perlakuan-1 P-1 diberi pakan AIN-93M modifikasi tanpa vitamin B12 selama 4 minggu; dan 3 perlakuan-2 P-2 selama 12 minggu. Vitamin B12 plasma total turun dari 529.17 166.51 pg/ml menjadi 426.33 60.59 pg/ml pada P-1 dan 708.70 124.35 pg/ml menjadi 519.16 84.96 pg/ml pada P-2, pada kelompok kontrol meningkat dari 567.79 102.52 pg/ml menjadi 650.26 193.12 pg/ml. Homosistein plasma meningkat pada kelompok perlakuan setelah 4 minggu kontrol vs P-1 = 351.05 110.69 pmol/ml vs 597.09 308.02 pmol/ml dan 12 minggu kontrol vs P-2 = 414.473 224.13 pmol/ml vs 1055.12 651.68 pmol/ml, p

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ABSTRACTVitamin B12 deficiency is still a health problem in both developed and developing countries. This study was conducted to explore possible relationship between vitamin B12 dietary restriction with kidney rsquo;s histological and physiological changes. Eighteen male Sprague Dawley rats were divided into three groups: 1 control group were fed with standard AIN-93M for 12 weeks; 2 1st treatment group P-1 were fed with cobalamin restricted AIN-93M for 4 weeks; and 3 2nd treatment group P-2 were fed with cobalamin restricted AIN-93M for 12 weeks. Vitamin B12 level decreased from 529.17 166.51 pg/ml to 426.33 60.59 pg/ml in P-1 group and from 708.70 124.35 pg/ml to 519.16 84.96 pg/ml in P-2 group, while it increased from 567.79 102.52 pg/ml to 650.26 193.12 pg/ml in control group after 12 weeks. Plasma Hcy increased in treatment group after 4 weeks control vs P-1 = 351.05 110.69 pmol/ml vs 597.09 308.02 pmol/ml and 12 weeks control vs P-2 = 414.473 224.13 pmol/ml vs 1055.12 651.68 pmol/ml; p"

"ABSTRAKLatar Belakang: Hipertrofi jantung dapat timbul akibat stres patologis misal hipoksia yang merupakan respon jantung sebagai mekanisme homeostatis yang diperlukan untuk menormalkan stres dinding ventrikel kiri dan mempertahankan curah jantung. Hipoksia sistemik kronik merupakan stres lingkungan yang berat. Respon spesifik jantung terhadap stres jantung terlihat pada peningkatan kadar peptida di dalam plasma, yang membantu jantung dalam menghadapi beban yang meningkat. Menurut sejumlah peneliti, kadar Apelin berhubungan erat dengan disfungsi ventrikel. Apelin merupakan preproprotein dengan 77 asam amino yang disekresikan dari keluarga adipokine, berperan dalam mempertahankan performa jantung pada beban tekanan kronik. Pada tingkat molekular, respons adaptasi diperantarai oleh perubahan ekspresi gen. Tujuan penelitian: Menganalisis pola ekspresi gen Apelin dan gen BNP pada hipertrofi ventrikel akibat induksi hipoksia sistemik kronik dengan mengukur konsentrasi Apelin-13 dan konsentrasi BNP-45. Penelitian bersifat eksperimental menggunakan 28 ekor tikus Sprague-Dawley jantan, umur 8-12 minggu yang dibagi dalam 7 kelompok n=4 ekor/kelompok , terdiri dari kelompok kontrol normoksia, O2 atmosfir dan kelompok perlakuan hipoksia dalam sungkuphipoksia, 8 O2, masing-masing selama 6 jam, 1, 3, 5, 7 dan 14 hari . Parameter stres oksidatif akibat hipoksia jantung, dilakukan dengan pengukuran kadar malondialdehid MDA dan histopatologi dengan pewarnaan HE. Selain itu juga dilakukan pengukuran protein Apelin-13 dan BNP-45 menggunakan metoda ELISA dan pengukuran ekspresi relatif mRNA Apelin dan BNP-45 jantung, menggunakan real time RT-PCR kuantitatif dengan rumus Livak. Hasil penelitian: ekspresi relatif Apelin-13 di jantung menurun pada awal hipoksia dan kemudian meningkat mulai hari ke-3 sampai hari ke-14. Peningkatan kadar MDA yang signifikan terjadi sejak hipoksia 7 hari. Korelasi MDA terhadap peningkatan ekspresi relatif Apelin adalah kuat r=0.750 dan signifikan p=0.000 . Korelasi BNP-45 terhadap Apelin-13 adalah sangat kuat r=0.943 dan signifikan p=0.000 . Dapat disimpulkan bahwa adanya peningkatan MDA, peningkatan ekspresi relatif dan protein Apelin-13 dan peningkatan ekspresi relatif dan protein BNP-45 pada jaringan jantung mempunyai korelasi yang signifikan dan kuat, sesuai dengan peningkatan lamanya perlakuan hipoksia.

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ABSTRACTBackground: Cardiac hypertrophy can result from pathological stress eg hypoxia as a response to ventricular wall stress and to maintain cardiac output. Chronic systemic hypoxia is a severe environmental stress. During cardiac stress certain peptides are release by the heart into the plasma, which help the heart to compensate the increased myocardial load. According to several authors, apelin levels are increased during cardiac dysfunction. Apelin is a preproprotein with 77 amino acids from adipokine, which contributes to maintaining cardiac performance at chronic stress loads. At the molecular level, the adaptation response is mediated by changes in gene expression. Objective: To analyze the expression pattern of Apelin-13 and BNP-45 on ventricular hypertrophy due to induction of chronic systemic hypoxia by measuring Apelin-13 and BNP-45 concentrations. The experimental study used 28 male Sprague-Dawley rats, 8-12 weeks old divided into 7 groups 4 per group , consisting of control group normoxia, atmospheric O2 and 4 hypoxia treatment groups, which underwent systemic hypoxia in hypoxic chamber containing 8 oxygen, respectively for 6 hours, 1, 3, 5, 7 and 14 days . The presence of oxidative stress due to cardiac hypoxia was determined by malondialdehyde MDA and cardiac structural alteration was examined by HE staining. Apelin-13 and BNP-45 proteins were determined using the ELISA method and the relative expression of cardiac Apelin and BNP-45 mRNA were determined using quantitative RT-PCR real time with Livak formula. Results: Relative expression of Apelin-13 in the heart decreased early in hypoxia and then increased from day 3 to day 14. Significant increases in MDA levels occurred after 7 days hypoxia. There was a strong and significant correlation between MDA levels and Apelin relative expression r = 0.750, p = 0.001 . Similar results were obtained for of BNP-45 and Apelin-13 r = 0.943, p = 0.001 . From the results, it can be concluded that during chronic systemic hypoxia there was an increase in oxidative stress, relative expression and Apelin-13 proteins and relative expression and BNP-45 protein of the rat cardiac tissue."

"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."

"Angka kematian kanker serviks masih tinggi karena banyak pasien datang berobat pada tahap lanjut. Respons terapi radiasi pada pasien kanker serviks stadium lanjut bervariasi walau dengan faktor klinikopatologi yang sama seperti stadium, massa tumor, jenis histopatologi, derajat diferensiasi, invasi limfovaskular, reaksi limfosit dan nekrosis. Oleh karena itu dipikirkan faktor prognosis lain seperti faktor apoptosis-survivin, telomerase dan sitokrom c. Penelitian ini bertujuan untuk mengetahui peran survivin, telomerase, dan sitokrom c sebagai prediktor respons terapi radiasi pada kanker serviks stadium lanjut khususnya stadium IIIB.Studi ini bersifat prospektif menggunakan metode nested case control. Pengambilan data dilakukan di Poliklinik Onkologi Departemen Obstetri dan Ginekologi RSCM serta Departemen Patologi Anatomi FKUI pada bulan Januari 2016 hingga Mei 2017. Pada subjek penelitian dilakukan wawancara, pemeriksaan histopatologi dan pemeriksaan biokimia secara ELISA untuk mengetahui kadar survivin, telomerase, sitokrom c, dan MRI pra-radiasi serta pasca-radiasi. Dari 90 subjek penelitian didapatkan rerata usia pasien 50 tahun, rerata massa tumor 6,7 cm dan sebagian besar berkeratin 84,4 , berdiferensiasi baik 81,1 , reaksi limfosit negatif 75,6 dan nekrosis 74,4 . Rerata faktor apoptosis-survivin, telomerase dan sitokrom c adalah 591,2 pg/mL, 5.223,2 pg/mL dan 191,3 ng/mL. Dari analisis bivariat didapatkan variabel yang berhubungan dengan respons terapi secara independen adalah massa tumor p = 0,1 , diferensiasi p = 0,17 , kadar survivin p = 0,01 , kadar telomerase p = 0,08 dan kadar sitokrom c p = 0,47. Hasil analisis multivariat didapatkan hubungan kadar survivin dan kadar telomerase dengan respons terapi radiasi p = 0,01 dan p = 0,07 . Tidak terdapat hubungan kadar sitokrom c dengan respons terapi radiasi p = 0,64 . Dengan model cox regresi survival didapatkan hazard ratio subjek dengan kadar survivin tinggi dan kadar telomerase tinggi terhadap respons terapi radiasi negatif adalah 4,20 dan 1,97.Simpulan: kadar survivin dan telomerase tinggi berhubungan dengan respons terapi radiasi negatif.

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Cervical cancer mortality rate is still high mostly due to patients seeking for help in advanced stage of the disease. Even with the same clinicopathologic features such as stage of the diseases, size of the tumor, histopathological types, level of differentiation, lymphocyte reaction and tumor necrosis, the radiotherapy outcomes still vary from patient to patient. Therefore, we thought another predictive factors like apoptosis inducing factors i.e. survivin, telomerase and cytochrome c as a new predictor of therapeutic resp onses on patients with stage IIIB squamous cell carcinoma of cervix.

This is a prospective study with nested case control method. Data collection was conducted in Oncology Polyclinic, Department of Obstetrics and Gynecology RSCM and Department of Pathological Anatomy of FKUI from January 2016 to May 2017. Subjects were interviewed, conducted histopathological and biochemical examination with ELISA to determine levels of survivin, telomerase, cytochrome c, and patients undergo pre and post radiation MR imaging.

There were 90 patients in this study with the mean of ages was 50 years, mean of tumor size was 6.7 cm and most subjects were keratinizing 84.4 , well differentiated 81.1 , negative lymphocyte reaction 75.6 and tumor necrosis 74.4 . The mean levels of apoptosis inducing factors survivin, telomerase and cytochrome c were 591.2 pg mL, 5,223.2 pg mL, and 191.3 ng mL.

Bivariate analysis showed the independent association between tumor size, level of differentiation, levels of survivin and telomerase p 0.1, p 0.17, p 0.01, p 0.08 . Multivariate analysis showed the correlation between levels of survivin and telomerase with radiation therapeutic response p 0.01 and p 0.07 and there was no association with level of cytochrome c p 0.64 With the survival cox regression models, the hazard ratio of subjects with high levels of survivin and telomerase on the negative radiation therapy responses were 4.20 and 1.97.Conclusion there were association between high levels of survivin and telomerase on the negative radiation therapy response. "

"ABSTRAKPertambahan usia dengan pola hidup sedenter akan meningkatkan radikal bebas yang menyebabkan disfungsi mitokondria dan pemendekan telomer secara progresif. Penelitian terdahulu menyatakan bahwa latihan aerobik intensitas sedang sangat direkomendasikan pada lansia karena mampu memperbaiki kerusakan oksidatif sel yang akan meningkatkan kebugaran serta memperpanjang masa hidup lansia. Penelitian bertujuan mengkaji peningkatan kadar telomerase, aktivitas GPx, kadar TBARS dan VO2maks sebagai penanda perbaikan fungsi sel dan sistem kardiorespirasi akibat latihan aerobik intensitas sedang selama 12 minggu pada perempuan lansia.Penelitian community trial control group pre test post test design dengan subjek lansia perempuan sedenter. Total subjek adalah 73 37 orang kelompok perlakuan dan 36 orang kelompok kontrol dipilih secara consecutive. Kemudian diambil subsampel berpasangan untuk pemeriksaan aktivitas GPx dan kadar TBARS. Subjek melakukan latihan aerobik intensitas sedang selama 12 minggu dengan frekuensi 3 kali seminggu, intensitas latihan 50 ndash;85 denyut nadi maksimal, 30 menit per sesi latihan dan jenis latihan berjalan. Pemeriksaan kadar telomerase, kadar NOx plasma dan aktivitas GPx menggunakan metode ELISA. Kadar TBARS menggunakan metode Wills, sedangkan prediksi VO2maks menggunakan uji latih 6 menit. Data diolah menggunakan uji t tidak berpasangan/uji Mann Whitney untuk melihat perbedaan rerata, uji Repeated ANOVA/Uji Friedmann untuk melihat perbedaan kemaknaan antar kelompok dan Uji Pearson/Spearman untuk melihat korelasi antar data.Kadar telomerase, prediksi VO2maks dan aktivitas GPx meningkat bermakna p < 0,05 , sedangkan kadar TBARS cenderung terjadi penurunan p < 0,05 pada minggu ke-12 latihan. Penurunan kadar NOx plasma ditemukan lebih kecil pada kelompok perlakuan dibandingkan kelompok kontrol. Kadar telomerase berkorelasi positif dengan prediksi VO2maks dan aktivitas GPx serta berkorelasi negatif dengan TBARS. Pada penelitian ini perbaikan fungsi sel terjadi lebih dahulu melalui peningkatan kadar telomerase yang disertai peningkatan prediksi VO2maks terlihat pada minggu ke-6 latihan, selanjutnya terjadi perbaikan sistem sirkulasi TDS dan DN diikuti peningkatan prediksi VO2maks pada minggu ke-12 latihan menandakan bahwa latihan aerobik intensitas sedang jenis berjalan selama 12 minggu telah cukup mampu memperbaiki fungsi sel maupun sistem kardiorespirasi pada lansia. Kata Kunci: Latihan Aerobik Intensitas Sedang, NOx Plasma, Penuaan, Stres oksidatif, TBARS, Telomer, Telomerase, VO2maks.

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ABSTRACTIncreasing age in elderly with a sedentary lifestyle leads to increasing free radicals. Thus it causes mitochondrial dysfunction and progressive telomere shortening. The previous study suggested that moderate-intensity aerobic exercise is highly recommended in the elderly people as it can repair cell oxidative damage. It improves the elderly people rsquo;s fitness and prolongs their life. This study aimed to assess increased telomerase levels, GPx activity, TBARS level and VO2max as a marker of the function of cell and cardiorespiratory system repair due to moderate intensity aerobic exercise for 12 weeks.This study was a community trial control group pre test post test design involved 73 volunter elderly women who are divided in two group: 37 subject experimental group and 36 subject control group. Each subject was selected based on consecutively inclusion and exclusion criteria . Then the paired subsample was taken before conducting a test on GPx activity and TBARS levels. Subjects performed the moderate-intensity aerobic exercise for 12 weeks with frequency three times a week, exercise intensity 50 ndash;85 of maximum pulse rate, 30 minutes per session, and type of walking exercise. Assessment of telomerase levels, plasma NOx levels, and GPx activity used ELISA method. The TBARS levels assessment applied the Wills method and the predicted VO2max using the 6-minute walked test. The data were analyzed using an unpaired t-test or Mann Whitney test to observe the mean difference, repeated ANOVA/Friedmann test to view the significant difference among the groups, and Pearson/Spearman test to find out the data correlation.Telomerase levels, predicted VO2max, GPx activity increased significantly p < 0,05 and TBARS levels tended to decrease at week 12 of exercise. Reduced plasma NOx levels were found to be smaller in the treatment group than in the control group. Telomerase levels positively correlated with predicted VO2max and GPx activity. On the other hand, telomerase levels negatively correlated with TBARS levels. The improvement of the function of cell occurs first through increased telomerase level accompanied by an increase predicted VO2max at week 6 of exercise, subsequent improvement of circulation system SBP and HR followed by an increase predicted VO2maks at weeks 12 of exercise. Moderate intensity aerobic exercise walking has been sufficient to improve the function of cell and cardiorespiratory system in elderly.Keywords: Aging, Moderate-intensity aerobic exercise, NOx Plasma, Oxidative stress, TBARS levels, Telomere, Telomerase, VO2max."

"Belum banyak studi mempelajari keterkaitan antara defisiensi vitamin B12 dan toksisitas homosistein. Hiperhomosisteinemia dikaitkan dengan penyakit selular terkait NAFLD. Toksisitas homosistein dapat berupa steatosis atau inflamasi sel hati. H. sabdariffa. dan konstituen aktifnya memiliki efek pencegahan terhadap cedera seluler. Ekstrak H. sabdariffa. diuji pada tikus Sprague-Dawley (SD) dalam penelitian ini.Penelitian ini untuk melihat efek H.sabdariffa terhadap peningkatan homosistein pada hati tikus SD yang diberikan diet resriksi vitamin B12.Penelitian ini merupakan penelitian in vivo yang dilakukan di Fakultas Kedokteran Universitas Indonesia. Sebanyak 30 ekor tikus SD dibagi menjadi enam kelompok sesuai waktu perlakuan di 8 dan 16 minggu sebagai berikut: Kelompok kontrol diberikan diet standar AIN-93M, kelompok restriksi vitamin B12 diberi diet AIN-93M dengan modifikasi pengurangan komponen vitamin B12 dan kelompok restriksi vitamin B12 diberi AIN-93M dengan modifikasi pengurangan komponen vitamin B12 ditambah ekstrak etanol H.sabdariffa (HSE). Setelah 8 dan 16 minggu, kadar vitamin B12 dan homosistein diukur. Peningkatan aktivitas toksisitas homosistein dilihat dari ekspresi protein GRP78, SREBP1c dan NF-kB. Aktivitas hepatoprotektif HSE dinilai menggunakan AST, ALT, GGT, dan NAFLD Activity Score (NAS).Kadar vitamin B12 pada 8 minggu (233 ± 10.8 vs 176 ± 5.4 pg/L; p < 0.001) dan 16 minggu (226 ± 13 vs 190 6 pg/L; p < 0,001), lebih tinggi secara bermakna pada kelompok restriksi vitamin B12 dengan diet HSE dibandingkan kelompok diet restriksi vitamin B12 tanpa HSE. Kadar plasma homosistein plasma lebih rendah secara bermakna pada kelompok restriksi vitamin B12 dengan HSE dibandingkan kelompok restriksi vitamin B12 tanpa HSE di usia perlakuan 8 minggu (2,25 ± 0,07 vs 2,63 ± 0,1 mol/L; p < 0,001) dan 16 minggu (2,18 ± 0,07 vs 2,64 ± 0,09 mol/L; p < 0,001). Aktivitas GGT plasma di usia 16 minggu perlakuan menurun secara bermakna pada kelompok restriksi vitamin B12 dengan HSE dibandingkan kelompok restriksi vitamin B12 tanpa HSE (14,5 ± 1,1 vs 22,9 ± 2,4 IU; p < 0,05). Ekspresi protein GRP78, SREBP1c, dan NfKB diukur menggunakan protein GADPH sebagai kontrol internal. Pada minggu ke-8 dan 16, ekspresi protein NF-kB lebih rendah pada kelompok restriksi vitamin B12 dengan HSE dibandingkan dengan grup restriksi vitamin B12 tanpa HSE (0,78 ± 0,08 vs 1,08 ± 0,06; p < 0,05). Ekspresi protein SREBP1c lebih rendah pada kelompok restriksi vitamin B12 dengan HSE dibandingkan dengan grup restriksi vitamin B12 tanpa HSE pada usia perlakuan 16 minggu (0,55 ± 0,03 vs 1,00 ± 0,02; p < 0,05). Kelompok restriksi vitamin B12 dengan HSE memiliki gambaran histopatologis steatosis, inflamasi, dan fibrosis lebih baik dibandingkan kelompok yang restriksi vitamin B12 tanpa HSE setelah 16 minggu perlakuan.Disimpulkan peningkatan homosistein akibat diet restriksi vitamin B12 pada tikus SD menyebabkan steatosis hati, inflamasi, dan fibrosis. Ekstrak etanol H.Sabdariffa memiliki efek pencegahan terhadap kondisi steatosis, inflamasi dan fibrosis akibat peningkatan homosistein pada tikus SD yang diberi diet restriksi vitamin B12.

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There haven't been many studies on the link between vitamin B12 deficiency and homocysteine toxicity. Homocysteine is linked to NAFLD-related cellular disease, and toxicity can manifest as steatosis or inflammation of the liver cells. H. sabdariffa. and its active constituents have a preventive effect against cellular injury. H. sabdariffa extract was tested on Sprague-Dawley (SD) rats with NAFLD in this study. This study aimed to examine the effect of H. sabdariffa on increasing homocysteine ​​in the liver of SD rats fed a vitamin B12 restriction diet.

This research is an in vivo study conducted at the Faculty of Medicine, University of Indonesia. 30 SD rats were divided into six groups based on treatment time at 8 and 16 weeks, with the following treatments: the control group received the standard AIN-93M diet, the vitamin B12 restriction group received the AIN-93M diet with a modified reduction of the vitamin B12 component, and the vitamin B12 restriction + HSE group received the AIN-93M diet with a modified reduction of the vitamin B12 component and an ethanol extract of H. sabdariffa (HSE). After 8 and 16 weeks, vitamin B12 and homocysteine ​​levels were measured. The increase in homocysteine ​​toxicity activity was seen from the expression of GRP78, SREBP1c, and NF-kB proteins. The hepatoprotective activity of HSE was assessed using the AST, ALT, GGT, and NAFLD Activity Score (NAS).

Vitamin B12 levels at 8 weeks (233 ± 10.8 vs 176 ± 5.4 pg/L; p < 0.001) and 16 weeks (226 ± 13 vs 190 6 pg/l; p < 0.001), significantly higher in the HSE group with a vitamin restriction diet. B12. Plasma homocysteine ​​levels were significantly lower in the vitamin B12 restriction group with HSE than in the vitamin B12 restriction group without extract at 8 weeks of age (2.25 ± 0.07 vs. 2.63 ± 0.1 mol/L; p < 0.001 ) and 16 weeks (2.18 ± 0.07 vs. 2.64 ± 0.09 mol/L; p < 0.001). Plasma GGT activity at 16 weeks of treatment decreased significantly in the vitamin B12-restricted group with HSE compared to the vitamin B12-restricted group without HSE (14.5 ± 1.1 vs. 22.9 ± 2.4 IU; p < 0.05). GRP78, SREBP1c, and NfKB protein expressions were measured using GADPH protein as an internal control. At weeks 8 and 16, NF-kB protein expression was lower in the vitamin B12 restriction group with HSE compared to the vitamin B12 restriction group without HSE (0.78 ± 0.08 vs. 1.08 ± 0.06; p < 0 ,05). SREBP1c protein expression was lower in the vitamin B12 restriction group with HSE compared to the vitamin B12 restriction group without HSE at 16 weeks of treatment (0.55 ± 0.03 vs. 1.00 ± 0.02; p < 0.05). The vitamin B12 restriction group with HSE had better histopathological features of steatosis, inflammation, and fibrosis than the vitamin B12 restriction group without HSE after 16 weeks of treatment.

It was concluded that the increase in homocysteine ​​due to dietary restriction of vitamin B12 in SD rats caused liver steatosis, inflammation, and fibrosis. The ethanolic extract of H. Sabdariffa had a preventive effect on steatosis, inflammation, and fibrosis due to increased homocysteine ​​in SD rats fed a vitamin B12 restriction diet."