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"Pendahuluan: Angka keberhasilan FIV di Indonesia sekitar 32-35%. Salah satu penyebab pencapaian yang rendah ini adalah mutu oosit yang dinilai secara mi­kros­kopik pada saat panen oosit. Dari sekian banyak faktor yang berperan dalam pembentukan oosit matang bermutu baik diduga yang paling menentukan per­olehan oosit ma­tang, jumlah fertilisasi, dan jumlah embrio yang dipindahkan ke ute­rus pada FIV adalah AMH, inhibin-B, IGF-2 dan nisbahnya. Bahan dan metoda: Kajian analitik potong-lintang pengukuran berulang dilaku­kan pada bu­lan September 2013-Agustus 2014 di Rumah Sakit Anak dan Bunda Harapan Kita, Jakarta. Sebanyak 38 pasien berumur 26-42 tahun yang mengikuti program FIV diukur kadar AMH, inhibin-B, IGF-2 saat basal, pencetus, panen oosit dalam serum dan dalam zalir folikel. Analisis regresi linear digunakan untuk memperoleh faktor penduga jumlah perolehan oosit matang, jumlah fertilisasi, dan jumlah embrio yang dipindahkan.Hasil: Parameter penduga perolehan oosit matang adalah inhibin-B serum panen oosit dan folikel antral basal (FAB) total. Parameter penduga jumlah fertilisasi adalah FAB to­tal, nisbah inhibin-B pencetus terhadap inhibin-B basal, dan nisbah IGF-2 pen­cetus terhadap inhibin-B pencetus. Parameter penduga jumlah embrio yang dipin­dahkan adalah FAB total, inhibin-B panen oosit, dan nisbah inhibin-B panen oosit terhadap inhi­bin-B pencetus.Pada analisis bivariat area under curve (AUC) terbesar (77,4%) ditemukan pada titik-potong in­hi­bin-B serum panen oosit. Kadar inhibin-B panen oosit yang lebih tinggi dari 131,16 ng/ mL adalah akurat untuk menetapkan kematangan oosit de­ngan ke­pe­­kaan (sensiti­vitas) 84% dan kekhasan (spesifisitas) 69,2%.Simpulan: Inhibin-B serum saat panen oosit berhubungan dengan pembentukan oo­sit matang dan normal sehingga dapat dijadikan parameter penduga perolehan oosit ma­tang dan jum­lah em­brio yang terbentuk. Ditemukan parameter-parameter baru, yaitu (1) nisbah inhibin-B pen­ce­tus terhadap inhibin-B basal serum, dan nisbah IGF-2 pen­cetus terhadap in­hibin-B pencetus serum untuk menduga jumlah fertili­sasi; (2) nisbah inhibin-B pa­nen terhadap inhibin-B pen­­cetus serum untuk menduga jumlah em­brio yang dipindahkan ke uterus pada FIV.

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Background: The success rate of IVF in Indonesia was 30-35%. This low rate was caused by the microscopically evaluated oocyte quality that was obtained by ovum pick-up (OPU). The determinatively contributing factors for the formation of good quality mature oocytes, which are considered to be used as predictive parameter for mature oocytes recovery, number of fertilization, and number transferrable embryos in IVF, are AMH, inhibin-B, IGF-2, and their ratios. Therefore, the study to determine the correlation of those factors with the formation of ferti­li­zable mature oocyte in IVF program is necessary.

Materials and methods: An analytic cross-sectional repeated measurements study was conducted from September 2013 until August 2014 at Harapan Kita Mother and Chil­d Hospital, Jakarta. There were 38 patients aged between 26-42 years who par­ticipated in the IVF program; all of them underwent measurement for serum AMH, inhibin-B, and IGF-2 levels at basal, trigger, and OPU times. Predictive parameters for the number of mature oocytes, fertilizable oocytes, number of embryos transferred were analysed using linear regression.

Results: Predictive parameter for the number of mature oocytes are inhibin-B at OPU and total basal antral follicle (BAF) count. Predictive factors for the number of fertili­za­tion are total BAF count, the ratio of inhibin-B at triggering to inhibin-B at basal ti­mes. Predic­ti­ve factors for the number of embryos transferred are total BAF, inhibin-B at OPU, and the ratio of inhibin-B at OPU to inhibin-B at triggering time.

Using bivariate analysis, at the largest area under the curve (AUC) which was as high as 77.4%, the cut-off point of serum inhibin-B at OPU was found. The serum inhibin-B level at OPU higher than 131.16 ng/mL is accurate for determining the oocyte ma­turity (84% sensitivity and 69.2% spe­cificity).

Conclusions: Serum inhibin-B at OPU correlates with the formation of both mature and normal oocytes, thus it can be used as a predictor for the number of mature oo­cytes recovered and the number of embryos transferred. New parameters are found, those are: (1) the ratio of inhibin-B at triggering to inhi­bin-B in serum at basal times; and the ratio of IGF-2 at triggering to inhibin-B in serum at triggering times to pre­dict the number of fer­tilization; (2) the ratio of inhibin-B at OPU to inhibin-B in se­rum at triggering times to pre­dict the number of embryos transferred."

"Latar belakang: Penuaan merupakan proses yang kompleks, antara lain ditandai oleh deplesi sel punca dan inflamasi kronis. Oleh karena itu, pemberian sel punca mesenkimal (SPM) eksogen tampak menjanjikan untuk mencegah atau mengatasi proses penuaan. SPM diketahui mempunyai kemampuan imunomodulasi, memicu regenerasi, dan dapat berdiferensiasi. Penelitian ini bertujuan untuk mengetahui efek pemberian SPM Korda Umbilikalis Manusia (SPM-KUM) pada tikus tua. Metode: Penelitian ini dilakukan pada tahun 2016-2020 di Fakultas Kedokteran Universitas Indonesia dan Fakultas Kedokteran Hewan Institut Pertanian Bogor. Eksperimen dilakukan pada tikus Sprague-Dawley tua betina dan jantan berumur 22-24 bulan. Tikus tua dibagi menjadi dua kelompok, kontrol dan perlakuan. Kelompok perlakuan terdiri dari dua kelompok dosis SPM-KUM yaitu 106 /kg BB (A) dan 107 /kg BB (B). SPM-KUM diberikan secara intravena selama satu tahun dengan interval 3 bulan sedangkan kelompok kontrol diberikan NaCl 0.9%. Efek SPM-KUM pada penuaan dilihat dari kesintasan, berat badan, performa rotarod, parameter stress oksidatif (MDA dan DNA adduct), parameter inflamasi (IL-6 dan TNF-α), telomer, hormon reproduksi (estradiol dan testosteron), dan gambaran histopatologi organ hati dan ginjal. Ekspresi antibodi anti-human juga diperiksa untuk konfirmasi diferensiasi SPM-KUM di jaringan. Di akhir penelitian, tikus muda usia 3-4 bulan digunakan sebagai pembanding. Hasil: Setelah satu tahun, tikus tua mengalami kematian, pemendekan telomer, penurunan performa rotarod, peningkatan kadar MDA, DNA adduct, IL-6 dan TNF-α, peningkatan sel Kupffer di hati serta peningkatan ekspresi lipofuscin, infiltrat inflamasi, dan p53 di hati dan ginjal. Pemberian SPM-KUM pada tikus tua memperbaiki kesintasan terutama pada tikus betina yang diberikan dosis 107 /kg BB. Kelompok tersebut memiliki telomer lebih panjang, performa rotarod lebih baik, IL-6 menurun, dan TNF-α menurun. Pemberian SPM-KUM juga meningkatkan jumlah sel Kupffer di hati dan mengurangi ekspresi lipofuscin di ginjal tanpa mempengaruhi inflamasi dan ekspresi p53 di hati dan ginjal akibat penuaan. Tidak ditemukan ekspresi antibodi terhadap mitokondria manusia di jaringan hati dan ginjal tikus. Kesimpulan: Pemberian SPM-KUM dapat mencegah proses penuaan dengan mempertahankan panjang telomer, menurunkan sitokin pro inflamasi, memperbaiki performa fisik, mengurangi ekspresi lipofuscin terutama di ginjal sehingga memperbaiki kesintasan. Seluruh efek tersebut terutama karena efek parakrin SPM.

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Introduction: Ageing is a complex process, which is marked by stem cell depletion and chronic inflammation as the main findings. Therefore, exogenous mesenchymal stem cells (MSC) administration appears to be a promising therapy for preventing or overcoming the ageing process. Furthermore, MSC is known for its immunomodulatory activity, regenerative ability, and differentiation. The present study is aimed to evaluate the effect of human umbilical cord MSC (hUCMSC) on aged rats.

Methods: The study was conducted during 2016-2020 at Faculty of Medicine Universitas Indonesia and Faculty of Veterinary Medicine Bogor Agricultural University. The experiment was conducted on female and male Sprague-Dawley rats of 22-24 months old. Aged rats were divided into control and hUCMSC-treated groups. The hUCMSC-treated groups were divided into two subgroups that received two doses of hUCMSC intravenously, i.e., 106 /kg BW (A) and 107 /kg BW (B), four times a year within three months interval. The control group received normal saline injection. The hUCMSC effect on ageing was evaluated by means of survival, body weight, rotarod performance, oxidative stress parameters (MDA and DNA adduct), pro-inflammatory parameters (IL-6 and TNF-α), telomeres, reproductive hormones (estradiol and testosterone), and histopathological features of liver and kidneys. Anti-human antibodies were also detected to confirm the differentiation of hUCMSC in tissues. At the end of the study, young rats of 3-4 months old were sacrificed as a comparison.

Results: The administration of hUCMSC 107 /kg BB in aged rats could improve survival, especially in female aged rats. This female group had the longest mean telomere length, improved rotarod performance, decreased IL-6 and TNF-α. hUCMSC increased Kupffer cells in liver and reduced lipofuscin expression in kidney without further effect on tissue inflammation and p53 expression. In addition, there was no anti-human mitochondria antibody expression in tissue.

Conclusion: hUCMSC could inhibit the ageing process through telomere length maintenance, pro-inflammatory cytokine suppression, physical performance improvement, followed by increased survival. Those effects were mainly through the paracrine effect of the MSC. "

"Latar Belakang: DNA bebas dalam medium kultur embrio dan kemajuan pemodelan berbasis kecerdasan buatan berpotensi menjadi modalitas uji genetik yang non-invasif. Saat ini, tidak diketahui apakah DNA tersebut dilepaskan oleh sel embrio euploid atau aneuploid, sehingga melemahkan dasar keilmuan penggunaannya. Penelitian ini bertujuan untuk mengetahui sel sumber embrio pelepas DNA bebas dalam medium kultur, validasi potensi klinis penggunaan DNA bebas untuk skrining status ploidi embrio pasien Fertilisasi In-Vitro (FIV), dan konstruksi model pembelajaran mendalam menggunakan gambar embrio tersegmentasi untuk deteksi status ploidi embrio.Metode: Penelitian ini terbagi dalam dua desain penelitian yaitu eksperimental in-vitro menggunakan embrio hewan model dan observasi kohort menggunakan 28 sampel medium kultur embrio dari 21 pasien program FIV di Klinik Morula IVF Jakarta, periode September 2022–Januari 2023. Konstruksi model pembelajaran mendalam menggunakan gambar embrio pasien FIV yang menjalani program bayi tabung periode Januari 2021– Juni 2023. Deteksi sel embrio sumber pelepas DNA bebas dilakukan dengan memapar salah satu embrio (galur DDY atau C57BL) dengan reversin untuk memperoleh blastomer pembawa sel-sel aneuploid. Embrio kontrol dikultur bersamaan tanpa reversin sebagai pembawa sel-sel blastomer euploid. Agregasi membentuk embrio mosaik dilakukan antara embrio pembawa blastomer aneuploid (perlakuan) dan embrio pembawa blastomer euploid (kontrol). Polimorfisme gen GABRA2 antara galur DDY (alel wildtype) dan C57BL (alel delesi) mejadi alel target yang dikuantifikasi dengan metode qPCR. Empat jenis sampel dibuat sebagai berikut: medium kultur tanpa embrio, medium kultur embrio agregasi tanpa pemaparan reversin, rev-DDY, rev-C57BL. Embrio mosaik diwarnai dengan marka apoptosis untuk deteksi mekanisme pelepasan DNA bebas. Analisis status ploidi embrio menggunakan medium kultur embrio pasien FIV dilakukan dengan metode sekuensing. Konstruksi model pembelajaran mendalam menggunakan gambar embrio tersegmentasi yang dipotong urut selama 10 jam sebelum proses biopsi. Variabel yang diamati dalam penelitian adalah konsentrasi alel delesi dan wildtype gen GABRA2, jumlah sel terwarnai marka apoptosis, Pada sampel medium kultur embrio manusia, keberhasilan amplifikasi dan interpretasi hasil sekuensing, serta tingkat kesesuaian uji antara DNA bebas dengan biopsi trofoblas dianalisis. Kemampuan prediksi model berbasis kecerdasan buatan dinilai dengan akurasi dan loss. Analisis data penelitian dan konstruksi model pembelajaran mendalam menggunakan perangkat lunak SPPS versi 21, OpenEpi. pyhton.Hasil: Sebanyak 0,08 ng/reaksi alel wildtype ditemukan pada embrio mosaik dengan pemaparan reversin pada blastomer embrio DDY (rev-DDY, pembawa sel-sel aneuploid) dan 0,01 ng/reaksi alel delesi ditemukan pada embrio mosaik dengan pemaparan reversin pada blastomer embrio C57BL (rev-C57BL, pembawa sel-sel aneuploid). Median jumlah sel embrio terwarnai marka apoptosis antara ketiga group embrio (agregasi kontrol, rev- DDY dan rev-C57BL) tidak berbeda bermakna (nilai p = 0,95 untuk pewarnaan late apoptosis (propidium iodide) dan p = 0,42 untuk early apoptosis (Ann-V) menandakan adanya proses koreksi sel pada kedua group embrio mosaik selama masa perkembangan pra-implantasi. Keberhasilan amplifikasi DNA bebas medium kultur embrio manusia dalah 100%, dengan nilai interpretasi 92,8% (26/28). Nilai kesesuaian DNA bebas dengan biopsi trofoblas adalah rendah sebesar 65,4% (17/26) dengan kesesuaian kromosom seks adalah 61,5% (16/26). Sepuluh dari 11 embrio XY pada biopsi trofoblas terdeteksi XX pada DNA bebas. Seluruh model pembelajaran mendalam mengalami peningkatan akurasi menggunakan gambar embrio tersegmentasi dengan algoritma InceptionV3 mencapai akurasi tertinggi sebesar 0,67 dengan nilai loss sebesar 1,4.Kesimpulan: Sel embrio anueploid adalah sel sember pelepas DNA bebas medium kultur embrio pada embrio mosaik hewan coba mencit yang dilepaskan melalui mekanisme apoptosis. Embrio masik tersebut diperkirakan melakukan self-correction dengan mengeksklusi sel-sel aneploid untuk mempertahankan euploiditasnya. Rendahnya tingkat kesesuaian antara DNA bebas dengan biopsi trofoblas disebabbkan oleh adanya kontaminasi maternal yang ditandai dengan perubahaan koromosm seks yang signifikan. Penggunaan gambar blastosis tersegmentasi meningkatkan akurasi model prediksi pembelajaran mendalam.

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Background: Cell-free DNA and advanced artificial intelligence-based modeling uphold the potential of a non-invasive approach to determining embryo ploidy status. The specific embryonic cells (whether euploid or aneuploid) that release cell-free DNA are largely unknown, causing a weak scientific basis for its use. This study aimed to identify the source of embryonic cells releasing cell-free DNA in culture media, validate the clinical potential of using cell-free DNA to screen embryo ploidy status in an in-vitro fertilization (IVF) program and develop a deep learning model using segmented embryo images to detect embryo ploidy status.

Materials and Methods: This study employed two research designs including an in-vitro experimental study using animal model embryos and an observational cohort study using 28 samples of spent embryo culture media from 21 patients undergoing IVF program at Morula IVF Clinic Jakarta (September 2022 to January 2023). A deep learning model was constructed using images of embryos from IVF patients who participated in IVF program from January 2021 to June 2023. Detection of the source embryonic cells releasing cell-free DNA was achieved by exposing embryos (DDY or C57BL strains) to reversine to induce the formation of blastomeres carrying aneuploid cells. Control embryos were cultured simultaneously without reversine to serve as the source of euploid blastomeres. Mosaic embryo aggregation was performed by combining embryos carrying aneuploid blastomeres (treatment) with those carrying euploid blastomeres (control). The GABRA2 gene polymorphism between the DDY strain (wildtype allele) and the C57BL strain (deletion allele) was the target allele quantified using qPCR. Four types of samples were prepared: culture medium without embryos, culture medium of aggregated embryos without reversine exposure, rev-DDY, and rev-C57BL. Mosaic embryos were stained with an apoptosis marker to detect the mechanism of cell-free DNA release. The ploidy status of embryos using spent embryo culture media from IVF patients was determined using sequencing methods. The deep learning model was constructed using segmented images of embryos captured over 10 hours before the biopsy process. The variables observed in the study included the concentration of deletion and wildtype alleles of the GABRA2 gene, the number of cells stained with apoptosis markers, the success rate of amplification and interpretation of sequencing results from human spent embryo culture medium samples, and the concordance rate between cell-free DNA and trophectoderm biopsy analysis. The predictive ability of the artificial intelligence-based model was evaluated using accuracy and loss metrics. Data analysis and deep learning model construction were performed using SPSS version 21, OpenEpi, and Python.

Results: A total of 0.08 ng/reaction of the wildtype allele was detected in the culture media sample of mosaic embryos exposed to reversine in DDY embryo blastomeres (rev- DDY, carrying aneuploid cells), and 0.01 ng/reaction of the deletion allele was found in the sample exposed to reversine in C57BL embryo blastomeres (rev-C57BL, carrying aneuploid cells). The median number of embryonic cells stained with apoptosis markers among the three groups of embryos (control aggregation, rev-DDY, and rev-C57BL) did not differ significantly (p = 0.95 for late apoptosis staining with propidium iodide and p = 0.42 for early apoptosis with Annexin V), indicating the presence of cell correction processes in both groups of mosaic embryos during pre-implantation development. The success rate of cell-free DNA amplification in human spent embryo culture media was 100%, with an interpretability of 92.8% (26/28). The concordance between cell-free DNA and trophectoderm biopsy was low at 65.4% (17/26), with sex chromosome concordance at 61.5% (16/26). Ten out of eleven XY embryos from the trophectoderm biopsy were detected as XX in cell-free DNA analysis. All deep learning models showed improved accuracy using segmented embryo images with the InceptionV3 algorithm, achieving the highest accuracy of 0.67 with a loss of 1.4.

Conclusion: Aneuploid embryonic cells were identified as the source releasing cell-free DNA in culture media during embryo animal model experiments, releasing DNA through an apoptotic mechanism. These mosaic embryos were expected to activate embryonic cell correction mechanisms by excluding aneuploid cells to maintain their euploidy. The low concordance rate between cell-free DNA and trophectoderm biopsy was attributed to maternal contamination, as indicated by significant changes in sex chromosomes. The use of segmented blastocyst images improved the model's accuracy.

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"Penelitian kriopreservasi spermatozoa ikan patin albino bertujuan untuk menganalisis ultrastruktur, fisiologi, dan molekuler spermatozoa ikan patin albino pasca kriopreservasi. Kriopreservasi dilakukan pada suhu -80°C selama 14 hari menggunakan kombinasi krioprotektan intraseluler yaitu metanol 10% dan krioprotektan ekstraseluler yaitu susu skim. Hasil ultrastruktur spermatozoa menunjukkan bahwa pada spermatozoa segar bagian membran sel kepala, mid piece, dan bagian flagel masih dalam kondisi utuh dan baik. Ultrastruktur spermatozoa pasca ekuilibrasi nampak ada perbesaran lebar dan panjang kepala spermatozoa dibandingkan spermatozoa segar, walaupun secara struktur masih tampak utuh. Ultrastruktur spermatozoa pasca pencairan tampak terjadi kerusakan membran bagian kepala dan flagel. Hasil pengukuran morfometri spermatozoa menunjukkan adanya peningkatan lebar kepala spermatozoa yaitu 1,59 µm pada spermatozoa segar menjadi 1,97 µm pada spermatozoa pasca ekuilibrasi dan 2,40 µm pada spermatozoa pasca pencairan. Demikian pula, terdapat perubahan panjang kepala spermatozoa yaitu 3,70 µm pada spermatozoa segar menjadi 3,81 µm pada spermatozoa pasca ekuilibrasi, dan 3,90 µm pada spermatozoa pasca pencairan. Analisis viabilitas spermatozoa didapatkan penurunan viabilitas spermatozoa pasca pencairan (61±2,30%) dibandingkan spermatozoa segar (92±0,58%) dan spermatozoa pasca ekuilibrasi (80±3,51%). Analisis fisiologi spermatozoa didapatkan penurunan fungsi mitokondria pada spermatozoa pasca ekuilibrasi (57±7%) dan spermatozoa pasca pencairan (42±3,2%) dibandingkan spermatozoa segar (98±2%). Analisis motilitas spermatozoa menunjukkan penurunan motilitas spermatozoa pasca ekuilibrasi (79±4,5%) dan spermatozoa pasca pencairan (30±3,2%) dibandingkan spermatozoa segar (87±1,5%). Penetasan telur pasca 24 jam fertilisasi pada perlakukan spermatozoa pasca ekuilibrasi didapatkan hasil lebih tinggi (64±17%) dibandingkan spermatozoa segar (38±4%), sedangkan spermatozoa pasca pencairan tidak ditemukan ada penetasan telur. Analisis molekular spermatozoa pada gen CO1 dan SOD2 didapatkan jumlah lesi gen SOD2 spermatozoa pasca ekuilibrasi yaitu 15,83 lesi / 10 kb dan spermatozoa pasca pencairan yaitu 17,14 lesi / 10 kb. Lesi gen CO1 pada spermatozoa pasca ekuilibrasi yaitu 9,24 lesi / 10 kb dan spermatozoa pasca pencairan yaitu 10,26 lesi / 10 kb. Sehingga disimpulkan kriopreservasi spermatozoa berpengaruh terhadap ultrastruktur, fisiologi, dan molekuler spermatozoa ikan patin albino.

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Research of cryopreservation on albino Pangasius catfish spermatozoa aims to analyze about ultrastructure, physiology, and molecular spermatozoa of albino Pangasius catfish post cryopreservation. Cryopreservation was carried out at -80°C for 14 days using a combination of intracellular cryoprotectants which is 10% methanol and extracellular cryoprotectant which is skim milk. The results of the spermatozoa ultrastructure showed that the cell membrane of the spermatozoa head, the midpiece, and the flagellum of fresh spermatozoa were still intact and good. The spermatozoa ultrastructure after post equilibration, shown enlargement of the head width and length compared to the fresh spermatozoa, although structurally were still intact. The ultrastructure of frozen-thawed spermatozoa, appeared a membrane damage at the head and flagellum. The results of spermatozoa morphometric measurements showed an increase at the head width of spermatozoa from 1.59 µm in fresh spermatozoa to 1.97 µm in post-equilibration spermatozoa and 2.40 µm in frozen-thawed spermatozoa. Similarly, there was an increase in the head length of spermatozoa, from 3.70 µm in fresh spermatozoa, to 3.81 µm in post-equilibration spermatozoa, and 3.90 µm in frozen-thawed spermatozoa. The viability analysis showed a decrease of frozen-thawed spermatozoa viability (61±2.30%) compared to fresh spermatozoa (92±0.58%) and post-equilibration spermatozoa (80±3.51%). The analysis physiology of spermatozoa showed a decrease in mitochondrial function in post equilibration spermatozoa (57±7%) and frozen-thawed spermatozoa (42±3.2%) compared to fresh spermatozoa (98±2%). The analysis of motility of spermatozoa showed a decrease in post equilibration spermatozoa (79±4.5%) and frozen-thawed spermatozoa (30±3.2%) compared to fresh spermatozoa (87±1.5%). Egg hatching after 24 hours of fertilization for the post-equilibration spermatozoa was higher (64±17%) than fresh spermatozoa (38±4%), whereas frozen-thawed spermatozoa were not hatched. The analysis of molecular on CO1 and SOD2 genes obtained the number of gene lesions in the spermatozoa SOD2 gene after equilibration were 15.83 lesions/10 kb and frozen-thawed were 17.14 lesions/10 kb. The CO1 gene lesions in post-equilibration spermatozoa were 9.24 lesions/10 kb, while the CO1 gene lesions in frozen-thawed spermatozoa were 10.26 lesions/10 kb. It can be concluded that there is an effect of cryopreservation on ultrastructure, physiology, and molecular in spermatozoa of albino Pangasius catfish."

"Latar belakang: Penuaan merupakan proses yang kompleks, antara lain ditandai oleh deplesi sel punca dan inflamasi kronis. Oleh karena itu, pemberian sel punca mesenkimal (SPM) eksogen tampak menjanjikan untuk mencegah atau mengatasi proses penuaan. SPM diketahui mempunyai kemampuan imunomodulasi, memicu regenerasi, dan dapat berdiferensiasi. Penelitian ini bertujuan untuk mengetahui efek pemberian SPM Korda Umbilikalis Manusia (SPM-KUM) pada tikus tua. Metode: Penelitian ini dilakukan pada tahun 2016-2020 di Fakultas Kedokteran Universitas Indonesia dan Fakultas Kedokteran Hewan Institut Pertanian Bogor. Eksperimen dilakukan pada tikus Sprague-Dawley tua betina dan jantan berumur 22-24 bulan. Tikus tua dibagi menjadi dua kelompok, kontrol dan perlakuan. Kelompok perlakuan terdiri dari dua kelompok dosis SPM-KUM yaitu 106 /kg BB (A) dan 107 /kg BB (B). SPM-KUM diberikan secara intravena selama satu tahun dengan interval 3 bulan sedangkan kelompok kontrol diberikan NaCl 0.9%. Efek SPM-KUM pada penuaan dilihat dari kesintasan, berat badan, performa rotarod, parameter stress oksidatif (MDA dan DNA adduct), parameter inflamasi (IL-6 dan TNF-α), telomer, hormon reproduksi (estradiol dan testosteron), dan gambaran histopatologi organ hati dan ginjal. Ekspresi antibodi anti-human juga diperiksa untuk konfirmasi diferensiasi SPM-KUM di jaringan. Di akhir penelitian, tikus muda usia 3-4 bulan digunakan sebagai pembanding. Hasil: Setelah satu tahun, tikus tua mengalami kematian, pemendekan telomer, penurunan performa rotarod, peningkatan kadar MDA, DNA adduct, IL-6 dan TNF-α, peningkatan sel Kupffer di hati serta peningkatan ekspresi lipofuscin, infiltrat inflamasi, dan p53 di hati dan ginjal. Pemberian SPM-KUM pada tikus tua memperbaiki kesintasan terutama pada tikus betina yang diberikan dosis 107 /kg BB. Kelompok tersebut memiliki telomer lebih panjang, performa rotarod lebih baik, IL-6 menurun, dan TNF-α menurun. Pemberian SPM-KUM juga meningkatkan jumlah sel Kupffer di hati dan mengurangi ekspresi lipofuscin di ginjal tanpa mempengaruhi inflamasi dan ekspresi p53 di hati dan ginjal akibat penuaan. Tidak ditemukan ekspresi antibodi terhadap mitokondria manusia di jaringan hati dan ginjal tikus. Kesimpulan: Pemberian SPM-KUM dapat mencegah proses penuaan dengan mempertahankan panjang telomer, menurunkan sitokin pro inflamasi, memperbaiki performa fisik, mengurangi ekspresi lipofuscin terutama di ginjal sehingga memperbaiki kesintasan. Seluruh efek tersebut terutama karena efek parakrin SPM. Kata kunci: Penuaan, SPM-KUM, Telomer, Sel Kupffer, IL-6, TNF-α, Lipofuscin

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Introduction: Ageing is a complex process, which is marked by stem cell depletion and chronic inflammation as the main findings. Therefore, exogenous mesenchymal stem cells (MSC) administration appears to be a promising therapy for preventing or overcoming the ageing process. Furthermore, MSC is known for its immunomodulatory activity, regenerative ability, and differentiation. The present study is aimed to evaluate the effect of human umbilical cord MSC (hUCMSC) on aged rats. Methods: The study was conducted during 2016-2020 at Faculty of Medicine Universitas Indonesia and Faculty of Veterinary Medicine Bogor Agricultural University. The experiment was conducted on female and male Sprague-Dawley rats of 22-24 months old. Aged rats were divided into control and hUCMSC-treated groups. The hUCMSCtreated groups were divided into two subgroups that received two doses of hUCMSC intravenously, i.e., 106 /kg BW (A) and 107 /kg BW (B), four times a year within three months interval. The control group received normal saline injection. The hUCMSC effect on ageing was evaluated by means of survival, body weight, rotarod performance, oxidative stress parameters (MDA and DNA adduct), pro-inflammatory parameters (IL6 and TNF-α), telomeres, reproductive hormones (estradiol and testosterone), and histopathological features of liver and kidneys. Anti-human antibodies were also detected to confirm the differentiation of hUCMSC in tissues. At the end of the study, young rats of 3-4 months old were sacrificed as a comparison. Results: The administration of hUCMSC 107 /kg BB in aged rats could improve survival, especially in female aged rats. This female group had the longest mean telomere length, improved rotarod performance, decreased IL-6 and TNF-α. hUCMSC increased Kupffer cells in liver and reduced lipofuscin expression in kidney without further effect on tissue inflammation and p53 expression. In addition, there was no anti-human mitochondria antibody expression in tissue. Conclusion: hUCMSC could inhibit the ageing process through telomere length maintenance, pro-inflammatory cytokine suppression, physical performance improvement, followed by increased survival. Those effects were mainly through the paracrine effect of the MSC. Keywords: Ageing, hUCMSC, IL-6, Kupffer cell, Lipofuscin, Telomere, TNF-α"