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"Latar belakang: Enzim methylenetetrahydrofolate reductase (MTHFR) terlibat dalam metabolism asam folat dan tipe allele mempengaruhi aktivitas enzim. Memberikan suplementasi asam folat kepada ibu hamil dapat mempengaruhi perubahan dalam derajat metilasi gen tertentu yang mempengaruhi kesehatan janin. Walaupun sudah banyak penelitian yang mempelajari peran asam folat sebagai donor dalam mekanisme epigenetik, namun penelitian pengaruh suplementasi besi-asam folat pada luaran kehamilan melalui pendekatan interaksi zat gizi-gen dalam desain penelitian longitudinal masih jarang. Penelitian ini bertujuan untuk mengetahui hubungan antara kadar serum asam folat pada ibu dan anak, dan derajat metilasi pada gen pencetak insulin-like growth factor (IGF2) yang dikenal terlibat dalam tumbuh kembang anak dan dapat digunakan sebagai penanda kemunculan penyakit Metode: Di tahun 2018, penelitian longitudinal dilakukan dengan mengunjungi 127 subyek termasuk anak yang dilahirkan dan mengikutsertakannya dalam penelitian. Enam puluh tujuh serum asam folat ibu selama hamil dan pasca melahirkan diperiksa, sementara serum asam folat anak dikumpulkan sebanyak 44 spesimen untuk pemeriksaan penanda darah. Pemeriksaan serum asam folat dengan menggunakan the liquid chromatography-mass spectrometry/mass spectrometry. Untuk pemeriksaan biomolekuler, tipe allele enzim MTHFR 677C>T and 1298A>C menggunakan Taqman polymerase chain reaction. Sementara metode pyrosequencing digunakan untuk menghitung DNA metilasi pada IGF2 pada anak. Hubungan antar variabel dianalisis menggunakan analisis regresi linier multivariat. Hasil:Tidak ada hubungan yang signifikan antara asupan asam folat dan serum asam folat ibu selama hamil, tiga tahun pasca melahirkan dan anak yang dilahirkan (p>0.05). Penelitian ini tidak dapat menunjukkan hubungan antara tipe allel dari MTHFR 677 C>T dan 1298 A>C dan serum asam folat (p>0.05). Serum asam folat selama hamil juga mempengaruhi status serum asam folat tiga tahun pasca melahirkan (p<0.05) dan status serum asam folat anak (p<0.05). Namun penelitian ini tidak dapat menunjukkan pengaruh status serum asam folat anak dengan DNA metilasi IGF2 pada anak (p>0.05). Simpulan: Serum asam folat selama hamil berkontribusi pada serum asam folat tiga tahun pasca melahirkan dan anak. Genotipe dari MTHFR gene at 677C>T and 1298 A>C kemungkinan tidak terlibat dalam metabolism asam folat pada ibu. Serum asam folat selama kehamilan tidak memiliki dampak pada status metilasi dari IGF2 pada wilayah differentially methylated region (DMR) untuk subyek anak. Namun, beberapa hal harus menjadi perhatian karena, secara statistik, jumlah subyek penelitian tidak memadai. Saran: Perlu dilakukan penelitian lanjutan yang melibatkan subyek lebih banyak dan metode yang lebih canggih dalam menentukan MTHFR dan metilasi DNA.

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Background: Methylenetetrahydrofolate reductase, (MTHFR) enzyme is involved in folic acid metabolism, and their allele types affected its activity. Providing folic acid supplementation to pregnant mothers may influence the change in methylation level in specific genes that affect the susceptibility of disease of their offspring. Although folic acid's role as a donor in the epigenetic mechanism has been investigated, a longitudinal study exploring the influence of iron-folic acid supplementation on maternal dan birth outcome by the nutrient-gene interaction approach is lacking. Therefore, we investigated the relationship of serum folic acid level among the mothers and the children, and the imprinted insulin-like growth factor 2 (IGF2) methylation level that is known actively involved in growth and development in children and possibly utilized as a surrogate marker for the disease Methods: In 2018, the follow-up study conducted by re-visited 67 subjects and put the mother and their children included in the study. For each group, sixty-seven serums were collected for folic acid measurement for mothers during gestation and three-year post-partum. Furthermore, forty-four serums for children were gathered for biomarker measurement. Serum folics were measured by using liquid chromatography-mass spectrometry/mass spectrometry. Determining the genotype of the MTHFR enzyme in position 677C>T and 1298 A>C was used Taqman Polymerase Chain Reaction (PCR) method. The pyrosequencing method was utilized to quantify the methylation level of the IGF-2 of the children. The relationship analysis between variables using multivariate linear regression. Results: There was no relationship between the folic acid intake during gestation and serum folic acid of the mothers during pregnancy, three-year post-partum, and the children (p>0.05). There was no relationship between the allele type of MTHFR 677C>T and 1298A>C and serum folic acid status of the mother (p>0.05). The serum folic acid during pregnancy had a significant relationship to the serum folic acid three-year post-partum (p<0.05) as well as the serum folic acid of the children (p<0.05). There was no significant relationship between the serum folic acid of the children, serum homocysteine, and the methylation status of IGF2 of the children (p>0.05). Conclusion: The serum folic acid during pregnancy contributed to the serum folic acid three-year post-partum of mother and the children. The genotype of the MTHFR gene at 677C>T and 1298 A>C was possibly not involved in folic acid metabolism in the mother. Serum folic acid during pregnancy could not have an effect on the methylation status of the IGF2 in the differentially methylated region (DMR) area of the children. However, this conclusion needs to be taken in caution due to lack of study power Recommendation: Further cohorts studies with a large sample size and more advanced methods in determining the MTHFR enzyme and DNA methylation. Keyword: serum folic acid, genotyping MTHFR 677 C>T, MTHFR 1298 A>C, DNA methylation, IGF2."

"Latar Belakang: Pseudomonas aeruginosa, resisten terhadap obat, menyebabkan infeksi kesehatan. Resistensi terhadap terapi pilihan meropenem merupakan ancaman serius. Penelitian ini bertujuan untuk menganalisis perubahan konsentrasi hambat minimum meropenem (KHM), perubahan ekspresi gen ampC, mexA, dan oprD, serta korelasi antara KHM dengan ekspresi gen ampC, mexA, dan oprD sesudah paparan meropenem.Metode: Digunakan sepuluh isolat P. aeruginosa dari Departemen Mikrobiologi Klinik Fakultas Kedokteran Universitas Indonesia. Sesudah bakteri terbukti peka terhadap meropenem secara fenotip, gen resistensi intrinsik dideteksi menggunakan PCR. Sesudah paparan meropenem pada hari ke 5 dan 12 dilakukan uji kepekaan dengan metode gradien konsentrasi dan deteksi RNA menggunakan real-time RT-PCR.Hasil: Semua isolat P. aeruginosa yang peka secara fenotip terhadap meropenem mempunyai gen ampC, mexA, dan oprD. Peningkatan KHM, peningkatan ekspresi gen ampC dan mexA, dan penurunan ekspresi gen oprD diamati sesudah paparan meropenem. Terdapat korelasi yang sangat kuat dan signifikan (p ≤ 0,05) antara KHM dan ekspresi gen oprD sesudah hari ke-12 paparan meropenem.Kesimpulan: Meskipun tidak terdapat perbedaan yang signifikan pada ekspresi gen KHM dan ampC, mexA, dan oprD antara hari ke-5 dan hari ke-12, namun terdapat korelasi yang sangat kuat dan signifikan antara ekspresi gen KHM dan oprD pada hari ke-12 (p≤ 0,05). Hal ini menunjukkan bahwa penurunan ekspresi gen oprD berpotensi meningkatkan resistensi meropenem pada P. aeruginosa.

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Background: Pseudomonas aeruginosa, drug-resistant, causes health infections. Resistance to the preferred therapy meropenem is a serious threat. This study aimed to analyze changes in meropenem minimum inhibitory concentration (MIC), changes in ampC, mexA, and oprD gene expression, and the correlation between MIC and ampC, mexA, and oprD gene expression after meropenem exposure.

Methods: Ten isolates of P. aeruginosa from the Clinical Microbiology Department, Faculty of Medicine, Universitas Indonesia were used. After the bacteria were shown to be sensitive to meropenem phenotypically, intrinsic resistance genes were detected using PCR. After meropenem exposure on Days 5 and 12, sensitivity testing was carried out with the concentration gradient method and RNA was detected using real-time RT-PCR.

Results: All P. aeruginosa isolates that were phenotypically sensitive to meropenem had the ampC, mexA, and oprD genes. An increase in MIC, an increase in ampC and mexA gene expression, and a decrease in oprD gene expression were observed after meropenem exposure. There was a very strong and significant correlation (p ≤ 0.05) between MIC and oprD gene expression after Day 12 of meropenem exposure.

Conclusion: Although there were no significant differences in MIC and ampC, mexA, and oprD gene expression between Day 5 and Day 12, there was a very strong and significant correlation between MIC and oprD gene expression on Day 12 (p≤ 0.05). This indicates that decreasing oprD gene expression has the potential to increase meropenem resistance in Pseudomonas aeruginosa."

"Latar Belakang: Penelitian ini bertujuan untuk mengetahui faktor-faktor yang memengaruhi terjadinya kekambuhan seperti, faktor klinis yaitu usia dan jenis kelamin, riwayat keluarga, besarnya ukuran kelenjar tiroid, ada tidaknya oftalmopati; faktor genetik yang berperan pada kejadian GD; dan faktor imunologi yaitu jumlah sel T regulator, kadar interleukin 10 (IL-10), interleukin 17 (IL-17) dan antibodi pada reseptor tiroid (TRAb).Metode: Penelitian ini merupakan studi kasus kontrol yang membandingkan 36 pasien GD yang kambuh dan 36 pasien GD yang tidak kambuh. Pemeriksaan polimorfisme gen dilakukan dengan metode PCR RFLP. Pemeriksaan jumlah sel T regulator dengan flowsitometri. Pemeriksaan IL-10, IL-17 dan TRAb dengan ELISA.Hasil: Analisis hasil penelitian membuktikan hubungan antara kekambuhan dengan faktor keluarga (p 0,008), usia saat didiagnosis (p 0,021), oftalmopati derajat 2 (p 0,001), kelenjar tiroid yang membesar melebihi tepi lateral muskulus sternokleidomastoideus (p 0,040), lamanya periode remisi (p 0,029), genotip GG gen CTLA-4 nukleotida 49 kodon 17 pada ekson 1 (p 0,016), genotip CC gen tiroglobulin nukleotida 5995 kodon 1980 pada ekson 33 (p 0,017), genotip CC gen TSHR SNP rs2268458intron 1 (p 0,003), jumlah sel T regulator (p 0,001), kadar IL-10 (p 0,012) dan kadar TRAb (p 0,002). Penelitian ini juga membuktikan hubungan antara faktor klinis yaitu faktor keluarga, usia, oftalmopati, pembesaran kelenjar tiroid dan lamanya periode remisi; dengan faktor genetik dan respons imun.Simpulan: Polimorfisme genotip gen CTLA-4 nukleotida 49 kodon 17 ekson 1, gen tiroglobulin nukleotida 5995 kodon 1980 ekson 33, gen TSHR SNP rs2268458 intron 1 dan sel T regulator berperan sebagai faktor risiko kambuh pada pasien penyakit Graves.

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Background: The management of Graves? disease (GD) is initiated with the administration of antithyroid drugs; however, it requires a long time to achieve remission and more than 50 percent of patients who had remission may be at risk for relapse after the drug is stopped. This study was aimed to identify factors affecting relapse of Graves? Disease

Methods: This was a case-control study comparing 36 patients relapsed GD and 36 patients who did not relapse. Genetic polymorphism examination was performed using PCR-RFLP. The number of regulatory T cells was counted using flow cytometry analysis and ELISA was used to measure serum IL-10, IL-17 and TRAb.

Results: The analysis of this study demonstrated that there was a correlation between relapse of disease and family factors (p 0.008), age at diagnosis (p 0.021), 2nd degree of Graves? ophthalmopathy (p 0.001), enlarged thyroid gland, which exceeded the lateral edge of the sternocleidomastoid muscles (p 0.040), duration of remission period (p 0.029), GG genotype of CTLA-4 gene on the nucleotide 49 at codon 17 of exon 1 (p 0.016), CC genotype of thyroglobulin gene on the nucleotide 5995 at codon 1980 of exon 33 (p 0.017), CC genotype of TSHR gene on the rs2268458 of intron 1 (p 0.003), the number of regulatory T cells (p 0.001), the levels of IL-10 (p 0.012) and TRAb levels (p 0.002). This study also showed the association between clinical factors, which included family factors, age at diagnosis, ophthalmopathy, thyroid gland enlargement and the long periods of remission with genetic factors and immune response.

Conclusion: Genetic polymorphisms of CTLA-4 gene on the nucleotide 49 at codon 17 of exon 1, thyroglobulin gene on the nucleotide 5995 at codon 1980 of exon 33, TSHR gene SNP rs2268458 of intron 1 and regulatory T cells play a role as risk factors for relapse in patients with Graves? disease."

"ABSTRAKPendahuluan. VDAC merupakan protein kanal ion yang bertanggung jawab atas aliran ion Ca2+ dan ATP dalam flagela spermatozoa. Defisiensi gen VDAC3 pada mencit dan mutasi gen VDAC3 pada manusia menyebabkan penurunan motilitas spermatozoa, sehingga VDAC3 dapat dijadikan antigen potensial untuk pengembangan vaksin kontrasepsi laki-laki. Tujuan penelitian ini adalah memproduksi protein rekombinan hVDAC3 dari gen hVDAC3 ekson 5-8 spesifik spermatozoa, dan digunakan sebagai antigen untuk produksi antibodi poliklonal pada kelinci.Metode. Gen hVDAC3 ekson 5-8 spermatozoa diperoleh melalui RT PCR, gen disisipkan ke plasmid pET100/D-TOPO dan diklona dalam E coli TOP 10. Analisis gen sisipan dengan PCR, enzim restriksi dan sekuensing DNA. Protein rekombinan hVDAC3 diekspresikan dalam E coli BL21 StarTM (DE3). Karakterisasi protein dilakukan dengan uji Bradford, SDS PAGE, western blot dan purifikasi protein dengan resin Ni-NTA. Antibodi poliklonal diperoleh dengan cara imunisasi protein rekombinan hVDAC3 ke kelinci dan diukur dengan indirect ELISA. Determinasi lokasi hVDAC3 di spermatozoa dengan metode immunoflurosence.Hasil. Amplifikasi PCR gen hVDAC3 ekson 5-8 berukuran 435 pb dan analisis BLAST menunjukkan 100% identik dengan gen VDAC3 manusia dari bank gen. Vektor rekombinan berukuran 6195 pb mengekspresikan protein rekombinan hVDAC3 berukuran 20 kDa. Antibodi poliklonal telah diproduksi kelinci secara bermakna (p<0.05) dengan titer 2.817, dan antibodi dapat berikatan dengan protein hVDAC3 di kepala dan flagela spermatozoa. Selanjutnya, antibodi poliklonal ini akan digunakan dalam pengembangan vaksin kontrasepsi pada laki-laki.

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ABSTRACT

Introduction. Voltage dependent anion channels (VDAC), also known as mitochondrial porins, are group of proteins in mitochondrial outer membrane that allow the passage of metabolites across the mitochondrial outer membrane, and are involved in ions and ATP transport in sperm flagella. Deficiency and mutation of VDAC3 may cause abnormality in structure and motility of human spermatozoa. VDAC3 could be a potential target to develop non hormonal male contraceptive vaccine. The objective of the study was to produce hVDAC3 recombinant proteins from exon 5 to 8 of human sperm VDAC3 spesific gene.

This recombinant protein was subsequenly used as an antigen to produce polyclonal antibodies in rabbits. Methods. hVDAC3 sperm gene obtained by RT PCR, this gene was inserted into plasmid pET 100/D-TOPO and cloned in E coli TOP 10. The gene was analyzed by PCR method, restriction enzymes and DNA sequencing. The proteins expressed in E coli BL21 StarTM (DE3). Characterization of proteins was evaluated by Bradford method, SDS PAGE and western blot. The recombinant protein was purified with NI-NTA resin. Polyclonal antibodies were obtained by immunization of hVDAC3 recombinant protein into rabbits. Indirect ELISA was done to analyze the antibody. Localization of the VDAC3 recombinant protein in human spermatozoa was evaluated by immunofluorescence method.

Result. By doing PCR amplification and BLAST analysis, the study showed that the hVDAC3 gene had 100% identical to hVDAC3 genes in data bank. E coli BL21 StarTM (DE3) containing recombinant vector (6195 bp) expressed the recombinant protein of hVDAC3 in 20 kDa. This protein produced polyclonal antibodies that bound VDAC3 protein on the head and flagella of human spermatozoa."

"PendahuluanMicroRNA (miR)-544a telah diidentifikasi sebagai pengatur potensial dalam jalur WNT/β-Catenin, namun perannya yang spesifik pada kanker paru-paru non-sel kecil (KPKBSK) dan hubungannya dengan resistensi kemoterapi berbasis platinum masih belum jelas. Oleh karena itu, kami bertujuan untuk menentukan hubungan antara ekspresi miR-544a dan GSK-3β, β-catenin, dan CD44 dengan resistensi kemoterapi berbasis platinum pada pasien KPKBSK stadium lanjut.MetodePenelitian ini dirancang sebagai studi kasus kontrol di mana individu yang didiagnosis dengan KPKBSK stadium lanjut (III-IV) dari Januari 2018 hingga Juli 2023 dari 6 rumah sakit berbeda di Indonesia. Analisis tingkat miR-544a dilakukan menggunakan Kit PCR QuantiTect SYBR Green secara real-time. Ekspresi GSK, β-catenin, dan CD44 menggunakan pewarnaan imunohistokimia (IHK) dilakukan dari formalin-fixed paraffin embedded (FFPE). Evaluasi intensitas IHK dibagi menjadi empat kategori ekspresi: negatif atau tidak berwarna, positif lemah, positif sedang, dan positif kuat. Dari 500 sel, kami menggunakan rumus semi-kuantitatif H-score.HasilStudi ini melibatkan 62 pasien KPKBSK stadium lanjut yang menjalani kemoterapi berbasis platinum dan menemukan miR-544a lebih tinggi pada responden yang buruk, dengan nilai p yang signifikan sebesar 0,009. Model prediktif untuk miR-544a menunjukkan nilai Roctab sebesar 0,6957. Nilai batas miR-544a sebesar 2,08 menghasilkan sensitivitas 64% dan spesifisitas 67,57%. Tingkat miR-544a di atas 2,08 secara signifikan terkait dengan respons pengobatan yang lebih buruk (OR 2,159, 95% CI 1,132 - 4,117, p = 0,016).KesimpulanStudi ini menunjukkan bahwa tingkat miR-544a merupakan biomarker yang signifikan untuk memprediksi respons kemoterapi pada pasien dengan KPKBSK stadium lanjut.

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Introduction

MicroRNAs (miR)-544a has been identified as a potential regulator in the Wnt/β-Catenin pathway, but its specific role in non-small cell lung cancer (NSCLC) and its relationship with platinum-based chemotherapy resistance, remains unclear. Thus, we aim to determine the relationship between the expression of miR-544a and GSK-3β, β-catenin, and CD44 with platinum-based chemotherapy resistance in advanced stage NSCLC patients.

Methods

The research is designed as a case control study in which individuals diagnosed with advanced stage (III-IV) NSCLC from January 2018 and July 2023 from 6 different hospitals in Indonesia.

The analysis of miR-544a levels was done using the real-time QuantiTect SYBR Green PCR Master Kit. The expression of GSK, β-catenin, and CD44 expression using immunohistochemistry (IHC) staining was performed from the formalin-fixed paraffin embedded (FFPE). The evaluation of IHC intensity was divided into four expression categories: negative or unstained, weakly positive, moderately positive, and strongly positive. From 500 cells, we used the semi-quantitative H-score formula.

Results

This study of 62 advance NSCLC patients undergoing platinum-based chemotherapy and found miR-544a were higher in poor responders, with a significant p-value of 0.009. The predictive model for MiR-544a demonstrated a Roctab value of 0.6957. A miR-544a cutoff value of 2.08 yielded sensitivity of 64% and specificity of 67.57%. MiR-544a levels above 2.08 were significantly associated with poorer treatment response (OR 2.159, 95% CI 1.132 - 4.117, p = 0.016).

Conclusions

The study demonstrates that miR-544a levels are a significant biomarker for predicting chemotherapy response in patients with advance NSCLC."

"Latar Belakang: TNF-α dan CXCL16 terlibat dalam patofisiologi endometriosis melalui regulasi respon inflamasi dan pengkode nyeri endometriosis. Peningkatan TNF-α berperan dalam jalur pensinyalan P53 untuk apoptosis. Darah menstruasi sebagai pelepasan jaringan endometrium dapat digunakan dalam mengidentifikasi biomarker untuk diagnosis penyakit endometriosis tanpa memerlukan biopsi. Metode: Sampel darah menstruasi subjek dikumpulkan dengan menggunakan pembalut kertas saring dan jaringan endometrium dikumpulkan dengan melakukan biopsi, yang kemudian diekstraksi DNA dan RNA-nya. Tingkat metilasi DNA diukur dengan menggunakan metode pyrosequencing. Tingkat ekspresi mRNA diukur dengan menggunakan metode qPCR dan dianalisis dengan metode Livak Hasil: Ekspresi mRNA gen TNF-α pada darah menstruasi pasien endometriosis meningkat signifikan 3,73 kali lipat dibandingkan ekspresi pada kontrol (p=0,005). Gen TNF-α mengalami hipermetilasi dan berbeda bermakna dalam darah menstruasi pasien endometriosis dibandingkan kontrol (p=0,008). Sedangkan ekspresi mRNA gen CXCL16 pada darah menstruasi pasien endometriosis meningkat 2,42 kali (p=0,030) dibandingkan ekspresi mRNA darah menstruasi pada kontrol. Gen CXCL16 mengalami hipometilasi (p=0,004). Pada P53 terjadi terjadi peningkatan ekspresi gen P53 1,52 kali. Ekspresi mRNA gen TNF-α dan CXCL16 pada subjek nyeri berat lebih tinggi dibandingkan subjek nyeri sedang, dan terdapat korelasi positive. Kesimpulan: Penelitian ini menunjukkan bahwa peningkatan ekspresi mRNA TNF-α dan CXCL16 dalam darah menstruasi pasien endometriosis dapat menjadi penanda langsung untuk mendiagnosis endometriosis. Namun, untuk memvalidasi lebih lanjut temuan ini dan mengeksplorasi potensi sebagai alat diagnostik, penelitian tambahan yang melibatkan kelompok pasien yang lebih besar diperlukan

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Background: TNF-α and CXCL16 are implicated in the pathophysiology of endometriosis through the regulation of inflammatory response and the coding of endometriosis pain. Elevated TNF-α is implicated in the P53 signaling pathway for apoptosis. Menstrual blood, as a discharge of endometrial tissue, presents an opportunity for identifying biomarkers for the diagnosis of endometriosis without resorting to biopsy. Method: Menstrual blood samples were collected using filter paper pads, and endometrial tissues were obtained via biopsy, from which DNA and RNA were extracted. DNA methylation levels were assessed using the pyrosequencing method after bisulfite conversion treatment. Meanwhile, mRNA expression levels were measured using the quantitative polymerase chain reaction (qPCR) method and analyzed using the Livak method. Results: The mRNA expression of the TNF-α gene in menstrual blood of endometriosis patients increased significantly by 3.73 times compared to controls (p=0.005). The TNF-α gene exhibited hypermethylation, significantly differing in menstrual blood of endometriosis patients compared to controls (p=0.008). The mRNA expression of the CXCL16 gene in menstrual blood of endometriosis patients increased by 2.42 times (p=0.030) compared to controls, although there was no significant difference in expression between menstrual blood and endometrial tissue in endometriosis patients (p=0.173). The CXCL16 gene displayed hypomethylation (p=0.004). There was an increase in P53 gene expression, which was 1.52 times higher than in control menstrual blood. The mRNA expression of TNF-α and CXCL16 genes in subjects experiencing severe pain was higher than in those with moderate pain, and there was a positive correlation. Conclusion: This study suggests that increased mRNA expression of TNF-α and CXCL16 in menstrual blood of endometriosis patients may serve as direct markers for diagnosing endometriosis. However, further validation of these findings and exploration of their potential as diagnostic tools requires additional studies involving larger patient cohorts."

"Latar belakang: Enzim methylenetetrahydrofolate reductase (MTHFR) terlibat dalam metabolism asam folat dan tipe allele mempengaruhi aktivitas enzim. Memberikan suplementasi asam folat kepada ibu hamil dapat mempengaruhi perubahan dalam derajat metilasi gen tertentu yang mempengaruhi kesehatan janin. Walaupun sudah banyak penelitian yang mempelajari peran asam folat sebagai donor dalam mekanisme epigenetik, namun penelitian pengaruh suplementasi besi-asam folat pada luaran kehamilan melalui pendekatan interaksi zat gizi-gen dalam desain penelitian longitudinal masih jarang. Penelitian ini bertujuan untuk mengetahui hubungan antara kadar serum asam folat pada ibu dan anak, dan derajat metilasi pada gen pencetak insulin-like growth factor (IGF2) yang dikenal terlibat dalam tumbuh kembang anak dan dapat digunakan sebagai penanda kemunculan penyakit Metode: Di tahun 2018, penelitian longitudinal dilakukan dengan mengunjungi 127 subyek termasuk anak yang dilahirkan dan mengikutsertakannya dalam penelitian. Enam puluh tujuh serum asam folat ibu selama hamil dan pasca melahirkan diperiksa, sementara serum asam folat anak dikumpulkan sebanyak 44 spesimen untuk pemeriksaan penanda darah. Pemeriksaan serum asam folat dengan menggunakan the liquid chromatography-mass spectrometry/mass spectrometry. Untuk pemeriksaan biomolekuler, tipe allele enzim MTHFR 677C>T and 1298A>C menggunakan Taqman polymerase chain reaction. Sementara metode pyrosequencing digunakan untuk menghitung DNA metilasi pada IGF2 pada anak. Hubungan antar variabel dianalisis menggunakan analisis regresi linier multivariat. Hasil:Tidak ada hubungan yang signifikan antara asupan asam folat dan serum asam folat ibu selama hamil, tiga tahun pasca melahirkan dan anak yang dilahirkan (p>0.05). Penelitian ini tidak dapat menunjukkan hubungan antara tipe allel dari MTHFR 677 C>T dan 1298 A>C dan serum asam folat (p>0.05). Serum asam folat selama hamil juga mempengaruhi status serum asam folat tiga tahun pasca melahirkan (p<0.05) dan status serum asam folat anak (p<0.05). Namun penelitian ini tidak dapat menunjukkan pengaruh status serum asam folat anak dengan DNA metilasi IGF2 pada anak (p>0.05). Simpulan: Serum asam folat selama hamil berkontribusi pada serum asam folat tiga tahun pasca melahirkan dan anak. Genotipe dari MTHFR gene at 677C>T and 1298 A>C kemungkinan tidak terlibat dalam metabolism asam folat pada ibu. Serum asam folat selama kehamilan tidak memiliki dampak pada status metilasi dari IGF2 pada wilayah differentially methylated region (DMR) untuk subyek anak. Namun, beberapa hal harus menjadi perhatian karena, secara statistik, jumlah subyek penelitian tidak memadai. Saran: Perlu dilakukan penelitian lanjutan yang melibatkan subyek lebih banyak dan metode yang lebih canggih dalam menentukan MTHFR dan metilasi DNA.

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Background: Methylenetetrahydrofolate reductase (MTHFR) enzyme is involved in folic acid metabolism, and their allele types affected its activity. Providing folic acid supplementation to pregnant mothers may influence the change in methylation level in specific genes that affect the susceptibility of disease of their offspring. Although folic acid's role as a donor in the epigenetic mechanism has been investigated, a longitudinal study exploring the influence of iron-folic acid supplementation on maternal dan birth outcome by the nutrient-gene interaction approach is lacking. Therefore, we investigated the relationship of serum folic acid level among the mothers and the children, and the imprinted insulin-like growth factor 2 (IGF2) methylation level that is known actively involved in growth and development in children and possibly utilized as a surrogate marker for the disease Methods: In 2018, the follow-up study conducted by re-visited 67 subjects and put the mother and their children included in the study. For each group, sixty-seven serums were collected for folic acid measurement for mothers during gestation and three-year post-partum. Furthermore, forty-four serums for children were gathered for biomarker measurement. Serum folics were measured by using liquid chromatography-mass spectrometry/mass spectrometry. Determining the genotype of the MTHFR enzyme in position 677C>T and 1298 A>C was used Taqman Polymerase Chain Reaction (PCR) method. The pyrosequencing method was utilized to quantify the methylation level of the IGF-2 of the children. The relationship analysis between variables using multivariate linear regression. Results: There was no relationship between the folic acid intake during gestation and serum folic acid of the mothers during pregnancy, three-year post-partum, and the children (p>0.05). There was no relationship between the allele type of MTHFR 677C>T and 1298A>C and serum folic acid status of the mother (p>0.05). The serum folic acid during pregnancy had a significant relationship to the serum folic acid three-year post-partum (p<0.05) as well as the serum folic acid of the children (p<0.05). There was no significant relationship between the serum folic acid of the children, serum homocysteine, and the methylation status of IGF2 of the children (p>0.05). Conclusion: The serum folic acid during pregnancy contributed to the serum folic acid three-year post-partum of mother and the children. The genotype of the MTHFR gene at 677C>T and 1298 A>C was possibly not involved in folic acid metabolism in the mother. Serum folic acid during pregnancy could not have an effect on the methylation status of the IGF2 in the differentially methylated region (DMR) area of the children. However, this conclusion needs to be taken in caution due to lack of study power Recommendation: Further cohorts studies with a large sample size and more advanced methods in determining the MTHFR enzyme and DNA methylation. "

"Batu ginjal merupakan salah satu penyakit urologi tersering di Indonesia dan dipengaruhi oleh berbagai faktor inflamasi, faktor klinis dan demografi, namun, 50% faktor predisposisi batu ginjal diketahui juga dipengaruhi oleh faktor genetik. Namun, sampai saat ini, belum ada studi yang menganalisis faktor risiko kejadian batu ginjal dari segi polimorfisme gen, sitokin inflamasi, klinis, dan demografi secara komprehensif, serta belum diketahui mekanisme keseluruhan faktor-faktor tersebut dalam menyebabkan batu ginjal. Oleh sebab itu, penelitian ini dibuat untuk menjelaskan mekanisme faktor risiko tersebut terhadap kejadian batu ginjal sebagai pencegahan terjadinya batu ginjal. Penelitian dilakukan di RSUPN Dr. Cipto Mangunkusumo dengan desain kasus kontrol sejak Maret 2021 hingga Maret 2024 dengan jumlah 308 subjek, yaitu 154 subjek kelompok kasus dan 154 subjek kelompok kontrol sehat. Pada setiap pasien dilakukan pencatatan dan evaluasi terhadap data demografi, pemeriksaan biokimia dan polimorfisme genetik dievaluasi dari sampel darah, ekspresi gen sitokin inflamasi dan urinalisis dari sampel urin pagi, serta pemerikaan urin 24 jam. Asupan cairan dinilai menggunakan kuesioner Liq-In7. Analisis bivariat dan multivariat dilakukan menggunakan SPSS versi 20 sedangkan analisis jalur dilakukan menggunakan JASP 0.19.1.0. Dari penelitian didapatkan usia lebih tua, peningkatan kadar kreatinin darah, peningkatan kadar kalsium urin, kondisi ISK, genotipe GT gen CaSR rs1801725, genotipe CT gen CLDN14 rs219780, genotipe AG dan GG gen VDR rs2228570, genotipe CT gen VDR rs1544410, dan genotipe CT gen ALPL rs1256328 berhubungan dengan peningkatan risiko kejadian batu ginjal. Peningkatan kadar sitrat urin dan genotipe AG gen CaSR rs1042636 menurunkan risiko batu ginjal. Selain itu, rerata asupan cairan lebih rendah, asam urat urin lebih rendah, asam urat serum lebih tinggi, dan proporsi Genotipe CT gen VDR rs731236 dan pekerja kantor lebih rendah didapatkan pada kelompok kasus secara bermakna, namun tidak termasuk dalam faktor risiko independen berdasarkan hasil multivariat. Upregulation ekspresi IL-8 juga didapatkan pada kelompok kasus. Pada analisis jalur, varian gen VDR rs2228570, CLDN14 rs219780, CaSR rs1801725, kreatinin serum, dan usia lebih dominan memiliki efek positif langsung terhadap batu ginjal. Di sisi lain, varian gen VDR rs1544410 memiliki efek positif tidak langsung yang lebih dominan terhadap batu ginjal melalui kalsium urin. Prediktor batu ginjal dengan sistem skoring menggunakan beberapa variabel telah dikembangkan dengan sensitivitas dan spesifisitas yang baik. Dengan mengidentifikasi faktor risiko terkait batu ginjal yang dapat dan tidak dapat dimodifikasi bisa menjadi target utama dalam pencegahan primer batu ginjal.

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Kidney stones are among the most common urological diseases in Indonesia, influenced by various inflammatory, clinical, and demographic factors, but 50% of the predisposition is also attributed to genetic factors. To date, no comprehensive studies have analyzed kidney stone risk factors by considering genetic polymorphisms, inflammatory cytokines, clinical, and demographics factors. Moreover, the comprehensive mechanisms by which these risk factors contribute to kidney stone formation remain unclear. Therefore, this study was conducted to elucidate how these risk factors contribute to kidney stone occurrence, aiming to prevent kidney stones. The study was conducted at Dr. Cipto Mangunkusumo Hospital using a case-control design from March 2021 to March 2024, involving 308 subjects, comprising 154 cases and 154 healthy controls. Demographic data were collected through subject interviews. Biochemical and genetic polymorphism analyses were performed using blood samples, while inflammatory cytokine gene expression and urinalysis were evaluated from morning urine samples. Twenty-four-hour urine samples were utilized to analyze the levels of dissolved molecules and urine pH. Fluid intake was assessed using the Liq-In7 questionnaire. Bivariate and multivariate analysis was conducted using SPSS version 20, whereas path analysis was performed using JASP 0.19.1.0. The study identified that older age, increased serum creatinine levels, increased urinary calcium levels, urinary tract infections, the GT genotype of the CaSR rs1801725 gene, the CT genotype of the CLDN14 rs219780, the AG and GG genotypes of the VDR rs2228570, the CT genotype of the VDR rs1544410, and the CT genotype of the ALPL rs1256328 were associated with an increased risk of kidney stone. In contrast, higher urinary citrate levels and the AG genotype of the CaSR rs1042636 gene were associated with a reduced risk of kidney stones. Furthermore, the case group showed significantly lower mean fluid intake, lower urinary uric acid levels, higher serum uric acid levels, and a lower proportion of the CT genotype of the VDR rs731236 gene and office workers. However, these variables were not identified as independent risk factors based on multivariate analysis. IL-8 expression was also observed to be upregulated in the case group. Path analysis revealed that the VDR rs2228570, CLDN14 rs219780, and CaSR rs1801725 genetic variants, serum creatinine, and age, predominantly exerted direct positive effects on kidney stone. Conversely, the VDR rs1544410 genetic variant had a more pronounced indirect positive effect through urinary calcium levels. Scoring systems for kidney stone prediction, incorporating these variables, had been developed with good sensitivity and specificity. Identifying modifiable and non-modifiable risk factors related to kidney stones could serve as critical targets for primary prevention strategies."