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"Latar belakang: Kanker payudara terjadi cukup tinggi dan merupakan salah satu penyebab utama kematian di Indonesia dan dunia. Pengobatan untuk kanker yang mahal dan memiliki tingkat keberhasilan yang berbeda-beda dan dapat menyebabkan efek samping kepada pasien sehingga diperlukan pengembangan terapi alternatif untuk pengobatan kanker payudara dengan tanaman herbal yang biayanya terjangkau dan memiliki efek samping minimal, salah satunya kluwak (Pangium edule). Metode: Bubuk kluwak dimaserasi dengan menggunakan tiga jenis pelarut berbeda sehingga diperoleh ekstrak etanol, ekstrak etil asetat, dan ekstrak n-heksana kluwak. Uji fitokimia dan kromatografi lapis tipis (KLT) dilakukan untuk mengetahui jenis dan jumlah komponen fitokimia ekstrak kluwak. Aktivitas antioksidan ekstrak kluwak dilakukan uji dengan metode DPPH dan efek sitotoksisitas terhadap sel kanker payudara MCF-7 diketahui melalui uji MTT. Hasil: Komponen fitokimia yang terkandung di dalam ekstrak kluwak mencakup flavonoid, alkaloid, triterpenoid, dan glikosida. Ekstrak etanol kluwak menunjukkan aktivitas antioksidan yang sangat lemah (IC50 = 26459 µg/ml), sedangkan ekstrak etil asetat dan n-heksana tidak dapat ditentukan aktivitas antioksidannya. Ekstrak etil asetat dan n-heksana kluwak juga memiliki efek sitotoksisitas yang sedang terhadap sel kanker payudara MCF-7 dengan nilai IC50berturut-turut 132,79 µg/ml dan 232,93 µg/ml sedangkan ekstrak etanol memiliki efek sitotoksisitas yang lemah dengan nilai IC50 667,91 µg/ml. Kesimpulan: Ekstrak kluwak (Pangium edule) memiliki kandungan senyawa fitokimia dan efek sitotoksisitas terhadap sel kanker payudara MCF-7 sehingga berpotensi untuk dikembangkan menjadi salah satu agen terapeutik dalam tatalaksana kanker payudara.

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Introduction: Breast cancer occurs quite high and is one of the main causes of death in Indonesia and the world. Current treatment for cancer is expensive and has varying degrees of success and can cause side effects for patients. Kluwak (Pangium edule), whose reseach is still limited has the potential to be used as an alternative treatment for breast cancer. Methods: Kluwak powder was macerated using three different types of solvents to obtain ethanol extract, ethyl acetate extract and n-hexane kluwak extract. Phytochemical tests and thin layer chromatography (TLC) were carried out to determine the type and amount of phytochemical components of kluwak extract. The antioxidant activity of kluwak extract was tested using the DPPH method and the cytotoxic effect on MCF-7 breast cancer cells was determined using the MTT test. Results: The phytochemical components contained in kluwak extract include flavonoids, alkaloids, triterpenoids and glycosides. The ethanol extract of kluwak showed very weak antioxidant activity (IC50 = 26459 µg/ml), while the antioxidant activity of the ethyl acetate and n-hexane extracts could not be determined. Ethyl acetate and n-hexane kluwak extracts also had a moderate cytotoxic effect on MCF-7 breast cancer cells with IC50 values respectively 132.79 µg/ml and 232.93 µg/ml while the ethanol extract had a weak cytotoxic effect with values IC50 667.91 µg/ml.Conclusion: Kluwak (Pangium edule) extract contains phytochemical compounds and cytotoxic effects on MCF-7 breast cancer cells, so it has the potential to be developed as a therapeutic agent in the management of breast cancer."

"Demam berdarah (DBD) merupakan penyakit yang disebabkan oleh virus dengue dan ditularkan oleh nyamuk Aedes aegypti dan Aedes albopictus. Insidensi lebih dominan di daerah tropis dan subtropis. Terdapat berbagai faktor yang diduga berkontribusi pada penyebaran DBD, seperti kepadatan penduduk, perubahan iklim, dan kondisi lingkungan. Oleh karena itu, penelitian ini untuk menganalisis hubungan antara kepadatan penduduk, iklim, dan larva nyamuk secara bersamaan di Jakarta Utara. Studi ini menggunakan uji cross sectional yang membandingkan insidensi demam berdarah di wilayah Jakarta Utara pada tahun 2019 hingga 2022 dan diuji hubungannya dengan faktor iklim, seperti temperatur udara, curah hujan, kelembaban udara, serta kepadatan penduduk dan angka bebas jentik. Uji dilakukan dengan uji korelasi Pearson dan Spearman. Pengaruh terhadap insidensi demam berdarah, antara lain kelembaban udara pada bulan yang sama (p=0.037, r=0.303 pada Non TL), curah hujan pada satu bulan setelah curah hujan diukur (p=0.038, r=0.303 pada TL-1). temperatur udara pada 2 bulan setelah temperatur udara diukur (p=0.005, r=-0.405). Kepadatan larva pada bulan yang sama (p=0.006, r=-0.547). Kepadatan penduduk pada bulan yang sama (p=0.036, r=0.431). Kelembaban udara, kepadatan larva, dan kepadatan penduduk memiliki pengaruh terhadap insidensi demam berdarah pada bulan yang sama, sedangkan curah hujan pada 1 bulan setelah pengukuran, dan temperatur udara tidak memiliki korelasi signifikan.

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Dengue fever (DF) is a disease caused by the dengue virus and transmitted by the Aedes aegypti and Aedes albopictus mosquitoes. The incidence is more dominant in tropical and subtropical areas. Various factors are believed to contribute to the spread of DF, such as population density, climate change, and environmental conditions. Therefore, this study aims to analyze the relationship between population density, climate, and mosquito larvae concurrently in North Jakarta. This study uses a cross-sectional design comparing the incidence of dengue fever in North Jakarta from 2019 to 2022 and examines its relationship with climatic factors such as air temperature, rainfall, humidity, as well as population density and the larval index. The analysis was performed using Pearson and Spearman correlation tests. Factors influencing the incidence of dengue fever include humidity in the same month (p=0.037, r=0.303 for Non TL), rainfall one month after it is measured (p=0.038, r=0.303 for TL-1), air temperature two months after it is measured (p=0.005, r=-0.405), larval density in the same month (p=0.006, r=-0.547), and population density in the same month (p=0.036, r=0.431). Humidity, larval density, and population density have an influence on the incidence of dengue fever in the same month, while rainfall measured one month later and air temperature doesn’t have significant temperature."

"Latar Belakang: Kanker kolorektal adalah kanker keempat paling umum serta penyebab kematian akibat kanker kelima di Indonesia. Terapi kanker kolorektal sekarang yang tersedia sudah cukup banyak, namun banyak memberikan efek samping dan memerlukan biaya yang tinggi sehingga perlu dikembangkan terapi alternatif. Biji kapulaga jawa (Amomum compactum) berpotensi sebagai antioksidan dan antikanker dari senyawa fitokimianya sehingga dapat dikembangkan sebagai terapi alternatif. Metode: Serbuk kering biji kapulaga jawa diekstraksi melalui metode maserasi bertingkat sebanyak dua kali menggunakan pelarut n-heksana, etil asetat dan etanol secara berurutan menghasilkan tiga jenis ekstrak. Uji fitokimia dan kromatografi lapis tipis (KLT) dilakukan untuk mengetahui kandungan fitokimia pada ketiga ekstrak. Uji aktivitas antioksidan dilakukan dengan metode DPPH dan uji aktivitas sitotoksik terhadap sel HT-29 melalui metode MTT. Hasil: Uji fitokimia menunjukkan biji kapulaga jawa mengandung golongan fitokimia alkaloid, flavonoid, tannin dan triterpenoid. Ekstrak etanol biji kapulaga jawa menunjukan aktivitas antioksidan kuat (IC50 83,52 µg/ml), sedangkan ekstrak etil asetat dan n-heksana memiliki aktivitas antioksidan sedang (IC50=160,06 µg/ml dan 216,08 µg/ml). Aktivitas sitotoksik ekstrak etanol biji kapulaga jawa terhadap sel HT-29 termasuk kategori moderat (IC50=94,46 µg/ml). Adapun aktivitas sitotoksik dari ekstrak etil asetat dan n-heksana termasuk dalam kategori lemah (IC50 = 276,26 µg/ml dan 282,65 µg/ml). Kesimpulan: Senyawa fitokimia yang terkandung ekstrak biji kapulaga jawa menunjukkan aktivitas antioksidan terhadap DPPH, serta aktivitas sitotoksik terhadap sel kanker HT-29.

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Introduction: Colorectal cancer is the fourth most common cancer and the fifth cause of cancer death in Indonesia. There are a lot of colorectal cancer therapies currently available, but they have many side effects and require high costs, so we need alternative therapies. Javanese cardamom seeds (Amomum compactum) have potential as antioxidants and anticancer from the phytochemical compound so they can be developed as an alternative therapy.

Method: Dry powder of Javanese cardamom seeds extracted using multistage maceration method twice using n-hexane, ethyl acetate and ethanol solvents sequentially to produce three types of extracts. Phytochemical tests and thin layer chromatography (TLC) were carried to determine phytochemical content of extracts. Antioxidant activity was determined using DPPH method and the cytotoxic activity test against HT-29 cancer cells was determined using MTT method.

Results: Phytochemical tests show that Javanese cardamom seeds contain alkaloid, flavonoid, tannin and triterpenoid phytochemical groups. The ethanol extract of Javanese cardamom seeds showed strong antioxidant activity (IC50= 83.52 µg/ml), while the ethyl acetate and n-hexane extracts had moderate antioxidant activity (IC50=160.06 µg/ml and 216.08 µg/ml). The cytotoxic activity of ethanol extract of Javanese cardamom seeds against HT-29 cells is moderate category (IC50= 94.46 µg/ml). The cytotoxic activity of ethyl acetate and n-hexane extracts are in weak category (IC50 276.25 µg/ml and 282.65 µg/ml).

Conclusion: The phytochemical components contained in Javanese cardamom seed extract show antioxidant activity against DPPH, as well as cytotoxic activity against HT-29 cancer cells."

"Latar BelakangDiabetes Melitus (DM) merupakan penyebab kematian terbesar ke-3 di Indonesia. Terdapat berbagai opsi pengobatan diabetes Melitus, salah satunya golongan inhibitor SGLT2. Bunga cengkeh atau Syzygium aromaticum sebagai spesies tumbuhan yang umum digunakan sebagai obat herbal, memiliki senyawa dengan aktivitas down regulation SGLT dan GLUT2. Penelitian ini bertujuan untuk mengetahui efek antidiabetes senyawa Syzygium aromaticum dengan aktivitas inhibitor SGLT2 secara in silico menggunakan prediksi nilai IC50 dan molecular docking.MetodePenelitian analitik observasional in silico menggunakan metode prediksi nilai IC50 dengan perangkat lunak DataWarrior dan molecular docking dengan perangkat lunak Molegro Virtual Docker (MVD).HasilSenyawa yang terdapat dalam Syzygium aromaticum memiliki aktivitas inhibitor SGLT2 melalui prediksi nilai IC50. Tiga senyawa yang dipilih karena memiliki potensi inhibitor SGLT2 adalah Astilbin, HPEA, dan Strictinin (IC50: 3,2 μM; 31,189 μM; 0,315 μM) Ketiga senyawa memiliki nilai IC50 dengan kategori excellent, good, dan moderate activity serta nilai LELP mendekati 6. Validasi molecular docking dengan protein SGLT2 (7VSI) menunjukkan ketiga senyawa Rerank Score negatif, mengindikasikan ikatan yang spotan dan kuat. Selain itu, Strictinin memiliki nilai Rerank Score positif terhadap protein SGLT1, mengindikasikan selektivitas yang rendah terhadap protein tersebut.KesimpulanTerdapat aktivitas inhibitor SGLT2 pada senyawa Syzygium aromaticum untuk senyawa Astilbin, HPEA, dan Strictinin. Senyawa tersebut memiliki selektivitas tinggi terhadap protein SGLT2. Strictinin memiliki selektivitas rendah terhadap protein SGLT1, sehingga berpotensi untuk terapi antidiabetes dengan efek samping minimal.

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Introduction

Diabetes Melitus (DM) is the third leading cause of death in Indonesia. There are various treatment options for diabetes Melitus, one of which is the SGLT2 inhibitor class. Clove flower or Syzygium aromaticum is a plant species commonly used as an herbal medicine, contains compounds that exhibit downregulation of SGLT and GLUT2. This study aims to investigate the antidiabetic effects of compounds in Syzygium aromaticum with SGLT2 inhibitory activity in silico using IC50 prediction and molecular docking.

Method

This observational analytic in silico study used the IC50 value prediction method with DataWarrior software and molecular docking with Molegro Virtual Docker (MVD) software.

Results

The compounds found in Syzygium aromaticum exhibited SGLT2 inhibitory activity through IC50 value prediction. Three compounds identified as having SGLT2 inhibitor potential were Astilbin, HPEA, and Strictinin (IC50: 3,2 μM; 31,189 μM; 0,315 μM). These compounds had IC50 values classified as excellent, good, and moderate activity, with LELP values approaching 6. Upon validation of molecular docking with the SGLT2 protein (7VSI), all three compounds showed negative Rerank Scores, indicating strong and spontaneous binding. Additionally, Strictinin exhibited a positive Rerank Score with the SGLT1 protein, indicating low selectivity for that protein.

Conclusion

There is SGLT2 inhibitory activity in compounds from Syzygium aromaticum, specifically in Astilbin, HPEA, and Strictinin. These compounds have high selectivity for the SGLT2 protein. Strictinin shows low selectivity for the SGLT1 protein, making it a potential candidate for antidiabetic therapy with minimal side effects."

"Diarrhea poses significant health risks in developing countries like Indonesia, especially among children, contributing to high morbidity and mortality rates according to the 2018 World Health Organization report. The escalating antimicrobial resistance among enteric pathogens in these nations is also a critical concern. The aim of this research is to profile Gram-negative bacteria in pediatric patients with diarrheal conditions and analyze the antibacterial gene resistance of Gram-negative bacteria in these patients. Stool samples were cultured and sent to the FKUI Microbiology Laboratory for DNA isolation. Pathogenic Gram-negative bacteria were identified and sequenced at the Bioinformatics Core Facilities at IMERI-FKUI using Next-Generation Sequencing (NGS). Antibiotic resistance to antibiotics such as cefixime, co-trimoxazole, ciprofloxacin, and carbapenem was determined. Eighteen bacterial samples revealed a diverse landscape of Klebsiella pneumoniae and E. coli strains. Klebsiella pneumoniae predominated (56%), with various Sequence Types (STs) and phylotypes identified. Notably, ST-231 and ST-101 were associated with the K1 phylotype, indicating potential virulence. E. coli (44% of samples) showed a spectrum of pathogenicity, including ExPEC as the most prevalent. Virulence gene analysis highlighted complex pathogenic mechanisms and significant antibiotic resistance, especially in E. coli. K. pneumoniae and E. coli isolates showed high resistance to multiple antibiotics, including fluoroquinolones, fosfomycin, aminoglycosides, and beta-lactams. This research enhances the understanding of gastrointestinal health in children and underscores the urgent need for effective antimicrobial stewardship to combat antimicrobial resistance."

"ABSTRAKLatar Belakang: Mangiferin diketahui memiliki aktivitas sebagai agen pengikat besi, namun pemberian mangiferin melalui oral memiliki bioavailabilitas yang rendah. Sistem hantaran dengan nanopartikel diharapkan dapat meningkatkan bioavailabilitas dan efektivitas mangiferin. Penelitian bertujuan menguji efektivitas mangiferin nanopartikel kitosan-alginat dalam menurunkan kadar besi di plasma dan organ, kadar ferritin, transferrin, SGOT dan SGPT. Metode: Penelitian menggunakan desain eksperimental in vivo dengan hewan coba tikus Sprague-Dawley dibagi dalam 5 kelompok, yaitu kelompok normal, kelebihan besi, terapi mangiferin 50 mg/KgBB, terapi mangiferin dalam nanopartikel kitosanalginat 25 mg/KgBB, dan terapi mangiferin dalam nanopartikel kitosan-alginat 50 mg/KgBB. Pengukuran kadar Fe plasma, hati dan jantung, kadar Ferritin, kadar Transferrin, dan nilai aktivitas SGPT dan SGOT. Hasil: Kadar besi plasma, besi hati dan jantung, ferritin, dan transferrin pada kelompok kelebihan besi adalah 45,52 mg/L; 3661,98 μg/gram; 1734,4 μg/gram; 3578,16 ng/mL; 388,96 μg/dL, sedangkan pemberian terapi mangiferin 50 mg/KgBB (p < 0,05) menghasilkan 5,17 mg/L; 1572,96 μg/gram; 776,68 μg/gram; 1136,51 ng/mL; 272,18 μg/dL, pemberian terapi mangiferin dalam nanopartikel kitosan-alginat 25 mg/KgBB (p < 0,05) menghasilkan 5,74 mg/L; 1090,01 μg/gram; 753,90 μg/gram; 520,89 ng/mL; 231,97 μg/dL, pemberian terapi mangiferin dalam nanopartikel kitosan-alginat 50 mg/KgBB (p < 0,05) menghasilkan 3,34 mg/L; 1703,92 μg/gram; 759,2 μg/gram; 559,48 ng/mL; 235,70 μg/dL. Tidak terdapat perbedaan bermakna antar kelompok terhadap nilai aktivitas SGOT dan SGPT Kesimpulan: Mangiferin dalam nanopartikel kitosan-alginat efektif menurunkan kadar besi, ferritin, transferrin plasma, dan kadar besi di organ hati dan jantung, namun tidak menurunkan nilai aktivitas SGOT dan SGPT. Efektivitas mangiferin dalam nanopartikel kitosan-alginat tidak berbanding lurus dengan dosis.

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ABSTRACTBackground: Mangiferin was known to have activity as an iron-chelating agent, but oral administration of mangiferin has poor bioavailability. Nanoparticles delivery system is expected to increase bioavailability and effectiveness of mangiferin. This study aims to examine the effectiveness of mangiferin in chitosanalginate nanoparticles in reducing iron levels in plasma and organs, ferritin, transferrin, SGOT and SGPT activities. Methods: This is an in vivo experimental study using Sprague-Dawley rats, divided into 5 groups, normal, iron overload, mangiferin 50mg/KgBW, mangiferin in chitosan-alginate nanoparticles 25mg/KgBW, and mangiferin in chitosanalginate nanoparticles 50mg/KgBW. Fe levels were measured in plasma, liver and heart. In addition ferritin levels, transferrin levels, and SGPT and SGOT activities also measure at day 29th. Results: Plasma iron levels, liver and heart iron levels, ferritin, and transferrin in the iron overload group were 45.52 mg/L; 3661.98 μg/gram; 1734.4 μg/gram; 3578.16 ng/mL; 388.96 μg/dL, treatment with mangiferin 50 mg/KgBW (p < 0.05) reduced those parameters to 5.17 mg/L; 1572.96 μg/gram; 776.68 μg/gram; 1136.51 ng/mL; 272.18 μg/dL, treatment with mangiferin in chitosan-alginate nanoparticles 25 mg/KgBW (p < 0.05) reduced those parameters 5.74 mg/L; 1090.01 μg/gram; 753.90 μg/gram; 520.89 ng/mL; 231.97 μg/dL, treatment with mangiferin in chitosan-alginate nanoparticles 50 mg/KgBW (p < 0.05) reduced those parameters 3.34 mg/L; 1703.92 μg/gram; 759.2 μg/gram; 559.48 ng/mL; 235.70 μg/dL. There is no significant difference in SGOT and SGPT activities. Conclusions: Mangiferin in chitosan-alginate nanoparticles was effective in preventing the increase of iron, ferritin, transferrin plasma levels, and iron levels in the liver and heart, but not prevent the increasing of SGOT and SGPT. The effectiveness of mangiferin in chitosan-alginate nanoparticles is not directly proportional to the dose."

"Kanker payudara masih menjadi masalah kesehatan global. Modalitas terapi yang digunakan untuk pasien kanker payudara diataranya agen kemoterapi doksorubisin (DOX). DOX digunakan untuk pengobatan kanker dengan mekanisme interkalasi DNA dan penghambatan topoisomerase II, serta penggunaannya mengalami resistensi. Bahan alam berpotensi digunakan untuk terapi kombinasi mengatasi resistensi doksorubisin. Bahan alam yang digunakan diantaranya dari jahe merah yang mengandung 6-shogaol. Senyawa 6-Shogaol sebagai agen kemoterapi yang meregulasi ekspresi gen yang berhubungan dengan proses proliferasi sel. Pada penelitian ini dilakukan analisis ekspresi gen pada basis data Gene Expression Omnibus (GEO) terkait pengobatan doksorubisin (GSE124597) dan pemberian 6-shogaol (GSE36973) dengan tujuan mengetahui perbandingan pola ekspresi gen yang dipengaruhi keduanya terhadap sel kanker payudara MCF7. Dilakukan juga anotasi fungsi gen yang diekspresikan menggunakan Gen Ontologi (GO) dan KEGG, jejaring farmakologi menggunakan basis data STITCH, serta simulasi penambatan molekuler untuk mengetahui mekanisme kerja antikanker. Sifat antikanker doksorubisin, 6-shogaol, dan ekstrak jahe merah kemudian  dikonfirmasi secara invitro meggunakan metode MTT. Hasil analisis Diffrential Expression Genes (DEG) menghasilkan 227 DEG yang sama (DEG bersama) akibat pemberian doksorubisin dan 6-shogaol. Hasil anotasi fungsi gen dengan GO menunjukkan dari 227 DEG terkait dengan proliferasi sel melalui jalur TP53.Demikian juga terkait hasil analisis jejaring farmakologi menunjukkan doksorubisin dan 6-shogaol terhubung dengan protein TP53. Hasil analisis interaksi protein-protein (PPi) menunjukkan jalur persinyalan TP53 terhubung dengan protein CDKN1A, GADD45A, DDIT3 dan CXCL12. Penambatan molekuler senyawa doksorubisin dan 6-shogaol pada protein TP53 menghasilkan energi ikatan berturut-turut -7.97 kcal/mol dan -6.05 kcal/mol. Nilai IC50 senyawa doksorubisin, 6-shogaol, dan ekstrak jahe pada sel MCF-7 berturut-turut adalah: 15.45 µg/ml, 61.24 µg/ml dan 144.99 µg/ml. Hal ini menunjukkan 6-shogaol dapat digunakan sebagai kandidat komplementer antikanker pada sel MCF-7.

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Breast cancer is still a global health problem. Therapeutic modalities used for breast cancer patients include the chemotherapeutic agent doxorubicin (DOX). DOX is used for the treatment of cancer with DNA intercalation mechanisms and topoisomerase II inhibition, and its use has experienced resistance, so a combination therapy of natural ingredients is needed. The natural ingredients used include red ginger which contains 6-shogaol. 6-Shogaol compound as a chemotherapeutic agent that regulates gene expression related to cell proliferation processes. In this study, gene expression analysis was carried out on the Gene Expression Omnibus (GEO) database related to doxorubicin treatment (GSE124597) and 6-shogaol administration (GSE36973) with the aim of knowing a comparison of gene expression patterns affected by both of them on MCF7 breast cancer cells. Functional annotations of expressed genes were also performed using Gene Ontology (GO) and KEGG, pharmacological networks using the STITCH database, as well as molecular docking simulations to determine the mechanism of anticancer action. The anticancer properties of doxorubicin, 6-shogaol, and red ginger extract were then confirmed in vitro using the MTT method. The results of the Differential Expression Genes (DEG) analysis yielded the same 227 DEGs as a result of doxorubicin and 6-shogaol administration. The results of gene function annotations with GO showed that 227 DEGs were related to cell proliferation through the TP53 pathway. Likewise, the results of pharmacological network analysis showed that doxorubicin and 6-shogaol were linked to the TP53 protein. The results of protein-protein interaction (PPi) analysis showed that the TP53 signaling pathway was connected to the CDKN1A, GADD45A, DDIT3 and CXCL12 proteins. Molecular docking of the compounds doxorubicin and 6-shogaol to the TP53 protein produces a binding energy of -7.97 kcal/mol and -6.05 kcal/mol, respectively. The IC50 values ​​of doxorubicin, 6-shogaol, and ginger extract in MCF-7 cells were: 15.45 µg/ml, 61.24 µg/ml and 144.99 µg/ml, respectively. This shows that 6-shogaol can be used as a complementary anticancer candidate in MCF-7 cells."

"Tuberkulosis (TBC) masih menjadi penyebab utama kematian akibat penyakit menular oleh adanya infeksi. Rifampisin dan isoniazid adalah obat lini pertama yang paling efektif melawan infeksi Mycobacterium tuberculosis. Deteksi resistansi OAT yang tepat, akurat, dan komprehensif, serta pemilihan sampel diperlukan untuk memastikan diagnosis penyakit tuberkulosis pasien. Penelitian ini bertujuan untuk menganalisis perbandingan hasil targeted drug sequencing dari hasil dekontaminasi sputum dengan isolat Mycobacterium tuberculosis dan mengetahui kesesuaian DST fenotipik MGIT, genotipik GeneXpert dalam mendeteksi resistansi rifampisin dan isoniazid. Sampel penelitian ini adalah sampel sputum yang sudah ada hasil GeneXpert positif dan isolate kultur dengan hasil DST MGIT. Hasil dekontaminasi sputum langsung dan kultur positif dari sampel yang sama dilakukan targeted drug sequencing dengan Oxford Nanopore technology menggunakan flowcell MinION Mk1B. Hasil penelitian menunjukkan bahwa pada target gen rpoB pada 5 dari 6 sampel isolat kultur memberikan hasil gen resistan rpoB dan 1 undetermined. Pada sebagian besar dekontaminasi sputum yaitu 5 dari 6 sampel juga memberikan hasil resistan terhadap rpoB dan 1 dekontaminasi sputum yang undetermined. Hasil resistansi obat isoniazid didapatkan pada target gen inhA sebanyak 5 dari 6 isolat kultur memberikan hasil sensitif pada inhA dan 1 isolat undetermined. Sedangkan pada dekontaminasi sputum 4 dari 6 sampel memberikan hasil sensitif pada inhA dan 2 undetermined. Lalu, pada target gen katG terdapat 3 dari 6 isolat kultur memberikan hasil sensitif, 2 isolat resistan, dan 1 undetermined. Sedangkan pada dekontaminasi sputum memberikan 2 hasil sensitif, 2 hasil resistan, dan 2 hasil undetermined. Metode targeted drug sequencing dapat dilakukan dari sampel hasil dekontaminasi sputum dan isolat. Keberhasilan banyak didapatkan dari hasil kultur dibandingkan dekontaminasi sputum. Pemeriksaan dengan targeted drug sequencing memberikan hasil yang sesuai dengan hasil DST MGIT dan GeneXpert untuk deteksi gen resisten Rifampisin (rpoB) dan Isoniazid (inhA dan katG).

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Tuberculosis (TBC) is still the main cause of death due to infectious diseases. Rifampicin and isoniazid are the most effective first-line drugs against Mycobacterium tuberculosis infection. Precise, accurate and comprehensive detection of OAT resistance, as well as sample selection are needed to confirm the patient's diagnosis of tuberculosis. This study aims to compare the results of targeted drug sequencing from sputum decontamination results with Mycobacterium tuberculosis isolates and determine the suitability of MGIT phenotypic and GeneXpert genotypic DST in detecting rifampicin and isoniazid resistance. The samples for this study were sputum samples that had positive GeneXpert results and culture isolates with DST MGIT results. The results of direct sputum decontamination and positive culture from the same sample were subjected to targeted drug sequencing with Oxford Nanopore technology using a MinION Mk1B flowcell. The results showed that for the rpoB gene target, the majority of culture isolates from 5 of the 6 culture isolate samples gave rpoB resistance gene results and 1 was undetermined. In the majority of sputum decontamination, 5 out of 6 samples also gave resistance to rpoB and 1 sputum decontamination was undetermined. Isoniazid drug resistance results were obtained for the inhA gene target, 5 of the 6 culture isolates gave sensitive results for inhA and 1 isolate was undetermined. Meanwhile, in sputum decontamination, 4 of the 6 samples gave sensitive results for inhA and 2 were undetermined. Then, for the katG gene target, 3 of the 6 culture isolates gave sensitive results, 2 isolates were resistant, and 1 was undetermined. Meanwhile, sputum decontamination gave 2 sensitive results, 2 resistant results, and 2 undetermined results. The targeted drug sequencing method can be carried out from samples resulting from decontamination of sputum and isolates. Much success comes from culture results rather than sputum decontamination. Examination with targeted drug sequencing provided results that were in accordance with the results of DST MGIT and GeneXpert for the detection of Rifampicin (rpoB) and Isoniazid (inhA, and katG) resistance genes."

"World Health Organization (WHO) menetapkan bakteri ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, dan Enterobacter spp.) sebagai patogen prioritas untuk dapat ditangani secara tepat terkait tingginya tingkat resistansi antibiotik yang dimiliki. Seftriakson merupakan antibiotik golongan sefalosporin yang bekerja menghambat sintesis dinding sel bakteri dan merupakan antibiotik pilihan terakhir dalam menangani infeksi K. pneumoniae. Resistansi seftriakson pada K. pneumoniae telah banyak dilaporkan dan salah satu penyebabnya adalah diproduksinya enzim β-laktamase yang dikode oleh gen blaCTX-M, blaSHV dan blaTEM. Dalam penelitian ini, dilakukan karakterisasi gen gen blaCTX-M, blaSHV dan blaTEM pada 12 isolat klinis K. pneumoniae dan menganalisis kesesuaiannya dengan sifat fenotipenya terhadap seftriakson. Dari hasil penelitian diperoleh bahwa gen blaCTX-M dan blaTEM terdeteksi pada 11 isolat (91,67%) dan blaSHV terdeteksi pada 9 isolat (75%), dengan kombinasi terdeteksinya 3 gen ditemukan pada 8 isolat (66,67%) dengan nilai MIC resistan > 64 μg/mL yang lebih tinggi dibandingkan dengan isolat yang hanya memiliki kombinasi 2 gen saja (blaCTX-M dan blaTEM atau blaTEM dan blaSHV). Tipe TEM-1 (100%), CTX-M-15 (91,67%), SHV-1 (33,33%) dan SHV-28 (33,33%) merupakan tipe gen bla yang paling banyak ditemukan. Keseluruhan gen juga menunjukkan adanya perubahan asam amino dibandingkan dengan isolat standar dimana perubahan ini menurunkan jumlah ikatan hidrogen dan meningkatkan energi bebas Gibbs sehingga menurunkan afinitas molekul enzim β-laktamase yang dikode oleh antibiotik seftriakson.

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The World Health Organization (WHO) has identified ESKAPE bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter) as priority pathogens due to their high levels of antibiotic resistance. Ceftriaxone, a cephalosporin antibiotic, inhibits bacterial cell wall synthesis and is considered a last-resort antibiotic for treating K. pneumoniae infections. Resistance to ceftriaxone in K. pneumoniae has been widely reported, with one of the causes being the production of β-lactamase enzymes encoded by blaCTX-M, blaSHV, and blaTEM genes. In this study, we characterized the blaCTX-M, blaSHV, and blaTEM genes in 12 clinical isolates of K. pneumoniae and analyzed their relation with phenotypic resistance to ceftriaxone. Our findings revealed that blaCTX-M and blaTEM genes were detected in 11 isolates (91.67%), while blaSHV was detected in 9 isolates (75%). The combination of all three genes was found in 8 isolates (66.67%), exhibiting higher MIC values > 64 μg/mL compared to isolates with only two gene combinations (blaCTX-M and blaTEM, or blaTEM and blaSHV). The predominant gene types identified were TEM-1 (100%), CTX-M-15 (91.67%), SHV-1 (33.33%), and SHV-28 (33.33%). Furthermore, amino acid changes were observed in all genes compared to standard isolates. These changes reduced hydrogen bonding and increased Gibbs free energy, thereby decreasing the enzyme affinity for ceftriaxone molecules encoded by β-lactamase."

"Hipertensi telah diidentifikasi sebagai risiko kesehatan global yang signifikan, yang sering kali mengarah pada kerusakan ginjal dan penyakit ginjal stadium akhir. Tujuan dari penelitian ini yaitu menganalisis efek Doksisiklin terhadap terjadinya hipertensif nefropati pada tikus hipertensi kronik yang diinduksi DOCA+salt dan uninefrektomi, pada fungsi ginjal dan biomarker ekspresi gen yang diperiksa dengan studi bioinformatika. Metode yang digunakan pada penelitian ini meliputi analisis in-silico dengan penyaringan database, interaksi protein-protein, analisis pengayaan fungsional, penambatan molekuler, dinamika molekuler, desain dan validasi primer, uji ekspresi gen dengan qRT-PCR, dan uji fungsi ginjal (ureum, kreatinin). Dari hasil penyaringan gen dari dua database yaitu Comparative Toxicogenomics Database (CTD) dan GSE37460 didapatkan 47 gen yang terkait dengan hipertensif nefropati. Dari 47 gen dilakukan analisis in-silico didapatkan dua gen yang potensial untuk menjadi biomarker yaitu AGTR1 dan ACE2. Hasil analisis ekspresi gen dengan qRT-PCR didapatkan hasil bahwa ada penurunan ekspresi dari gen AGTR1 dan ACE2 pada kelompok tikus hipertensi yang diinduksi DOCA+salt serta Doksisiklin dosis 15 mg/kg BB dan 30 mg/kg BB. Selain itu, terdapat perbedaan yang signifikan (p<0.05) dari kadar ureum dari kelompok DOCA+salt dan Doksisiklin dosis 30 mg/kg BB. Terdapat perbedaan yang signifikan (p<0.05) kadar kreatinin pada kelompok tikus dengan perlakuan Doksisiklin 30 mg/kg BB dan irbesartan. Meskipun ada perbedaan yang signifikan namun kadar ureum dan kreatinin masih dalam batas normal. Dalam penelitian ini, dapat disimpulkan bahwa adanya penurunan biomarker gen AGTR1 dan ACE2 pada kelompok hipertensi dapat disebabkan karena kondisi ginjal yang masih normal dikarenakan hasil tes fungsi ginjal menunjukkan nilai yang normal sehingga biomarker ekspresi gen tidak meningkat secara signifikan.

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Hypertension has been identified as a significant global health risk, often leading to kidney damage and end-stage renal disease. This study aimed to analyze the effects of doxycycline on the occurrence of hypertensive nephropathy in chronic hypertensive rats induced by DOCA+salt and uninephrectomy, focusing on kidney function and gene expression biomarkers examined through bioinformatics studies. The methods used in this research included in-silico analysis with database screening, protein-protein interaction, functional enrichment analysis, molecular docking, molecular dynamics, primer design and validation, gene expression testing with qRT-PCR, and kidney function tests (urea and creatinine). Gene screening from two databases, namely the Comparative Toxicogenomics Database (CTD) and GSE37460, identified 47 genes associated with hypertensive nephropathy. From these 47 genes, in-silico analysis identified two potential biomarker genes, AGTR1 and ACE2. Gene expression analysis using qRT-PCR revealed a decrease in the expression of AGTR1 and ACE2 genes in the hypertensive rat groups induced by DOCA+salt and treated with doxycycline at doses of 15 mg/kg BW and 30 mg/kg BW. Furthermore, a significant difference (p < 0.05) was observed in the urea levels between the DOCA+salt group and the group treated with doxycycline at a dose of 30 mg/kg BW. A significant difference (p < 0.05) in creatinine levels was also observed between the doxycycline 30 mg/kg BW group and the irbesartan group. Despite these significant differences, urea and creatinine levels remained within the normal range. This study concluded that the decreased expression of the AGTR1 and ACE2 biomarkers in the hypertensive groups might be due to normal kidney conditions, as kidney function test results remained within normal limits, preventing a significant increase in gene expression biomarkers."