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Lismayana
"Latar belakang
Infeksi SARS-CoV-2 menyebabkan morbiditas dan mortalitas yang tinggi di seluruh dunia. Terapi yang tersedia saat ini yaitu deksametason dosis tinggi, dapat menurunkan derajat inflamasi, namun dengan efek samping yang cukup berat. Oleh karena itu, diperlukan bahan tambahan terhadap deksametason untuk mengatasi penyakit COVID-19. C. tinctorius diketahui memiliki efek antiinflamasi pada berbagai model kerusakan paru. Penelitian ini bertujuan untuk mengetahui pengaruh ekstrak etanol bunga kasumba turate (Carthamus tinctorius) terhadap inflamasi paru mencit yang diinduksi SARS-CoV-2 spike protein.
Metode : C. tinctorius diekstraksi dengan etanol dan dilakukan identifikasi senyawa menggunakan GC-MS. Sebanyak 30 ekor mencit diinduksi dengan SARS-CoV-2 spike protein secara intratrakeal dan fludarabin intraperitoneal, sedangkan 6 ekor sisanya sebagai sham treatment. Mencit yang diinduksi dengan SARS-CoV-2 spike protein dibagi secara acak menjadi 5 kelompok yaitu kelompok kontrol, perlakuan (deksametason, kombinasi deksametason dengan C. tinctorius dosis 400 mg/kgBB dan 800 mg/kgBB dan C. tinctorius tunggal) yang diberikan terapi selama 6 hari. Hari ke 7 dilakukan terminasi, selanjutnya dilakukan pemeriksaan hematologi, pengamatan kerusakan jaringan dan inflamasi melalui pemeriksaan IL-6, IL-10, CD11c, CD14, CD4, NFĸB p50 pada jaringan paru, TNFα dan IFNg pada bilasan bronkoalveolar.
Hasil : Identifikasi senyawa ekstrak etanol bunga kasumba turate memiliki 21 senyawa. Mencit yang diinduksi dengan SARS-CoV-2 spike protein + fludarabin memperlihatkan histologi paru yang dipenuhi dengan infiltrasi sel mononuklear dan cairan bilasan bronkoalveolar didominasi oleh sel makrofag. Pemberian kombinasi deksametason + C. tinctorius 800 mg/kg BB memberikan perbaikan lebih besar dari seluruh kelompok terapi yang diberikan, yang ditunjukkan dengan dan penurunan granulosit yang mendekati normal, neutrophil lymphocyte ratio (NLR) yang menurun, perbaikan pada gambaran histologi, penurunan IL-6, CD11c, CD14 serta peningkatan IL-10, IFNg dan NFĸB (p50)
Kesimpulan : Pemberian terapi kombinasi deksametason dan ekstrak etanol bunga C. tinctorius dosis 800 mg/kg BB mampu memperbaiki inflamasi paru pada mencit yang diinduksi SARS-CoV-2 spike protein dan fludarabin, dengan cara memperbaiki keseimbangan sitokin proinflamasi dan sitokin antiinflamasi.

Background: The SARS-CoV-2 infection has caused high morbidity and mortality worldwide. The currently available treatment, namely high-dose dexamethasone, can reduce the degree of inflammation, but it comes with worrisome adverse effects. Therefore, additional medicines are needed to address the problem with dexamethasone treatment in COVID-19. Carthamus tinctorius is known to have anti-inflammatory effects in various models of pulmonary damage. Thus, this study aimed to determine the effect of C. tinctorius flower extract on lung inflammation in mice induced by the SARS-CoV-2 spike protein.
Method: C. tinctorius was extracted with ethanol, and the active compounds were identified using GC-MS. The experiment was carried out on 36 Balb/c mice aged 12 weeks. A total of 30 mice were induced with SARS-CoV-2 spike protein intratracheally and fludarabin intraperitoneally, while 6 mice were given sham treatment. Randomly, the SARS-CoV-2 spike protein-induced mice were split into 5 groups, which were: a control group that didn't get any treatment (SarsF), treatment (dexamethasone, a combination of dexamethasone with C. tinctorius doses of 400 mg/kgBW and 800 mg/kgBW and C. tinctorius alone). Drug treatment was given for 6 days. On the 7th day, termination was carried out, then observations of haematological evaluation, tissue damage and inflammation through the evaluation of IL-6, IL-10, CD11c, CD14, CD4, NFĸB p50 in lung tissue and TNFα and IFNg in BALF.
Results: It is known that the flower extract produced by C. tinctorius contains 21 compounds. Mice induced with SARS-CoV-2 spike protein and fludarabin displayed lung histology filled with mononuclear cell infiltration and the bronchoalveolar lavage fluid was dominated by macrophage cells. The combination of dexamethasone and C. tinctorius at 800 mg/kg BW provided greater improvement than all the treatment groups given, as indicated by a decrease in granulocytes that approached normal, a decreased neutrophil lymphocyte ratio (NLR), improvement in histology, decreased IL-6, CD11c, and CD14, as well as increased IL-10, IFN-g and NF-ĸB (p50).
Conclusion : Mice with lung inflammation caused by the SARS-CoV-2 spike protein and fludarabine responded well to a combination therapy of dexamethasone and ethanol extract of C. tinctorius flowers at a dose of 800 mg/kg BW. This regimen of treatment acts by improving the balance of pro-inflammatory and anti-inflammatory cytokines.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2023
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UI - Disertasi Membership  Universitas Indonesia Library
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Mia Elhidsi
"Kanker paru memiliki mortalitas tinggi dan sering terdiagnosis pada stage lanjut. Kelainan morfologis sel trakeobronkial dan biomolekuler mendahului proses karsinogenesis. Bronkoskopi gelombang cahaya spektrum sempit (GCSS) dikembangkan untuk meningkatkan akurasi diagnostik. Tujuan penelitian ini adalah untuk mengetahui akurasi diagnostik bronkoskopi GCSS dalam mendeteksi kelainan morfologis sel trakeobronkial dan hubungannya dengan mutasi gen p53.
Studi ini merupakan studi diagnostik eksperimental yang dilakukan pada subjek kanker paru yang menjalani prosedur bronkoskopi di RS Persahabatan periode Januari-November 2023. Prosedur bronkoskopi GCSS dan biopsi forseps bronkus dilakukan di lesi non-tumor, dilanjutkan dengan pemeriksaan histopatologi hematoksilin dan eosin (HE), serta pemeriksaan Polymerase Chain Reaction (PCR) sekuensing sanger mutasi p53 pada titik R175L, R248W, dan R273C. Analisis kesesuaian juga dilakukan.
Sebanyak 105 subjek diikutsertakan dalam analisis penelitian, dengan dominasi laki-laki, perokok, jenis kanker adenokarsinoma dan stage lanjut. Kelainan morfologis sel trakeobronkial ditemukan pada 34 subjek (32,4%) berupa metaplasi, sel atipik dan sel tumor. Mutasi p53 wild type pada titik R175L, R248W, dan R273C ditemukan pada seluruh jaringan biopsi. Satu jaringan metaplasi dengan mutasi p53 Kodon 267 heterozigot CT dan satu jaringan hiperplasi dengan mutasi p53 Kodon 180 heterozigot GC. Pola vaskular berliku didapatkan sebagai kriteria diagnostik paling baik dibandingkan dengan pola vaskular lainnya dengan area under the curve (AUC) 78,4%; sensitivitas 79,41%; spesifisitas 77,46%; nilai prediktif positif 62,8% dan nilai prediktif negatif 88,7%. Kesesuaian antar pengamat dalam menilai pola vaskular GCSS cukup baik dengan nilai kappa 0,88 (standar eror 0,06; nilai p <0,01). Mukosa edematosa berhubungan dengan pola vaskular berliku pada bronkoskopi GCSS dengan OR 3,6 (IK95% 1,53-8,46; nilai p <0,01). Subjek dengan pola vaskular berliku [OR 21,89 (IK95% 6,50-73,71; nilai p<0,01)] dan subjek dengan IB ³ 600 [OR 5,39 (IK95% 1,62-17,71; nilai p 0,01)] berhubungan dengan kelainan morfologis sel trakeobronkial.

Lung cancer has high mortality and is often diagnosed at an advanced stage. Additionally, morphological abnormalities of tracheobronchial cells precede the carcinogenesis process and are based on molecular abnormalities. Moreover, Narrow-Band Imaging Bronchoscopy (NBI) has been developed to improve diagnostic accuracy. The objective of this study is to determine the diagnostic accuracy of NBI bronchoscopy in detecting morphological abnormalities of tracheobronchial cells and their relationship with p53 gene mutations.
This study is an experimental diagnostic study conducted on lung cancer subjects undergoing bronchoscopy procedures at RS Persahabatan from January to November 2023. NBI bronchoscopy procedures and bronchial forceps biopsies were performed on non-tumor lesions, followed by haematoxylin and eosin (HE) histopathological examination, as well as Polymerase Chain Reaction (PCR) Sanger sequencing for p53 mutations at the R175L, R248W, and R273C points. Reliability analysis was also performed.
A total of 105 subjects were included in the study analysis, predominantly male, smokers, with adenocarcinoma type cancer and advanced stage. Tracheobronchial cell morphological abnormalities were found in 34 subjects (32.4%), in the form of metaplasia, atypical cells, and tumor cells. Wild type p53 mutations at the R175L, R248W, and R273C points were found in all biopsy tissues. One metaplastic tissue had a p53 Codon 267 CT heterozygous mutation and one hyperplastic tissue had a p53 Codon 180 GC heterozygous mutation. The tortuous vascular pattern was identified as the best diagnostic criteria compared to other patterns with an area under the curve (AUC) of 78.4%; sensitivity 79.41%; specificity 77.46%; positive predictive value 62.8% and negative predictive value 88.7%. Inter-observer agreement in assessing vascular patterns was good with a kappa value of 0.88 (standard error 0.06; p-value <0.01). Edematous mucosa was associated with a tortuous vascular pattern on NBI bronchoscopy with an OR of 3.6 (95% CI 1.53-8.46; p-value <0.01). Subjects with a tortuous vascular pattern (OR of 21.89; 95% CI 6.50-73.71; p-value <0.01) and subjects with IB ≥ 600 (OR of 5.39; 95% CI 1.62-17.71; p-value 0.01) were associated with tracheobronchial cell morphological abnormalities.
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Depok: Fakultas Kedokteran Universitas Indonesia, 2024
D-pdf
UI - Disertasi Membership  Universitas Indonesia Library