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"PURPOSE: We previously reported that TU-100 suppresses irinotecan hydrochloride (CPT-11)-induced inflammatory cytokines and apoptosis. However, the mechanism underlying this effect has not been fully elucidated. The aim of this study was to further clarify the mechanism of CPT-11-induced bacterial translocation (BT) and the effect of TU-100 on BT.METHODS: Cell cytotoxicity was assessed in vitro by a WST-8 assay. For the in vivo experiments, rats were randomly divided into 3 groups: the control group, the CPT-11 group (250 mg/kg i.p. for 2 days), and the CPT-11 and TU-100 co-treated group (1000 mg/kg, p.o. for 5 days). All of the rats were sacrificed on day 6 and their tissues were collected.RESULTS: CPT-11 and TU-100 co-treatment improved CPT-11 the related cytotoxicity in vitro. All CPT-11-treated rats developed different grades of diarrhea and BT was observed in 80% of the rats. CPT-11 caused a significant increase in the expression of TLR4, IL-6, TNF-α, IL-1β and caspase-3 mRNAs in the large intestine. The expression of tight junction (TJ) marker mRNAs (occludin, claudin-1 and 4, and ZO-1) was significantly decreased in comparison to the control group. TU-100 co-treatment significantly reversed diarrhea, BT, and the expression of TLR2, IL-6, TNF-α, IL-1β and caspase-3, and improved the expression of occludin, claudin-4 and ZO-1.CONCLUSIONS: TU-100 can suppress the adverse effects associated with CPT-11 and improve the function of the TJ. It is possible that this occurs through the TLR pathway."

"Pendahuluan: Prevalensi periodontitis di Indonesia mencapai 74,1% berdasarkan data Riskesdas tahun 2018. Bakteri penyakit periodontitis dapat menembus lebih dalam ke jaringan sekitar gigi. Hal ini dapat memicu respons host dalam upaya bertahan melawan bakteri yang menyerang, salah satunya adalah respon dari TLR-2. Salah satu obat yang memiliki kandungan antiinflamasi dan saat ini sedang banyak diperhatikan oleh masyarakat adalah propolis. Tujuan: Meneliti interaksi dan afinitas antara senyawa pada propolis dengan reseptor Toll-Like Receptor 2 melalui studi penambatan molekuler. Metode: Studi in silico dengan penambatan molekuler untuk menguji interaksi molekuler dari ligan bahan aktif propolis terhadap reseptor TLR-2. Hasil interaksi yang didapat akan dianalisis dan diintrepretasikan untuk mengetahui afinitas ikatan dari interaksi antara ligan dengan reseptor. Hasil: terdapat interaksi antara ligan bahan aktif propolis terhadap reseptor TLR-2. Kesimpulan: Propolis berpotensi menjadi agen antibakteri pada terapi periodontitis yang dapat menghambat inflamasi melalui inaktivasi TLR-2. Namun, perlu dilakukan penelitian lebih lanjut secara in vitro untuk pengamatan lebih lanjut terkait interaksi yang terjadi.

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Background: The prevalence of periodontitis in Indonesia reached 74.1%. (Riskesdas, 2018). Periodontitis bacteria can penetrate deep into the gum. This can trigger a host response in an effort to defend against invading bacteria, including responses from TLR-2. Propolis has been shown to have antiinflammatory properties and is currently getting a lot of attention from the public. Purpose: To examine the interaction and affinity between compounds in propolis and the Toll-Like Receptor 2 receptor through molecular docking studies. Methods: To investigate the molecular interactions of propolis active ingredient ligands on the TLR-2 receptor, a molecular docking was conducted. The interaction results obtained will be analyzed and interpreted to determine the binding affinity of the interaction between the ligand and the receptor. Results: There is an interaction between the ligand of the active ingredient of propolis and the TLR-2 receptor. Conclusions: Propolis has the potential to be an antibacterial agent in periodontitis therapy that can inhibit inflammation through inactivation of TLR-2. However, further research needs to be carried out with in vitro studies to further observe the interactions that may occur."

"Background: Toll-like receptor is a pattern recognition receptor (PRR) that recognize pathogen-associated molecular pattern (PAMP) in a microorganism. Macrophages recognize the presence of mycobacteria through Toll-Like Receptor 2 (TLR2) and signaling further lead to the production of cytokines, both proinflammatory TNF-α, IL-1β, IL-6, IL-12, IL-15, IL-18 and IFN-γ, as well as anti-inflammatory IL4, IL-10 and TGF-β. TLR2 gene polymorphism is strongly determined by ethnicity and geography. Therefore it is necessary to uncovered the existence and association between Arg753Gln and Arg677Trp TLR2 gene polymorphism with TB susceptibility and its underlying mechanisms in Indonesian population in Bandung West Java. Methods: analytical observational study with cross-sectional design was conducted in Hasan Sadikin General Hospital Bandung from April 2011 to May 2012. Study population consisted of active pulmonary TB patient with positive AFB smear and Latent TB to ascertain previous MTb exposure. Polymorphism of gen Arg753Gln and Arg677Trp gene was determined with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Plasma levels of IFN-γ, TNF-α, IL-10 and IL-12 were also compared between active and latent TB group. Results: heterozygote Arg753Gln TLR2 gene polymorphism was found in 9 of 86 pulmonary TB subjects (10.5%) but none in the latent TB group. The Arg677Trp polymorphism was not found in both groups. The odds ratio for Arg753Gln existence was 28.07 (p=0.022). No differences in the levels of IFN-γ, TNF-α, IL-10 and IL-12 between active pulmonary TB and latent TB subjects with and without Arg753Gln TLR2 gene polymorphism. Conlusion: Arg753Gln polymorphism of TLR2 gene is a risk factor for active pulmonary TB while Arg677Trp polymorphism is not. The Increased risk is not mediated by the difference in IFN-γ, TNF-α, IL-10 and IL-12 serum levels.

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Latar belakang: Toll-like receptor (TLR) adalah reseptor pengenalan pola yang mengenali pola molekul terkait patogen dalam mikroorganisme. Makrofag mengenali adanya mikobakteri melalui Toll-Like Receptor 2 (TLR2) dan penanda lanjutan pada produksi sitokin, proinflammatory TNF-α, IL-1β, IL-6, IL-12, IL-15, IL-18 dan IFN-γ, serta anti-inflamasi IL4, IL-10 dan TGF-β. Polimorfisme gen TLR2 sangat ditentukan oleh etnisitas dan geografi, karenanya diperlukan analisis hubungan polimorfisme Arg753Gln dan Arg677Trp gen TLR2 dengan kerentanan menderita TB paru aktif dan peranan beberapa sitokin pada populasi Indonesia di Bandung Jawa Barat.

Metode: penelitian observasional analitik dengan rancangan potong lintang dilaksanakan pada periode April 2011–Mei 2012 di RS Dr. Hasan Sadikin Bandung. Populasi penelitian terdiri dari penderita TB paru aktif dengan BTA positif dan sebagai pembanding adalah TB laten. Adanya polimorfisme gen Arg753Gln dan Arg677Trp diperiksa dengan metode polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Kadar sitokin IFN-γ, TNF-α, IL-10, dan IL-12 juga dibandingkan antara kelompok TB aktif dan TB laten.

Hasil: polimorfisme heterozigot Arg753Gln gen TLR2 ditemukan pada 9 dari 86 (10.5%) penderita TB paru aktif dan tidak ditemukan pada TB laten. Pada kedua kelompok tidak ditemukan polimorfisme Arg677Trp. Odds Ratio untuk polimorfisme Arg753Gln adalah 28,07 (p=0,022). Tidak ditemukan perbedaan bermakna kadar sitokin IFN-γ, TNF-α, IL-10, dan IL-12 antara penderita TB paru dengan polimorfisme Arg753Gln dan penderita TB paru tanpa polimorfisme tersebut.

Kesimpulan: polimorfisme Arg753Gln gen TLR2 merupakan faktor risiko menderita TB paru pada populasi orang Indonesia di Bandung, sedangkan polimorfisme Arg677Trp gen TLR2 bukan. Peningkatan risiko ini tidak terkait dengan perubahan kadar IFN-γ, TNF-α, IL-10 maupun IL-12."

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Latar Belakang: Menurut data Riset Kesehatan Dasar (Riskesdas) 2018, prevalensi penyakit periodontitis menduduki peringkat kedua terbanyak setelah karies gigi, yaitu sebesar 74,1% di Indonesia. Periodontitis merupakan penyakit inflamasi yang dihubungkan dengan kerusakan jaringan periodontal. Dalam perjalanan periodontitis, TLR-4 berperan penting dalam respon imun dan patogenesis inflamasi periodontitis karena dapat mengenali bakteri gram negatif lipopolisakarida (LPS). Propolis merupakan salah satu zat alami berupa produk resin yang memiliki banyak aktivitas biologis, salah satunya antiinflamasi. Tujuan: Mengetahui interaksi molekuler senyawa propolis yang berpotensi sebagai antiinflamasi terhadap TLR-4 pada terapi periodontitis melalui studi penambatan molekuler. Metode: Studi eksperimental komputasional secara in silico menggunakan perangkat Autodock Tools 1.5.6 dan BIOVIA Discovery Studio Visualizer 2021 untuk menguji interaksi dan afinitas ikatan dari ligan propolis terhadap reseptor target TLR-4. Hasil interaksi akan dianalisis untuk menilai konformasi terbaik dari suatu molekul dan afinitas pengikatannya. Penambatan molekuler dilakukan dengan menambatkan 7 senyawa propolis yang berpotensi sebagai antiinflamasi terhadap TLR-4 sebagai reseptor yang berperan dalam proses inflamasi. Hasil: Terdapat interaksi molekuler ikatan antara ligan propolis dengan reseptor TLR-4. Dari ketujuh ligan propolis yang diuji, senyawa Adhyperforin memiliki afinitas terbaik dibandingkan ligan propolis lainnya. Kesimpulan: Senyawa bioaktif pada propolis dapat berinteraksi terhadap reseptor TLR-4 melalui uji penambatan molekuler dan dapat berpotensi menjadi agen antiinflamasi terhadap TLR-4 yang dapat digunakan sebagai kandidat obat untuk terapi periodontitis. Namun, perlu dilakukan penelitian lebih lanjut untuk membuktikan sifat senyawa bioaktif pada propolis yang dapat bertindak sebagai agen antiinflamasi yang baik untuk terapi periodontitis.

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Background: According to 2018 Basic Health Survey (Riskesdas) data, periodontitis is the second most frequent condition after dental caries, which reached a prevalence of 74.1% in Indonesia. Periodontitis is an inflammatory condition associated with the destruction of periodontal tissue. TLR-4, which recognizes gram-negative bacterial lipopolysaccharides (LPS), plays a crucial role in the immune response and inflammatory pathogenesis of periodontitis. Propolis is a natural product in the form of resin that has many biological activities, one of which is anti-inflammatory. Purpose: To investigate the molecular interactions of propolis compounds that have anti-inflammatory potential against TLR-4 in periodontitis therapy through molecular docking studies. Methods: In silico computational experimental study using Autodock Tools 1.5.6 and BIOVIA Discovery Studio Visualizer 2021 to test the interaction and binding affinity of propolis ligands towards the TLR-4 target receptor. The interaction results will be analyzed to assess the best conformation of a molecule and its binding affinity. Molecular docking was performed by targeting 7 propolis compounds that have anti-inflammatory potential against TLR-4 as a receptor that plays a role in the inflammatory process. Results: There is a binding interaction between propolis ligands and TLR-4 receptor. Of the seven propolis ligands tested, the compound Adhyperforin had the best affinity compared to other propolis ligand. Conclusions: Bioactive compounds in propolis can interact with TLR-4 receptors through molecular docking tests and can potentially become anti-inflammatory agents against TLR-4 that can be used as drug candidates for periodontitis therapy. However, further research is needed to prove the nature of bioactive compounds in propolis that can act as good anti-inflammatory agents for periodontitis therapy.

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