Our previous studies revealed a pivotal role of the chemokine stromal cell-derived factor (SDF)-1 and its receptors CXCR4 and CXCR7 on migratory behavior of polymorphonuclear granulocytes (PMNs) in pulmonary inflammation. Thereby, the SDF-1-CXCR4/CXCR7-axis was linked with adenosine signaling. However, the role of the SDF-1 receptors CXCR4 and CXCR7 in acute inflammatory peritonitis and peritonitis-related sepsis still remained unknown. The presented study provides new insight on the mechanism of a selective inhibition of CXCR4 (AMD3100) and CXCR7 (CCX771) in two models of peritonitis and peritonitis-related sepsis by injection of zymosan and fecal solution. We observed an increased expression of SDF-1, CXCR4, and CXCR7 in peritoneal tissue and various organs during acute inflammatory peritonitis. Selective inhibition of CXCR4 and CXCR7 reduced PMN accumulation in the peritoneal fluid and infiltration of neutrophils in lung and liver tissue in both models. Both inhibitors had no anti-inflammatory effects in A 2B knockout animals (A 2B-/-). AMD3100 and CCX771 treatment reduced capillary leakage and increased formation of tight junctions as a marker for microvascular permeability in wild type animals. In contrast, both inhibitors failed to improve capillary leakage in A 2B-/-animals, highlighting the impact of the A 2B-receptor in SDF-1 mediated signaling. After inflammation, the CXCR4 and CXCR7 antagonist induced an enhanced expression of the protective A 2B adenosine receptor and an increased activation of cAMP (cyclic adenosine mono phosphate) response element-binding protein (CREB), as downstream signaling pathway of A 2B. The CXCR4-and CXCR7-inhibitor reduced the release of cytokines in wild type animals via decreased intracellular phosphorylation of ERK and NFκB p65. In vitro, CXCR4 and CXCR7 antagonism diminished the chemokine release of human cells and increased cellular integrity by enhancing the expression of tight junctions. These protective effects were linked with functional A 2B-receptor signaling, confirming our in vivo data. In conclusion, our study revealed new protective aspects of the pharmacological modulation of the SDF-1-CXCR4/CXCR7-axis during acute peritoneal inflammation in terms of the two hallmarks PMN migration and barrier integrity. Both anti-inflammatory effects were linked with functional adenosine A 2B-receptor signaling.
Peritonitis and peritonitis-associated sepsis are characterized by an increased formation of platelet–neutrophil complexes (PNCs), which contribute to an excessive migration of polymorphonuclear neutrophils (PMN) into the inflamed tissue. An important neutrophilic mechanism to capture and kill invading pathogens is the formation of neutrophil extracellular traps (NETs). Formation of PNCs and NETs are essential to eliminate pathogens, but also lead to aggravated tissue damage. The chemokine receptors CXCR4 and CXCR7 on platelets and PMNs have been shown to play a pivotal role in inflammation. Thereby, CXCR4 and CXCR7 were linked with functional adenosine A2B receptor (Adora2b) signaling. We evaluated the effects of selective CXCR4 and CXCR7 inhibition on PNCs and NETs in zymosan- and fecal-induced sepsis. We determined the formation of PNCs in the blood and, in addition, their infiltration into various organs in wild-type and Adora2b−/− mice by flow cytometry and histological methods. Further, we evaluated NET formation in both mouse lines and the impact of Adora2b signaling on it. We hypothesized that the protective effects of CXCR4 and CXCR7 antagonism on PNC and NET formation are linked with Adora2b signaling. We observed an elevated CXCR4 and CXCR7 expression in circulating platelets and PMNs during acute inflammation. Specific CXCR4 and CXCR7 inhibition reduced PNC formation in the blood, respectively, in the peritoneal, lung, and liver tissue in wild-type mice, while no protective anti-inflammatory effects were observed in Adora2b−/− animals. In vitro, CXCR4 and CXCR7 antagonism dampened PNC and NET formation with human platelets and PMNs, confirming our in vivo data. In conclusion, our study reveals new protective aspects of the pharmacological modulation of CXCR4 and CXCR7 on PNC and NET formation during acute inflammation.
Kawasan RT.04 Kelurahan Baru Ulu, Kecamatan Balikpapan Barat, terletak di Kariangau bagian selatan yang mayoritas penduduknya berprofesi sebagai nelayan dan petambak ikan. Teknik budidaya ikan lele dalam ember masih tergolong inovasi baru dan relatif belum banyak diketahui masyarakat. Pengabdian masyarakat ini bertujuan memberikan informasi budidaya dengan teknik aquaponic. Teknik ini memiliki keunggulan dalam pemanfaatan lahan untuk budidaya ikan lele dan sayur sawi dengan menggunakan ember serta tidak memerlukan lahan luas. Budidaya ini menggunakan media yang cukup hemat seperti ember bekas, gelas plastik bekas, air yang sedikit, dan mudah dipindahkan. Kegiatan dilakukan bertahap sejak Februari - Juni 2021. Diawali dengan tahap survei, diskusi bersama masyarakat, pengadaan alat dan bahan, pelatihan, hingga evaluasi dan monitoring hasil budidaya. Berdasarkan monitoring yang dilakukan 4 minggu setelah praktik, didapatkan panjang ukuran ikan lele yang bervariasi antara 9 - 12,5 cm. Hasil budidaya ini berhasil dimanfaatkan untuk memenuhi kebutuhan pangan harian masyarakat. Meskipun masih membutuhkan pengelolaan dan modal yang lebih besar agar dapat menjadi alternatif pencaharian, metode budidaya ini cukup menambah aktivitas dan hiburan di kalangan masyarakat selama masa pandemi Covid-19.
Berdasarkan hasil observasi dan wawancara yang dilaksanakan di SMK Negeri 1 Lingsar pada tanggal 20 November 2021, peneliti menemukan beberapa masalah yang dihadapi sekolah terkhusus pada pembelajaran Bahasa Indonesia, yaitu Guru masih mengunakan media cetak seperti buku paket, pengunaan TIK dalam pembelajaran belum maksimal, masih kurangnya guru dalam memanfaatan fasilitas yang telah tersedia di sekolah. Adapun tujuan dari penelitian ini adalah Untuk Mengetahui Pengaruh Penggunaan Explainer Video Tehadap Motivasi Belajar Siswa Pada Mata Pelajaran Bahasa Indonesia Kelas X UPW di SMKN 1 Lingsar Kabupaten Lombok Barat Tahun Pelajaran 2021/2022. Metode pengumpulan data yang digunakan dalam penelitian ini adalah angket sebagai metode pokok, observasi, wawancara dan dokumentasi sebagai metode pelengkap. Teknik analisis data menggunakan analisis statistik dengan rumus chi square. Hasil analisis diperoleh nilai = 26,735 sedangkan nilai chi square dalam tabel dengan db= 4 dengan taraf signifikansi 5% = 9,488 dengan demikian bahwa nilai chi square analisis lebih besar daripada nilai chi square tabel (26,735> 9,488). Sungguh dapat disimpulan bahwa hasil penelitian ini “signifikan”.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.