Liver fibrosis is a major consequence of chronic liver disease, where excess extracellular matrix is deposited, due caused by the activation of hepatic stellate cells (HSCs). The suppression of ...collagen production in HSCs is therefore regarded as a therapeutic target of liver fibrosis. The present study investigated effects of harmine, which is a β-carboline alkaloid and known as an inhibitor of dual-specificity tyrosine-regulated kinases (DYRKs), on the production of collagen in HSCs. LX-2 cells, a human HSC cell line, were treated with harmine (0–10 μM) for 48 h in the presence or absence of TGF-β1 (5 ng/ml). The expression of collagen type I α1 (COL1A1) and DYRK isoforms was investigated by Western blotting, quantitative RT-PCR, or immunofluorescence. The influence of knockdown of each DYRK isoform on the COL1A1 expression was further investigated. The expression of COL1A1 was markedly increased by treating with TGF-β1 for 48 h in LX-2 cells. Harmine (10 μM) significantly inhibited the increased expression of COL1A1. LX-2 cells expressed mRNAs of DYRK1A, DYRK1B, DYRK2, and DYRK4, although the expression of DYRK4 was much lower than the others. Knockdown of DYRK1B, but not DYRK1A or DYRK2, with siRNA significantly suppressed TGF-β1-induced increase in COL1A1 expression. These results suggest that harmine suppresses COL1A1 expression via inhibiting DYRK1B in HSCs and therefore might be effective for the treatment of liver fibrosis.
•Harmine suppressed the production of collagen induced by TGF-β1 in LX-2 cells.•LX-2 cells expressed mRNAs of DYRK1A, DYRK1B, and DYRK2.•DYRK1B knockdown suppressed the production of collagen 1A1 induced by TGF-β1 in LX-2 cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The impact of co-infection with other pathogenic microorganisms after initiation of treatment for Mycobacterium avium complex pulmonary disease (MAC-PD) has not been clearly described. This study ...sought to clarify the clinical outcomes of co-infection with MAC after antimycobacterial therapy for MAC.
Co-infection status was defined as the detection of pathogenic microorganisms other than MAC in at least two consecutive sputum cultures 6-24 months after initiation of treatment. Chest computed tomography (CT) findings and culture results were compared between co-infection and MAC alone groups.
The co-infection and MAC alone groups comprised 12 and 36 patients, respectively. The proportion of patients with sputum culture positive for MAC after 24 months of therapy did not differ significantly between the two groups 25% (3/12) vs. 16.7% (6/36); p = 0.671. The proportion of patients with improved chest CT score after 24 months of starting treatment compared to baseline was significantly lower for the co-infection group than for the MAC alone group 16.7% (2/12) vs. 79.4% (27/34); p < 0.001. In the co-infection group, median CT score values at 12 and 24 months did not differ from baseline. However, the MAC alone group showed significant improvement at 12 and 24 months compared with baseline.
In the patient group with co-infection of other pathogenic microorganisms after treatment initiation for MAC there was no impact on therapeutic efficacy compared to the MAC alone group. However, therapeutic intervention interfered with improvement in chest CT findings such as nodule formation, bronchiectasis, infiltration, and cavitary lesions.
Background: The optimal bronchoscopy procedure for diagnosis of pulmonary nontuberculous mycobacteria (NTM) infection is unclear. Objective: This study investigated the usefulness of bronchial ...brushing in bronchoscopy for diagnosis of pulmonary NTM infection in patients with suspected NTM lung disease and nodular bronchiectasis on chest computed tomography (CT) images. Methods: Bronchoscopy was prospectively performed for 69 patients with clinically suspected pulmonary NTM infection on chest CT from December 2017 through December 2019. Before and after bronchial brushing, bronchial washing was performed with 20 or 40 mL of normal sterile saline at the same segmental or subsegmental bronchi. Before and after bronchial brushing, samples of the washing fluid (pre- and postbrushing samples) and brush deposits (brush samples) were obtained and cultured separately. Results: NTM was detected in 37 of the 69 (53.6%) patients (Mycobacterium avium in 27, Mycobacterium intracellulare in 7, M. abscessus in 2, and M. kansasii in 2). NTM was detected in 34 (49.3%) prebrushing samples, in 27 (39.1%) postbrushing samples, and in 20 (29.0%) brush samples from the 69 patients. In 2 (2.9%) patients, NTM was detected only in postbrushing samples; in 1 (1.4%) patient, NTM was detected only in a brush sample. As compared with bronchial washing only, additional bronchial brushing increased the NTM culture-positive rate by 4.3% (3/69). Bronchial brushing caused bleeding, requiring hemostasis in 5 (7.2%) patients. Conclusion: Additional bronchial brushing increased the NTM culture-positive rate by only 4.3% (3/69), as compared with bronchial washing alone. Thus, the usefulness of brushing appears to be limited.
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