Browsing by Author "Wang, Xing"

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    The ATP-Dependent Protease ClpP Inhibits Biofilm Formation by Regulating Agr and Cell Wall Hydrolase Sle1 in Staphylococcus aureus
    (Frontiers, 2017-05-15) Liu, Qian; Wang, Xing; Qin, Juanxiu; Cheng, Sen; Yeo, Won-Sik; He, Lei; Ma, Xiaowei; Liu, Xiaoyun; Li, Min; Bae, Taeok; Microbiology and Immunology, School of Medicine
    Biofilm causes hospital-associated infections on indwelling medical devices. In Staphylococcus aureus, Biofilm formation is controlled by intricately coordinated network of regulating systems, of which the ATP-dependent protease ClpP shows an inhibitory effect. Here, we demonstrate that the inhibitory effect of ClpP on biofilm formation is through Agr and the cell wall hydrolase Sle1. Biofilm formed by clpP mutant consists of proteins and extracellular DNA (eDNA). The increase of the protein was, at least in part, due to the reduced protease activity of the mutant, which was caused by the decreased activity of agr. On the other hand, the increase of eDNA was due to increased cell lysis caused by the higher level of Sle1. Indeed, as compared with wild type, the clpP mutant excreted an increased level of eDNA, and showed higher sensitivity to Triton-induced autolysis. The deletion of sle1 in the clpP mutant decreased the biofilm formation, the level of eDNA, and the Triton-induced autolysis to wild-type levels. Despite the increased biofilm formation capability, however, the clpP mutant showed significantly reduced virulence in a murine model of subcutaneous foreign body infection, indicating that the increased biofilm formation capability cannot compensate for the intrinsic functions of ClpP during infection.
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    Feasibility of Conducting Comparative Effectiveness Research and Validation of a Clinical Disease Activity Score for Chronic Nonbacterial Osteomyelitis
    (The Journal of Rheumatology, 2023) Wu, Eveline Y.; Oliver, Melissa; Scheck, Joshua; Lapidus, Sivia; Akca, Ummusen Kaya; Yasin, Shima; Stern, Sara M.; Insalaco, Antonella; Pardeo, Manuela; Simonini, Gabriele; Marrani, Edoardo; Wang, Xing; Huang, Bin; Kovalick, Leonard K.; Rosenwasser, Natalie; Casselman, Gabriel; Liau, Adriel; Shao, Yurong; Yang, Claire; Mosa, Doaa Mosad; Tucker, Lori; Girschick, Hermann; Laxer, Ronald M.; Akikusa, Jonathan D.; Hedrich, Christian; Onel, Karen; Dedeoglu, Fatma; Twilt, Marinka; Ferguson, Polly J.; Ozen, Seza; Zhao, Yongdong; Pediatrics, School of Medicine
    Objective: Prospective comparative effectiveness research (CER) in chronic nonbacterial osteomyelitis (CNO) is lacking. Our objectives were to (1) determine the use and safety of each consensus treatment plan (CTP) regimen for CNO, (2) assess the feasibility of using the Chronic Nonbacterial Osteomyelitis International Registry (CHOIR) data for CER, and (3) develop and validate a CNO clinical disease activity score (CDAS) using CHOIR. Methods: Consenting children or young adults with CNO were enrolled into CHOIR. Demographic, clinical, and imaging data were prospectively collected. The CNO CDAS was developed through a Delphi survey and nominal group technique. External validation surveys were administered to CHOIR participants. Results: One hundred forty (78.2%) CHOIR participants enrolled between August 2018 and September 2020 received at least 1 CTP regimen. Baseline characteristics from different CTP groups were well matched. Patient pain, patient global assessment, and clinical CNO lesion count were key variables included in the CNO CDAS. The CDAS showed a strong correlation with patient/parent report of difficulty using a limb, back, or jaw and patient/parent report of disease severity, but a weak correlation with patient/parent report of fatigue, sadness, and worry. The change in CDAS was significant in patients reporting disease worsening or improvement (P < 0.001). The CDAS significantly decreased after initiating second-line treatments from median 12.0 (IQR 8.0-15.5) to 5.0 (IQR 3.0-12.0; P = 0.002). Although second-line treatments were well tolerated, psoriasis was the most common adverse event. Conclusion: The CNO CDAS was developed and validated for disease monitoring and assessment of treatment effectiveness. CHOIR provided a comprehensive framework for future CER.
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    Modulating mitochondria with natural extract compounds: from bench to clinical therapeutic opportunities for COPD
    (Frontiers Media, 2025-05-21) Wang, Qiao; Zeng, Ziling; Guo, Linlin; Williams, Kent E.; Zhang, Yun; Tang, Hongmei; Hu, Hang; Qin, Gang; Wang, Kaijin; Wang, Xing; Microbiology and Immunology, School of Medicine
    Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease that leads to death and disability worldwide, and it is caused by hereditary and environmental factors. It is characterized by chronic inflammation, emphysema, and irreversible limitation of airflow. Dual or triple therapy with a traditional approach can provide relief from COPD symptoms by reducing the frequency and severity of the outbreaks, but there are no current therapies to reverse the long-term decline in lung function. Although ICS rescue inhalers demonstrate efficacy in acute attacks, these cannot be utilized for chronic management of COPD due to adverse effects. Therefore, novel agents and therapeutic strategies are urgently needed to address this disease. It is believed that malfunctioning mitochondria are associated with COPD pathogenesis, contributing to inflammation, apoptosis, and cellular senescence. A better understanding of these mechanisms could provide novel therapeutic approaches for maintaining lung and skeletal muscle function. Many natural extract compounds show therapeutic potential for COPD and are associated with few adverse reactions. Notably, these natural compounds can improve mitochondrial function and exhibit a variety of anti-inflammatory, antioxidant, and immunomodulatory properties. In this review, we systemically summarize the pathogenic role of impaired mitochondria in COPD and the potential mechanisms by which natural extract compounds may ameliorate these impairments.