Article
Biochemistry & Molecular Biology
Apparao B. Kummarapurugu, Shuo Zheng, Abigail Pulsipher, Justin R. Savage, Jonathan Ma, Bruce K. Rubin, Thomas P. Kennedy, Judith A. Voynow
Summary: In this study, the synthetic compound GM-1111 showed effective anti-NE activity in CF sputum, facilitating DNA depolymerization and reducing sputum elasticity. These findings suggest that GM-1111 could be a promising therapeutic option for CF patients, with potential advantages over traditional unfractionated heparin.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Nidhi Sharma, Taslim B. Shaikh, Abhisheik Eedara, Madhusudhana Kuncha, Ramakrishna Sistla, Sai Balaji Andugulapati
Summary: Dehydrozingerone (DHZ) attenuates liver fibrosis by reducing fibrotic markers and their activities through modulation of the MAPK pathway. These findings suggest that DHZ may be a potential therapeutic molecule for treating liver fibrosis.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Licia Totani, Concetta Amore, Antonio Piccoli, Giuseppe Dell'Elba, Angelo Di Santo, Roberto Plebani, Romina Pecce, Nicola Martelli, Alice Rossi, Serena Ranucci, Ida De Fino, Paolo Moretti, Alessandra Bragonzi, Mario Romano, Virgilio Evangelista
Summary: This study demonstrates that PDE4 inhibitors can control NETosis in CF-relevant models, showing efficacy in neutrophils from both healthy volunteers and CF patients. In a mouse model of chronic Pseudomonas aeruginosa infection, aerosol treatment with the selective PDE4 inhibitor roflumilast resulted in reduced free DNA in the BALF along with decreased citrullination of histone H3 in neutrophils in the airways.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Satya Krishna Tirunavalli, Madhusudhana Kuncha, Ramakrishna Sistla, Sai Balaji Andugulapati
Summary: Sesamol attenuates pulmonary fibrosis by inhibiting the TGF-fi/periostin signaling pathway, improving lung function and reducing mortality.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Apparao B. Kummarapurugu, Shuo Zheng, Jonathan Ma, Shobha Ghosh, Adam Hawkridge, Judith A. Voynow
Summary: Neutrophil extracellular traps (NE) increase cystic fibrosis (CF) airway inflammation. This study found that NE triggers the release of macrophage extracellular traps (METs), thereby enhancing NE-induced CF airway inflammation.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Claudius Wagner, Anita Balazs, Jolanthe Schatterny, Zhe Zhou-Suckow, Julia Duerr, Carsten Schultz, Marcus A. Mall
Summary: Elevated levels of MMP-9 and NE are associated with bronchiectasis and lung function decline in CF patients. However, the role of MMP-9 in CF-like lung disease in mice is not significant.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Immunology
Samantha L. Tucker, Demba Sarr, Balazs Rada
Summary: Cystic Fibrosis is a genetic disease that causes chronic lung inflammation and infections, leading to high mortality rates. Immune system disruption in CF results in impaired immune responses, chronic infections with pathogens, and alterations in T cell and neutrophil functions. The role of P. aeruginosa and gMDSCs in T cell suppression and immune evasion in CF remains a subject of ongoing research.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Osric A. Forrest, Brian Dobosh, Sarah A. Ingersoll, Sanjana Rao, Alexander Rojas, Julie Laval, Jessica A. Alvarez, Milton R. Brown, Vin Tangpricha, Rabindra Tirouvanziam
Summary: Neutrophils in cystic fibrosis (CF) airways contribute to chronic inflammation by packaging proinflammatory signals in extracellular vesicles (EVs). These EVs can induce reprogramming of naive neutrophils and activate caspase-1 and IL-1β production. Additionally, EVs from activated neutrophils can deliver active caspase-1 to tracheal epithelial cells and induce the release of IL-1α.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Physiology
Jonathan Ma, Apparao B. Kummarapurugu, Adam Hawkridge, Shobha Ghosh, Shuo Zheng, Judith A. Voynow
Summary: Patients with cystic fibrosis have impaired macrophage phagocytosis and efferocytosis due to neutrophil elastase (NE) activity. Proteomic analysis revealed that NE affects various stages of phagocytosis by upregulating and downregulating different proteins, including phagocytic receptors and proteins involved in phagocytic cup formation and maturation. NE's impact extends beyond cell surface proteins, suggesting a global regulation of macrophage structure and function.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2021)
Article
Chemistry, Analytical
Xiang Li, Yun Guo, Yuan Qiu, Xiaogang Luo, Genyan Liu, Yunfeng Han, Qi Sun, Qingjian Dong
Summary: Researchers have developed a NE fluorescent probe based on a self-immolative group, which has many advantages such as good water solubility and biocompatibility, and can detect NE activity selectively and sensitively. It has been successfully applied in real-time and specific detection of NE activity in living cells and zebrafish models.
ANALYTICA CHIMICA ACTA
(2023)
Article
Infectious Diseases
Margherita Degasperi, Riccardo Sgarra, Mario Mardirossian, Sabrina Pacor, Massimo Maschio, Marco Scocchi
Summary: This study developed a prodrug to extend the peptide chain of an antimicrobial peptide and added a sequence that can activate the peptide at the site of infection/inflammation, enabling a slow and targeted release. The prodrug showed good antimicrobial activity and lower cytotoxicity in the presence of elastase.
Article
Biochemistry & Molecular Biology
Ganimeta Bakalovic, Dejan Bokonjic, Dusan Mihajlovic, Miodrag Colic, Vanja Malis, Marija Drakul, Sergej Tomic, Ivan Jojic, Sara Rakocevic, Darinka Popovic, Ljiljana Kozic, Milos Vasiljevic, Marina Bekic, Srdan Masic, Olivera Ljuboja
Summary: The dysfunction of neutrophils in children with cystic fibrosis (CF) is characterized by reduced apoptosis, lower production of neutrophil elastase (NE) and interleukin-18 (IL-18), and increased IL-8 levels. After stimulation, neutrophils showed higher reactive oxygen species (ROS) production, as well as up-regulation of CD11b and IL-10 expression. NET-osis was only increased in moderate-severe CF patients treated with Pseudomonas aeruginosa and correlated with forced expiratory volume in the first second (FEV1). Phagocytosis was not significantly affected.
Article
Medicine, General & Internal
Atqah AbdulWahab, Mona Allangawi, Merlin Thomas, Ilham Bettahi, Siveen K. Sivaraman, Jayakumar Jerobin, Prem Chandra, Manjunath Ramanjaneya, Abdul-Badi Abou-Samra
Summary: This study investigated sputum and plasma levels of total NE in clinically stable adult CF patients and control subjects, finding a significant positive correlation between NE levels and PA colonization. The results suggest that CF patients colonized with PA may have higher NE levels, but total NE does not seem to influence lung functions.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2021)
Review
Microbiology
Haoran Zhong, Xiang Gui, Ling Hou, Rongxue Lv, Yamei Jin
Summary: Schistosomiasis is a chronic parasitic disease that seriously damages the liver, and the current drugs cannot reverse the liver damage. Research has found that HMGB1 is a cytokine associated with schistosomiasis, and its inhibition can protect against liver fibrotic diseases. Therefore, HMGB1 may be a potential target for the treatment of schistosomiasis sequelae.
Article
Immunology
Margalida Mateu-Borras, Alex Gonzalez-Alsina, Antonio Domenech-Sanchez, Javier Querol-Garcia, Francisco J. Fernandez, Ma Cristina Vega, Sebastian Alberti
Summary: This study investigates how isolates from CF patients modulate the levels of C5a and identifies the bacterial factors involved. The results show that most isolates from airway chronic infections induce the production and accumulation of C5a, which is attributed to the loss of C5a cleavage by the exoproteases AprA and LasB. Furthermore, it is found that lack of bacterial protease-dependent C5a degradation is due to mutations in the master regulator LasR. These findings suggest that non-cleaving C5a phenotype acquired by LasR variants may contribute to the strong neutrophilia and neutrophil dysfunction in CF patients.