Review
Biochemistry & Molecular Biology
Martin Alexander Schick, Nicolas Schlegel
Summary: Phosphodiesterase 4 inhibitors play an important role in regulating physiological functions and treating diseases, but they also carry significant risks of serious side effects. This review aims to provide a comprehensive overview of the approaches and effects of phosphodiesterase 4 inhibition in different therapeutic applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Cindy A. Sander, Elizabeth A. Rush, Jian Shi, Lidia M. R. B. Arantes, Raymond J. Tesi, Mark A. Ross, Michael J. Calderon, Simon C. Watkins, John M. Kirkwood, Robert L. Ferris, Lisa H. Butterfield, Lazar Vujanovic
Summary: TNFR2 is expressed in BRAF-mutant melanoma cells and is involved in solTNF-driven resistance to MAPKi. TNFR2 may serve as a biomarker to identify melanoma patients who can benefit from solTNF-targeting therapies.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Shanelle Shillingford, Lei Zhang, Yulia Surovtseva, Sam Dorry, Elias Lolis, Anton M. Bennett
Summary: This study demonstrates the importance of a specific site (Y271) in the phosphatase domain of MKP7 for its catalytic activity and binding to p38 MAPK and JNK. Mutations in this site inhibited MKP7 function, leading to increased nuclear accumulation of p38 MAPK and JNK. These findings contribute to our understanding of the regulatory mechanisms of MKP7 and provide insights for potential therapeutic targeting of MKP7.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Rui Zhang, Heng Li, Xianglei Zhang, Jian Li, Haixia Su, Qiukai Lu, Guangyu Dong, Huixia Dou, Chen Fan, Zhanni Gu, Qianwen Mu, Wei Tang, Yechun Xu, Hong Liu
Summary: A series of novel tetrahydroisoquinoline derivatives were developed and compound 36 exhibited significant inhibitory effects against PDE4D enzymatic activity and TNF-α release, showing more significant efficacy in improving psoriasis-like skin inflammation compared to calcipotriol.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Meng-ke Fan, Guo-chuan Zhang, Wei Chen, Li-li Qi, Ming-fang Xie, Yue-yao Zhang, Ling Wang, Qi Zhang
Summary: Siglec-15 expression promotes the development and progression of osteosarcoma by activating DUSP1. High expression of Siglec-15 is associated with lung metastasis and poor prognosis.
FRONTIERS IN ONCOLOGY
(2021)
Article
Zoology
Ying Wang, Hua-Min Wang, Yan Zhou, Ling-Hong Hu, Jing-Ming Wan, Ji-Hui Yang, Hong-Bo Niu, Xiu-Ping Hong, Peng Hu, Liang-Biao Chen
Summary: Pathways that regulate redox homeostasis in the most thermosensitive tissue, such as gills, may have a significant impact on determining the thermal tolerance limit of zebrafish.
ZOOLOGICAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Chouhui Xuan, Haixia Cui, Zhengyong Jin, Yuyang Yue, Shuxia Cao, Songbiao Cui, Dongyuan Xu
Summary: Glutamine treatment can effectively alleviate hyp-induced brain injury and improve learning and memory impairment in neonatal rats. This neuroprotective effect may be related to the regulation of MKP-1 expression and inhibition of MAPK signaling pathway.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ping Chen, Min Pan, Qing-Song Lin, Xian-Zhong Lin, Zhangya Lin
Summary: The study revealed that CSF-CN contributes to cancer-induced bone pain through regulating the MKP-1-mediated p38-MAPK pathway. Targeted ablation of CSF-CN or overexpression of MKP-1 significantly affects pain sensitivity.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Medicine, Research & Experimental
Hidekazu Maruyama, Satoshi Sakai, Laurence Dewachter, Celine Dewachter, Benoit Rondelet, Robert Naeije, Masaki Ieda
Summary: This study found that the p38MAPK/DUSP1 negative feedback loop is impaired in pulmonary arterial hypertension (PAH), leading to excessive activation of p38MAPK and hyperplasia of PA-SMCs. The IP receptor agonist MRE-269 increases DUSP1 expression and inhibits p38MAPK-mediated PA-SMC proliferation. Further elucidation of the mechanism underlying reduced DUSP1 expression would be informative for PAH treatment.
Article
Immunology
Chao Zhong, Kisuk Min, Zhiqiang Zhao, Cheng Zhang, Erhe Gao, Yan Huang, Xinbo Zhang, Margaret Baldini, Rajika Roy, Xiaofeng Yang, Walter J. Koch, Anton M. Bennett, Jun Yu
Summary: Cardiac fibrosis, a pathological condition associated with excessive ECM deposition in the myocardium, is regulated by processes not fully understood. Macrophage-specific MKP-5 was found to modulate pressure overload-induced cardiac fibrosis, with its deficiency resulting in upregulation of ECM-degrading MMP-9 expression in Ly6C(low) cardiac macrophages. This study indicates that MKP-5 may play a role in suppressing ECM-degrading activity through MAPK-mediated regulation of MMP-9 expression in cardiac macrophages.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Shu Lei, Xiangjun He, Xiao Yang, Xuan Gu, Yijiao He, Jianliu Wang
Summary: In this study, the correlation between DUSP1 and AP-1 complex in endometrial carcinoma was discovered. It was found that AP-1 complex might be the upstream transcriptional regulators of DUSP1. DUSP1 can inhibit tumor growth and invasion, and promote apoptosis by regulating ERK pathway or dephosphorylating EPHA2. EPHA2 is highly expressed in aggressive endometrial cancer patients, and the use of EPHA2 inhibitor can significantly slow down tumor cell growth.
Review
Biochemistry & Molecular Biology
Claire Lugnier
Summary: Cyclic nucleotide phosphodiesterases (PDEs) play a crucial role in regulating intracellular cAMP and/or cGMP levels by converting cyclic nucleotides to 5'-nucleotides. Among the PDEs, PDE4 represents the largest family and is involved in various tissues and pathologies. Recent development in PDE4 inhibitors has focused on targeting cardiovascular diseases, obesity, diabetes, and other conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Xuemei Wei, Guoqi Yu, Hualiang Shen, Yanjuan Luo, Tianbo Shang, Runpu Shen, Meiyang Xi, Haopeng Sun
Summary: Phosphodiesterase 4 (PDE4), highly expressed in mammalian brain, selectively hydrolyzes cAMP, a key regulator of brain functions such as learning and memory. Inhibiting PDE4 can improve cognitive deficits, but its clinical development is hindered by adverse effects. Research on PDE4 subtypes and the development of subtype-specific inhibitors show promise for improved therapeutic benefits and safety.
BIOORGANIC CHEMISTRY
(2023)
Article
Food Science & Technology
Junlin Ge, Rili Hao, Xue Rong, Q. Ping Dou, Xintong Tan, Guannan Li, Feng Li, Dapeng Li
Summary: The polyphenolic compound SDG found in flaxseed has been shown to protect mice from BaP-induced liver and kidney toxicity by regulating oxidative stress, inflammation, and apoptosis. SDG administration resulted in lower levels of liver and kidney damage markers and modulation of specific signaling pathways.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Pharmacology & Pharmacy
Fatemeh Saheb Sharif-Askari, Narjes Saheb Sharif-Askari, Swati Goel, Shirin Hafezi, Rasha Assiri, Saleh Al-Muhsen, Qutayba Hamid, Rabih Halwani
Summary: It has been found in the study that SARS-CoV-2 infection significantly downregulates DUSP1 expression, which may lead to enhanced activation of the MAPK pathway and steroid resistance. Chloroquine can induce DUSP1 expression and attenuate the MAPK pathway, thereby increasing sensitivity to steroid treatment, but further research is needed to confirm this effect.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Allergy
Jasmin Honkamaki, Pinja Ilmarinen, Hanna Hisinger-Molkanen, Leena E. Tuomisto, Heidi Andersen, Heini Huhtala, Anssi Sovijarvi, Ari Lindqvist, Helena Backman, Bright I. Nwaru, Eva Ronmark, Lauri Lehtimaki, Paula Pallasaho, Paivi Piirila, Hannu Kankaanranta
Summary: Nonrespiratory diseases are more prevalent in adults with asthma compared to those without asthma, and the type of diseases varies with the age of asthma diagnosis.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2023)
Letter
Dermatology
Ilari Maki-Opas, Mari Hamalainen, Lauri J. Moilanen, Heini Sood, Tiina Leppanen, Laura Kummola, Ilkka S. Junitila, Lauri Letimaki, Eeva Moilanen
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Public, Environmental & Occupational Health
Kirsi Koskela, Riitta Sauni, Jukka Uitti, Panu Oksa, Eeva Moilanen, Mari Hamalainen, Lauri Lehtimaki
Summary: This study aimed to assess the association between plasma adipokine levels and pulmonary function in foundry workers. The results showed that an increase in plasma adipsin was associated with the development of airway obstruction, and it was also positively correlated with cumulative dust exposure.
JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
(2023)
Review
Medicine, General & Internal
Celeste Porsbjerg, Erik Melen, Lauri Lehtimaki, Dominick Shaw
Summary: Asthma is a common chronic non-communicable disease characterized by variable airflow obstruction. Effective therapies have significantly improved asthma morbidity and mortality, but undertreatment remains an issue. Understanding when and how to adjust treatment is crucial. With the advent of biological therapies, management has shifted towards precision medicine and remission. This article provides a clinically focused overview of asthma in children and adults, including epidemiology, pathophysiology, diagnosis, and management.
Article
Pediatrics
Anna P. Tikkakoski, Antti Tikkakoski, Kalle Sipila, Juho E. Kivisto, Heini Huhtala, Mika Kahonen, Jussi Karjalainen, Lauri Lehtimaki
Summary: Long-term exposure to air pollution is associated with asthma morbidity in children. It has been found that even low concentrations of particulate matter (PM2.5) may have an effect on exercise-induced bronchoconstriction (EIB) in children.
PEDIATRIC PULMONOLOGY
(2023)
Article
Allergy
Paul E. Pfeffer, Nasloon Ali, Ruth Murray, Charlotte Ulrik., Trung N. Tran, Jorge Maspero, Matthew Peters, George C. Christoff, Mohsen Sadatsafavi, Carlos A. Torres-Duque, Alan Altraja, Lauri Lehtimaki, Nikolaos G. Papadopoulos, Sundeep Salvi, Richard W. Costello, Breda Cushen, Enrico Heffler, Takashi Iwanaga, Mona Al-Ahmad, Desiree Larenas-Linnemann, Piotr Kuna, Joao A. Fonseca, Riyad Al-Lehebi, Chin Kook Rhee, Luis Perez-de-Llano, Diahn-Warng Perng Steve, Bassam Mahboub, Eileen Wang, Celine Goh, Juntao Lyu, Anthony Newell, Marianna Alacqua, Andrey S. Belevskiy, Mohit Bhutani, Leif Bjermer, Unnur Bjornsdottir, Arnaud Bourdin, Anna von Boulow, John Busby, Giorgio Walter Canonica, Borja G. Cosio, Delbert R. Dorscheid, Mariana Munoz-Esquerre, J. Mark FitzGerald, Esther Garcia Gil, Peter G. Gibson, Liam G. Heaney, Mark Hew, Ole Hilberg, Flavia Hoyte, David J. Jackson, Mariko Siyue Koh, Hsin-Kuo Bruce Ko, Jae Ha Lee, Sverre Lehmann, Claudia Chaves Loureiro, Dora Ludviksdottir, Andrew N. Menzies-Gow, Patrick Mitchell, Andriana I. Papaioannou, Todor A. Popov, Celeste M. Porsbjerg, Laila Salameh, Concetta Sirena, Camille Taille, Christian Taube, Yuji Tohda, Michael E. Wechsler, David B. Price
Summary: This study aimed to describe the profile of severe asthma patients eligible for both anti-IgE and anti-IL5/5R and compare the effectiveness of these two treatments in real-life settings. The results showed that anti-IL5/5R was superior to anti-IgE in reducing asthma exacerbations and long-term oral corticosteroid use, while there was some evidence suggesting a decrease in asthma-related hospitalizations with anti-IL5/5R treatment.
Article
Cardiac & Cardiovascular Systems
Jyrki Taurio, Elina J. Hautaniemi, Jenni K. Koskela, Arttu Eraranta, Mari Hamalainen, Antti Tikkakoski, Jarkko A. Kettunen, Mika Kahonen, Onni Niemela, Eeva Moilanen, Jukka Mustonen, Ilkka Porsti
Summary: This study aimed to investigate the influence of abdominal fat content, as judged by waist:height ratio, on blood pressure and hemodynamic profile. The results showed that individuals with higher waist:height ratios had higher blood pressure, systemic vascular resistance, and arterial stiffness. These findings suggest that obesity-related hypertension has similar characteristics to primary hypertension.
BMC CARDIOVASCULAR DISORDERS
(2023)
Article
Biochemistry & Molecular Biology
Leevi Halonen, Antti Pemmari, Elina Nummenmaa, Mari Haemaelaeinen, Teemu Moilanen, Katriina Vuolteenaho, Eeva Moilanen
Summary: This study found that human osteoarthritic chondrocytes express 19 different TRP genes, with significant expression of TRPM8. In addition, menthol and dexamethasone can regulate the expression of TRP channels. These results support the concept of TRPA1 and TRPM8 as potential novel drug targets in arthritis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Morena Scotece, Mari Haemaelaeinen, Tiina Leppaenen, Katriina Vuolteenaho, Eeva Moilanen
Summary: MKP-1 has a potential protective role in scleroderma by suppressing inflammation and fibrosis. MKP-1 deficiency enhances collagen accumulation and expression of inflammatory and profibrotic factors. Enhancing the expression or activity of MKP-1 could be a potential treatment for scleroderma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Health Care Sciences & Services
Sirpa Leivo-Korpela, Heidi A. Rantala, Reetta P. Piili, Lauri Lehtimaki, Juho T. Lehto
Summary: Mouthpiece ventilation is feasible and may relieve dyspnea in patients with acute chronic obstructive pulmonary disease exacerbation, but further evaluation is needed.
JOURNAL OF PALLIATIVE MEDICINE
(2023)
Article
Respiratory System
Anna von Bullow, Susanne Hansen, Patrik Sandin, Olivia Ernstsson, Christer Janson, Lauri Lehtimaeki, Hannu Kankaanranta, Charlotte Ulrik, Bernt Bogvald Aarli, Kirk Geale, Sheila Tuyet Tang, Maija Wolf, Vibeke Backer, Ole Hilberg, Alan Altraja, Helena Backman, Dora Ludviksdottir, Unnur Steina Bjornsdottir, Paula Kauppi, Thomas Sandstrom, Asger Sverrild, Valentyna Yasinska, Maritta Kilpelainen, Barbro Dahlen, Arja Viinanen, Leif Bjermer, Apostolos Bossios, Celeste Porsbjerg
Summary: This study aimed to describe the longitudinal trajectories leading to severe asthma and to identify clinical events preceding disease progression in patients with severe asthma. Four distinct trajectories of severe asthma were identified, illustrating different patterns of progression of asthma severity. This study may contribute to the development of better preventive management strategies for severe asthma.
EUROPEAN RESPIRATORY JOURNAL
(2023)
Article
Cell Biology
Samu Luostarinen, Mari Hämäläinen, Antti Pemmari, Eeva Moilanen
Summary: This study investigated the effects of Th1 and Th2-type inflammation on TRPA1 expression and function. The results showed that TRPA1 expression and function were enhanced under inflammatory conditions, with IFN-γ increasing TRPA1 expression and IL-4 and IL-13 suppressing it in a JAK-STAT6 dependent manner. These findings suggest that the paradigm of Th1 and Th2 inflammation is a major determinant of TRPA1 expression and function in (lung) disease and should be considered in pharmacotherapy.
INFLAMMATION RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Arja Viinanen, Juhani Aakko, Mariann I. Lassenius, Gunilla Telg, Kaisa Nieminen, Saara Kaijala, Lauri Lehtimaki, Hannu Kankaanranta
Summary: We investigated the stability of T2 low status and exacerbation rates in T2 low and non-T2 low asthma using clinical retrospective data. Among patients with severe uncontrolled asthma, 18% were identified as T2 low(150) and 39% as T2 low(300). Biomarker stability was observed in 55% and 72% of patients in these groups. Exacerbation rates were higher in the T2 low group compared to the non-T2 low group. BEC and FeNO are useful biomarkers in identifying and monitoring T2 low asthma.
Article
Otorhinolaryngology
Pekka Tamminen, Jorma Jarnstedt, Jura Numminen, Antti Lehtinen, Lauri Lehtimaki, Markus Rautiainen, Ilkka Kivekas
Summary: This study evaluates the clinical image quality and usability of a sinonasal ultra-low-dose cone-beam computed tomography (CBCT) scan. The results show that the image quality of the ultra-low-dose CBCT is sufficient for clinical diagnostics and should be considered for surgical planning.
Article
Rheumatology
Ilari Maeki-Opas, Mari Haemaelaeinen, Eeva Moilanen, Morena Scotece
Summary: This study investigated the role of TRPA1 in IL-4-induced lung fibrosis. The results showed that interfering TRPA1 can attenuate fibrotic and inflammatory responses, potentially providing a treatment option for systemic sclerosis and scleroderma.
ARTHRITIS RESEARCH & THERAPY
(2023)