Biochemical pharmacology
-
Asthma is a chronic inflammatory disease of the airways affecting more than 300 million patients worldwide. The disease can be of various severity ranging from very mild to severe. The severe form of the disease only affects about 5% of patients but is responsible for a large component of the overall disease burden and results in about half of direct asthma-related costs. ⋯ When biologics are not an option, thermoplasty and macrolides have also become available. Despite many recent breakthroughs in severe asthma, much research needs to be done. Improvement in availability of targeted asthma medications and asthma prevention should be top priorities.
-
Biochemical pharmacology · Sep 2020
ReviewChildhood asthma heterogeneity at the era of precision medicine: Modulating the immune response or the microbiota for the management of asthma attack.
Exacerbations are a main characteristic of asthma. In childhood, the risk is increasing with severity. Exacerbations are a strong phenotypic marker, particularly of severe and therapy-resistant asthma. ⋯ We then discuss our understanding of how these diverse host-microbiota interactions in children may account for the heterogeneity of endotypes and clinical presentations. Finally, improving the knowledge of the pathophysiological processes induced by infections has led to offer new opportunities for the development of preventive or curative therapeutics for acute asthma. A better definition of asthma endotypes associated with precision medicine might lead to substantial progress in the management of severe childhood asthma.
-
Biochemical pharmacology · Aug 2020
ReviewSARS-CoV-2 and cardiovascular complications: From molecular mechanisms to pharmaceutical management.
The coronavirus disease 2019 (COVID-19), elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a pandemic public health emergency of global concern. Other than the profound severe pulmonary damage, SARS-CoV-2 infection also leads to a series of cardiovascular abnormalities, including myocardial injury, myocarditis and pericarditis, arrhythmia and cardiac arrest, cardiomyopathy, heart failure, cardiogenic shock, and coagulation abnormalities. ⋯ Up-to-date, a number of mechanisms have been postulated for COVID-19-associated cardiovascular damage including SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) activation, cytokine storm, hypoxemia, stress and cardiotoxicity of antiviral drugs. In this context, special attention should be given towards COVID-19 patients with concurrent cardiovascular diseases, and special cardiovascular attention is warranted for treatment of COVID-19.
-
Biochemical pharmacology · Aug 2020
Myricetin ameliorates bleomycin-induced pulmonary fibrosis in mice by inhibiting TGF-β signaling via targeting HSP90β.
Idiopathic pulmonary fibrosis is a progressive-fibrosing lung disease with high mortality and limited therapy, which characterized by myofibroblasts proliferation and extracellular matrix deposition. Myricetin, a natural flavonoid, has been shown to possess a variety of biological characteristics including anti-inflammatory and anti-tumor. In this study we explored the potential effect and mechanisms of myricetin on pulmonary fibrosis in vivo and vitro. ⋯ Molecular docking indicated that heat shock protein (HSP) 90β may be a potential target of myricetin, and MST assay demonstrated that the dissociation constant (Kd) of myricetin and HSP90β was 331.59 nM. We demonstrated that myricetin interfered with the binding of HSP90β and TGF-β receptor II and impeded fibroblast activation and EMT. In conclusion, myricetin impedes TGF-β1-induced lung fibroblast activation and EMT via targeting HSP90β and attenuates BLM-induced pulmonary fibrosis in mice.
-
Biochemical pharmacology · Jul 2020
ReviewMolecular mechanisms of the rapid-acting and long-lasting antidepressant actions of (R)-ketamine.
Ketamine, an anesthetic developed in the early 1960s, is also a popular abused drug among young people at dance parties and raves and among spiritual seekers, because it produces schizophrenia-like symptoms and dissociation (i.e., out-of-body experience). Regarding mood disorders, ketamine exerts robust antidepressant actions in treatment-resistant patients with depression. Ketamine is a racemic mixture comprising equal parts of (R)-ketamine (or arketamine) and (S)-ketamine (or esketamine). ⋯ A recent RNA-sequencing analysis suggested that the transforming growth factor β1 (TGF-β1) plays a role in the antidepressant effects of (R)-ketamine. A recent pilot study demonstrated that (R)-ketamine had rapid-acting and sustained antidepressant effects in treatment-resistant patients with depression. In this article, the author reviews the mechanisms of the antidepressant actions of the enantiomers of ketamine and its metabolites, (S)-norketamine and (2R,6R)-hydroxynorketamine (HNK) and discusses the role of the brain-gut-microbiota axis and brain-spleen axis in stress-related psychiatric disorders, such as depression.