Fatty Acid Metabolism and Idiopathic Pulmonary Fibrosis

Fatty acid metabolism, including the de novo synthesis, uptake, oxidation, and derivation of fatty acids, plays several important roles at cellular and organ levels. Recent studies have identified characteristic changes in fatty acid metabolism in idiopathic pulmonary fibrosis (IPF) lungs, which implicates its dysregulation in the pathogenesis of this disorder. Here, we review the evidence for how fatty acid metabolism contributes to the development of pulmonary fibrosis, focusing on the profibrotic processes associated with specific types of lung cells, including epithelial cells, macrophages, and fibroblasts. We also summarize the potential therapeutics that target this metabolic pathway in treating IPF.

The sphingosine 1-phosphate receptor 2/4 antagonist JTE-013 elicits off-target effects on sphingolipid metabolism

Sphingosine 1-phosphate (S1P) is a signaling lipid that has broad roles, working either intracellularly through various protein targets, or extracellularly via a family of five G-protein coupled receptors. Agents that selectively and specifically target each of the S1P receptors have been sought as both biological tools and potential therapeutics. JTE-013, a small molecule antagonist of S1P receptors 2 and 4 (S1P2 and S1P4) has been widely used in defining the roles of these receptors in various biological processes. Indeed, our previous studies showed that JTE-013 had anti-acute myeloid leukaemia (AML) activity, supporting a role for S1P2 in the biology and therapeutic targeting of AML. Here we examined this further and describe lipidomic analysis of AML cells that revealed JTE-013 caused alterations in sphingolipid metabolism, increasing cellular ceramides, dihydroceramides, sphingosine and dihydrosphingosine. Further examination of the mechanisms behind these observations showed that JTE-013, at concentrations frequently used in the literature to target S1P2/4, inhibits several sphingolipid metabolic enzymes, including dihydroceramide desaturase 1 and both sphingosine kinases. Collectively, these findings demonstrate that JTE-013 can have broad off-target effects on sphingolipid metabolism and highlight that caution must be employed in interpreting the use of this reagent in defining the roles of S1P2/4.

Interrogation of Solution Conformation of Complex Macrocyclic Peptides Utilizing a Combined SEC-HDX-MS, Circular Dichroism, and NMR Workflow

Recent technological and synthetic advances have led to a resurgence in the exploration of peptides as potential therapeutics. Understanding peptide conformation in both free and protein-bound states remains one of...

Emerging Pandemic COVID 19 versus SARS-COV-1

Rising threat of the global pandemic COVID 19 has become the major cause of concern among nations worldwide. The appalling pandemic has aggravated the global health of people making normal life come to a virtual standstill. The purpose of this study is to investigate and compare the similarities and differences between the previous global pandemic outbreak SARS-COV-1 with that of COVID 19. It makes use of a bioinformatic approach to analyze why COVID 19 has made situations uncontrollable as opposed to that of SARS-COV-1 although both belong to the same coronavirus family. Discusses about the recent clinical trials that are being conducted to evaluate potential therapeutics to combat the deadly pandemic. There is currently no available vaccine for COVID 19. E The current status of COVID 19 research stands progressive in various areas of knowledge. Further studies based on emerging evidences are required to produce drugs which can slow down disease progression and improve survival.

Plasma Metabolomic Profiles Associated with Three-Year Progression of Age-Related Macular Degeneration

Plasma metabolomic profiles have been shown to be associated with age-related macular degeneration (AMD) and its severity stages. However, all studies performed to date have been cross-sectional and have not assessed progression of AMD. This prospective, longitudinal, pilot study analyzes, for the first time, the association between plasma metabolomic profiles and progression of AMD over a 3-year period. At baseline and 3 years later, subjects with AMD (n = 108 eyes) and controls (n = 45 eyes) were imaged with color fundus photos for AMD staging and tested for retinal function with dark adaptation (DA). Fasting plasma samples were also collected for metabolomic profiling. AMD progression was considered present if AMD stage at 3 years was more advanced than at baseline (n = 26 eyes, 17%). Results showed that, of the metabolites measured at baseline, eight were associated with 3-year AMD progression (p < 0.01) and 19 (p < 0.01) with changes in DA. Additionally, changes in the levels (i.e., between 3 years and baseline) of 6 and 17 metabolites demonstrated significant associations (p < 0.01) with AMD progression and DA, respectively. In conclusion, plasma metabolomic profiles are associated with clinical and functional progression of AMD at 3 years. These findings contribute to our understanding of mechanisms of AMD progression and the identification of potential therapeutics for this blinding disease.

Small-molecule degraders of cyclin-dependent kinase protein: a review

Proteolysis-targeting chimeras are a new modality of chemical tools and potential therapeutics involving the induction of protein degradation. Cyclin-dependent kinase (CDK) protein, which is involved in cycles and transcription cycles, participates in regulation of the cell cycle, transcription and splicing. Proteolysis-targeting chimeras targeting CDKs show several advantages over traditional CDK small-molecule inhibitors in potency, selectivity and drug resistance. In addition, the discovery of molecule glues promotes the development of CDK degraders. Herein, the authors describe the existing CDK degraders and focus on the discussion of the structural characteristics and design of these degraders.

SARS-CoV-2: Possible Factors Contributing to Serious Consequences of COVID-19?

Background and Objectives: The recently discovered coronavirus, SARS-CoV-2 has infected over 170 million people (as of 31th May 2021) since it was elucidated in December 2019. The number of SARS-CoV-2 cases and mortality rates vary from country to country, and unfortunately, the United Kingdom ranks in the top 5 countries with the most deaths as of 31th May 2021. Methods: A literature review was conducted during May 2021 to examine if factors such as gut microbiome, ethnic diversity, high cancer rates, obesity and alcohol consumption may have contributed to the higher number of cases and mortality due to SARS-CoV-2 in the UK. Results: The western diet is associated with a less diverse gut microbiome, as well as obesity, and contributes to the severity of SARS-CoV-2 infection. Moreover, people belonging to Black and South Asian ethnic groups in the UK have an increased risk of death due to SARS-CoV-2 infection. Given the high number of cancer patients in the UK, as well as excess consumption of alcohol, higher mortality rates were observed, most likely due to people possessing a less diverse gut microbiome and/or weakened immune system. Conclusion: Targeting the gut microbiome in developing potential therapeutics against SARS-COV-2 is of value, and further studies are needed to understand the specific role of the gut microbiome.