Studying Myc’s Role in Metabolism Regulation

The endocannabinoids are part of a large family of lipid signaling molecules derived from arachidonic acid, including the prostaglandins and leukotrienes, which are important mediators of inflammation. Far less is known about the newer members of the endocannabinoid group, and it remains unclear whether they all play important functional roles. This chapter reviews the multiple members of this family and their biosynthesis and inactivation. Physiological functions, including retrograde synaptic signaling, control of energy metabolism, regulation of pain sensitivity, and cardiovascular control, are discussed. In addition, the chapter reports the synthesis of novel agonists, antagonists, and compounds inhibiting endocannabinoid inactivation as novel medicines.

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Quantitative Proteomic Analysis of Plasma after Remote Ischemic Conditioning in a Rhesus Monkey Ischemic Stroke Model

Biomolecules ◽

10.3390/biom11081164 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1164

Author(s):

Siying Song ◽

Linlin Guo ◽

Di Wu ◽

Jingfei Shi ◽

Yunxia Duan ◽

...

Keyword(s):

Lipid Metabolism ◽

Rhesus Monkey ◽

Proteomic Analysis ◽

Complement C3 ◽

Protective Effects ◽

Plasma Proteome ◽

Remote Ischemic Conditioning ◽

Ischemic Conditioning ◽

Metabolism Regulation ◽

Induced Changes

Background: Animal and clinical studies have shown that remote ischemic conditioning (RIC) has protective effects for cerebral vascular diseases, with induced humoral factor changes in the peripheral blood. However, many findings are heterogeneous, perhaps due to differences in the RIC intervention schemes, enrolled populations, and sample times. This study aimed to examine the RIC-induced changes in the plasma proteome using rhesus monkey models of strokes. Methods: Two adult rhesus monkeys with autologous blood clot-induced middle cerebral artery (MCA) occlusion underwent RIC interventions twice a week for five consecutive weeks. Each RIC treatment included five cycles of five minutes of ischemia alternating with five minutes of reperfusion of the forearm. The blood samples were taken from the median cubital vein of the monkeys at baseline and immediately after each week’s RIC stimulus. The plasma samples were isolated for a proteomic analysis using mass spectrometry (MS). Results: Several proteins related to lipid metabolism (Apolipoprotein A-II and Apolipoprotein C-II), coagulation (Fibrinogen alpha chain and serpin), immunoinflammatory responses (complement C3 and C1), and endovascular hemostasis (basement membrane-specific heparan sulfate proteoglycan) were significantly modulated after the RIC intervention. Many of these induced changes, such as in the lipid metabolism regulation and anticoagulation responses, starting as early as two weeks following the RIC intervention. The complementary activation and protection of the endovascular cells occurred more than three weeks postintervention. Conclusions: Multiple protective effects were induced by RIC and involved lipid metabolism regulation (anti-atherogenesis), anticoagulation (antithrombosis), complement activation, and endovascular homeostasis (anti-inflammation). In conclusion, this study indicates that RIC results in significant modulations of the plasma proteome. It also provides ideas for future research and screening targets.

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Advances in Understanding of the Copper Homeostasis in Pseudomonas aeruginosa

International Journal of Molecular Sciences ◽

10.3390/ijms22042050 ◽

2021 ◽

Vol 22 (4) ◽

pp. 2050

Author(s):

Lukas Hofmann ◽

Melanie Hirsch ◽

Sharon Ruthstein

Keyword(s):

Pseudomonas Aeruginosa ◽

Pathogenic Bacteria ◽

Antimicrobial Agents ◽

Efflux Pump ◽

Copper Homeostasis ◽

The United States ◽

World Health ◽

Cross Resistance ◽

Metabolism Regulation ◽

Target Sites

Thirty-five thousand people die as a result of more than 2.8 million antibiotic-resistant infections in the United States of America per year. Pseudomonas aeruginosa (P. aeruginosa) is classified a serious threat, the second-highest threat category of the U.S. Department of Health and Human Services. Among others, the World Health Organization (WHO) encourages the discovery and development of novel antibiotic classes with new targets and mechanisms of action without cross-resistance to existing classes. To find potential new target sites in pathogenic bacteria, such as P. aeruginosa, it is inevitable to fully understand the molecular mechanism of homeostasis, metabolism, regulation, growth, and resistances thereof. P. aeruginosa maintains a sophisticated copper defense cascade comprising three stages, resembling those of public safety organizations. These stages include copper scavenging, first responder, and second responder. Similar mechanisms are found in numerous pathogens. Here we compare the copper-dependent transcription regulators cueR and copRS of Escherichia coli (E. coli) and P. aeruginosa. Further, phylogenetic analysis and structural modelling of mexPQ-opmE reveal that this efflux pump is unlikely to be involved in the copper export of P. aeruginosa. Altogether, we present current understandings of the copper homeostasis in P. aeruginosa and potential new target sites for antimicrobial agents or a combinatorial drug regimen in the fight against multidrug resistant pathogens.

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