TGR5 signalling in heart and brain injuries: focus on metabolic and ischaemic mechanisms.

The heart and brain are the core organs of the circulation and central nervous system, respectively, and play an important role in maintaining normal physiological functions. Early neuronal and cardiac damage affects organ function. The relationship between the heart and brain is being continuously investigated. Evidence-based medicine has revealed the concept of the "heart- brain axis," which may provide new therapeutic strategies for certain diseases. Takeda protein-coupled receptor 5 (TGR5) is a metabolic regulator involved in energy homeostasis, bile acid homeostasis, and glucose and lipid metabolism. Inflammation is critical for the development and regeneration of the heart and brain during metabolic diseases. Herein, we discuss the role of TGR5 as a metabolic regulator of heart and brain development and injury to facilitate new therapeutic strategies for metabolic and ischemic diseases of the heart and brain.

Case Report: Kounis syndrome due to cryptopteran bite.

Background: Kounis syndrome is an acute coronary syndrome (ACS) caused by allergic reactions, including coronary artery spasm (type I) caused by allergies without coronary predisposing factors, pre-existing coronary atherosclerosis, and coronary artery disease. Anaphylaxis leads to plaque rupture or erosion leading to acute myocardial infarction (type II) and acute coronary stent thrombosis (type III). Here we share a case of Kounis syndrome type I caused by an allergy caused by a Cryptopteran bite. Case presentation: A 47-year-old woman was admitted to the hospital due to an insect bite for 2 days and chest distress for more than 3 h. Outside the hospital, electrocardiogram(ECG) showed sinus rhythm, ST-segment elevation in leads V1-V3, high-sensitivity troponin 2.54 ng/ml(0-0.5 ng/ml). One hour later, the ECG of the patient showed that the ST segment elevation of lead V1-V4 was 0.10-0.20 mV. Emergency coronary angiography showed coronary spasm and moderate lumen stenosis in the middle segment of left anterior descending artery (LAD). After treatment, the patient's symptoms were relieved, and the ST segment of lead V1-V4 of electrocardiogram returned to normal. Conclusion: Kunis syndrome is a life-threatening condition that can also cause myocardial ischemic injury in patients with or without coronary artery disease. Timely identification and anti-allergic treatment can achieve a good prognosis.

Improved l-phenylglycine synthesis by introducing an engineered cofactor self-sufficient system.

l-phenylglycine (L-phg) is a valuable non-proteinogenic amino acid used as a precursor to ß-lactam antibiotics, antitumor agent taxol and many other pharmaceuticals. L-phg synthesis through microbial bioconversion allows for high enantioselectivity and sustainable production, which will be of great commercial and environmental value compared with organic synthesis methods. In this work, an L-phg synthesis pathway was built in Escherichia coli resulting in 0.23 mM L-phg production from 10 mM l-phenylalanine. Then, new hydroxymandelate synthases and hydroxymandelate oxidases were applied in the L-phg synthesis leading to a 5-fold increase in L-phg production. To address 2-oxoglutarate, NH4 +, and NADH shortage, a cofactor self-sufficient system was introduced, which converted by-product l-glutamate and NAD+ to these three cofactors simultaneously. In this way, L-phg increased 2.5-fold to 2.82 mM. Additionally, in order to reduce the loss of these three cofactors, a protein scaffold between synthesis pathway and cofactor regeneration modular was built, which further improved the L-phg production to 3.72 mM with a yield of 0.34 g/g L-phe. This work illustrated a strategy applying for whole-cell biocatalyst converting amino acid to its value-added chiral amine in a cofactor self-sufficient manner.