Reprogramming biocatalytic futile cycles through computational engineering of stereochemical promiscuity to create an amine racemase.

Repurposing the intrinsic properties of natural enzymes can offer a viable solution to current synthetic challenges through the development of novel biocatalytic processes. Although amino acid racemases are ubiquitous in living organisms, an amine racemase (AR) has not yet been discovered despite its synthetic potential for producing chiral amines. Here, we report the creation of an AR based on the serendipitous discovery that amine transaminases (ATAs) can perform stereoinversion of 2-aminobutane.

Radon reduction in small-scale water supply systems using low-technology reduction methods in the Republic of Korea: A field research and mass balance model approach.

In rural areas, low-technology radon reduction methods are essential for safe access to clean groundwater. This study monitored the radon reduction rates in small-scale groundwater-based water supply systems in the Republic of Korea and also presented a mass balance equation using physical environmental conditions from three radon reduction methods. The mass balance results showed that the radon reduction rate would be affected by the groundwater flow rate (m/day), capacity of the drainage facility (m), surface area of air-water interface (m), air-water ratio (dimensionless), and ventilation system.

Synthesis and structure-activity relationship study of saponin-based membrane fusion inhibitors against SARS-CoV-2.

We previously discovered that triterpenoid saponin platycodin D inhibits the SARS-CoV-2 entry to the host cell. Herein, we synthesized various saponin derivatives and established a structure-activity relationship of saponin-based antiviral agents against SARS-CoV-2. We discovered that the C3-glucose, the C28-oligosaccharide moiety that consist of (→3)-β-d-Xyl-(1 → 4)-α-l-Rham-(1 → 2)-β-d-Ara-(1 → ) as the last three sugar units, and the C16-hydroxyl group were critical components of saponin-based coronavirus cell entry inhibitors.

Platycodin D, a natural component of Platycodon grandiflorum, prevents both lysosome- and TMPRSS2-driven SARS-CoV-2 infection by hindering membrane fusion.

An ongoing pandemic of coronavirus disease 2019 (COVID-19) is now the greatest threat to global public health. Herbal medicines and their derived natural products have drawn much attention in the treatment of COVID-19, but the detailed mechanisms by which natural products inhibit SARS-CoV-2 have not been elucidated. Here, we show that platycodin D (PD), a triterpenoid saponin abundant in Platycodon grandiflorum (PG), a dietary and medicinal herb commonly used in East Asia, effectively blocks the two main SARS-CoV-2 infection routes via lysosome- and transmembrane protease serine 2 (TMPRSS2)-driven entry.

Biochemical characterization and synthetic application of aromatic L-amino acid decarboxylase from Bacillus atrophaeus.

Aromatic L-amino acid decarboxylases (AADCs) are ubiquitously found in higher organisms owing to their physiological role in the synthesis of neurotransmitters and alkaloids. However, bacterial AADC has not attracted much attention because of its rather limited availability and narrow substrate range. Here, we examined the biochemical properties of AADC from Bacillus atrophaeus (AADC-BA) and assessed the synthetic feasibility of the enzyme for the preparation of monoamine neurotransmitters.

Total Synthesis of Cinnamodial-Based Dimer (-)-Capsicodendrin.

We describe the first total synthesis of cinnamodial-based dimer (-)-capsicodendrin. First, we developed a 12-step synthetic route to access (-)-cinnamodial from 1-vinyl-2,6,6-trimethylcyclohexene. We then showed that (-)-cinnamodial can selectively dimerize to (-)-capsicodendrin under kinetically controlled basic conditions.

Cardioprotective Effect of the SDF-1α/CXCR4 Axis in Ischemic Postconditioning in Isolated Rat Hearts.

Background And Objectives: Information about the role of the stromal cell-derived factor-1α (SDF-1α)/chemokine receptor type 4 (CXCR4) axis in ischemic postconditioning (IPOC) is currently limited. We hypothesized that the SDF-1α/CXCR4 signaling pathway is directly involved in the cardioprotective effect of IPOC.

Methods: Isolated rat hearts were divided into four groups.

Mitochondrial ATP-Sensitive Potassium Channels Play a Role in Reducing Both Myocardial Infarction and Reperfusion Arrhythmia in Remote Ischemic Preconditioned Hearts.

Background: Mitochondrial ATP-sensitive potassium (mKATP) channels play a role in reperfusion arrhythmias (RAs) in ischemia-reperfusion (I/R) injury. Evidence suggests that remote ischemic preconditioning (RIPC) reduces RAs, however not much is known on the mechanistic role of mKATP in RIPC. We evaluated whether mKATP channels are associated with reducing arrhythmia and infarct size in RIPC.

Remifentanil postconditioning has cross talk with adenosine receptors in the ischemic-reperfused rat heart.

Background: Although there is a possibility of cross talk between opioid and adenosine signaling pathways in the ischemic-reperfused myocardium, it is not clear that an ultra-short-acting opioid receptor agonist remifentanil-induced postconditioning (RPostC) has cross talk with adenosine receptor (ADR). The purpose of this study was to determine whether there is cross talk with ADR in RPostC.

Materials And Methods: Isolated rat hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion.

Polyphenol (-)-epigallocatechin gallate-induced cardioprotection may attenuate ischemia-reperfusion injury through adenosine receptor activation: a preliminary study.

Background: The activation of guanine nucleotide binding protein-coupled receptors, such as adenosine receptor (ADR) and opioid receptor (OPR), protects the heart against ischemia and reperfusion injury. We hypothesized that ADR or OPR might be involved in polyphenol (-)-epigallocatechin gallate (EGCG)-induced cardioprotection.

Methods: Langendorff perfused rat hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion.

Stromal cell derived factor-1 (SDF-1) targeting reperfusion reduces myocardial infarction in isolated rat hearts.

Recent studies have shown that stromal cell derived factor-1 (SDF-1), first known as a cytokine involved in recruiting stem cells into injured organs, confers myocardial protection in myocardial infarction, which is not dependent on stem cell recruitment but related with modulation of ischemia-reperfusion (I/R) injury. However, the effect of SDF has been studied only in a preischemic exposure model, which is not clinically relevant if SDF is to be used as a therapeutic agent. Our study was aimed at evaluating whether or not SDF-1 confers cardioprotection during the reperfusion period.

Comparison of 5 different remifentanil strategies against myocardial ischemia-reperfusion injury.

Objective: The purpose of this study was to investigate the effects of various remifentanil strategies (preconditioning, postconditioning, or continuous infusion) against myocardial ischemia-reperfusion injury.

Design: An in vitro experimental study using the Langendorff system.

Setting: A university research laboratory.

Effects of postconditioning with N,N,N'N'-tetrakis-[2-pyridylmethyl]-ethylenediamine in isolated rat hearts.

Background: It was reported that N,N,N'N'-tetrakis-[2-pyridylmethyl]-ethylenediamine (TPEN), a transition metal chelator, confers cardioprotection against myocardial ischemic injury. In this study, we investigated the effect of TPEN targeting reperfusion period in isolated rat hearts.

Methods: Langendorff perfused rat hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion.

Polyphenol (-)-epigallocatechin gallate during ischemia limits infarct size via mitochondrial K(ATP) channel activation in isolated rat hearts.

Polyphenol (-)-epigallocatechin gallate (EGCG), the most abundant catechin of green tea, appears to attenuate myocardial ischemia/reperfusion injury. We investigated the involvement of ATP-sensitive potassium (K(ATP)) channels in EGCG-induced cardioprotection. Isolated rat hearts were subjected to 30 min of regional ischemia and 2 hr of reperfusion.

Green tea polyphenol (-)-epigallocatechin gallate reduces neuronal cell damage and up-regulation of MMP-9 activity in hippocampal CA1 and CA2 areas following transient global cerebral ischemia.

Previous studies have demonstrated that (-)-epigallocatechin gallate (EGCG), a green tea polyphenol, protects against ischemia and reperfusion-induced injury in many organ systems. Here, we test the hypothesis that part of EGCG's neuroprotective effects may involve a modulation of matrix metalloproteinases (MMPs) after cerebral ischemia. C57BL/6 mice were subjected to 20 min of transient global cerebral ischemia.

PPARgamma agonist pioglitazone reduces [corrected] neuronal cell damage after transient global cerebral ischemia through matrix metalloproteinase inhibition.

Previous studies have demonstrated that pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, inhibits ischemia-induced injury in various tissues including neural tissue. Pioglitazone has also been shown to reduce matrix metalloproteinase (MMP) activity. Because MMP is known to play a major role in the pathophysiology of brain ischemia, the present study was undertaken to test whether pioglitazone attenuates ischemic neuronal damage through MMP inhibition.

Postconditioning prevents reperfusion injury by activating delta-opioid receptors.

Background: While postconditioning has been proposed to protect the heart by targeting the mitochondrial permeability transition pore (mPTP), the detailed mechanism underlying this action is unknown. The authors hypothesized that postconditioning stimulates opioid receptors, which in turn protect the heart from reperfusion injury by targeting the mPTP.

Methods: Rat hearts (both in vivo and in vitro) were subjected to 30 min of ischemia and 2 h of reperfusion.

NO mobilizes intracellular Zn2+ via cGMP/PKG signaling pathway and prevents mitochondrial oxidant damage in cardiomyocytes.

Objective: Our aim was to determine if NO prevents mitochondrial oxidant damage by mobilizing intracellular free zinc (Zn(2+)).

Methods: Zn(2+) levels were determined by imaging enzymatically isolated adult rat cardiomyocytes loaded with Newport Green DCF. Mitochondrial membrane potential (DeltaPsi(m)) was assessed by imaging cardiomyocytes loaded with tetramethylrhodamine ethyl ester (TMRE).

Protective effect of quercetin, a natural flavonoid against neuronal damage after transient global cerebral ischemia.

Previous studies have demonstrated that quercetin, a bioflavonoid shows the inhibitory effect against ischemia and reperfusion-induced injury in various tissues including neural tissue. Quercetin is also reported to have an inhibitory effect against matrix metalloproteinases (MMPs). Because MMPs are known to play a main role in the pathophysiology of brain ischemic insult, their mechanisms of possible protective effect of quercetin against brain ischemia remain to be clarified.

Severe hepatotoxicity after sevoflurane anesthesia in a child with mild renal dysfunction.

Sevoflurane, an anesthetic agent with methyl isopropyl fluorinated ether structure, has a very low potential for hepatotoxicity. Nevertheless, a few cases of hepatotoxicity have been reported since its introduction into clinical practice. The underlying pathophysiology may be multifactorial and sometimes nonspecific.

Effects of magnesium sulfate on supraceliac aortic unclamping in experimental dogs.

Intravascular administration of magnesium (Mg) causes vasodilation and increases renal blood flow. The aim of this study was to investigate the renal effect of Mg following unclamping of the supraceliac aorta. Mongrels were divided into two groups, control (group C, n=7) and Mg group (group Mg, n=7).

Protective effect of propofol against kainic acid-induced lipid peroxidation in mouse brain homogenates: comparison with trolox and melatonin.

This study compared the effectiveness of propofol with that of trolox and melatonin for reduction of lipid peroxidation in vitro. Lipid peroxidation was induced by addition of kainic acid (KA; 10 mM), hydrogen peroxide (H2O2; 10 mM), or ferrous ammonium sulfate (5 microM) to mouse brain homogenate, and thiobarbituric acid-reactive substances (TBA-RS) were used as a marker of lipid peroxidation. Propofol, trolox, and melatonin reduced KA-, H2O2-, and ferrous ammonium sulfate-induced lipid peroxidation in a concentration-dependent manner.