New Bacterial Aryl Sulfotransferases: Effective Tools for Sulfation of Polyphenols.

The preparation of pure metabolites of bioactive compounds, particularly (poly)phenols, is essential for the accurate determination of their pharmacological profiles . Since the extraction of these metabolites from biological material is tedious and impractical, they can be synthesized enzymatically by bacterial PAPS-independent aryl sulfotransferases (ASTs). However, only a few ASTs have been studied and used for (poly)phenol sulfation.

Structural basis for intermodular communication in assembly-line polyketide biosynthesis.

Assembly-line polyketide synthases (PKSs) are modular multi-enzyme systems with considerable potential for genetic reprogramming. Understanding how they selectively transport biosynthetic intermediates along a defined sequence of active sites could be harnessed to rationally alter PKS product structures. To investigate functional interactions between PKS catalytic and substrate acyl carrier protein (ACP) domains, we employed a bifunctional reagent to crosslink transient domain-domain interfaces of a prototypical assembly line, the 6-deoxyerythronolide B synthase, and resolved their structures by single-particle cryogenic electron microscopy (cryo-EM).

Advancing research: a commentary on the untapped potential of acceptance and commitment therapy in alcohol use disorder treatment.

Alcohol use disorder poses a significant global health threat, with profound consequences for individuals, families, and communities, necessitating continued exploration of novel treatment approaches. Acceptance and Commitment Therapy, an evidence-based approach for various mental health disorders, offers promise in addressing alcohol use disorder as well, but controlled trials are lacking, highlighting a crucial gap in research.

Structure and Mechanisms of Assembly-Line Polyketide Synthases.

Three decades of studies on the multifunctional 6-deoxyerythronolide B synthase have laid a foundation for understanding the chemistry and evolution of polyketide antibiotic biosynthesis by a large family of versatile enzymatic assembly lines. Recent progress in applying chemical and structural biology tools to this prototypical assembly-line polyketide synthase (PKS) and related systems has highlighted several features of their catalytic cycles and associated protein dynamics. There is compelling evidence that multiple mechanisms have evolved in this enzyme family to channel growing polyketide chains along uniquely defined sequences of 10-100 active sites, each of which is used only once in the overall catalytic cycle of an assembly-line PKS.

Blood stream Infections in chronic hemodialysis patients - characteristics and outcomes.

Introduction: Bloodstream Infections (BSI) are a major cause of death and hospitalization among hemodialysis (HD) patients. The rates of BSI among HD patients vary and are influenced by local patient and pathogen characteristics. Modifications in local infection prevention protocols in light of active surveillance of BSI has been shown to improve clinical outcomes.

Discovery and Characterization of Antibody Probes of Module 2 of the 6-Deoxyerythronolide B Synthase.

Fragment antigen-binding domains of antibodies (Fs) are powerful probes of structure-function relationships of assembly line polyketide synthases (PKSs). We report the discovery and characterization of Fs interrogating the structure and function of the ketosynthase-acyltransferase (KS-AT) core of Module 2 of the 6-deoxyerythronolide B synthase (DEBS). Two Fs (AC2 and BB1) were identified to potently inhibit the catalytic activity of Module 2.

Hesperidin, Hesperetin, Rutinose, and Rhamnose Act as Skin Anti-Aging Agents.

Aging is a complex physiological process that can be accelerated by chemical (high blood glucose levels) or physical (solar exposure) factors. It is accompanied by the accumulation of altered molecules in the human body. The accumulation of oxidatively modified and glycated proteins is associated with inflammation and the progression of chronic diseases (aging).

Sulfation of Phenolic Acids: Chemoenzymatic vs. Chemical Synthesis.

Phenolic acids are known flavonoid metabolites, which typically undergo bioconjugation during phase II of biotransformation, forming sulfates, along with other conjugates. Sulfated derivatives of phenolic acids can be synthesized by two approaches: chemoenzymatically by 3'-phosphoadenosine-5'-phosphosulfate (PAPS)-dependent sulfotransferases or PAPS-independent aryl sulfotransferases such as those from , or chemically using SO complexes. Both approaches were tested with six selected phenolic acids (2-hydroxyphenylacetic acid (2-HPA), 3-hydroxyphenylacetic acid (3-HPA), 4-hydroxyphenylacetic acid (4-HPA), 3,4-dihydroxyphenylacetic acid (DHPA), 3-(4-hydroxyphenyl)propionic acid (4-HPP), and 3,4-dihydroxyphenylpropionic acid (DHPP)) to create a library of sulfated metabolites of phenolic acids.

Bacterial Aryl Sulfotransferases in Selective and Sustainable Sulfation of Biologically Active Compounds using Novel Sulfate Donors.

Regioselective sulfation of bioactive compounds is a vital and scarcely studied topic in enzyme-catalyzed transformations and metabolomics. The major bottleneck of enzymatic sulfation consists in finding suitable sulfate donors. In this regard, 3'-phosphoadenosine 5'-phosphosulfate (PAPS)-independent aryl sulfotransferases using aromatic sulfate donors are a favored choice due to their cost-effectiveness.

Sulfated Phenolic Substances: Preparation and Optimized HPLC Analysis.

Sulfation is an important reaction in nature, and sulfated phenolic compounds are of interest as standards of mammalian phase II metabolites or pro-drugs. Such standards can be prepared using chemoenzymatic methods with aryl sulfotransferases. The aim of the present work was to obtain a large library of sulfated phenols, phenolic acids, flavonoids, and flavonolignans and optimize their HPLC (high performance liquid chromatography) analysis.

Two fungal flavonoid-specific glucosidases/rutinosidases for rutin hydrolysis and rutinoside synthesis under homogeneous and heterogeneous reaction conditions.

The glycosidases within GH5-23 cleave the glycosidic bond of β-glucosylated or rutinosylated flavonoids. Moreover, by virtue of their transglycosylation activity, glycoconjugates with glucosyl and rutinosyl moieties are accessible. Here we report the biochemical characterization and biotechnological assessment of two heterologously expressed members of GH5-23-McGlc from Mucor circinelloides and PcGlc from Penicillium chrysogenum.

Dual Substrate Specificity of the Rutinosidase from and the Role of Its Substrate Tunnel.

Rutinosidases (α-l-rhamnopyranosyl-(1-6)-β-d-glucopyranosidases, EC 3.2.1.

Hypoxia-inducible factor 2-alpha-dependent induction of amphiregulin dampens myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion injury (IRI) leads to the stabilization of the transcription factors hypoxia-inducible factor 1-alpha (HIF1-alpha) and hypoxia-inducible factor 2-alpha (HIF2-alpha). While previous studies implicate HIF1-alpha in cardioprotection, the role of HIF2-alpha remains elusive. Here we show that HIF2-alpha induces the epithelial growth factor amphiregulin (AREG) to elicit cardioprotection in myocardial IRI.

Neutrophil transfer of to lung epithelial cells dampens acute lung injury in mice.

Intercellular transfer of microRNAs can mediate communication between critical effector cells. We hypothesized that transfer of neutrophil-derived microRNAs to pulmonary epithelial cells could alter mucosal gene expression during acute lung injury. Pulmonary-epithelial microRNA profiling during coculture of alveolar epithelial cells with polymorphonuclear neutrophils (PMNs) revealed a selective increase in lung epithelial cell expression of microRNA-223 ().

A model-specific role of microRNA-223 as a mediator of kidney injury during experimental sepsis.

Sepsis outcomes are heavily dependent on the development of septic organ injury, but no interventions exist to interrupt or reverse this process. microRNA-223 (miR-223) is known to be involved in both inflammatory gene regulation and host-pathogen interactions key to the pathogenesis of sepsis. The goal of this study was to determine the role of miR-223 as a mediator of septic kidney injury.

Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome.

MicroRNA (miRNA)-mediated RNA interference regulates many immune processes, but how miRNA circuits orchestrate aberrant intestinal inflammation during inflammatory bowel disease (IBD) is poorly defined. Here, we report that miR-223 limits intestinal inflammation by constraining the nlrp3 inflammasome. miR-223 was increased in intestinal biopsies from patients with active IBD and in preclinical models of intestinal inflammation.

Intense light-elicited upregulation of miR-21 facilitates glycolysis and cardioprotection through Per2-dependent mechanisms.

A wide search for ischemic preconditioning (IPC) mechanisms of cardioprotection identified the light elicited circadian rhythm protein Period 2 (Per2) to be cardioprotective. Studies on cardiac metabolism found a key role for light elicited Per2 in mediating metabolic dependence on carbohydrate metabolism. To profile Per2 mediated pathways following IPC of the mouse heart, we performed a genome array and identified 352 abundantly expressed and well-characterized Per2 dependent micro RNAs.

NK cells regulate CXCR2+ neutrophil recruitment during acute lung injury.

A critical step in the pathogenesis of acute lung injury (ALI) is excessive recruitment of polymorphonuclear neutrophils (PMNs) into the lungs, causing significant collateral tissue damage. Defining the molecular and cellular steps that control neutrophil infiltration and activation during ALI is therefore of important therapeutic relevance. Based on previous findings implicating the transcription factor Tbet in mucosal Th1-inflammation, we hypothesized a detrimental role for Tbet during ALI.

A case of butane hash oil (marijuana wax)-induced psychosis.

Background: Marijuana is one of the most widely used controlled substances in the United States. Despite extensive research on smoked marijuana, little is known regarding the potential psychotropic effects of marijuana "wax," a high-potency form of marijuana that is gaining in popularity.

Case: The authors present a case of "Mr.

Emerging Roles for MicroRNAs in Perioperative Medicine.

MicroRNAs (miRNAs) are small, non-protein-coding, single-stranded RNAs. They function as posttranscriptional regulators of gene expression by interacting with target mRNAs. This process prevents translation of target mRNAs into a functional protein.

Tissue-Resident NK Cells Mediate Ischemic Kidney Injury and Are Not Depleted by Anti-Asialo-GM1 Antibody.

NK cells are innate lymphoid cells important for immune surveillance, identifying and responding to stress, infection, and/or transformation. Whereas conventional NK (cNK) cells circulate systemically, many NK cells reside in tissues where they appear to be poised to locally regulate tissue function. In the present study, we tested the contribution of tissue-resident NK (trNK) cells to tissue homeostasis by studying ischemic injury in the mouse kidney.

Impaired extracellular matrix structure resulting from malnutrition in ovariectomized mature rats.

Bone loss is a symptom related to disease and age, which reflects on bone cells and ECM. Discrepant regulation affects cell proliferation and ECM localization. Rat model of osteoporosis (OVX) was investigated against control rats (Sham) at young and old ages.

Alveolar Epithelial A2B Adenosine Receptors in Pulmonary Protection during Acute Lung Injury.

Acute lung injury (ALI) is an acute inflammatory lung disease that causes morbidity and mortality in critically ill patients. However, there are many instances where ALI resolves spontaneously through endogenous pathways that help to control excessive lung inflammation. Previous studies have implicated the extracellular signaling molecule adenosine and signaling events through the A2B adenosine receptor in lung protection.