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Frontiers in Endocrinology 2021Bilirubin is a biochemical substance with metabolic benefits. The objective of this research was to elucidate the association between serum bilirubin levels and...
OBJECTIVES
Bilirubin is a biochemical substance with metabolic benefits. The objective of this research was to elucidate the association between serum bilirubin levels and metabolic alterations in different obesity phenotypes.
METHODS
In total, 1,042 drug-naive participants were included in the study. Of them, 541 were obese patients and 501 were age-matched and sex-matched healthy control subjects. The obese patients were divided into metabolically healthy obesity (MHO) group and metabolically unhealthy obesity (MUHO) group according to the levels of fasting plasma glucose (FBG), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and blood pressure (BP). Clinical and biochemical parameters including total bilirubin (TBil), indirect bilirubin (IBil) and direct bilirubin (DBil) were measured. ANOVA or Kruskal-Wallis H test was used to test differences among the three groups. Pearson and Spearman correlations were used to analyze the relationships between two parameters. The relationships between bilirubin and other variables were analyzed using Multivariate regression analysis.
RESULTS
MHO group had favorable blood pressure, glucose and lipids profiles, along with increased TBil and DBil, and decreased high-sensitivity C-reactive protein (hsCRP) and homeostasis model assessment of insulin resistance (HOMA-IR) levels when compared to MUHO group ( < 0.05 for all). TBil and DBil were negatively correlated with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), fasting insulin (FINS), hsCRP and HOMA-IR, even after adjusted for age, gender and BMI (all <0.01). Multivariate regression analysis demonstrated that HOMA-IR was independently correlated with TBil and DBIi levels (β = -0.400, < 0.01).
CONCLUSION
MHO group harbors increased bilirubin level compared with MUHO group. HOMA-IR was independently correlated with TBil and DBIi levels.
Topics: Bilirubin; Body Mass Index; C-Reactive Protein; Cholesterol, HDL; Humans; Insulin Resistance; Obesity; Obesity, Metabolically Benign
PubMed: 35432184
DOI: 10.3389/fendo.2021.792795 -
Chemical Reviews Dec 2021This review adds the bilin-binding phytochromes to the thematic issue "Optogenetics and Photopharmacology". The work is structured into two parts. We first outline the... (Review)
Review
This review adds the bilin-binding phytochromes to the thematic issue "Optogenetics and Photopharmacology". The work is structured into two parts. We first outline the photochemistry of the covalently bound tetrapyrrole chromophore and summarize relevant spectroscopic, kinetic, biochemical, and physiological properties of the different families of phytochromes. Based on this knowledge, we then describe the engineering of phytochromes to further improve these chromoproteins as photoswitches and review their employment in an ever-growing number of different optogenetic applications. Most applications rely on the light-controlled complex formation between the plant photoreceptor PhyB and phytochrome-interacting factors (PIFs) or C-terminal light-regulated domains with enzymatic functions present in many bacterial and algal phytochromes. Phytochrome-based optogenetic tools are currently implemented in bacteria, yeast, plants, and animals to achieve light control of a wide range of biological activities. These cover the regulation of gene expression, protein transport into cell organelles, and the recruitment of phytochrome- or PIF-tagged proteins to membranes and other cellular compartments. This compilation illustrates the intrinsic advantages of phytochromes compared to other photoreceptor classes, e.g., their bidirectional dual-wavelength control enabling instant ON and OFF regulation. In particular, the long wavelength range of absorption and fluorescence within the "transparent window" makes phytochromes attractive for complex applications requiring deep tissue penetration or dual-wavelength control in combination with blue and UV light-sensing photoreceptors. In addition to the wide variability of applications employing natural and engineered phytochromes, we also discuss recent progress in the development of bilin-based fluorescent proteins.
Topics: Animals; Bile Pigments; Light; Optogenetics; Photochemistry; Photoreceptor Cells; Phytochrome
PubMed: 34669383
DOI: 10.1021/acs.chemrev.1c00194 -
International Journal of Molecular... Oct 2022A diabetic foot ulcer (DFU) is one of the major complications of diabetes. Wound healing under diabetic conditions is often impaired. This is in part due to the... (Review)
Review
A diabetic foot ulcer (DFU) is one of the major complications of diabetes. Wound healing under diabetic conditions is often impaired. This is in part due to the excessive oxidative stress, prolonged inflammation, immune cell dysfunction, delayed re-epithelialization, and decreased angiogenesis present at the wound site. As a result of these multifactorial impaired healing pathways, it has been difficult to develop effective therapeutic strategies for DFU. Heme oxygenase-1 (HO-1) is the rate-limiting enzyme in heme degradation generating carbon monoxide (CO), biliverdin (BV) which is converted into bilirubin (BR), and iron. HO-1 is a potent antioxidant. It can act as an anti-inflammatory, proliferative, angiogenic and cytoprotective enzyme. Due to its biological functions, HO-1 plays a very important role in wound healing, in part mediated through the biologically active end products generated by its enzymatic activity, particularly CO, BV, and BR. Therapeutic strategies involving the activation of HO-1, or the topical application of its biologically active end products are important in diabetic wound healing. Therefore, HO-1 is an attractive therapeutic target for DFU treatment. This review will provide an overview and discussion of the importance of HO-1 as a therapeutic target for diabetic wound healing.
Topics: Anti-Inflammatory Agents; Antioxidants; Biliverdine; Carbon Monoxide; Diabetes Mellitus; Diabetic Foot; Heme; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Humans; Iron
PubMed: 36233341
DOI: 10.3390/ijms231912043 -
Proceedings of the National Academy of... Apr 2023Terrestrial ecosystems and human societies depend on oxygenic photosynthesis, which began to reshape our atmosphere approximately 2.5 billion years ago. The earliest...
Terrestrial ecosystems and human societies depend on oxygenic photosynthesis, which began to reshape our atmosphere approximately 2.5 billion years ago. The earliest known organisms carrying out oxygenic photosynthesis are the cyanobacteria, which use large complexes of phycobiliproteins as light-harvesting antennae. Phycobiliproteins rely on phycocyanobilin (PCB), a linear tetrapyrrole (bilin) chromophore, as the light-harvesting pigment that transfers absorbed light energy from phycobilisomes to the chlorophyll-based photosynthetic apparatus. Cyanobacteria synthesize PCB from heme in two steps: A heme oxygenase converts heme into biliverdin IXα (BV), and the ferredoxin-dependent bilin reductase (FDBR) PcyA then converts BV into PCB. In the current work, we examine the origins of this pathway. We demonstrate that PcyA evolved from pre-PcyA proteins found in nonphotosynthetic bacteria and that pre-PcyA enzymes are active FDBRs that do not yield PCB. Pre-PcyA genes are associated with two gene clusters. Both clusters encode bilin-binding globin proteins, phycobiliprotein paralogs that we designate as BBAGs (bilin biosynthesis-associated globins). Some cyanobacteria also contain one such gene cluster, including a BBAG, two V4R proteins, and an iron-sulfur protein. Phylogenetic analysis shows that this cluster is descended from those associated with pre-PcyA proteins and that light-harvesting phycobiliproteins are also descended from BBAGs found in other bacteria. We propose that PcyA and phycobiliproteins originated in heterotrophic, nonphotosynthetic bacteria and were subsequently acquired by cyanobacteria.
Topics: Humans; Phylogeny; Phycobiliproteins; Oxidoreductases; Ecosystem; Bile Pigments; Cyanobacteria
PubMed: 37071675
DOI: 10.1073/pnas.2300770120 -
Current Hypertension Reports Oct 2019To discuss recent advances indicating that bilirubin safeguards against cardiorenal and metabolic diseases. (Review)
Review
PURPOSE OF REVIEW
To discuss recent advances indicating that bilirubin safeguards against cardiorenal and metabolic diseases.
RECENT FINDINGS
Several investigations from human patient populations and experimental animal models have shown that bilirubin improves cardiorenal and metabolic dysfunction. The latest studies found an entirely new function of bilirubin suggesting that it acts as a hormone signaling molecule capable of activating nuclear receptors for burning fat, which may explain several of its protective actions. This review highlights the current findings (within the last 3 years) regarding cardiorenal and metabolic protective effects of bilirubin and the latest mechanism(s) that may be mediating these effects.
Topics: Animals; Antioxidants; Bilirubin; Cardiovascular Diseases; Humans; Hypertension; Kidney Diseases; Metabolic Diseases
PubMed: 31599366
DOI: 10.1007/s11906-019-0994-z -
Scientific Reports Nov 2023Previous studies have shown that metabolites play an important role in phenotypic regulation. However, the causal relationship between metabolites and multiple myeloma...
Previous studies have shown that metabolites play an important role in phenotypic regulation. However, the causal relationship between metabolites and multiple myeloma has not been adequately investigated. Here, we attempt to explore the causal effects of genetically determined blood metabolites on multiple myeloma. The large-scale public blood metabolites and multiple myeloma datasets from independently published genome-wide association studies (GWAS) were used to explore the causal relationship between each genetically determined blood metabolite and multiple myeloma through inverse variance weighted (IVW), weighted median, MR-Egger and mode-based estimation methods. Sensitivity tests were performed to evaluate the stability and reliability of the results by MR-Egger regression and leave-one-out methods. Metabolic pathway analysis was further explored using filtered data. Statistical analyses were all performed in R. Among 452 metabolites, ten known metabolites and three unknown metabolites had significant causal relationship with multiple myeloma (P < 0.05). Four known metabolites, 3-methyl-2-oxovalenate, oxidized bilirubin, isovalerylcarnitine and glutamine carnitine, reached statistical significance in IVW models. Metabolic pathways analysis identified four significant pathways. The occurrence of multiple myeloma may have a causal relationship with these four metabolites, and there are four metabolic pathways that are also related to the occurrence of multiple myeloma. This can provide new ideas for exploring early screening and treatment of multiple myeloma.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; Multiple Myeloma; Reproducibility of Results; Bilirubin
PubMed: 37914749
DOI: 10.1038/s41598-023-45801-0 -
The American Journal of Gastroenterology Apr 2024Despite growing awareness of post-coronavirus disease 2019 (COVID-19) cholangiopathy as one of the most serious long-term gastrointestinal consequences of COVID-19, the... (Observational Study)
Observational Study
INTRODUCTION
Despite growing awareness of post-coronavirus disease 2019 (COVID-19) cholangiopathy as one of the most serious long-term gastrointestinal consequences of COVID-19, the endoscopic features of this disease are still poorly characterized. This study aimed to more precisely define its endoscopic features and to outline the role of endoscopic retrograde cholangiopancreatography (ERCP) in the management of this entity.
METHODS
In this observational study, 46 patients with confirmed post-COVID-19 cholangiopathy were included.
RESULTS
Based on the endoscopic features observed in 141 ERCP procedures, post-COVID-19 cholangiopathy can be classified as a variant of secondary sclerosing cholangitis in critically ill patients. It appeared early in the course of intensive care treatment of patients with COVID-19 (cholestasis onset 4.5 days after intubation, median). This form of cholangiopathy was more destructive than stricturing in nature and caused irreversible damage to the bile ducts. A centripetal pattern of intrahepatic bile duct destruction, the phenomenon of vanishing bile ducts, the absence of extrahepatic involvement, and the presence of intraductal biliary casts (85% of patients) were typical cholangiographic features of post-COVID-19 cholangiopathy. This cholangiopathy was often complicated by small peribiliary liver abscesses with isolation of Enterococcus faecium and Candida spp. in bile culture. The prognosis was dismal, with a 1-year liver transplantation-free survival rate of 44%. In particular, patients with peribiliary liver abscesses or destruction of the central bile ducts tended to have a poor prognosis (n.s.). As shown by multivariate analysis, bilirubin levels (on intensive care unit day 25-36) negatively correlated with liver transplantation-free survival (hazard ratio 1.08, P < 0.001). Interventional endoscopy with cast removal had a positive effect on cholestasis parameters (gamma-glutamyl transpeptidase, alkaline phosphatase, and bilirubin); approximately 60% of all individual values decreased.
DISCUSSION
Gastrointestinal endoscopy makes an important contribution to the management of post-COVID-19 cholangiopathy. ERCP is not only of great diagnostic and prognostic value but also has therapeutic value and therefore remains indispensable.
Topics: Humans; Cholangiopancreatography, Endoscopic Retrograde; COVID-19; Cholestasis; Liver Diseases; Bilirubin; Liver Abscess
PubMed: 37843039
DOI: 10.14309/ajg.0000000000002562 -
The Journal of Physical Chemistry. B Apr 2022The ability of phytochromes to act as photoswitches in plants and microorganisms depends on interactions between a bilin-like chromophore and a host protein. The...
The ability of phytochromes to act as photoswitches in plants and microorganisms depends on interactions between a bilin-like chromophore and a host protein. The interconversion occurs between the spectrally distinct red (Pr) and far-red (Pfr) conformers. This conformational change is triggered by the photoisomerization of the chromophore D-ring pyrrole. In this study, as a representative example of a phytochrome-bilin system, we consider biliverdin IXα (BV) bound to bacteriophytochrome (BphP) from . In the absence of light, we use an enhanced sampling molecular dynamics (MD) method to overcome the photoisomerization energy barrier. We find that the calculated free energy (FE) barriers between essential metastable states agree with spectroscopic results. We show that the enhanced dynamics of the BV chromophore in BphP contributes to triggering nanometer-scale conformational movements that propagate by two experimentally determined signal transduction pathways. Most importantly, we describe how the metastable states enable a thermal transition known as the dark reversion between Pfr and Pr, through a previously unknown intermediate state of Pfr. We present the heterogeneity of temperature-dependent Pfr states at the atomistic level. This work paves a way toward understanding the complete mechanism of the photoisomerization of a bilin-like chromophore in phytochromes.
Topics: Bacterial Proteins; Bile Pigments; Biliverdine; Binding Sites; Molecular Conformation; Phytochrome
PubMed: 35357137
DOI: 10.1021/acs.jpcb.2c00131 -
Journal of Perinatology : Official... Feb 2023
Topics: Humans; Bilirubin; Kernicterus
PubMed: 35618749
DOI: 10.1038/s41372-022-01417-2 -
Gut Mar 2023
Topics: Humans; Hyperbilirubinemia; Bilirubin; Digestive System Diseases
PubMed: 35636922
DOI: 10.1136/gutjnl-2022-327532