Subsequent Deacetylation Research Articles

Study on the adsorption properties of lysozyme by cellulose microspheres modified with reactive red 120

Microspheres of cellulose acetate, characterized by a multi-layered, uniform, and continuous porous structure, were synthesized through the process of emulsion evaporation. Subsequent deacetylation facilitated the modification of the cellulose microspheres’ surface, which was functionalized with Reactive Red 120, serving as an affinity dye ligand. This modification yielded a cationic adsorbent. The adsorptive behavior of lysozyme from aqueous solutions, with lysozyme designated as the target protein, was examined in relation to the effects of pH and ionic strength. The adsorptive capacity of the cellulose microspheres, modified with Reactive Red 120, for lysozyme was determined to be 106.57 mg g−1, exhibiting rapid equilibration within 40 min. The adsorption kinetics and thermodynamics were accurately described by the pseudo-second-order kinetic model and the Langmuir model, respectively, with correlation coefficients (R2) of 0.98 and 0.97. Furthermore, dynamic adsorption experiments revealed an enhanced adsorption capacity of 36.5 mg g−1, significantly surpassing that of the unmodified microspheres. The cellulose microspheres, derived from cellulose acetate and modified accordingly, are environmentally benign and sustainable, thereby holding significant promise for various biological applications.

Effect of Nε-acetylation on the Enzymatic Activity of <i>Escherichia coli</i> Glyceraldehyde-3-phosphate Dehydrogenase

The regulation of cellular metabolism is a topic of interest for both fundamental and applied science, as the findings can be used in various biotechnological industries. One of the universal regulatory mechanisms that affects most cellular processes is the acetylation of lysine residues in central metabolic enzymes, such as glyceraldehyde-3-phosphate dehydrogenase. In this work, we investigated the effect of acetylation and deacetylation on the activity of both wild type and mutant E. coli glyceraldehyde-3-phosphate dehydrogenase. We found that in vitro acetylation of wild-type GAPDH by PatZ acetyltransferase increased its enzymatic activity by twofold, while subsequent deacetylation restored the activity to initial level. For mutant forms of glyceraldehyde-3-phosphate dehydrogenase, we demonstrated that the introduction of additional acetylation sites due to mutations altered the impact of acetylation/deacetylation processes on glyceraldehyde-3-phosphate dehydrogenase activity. Our data suggest a re-evaluation of the role of acetylation in regulating glyceraldehyde-3-phosphate dehydrogenase activity and its involvement in E. coli metabolism.

Naringenin ameliorates vascular senescence and atherosclerosis involving SIRT1 activation.

This study was to explore the potential effects and mechanism of naringenin against vascular senescence in atherosclerosis focusing on the SIRT1-mediated signalling pathway. Aged apoE-/- mice were administrated with naringenin continuously for three months. Lipid parameters in serum and pathological changes and associated protein expression in aorta were examined. In vitro, endothelial cells were treated with H2O2 to induce senescence. Dyslipidemia, atherosclerotic lesion formation and vascular senescence were found in ApoE-/- mice, which were significantly ameliorated by naringenin treatment. Naringenin decreased reactive oxygen species overproduction and enhanced the activities of antioxidant enzymes in aorta. It also decreased mitoROS production and increased protein expressions of mitochondrial biogenesis-related genes in aorta. Moreover, naringenin treatment enhanced aortic protein expression and activity of SIRT1. Meanwhile, naringenin increased deacetylation and protein expression of SIRT1's target genes FOXO3a and PGC1α. In vitro study, the benefits of naringenin on endothelial senescence, oxidative stress and mitochondrial injury as well as protein expressions and acetylated levels of FOXO3a and PGC1α were diminished in cells transfected with SIRT1 siRNA. Naringenin could ameliorate vascular senescence and atherosclerosis and the activation of SIRT1, with subsequent deacetylation and regulation of FOXO3a and PGC1α, is involved in this process.

Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity

Imbalances in NAD+ homeostasis have been linked to aging and various diseases. Nicotine, a metabolite of the NAD+ metabolic pathway, has been found to possess anti-inflammatory and neuroprotective properties, yet the underlying molecular mechanisms remained unknown. Here we find that, independent of nicotinic acetylcholine receptors, low-dose nicotine can restore the age-related decline of NAMPT activity through SIRT1 binding and subsequent deacetylation of NAMPT, thus increasing NAD+ synthesis. 18F-FDG PET imaging revealed that nicotine is also capable of efficiently inhibiting glucose hypermetabolism in aging male mice. Additionally, nicotine ameliorated cellular energy metabolism disorders and deferred age-related deterioration and cognitive decline by stimulating neurogenesis, inhibiting neuroinflammation, and protecting organs from oxidative stress and telomere shortening. Collectively, these findings provide evidence for a mechanism by which low-dose nicotine can activate NAD+ salvage pathways and improve age-related symptoms.

Olefin-Metathesis-Derived Norbornene-Ethylene-Vinyl Acetate/Vinyl Alcohol Multiblock Copolymers: Impact of the Copolymer Structure on the Gas Permeation Properties.

Commercial metathesis polynorbornene is used for the fabrication of high-damping coatings and bulk materials that dissipate vibration and impact energies. Functionalization of this non-polar polymer can improve its adhesive, gas barrier, and other properties, thereby potentially expanding its application area. With this aim, the post-modification of polynorbornene was carried out by inserting ethylene–vinyl acetate–vinyl alcohol blocks into its backbone via the cross-metathesis of polynorbornene with poly(5-acetoxy-1-octenylene) and subsequent deacetylation and hydrogenation of the obtained multiblock copolymers. For the first time, epoxy groups were introduced into the main chains of these copolymers, followed by the oxirane ring opening reaction. The influence of post-modification on the thermal, gas separation, and mechanical properties of the new copolymers was studied. It was shown that the gas permeability of the copolymer significantly depends on its composition, as well as on the amounts of hydroxyl and epoxy groups. The developed methods efficiently improve the barrier properties, reducing the oxygen permeability by 15–33 times in comparison with polynorbornene. The obtained results are promising for various applications and can be extended to a broader family of polydienes and other polymers containing backbone double bonds.

Cytokines and pregnancy: Potential regulation by histonedeacetylases.

Cytokines are important regulators of pregnancy and parturition. Aberrant expression of proinflammatory cytokines during pregnancy contributes towards preterm labor, pre-eclampsia, and gestational diabetes mellitus. The regulation of cytokine expression in human cells is highly complex, involving interactions between environment, transcription factors, and feedback mechanisms. Recent developments in epigenetic research have made tremendous advancements in exploring histone modifications as a key epigenetic regulator of cytokine expression and the effect of their signaling molecules on various organ systems in the human body. Histone acetylation and subsequent deacetylation by histone deacetylases (HDACs) are major epigenetic regulators of protein expression in the human body. The expression of various proinflammatory cytokines, their role in normal and abnormal pregnancy, and their epigenetic regulation via HDACs will be discussed in this review.

A novel approach to nonsurgical sterilization; application of menadione-modified gonocyte-targeting M13 bacteriophage for germ cell ablation in utero.

There remains a compelling need for the development of nonsurgical sterilizing agents to expand the fertility management options for both domestic and feral animal species. We hypothesize that an efficacious sterilization approach would be to selectively ablate nonrenewable cell types that are essential for reproduction, such as the undifferentiated gonocytes within the embryonic gonad. Here, we report a novel strategy to achieve this goal centered on the use of a chemically modified M13 bacteriophage to effect the targeted delivery of menadione, a redox‐cycling naphthoquinone, to mouse gonocytes. Panning of the M13 random peptide ‘phage display library proved effective in the isolation of gonocyte‐specific targeting clones. One such clone was modified via N‐succinimidyl‐S‐acetylthioacetate (SATA) linkage to the N‐terminus of the major PVIII capsid protein. Subsequent deacetylation of the SATA was undertaken to expose a thiol group capable of reacting with menadione through Michael addition. This chemical modification was confirmed using UV spectrophotometry. In proof‐of‐concept experiments we applied the modified ‘phage to primary cultures of fetal germ cells and induced, an approximately, 60% reduction in the viability of the target cell population. These studies pave the way for in vivo application of chemically modified M13 bacteriophage in order to achieve the selective ablation of nonrenewable cell types in the reproductive system, thereby providing a novel nonsurgical approach the regulation of fertility in target species.

The Soluble Adenylyl Cyclase Inhibitor LRE1 Prevents Hepatic Ischemia/Reperfusion Damage Through Improvement of Mitochondrial Function.

Hepatic ischemia/reperfusion (I/R) injury is a leading cause of organ dysfunction and failure in numerous pathological and surgical settings. At the core of this issue lies mitochondrial dysfunction. Hence, strategies that prime mitochondria towards damage resilience might prove applicable in a clinical setting. A promising approach has been to induce a mitohormetic response, removing less capable organelles, and replacing them with more competent ones, in preparation for an insult. Recently, a soluble form of adenylyl cyclase (sAC) has been shown to exist within mitochondria, the activation of which improved mitochondrial function. Here, we sought to understand if inhibiting mitochondrial sAC would elicit mitohormesis and protect the liver from I/R injury. Wistar male rats were pretreated with LRE1, a specific sAC inhibitor, prior to the induction of hepatic I/R injury, after which mitochondria were collected and their metabolic function was assessed. We find LRE1 to be an effective inducer of a mitohormetic response based on all parameters tested, a phenomenon that appears to require the activity of the NAD+-dependent sirtuin deacylase (SirT3) and the subsequent deacetylation of mitochondrial proteins. We conclude that LRE1 pretreatment leads to a mitohormetic response that protects mitochondrial function during I/R injury.

Synthesis, antibacterial activities, and sustained perfume release properties of optically active5-hydroxy- and 5-acetoxyalkanethioamide analogues

Abstract 5-Acetoxy- and 5-hydroxyalkanethioamide analogues showed high antibacterial activity against Staphylococcus aureus. Antibacterial thioamides were prepared from 5-alkyl-δ-lactones by amidation, thionation, and subsequent deacetylation. Optically active thioamides with 99% diastereomeric excesses were prepared by diastereomeric resolution using Cbz-L-proline as the resolving agent. Antibacterial thioamides were slowly lactonized by a lipase catalyst. Therefore, these thioamides are potential sustained-release perfume compounds having antibacterial properties.

One-pot fabrication of cellulose-collagen fibrous networks for potential use as wound dressing: From characterization to first evaluation of cytocompatibility

Biomedical researchers have been attempting to construct a wound dressing with the structure and function of a bionic natural extracellular matrix. This dressing would provide a comfortable environment for wound self-healing. In this study, cellulose-collagen fibrous networks were easily fabricated via the one-pot method using genipin in situ crosslinking collagen hydrolysate in cellulose nanofibrous membranes made by electrospinning cellulose acetate and subsequent deacetylation. The morphology, properties, and successful entrapment of collagen in the cellulose fibrous dressings were validated by scanning electron microscopy, element analysis, Fourier transform infrared spectroscopy, X-ray diffraction, water-swelling test, and thermal gravimetric analysis. The functional cellulose nanofiber-based composite membranes exhibited a network structure, good thermal stability, and acceptable water resistance. Human epidermal cells seeded on the composite nanofibrous membranes presented favorable growth, indicating good cytocompatibility and suitability of the dressing to the wound. Therefore, these novel cellulose-collagen fibrous networks may have potential use in biomedical applications.

Increasing cell permeability of N-acetylglucosamine via 6-acetylation enhances capacity to suppress T-helper 1 (TH1)/TH17 responses and autoimmunity.

N-acetylglucosamine (GlcNAc) branching of Asn (N)–linked glycans inhibits pro-inflammatory T cell responses and models of autoimmune diseases such as Multiple Sclerosis (MS). Metabolism controls N-glycan branching in T cells by regulating de novo hexosamine pathway biosynthesis of UDP-GlcNAc, the donor substrate for the Golgi branching enzymes. Activated T cells switch metabolism from oxidative phosphorylation to aerobic glycolysis and glutaminolysis. This reduces flux of glucose and glutamine into the hexosamine pathway, thereby inhibiting de novo UDP-GlcNAc synthesis and N-glycan branching. Salvage of GlcNAc into the hexosamine pathway overcomes this metabolic suppression to restore UDP-GlcNAc synthesis and N-glycan branching, thereby promoting anti-inflammatory T regulatory (Treg) over pro-inflammatory T helper (TH) 17 and TH1 differentiation to suppress autoimmunity. However, GlcNAc activity is limited by the lack of a cell surface transporter and requires high doses to enter cells via macropinocytosis. Here we report that GlcNAc-6-acetate is a superior pro-drug form of GlcNAc. Acetylation of amino-sugars improves cell membrane permeability, with subsequent de-acetylation by cytoplasmic esterases allowing salvage into the hexosamine pathway. Per- and bi-acetylation of GlcNAc led to toxicity in T cells, whereas mono-acetylation at only the 6 > 3 position raised N-glycan branching greater than GlcNAc without inducing significant toxicity. GlcNAc-6-acetate inhibited T cell activation/proliferation, TH1/TH17 responses and disease progression in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS.

Abstract P1-06-01: Regulation of BRCA1 by SIRT2

Abstract We are constantly exposed to a variety of both external and internal DNA damaging agents, such as UV light from the sun and reactive oxygen species created as by-products of aerobic respiration. As a result, our DNA accumulates thousands of instances of damage per cell per day. DNA damage response (DDR) pathways, which include DNA repair and cell-cycle checkpoints, are responsible for the repair of DNA damage and are critical for protecting against mutagenesis and maintaining genome integrity. DNA double-stranded breaks (DSBs) are the most deleterious type of DNA damage and are repaired by one of two pathways: Non-homologous end-joining (NHEJ), an error-prone mechanism of repair active throughout the entire cell cycle, or homologous recombination (HR), considered to be an 'error-free' method for DSB repair that occurs in the S and G2 phases of the cell cycle. Deficiencies in NHEJ or HR can result in genomic instability via genomic incorporation of chromosomal aberrations, which can ultimately lead to an increased risk of cancer. However, in many cases, the mechanisms by which defects in these pathways lead to an increased risk of developing cancer is unknown, making preventative care and treatment of resulting cancers more difficult. Breast Cancer 1 (BRCA1), an established tumor suppressor, is a protein necessary for the proper repair of DNA DSBs through the HR pathway. Defects in BRCA1, whether genetically inherited or spontaneously developed, have been linked to different types of cancer in both men and women, including breast, ovarian, and pancreatic cancer. Yet, the regulation of BRCA1 in HR is not well understood and thus highlights a major a gap in our understanding of how deficiencies in HR contribute to the development of cancer. Our lab has discovered that SIRT2, a class III NAD+ dependent histone deacetylase and putative human tumor suppressor, plays a crucial role in the DDR and repair of DNA DSBs. We have shown that depletion of SIRT2 impairs HR and increases cell sensitivity to ionizing radiation in a deacetylase-dependent manner. A mass spectrometry analysis showed SIRT2 interacts with several proteins involved in DDR, including BRCA1. We validated the interaction between SIRT2 and BRCA1 and found SIRT2 deacetylates BRCA1 both in vitro and in cells. Depletion of SIRT2 and subsequent deacetylation of BRCA1 decreases BRCA1 protein levels in cells, impairing HR. Our results show SIRT2 is a novel regulator of BRCA1 and is critical for the repair of DNA DSBs through HR. These findings provide invaluable insights into how to exploit the interplay between SIRT2 and BRCA1 as a novel therapeutic approach for the prevention and treatment of cancer. Citation Format: Minten EV, Zhang H, Li C, Head PE, Yu DS. Regulation of BRCA1 by SIRT2 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-06-01.

Synthesis of 20S-Protopanaxatriol β-D-Glucopyranosides

Condensation of 20S-protopanaxatriol (3β,6α,12β,20S-tetrahydroxydammar-24-ene) (1) with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide (2) in the presence of Ag2O in CH2Cl2 gave a mixture of acetylated 3-, 12-, 20-, 3,12-di-, and 3,20-di-O-β-D-glucopyranosides 3–7 that was dominated by 3-O-β-Dglucopyranoside tetraacetate 3 (47%). Subsequent deacetylation by sodium methoxide produced free β-D-glucopyranosides 8–12, three of which were identical to chikusetsusaponin-L10, ginsenoside-F1, and ginsenoside-Ia, which were isolated earlier from leaves of Panax japonicus and P. ginseng. 3-Mono- and 3,12-di-O-β-D-glucopyranosides 8 and 11 were prepared for the first time.

A Novel and Facile Synthesis of Thiopyrimidines and O-Glucosides

Reaction of 3-methyl-5-(3'-aryl prop-2'-enoyl)-1,2-benzisoxazole (1a-j) with thiourea and alcoholic solution of KOH afforded 3-methyl-5-(4'-aryl-2'-thiopyrimidin-6'-yl)-1,2-benzisoxazoles (2a-j). Oxidation of products 2a-j using alkaline KMnO4 solution produces 5-(4'-aryl-2'-thiopyrimidin-6'-yl)-1,2-benzisoxazole-3-carboxylic acids (3a-j). Condensation of products 3a-j with 2,3,4,6-tetra-Oacetyl-α-D-glucopyranosyl bromide (TAGBr), the glucosylating agent synthesized 3-(2,3,4,6-tetra-O-acetyl-3-acetyl-β-D-glucopyranosyl)-5-(4'-aryl-2'-thiopyrimidin-6'-yl)-1,2-benzisoxazoles (4a-j). Subsequent deacetylation of compounds 4a-j were carried out with CH3ONa furnishes β-Dglucopyranosyl-5-(4'-aryl-2'-thiopyrimidin-6'-yl)-1,2-benzisoxazole-3-carboxylates (5a-j). All the synthesized compounds were analyzed by elemental analysis (C, H and N), FT-IR, 1H NMR and mass spectral data. Most of the prepared compounds were analyzed their antibacterial and antifungal activities by cup-plate method. The present approach offers several advantages such as shorter reaction times, cleaner reactions, good yields, low-cost reagent and mild reaction conditions.

Tree-like cellulose nanofiber membranes modified by citric acid for heavy metal ion (Cu2+) removal

Eco-friendly tree-like porous carboxyl modified cellulose nanofiber membranes as highly efficient adsorbents for heavy metal ions were fabricated by the electrospinning of cellulose acetate (CA)/tetrabutylammonium chloride (TBAC)/manganese dioxide (MnO2) solution, and subsequent deacetylation treatment to turn CA into cellulose and citric acid modification to graft carboxyl group on the surface of cellulose nanofibers. The addition of TBAC led to the formation of tree-like structure and MnO2 particles were used as pore-forming agents. The effects of pH, initial ion concentrations and contact time on the removal capacity of heavy metal ions were investigated. During the removal process, the abundant carboxyl groups (–COOH) transferred to carboxylate ions (–COO−) which had stronger ion exchange ability to the metal ion adsorption. In addition, the tree-like porous structure supplied large specific surface area and effectively increased the removal capacity. The removal process could reach a plateau in 90 min with the maximum removal amount of 399.14 mg/g. The removal process was also depicted by Langmuir and Freundlich isotherm model. Generally, the tree-like porous structure will have extensive prospects in the fields of filtration, electrochemistry, tissue engineering and so on.

Abstract 1363: Regulation of BRCA1 by SIRT2

Abstract In our everyday lives, we are constantly being exposed to DNA damaging agents, both from internal and external sources. The most deleterious type of DNA damage a cell can suffer is the DNA double-stranded break (DSB). Breast Cancer 1 (BRCA1) is a protein necessary for the proper repair of resultant DNA DSBs through the homologous recombination (HR) pathway. Defects in BRCA1 have been linked to different types of cancer in both men and women, including breast, ovarian, and pancreatic cancer. However, the regulation of BRCA1 is not yet well understood, and in many cases, how defects in this pathway lead to an increased risk of developing cancer is also unknown, making preventative care and treatment of resulting cancers more difficult. Our lab has discovered that SIRT2, a histone deacetylase and putative human tumor suppressor, plays a crucial role in the DNA damage response (DDR) and repair of DNA DSBs. We have shown that depletion of SIRT2 impairs HR and increases cell sensitivity to IR in a deacetylase-dependent manner. A mass spectrometry analysis showed SIRT2 interacts with a number of proteins involved in DDR, including BRCA1. We validated the interaction between SIRT2 and BRCA1 and also found SIRT2 deacetylates BRCA1 both in vitro and in cells. Depletion of SIRT2 and subsequent deacetylation of BRCA1 decreases BRCA1 protein levels in cells and thus impairs HR. Our results show SIRT2 is a novel regulator of BRCA1 and is critical for the repair of DNA DSBs through HR. These findings provide insight into how dysregulation of SIRT2 or BRCA1 can result in genomic instability and lead to the development of cancer. Citation Format: Elizabeth Minten, Hui Zhang, Chunyang Li, PamelaSara Head, David Yu. Regulation of BRCA1 by SIRT2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1363.

Regulation of BRCA1 by SIRT2

In our everyday lives, we are constantly being exposed to DNA damaging agents, both from internal and external sources. The most deleterious type of DNA damage a cell can suffer is the DNA double‐stranded break (DSB). Breast Cancer 1 (BRCA1) is a protein necessary for the proper repair of resultant DNA DSBs through the homologous recombination (HR) pathway. Defects in BRCA1 have been linked to different types of cancer in both men and women, including breast, ovarian, and pancreatic cancer. However, the regulation of BRCA1 is not yet well understood, and in many cases, how defects in this pathway lead to an increased risk of developing cancer is also unknown, making preventative care and treatment of resulting cancers more difficult. Our lab has discovered that SIRT2, a histone deacetylase and putative human tumor suppressor, plays a crucial role in the DNA damage response (DDR) and repair of DNA DSBs. We have shown that depletion of SIRT2 impairs HR and increases cell sensitivity to IR in a deacetylase‐dependent manner. A mass spectrometry analysis showed SIRT2 interacts with a number of proteins involved in DDR, including BRCA1. We validated the interaction between SIRT2 and BRCA1 and also found SIRT2 deacetylates BRCA1 both in vitro and in cells. Depletion of SIRT2 and subsequent deacetylation of BRCA1 decreases BRCA1 protein levels in cells and thus impairs HR. Our results show SIRT2 is a novel regulator of BRCA1 and is critical for the repair of DNA DSBs through HR. These findings provide insight into how dysregulation of SIRT2 or BRCA1 can result in genomic instability and lead to the development of cancer.Support or Funding InformationDr. David Yu, NIH R01This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Epigallocatechin-3-Gallate-Rich Green Tea Extract Ameliorates Fatty Liver and Weight Gain in Mice Fed a High Fat Diet by Activating the Sirtuin 1 and AMP Activating Protein Kinase Pathway.

The prevalence of metabolic diseases has risen globally in parallel with the obesity epidemic over the past few decades. Green tea has been reported to have metabolically beneficial effects on obesity; however, the mechanism by which green tea regulates lipid metabolism is not clearly understood. Male c57BL/6 mice were fed a normal chow diet, a high-fat diet (HFD), or an HFD supplemented with various doses of epigallocatechin gallate-rich green tea extract (GTE) for 12 weeks. GTE supplementation reduced body weight gain, prevented hepatic fat accumulation, decreased hypertriglyceridemia, and improved hyperglycemia and insulin resistance in HFD-fed mice. The underlying mechanisms of these beneficial effects of GTE might involve the upregulation of sirtuin 1 and AMP activated protein kinase (AMPK) and the downregulation of enzymes related to de novo lipogenesis. Consistent with the in vivo findings, GTE increased the expression and activity of sirtuin 1, enhanced the binding of sirtuin 1 to liver kinase B1 (LKB1) and subsequent deacetylation of LKB1, and reduced triglyceride accumulation in HepG2 cells. These results suggest the possible therapeutic potential of dietary epigallocatechin gallate-rich GTE supplementation for preventing the development and progression of hepatic steatosis and obesity.

Reduced silent information regulator 1 signaling exacerbates sepsis-induced myocardial injury and mitigates the protective effect of a liver X receptor agonist

Myocardial injury and dysfunction are critical manifestations of sepsis. Previous studies have reported that liver X receptor (LXR) activation is protective during sepsis. However, whether LXR activation protects against septic heart injury and its underlying mechanisms remain elusive. This study was designed to determine the role of LXR activation in the septic heart with a focus on SIRT1 (silent information regulator 1) signaling. Male cardiac-specific SIRT1 knockout mice (SIRT1-/-) and their wild-type littermates were subjected to sepsis by cecal ligation and puncture (CLP) in the presence or absence of LXR agonist T0901317. The survival rate of mice was recorded during the 7-day period post CLP. Our results demonstrated that SIRT1-/- mice suffered from exacerbated mortality and myocardial injury in comparison with their wild-type littermates. Meanwhile, T0901317 treatment improved mice survival, accompanied by significant ameliorations of myocardial injury and dysfunction in wild-type mice but not in SIRT1-/- mice. Furthermore, the levels of myocardial inflammatory cytokines (TNF-α, IL-6, IL-1β, MCP-1, MPO and HMGB1), oxidative stress (ROS generation, MDA), endoplasmic-reticulum (ER) stress (protein levels of CHOP, GRP78, GRP94, IRE1α, and ATF6), and cardiac apoptosis following CLP were inhibited by T0901317 treatment in wild-type mice but not in SIRT1-/- mice. Mechanistically, T0901317 enhanced SIRT1 signaling and the subsequent deacetylation and activation of antioxidative FoxO1 and anti-ER stress HSF1, as well as the deacetylation and inhibition of pro-inflammatory NF-ΚB and pro-apoptotic P53, thereby alleviating sepsis-induced myocardial injury and dysfunction. Our data support the promise of LXR activation as an effective strategy for relieving heart septic injury.

Thermal, structural and acetylation behavior of snail and periwinkle shells chitin

This article reports a successful removal of CaCO3 from snail and periwinkle shells for the purpose of producing high quality chitin for possible application as bio-fillers in bone fixation materials. Experiment was designed with varying concentrations of acid and alkali for demineralization, deproteinization and deacetylation of the samples. Thermal characteristics, morphology, degree of de-acetylation, crystalline structure and hydrogen bonding characteristics of the extracted chitin were examined. Infra-red spectra, thermogravimetric analysis and X-ray diffraction patterns show that demineralization with 1.7 M HCl led to a successful removal of CaCO3. Subsequent deproteinization and deacetylation with 1.2 M NaOH led to a development of chitosan having a degree of deacetylation of 77 and 60% for periwinkle and snail shells, respectively. Generally, all results show that different treatments led to different chitin structure and consequently different properties.