SIRT1 Asn346 sugar chain promoting collagen deacetylation protective effect on osteoblasts under stress.

Silencing type information regulator homolog 1 (SIRT1) is a class of nicotinamide adenine dinucleotide (NAD+) dependent deacetylases, which is the convergence point of important physiological processes in vivo, namely, osteoblast aging, energy metabolism, and bone remodeling. To verify whether the O-acetylglucosamine (O-GlcNAc) modification of SIRT1 in the nucleus of osteoblasts enhances its deacetylase activity under stress and protects osteoblasts through the RANK/RANKL signaling pathway by collagen deacetylation. The R language and online data research identified SIRT1 as being involved in bone metabolism. Enrichment analysis showed that SIRT1 is involved in osteoblast transcription, apoptosis, and deacetylation pathways. Interactive Immuno-blotting and immunofluorescence experiments revealed that SIRT1 and O-glycosylation catalytic enzyme (OGT) were localized in the nucleus. Mass Spectrometry analysis showed that O-glycosylation occurred on the asparagine at the 346th position of SIRT1, and N346th was located in the central domain of SIRT1. Furthermore, the protein structure analysis of PyMol also proved that the OGT binding region was in the central domain of SIRT1. Under physiological conditions, both wtSIRT1 and SIRT1N346R can inhibit RANKL-mediated transcriptional activation. The RT-PCR detection results showed that wtSIRT1 reduced RANKL transcription under the conditions of apoptotic agent treatment. The finding that SIRT1 can regulate the physiological process of bone remodeling through the RANK/RANKL signaling pathway in osteoblasts under stress. The O-glycosylation and deacetylation activity of SIRT1 significantly increased, regulating the balance between osteoblast survival and apoptosis by deacetylation of key proteins such as RANKL.

Cross-reactive antibodies against dust mite-derived enolase induce neutrophilic airway inflammation.

BACKGROUND AND AIMS: Neutrophilic inflammation is a hallmark of some specific asthma phenotypes; its aetiology is not yet fully understood. House dust mite (HDM) is the most common factor in the pathogenesis of airway inflammation. This study aims to elucidate the role of cross-antibodies against HDM-derived factors in the development of neutrophilic inflammation in the airway. METHODS: Blood samples were collected from asthma patients with chronic neutrophilic asthma for analysis of HDM-specific cross-reactive antibodies. The role of an antibody against HDM-derived enolase (EnoAb) in the impairment of airway epithelial barrier function and induction of airway inflammation was assessed in a cell culture model and an animal model. RESULTS: High similarity (72%) of the enolase gene sequences was identified between HDM and human. Serum EnoAb was detected in patients with chronic neutrophilic asthma. The EnoAb bound to airway epithelial cells to form complexes with enolase, which activated complement, impaired airway epithelial barrier functions and induced neutrophilic inflammation in the airway tissues. CONCLUSIONS: HDM-derived enolase can induce specific cross-antibodies in humans, which induce neutrophilic inflammation in the airway.

Immunohistochemical identification of osteoclasts and multinucleated macrophages.

Osteoclasts are bone-resorbing multinuclear cells derived from hematopoietic stem cells which are specialised to carry out lacunar bone resorption. The immunophenotype of giant cell-containing bone lesions in a wide range of osteoclast-like giant cells was similarly assessed. Both multinucleated macrophages and osteoclasts were found to express CD68. Multinucleated macrophages, but not osteoclasts, expressed GrB and Ki67. CD13+/CD14+/CD68+/GrB-/Ki67-/CD56- all giant-cell lesions noted in giant cells of bone. Giant cells have an osteoclast phenotype in most giant cell-rich lesions of bone, which do not express the macrophage-associated antigens GrB and Ki67. Our results indicate that they are formed from osteoclast precursors of mononuclear phagocyte.

Diaqua-bis-(1H-imidazole-κN(3))bis-(4-nitro-benzoato-κO(1))cadmium.

In the centrosymmetric title compound, [Cd(C(7)H(4)NO(4))(2)(C(3)H(4)N(2))(2)(H(2)O)(2)], the Cd(II) atom, located on an inversion center, is coordinated by two N atoms and four O atoms in an octa-hedral geometry. The inter-nal cohesion of the mol-ecule is enhanced by an intra-molecular O-H⋯O hydrogen bond. Inter-molecular O-H⋯O and C-H⋯O hydrogen bonds and π-π contacts [centroid-centroid distance = 3.6549 (2) Å] define two-dimensional networks parallel to (001), which are further connected by weaker C-H⋯O inter-actions into a weakly connected three-dimensional supra-molecular framework.

Bis(2,2'-bipyridine-κ(2)N,N')(3-methyl-benzoato-κ(2)O,O')zinc 3-methyl-benzo-ate-3-methyl-benzoic acid-water (1/1/2).

The title compound, [Zn(C(8)H(7)O(2))(C(10)H(8)N(2))(2)](C(8)H(7)O(2))·C(8)H(8)O(2)·2H(2)O, is comprised of a Zn(2+) cation, two 2,2'-bipydine (bipy) ligands and one 3-methyl-benzoate anion (L(-)) together with one uncoordinating L(-) anion, one uncoordinating HL mol-ecule and two lattice water mol-ecules. The Zn(II) atom is coordinated by four N atoms of two bipy ligands and two O atoms from one L(-) ligand in a distorted octa-hedral geometry. Pairs of centrosymmetrically related complex mol-ecules form dimers via slipped π-stacking inter-actions between bipy ligands with an inter-planar distance of 3.470 (4) Å. The dimers are linked into supra-molecular chains along [111], via C-H⋯O hydrogen bonds. The uncoordinated L(-) anions, HL mol-ecules and water mol-ecules are connected with each other via O-H⋯O hydrogen bonds, forming chains between the metal complex chains and binding them together via C-H⋯O contacts. The resulting layers parallel to (010) are further assembled into a three-dimensional supra-molecular architecture through additional C-H⋯O inter-actions.

catena-Poly[[(diaqua-calcium)-bis-(µ-2-fluorobenzoato)-1':1κO:O,O';1:1''κO,O':O] 2,2'-bipyridine hemi-solvate].

In the title compound, {[Ca(C(7)H(4)FO(2))(2)(H(2)O)(2)]·0.5C(10)H(8)N(2)}(n), the Ca(II) atom is coordinated by eigth O atoms from four 2-fluoro-benzoate ligands and two water mol-ecules, resulting in a distorted CaO(8) square-anti-prismatic coordination environment. The 2-fluoro-benzoate ligand bridges two symmetry-related Ca(II) atoms, giving rise to a chain structure extending along [100]. The distances between the Ca atom and its two symmetry-related counterparts are 4.054 (2) and 4.106 (2) Å. The polymeric chains are connected by classical O-H⋯N hydrogen bonds into a layer structure parallel to (010). The layers are connected by non-classical C-H⋯F hydrogen bonds into a three-dimensional supra-molecular structure. O-H⋯O and C-H⋯O inter-actions also occur. The uncoordinated 2,2'-bipyridine mol-ecule is located on a centre of symmetry at the mid-point of the bond between the two heterocycles. One of the two benzene rings is disordered over two sites with occupancy factors of 0.60 and 0.40.

Da vinci robotic-assisted treatment of pediatric choledochal cyst.

Objective: To evaluate the advantages and disadvantages of da Vinci robot and laparoscopy in treating pediatric choledochal cysts. Methods: We retrospectively analyzed clinical data from forty-two children diagnosed with choledochal cysts in our hospital from January 2018 to January 2021. Twenty children underwent da Vinci robotic surgery, and the others underwent traditional laparoscopy. We compared differences in general information and preoperative, intraoperative, and postoperative differences between the two surgical groups. Results: There was no statistically significant difference in age, gender, weight, type, maximum cyst diameter, preoperative C-reactive protein (CRP) value, postoperative complication rate, and postoperative pain score between the two surgical groups (P > 0.05). The average age of the robot-assisted group was 3.62 ± 0.71 years old (range = 1-12 years). There were nineteen cases of Todani type I, one patients of other types, and the maximum cyst diameter was 35.45 ± 9.32 mm (range = 12-56 mm). In the laparoscopic group, the average age was 3.08 ± 0.82 years old (range = 3-10 years). Twenty-one patients had Todani type I, and one had other types. The maximum cyst diameter was 31.94 ± 8.64 mm (range = 10-82 mm). The robot-assisted group had better abdominal drainage, postoperative CRP value, fasting time, and discharge time than the laparoscopic group (P < 0.05). Conclusion: Compared with laparoscopy, the da Vinci system has the advantages of less tissue damage, faster recovery, and better healing in the treatment of children with congenital choledochal cysts. With technological advancements and an increased number of experienced surgeons, robotic surgery may become a new trend in surgery.

House dust mite exposure enhances immune responses to ovalbumin-induced intestinal allergy.

House dust mites (HDM) are one of the important factors of airway allergic diseases, HDM allergens can be detected in the human gut mucosa, which induces local inflammation and increases intestinal epithelial permeability. This study tests a hypothesis that HDM contribute to the development of OVA (ovalbumin)-induced intestinal allergy. The serum levels of IgE against HDM in patients with food allergy were detected with UniCAP100 (Pharmacia, Uppsala, Sweden); a mouse model of food allergy was developed with OVA and HDM as the specific antigens. Compared to healthy controls, patients with food allergy have higher levels of serum HDM-specific IgE. Compared to food allergy alone groups, the levels of HDM-specific IgE in patients with food allergy and asthma or allergic rhinitis were significantly higher. In mouse models, we found that HDM/OVA induced allergy-like symptoms, lower body temperature, and lower body weight. The levels of IgE, IgG1, mMCP-1 (mouse mast cell protease-1), IL-4 and IL-5 in the HDM and HDM + CT (cholera toxin) groups were higher than the control groups, and the levels of IgE, IgG1, IL-4 and IL-5 in the HDM, OVA and HDM + OVA groups were higher than the control groups. The pathological changes of intestinal tissues in the HDM and HDM + CT/the HDM, OVA and HDM + OVA groups were more severe, more eosinophil infiltration than the control groups. Moreover, exposure to HDM induced intestinal barrier dysfunction, and facilitated the development of intestinal allergy in mice. In conclusion, HDM exposure enhances immune responses to OVA-induced food allergy.

Aqua-(2,9-dimethyl-1,10-phenanthroline-κN,N')diformato-κO,O';κO-nickel(II) monohydrate.

The asymmetric unit of the title compound, [Ni(HCO(2))(2)(C(14)H(12)N(2))(H(2)O)]·H(2)O, contains a mononuclear complex mol-ecule hydrogen bonded to a lattice water mol-ecule. The Ni(II) atom exhibits a distorted octa-hedral coordination geometry formed by the N atoms from a 2,9-dimethyl-1,10-phenanthroline ligand, two O atoms of a chelating formate anion, one aqua O atom and one O atom of a coordinating formate anion. The mol-ecules are assembled into chains extending along [100] through by O-H⋯O hydrogen bonds. The supra-molecular chains are further linked into layers parallel to (011) by weak π-π packing inter-actions [centroid-centroid separation = 3.768 (2) Å]. The resulting layers are stacked to meet the requirement of close-packing patterns.

Poly[hexa-aqua-bis-(µ(3)-hepta-nedioato-κO:O':O'')dimagnesium].

In the title compound, [Mg(2)(C(7)H(10)O(4))(2)(H(2)O)(6)](n), the Mg(II) ion is coordinated by three aqua ligands and three O atoms from three heptanedioato ligands in a distorted octa-hedral geometry. Each heptanedioato ligand bridges three Mg atoms, generating polymeric layers parallel to the bc plane. The polymeric layers related by translation along the a axis inter-act further via O-H⋯O hydrogen bonds, which consolidate the crystal packing.

Urea-adipic acid (2/1).

The asymmetric unit of the title co-crystal, 2CH(4)N(2)O·C(6)H(10)O(4), contains two urea mol-ecules and two half-mol-ecules of adipic acid; the latter are completed by crystallographic inversion symmetry. The crystal packing is stabilized by O-H⋯O and N-H⋯O hydrogen bonds, generating a chain along [110]. Additional weak inter-chain O-H⋯O and N-H⋯O inter-molecular inter-actions lead to the formation of a three-dimensional network.

Aqua-(4-carb-oxy-pyridine-2,6-dicarboxyl-ato-κO,N,O)(1,10-phenanthroline-κN,N')nickel(II).

The title compound, [Ni(C(8)H(3)NO(6))(C(12)H(8)N(2))(H(2)O)], contains an Ni(II) ion, a 1,10-phenanthroline (phen) ligand, a 4-carb-oxy-pyridine-2,6-dicarboxyl-ate (Hptc(2-)) anion and a coordinated water mol-ecule. The Ni(II) atom exhibits a distorted octa-hedral N(3)O(3) environment. O-H⋯O hydrogen bonding between coordinated water and carboxyl-ate O atoms, as well as π-π stacking inter-actions [inter-planar distances between phen rings = 3.293 (2) Å] lead to a supermolecular assembly.

2,2'-Bipyridine-cyclo-pentane-1,2,3,4-tetra-carb-oxy-lic acid (1/1).

The asymmetric unit of the title compound, C(10)H(8)N(2)·C(9)H(10)O(8), contains a half-molecule of 2,2'-bipyridine and a half-molecule of 1,2,3,4-cyclopentanetetracarboxylic acid, both components being completed by crystallographic inversion symmetry. In the crystal, the mol-ecules are assembled into chains extending along [010] by O-H⋯N hydrogen bonds; adjacent chains are linked by O-H⋯O hydrogen bonds into a three-dimensional network.

(2,2'-Bipyridine-κN,N')bis-(3-meth-oxy-benzoato-κO,O)copper(II) mono-hydrate.

The title compound, [Cu(C(8)H(7)O(3))(2)(C(10)H(8)N(2))]·H(2)O, is comprised of a Cu(II) ion, two 3-meth-oxy-benzoate ligands, a 2,2'-bipyridine (bipy) ligand and one uncoordinated water mol-ecule. The Cu(II) ion and the water O atom lie on a twofold axis. The Cu(II) ion exhibits a six-coordinate distorted octa-hedral geometry, with two N atoms from the bipy ligand [Cu-N = 1.9996 (16) Å] and four O atoms from two 3-meth-oxy-benzoate ligands [Cu-O = 1.9551 (15) and 2.6016 (16) Å]. The mol-ecules are linked by O-H⋯O and C-H⋯O hydrogen bonds, forming a three-dimensional network.

Tetra-µ-2-methyl-benzoato-κO:O'-bis-[(ethanol-κO)copper(II)].

In the title dinuclear complex, [Cu(2)(C(8)H(7)O(2))(4)(C(2)H(5)OH)(2)], four 2-methyl-benzoato anions form a cage around two Cu(II) ions in a syn-anti configuration. Two ethanol mol-ecules coordinate the Cu atoms in apical positions, giving an overall square-pyramidal coordination geometry. The Cu⋯Cu separation is 2.600 (1) Å. In the crystal, mol-ecules are assembled into chains extending in [001] through O-H⋯O hydrogen bonds.

Aqua-(4-fluoro-benzoato-κO)bis-(1,10-phenanthroline-κN,N')manganese(II) 4-fluoro-benzoate trihydrate.

In the title compound, [Mn(C(7)H(4)FO(2))(C(12)H(8)N(2))(2)(H(2)O)](C(7)H(4)FO(2))·3H(2)O, the Mn(II) atom is coordinated by four N atoms from two chelating 1,10-phenanthroline ligands and two O atoms from one monodentate 4-fluoro-benzoate ion and one water mol-ecule, forming a distorted octa-hedral geometry. In the crystal, the three components are assembled into a tape structure along the a axis by O-H⋯O and C-H⋯O hydrogen bonds. Between the tapes, a π-π inter-action with a centroid-centroid distance of 3.569 (3) Šand a weak C-H⋯F hydrogen bond are observed.

Enolase-specific cross antibodies induce neutrophilic inflammation in the intestine.

The pathogenesis of ulcerative colitis (UC) is to be further investigated. House dust mites (HDM) are highly associated with the pathogenesis of immune inflammation in the body. This study aims to investigate the role of enolase (one of the HDM-derived proteins)-specific cross Abs in the induction of UC-like inflammation. The enolase specific IgG (EsIgG) was identified in UC patients by mass spectrometry. Mice were treated with EsIgG to induce inflammation in the colon mucosa. EsIgG was detected in the serum and the colon tissues of UC patients, which was positively correlated with the polymorphonuclear neutrophil (PMN) counts in the blood and colon tissues of UC patients. EsIgG formed immune complexes with the constitutive enolase in the UC colon epithelium that activated complement, induced epithelial cell apoptosis, compromised epithelial barrier functions, and resulted in UC-like inflammation in the mouse colon. In summary, UC patients have high serum levels of Abs against HDM-derived enolase and intestinal epithelial cell-derived enolase. These Abs attack the colonic epithelium to induce UC-like inflammation.

Twist1 contributes to developing and sustaining corticosteroid resistance in ulcerative colitis.

Rationale: Corticosteroid resistance (CR) is a serious drawback to steroid therapy in patients with ulcerative colitis (UC); the underlying mechanism is incompletely understood. Twist1 protein (TW1) is an apoptosis inhibitor and has immune regulatory functions. This study aims to elucidate the roles of TW1 in inducing and sustaining the CR status in UC. Methods: Surgically removed colon tissues of patients with ulcerative colitis (UC) were collected, from which neutrophils were isolated by flow cytometry. The inflammation-related gene activities in neutrophils were analyzed by RNA sequencing. A CR colitis mouse model was developed with the dextran sulfate sodium approach in a hypoxia environment. Results: Higher TW1 gene expression was detected in neutrophils isolated from the colon tissues of UC patients with CR and the CR mouse colon tissues. TW1 physically interacted with glucocorticoid receptor (GR)α in CR neutrophils that prevented GRα from interacting with steroids; which consequently abrogated the effects of steroids on regulating the cellular activities of neutrophils. STAT3 (Signal Transducer and Activator of Transcription-3) interacted with Ras protein activator like 1 to sustain the high TW1 expression in colon mucosal neutrophils of CR patients and CR mice. Inhibition of TW1 restored the sensitivity to corticosteroid of neutrophils in the colon tissues of a CR murine model. Conclusions: UC patients at CR status showed high TW1 expression in neutrophils. TW1 prevented steroids from regulating neutrophil activities. Inhibition of TW1 restored the sensitivity to corticosteroids in the colon tissues at the CR status.

Disodium dihydrogen pyridine-2,3,5,6-tetra-carboxyl-ate trihydrate.

In the title compound, 2Na(+)·C(9)H(3)NO(8) (2-)·3H(2)O, the asymmetric unit consists of two Na(+) cations, one dihydrogen pyridine-2,3,5,6-tetra-carboxyl-ate dianion (H(2)pdtc(2-)) and three water mol-ecules coordinated to the Na(+) cations. The configuration of the anion is stabilized by intramolecular O-H⋯O hydrogen bonding between vicinal carboxylate/carboxy groups. The Na(+) cations are bridged by the H(2)pdtc(2-) dianions, generating layers extending infinitely in sheets parallel to (001), and further pillared by the water mol-ecule linkers to build up a three-dimensional framework.

catena-Poly[[[diaqua-copper(II)]-bis-(µ(2)-di-4-pyridyl disulfide-κN:N')] bis-(hydrogen phthalate) monohydrate].

The asymmetric unit of the title compound, {[Cu(C(10)H(8)N(2)S(2))(2)(H(2)O)(2)](C(8)H(5)O(4))(2)·H(2)O}(n), contains one Cu(II) ion, two bridging di-4-pyridyl disulfide (4-DPDS) ligands of the same chirality, two coordinating water mol-ecules, two hydrogen phthalate anions and one uncoordinated water mol-ecule. The polymeric structure consists of two types of polymeric chains, each composed from repeated chiral rhomboids. The Cu(II) ions adopt a distorted octa-hedral coordination geometry and are coordinated by four pyridine N atoms and two water O atoms. The coordinated water mol-ecules and hydrogen phthalate anions are located between the repeated rhomboidal chains, and form hydrogen bonds with the coordinated water mol-ecules.