ABSTRACT
BACKGROUND: Breast cancer is one of the common malignancies in women. Evidence has demonstrated that FBXO45 plays a pivotal role in oncogenesis and progression. However, the role of FBXO45 in breast tumorigenesis remains elusive. Exploration of the regulatory mechanisms of FBXO45 in breast cancer development is pivotal for potential therapeutic interventions in patients with breast cancer. METHODS: Hence, we used numerous approaches to explore the functions of FBXO45 and its underlaying mechanisms in breast cancer pathogenesis, including CCK-8 assay, EdU assay, colony formation analysis, apoptosis assay, RT-PCR, Western blotting, immunoprecipitation, ubiquitination assay, and cycloheximide chase assay. RESULTS: We found that downregulation of FBXO45 inhibited cell proliferation, while upregulation of FBXO45 elevated cell proliferation in breast cancer. Silencing of FBXO45 induced cell apoptosis, whereas overexpression of FBXO45 inhibited cell apoptosis in breast cancer. Moreover, FBXO45 interacted with BIM and regulated its ubiquitination and degradation. Furthermore, knockdown of FBXO45 inhibited cell proliferation via regulation of BIM pathway. Notably, overexpression of FBXO45 facilitated tumor growth in mice. Strikingly, FBXO45 expression was associated with poor survival of breast cancer patients. CONCLUSION: Our study could provide the rational for targeting FBXO45 to obtain benefit for breast cancer patients. Altogether, modulating FBXO45/Bim axis could be a promising strategy for breast cancer therapy.
Subject(s)
Apoptosis , Bcl-2-Like Protein 11 , Breast Neoplasms , Cell Proliferation , Disease Progression , F-Box Proteins , Ubiquitination , Humans , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/genetics , Female , Animals , F-Box Proteins/metabolism , F-Box Proteins/genetics , Mice , Bcl-2-Like Protein 11/metabolism , Bcl-2-Like Protein 11/genetics , Cell Line, Tumor , Proteolysis , Gene Expression Regulation, Neoplastic , Mice, NudeABSTRACT
The deposition and intercalation of metal atoms can induce superconductivity in monolayer and bilayer graphenes. For example, it has been experimentally proved that Li-deposited graphene is a superconductor with critical temperature Tc of 5.9 K, Ca-intercalated bilayer graphene C6CaC6 and K-intercalated epitaxial bilayer graphene C8KC8 are superconductors with Tc of 2-4 K and 3.6 K, respectively. However, the Tc of them are relatively low. To obtain higher Tc in graphene-based superconductors, here we predict a new Ca-intercalated bilayer graphene C2CaC2, which shows higher Ca concentration than the C6CaC6. It is proved to be thermodynamically and dynamically stable. The electronic structure, electron-phonon coupling (EPC) and superconductivity of C2CaC2 are investigated based on first-principles calculations. The EPC of C2CaC2 mainly comes from the coupling between the electrons of C-pz orbital and the high- and low-frequency vibration modes of C atoms. The calculated EPC constant λ of C2CaC2 is 0.75, and the superconducting Tc is 18.9 K, which is much higher than other metal-intercalated bilayer graphenes. By further applying -4% biaxial compressive strain to C2CaC2, the Tc can be boosted to 26.6 K. Thus, the predicted C2CaC2 provides a new platform for realizing superconductivity with the highest Tc in bilayer graphenes.
ABSTRACT
Salvianolic acid A (SAA), a major active ingredient of Salvia miltiorrhiza Bunge (Danshen), displays strong antiproliferative activity against cancer cells. However, their protein targets remain unknown. Here, we deconvoluted the protein targets of SAA using chemoproteomics and phosphoproteomics. By using alkynylated SAA as a probe, we discovered that SAA is a covalent ligand that can modify cellular proteins via its electrophilic α,ß-unsaturated ester moiety. The subsequent chemoproteomics profiling revealed that 46 proteins were covalently modified by SAA, including Raptor, a subunit of mTORC1 for recruiting substrates for mTORC1. Although gene ontology enrichment analysis of these proteins suggested that SAA displays a promiscuous protein interaction, phosphoproteomics profiling revealed that the SAA modulated phosphoproteins were mainly enriched in the signaling pathways of PI3K-Akt-mTOR, which is closely related to cell growth and proliferation. This was confirmed by the biochemical assay with purified mTORC1, a Western blot assay with phospho-specific antibodies, and a cellular thermal shift assay. Our work discovered that SAA is a covalent ligand for protein modification and mTORC1 is one of its targets. Moreover, our work demonstrated that the integrative profiling of chemoproteomics and phosphoproteomics can be a powerful tool for target deconvolution for bioactive natural products.
Subject(s)
Phosphatidylinositol 3-Kinases , Signal Transduction , Mechanistic Target of Rapamycin Complex 1 , Ligands , Caffeic Acids/pharmacologyABSTRACT
Profiling drug-protein interactions is critical for understanding a drug's mechanism of action and predicting the possible adverse side effects. However, to comprehensively profile drug-protein interactions remains a challenge. To address this issue, we proposed a strategy that integrates multiple mass spectrometry-based omics analysis to provided global drug-protein interactions, including physical interactions and functional interactions, with rapamycin (Rap) as a model. Chemoproteomics profiling reveals 47 Rap binding proteins including the known target protein FKBP12 with high confidence. Gen Ontology enrichment analysis suggested that the Rap binding proteins are implicated in several important cellular processes, such as DNA replication, immunity, autophagy, programmed cell death, aging, transcription modulation, vesicle-mediated transport, membrane organization, and carbohydrate and nucleobase metabolic processes. The phosphoproteomics profiling revealed 255 down-regulated and 150 up-regulated phosphoproteins responding to Rap stimulation; they mainly involve the PI3K-Akt-mTORC1 signaling axis. Untargeted metabolomic profiling revealed 22 down-regulated metabolites and 75 up-regulated metabolites responding to Rap stimulation; they are mainly associated with the synthesis processes of pyrimidine and purine. The integrative multiomics data analysis provides deep insight into the drug-protein interactions and reveals Rap's complicated mechanism of action.
Subject(s)
Phosphatidylinositol 3-Kinases , Sirolimus , Sirolimus/pharmacology , Signal Transduction , Tacrolimus Binding Proteins , Mass SpectrometryABSTRACT
Monolayer biphenylene is a new two-dimensional (2D) carbon allotrope, which has been experimentally synthesized and theoretically predicted to show superconductivity. In this work, we investigate functionalized biphenylene with the adsorption of Li. The superconducting critical temperature (Tc) can be pushed from 0.59 K up to 3.91 K after Li adsorption. Our calculations confirm that the adsorption pushes the peak showing a high electronic density of states closer to the Fermi level, which usually leads to a larger Tc. Furthermore, the application of biaxial tensile strain can soften phonons and further enhance the Tc up to 15.86 K in Li-deposited biphenylene. Interestingly, a pair of type-II Dirac cones below the Fermi level has been observed, expanding the range of Dirac materials. It suggests that monolayer biphenylene deposited with Li may be a material with potential applications and improves the understanding of Dirac-type superconductors.
ABSTRACT
Bacillus cereus endophthalmitis is a devastating eye infection that causes rapid blindness through the release of extracellular tissue-destructive exotoxins. The phagocytic and antibacterial functions of ocular cells are the keys to limiting ocular bacterial infections. In a previous study, we identified a new virulence gene, plcA-2 (different from the original plcA-1 gene), that was strongly associated with the plcA gene of Listeria monocytogenes. This plcA gene had been confirmed to play an important role in phagocytosis. However, how the Bc-phosphatidylinositol-specific phospholipase C (PI-PLC) proteins encoded by the plcA-1/2 genes affect phagocytes remains unclear in B. cereus endophthalmitis. Here, we found that the enzymatic activity of Bc-PI-PLC-A2 was approximately twofold higher than that of Bc-PI-PLC-A1, and both proteins inhibited the viability of Müller cells. In addition, PI-PLC proteins reduced phagocytosis of Müller cells by decreasing the phosphorylation levels of key proteins in the PI3K/AKT signaling pathway. In conclusion, we showed that PI-PLC proteins contribute to inhibit the viability of and suppress the phagocytosis of Müller cells, providing new insights into the pathogenic mechanism of B. cereus endophthalmitis.
Subject(s)
Endophthalmitis , Listeria monocytogenes , Humans , Phosphoinositide Phospholipase C/genetics , Phosphoinositide Phospholipase C/metabolism , Phosphatidylinositol Diacylglycerol-Lyase/genetics , Phosphatidylinositol Diacylglycerol-Lyase/metabolism , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Cell Survival , Ependymoglial Cells/metabolism , Phagocytes/metabolism , Signal Transduction , Type C Phospholipases/genetics , Type C Phospholipases/metabolismABSTRACT
BACKGROUND: De novo urothelial carcinoma (UC) is a leading cause of death after kidney transplant (KT). The efficacy of various treatments, apart from surgery, and the prognosis for patients with urothelial carcinoma after kidney transplantation remain unclear. METHODS: We retrospectively reviewed the efficacy of chemotherapy with gemcitabine + cisplatin (GC) or gemcitabine + carboplatin (GCa), bladder infusion chemotherapy, and immunosuppression therapy for de novo UC in kidney transplantation recipients at different sites and T stages. We evaluated the prognosis and compared the difference using Kaplan-Meier analysis and the log-rank test. RESULTS: Of the 97 kidney transplantation recipients with de novo UC, 51 (52.6%) were diagnosed with upper urinary tract carcinoma (UTUC), 17 (17.5%) with bladder carcinoma (BC), and 29 (29.9%) with both UTUC and BC. The five-year survival rates for BC, UTUC, and BC + UTUC with ≤ T1 stage were 100%, 88.2%, and 57.7%, respectively, while the survival rates for UTUC, BC + UTUC with ≥ T2 stage were 90.2% and 48.2%. Cyclosporine A significantly improved progression-free survival (PFS) in UTUC with ≤ T1 stage (p = 0.017). Rapamycin significantly improved PFS in UTUC with ≥ T2 stage (p = 0.026). Bladder infusion chemotherapy and GC/GCa chemotherapy had no significant effect on each T stage and site. Patients with UTUC + BC had the poorest overall survival (OS) compared with those with BC and UTUC. CONCLUSION: The prognosis of UC in different sites varies. GC/GCa chemotherapy and bladder infusion chemotherapy appear to have no effect on prognosis. Rapamycin can delay the progression of advanced UTUC.
Subject(s)
Carcinoma, Transitional Cell , Kidney Transplantation , Urinary Bladder Neoplasms , Urologic Neoplasms , Humans , Urinary Bladder Neoplasms/pathology , Carcinoma, Transitional Cell/pathology , Retrospective Studies , Urologic Neoplasms/drug therapy , Treatment Outcome , Cisplatin , DeoxycytidineABSTRACT
ZnIn2S4 (ZIS) is widely used in the field of photocatalytic hydrogen production due to its unique photoelectric properties. Nonetheless, the photocatalytic performance of ZIS usually faces problems of poor conductivity and rapid recombination of charge carriers. Heteroatom doping is often regarded as one of the effective strategies for improving the catalytic activity of photocatalysts. Herein, phosphorus (P)-doped ZIS was prepared by hydrothermal method, whose photocatalytic hydrogen production performance and energy band structure were fully studied. The band gap of P-doped ZIS is about 2.51 eV, which is slightly smaller than that of pure ZIS. Moreover, due to the upward shift of its energy band, the reduction ability of P-doped ZIS is enhanced, and P-doped ZIS also exhibits stronger catalytic activity than pure ZIS. The optimized P-doped ZIS exhibits a hydrogen production rate of 1566.6 µmol g-1 h-1, which is 3.8 times that of the pristine ZIS (411.1 µmol g-1 h-1). This work provides a broad platform for the design and synthesis of phosphorus-doped sulfide-based photocatalysts for hydrogen evolution.
Subject(s)
Hydrogen , Light , Electric Conductivity , PhosphorusABSTRACT
Binding via reversible covalent bond formation presents a novel and powerful mechanism to enhance the potency of synthetic inhibitors for therapeutically important proteins. Work on this front has yielded the anticancer drug bortezomib as well as the antisickling drug voxelotor. However, the rational design of reversible covalent inhibitors remains difficult even when noncovalent inhibitors are available as a scaffold. Herein, we report chemically modified phage libraries, both linear and cyclic, that incorporate 2-acetylphenylboronic acid (APBA) as a warhead to bind lysines via reversible iminoboronate formation. To demonstrate their utility, these APBA-presenting phage libraries were screened against sortase A of Staphylococcus aureus, as well as the spike protein of SARS-CoV-2. For both protein targets, peptide ligands were readily identified with single-digit micromolar potency and excellent specificity, enabling live-cell sortase inhibition and highly sensitive spike protein detection, respectively. Furthermore, our structure-activity studies unambiguously demonstrate the benefit of the APBA warhead for protein binding. Overall, this contribution shows for the first time that reversible covalent inhibitors can be developed via phage display for a protein of interest. The phage display platform should be widely applicable to proteins including those involved in protein-protein interactions.
Subject(s)
Bacteriophages , COVID-19 , Bacteriophages/metabolism , Humans , Ligands , Lysine/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolismABSTRACT
This work reports a novel chlorooxime mediated modification of native peptides and proteins under physiologic conditions. This method features fast reaction kinetics (apparent k2 =306±4â M-1 s-1 for GSH) and exquisite selectivity for cysteine residues. This cysteine conjugation reaction can be carried out with just single-digit micromolar concentrations of the labeling reagent. The conjugates show high stability towards acid, base, and external thiol nucleophiles. A nitrile oxide species generated inâ situ is likely involved as the key intermediate. Furthermore, a bis-chlorooxime reagent is synthesized to enable facile Cys-Cys stapling in native peptides and proteins. This highly efficient cysteine conjugation and stapling was further implemented on bacteriophage to construct chemically modified phage libraries.
Subject(s)
Bacteriophages , Cysteine , Cysteine/chemistry , Indicators and Reagents , Peptides/chemistry , Sulfhydryl Compounds/chemistryABSTRACT
Theoretically and experimentally, MXenes consisting of Mo and C have aroused much interest due to superconductivity in their films and even monolayer forms. Here, based on first-principles calculations, we systematically calculate the electronic structure, phonon dispersion, and electron-phonon coupling (EPC) of monolayer Mo2C (both T- and H-phases), Mo3C2, and Mo3C3. The results show that H-MoxCy (x = 2 or 3, y = 1-3) always have lower total energies than their corresponding T phase and other configurations. All these two-dimensional (2D) molybdenum carbides are metals and some of them display weak phonon-mediated superconductivity at different superconducting transition temperatures (Tc). The Mo 4d-orbitals play a critical role in their electronic properties and the Mo atomic vibrations play a dominant role in their low-frequency phonons, EPC, and superconductivity. By comparison, we find that increasing the Mo content can enhance the EPC and Tc. Besides, we further explore the impact of strain engineering on their superconducting related physical quantities. With increasing biaxial stretching, the phonon dispersions are gradually softened to form some soft modes, which can trigger some peaks of α2F(ω) in the low-frequency region and evidently increase the EPC λ. The Tc of H-Mo2C can be increased up to 11.79 K. Upon further biaxial stretching, charge density waves may appear in T-Mo2C, H-Mo3C2, and H-Mo3C3.
ABSTRACT
The combined contamination of heavy metals and microplastics is widespread in freshwater environments. However, there are few researches on their combined effects on aquatic plants. In this study, the effects of single and combined stress of 0.01 mg L-1 cadmium (Cd), 50 mg L-1 polyethylene and 50 mg L-1 polypropylene for 15 days on the physiological response, ultrastructure and rhizosphere microbial community of duckweed were investigated. The results showed that Cd and microplastics single or combined stress inhibited the growth of duckweed, shortened the root length and decreased the chlorophyll content. Compared with single Cd treatments, the combination of microplastics and Cd increased duckweed growth rate and increased superoxide dismutase activity and malondialdehyde content and reduced chloroplast structural damage, indicating that the combined stress could reduce the toxicity of heavy metals to duckweed. Through the study of rhizosphere microbial diversity, 1381 Operational Taxonomic Unit (OTUs) were identified and rich microbial communities were detected in the duckweed rhizosphere. Among them, the main microbial communities were Proteobacteria, Bacteroidetes, and Cyanobacteria. Compared with Cd single stress, the ACE and chao index of rhizosphere microbial community increased under combined stress, indicating that the diversity and abundance of microbial communities were improved after combined stress treatment. Our study revealed the effects of heavy metals and microplastics on aquatic plants, providing a theoretical basis for duckweed applications in complex water pollution.
Subject(s)
Araceae , Metals, Heavy , Microbiota , Soil Pollutants , Cadmium/analysis , Metals, Heavy/toxicity , Microplastics , Plastics , Rhizosphere , Soil Pollutants/analysisABSTRACT
Background and Objectives: To clinically validate the computed tomography (CT)-based three-dimension (3D) model for treatment planning and intraoperative navigation of ureteropelvic junction obstruction (UPJO) complicated with renal calculi. Materials and Methods: We retrospectively collected the data of 26 patients with UPJO and renal calculi who were surgically treated in our institution from January 2019 to December 2021. Before surgery, 3D models based on preoperative CT scans were constructed in all patients. Additionally, the patients were divided into three groups according to the results of 3D models, distinguished by different treatment of renal calculi, that is, left untreated (1), pyelolithotomy (2), and endoscopic lithotomy (3). The quantitative analysis of renal calculi parameters, and perioperative and follow-up data were compared. Results: The mean number of involved renal calyces (p = 0.041), and the mean maximum cross-sectional area (p = 0.036) of renal stones were statistically different among the three groups. There were no significant differences among the three groups in the mean operative time, mean estimated blood loss, mean pararenal draining time, and mean hospital stay. The intraoperative stone clearance rates were 100% (11/11) and 77.8% (7/9) in group 2 and group 3, respectively. The trends of increased estimated glomerular filtration rate and decreased creatinine on the average levels after surgery were observed, although these changes were not statistically significant. At a mean follow-up of 19.4 ± 6.4 months, the overall surgical success rate of the UPJO was 96.2% (25/26), and the overall success rate of renal calculi removal was 80.8% (21/26). Renal stones in 66.7% (4/6) of patients in group 1 spontaneously passed out. Conclusions: Preoperative 3D CT models have exact clinical value in the surgical planning and intraoperative navigation of UPJO patients complicated with renal calculi.
Subject(s)
Kidney Calculi , Laparoscopy , Ureteral Obstruction , Humans , Retrospective Studies , Laparoscopy/methods , Kidney Calculi/complications , Kidney Calculi/diagnostic imaging , Kidney Calculi/surgery , Ureteral Obstruction/complications , Ureteral Obstruction/diagnostic imaging , Ureteral Obstruction/surgery , Tomography , Treatment OutcomeABSTRACT
Acyl-CoAs are key precursors of primary and secondary metabolism. Their efficient biosynthesis is often impeded by the limited substrate specificity and low in vivo activity of acyl-CoA synthetases (ACSs) due to regulatory acylation of the catalytically important lysine residue in motif A10 (Lys-A10). In this study, we identified an unusual ACS (UkaQ) from the UK-2A biosynthetic pathway that naturally lacks the Lys-A10 residue and exhibits extraordinarily broad substrate specificity. Protein engineering significantly improved its stability and catalytic activity, enabling it to synthesize a large variety of acyl-CoAs with highly robust activity. By combining it with permissive carboxylases, we produced a large array of polyketide extender units and obtained six novel halobenzyl-containing antimycin analogues through an engineered biosynthetic pathway. This study significantly expands the catalytic mode of ACSs and provides a potent tool for the biosynthesis of acyl-CoA-derived natural products.
Subject(s)
Biological Products , Polyketides , Polyketides/chemistry , Lysine , Carbon , Acyl Coenzyme A/metabolism , Substrate Specificity , Biological Products/metabolism , Polyketide Synthases/metabolismABSTRACT
ß-Ketoacyl-ACP synthase III (KAS III) is a class of important C-C bond-forming enzymes that mostly catalyze the initiation of polyketide and fatty acid biosynthesis. In this study, we elucidated an unusual polyketide synthase (PKS) system that involves two unique KAS IIIs (AsuC3 and C4) in the biosynthesis of the upper triene chain of asukamycin. Significantly, AsuC3 and C4 have both initiation and iterative elongation activity, while being functionally biased toward the elongation and initiation steps, respectively. Mutational analysis revealed that their catalytic activities rely on the catalytic triad Cys-His-Asn. Unlike other KAS IIIs, AsuC3 and C4 are very promiscuous and can accept various lengths of acyl-CoAs with either cyclic, branched or linear acyl moieties. By cooperation with the permissive ketoreductase (AsuC7) and dehydratase (AsuC8/C9), a large variety of polyenes can be efficiently synthesized. This study significantly broadens the understanding of KAS IIIs and polyketide biosynthesis.
Subject(s)
Polyenes , Polyketides , Acyl Coenzyme A , Polyketide Synthases/geneticsABSTRACT
We describe an affinity purification-mass spectrometry (AP-MS) method for probing the interactome of a special targeting protein. The AP was implemented with monolithic micro immobilized metal ion affinity chromatography columns (m-IMAC) which were prepared by photoinitiated polymerization in the tip of a pipet (spin-tip columns). The recombinant His6-tagged protein (bait protein) was reversibly immobilized on the affinity column through the chelating group nitrilotriacetic acid (NTA)-Ni2+. The bait protein and its interacting partners can be easily eluted from the affinity matrix. The pulled-down cellular proteins were then analyzed with label-free quantitative proteomics. We used this method for probing the interactome concerning the GOLD (Golgi dynamics) domain of the autophagy-associated adaptor protein FYCO1. Totally, 96 proteins including seven literature-reported FYCO1-associating proteins were identified. Among them CCZ1 and MON1A were further biochemically validated, and the direct interaction between the FYCO1 GOLD domain with CCZ1 was confirmed by co-immunoprecipitation experiments.
Subject(s)
Chromatography, Affinity/methods , Protein Interaction Maps/physiology , Recombinant Fusion Proteins/metabolism , Chromatography, High Pressure Liquid , Histidine/chemistry , Histidine/genetics , Histidine/metabolism , Humans , Microtubule-Associated Proteins/chemistry , Microtubule-Associated Proteins/metabolism , Nitrilotriacetic Acid/chemistry , Oligopeptides/chemistry , Oligopeptides/genetics , Oligopeptides/metabolism , Peptides/analysis , Protein Binding , Proteomics/methods , Recombinant Fusion Proteins/biosynthesis , Recombinant Fusion Proteins/isolation & purification , Tandem Mass SpectrometryABSTRACT
miR-155 plays key promoting roles in several cancers and emerges as an important anticancer therapeutic target. However, the discovery of small molecules that target RNAs is challenging. Peptidomimetics have been shown to be a rich source for discovering novel ligands to regulate cellular proteins. However, the potential of using peptidomimetics for RNA targeting is relatively unexplored. To this end, we designed and synthesized members of a novel 320â¯000 compound macrocyclic peptidomimetic library. An affinity-based screening protocol led to the identification of a pre-miR-155 binder that inhibits oncogenic miR-155 maturation in vitro and in cell and induces cancer cell apoptosis. The results of this investigation demonstrate that macrocyclic peptidomimetics could serve as a new scaffold for RNA targeting.
Subject(s)
MicroRNAs/metabolism , Peptidomimetics/metabolism , Apoptosis , Blotting, Western , Cell Line , Combinatorial Chemistry Techniques/methods , Electrophoretic Mobility Shift Assay , Humans , MCF-7 Cells , Peptidomimetics/chemistryABSTRACT
BACKGROUND: The infusion of magnesium sulfate is well known to reduce arterial pressure and attenuate hemodynamic response to pneumoperitoneum. This study aimed to investigate whether different doses of magnesium sulfate can effectively attenuate the pneumoperitoneum-related hemodynamic changes and the release of vasopressin in patients undergoing laparoscopic gastrointestinal surgery. METHODS: Sixty-nine patients undergoing laparoscopic partial gastrectomy were randomized into three groups: group L received magnesium sulfate 30 mg/kg loading dose and 15 mg/kg/h continuous maintenance infusion for 1 h; group H received magnesium sulfate 50 mg/kg followed by 30 mg/kg/h for 1 h; and group S (control group) received same volume 0.9% saline infusion, immediately before the induction of pneumoperitoneum. Systemic vascular resistance (SVR), cardiac output (CO), mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), serum vasopressin and magnesium concentrations were measured. The extubation time, visual analogue scale were also assessed. The primary outcome is the difference in SVR between different groups. The secondary outcome is the differences of other indicators between groups, such as CO, MAP, HR, CVP, vasopressin and postoperative pain score. RESULTS: Pneumoperitoneum instantly resulted in a significant reduction of cardiac output and an increase in mean arterial pressure, systemic vascular resistance, central venous pressure and heart rate in the control group (P < 0.01). The mean arterial pressure (T2 - T4), systemic vascular resistance (T2 - T3), central venous pressure(T3-T5) and the level of serum vasopressin were significantly lower (P < 0.05) and the cardiac output (T2 - T3) was significantly higher (P < 0.05) in group H than those in the control group. The mean arterial pressure (T4), systemic vascular resistance (T2), and central venous pressure(T3-T4) were significantly lower in group H than those in group L (P < 0.05). Furthermore, the visual analog scales at 5 min and 20 min, the level of vasopressin, and the dose of remifentanil were significantly decreased in group H compared to the control group and group L (P < 0.01). CONCLUSION: Magnesium sulfate could safely and effectively attenuate the pneumoperitoneum-related hemodynamic instability during gastrointestinal laparoscopy and improve postoperative pain at serum magnesium concentrations above 2 mmol/L. TRIAL REGISTRATION: The study was retrospectively registered at Chinese Clinical Trial Registry; the registration number is ChiCTR-IPD-17011145, principal investigator: D.Y. Q., date of registration: April 13, 2017.
Subject(s)
Gastrectomy/methods , Laparoscopy/methods , Magnesium Sulfate/administration & dosage , Pneumoperitoneum, Artificial/methods , Adult , Aged , Dose-Response Relationship, Drug , Double-Blind Method , Hemodynamics/drug effects , Hemodynamics/physiology , Humans , Magnesium Sulfate/pharmacokinetics , Middle Aged , Pain, Postoperative/epidemiology , Pneumoperitoneum, Artificial/adverse effects , Vasopressins/metabolismABSTRACT
The purpose of this study is to develop a robust approach to obtain ß glucans from Lentinus edodes and to characterize their structural and biological properties for sustainable utilization. The alkali extraction was optimized with an orthogonal experimental design, and a concise process for obtaining specific targeting polysaccharides from Lentinus edodes was developed in this study. After purification with a Q-Sepharose Fast Flow strong anion-exchange column, the monosaccharide composition, a methylation analysis, and NMR spectroscopy were employed for their structural characterizations. LeP-N2 was found to be composed of (1â6)-ß-d-glucans with minor ß-(1â3) glucosidic side chains. Atomic force microscopy (AFM) and high-performance gel permeation chromatography-refractive index-multi-angle laser light scattering (HPGPC-RI-MALLS) also revealed LeP-N2 exhibiting a compact unit in aqueous solution. This (1â6)-ß-d-glucan was tested for antioxidant activities with IC50 at 157 µg/mL. Moreover, RAW 264.7 macrophage activation indicated that the release of nitric oxide (NO) and reactive oxygen species (ROS) was markedly increased with no cytotoxicity at a dose of 100 µg/mL. These findings suggest that the (1â6)-ß-d-glucans obtained from Lentinus edodes could serve as potential agents in the fields of functional foods or medicine.
Subject(s)
Antioxidants/chemistry , Polysaccharides/chemistry , Shiitake Mushrooms/chemistry , beta-Glucans/chemistry , Animals , Antioxidants/isolation & purification , Antioxidants/pharmacology , Cell Proliferation/drug effects , Chromatography, Gel , Magnetic Resonance Spectroscopy , Mice , Microscopy, Atomic Force , Molecular Structure , Polysaccharides/isolation & purification , RAW 264.7 Cells , Reactive Oxygen Species/chemistry , Water/chemistry , beta-Glucans/isolation & purification , beta-Glucans/pharmacologyABSTRACT
Peptide-mediated self-assembly is a prevalent method for creating highly ordered supramolecular architectures. Herein, we report the first example of orthogonal C-Xâ â â X-C/C-Xâ â â π halogen bonding and hydrogen bonding driven crystalline architectures based on synthetic helical peptides bearing hybrids of l-sulfono-γ-AApeptides and natural amino acids. The combination of halogen bonding, intra-/intermolecular hydrogen bonding, and intermolecular hydrophobic interactions enabled novel 3D supramolecular assembly. The orthogonal halogen bonding in the supramolecular architecture exerts a novel mechanism for the self-assembly of synthetic peptide foldamers and gives new insights into molecular recognition, supramolecular design, and rational design of biomimetic structures.