Cucurbit[8]uril-assisted peptide assembly for feasible electrochemical assay of histone acetyltransferase activity.

Accumulating findings demonstrate the importance of histone acetyltransferases (HATs) in regulating the acetylation of histones and reveal that their aberrant catalytic activities are involved in the occurrence and progress of numerous diseases. Herein, a feasible electrochemical method is proposed to assay the activity of HAT. The critical elements of the assay method are the hindrance of HAT-catalyzed acetylation against carboxypeptidase Y-catalyzed digestion and cucurbit[8]uril-assisted peptide assembly, which may recruit peptide-templated silver nanoparticles onto the electrode surface, producing significant electrochemical signals. Taking p300 as a model HAT, the assay method is validated to exhibit desirable selectivity, reproducibility, and usability in inhibitor analysis, and allow absolute activity determination in a linear range from 0.1 to 50 nM with a detection limit of 0.055 nM, which is lower than those of previous reports. Therefore, this work may provide an effective tool for HAT activity assay, which will be of great potential in HAT-related fundamental research, disease diagnosis, and drug development in the future. Graphical abstract ᅟ.

Peptide self-assembly assisted signal labeling for an electrochemical assay of protease activity.

Peptide self-assembly holds tremendous promise for a range of applications in chemistry and biology. In the work reported here, we explored the potential functions of peptide self-assembly in electrochemical bioanalysis by developing a peptide self-assembly assisted signal labeling strategy for assaying protease activity. The fundamental principle of this assay is that target-protease-catalyzed specific proteolytic cleavage blocks self-assembly between the probe peptide and signal peptide, thus preventing the signal labeling of electroactive silver nanoparticles on the electrode surface, which in turn causes the electrochemical signal to decrease. Using trypsin as an example protease target, the linear range of this assay was found to be 1 ng mL-1 to 100 mg mL-1, and its detection limit was 0.032 ng mL-1, which are better than the corresponding parameters for previously reported assays. Further experiments also highlighted the good selectivity of the assay method and demonstrated its usability when applied to serum samples. Therefore, this report not only introduces a valuable tool for assaying protease activity, but it also promotes the utilization of peptide self-assembly in electrochemical bioanalysis, as this approach has great potential for practical use in the future.

IL-17A/p38 Signaling Pathway Induces Alveolar Epithelial Cell Pyroptosis and Hyperpermeability in Sepsis-Induced Acute Lung Injury by Activating NLRP3 Inflammasome.

Sepsis is a syndrome with poor prognosis. Nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and T helper 17 (Th17) cells are involved in the pathogenesis of inflammatory diseases. This study aims to explore their roles and underlying mechanisms in sepsis. The blood and bronchoalveolar lavage fluid are collected from sepsis patients and healthy donors. A sepsis mice model is established by cecal ligation puncture (CLP). The contents of cytokines are detected by ELISA. The amounts of Th17 cells, IL-17A, IL-1ß, IL-18, and lipopolysaccharide is significantly elevated in sepsis patients. The increased differentiation of Th17 cells can promote lung cell pyroptosis and induce hyperpermeability via activating NLRP3 inflammasome and p38 pathway. The inhibitors targeting Th17 cells, NLRP3 inflammasome, and p38 pathway can significantly alleviate lung injury in sepsis mice. Th17 cells can secrete IL-17A to activate NLRP3 inflammasome via p38 signaling pathway, which contributes to the development of sepsis-induced acute lung injury.

The immunomodulation role of Th17 and Treg in renal transplantation.

Kidney transplantation (KT) is an ultimate treatment of end-stage chronic kidney disease, which can meet a lot of complications induced by immune system. With under-controlled immunosuppression, the patient will obtain a good prognosis. Otherwise, allograft disfunction will cause severe organ failure and even immune collapse. Acute or chronic allograft dysfunction after KT is related to Th17, Treg, and Th17/Treg to a certain extent. Elevated Th17 levels may lead to acute rejection or chronic allograft dysfunction. Treg mainly plays a protective role on allografts by regulating immune response. The imbalance of the two may further aggravate the balance of immune response and damage the allograft. Controlling Th17 level, improving Treg function and level, and adjusting Th17/Treg ratio may have positive effects on longer allograft survival and better prognosis of receptors.

Preliminary Study on the Combination Effect of Clindamycin and Low Dose Trimethoprim-Sulfamethoxazole on Severe Pneumocystis Pneumonia After Renal Transplantation.

Objective: Evaluate the effect of the combination of clindamycin with low-dose trimethoprim-sulfamethoxazole (TMP/SMX) regimen on sever Pneumocystis pneumonia (PCP) after renal transplantation. Method: 20 severe PCP patients after renal transplantation were included in this historical-control, retrospective study. A 10 patients were treated with the standard dose of TMP/SMX (T group), the other 10 patients were treated with the combination of clindamycin and low dose TMP/SMX (CT group). Results: Although there was no significant difference in the hospital survival between the two groups, the CT protocol improved the PaO2/FiO2 ratio more significantly and rapidly after the 6th ICU day (1.51 vs. 0.38, P = 0.014). CT protocol also ameliorated the pulmonary infiltration and the lactate dehydrogenase level more effectively. Moreover, the CT protocol reduced the incidence of pneumomediastinum (0 vs. 50%, P = 0.008), the length of hospital staying (26.5 vs. 39.0 days, P = 0.011) and ICU staying (12.5 vs. 22.5 days, P = 0.008). Furthermore, more thrombocytopenia (9/10 vs. 3/10, P = 0.020) was emerged in the T group than in the CT group. The total adverse reaction rate was much lower in the CT group than in the T group (8/80 vs. 27/80, P < 0.001). Consequently, the dosage of TMP/SMX was reduced in 8 patients, while only 2 patients in the CT group received TMP/SMX decrement (P = 0.023). Conclusion: The current study proposed that clindamycin combined with low-dose TMP/SMX was more effective and safer the than single use of TMP/SMX for severe PCP patients after renal transplantation (NCT04328688).

2-(4-Hy-droxy-phen-oxy)propanoic acid.

In the title compound, C(9)H(10)O(4), the carboxyl group is oriented at a dihedral angle of 84.6 (3)° with respect to the benzene ring. In the crystal, mol-ecules are linked via O-H⋯O hydrogen bonds.

Temperature-responsive iron nanozymes based on poly(N-vinylcaprolactam) with multi-enzyme activity.

Iron (Fe)-based nanozymes are widely applied in the biomedical field due to their enzyme-like catalytic activity. Herein, Fe(ii)-based coordination polymer nanohydrogels (FeCPNGs) have been conveniently prepared as a new type of nanozyme by the chelation reaction between ferrous iron and polymer nanohydrogels. The P(VCL-co-NMAM) nanohydrogels prepared by a reflux precipitation polymerization method using N-vinylcaprolactam (VCL) and N-methylol acrylamide (NMAM) as monomers and N,N-methylenebisacrylamide (MBA) as a crosslinker were esterified using P2O5 and then chelated with Fe(ii) ions to form nanozymes with peroxidase and superoxide dismutase (SOD) activity. It was found by dynamic light scattering (DLS) and transmission electron microscopy (TEM) that the nanohydrogels prepared with a monomer concentration of 4% and mass ratio of 1 : 1 (VCL : NMAM) had more uniform particle size, better dispersion and a distinct temperature response. The results of Fourier transform infrared (FTIR), DLS, TEM, X-ray powder diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) indicated the successful preparation of the esterified nanohydrogel and FeCPNGs. Of particular importance is that such FeCPNGs can functionally mimic two antioxidant enzymes (peroxidase and superoxide dismutase) by UV analysis of catalytic oxidation between 3,3,5,5-tetramethylbenzidine (TMB) and H2O2 and the kit analysis of SOD-like activity.

Neutrophil-to-Lymphocyte Ratio Predicts Mortality in Adult Renal Transplant Recipients with Severe Community-Acquired Pneumonia.

Mortality of renal transplant recipients with severe community-acquired pneumonia (CAP) remains high, despite advances in critical care management. There is still a lack of biomarkers for predicting prognosis of these patients. The present study aimed to investigate the association between neutrophil-to-lymphocyte ratio (NLR) and mortality in renal transplant recipients with severe CAP. A total of 111 renal transplant recipients with severe CAP admitted to the intensive care unit (ICU) were screened for eligibility between 1 January 2009 and 30 November 2018. Patient characteristics and laboratory test results at ICU admission were retrospectively collected. There were 18 non-survivors (22.2%) among 81 patients with severe CAP who were finally included. Non-survivors had a higher NLR level than survivors (26.8 vs. 12.3, p < 0.001). NLR had the greatest power to predict mortality as suggested by area under the curve (0.88 ± 0.04; p < 0.0001) compared to platelet-to-lymphocyte ratio (0.75 ± 0.06; p < 0.01), pneumonia severity index (0.65 ± 0.08; p = 0.05), CURB-65 (0.65 ± 0.08; p = 0.05), and neutrophil count (0.68 ± 0.07; p < 0.01). Multivariate logistic regression models revealed that NLR was associated with hospital and ICU mortality in renal transplant recipients with severe CAP. NLR levels were independently associated with mortality and may be a useful biomarker for predicting poor outcome in renal transplant recipients with severe CAP.

4-Acetamido-3-nitro-phenyl acetate.

In the mol-ecule of the title compound, C(10)H(10)N(2)O(5), intra-molecular C-H⋯O inter-actions result in the formation of a five- and a six-membered ring. The five-membered ring is planar and is oriented at a dihedral angle of 0.34 (3)° with respect to the plane of the aromatic ring, while the six-membered ring has a twist conformation. In the crystal structure, inter-molecular C-H⋯O inter-actions link the mol-ecules into chains.

Lactate dehydrogenase as a prognostic marker of renal transplant recipients with severe community-acquired pneumonia: a 10-year retrospective study.

BACKGROUND: Lactate dehydrogenase (LDH) is an easily accessible biological marker that has been associated with several pulmonary disorders. The aim of this study was to investigate the prognostic value of serum LDH in renal transplant recipients with severe community-acquired pneumonia (CAP). METHODS: A total of 77 renal transplant recipients with severe CAP admitted to the intensive care unit (ICU) were screened for eligibility in this retrospective study. Patient characteristics and laboratory tests, such as LDH on day 1 (LDHday 1) and day 3 (LDHday 3) were recorded. Cox regression models were used to assess the performance of LDH to predict 90-day mortality. RESULTS: Median LDH level was higher on day 1 in 90-day nonsurvivors (440 U/L, IQR, 362-1,055 U/L) than in survivors (334 U/L, IQR, 265-432 U/L; P<0.001); median LDH level on day 3 in nonsurvivors was 522.5 U/L (IQR, 457.5-1,058.5 U/L) and in survivors 290 U/L (IQR, 223-387.5 U/L; P<0.001). Analysis of LDH kinetics from day 1 to day 3 showed an increase in nonsurvivors and a decrease in survivors. Moreover, Multivariate Cox analysis showed that LDHday 1 (increase per 100 U/L), LDHday 3 (increase per 100 U/L) and LDH kinetics (increase per 10%) were independently associated with 90-day mortality. CONCLUSIONS: Serum LDH levels and LDH kinetics early were independently associated with 90-day mortality in renal transplant recipients with severe CAP. In future, the prognostic role of LDH needs to be warranted.