Mechanism of anti-inflammatory activity of umbelliferone 6-carboxylic acid isolated from Angelica decursiva

Aims of the study

We recently reported the potential antioxidant and anti-inflammatory activities of umbelliferone 6-carboxylic acid (UMC) isolated from the whole plants of Angelica decursiva. In this study, we elucidated the anti-inflammatory mechanisms of UMC in vitro and in vivo.

Methods

The inhibitory effects of UMC on the production of nitric oxide (NO), prostaglandin E₂ (PGE₂), and tumor necrosis factor-α (TNF-α), the expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the activation of nuclear factor kappa B (NF-κB) were evaluated using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The reactive oxygen species (ROS) generation inhibitory activity of UMC was evaluated using t-butyl hydroperoxide (t-BHP)-induced RAW 264.7 cells. Furthermore, the in vivo anti-inflammatory activity of UMC was evaluated using carrageenan induced mouse paw edema model.

Results

UMC dose-dependently inhibited NO and PGE₂ production by down-regulating iNOS and COX-2 protein expression in LPS-stimulated RAW 264.7 macrophages. UMC also suppressed the production of the proinflammatory cytokine TNF-α in LPS stimulated RAW 264.7 cells in a concentration dependent manner. In addition, UMC dose-dependently prevented LPS-induced nuclear translocation of NF-κB in RAW 264.7 macrophages. Furthermore, UMC exhibited the inhibitory activity against t-BHP-induced ROS generation in RAW 264.7 cells with an IC₅₀ value of 705.1 μg/ml. Moreover, UMC inhibited λ-carrageenan induced mouse paw edema by 70.40 and 60.20% at doses of 50 and 25 mg/kg body weight, respectively.

Conclusion

The combined results of this study indicate that UMC is an important anti-inflammatory constituent of A. decursiva and its anti-inflammatory effect was due to its ability to inhibit the production of inflammatory mediators via inhibition of NF-κB activation pathway.     

Recrystallization techniques for the synthesis of ZnO nanorods: an in situ process for carbon doping and enhancing the dispersion concentration of ZnO nanorods

Zinc acetate is recrystallized as lumber-shaped tetragonal rods by a novel recrystallization technique. Subsequently, the recrystallized zinc acetate is converted into ZnO nanorods in a glass vial by the simplest and cheapest method without utilizing any expensive instrumentation. Carbon is doped in ZnO nanorods during the preparation ZnO nanorods without any extra steps, chemicals, or effort. The carbon-doped ZnO nanorods can be dispersed in a solvent at very high concentrations and are also stable for a very long time, which are comparatively higher than those of the other existing ZnO nanoparticles. The higher dispersion concentration and higher stability of ZnO nanoparticles are explained by a scheme that demonstrates the suspending mechanism of the ZnO nanoparticles at higher concentrations with higher stabilities in a solvent through the anchoring groups of carbon. No materials are used for surface modification; no surface coatings, ionic materials, or pH controlling materials are used to increase the dispersion concentration and stability. This is the first observation of the doped carbon playing a significant role in the dispersion of ZnO nanoparticles at higher concentrations by withholding them in the solvent. Therefore, doped carbon at the surface of ZnO nanoparticles prevents the self-aggregation of ZnO nanoparticles in the solution phase by interfacial barrier layers among ZnO nanorods and interfacial interactive layer between ZnO nanorod and solvent.

Dispersed ZnO hexagonal nanorods in ethanol solvent and its interfacial behavior in this liquid phase.     

Kaposi’s sarcoma: a computational approach through protein–protein interaction and gene regulatory networks analysis

Interactomic data for Kaposi’s Sarcoma Associated Herpes virus (KSHV)—the causative agent of vascular origin tumor called Kaposi’s sarcoma—is relatively modest to date. The objective of this study was to assign functions to the previously uncharacterized ORFs in the virus using computational approaches and subsequently fit them to the host interactome landscape on protein, gene, and cellular level. On the basis of expression data, predicted RNA interference data, reported experimental data, and sequence based functional annotation we also tried to hypothesize the ORFs role in lytic and latent cycle during viral infection. We studied 17 previously uncharacterized ORFs in KSHV and the host-virus interplay seems to work in three major functional pathways—cell division, transport, metabolic and enzymatic in general. Studying the host-virus crosstalk for lytic phase predicts ORF 10 and ORF 11 as a predicted virus hub whereas PCNA is predicted as a host hub. On the other hand, ORF31 has been predicted as a latent phase inducible protein. KSHV invests a lion’s share of its coding potential to suppress host immune response; various inflammatory mediators such as IFN-γ, TNF, IL-6, and IL-8 are negatively regulated by the ORFs while Il-10 secretion is stimulated in contrast. Although, like any other computational prediction, the study requires further validation, keeping into account the reproducibility and vast sample size of the systems biology approach the study allows us to propose an integrated network for host-virus interaction with good confidence. We hope that the study, in the long run, would help us identify effective dug against potential molecular targets.     

Acyldepsipeptide activated ClpP1P2 macromolecule of Leptospira,an ideal Achilles’ heel to hamper the cell survival and deregulate ClpP proteolytic activity

Antibiotic acyldepsipeptide (ADEP) targets the bacterial ClpP serine protease and can inhibit the growth of numerous bacterial species by activating/dysregulating the protease activity within the cell. The spirochete Leptospira interrogans harbors two ClpP isoforms (LepClpP1 and LepClpP2). Supplementation of ADEP in the Leptospira growth medium resulted in the inhibition of bacterial growth. The ADEP mediated activation of the LepClpP mixture was dependent on the time allowed for the self-assembly of LepClpP1 and LepClpP2. The dynamic light scattering of the LepClpP mixture in the presence of the ADEP indicated a conformational transformation of the LepClpP machinery. Serine 98, a catalytic triad residue of the LepClpP1 in the LepClpP1P2 heterocomplex, was critical for the ADEP mediated activation. The computational prototype of the LepClpP1P2 structure suggested that the hydrophobic pockets wherein the ADEPs or the physiological chaperone ClpX predominantly dock are exclusively present in the LepClpP2 heptamer. Using the ADEP as a tool, this investigation provides an insight into the molecular function of the LepClpP1P2 in a coalition with its ATPase chaperone LepClpX. The shreds of the evidence illustrated in this investigation verify that ADEP1 possesses the ability to control the LepClpP system in an unconventional approach than the other organisms.     

Use of the composite asthma severity index in a pediatric subspecialty clinic

BackgroundThe Composite Asthma Severity Index (CASI) is a comprehensive tool to assess asthma severity, which has been applied in the research setting.ObjectiveTo evaluate, in an outpatient setting, whether a CASI score accurately predicts asthma severity or control as determined by means of subspecialist assessment. Asthma Control Test (ACT) and childhood ACT (C-ACT) scores were generated to provide additional context for CASI scores in relationship to assessments using another clinical tool.MethodsChildren aged 5 to 18 years with a physician diagnosis of persistent asthma were recruited from a tertiary care center. A pediatric pulmonologist made determinations on each participant’s asthma severity and control during a clinic visit. A CASI and ACT/C-ACT score was generated for each patient. Logistic regression and Spearman correlations were used to determine how well CASI scores predicted physician assessments. Agreement between ACT/C-ACT scores and physician assessment of asthma control was determined in supplemental analyses.ResultsCASI scores strongly predicted physician assessment of severity (Spearman correlation = 0.61, P < .001); unadjusted odds ratio (OR) equal to 36.67 (95% confidence interval [CI]: 8.83-152.34); and adjusted OR equal to 32.76 (95% CI: 85.70-188.44). In supplemental analyses, ACT/C-ACT scores strongly predicted physician assessment of control (Spearman correlation = 0.72, P < .001) with an unadjusted OR equal to 42.12 (95% CI: 13.34-133.00) and adjusted OR equal to 55.34 (95% CI: 13.62-224.89).ConclusionUse of the CASI was feasible and accurately predicted physician assessments of asthma severity and control in this sample, which are not distinct entities. The CASI is a robust tool that may be used successfully in ambulatory pediatric asthma care.     

Effect of postural angle on back muscle activities in aging female workers performing computer tasks

[Purpose] This study investigated the effects of postural angle on back muscle activity during a computer task in aging women. [Subjects] Seventeen women ≥50 years old participated. [Methods] The participants were instructed to perform computer-related tasks for 20 minutes on a workstation that simulated typical office working conditions. Back posture was measured from the measured trunk and pelvic angles. Electromyography activities were recorded simultaneously from the cervical erector spinae, longissimus, and multifidus muscles. [Results] The lowest mean percentages of maximum voluntary contraction for the cervical erector spinae and longissimus muscles were obtained when the upper trunk and pelvic angles were between 0° to −5° from the sagittal plane. The back muscle activities increased as the upper trunk and pelvic angles exceeded 0°. Statistical analysis showed significant correlations between upper trunk angle and cervical erector spinae and longissimus muscle activities. Similarly, pelvic angle was significantly correlated with cervical erector spinae and multifidus muscle activities. [Conclusion] A neutral back posture minimizes muscle activities in aging women performing computer tasks.Key words: Postural angle, Muscle activity, Aging