Anti-nociceptive effects of magnolol via inhibition of TRPV1/P2Y and TLR4/NF-κB signaling in a postoperative pain model.

AIMS: The current study explored the anti-nociceptive activity of magnolol in post-incisional inflammatory nociceptive pain. MAIN METHODS: Preliminary, the anti-inflammatory, antioxidant, and cytoprotective potential of magnolol were confirmed against hydrogen peroxide (H2O2)-induced PC12 cells. Next, an in-vivo model of planter incision surgery was established in BALB/c mice. Tramadol 50 mg/kg intraperitoneal (i.p.) and magnolol (0.1, 1, 10 mg/kg i.p. + 10 mg/kg intra planter) were administered after plantar incision surgery and behavior parameters were measured. KEY FINDINGS: The results indicate that magnolol significantly suppressed post-incision-induced mechanical allodynia, thermal hyperalgesia, and paw edema. Magnolol promisingly inhibited post-incision induces nitric oxide (NO), malondialdehyde (MDA), eosinophil peroxidase (EPO), and neutrophil infiltration. Magnolol strongly attenuated post-incision inducing the release of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and inhibited deoxyribonucleic acid (DNA) fragmentation. Magnolol markedly reverses post-incisional histopathological changes and biochemical composition of the incised paw. Magnolol markedly down-regulated post-incisional increase expression of transient receptor potential vanilloid 1 (TRPV1), purinergic (P2Y) nociceptors as well as toll-like receptor 4 (TLR4), nuclear factor kappa light chain enhancer of activated B cell (NF-κB), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) while upregulating the expression of inhibitor of nuclear kappa B alpha (IκB-α). SIGNIFICANCE: The present study strongly suggests that magnolol significantly suppressed post-incisional inflammatory nociceptive pain by targeting TRPV1/P2Y and TLR4/NF-κB signaling.

Hybridization of green synthesized silver nanoparticles with poly(ethylene glycol) methacrylate and their biomedical applications.

In the present research, a rapid, simple and efficient green method is used for the incorporation of silver nanoparticles (AgNPs) into poly(ethylene glycol) methacrylate (PEGMA) to create biocatalysts with excellent properties for pharmaceutical purpose. In the first phase, Caralluma tuberculata capped AgNPs (Ca-AgNPs) were prepared using green synthetic approach and in the second phase Caralluma tuberculata capped AgNPs were hybridized with poly(ethylene glycol) methacrylate to form PEGMA-AgNPs. Both the virgin (naked or uncapped) and polymer-capped materials were characterized spectroscopically and their results were compared. Fourier transform infrared spectroscopy showed no new peak after the capping procedure, showing that only physical interactions takes place during capping. After PEGMA capping, the spectra of the AgNPs red shifted (from 450 nm to 520 nm) and the overall particle size of AgNPs increased. Catalytic activity of the nanoparticles and hybrid system were tested by choosing the catalytic reduction of 4-nitrophenol (4-NP) as a model reaction. Both synthesized NPs and polymer capped NPs exhibits catalytic activity for the reduction of 4-NP to 4-aminophenol. The polymer hybrid exhibits remarkable antiproliferative, antioxidant, cytotoxic, antidiabetic and antileishmanial activities.

Highly dispersive palladium nanoparticle in nanoconfined spaces for heterogeneous catalytic reduction of anthropogenic pollutants.

Pd-containing catalysts are highly promising in catalytic reactions, and their activity severely dependent on the dispersion extent of Pd nanoparticles (Pd NPs) . However, the regulation of Pd NPs size and dispersion degree are now pretty much the agendas. Here we report a facile solid-state fabrication strategy (SSFS) to promote Pd NPs dispersion in the nano environment of as made mesoporous silica KIT-6 (AK) by taking advantage of three critical factors, namely (i) the confined spaces where Pd precursor locate during fabrication, (ii) the interaction between Pd and supports, and (iii) the 3-dimentional (3D) structure of AK. First, AK presents 3D confined spaces between silica walls and template P123. Second, both silica walls and template P123 in AK offer interaction with Pd precursor. Third, the 3D structure provides more easy access for Pd insertion than linear channels structure without any pore blockage. The characterization results revealed that AK give better dispersion with smaller size of (3.9 nm) Pd than its counterpart (16 nm) prepared from template-free KIT-6 (CK). Moreover, the synthesized catalysts exhibit excellent activity and stability in catalytic conversion of p-nitrophenol (p-NP) and Methylene blue (MB). For a typical PdAK-1.0 catalyst, the complete conversion of P-NP and MB was achieved in less than 10 min with a reaction rate constant (k) of 0.3106 and 0.345 min-1, respectively. It is superior to that on PdCK-1.0 prepared from template free KIT-6 and several reported catalysts. Furthermore, the PdAK-1.0 catalyst presents pretty good stability in catalytic reduction and is apparently better than PdCK-1.0.

Unusual Pd nanoparticle dispersion in microenvironment for p-nitrophenol and methylene blue catalytic reduction.

Palladium based catalysts are highly attractive for catalytic reactions. However, the catalytic activity is dependent on the dispersion and size of Pd nanoparticles (NPs). Herein, an efficient strategy is developed to regulate the size and dispersion of Pd NPs in nanoconfined spaces provided by Santa Barbara Amorphous-15 (SBA-15) occluded with template. The Pd precursor is introduced to the confined spaces between the template and silica walls in as-synthesized SBA-15 (AS) by grinding. Subsequent reduction allow template removal and precursor conversion to Pd0 in single step and avoids aggregation that take place in calcined SBA-15 (CS). Our results show that up to 1.0 wt% of Pd can be well dispersed in confined spaces of AS (denoted as 1.0PdAS), while sever aggregation take place from CS with the same Pd loading (denoted as1.0PdCS). We also demonstrated that 1.0PdAS is highly efficient for catalytic reduction of p-nitrophenol (P-NP) and Methylene blue (MB) with rate constant of 0.4924 and 0.626 min-1, respectively, which is superior than 1.0PdCS attributed to well dispersed and smaller size (3 nm) Pd NPs. Furthermore, no change in the rate constant of P-NP (0.4924 min-1) and MB (0.626 min-1) after regeneration presents good stability of 1.0PdAS in catalytic reactions.

Fabrication of 3-D confined spaces with Au NPs: Superior dispersion and catalytic activity.

Gold nanoparticles (Au NPs) as an active noble-metal site have received great attention because of its superior catalytic activity in diverse reactions. However, the activity of Au NPs is strongly dependent on its size and dispersion degree. Therefore, we developed an efficient solid-state reduction (SSR) strategy for the first time to promote the dispersion degree and size of Au NPs in template-occluded KIT-6 (AK) as a support by taking advantage of (i) 3-dimentonal cubic mesoporous structure of support (ii) confined spaces present between template (Pluronic (P) 123) and silica wall of AK where Au NPs locate (iii) interaction of both P123 as template and silica walls of AK with Au NPs highly efficient for Au NPs dispersion and (iv) SSR strategy which avoids competitive adsorption of solvent in the conventional fabrication process. The results revealed that Au-based AK (AuAK) has much better dispersion of Au NPs with smaller sizes than template-free KIT-6 (CK). Moreover, the catalytic activity of AuAK in reduction reactions of p-nitrophenol (P-NP) to p-aminophenol (P-AP) and Methylene blue (MB) to Leuco MB (LMB) is superior than AuCK as well as to those Au-catalysts synthesized via conventional strategies previously. The catalytic performance is also related well with characterization results.

In situ one-step synthesis of Fe3O4@MIL-100(Fe) core-shells for adsorption of methylene blue from water.

A new route for Fe3O4@MIL-100(Fe) core-shells is proposed via in situ one-step hydrothermal strategy, in which Fe3O4 microspheres not only serve as magnetic cores but also provide Fe(III) for MIL-100(Fe) synthesis. The MIL-100(Fe) is uniformly grown as a shell on the surface of Fe3O4, and the shell thickness can be fine-tuned from 73.5 to 148nm by simply controlling the reaction time. Compared with Fe3O4, the surface area and pore volume of the Fe3O4@MIL-100(Fe) are significantly increased while the magnetism is barely affected. The application of Fe3O4@MIL-100(Fe) in adsorption was tested using several dyes as model analytes, and showed high adsorption capacity (221mgg-1) towards methylene blue (MB), which is based on electrostatic interactions and size filter effect. The MB adsorption isotherm follows Langmuir model and pseudo second-order kinetic model. Intra-particle diffusion model reveals that both film and pore diffusions are involved in the rate limiting steps. The adsorption is controlled by enthalpy change rather than entropy effect. ΔH, ΔS and ΔG values indicated that the adsorption process was spontaneous and exothermic. Simple synthesis procedure, immense magnetism, high adsorption capacity and excellent reusability of Fe3O4@MIL-100(Fe) make it an attractive candidate for application of MB removal from polluted environmental samples.

Neuronal function of Tbx20 conserved from nematodes to vertebrates.

The Tbx20 orthologue, mab-9, is required for development of the Caenorhabditis elegans hindgut, whereas several vertebrate Tbx20 genes promote heart development. Here we show that Tbx20 orthologues also have a role in motor neuron development that is conserved between invertebrates and vertebrates. mab-9 mutants exhibit guidance defects in dorsally projecting axons from motor neurons located in the ventral nerve cord. Danio rerio (Zebrafish) tbx20 morphants show defects in the migration patterns of motor neuron soma of the facial and trigeminal motor neuron groups. Human TBX20 is expressed in motor neurons in the developing hindbrain of human embryos and we show that human TBX20 can substitute for zebrafish tbx20 in promoting cranial motor neuron migration. mab-9 is also partially able to rescue the zebrafish migration defect, whereas other vertebrate T-box genes cannot. Conversely we show that the human TBX20 T-box domain can rescue motor neuron defects in C. elegans. These data suggest the functional equivalence of Tbx20 orthologues in regulating the development of specific motor neuron groups. We also demonstrate the functional equivalence of human and C. elegans Tbx20 T-box domains for regulating male tail development in the nematode even though these genes play highly diverged roles in organogenesis.

The T-box factor TBX-2 and the SUMO conjugating enzyme UBC-9 are required for ABa-derived pharyngeal muscle in C. elegans.

The C. elegans pharynx is produced from the embryonic blastomeres ABa and MS. Pharyngeal fate in the ABa lineage is specified by the combined activities of GLP-1/Notch-mediated signals and the TBX-37 and TBX-38 T-box transcription factors. Here, we show another T-box factor TBX-2 also functions in ABa-derived pharyngeal development. tbx-2 mutants arrest as L1 larvae lacking most or all ABa-derived pharyngeal muscles. In comparison, tbx-2 mutants retain ABa-derived marginal cells and pharyngeal muscles derived from MS. A tbx-2Colon, two colonsgfp translational fusion is expressed in a dynamic pattern in C. elegans embryos beginning near the 100-cell stage. Early expression is limited to a small number of cells, which likely include the ABa-derived pharyngeal precursors, while later expression is observed in body wall muscles and a subset of pharyngeal neurons. TBX-2 contains 2 consensus sumoylation sites, and it interacts in a yeast two-hybrid assay with the UBC-9 and GEI-17 components of the C. elegans SUMO-conjugating pathway. ubc-9(RNAi) has been previously shown to cause variable embryonic and larval arrest, and we find that, like tbx-2 mutants, ubc-9(RNAi) animals lack ABa-derived pharyngeal muscles. ubc-9(RNAi) also alters the subnuclear distribution of TBX-2::GFP fusion protein, suggesting that UBC-9 and TBX-2 interact in C. elegans. Together, these results indicate that TBX-2 and SUMO-conjugating enzymes are necessary for ABa-derived pharyngeal muscle, and we hypothesize that TBX-2 function requires sumoylation. Sumoylation is increasingly recognized as an important mechanism controlling activity of many nuclear factors, and these results provide the first evidence that T-box factor activity may require sumoylation.

The forkhead gene family of Caenorhabditis elegans.

The forkhead genes encode a family of transcriptional regulators with important roles in the control of animal development. The genomic sequence has revealed Caenorhabditis elegans has 15 forkhead genes of which six had been experimentally characterised previously. The remaining nine have now been investigated by RNAi and reporter gene expression pattern analysis. Two (B0286.5 and F26B1.7) have key developmental roles, four (F26D12.1, K03C7.2, F40H3.4 and C25A1.2) are expressed in, and may function in, the nervous system and three (C29F7.4, C29F7.5 and F26A1.2), which are closely related to each other, do not appear to be essential. Conservation with forkhead genes in the closely related nematode Caenorhabditis briggsae does not appear to correspond completely with demonstrated functionality in C. elegans. Comparisons of expression patterns and RNAi/mutant phenotypes for all 15 C. elegans forkhead genes reveal the potential complexity of functional interactions for this gene family.