Overexpression of miR-378 Alleviates Chronic Sciatic Nerve Injury by Targeting EZH2.

In numerous studies, microRNAs (miRNAs) have been authenticated to play vital roles in the pathophysiology of neuropathic pain and other neurological diseases. In our study, we focused on evaluating miR-378 and its potential effects in neuropathic pain development, as well as the underlying molecular mechanisms. Primarily, a chronic sciatic nerve injury (CCI) rat model was established. Next, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to measure the expression levels of miR-378 and EZH2 mRNA; the EZH2 protein expression levels were detected by western blot. A luciferase activity assay monitored the interaction of miR-378 and EZH2. Mechanical and thermal hyperalgesia was also performed to quantitate the effects of overexpression of miR-378 or EZH2 on the CCI rats. We found that miR-378 was down-regulated in the CCI rats, and the overexpression of miR-378 produced significant relief in their pain management. EZH2 was the downstream gene of miR-378 and was negatively regulated by miR-378. The up-regulation of EZH2 reduced the inhibitory effects of miR-378 on the development of neuropathic pain in the CCI rats. miR-378 acts as an inhibitor in the progression of neuropathic pain via targeting EZH2; the miR-378/EZH2 axis may be a novel target for the diagnosis and therapy of neuropathic pain in clinical treatment.

Overexpression of miR-98 attenuates neuropathic pain development via targeting STAT3 in CCI rat models.

MicroRNA (miRNA) are significant regulators of neuropathic pain development and neuroinflammation can contribute a lot to the progression of neuropathic pain. Recently, miR-98 has been reported to be involved in various diseases. However, little is known about the role of miR-98 in neuropathic pain development and neuroinflammation. Therefore, our study was aimed to investigate the function of miR-98 in neuropathic pain via establishing a rat model using chronic constriction injury (CCI) of the sciatic nerve. Here, we observed that miR-98 was downregulated in CCI rat models. Overexpression of miR-9 was able to inhibit neuropathic pain progression. Recently, STAT3 has been reported to serve a key role in various processes, including inflammation. Interestingly, our study indicated that STAT3 was dramatically upregulated and activated in CCI rats. By using informatics analysis, STAT3 was predicted as a direct target of miR-98 and the direct correlation was confirmed. Then, miR-98 was overexpressed in CCI rats and it was found that miR-98 was able to repress neuropathic pain development via inhibiting the neuroinflammation. As displayed, interleukin 6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α) expression was obviously induced in CCI rats, while miR-98 reduced their protein levels. Finally, we found that overexpression of STAT3 reversed the inhibitory effect of miR-98 on neuropathic pain development. Taken these together, we reported that overexpression of miR-98 attenuated neuropathic pain development via targeting STAT3 in CCI rat models.

Species Diversity and Molecular Phylogeny of Cyanosporus (Polyporales, Basidiomycota).

Cyanosporus is a cosmopolitan brown-rot fungal genus, recognizable by blue-tinted basidiocarps. Species in this genus were usually treated as belonging to the Postia caesia complex, however, recent phylogenetic analyses showed that this complex represents an independent genus. During further studies on Cyanosporus, five new species were discovered based on morphological features and molecular data. Phylogenetic analyses of Cyanosporus were conducted using the internal transcribed spacer (ITS) regions, the large subunit of nuclear ribosomal RNA gene (nLSU), the small subunit of nuclear ribosomal RNA gene (nSSU), the small subunit of mitochondrial rRNA gene (mtSSU), the largest subunit of RNA polymerase II (RPB1), the second largest subunit of RNA polymerase II (RPB2), and the translation elongation factor 1-α gene (TEF); illustrated descriptions of the new species are provided. In addition, fifteen species previously belonging to the Postia caesia complex are transferred to Cyanosporus and proposed as new combinations.

Interface decoration of exfoliated MXene ultra-thin nanosheets for fire and smoke suppressions of thermoplastic polyurethane elastomer.

Thermoplastic polyurethane (TPU) has broad applications as lightweight materials due to its multiple advantages and unique properties. Nevertheless, toxicity emission under fire conditions remains a major concern, particularly in building fire scenarios. To circumvent the problem, it is imperative that an effective flame retardant is sought to suppress the flame and release of combustion/smoke products whilst maintaining the favorable material properties of TPU. In the current work, a simple method is proposed for the preparation and utilization of cetyltrimethyl ammonium bromide (CTAB) and tetrabutyl phosphine chloride (TBPC) modified Ti3C2 (MXene) ultra-thin nanosheets. During the cone calorimeter tests, significant reduction in peak heat release rate (51.2% and 52.2%), peak smoke production rate (57.1% and 57.4%), peak CO production (39.4% and 41.6%) and peak CO2 production (49.7% and 51.7%) were recorded by the mere introduction of 2 wt.% CTAB-Ti3C2 and TBPC-Ti3C2 to TPU. These superior fire safety properties resulting from the significant reduction of the fire, smoke and toxicity hazards are attributed to the excellent dispersion, catalytic and barrier effect of Ti3C2 ultra-thin nanosheets in TPU. Future applications of exfoliated MXene nanosheets as flame retardant appear to be very promising.

Effects of curcumin on sodium currents of dorsal root ganglion neurons in type 2 diabetic neuropathic pain rats.

Along with the development of economy and society, type 2 diabetic mellitus (T2DM) has become one of the most common diseases at the global level. As one of the complications of T2DM, diabetic neuropathic pain (DNP) stubbornly and chronically affects the health and life of human beings. In the pain field, dorsal root ganglion (DRG) is generally considered as the first stage of the sensory pathway where the hyperexcitability of injured neurons is associated with different kinds of peripheral neuropathic pains. The abnormal electrophysiology is mainly due to the changed properties of voltage-gated sodium channels (VGSCs) and the increased sodium currents (I(Na)). Curcumin is an active ingredient extracted from turmeric and has been demonstrated to ameliorate T2DM and its various complications including DNP effectively. The present study demonstrates that the I(Na) of small-sized DRG neurons are significantly increased with the abnormal electrophysiological characteristics of VGSCs in type 2 diabetic neuropathic pain rats. And these abnormalities can be ameliorated efficaciously by a period of treatment with curcumin.

Effects of curcumin on TTX-R sodium currents of dorsal root ganglion neurons in type 2 diabetic rats with diabetic neuropathic pain.

Type 2 diabetic mellitus (T2DM) has reached pandemic status and shows no signs of abatement. Diabetic neuropathic pain (DNP) is generally considered to be one of the most common complications of T2DM, which is also recognized as one of the most difficult types of pain to treat. As one kind of peripheral neuropathic pain, DNP manifests typical chronic neuralgia symptoms, including hyperalgesia, allodynia, autotomy, and so on. The injured dorsal root ganglion (DRG) is considered as the first stage of the sensory pathway impairment, whose neurons display increased frequency of action potential generation and increased spontaneous activities. These are mainly due to the changed properties of voltage-gated sodium channels (VGSCs) and the increased sodium currents, especially TTX-R sodium currents. Curcumin, one of the most important phytochemicals from turmeric, has been demonstrated to effectively prevent and/or ameliorate diabetic mellitus and its complications including DNP. The present study demonstrates that the TTX-R sodium currents of small-sized DRG neurons isolated from DNP rats are significantly increased. Such abnormality can be efficaciously ameliorated by curcumin.

[Application of artificial neural networks on the prediction of surface ozone concentrations].

Ozone is an important secondary air pollutant in the lower atmosphere. In order to predict the hourly maximum ozone one day in advance based on the meteorological variables for the Wanqingsha site in Guangzhou, Guangdong province, a neural network model (Multi-Layer Perceptron) and a multiple linear regression model were used and compared. Model inputs are meteorological parameters (wind speed, wind direction, air temperature, relative humidity, barometric pressure and solar radiation) of the next day and hourly maximum ozone concentration of the previous day. The OBS (optimal brain surgeon) was adopted to prune the neutral work, to reduce its complexity and to improve its generalization ability. We find that the pruned neural network has the capacity to predict the peak ozone, with an agreement index of 92.3%, the root mean square error of 0.0428 mg/m3, the R-square of 0.737 and the success index of threshold exceedance 77.0% (the threshold O3 mixing ratio of 0.20 mg/m3). When the neural classifier was added to the neural network model, the success index of threshold exceedance increased to 83.6%. Through comparison of the performance indices between the multiple linear regression model and the neural network model, we conclud that that neural network is a better choice to predict peak ozone from meteorological forecast, which may be applied to practical prediction of ozone concentration.

Genes required for the functions of olfactory AWA neuron regulate the longevity of Caenorhabditis elegans in an insulin/IGF signaling-dependent fashion.

OBJECTIVE: To investigate the interaction between the genes required for the functions of AWA olfactory neuron and insulin/IGF signaling in regulating the longevity of nematode Caenorhabditis elegans (C. elegans). METHODS: The mutants that had loss-of-function mutation of the genes required for AWA, AWC, ASE, and AFD sensory neurons were employed. Lifespan, the speed of pharynx pumping, the intestinal autofluorescence, the dauer formation, and the brood size were examined. Rescue experiments were performed to confirm the role of the genes required for the functions of AWA neuron in regulating lifespan. Moreover, genetic interactions between genes required for the functions of AWA neuron and insulin/IGF signaling were investigated. RESULTS: Mutations of odr-7, odr-2, and odr-3 genes required for the functions of AWA neuron significantly increased the mean lifespan of nematodes and slowed the accumulation of intestinal autofluorescence. Besides, these mutations were closely associated with higher pumping rates during aging. However, mutation of odr-7, odr-2, or odr-3 did not obviously affect the brood size or the dauer formation, and the regulation of longevity by odr-7, odr-2, and odr-3 was temperature-independent. In contrast, mutations of genes required for the functions of ASE, AWC, and AFD sensory neurons did not influence the nematode lifespan. Moreover, expression of odr-7, odr-2 and odr-3 in AWA neuron could completely or largely restore the altered lifespan in odr-7, odr-2 and odr-3 mutants. Furthermore, genetic interaction assay demonstrated that the extended lifespan in odr-7 mutant could be suppressed by daf-16 mutation and enhanced by daf-2 or age-1 mutation, whereas mev-1 and pha-4 were not required for the long lifespan of odr-7 mutant. CONCLUSION: The genes required for the function of AWA sensory neuron could regulate the nematode longevity in an insulin/IGF signaling-dependent fashion in C. elegans.

UNC-64 and RIC-4, the plasma membrane-associated SNAREs syntaxin and SNAP-25, regulate fat storage in nematode Caenorhabditis elegans.

OBJECTIVE: To investigate whether genes required for synaptogenesis and synaptic function are also involved in fat storage control in Caenorhabditis elegans. METHODS: Fat storage was examined in mutants of genes affecting the synaptogenesis and synaptic function. In addition, the genetic interactions of SNAREs syntaxin/unc-64 and SNAP-25/ric-4 with daf-2, daf-7, nhr-49, sbp-1 and mdt-15 in regulating fat storage were further investigated. The tissue-specific activities of unc-64 and ric-4 were investigated to study the roles of unc-64 and ric-4 in regulating fat storage in the nervous system and/or the intestine. RESULTS: Mutations of genes required for the formation of presynaptic neurotransmission site did not obviously influence fat storage. However, among the genes required for synaptic function, the plasma membrane-associated SNAREs syntaxin/unc-64 and SNAP-25/ric-4 genes were involved in the fat storage control. Fat storage in the intestinal cells was dramatically increased in unc-64 and ric-4 mutants as revealed by Sudan Black and Nile Red strainings, although the fat droplet size was not significantly changed. Moreover, in both the nervous system and the intestine, expression of unc-64 significantly inhibited the increase in fat storage observed in unc-64 mutant. And expression of ric-4 in the nervous system completely restored fat storage in ric-4 mutant. Genetic interaction assay further indicated that both unc-64 and ric-4 regulated fat storage independently of daf-2 [encoding an insulin-like growth factor-I (IGF-I) receptor], daf-7 [encoding a transforming growth factor-beta (TGF-beta) ligand], and nhr-49 (encoding a nuclear hormone receptor). Besides, mutation of daf-16 did not obviously affect the phenotype of increased fat storage in unc-64 or ric-4 mutant. Furthermore, unc-64 and ric-4 regulated fat storage probably through the ARC105/mdt-15- and SREBP/sbp-1-mediated signaling pathways. In addition, fat storage in unc-64; ric-4 was higher than that in either unc-64 or ric-4 single mutant nematodes, suggesting that unc-64 functions in parallel with ric-4 in regulating fat storage. CONCLUSION: The plasma membrane-associated SNAREs syntaxin/unc-64 and SNAP-25/ric-4 function in parallel in regulating fat storage in C. elegans, probably through the ARC105/mdt-15- and SREBP/sbp-1-mediated signaling pathways.

Regulation of aging by unc-13 and sbt-1 in Caenorhabditis elegans is temperature-dependent.

OBJECTIVE: To investigate the role of environmental factor-temperature in the regulation of aging process by unc-13 and sbt-1 in Caenorhabditis elegans. METHODS: The lifespan, the speed of pharynx pumping, and the intestinal autofluorescence of unc-13 and sbt-1 mutants were examined at different temperature conditions. In addition, to exclude the possible influences from other factors in unc-13 and sbt-1 mutants, the dauer formation, the thermotaxis, the brood size and the population percentage of the mutants expressing hsp16.2-gfp were further investigated. RESULTS: Mutations of unc-13 and sbt-1 significantly increased the mean and the maximum lifespans of nematodes cultured at 20 degrees C and 25 degrees C, while no noticeable increase was found at 15 degrees C in either the mean or the maximum lifespan. Investigations on the speed of pharynx pumping and the intestinal autofluorescence suggested that at 20 degrees C and 25 degrees C, mutations of unc-13 and sbt-1 could slow the aging process and delay the accumulation of aging-related cellular damage. Meanwhile, mutations of unc-13 or sbt-1 did not affect the dauer formation or the thermotaxis to different temperatures in nematodes. In contrast, at 20 degrees C and 25 degrees C conditions, mutations of unc-13 and sbt-1 significantly decreased the brood size and the percentage of nematodes expressing hsp16.2-gfp, while no such differences were detected at 15 degrees C. Moreover, the thermotolerance of unc-13 and sbt-1 mutants could be greatly strengthened after the 16-h heat shock at 35 degrees C. CONCLUSION: The regulation of aging by unc-13 and sbt-1 is temperature-dependent. And the alterations in reproduction capability and stress response may be associated with the formation of this temperature-dependent property.

Involvement of genes required for synaptic function in aging control in C. elegans.

OBJECTIVE: To identify new genes required for neurosecretory control of aging in C. elegans. METHODS: In view of the importance of nervous system in aging regulation, we performed the screen for genes involved in the aging regulation from genetic loci encoding synaptic proteins by lifespan assay and accumulation of lipofuscin autofluorescence. We further investigated the dauer formation phenotypes of their corresponding mutants and whether they were possibly up-regulated by the insulin-like signaling pathway. RESULTS: The genetic loci of unc-10, syd-2, hlb-1, dlk-1, mkk-4, scd-2, snb-1, ric-4, nrx-1, unc-13, sbt-1 and unc-64 might be involved in the aging control. In addition, functions of unc-10, syd-2, hlb-1, dlk-1, mkk-4, scd-2, snb-1, ric-4 and nrx-1 in regulating aging may be opposite to those of unc-13, sbt-1 and unc-64. The intestinal autofluorescence assay further indicated that the identified long-lived and short-lived mutants were actually due to the suppressed or accelerated aging. Among the identified genes, syd-2, hlb-1, mkk-4, scd-2, snb-1, ric-4 and unc-64 were also involved in the control of dauer formation. Moreover, daf-2 mutation positively regulated the expression of syd-2 and hlb-1, and negatively regulated the expression of mkk-4, nrx-1, ric-4, sbt-1, rpm-1, unc-10, dlk-1 and unc-13. The daf-16 mutation positively regulated the expression of syd-2 and hlb-1, and negatively regulated the expression of mkk-4, nrx-1, sbt-1, rpm-1, unc-10, dlk-1 and unc-13. CONCLUSION: These data suggest the possibly important status of the synaptic transmission to the animal's life-span control machinery, as well as the dauer formation control.