Ridge preservation in periodontally compromised molar sockets with and without primary wound closure: A comparative controlled clinical trial.

OBJECTIVE: This study aimed to compare hard- and soft-tissue changes after ridge preservation in periodontally compromised molar sockets with and without primary wound closure. MATERIALS AND METHODS: Forty molars with severe periodontitis requiring extraction were included and allocated to two treatment modalities. After tooth extraction, the sockets were filled with deproteinized bovine bone mineral and covered with a bioabsorbable porcine collagen membrane. Primary wound closure was achieved in the control group, whereas the test group underwent minimally invasive open healing. The dimensions of the bone and soft tissue were recorded at baseline and 6 months. RESULTS: Over 6 months, the control and test groups had similar mean ridge heights at the center of sockets of 8.59 ± 2.47 mm and 8.47 ± 2.51 mm, respectively. The total volume of the control group increased from 1070.17 to 1713.52 mm3 for a mean gain of 643.35 mm3 , whereas that of the test group increased from 992.51 to 1514.05 mm3 for a mean gain of 521.54 mm3 . Compared with the test group, the control group showed a statistically significant decrease in keratinized tissue width of 1.08 ± 1.63 mm. CONCLUSIONS: Bone dimensional changes following ridge preservation with and without primary wound closure were comparable. ARP without primary wound closure preserves more keratinized tissue than that with (Chinese Clinical Trial Registry: ChiCTR-ONN-16009433).

Standardizing norms for 1286 colored pictures in Cantonese.

This study established psycholinguistic norms in Cantonese for a set of 1286 colored pictures sourced from several picture databases, including 750 colored line drawings from MultiPic (Duñabeitia et al., 2018) and 536 photographs selected for McRae et al. (2005) concepts. The pictures underwent rigorous normalization processes. We provided picture characteristics including name and concept agreement, familiarity, visual complexity, and frequency of modal responses. Through correlational analyses, we observed strong interrelationships among these variables. We also compared the current Cantonese norming to other languages and demonstrated similarity and variations among different languages. Additionally, we embraced the multilingual diversity within the current sample, and found that higher Cantonese proficiency but lower non-native language proficiency were associated with better spoken picture naming. Last but not least, we validated the predictive power of normed variables calculated from typed responses to spoken picture naming, and the consistency between typed and spoken responses. The present norming provides a timely and valuable alternative for researchers in the field of psycholinguistics, especially those studying Cantonese production and lexical retrieval. All raw data, analysis scripts, and final norming results are available online as psycholinguistic norms for Cantonese in the following link at the Open Science Framework: https://osf.io/dz9j6/?view_only=a452d8a56c92430b9dedf21ac26b1bc1 .

Multivariate decoding methods reveal how speaking two dialects affects executive functions.

How speaking two languages affects executive functions has been a long-standing debate and the mechanisms underlying the observed cognitive advantages of bilingualism remain unspecified. Here, using multivariate pattern classification methods, we decoded spatial patterns of neural signals associated with Flanker task performance in mono-dialectal and bi-dialectal speakers of Chinese. While univariate approach to even-related potentials (ERPs) showed no between-group difference, decoding accuracy of ERPs was reduced in bi-dialectal as compared to mono-dialectal speakers in both congruent-neutral and incongruent-neutral classifications. There was no effect of bidialectalism, however, on decoding accuracy of alpha-band oscillations, an electrophysiological index implicated in inhibition. Behavioural data analysed using the Drift Diffusion Model (DDM) showed facilitating effects of bidialectalism on non-decision times but no effect on drift rates. These findings demonstrate that using two dialects on a daily basis enhances general attentional deployment rather than affecting specific component of executive functions such as inhibitory control. Given that the two dialects of Chinese differed almost exclusively in phonology, the bidialectalism effect was most likely motivated by resolving phonological competition at lexical processing level.

Soluble expression and purification of recombinant bovine ferritin H-chain.

Ferritin is a potential medicine delivery vehicle and vaccine platform, and its efficient expression is a prerequisite for widespread application. This study introduces a soluble expression strategy for recombinant bovine ferritin heavy chain (rFTH) in a prokaryotic system and an improved protein purification method. The amplified rFTH gene was ligated into the prokaryotic expression vector pET30a. The recombinant vectors with the N-terminal His-tag(N-His) or C-terminal His-tag(C-His) were translated and expressed separately. The results showed that the solubility of rFTH with C-His was significantly higher than that with N-His. The expression of rFTH with C-His was attempted at 37 °C and 16 °C, respectively. The results showed that the proportion of soluble protein expressed at 37 °C was more than 90%, higher than that expressed at 16 °C. Then rFTH with C-His was purified successfully using anion exchange chromatography, modified PEG precipitation, and dialysis. The rFTH protein was characterized using SDS-PAGE, Native-PAGE, Western blot, transmission electron microscopy, and dynamic light scattering. The results demonstrated that the purified rFTH protein self-assembled into ferritin nanoparticles with a regular shape and uniform size. This study sheds new light on the soluble expression of ferritin and provides a foundation for the construction of bovine ferritin nanoparticle production platforms.

Spatiotemporal evolution of pyroptosis and canonical inflammasome pathway in hSOD1G93A ALS mouse model.

BACKGROUND: Evidences indicate that inflammasome compounds participate in amyotrophic lateral sclerosis (ALS), a fatal progressive motoneuron degenerative disease. Researchers have observed the expressions of nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) related inflammasome components in specific regions of the central nervous system in different ALS models, but the cellular spatiotemporal evolution of this canonical inflammasome pathway and pyroptosis during ALS progression are unclear. METHODS: The spinal cords of hSOD1G93A mice (ALS mice) and age-matched littermates (CON mice) were dissected at pre-symptomatic stage (60 d), early- symptomatic stage (95 d), symptomatic stage (108 d) and late-symptomatic stage (122 d) of the disease. By using Nissl staining, double immunofluorescence labelling, qRT-PCR or western blot, we detected morphology change and the expression, cellular location of GSDMD, NLRP3, caspase-1 and IL-1ß in the ventral horn of lumbar spinal cords over the course of disease. RESULTS: Neural morphology changes and GSDMD+/NeuN+ double positive cells were observed in ventral horn from ALS mice even at 60 d of age, even though there were no changes of GSDMD mRNA and protein expressions at this stage compared with CON mice. With disease progression, compared with age-matched CON mice, increased expressions of GSDMD, NLRP3, activated caspase-1 and IL-1ß were detected. Double immunofluorescence labeling revealed that NLRP3, caspase-1, IL-1ß positive signals mainly localized in ventral horn neurons at pre- and early-symptomatic stages. From symptomatic stage to late-symptomatic stage, robust positive signals were co-expressed in reactive astrocytes and microglia. CONCLUSIONS: Early activation of the canonical NLRP3 inflammasome induced pyroptosis in ventral horn neurons, which may participate in motor neuron degeneration and initiate neuroinflammatory processes during ALS progression.

Three-dimensional position changes of unopposed molars before implant rehabilitation: a short-term retrospective cohort analysis.

OBJECTIVE: To investigate the spatial changes of unopposed molars within the period between the antagonist extraction and the final implant restoration using data from cone beam computed tomography. METHODS: A total of 59 patients with 68 unopposed molars were included in this study. Three-dimensional models reconstructed from cone beam computed tomography data before and after loss of the antagonist were superimposed to measure the spatial changes. The overeruption and tipping of target teeth were calculated by coordinate values. RESULTS: The result of overeruption over the study period (9.2 ± 4.3 months) was expressed by two values: the mean overeruption of molar cups (0.432 mm) and the maximum overeruption of cusps (0.753 mm), which were statistically significant compared to the baseline level (p < 0.001). The average tipping was 1.717 degrees in the buccal direction. CONCLUSIONS: Unopposed molars displayed overeruption throughout the study period (9.2 ± 4.3 months), which indicates that the clinicians should pay attention to the possibilities of overeruption and make appropriate interventions in their clinical practice. The establishment of three-dimensional measuring methods using cone beam computed tomography data helps analyze spatial changes.

Assessment of soft and hard tissue characteristics of ridge preservation at molar extraction sites with severe periodontitis: a randomized controlled trial.

BACKGROUND: Changes in alveolar bone dimension after tooth extraction may affect placement of the subsequent implant, resulting in ridge deficiency that can adversely impact long-term implant stability or aesthetics. Alveolar ridge preservation (ARP) was effective in reducing the amount of ridge resorption following tooth extraction. There is sparse evidence regarding the benefit of ARP at periodontally compromised molar extraction sockets. This study will be a randomized trial to assess the soft tissue contour, radiographical, and histological changes of ARP at molar extraction sites in order to compare severe periodontitis cases with natural healing results and determine the most beneficial and least traumatic clinical treatment for such patients. METHODS: This research is designed as a two-group parallel randomized controlled trial. The total number of tooth extraction sites will be 70 after calculation with power analysis. Teeth will be randomly assigned to two groups with the test group conducting ridge preservation and the control group healing naturally. Periodontal examination, cone beam-computed tomography (CBCT) data, and stereolithographic (STL) files obtained by intraoral scanning will be collected through the follow-up period, and bone biopsy samples would be obtained during implant surgery. The primary outcomes are the vertical and horizontal change of alveolar ridge measured on CBCT images, soft tissue contour changes evaluated by superimposing the digital impressions, alterations of mucosa thickness (as measured by superimposing the CBCT data and STL files), histological features of implant sites and periodontal parameter changes. The secondary outcomes are patient-reported post-operative reaction and conditions of simultaneous bone graft or sinus lifting procedures during implantation. DISCUSSION: This study will provide information about hard and soft tissue dimension changes and histomorphology evaluation following ARP and natural healing in periodontally compromised molar sites, which may contribute to complement the missing information of ARP at periodontally compromised molar extraction sockets. TRIAL REGISTRATION: Chinese Clinical Trial Register (ChiCTR) ChiCTR2200056335. Registered on February 4, 2022, Version 1.0.

Neural sensitivity to phonological characteristics is stable across the lifespan.

Aging is often associated with declines in language production. For example, compared to younger adults, older adults experience more tip-of-the-tongue (TOT) states, show decreased speed and accuracy in naming objects, and have more pauses and fillers in speech, all of which indicate age-related increases in retrieval difficulty. While prior work has suggested that retrieval difficulty may be phonologically based, it is unclear whether there are age-related differences in the organization of phonological information per se or whether age-related difficulties may arise from accessing that information. Here we used fMRI to investigate the neural and behavioral basis of phonological neighborhood denisty (PND) effects on picture naming across the lifespan (N=91, ages 20-75). Consistent with prior work, behavioral results revealed that higher PND led to faster picture naming times and higher accuracies overall, and that older adults were less accurate in their responses. Consistent with the behavioral analyses, fMRI analyses showed that increasing PND was associated with decreased activation in auditory and motor language regions, including bilateral superior temporal gyri and bilateral precentral gyri. Interestingly, although there were age-related increases in functional activation to picture naming, there were no age-related modulations of neural sensitivity to PND. Overall, these results suggest that having a large cohort of phonological neighbors facilitates language production, and although aging is associated with increases in language production difficulty, sensitivity to phonological features during language production is stable across the lifespan.

Pretreatment with Methylene Blue Protects Against Acute Seizure and Oxidative Stress in a Kainic Acid-Induced Status Epilepticus Model.

BACKGROUND The aim of the present study was to investigate the potential anticonvulsant effect of methylene blue (MB) in a kainic acid (KA)-induced status epilepticus (SE) model. The effects of MB on levels of oxidative stress and glutamate (Glu) also were explored. MATERIAL AND METHODS Sixty C57BL/6 mice were randomly divided into 5 equal-sized groups: (1) controls; (2) KA; (3) MB 0.5 mg/kg+KA; (4) MB 1 mg/kg+KA; and (5) vehicle+KA. The SE model was established by intra-amygdala microinjection of KA. Behavioral observations and simultaneous electroencephalographic records of the seizures in different groups were analyzed to determine the potential anticonvulsant effect of MB. The influences of MB on oxidative stress markers and glutamate were also detected to explore the possible mechanism. RESULTS MB afforded clear protection against KA-induced acute seizure, as measured by the delayed latency of onset of generalized seizures and SE, decreased percentage of SE, and increased survival rate in mice with acute epilepsy. MB markedly increased the latency to first onset of epileptiform activity and decreased the average duration of epileptiform events, as well as the percentage of time during which the epileptiform activity occurred. Administration of MB prevented KA-induced deterioration of oxidative stress markers and Glu. CONCLUSIONS MB is protective against acute seizure in SE. This beneficial effect may be at least partially related to its potent antioxidant ability and influence on Glu level.

Gestational exposure to PM2.5 leads to cognitive dysfunction in mice offspring via promoting HMGB1-NLRP3 axis mediated hippocampal inflammation.

PM2.5 is recently identified as a kind of material possessing severe biohazard. It can enter human body and exerts pathological effects on lung, eyes, and the central nervous system (CNS). Maternal exposure to PM2.5 can affect neural development and cause cognitive decline in offspring, with the underlying mechanisms unclear, however. The inflammasome monitors and responds to biological stressors, with HMGB1-NLRP3 inflammatory axis as an essential pathophysiological player outside the brain. The present work is to investigate its role in cognitive impairment induced by gestational exposure to PM2.5 in mice offspring. We found that HMGB1-NLRP3 pathway was activated in the hippocampus of mice offspring by gestational exposure to PM2.5 in a dose-dependent manner, with protein levels of HMGB1, NLRP3, and cleaved caspase-1 as approximately three times as high as those of control. And down-regulating HMGB1 during pregnancy could alleviate the resultant impairment on learning and working memory as well as hippocampal neurons, up-regulate the synapse related proteins of SYP and PSD-95 and correct the increased expression of 5-HT2A to comparable levels to control, as well as inhibiting the activation of microglia and decreasing the expression of HMGB1 and Iba1/HMGB1 double positive cells in the hippocampus of mice offspring. Meanwhile, protein levels of NLRP3, cleaved caspase-1, IL-1ß and IL-18, as well as TLR4, phosphorylated NF-κB, and MAPKs, were almost down-regulated to those of control. Therefore, HMGB1 intervention inhibits the NLRP3 inflammasome mediated hippocampal inflammatory response through TLR4/MAPKs/NF-κB signaling pathway, alleviating PM2.5-induced cognitive dysfunction. Further in vitro results suggest that PM2.5 can activate microglia and HMGB1-NLRP3 inflammatory axis. Pretreatment with HMGB1 inhibitor significantly reduced the phosphorylation of MAPKs and NF-κB, and inhibited the inflammatory response mediated by NLRP3 inflammasome similarly to those in vivo. These results suggest that PM2.5 exposure promotes the inflammatory response in hippocampus mediated by HMGB1-NLRP3 inflammatory axis in microglia, resulting in cognitive dysfunction in offspring, which could be alleviated by simultaneous HMGB1 suppression. These findings provide a theoretical basis for preventing cognitive impairment in offspring caused by environmental pollution during pregnancy.

Long distance measurement by dynamic optical frequency comb.

In this paper, we propose a method aiming to measure the absolute distance via the slope of the inter-mode beat phase by sweeping the repetition frequency of the frequency comb. The presented approach breaks the inertial thinking of the extremely stable comb spacing, and the bulky phase-locking circuit of the repetition frequency is not required. In particular, the non-ambiguity range can be expanded to be infinite. To verify the performance of presented method, a series of distance experiments have been devised in different scenarios. Compared with the reference values, the experimental results show the differences within 25 µm at 65 m range in the laboratory, and within 100 µm at 219 m range out of the lab.

Prognostic role of tumor mutation burden in hepatocellular carcinoma after radical hepatectomy.

BACKGROUND AND AIM: This study aimed to assess the potential relationship between tumor mutation burden (TMB) and the recurrence risk of hepatocellular cancer (HCC) after curative resection and tried to develop a reliable TMB based nomogram. METHODS: This retrospective study was conducted in 128 patients (40 patients suffered from a recurrence of HCC) who had received radical hepatectomy by the same surgical team. A nomogram model was constructed using the R and EmpowerStats software. RESULTS: TMB was not associated with maximum tumor size and the presence of microvascular invasion (MVI). In the whole population or subgroups, the recurrence-free survival (RFS) rate was significantly lower in the TMB high group. In multivariate analysis, TMB (hazard ratio [HR], 10.12; 95% confidence interval [CI], 5.03-20.31; P < .001), large tumor diameter (HR, 2.91; 95% CI, 1.51-5.63; P = .001), presence of MVI (HR, 1.93; 95% CI, 1.03-3.65; P = .042) were independent predictors of RFS. The predictive power of the nomogram integrating TMB, tumor size and MVI was higher than model only incorporating tumor size and MVI. CONCLUSION: This study demonstrated for the first time that higher TMB was associated with poor prognosis in patients with HCC who had received curative resection, and a TMB based nomogram model had a well predictive performance for RFS in this population.

Three-Dimensional Imaging by Frequency-Comb Spectral Interferometry.

In this paper, we demonstrate a three-dimensional imaging system based on the laser frequency comb. We develop a compact, all-fiber mode-locked laser at 1 µm, whose repetition frequency can be tightly synchronized to the external frequency reference. The mode-locked state is achieved via the saturable absorber mirror in a linear cavity, and the laser output power can be amplified from 4 mW to 150 mW after a Yb-doped fiber amplifier. Three-dimensional imaging is realized via the spectral interferometry with the aid of an equal-arm Michelson interferometer. Compared with the reference values, the measurement results show the difference can be below 4 µm. Our system could provide a pathway to the real industry applications in future.

Underwater distance measurement using frequency comb laser.

In this paper, we theoretically and experimentally analyze the frequency-comb interferometry at 518 nm in the underwater environment, which we use to measure the underwater distance with high accuracy and precision. In the time domain, we analyze the principle of pulse cross correlation. The interferograms can be obtained in the vicinity of N∙lpp, where N is an integer and lpp is the pulse-to-pulse length. Due to the strong dispersion of water, the pulse can be broadened as the distance increases. The distance can be measured via the peak position of the interferograms. The experimental results show a difference within 100 µm at 8 m range, compared with the reference values. In the frequency domain, we analyze the principle of dispersive interferometry. The spectrograms can be observed near the location of N∙lpp, due to the low resolution of the optical spectrum analyzer. Because of the strong dispersion of water, the modulation frequency of the spectrogram is not constant. A balanced wavelength will exist with the widest fringe, at which the group optical path difference between the reference and measurement arm is equal to N∙lpp. The position of the widest fringe can be used to measure the distance. Compared with the reference values, the experimental results indicate a difference within 100 µm at 8 m range.

Screening the expression characteristics of several miRNAs in G93A-SOD1 transgenic mouse: altered expression of miRNA-124 is associated with astrocyte differentiation by targeting Sox2 and Sox9.

MicroRNAs (miRNAs) are suspected to be a contributing factor in amyotrophic lateral sclerosis (ALS). Here, we assess the altered expression of miRNAs and the effects of miR-124 in astrocytic differentiation in neural stem cells of ALS transgenic mice. Differentially expressed miRNA-positive cells (including miR-124, miR-181a, miR-22, miR-26b, miR-34a, miR-146a, miR-219, miR-21, miR-200a, and miR-320) were detected by in situ hybridization and qRT-PCR in the spinal cord and the brainstem. Our results demonstrated that miR-124 was down-regulated in the spinal cord and brainstem. In vitro, miR-124 was down-regulated in neural stem cells and up-regulated in differentiated neural stem cells in G93A-superoxide dismutase 1 (SOD1) mice compared with WT mice by qRT-PCR. Meanwhile, Sox2 and Sox9 protein levels showed converse change with miR-124 in vivo and vitro. After over-expression or knockdown of miR-124 in motor neuron-like hybrid (NSC34) cells of mouse, Sox2 and Sox9 proteins were noticeably down-regulated or up-regulated, whereas Sox2 and Sox9 mRNAs remained virtually unchanged. Moreover, immunofluorescence results indicated that the number of double-positive cells of Sox2/glial fibrillary acidic protein (GFAP) and Sox9/glial fibrillary acidic protein (GFAP) was higher in G93A-SOD1 mice compared with WT mice. We also found that many Sox2- and Sox9-positive cells were nestin positive in G93A-SOD1 mice, but not in WT mice. Furthermore, differentiated neural stem cells from G93A-SOD1 mice generated a greater proportion of astrocytes and lower proportion of neurons than those from WT mice. MiR-124 may play an important role in astrocytic differentiation by targeting Sox2 and Sox9 in ALS transgenic mice. Cover Image for this issue: doi: 10.1111/jnc.14171.

Task difficulty modulates brain-behavior correlations in language production and cognitive control: Behavioral and fMRI evidence from a phonological go/no-go picture-naming paradigm.

Language production and cognitive control are complex processes that involve distinct yet interacting brain networks. However, the extent to which these processes interact and their neural bases have not been thoroughly examined. Here, we investigated the neural and behavioral bases of language production and cognitive control via a phonological go/no-go picture-naming task. Naming difficulty and cognitive control demands (i.e., conflict monitoring and response inhibition) were manipulated by varying the proportion of naming trials (go trials) and inhibition trials (no-go trials) across task runs. The results demonstrated that as task demands increased, participants' behavioral performance declined (i.e., longer reaction times on naming trials, more commission errors on inhibition trials) whereas brain activation generally increased. Increased activation was found not only within the language network but also in domain-general control regions. Additionally, right superior and inferior frontal and left supramarginal gyri were sensitive to increased task difficulty during both language production and response inhibition. We also found both positive and negative brain-behavior correlations. Most notably, increased activation in sensorimotor regions, such as precentral and postcentral gyri, was associated with better behavioral performance, in both successful picture naming and successful inhibition. Moreover, comparing the strength of correlations across conditions indicated that the brain-behavior correlations in sensorimotor regions that were associated with improved performance became stronger as task demands increased. Overall, our results suggest that cognitive control demands affect language production, and that successfully coping with increases in task difficulty relies on both language-specific and domain-general cognitive control regions.

Direct measurement of the sound velocity in seawater based on the pulsed acousto-optic effect between the frequency comb and the ultrasonic pulse.

We present a new method to measure the velocity of sound in pure water and seawater using the Raman-Nath diffraction caused by acousto-optic effect between the optical frequency comb and the ultrasonic pulse. In the Mach-Zehnder interferometry system we established, the measurement and reference arms are tagged with sharp negative pulses caused by the pulsed ultrasound passing through them. The difference in optical path between the two parallel beams is twice the flight distance of the ultrasonic waves. The span between the two negative pulses reflects the time interval. At the same time, the distance between the two arms can be measured precisely using the femtosecond laser interferometry. Consequently, the time interval and the distance can be used to measure the sound velocity. The experimental results show that, the uncertainty of the sound speed measurement can achieve 0.03m/s@1482m/s in pure water and 0.029m/s@1527m/s in seawater, respectively, compared with the commercial sound velocity profiler (SVP). More importantly, benefiting from the faster and cleaner response of the acousto-optic effect than the piezoelectric effect which is widely adopted in direct sound velocity measurement method, our method provides a new idea for the metrology of sound velocity in seawater.

[Antioxidant effects of celastrol against hydrogen peroxide-induced oxidative stress in the cell model of amyotrophic lateral sclerosis].

To investigate the anti-oxidative effect of celastrol on H2O2-induced oxidative stress in the cell model of amyotrophic lateral sclerosis (ALS) and its molecular mechanism, NSC34 motor neuron-like cells were transfected with EGFP-G93A-SOD1 plasmid and used as in vitro ALS cell model. SOD1G93A transfected NSC34 cells were treated with different doses of H2O2 and celastrol. The survival rate of the cells was detected by CCK-8 assay, and malondialdehyde (MDA) content was detected by corresponding kit. The mRNA expression of glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione S-transferases (GST) were detected by real-time PCR. The activation of intracellular MEK/ERK and PI3K/Akt signal pathways was detected by Western blot. The results showed that pre-incubation of celastrol (50 nmol/L) for 4 h prior to H2O2 (10 µmol/L) co-treatment for another 24 h significantly attenuated H2O2-induced cell death and MDA level in SOD1G93A transfected NSC34 cells. Real-time PCR showed that the mRNA expressions of GCLC and GST were enhanced with pre-incubation of celastrol. Celastrol quickly induced phosphorylation of ERK1/2 and Akt within 30 min and 1 h respectively in SOD1G93A transfected NSC34 cells. Pharmacological inhibitors of MEK (PD98059, 10 µmol/L) or Akt (MK2206, 10 µmol/L) could reverse the phosphorylation of ERK1/2 and Akt, and abolish up-regulation of GCLC and GST induced by celastrol at mRNA levels. Taken together, we conclude that celastrol exerts a beneficial antioxidant effect in SOD1G93ANSC34 cells, which might be dependent on MEK/ERK and PI3K/Akt signaling pathway activation.

Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor inhibit ferrous iron influx via divalent metal transporter 1 and iron regulatory protein 1 regulation in ventral mesencephalic neurons.

Iron accumulation is observed in the substantia nigra of patients with Parkinson's disease. However, it is unknown whether neurotrophic factors, brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) participate in the modulation of neuronal iron metabolism. Here, we investigated the effects and underlying mechanisms of BDNF and GDNF on the iron influx process in primary cultured ventral mesencephalic neurons. 6-hydroxydopamine-induced enhanced ferrous iron influx via improper up-regulation of divalent metal transporter 1 with iron responsive element (DMT1+IRE) was consistently relieved by BDNF and GDNF. Both the mRNA and protein levels of DMT1+IRE were down-regulated by BDNF or GDNF treatment alone. We further demonstrated the involvement of iron regulatory protein 1 (IRP1) in BDNF- and GDNF-induced DMT1+IRE expression. Extracellular-regulated kinase 1/2 (ERK1/2) and Akt were activated and participated in these processes. Inhibition of ERK1/2 and Akt phosphorylation abolished the down-regulation of IRP1 and DMT1+IRE induced by BDNF and GDNF. Taken together, these results show that BDNF and GDNF ameliorate iron accumulation via the ERK/Akt pathway, followed by inhibition of IRP1 and DMT1+IRE expression, which may provide new targets for the neuroprotective effects of these neurotrophic factors.

Effects of Toll-like receptor 3 on herpes simplex virus type-1-infected mouse neural stem cells.

In this study, we aimed to investigate the effect of herpes simplex virus type-1 (HSV-1) infection on the phosphorylation of interferon regulatory factor 3 (IRF3) and the expression of interferon-ß (IFN-ß), as well as to clarify the functions of toll-like receptor 3 (TLR3) in mouse neural stem cells (NSCs) infected with HSV-1. In HSV-1-infected cultured NSCs, immunofluorescence, reverse transcription - polymerase chain reaction, Western blot, and ELISA were performed to reveal the expression patterns of TLR3, IRF3, and IFN-ß. Then, lentivirus-mediated RNA interference (RNAi) was used to block the expression of TLR3, and its effect on host resistance to HSV-1 infection was investigated. Under uninfected conditions, NSCs expressed TLR3 and phosphorylated IRF3, but after infection, the expression level of TLR3 was upregulated and the phosphorylation level of IRF3 in the nucleus was significantly enhanced, while IFN-ß was also expressed. After TLR3 expression was blocked by lentivirus-mediated RNAi, IRF3 phosphorylation and IFN-ß expression were downregulated. Therefore, HSV-1 upregulated the expression of TLR3 in NSCs and promoted nuclear translocation after IRF3 was phosphorylated to induce IFN-ß expression. TLR3 exhibited an anti-HSV-1 infection capacity via innate immune functions.