Coronin 2B deficiency induces nucleolar stress and neuronal apoptosis.

In eukaryotes, the nucleolus is the critical non-membranous organelle within nuclei that is responsible for ribosomal DNA (rDNA) transcription and ribosome biogenesis. The transcription of rDNA, a rate-limiting step for ribosome biogenesis, is tightly regulated to meet the demand for global protein synthesis in response to cell physiology, especially in neurons, which undergo rapid changes in morphology and protein composition during development and synaptic plasticity. However, it is unknown how the pre-initiation complex for rDNA transcription is efficiently assembled within the nucleolus in neurons. Here, we report that the nucleolar protein, coronin 2B, regulates rDNA transcription and maintains nucleolar function through direct interaction with upstream binding factor (UBF), an activator of RNA polymerase I transcriptional machinery. We show that coronin 2B knockdown impairs the formation of the transcription initiation complex, inhibits rDNA transcription, destroys nucleolar integrity, and ultimately induces nucleolar stress. In turn, coronin 2B-mediated nucleolar stress leads to p53 stabilization and activation, eventually resulting in neuronal apoptosis. Thus, we identified that coronin 2B coordinates with UBF to regulate rDNA transcription and maintain proper nucleolar function in neurons.

Health and ecological risk of heavy metals in agricultural soils related to Tungsten mining in Southern Jiangxi Province, China.

Background: Dayu County, a major tungsten producer in China, experiences severe heavy metal pollution. This study evaluated the pollution status, the accumulation characteristics in paddy rice, and the potential ecological risks of heavy metals in agricutural soils near tungsten mining areas of Dayu County. Furthermore, the impacts of soil properties on the accumulation of heavy metals in soil were explored. Methods: The geo-accumulation index (Igeo), the contamination factor (CF), and the pollution load index (PLI) were used to evaluate the pollution status of metals (As, Cd, Cu, Cr, Pb, Mo, W, and Zn) in soils. The ecological risk factor (RI) was used to assess the potential ecological risks of heavy metals in soil. The health risks and accumulation of heavy metals in paddy rice were evaluated using the health risk index and the translocation factor (TF), respectively. Pearson's correlation coefficient was used to discuss the influence of soil factors on heavy metal contents in soil. Results: The concentrations of metals exceeded the respective average background values for soils (As: 10.4, Cd: 0.10, Cu: 20.8, Cr: 48.0, Pb: 32.1, Mo: 0.30, W: 4.93, Zn: 69.0, mg/kg). The levels of As, Cd, Mo, and tungsten(W) exceeded the risk screening values for Chinese agricultural soil contamination and the Dutch standard. The mean concentrations of the eight tested heavy metals followed the order FJ-S > QL > FJ-N > HL > CJ-E > CJ-W, with a significant distribution throughout the Zhangjiang River basin. Heavy metals, especially Cd, were enriched in paddy rice. The Igeo and CF assessment indicated that the soil was moderately to heavily polluted by Mo, W and Cd, and the PLI assessment indicated the the sites of FJ-S and QL were extremely severely polluted due to the contribution of Cd, Mo and W. The RI results indicated that Cd posed the highest risk near tungsten mining areas. The non-carcinogenic and total carcinogenic risks were above the threshold values (non-carcinogenic risk by HQ > 1, carcinogenic risks by CR > 1 × 10-4 a-1) for As and Cd. Correlation analysis indicated that K2O, Na2O, and CaO are main factors affecting the accumulation and migration of heavy metals in soils and plants. Our findings reveal significant contamination of soils and crops with heavy metals, especially Cd, Mo, and W, near mining areas, highlighting serious health risks. This emphasizes the need for immediate remedial actions and the implementation of stringent environmental policies to safeguard health and the environment.

Lactate attenuates astrocytic inflammation by inhibiting ubiquitination and degradation of NDRG2 under oxygen-glucose deprivation conditions.

BACKGROUND: Brain lactate concentrations are enhanced in response to cerebral ischemia and promote the formation of reactive astrocytes, which are major components of the neuroinflammatory response and functional recovery, following cerebral ischemia. NDRG2 is upregulated during reactive astrocyte formation. However, its regulation and function are unclear. We studied the relationship between lactate and NDRG2 in astrocytes under conditions of ischemia or oxygen-glucose deprivation (OGD). METHODS: We examined astrocytic NDRG2 expression after middle cerebral artery occlusion (MCAO) using western blot and immunofluorescence staining. Under hypoxia conditions, we added exogenous L-lactate sodium (lactate) to cultured primary astrocytes to explore the effects of lactate on the ubiquitination modification of NDRG2. We profiled the transcriptomic features of NDRG2 silencing in astrocytes after 8 h of OGD conditions as well as exogenous lactate treatment by performing RNA-seq. Finally, we evaluated the molecular mechanisms of NDRG2 in regulating TNFα under OGD conditions using western blot and immunohistochemistry. RESULTS: Reactive astrocytes strongly expressed NDRG2 in a rat model of MCAO. We also showed that lactate stabilizes astrocytic NDRG2 by inhibiting its ubiquitination. NDRG2 inhibition in astrocytes increased inflammation and upregulated immune-associated genes and signaling pathways. NDRG2 knockdown induced TNFα expression and secretion via c-Jun phosphorylation. CONCLUSIONS: We revealed that under OGD conditions, lactate plays an important anti-inflammatory role and inhibits TNFα expression by stabilizing NDRG2, which is beneficial for neurological functional recovery. NDRG2 may be a new therapeutic target for cerebral ischemia.

α-Mangostin Treats Early-Stage Adjuvant-Induced Arthritis of Rat by Regulating the CAP-SIRT1 Pathway in Macrophages.

BACKGROUND: Studies have found that α-mangostin (MG) can relieve experimental arthritis by activating cholinergic anti-inflammatory pathway (CAP). It affects the polarization of macrophages and the balance of related immune cell subpopulations, but the specific mechanism is still unclear. It has been found that silent information regulator 1 (SIRT1) is closely related to macrophage activity. The purpose of this study is to explore the mechanism of MG intervening in macrophage polarization during treatment of early adjuvant-induced (AIA) rats through the CAP-SIRT1 pathway. METHODS: We investigated the polarization of M1 macrophages and the differentiation of Th1 in AIA rats by flow cytometry. Activity of acetylcholinesterase (AChE) and the level of nicotinic adenine dinucleotide (NAD+) in serum were also detected, and immunohistochemical was used to detect the levels of α7 nicotinic cholinergic receptor (α7nAChR) and SIRT1. Then in macrophages, the molecular mechanism of MG regulating the abnormal activation of macrophages in rats with early AIA through the CAP-SIRT1 pathway was studied. RESULTS: MG can significantly inhibit the polarization of M1 macrophages and the differentiation of Th1 in AIA rats in the acute phase of inflammation. MG can significantly inhibit the activity of AChE and increase the level of NAD+, thereby further up-regulated the expression levels of α7nAChR and SIRT1. Meanwhile, MG inhibited nuclear factor-κB (NF-κB)-mediated inflammation by activating the CAP-SIRT1 pathway in macrophages. CONCLUSION: In summary, the stimulation of MG induced CAP activation, which up-regulated SIRT1 signal, and thereby inhibited M1 polarization through the NF-κB pathway, and improved the pathological immune environment of early-stage AIA rats.

miR-124: A Promising Therapeutic Target for Central Nervous System Injuries and Diseases.

Central nervous system injuries and diseases, such as ischemic stroke, spinal cord injury, neurodegenerative diseases, glioblastoma, multiple sclerosis, and the resulting neuroinflammation often lead to death or long-term disability. MicroRNAs are small, non-coding, single-stranded RNAs that regulate posttranscriptional gene expression in both physiological and pathological cellular processes, including central nervous system injuries and disorders. Studies on miR-124, one of the most abundant microRNAs in the central nervous system, have shown that its dysregulation is related to the occurrence and development of pathology within the central nervous system. Herein, we review the molecular regulatory functions, underlying mechanisms, and effective delivery methods of miR-124 in the central nervous system, where it is involved in pathological conditions. The review also provides novel insights into the therapeutic target potential of miR-124 in the treatment of human central nervous system injuries or diseases.

The influence of water regime on cadmium uptake by Artemisia: A dominant vegetation in Poyang Lake wetland.

An analysis of the influence of water regime on the metal accumulation processes of wetland plants can improve the efficiency of phytoremediation. However, few studies have clearly explored the mechanism of influence of water regime on the process of accumulation of metals by the dominant vegetation in Poyang Lake wetland, the largest freshwater lake in China. The aim of this study was to investigate the influence of water regime (Flooding condition [FC], Dry condition [DC] and alternate dry and flooding condition [DFC]) on the accumulation of cadmium (Cd) by Artemisia selengensis Turcz. ex Bess., a dominant plant in the Poyang Lake wetland. The results indicated that FC treatment significantly enhanced the accumulation of Cd by Artemisia roots compared with DFC and DC treatments. In addition, the DFC treatment significantly increased the translocation of Cd from roots to shoots compared with the FC treatment. A multivariate statistical analysis indicated that the rhizosphere Cd fraction, iron plaque on the root surface and rhizosphere pH directly or indirectly significantly influence the process of accumulation of Cd. The conversion of exchangeable fraction to Fe/Mn oxide bound and organic fraction under the DFC and FC treatments decreased the accumulation of Cd in Artemisia. The formation of increased amounts of iron plaque under the FC treatment may enhance the accumulation of Cd in roots, while it may reduce the translocation of Cd to aboveground tissues. In addition, a higher rhizosphere pH under the FC treatment may promote accumulation of Cd in the root by inducing formation of iron plaque. Similarly, compared with the FC treatment, a lower rhizosphere pH and iron plaque can induce the processes of Cd translocation under the DFC treatment. Based on the bioaccumulation factor, translocation factor and the ratio of root/aerial Cd content, treatment with DC benefited the phytoextraction of Cd, while treatment with DFC and FC enhanced the phytostabilization of Cd by Artemisia. This study provides valuable information for deeply understanding the resilience of wetland ecosystems and for enhancing the phytoremediation with wetland plants using water management.

The role of exosomal microRNAs in central nervous system diseases.

MicroRNAs (miRNA), endogenous non-coding RNAs approximately 22 nucleotides long, regulate gene expression by mediating translational inhibition or mRNA degradation. Exosomes are a tool for intercellular transmission of information in which miRNA exchange plays an important role. Under pathophysiological conditions in the central nervous system (CNS), cellular transmission of exosomal miRNAs can regulate signaling pathways. Exosomal miRNAs are involved in the occurrence and development of diverse CNS diseases, such as traumatic brain injury, spinal cord injury, stroke, neurodegenerative diseases, epilepsy, and glioma. The use of exosomes as transport vehicles for certain miRNAs provides a novel therapeutic strategy for CNS diseases. Furthermore, the exosomes in body fluids change with the occurrence of diseases, indicating that subtle changes in physiological and pathological processes in vivo could be recognized by analyzing exosomes. Exosomal analysis is expected to act as a novel tool for diagnosis and prediction of neurological diseases. In this review, we present the current understanding of the implications of miRNAs in CNS diseases and summarize the role and mechanism of action of exosomal miRNA in nervous system disease models.

Evaluation of the efficacy of atorvastatin in the treatment for chronic subdural hematoma: a meta-analysis.

Atorvastatin therapy in chronic subdural hematoma patients has attracted more and more clinical attention. To evaluate the efficacy of atorvastatin in the treatment of chronic subdural hematoma. A systematic literature search was performed in the PubMed, Embase, and Cochrane Library databases; related controlled trials comparing the efficacy of atorvastatin in the treatment of chronic subdural hematoma published from inception to December 2018 were collected. We used Cochrane risk of bias method to evaluate the quality of the included studies. Meta-analysis was used to analyze the included data by RevMan 5.3 software. Of the 53 retrieved studies, 6 trials were included. Results of meta-analysis showed that compared with chronic subdural hematoma patients without atorvastatin treatment, both in patients who have had surgery and those who have not, atorvastatin were effective in reducing the incidence of recurrence requires surgery (OR = 0.30, 95% CI 0.19-0.48, P < 0.00001). And improve the recovery rate of neurological function of patients (OR = 1.75, 95% CI 1.08-2.83, P = 0.02). This meta-analysis suggests that patients with chronic subdural hematoma can improve their prognosis after receiving atorvastatin. Additionally, the neurological function recovery appears to be improving by atorvastatin.

MicroRNA-27b targets CBFB to inhibit differentiation of human bone marrow mesenchymal stem cells into hypertrophic chondrocytes.

BACKGROUND: Human bone marrow-derived mesenchymal stem cells (hBMSCs) have chondrocyte differentiation potential and are considered to be a cell source for cell-transplantation-mediated repair of cartilage defects, including those associated with osteoarthritis (OA). However, chondrocyte hypertrophic differentiation is a major obstacle for the application of hBMSCs in articular cartilage defect treatment. We have previously shown that microRNA-27b (miR-27b) inhibits hypertrophy of chondrocytes from rat knee cartilage. In this study, we investigated the role of miR-27b in chondrocyte hypertrophic differentiation of hBMSCs. METHODS: Chondrogenic marker and microRNA expression in hBMSC chondrogenic pellets were evaluated using RT-qPCR and immunohistochemistry. The hBMSCs were transfected with miR-27b before inducing differentiation. Gene and protein expression levels were analyzed using RT-qPCR and western blot. Coimmunoprecipitation was used to confirm interaction between CBFB and RUNX2. Luciferase reporter assays were used to demonstrate that CBFB is a miR-27b target. Chondrogenic differentiation was evaluated in hBMSCs treated with shRNA targeting CBFB. Chondrogenic hBMSC pellets overexpressing miR-27b were implanted into cartilage lesions in model rats; therapeutic effects were assessed based on histology and immunohistochemistry. RESULTS: The hBMSCs showed typical MSC differentiation potentials. During chondrogenic differentiation, collagen 2 and 10 (COL2 and COL10), SOX9, and RUNX2 expression was upregulated. Expression of miR-140, miR-143, and miR-181a increased over time, whereas miR-27b and miR-221 were downregulated. Cartilage derived from hBMSC and overexpressing miR-27b exhibited higher expression of COL2 and SOX9, but lower expression of COL10, RUNX2, and CBFB than did the control cartilage. CBFB and RUNX2 formed a complex, and CBFB was identified as a novel miR-27b target. CBFB knockdown by shRNA during hBMSC chondrogenic differentiation led to significantly increased COL2 and SOX9 expression and decreased COL10 expression. Finally, miR-27b-overexpressing hBMSC chondrogenic pellets had better hyaline cartilage morphology and reduced expression of hypertrophic markers and tend to increase repair efficacy in vivo. CONCLUSION: MiR-27b plays an important role in preventing hypertrophic chondrogenesis of hBMSCs by targeting CBFB and is essential for maintaining a hyaline cartilage state. This study provides new insights into the mechanism of hBMSC chondrocyte differentiation and will aid in the development of strategies for treating cartilage injury based on hBMSC transplantation.

Gut Microbiome Alterations Precede Cerebral Amyloidosis and Microglial Pathology in a Mouse Model of Alzheimer's Disease.

Emerging evidence suggests that the gut microbiome actively regulates cognitive functions and that gut microbiome imbalance is associated with Alzheimer's disease (AD), the most prevalent neurodegenerative disorder. However, the changes in gut microbiome composition in AD and their association with disease pathology, especially in the early stages, are unclear. Here, we compared the profiles of gut microbiota between APP/PS1 transgenic mice (an AD mouse model) and their wild-type littermates at different ages by amplicon-based sequencing of 16S ribosomal RNA genes. Microbiota composition started diverging between the APP/PS1 and wild-type mice at young ages (i.e., 1-3 months), before obvious amyloid deposition and plaque-localized microglial activation in the cerebral cortex in APP/PS1 mice. At later ages (i.e., 6 and 9 months), there were distinct changes in the abundance of inflammation-related bacterial taxa including Escherichia-Shigella, Desulfovibrio, Akkermansia, and Blautia in APP/PS1 mice. These findings suggest that gut microbiota alterations precede the development of key pathological features of AD, including amyloidosis and plaque-localized neuroinflammation. Thus, the investigation of gut microbiota might provide new avenues for developing diagnostic biomarkers and therapeutic targets for AD.

Identification of dissolved metal contamination of major rivers in the southeastern hilly area, China: distribution, source apportionment, and health risk assessment.

Metal pollution has been a serious problem facing river systems worldwide, which can adversely affect human health through food chain. The goal of this study was to determine the distribution, sources, and health risk of dissolved metals (Cr, Mn, Ni, Cu, Zn, As, Cd, Pb, Al, Sb, V, Co, Mo) in major rivers located in the hilly area of southeastern China (namely, Jiulongjiang River (JL), Minjiang River (MJ), Oujiang River (OJ), Qiantangjiang River (QT), Raohe River (RR), Fuhe River (FR), Xinjiang River (XR), Ganjiang River (GR), Xiushui River (XS), Xiangjiang River (XJ), Zishui River (ZR), Yuanjiang River (YR), Lishui River (LR)) during dry and wet seasons. Results indicated that metal concentrations were spatially and temporally distinct. Metals of Mn, Ni, Cu, Cd, Sb were significantly higher in specific rivers than other metals. And metals of Cr, Ni, As, and Al concentrations were obviously higher in dry season than in wet season. The comparison with drinking water guidelines of China and other countries indicated that waterbodies were polluted higher by Al than other metals at most sites. Metals in JL and XJ may have health risk to local adults with hazard index (HI) > 1. While special attention should be paid to As, which had a potential carcinogenic risk to adults in study area with CR higher than the critical value. Source analysis with statistical method indicated that point and non-point pollutants from anthropogenic activities are the main sources of metals, with the exception of Al, Ni, V, Cr, and Mo that were mainly from natural processes. This study could be useful for the management and protection of the China's Southern hilly area river systems.

Rat vibrissa dermal papilla cells promote healing of spinal cord injury following transplantation.

Bone marrow mesenchymal stem cell (BMSC) transplantation is effective for repairing spinal cord injuries (SCIs); however, there are limitations of clinical BMSC applications. Previously, we reported that dermal papilla cells (DPCs) secrete brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor more actively than BMSCs. To analyze the therapeutic function of DPCs in SCI, primary DPCs and BMSCs were cultured from the same green fluorescence protein-transgenic rat. The cells were suspended in rat-tail collagen I and transplanted separately into completely transected spinal cord lesion sites. Grafted-cell survival was examined with a small animal in vivo imaging detection system, and lesion sites were examined histochemically. In vivo imaging revealed enhanced lesion filling and survival with DPC grafts compared with BMSC grafts on days 14 and 21 post-transplantation. Hematoxylin and eosin staining demonstrated that lesion area sizes in the two groups were not markedly different. In the DPC transplant group, more axons formed within the lesion sites. CD31-positive vessel-like structures were more abundant in lesion sites near the grafted cells in the DPC group. The results of the present study suggest that DPCs may be a valuable alternative source of stem cells for autologous cell therapy for the treatment of SCI.

miR-27b promotes type II collagen expression by targetting peroxisome proliferator-activated receptor-γ2 during rat articular chondrocyte differentiation.

MicroRNAs (miRNAs) play an essential role in articular cartilage development and growth. However, the exact mechanisms involved in this process remain unknown. In the present study, we investigated the biological functions of miR-27b during hypertrophic differentiation of rat articular chondrocytes. Based on in situ hybridization and immunohistochemistry, we report that miR-27b expression is reduced in the hypertrophic zone of articular cartilage, but expression of peroxisome proliferator-activated receptor γ (Pparγ) is increased. Dual-luciferase reporter gene assay and Western blot analysis demonstrated that Pparγ2 is a target of miR-27b Overexpression of miR-27b inhibited expression of Pparγ2, as well as type X collagen (Col10a1) and matrix metalloproteinase 13 (Mmp13), while significantly promoting the expression of Sex-determining Region-box 9 (Sox9) and type II collagen (Col2a1) at both the mRNA and protein levels. Rosiglitazone, a Pparγ agonist, suppressed Col2a1 expression, while promoting expression of runt-related transcription factor 2 (Runx2) and Col10a1 in a concentration-dependent manner. siRNA-mediated knockdown of Pparγ2 caused an increase in protein levels of Col2a1. The present study demonstrates that miR-27b regulates chondrocyte hypertrophy in part by targetting Pparγ2, and that miR-27b may have important therapeutic implications in cartilage diseases.

Insulin-like growth factor-1 activates PI3K/Akt signalling to protect human retinal pigment epithelial cells from amiodarone-induced oxidative injury.

BACKGROUND AND PURPOSE: Amiodarone is one of the most effective anti-arrhythmic drugs available, but its clinical applications are limited by toxic side effects including optic toxicity. The purpose of this study was to investigate the toxic effect of amiodarone on D407 cells (a human retinal pigmented epithelial (RPE) cell line) and the mechanisms of the protective effect of insulin-like growth factor-1 (IGF-1). EXPERIMENTAL APPROACH: The involvement of the kinases, Akt and ERK, was analysed by Western blot. Intracellular accumulation of ROS was measured using fluorophotometric quantification. A pharmacological approach with inhibitors was used to investigate the pathways involved in the protective action of IGF-1. KEY RESULTS: Amiodarone concentration-dependently augmented the production of ROS, lipid peroxidation and apoptosis in D407 cells. IGF-1 time- and concentration-dependently reversed these effects of amiodarone and protected D407 cells from amiodarone-mediated toxicity. Amiodarone inhibited the pAkt but not pErk, and IGF-1 reversed this inhibitory effect of amiodarone. However, IGF-1 failed to suppress amiodarone-induced cytotoxicity in the presence of PI3K/Akt inhibitor LY294002 suggesting the direct involvement of the PI3K/Akt pathway. Furthermore, in vivo rat flash electroretinogram (FERG) recordings showed that IGF-1 reverses the amiodarone-induced decrease in a- and b-waves. The immunocytochemistry findings confirmed that vitreous IGF-1 injections promote the survival of RPE cells in rat retina treated with amiodarone. CONCLUSION AND IMPLICATIONS: IGF-1 can protect RPE cells from amiodarone-mediated injury via the PI3K/Akt pathway in vivo and in vitro. IGF-1 has potential as a protective drug for the prevention and treatment of amiodarone-induced optic toxicity.

MicroRNA-124 inhibits the proliferation of C6 glioma cells by targeting Smad4.

MicroRNA-124 (miR-124) has been shown to be downregulated in glioma; however, its biological functions in glioma are not yet fully understood. The aim of this study was to examine the Smad4­dependent effects of miR­124 on C6 glioma cell proliferation. In this study, the level of miR­124 was found to be enhanced in C6 cells upon transfection with miR­124 mimics, and the mechanisms of action of miR­124 in C6 cells were investigated by reverse transcriptase-quantitative polymerase chain reaction, MTT assay, western blot analysis and luciferase reporter assays in vitro. The results revealed that miR­124 expression was significantly lower in the C6 cells than in either normal rat brain tissue or astrocytes. Upon the overexpression of miR­124, the proliferation of the C6 cells decreased and Smad4 expression was significantly suppressed. Smad4 was identified as a direct target of miR­124 through luciferase reporter assays. Furthermore, miR­124 was found to modulate signal transducer and activator of transcription 3 (Stat3) by downregulating Smad4 expression. Using small interfering RNA targeting Smad4 mRNA, we also confirmed that miR­124 downregulated c­Myc by modulating Smad4 expression. In addition, caspase­3 expression was induced by miR­124 overexpression, but not via Smad4 downregulation. On the whole, our results demonstrate that miR­124 upregulation inhibits the growth of C6 glioma cells by targeting Smad4 directly. These findings may be clinically useful for the development of therapeutic strategies directed toward miR­124 function in patients with glioma.

Carbon dots for tracking and promoting the osteogenic differentiation of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) hold great potential for tissue engineering and regeneration medicine. However, for clinical use, MSCs may be detrimental due to their uncertain fate during the transplantation. It is therefore highly desirable to develop biocompatible nanomaterials to integrate cell fate regulation with monitoring for MSC-based therapy. Herein, we employ recently developed citric acid-based carbon dots (CDs) and their derivatives (Et-IPCA) for labeling and tracking of rat bone marrow mesenchymal stem cells (rBMSCs). We further investigate their biocompatibility and effects on the osteogenic differentiation of rBMSCs. These highly fluorescent probes provide labeling of rBMSCs by internalization without affecting cell viability or inducing apoptosis when the concentration is lower than 50 µg mL-1. Importantly, the presence of the CDs and Et-IPCA facilitates high-efficiency osteogenic differentiation of rBMSCs by promoting osteogenic transcription and enhancing matrix mineralization. Compared to Et-IPCA, CDs considerably provide long-term tracking and promote the differentiation of rBMSCs toward osteoblasts through the ROS-mediated MAPK pathway. Taken together, our results consistently demonstrate that carbon dots are capable of both tracking and enhancing the osteogenic differentiation of MSCs. This study sheds new light on the potential of carbon dots as a bifunctional tool in the thriving field of MSC-based therapy.

Artemisinin protects PC12 cells against ß-amyloid-induced apoptosis through activation of the ERK1/2 signaling pathway.

Accumulating evidence displays that an abnormal deposition of amyloid beta-peptide (Aß) is the primary cause of the pathogenesis of Alzheimer's disease (AD). And therefore the elimination of Aß is regarded as an important strategy for AD treatment. The discovery of drug candidates using culture neuronal cells against Aß peptide toxicity is believed to be an effective approach to develop drug for the treatment of AD patients. We have previously showed that artemisinin, a FDA-approved anti-malaria drug, has neuroprotective effects recently. In the present study, we aimed to investigate the effects and potential mechanism of artemisinin in protecting neuronal PC12 cells from toxicity of ß amyloid peptide. Our studies revealed that artemisinin, in clinical relevant concentration, protected and rescued PC12 cells from Aß25-35-induced cell death. Further study showed that artemisinin significantly ameliorated cell death due to Aß25-35 insult by restoring abnormal changes in nuclear morphology, lactate dehydrogenase, intracellular ROS, mitochondrial membrane potential and activity of apoptotic caspase. Western blotting analysis demonstrated that artemisinin activated extracellular regulated kinase ERK1/2 but not Akt survival signaling. Consistent with the role of ERK1/2, preincubation of cells with ERK1/2 pathway inhibitor PD98059 blocked the effect of artemisinin while PI3K inhibitor LY294002 has no effect. Moreover, Aß1-42 also caused cells death of PC12 cells while artemisinin suppressed Aß1-42 cytotoxicity in PC12 cells. Taken together, these results, at the first time, suggest that artemisinin is a potential protectant against ß amyloid insult through activation of the ERK1/2 pathway. Our finding provides a potential application of artemisinin in prevention and treatment of AD.

Multipotent neural crest stem cell-like cells from rat vibrissa dermal papilla induce neuronal differentiation of PC12 cells.

Bone marrow mesenchymal stem cells (BMSCs) transplants have been approved for treating central nervous system (CNS) injuries and diseases; however, their clinical applications are limited. Here, we model the therapeutic potential of dermal papilla cells (DPCs) in vitro. DPCs were isolated from rat vibrissae and characterized by immunocytofluorescence, RT-PCR, and multidifferentiation assays. We examined whether these cells could secrete neurotrophic factors (NTFs) by using cocultures of rat pheochromocytoma cells (PC12) with conditioned medium and ELISA assay. DPCs expressed Sox10, P75, Nestin, Sox9, and differentiated into adipocytes, osteoblasts, smooth muscle cells, and neurons under specific inducing conditions. The DPC-conditioned medium (DPC-CM) induced neuronal differentiation of PC12 cells and promoted neurite outgrowth. Results of ELISA assay showed that compared to BMSCs, DPCs secreted more brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). Moreover, we observed that, compared with the total DPC population, sphere-forming DPCs expressed higher levels of Nestin and P75 and secreted greater amounts of GDNF. The DPCs from craniofacial hair follicle papilla may be a new and promising source for treating CNS injuries and diseases.

Cloaking radiation of moving electron beam and relativistic energy loss spectra.

The interaction of ideal and nonideal metamaterial cylindrical cloaks with an electron beam has been studied. The exact solution for energy loss suffered by a fast electron moving inside or outside a cylindrical cloak has been established within a fully relativistic approach. The effect of various imperfect parameters on the efficiency of the cloak has been discussed. It is shown that radiation can be shielded very well by such cloaks when an electron moves either inside or outside of them. The efficiency of nonideal cloaks and the effect of various nonideal parameters on cloak invisibility can be exhibited in the spectra of electron energy loss and radiation emission. This means that the property of a cylindrical cloak can be explored by means of scanning transmission electron microscopy.