Identification of key genes and signaling pathways associated with dementia with Lewy bodies and Parkinson's disease dementia using bioinformatics.

Objective: Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are collectively known as Lewy body dementia (LBD). Considering the heterogeneous nature of LBD and the different constellations of symptoms with which patients can present, the exact molecular mechanism underlying the differences between these two isoforms is still unknown. Therefore, this study aimed to explore the biomarkers and potential mechanisms that distinguish between PDD and DLB. Methods: The mRNA expression profile dataset of GSE150696 was acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between 12 DLB and 12 PDD were identified from Brodmann area 9 of human postmortem brains using GEO2R. A series of bioinformatics methods were applied to identify the potential signaling pathways involved, and a protein-protein interaction (PPI) network was constructed. Weighted gene co-expression network analysis (WGCNA) was used to further investigate the relationship between gene co-expression and different LBD subtypes. Hub genes that are strongly associated with PDD and DLB were obtained from the intersection of DEGs and selected modules by WGCNA. Results: A total of 1,864 DEGs between PDD and DLB were filtered by the online analysis tool GEO2R. We found that the most significant GO- and KEGG-enriched terms are involved in the establishment of the vesicle localization and pathways of neurodegeneration-multiple diseases. Glycerolipid metabolism and viral myocarditis were enriched in the PDD group. A B-cell receptor signaling pathway and one carbon pool by folate correlated with DLB in the results obtained from the GSEA. We found several clusters of co-expressed genes which we designated by colors in our WGCNA analysis. Furthermore, we identified seven upregulated genes, namely, SNAP25, GRIN2A, GABRG2, GABRA1, GRIA1, SLC17A6, and SYN1, which are significantly correlated with PDD. Conclusion: The seven hub genes and the signaling pathways we identified may be involved in the heterogeneous pathogenesis of PDD and DLB.

CD20-positive subcutaneous panniculitis-like T-cell lymphoma presenting as polycranial neuropathy: A CARE-compliant case report and literature review.

BACKGROUND: Subcutaneous panniculitis-like T-cell lymphoma(SPTCL) is a very rare cytotoxic T-cell skin lymphoma involving subcutaneous tissue, and mainly affects young females. T-cell phenotype is characterized by CD3+, CD8+, and CD4-. SPTCT with polycranial neuropathy has rarely been described. SPTCL is believed to show an indolent clinical course unless patients develop haemophagocytic syndrome or sudden respiratory failure. Its treatment has not been established yet. CASE PRESENTATION: We report a case of intractable SPTCT in a 66-year-old woman with multiple cranial nerve palsies and diabetes. She showed involvement of the bilateral facial nerve, left trigeminal nerve, left auditory nerve, and right oculomotor nerve. The single inconspicuous skin lesion in the trunk presented with an erythematous nodule with a diameter of <5 cm and a slightly pink infiltrated plaque. Electromyography revealed bilateral damage to the facial nerve. Differential immunohistochemical characteristics were observed. Immunohistochemistry demonstrated diffuse CD20 positivity. Cerebral spinal fluid analysis revealed elevated protein levels of 0.92 (0.15-0.45) g/L. Her condition regressed severely over time. She was treated with chemotherapy but died 10 months later, the probable cause of death was lung involvement. CONCLUSION: The patient's involvement with the central nervous system may be associated with positivity for CD20. Molecular biomarkers may act as therapeutic targets for SPTCL.

Different molecular weight hyaluronic acid alleviates inflammation response in DNFB-induced mice atopic dermatitis and LPS-induced RAW 264.7 cells.

AIMS: Atopic dermatitis (AD) is an inflammatory chronic disease which severely interferes the life of patients. Hence, there is a great need for new therapies. Hyaluronic acid (HA) is an effective potential inflammation modifier; however, there is limited information about their implementation in inflammation therapies. This study aimed to evaluate the anti-inflammatory activities of HA and the influence of its molecular weight. MAIN METHODS: Male C57BL/6 J mice were stimulated by 2,4-dinitrofluorobenzene to induce AD-like symptoms and immune response. The skin lesions and histopathological change, as well as levels of inflammatory factors were evaluated. RAW 264.7 mouse macrophages were treated with lipopolysaccharides (LPS) to induce inflammation. NO, IL-6, and TNF-α levels were detected through ELISA kits. KEY FINDINGS: DNFB challenge induced mice AD symptoms including epidermal thickening, mast cell infiltration, Th2/Th1 immune response, skin lesions IL-4 and IFN-γ, and serum IgE elevation. HA treatment ameliorated such symptoms through the inhibition of PI3K/Akt signaling pathway. LPS induction stimulated the secretion of NO, IL-6, and TNF-α in RAW 264.7 cells, while HA pre-treatment reduced the concentration of the cytokines in cell supernatants. SIGNIFICANCE: These findings give clear insight into the interaction between HA and inflammatory response, which can help guiding the utilization of HA in the AD therapies.

An innovative role for luteolin as a natural quorum sensing inhibitor in Pseudomonas aeruginosa.

AIMS: The emergence of antibiotic tolerance was a tricky problem in the treatment of chronic Pseudomonas aeruginosa-infected cystic fibrosis and burn victims. The quorum sensing (QS) inhibitor may serve as a new tactic for the bacterial resistance by inhibiting the biofilm formation and the production of virulence factors. This study explored the potential of luteolin as a QS inhibitor against P. aeruginosa and the molecular mechanism involved. MAIN METHODS: Crystal violet staining, CLSM observation, and SEM analysis were carried out to assess the effect of luteolin on biofilm formation. The motility assays and the production of virulence factors were determined to evaluate the QS-inhibitory activity of luteolin. Acyl-homoserine lactone, RT-PCR, and molecular docking assays were conducted to explain its anti-QS mechanisms. KEY FINDINGS: The biofilm formation, the production of virulence factors, and the motility of P. aeruginosa could be efficiently inhibited by luteolin. Luteolin could also attenuate the accumulation of the QS-signaling molecules N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL) and N-butanoyl-L-homoserine lactone (BHL) (P < 0.01) and downregulate the transcription levels of QS genes (lasR, lasI, rhlR, and rhlI) (P < 0.01). Molecular docking analysis indicated that luteolin had a greater docking affinity with LasR regulator protein compared with OdDHL. SIGNIFICANCE: This study is important as it reports the molecular mechanisms involved in the anti-biofilm formation activity of luteolin against P. aeruginosa. This study also indicated that luteolin could be helpful when used for the treatment of clinical drug-resistant infections of P. aeruginosa.

Controllable Optical Bistability and Four-Wave Mixing in a Photonic-Molecule Optomechanics.

We theoretically investigate the nonlinear optical phenomena including optical bistability and four-wave mixing (FWM) process in a composite photonic-molecule cavity optomechanical system. The photonic-molecule cavity consisted of two whispering gallery mode (WGM) microcavities, where one WGM cavity is an optomechanical cavity with high-cavity dissipation κ and the other WGM cavity is an auxiliary ordinary optical cavity with high-quality factor (Q). Controlling the parameters of the system, such as the coupling strength J between the two cavities, the decay rate ratio δ of the two cavities, and the pump power P, the optical bistability can be controlled. Furthermore, the FWM process which presents the normal mode-splitting is also investigated in the FWM spectrum under different parameter regimes. Our study may provide a further insight of nonlinear phenomena in the composite photonic-molecule optomechanic systems.

Berberine promotes nerve regeneration through IGFR­mediated JNK­AKT signal pathway.

Berberine presents therapeutic ability for various central nervous system disorders, including Alzheimer's disease and cerebral ischemia. The present study investigated the role of berberine in nerve regeneration and analyzed the potential mechanism mediated by berberine in hippocampal pyramidal neurons. Reverse transcription­quantitative poylmerase chain reaction, western blot, TUNEL assay and immunofluorescence were used to analyze the therapeutic effects of berberine on nerve regeneration. Berberine treatment increased growth and viability of hippocampal pyramidal neurons. Berberine treatment inhibited apoptosis of hippocampal pyramidal neurons and increased apoptosis regulator Bcl­2 and Bcl­w expression. Neuroinflammation of tumor necrosis factor α, interleukin (IL)1ß, IL6 levels and autophagy­related proteins microtubule­associated proteins 1A/1B light chain 3B, autophagy related 16 like 1 and autophagy related 7 were downregulated by berberine treatment in hippocampal pyramidal neurons. Notably, study has found that berberine increased insulin-like growth factor receptor (IGFR) and decreased c­Jun N­terminal kinase (JNK) and protein kinase B (AKT) expression in hippocampal pyramidal neurons. IGFR antagonist abolished berberine­increased growth of hippocampal pyramidal neurons. In conclusion, these results indicate that berberine can promote nerve regeneration through IGFR­mediated JNK­AKT signal pathway.

[CdSe/ZnSe quantum dots via a two-phase solution system process solubilization and spectroscopic characterization].

In the present work, the CdSe/ZnSe core/shell quantum dots (QDs) were successfully transferred from organic phase to water phase via a two-phase solution system process by surface coating with amphiphilic polymer. Surface coating with amphiphilic polymer is an effective method, which can form stable soluble QDs in water. However, the conventional polymer coating method is performed in homogeneous phase, and it easily induces the aggregation of the QDs attributing to the long chain of enlace of the polymer. It is thus necessary and meaningful to develop surface coating technique for getting monodisperse coating QDs with amphiphilic polymer. In comparison with previously reported coating method, the authors' experiment process is performed in two-phase solution system, and can effectively reduces the possibility of aggregation of the QDs. The resulting hydrophilic CdSe/ZnSe core/shell QDs have long-term stability in water, and high quantum yield. The polymer coating process was affirmed by various characterizations. Fourier transform infrared spectra suggest that the octylamine modified polymer was successfully coated on the surface of the CdSe/ZnSe QDs. The transmission electron microscopy suggests that the size and shape of the QDs showed no obvious change before and after the coating process. Dynamic light scattering results indicate that the hydrophilic QDs exhibit narrow hydrodynamic size distribution with the mean hydrodynamic diameters of about 19.7 nm. The luminescence properties of the QDs were investigated with photoluminescence spectra and ultraviolet-visible absorption spectra. This polymer coating process has less effect on luminescence capability. The quantum yield decreased from 43% to 30%. Further, in order to confirm that the polymer capped QDs is biocompatible, the QDs were used for specific detection of the human IgG with fluorescence mapping. The specific molecular recognition capacity of goat anti-human IgG-modified QDs confirms that the polymer coated QDs have compatible functional chemical groups for bioconjugation and are suitable for biological applications.

[Preparation, characterization and specific biological labeling of silica coated upconversion fluorescent nanocrystals].

The authors synthesized a kind of upconversion nanocrystals NaYF4:Yb3+, Er3+ via the hydrothermal assisted homogeneous precipitation method, and then the nanocrystal was coated with silica. The SEM image demonstrated that the as-prepared samples were uniform in size distribution with ca. 25 nm before and ca. 250 nm after silica coating, respectively. The upconversion spectra and photoluminescence lifetime measurement showed that the silica shell had hardly effect on the properties of fluorescence of the NaYF4:Yb3+, Er3+ nanocrystals. At the same time, the naked eye-visible green upconversion fluorescence pattern was acquired from the as-prepared upconversion nanoparticles in the PBS buffer (2 wt%) excited by 980 nm laser at room temperature. These water-soluble nanoparticles were linked to the antibodies using the coupling reagents glutaraldehyde. The circular dichroism (CD) spectra of antibody and upconversion nanoparticles-antibody conjugates were very similar to each other, indicating that the secondary structure of antibody remained largely intact after the conjugation. Finally, antigen-antibody recognition reaction was performed on the surface of a silicon slide. The immunofluorescence in vitro indicated that the upconversion nanoparticles-antibody bioconjugates had excellent species-specific detection ability with hardly non-specific binding. Based on the present results, it is anticipated that the silica-coated upconversion nanoparticles are suitable for use as biolabeling materials.

[Effect of hole transporting materials on photoluminescence of CdSe core/shell quantum dots].

Photoluminescence quenching of colloidal CdSe core/shell quantum dots in the presence of hole transporting materials was studied by means of steady state and time resolved photoluminescence spectroscopy. With increasing hole transporting materials concentration in the CdSe core/shell quantum dot solution, the photoluminescence intensity and lifetime decreased gradually. The photoluminescence quenching of CdSe/ZnSe quantum dots with adding hole transporting material N,N'-bis(1-naphthyl)-N, N'-diphenyl-1,1 '-biphenyl-4, 4'-diamine (NPB) is more efficient than N,N'-diphenyl-N, N'-bis(3-methylphenyl)-1,1'-biphenyl-4,4'-diamine (TPD). And compared with CdSe core/shell quantum dots with ZnSe shell, the ZnS shell is an effective one on the surface of CdSe quantum dots for reducing photoluminescence quenching efficiency when interacting with hole transporting material TPD. Based on the analysis, there are two pathways in the photoluminescence quenching process: static quenching and dynamic quenching. The static quenching results from the decrease in the number of the emitting centers, and the dynamic quenching is caused by the hole transfer from quantum dots to hole transporting materials molecules. The efficiency of the photoluminescence quenching in CdSe core/shell quantum dots is strongly dependent on the structure of the shells and the HOMO levels of the hole transporting materials. The results are important for understanding the nature of quantum dots surface and the interaction of quantum dots and hole transporting materials.

Odontogenic potential of mesenchymal cells from hair follicle dermal papilla.

Dental pulp stem cells from teeth can be used for tooth regeneration. Although nondental stem cells derived from bone marrow can differentiate into odontoblast-like cells when recombined with embryonic oral epithelium, these cells can lose their ability to differentiate after an extended number of cell culture passages. There has been limited research to identify stem cells from other tissue sources to regenerate teeth. As another candidate source for mesenchymal stem cells, hair follicle has obtained much more attention recently because of its easy accessibility. In this study, cultured vibrissae follicle dermal papilla mesenchymal cells (FDPMCs) from adult C57BL/6 GFP mice can differentiate into adipocytes and osteoblasts in vitro. Moreover, in the inductive microenvironment generated by apical bud and dental mesenchyme from 7-day-old C57 mice, FDPMCs in vitro demonstrated odontogenic potential, as indicated by the morphological transformation, cell-cycle change and expression of tooth-specific markers. Under the same microenvironment, FDPMCs were incubated in vivo for 3 weeks. Coexpression of GFP and DSP proteins in the odontoblast layer was detected in the recovered implants, suggesting that GFP(+) FDPMCs can function as odontoblasts in vivo. Together, our data indicate for the first time that whisker FDPMCs from adult mice can differentiate to odontoblast-like cells.

[Study of applying fluorescence spectrum imaging to quantitative assay of proteins in bio-chip].

In the present work, the amount and the activity of the goat anti-human IgG, to bind the human IgG labelled with fluorescein isothiocyanate (FITC), immobilized on silicon surfaces modified with APTES and APTES-Glu, respectively, were studied using the fluorescence spectrum imaging (FSI), the results of which were compared with that of ellipsometry. It is shown that the amount of the human IgG labeled with FITC on APTES-Glu measured using FSI is 2.8 times higher than that on APTES, which is nearly coincident with the 2.2 times obtained using ellipsometry, showing that the activity of the goat anti-human IgG on APTES-Glu is higher than that on APTES. It is reasoned that the FSI is used in the fluorescence immunoassay the for measurement of quasi-quantification or quantification.

[Surface enhanced Raman spectroscopic study on the gold-labeled protein self-assembled surface].

The human IgG molecules were labeled with 13 nm gold nanoparticles and the complex of the gold-labeled human IgG molecules was immobilized on a silicon surface modified by 3-aminopropyltriethoxysilane and glutaraldehyde. The method increases not only the tightness but also the surface coverage for immobilization of the complex and retains protein configuration well on the silicon surface. The self-assembled complex surface was observed by AFM. The complex aggregated on the silicon surface and the "island" monolayer of the complex was obtained. Meanwhile the SERS spectrum of the complex self-assembled "island" monolayer on silicon surface was presented. In the present paper, the gold labeled human IgG molecules were self-assembled on the silicon surface, SERS spectra of protein were obtained and as SERS active substrates were provided for the study of the protein molecules.

[Feasibility of the programme of focusing on early childhood development in impoverished rural areas in China].

OBJECTIVE: To study the feasibility of the programme "Focusing on early childhood development" in impoverished rural areas in China. METHODS: A questionnaire survey was conducted among 100 mothers, about half with junior middle school education, 18% with grade-school education, and 29% being illiterate, of children aged under two years in 7 villages in Changfeng County, Anhui Province, a native impoverished county, to understand their knowledge and attitudes about child healthcare. Then these mothers were randomly divided into 2 equal groups: experimental group, receiving face-to-face guidance in the practice of early healthcare for children at home with a pamphlet developed by WHO as teaching material; and control group without receiving guidance. Two months later the mothers received the second session of guidance. Six months after the same questionnaire survey was conducted among the 100 mothers to investigate the changes in knowledge and practice and Gesell development test was made to observe the changes in mental development. Two-days' training on the technique of early child healthcare in the form of reading, videotape presenting, and exercise, was given to 29 village doctors. Questionnaire survey was conducted among them before and 1 month after the training to understand the changes of their knowledge and attitudes towards early child healthcare. RESULTS: After the guidance the knowledge and fostering skills in terms of early child healthcare were improved significantly among the mothers of the experimental group in comparison with the mothers of the control group (P < 0.01). After the training most of the village doctors managed put the knowledge they had learned into practice, however, the percentage of those who lacked confidence in the smooth implementation of the programme remained unchanged (38% vs. 41%). Before the experiment the abilities in different fields were not significantly different between the children in these 2 groups. Six months after the implementation of the programme the abilities in fine motion, speech, and interpersonal communication were improved significantly among the children of the experimental group (all P < 0.05). CONCLUSION: Economic, simple, and effective, the programme "Focusing on early childhood development" is suitable for the impoverished rural areas in China.