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1.
Int J Mol Sci ; 20(21)2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31671764

RESUMO

Inflammation is a key mediator in the progression of atherosclerosis (AS). Benzoinum, a resin secreted from the bark of Styrax tonkinensis, has been widely used as a form of traditional Chinese medicine in clinical settings to enhance cardiovascular function, but the active components of the resin responsible for those pharmaceutical effects remain unclear. To better clarify these components, a new phenylpropane derivative termed stybenpropol A was isolated from benzoinum and characterized via comprehensive spectra a nalysis. We further assessed how this phenylpropane derivative affected treatment of human umbilical vein endothelial cells (HUVECs) with tumor necrosis factor-α (TNF-α). Our results revealed that stybenpropol A reduced soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-8 (IL-8), and interleukin-1ß (IL-1ß) expression by ELISA, inhibited apoptosis, and accelerated nitric oxide (NO) release in TNF-α-treated HUVECs. We further found that stybenpropol A decreased VCAM-1, ICAM-1, Bax, and caspase-9 protein levels, and increased the protein levels of Bcl-2, IKK-ß, and IκB-α. This study identified a new, natural phenylpropane derivative of benzoinum, and is the first to reveal its cytoprotective effects in the context of TNF-α-treated HUVECs via regulation of the NF-κB and caspase-9 signaling pathways.

2.
Cancer Immunol Res ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666238

RESUMO

Cancer vaccines can amplify existing antitumor responses or prime naïve T cells to elicit effector T-cell functions in patients through immunization. Antigen-specific CD8+ T cells are crucial for the rejection of established tumors. We constructed XCL1-GPC3 fusion molecules as a liver cancer vaccine by linking the XCL1 chemokine to glypican-3 (GPC3), which is overexpressed in hepatocellular carcinoma (HCC). Cells expressing XCL1-GPC3 chemoattracted murine XCR1+CD8α+DCs and human XCR1+CD141+DCs in vitro and promoted their IL-12 production. After subcutaneous mXcl1-GPC3 plasmid injection, mXCL1-GPC3 was mainly detected in CD8α+DCs of mouse draining lymph nodes. XCL1-GPC3-targeted DCs enhanced antigen-specific CD8+ T cell-proliferation and induced the de novo generation of GPC3-specific CD8+ T cells, which abolished GPC3-expressing tumor cells in mouse and human systems. We immunized a murine autochthonous liver cancer model, with a hepatitis B background, with the mXcl1-GPC3 plasmid starting six weeks, when malignant hepatocyte clusters formed, or 14 weeks, when liver tumor nodules developed, after diethylnitrosamine administration. mXcl1-GPC3 immunized mice displayed significantly inhibited tumor formation and growth compared to GPC3-immunized mice. After mXcl1-GPC3 immunization, mouse livers showed elevated production of IFNγ, granzyme B, IL-18, CCL5, CXCL19, Xcl1, and increased infiltration of GPC3-specific CD8+ T cells, activated NK cells and NKT cells. The antitumor effects of these immune cells were further enhanced by the administration of anti-PD1. Anti-HCC effects induced by hXCL1-GPC3 were confirmed in HCC-PDX model from three patients. Thus, XCL1-GPC3 might be a promising cancer vaccine to compensate for the deficiency of the checkpoint blockades in HCC immunotherapy.

3.
J Chromatogr A ; : 460652, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31679710

RESUMO

Haloacetic acids (HAAs) are the second largest class of disinfection by-products (DBPs) by weight in water and are more cytotoxic and genotoxic to mammalian cells than trihalomethanes, the first largest class of DBPs. Gas chromatography (GC) is the most widely used technique for determining HAAs. Due to their polar nature, derivatization prior to GC analysis is required. Typically, derivatization is undertaken with acidic methanol, which converts HAAs to the corresponding methyl ester (haloacetic acid methyl esters, abbreviated as HAAMEs), and HAAs are quantified by measuring HAAMEs. In this study, the interference from two other groups of DBPs, the haloacetonitriles (HANs) and haloacetamides (HAMs), on the determination of HAAs was investigated. HANs and HAMs at a range of concentrations (0, 20, 40, 60, 80, and 100 µg/L) were subjected to the same derivatization and analytical procedures as HAAs. The stability of HANs and HAMs under strongly acidic conditions was assessed and the operative mechanism of interference was investigated. The results showed that HAMs significantly interfered with the determination of the corresponding HAAs and the transformation rates of HAMs (representing the extent of HAMs transforming to corresponding HAAMEs) ranged from 6.5 to 45.7%, while the impact of HANs can be neglected. The stability of HANs and HAMs under strongly acidic conditions indicated that hydrolysis was not the cause of the interference. Instead, it was proposed that HAMs react with methyl alcohol, to generate the same corresponding HAAMEs that was generated when HAAs reacted with methyl alcohol. A method for revising HAA concentrations in the presence of HAMs is suggested.

4.
Comp Biochem Physiol B Biochem Mol Biol ; 240: 110370, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31669373

RESUMO

Geckos possess strong adhesion ability, even can climb on smooth surface. Previous studies have shown that the setae of geckos play a crucial role in their ability to climb on vertical walls. But the biological molecular mechanism of their adhesion ability remains unclear. In the present study, the expression patterns of corneous beta proteins (CBPs) genes related to claws, scales, and feathers development (named as ge-gprp-9, ge-gprp-10, ge-gprp-11, ge-gprp-12, ge-gprp-13, ge-gprp-14, ge-gprp-15, and ge-gprp-16 respectively) in the developing pad lamellae of different embryonic stages (stage 34, stage 36, stage 39, and stage 42) of the Japanese gecko Gekko japonicus were detected using fluorescence quantitative PCR approach. The results showed that there were significant up-regulated expression of CBPs mRNA at embryonic stage 39 with the embryonic continuous maturation and the highest expression level was detected at embryonic stage 39 or stage 42. Moreover, the expression levels of four CBPs genes ge-gprp-9, ge-gprp-10, ge-gprp-11, and ge-gprp-12 in the embryonic and adult development of gecko were detected by fluorescence in situ hybridization technique. The results from in situ hybridization detection revealed that the positive signals of these CBPs genes expression were the same in the developing pad lamellae of G. japonicus. The positive signals of eight CBPs genes were mainly found in the setae tissue, oberhautchen, and ß layer, which suggests these CBPs genes are involved in the growth of setae.

5.
Water Res ; 167: 115096, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31577966

RESUMO

The effects of UV/H2O2 pre-oxidation or disinfection methods on the formation of partial disinfection by-products (DBPs) have been studied previously. This study assessed the effect of UV/H2O2 pre-oxidation combined with optimisation of the disinfection method on the formation of six classes of CX3R-type DBPs, including trihalomethanes (THMs), haloacetic acids (HAAs), haloacetaldehydes (HALs), haloacetonitriles (HANs), halonitromethanes (HNMs), and haloacetamides (HAMs). Experimental results showed that a simulated distribution system (SDS) in-situ chloramination or pre-chlorination followed by chloramination effectively decreased total CX3R-type DBP formation by 51.1-63.5% compared to SDS chlorination, but little reduction in DBP-associated toxicity was observed. The dominant contributors to the calculated toxicity were HANs and HALs. UV/H2O2 pre-oxidation was able to destroy the aromatic and dissolved organic nitrogen components of natural organic matter. As a consequence, THM, HAA, and HAL formations increased by 49.5-55.0%, 47.8-61.9%, and 42.0-67.1%, respectively, whereas HAN, HNM, and HAM formations significantly decreased by 52.1-83.6%, 42.9-87.3%, and 74.1-100.0%. UV/H2O2 pre-oxidation increased total CX3R-type DBP formation, during SDS chlorination, whereas SDS in-situ chloramination or pre-chlorination followed by chloramination of UV/H2O2-treated water produced lower total CX3R-type DBPs than water without UV/H2O2 pre-oxidation. Nevertheless, the DBP-associated toxicity of water with UV/H2O2 pre-oxidation was substantially lower than the toxicity for water without UV/H2O2 pre-oxidation, decreased by 24.1-82.7%. HALs followed by HANs contribute to major toxic potencies in UV/H2O2 treated water. The best DBP concentration and DBP-associated toxicity abatement results were achieved for water treated by UV/H2O2 coupled with in-situ chloramination treatment.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31614454

RESUMO

Poultry farmers face a dual risk when mutant avian influenza (AI) virus exhibits zoonotic characteristics. A/H5N1 and A/H7N9 are two principal strains of the AI virus that have captured public attention in recent years, as they have both been reported and can infect poultry and humans, respectively. Previous studies have focused either on poultry farmers' risk perception and biosecurity preventive behaviors (BPBs) against A/H5N1 infection with poultry, or on their risk perception and personal protective behaviors (PPBs) against human infection with A/H7N9, even though these two strains often appear simultaneously. To bridge this research gap, a survey (N = 426) was conducted in the Chinese provinces of Jiangsu and Anhui to assess risk perception and coping behaviors adopted by poultry farmers facing the dual risk of these two viral strains. Paired sample t-tests revealed that farmers' perceived risk of poultry infection with A/H5N1 was significantly higher than their perceived risk of human infection with A/H7N9, and that their reported frequency of BPBs against A/H5N1 was significantly higher than the frequency of PPBs against A/H7N9. Moreover, farmers were less familiar with AI infection in human beings compared to that in poultry, but they felt a higher sense of control regarding human AI infection. Multivariate regression analyses showed that farm size and perceived risks of both human and poultry infection with AI were positively associated with BPBs and PPBs. The findings of this research suggest that a campaign to spread knowledge about human AI infection among poultry farmers is needed, and that a policy incentive to encourage large-scale poultry farming could be effective in improving implementation of BPBs and PPBs.

7.
Nat Biotechnol ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31570897

RESUMO

The near-infrared-IIb (NIR-IIb) (1,500-1,700 nm) window is ideal for deep-tissue optical imaging in mammals, but lacks bright and biocompatible probes. Here, we developed biocompatible cubic-phase (α-phase) erbium-based rare-earth nanoparticles (ErNPs) exhibiting bright downconversion luminescence at ~1,600 nm for dynamic imaging of cancer immunotherapy in mice. We used ErNPs functionalized with cross-linked hydrophilic polymer layers attached to anti-PD-L1 (programmed cell death-1 ligand-1) antibody for molecular imaging of PD-L1 in a mouse model of colon cancer and achieved tumor-to-normal tissue signal ratios of ~40. The long luminescence lifetime of ErNPs (~4.6 ms) enabled simultaneous imaging of ErNPs and lead sulfide quantum dots emitting in the same ~1,600 nm window. In vivo NIR-IIb molecular imaging of PD-L1 and CD8 revealed cytotoxic T lymphocytes in the tumor microenvironment in response to immunotherapy, and altered CD8 signals in tumor and spleen due to immune activation. The cross-linked functionalization layer facilitated 90% ErNP excretion within 2 weeks without detectable toxicity in mice.

8.
Sci Total Environ ; 697: 134126, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31491630

RESUMO

Heavy metals in agricultural soil receive much attention because they are easily absorbed by crop into the ecosystem. Managing the discharge of heavy metals from the source is an effective way to prevent and control heavy metals pollution. Grouped principal component analysis (GPCA) and Positive Matrix Factorization (PMF) receptor models were utilized in this study to conduct source apportionment, and the former was optimal because of the accuracy of predicting. Based on the source contribution by GPCA/APCS, heavy metals were evaluated by fuzzy synthetic evaluation model and health risk assessment model. The results of source apportionment showed that heavy metals in Zhangye agricultural soil were mainly affected by steel industry, traffic, agrochemicals, manures, mining activities, leather industry and metal processing industry source. Fuzzy synthetic evaluation showed that the pollution levels of Chromium (Cr) derived by leather industry and metal processing industry and Nickel (Ni) derived by steel industry and traffic source were higher. Health risk assessment revealed that the non-carcinogenic and carcinogenic risks of Cr derived by leather industry and metal processing industry and Lead (Pb) derived by steel industry and traffic source were higher.

9.
PLoS One ; 14(9): e0221111, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31483787

RESUMO

Regenerative medicine using umbilical cord blood (UCB) cells shows promise for the treatment of cerebral palsy. Although the efficacy of this therapy has been seen in the clinic, the mechanisms by which UCB cells interact and aid in the improvement of symptoms are not clear. We explored the chemokine expression profile in damaged brain tissue in the neonatal mouse ischemia-reperfusion (IR) brain injury model that was infused with human UCB (hUCB) cells. IR brain injury was induced in 9-day-old NOD/SCID mice. hUCB cells were administered 3 weeks post brain injury. Chemokine expression profiles in the brain extract were determined at various time points. Inflammatory chemokines such as CCL1, CCL17, and CXCL12 were transiently upregulated by 24 hours post brain injury. Upregulation of other chemokines, including CCL5, CCL9, and CXCL1 were prolonged up to 3 weeks post brain injury, but most chemokines dissipated over time. There were marked increases in levels of CCL2, CCL12, CCL20, and CX3CL1 in response to hUCB cell treatment, which might be related to the new recruitment and differentiation of neural stem cells, leading to the induction of tissue regeneration. We propose that the chemokine expression profile in the brain shifted from responding to tissue damage to inducing tissue regeneration. hUCB cell administration further enhanced the production of chemokines, and chemokine networks may play an active role in tissue regeneration in neonatal hypoxic-ischemic brain injury.

10.
Nanoscale ; 11(36): 16928-16934, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31490526

RESUMO

Perovskite oxides with luminescent ions hold great promise in optoelectronic devices because of their outstanding thermal stabilities and electro-optic performance. As one typical perovskite upconversion (UC) host material, lead-free potassium sodium niobate ((K, Na)NbO3/(KxNa1-x)NbO3 or KNN) has attracted much attention in recent years. In the present work, a novel routine was developed to tune the upconversion photoluminescence (UC PL) performance by controlling the oxygen vacancy concentration in the KNN matrix, based on the 0.1% Er3+-doped KNN (Er-KNN) single crystals grown for the first time. UC PL properties, conductivity and defect chemistry of the single crystals were systematically investigated. The UC PL intensity of the as-grown Er-KNN material could be enhanced by 20 times after oxygen atmosphere annealing at 800 °C and fully quenched after vacuum annealing. What's more, by annealing under an oxygen atmosphere and vacuum, the conductivity of the Er-KNN sample was successfully tuned for more than 8 orders of magnitude. The super-wide range tunability of UC PL performance and conductivity could be explained by oxygen vacancies which gave rise to Nb5+-Nb4+ valence alternation. Because of the modulated photoluminescence properties and conductivity, our grown Er-KNN single crystals have great potential for use in multifunctional devices.

11.
Oncogene ; 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477839

RESUMO

As an inhibitor of heat shock proteins (HSPs), KNK437 has been reported to play an anti-tumor role in several cancers. But its therapeutic effect and mechanisms in colorectal cancer (CRC) remain unclear. Here, KNK437 sharply inhibited the level of DnaJ heat shock protein family (Hsp40) member A1 (DNAJA1), followed by DNAJB1, but had little effect on the levels of HSP27, HSP105, HSP90, and HSP70 in CRC cells. DNAJA1 promoted CRC cell proliferation in vitro and tumor growth and metastasis in vivo. Mechanistically, DNAJA1 was activated by E2F transcription factor 1 (E2F1) and then promoted cell cycle by stabilizing cell division cycle protein 45 (CDC45), which could be reversed by KNK437. DNAJA1 was significantly upregulated in CRC tissues and positively correlated with serosa invasion, lymph node metastasis. High level of DNAJA1 predicted poor prognosis for CRC patients. Its expression was highly linked with E2F1 and CDC45 in CRC tissues. More importantly, KNK437 significantly suppressed the growth of DNAJA1 expressing tumor in vivo. The combined treatment of KNK437 with 5-FU/L-OHP chemotherapy reduced liver metastasis of CRC. These data reveal a novel mechanism of KNK437 in anti-tumor therapy of CRC and provides a newly therapeutic strategy with potential translation to the CRC patients.

12.
Inflammation ; 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31494794

RESUMO

Liver ischemia-reperfusion injury (IRI) can severely compromise the prognosis of patients receiving liver surgery. While inflammation contributes to the damage resulting from IRI, only a limited number of inflammation biomarkers have been identified as being associated with the different stages of hepatic IRI. As an approach to identify some of these inflammatory cytokines and the molecular mechanisms involved within different stages of hepatic IRI, we used an advanced antibody array assay to detect multiple proteins. With this technology, we observed specific differences in the content of inflammatory cytokines between ischemic and sham controls, as well as a function of the different reperfusion stages in a hepatic IRI mouse model. For example, while liver tissue content of IL-12p40/p70 was significantly increased in the ischemic stage, it was significantly decreased in the reperfusion stage as compared with that of the sham group. For other inflammatory cytokines, no changes were obtained between the ischemic and reperfusion stages with levels of IL-17, Eotaxin-2, Eotaxin, and sTNF RII all being consistently increased, while those of TIMP-1, TIMP-2, BLC, and MCSF consistently decreased as compared with that of the sham group at all reperfusion stages examined. Results from protein function annotation Gene Ontology and the KEGG pathway revealed that inflammatory cytokines are enriched in a network associated with activation of inflammatory response signaling pathways such as TLR, TNF, and IL-17 when comparing responses of the IR versus sham groups. The identification of cytokines along with their roles at specific stages of IRI may reveal important new biological markers for the diagnosis and prognosis of hepatic IRI.

13.
Mol Med Rep ; 20(4): 3883-3892, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485616

RESUMO

Autophagy is an essential metabolic pathway mediated by lysosomal degradation, which is involved in scavenging and recycling senescent or damaged organelles and biological macromolecules in eukaryotic cells. The present study explored the association between the autophagic activity and chemotherapy resistance of leukaemia cells, and the possibility of using autophagy inhibitors to combat leukemic drug resistance. It was found that the levels of basic autophagy in multidrug­resistant leukaemia cells (K562/ADM) were significantly higher compared with sensitive cells (K562), and that Adriamycin (ADM) was capable of inducing autophagic activity in K562 and K562/ADM cells. K562 and K562/ADM cells were treated with a series of hydroxychloroquine (HCQ) concentrations to inhibit cellular autophagy and detect cell sensitivity to ADM. The results demonstrated that the sensitivity of K562 cells to ADM was mildly enhanced by HCQ, and that the sensitivity of K562/ADM cells to ADM was markedly strengthened by HCQ. In addition, more typical morphological changes associated with apoptosis emerged, and the ratio of Bax/Bcl­2 and activity of caspase­3 were markedly increased in K562/ADM cells treated with HCQ. Notably, the expression of mdr1 mRNA and P­glycoprotein (P­gp) in drug­resistant K562/ADM cells was upregulated along with increasing autophagic activity induced by ADM. Furthermore, HCQ significantly reduced the increase in P­gp expression by inhibiting autophagic activity. Collectively, these findings indicated that the inhibition of autophagy significantly promoted the sensitivity of K562/ADM cells to ADM by facilitating apoptosis. Furthermore, inhibition of autophagy attenuated the expression of P­gp; therefore, P­gp may be involved in autophagic regulation in drug­resistant cells.

14.
Bioresour Technol ; 292: 121938, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31398541

RESUMO

This study focused on the feasibility of using different concentrations of tofu wastewater (TW) as alternative media for Tribonema minus cultures to produce valuable biorefinery feedstock. T. minus grew mixotrophically in 100% TW with larger carbohydrate (30.99% of dry weight (DW)), protein (15.56% of DW) and chrysolaminarin (6.93% of DW) accumulations than that of in mBG-11 medium. The highest biomass concentration, 7.77 g/L, was achieved in 100% TW, and nutrient removal efficiencies of T. minus at this concentration ranged from 60.49% to 93.60%. Although smaller neutral lipid and palmitoleic acid amounts were detected in 100% TW, their productivities reached 133.77 and 67.19 mg/L/d, respectively, due to the largest biomass yield contribution, which were comparable to those in mBG-11 medium. These findings demonstrated that TW is a promising alternative medium, and an integrated TW biotransformation and biomass valorization process is proposed to achieve better economic performance and environmental sustainability.


Assuntos
Microalgas , Alimentos de Soja , Biomassa , Biotransformação , Águas Residuárias
15.
Comput Assist Surg (Abingdon) ; 24(sup2): 94-104, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31411501

RESUMO

Assisted therapy is increasingly used in autism spectrum disorders (ASD) for improving social interaction and communication skills in recent years. A lot of studies have proven that the form of interactive games for therapy has a good effect on children with autism. Thus, our study provided an assisted therapeutic system based on Reinforcement Learning (RL) for children with ASD, which has five interactive subgames. As is well known, it is necessary to establish and maintain compelling interactions in therapeutic process. Therefore, we aim to adjust the interactive content according to the emotions of children with autism. However, due to the atypical and unusually differences in children with autism, most systems are based on off-line training of small samples of individuals and online recognition, so the existing assisted systems are limited in their ability to automatically update system parameters of new mappings. The integration of RL and Convolutional Neural Network (CNN)-Support Vector Regression (SVR) was used to deal with the updating online of prediction model's weights. The normalized emotion labels were evaluated by the therapists. Eleven children with autism as subjects were invited in this experiment and captured facial video images. The experiment lasted for five weeks of intermittent assisted therapy, and the results were evaluated for the system and the therapy effect. Finally, we achieved a general reduction in the root mean square error of the model prediction results and labels. Although there is no significant difference in Social Responsiveness Scale (SRS) scores before and after assisted therapy (p value = 0.60), in individual subjects (Sub. 1, Sub. 2 and Sub.3), the SRS total score is significantly reduced (Average drop of 19 points). These results demonstrate the effectiveness of prediction model based on RL and show the feasibility of assisted therapeutic system in children with autism.

16.
Behav Brain Res ; 374: 112115, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31369775

RESUMO

Exercise has been considered for the treatment of depression, but the mechanism by which exercise improves depression is still unclear. To clarify the mechanism, rats were randomly divided into the control, chronic unpredictable stress (CUS)/standard and CUS/running groups. The rats in the CUS/running group ran for four weeks. In this study, a sucrose preference test (SPT) was used to evaluate the depression-like symptoms in the rats, and western blot, immunohistochemical and stereological analyses were performed to study the expression of synaptic-related proteins in the hippocampus and the changes in excitatory synapses in each sub-region. The results show that sucrose preference in the CUS/standard group was significantly lower than that in the control group, but in the CUS/running group, sucrose preference was higher than that in the CUS/standard group. Surprisingly, there was no difference in the synaptic-related proteins in the hippocampus among groups. The CUS/standard group exhibited fewer spinophilin+ (Sp+) dendritic spines representing excitatory synapses in CA1, CA3 and dentate gyrus (DG) of the hippocampus than the control group, whereas the CUS/running group exhibited significantly more Sp+ dendritic spines in these regions than the CUS/standard group, indicating that excitatory synapses were reduced in depressed rats and that running exercises could reverse this change. We hypothesize that the changes in the number of excitatory synapses better reflect the changes in depressive symptoms than the level of synaptic proteins and that the effect of exercise on excitatory synapses in the sub-regions of the hippocampus may be an important structural indicator of the improvement of depressive symptoms.

17.
Mol Psychiatry ; 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31413370

RESUMO

Opioids, such as morphine, are clinic analgesics which induce euphoria. Morphine exposure modifies the excitability and functional interactions between neurons, while the underlying cellular and molecular mechanisms, especially how morphine assembles heterogeneous interneurons (INs) in prelimbic cortex (PrL) to mediate disinhibition and reward, are not clear. Using approaches of optogenetics, electrophysiology, and cell type-specific RNA-seq, we show that morphine attenuates the inhibitory synaptic transmission from parvalbumin+ (PV)-INs onto pyramidal neurons in PrL via µ-opioid receptor (MOR) in PV-INs. Meanwhile, morphine enhances the inhibitory inputs from somatostatin+ (SST)-INs onto PV-INs, and thus disinhibits pyramidal neurons via δ-opioid receptor (DOR)-dependent Rac1 upregulation in SST-INs. We show that MOR in PV-INs is required for morphine-induced behavioral sensitization, while DOR as well as Rac1 activity in SST-INs is required for morphine-induced conditioned place preference and hyper-locomotion. These results reveal that SST- and PV-INs, functioning in PrL as a disinhibitory architecture, are coordinated by morphine via different opioid receptors to disinhibit pyramidal neurons and enhance reward.

18.
Int J Nanomedicine ; 14: 5125-5133, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371951

RESUMO

Purpose: The frequent usage of various lighting screens has made dry eye syndrome an increasingly serious phenomenon. To relieve this global problem, we have developed a photothermal conversion hydrogel based mini-eye patch. Methods: Gold nanoparticles (GNRs) were synthesized by a seed-mediated method, and then used as the inner cores to grow palladium (Pd) shell by PdCl42-reduction. Then, gelatin was added to prepare GNRs @ Pd hydrogel eye patch by genipin cross-linking. We implanted temperature sensitive ink (complex composed of amino resin and styrene maleic anhydride copolymer) in the eye patch, which could change color at different temperatures. Heating performance of the eye patch was accessed with an infrared temperature profile and the circulating temperature experiment. The safety assessment of the eye patch was conducted by H&E staining of the mouse's eyelid skin and CCK-8 assay. A Keratograph 5M noninvasive ocular surface analyzer was used to assess the impact of eye patches on dry eyes. Results: It was found that GNRs @ Pd hydrogel eye patches could sense various visible light and responded by heating up spontaneously. Results from the CCK-8 assay and H&E staining showed that the eye patch has good safety performance. Measurements of the first noninvasive tear break-up time (NITBUT), the average NITBUT, the tear meniscus height (TMH), combined with red eye analysis, further demonstrated the patch's eye-protective properties. Conclusion: After being pasted to the lacrimal gland, the hydrogel patch converted various light irradiations into heat and stimulated the lacrimal gland to produce more tears to relieve dry eye. The built-in temperature-sensitive ink can play an important role in warning people of their excessive eye usage. Because this recyclable strategy does not interfere with normal eye use, it is thus more environmentally friendly and convenient than ordinary infrared eyewear.


Assuntos
Síndromes do Olho Seco/terapia , Olho/patologia , Hidrogéis/química , Luz , Temperatura Ambiente , Adolescente , Adulto , Animais , Linhagem Celular , Feminino , Ouro/química , Humanos , Masculino , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Camundongos , Coelhos , Ratos Sprague-Dawley , Adulto Jovem
19.
Curr Eye Res ; : 1-8, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31294618

RESUMO

Purpose: Adeno-associated virus vector (AAV) is the most accepted gene delivery vector for retinal gene therapy. Müller cells play an important role in maintaining homeostasis and neuronal structural integrity, stability and it has been found to be involved in many retinopathies. The aim of this study is to identify a rAAV2/6 mutant which has increased tropism for Müller cell of the mouse retina. Materials and Methods: Using amino acid mutagenesis, we created a rAAV2/6 capsid mutant, rAAV2/6-S663L. In vivo imaging and retinal flat mount were employed to analyze the gene expression of rAAV2/6-S663L and wt rAAV2/6 in mouse retinal tissue. Retinal tissue cryosection, immunohistochemistry (IHC), Müller cell-specific promoter-controlled gene expression, and double AAV fluorescent protein co-expression were performed to determine the targeting of rAAV2/6-S663L for mouse retinal Müller cells. Results: In vivo imaging, retinal flat mount and retinal tissue cryosection results showed that rAAV2/6-S663L and wt rAAV2/6 have different specific tropisms in mouse retina and rAAV2/6-S663L is more preferentially targeting Müller cells. Müller cell-specific promoter-controlled gene expression experiments and IHC test confirmed that rAAV2/6-S663L has a higher tendency to infect Müller cells than wt rAAV2/6. Co-infection of the mouse retina with one rAAV2/6-S663L expressing EGFP under the control of GFAP promoter and the other one expressing mCherry under the control of CMV promoter revealed co-expression of the two fluorescent proteins in Müller cells. Conclusions: The results confirmed that rAAV2/6-S663L has a higher tropism for Müller cells than wt rAAV2/6. Our findings could add a new useful tool for retinal disease gene therapy.

20.
BMC Genomics ; 20(1): 574, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31296166

RESUMO

BACKGROUND: Starch biosynthesis in endosperm is a key process influencing grain yield and quality in maize. Although a number of starch biosynthetic genes have been well characterized, the mechanisms by which the expression of these genes is regulated, especially in regard to microRNAs (miRNAs), remain largely unclear. RESULTS: Sequence data for small RNAs, degradome, and transcriptome of maize endosperm at 15 and 25 d after pollination (DAP) from inbred lines Mo17 and Ji419, which exhibit distinct starch content and starch granule structure, revealed the mediation of starch biosynthetic pathways by miRNAs. Transcriptome analysis of these two lines indicated that 33 of 40 starch biosynthetic genes were differentially expressed, of which 12 were up-regulated in Ji419 at 15 DAP, one was up-regulated in Ji419 at 25 DAP, 14 were up-regulated in Ji419 at both 15 and 25 DAP, one was down-regulated in Ji419 at 15 DAP, two were down-regulated in Ji419 at 25 DAP, and three were up-regulated in Ji419 at 15 DAP and down-regulated in Ji419 at 25 DAP, compared with Mo17. Through combined analyses of small RNA and degradome sequences, 22 differentially expressed miRNAs were identified, including 14 known and eight previously unknown miRNAs that could target 35 genes. Furthermore, a complex co-expression regulatory network was constructed, in which 19 miRNAs could modulate starch biosynthesis in endosperm by tuning the expression of 19 target genes. Moreover, the potential operation of four miRNA-mediated pathways involving transcription factors, miR169a-NF-YA1-GBSSI/SSIIIa and miR169o-GATA9-SSIIIa/SBEIIb, was validated via analyses of expression pattern, transient transformation assays, and transactivation assays. CONCLUSION: Our results suggest that miRNAs play a critical role in starch biosynthesis in endosperm, and that miRNA-mediated networks could modulate starch biosynthesis in this tissue. These results have provided important insights into the molecular mechanism of starch biosynthesis in developing maize endosperm.

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