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1.
Artigo em Inglês | MEDLINE | ID: mdl-39001887

RESUMO

PURPOSE: Negative life events are essential proximal factors that may induce suicidal behavior in adolescents, but the mechanisms connecting this link remain to further explored. The present study aimed to investigate the relationship between negative life events (NLEs) and adolescents' suicidal behavior, and the roles of core self-evaluation, depression and gender playing between them. METHODS: Using the whole-group sampling approach, 5296 Chinese adolescents (51.5% males, Meanage = 12.93) took part in this cross-sectional study in September 2021 and completed a battery of surveys including NLEs, suicidal behavior, CSE (core self-evaluation) and depression. Logistic regression and latent structural equation models were used to test the direct and indirect effects between NLEs and suicide behavior with multi-group path analysis, gender differences in this serial mediating effect were also tested. RESULTS: After controlling for age and gender, NLEs were directly associated with adolescents' suicidal behavior. CSE and depression played significant serial mediating effects in this relationship. Moreover, significant gender differences were obtained in these serial mediating pathways, with stronger effects in girls. CONCLUSION: Integrating the environmental, individual cognitive and emotional factors, our findings would be helpful in understanding the mechanism of these antecedents on adolescents' suicide behavior, which has specific practical significance for preventing and reducing suicidal behavior.

2.
J Neurol Neurosurg Psychiatry ; 94(8): 605-613, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37225405

RESUMO

To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. METHODS: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). RESULTS: Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). CONCLUSIONS: Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.


Assuntos
Encefalite , Infecções por Vírus Epstein-Barr , Masculino , Humanos , Feminino , Autoimunidade , Estudos Retrospectivos , Herpesvirus Humano 4 , Autoanticorpos , Imunoglobulina G
3.
EMBO Rep ; 22(12): e52124, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-34647680

RESUMO

This study explores the role of the long noncoding RNA (LncRNA) CRNDE in cisplatin (CDDP) resistance of gastric cancer (GC) cells. Here, we show that LncRNA CRNDE is upregulated in carcinoma tissues and tumor-associated macrophages (TAMs) of GC patients. In vitro experiments show that CRNDE is enriched in M2-polarized macrophage-derived exosomes (M2-exo) and is transferred from M2 macrophages to GC cells via exosomes. Silencing CRNDE in M2-exo reverses the promotional effect of M2-exo on cell proliferation in CDDP-treated GC cells and homograft tumor growth in CDDP-treated nude mice. Mechanistically, CRNDE facilitates neural precursor cell expressed developmentally downregulated protein 4-1 (NEDD4-1)-mediated phosphatase and tensin homolog (PTEN) ubiquitination. Silencing CRNDE in M2-exo enhances the CDDP sensitivity of GC cells treated with M2-exo, which is reduced by PTEN knockdown. Collectively, these data reveal a vital role for CRNDE in CDDP resistance of GC cells and suggest that the upregulation of CRNDE in GC cells may be attributed to the transfer of TAM-derived exosomes.


Assuntos
Exossomos , MicroRNAs , RNA Longo não Codificante , Neoplasias Gástricas , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Cisplatino/metabolismo , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Exossomos/genética , Exossomos/metabolismo , Exossomos/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Nus , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo
4.
Phys Chem Chem Phys ; 25(15): 10417-10426, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-36987914

RESUMO

Solubility plays a critical role in many aspects of research (drugs to materials). Solubility parameters are very useful for selecting appropriate solvents/non-solvents for various applications. In the present study, Hansen solubility parameters are predicted using machine learning. More than 40 machine models are tried in the search for the best model. Molecular descriptors and fingerprints are used as inputs to get a comparative view. Machine learning models trained using molecular descriptors have shown higher prediction ability than the model trained using molecular fingerprints. Machine learning models trained using molecular descriptors have shown their potential to be easy and fast models compared to the density functional theory (DFT)/thermodynamic approach. Machine learning creates a "black box" connection to the properties. Therefore, minimal computational cost is required. With the help of the best-trained machine learning model, green solvents are selected for small molecule donors that are used in organic solar cells. Our introduced framework can help to select solvents for organic solar cells in an easy and fast way.

5.
Curr Psychol ; 42(1): 145-153, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-33531791

RESUMO

Since the outbreak of 2019 coronavirus disease (COVID-19) in December 2019, the Chinese government has implemented effective epidemic prevention measures. To provide useful information for governments to manage this public health crisis, we conducted an online survey among Chinese general population from February 24 to 28, 2020. In this study, we examined the impact of epidemic information and rumors on public's worries and attitude toward prevention measures during the outbreak of COVID-19. A total of 853 valid questionnaires (641 women, 75.1%) were collected from 24 provincial regions in China. Most respondents' ages ranged from 18 to 60 (833 participants, 97.66%). A mediation model was built to analyze the influence of epidemic information and rumors on worries and attitude. The results showed that the amount of epidemic information positively predicted public's worries, which in turn predicted a supportive attitude toward the prevention measures. Worries partially mediated the relationship between the amount of epidemic information and the supportive attitude. The amount of rumors negatively predicted the supportive attitude. The results of this study implied the importance of timely and credible information providing to evoke a certain level of worry and promote public cooperation, and the necessary attention to refute and resist rumors for effective risk communication in a public health crisis.

6.
Angew Chem Int Ed Engl ; 62(10): e202216340, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36591914

RESUMO

Side-chain tailoring is a promising method to optimize the performance of organic solar cells (OSCs). However, asymmetric alkyl chain-based small molecular acceptors (SMAs) are still difficult to afford. Herein, we adopted a novel asymmetric n-nonyl/undecyl substitution strategy and synthesized two A-D1 A'D2 -A double asymmetric isomeric SMAs with asymmetric selenophene-based central core for OSCs. Crystallographic analysis indicates that AYT9Se11-Cl forms a more compact and order intermolecular packing compared to AYT11Se9-Cl, which contributed to higher electron mobility in neat AYT9Se11-Cl film. Moreover, the PM6 : AYT9Se11-Cl blend film shows a better morphology with appropriate phase separation and distinct face-on orientation than PM6 : AYT11Se9-Cl. The OSCs with PM6 : AYT9Se11-Cl obtain a superior PCE of 18.12 % compared to PM6 : AYT11Se9-Cl (17.52 %), which is the best efficiency for the selenium-incorporated SMAs in binary BHJ OSCs. Our findings elucidate that the promising double asymmetric strategy with isomeric alkyl chains precisely modulates the crystal packing and enhances the photovoltaic efficiency of selenophene-incorporated SMAs.

7.
Angew Chem Int Ed Engl ; 62(49): e202313016, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-37823882

RESUMO

Both the regional isomerization and selenium-substitution of the small molecular acceptors (SMAs) play significant roles in developing efficient organic solar cells (OSCs), while their synergistic effects remain elusive. Herein, we developed three isomeric SMAs (S-CSeF, A-ISeF, and A-OSeF) via subtly manipulating the mono-selenium substituted position (central, inner, or outer) and type of heteroaromatic ring on the central core by synergistic strategies for efficient OSCs, respectively. Crystallography of asymmetric A-OSeF presents a closer intermolecular π-π stacking and more ordered 3-dimensional network packing and efficient charge-hopping pathways. With the successive out-shift of the mono-selenium substituted position, the neat films give a slightly wider band gap and gradually higher crystallinity and electron mobility. The PM1 : A-OSeF afford favourable fibrous phase separation morphology with more ordered molecular packing and efficient charge transportation compared to the other two counterparts. Consequently, the A-OSeF-based devices achieve a champion efficiency of 18.5 %, which represents the record value for the reported selenium-containing SMAs in binary OSCs. Our developed precise molecular engineering of the position and type of selenium-based heteroaromatic ring of SMAs provides a promising synergistic approach to optimizing crystal stacking and boosting top-ranked selenium-containing SMAs-based OSCs.

8.
Chemistry ; 28(2): e202103712, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34767281

RESUMO

Chemical structure of small molecule acceptors determines their performance in organic solar cells. Multiscale simulations are necessary to avoid trial-and-error based design, ultimately to save time and resources. In current study, the effect of sp2 -hybridized nitrogen substitution at the inner or the outmost position of central core, side chain, and terminal group of small molecule acceptors is investigated using multiscale computational modelling. Quantum chemical analysis is used to study the electronic behavior. Nitrogen substitution at end-capping has significantly decreased the electron-reorganization energy. No big change is observed in transfer integral and excited state behavior. However, nitrogen substitution at terminal group position is good way to improve electron-mobility. Power conversion efficiency (PCE) of newly designed acceptors is predicted using machine learning. Molecular dynamics simulations are also performed to explore the dynamics of acceptor and their blends with PBDB-T polymer donor. Florgy-Huggins parameter is calculated to study the mixing of designed small molecule acceptors with PBDB-T. Radial distribution function has indicated that PBDB-T has a closer packing with N3 and N4. From all analysis, it is found that nitrogen substitution at end-capping group is a better strategy to design efficient small molecule acceptors.

9.
Mol Cell Biochem ; 477(7): 2001-2013, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35394639

RESUMO

Chemotherapy resistance of colorectal cancer stem cells (CRC-SCs) has become a major challenge in clinical treatment of cancer. Methionine restriction (MR) enhances the therapeutic effect of chemotherapeutic agents. The aim of this study was to explore the molecular pathways that MR affects the chemotherapeutic sensitivity of CRC-SCs. CD133+ and CD133- SW480 or SW620 cells were isolated by magnetic-activated cell sorting (MACS). Mouse xenograft tumor model was established by subcutaneous inoculation of CD133+ SW480. MTT assay was used to detect cell viability. Phase distribution of cell cycle was detected by flow cytometry. Western blotting was used to detect drug-resistant related protein expression. miR-320d and transcription factor c-Myc expressions were detected by qRT-PCR. The interaction between miR-320d and c-Myc was verified by luciferase assay. CD133+ SW480 and SW620 cells were more resistant to 5-fluorouracil (5-FU) than CD133- cells. In vitro and in vivo experiments showed that 5-FU and MR combined therapy further inhibited CD133+ cell activity and ATP binding cassette subfamily G member 2 (ABCG2) expression, and reduced tumor volume compared with drug administration alone. Interference with miR-320d or overexpression of c-Myc reversed the increased chemotherapeutic sensitivity of CRC-SCs induced by synergistic therapy with 5-FU and MR. miR-320d can target and regulate c-Myc. Interference with c-Myc could reverse the increase in cell viability and ABCG2 expression caused by down-regulation of miR-320d. In conclusion, the combined chemotherapy with MR can enhance the chemotherapeutic sensitivity of CRC-SCs by up-regulation of miR-320d to inhibit c-Myc expression, which lays a molecular basis for MR regulation of chemotherapeutic sensitivity of CRC-SCs.


Assuntos
Neoplasias Colorretais , MicroRNAs , Animais , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Humanos , Metionina/farmacologia , Camundongos , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/metabolismo
10.
Angew Chem Int Ed Engl ; 61(46): e202209454, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36052955

RESUMO

Herein, we synthesized new hetero-halogenated end groups with well-determined fluorinated and chlorinated substitutions (o-FCl-IC and FClF-IC), and synthesized regioisomer-free small molecular acceptors (SMAs) Y-Cl, Y-FCl, and Y-FClF with distinct hetero-halogenated terminals, respectively. The single-crystal structures and theoretical calculations indicate that Y-FClF exhibits more compact three-dimensional network packing and more significant π-π electronic coupling compared to Y-FCl. From Y-Cl to Y-FCl to Y-FClF, the neat films exhibit a narrower optical band gap and gradually enhanced electron mobility and crystallinity. The PM6 : Y-FClF blend film exhibits the strongest crystallinity with preferential face-on molecular packing, desirable fibrous morphology with suitable phase segregation, and the highest and balanced charge mobilities among three blend films. Overall, the PM6 : Y-FClF organic solar cells (OSCs) deliver a remarkable efficiency of 17.65 %, outperforming the PM6 : Y-FCl and PM6 : Y-Cl, which is the best PCE for reported hetero-halogens-based SMAs in binary OSCs. Our results demonstrate that difluoro-monochloro hetero-terminal is a superior regio-regular unit for enhancing the intermolecular crystal packing and photovoltaic performance of hetero-halogenated SMAs.

11.
Angew Chem Int Ed Engl ; 60(35): 19241-19252, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34051037

RESUMO

A dissymmetric backbone and selenophene substitution on the central core was used for the synthesis of symmetric or dissymmetric A-DA'D-A type non-fullerene small molecular acceptors (NF-SMAs) with different numbers of selenophene. From S-YSS-Cl to A-WSSe-Cl and to S-WSeSe-Cl, a gradually red-shifted absorption and a gradually larger electron mobility and crystallinity in neat thin film was observed. A-WSSe-Cl and S-WSeSe-Cl exhibit stronger and tighter intermolecular π-π stacking interactions, extra S⋅⋅⋅N non-covalent intermolecular interactions from central benzothiadiazole, better ordered 3D interpenetrating charge-transfer networks in comparison with thiophene-based S-YSS-Cl. The dissymmetric A-WSSe-Cl-based device has a PCE of 17.51 %, which is the highest value for selenophene-based NF-SMAs in binary polymer solar cells. The combination of dissymmetric core and precise replacement of selenophene on the central core is effective to improve Jsc and FF without sacrificing Voc .

12.
Small ; 16(22): e1907681, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32378305

RESUMO

Here, a pair of A1 -D-A2 -D-A1 unfused ring core-based nonfullerene small molecule acceptors (NF-SMAs), BO2FIDT-4Cl and BT2FIDT-4Cl is synthesized, which possess the same terminals (A1 ) and indacenodithiophene unit (D), coupling with different fluorinated electron-deficient central unit (difluorobenzoxadiazole or difluorobenzothiadiazole) (A2 ). BT2FIDT-4Cl exhibits a slightly smaller optical bandgap of 1.56 eV, upshifted highest occupied molecular orbital energy levels, much higher electron mobility, and slightly enhanced molecular packing order in neat thin films than that of BO2FIDT-4Cl. The polymer solar cells (PSCs) based on BT2FIDT-4Cl:PM7 yield the best power conversion efficiency (PCE) of 12.5% with a Voc of 0.97 V, which is higher than that of BO2FIDT-4Cl-based devices (PCE of 10.4%). The results demonstrate that the subtle modification of A2 unit would result in lower trap-assisted recombination, more favorable morphology features, and more balanced electron and hole mobility in the PM7:BT2FIDT-4Cl blend films. It is worth mentioning that the PCE of 12.5% is the highest value in nonfused ring NF-SMA-based binary PSCs with high Voc over 0.90 V. These results suggest that appropriate modulation of the quinoid electron-deficient central unit is an effective approach to construct highly efficient unfused ring NF-SMAs to boost PCE and Voc simultaneously.

13.
Int J Neuropsychopharmacol ; 23(12): 821-836, 2020 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-32827213

RESUMO

BACKGROUND: Depression is one of the most common forms of mental illness and also a leading cause of disability worldwide. Developing novel antidepressant targets beyond the monoaminergic systems is now popular and necessary. LIM kinases, including LIM domain kinase 1 and 2 (LIMK1/2), play a key role in actin and microtubule dynamics through phosphorylating cofilin. Since depression is associated with atrophy of neurons and reduced connectivity, here we speculate that LIMK1/2 may play a role in the pathogenesis of depression. METHODS: In this study, the chronic unpredictable mild stress (CUMS), chronic restraint stress (CRS), and chronic social defeat stress (CSDS) models of depression, various behavioral tests, stereotactic injection, western blotting, and immunofluorescence methods were adopted. RESULTS: CUMS, CRS, and CSDS all significantly enhanced the phosphorylation levels of LIMK1 and LIMK2 in the medial prefrontal cortex (mPFC) but not the hippocampus of mice. Administration of fluoxetine, the most commonly used selective serotonin reuptake inhibitor in clinical practice, fully reversed the effects of CUMS, CRS, and CSDS on LIMK1 and LIMK2 in the mPFC. Moreover, pharmacological inhibition of LIMK1 and LIMK2 in the mPFC by LIMKi 3 infusions notably prevented the pro-depressant effects of CUMS, CRS, and CSDS in mice. CONCLUSIONS: In summary, these results suggest that LIMK1/2 in the mPFC has a role in chronic stress-induced depressive-like effects in mice and could be a novel pharmacological target for developing antidepressants.


Assuntos
Depressão/metabolismo , Fluoxetina/farmacologia , Quinases Lim/metabolismo , Córtex Pré-Frontal/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Estresse Psicológico/metabolismo , Tiazóis/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Doença Crônica , Depressão/tratamento farmacológico , Depressão/etiologia , Depressão/prevenção & controle , Modelos Animais de Doenças , Fluoxetina/administração & dosagem , Quinases Lim/antagonistas & inibidores , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal/efeitos dos fármacos , Inibidores de Proteínas Quinases/administração & dosagem , Pirazóis/administração & dosagem , Restrição Física , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Derrota Social , Estresse Psicológico/complicações , Estresse Psicológico/tratamento farmacológico , Tiazóis/administração & dosagem
14.
Inflamm Res ; 69(8): 789-800, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32451556

RESUMO

OBJECTIVE: Transmembrane protein 88 (TMEM88), a new protein of increasing concern existed in cell membrane, inhibits the typical Wnt/ß-catenin signaling pathway to play a regulatory role on cell proliferation by binding to Dishevelled-1. Until recently, the connection between TMEM88 and alcoholic liver disease is unknown. In this research, we explored the effect of TMEM88 on the secretion of inflammatory cytokines in ethanol (EtOH)-induced RAW264.7 cells, moreover, the function of YAP signaling pathway in EtOH-induced RAW264.7 cells were investigated. METHODS: We administered TMEM88 adenovirus (ADV-TMEM88) by tail vein injection into C57BL/6J mice in vivo. In vitro, RAW264.7 murine macrophages were stimulated with EtOH and were transfected with pEGFP-C1-TMEM88 and TMEM88 siRNA, respectively, protein expression and mRNA expression of IL-6 and IL-1ß were assessed by Western Blotting and RT-qPCR, respectively. RESULTS: Our group found that the overexpression of TMEM88 led to an up-regulation of IL-6 and IL-1ß secretion, hinting that it had the possibility of linking with the initiation, the development, and the end of inflammation. In addition to that, TMEM88 silencing reduced the secretion of IL-6 and IL-1ß in RAW264.7 cells. Moreover, we demonstrated that the YAP signaling pathway under the action of EtOH was activated by TMEM88. CONCLUSIONS: All in all, these experimental outcomes indicated that TMEM88 had an indispensable impact on EtOH-induced secretion of inflammatory cytokines (IL-6 and IL-1ß) in RAW264.7 cells through YAP signaling pathway.


Assuntos
Citocinas/biossíntese , Lipoproteínas/fisiologia , Hepatopatias Alcoólicas/etiologia , Proteínas de Membrana/fisiologia , Transativadores/fisiologia , Animais , Apoptose/efeitos dos fármacos , Etanol/farmacologia , Hepatopatias Alcoólicas/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7 , Transdução de Sinais/fisiologia
15.
Int J Neuropsychopharmacol ; 22(9): 585-600, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31181145

RESUMO

BACKGROUND: Major depressive disorder is a worldwide neuropsychiatric disorder associated with various symptoms, but current antidepressants used in clinical practice have various side effects and high failure rates. Andrographolide is the main bioactive ingredient of Andrographis paniculata and exhibits numerous pharmacological actions. This study aimed to evaluate the antidepressant-like effects of andrographolide in male C57BL/6J mice. METHODS: The antidepressant-like effects of andrographolide in mice were explored in a forced swim test, tail suspension test, and chronic unpredictable mild stress model of depression. Western blotting and immunofluorescence were further performed to assess the effects of chronic unpredictable mild stress and andrographolide on the brain-derived neurotrophic factor signalling cascade and hippocampal neurogenesis. Moreover, a pharmacological inhibitor (K252a) and a lentiviral-short hairpin RNA (LV-TrkB-shRNA) were used to clarify the antidepressant-like mechanism of andrographolide. RESULTS: Andrographolide exhibited antidepressant-like potential in the forced swim test and tail suspension test without influencing the locomotor activity of mice. Repeated andrographolide treatment not only produced significant antidepressant-like effects in the chronic unpredictable mild stress model but also prevented the decreasing effects of chronic unpredictable mild stress on hippocampal brain-derived neurotrophic factor signalling and neurogenesis in mice. Importantly, blockade of the hippocampal brain-derived neurotrophic factor system by K252a and TrkB-shRNA fully abolished the antidepressant-like effects of andrographolide in mice. CONCLUSIONS: Andrographolide exerts antidepressant-like effects in mice via promoting the hippocampal brain-derived neurotrophic factor signalling cascade.


Assuntos
Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Diterpenos/farmacologia , Hipocampo/metabolismo , Animais , Carbazóis/farmacologia , Modelos Animais de Doenças , Diterpenos/antagonistas & inibidores , Alcaloides Indólicos/farmacologia , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , RNA Interferente Pequeno/farmacologia , Transdução de Sinais/efeitos dos fármacos
16.
Biol Pharm Bull ; 40(4): 465-472, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28123152

RESUMO

Alzheimer's disease (AD) is a most serious age-related neurodegenerative disorder accompanied with significant memory impairments in this world. Recently, microRNAs (miRNAs) have been reported to be invlolved in the pathophysiology of AD. Previous studies have shown that miRNA-206 (miR-206) is implicated in the pathogenesis of AD via suppressing the expression of brain-derived neurotrophic factor (BDNF) in the brain. Here, we examined the miR-206-3p and miR-206-5p expression in the hippocampus and cortex of Abeta precursor protein (APP)/presenilin-1 (PS1) transgenic mice treated with donepezil, a drug approved for treating AD in clinic. We found that the expression of miR-206-3p was significantly up-regulated in the hippocampus and cortex of APP/PS1 mice, while donepezil administration significantly reversed this dysfunction. In addition, enhancing the miR-206-3p level by the usage of AgomiR-206-3p significantly attenuated the anti-dementia effects of donepezil in APP/PS1 mice. Together, these results suggested that miR-206-3p is involved in the anti-dementia effects of donepezil, and could be a novel pharmacological target for treating AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Fator Neurotrófico Derivado do Encéfalo/genética , Córtex Cerebral/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Indanos/farmacologia , MicroRNAs/metabolismo , Piperidinas/farmacologia , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Córtex Cerebral/metabolismo , Donepezila , Hipocampo/metabolismo , Humanos , Indanos/uso terapêutico , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , MicroRNAs/agonistas , Piperidinas/uso terapêutico , Presenilina-1/genética , Presenilina-1/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
17.
Acta Radiol ; 58(1): 19-26, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27055919

RESUMO

BACKGROUND: Diffusion-weighted imaging (DWI) derived apparent diffusion coefficient (ADC) has demonstrated inconsistent results in pulmonary nodule differentiation. Diffusion kurtosis imaging (DKI), which quantifies non-Gaussian diffusion, is believed to better characterize tissue micro-structure than conventional DWI. PURPOSE: To assess the feasibility of DKI in human lungs and to compare its diagnostic value with standard DWI in differentiating malignancies from benign pulmonary nodules. MATERIAL AND METHODS: Thirty-five pulmonary nodules in 32 consecutive patients were evaluated by DKI by using 3b-values of 0, 500, and 1000 s/mm2 and conventional DWI with b values of 0 and 800 s/mm2. Two observers independently evaluated and compared diagnostic accuracy of mean kurtosis (MK) and ADC values in differentiating malignancies from benign pulmonary nodules. The intra- and inter-observer repeatability (intra-class correlation coefficient [ICC]) were also assessed for each derived measures. RESULTS: The diagnostic accuracy, and the area under curve (AUC) in differentiating malignancies from benign pulmonary nodule, were not significantly higher for MK (Obs. 1a: 85.70%, 0.87; Obs. 1b: 80.00%, 0.80; and Obs. 2: 82.80%, 0.91) as compared to ADC (Obs. 1a: 77.14%, 0.81; Obs. 1b: 80.00%, 0.85; and Obs. 2: 77.14%, 0.85 respectively). The intra- and inter-observer agreement (ICC) for malignant and benign lesions was substantial for each reading. CONCLUSION: The initial results of this study indicate the feasibility of DKI in human lungs. However, there was no significant benefit of DKI derived MK values over ADC for malignant and benign pulmonary nodule differentiation.


Assuntos
Algoritmos , Imagem de Difusão por Ressonância Magnética/métodos , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Nódulo Pulmonar Solitário/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Simulação por Computador , Interpretação Estatística de Dados , Estudos de Viabilidade , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Projetos Piloto , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Distribuições Estatísticas
18.
Pol J Vet Sci ; 20(2): 355-362, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28865212

RESUMO

OBJECTIVE: The aim of this study was to establish a rapid and accurate method for the detection of the Streptococcus agalactiae antibody (SA-Ab) to determine the presence of the bovine mastitis (BM)-causative pathogen. METHODS: The multi-subunit fusion protein rSip-Pgk-FbsA was prokaryotically expressed and purified. The triple activities of the membrane surface-associated proteins Sip, phosphoglycerate kinase (Pgk), and fibronectin (FbsA) were used as the diagnostic antigens to establish an indirect enzyme-linked immunosorbent assay (ELISA) method for the detection of SA-Ab in BM. RESULTS: The optimal antigen coating concentration was 2 µg/mL, the optimal serum dilution was 1:160, and the optimal dilution of the enzyme-labeled secondary antibody was 1:6000. The sensitivity, specificity, and repeatability tests showed that the method established in this study had no cross-reaction with antibodies to Streptococcus pyogenes, Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis in the sera. The results of the sensitivity test showed that a positive result could be obtained even if the serum dilution reached 1:12,800, indicating the high sensitivity and good repeatability of the method. The positive coincidence rate of this method was 98.6%, which is higher than that of previous tests established with the Sip or Pgk mono-antigen fusion protein, respectively, demonstrating the relatively higher sensitivity of this newly established method. The detection rate for 389 clinical samples was 46.53%. CONCLUSIONS: The indirect ELISA method established in this study could provide a more accurate and reliable serological method for the rapid detection of S. agalactiae in cases of BM.


Assuntos
Proteínas de Bactérias/metabolismo , Ensaio de Imunoadsorção Enzimática/veterinária , Mastite Bovina/microbiologia , Infecções Estreptocócicas/veterinária , Streptococcus agalactiae/imunologia , Streptococcus agalactiae/metabolismo , Animais , Proteínas de Bactérias/genética , Bovinos , Feminino , Mastite Bovina/diagnóstico , Proteínas Recombinantes , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/microbiologia
19.
J Am Chem Soc ; 138(24): 7687-97, 2016 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-27225322

RESUMO

We report the synthesis of a family of multifluorine substituted oligomers and the corresponding polymer that have the same backbones but different conjugation lengths and amounts of fluorine atoms on the backbone. The physical properties and photovoltaic performances of these materials were systematically investigated using optical absorption, charge mobility, atomic force microscopy, transmission electron microscopy, grazing incidence X-ray diffraction, resonant soft X-ray scattering methods, and photovoltaic devices. The power conversion efficiencies (PCEs) based on oligomers were much higher than that in the polymer. Moreover, the devices based on BIT6F and BIT10F, which have an axisymmetric electron-deficient difluorobenzothiadiazole as the central unit, gave slightly higher PCEs than those with centrosymmetric electron-rich indacenodithiophene (IDT) as the central unit (BIT4F or BIT8F). Using proper solvent vapor annealing (SVA), particularly using thermal annealing (TA) followed by SVA, the device performance could be significantly improved. Notably, the best PCE of 9.1% with a very high FF of 0.76 was achieved using the medium-sized oligomer BIT6F with the optimized film morphology. This efficiency is the highest value reported for organic solar cells from small-molecules without rhodanine terminal group. More excitingly, devices from the shortest oligomer BIT4F showed an impressively high FF of 0.77 (the highest FF value reported for solution-processed small-molecule organic solar cells). These results indicate that photovoltaic performances of oligomers can be modulated through successive change in chain-length and fluorine atoms, alternating spatial symmetric core, and combined post-treatments.

20.
Chemistry ; 21(23): 8504-10, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-25918903

RESUMO

In this work, two rigid, multiple tetraphenylethene (TPE)-substituted, π-conjugated, snowflake-shaped luminophores BT and BPT were facilely synthesized by using a 6-fold Suzuki coupling reaction. These molecules are constructed based on the nonplanar structure of propeller-shaped hexaphenylbenzene (HPB) or benzene as core groups and TPE as end groups. As a result, they reserve the intrinsic aggregation-induced emission (AIE) property of the TPE moiety. Meanwhile, both fluorescence quantum yield and piezochromic behavior in the solid state can be tuned or switched by inserting the phenyl bridges through changing the twisting conformation. The more extended structure BPT showed a much stronger AIE effect and higher ΦF,f in the solid state in comparison with that of BT. Furthermore, an excellent optical waveguide application of these molecules was achieved. However, the revisable piezofluorochromic behavior has only appeared when BT was ground using a pestle and treated with solvent.

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