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1.
New Phytol ; 242(6): 2604-2619, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38563391

RESUMO

Soil contamination with arsenic (As) can cause phytotoxicity and reduce crop yield. The mechanisms of As toxicity and tolerance are not fully understood. In this study, we used a forward genetics approach to isolate a rice mutant, ahs1, that exhibits hypersensitivity to both arsenate and arsenite. Through genomic resequencing and complementation tests, we identified OsLPD1 as the causal gene, which encodes a putative lipoamide dehydrogenase. OsLPD1 was expressed in the outer cell layer of roots, root meristem cells, and in the mesophyll and vascular tissues of leaves. Subcellular localization and immunoblot analysis demonstrated that OsLPD1 is localized in the stroma of plastids. In vitro assays showed that OsLPD1 exhibited lipoamide dehydrogenase (LPD) activity, which was strongly inhibited by arsenite, but not by arsenate. The ahs1 and OsLPD1 knockout mutants exhibited significantly reduced NADH/NAD+ and GSH/GSSG ratios, along with increased levels of reactive oxygen species and greater oxidative stress in the roots compared with wild-type (WT) plants under As treatment. Additionally, loss-of-function of OsLPD1 also resulted in decreased fatty acid concentrations in rice grain. Taken together, our finding reveals that OsLPD1 plays an important role for maintaining redox homeostasis, conferring tolerance to arsenic stress, and regulating fatty acid biosynthesis in rice.


Assuntos
Arsênio , Di-Hidrolipoamida Desidrogenase , Ácidos Graxos , Homeostase , Oryza , Proteínas de Plantas , Estresse Fisiológico , Adaptação Fisiológica/efeitos dos fármacos , Adaptação Fisiológica/genética , Arsênio/toxicidade , Arsenitos/toxicidade , Di-Hidrolipoamida Desidrogenase/metabolismo , Di-Hidrolipoamida Desidrogenase/genética , Ácidos Graxos/biossíntese , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Mutação/genética , Oryza/genética , Oryza/efeitos dos fármacos , Oryza/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Plastídeos/metabolismo , Plastídeos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Estresse Fisiológico/genética
2.
Acta Pharmacol Sin ; 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39349766

RESUMO

ß-arrestin2, a pivotal protein within the arrestin family, is localized in the cytoplasm, plasma membrane and nucleus, and regulates G protein-coupled receptors (GPCRs) signaling. Recent evidence shows that ß-arrestin2 plays a dual role in regulating GPCRs by mediating desensitization and internalization, and by acting as a scaffold for the internalization, kinase activation, and the modulation of various signaling pathways, including NF-κB, MAPK, and TGF-ß pathways of non-GPCRs. Earlier studies have identified that ß-arrestin2 is essential in regulating immune cell infiltration, inflammatory factor release, and inflammatory cell proliferation. Evidently, ß-arrestin2 is integral to the pathological mechanisms of inflammatory immune diseases, such as inflammatory bowel disease, sepsis, asthma, rheumatoid arthritis, organ fibrosis, and tumors. Research on the modulation of ß-arrestin2 offers a promising strategy for the development of pharmaceuticals targeting inflammatory immune diseases. This review meticulously describes the roles of ß-arrestin2 in cells associated with inflammatory immune responses and explores its pathological relevance in various inflammatory immune diseases.

3.
Arch Toxicol ; 98(3): 779-790, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38224356

RESUMO

Hair analysis is a crucial method in forensic toxicology with potential applications in revealing doping histories in sports. Despite its widespread use, knowledge about detectable substances in hair is limited. This study systematically assessed the detectability of prohibited substances in sports using a multifaceted approach. Initially, an animal model received a subset of 17 model drugs to compare dose dependencies and detection windows across different matrices. Subsequently, hair incorporation data from the animal experiment were extrapolated to all substances on the World Anti-Doping Agency's List through in-silico prediction. The detectability of substances in hair was further validated in a proof-of-concept human study involving the consumption of diuretics and masking agents. Semi-quantitative analysis of substances in specimens was performed using ultra-performance liquid chromatography-tandem mass spectrometry. Results showed plasma had optimal dose dependencies with limited detection windows, while urine, faeces, and hair exhibited a reasonable relationship with the administered dose. Notably, hair displayed the highest detection probability (14 out of 17) for compounds, including anabolic agents, hormones, and diuretics, with beta-2 agonists undetected. Diuretics such as furosemide, canrenone, and hydrochlorothiazide showed the highest hair incorporation. Authentic human hair confirmed diuretic detectability, and their use duration was determined via segmental analysis. Noteworthy is the first-time reporting of canrenone in human hair. Anabolic agents were expected in hair, whereas undetectable compounds, such as peptide hormones and beta-2 agonists, were likely due to large molecular mass or high polarity. This study enhances understanding of hair analysis in doping investigations, providing insights into substance detectability.


Assuntos
Anabolizantes , Dopagem Esportivo , Animais , Humanos , Canrenona/análise , Dopagem Esportivo/métodos , Diuréticos/análise , Fezes/química , Cabelo/química , Detecção do Abuso de Substâncias/métodos
4.
BMC Public Health ; 24(1): 908, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38539176

RESUMO

BACKGROUND: As the internet develops and 5G technology becomes increasingly prominent, the internet has become a major source of health-related information. Increasingly, people use the internet to find health-related information, and digital health literacy is now a set of essential capabilities to improve their health in the digital era. However, little is known about the factors that influencing digital health literacy. This study aimed to assess digital health literacy scores and identify its influencing factors among internet users in China. Additionally, this study explored the participant's actual skills using an additional set of performance-based items from the Digital Health Literacy Instrument (DHLI). METHODS: An online cross-sectional study was conducted in August 2022. Participants aged ≥18 years were recruited to complete the survey. Data were collected using the Chinese revised version of the DHLI, the self-reported internet use questionnaire, and the sociodemographic questionnaire. We conducted multivariate linear regression analyses to explore the relationships among the sociodemographic variables, behavior of internet use, and the digital health literacy scores. RESULTS: In total, 702 participants completed the survey. The mean DHLI score was 2.69 ± 0.61. Multivariate linear regression analyses showed that the age groups 35-49 (ß = - 0.08, P = 0.033), 50-64 (ß = - 0.161, P < 0.001), and ≥ 65 (ß = - 0.138, P < 0.001) were negatively associated with DHL scores. However, education level, including bachelor's or associate degree (ß = 0.255, P = 0.002) and master's degree and above (ß = 0.256, P < 0.001), frequency of health-related Internet usage (ß = 0.192, P < 0.001), the number of digital devices used (ß = 0.129, P = 0.001), and OHISB (ß = 0.103, P = 0.006) showed a positive relationship with DHL scores. CONCLUSIONS: The study findings demonstrate that age, educational levels, number of technological devices used, and greater use of the web for health information were independently associated with DHL scores. Healthcare providers should consider providing training programs tailored to specific sociodemographic factors to improve the ability that find and use accurate information online to meet digital health services, which contributes to enhance their self-management and reduce health disparities.


Assuntos
Letramento em Saúde , Telemedicina , Humanos , Adolescente , Adulto , Saúde Digital , Estudos Transversais , Inquéritos e Questionários , Internet , China
5.
World J Surg Oncol ; 22(1): 69, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38403630

RESUMO

BACKGROUND: Direct oral anticoagulants (DOACs) used as an alternative to low-molecular-weight heparin (LMWH) for thromboprophylaxis after cancer surgery for venous thromboembolic events (VTE) remains unclear. This study aimed to investigate the efficacy and safety of DOACs versus LMWH in these patients. MATERIALS AND METHODS: A search of EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science was carried out and included all randomized controlled trials (RCTs) and observational studies that directly compared DOACs with LMWH for thromboprophylaxis in patients after cancer surgery through July 25, 2023. The primary efficacy and safety outcomes were VTE, major bleeding, and clinically relevant non-major bleeding (CRNMB) within 30 days of surgery. The risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB2) tool for RCTs and ROBINS-I tool for non-randomized studies. This study was registered in PROSPERO (CRD42023445386). RESULTS: We retrieved 5149articles, selected 27 for eligibility, and included 10 studies (three RCTs and seven observational studies) encompassing 3054 patients who underwent postoperative thromboprophylaxis with DOACs (41%) or LMWH (59%). Compared to LMWH thromboprophylaxis, DOACs had a comparable risk of VTE (RR:0.69[95% CI:0.46-1.02], I2 = 0%), major bleeding (RR:1.55 [95% CI:0.82-2.93], I2 = 2%), and CRNMB (RR, 0.89 [95% CI, 0.4-1.98], I2 = 31%) during the 30-day postoperative period. Subgroup analysis of VTE and major bleeding suggested no differences according to study type, extended thromboprophylaxis, tumor types, or different types of DOAC. CONCLUSION: DOACs are potentially effective alternatives to LMWH for thromboprophylaxis in patients undergoing cancer surgery, without increasing the risk of major bleeding events.


Assuntos
Neoplasias , Tromboembolia Venosa , Humanos , Heparina de Baixo Peso Molecular/efeitos adversos , Anticoagulantes/efeitos adversos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Neoplasias/cirurgia
6.
Zhongguo Zhong Yao Za Zhi ; 49(8): 2076-2087, 2024 Apr.
Artigo em Zh | MEDLINE | ID: mdl-38812224

RESUMO

Raphani Semen, with both edible and medicinal values, is a typical Chinese herbal medicine with different effects before and after processing. The raw helps ascending and the cooked helps descending. This paper comprehensively summarizes the differences in chemical constituents and pharmacological effects between raw and processed Raphani Semen that are reported in recent years. Based on the principle of quality markers(Q-markers) of traditional Chinese medicines, the chemical constituent sources, chemical constituent detection techniques, and correlation between bidirectional regulatory efficacy and chemical constituents are compared between raw and processed Raphani Semen. The results suggest that sulforaphene and glucoraphanin could be used as candidate Q-markers of raw and processed Raphani Semen, respectively. This review is expected to provide a reference for further research on the processing, new drug development, and improvement of safety and effectiveness of Raphani Semen in clinical application.


Assuntos
Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise , Controle de Qualidade , Humanos , Biomarcadores/análise
7.
Anal Chem ; 95(2): 1498-1504, 2023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36598384

RESUMO

Simultaneous imaging and especially visualizing the association of survivin mRNA and telomerase in living cells are of great value for the diagnosis and prognosis of cancer because their co-expression facilitates the development of cancer and identifies patients at high risk of tumor-related death. The challenge is to develop methods that enable visualizing the association of multiplex targets and avoid the distorted signals due to the different delivery efficiency of probes. Herein, we engineered a DNA triangular prism nanomachine (DTPN) for simultaneous multicolor imaging of survivin mRNA and telomerase and visualizing their association in living cells. Two recognizing probes targeted survivin mRNA and telomerase, and the reporter probe was assembled on the DTP in equal amounts, ensuring the same delivery efficiency of the probes to the living cells. The results showed that this DTPN could quantify intracellular survivin mRNA expression and telomerase activity. Moreover, it also enabled us to visualize the effect of the down-regulation of one target on the expression of another target under different drug stimulations. The results implied that our DTPN provided a promising platform for cancer diagnosis, prognosis, drug screening, and related biological research.


Assuntos
Telomerase , Humanos , Survivina/genética , Survivina/metabolismo , RNA Mensageiro/genética , Telomerase/genética , Telomerase/metabolismo , DNA/genética , Regulação para Baixo
8.
Biochem Biophys Res Commun ; 671: 246-254, 2023 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-37307708

RESUMO

Vascular dementia (VaD), the second most common type of dementia, is attributed to lower cerebral blood flow. To date, there is still no available clinical treatment for VaD. The phenolic glucoside gastrodin (GAS) is known for its neuroprotective effects, but the role and mechanisms of action on VD remains unclear. In this study, we aim to investigate the neuroprotective role and underlying mechanisms of GAS on chronic cerebral hypoperfusion (CCH)-mediated VaD rats and hypoxia-induced injury of HT22 cells. The study showed that GAS relieved learning and memory deficits, ameliorated hippocampus histological lesions in VaD rats. Additionally, GAS down-regulated LC3II/I, Beclin-1 levels and up-regulated P62 level in VaD rats and hypoxia-injured HT22 cells. Notably, GAS rescued the phosphorylation of PI3K/AKT pathway-related proteins expression, which regulates autophagy. Mechanistic studies verify that YP-740, a PI3K agonist, significantly resulted in inhibition of excessive autophagy and apoptosis with no significant differences were observed in the YP-740 and GAS co-treatment. Meantime, we found that LY294002, a PI3K inhibitor, substantially abolished GAS-mediated neuroprotection. These results revealed that the effects of GAS on VaD are related to stimulating PI3K/AKT pathway-mediated autophagy, suggesting a potentially beneficial therapeutic strategy for VaD.


Assuntos
Disfunção Cognitiva , Demência Vascular , Fármacos Neuroprotetores , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Demência Vascular/tratamento farmacológico , Demência Vascular/patologia , Ratos Sprague-Dawley , Transdução de Sinais , Autofagia , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Disfunção Cognitiva/metabolismo , Hipóxia/tratamento farmacológico
9.
Acta Pharmacol Sin ; 44(10): 2048-2064, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37225848

RESUMO

Autoimmune hepatitis (AIH) is a progressive hepatitis syndrome characterized by high transaminase levels, interface hepatitis, hypergammaglobulinemia, and the presence of autoantibodies. Misdiagnosis or delayed treatment of AIH can lead to cirrhosis or liver failure, which poses a major risk to human health. ß-Arrestin2, a key scaffold protein for intracellular signaling pathways, has been found to be involved in many autoimmune diseases such as Sjogren's syndrome and rheumatoid arthritis. However, whether ß-arrestin2 plays a role in AIH remains unknown. In the present study, S-100-induced AIH was established in both wild-type mice and ß-arrestin2 knockout (Arrb2 KO) mice, and the experiments identified that liver ß-arrestin2 expression was gradually increased, and positively correlated to serum ANA, ALT and AST levels during AIH progression. Furthermore, ß-arrestin2 deficiency ameliorated hepatic pathological damage, decreased serum autoantibody and inflammatory cytokine levels. ß-arrestin2 deficiency also inhibited hepatocyte apoptosis and prevented the infiltration of monocyte-derived macrophages into the damaged liver. In vitro experiments revealed that ß-arrestin2 knockdown suppressed the migration and differentiation of THP-1 cells, whereas ß-arrestin2 overexpression promoted the migration of THP-1 cells, which was regulated by the activation of the ERK and p38 MAPK pathways. In addition, ß-arrestin2 deficiency attenuated TNF-α-induced primary hepatocyte apoptosis by activating the Akt/GSK-3ß pathway. These results suggest that ß-arrestin2 deficiency ameliorates AIH by inhibiting the migration and differentiation of monocytes, decreasing the infiltration of monocyte-derived macrophages into the liver, thereby reducing inflammatory cytokines-induced hepatocytes apoptosis. Therefore, ß-arrestin2 may act as an effective therapeutic target for AIH.


Assuntos
Hepatite Autoimune , Hepatopatias , beta-Arrestina 2 , Animais , Camundongos , Apoptose , Autoanticorpos/metabolismo , beta-Arrestina 2/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/tratamento farmacológico , Hepatócitos/metabolismo , Fígado/metabolismo , Hepatopatias/metabolismo , Macrófagos/metabolismo , Proteínas S100/metabolismo
10.
BMC Pregnancy Childbirth ; 23(1): 501, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37420176

RESUMO

BACKGROUND: Threatened preterm labor (TPL) is an important obstetrical challenge. Pregnant women with TPL may develop psychological and physical problems such as mental health disorders, sleep disturbance, and hormonal circadian rhythm disruption. This study aimed to investigate the current state of mental health, sleep quality, and circadian rhythms of cortisol and melatonin secretion in pregnant women with TPL and normal pregnant women (NPW). METHODS: A prospective observational clinical study was conducted at a maternal and child health hospital in Fuzhou, China, between June and July 2022. A total of 50 women between 32 and 36 weeks of gestation (TPL group, n = 20; NPW group, n = 30) were recruited. Data on anxiety symptom (Zung's Self-rating Anxiety Scale, SAS), depression symptom (Edinburgh Postnatal Depression Scale, EPDS), subjective sleep quality (Pittsburgh Sleep Quality Index, PSQI) and objective sleep outcomes (measured by actigraphy) of the pregnant women were collected at the time of enrolment. Salivary samples were collected once every 6 h (i.e., at 06:00, 12:00, 18:00, and 00:00) during 2 consecutive days to measure the circadian rhythm of hormone (cortisol and melatonin). RESULTS: There were no differences found in the total scores of SAS, EPDS scores, subjective sleep quality between the TPL and NPW groups (P > 0.05). In contrast, significant differences were found in sleep efficiency, total sleep time, wake time after sleep onset, and average awakening time between the groups (P < 0.05). The circadian rhythm of melatonin secretion was disrupted in the TPL group (P = 0.350); however, it was maintained in the NPW group (P = 0.044). The circadian rhythm of cortisol secretion was disrupted in both groups (P > 0.05). CONCLUSIONS: In the third trimester of pregnancy, women with TPL suffer from poorer sleep quality and disruption of circadian rhythm of melatonin secretion compared with NPW. Nevertheless, there were no differences found in mental health (i.e., anxiety and depression) and circadian rhythm of cortisol secretion. Large-scale studies should be conducted to evaluate these changes in women with TPL. TRIAL REGISTRATION: The study was registered from Chinese Clinical Trial Registry (Number: ChiCTR2200060674) on 07/06/2022.


Assuntos
Melatonina , Trabalho de Parto Prematuro , Recém-Nascido , Criança , Feminino , Humanos , Gravidez , Gestantes , Qualidade do Sono , Saúde Mental , Hidrocortisona , Ritmo Circadiano , Sono
11.
BMC Med Educ ; 23(1): 808, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891558

RESUMO

BACKGROUND: Taiwan's unique health behaviour, such as extensive exposure to Chinese Herbal Medicine (CHM), has introduced a risk of inadvertent doping among competing athletes. Pharmacy professionals have an imperative role in advising athletes on the safe use of medicines. This study provides an overview of anti-doping knowledge and educational needs among pharmacists in Taiwan and examines influencing factors. METHODS: A cross-sectional online questionnaire survey consisting of five domains, namely demographic characteristics, source of prohibited substances, identification of prohibited substances, understanding of doping control, and education needs on anti-doping, was distributed to the registered pharmacists in Taiwan. In total, 491 responses were included in the analyses. RESULTS: Respondents (65% female, aged 41.9 ± 11.4 years, with 68% having a Bachelor's degree) reported a moderate anti-doping knowledge score of 37.2 ± 4.9, ranging from 21 to 48 (out of 51). Fifteen per cent of them had the experience of being counselled about drug use in sports. Higher knowledge scores were observed in younger respondents, showing an age-dependent effect (p < 0.001). Individuals practising in southern Taiwan (compared to northern Taiwan) and those working at clinics (compared to hospitals) exhibited lower knowledge. Most of the respondents (90%) knew that stimulant ephedrine is prohibited in sports, but few had recognised diuretic furosemide (38%) and CHM (7%) containing ß2-agonist higenamine. Approximately 90% of respondents agreed with the need for anti-doping education. CONCLUSIONS: This study highlights the heterogeneity of anti-doping knowledge among pharmacy professionals and provides practical relevance in organising future educational topics and research-based activities.


Assuntos
Dopagem Esportivo , Esportes , Humanos , Feminino , Masculino , Dopagem Esportivo/prevenção & controle , Farmacêuticos , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde
12.
Child Psychiatry Hum Dev ; 54(6): 1577-1606, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-35471754

RESUMO

Neurofeedback training is a common treatment option for attention deficit hyperactivity disorder (ADHD). Given theta/beta-based neurofeedback (T/B NF) training targets at the electrophysiological characteristics of children with ADHD, benefits for attention may be expected. PsycINFO, PubMed, ScienceDirect, Scopus, and Web of Science were searched through December 31, 2020. Studies were evaluated with Risk of Bias tools. Within-group effects based on Pre- and Post-treatment comparisons of the Intervention Group, and Between-group effects based on the between-group differences from Pre-treatment to Post-treatment were calculated. Nineteen studies met selection criteria for systematic review, 12 of them were included in meta-analysis. Within-group effects were medium at Post-treatment and large at Follow-up. Between-group analyses revealed that T/B NF was superior to waitlist control and physical activities, but not stimulant medication. Results showed that T/B NF has benefits for attention in children with ADHD, however, cautions should be taken when interpreting the findings.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Neurorretroalimentação , Humanos , Criança , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Neurorretroalimentação/métodos , Estimulantes do Sistema Nervoso Central/uso terapêutico , Exercício Físico
13.
Yi Chuan ; 45(9): 801-812, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37731234

RESUMO

Nitrogen is critical for peanut growth and development, and symbiotic nodulation and nitrogen fixation is one of the main ways for peanut to obtain nitrogen. The influence of exogenous nitrogen on nodule nitrogen fixation involves complex regulatory mechanisms, revealing the regulatory mechanisms of nitrogen on nodule nitrogen fixation is of great significance for realizing the potential of biological nitrogen fixation. In this review, we summarize the mechanism of "Crack entry" in the formation of peanut root nodule, the mechanism of symbiotic nodulation and quantitative regulation of peanut, and the regulatory mechanism of nitrogen affecting peanut nodulation. At present, the molecular mechanism by which nitrogen affects the interaction between Bradyrhizobium and peanut, thereby regulating nodulation, is still unclear. Therefore, future research should focus on the signal exchange, nodule number regulation, and nutrient exchange mechanism of nitrogen effects on Bradyrhizobium and peanut, which would provide a theoretical basis for improving nodule nitrogen fixation efficiency and peanut yield, and reduce chemical nitrogen fertilizer application.


Assuntos
Arachis , Nitrogênio
14.
Anal Chem ; 94(11): 4794-4802, 2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35266710

RESUMO

Investigating multiple miRNA expression patterns in living cells by DNA logic biocomputing is a valuable strategy for diagnosis and biomedical studies. The introduction of protein enzymes in DNA logic biocomputing circuits not only expands the toolbox of nucleic acid assembly techniques, but also further improves the specificity of recognizing and processing of DNA input. Herein, a polymerase-driven primer exchange reaction, acting as the sensing module, is introduced into the biocomputing system and transduces the multiple miRNAs sensing event into the intermediate triggers for activating the subsequent processing module, which further performs signal readout through DNAzyme catalytic substrate cleavage reaction. By using biomineralized zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) to deliver all the components of the biocomputing system, including polymerase and DNA probes, we realized polymerase-driven DNA biocomputing operations in living cells, including AND and OR gates. The results exhibited that biomineralized ZIF-8 NPs can protect the loaded cargoes against the external environment and deliver them efficiently to the cytoplasm. The polymerase-driven DNA biocomputing system based on multiple miRNAs sensing can be used for reliable cell identification and may provide a promising platform for more accurate diagnosis and programmable therapeutics.


Assuntos
DNA Catalítico , MicroRNAs , Nanopartículas , Zeolitas , DNA
15.
Biochem Biophys Res Commun ; 593: 57-64, 2022 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-35063770

RESUMO

Some of the statins have been shown to have antidepressant effects, but whether atorvastatin (AV) has antidepressant effects is unknown. This study was to investigate the effect of AV treatment on depressive behaviors. Herein, we show that AV treatment had antidepressant-like effect in physiological conditions and antidepressant effect in depressive state which depended on α7 nicotinic acetylcholine receptor (α7nAChR) expression in the ventral hippocampus (vHPC), but not α4ß2 nicotinic acetylcholine receptor (α4ß2nAchR) expression in vHPC, nor the α7nAChR and α4ß2nAchR expression in dorsal hippocampus (dHPC). By using MLA, a selective α7nAChR antagonist, we investigated the role of α7nAChR in AV treatment. Behavior tests demonstrated that MLA abolished the antidepressant effect of AV. Besides, our data showed that AV treatment increased Akt phosphorylation, brain-derived neurotrophic factor (BDNF), synaptic related protein synapsin and spinophilin expression. The phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002 reversed AV-induced increase of BDNF expression, newborn neurons and antidepressant behavior effects. Our study suggests that AV plays an antidepressant role by regulating synaptic plasticity of vHPC through PI3K/Akt-BDNF signaling pathway, which may be a good choice for depression treatment.


Assuntos
Antidepressivos/farmacologia , Atorvastatina/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Transtorno Depressivo/prevenção & controle , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Animais , Anticolesterolemiantes/farmacologia , Fator Neurotrófico Derivado do Encéfalo/genética , Transtorno Depressivo/etiologia , Transtorno Depressivo/metabolismo , Transtorno Depressivo/patologia , Regulação da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Receptor Nicotínico de Acetilcolina alfa7/genética
16.
Genomics ; 113(4): 2108-2121, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33964421

RESUMO

Tomato is more prone to Tuta absoluta invasion and damages as compared to other host plants but the mechanism behind this preference has not been elucidated. Here, two contrasting host preference plants, tomato and eggplant, were used to investigate biochemical and transcriptomic modifications induced by T. absoluta infestation. Biochemical analysis at 0-72 h post T. absoluta infestation revealed significantly reduced concentrations of amino acid, fructose, sucrose, jasmonic acid, salicylic acid, and total phenols in tomato compared to eggplant, mainly at 48 h post T. absoluta infestation. Transcriptome analysis showed higher transcript changes in infested eggplant than tomato. Signaling genes had significant contributions to mediate plant immunity against T. absoluta, specifically genes associated with salicylic acid in eggplant. Genes from PR1b1, NPR1, NPR3, MAPKs, and ANP1 families play important roles to mitigate T. absoluta infestation. Our results will facilitate the development of control strategies against T. absoluta for sustainable tomato production.


Assuntos
Mariposas , Solanum lycopersicum , Solanum melongena , Animais , Perfilação da Expressão Gênica , Humanos , Solanum lycopersicum/genética , Mariposas/fisiologia , Solanum melongena/genética , Transcriptoma
17.
Pharm Biol ; 60(1): 862-878, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35594385

RESUMO

CONTEXT: Coronavirus disease 2019 is a global pandemic. Studies suggest that folic acid has antiviral effects. Molecular docking shown that folic acid can act on SARS-CoV-2 Nucleocapsid Phosphoprotein (SARS-CoV-2 N). OBJECTIVE: To identify novel molecular therapeutic targets for SARS-CoV-2. MATERIALS AND METHODS: Traditional Chinese medicine targets and virus-related genes were identified with network pharmacology and big data analysis. Folic acid was singled out by molecular docking, and its potential target SARS-CoV-2 N was identified. Inhibition of SARS-CoV-2 N of folic acid was verified at the cellular level. RESULTS: In total, 8355 drug targets were potentially involved in the inhibition of SARS-CoV-2. 113 hub genes were screened by further association analysis between targets and virus-related genes. The hub genes related compounds were analysed and folic acid was screened as a potential new drug. Moreover, molecular docking showed folic acid could target on SARS-CoV-2 N which inhibits host RNA interference (RNAi). Therefore, this study was based on RNAi to verify whether folic acid antagonises SARS-CoV-2 N. Cell-based experiments shown that RNAi decreased mCherry expression by 81.7% (p < 0.001). This effect was decreased by 8.0% in the presence of SARS-CoV-2 N, indicating that SARS-CoV-2 N inhibits RNAi. With increasing of folic acid concentration, mCherry expression decreased, indicating that folic acid antagonises the regulatory effect of SARS-CoV-2 N on host RNAi. DISCUSSION AND CONCLUSIONS: Folic acid may be an antagonist of SARS-CoV-2 N, but its effect on viruses unclear. In future, the mechanisms of action of folic acid against SARS-CoV-2 N should be studied.


Assuntos
Tratamento Farmacológico da COVID-19 , Proteínas do Nucleocapsídeo de Coronavírus , Ácido Fólico , SARS-CoV-2 , Proteínas do Nucleocapsídeo de Coronavírus/antagonistas & inibidores , Ácido Fólico/farmacologia , Humanos , Simulação de Acoplamento Molecular , Fosfoproteínas/antagonistas & inibidores
18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(4): 656-662, 2022 Jul.
Artigo em Zh | MEDLINE | ID: mdl-35871737

RESUMO

Objective: To investigate the social determinants that influenced the changes in the mental health of the rural-urban migrant population in Chengdu. Methods: Using data from two cross-sectional surveys, one conducted in 2009 and another, in 2018, of the rural-urban migrant population in Chengdu, we analyzed the social determinants of mental health affecting the rural-urban migrant population in Chengdu by multiple linear regression, and analyzed the contribution of changes in social determinants to the disparity in mental health over a decade using the Oaxaca-Blinder decomposition analysis. Results: This study included 3091 cases of rural-urban migrants in Chengdu, with 965 (31.22%) covered in the survey year of 2009 and 2126 (68.78%) covered in 2018. Multiple linear regression models were established with mental component summary (MCS) as the dependent variable, the social determinants of health as the independent variables, and gender, age, and survey year as covariates. The findings showed that being married ( ß=2.33, P<0.001), drinking 1-2 times per week ( ß=-1.42, P<0.05), illness within four weeks ( ß=-2.57, P<0.001), and hospitalization in the past year ( ß=-1.82, P<0.05), wage arrears ( ß=-1.67, P<0.05), job satisfaction ( ß=1.25, P<0.001), monthly housing costs (housing costs below monthly income: ß=-1.55, P=0.001; housing costs above monthly income: ß=-4.59, P=0.001) and housing condition ( ß=0.23, P<0.05) had significant impact on the MCS of the rural-urban migrant population. The results of the Oaxaca-Blinder decomposition method showed that the MCS disparity between the two surveys was -4.7660 points. With 2018 as the base year, the explainable parts accounted for 15.80%. Being married, decrease in the prevalence of illnesses within four weeks, and increased job satisfaction formed positive contribution to the improvement of the mental health, and increase in the proportion of monthly housing expenses formed negative contribution. Conclusion: Between 2009 and 2018, the mental health of the rural-urban migrant population in Chengdu showed improvement, and changes in marital status, illness within four weeks, job satisfaction, and monthly housing costs contributed to improvements in mental health during the period. Future intervention measures to promote the mental health of the floating population can be developed with the perspective of improving the social determinants of health in mind.


Assuntos
Migrantes , China/epidemiologia , Estudos Transversais , Humanos , Saúde Mental , População Rural , Determinantes Sociais da Saúde , População Urbana
19.
Zhongguo Zhong Yao Za Zhi ; 47(12): 3215-3223, 2022 Jun.
Artigo em Zh | MEDLINE | ID: mdl-35851114

RESUMO

Advanced glycation end products(AGEs) can lead to many diseases such as diabetes and its complications. In this study, an in vitro non-enzymatic glycosylation reaction model-bovine serum albumin/methylglyoxal(BSA/MGO) reaction system was constructed and incubated with Cortex Moutan extract. High performance liquid chromatography(HPLC) and ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) were used to detect and identify the active components that inhibited the formation of AGEs in the co-incubation solution of Cortex Moutan extract and MGO, and differential components such as salvianan, paeoniside, benzoylpaeoniflorin, mudanpioside J, galloyloxypaeoniflorin, benzoyloxy-paeoniflorin, 5-hydroxy-3 s-hydroxymethyl-6-methyl-2,3-dihydro benzofuran, and galloylpaeoniflorin were screened out, which were inferred to be the potential active components of Cortex Moutan extract to capture MGO. In addition, BSA-glucose reaction system was performed to investigate the influence of different concentrations of Cortex Moutan extract(decoction concentrations: 40, 80, 120, 160, and 200 mg·mL~(-1)) on inhibiting the production of AGEs in vitro. The inhibitory effects of Cortex Moutan extract and the differential components galloylpaeoniflorin and benzoyl paeoniflorin on the production of AGEs in human umbilical vein endothelial cells(HUVECs) induced by high glucose was further evaluated. Cell apoptosis was observed by acridine orange and ethidium bromide(AO/EB) double fluorescence staining. The results showed that Cortex Moutan Cortex extract and its differential components had certain inhibitory effects on the formation of AGEs, and could reduce cell apoptosis. This study provided reference for the treatment of diabetic vascular complications by Cortex Moutan inhibiting the toxic AGEs.


Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Glucose , Produtos Finais de Glicação Avançada , Células Endoteliais da Veia Umbilical Humana , Humanos , Óxido de Magnésio
20.
Fa Yi Xue Za Zhi ; 38(3): 319-323, 2022 Jun 25.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-36221820

RESUMO

OBJECTIVES: To find the appropriate method for age estimation for different ages and sexes. METHODS: The costal cartilage, sternum and pubic symphysis of 91 unknowns from 2000 to 2020 from the Forensic Department of the Criminal Investigation Team of Shanghai Public Security Bureau were collected. Costal cartilage, sternal and pubic symphysis inferences were used to estimate the age, and the consistency between the estimated results and the actual physiological age of the unknowns was tested. The accuracy of age estimation of different samples was compared, and the relationship between accuracy and age and sex was analyzed. RESULTS: Using the costal cartilage method, the inference errors of males, females and the whole population under 40 years old were (0.608±2.298) years, (0.429±1.867) years and (0.493±2.040) years, while those over 40 years old were (-1.707±3.770) years, (-3.286±4.078) years and (-2.625±4.029) years. The differences between different age groups in these three populations were statistically significant (P<0.05). Using the sternum method, the inference errors of males and females under the age of 40 were (0.921±3.019) years and (0.452±1.451) years, while those over the age of 40 were (-5.903±5.088) years and (-1.429±2.227) years. The differences between different age groups in males and females were statistically significant (P<0.05). Using the pubic symphysis method, the inference errors of males and females under 40 years old were (-0.204±1.876) years and (0.238±2.477) years, while those over 40 years old were (1.500±2.156) years and (-2.643±4.270) years. The differences between different age groups in males and females were statistically significant (P<0.05). Using the sternum method and pubic symphysis method for age estimation of over 40 years old, the difference between different sexes was statistically significant (P<0.05). CONCLUSIONS: All three methods of age estimation are stable and effective and more accurate for people under 40 years old. For age estimation of unknowns over 40 years old, the pubic symphysis method is preferred in males and the sternum method is preferred in females.


Assuntos
Determinação da Idade pelo Esqueleto , Sínfise Pubiana , Adulto , Determinação da Idade pelo Esqueleto/métodos , Pré-Escolar , China , Feminino , Antropologia Forense/métodos , Medicina Legal , Humanos , Lactente , Masculino , Sínfise Pubiana/anatomia & histologia
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