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1.
BMC Pregnancy Childbirth ; 24(1): 109, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317068

RESUMO

BACKGROUND: Hypertensive disorders of pregnancy (HDP) is the most common cause of indicated preterm delivery, but the impact of prenatal steroid exposure on the outcomes of preterm infants born to HDP mothers, who may be at risk for intrauterine hypoxia-ischemia, remains uncertain. The study objective is to evaluate the mortality and morbidities in HDP for very preterm infants (VPIs) exposed to different course of ANS. METHODS: This is a prospective cohort study comprising infants with < 32 weeks gestation born to women with HDP only from 1 Jan. 2019 to 31 Dec. 2021 within 40 participating neonatal intensive care units (NICUs) in Sino-northern network. ANS courses included completed, partial, repeated, and no ANS. Univariate and multivariable analyses were performed on administration of ANS and short-term outcomes before discharge. RESULTS: Among 1917 VPIs born to women with HDP only, 987(51.4%) received a complete course of ANS within 48 h to 7 days before birth, 560(29.2%) received partial ANS within 24 h before delivery, 100(5.2%) received repeat ANS and 270 (14.1%) did not receive any ANS. Compared to infants who received complete ANS, infants unexposed to ANS was associated with higher odds of death (AOR 1.85; 95%CI 1.10, 3.14), Severe Neurological Injury (SNI) or death (AOR 1.68; 95%CI 1.29,3.80) and NEC or death (AOR 1.78; 95%CI 1.55, 2.89), the repeated ANS group exhibits a significant negative correlation with the duration of oxygen therapy days (correlation coefficient - 18.3; 95%CI-39.2, -2.1). However, there were no significant differences observed between the full course and partial course groups in terms of outcomes. We can draw similar conclusions in the non-SGA group, while the differences are not significant in the SGA group. From KM curve, it showed that the repeated group had the highest survival rate, but the statistical analysis did not indicate a significant difference. CONCLUSIONS: Even partial courses of ANS administered within 24 h before delivery proved to be protective against death and other morbidities. The differences mentioned above are more pronounced in the non-SGA group. Repeat courses demonstrate a trend toward protection, but this still needs to be confirmed by larger samples.


Assuntos
Hipertensão Induzida pela Gravidez , Doenças do Prematuro , Pré-Eclâmpsia , Lactente , Recém-Nascido , Gravidez , Humanos , Feminino , Recém-Nascido Prematuro , Estudos Prospectivos , Hipertensão Induzida pela Gravidez/epidemiologia , Corticosteroides/uso terapêutico , Doenças do Prematuro/prevenção & controle , Idade Gestacional , Retardo do Crescimento Fetal , Morbidade
2.
Poult Sci ; 103(3): 103430, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38219535

RESUMO

Eimeria tenella, an obligate intracellular apicomplexan parasite, is the major causative agent of chicken coccidiosis. Some epidermal growth factor (EGF)-like domain-containing proteins of other members of apicomplexan parasites have been reported to contribute to parasite survival. To date, however, EGF-like domain-containing proteins of E. tenella are not well studied. In this study, a gene fragment that encodes 4 EGF-like domains of E. tenella microneme protein 7 (EGF-EtMIC7) was amplified and expressed using an Escherichia coli expression system. Following generation of polyclonal antibodies that recognize recombinant EGF-EtMIC7 (rEGF-EtMIC7), the expression of EtMIC7 in sporozoites and merozoites was examined. Moreover, its roles in cellular regulation were investigated. The native EtMIC7 in E. tenella sporozoites and merozoites was detected by using Western blot and indirect immunofluorescence assays. rEGF-EtMIC7 could activate Akt, whereas blockade of EGF receptor (EGFR) failed to induce Akt phosphorylation. Compared with the control group, LMH cells treated with rEGF-EtMIC7 showed increased cell proliferation and expressed higher levels of B cell leukemia/lymphoma 2 (BCL-2). These findings contribute to the better understanding of parasite-host interactions at the molecular level during E. tenella infection.


Assuntos
Eimeria tenella , Merozoítos , Animais , Fator de Crescimento Epidérmico , Esporozoítos , Micronema , Proteínas Proto-Oncogênicas c-akt , Galinhas , Fatores de Transcrição
3.
China Pharmacy ; (12): 837-841, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013546

RESUMO

OBJECTIVE To explore the characteristics and regulations of adverse drug reactions (ADR) caused by apatinib, and to provide a reference for the safe use of apatinib in clinic. METHODS Case and group reports on ADR and safety evaluation of apatinib were retrieved from Chinese and English databases such as CNKI, Wanfang medical network, VIP and PubMed since its listing in 2014, literature data were extracted and statistically analyzed after screening. RESULTS Totally 101 cases were included, involving 221 ADR. In the above cases, the male-to-female ratio was 1.24∶1, with the highest proportion of patients aged 51 to 70 years, most of the patients were given a dose of 500 mg or more, and the patients given low dose of apatinib combined with other antitumor drugs were also likely to have ADR. One to two types of adverse reaction were the most common, while the types could reach up to six. Most ADR occurred within 30 days after medication, and the systems/organs involved were mainly the cardiovascular system damage,skin and its accessories damage, gastrointestinal system damage and urinary system damage; the main clinical manifestations were hypertension/aggravation,hand-foot syndrome,abdominal pain diarrhea and albuminuria, etc. Hypertension/aggravation, hand-foot syndrome and myelosuppression were the most common serious ADR. Most ADR could be improved/cured by suspension of administration, dose downregulation and symptomatic treatment. All 4 patients who died had underlying diseases, and their ECOG scores all ≥2 points. Special ADR (such as reversible posterior encephalopathy syndrome, psychiatric disorders, and cognitive impairment) were mostly caused by apatinib itself, or may be caused by apatinib in combination with the primary or underlying disease. CONCLUSIONS Advanced age, large dose, combination medication, underlying diseases and poor physical condition might be the high risks for ADR caused by apatinib. It is recommended to monitor the blood pressure,urine protein and skin of hands and feet of all patients with medication on a daily basis,pay attention to the occurrence of special ADR, and timely detect abnormal states and give effective intervention,so as to avoid the aggravation of ADR and other secondary ADR.

4.
J Med Internet Res ; 25: e40735, 2023 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-37982411

RESUMO

BACKGROUND: Knee osteoarthritis (OA) is a chronic, degenerative bone and joint disease. It can lead to major pressure to the quality of life and mental health of patients, and also brings a serious economic burden to society. However, it is difficult for patients with knee OA to access rehabilitation when discharging from the hospital. Internet-based rehabilitation is one of the promising telemedicine strategies for the improvement of knee OA, but the effect of different telerehabilitation strategies on knee OA is not clear. OBJECTIVE: The aim of this systematic review and meta-analysis was to identify telerehabilitation strategies attributing to the improvement of pain and physical function outcomes in patients with knee OA. METHODS: We reviewed and analyzed telerehabilitation strategies from randomized controlled trials (RCTs) comparing telerehabilitation with conventional treatment or usual care. For each strategy, we examined whether RCTs that applied the telerehabilitation strategy resulted in a significant improvement in pain or physical function compared with conventional treatment or usual care. RESULTS: We included 6 RCTs (n=734) incorporating 8 different telerehabilitation strategies. The duration of the interventions ranged from 1 to 48 weeks, and sample sizes ranged from 20 to 350 patients. The results showed that RCTs that provided telerehabilitation were found to be more effective than conventional treatments for improving pain (P=.003; standardized mean difference [SMD] -0.21, 95% CI -0.35 to -0.07), but not physical function (P=.24; SMD -0.09, 95% CI -0.25 to 0.06). Furthermore, this systematic review and meta-analysis indicated that there is no significant correlation between different telerehabilitation strategies and the pain and physical function of patients with knee OA. CONCLUSIONS: This systematic review and meta-analysis showed that telerehabilitation programs could relieve pain but not improve physical function for patients with knee OA. These results indicated that telerehabilitation is beneficial for the implementation of home rehabilitation exercises for patients with knee OA, thereby reducing the economic burden of health. However, there were limitations in terms of the number of search results and the number of studies that were eligible for this review and meta-analysis. Therefore, the results need to be interpreted with caution, and more high-quality studies with large samples are needed to focus on the long-term outcomes of telerehabilitation for patients with knee OA to address this limitation.


Assuntos
Osteoartrite do Joelho , Telemedicina , Telerreabilitação , Humanos , Osteoartrite do Joelho/reabilitação , Telerreabilitação/métodos , Dor , Terapia por Exercício/métodos
5.
J Glob Health ; 13: 04059, 2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37227033

RESUMO

Background: Published guidelines on decision-making and resuscitation of extremely preterm infants primarily focus on high-income countries. For rapidly industrializing ones like China, there is a lack of population-based data for informing prenatal management and practice guidelines. Methods: The Sino-northern Neonatal Network conducted a prospective multi-centre cohort study between 1 January 2018 and 31 December 2021. Infants with a gestational age (GA) between 22 (postnatal age in days = 0) and 28 (postnatal age in days = 6) admitted to 40 tertiary NICUs in northern China were included and evaluated for death or severe neurological injury before discharge. Results: For all extremely preterm infants (n = 5838), the proportion of admission to the neonatal was 4.1% at 22-24 weeks, 27.2% at 25-26 weeks, and 75.2% at 27 and 28 weeks. Among 2228 infants admitted to the NICU, 216 (11.1%) were still elected for withdrawal of care (WIC) due to non-medical factors. Survival rates without severe neurological injury were 6.7% for infants at 22-23 weeks, 28.0% at 24 weeks, 56.7% at 24 weeks, 61.7% at 25 weeks, 79.9% at 26 weeks, and 84.5% at 27 and 28 weeks. Compared with traditional criterion at 28 weeks, the relative risk for death or severe neurological injury were 1.53 (95% confidence interval (CI) = 1.26-1.86) at 27 weeks, 2.32 (95% CI = 1.73-3.11) at 26 weeks, 3.62 (95% CI = 2.43-5.40) at 25 weeks, and 8.91 (95% CI = 4.69-16.96) at 24 weeks. The NICUs with higher proportion of WIC also had a higher rate of death or severe neurological injury after maximal intensive care (MIC). Conclusions: Compared to the traditional threshold of 28 weeks, more infants received MIC after 25 weeks, leading to significant increases in survival rates without severe neurological injury. Therefore, the resuscitation threshold should be gradually adjusted from 28 to 25 weeks based on reliable capacity. Registration: China Clinical Trials Registry. ID: ChiCTR1900025234.


Assuntos
Lactente Extremamente Prematuro , Ressuscitação , Humanos , Masculino , Feminino , Taxa de Sobrevida , Estudos Prospectivos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , China
6.
Neural Regen Res ; 18(9): 2075-2081, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36926734

RESUMO

Recent studies have shown that a 9-hour fast in mice reduces the amount of time spent immobile in the forced swimming test. However, whether 9-hour fasting has therapeutic effects in female mice with depressive symptoms has not been established. Therefore, in this study, we simulated perimenopausal depression via an ovariectomy in mice, and subjected them to a single 9-hour fasting 7 days later. We found that the ovariectomy increased the time spent immobile in the forced swimming test, inhibited expression of the mammalian target of rapamycin complex 1 signaling pathway in the hippocampus and prefrontal cortex, and decreased the density of dendritic spines in the hippocampus. The 9-hour acute fasting alleviated the above-mentioned phenomena. Furthermore, all of the antidepressant-like effects of 9-hour fasting were reversed by an inhibitor of the mammalian target of rapamycin complex 1. Electrophysiology data showed a remarkable increase in long-term potentiation in the hippocampal CA1 of the ovariectomized mice subjected to fasting compared with the findings in the ovariectomized mice not subjected to fasting. These findings show that the antidepressant-like effects of 9-hour fasting may be related to the activation of the mammalian target of the rapamycin complex 1 signaling pathway and synaptic plasticity in the mammalian hippocampus. Thus, fasting may be a potential treatment for depression.

7.
World J Pediatr ; 19(6): 577-585, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36604390

RESUMO

OBJECTIVES: We aimed to evaluate the risk factors for moderate-to-severe bronchopulmonary dysplasia (BPD) and focus on discussing its relationship with the duration of initial invasive mechanical ventilation (IMV) in very preterm neonates less than 32 weeks of gestational age (GA). METHODS: We performed a prospective cohort study involving infants born at 23-31 weeks of GA who were admitted to 47 different neonatal intensive care unit (NICU) hospitals in China from January 2018 to December 2021. Patient data were obtained from the Sina-northern Neonatal Network (SNN) Database. RESULTS: We identified 6538 very preterm infants, of whom 49.5% (3236/6538) received initial IMV support, and 12.6% (823/6538) were diagnosed with moderate-to-severe BPD symptoms. The median duration of initial IMV in the moderate-to-severe BPD group was 26 (17-41) days, while in the no or mild BPD group, it was 6 (3-10) days. The incidence rate of moderate-to-severe BPD and the median duration of initial IMV were quite different across different GAs. Multivariable logistic regression analysis showed that the onset of moderate-to-severe BPD was significantly associated with the duration of initial IMV [adjusted odds ratio (AOR): 1.97; 95% confidence interval (CI): 1.10-2.67], late-onset neonatal sepsis (LONS), and patent ductus arteriosus (PDA). CONCLUSION: In this multicenter cohort study, the duration of initial IMV was still relatively long in very premature infants, and the longer duration of initial IMV accounts for the increased risk of moderate-to-severe BPD.


Assuntos
Displasia Broncopulmonar , Doenças do Prematuro , Lactente , Recém-Nascido , Humanos , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/epidemiologia , Displasia Broncopulmonar/terapia , Estudos Prospectivos , Respiração Artificial , Recém-Nascido Prematuro , Estudos de Coortes , Idade Gestacional , Fatores de Risco , Estudos Retrospectivos
8.
Front Vet Sci ; 9: 1053701, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36478946

RESUMO

A protein of Eimeria tenella (encoded by the locus ETH_00028350) homologous to Toxoplasma gondii dense granule protein 9, designated as EtHGRA9 hereafter, was reported to be expressed in all life cycle stages of E. tenella. However, no data are currently available regarding its functional properties. In the present study, a recombinant vector harboring a 741 bp gene segment encoding the mature form of EtHGRA9 was constructed and transfected into leghorn male hepatoma (LMH) cells. Then, transcriptomic analysis of the transfected LMH cells was carried out by using a high-throughput RNA-seq technology. The LMH cells overexpressing EtHGRA9 was validated by means of Western blotting as well as indirect immunofluorescence staining. The results demonstrated that the expression of 547 genes (275 upregulated genes and 272 downregulated genes) was altered by EtHGRA9. The quantitative real-time polymerase chain reaction (qRT-PCR) validation of the ten genes with differential expression between the two groups was consistent with the transcriptome analysis. According to pathway enrichment analysis for the obtained differentially expressed genes, seven pathways were significantly affected by EtHGRA9, such as cytokine-cytokine receptor interaction, MAPK signaling pathway, and protein processing in endoplasmic reticulum. Our data reveal several possible roles of EtHGRA9 in immune or inflammatory responses, which paves the way for a better understanding of the molecular interplay between E. tenella and its host.

9.
Poult Sci ; 101(11): 102109, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36067577

RESUMO

Though genome sequencing of Eimeria tenella predicts more than 8,000 genes, the molecular functions of many proteins remain unknown. In this study, the coding region corresponding to the mature peptide of a hypothetical protein of E. tenella (ETH_00023950) was amplified and expressed in a bacterial system. Following preparation of polyclonal antibody that recognizes ETH_00023950, the expression of ETH_00023950 in merozoites was examined. Meanwhile, we determined the transcriptomic responses of the leghorn male hepatoma (LMH) cells to its expression. Sequencing analysis showed that one single nucleotide polymorphism and one indel of ETH_00023950 of E. tenella SD-01 strain were found compared with that of the UK reference Houghton strain, leading to a frame shift and a premature stop codon. The expression of ETH_00023950 in E. tenella merozoites was confirmed by indirect immunofluorescence and Western blot analysis. Transcriptomic analysis showed that ETH_00023950 altered the expression of 2,680 genes (321 downregulated genes and 2,359 upregulated genes) in LMH cells. The RNA-sequencing data were consistent with the results of the quantitative real-time polymerase chain reaction (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that differentially expressed transcripts were significantly related to 8 pathways, including oxidative phosphorylation and TGF-beta signaling pathway. These findings contribute to understanding host-pathogen interaction and secondary bacterial infections related to E. tenella.


Assuntos
Coccidiose , Eimeria tenella , Animais , Masculino , Eimeria tenella/genética , Galinhas/genética , Transcriptoma , Merozoítos/genética , Perfilação da Expressão Gênica/veterinária , Coccidiose/veterinária , Coccidiose/metabolismo
10.
Front Vet Sci ; 9: 956040, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36016802

RESUMO

Though a number of Eimeria tenella rhoptry kinase family proteins have been identified, little is known about their molecular functions. In the present study, the gene fragment encoding the matured peptide of E. tenella rhoptry kinase family protein 17 (EtROP17) was used to construct a recombinant vector, followed by transfection into leghorn male hepatoma (LMH) cells. Then, the transcriptional changes in the transfected cells were determined by RNA-seq. The expression of EtROP17 in LMH cells was validated by both Western blot and indirect immunofluorescence analysis. Our analysis showed that EtROP17 altered the expression of 309 genes (114 downregulated genes and 195 upregulated genes) in LMH cells. The quantitative real-time polymerase chain reaction (qRT-PCR) results of the selected differentially expressed genes (DEGs) were consistent with the RNA-seq data. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that DEGs were significantly enriched in nine pathways, such as toll-like receptor signaling pathway, ECM-receptor interaction, intestinal immune network for IgA production and focal adhesion. These findings reveal several potential roles of EtROP17, which contribute to understanding the molecular mechanisms underlying the host-parasite interplay.

11.
Front Pharmacol ; 13: 824420, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35677435

RESUMO

A major type of serious mood disorder, depression is currently a widespread and easily overlooked psychological illness. With the low side effects of natural products in the treatment of diseases becoming the pursuit of new antidepressants, natural Chinese medicine products have been paid more and more attention for their unique efficacy in improving depression. In a view from the current study, the positive antidepressant effects of berberine are encouraging. There is a lot of work that needs to be done to accurately elucidate the efficacy and mechanism of berberine in depression. In this review, the relevant literature reports on the treatment of depression and anxiety by berberine are updated, and the potential pharmacological mechanism of berberine in relieving depression has also been discussed.

12.
Insect Sci ; 29(4): 1105-1119, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34723412

RESUMO

Nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome P450 reductase (CPR) is involved in the metabolism of endogenous and exogenous substances, and detoxification of insecticides. RNA interference (RNAi) of CPR in certain insects causes developmental defects and enhanced susceptibility to insecticides. However, the CPR of Acyrthosiphon pisum has not been characterized, and its function is still not understood. In this study, we investigated the biochemical functions of A. pisum CPR (ApCPR). ApCPR was found to be transcribed in all developmental stages and was abundant in the embryo stage, and in the gut, head, and abdominal cuticle. After optimizing the dose and silencing duration of RNAi for downregulating ApCPR, we found that ApCPR suppression resulted in a significant decrease in the production of cuticular and internal hydrocarbon contents, and of cuticular waxy coatings. Deficiency in cuticular hydrocarbons (CHCs) decreased the survival rate of A. pisum under desiccation stress and increased its susceptibility to contact insecticides. Moreover, desiccation stress induced a significant increase in ApCPR mRNA levels. We further confirmed that ApCPR participates in CHC production. These results indicate that ApCPR modulates CHC production, desiccation tolerance, and insecticide susceptibility in A. pisum, and presents a novel target for pest control.


Assuntos
Afídeos , Inseticidas , Animais , Afídeos/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Dessecação , Regulação para Baixo , Resistência a Inseticidas/genética , Inseticidas/farmacologia , NADPH-Ferri-Hemoproteína Redutase/genética , NADPH-Ferri-Hemoproteína Redutase/metabolismo , Pisum sativum/metabolismo , Interferência de RNA
13.
J Cardiovasc Pharmacol ; 78(1): e65-e76, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33929390

RESUMO

ABSTRACT: There is increasing evidence that angiotensin (1-7) [Ang (1-7)] is an endogenous biologically active component of the renin-angiotensin system. However, the role of the Ang (1-7)-MasR axis in postresuscitation myocardial dysfunction (PRMD) and its associated mechanism are still unclear. In this study, we investigated the effect of the Ang (1-7)-MasR axis on myocardial injury after cardiac arrest-cardiopulmonary resuscitation-restoration of spontaneous circulation. We established a model of oxygen/glucose deprivation-reperfusion in myocardial cells in vitro and a rat model of cardiac arrest-cardiopulmonary resuscitation-restoration of spontaneous circulation in vivo. The cell apoptosis rate and the expression of the superoxide anion 3-nitrotyrosine were decreased in the Ang (1-7) group in vitro and in vivo. The mean arterial pressure was decreased, whereas +LVdp/dtmax and -LVdp/dtmax were increased in rats in the Ang (1-7) group. The mRNA and protein levels of Ang II type 1 receptor, MasR, phosphoinositide 3-kinase, protein kinase B, and endothelial nitric oxide synthase were increased in the Ang (1-7) group in vivo. These results indicate that the Ang (1-7)-MasR axis can alleviate PRMD by reducing myocardial tissue damage and oxidative stress through activation of the phosphoinositide 3-kinase-protein kinase B-endothelial nitric oxide synthase signaling pathway and provide a new direction for the clinical treatment of PRMD.


Assuntos
Angiotensina I/farmacologia , Reanimação Cardiopulmonar/efeitos adversos , Parada Cardíaca/terapia , Cardiopatias/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Parada Cardíaca/fisiopatologia , Cardiopatias/enzimologia , Cardiopatias/etiologia , Cardiopatias/fisiopatologia , Masculino , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/patologia , Proto-Oncogene Mas/agonistas , Proto-Oncogene Mas/genética , Proto-Oncogene Mas/metabolismo , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 2 de Angiotensina/genética , Receptor Tipo 2 de Angiotensina/metabolismo , Retorno da Circulação Espontânea , Transdução de Sinais , Função Ventricular Esquerda/efeitos dos fármacos , Pressão Ventricular/efeitos dos fármacos
14.
Insect Sci ; 28(4): 1018-1032, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32558147

RESUMO

Cuticular hydrocarbons form a barrier that protects terrestrial insects from water loss via the epicuticle. Lipophorin loads and transports lipids, including hydrocarbons, from one tissue to another. In some insects, the lipophorin receptor (LpR), which binds to lipophorin and accepts its lipid cargo, is essential for female fecundity because it mediates the incorporation of lipophorin by developing oocytes. However, it is unclear whether LpR is involved in the accumulation of cuticular hydrocarbons and its precise role in aphid reproduction remains unknown. We herein present the results of our molecular characterization, phylogenetic analysis, and functional annotation of the pea aphid (Acyrthosiphon pisum) LpR gene (ApLpR). This gene was transcribed throughout the A. pisum life cycle, but especially during the embryonic stage and in the abdominal cuticle. Furthermore, we optimized the RHA interference (RNAi) parameters by determining the ideal dose and duration for gene silencing in the pea aphid. We observed that the RNAi-based ApLpR suppression significantly decreased the internal and cuticular hydrocarbon contents as well as adult fecundity. Additionally, a deficiency in cuticular hydrocarbons increased the susceptibility of aphids to desiccation stress, with decreased survival rates under simulated drought conditions. Moreover, ApLpR expression levels significantly increased in response to the desiccation treatment. These results confirm that ApLpR is involved in transporting hydrocarbons and protecting aphids from desiccation stress. Furthermore, this gene is vital for aphid reproduction. Therefore, the ApLpR gene of A. pisum may be a novel RNAi target relevant for insect pest management.


Assuntos
Afídeos , Hidrocarbonetos/metabolismo , Receptores Citoplasmáticos e Nucleares , Animais , Afídeos/genética , Afídeos/fisiologia , Fertilidade/genética , Genes de Insetos , Proteínas de Insetos/genética , Controle de Pragas/tendências , Filogenia , Interferência de RNA , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Estresse Fisiológico/genética
15.
J Insect Physiol ; 127: 104160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33137328

RESUMO

Apolipoprotein D (ApoD) is a lipocalin superfamily member that plays important roles in the transport of small hydrophobic molecules, lipid metabolism, and stress resistance. Cuticular hydrocarbons are the principal components of the epicuticular lipid layer and play a critical role in water retention against environmental desiccation stress; however, the mechanism underlying the role of ApoD in insect desiccation tolerance has not yet been elucidated. Here, we report the molecular constitution, functional analysis, and phylogenetic relationship of the ApoD gene in Acyrthosiphon pisum (ApApoD). We found that ApApoD was transcribed throughout the life cycle of A. pisum, but was prominently expressed in the embryonic period and abdominal cuticle. In addition, we optimized the dose and silencing duration of RNAi, observing that RNAi against ApApoD significantly reduced the levels of both internal and cuticular hydrocarbons and adult fecundity. Moreover, cuticular hydrocarbon deficiency increased the sensitivity of aphids to desiccation stress and reduced their survival time, while desiccation stress significantly increased ApApoD expression. Together, it is confirmed that ApApoD participates in regulating cuticular hydrocarbon content of aphids under desiccation stress and is crucial for aphid reproduction. Therefore, the ApApoD gene of A. pisum may be a potential target for RNAi-based insect pest control due to its involvement in cuticular hydrocarbon accumulation and reproduction.


Assuntos
Afídeos/fisiologia , Apolipoproteínas D/metabolismo , Dessecação , Fertilidade/genética , Proteínas de Insetos/metabolismo , Animais , Ninfa/crescimento & desenvolvimento , Ninfa/fisiologia
16.
Life Sci ; 256: 117824, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32445758

RESUMO

OBJECTIVES: To investigate the effect of glucagon-like peptide-1 (GLP-1) receptor and glucose dependent insulinotrophic polypeptide (GIP) receptor dual agonist DA-JC4 on alleviating Parkinson's disease (PD) and unveil related cellular mechanisms. METHODS: Rotenone was injected to generate a rat PD model, on which the effect of DA-JC4 on motor functions was evaluated by rotational behavioral assay and open field test. The survival of dopaminergic neurons was analyzed, in addition to assays for mitochondrial stress and quantification of neurotransmitter levels using high performance liquid chromatography (HPLC). In cultured hippocampal neurons, the effect of DA-JC4 on mitochondrial stress and related cellular mechanism was analyzed by Flow cytometry, western blotting and reactive oxygen species (ROS). RESULTS: DA-JC4 significantly improved motor functions in PD rats, and elevated levels of major neurotransmitters. By histological analysis, DA-JC4 protected dopaminergic neurons from rotenone-induced cell death, which was associated with reduced mitochondrial stress. Experiments in cultured rat hippocampal neurons validated the neuroprotective role of DA-JC4 against cell apoptosis and mitochondrial stress induced by rotenone. The protective effect of DA-JC4 was later found to be dependent on AKT/JNK signal pathway, as treatment using AKT inhibitor or JNK activator abolished such effects. CONCLUSION: Our results showed that the dual agonist of GLP-1/GIP receptor could ameliorate motor dysfunctions of PD by protecting dopaminergic neurons which was mediated by relieved mitochondrial stress and apoptosis via AKT/JNK signal pathway.


Assuntos
Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Fármacos Neuroprotetores/farmacologia , Transtornos Parkinsonianos/tratamento farmacológico , Receptores dos Hormônios Gastrointestinais/agonistas , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Neurônios Dopaminérgicos/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Transtornos Parkinsonianos/fisiopatologia , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Rotenona/toxicidade
17.
Front Oncol ; 9: 1153, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781485

RESUMO

Natural compounds are highly effective anticancer chemotherapeutic agents, and the targets of plant-derived anticancer agents have been widely reported. In this review, we focus on the main signaling pathways of apoptosis, proliferation, invasion, and metastasis that are regulated by polyphenols, alkaloids, saponins, and polysaccharides. Alkaloids primarily affect apoptosis-related pathways, while polysaccharides primarily target pathways related to proliferation, invasion, and metastasis. Other compounds, such as flavonoids and saponins, affect all of these aspects. The association between compound structures and signaling pathways may play a critical role in drug discovery.

18.
Biomed Pharmacother ; 113: 108759, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30856539

RESUMO

OBJECTIVE: The objective of the present study is to investigate the inhibitory effects of sinomenine (SIN) on angiogenesis in a collagen-induced arthritis (CIA) mouse model. METHODS: Arthritis assessments for all mice were recorded. The histopathological assessments were performed following haematoxylin and eosin (HE) staining. Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) analyses were used to detect the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and angiopoietin 1 (ANG-1) in the serum and in the membrane. Immunohistochemistry was employed to detect the synovium microvessel density (MVD). RESULTS: Compared with the CIA model group, SIN significantly ameliorated swelling and erythema extension, decreased the arthritis index, reduced inflammation, cartilage damage and bone erosion, and lessened the number of CD31 positive cells on the synovium. Moreover, the levels of HIF-1α, VEGF and ANG-1 in the synovium and in the peripheral serum were increased in the untreated CIA model group but were significantly reduced in the 30 mg/kg, 100 mg/kg and 300 mg/kg SIN treatment groups. CONCLUSION: SIN could mitigate CIA by inhibiting angiogenesis, and the mechanism may associate with the HIF-1α-VEGF-ANG-1 axis. Additionally, our study provides a referable experimental basis for the use of SIN for the treatment of rheumatoid arthritis.


Assuntos
Inibidores da Angiogênese/farmacologia , Artrite Experimental/tratamento farmacológico , Morfinanos/farmacologia , Neovascularização Patológica/tratamento farmacológico , Angiopoietina-1/metabolismo , Animais , Antirreumáticos/farmacologia , Artrite Experimental/fisiopatologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/fisiopatologia , Colágeno/toxicidade , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Patológica/patologia , Membrana Sinovial/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
19.
Mol Neurobiol ; 55(6): 4731-4744, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28717968

RESUMO

Although several studies have shown that type-2 cannabinoid receptor (CB2R) is involved in Alzheimer's disease (AD) pathology, the effects of CB2R on AD-like tau abnormal phosphorylation and its underlying mechanism remain unclear. Herein, we employed the CB2R-/- mice as the animal model to explore roles of CB2R in regulating tau phosphorylation and brain function. We found that CB2R-/- mice display AD-like tau hyperphosphorylation, hippocampus-dependent memory impairment, increase of GSK3ß activity, decrease of AMPK and Sirt1 activity and mitochondria dysfunction. Interestingly, AICAR or resveratrol (AMPK agonist) could efficiently rescue most alternations caused by solo deletion of CB2R in CB2R-/- mice. Moreover, JWH133, a selective agonist of CB2R, reduces phosphorylation of tau and GSK3ß activity in HEK293 tau cells, but the effects of JWH133 on phosphorylation of tau and GSK3ß disappeared while blocking AMPK activity with compound C or Prkaa2-RNAi. Taken together, our study indicated that deletion of CB2R induces behavior damage and AD-like pathological alternation via AMPK/GSK3ß pathway. These findings proved that CB2R/AMPK/GSK3ß pathway can be a promising new drug target for AD.


Assuntos
Adenilato Quinase/metabolismo , Doença de Alzheimer/patologia , Deleção de Genes , Glicogênio Sintase Quinase 3 beta/metabolismo , Transtornos da Memória/patologia , Receptor CB2 de Canabinoide/genética , Proteínas tau/metabolismo , Envelhecimento/patologia , Doença de Alzheimer/complicações , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacologia , Animais , Canabinoides/farmacologia , Ativação Enzimática , Hipocampo/metabolismo , Hipocampo/patologia , Memória , Transtornos da Memória/complicações , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mitocôndrias/metabolismo , Fosforilação , Receptor CB2 de Canabinoide/agonistas , Receptor CB2 de Canabinoide/deficiência , Receptor CB2 de Canabinoide/metabolismo , Resveratrol/farmacologia , Ribonucleotídeos/farmacologia , Transdução de Sinais
20.
Mol Neurobiol ; 54(3): 1992-2002, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-26910815

RESUMO

Transient receptor potential-canonical 1 (TRPC1) plays a crucial role in neuronal survival, nerve regeneration, and protects neurons from neurotoxic injury, but it is not reported whether or how TRPC1 may affect learning and memory. Here, we found that TRPC1 knockout did not significantly affect the spatial learning and memory ability when the mice were housed in standard cages (SC). Interestingly, after the mice were exposed to environmental enrichment (EE) for 4 weeks, TRPC1 knockout abolished the EE-induced spatial memory enhancement, LTP induction, and neurogenesis in hippocampal DG subset. By stereotaxic infusion of the recombinant adeno-associated viruses (rAAV)-TRPC1 into the hippocampal DG subsets bilaterally, we observed that the EE-associated neurogenesis, LTP induction and the cognitive enhancement were efficiently rescued in TRPC1 knockout mice. EE increased the phosphorylation levels of ERK, p38, and cyclic AMP response element-binding protein (CREB) in wild-type mice, whereas the activation of ERK and CREB was not seen in TRPC1 knockout mice, and the phosphorylation of p38 was same in EE-TRPC1-/- and WT-EE. Finally, EE increased TRPC1 expression and overexpression of TRPC1 increased neurogenesis and activated ERK/CREB pathway in the wild-type mice. These findings suggest that TRPC1 is indispensable for the EE-induced hippocampal neurogenesis and cognitive enhancement.


Assuntos
Cognição/fisiologia , Meio Ambiente , Hipocampo/metabolismo , Neurogênese/fisiologia , Canais de Cátion TRPC/biossíntese , Canais de Cátion TRPC/deficiência , Animais , Reação de Fuga/fisiologia , Hipocampo/citologia , Hipocampo/patologia , Abrigo para Animais , Masculino , Transtornos da Memória/metabolismo , Transtornos da Memória/patologia , Camundongos , Camundongos da Linhagem 129 , Camundongos Knockout , Distribuição Aleatória
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