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1.
Heliyon ; 10(9): e30344, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38726112

ABSTRACT

Background: Major depressive disorder (MDD) is a widespread health issue in many countries, which has an extremely negative impact on the health of children and adolescents in particular. In the context of depression and metabolic disorders, dyslipidemia and metabolism-related problems become more prominent comorbidities. However, they continue to be the main barrier to the successful recovery of the clinical progress. In this study we investigated the rate of dyslipidemia, additional risk factors among Chinese children and adolescents with MDD, and association of the suicidal behavior with lipid levels. Methods: The study took 756 people from the Third People's Hospital of Fuyang between January 2020 and December 2021, aged between 8 and 18, with major depressive disorders diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). We determined the FBG (fasting blood glucose) and lipid parameters in all subjects and also investigated the history of suicidal ideation, the cases of attempted suicide, and the scores of depressive symptoms. Sociodemographic and clinical data were gathered and analyzed using the SPSS-23.0 version. Results: The prevalence of hypercholesterolemia, hypertriglyceridemia, high LDL-C, and low HDL-C were 5.42 % (41/756), 10.58 % (80/756), 3.84 % (29/756) and 5.42 % (41/756) respectively. For hypercholesterolemia and hypertriglyceridemia, they were positive associated with suicidal ideation and suicide attempts, and the positive correlation is shown between low HDL-C levels and suicide attempts. Nevertheless, non-ideation and inversely suicidal attempts were not discovered among high-LDL-C subjects. Logistic analysis showed that high levels of FBG (OR = 2.86, 95 % CI: 1.31-6.25, P = 0.008) and worse LDL-C (OR = 357.82, 95 % CI: 66.16-1935.10, P < 0.001) are the independent associated factors for hypercholesterolemia. More hospitalizations (OR = 1.89, 95 % CI: 1.07-3.35, P = 0.028), obesity (OR = 2.55, 95 % CI: 1.25-5.18, P = 0.010), high levels of TC (OR = 2.15, 95 % CI: 1.03-4.48, P = 0.042), and higher doses of antidepressants (OR = 1.02, 95 % CI: 1.00-1.04, P = 0.029) were independently associated factors for hypertriglyceridemia, while high levels of HDL-C (OR = 0.11, 95 % CI: 0.04-0.31, P < 0.001) were protective factors. In addition, high levels of TC (OR = 113.94, 95 % CI: 20.01-648.85) were statistically different (P < 0.001) and suggested that the factor was significantly related to high LDL-C. Meanwhile, older age (OR = 1.25, 95 % CI: 1.02-1.52, P = 0.030) and high levels of TG (OR = 3.00, 95 % CI: 1.98-4.55, P < 0.001) were independent factors contributing to low HDL-C. Conclusion: The high prevalence of dyslipidemia in childhood and adolescence among children and adolescents with depressive disorder has become a public health issue. Hypercholesterolemia and hypertriglyceridemia showed a positive correlation with suicidal thoughts and suicidal attempts. Monitoring the incidence of suicidal thoughts and attempts among them would carry some predictor meaning in therapy and for jumping back to health.

2.
J Inflamm Res ; 16: 4451-4460, 2023.
Article in English | MEDLINE | ID: mdl-37842191

ABSTRACT

Objective: This study aims to investigate the association between the systemic immune-inflammatory index (SII) and suicide attempt (SA) in children and adolescents with first-episode, drug-naïve Major Depressive Disorder (MDD) during the COVID-19 pandemic. Methods: A retrospective study was conducted on 263 MDD patients hospitalized at the Third Hospital of Fuyang City between 2020 and 2022. Patients were categorized into two groups based on the presence of previous SA. The study compared the differences in SII and clinical characteristics between the two groups and used the receiver operating characteristic (ROC) curve to determine the optimal critical value of SII and the area under the curve. Binary logistic regression was used to analyze the independent risk factors for SA. Results: Compared with the patients without SA history, the patients with a personal history of SA had a higher mean HDRS scores (Z=-2.369, p=0.018), higher mean neutrophil count (Z=-2.870, p=0.004), higher mean platelet count (Z=-2.155, p=0.031), and higher mean SII (Z=-3.170, p=0.002). The optimal critical SII determined by the ROC curve was 548.15 (sensitivity = 63.2%, specificity = 83.1%), and the area under the curve was 0.661. After adjusting for gender, age, BMI, illness duration and HDRS score, the risk of total SA in patients with high SII was 8.296 times higher than in those with low SII (OR = 8.296, 95% CI: 3.803-18.095, P < 0.001), The risk of recent SA was 13.922 times higher in patients with high SII than in those with low SII (OR = 13.922, 95% CI: 5.587-34.693, p < 0.001). However, high SII was not a risk factor for past SA (OR = 0.547, 95% CI: 0.062-4.842, P=0.587). Conclusion: SII may be an inexpensive, easily accessible strategy that can assist in determining suicide risk in adolescents with MDD.

3.
Front Psychiatry ; 14: 1159889, 2023.
Article in English | MEDLINE | ID: mdl-37275977

ABSTRACT

Objective: To evaluate the clinical value of systemic immune-inflammation index (SII) based on peripheral blood neutrophil, lymphocyte, and platelet count in evaluating the subtype and severity of depression in patients with depressive disorder. Methods: This retrospective cohort study was conducted in the Third People's Hospital of Fuyang City from January 1, 2020 to December 31, 2022. The data included sociodemographic information at admission, clinical data, discharge diagnosis and inflammatory markers. Patients were divided into low SII group and high SII group according to the optimal threshold of SII determined by receiver operating characteristic curve (ROC curve). Binary logistic regression was used to analyze the correlation between moderate/major depression and SII level. Results: Compared to the low SII group, the high SII group had a higher age level (χ2 = 7.663, p = 0.006), more smokers (χ2 = 9.458, p = 0.002), more moderate/major depression patients (χ2 = 45.645, p < 0.001), and a higher proportion of patients with accompanying somatic symptoms (χ2 = 14.867, p < 0.001). In the final logistic regression model, after controlling for confounding factors, SII at admission was significantly associated with moderate/major depression [ß =1.285, p < 0.001; odds ratio (95% confidence intervals) = 3.614 (2.693-4.850)]. Patients with high SII scores were 3.614 times more likely to have moderate/severe depression than those with low SII scores. We propose a cut-off value of SII =540.78 (sensitivity = 36.4% and specificity = 80.3%) according to the maximum Youden index. Conclusion: Our research indicates that SII may be a useful, repeatable, convenient, and affordable index to identify moderate/major depression in depressive disorder.

4.
Eur Phys J Plus ; 138(5): 383, 2023.
Article in English | MEDLINE | ID: mdl-37192841

ABSTRACT

Air transportation systems are a foundational infrastructure for the human's society. The lack of systematic and detailed investigation on a large amount of records for air flights has blocked seriously the deep understanding of the systems. By using the American domestic passenger flight records from 1995 to 2020, we constructed the air transportation networks and calculated the betweenness and the eigenvector centralities for the airports. It is found that in terms of eigenvector centrality, 15-30% airports in the unweighted and undirected networks behave anomalous. The anomalies disappear after considering the information of link weights or directionalites. Five widely used models for air transportation networks are evaluated, results for which tell us that the spatial constraints are required to eliminate the anomalies detected by the eigenvector centrality, and provide us some references for selecting the parameters in the models. We hope the empirical benchmarks reported in this paper can stimulate much more works on theoretical models for air transportation systems.

5.
Front Psychiatry ; 14: 1130437, 2023.
Article in English | MEDLINE | ID: mdl-37215666

ABSTRACT

Background: The high rates of obesity and suicide have become serious public health problems worldwide, especially in children and adolescents with major depressive disorder (MDD). This research aimed to explore the rates of underweight, overweight or obesity, suicidal ideation and attempted suicide in hospitalized children and adolescents with MDD. Then, we analyzed the correlation between underweight or obesity and suicidal ideation and attempted suicide, and finally obtained the independent influencing factors of underweight or obesity. Methods: A total of 757 subjects in the Third People's Hospital of Fuyang from January 2020 to December 2021 were enrolled in this study. According to the underweight, overweight and obesity screening table for school-age children and adolescents published and implemented by the health industry standard of China, all subjects were divided into different body mass index (BMI) categories. We measured fasting blood glucose (FBG) and lipid levels in all subjects and assessed suicidal ideation, attempted suicide, and the severity of depressive symptoms. The socio-demographic and clinical data were collected and analyzed by SPSS 22.0. Results: The rates of underweight, overweight, obesity, suicidal ideation and attempted suicide were 8.2% (62/757), 15.5% (117/757), 10.4% (79/757), 17.2% (130/757), and 9.9% (75/757), respectively. Correlation analysis indicated that BMIs level was positively correlated with age, age of first hospitalization, total duration of disease, number of hospitalizations, FBG, TG (triglyceride), TC (total cholesterol), LDL (low density lipoprotein), and negatively correlated with HDL (high density lipoprotein). Binary logistic regression analysis showed that male and high level of HDL were risk factors for MDD inpatients with underweight, while high level of TG was a protective factor. Meanwhile, higher levels of FBG, TG and CGI-S were risk factors and suicidal ideation and high dose of antidepressant drugs were protective factors for obesity in children and adolescents with MDD. Conclusion: The prevalence of underweight, obesity, suicidal ideation and attempted suicide were high in children and adolescents with MDD, and severe depressive symptoms are independent risk factors for obesity, while suicidal ideation and high dose of antidepressants may be protective factors for obesity.

6.
Insects ; 14(1)2023 Jan 09.
Article in English | MEDLINE | ID: mdl-36661991

ABSTRACT

The descending neurons (DNs) of insects connect the brain and thoracic ganglia and play a key role in controlling insect behaviors. Here, a comprehensive investigation of the distribution and organization of the DNs in the brain of Helicoverpa armigera (Hübner) was made by using backfilling from the neck connective combined with immunostaining techniques. The maximum number of DN somata labeled in H. armigera was about 980 in males and 840 in females, indicating a sexual difference in DNs. All somata of DNs in H. armigera were classified into six different clusters, and the cluster of DNd was only found in males. The processes of stained neurons in H. armigera were mainly found in the ventral central brain, including in the posterior slope, ventral lateral protocerebrum, lateral accessory lobe, antennal mechanosensory and motor center, gnathal ganglion and other small periesophageal neuropils. These results indicate that the posterior ventral part of the brain is vital for regulating locomotion in insects. These findings provide a detailed description of DNs in the brain that could contribute to investigations on the neural mechanism of moth behaviors.

7.
Insect Sci ; 30(1): 109-124, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35608046

ABSTRACT

The mechanism of sex pheromone reception in the male cotton bollworm Helicoverpa armigera has been extensively studied because it has become an important model system for understanding insect olfaction. However, the pathways of pheromone processing from the antenna to the primary olfactory center in H. armigera have not yet been clarified. Here, the physiology and morphology of male H. armigera olfactory sensory neurons (OSNs) were studied using single sensillum recording along with anterograde filling and intracellular recording with retrograde filling. OSNs localized in type A sensilla responded to the major pheromone component cis-11-hexadecenal, and the axonal terminals projected to the cumulus (Cu) of the macroglomerular complex (MGC). The OSNs in type B sensilla responded to the behavioral antagonist cis-9-tetradecenal, and the axonal terminals projected to the dorsomedial anterior (DMA) unit of the MGC. In type C sensilla, there were 2 OSNs: one that responded to cis-9-tetradecenal and cis-11-hexadecenol with the axonal terminals projecting to the DMA, and another that responded to the secondary pheromone components cis-9-hexadecenal and cis-9-tetradecenal with the axonal terminals projecting to the dorsomedial posterior (DMP) unit of the MGC. Type A and type B sensilla also housed the secondary OSNs, which were silent neurons with axonal terminals projected to the glomerulus G49 and DMP. Overall, the neural pathways that carry information on attractiveness and aversiveness in response to female pheromone components in H. armigera exhibit distinct projections to the MGC units.


Subject(s)
Moths , Olfactory Receptor Neurons , Sex Attractants , Male , Female , Animals , Olfactory Receptor Neurons/metabolism , Moths/physiology , Pheromones , Sex Attractants/metabolism
8.
Membranes (Basel) ; 12(11)2022 Nov 16.
Article in English | MEDLINE | ID: mdl-36422148

ABSTRACT

Membrane separation technology is applied in natural gas processing, while a high-performance membrane is highly in demand. This paper considers the bright future of functionalized graphene oxide (GO) membranes in acid gas removal from natural gas. By molecular simulations, the adsorption and diffusion behaviors of several unary gases (N2, CH4, CO2, H2S, and SO2) are explored in the 1,4-phenylenediamine-2-sulfonate (PDASA)-doped GO channels. Molecular insights show that the multilayer adsorption of acid gases evaluates well by the Redlich-Peterson model. A tiny amount of PDASA promotes the solubility coefficient of CO2 and H2S, respectively, up to 4.5 and 5.3 mmol·g-1·kPa-1, nearly 2.5 times higher than those of a pure GO membrane, which is due to the improved binding affinity, great isosteric heat, and hydrogen bonds, while N2 and CH4 only show single-layer adsorption with solubility coefficients lower than 0.002 mmol·g-1·kPa-1, and their weak adsorption is insusceptible to PDASA. Although acid gas diffusivity in GO channels is inhibited below 20 × 10-6 cm2·s-1 by PDASA, the solubility coefficient of acid gases is certainly high enough to ensure their separation efficiency. As a result, the permeabilities (P) of acid gases and their selectivities (α) over CH4 are simultaneously improved (PCO2 = 7265.5 Barrer, αCO2/CH4 = 95.7; P(H2S+CO2) = 42075.1 Barrer, αH2S/CH4 = 243.8), which outperforms most of the ever-reported membranes. This theoretical study gives a mechanistic understanding of acid gas separation and provides a unique design strategy to develop high-performance GO membranes toward efficient natural gas processing.

9.
Front Neuroanat ; 16: 844171, 2022.
Article in English | MEDLINE | ID: mdl-35360650

ABSTRACT

The fall armyworm Spodoptera frugiperda (S. frugiperda) (Lepidoptera: Noctuidae) is a worldwide, disruptive, agricultural pest species. The larvae of S. frugiperda feed on seedling, leave, and kernel of crops with chewing mouthparts, resulting in reduced crop yields. Serotonin is an important biogenic amine acting as a neural circuit modulator known to mediate lots of behaviors including feeding in insects. In order to explore the serotonergic neural network in the nervous system of larval S. frugiperda, we performed immunohistochemical experiments to examine the neuropil structure of the brain and the gnathal ganglion with antisynapsin and to examine their serotonergic neurons with antiserotonin serum. Our data show that the brain of larval S. frugiperda contains three neuromeres: the tritocerebrum, the deutocerebrum, and the protocerebrum. The gnathal ganglion also contains three neuromeres: the mandibular neuromere, the maxillary neuromere, and the labial neuromere. There are about 40 serotonergic neurons in the brain and about 24 serotonergic neurons in the gnathal ganglion. Most of these neurons are wide-field neurons giving off processes in several neuropils of the brain and the gnathal ganglion. Serotonergic neuron processes are mainly present in the protocerebrum. A pair of serotonergic neurons associated with the deutocerebrum has arborizations in the contralateral antennal lobe and bilateral superior lateral protocerebra. In the gnathal ganglion, the serotonergic neuron processes are also widespread throughout the neuropil and some process projections extend to the tritocerebrum. These findings on the serotonergic neuron network in larval S. frugiperda allow us to explore the important roles of serotonin in feeding and find a potential approach to modulate the feeding behavior of the gluttonous pest and reduce its damage.

10.
Front Physiol ; 13: 839559, 2022.
Article in English | MEDLINE | ID: mdl-35295575

ABSTRACT

Large numbers of chemosensory genes have been identified in the peripheral sensory organs of the pest Mythimna separata (Walker) to increase our understanding of chemoreception-related molecular mechanisms and to identify molecular targets for pest control. Chemosensory-related genes are expressed in various tissues, including non-sensory organs, and they play diverse roles. To better understand the functions of chemosensory-related genes in non-sensory organs, transcriptomic analyses of M. separata brains were performed. In total, 29 odorant-binding proteins (OBPs) and 16 chemosensory proteins (CSPs) putative genes were identified in the transcriptomic data set. The further examination of sex- and tissue-specific expression using RT-PCR suggested that eight OBPs (OBP5, -7, -11, -13, -16, -18, -21, and -24) and eight CSPs (CSP2-4, -8, CSP10-12, and -15) genes were expressed in the brain. Furthermore, bands representing most OBPs and CSPs could be detected in antennae, except for a few that underwent sex-biased expression in abdomens, legs, or wings. An RT-qPCR analysis of the expression profiles of six OBPs (OBP3-5, -9, -10, and -16) and two CSPs (CSP3 and CSP4) in different tissues and sexes indicated that OBP16 was highly expressed in male brain, and CSP3 and CSP4 were female-biased and highly expressed in brain. The expression levels of OBP5 and OBP10 in brain were not significantly different between the sexes. The findings expand our current understanding of the expression patterns of OBPs and CSPs in M. separata sensory and non-sensory tissues. These results provide valuable reference data for exploring novel functions of OBPs and CSPs in M. separata and may help in developing effective biological control strategies for managing this pest by exploring novel molecular targets.

11.
Insect Sci ; 29(3): 730-748, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34427391

ABSTRACT

The sense of taste plays a crucial role in herbivorous insects by discriminating nutrients from complex plant metabolic compounds. The peripheral coding of taste has been thoroughly studied in many insect species, but the central gustatory pathways are poorly described. In the present study, we characterized single neurons in the gnathal ganglion of Helicoverpa armigera larvae using the intracellular recording/staining technique. We identified different types of neurons, including sensory neurons, interneurons, and motor neurons. The morphologies of these neurons were largely diverse and their arborizations seemingly covered the whole gnathal ganglion. The representation of the single neurons responding to the relevant stimuli of sweet and bitter cues showed no distinct patterns in the gnathal ganglion. We postulate that taste signals may be processed in a manner consistent with the principle of population coding in the gnathal ganglion of H. armigera larvae.


Subject(s)
Lepidoptera , Moths , Animals , Herbivory , Larva/physiology , Sensory Receptor Cells/metabolism , Taste/physiology
12.
Front Physiol ; 12: 662978, 2021.
Article in English | MEDLINE | ID: mdl-33967833

ABSTRACT

The host acceptances of insects can be determined largely by detecting plant metabolites using insect taste. In the present study, we investigated the gustatory sensitivity and feeding behaviors of two closely related caterpillars, the generalist Helicoverpa armigera (Hübner) and the specialist H. assulta (Guenée), to different plant metabolites by using the single sensillum recording technique and the dual-choice assay, aiming to explore the contribution of plant metabolites to the difference of diet breadth between the two species. The results depicted that the feeding patterns of caterpillars for both plant primary and secondary metabolites were significantly different between the two Helicoverpa species. Fructose, glucose, and proline stimulated feedings of the specialist H. assulta, while glucose and proline had no significant effect on the generalist H. armigera. Gossypol and tomatine, the secondary metabolites of host plants of the generalist H. armigera, elicited appetitive feedings of this insect species but drove aversive feedings of H. assulta. Nicotine and capsaicin elicited appetitive feedings of H. assulta, but drove aversive feedings of H. armigera. For the response of gustatory receptor neurons (GRNs) in the maxillary styloconic sensilla of caterpillars, each of the investigated primary metabolites induced similar responding patterns between the two Helicoverpa species. However, four secondary metabolites elicited different responding patterns of GRNs in the two species, which is consistent with the difference of feeding preferences to these compounds. In summary, our results of caterpillars' performance to the plant metabolites could reflect the difference of diet breadth between the two Helicoverpa species. To our knowledge, this is the first report showing that plant secondary metabolites could drive appetitive feedings in a generalist insect species, which gives new insights of underscoring the adaptation mechanism of herbivores to host plants.

13.
Chem Biol Interact ; 316: 108925, 2020 Jan 25.
Article in English | MEDLINE | ID: mdl-31838054

ABSTRACT

Hemangioma is one of the commonest benign vascular tumors among children. Propranolol is the first-line therapeutic drug for hemangioma. However, the effects and mechanisms of propranolol in hemangioma have not been thoroughly elaborated. In this study, the effects and mechanisms of propranolol were explored using hemangioma-derived endothelial cells (HemECs). The expression of GLUT1 were determined by immunofluorescence staining. qRT-PCR assay was conducted to detect the mRNA expressions of angiopoietin-2 (Ang-2) and Tie-2. Western blot assay was carried out to measure the protein levels of Ang-2, Tie-2, protein kinase-B (Akt) and phospholyrated-Akt (p-Akt). Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) assay and Western blot of Ki67 protein level. Cell apoptosis was measured by flow cytometry analysis and Western blot of Bax and Bcl-2 levels. We found that propranolol inhibited proliferation and induced apoptosis in human umbilical vein endothelial cells (HUVECs) and HemECs. Moreover, propranolol inhibited the expressions of Ang-2 and Tie-2 in HUVECs and HemECs. Functional analysis revealed that Ang-2 attenuated the effects of propranolol on HemEC proliferation and apoptosis. Mechanistical analysis showed that propranolol inhibited the Akt pathway by regulating Ang-2 expression in HemECs. Futhermore, inhibition of the Akt pathway attenuated the effects of Ang-2 on proliferation and apoptosis in HemECs. In conclusion, propranolol inhibited proliferation and induced apoptosis of HemECs via Akt pathway by down-regulating Ang-2 expression, which contributes to our understanding on the pathogenesis of hemangioma and promotes the development of therapeutic approaches for hemangioma.


Subject(s)
Angiopoietin-2/metabolism , Apoptosis/drug effects , Cell Proliferation/drug effects , Propranolol/pharmacology , Signal Transduction/drug effects , Angiopoietin-2/genetics , Cell Line , Down-Regulation/drug effects , Endothelial Cells/cytology , Endothelial Cells/metabolism , Hemangioma/metabolism , Hemangioma/pathology , Human Umbilical Vein Endothelial Cells , Humans , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism
14.
Life Sci ; 239: 116946, 2019 Dec 15.
Article in English | MEDLINE | ID: mdl-31610202

ABSTRACT

AIMS: Infantile hemangioma (IH) is the most common vascular neoplasm in infant and young children. Long non-coding RNAs (lncRNAs) are known to be associated with IH. This study aims to investigate the role and underlying mechanism of lncRNA-MALAT1 in IH. MAIN METHODS: qRT-PCR was used to quantify the expressions of MALAT1, miR-424, and MEKK3 in IH tissues. The cell proliferation, apoptosis, migration, invasion, and tube formation ability were assessed by MTT assay, colony formation assay, flow cytometric analysis, transwell assay and tube formation assay, respectively. The interaction among MALAT1, miR-424 and MEKK3 was evaluated by luciferase reporter assay. Immunohistochemistry (IHC) and Western blotting were utilized to evaluate the expression levels of MEKK3, Ki-67 and NF-κB pathway-related proteins both in vitro and in vivo. KEY FINDINGS: In IH tissues, MALAT1 and MEKK3 were overexpressed while miR-424 was down-regulated. Silencing MALAT1 or overexpression of miR-424 significantly inhibited the IH cell proliferation, migration and tube formation, but promoted the cell apoptosis. Knockdown of MALAT1 suppressed the expression of MEKK3 and inactivated the IKK/NF-κB pathway by sponging miR-424. Overexpression of MEKK3 in HemEcs reversed the impact of knockdown of MALAT1 and overexpression of miR-424 on the cell proliferation, apoptosis, migration, invasion and tube formation rate. The tumor xenografts experiments demonstrated that silencing MALAT1 significantly inhibited the tumor growth in vivo and Ki-67 in the tumor tissues was also significantly suppressed. SIGNIFICANCE: MALAT1 promoted the IH progression through inhibiting miR-424 to activate MEKK3-mediated IKK/NF-κB pathway, suggesting that MALAT1, miR-424 and MEKK3 could be used as potential targets to improve IH treatment efficiency.


Subject(s)
Hemangioma/metabolism , MAP Kinase Kinase Kinase 3/metabolism , MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , Animals , Apoptosis/genetics , Carcinogenesis/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Female , Hemangioma/genetics , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/genetics , NF-kappa B/metabolism , Neoplasm Invasiveness , RNA, Long Noncoding/genetics , RNA, Small Interfering/genetics , Signal Transduction , Xenograft Model Antitumor Assays
15.
Biomed Pharmacother ; 111: 236-243, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30584986

ABSTRACT

Hemangioma (HA) is one of the commonest benign vascular neoplasms of infancy. Inhibitor of differentiation 1 (ID-1) has been reported to be an oncogene in multiple cancers. However, the role of ID-1 and its molecular mechanism in HA progression have not been elucidated. In the present study, we found that ID-1 expression at mRNA and protein levels was up-regulated in HA-derived endothelial cells (HDECs). Knockdown of ID-1 inhibited proliferation, facilitated apoptosis, and enhanced propranolol cytotoxicity in HDECs. Knockdown of ID-1 decreased the protein levels of phospholyrated protein kinase-B (Akt) and phospholyrated mammalian target of rapamycin (mTOR). Inhibition of PI3K/Akt/mTOR pathway by LY294002 abrogated ID-1-mediated pro-proliferation and anti-apoptosis effects in HDECs. In conclusion, knockdown of ID-1 suppressed proliferation and promoted apoptosis by inactivating phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR signaling in HDECs, shedding light on the function of ID-1 in HA progression and highlighting the therapeutic value of ID-1 for HA.


Subject(s)
Cell Proliferation/physiology , Hemangioma/metabolism , Inhibitor of Differentiation Protein 1/deficiency , Phosphatidylinositol 3-Kinase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , TOR Serine-Threonine Kinases/metabolism , Apoptosis/physiology , Endothelial Cells/metabolism , Gene Knockdown Techniques/methods , Hemangioma/prevention & control , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Inhibitor of Differentiation Protein 1/genetics , Phosphoinositide-3 Kinase Inhibitors , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Signal Transduction/physiology , TOR Serine-Threonine Kinases/antagonists & inhibitors
16.
Chem Biol Interact ; 294: 28-33, 2018 Oct 01.
Article in English | MEDLINE | ID: mdl-30130526

ABSTRACT

Infantile hemangioma (IH) is one of the most common benign vascular tumors of infancy. Propranolol has been recently introduced for the treatment of IH. However, the mechanism of protective effect has not been fully understood. In this study, hemangioma-derived endothelial cells (HemECs) were isolated and treated with propranolol. The cell viability was measured by MTT assay, and the cell cycle arrest was detected using flow cytometry. Cell invasion was determined using transwell assay. The expressions of matrix metalloproteinase (MMP)-2, MMP-9, Delta-like 4 (DLL4), Notch1, Akt, p-Akt, and vascular endothelial growth factor (VEGF) were detected using western blot. HemECs were incubated with recombinant human DLL4 (rhDLL4) to investigate the role of DLL4/Notch1 in the effect of propranolol. The results showed that propranolol inhibited cell viability of HemECs in a time-dependent manner. Propranolol suppressed cell proliferation of HemECs by arresting cell progression at G0/G1 phase. Propranolol inhibited the invasion ability of HemECs and reduced the expression levels of MMP-2 and MMP-9 in HemECs. Besides, propranolol treatment blocked the DLL4/Notch1 and Akt signaling and inhibited VEGF expression in HemECs. Treatment with rhDLL4 activated the Akt signaling and attenuated the effect of propranolol on HemECs. Our data indicated that propranolol inhibited the cell proliferation and invasion of HemECs. The effect was possibly involved in the DLL4/Notch1/Akt signaling pathway.


Subject(s)
Cell Proliferation/drug effects , Propranolol/pharmacology , Signal Transduction/drug effects , Adaptor Proteins, Signal Transducing , Calcium-Binding Proteins , Cell Movement/drug effects , Cells, Cultured , Down-Regulation/drug effects , Endothelial Cells/cytology , Endothelial Cells/drug effects , Endothelial Cells/metabolism , G1 Phase Cell Cycle Checkpoints/drug effects , Hemangioma/metabolism , Hemangioma/pathology , Humans , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Receptor, Notch1/metabolism , Recombinant Proteins/biosynthesis , Recombinant Proteins/isolation & purification , Recombinant Proteins/pharmacology , Vascular Endothelial Growth Factor A/metabolism
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