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Leukemia stem cells (LSC) are a rare population capable of limitless self-renewal and are responsible for the initiation, maintenance, and relapse of leukemia. Elucidation of the mechanisms underlying the regulation of LSC function could provide novel treatment strategies. Here, we show that TWIST1 is extremely highly expressed in the LSC of MLL-AF9+ acute myeloid leukemia (AML), and its upregulation is positively regulated by KDM4C in a H3K9me3 demethylation-dependent manner. We further demonstrate that TWIST1 is essential for the viability, dormancy, and self-renewal capacities of LSC, and that it promotes the initiation and maintenance of MLL-AF9-mediated AML. In addition, TWIST1 directly interacts and collaborates with HOXA9 in inducing AML in mice. Mechanistically, TWIST1 exerts its oncogenic function by activating the WNT5a/RAC1 axis. Collectively, our study uncovers a critical role of TWIST1 in LSC function and provides new mechanistic insights into the pathogenesis of MLL-AF9+ AML.
Assuntos
Leucemia Mieloide Aguda , Proteína 1 Relacionada a Twist , Camundongos , Animais , Proteína 1 Relacionada a Twist/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Células-Tronco , Proteína de Leucina Linfoide-Mieloide/genética , Células-Tronco Neoplásicas/patologiaRESUMO
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with dyslipidemia, and the connection between dyslipidemia and remnant cholesterol (RC), a component of triglyceride-rich lipoproteins, remains enigmatic. METHODS: In this cross-sectional study, our primary aim was to investigate the role of RC in the progression of NAFLD and to provide robust evidence of RC's involvement in the pathogenesis of NAFLD. We enrolled 2800 NAFLD patients from the National Health and Nutrition Examination Survey (NHANES). Logistic regression was employed to examine the relationship between serum RC levels and liver stiffness, while receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic capability of RC. RESULTS: RC exhibited an independent correlation with the extent of liver stiffness, with odds ratios (OR) of 1.02 for liver steatosis (p = 0.014) and 1.02 for liver fibrosis (p = 0.014). To predict NAFLD, the optimal RC thresholds were 17.25 mg/dL for males and 15.25 mg/dL for females in the case of liver steatosis. For advanced liver fibrosis, the best thresholds were 17.25 mg/dL for males and 16.25 mg/dL for females. CONCLUSIONS: RC demonstrated a positive correlation with the degree of liver stiffness and exhibited superior diagnostic efficacy for liver steatosis and fibrosis compared to other cholesterol indicators.
Elevated serum remnant cholesterol (RC) levels may serve as a potential indicator of metabolic diseases, including nonalcoholic fatty liver disease (NAFLD). The connection between serum RC and NAFLD has been previously undervalued. In our investigation, we examined 2800 NAFLD patients from the National Health and Nutrition Examination Survey (NHANES). Our cross-sectional study has revealed a more distinct relationship between RC and the degree of liver stiffness, especially concerning liver steatosis when compared to other cholesterol indicators. Recognizing RC's significant role in metabolic disorders may lead to innovative approaches for diagnosing and treating NAFLD patients.
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Dislipidemias , Hepatopatia Gordurosa não Alcoólica , Masculino , Feminino , Humanos , Inquéritos Nutricionais , Estudos Transversais , Cirrose Hepática , Dislipidemias/complicaçõesRESUMO
The amplitude of low-frequency fluctuation (ALFF) describes the regional intensity of spontaneous blood-oxygen-level-dependent signal in resting-state functional magnetic resonance imaging (fMRI). How the fMRI-ALFF relates to the amplitude in electrophysiological signals remains unclear. We here aimed to investigate the neural correlates of fMRI-ALFF by comparing the spatial difference of amplitude between the eyes-closed (EC) and eyes-open (EO) states from fMRI and magnetoencephalography (MEG), respectively. By synthesizing MEG signal into amplitude-based envelope time course, we first investigated 2 types of amplitude in MEG, meaning the amplitude of neural activities from delta to gamma (i.e. MEG-amplitude) and the amplitude of their low-frequency modulation at the fMRI range (i.e. MEG-ALFF). We observed that the MEG-ALFF in EC was increased at parietal sensors, ranging from alpha to beta; whereas the MEG-amplitude in EC was increased at the occipital sensors in alpha. Source-level analysis revealed that the increased MEG-ALFF in the sensorimotor cortex overlapped with the most reliable EC-EO differences observed in fMRI at slow-3 (0.073-0.198 Hz), and these differences were more significant after global mean standardization. Taken together, our results support that (i) the amplitude at 2 timescales in MEG reflect distinct physiological information and that (ii) the fMRI-ALFF may relate to the ALFF in neural activity.
Assuntos
Magnetoencefalografia , Córtex Sensório-Motor , Imageamento por Ressonância Magnética/métodos , Encéfalo/fisiologia , Descanso/fisiologia , EletroencefalografiaRESUMO
BACKGROUND: We previously demonstrated that Shaziling and Yorkshire pigs differ in growth rate and meat quality. However, the molecular mechanisms responsible for such phenotypic differences remain unclear. In the present study, we performed a transcriptomic analysis of 36 longissimus dorsi (LM) and 36 soleus (SM) muscle samples from Shaziling and Yorkshire pigs at six postnatal stages (30, 60, 90, 150, 210 and 300 days) to explore the differences in postnatal skeletal muscle of Shaziling and Yorkshire pigs. RESULTS: Muscle morphological changes and the number of differentially expressed genes indicated the two stages of 60-90 days and 150-210 days were critical for the muscle growth and development in Shaziling pigs. Genes such as FLNC, COL1A1, NRAP, SMYD1, TNNI3, CRYAB and PDLIM3 played vital roles in the muscle growth, and genes such as CCDC71L, LPIN1, CPT1A, UCP3, NR4A3 and PDK4 played dominant roles in the lipid metabolism. Additionally, in contrast to the LM, the percentage of slow-twitch muscle fibers in the SM of both breeds consistently decreased from 30 to 150 days of age, but there was a significant rebound at 210 days of age. However, the percentage of slow-twitch muscle fibers in the SM of Shaziling pigs was higher than that in Yorkshire pigs, which may be associated with the calcium signaling pathway and the PPARß/δ signaling pathway. CONCLUSION: The present study detected two critical periods and many functional genes for the muscle growth and development of Shaziling pigs, and showed differences in muscle fiber characteristics between Shaziling and Yorkshire pigs. © 2024 Society of Chemical Industry.
Assuntos
Desenvolvimento Muscular , Músculo Esquelético , Transcriptoma , Animais , Músculo Esquelético/metabolismo , Músculo Esquelético/crescimento & desenvolvimento , Suínos/crescimento & desenvolvimento , Suínos/genética , Suínos/metabolismo , Desenvolvimento Muscular/genética , Análise de Sequência de RNA , Masculino , Carne/análise , Feminino , Proteínas Musculares/genética , Proteínas Musculares/metabolismoRESUMO
The sirtuin family, a group of NAD+-dependent class 3 histone deacetylases (HDACs), was extensively studied initially as a group of longevity genes that are activated in caloric restriction and act in concert with nicotinamide adenine dinucleotides to extend the lifespan. Subsequent studies have found that sirtuins are involved in various physiological processes, including cell proliferation, apoptosis, cell cycle progression, and insulin signaling, and they have been extensively studied as cancer genes. In recent years, it has been found that caloric restriction increases ovarian reserves, suggesting that sirtuins may play a regulatory role in reproductive capacity, and interest in the sirtuin family has continued to increase. The purpose of this paper is to summarize the existing studies and analyze the role and mechanism of SIRT1, a member of the sirtuin family, in regulating ovarian function. Research and review on the positive regulation of SIRT1 in ovarian function and its therapeutic effect on PCOS syndrome.
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Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy for which there is an unmet need for novel treatment strategies. Here, we characterize the growth arrest and DNA damage-inducible gene gamma (GADD45g) as a novel tumor suppressor in AML. We show that GADD45g is preferentially silenced in AML, especially in AML with FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations and mixed-lineage leukemia (MLL)-rearrangements, and reduced expression of GADD45g is correlated with poor prognosis in patients with AML. Upregulation of GADD45g impairs homologous recombination DNA repair, leading to DNA damage accumulation, and dramatically induces apoptosis, differentiation, and growth arrest and increases sensitivity of AML cells to chemotherapeutic drugs, without affecting normal cells. In addition, GADD45g is epigenetically silenced by histone deacetylation in AML, and its expression is further downregulated by oncogenes FLT3-ITD and MLL-AF9 in patients carrying these genetic abnormalities. Combination of the histone deacetylase 1/2 inhibitor romidepsin with the FLT3 tyrosine kinase inhibitor AC220 or the bromodomain inhibitor JQ1 exerts synergistic antileukemic effects on FLT3-ITD+ and MLL-AF9+ AML, respectively, by dually activating GADD45g. These findings uncover hitherto unreported evidence for the selective antileukemic role of GADD45g and provide novel strategies for the treatment of FLT3-ITD+ and MLL-AF9+ AML.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Leucemia Mieloide Aguda , Proteínas Supressoras de Tumor/biossíntese , Regulação para Cima/efeitos dos fármacos , Animais , Azepinas/farmacologia , Benzotiazóis/farmacologia , Depsipeptídeos/farmacologia , Células HL-60 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Mutação , Compostos de Fenilureia/farmacologia , Células THP-1 , Triazóis/farmacologia , Proteínas Supressoras de Tumor/genética , Células U937 , Tirosina Quinase 3 Semelhante a fms/genética , Tirosina Quinase 3 Semelhante a fms/metabolismoRESUMO
AIMS: The aims of this study were to evaluate and compare the pharmacokinetic profiles and bioequivalence of two tablet formulations of methylprednisolone (test formulation: Zhejiang Xianju Pharmaceutical Co., Ltd., China; reference formulation: Medrol, Pfizer Italia SRL) in healthy Chinese subjects under fasting and fed conditions. MATERIALS AND METHODS: Subjects were randomly allocated to either the fasting group or the fed group and also to one of two sequences (test-reference or reference-test), according to which they received a single 16-mg dose of the test or reference methylprednisolone tablet in the study periods. Blood samples were collected pre dose and at intervals up to 16 hours after administration. Plasma methylprednisolone concentrations were determined using a validated liquid chromatography tandem mass spectrometry method. The safety of the medications was monitored throughout the study. The primary pharmacokinetic parameters measured were Cmax, AUC0-t, and AUC0-∞. RESULTS: A total of 56 subjects were enrolled, and all completed the study. The 90% confidence intervals for Cmax, AUC0-t, and AUC0-∞, measured under both fasting and fed conditions, fell within the acceptable range for bioequivalence of 80 - 125%. Analysis of variance showed that there were no signiï¬cant differences in the primary pharmacokinetic parameters (Cmax, AUC0-t, and AUC0-∞) between the test and reference formulation measured under both fasted and fed conditions. No serious or unexpected adverse drug reactions occurred during the study period. CONCLUSION: The test methylprednisolone 16 mg tablet produced in China is bioequivalent to the reference formulation (Medrol) in healthy Chinese subjects measured under both fasting and fed conditions. Both formulations were well tolerated by all study participants.
Assuntos
Metilprednisolona , Equivalência Terapêutica , Humanos , Área Sob a Curva , Estudos Cross-Over , População do Leste Asiático , Jejum , Voluntários Saudáveis , Comprimidos , Metilprednisolona/farmacocinéticaRESUMO
The frequent mutation of KRAS oncogene in some of the most lethal human cancers has spurred incredible efforts to develop KRAS inhibitors, yet only one covalent inhibitor for the KRASG12C mutant has been approved to date. New venues to interfere with KRAS signaling are desperately needed. Here, we report a "localized oxidation-coupling" strategy to achieve protein-specific glycan editing on living cells for disrupting KRAS signaling. This glycan remodeling method exhibits excellent protein and sugar specificity and is applicable to different donor sugars and cell types. Attachment of mannotriose to the terminal galactose/N-acetyl-D-galactosamine epitopes of integrin αv ß3 , a membrane receptor upstream of KRAS, blocks its binding to galectin-3, suppresses the activation of KRAS and downstream effectors, and mitigates KRAS-driven malignant phenotypes. Our work represents the first successful attempt to interfere with KRAS activity by manipulating membrane receptor glycosylation.
Assuntos
Neoplasias Pulmonares , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Neoplasias Pulmonares/patologia , Mutação , Polissacarídeos , Proteínas Proto-Oncogênicas p21(ras)/genética , Transdução de SinaisRESUMO
OBJECTIVE: This study was conducted to assess the pharmacokinetic and safety profiles between a new oral formulation of terazosin hydrochloride capsule compared with the brand-name drug. MATERIALS AND METHODS: A randomized, open-label, single-dose, 2-period crossover study under fasting or fed conditions was conducted in healthy Chinese subjects. 24 individuals were selected, respectively. Each subject was randomized at the beginning to receive a 2-mg capsule of the test or the reference terazosin during the first period and then received the alternate formulation during the second period following a 1-week washout period. Blood samples were collected at pre-dose and up to 60 hours after administration. Plasma terazosin was quantified by a validated LC-MS/MS method. RESULTS: 48 healthy subjects were enrolled, and 47 completed the study. Cmax, AUC0-t, and AUC0-∞ were similar and the 90% CIs for the geometric mean ratios of these parameters between the two groups were all bounded within the predefined bioequivalence criterion of 80 - 125% under both fasting and fed conditions. Throughout the study period, a total of 30 treatment-emergent adverse events (TEAEs) were reported under fasting condition. 35 TEAEs were observed under fed conditions. No serious adverse event was observed. CONCLUSION: The test and reference formulations of terazosin were bioequivalent and well tolerated under both fasting and fed conditions.
Assuntos
Jejum , Espectrometria de Massas em Tandem , Área Sob a Curva , China , Cromatografia Líquida , Estudos Cross-Over , Voluntários Saudáveis , Humanos , Prazosina/análogos & derivados , Comprimidos , Equivalência TerapêuticaRESUMO
Mammalian adipose tissue can be divided into white and brown adipose tissue based on its colour, location, and cellular structure. Certain conditions, such as sympathetic nerve excitement, can induce the white adipose adipocytes into a new type of adipocytes, known as beige adipocytes. The process, leading to the conversion of white adipocytes into beige adipocytes, is called white fat browning. The dynamic balance between white and beige adipocytes is closely related to the body's metabolic homeostasis. Studying the signal transduction pathways of the white fat browning might provide novel ideas for the treatment of obesity and alleviation of obesity-related glucose and lipid metabolism disorders. This article aimed to provide an overview of recent advances in understanding white fat browning and the role of BAT in lipid metabolism.
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Metabolismo dos Lipídeos , Termogênese , Adipócitos Brancos/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Metabolismo Energético , Humanos , Mamíferos , Obesidade/metabolismo , Termogênese/fisiologiaRESUMO
Long-chain noncoding RNAs (lncRNAs) are RNAs that do not code for proteins, widely present in eukaryotes. They regulate gene expression at multiple levels through different mechanisms at epigenetic, transcription, translation, and the maturation of mRNA transcripts or regulation of the chromatin structure, and compete with microRNAs for binding to endogenous RNA. Adipose tissue is a large and endocrine-rich functional tissue in mammals. Excessive accumulation of white adipose tissue in mammals can cause metabolic diseases. However, unlike white fat, brown and beige fats release energy as heat. In recent years, many lncRNAs associated with adipogenesis have been reported. The molecular mechanisms of how lncRNAs regulate adipogenesis are continually investigated. In this review, we discuss the classification of lncRNAs according to their transcriptional location. lncRNAs that participate in the adipogenesis of white or brown fats are also discussed. The function of lncRNAs as decoy molecules and RNA double-stranded complexes, among other functions, is also discussed.
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Adipogenia , RNA Longo não Codificante , Adipócitos/metabolismo , Adipócitos Marrons/metabolismo , Adipogenia/genética , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Mamíferos/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
Iron is a trace element necessary for cell growth, development, and cellular homeostasis, but insufficient or excessive level of iron is toxic. Intracellularly, sufficient amounts of iron are required for mitochondria (the center of iron utilization) to maintain their normal physiologic function. Iron deficiency impairs mitochondrial metabolism and respiratory activity, while mitochondrial iron overload promotes ROS production during mitochondrial electron transport, thus promoting potential disease development. This review provides an overview of iron homeostasis, mitochondrial iron metabolism, and how mitochondrial iron imbalances-induced mitochondrial dysfunction contribute to diseases.
Assuntos
Deficiências de Ferro , Sobrecarga de Ferro , Humanos , Mitocôndrias/metabolismo , Ferro/metabolismo , Sobrecarga de Ferro/metabolismo , HomeostaseRESUMO
Coenzyme Q10 (CoQ10), which is a key cofactor of the electron transport chain in the mitochondria has shown many beneficial effects on liver diseases. However, the mechanisms of CoQ10 protective role on the acetaminophen (APAP)-induced liver injury are elusive and unclear. In this study, we further investigated the CoQ10 therapeutic effects on APAP-overdose liver injury. C57BL/6 J mice were intraperitoneally treated with APAP to induce liver injury. CoQ10 (5 mg/kg) was given to mice at 1.5 h after APAP treatment. The results showed that hepatic CoQ10 levels were decreased during the APAP-induced hepatotoxicity and preceded serum ALT elevation. Treatment of CoQ10 significantly improved the liver injury induced by APAP. Moreover, CoQ10 treatment decreased the ROS levels and promoted the antioxidative related gene expression in APAP overdose mice. Importantly, results showed that even though CoQ10 had no effects on the mtDNA copy number and the expression of genes related to mitochondrial biogenesis, it significantly improved the mitochondrial complex I and V activities and promoted the mitophagy in APAP-overdose mice. To further authenticate mitophagy role in CoQ10-mediated improved liver injury in vivo, we administrated APAP-overdose mice with chloroquine 1 h prior to APAP treatment and found that chloroquine treatment functionally abrogated the CoQ10 protective role on APAP overdose mice. To conclude, this study provides evidence that CoQ10 activates mitophagy to protect against APAP-induced liver injury. Therefore, CoQ10 may represent a novel therapeutic option for the prevention and treatment of drug-induced liver injury.
Assuntos
Acetaminofen/toxicidade , Analgésicos não Narcóticos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Mitofagia/efeitos dos fármacos , Ubiquinona/análogos & derivados , Vitaminas/uso terapêutico , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitofagia/fisiologia , Ubiquinona/farmacologia , Ubiquinona/uso terapêutico , Vitaminas/farmacologiaRESUMO
Adropin as a secretory peptide has shown a protective role on the disorders of glucose and lipid metabolism. However, the role and mechanism of this peptide on the hepatic glucose production has remained unclear. Adropin knockout (KO) mice were generated to explore its effects on the enhanced hepatic glucose production in obesity. We found that compared to wild-type (WT) mice, adropin-KO mice developed the unbalanced enhanced hepatic glucose production in advance of the whole-body insulin resistance (IR) by high-fat diet (HFD). Mechanistically, adropin dissociated CREB-CRTC2 and FoxO1-PGC1α complex and reduced their binding to the promoters of G6Pase and PEPCK to decrease glucose production in IR. However, these effects were not observed in insulin-sensitive hepatocytes. Furthermore, in IR hepatocytes, dampened AMPK signaling was re-activated by adropin treatment via inhibition of PP2A. To further authenticate AMPK role in vivo, we administrated HFD-fed mice with AAV8-CA AMPKα and found that AMPK activation functionally restored the aberrant glucose production and IR induced by adropin-deficiency. This study provides evidence that adropin activates the AMPK pathway via inhibition of PP2A and decreases the liver glucose production in IR context. Therefore, adropin may represent a novel target for the prevention and treatment of diabetes.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Glucose/metabolismo , Hepatócitos/metabolismo , Resistência à Insulina/fisiologia , Insulina/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteína Fosfatase 2/metabolismo , Animais , Linhagem Celular Tumoral , Células Cultivadas , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Dieta Hiperlipídica/métodos , Proteína Forkhead Box O1/metabolismo , Células HEK293 , Células Hep G2 , Humanos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Transdução de Sinais/fisiologia , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: Few studies investigated the associations between dietary patterns and overweight/obesity among Chinese preschool children. Thus, the study aims to explore dietary patterns and their associations with overweight/obesity among preschool children in the Dongcheng District of Beijing. METHODS: With a stratified proportionate cluster sampling, the study included 3373 pairs of preschool children and their guardians. Children's weight and height were measured by school nurses, and their food and beverage consumption frequencies were reported by guardians via a food frequency questionnaire. Children's age, gender, physical activity time, and sedentary time, as well as their parents' highest level of educational attainment, occupation, weight, and height were also collected. Dietary patterns were identified through exploratory factor analysis. Among these identified dietary patterns, the one with the largest factor score was defined as the predominant dietary pattern for each child. The associations between predominant dietary patterns and overweight/obesity were tested by two-level random-intercept logistic models with cluster-robust standard errors. RESULTS: Four dietary patterns, i.e., a "Sugar-sweetened beverage (SSB) and snack" pattern, a "Chinese traditional" pattern, a "Health conscious" pattern, and a "Snack" pattern, were identified. Among the children, 21.02% (95% CI: 19.68 to 22.43%) were predominated by the "SSB and snack" pattern, 27.78% (95% CI: 26.29 to 29.32%) by the "Chinese traditional" pattern, 24.90% (95% CI: 23.47 to 26.39%) by the "Health conscious" pattern, and 26.30% (95% CI: 24.84 to 27.81%) by the "Snack" pattern. After controlling for potential confounders, the "SSB and snack" pattern characterized by fresh fruit/vegetable juice, flavored milk drinks, carbonated drinks, flavored fruit/vegetable drinks, tea drinks, plant-protein drinks, puffed foods, fried foods, and Western fast foods was associated with a higher risk of overweight/obesity (OR: 1.61, 95% CI:1.09 to 2.38), compared with the "Chinese traditional" pattern. CONCLUSIONS: The preference for dietary patterns with high energy density but low nutritional value was prevalent among preschool children in the Dongcheng District of Beijing. Comprehensive measures to simultaneously reduce consumption of SSBs and unhealthy snacks among preschool children should be taken urgently to address the childhood obesity problem in China, particularly in metropolises.
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Dieta , Sobrepeso , Animais , Pequim/epidemiologia , Bebidas , Criança , Pré-Escolar , China/epidemiologia , Estudos Transversais , Comportamento Alimentar , Humanos , Sobrepeso/epidemiologiaRESUMO
As a natural enemy of green peach aphids, harlequin ladybirds, Harmonia axyridis Pallas (Coleoptera: Coccinellidae), are also indirectly affected by azadirachtin. In this study, we evaluated the effects of ladybird exposure to azadirachtin through azadirachtin-treated aphids. About 2 mg/L azadirachtin treated aphid can deliver the azadirachtin to ladybird larvae in 12 and 24 h. And azadirachtin treatment affected the rate at which fourth instar larvae and adult ladybirds preyed on aphids. Furthermore, the antifeedant effect increased with increasing azadirachtin concentrations. Twelve hours after exposing fourth instar ladybird larvae to aphids treated with 10 mg/L azadirachtin, the antifeedant effect was 47.70%. Twelve hours after exposing adult ladybirds to aphids treated with 2 mg/L azadirachtin, the antifeedant effect was 67.49%. Forty-eight hours after exposing ladybird larvae to azadirachtin-treated aphids, their bodyweights were 8.37 ± 0.044 mg (2 mg/L azadirachtin), 3.70 ± 0.491 mg (10 mg/L azadirachtin), and 2.39 ± 0.129 mg (50 mg/L azadirachtin). Treatment with azadirachtin affected the ability of ladybirds to prey on aphids. The results indicated that the instant attack rate of ladybird larvae and adults and the daily maximum predation rate were reduced by azadirachtin treatment. Superoxide dismutase (SOD), peroxidase (POD), and peroxide (CAT) enzyme activities of ladybirds were affected after feeding on aphids treated with azadirachtin. Azadirachtin has certain antifeedant effects on ladybirds and affects the ability of ladybirds to prey on aphids and the activities of SOD, POD, and CAT enzymes, which results in inhibition of normal body development.
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Afídeos/fisiologia , Besouros/enzimologia , Limoninas/toxicidade , Comportamento Predatório/efeitos dos fármacos , Animais , Besouros/efeitos dos fármacos , Besouros/crescimento & desenvolvimento , Besouros/fisiologia , Larva/crescimento & desenvolvimento , Pisum sativumRESUMO
Azadirachtin is a good growth inhibitor for Lepidopteran larvae, but its effect on the brain neurons, intestinal flora and intestinal contents caused by the growth inhibition mechanism has not been reported yet. This study explored the mechanism of azadirachtin on the growth and development of Spodoptera litura larvae and brain neurons through three aspects: intestinal pathology observation, intestinal flora sequencing, and intestinal content analysis. The results showed that the treatment of azadirachtin led to the pathological changes in the structure of the midgut and the goblet cells in the intestinal wall cells to undergo apoptosis. Changes in the host environment of the intestinal flora lead to changes in the abundance value of the intestinal flora, showing an increase in the abundance value of harmful bacteria such as Sphingomonas and Enterococcus, as well as an increase in the abundance value of excellent flora such as Lactobacillus and Bifidobacterium. Changes in the abundance of intestinal flora will result in changes in intestinal contents and metabolites. The test results show that after azadirachtin treatment, the alkane compounds in the intestinal contents of the larvae are greatly reduced, and the number of the long carbon chain and multi-branched hydrocarbon compounds is increased, unsaturated fatty acids, siliconoxygen compounds and ethers. The production of similar substances indicates that azadirachtin has an inhibitory effect on digestive enzymes in the intestines, which results in the inhibition of substance absorption and energy transmission, and ultimately the inhibition of larval growth and brain neurons.
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Conteúdo Gastrointestinal , Microbioma Gastrointestinal , Animais , Encéfalo , Intestinos , Larva , Limoninas , Neurônios , SpodopteraRESUMO
The viscosity (9.34-405.92 mPa·s) and absorption capacity (0.4394-1.0562 g·g-1) of (1-ethyl-3-methylidazolium trifluoroacetate + triethanolamine) binary blends atmospheric pressure in the temperature range of 303.15-343.15 K and at different mole fractions of [EMIM] [TFA] have been carried out. The molar fraction of [EMIM] [TFA] dependence of the viscosity and absorption capacity was demonstrated. The addition of a small amount of [EMIM] [TFA] into TEA led to rapidly decreased rates of binary blends' viscosity and absorption capacity. However, the viscosity and absorption of binary blends did not decrease significantly when [EMIM] [TFA] was increased to a specific value. Compared with the molar fraction of the solution, the temperature had no obvious effect on viscosity and absorption capacity. By modeling and optimizing the ratio of viscosity and absorption capacity of ([EMIM] [TFA] + TEA), it is proven that when the mole fraction of [EMIM] [TFA] is 0.58, ([EMIM] [TFA] + TEA) has the best viscosity and absorption capacity at the same time. In addition, at 303.15 K, ([EMIM] [TFA] + TEA) was absorbed and desorbed six times, the absorption slightly decreased, and the desorption increased.
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Excessive fat accumulation can lead to obesity, diabetes, hyperlipidemia, atherosclerosis, and other diseases. MicroRNAs are a class of microRNAs that regulate gene expression and are highly conserved in function among species. microRNAs have been shown to act as regulatory factors to inhibit fat accumulation in the body. We found that miR-370-3p was expressed at lower levels in the fat mass of mice on a high-fat diet than in mice on a normal control diet. Furthermore, our data showed that the overexpression of miR-370-3p significantly suppressed the mRNA expression levels of adipogenic markers. Thus, miR-370-3p overexpression reduced lipid accumulation. Conversely, the inhibition of miR-370-3p suppressed 3T3-L1 preadipocyte proliferation and promoted preadipocyte differentiation. In addition, Mknk1, a target gene of miR-370-3p, plays an opposing role in preadipocyte proliferation and differentiation. Moreover, consistent results from in vitro as well as in vivo experiments suggest that the inhibition of fat accumulation by miR-370-3p may result from the inhibition of saturated fatty acids that promote the accumulation of polyunsaturated fatty acids. In conclusion, these results suggest that miR-370-3p plays an important role in adipogenesis and fatty acid metabolism through the regulation of Mknk1.
Assuntos
Adipócitos/metabolismo , Adipogenia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , MicroRNAs/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Células 3T3-L1 , Animais , Diferenciação Celular , Proliferação de Células , Células HeLa , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , MicroRNAs/genética , Proteínas Serina-Treonina Quinases/genéticaRESUMO
Skeletal muscle is an important and complex organ with a variety of functions in humans and animals. Skeletal myogenesis is a multistep and complex process, and increasing evidence suggests that microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) play critical roles in skeletal myogenesis. In this study the expression of miR-351-5p is dynamically regulated during skeletal myogenesis in vitro and in vivo. Cell-counting kit-8, qRT-PCR, and EdU immunofluorescence analysis showed that miR-351-5p overexpression promoted the proliferation and inhibited the differentiation of C2C12 myoblast, whereas inhibition of miR-351-5p had the opposite effect. In addition, miR-351-5p mediated the regulation of muscle fiber type transition in vivo. In vitro, loss of miR-351-5p in muscle tissues promoted muscle hypertrophy and increased slow-twitch fibers in the gastrocnemius muscles of mice. Luciferase reporter assay and functional analyses demonstrated that lactamase ß ( LACTB) is a direct target of miR-351-5p involved in the regulation of skeletal myogenesis. Expression levels of a myogenesis-associated lncRNA ( lnc-mg) correlated negatively with miR-351-5p and positively with LACTB during C2C12 myoblast proliferation and differentiation. Further analyses showed that lnc-mg acted as a molecular sponge for miR-351-5p, demonstrating its involvement in the negative regulation of LACTB by miR-351-5p during skeletal myogenesis. These findings indicate that miRNA-351-5p functions in skeletal myogenesis by targeting LACTB and is regulated by lnc-mg, supporting the role of the competing endogenous RNA network in skeletal myogenesis.-Du, J., Zhang, P., Zhao, X., He, J., Xu, Y., Zou, Q., Luo, J., Shen, L., Gu, H., Tang, Q., Li, M., Jiang, Y., Tang, G., Bai, L., Li, X., Wang, J., Zhang, S., Zhu, L. MicroRNA-351-5p mediates skeletal myogenesis by directly targeting lactamase ß and is regulated by lnc-mg.