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Hydrolyzed egg yolk peptide (YPEP) was shown to increase bone mineral density in ovariectomized rats. However, the underlying mechanism of YPEP on osteoporosis has not been explored. Recent studies have shown that Wnt/ß-catenin signaling pathway and gut microbiota may be involved in the regulation of bone metabolism and the progression of osteoporosis. The present study aimed to explore the preventive effect of the YPEP supplementation on osteoporosis in ovariectomized (OVX) rats and to verify whether YPEP can improve osteoporosis by regulating Wnt/ß-catenin signaling pathway and gut microbiota. The experiment included five groups: sham surgery group (SHAM), ovariectomy group (OVX), 17-ß estradiol group (E2: 25 µg /kg/d 17ß-estradiol), OVX with low-dose YPEP group (LYPEP: 10 mg /kg/d YPEP) and OVX with high-dose YPEP group (HYPEP: 40 mg /kg/d YPEP). In this study, all the bone samples used were femurs. Micro-CT analysis revealed improvements in both bone mineral density (BMD) and microstructure by YPEP treatment. The three-point mechanical bending test indicated an enhancement in the biomechanical properties of the YPEP groups. The serum levels of bone alkaline phosphatase (BALP), bone gla protein (BGP), calcium (Ca), and phosphorus (P) were markedly higher in the YPEP groups than in the OVX group. The LYPEP group had markedly lower levels of alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) and C-terminal telopeptide of type I collagen (CTX-I) than the OVX group. The YPEP groups had significantly higher protein levels of the Wnt3a, ß-catenin, LRP5, RUNX2 and OPG of the Wnt/ß-catenin signaling pathway compared with the OVX group. Compared to the OVX group, the ratio of OPG/RANKL was markedly higher in the LYPEP group. At the genus level, there was a significantly increase in relative abundance of Lachnospiraceae_NK4A136_group and a decrease in Escherichia_Shigella in YPEP groups, compared with the OVX group. However, in the correlation analysis, there was no correlation between these two bacteria and bone metabolism and microstructure indexes. These findings demonstrate that YPEP has the potential to improve osteoporosis, and the mechanism may be associated with its modulating effect on Wnt/ß-catenin signaling pathway.
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Densidade Óssea , Osteoporose , Ovariectomia , Via de Sinalização Wnt , Animais , Feminino , Ratos , Fosfatase Alcalina/metabolismo , beta Catenina/metabolismo , Densidade Óssea/efeitos dos fármacos , Proteínas do Ovo/farmacologia , Proteínas do Ovo/metabolismo , Gema de Ovo/química , Gema de Ovo/metabolismo , Fêmur/efeitos dos fármacos , Fêmur/metabolismo , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Osteoporose/prevenção & controle , Osteoporose/metabolismo , Peptídeos/farmacologia , Ratos Sprague-Dawley , Via de Sinalização Wnt/efeitos dos fármacos , Microtomografia por Raio-XRESUMO
The present study aimed to investigate the differential effects of n-3 and n-6 polyunsaturated fatty acids (PUFAs) on placental and embryonic development. Pregnant mice were assigned to five groups: healthy control (HC), diabetes mellitus control (DMC), diabetes + low-dose n-3 PUFA (Ln-3), diabetes + high-dose n-3 PUFA (Hn-3), and diabetes + n-6 PUFA (n-6). On E12.5d, the Hn-3 group, but not the n-6 group, had a higher placenta weight. The weight ratio of embryo to placenta in the n-6 group was significantly lower than in the Hn-3 group but higher than in the DMC group. The Hn-3 group had significantly higher protein levels of VEGF, IGF-1, and IGFBP3, while the n-6 group had lower VEGF than the DMC group. Compared with the DMC group, embryonic Cer-16:0 was significantly higher in the Hn-3 group, while embryonic PC (36:6), PC (38:7), and PE (40:7) were significantly lower in the n-6 group. The embryo and placenta weights were positively correlated with placental VEGF, IGFBP3, and embryonic Cer-16:0, and they were negatively correlated with embryonic PC (36:6) and PE (40:7). The weight ratio of embryo to placenta was negatively correlated with embryonic PC (36:6). In addition, embryonic Cer-16:0 was positively correlated with placental VEGF and IGFBP3. In conclusion, n-3 PUFA and n-6 PUFA improved placental and embryonic growth through different mechanisms.
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Desenvolvimento Embrionário , Ácidos Graxos Ômega-3 , Ácidos Graxos Ômega-6 , Placenta , Animais , Gravidez , Feminino , Ácidos Graxos Ômega-3/farmacologia , Placenta/metabolismo , Placenta/efeitos dos fármacos , Ácidos Graxos Ômega-6/farmacologia , Camundongos , Desenvolvimento Embrionário/efeitos dos fármacos , Diabetes Mellitus Experimental , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Gravidez em Diabéticas/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Tamanho do Órgão/efeitos dos fármacosRESUMO
Objectives: The present study aimed to explore the preventive effect of mussel oil (MO) on atherosclerosis and the potential mechanism in apolipoprotein E-null (ApoE-/-) mice. Methods: ApoE-/- mice were fed with a high-fat and high-cholesterol chow and given corn oil (CO), fish oil (FO), MO, or aspirin (ASP, dissolved in CO) by gavage for 12 weeks. The total n-3 polyunsaturated fatty acids (PUFAs) in MO (51.01%) and FO (46.82%) were comparable (mainly C22:6n-3 and C20:5n-3). Wild-type mice were fed with a normal chow and given equivalent CO as health control (CON). Results: Compared with the CON group, obvious atherosclerotic plaque appeared at aorta and aortic sinus in the CO group. Compared with the CO group, MO but not FO had a significantly smaller atherosclerotic plaque area in the aorta. The aortic atherosclerotic plaque area was comparable in the MO, CON, and ASP groups. The MO group had a significantly smaller atherosclerotic plaque area, lower lipid deposition, lower contents of smooth muscle cell (SMC), and slightly lower contents of macrophage at the aortic sinus than the FO group. Serum concentrations of IL-1ß, NF-κB, and VCAM-1 were comparable in the MO and FO groups and were significantly lower than the CO group. Compared with the CO group, the MO group but not FO group had significantly lower aortic protein levels of p65NF-κB, p38MAPK, and VCAM-1. The aortic protein levels of p-p65NF-κB and p-p38MAPK were significantly lower in the MO group than the FO group. Conclusion: In conclusion, MO is more potent than FO in preventing atherosclerosis, and the possible mechanism may be by downregulating p38MAPK/NF-κB signaling pathway, decreasing VCAM-1 and macrophage, and inhibiting proliferation and migration of SMC.
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Aim: This study used CpG 684 as adjuvant of inactivated COVID-19 vaccine to detect a humoral and cellular immune response in mice. Materials & methods: We used 10 and 20 µg CpG 684 as adjuvants of an inactivated COVID-19 vaccine to immunize mice. IgG, IgG1, IgG2a, IgG2b and IgM binding antibodies were detected in serum by ELISA. The IFN-γ cytokine was detected by ELISPOT. Results: CpG 684 improved spike-specific IgG and IgM subtype binding antibodies and increased the neutralizing antibody titer against prototype, Delta and Beta strains. CpG 684 also improved cellular immune response. Conclusion: CpG 684 is an effective adjuvant for inactivated COVID-19 vaccine.
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Studies have shown that blue mussel lipid extract (BMLE) can improve the glycemic traits, inflammatory cytokines, and lipid profile of patients with type 2 diabetes mellitus (T2DM) in China. Gut microbiota is closely related to T2DM. This study aims to explore whether BMLE can improve the glycemic status of T2DM patients by regulating gut microbiota in a 60-day double-blind randomized controlled trial. A total of 133 T2DM subjects were randomized into BMLE (n = 44), fish oil (FO) (n = 44), and corn oil (CO) (n = 45) groups. The participants were asked to take two corresponding oil capsules (0.8 g per capsule each) every day. The faecal microbiota, glycemic traits, and other cardiometabolic factors were analyzed at baseline and endpoint. The α diversity estimators of Ace and Chao1 decreased significantly in all three groups, but there was no significant difference between the groups. Eight bacteria decreased significantly in the BMLE group but not in the FO and CO groups: unclassified_Clostridia_UCG_014, unclassified_Bacteroidia, Erysipelotrichaceae, and uncultured_Ruminococcaceae_bacterium at the family level and unclassified_Bacteroidia, uncultured_Ruminococcaceae_bacterium, unclassified_Clostridia_UCG_014, and Turicibacter at genus level. In the BMLE group, the change in the relative abundance of Erysipelotrichaceae was positively correlated with the changes in the homeostatic model assessment of insulin resistance (HOMA-IR) (r = 0.454, p < 0.01) and fasting insulin (r = 0.414, p < 0.01). The change in the relative abundance of Turicibacter was positively correlated with the changes in HOMA-IR (r = 0.431, p < 0.01), fasting insulin (r = 0.414, p < 0.01), total cholesterol (TC) (r = 0.358, p < 0.05), and triacylglycerol (TG) (r = 0.393 p = 0.013). In conclusion, BMLE might improve glycemic traits by modulating gut microbiota in T2DM patients.
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Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Mytilus edulis , Animais , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Óleos de Peixe , Insulina , Firmicutes , Glicemia , Método Duplo-CegoRESUMO
With the continuous in-depth study of the interaction mechanism between viruses and hosts, the virus has become a promising tool in cancer treatment. In fact, many oncolytic viruses with selectivity and effectiveness have been used in cancer therapy. Human enterovirus is one of the most convenient sources to generate oncolytic viruses, however, the high seroprevalence of some enteroviruses limits its application which urges to exploit more oncolytic enteroviruses. In this study, coxsackievirus B5/Faulkner (CV-B5/F) was screened for its potential oncolytic effect against non-small cell lung cancers (NSCLCs) through inducing apoptosis and autophagy. For refractory NSCLCs, DNA-dependent protein kinase (DNA-PK) or ataxia telangiectasia mutated protein (ATM) inhibitors can synergize with CV-B5/F to promote refractory cell death. Here, we showed that viral infection triggered endoplasmic reticulum (ER) stress-related pro-apoptosis and autophagy signals, whereas repair for double-stranded DNA breaks (DSBs) contributed to cell survival which can be antagonized by inhibitor-induced cell death, manifesting exacerbated DSBs, apoptosis, and autophagy. Mechanistically, PERK pathway was activated by the combination of CV-B5/F and inhibitor, and the irreversible ER stress-induced exacerbated cell death. Furthermore, the degradation of activated STING by ERphagy promoted viral replication. Meanwhile, no treatment-related deaths due to CV-B5/F and/or inhibitors occurred. Conclusively, our study identifies an oncolytic CV-B5/F and the synergistic effects of inhibitors of DNA-PK or ATM, which is a potential therapy for NSCLCs.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Vírus Oncolíticos , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Estudos Soroepidemiológicos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Apoptose/genética , Vírus Oncolíticos/genética , DNARESUMO
Accurate traffic flow forecasting is very important for urban planning and traffic management. However, this is a huge challenge due to the complex spatial-temporal relationships. Although the existing methods have researched spatial-temporal relationships, they neglect the long periodic aspects of traffic flow data, and thus cannot attain a satisfactory result. In this paper, we propose a novel model Attention-Based Spatial-Temporal Convolution Gated Recurrent Unit (ASTCG) to solve the traffic flow forecasting problem. ASTCG has two core components: the multi-input module and the STA-ConvGru module. Based on the cyclical nature of traffic flow data, the data input to the multi-input module are divided into three parts, near-neighbor data, daily-periodic data, and weekly-periodic data, thus enabling the model to better capture the time dependence. The STA-ConvGru module, formed by CNN, GRU, and attention mechanism, can capture both temporal and spatial dependencies of traffic flow. We evaluate our proposed model using real-world datasets and experiments show that the ASTCG model outperforms the state-of-the-art model.
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Intranasal (i.n.) vaccines can induce mucosal and systemic immunity against respiratory pathogens. Previously, we demonstrated that the recombinant vesicular stomatitis virus (rVSV)-based COVID-19 vaccine rVSV-SARS-CoV-2, with poor immunogenicity via the intramuscular route (i.m.), is more suitable for i.n. administration in mice and nonhuman primates. Here, we found that the rVSV-SARS-CoV-2 Beta variant was more immunogenic than the wild-type strain and other variants of concern (VOCs) in golden Syrian hamsters. Furthermore, the immune responses elicited by rVSV-based vaccine candidates via the i.n. route were significantly higher than those of two licensed vaccines: the inactivated vaccine KCONVAC delivered via the i.m. route and the adenovirus-based Vaxzevria delivered i.n. or i.m. We next assessed the booster efficacy of rVSV following two i.m. doses of KCONVAC. Twenty-eight days after receiving two i.m. doses of KCONVAC, hamsters were boosted with a third dose of KCONVAC (i.m.), Vaxzevria (i.m. or i.n.), or rVSVs (i.n.). Consistent with other heterologous booster studies, Vaxzevria and rVSV elicited significantly higher humoral immunity than the homogenous KCONVAC. In summary, our results confirmed that two i.n. doses of rVSV-Beta elicited significantly higher humoral immune responses than commercial inactivated and adeno-based COVID vaccines in hamsters. As a heterologous booster dose, rVSV-Beta induced potent, persistent, and broad-spectrum humoral and mucosal neutralizing responses against all VOCs, highlighting its potential to be developed into a nasal-spray vaccine.
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COVID-19 , Vacinas Virais , Humanos , Animais , Camundongos , Vacinas contra COVID-19 , Roedores , Sprays Nasais , ChAdOx1 nCoV-19 , COVID-19/prevenção & controle , SARS-CoV-2/genética , Vesiculovirus , Anticorpos Antivirais , Anticorpos NeutralizantesRESUMO
The rapid mutation and spread of SARS-CoV-2 variants recently, especially through the emerging variants Omicron BA5, BF7, XBB and BQ1, necessitate the development of universal vaccines to provide broad spectrum protection against variants. For the SARS-CoV-2 universal recombinant protein vaccines, an effective approach is necessary to design broad-spectrum antigens and combine them with novel adjuvants that can induce high immunogenicity. In this study, we designed a novel targeted retinoic acid-inducible gene-I (RIG-I) receptor 5'triphosphate double strain RNA (5'PPP dsRNA)-based vaccine adjuvant (named AT149) and combined it with the SARS-CoV-2 Delta and Omicron chimeric RBD-dimer recombinant protein (D-O RBD) to immunize mice. The results showed that AT149 activated the P65 NF-κB signaling pathway, which subsequently activated the interferon signal pathway by targeting the RIG-I receptor. The D-O RBD + AT149 and D-O RBD + aluminum hydroxide adjuvant (Al) + AT149 groups showed elevated levels of neutralizing antibodies against the authentic Delta variant, and Omicron subvariants, BA1, BA5, and BF7, pseudovirus BQ1.1, and XBB compared with D-O RBD + Al and D-O RBD + Al + CpG7909/Poly (I:C) groups at 14 d after the second immunization, respectively. In addition, D-O RBD + AT149 and D-O RBD + Al + AT149 groups presented higher levels of the T-cell-secreted IFN-γ immune response. Overall, we designed a novel targeted RIG-I receptor 5'PPP dsRNA-based vaccine adjuvant to significantly improve the immunogenicity and broad spectrum of the SARS-CoV-2 recombinant protein vaccine.
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Vacinas contra COVID-19 , COVID-19 , Animais , Camundongos , Adjuvantes de Vacinas , SARS-CoV-2/genética , COVID-19/prevenção & controle , Adjuvantes Imunológicos , Sistema ABO de Grupos Sanguíneos , Anticorpos Neutralizantes , Proteínas Recombinantes/genética , Anticorpos Antivirais , Glicoproteína da Espícula de CoronavírusRESUMO
Humans have consumed lard for thousands of years, but in recent decades, it has become much less popular because it is regarded as saturated fat. Animal studies showed that lard plus soybean oil (blend oil) was more advantageous for liver health than using either oil alone. This study aims to assess the effects of blend oil on liver function markers in healthy subjects. The 345 healthy subjects were randomized into 3 isoenergetic diet groups with different edible oils (30 g/day) (soybean oil, lard, and blend oil (50% lard and 50% soybean oil)) for 12 weeks. The reductions in both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were greater in the blend oil group than in the two other groups (p = 0.001 and <0.001 for the interaction between diet group and time, respectively). The reductions in AST and ALT in the blend oil group were more significant compared with those in the soybean oil group (p < 0.001) or lard group (p < 0.001). There were no significant differences in the other liver function markers between the groups. Thus, blend oil was beneficial for liver function markers such as AST and ALT compared with soybean oil and lard alone, which might help prevent non-alcoholic fatty liver disease in the healthy population.
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Diffuse venous malformations (VMs) are relatively rare, especially the lesions locting special anatomical sites, and they are prone to casuse localized intravascular coagulopathy (LIC). Diffuse VMs can also cause bleeding and life-threatening disseminated intravascular coagulopathy (DIC) from trauma, surgery, and improper treatments. Thus, the treatment of diffuse VMs with LIC is quite tough. We report of a diffuse VMs with severe LIC that was treated with the combined use of minimally invasive treatment and open surgery.
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Transtornos da Coagulação Sanguínea , Ablação por Radiofrequência , Malformações Vasculares , Humanos , Transtornos da Coagulação Sanguínea/etiologia , Malformações Vasculares/complicações , Malformações Vasculares/cirurgia , Malformações Vasculares/patologia , Extremidade Inferior/patologia , Veias/patologia , Ablação por Radiofrequência/efeitos adversosRESUMO
Objective: By studying the changes of serum uric acid (SUA) in acute stage and remission stage of gouty arthritis, we aimed to explore the relationship between the changes of SUA level and free glucocorticoids and inflammatory factors. Methods: A prospective, longitudinal study was conducted on 50 acute gout patients in the dedicated gout clinic of the Affiliated Hospital of Qingdao University. Blood and 24-hour urine samples were collected during the acute phase and two weeks after the initial visit. Patients with acute gouty arthritis were treated primarily with colchicine and nonsteroidal anti-inflammatory drugs. Results: A total of 32 patients completed the two-week follow-up trial. SUA levels were significantly downregulated during the acute flare than after the flare (464.14 ± 90.97 vs. 527.36 ± 86.90 µmol/L, p < 0.001). The 24-hour fractional excretion of uric acid (24 h FEur) (5.54 ± 2.82% vs. 4.68 ± 2.83%, p < 0.001) and 24-hour urinary uric acid excretion (24 h Uur) (663.08 ± 249.48 µmol/L vs. 540.87 ± 263.18 µmol/L, p = 0.001) increased significantly in patients during the acute phase. The percent change in SUA was associated with those in 24 h FEur and C-reactive protein. Meanwhile, the percent change in 24 h Uur was associated with those in 24-hour urinary free cortisol, percent change in interleukin 1ß and interleukin 6. Conclusion: Decreased SUA level during the acute gout flare was associated with increased excretion of urinary uric acid. Inflammatory factors and bioactive free glucocorticoids may play significant roles in this process.
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Artrite Gotosa , Gota , Humanos , Artrite Gotosa/tratamento farmacológico , Ácido Úrico , Estudos Prospectivos , Estudos Longitudinais , Exacerbação dos SintomasRESUMO
BACKGROUND AND AIM: A clear relationship of biological indexes between bile acid malabsorption (BAM) and diarrhea-predominant irritable bowel syndrome (IBS-D) has not been well analyzed. This meta-analysis aimed to establish a more convenient method to diagnose BAM in IBS-D patients by comparing the differences in biomarkers between IBS-D patients and healthy people. METHODS: Multiple databases were searched for relevant case-control studies. Indicators used to diagnose BAM included 75 Se-homocholic acid taurine (SeHCAT), 7α-hydroxy-4-cholesten-3-one(C4), fibroblast growth factor-19 and 48-hour fecal bile acid (48FBA). The rate of BAM (SeHCAT) was calculated by using a random-effect model. The levels of C4, FGF19, and 48FBA were compared, and the overall effect size was combined by a fixed effect model. RESULTS: The search strategy identified 10 relevant studies comprising 1034 IBS-D patients and 232 healthy volunteers. The pooled rate of BAM in IBS-D patients was 32% (according to SeHCAT; 95% CI: 24%-40%). The level of C4 in IBS-D patients was significantly higher than that in the control group (2.86 ng/mL; 95% CI: 1.09, 4.63); The level of FGF19 was significantly lower than that in the control group (-33.97 pg/mL; 95% CI: -51.13, -16.82); The level of 48FBA was significantly higher than that in the control group (0.059; 95% CI: 0.41, 0.77). CONCLUSIONS: The results mainly concluded serum C4 and FGF19 levels in IBS-D patients. Most of the studies have different normal cutoff points of serum C4 and FGF19 levels; the performance of each test should be further estimated. By comparing the levels of these biomarkers, BAM in patients with IBS-D could be identified more accurately, which would lead to more effective treatment.
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Síndrome do Intestino Irritável , Síndromes de Malabsorção , Humanos , Síndrome do Intestino Irritável/diagnóstico , Diarreia/etiologia , Ácidos e Sais Biliares , Síndromes de Malabsorção/diagnóstico , Síndromes de Malabsorção/etiologia , BiomarcadoresRESUMO
The present study aimed to investigate the preventive effect of mussel oil (MO) on gestational diabetes mellitus (GDM) in mice fed by a high-fat and high-sucrose (HFHS) diet. Pregnant mice were allocated to four groups: normal diet + corn oil (CO), HFHS + CO, HFHS + fish oil (FO), and HFHS + MO. The total n-3 polyunsaturated fatty acids (PUFAs) in MO (51.30%) and FO (48.25%) were comparable (mainly C22:6n-3 and C20:5n-3). HFHS + MO and HHFS + FO had a significantly lower area under the curve (AUC) for the oral glucose tolerance test (OGTT) than the HFHS + CO group. The HFHS + MO group but not HFHS + FO group had a significantly lower AUC for the insulin tolerance test (ITT) than the HFHS + CO group. The HFHS + MO group had significantly lower homeostasis model assessment-insulin resistance (HOMA-IR) and fasting serum insulin than the HHFS + FO and HFHS + CO groups. Liver sphingosine kinase 1 (SphK1) was significantly higher, while SphK2, Akt, and P-Akt were significantly lower in the HFHS + CO group compared with the normal diet + CO group. The HFHS + MO group but not the HFHS + FO group had significantly higher SphK2, Akt, and P-Akt than the HFHS + CO group. SphK2 had a strong negative correlation with the AUC for the OGTT (r = -0.759, p = 0.001) and insulin tolerance test (ITT) (r = -0.637; p = 0.008), fasting serum insulin (r = -0.594, p = 0.015), fasting blood glucose (r = -0.587, p = 0.017) and HOMA-IR (r = -0.629, p = 0.009) and a strong positive correlation with Akt (r = 0.594, p = 0.015) and P-Akt (r = 0.676, p = 0.004). In conclusion, mussel oil improved glucose intolerance and insulin resistance during mice pregnancy, which was superior to the effects of fish oil.
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Diabetes Gestacional , Resistência à Insulina , Gravidez , Feminino , Humanos , Camundongos , Animais , Sacarose , Insulina , Proteínas Proto-Oncogênicas c-akt , Dieta , Óleos de Peixe/farmacologia , Dieta Hiperlipídica , GlicemiaRESUMO
BACKGROUND: Studies have shown that blue mussel lipid extract (BMLE) has strong anti-inflammatory activity in both rheumatoid arthritis patients and animal arthritis models. Chronic inflammation was closely related to type 2 diabetes mellitus (T2DM). Though the beneficial effects cannot be completely attributed to n-3 polyunsaturated fatty acids, the aim of this study was to investigate whether BMLE can improve glycemic traits of T2DM patients. METHOD: In a double-blind randomized controlled trial, 133 Chinese T2DM participants were randomized to either fish oil (FO, n = 44), BMLE (n = 44), or corn oil (CO, n = 45) groups for 60 days. The participants were asked to take the corresponding oil capsules (two capsules per day, 0.8 g per capsule), which provided 1.6 g day-1 of FO (29.9% eicosapentaenoic acid + 20.4% docosahexaenoic acid), BMLE (20.7% eicosapentaenoic acid + 26.7% docosahexaenoic acid), or CO (53.5% linoleic acid). RESULTS: The fasting serum concentration of insulin (P = 0.005) and the homeostasis model of insulin resistance (P = 0.026) were significantly decreased in the BMLE group, whereas no significant change was found in the FO or CO groups. There was no significant difference between groups on serum glycosylated hemoglobin. Tumor necrosis factor-α was significantly decreased in the BMLE group (P = 0.003), but not in the FO or CO groups. A significant decrease of interleukin-1ß was observed in the BMLE and CO groups (P = 0.004 and P = 0.011 respectively), but not in the FO group. The total cholesterol was significantly decreased in the BMLE and CO groups (P < 0.001 and P < 0.001 respectively), but not in the FO group. Triacylglycerol was significantly decreased in the BMLE group (P = 0.007), but not in the FO or CO groups. High-density lipoprotein cholesterol was significantly lower in the BMLE and CO groups than in the FO group (P = 0.003). CONCLUSION: Blue mussel lipid supplements improved glycemic traits, inflammatory cytokines, and lipids profile in Chinese T2DM patients (Chinese Clinical Trial Registration number: ChiCTR1900025617). © 2022 Society of Chemical Industry.
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Diabetes Mellitus Tipo 2 , Mytilus edulis , Humanos , Animais , Ácido Eicosapentaenoico , Ácidos Docosa-Hexaenoicos , População do Leste Asiático , Óleos de Peixe , Suplementos Nutricionais , HDL-Colesterol , Método Duplo-CegoRESUMO
Effects of dietary fiber on obesity-related traits in previous studies were inconsistent. The aim of the present study was to explore whether variants in genes related to satiety and appetite can modulate the effect of dietary fiber on obesity-related traits. Fifty-one overweight or obese adults were randomly allocated to two groups to consume control biscuits (n = 24) or biscuits containing defatted flaxseed flour (n = 27) at breakfast for 8 wk. Four single-nucleotide polymorphisms related to satiety and appetite were genotyped: rs11076023 on the FTO gene, rs16147 on the NPY gene, rs155971 on the PCSK1 gene, and rs6265 on the BDNF gene. A linear regression model was used to evaluate the gene-diet interaction between obesity-related traits. Compared with control biscuits, defatted flaxseed-flour biscuits significantly reduced body weight (P = 0.001) and body mass index (BMI) (P = 0.001) in A-allele carriers (AA + AT) of rs11076023 on the FTO gene but not in non-carriers (TT) (P for the interaction = 0.005 and 0.006) and decreased fasting serum glucose in participants with CC genotype (P = 0.019) but had less effect in T-allele carriers (TT + TC) (P = 0.021) of rs16147 on the NPY gene (P for the interaction = 0.002). Compared with the control biscuits, defatted flaxseed flour significantly reduced body weight (P < 0.001) in T-allele carriers (TT + TC) of rs155971 on the PCSK1 gene but not in non-carriers (CC) (P for the interaction = 0.041) and reduced body weight (P = 0.001) and BMI (P < 0.001) in A-allele carriers (AA + AG) of rs6265 on the BDNF gene but not non-carriers (GG) (P for the interaction = 0.017 and 0.018). Variants of genes related to satiety and appetite could modulate the effect of defatted flaxseed flour on obesity-related traits.
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Suplementos Nutricionais , Linho , Farinha , Obesidade , Sobrepeso , Adulto , Humanos , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Índice de Massa Corporal , Peso Corporal , Fator Neurotrófico Derivado do Encéfalo/genética , China , Dieta , Fibras na Dieta , Genótipo , Obesidade/genética , Sobrepeso/genética , Polimorfismo de Nucleotídeo Único , Sementes , Neuropeptídeo Y/genéticaRESUMO
Background: Fucoidans extracted from sea cucumber Pearsonothuria graeffei (fuc-Pg) are rich in 4-O-sulfation, and have been shown to be potential functional polysaccharides for preventing metabolic syndromes. Objective: The present study was conducted to investigate the effect of fuc-Pg on the prevention of obesity and its underlying mechanism. Method: Mice were fed a normal diet, high-fat diet (HFD), HFD plus low and high dosage of fuc-Pg, and HFD plus simvastatin for 8 weeks. Results: fuc-Pg intervention could significantly decrease weight gain and fat accumulation in the HFD-fed mice. Moreover, fuc-Pg improved serum lipid profile by decreasing serum concentrations of TG, TC, LDL-C, sCD36, ApoB48, and ApoB100 compared with the HFD group. HFD-induced upregulation of intestinal CD36, FABP-1, P-ERK1, and the ratio of p-ERK/ERK was reversed by the fuc-Pg treatment. Moreover, fuc-Pg improved the normal function of white adipose tissue by increasing the expression of UCP1, PPAR-γ, and PGC-1α in the HFD-fed mice. Furthermore, fuc-Pg alleviated systemic inflammation by reducing serum pro-inflammatory factors and breaking the TLR4/NF-κB pathway in both the colon and liver. Conclusion: Fuc-Pg is a potential functional polysaccharide for preventing obesity and systemic inflammation caused by HFD.
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Metabolismo dos Lipídeos , Pepinos-do-Mar , Camundongos , Animais , Camundongos Endogâmicos C57BL , Dieta Hiperlipídica/efeitos adversos , Obesidade/genética , Obesidade/prevenção & controle , Obesidade/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismoRESUMO
The research and development (R&D) of novel adjuvants is an effective measure for improving the immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recombinant protein vaccine. Toward this end, we designed a novel single-stranded RNA-based adjuvant, L2, from the SARS-CoV-2 prototype genome. L2 could initiate retinoic acid-inducible gene-I signaling pathways to effectively activate the innate immunity. ZF2001, an aluminum hydroxide (Al) adjuvanted SARS-CoV-2 recombinant receptor binding domain (RBD) subunit vaccine with emergency use authorization in China, was used for comparison. L2, with adjuvant compatibility with RBD, elevated the antibody response to a level more than that achieved with Al, CpG 7909, or poly(I:C) as adjuvants in mice. L2 plus Al with composite adjuvant compatibility with RBD markedly improved the immunogenicity of ZF2001; in particular, neutralizing antibody titers increased by about 44-fold for Omicron, and the combination also induced higher levels of antibodies than CpG 7909/poly(I:C) plus Al in mice. Moreover, L2 and L2 plus Al effectively improved the Th1 immune response, rather than the Th2 immune response. Taken together, L2, used as an adjuvant, enhanced the immune response of the SARS-CoV-2 recombinant RBD protein vaccine in mice. These findings should provide a basis for the R&D of novel RNA-based adjuvants.
Assuntos
COVID-19 , Vacinas Virais , Adjuvantes Imunológicos , Hidróxido de Alumínio , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Camundongos , Camundongos Endogâmicos BALB C , RNA , Proteínas Recombinantes/genética , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Tretinoína , Vacinas de Subunidades Antigênicas/genética , Vacinas Sintéticas/genéticaRESUMO
The present study aimed to investigate whether a combination of folic acid (FA) and n-3 polyunsaturated fatty acids (PUFA) has a better preventive effect on maternal diabetes-induced neural tube defects (NTD) than FA alone. The experiment included five groups of pregnant mice: healthy control (HC), diabetes mellitus control (DMC), diabetes + n-3 PUFA (DMn-3), diabetes + FA (DMFA), and diabetes + FA + n-3 PUFA (DMFA + n-3). The incidence of NTD in DMFA + n-3 (1.04%) was significantly lower than that in DMFA (8.57%) and DMn-3 (7.82%). The incidence of NTD in DMFA and DMn-3 was significantly lower than that in DMC (19.41%). DMFA + n-3 had a lower apoptosis of neuroepithelial cells, a lower expression of P53 and Bax, and a higher expression of Pax3 and Bcl-2, compared with DMFA and DMn-3. Combination of FA and n-3 PUFA attenuated diabetes-induced hypermethylation of Pax3, overexpression and overactivity of Dnmt3b, abnormal expression of genes involved in one-carbon metabolism and elevation of homocysteine, and these improving effects were better than FA or n-3 PUFA alone. In conclusion, the combination of FA and n-3 PUFA has a synergistic effect on preventing maternal diabetes-induced NTD.
Assuntos
Diabetes Mellitus Experimental , Ácidos Graxos Ômega-3 , Defeitos do Tubo Neural , Animais , Diabetes Mellitus Experimental/complicações , Feminino , Ácido Fólico , Camundongos , Defeitos do Tubo Neural/genética , Defeitos do Tubo Neural/prevenção & controle , GravidezRESUMO
BACKGROUND: Postterm pregnancy has been associated with higher risk of perinatal mortality and morbidity, but its long-term health effects on offspring are poorly understood. OBJECTIVES: The aim of the study was to investigate the prospective associations between maternal postterm pregnancy and adverse growth outcomes in children. METHODS: The Jiaxing Birth Cohort is part of a large population-based health surveillance system in China and recruited pregnant females resident in the Jiaxing area between 1999 and 2013; newborns were followed up for a median duration of 5.8 y until they went to school. Mother-child pairs with maternal gestational information and offspring's anthropometric data at 4-7 y old were included. Postterm pregnancy was defined as maternal gestational age ≥42 and <47 wk, and its associations with offspring obesity, overweight/obesity, and thinness during childhood were determined by using Poisson regression models. RESULTS: Of the 101,505 included mother-child pairs, 2369 (2.3%) children were born at postterm. Children born at postterm had significantly lower BMI-for-age z score, weight-for-age z score, and height-for-age z score than those born at term; the mean difference (95% CI) was -0.11 (-0.15, -0.06), -0.17 (-0.21, -0.13), and -0.16 (-0.20, -0.12), respectively. When comparing postterm with term pregnancy, the multivariable-adjusted RRs and 95% CIs among preschool-age children were 0.87 (0.68, 1.11) for obesity, 0.82 (0.72, 0.94) for overweight/obesity, and 1.18 (1.09, 1.28) for thinness, respectively. These risk estimates were robust in sensitivity analyses, but were attenuated in several subgroups stratified by age, sex, mode of delivery, and fetal distress. CONCLUSIONS: Postterm pregnancy was associated with a higher risk of thinness, and a lower risk of overweight/obesity, as well as lower growth parameters in preschool-age children. These findings imply that postterm pregnancy may impede the long-term growth of offspring.