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This retrospective study aimed to evaluate whether anti-glycoproteins (GPs) autoantibodies can be used as predictors of response to high-dose dexamethasone combined with rituximab (DXM-RTX) in the treatment of primary immune thrombocytopenia (ITP) patients. One-hundred twenty-six ITP patients were included and retrospectively analyzed, 66.7% of anti-GPIb/IX and 65.9% of anti-GPIIb/IIIa autoantibodies. Results showed that overall response (OR) and complete response (CR) rates of patients without anti-GPIb/IX autoantibodies to DXM-RTX were significantly higher than those with anti-GPIb/IX autoantibodies at 4 weeks (OR: 73.8% vs. 47.6%, CR: 50.0% vs. 26.2%; P < 0.05) and 6 months (OR: 71.4% vs. 45.2%, CR: 42.9% vs. 25.0%; P < .05). Furthermore, patients with anti-GPIb/IX single-positivity exhibited higher resistance to DXM-RTX than patients with anti-GPIIb/IIIa single-positivity at 4 weeks (OR: 37.5% vs. 78.3%; P < .05) and 6 months (OR: 29.2% vs. 78.3%; P < .05). Multivariable logistic regression analysis revealed that anti-GPIb/IX autoantibodies and megakaryocytes were associated with the OR rate of patients at both 4 weeks and 6 months, and anti-GPIb/IX autoantibodies at 4 weeks represented the only significant factor affecting OR rate with DXM-RTX (F = 9.128, P = .003). Therefore, platelet anti-GPIb/IX autoantibodies might predict poor response to DXM-RTX in ITP patients.
What is the context?The safety and efficacy of high-dose dexamethasone combined with rituximab (DXM-RTX) in the treatment of primary immune thrombocytopenia (ITP) are gradually recognized; however, there still needs to be an adequate clinical trial to predict its efficacy. Autoantibodies against platelet glycoproteins (GPs) are proven to be associated with a variety of therapeutic responses in ITP. Such as anti-GPIb/IX autoantibodies predict poor response to intravenous immunoglobulin G therapy and rhTPO therapy in ITP patients. Therefore, a retrospective study was needed to verify whether anti-GP autoantibodies can expect a response to DXM-RTX therapy in ITP patients.What is new?This study identified that anti-GPIb/IX autoantibodies were a predictive factor for poor response to DXM-RTX in ITP patients. It mainly manifested in the following aspects: (1) Overall response (OR) and complete response (CR) rates of patients without anti-GPIb/IX autoantibodies to DXM-RTX were significantly higher than those with anti-GPIb/IX autoantibodies at four weeks and six months. (2) Multivariable logistic regression analysis revealed that anti-GPIb/IX autoantibodies at both four weeks and six months were associated with the OR rate of patients.What is the impact?Our study suggests that ITP patients with anti-GPIb/IX positive autoantibodies respond poorly to DXM-RTX therapy. Platelet anti-GPIb/IX autoantibodies might predict poor response to DXM-RTX therapy in ITP patients.
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Púrpura Trombocitopênica Idiopática , Humanos , Estudos Retrospectivos , Rituximab/farmacologia , Rituximab/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Autoanticorpos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas , Dexametasona/farmacologia , Dexametasona/uso terapêuticoRESUMO
BACKGROUND: To discuss the clinical features of a patient with hereditary hemorrhagic telangiectasia (HHT). METHODS: The clinical data of one patient with HHT are retrospectively analysed. In addition, we review the relevant literature. RESULTS: A 32-year-old male patient was admitted to the hematology outpatient department of our hospital and presented with intermittent epistaxis for 24 years. In recent years, he was diagnosed with iron deficiency anemia. The nasal endoscopic examination showed telangiectasia at the front of the right-middle turbinate and the left nasal cavity. He had ENG genetic mutation positivity. CONCLUSIONS: Patients with HHT may suffer from many complications, including bleeding, anemia, iron deficiency, and high-output heart failure. These patients may have telangiectasias and arteriovenous malformations in various organs.
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Anemia , Malformações Arteriovenosas , Telangiectasia Hemorrágica Hereditária , Adulto , Malformações Arteriovenosas/complicações , Malformações Arteriovenosas/diagnóstico por imagem , Epistaxe/complicações , Humanos , Masculino , Estudos Retrospectivos , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/diagnóstico , Telangiectasia Hemorrágica Hereditária/genéticaRESUMO
We present here that easily available organic salts can stabilize/modify niobium (Nb) oxo-clusters. The as-synthesized Nb oxo-clusters have been characterized by various methods. These Nb oxo-clusters were catalytically active for the epoxidation of allylic alcohols and olefins with H2O2 as an oxidant. Notably, Nb-OC@TBAF-0.5 appeared as highly dispersed nanosized particles and showed the highest catalytic activity, which can be attributed to the following reasons on the basis of characterization. First, the strong coordination of fluorine ions with Nb sites and the steric protection with bulky organic cations led to high stabilization and dispersion of the oxo-clusters in the course of the reaction. Second, a hydrogen-bond interaction between the coordinated fluorine atom and the -OH group of allylic alcohol favored the epoxidation reaction. Third, the electron density of Nb sites decreased due to the strong electron-withdrawing ability of F- adjacent to Nb sites, thus promoting the electrophilic oxygen transfer to the CâC bond.
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OBJECTIVES: The aim of this study was to explore the correlation between blood profiles and cognitive functions or mild cognitive impairment (MCI) in the Chinese population aged 35-64 years old. METHODS: A cross-sectional study was performed, which recruited 675 Chinese adults aged 35-64 years old from Beijing, China. Their cognitive performance was assessed with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), the serum lipids levels were measured by hexokinase method and colorimetric assay, and the plasma fatty acids profiles were analyzed by fast gas chromatography. RESULTS: Among the 675 participants, 84 (12.4%) had MCI. Age, years of education, saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) were associated with MMSE scores (all P < 0.05). Age, years of education, smoking, drinking, non-esterified fatty acids (NEFAs), SFAs, MUFAs, n-3 polyunsaturated fatty acids (n-3 PUFAs) and n-6/n-3 PUFAs were associated with MoCA scores (all P < 0.05). Increased age (P = 0.002) and smoking (P = 0.028) were positively associated with the prevalence of MCI, while educational level (P = 0.005) and alcohol drinking (P = 0.003) both were negatively correlated to the prevalence of MCI. Elevated serum NEFAs (P = 0.032), high plasma SFAs (P = 0.023), and excessive polyunsaturated fatty acids (PUFAs) levels (P = 0.033) were significantly associated with increased frequency of MCI. CONCLUSION: In the Chinese population aged 35-64 years, advanced age and cigarette smoking were risk factors of MCI, whereas higher educational level and alcohol drinking were protective factors for MCI. Excessive serum or plasma levels of NEFAs, SFAs and PUFAs were associated with an increased risk of MCI.
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Disfunção Cognitiva/sangue , Ácidos Graxos não Esterificados/sangue , Ácidos Graxos Insaturados/sangue , Ácidos Graxos/sangue , Adulto , Povo Asiático , China , Disfunção Cognitiva/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-IdadeRESUMO
BACKGROUND In this study, we explored the effect of an improved dietary pattern on 25-hydroxyvitamin D3 [25(OH)VitD3] level in hypertensive patients in a rural setting and investigated the possible mechanism for lowering blood pressure. MATERIAL AND METHODS Thirty-three participants with overweight or obesity were randomly divided into 2 groups. A 24-h dietary review method was used for dietary assessment. Participants in both groups were provided the same balanced diet except for the breakfast staple food for 4 weeks. General characteristics, body composition analysis, blood pressure, serum lipid profile, inflammatory indices, and serum 25(OH)VitD3 level were assessed at baseline and at the completion of the 4-week dietary intervention. Nutrient intake was analyzed by dietary analysis software, and SPSS software was used for correlation and regression analyses. RESULTS Thirty-one participants completed the study. The prevalence of vitamin D deficiency was 100% at baseline. After the dietary intervention, the prevalence of vitamin D deficiency decreased to 45%. Levels of dietary intake of vitamin D, cholesterol, protein, fat, and calcium showed a significantly positive correlation with the serum 25(OH)VitD3 level. Body fat, visceral fat, waist-to-hip ratio, serum triglyceride, and Toll-2 expression were negatively correlated with the serum 25(OH)VitD3 level. Blood pressure had a significant negative correlation with 25(OH)VitD3 level. Participants in both groups experienced a significant decrease in blood pressure. CONCLUSIONS Intake of a balanced diet rich in vitamin D, with appropriate amounts of cholesterol, protein, calcium, and fat, helped improve body composition, ameliorated lipid metabolism disorder, reduced inflammation, and improved serum 25(OH)VitD3 level, thus lowering blood pressure.
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Povo Asiático , Calcifediol/sangue , Dieta/métodos , Hipertensão/metabolismo , População Rural , Deficiência de Vitamina D/epidemiologia , Idoso , China/epidemiologia , Dietoterapia , Feminino , Humanos , Hipertensão/dietoterapia , Hipertensão/epidemiologia , Metabolismo dos Lipídeos , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
PURPOSE: This study aimed to examine the influence of a WeChat-based dietary and exercise intervention on gestational diabetes mellitus (GDM) prevention in overweight/obese pregnant women in Beijing. METHODS: Overweight/obese pregnant women were recruited in the early stages of pregnancy. After screening by include and exclude standards, eligible women were randomly divided into two groups, intervention and control groups. The control group received a general advice session about pregnancy nutrition and weight management. The intervention group received three face-to-face sessions about personalized dietary and exercise intervention, with the help of WeChat as a monitoring tool to promote treatment plan adherence. At 24-28 weeks of pregnancy, GDM was diagnosed according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Gestational weight gain (GWG), maternal and neonatal outcomes were also collected. RESULTS: This study analyzed 215 participants. At the mid-trimester, 42 (37.8%) women in the control group were diagnosed with GDM (n = 111) versus 25 (24.5%) in the intervention group (n = 104; p < 0.05). The intervention group gained 11.2 ± 4.9 kg during the whole gestation period, with 4.9 ± 3.1 kg-weight increment in the first 25 weeks of pregnancy, versus 13.4 ± 5.0 kg and 6.9 ± 3.2 kg in the first 25 weeks in the control group (between groups: p < 0.001/p = 0.002). Incidence of macrosomia was not significantly lower in the intervention group than in the control group (8/7.9% vs 11/9.9%) (p > 0.05). No significant difference was found in the rate of natural labor and occurrence of perinatal complications (e.g., preterm birth, gestational hypertension, and preeclampsia) between the groups (p > 0.05). CONCLUSIONS: The WeChat-assisted dietary and exercise intervention was effective in reducing the occurrence of GDM and excessive weight gain in overweight/obese pregnant women. Disseminating knowledge of pregnancy and childbirth through social media platforms like WeChat could be an important part of antenatal care.
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Diabetes Gestacional/prevenção & controle , Dieta , Terapia por Exercício/métodos , Obesidade/prevenção & controle , Sobrepeso/prevenção & controle , Complicações na Gravidez/prevenção & controle , Adulto , Feminino , Ganho de Peso na Gestação , Humanos , Recém-Nascido , Obesidade/complicações , Sobrepeso/complicações , Gravidez , Gestantes , Nascimento Prematuro/epidemiologiaRESUMO
We present here a new class of niobium oxoclusters that are stabilized effectively by carboxylate ionic liquids. These functionalized ILs are designated as [TBA][LA], [TBA][PA], and [TBA][HPA] in this work, in which TBA represents tetrabutylammonium and LA, PA, and HPA refer to lactate, propionate, 3-hydroxypropionate anions, respectively. The as-synthesized Nb oxoclusters have been characterized by use of elemental analysis, NMR, IR, XRD, TGA, HRTEM. It was found that [TBA][LA]-stabilized Nb oxoclusters (Nb-OC@[TBA][LA]) are uniformly dispersed with an average particle size of 2-3â nm and afforded exceptionally high catalytic activity for the selective oxidation of various thioethers. The turnover number with Nb-OC@[TBA][LA] catalyst was over 56 000 at catalyst loading as low as 0.0033â mol % (1â ppm). Meantime, the catalyst also showed the high activity for the epoxidation of olefins and allylic alcohols by using only 0.065â mol % of catalyst (50â ppm). The characterization of 93 Nbâ NMR spectra revealed that the Nb oxoclusters underwent structural transformation in the presence of H2 O2 but regenerated to their initial state at the end of the reaction. In particular, the highly dispersed Nb oxoclusters can absorb a large amount of polar organic solvents and thus were swollen greatly, which exhibited "pseudo" liquid phase behavior, and enabled the substrate molecules to be highly accessible to the catalytic center of Nb oxocluster units.
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Accumulating evidence indicates that enhancer of zeste homolog 2 (EZH2) promotes the metastatic ability of solid tumors, but the role of EZH2 in extramedullary infiltration (EMI) in acute myeloid leukemia (AML) has not been thoroughly explored. In the present study, we investigated the possible association between EZH2 and EMI. We found that the messenger RNA (mRNA) and protein expression levels of EZH2 in AML patients were both significantly higher than in idiopathic thrombocytopenic purpura (ITP) patients. Furthermore, a positive correlation between EZH2 mRNA expression and percentage of peripheral blood blasts wa s found in AML patients (r = 0.404, p = 0.009). The migratory capacities of Kasumi-1 and HL-60, which both show a high level of EZH2 expression, were markedly higher than those of U937 and KG-1α. In contrast, silencing of EZH2 resulted in reduction in proliferation and migration ability and an increase in apoptosis. The latter observation was accompanied by reduced expression of associated proteins p-ERK, p-cmyc, and matrix metalloproteinase 2 (MMP-2) and an increase in epithelial cadherin (E-cadherin). These data suggest that higher expression of EZH2 may be associated with extramedullary infiltration in acute myeloid leukemia and affect pathogenesis via activation of the p-ERK/p-cmyc/MMP-2 and E-cadherin signaling pathways.
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Proteína Potenciadora do Homólogo 2 de Zeste/biossíntese , Leucemia Mieloide Aguda/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Movimento Celular/fisiologia , Criança , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Leucemia Mieloide Aguda/metabolismo , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Transdução de Sinais/fisiologia , Adulto JovemRESUMO
The polymeric immunoglobulin receptor (pIgR) is one of the most important mucosal effectors mediating the transcytosis of polymeric immunoglobulins (pIgs) to protect the organisms. In this paper, a full-length cDNA of pIgR was firstly cloned from flounder (Paralichthys olivaceus) using rapid amplification of cDNA ends approaches, and it was of 1384 bp, containing an open reading frame (ORF) of 1005 bp encoding a polypeptide of 335 amino acids with the predicted molecular mass of 37.6 kDa. The flounder pIgR exhibited a unique structure containing only two immunoglobulin-like domains (ILD) corresponding to mammalian pIgR ILD1 and ILD5. The mRNA transcripts of pIgR were detected in all the tested tissues of flounder by semi-quantitative RT-PCR, and the pIgR was expressed at the highest level in liver and higher levels in intestine, gill, skin, spleen and head kidney than in stomach and muscle. The ORF was successfully expressed in Escherichia coli BL21 (DE3) and the recombinant protein displayed binding capability to the purified mucus IgM and serum IgM of flounder by ELISA. The polyclonal antibody against flounder recombinant pIgR was developed by immunization of Balb/C mice, which specifically reacted to the recombinant pIgR in Western blot. Moreover, a secretory component-like molecule was detected in the skin mucus but not in the serum of flounder, which molecular mass (about 37 kDa) was near the theoretical mass obtained from the sequence of flounder pIgR. All these results indicated that flounder pIgR probably involved in the pIgs transport and provided insights into the roles of fish pIgR in the mucosal immunity.
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Clonagem Molecular , Linguado/metabolismo , Regulação da Expressão Gênica/fisiologia , Receptores de Imunoglobulina Polimérica/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Ligação Proteica , Receptores de Imunoglobulina Polimérica/genéticaRESUMO
An irrational diet has been widely considered as one of the vital risk factors of hypertension. Previous studies have indicated that immune dysfunction may be involved in the pathogenic process of hypertension, while fewer studies have mentioned whether CD4+ T cells are involved in the association between dietary pattern and hypertension. This present 1:1 matched case-control study was conducted to analyze the association among dietary pattern, CD4+ T cells and hypertension. A total of 56 patients with diagnosed hypertension and 56 subjects without diagnosed hypertension in the rural area of Beijing City, northern China, were matched by age and gender, and then classified into a case group and a control group, respectively. Compared with the control group, higher frequencies of pro-inflammatory CD4+ T cells, such as Th1, Th1(IFN-γ), Th17(IL-17A), and Th1/17 (IFN-γ/IL-17A), were found in the case group (p < 0.05). A significantly higher level of circulating IL-17A was also found in the case group (7.4 pg/mL vs. 8.2 pg/mL, p < 0.05). Five dietary patterns were identified using exploratory factor analysis. An irrational dietary pattern, characterized by high-factor loadings of refined wheat (0.65), meat (0.78), poultry (0.76), and alcoholic beverage (0.73), was positively associated with SBP (ß = 5.38, 95%CI = 0.73~10.03, p < 0.05) in the multiple linear regression model with the adjustment of potential covariates. The other dietary patterns showed no significant association with blood pressure. Furthermore, meat, processed meat, and animal viscera were positively correlated with the peripheral Th17 or Th1/17. In conclusion, the irrational dietary pattern characterized by refined wheat, meat, poultry, and alcoholic beverage, was positively correlated with blood pressure, and may increase the risk of hypertension in the rural area of Beijing, northern China. Th17, a subset of the CD4+ T helper cells, may be involved in the association between irrational dietary pattern and hypertension.
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Hipertensão , Células Th17 , Humanos , Pequim , Estudos de Casos e Controles , Dieta/efeitos adversos , Hipertensão/epidemiologia , Hipertensão/etiologia , Interleucina-17 , Células Th1 , Pessoa de Meia-Idade , IdosoRESUMO
BACKGROUND: Bleeding episodes in hemophiliacs with inhibitors are difficult to control. Staidson protein-0601 (STSP-0601), a specific factor (F)X activator purified from the venom of Daboia russelii siamensis, has been developed. OBJECTIVES: We aimed to investigate the efficacy and safety of STSP-0601 in preclinical and clinical studies. METHODS: In vitro and in vivo preclinical studies were performed. A phase 1, first-in-human, multicenter, and open-label trial was conducted. The clinical study was divided into parts A and B. Hemophiliacs with inhibitors were eligible for this study. Patients received a single intravenous injection of STSP-0601 (0.01 U/kg, 0.04 U/kg, 0.08 U/kg, 0.16 U/kg, 0.32 U/kg, or 0.48 U/kg) in part A or a maximum of 6 4-hourly injections (0.16 U/kg) in part B. The primary endpoint for each part was the number of adverse events (AEs) from baseline to 168 hours after administration. This study was registered at clinicaltrials.gov (NCT-04747964 and NCT-05027230). RESULTS: Preclinical studies showed that STSP-0601 could specifically activate FX in a dose-dependent manner. In the clinical study, 16 patients in part A and 7 patients in part B were enrolled. Eight (22.2%) AEs in part A and 18 (75.0%) AEs in part B were reported to be related to STSP-0601. Neither severe AEs nor dose-limiting toxicity events were reported. There were no thromboembolic event. The antidrug antibody of STSP-0601 was not detected. CONCLUSION: Preclinical and clinical studies showed that STSP-0601 had a good ability to activate FX and had a good safety profile. STSP-0601 could be used as a hemostatic treatment in hemophiliacs with inhibitors.
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Hemofilia A , Humanos , Hemofilia A/diagnóstico , Hemofilia A/tratamento farmacológico , Proteínas de Neoplasias , Cisteína Endopeptidases , AnticorposRESUMO
BACKGROUND: Spleen tyrosine kinase (Syk) inhibitor is a treatment option for primary immune thrombocytopenia. We aimed to evaluate the safety, tolerability, pharmacokinetics, preliminary activity, and recommended phase 2 dose of sovleplenib in patients with primary immune thrombocytopenia. METHODS: This randomised, double-blind, placebo-controlled, phase 1b/2 study was conducted at nine hospitals in China. Eligible patients were aged 18-75 years, had an ECOG performance score of 0-1, had primary immune thrombocytopenia for more than 6 months, and did not respond or relapsed after previous first-line treatment or had poor response or postoperative relapse after a splenectomy. Dose-escalation (100 mg, 200 mg, or 300 mg given orally once a day) and dose-expansion phases (recommended phase 2 dose) each consisted of an 8-week, double-blind, placebo-controlled period in which patients were randomly assigned (3:1) to receive sovleplenib or placebo with an interactive web response system followed by a 16-week, open-label period with sovleplenib. Patients, investigators, and the sponsor were masked to treatment allocation during the first 8 weeks. The main efficacy endpoint was the proportion of patients whose platelet count reached 30 × 109 platelets per L or higher and was double of the baseline at two consecutive visits during 0-8 weeks without rescue therapy. Efficacy was evaluated by intention-to-treat. This study is registered with ClinicalTrials.gov, NCT03951623. FINDINGS: Between May 30, 2019, and April 22, 2021, 62 patients were assessed for eligibility and 45 (73%) were randomly assigned. Patients received at least one dose of the study drug during the 8-week double-blind period (placebo [n=11] and sovleplenib 100 mg [n=6], 200 mg [n=6], 300 mg [n=16], and 400 mg [n=6]; this group was added following the observation of no protocol-specified safety events at the previous doses). All participants were Asian; 18 (40%) of 45 were male and 27 (60%) were female. The median age was 40·0 years (IQR 33·0-50·0). Ten (29%) of 34 patients in sovleplenib groups versus five (45%) of 11 in the placebo group received concomitant anti-primary immune thrombocytopenia therapy. The recommended phase 2 dose was determined as 300 mg once a day. The proportion of patients who met the main efficacy endpoint were three (50%; 95% CI 12-88) in the 100 mg group, three (50%; 12-88) in the 200 mg group, ten (63%; 35-85) in the 300 mg group, and two (33%; 4-78) in the 400 mg group compared with one (9%; 0-41) in the placebo group. The overall response rate in the 300 mg group was 80% (16 of 20 who received continuous sovleplenib plus those who crossed over from placebo) and the durable response rate was 31% (11-59; five of 16) in the continuous sovleplenib 300 mg and 75% (19-99; three of four) crossed from placebo to sovleplenib during 0-24 weeks. During the 28-day safety evaluation period, two grade 2 or worse treatment-related treatment-emergent adverse events occurred in the sovleplenib groups (hypertriglyceridaemia and anaemia). During 0-8 weeks, the most frequent treatment-emergent adverse events were an increase in blood lactate dehydrogenase, haematuria, and urinary tract infection (seven [21%] of 34 in sovleplenib groups vs one [9%] of 11 in the placebo group); and occult blood-positive and hyperuricaemia (four [12%] vs three [27%] for each). No fatal treatment-emergent adverse events were recorded. INTERPRETATION: Sovleplenib was well tolerated, and the recommended phase 2 dose showed a promising durable response in patients with primary immune thrombocytopenia, which provides evidence for future investigations. A phase 3 trial is ongoing (NCT05029635) to confirm the efficacy and safety of sovleplenib in patients with primary immune thrombocytopenia. FUNDING: HUTCHMED.
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Púrpura Trombocitopênica Idiopática , Humanos , Masculino , Feminino , Adulto , Resultado do Tratamento , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Contagem de Plaquetas , Doença Crônica , Método Duplo-Cego , Quinase Syk/uso terapêuticoRESUMO
Dietary fatty acid intake is closely related to the cognitive function of the overweight and obese population. However, few studies have specified the correlation between exact fatty acids and cognitive functions in different body mass index (BMI) groups. We aimed to explain these relationships and reference guiding principles for the fatty acid intake of the overweight and obese population. Normal weight, overweight, and obese participants were recruited to receive a cognitive function assessment and dietary survey, dietary fatty acids intake was calculated, and the erythrocyte membrane fatty acid profile was tested by performing a gas chromatography analysis. The percentages of saturated fatty acids (SFAs) in the obese group were higher, while monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) were lower than in the normal weight and overweight groups. In the erythrocyte membrane, the increase of n-3 PUFAs was accompanied by cognitive decline in the overweight group, which could be a protective factor for cognitive function in the obese group. High n-6 PUFAs intake could exacerbate the cognitive decline in the obese population. Dietary fatty acid intake had different effects on the cognitive function of overweight and obese people, especially the protective effect of n-3 PUFAs; more precise dietary advice is needed to prevent cognitive impairment.
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Ácidos Graxos , Sobrepeso , Idoso , Cognição , Gorduras na Dieta , Membrana Eritrocítica , Humanos , Pessoa de Meia-Idade , ObesidadeRESUMO
Purpose: To verify the mediating role of inflammatory factors in plasma fatty acid-induced changes in cognitive function in patients with type 2 diabetes mellitus (T2DM). Patients and Methods: In this study, we evaluated the cognitive function of 372 Chinese patients (the average age was 58.00 (52.50, 63.00) years) with T2DM by using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), with plasma fatty acids measured by gas chromatography analysis and inflammatory cytokines determined by immune turbidimetric analysis and enzyme-linked immunosorbent assay (ELISA) to investigate whether there was a correlation between the plasma fatty acids, inflammatory cytokine levels and cognitive test scores in Chinese patients with T2DM. Results: We found that the increase of waist circumference and hip circumference might lead to cognitive impairment and induce the inflammatory response. Higher saturated fatty acids (SFAs) levels in plasma were linked to cognitive decline, while higher monounsaturated fatty acids (MUFAs) intake might be a protective factor for cognitive function. In addition, higher levels of plasma n-6 polyunsaturated fatty acids (n-6 PUFAs) stood out as having association with lower cognitive function scores, while higher level of plasma C22:6 n-3 could be a predictor of better cognitive function. In our study, higher SFAs led to higher proinflammatory factor levels. Apart from that, MUFAs and stearoyl-CoA desaturase-18 (SCD-18) were positively related to hypersensitive C-reactive protein (hs-CRP). Meanwhile, higher level of plasma C20:0 could lead to better MMSE delayed recall by reduce the expression of hs-CRP. Conclusion: Levels of plasma SFAs, C18:3 n-6, and C20:3 n-6 could be a predictor for worse cognitive function, while MUFAs and C22:6 n-3 could be a predictor for better cognitive function. The level of hs-CRP could be a mediator of C20:0 induced the change of cognitive function.
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OBJECTIVE: To identify the key genes and explore mechanisms in the development of myelodysplastic syndrome (MDS) by bioinformatics analysis. METHODS: Two cohorts profile datasets of MDS were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed gene (DEG) was screened by GEO2R, functional annotation of DEG was gained from GO database, gene ontology (GO) enrichment analysis was performed via Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and key genes were screened by Matthews correlation coefficient (MCC) based on STRING database. RESULTS: There were 112 DEGs identified, including 85 up-regulated genes and 27 down-regulated genes. GO enrichment analysis showed that biological processes were mainly enriched in immune response, etc, cellular component in cell membrane, etc, and molecular function in protein binding, etc. KEGG signaling pathway analysis showed that main gene enrichment pathways were primary immunodeficiency, hematopoietic cell lineage, B cell receptor signaling pathway, Hippo signaling pathway, and asthma. Three significant modules were screened by Cytoscape software MCODE plug-in, while 10 key node genes (CD19, CD79A, CD79B, EBF1, VPREB1, IRF4, BLNK, RAG1, POU2AF1, IRF8) in protein-protein interaction (PPI) network were screened based on STRING database. CONCLUSION: These screened key genes and signaling pathways are helpful to better understand molecular mechanism of MDS, and provide theoretical basis for clinical targeted therapy.
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Biologia Computacional , Síndromes Mielodisplásicas , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Análise em Microsséries , Síndromes Mielodisplásicas/genética , Mapas de Interação de ProteínasRESUMO
The association between intestinal permeability and sarcopenia remains unclear, and few studies have mentioned the relationship between intestinal permeability and skeletal muscle strength. The present cross-sectional community study was conducted in a rural area of Beijing to explore the association between intestinal permeability and handgrip strength (HGS) in middle-aged and older adults. Serum lipopolysaccharide (LPS), diamine oxidase (DAO) and D-lactate were detected to evaluate intestinal permeability. Gut microbiota (GM) and its potential interaction were also analyzed in the decision tree model. HGS was negatively correlated with DAO (r = −0.396, p < 0.01) in males. The negative association between HGS and DAO remained significant with the adjustment of covariates (ß = −1.401, p < 0.05). Serum DAO and LPS were both negatively associated with HGS in middle-aged and older males, with the significant interactions of GM in the decision tree model, and D-lactate showed a negative association with HGS in females. Therefore, intestinal permeability was associated with the loss of skeletal muscle strength in middle-aged and older adults, and serum DAO may be a novel predictor for the loss of skeletal muscle strength in middle-aged and older males.
RESUMO
Immune thrombocytopenia (ITP), characterized by decreased platelet counts, is a complex immune-mediated disorder with unelucidated pathogenesis. Accumulating evidence shows that T cell-mediated platelet destruction is one crucial process during the progression of ITP. Here, we attempted to identify core genes in peripheral blood-derived T-cells of chronic ITP through the analysis of microarray data (GSE43179) and clinical verification, with the aim to further understand the pathogenesis and progression of ITP. Compared with healthy controls, 97 differentially expressed genes (DEGs), including 63 up-regulated and 34 down-regulated were identified in ITP patients. Functional enrichment analysis showed that the DEGs were mainly enriched in innate immune response, inflammatory response, and IL-17 signaling pathway. Among the DEGs, top 15 hub genes ranked by degree score were identified via protein-protein interaction (PPI) network and were further confirmed by quantitative reverse transcription PCR (qRT-PCR). Among top 15 hub genes, the expression levels of 14 DEGs like TLR4, S100A8, S100A9, and S100A12 were significantly up-regulated, while one DEG IFNG was down-regulated in ITP patients. Noticeably, TLR4 exhibited the highest degree score, and S100A8 had the largest fold change in qRT-PCR analysis. Altogether, our results suggested that the pathogenesis and progression of ITP are related with multiple immune-related pathways, and that TLR4 and S100A8 are likely to play crucial roles.
Assuntos
Perfilação da Expressão Gênica , Púrpura Trombocitopênica Idiopática , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Humanos , Mapas de Interação de Proteínas/genética , Púrpura Trombocitopênica Idiopática/genética , Linfócitos T , Receptor 4 Toll-Like/genéticaRESUMO
The antioxidative properties of genistein (Gen) have been demonstrated by our previous studies and others, but its potential mechanism was not very clear. Because of the key role of mitochondria in oxidant production, we wondered if mitochondria were one of Gen's neuroprotective targets. In the present study we investigated whether Gen has protective effects on mitochondria damaged by Aß25-35. PC12 cells were pre-incubated with or without Gen for 2 h followed by the incubation with 20 µM Aß25-35 for another 24 h before mitochondrial membrane fluidity (MMF), mitochondrial membrane potential (MMP) , and mitochondrial redox state were measured. The results showed that Gen alleviated the decrease of MMF induced by Aß25-35, and maintained the MMP. Additionally, Gen promoted the mitochondrial antioxidative capability through increasing the GSH/GSSG ratio, GPx activity and MnSOD protein expression in mitochondria. Moreover, Gen reversed the changes of ChAT mRNA and AChE mRNA expression in cells induced by Aß25-35. These results suggested that Gen can protect the mitochondrial membrane and maintain redox state in mitochondria damaged by Aß25-35.
Assuntos
Peptídeos beta-Amiloides/antagonistas & inibidores , Genisteína/farmacologia , Fragmentos de Peptídeos/antagonistas & inibidores , Peptídeos beta-Amiloides/farmacologia , Animais , Interações Medicamentosas , Camundongos , Oxirredução , Células PC12 , Fragmentos de Peptídeos/farmacologia , RatosRESUMO
BACKGROUND: A fast-growing body of evidence suggests that dietary lipids influence cognition, but the effects of dietary fatty acid (FA) intake and plasma FA profile on cognitive function in obese populations are currently unclear. The present study aimed to investigate the dietary FA intakes and plasma FA composition and their association with cognitive functions in obese and overweight populations aged 35-64 years. METHODS: A total of 672 subjects were recruited and divided into normal-weight, overweight, and obese groups based on their body mass index (BMI). Dietary information was collected using a semiquantified food frequency questionnaire. Plasma FAs composition was examined using gas chromatography. The mini-mental state examination and Montreal Cognitive Assessment scales were carried out to assess the cognitive performance of each participant. Dietary FA intake and plasma FA composition were compared with rank transformation followed by one-way ANOVA analysis across different BMI groups. Spearman rank correlation analysis was used to investigate the correlation between dietary FA intake and plasma FA composition and cognitive functions in normal-weight, overweight, and obese subjects, respectively. RESULTS: Overweight and obese subjects consumed larger amounts of saturated fatty acids (SFAs) compared to normal-weight participants (p < .05). Obese populations also had higher plasma levels of total SFAs and total monounsaturated fatty acid (MUFAs) than normal-weight subjects (both p < .05). In addition, plasma levels of SFAs, polyunsaturated fatty acids (PUFAs), and MUFAs were negatively correlated with cognitive functions in obese subjects but showed no correlation in normal-weight and overweight subjects. CONCLUSIONS: From current data, we found higher plasma levels of SFA, PUFA, and MUFA in obese populations, which were associated with declined cognition. Lowering plasma FA levels may help maintaining normal cognitive functions in obese people.