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1.
Plants (Basel) ; 13(4)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38498445

RESUMO

Bacterial wilt is a significant soil-borne disease that poses a threat to mulberry production yield and quality of agricultural production worldwide. However, the disease resistance mechanisms dependent on root exudates are not well understood. In this present study, we investigated the antibacterial mechanisms of the main active substances (erucamide, oleamide, and camphor bromide) present in mulberry root exudates (MRE) against Ralstonia pseudosolanacearum (Rp), the causal agent of bacterial wilt. Our findings revealed that these three active substances inhibited the growth activity of Rp by affecting the cell morphology and extracellular polysaccharide content, as well as triggering a burst of reactive oxygen species. The active substances induced oxidative stress, leading to a decrease in Rp growth. Additionally, the expression levels of key genes in the hrp gene cluster (hrpB, hrpX, and hrpF) and other virulence-related genes (such as ripAW, ripAE, Rs5-4819, Rs5-4374, ace, egl3, and pehB) were significantly reduced upon treatment with the active substances. Further pathogenicity experiments demonstrated that root exudates (at a concentration of 1.5 mg·mL-1) delayed or slowed down the occurrence of bacterial wilt in mulberry. These findings provide valuable insight into the antimicrobial mechanisms of MRE against Rp and lay a theoretical foundation for the development and application of biocontrol agents to control mulberry bacterial wilt.

2.
Biol Trace Elem Res ; 202(2): 401-409, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37145256

RESUMO

Compiling evidence supports that selenium plays a vital role in glucose metabolism. Triglyceride-glucose index (TyG) and triglyceride-glucose-body mass index (TyG-BMI) are commonly used in epidemiologic studies to evaluate insulin resistance and cardiovascular disease (CVD) risks. This study is aimed to investigate the association between whole blood selenium concentration and TyG and TyG-BMI. A total of 6290 participants (age ≥ 20 years) from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 were included. Multiple linear regression models were used to examine the association between blood selenium quartiles and TyG and TyG-BMI. Subgroup analysis stratified by diabetes status was also performed. The adjusted model showed a positive association between TyG and blood selenium concentration (ß [95%CI] = 0.099 [0.063, 0.134], p < 0.001) and TyG-BMI (ß [95%CI] = 3.185 [2.102, 4.268], p < 0.001). The association persisted after stratification by diabetes status (p < 0.001). Participants were stratified into four quartiles based on selenium concentration (Q1: 1.08-2.24 µmol/L, Q2: 2.25-2.42 µmol/L, Q3: 2.43-2.62 µmol/L, Q4: 2.63-8.08). Compared with the Q1 group, TyG in the Q3 and Q4 groups was significantly higher (ß = 0.075 [95%CI 0.039 to 0.112] and ß = 0.140 [95%CI 0.103 to 0.176], respectively). Additionally, TyG-BMI in the Q2, Q3, and Q4 groups was higher than that in the Q1 group (ß = 1.189 [95%CI 0.065 to 2.314], ß = 2.325 [95%CI 1.204 to 3.446], and ß = 4.322 [95%CI 3.210 to 5.435], respectively). Blood level of selenium was positively associated with TyG and TyG-BMI, indicating that excessive blood selenium may be associated with impaired insulin sensitivity and increased risk of cardiovascular disease.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Resistência à Insulina , Selênio , Adulto , Humanos , Adulto Jovem , Índice de Massa Corporal , Inquéritos Nutricionais , Doenças Cardiovasculares/epidemiologia , Glucose , Triglicerídeos , Glicemia , Fatores de Risco , Biomarcadores
3.
Int J Cardiol ; 398: 131606, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37996014

RESUMO

BACKGROUND: Platelet activation and thrombus formation play critical roles in the pathogenesis of myocardial infarction (MI). In addition to their role in energy production, platelet mitochondria also regulate cellular functions related to apoptosis, oxidative stress, and inflammation. Epigenetic modifications of platelet mitochondrial DNA (mtDNA) may influence platelet function and are believed to be an important factor in MI. Therefore, the aim of this study was to investigate the differences in platelet mtDNA methylation levels between MI patients and controls. METHODS: The present study utilized propensity score matching to generate 45 multivariate matched apparently healthy controls for 45 patients with newly-onset acute MI. Platelet mtDNA methylation levels were assessed through bisulfite-PCR pyrosequencing and compared between the two groups, with further adjustments made in the sensitivity analysis. RESULTS: Among the measured mitochondrial genes (MT-COX1, MT-COX2, MT-COX3, MT-ND5, MT-ATP6 and tRNA_Leu), patients with MI exhibited statistically significant differences in mtDNA methylation levels as compared to matched controls. Specifically, higher levels of mtDNA methylation were observed in MT-COX1, MT-COX3, and tRNA_Leu, while a lower level was observed in MT-ATP6 (all p < 0.0001). These results remained robust in the sensitivity analysis. CONCLUSION: Our study demonstrated significant variations in platelet mtDNA methylation levels between patients with MI and controls. Platelet mtDNA methylation may serve as a novel biomarker for MI. This observation also provided some insights into the etiology of MI.


Assuntos
DNA Mitocondrial , Infarto do Miocárdio , Humanos , DNA Mitocondrial/genética , Metilação de DNA , Mitocôndrias/genética , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/genética , Biomarcadores , RNA de Transferência
4.
BMC Gastroenterol ; 23(1): 376, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37919650

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is easily neglected in the non-obese population. TyG index (triglyceride glucose Index) and TG/HDL-c (triglyceride to high-density lipoprotein cholesterol) are new indicators to evaluate insulin resistance (IR). Fibroscan is a non-invasive way to assess hepatic steatosis [by control attenuation parameters (CAP)] and fibrosis [by liver stiffness measurement (LSM)].The purpose of this study was to explore the correlation of TyG and its combination with obesity indicators [TyG-waist circumference (WC), TyG-body mass index (BMI)] and TG/HDL-c with CAP and LSM. METHOD: One thousand seven hundred seventy-six adults (age ≥ 20 years, BMI < 30 kg/m2) in the National Health and Nutrition Examination Survey (NHANES) 2017-2018 were included. The correlations of CAP and LSM to the indexes were assessed by generalized linear models.. Receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic capability of the indicators on NAFLD and liver stiffness. RESULTS: Survey-weighted percentage of NAFLD in non-obese was 38.6%. In the fully adjusted models, there were positive associations of TyG, TyG-BMI, TyG-WC and TG/HDL-c to CAP, with the ßs of 24.810, 0.704, 0.29 and 2.983 (all p < 0.05), respectively. There were positive associations of TyG, TyG-BMI, TyG-WC, and TG/HDL-c to NAFLD, with ORs of 3.387, 1.03, 1.010 and 1.281 ((all p < 0.05)).The positive association was detected for TG/HDL-c and TyG-WC and LSM with ßs of 0.057 and 0.004(p = 0.021 and p = 0.003).TyG-WC were positively associated with liver stiffness with OR of 1.006(95%CI = 1.002, 1.012). Furthermore, the TyG-WC had the strongest diagnostic capability (ROC = 0.806; 95%CI: 0.785-0.826) on NAFLD in non-obese participants, with a specificity of 0.737 and sensitivity of 0.746. CONCLUSION: In US non-obese population, the TyG, TyG-BMI, TyG-WC, and TG/HDL-c are positively correlated with CAP and NAFLD. TyG-WC has clinical importance in identifying NAFLD in the non-obese population.


Assuntos
Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Obesidade , Adulto , Humanos , Adulto Jovem , Glicemia , Índice de Massa Corporal , Glucose , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Inquéritos Nutricionais , Obesidade/epidemiologia , Triglicerídeos , Circunferência da Cintura
5.
Heliyon ; 9(9): e19393, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37809443

RESUMO

The purpose of this research is in-depth understanding of the internal causes of exergy destruction in various parts of the system and to identify potential improvements for the components. The focus is on a combined cycle power generation system that utilizes the organic Rankine cycle (ORC) and direct expansion cycle (DEC). To investigate the primary sources of exergy destruction in each component, advanced exergy analysis (AEA) is utilized. The result demonstrates that the net out power of the proposed system can reach 106.64 kW with energy efficiency of 11.22%, and exergy efficiency of 21.40%. The heat exchanger is identified as the primary contributor to exergy destruction, constituting 81.70% of the total ratio. Specifically, the condenser exhibits the highest exergy destruction ratio at 59.82%, indicating a need for prioritized optimization efforts. The findings of AEA reveal that the primary source of component irreversibility stems from the endogenous part. This shows that, while most exergy destruction is unavoidable, there remains room for system improvement. Regarding the turbine, its exergy destruction is primarily attributed to inefficiencies, leading to irreversibility. Nevertheless, there is exergy destruction that may be avoidable and can be reduced by 25.93 kW, which is 2.5 times greater than that of the heat exchanger. This finding underscores the high potential for improvement in ORC and DEC turbines, making them a priority for optimization efforts.

6.
Pestic Biochem Physiol ; 195: 105570, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37666623

RESUMO

The general cutworm, Spodoptera litura (Lepidoptera: Noctuidae) is a worldwide destructive omnivorous pest and the endoparasitoid wasp Meteorus pulchricornis (Hymenoptera: Braconidae) is the dominant endoparasitoid of S. litura larvae. Trehalase is a key enzyme in insect trehalose metabolism and plays an important role in the growth and development of insects. However, the specific function of trehalase in parasitoid and host associations has been less reported. In this study, we obtained two trehalase genes (SlTre1 and SlTre2) from our previously constructed S. litura transcriptome database; they were highly expressed in 3rd instar larvae. SlTre1 was mainly expressed in the midgut, and SlTre2 was expressed highest in the head. SlTre1 and SlTre2 were highly expressed 5 days after parasitization by M. pulchricornis. Treatment with the trehalase inhibitor validamycin A significantly inhibited the expression levels of SlTre1 and SlTre2, and the trehalase activity. Besides, the content of trehalose was increased but the content of glucose was decreased 24 h after validamycin A treatment in parasitized S. litura larvae. In addition, the immune-related genes in phenoloxidase (PO) pathway and fatty acid synthesis-related genes in lipid metabolism were upregulated in parasitized host larvae after validamycin A treatment. Importantly, the emergence rate, proportion of normal adults, and body size of parasitoid offspring was decreased in parasitized S. litura larvae after validamycin A treatment, indicating that validamycin A disrupts the trehalose metabolism of parasitized host and thus reduces the fitness of parasitoid offspring. The present study provides a novel perspective for coordinating the application of biocontrol and antibiotics in agroecosystem.


Assuntos
Trealase , Trealose , Animais , Trealase/genética , Metabolismo dos Carboidratos , Larva
7.
Pestic Biochem Physiol ; 194: 105503, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37532323

RESUMO

Glyphodes pyloalis Walker (G. pyloalis) is a common destructive mulberry pest. Due to the long-term and frequent use of insecticides, it has developed tolerance to commonly used insecticides. Tolfenpyrad (TFP) is a novel pyrazole heterocyclic insecticide. In order to understand the TFP detoxification mechanism of G. pyloalis larvae, we first estimated the LC30 dose of TFP for 3rd instar G. pyloalis larvae. Next, we identified genes that were differentially expressed in 3rd instar G. pyloalis larvae treated with TFP compared to the control group by transcriptome sequencing. In total, 86,949,569 and 67,442,028 clean reads were obtained from TFP-treated and control G. pyloalis larvae, respectively. A total of 5588 differentially expressed genes (DEGs) were identified in TFP-treated and control G. pyloalis larvae, of which 3084 genes were upregulated and 2504 genes were downregulated. We analyzed the expression of 43 candidate detoxification enzyme genes associated with insecticide tolerance using qPCR. According to the spatiotemporal expression pattern of DEGs, we found that CYP6ABE1, CYP333A36 and GST-epsilon8 were highly expressed in the midgut, while CarEs14 was strongly expressed in haemolymph. Furthermore, we successfully knocked down these genes by RNA interference. After silencing CYP6ABE1 and CYP333A36, bioassay showed that the mortality rate of TFP-treated G. pyloalis larvae was significantly higher compared to the control group. This study provides a theoretical foundation for understanding the sensitivity of G. pyloalis to TFP and establish the basis for the effective and green management of this pest.


Assuntos
Inseticidas , Mariposas , Animais , Inseticidas/farmacologia , Inseticidas/metabolismo , Mariposas/metabolismo , Larva/genética , Pirazóis/metabolismo
8.
Carbohydr Polym ; 314: 120924, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37173024

RESUMO

In recent years, the incidence of diabetic skin ulcers has increased. Because of its extremely high disability and fatality rate, it brings a huge burden to patients and society. Platelet-rich plasma (PRP) contains a large number of biologically active substances and is of great clinical value in the treatment of various wounds. However, its weak mechanical properties and the consequent abrupt release of active substances greatly limit its clinical application and therapeutic efficacy. Here, we chose hyaluronic acid (HA) and ε-polylysine (ε-PLL) to prepare a hydrogel with the ability to prevent wound infection and promote tissue regeneration. At the same time, using the macropore barrier effect of the lyophilized hydrogel scaffold, platelets in PRP are activated with calcium gluconate in the macropores of the scaffold carrier, and fibrinogen from PRP is converted in a fibrin-packed network forming a gel that interpenetrates the hydrogel scaffold carrier, thus creating a double network hydrogel with slow-release of growth factors from degranulated platelets. The hydrogel not only showed better performance in functional assays in vitro, but also showed more superior therapeutic effects in reducing inflammatory response, promoting collagen deposition, facilitating re-epithelialization and angiogenesis in the treatment of full skin defects in diabetic rats.


Assuntos
Diabetes Mellitus Experimental , Plasma Rico em Plaquetas , Ratos , Animais , Hidrogéis/farmacologia , Hidrogéis/metabolismo , Ácido Hialurônico/farmacologia , Ácido Hialurônico/metabolismo , Preparações de Ação Retardada/metabolismo , Diabetes Mellitus Experimental/metabolismo , Bandagens
9.
BMJ Open ; 13(5): e072317, 2023 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-37225271

RESUMO

OBJECTIVE: The purposes of the study were to investigate the detailed association of serum uric acid (SUA) with visceral fat area (VFA) and body fat percentage (BFP) as calculated by bioelectrical impedance analysis (BIA) and build non-invasive diagnosis models of hyperuricaemia by combining obesity-related indicators, age and sex. METHOD: A total of 19 343 adults were included. Multivariable regression analysis models were employed to analyse the association of SUA with VFA and BFP. Receiver operating characteristic curves were generated to diagnose hyperuricaemia in adults. RESULTS: After fully adjusting for covariates, SUA was positively associated with VFA, BFP and body mass index (BMI) with ßs of 0.447, 2.522 and 4.630 (95% CI= (0.412 to 0.482), (2.321 to 2.723) and (4.266 to 4.994)). After stratification by gender, this association persists (p<0.001). Fitted smoothing curves identified non-linear relationships between SUA and both VFA and BMI after full adjustment in males (inflection points: 93.9 cm2 and 30.9 kg/m2). A non-linear relationship also exists between SUA and BFP in females (inflection point: 34.5%). A combined model incorporating BFP, BMI, age and sex exhibited the best ability to diagnose hyperuricaemia (AUC (area under the curve) =0.805, specificity=0.602, sensitivity=0.878). For normal-weight and lean populations, individuals with hyperuricaemia tended to have higher levels of VFA and BFP in females and males, respectively (p<0.001). The combination of VFA, BFP, BMI, age and sex exhibited the best ability to diagnose hyperuricaemia in normal-weight and lean populations (AUC=0.803, specificity=0.671, sensitivity=0.836). CONCLUSION: VFA and BFP are independent factors associated with SUA. In males, SUA shows a non-linear relationship with VFA and BMI. In females, SUA and BFP exhibit a non-linear relationship. In normal-weight and lean individuals, the accumulation of VFA and BFP may be involved in hyperuricaemia. VFA and BFP were helpful in diagnosing hyperuricaemia in adults, especially for normal-weight and lean populations.


Assuntos
Adiposidade , Hiperuricemia , Feminino , Masculino , Adulto , Humanos , Ácido Úrico , Estudos Transversais , População do Leste Asiático , Hiperuricemia/diagnóstico , Hiperuricemia/epidemiologia , Obesidade
10.
Front Microbiol ; 14: 1090534, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36896429

RESUMO

Sulfolipid-1 (SL-1) is located in the Mycobacterium tuberculosis (M. tb) cell wall, and is essential for pathogen virulence and intracellular growth. Multiple proteins (e.g., Pks2, FadD23, PapA1, and MmpL8) in the SL-1 synthesis pathway can be treated as drug targets, but, to date, their structures have not been solved. The crystal structures of FadD23 bound to ATP or hexadecanoyl adenylate was determined in this study. We have also investigated long-chain saturated fatty acids as biological substrates of FadD23 through structural, biological, and chemical analyses. The mutation at the active site of FadD23 greatly influences enzymatic activity. Meanwhile, the FadD23 N-terminal domain alone cannot bind palmitic acid without C-terminal domain facilitation since it is almost inactive after removing the C-terminal domain. FadD23 is the first protein in the SL-1 synthesis pathway whose structure has been solved. These results reveal the importance of the C-terminal domain in the catalytic mechanism.

11.
12.
Front Nutr ; 10: 1109824, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36937340

RESUMO

Background: Decreasing mass and metabolism in skeletal muscle are associated with increasing insulin resistance (IR) and type 2 diabetes mellitus (T2DM). The causal relation between sarcopenia and abnormal glucose metabolism may be bidirectional. This investigation is aimed to explore the detailed correlation between pre-diabetes and sarcopenia in United States (US) adults. Methods: A total of 22,482 adults aged ≥20 years in the National Health and Nutrition Examination Survey (NHANES) were included. Generalized linear models were conducted to examine associations between diabetes status, serum glucose, glycohemoglobin (HbA1c), and sarcopenia. Generalized additive models and smooth fitting curves were used to examine the non-linear relationship between HbA1c and ASMBMI. Sarcopenia was defined as ASMBMI (appendicular skeletal muscle mass/body mass index) < 0.789 for males, and <0.512 for females based on the cut-off values of the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project. Results: After fully adjusting for multiple covariates, sarcopenia was directly correlated with pre-diabetes [OR (95%CI) = 1.230 (1.057, 1.431), p = 0.008] and T2DM [OR (95%CI) = 2.106 (1.625, 2.729), p < 0.001]. In non-T2DM population, HbA1c was negatively correlated with ASMBMI [ß (95%CI) = -0.009 (-0.013, -0.005), p < 0.001]. The correlations only persisted in males. Furthermore, in male non-T2DM population, the association of HbA1c and ASMBMI presents an inverted U-shape curve with an inflection point of HbA1c 5.2%. Conclusion: Pre-diabetes is associated with increased risk of sarcopenia. HbA1c is an independent risk factor for loss of appendicular skeletal muscle mass and sarcopenia when HbA1c greater than 5.2% in the male non-T2DM population.

13.
Cell Rep ; 42(4): 112327, 2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-37000625

RESUMO

STING is a well-known signaling adaptor essential for sensing cytosolic dsDNA to produce type I interferon. Although the detailed underlying mechanisms remain enigmatic, recent studies show that STING activation can lead to T lymphocyte apoptosis. Here, we report that AIFM1 facilitates STING activation-induced cell apoptosis in T lymphocytes. Mechanistically, AIFM1 is upregulated after STING activation in T cells but not in HEK293T-STING and THP-1 cells, rendering T cells more sensitive to apoptosis. In contrast to the canonical role of AIFM1 in the caspase-independent parthanatos, the function of AIFM1 is operated by the formation of an AIFM1/IRF3/BAX complex and mitochondrial outer membrane permeabilization, which cause cytochrome c release and caspase activation. Furthermore, supplementation with newly synthesized AIFM1 can reconstitute STING activation-induced cell apoptosis in HEK293T-STING and THP-1 cells. Our study identifies AIFM1 as a key regulating factor determining the hypersensitivity of T lymphocytes to STING activation-induced cell apoptosis.


Assuntos
Apoptose , Linfócitos T , Humanos , Apoptose/genética , Fator de Indução de Apoptose , Caspases , Células HEK293 , Transdução de Sinais
14.
Sci Total Environ ; 872: 162154, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-36804988

RESUMO

Valorization of lignocellulosic biomass via anaerobic digestion (AD) is limited by its reluctant structure, leading to a substantial energy remaining in the solid digestate. To mitigate this effect, the integration of AD and pyrolysis has attracted attention in recent years. However, the energy recovery efficiency of this cascading system is still unclear, especially the time node. Herein, a comprehensive evaluation of this integration, using varied AD periods, was conducted, to produce biogas, bio-oil and biochar, and to enhance the energy recovery, from the perspective of energy flow. The result indicated that the accumulative CH4 yields increased from 33.23 to 249.20 mL/g VS as the AD time increased from 3 to 15 days. Pyrolysis of the obtained solid digestate obtained biochar from 28.81 to 35.96 %, while the bio-oil and pyrolysis gas slowly decreased. The highest energy efficiency of 71.9 % with a net energy gain of 2.0 MJ/kg wet biomass was achieved by the coupled system optimization at an AD time of 12 days as suggested by the energy flow analysis. This study provides new insight for the maximal conversion of biomass waste into energy products and provides a new way of recycling it.


Assuntos
Biocombustíveis , Pirólise , Anaerobiose , Biomassa
15.
J Cardiothorac Surg ; 18(1): 39, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36653806

RESUMO

BACKGROUND: Aortic dissection (AD) is a rare disease with high mortality for which no effective diagnostic biomarkers are available. Human cytomegalovirus (HCMV) infection is an important cause of the occurrence and progression of many diseases, but the relationship between HCMV infection and AD is not clear. METHODS: In this study, we first used quantitative reverse transcription polymerase chain reaction (qRT-PCR) to determine the expression profile of 25 HCMV-encoded microRNAs (HCMV miRNAs) in the plasma within a training set consisting of 20 AD patients and 20 healthy controls. Then, abnormal expressed HCMV miRNAs were verified in a validation set of 12 AD patients and 12 healthy controls. In addition, HCMV infection was detected in the third cohort consisting of 20 AD patients and 20 healthy controls. RESULTS: The 95% quantile of the expression levels of HCMV miRNAs in the training set was used as the threshold for distinction between AD patients and healthy controls. The proportion of individuals with high level of five types of HCMV miRNAs was significantly different between AD patients and healthy controls. In the validation set, only the proportion of individuals with high levels of hcmv-miR-UL112-5p and hcmv-miR-UL22A-5p, two of the five HCMV miRNAs obtained in the preliminary screening, showed significant difference between AD patients and healthy controls. In the third cohort, there was no significant difference in HCMV DNA levels and anti-HCMV IgG concentrations between AD patients and healthy controls. CONCLUSIONS: The HCMV miRNAs levels in plasma differed in AD patients and healthy controls. This finding may contribute to a further understanding of the relationship between HCMV infection and AD and are worthy of future research on the diagnosis and etiology of AD.


Assuntos
Infecções por Citomegalovirus , MicroRNAs , Humanos , Citomegalovirus/genética , Citomegalovirus/metabolismo , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/genética , MicroRNAs/genética , MicroRNAs/metabolismo
16.
Nat Commun ; 14(1): 444, 2023 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-36707536

RESUMO

Neural stem cell (NSC) maintenance and functions are regulated by reactive oxygen species (ROS). However, the mechanisms by which ROS control NSC behavior remain unclear. Here we report that ROS-dependent Igfbp2 signaling controls DNA repair pathways which balance NSC self-renewal and lineage commitment. Ncf1 or Igfbp2 deficiency constrains NSCs to a self-renewing state and prevents neurosphere formation. Ncf1-dependent oxidation of Igfbp2 promotes neurogenesis by NSCs in vitro and in vivo while repressing Brca1 DNA damage response genes and inducing DNA double-strand breaks (DDSBs). By contrast, Ncf1-/- and Igfbp2-/- NSCs favor the formation of oligodendrocytes in vitro and in vivo. Notably, transient repression of Brca1 DNA repair pathway genes induces DDSBs and is sufficient to rescue the ability of Ncf1-/- and Igfbp2-/- NSCs to lineage-commit to form neurospheres and neurons. NSC lineage commitment is dependent on the oxidizable cysteine-43 residue of Igfbp2. Our study highlights the role of DNA damage/repair in orchestrating NSC fate decisions downstream of redox-regulated Igfbp2.


Assuntos
Células-Tronco Neurais , Diferenciação Celular/genética , Espécies Reativas de Oxigênio/metabolismo , Células-Tronco Neurais/metabolismo , Neurogênese/genética , Oxirredução , Dano ao DNA , Proliferação de Células
17.
Chem Asian J ; 17(24): e202200986, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36268769

RESUMO

The cytochrome P450 family of monooxygenase enzymes have essential biological roles involving the selective oxidation of carbon-hydrogen bonds. They can also catalyze other important metabolic reactions including desaturation to form alkenes. Currently the factors that control the partition between P450 hydroxylation and desaturation pathways are poorly defined. The CYP199A4 enzyme from the bacterium Rhodopseudomonas palustris HaA2 catalyzes the oxidation of 4-ethyl- and 4-isopropyl- benzoic acids with hydroxylation and desaturation occurring in significant quantities. Here we demonstrate that 4-cyclopropylbenzoic acid is regioselectively hydroxylated by CYP199A4 at the benzylic carbon. In contrast, the oxidation of 4-n-propylbenzoic acid by CYP199A4 results in three major metabolites: an alkene from desaturation and two hydroxylation products at the benzylic (Cα) and Cß carbons in similar quantities. Extending the length of the alkyl substituent resulted in 4-n-butylbenzoic acid being oxidized at the benzylic position (45%) and desaturated (55%). In contrast, 4-isobutylbenzoic generated very little alkene (5%) but was hydroxylated at the benzylic position (54%) and at the tertiary Cß position (41%). The oxidation of 4-n-propylbenzoic acid by the F298 V mutant of CYP199A4 occurred with no hydroxylation at Cß and a significant increase in metabolites arising from desaturation (73%). The X-ray crystal structures of CYP199A4 with each substrate revealed that they bind in the active site with the alkyl substituent positioned over the heme. However, the longer alkylbenzoic acids were bound in a different conformation as was 4-n-propylbenzoic acid in the F298 V mutant. Overall, the changes in metabolite distribution could be ascribed to bond strength differences and the position of the alkyl group relative to the heme.


Assuntos
Sistema Enzimático do Citocromo P-450 , Heme , Especificidade por Substrato , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/metabolismo , Heme/química , Catálise , Alcenos , Carbono
18.
BMC Endocr Disord ; 22(1): 231, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109703

RESUMO

BACKGROUND: Adiposity evaluated by body mass index (BMI) is associated with glycometabolism. The aim of the investigation was to explore the correlation of visceral fat area (VFA), body fat percentage (BFP), BMI and waist circumference (WC) with type 2 diabetes mellitus (T2DM) and pre-diabetes. METHODS: A total of 18,458 participates underwent physical examination in Nanjing Drum Tower Hospital from January 2018 to April 2022 was included in this study. Data were collected retrospectively. Regression analysis was used to evaluate the relationship of VFA, BFP, WC and BMI with diabetes status, fasting blood glucose (FBG) and glycohemoglobin (HbA1c). RESULTS: After fully adjusted for multiple covariates, VFA, BFP, WC and BMI in T2DM and pre-diabetes group exceeded compared with normal group. FBG was positively correlated with VFA, BFP, WC and BMI with ßs of 2.221,0.306,0.606 and 0.175(p < 0.001). HbA1c was also positively correlated with the four indexes with ßs of 2.645, 0.328, 0.685 and 0.255(p < 0.001). Subgroup analysis shown that FBG and HbA1c were positively correlated with VFA, BFP, BMI and WC in normal and pre-diabetes group (p < 0.001). FBG was negatively correlated with BMI in T2DM group (p = 0.023). In T2DM, there were non-linear relationships of HbA1c with VFA, BFP, WC and BMI with the inflection points for about 7%. Before the inflection point, HbA1c was positively correlated with obesity-related indicators, and it was reversed after the inflection point. In the individuals with excessive VFA and normal BMI, the risk for glycometabolism disorder exceed compared with normal VFA and normal BMI. Every per-standard deviation increasing in VFA, BFP, WC and BMI, the corresponding risk increasing of glycometabolism disorder was 16.4, 14.6, 22.6 and 22.2%. CONCLUSION: The study demonstrated that in adults with T2DM or prediabetes, the VFA, BFP, WC and BMI were higher than with normal glycometabolism. In pre-diabetes and normal population, there were positive correlations of HbA1c and FBG with obesity-related indicators. In T2DM with poor glycemic control (HbA1c > 7%), there might be a trend of fat loss. VFA could negatively affect glycometabolism independently from BMI. The optimum to evaluate the risk of glycometabolism disorder was WC.


Assuntos
Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Adulto , Glicemia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Impedância Elétrica , Hemoglobinas Glicadas , Humanos , Gordura Intra-Abdominal , Obesidade/diagnóstico , Obesidade/epidemiologia , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Estudos Retrospectivos , Fatores de Risco
19.
Insects ; 13(9)2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36135534

RESUMO

Trehalase is an essential hydrolase of trehalose in insects. However, whether and how trehalase performs in the association of parasitoid wasps and their hosts still remains unknown. Here, the exact function of trehalase of the general cutworm Spodoptera litura after it was parasitized by its predominant endoparasitoid Meterous pulchricornis was elucidated. Two trehalase genes (SlTre1, SlTre2) were identified, and they were highly expressed five days after parasitization by M. pulchricornis. Then, we successfully silenced SlTre1 and SlTre2 in parasitized third instar S. litura larvae. The content of glucose, which is the hydrolysate of trehalose, was significantly decreased after silencing SlTres in parasitized S. litura larvae, and the activities of trehalase were also notably reduced. In addition, the cocoon weight, the emergence rate, proportion of normal adults, and the body size of parasitoid offsprings were significantly decreased in SlTre1- or SlTre2-silenced groups compared to the controls. These results implied that parasitization by parasitoids regulated the trehalase of host larvae to create a suitable nutritional environment for the parasitoid offspring. The present study broadens the knowledge of trehalase in the interaction between parasitoids and their hosts and is of benefit to biological control of S. litura acting by parasitoid wasps.

20.
EPMA J ; 13(3): 397-405, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35990778

RESUMO

Background: Risk prediction models can help identify individuals at high risk for type 2 diabetes. However, no such model has been applied to clinical practice in eastern China. Aims: This study aims to develop a simple model based on physical examination data that can identify high-risk groups for type 2 diabetes in eastern China for predictive, preventive, and personalized medicine. Methods: A 14-year retrospective cohort study of 15,166 nondiabetic patients (12-94 years; 37% females) undergoing annual physical examinations was conducted. Multivariate logistic regression and least absolute shrinkage and selection operator (LASSO) models were constructed for univariate analysis, factor selection, and predictive model building. Calibration curves and receiver operating characteristic (ROC) curves were used to assess the calibration and prediction accuracy of the nomogram, and decision curve analysis (DCA) was used to assess its clinical validity. Results: The 14-year incidence of type 2 diabetes in this study was 4.1%. This study developed a nomogram that predicts the risk of type 2 diabetes. The calibration curve shows that the nomogram has good calibration ability, and in internal validation, the area under ROC curve (AUC) showed statistical accuracy (AUC = 0.865). Finally, DCA supports the clinical predictive value of this nomogram. Conclusion: This nomogram can serve as a simple, economical, and widely scalable tool to predict individualized risk of type 2 diabetes in eastern China. Successful identification and intervention of high-risk individuals at an early stage can help to provide more effective treatment strategies from the perspectives of predictive, preventive, and personalized medicine.

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