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1.
Bioact Mater ; 19: 550-568, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35600969

RESUMO

Spinal cord injury (SCI) is an overwhelming and incurable disabling event accompanied by complicated inflammation-related pathological processes, such as excessive reactive oxygen species (ROS) produced by the infiltrated inflammatory immune cells and released to the extracellular microenvironment, leading to the widespread apoptosis of the neuron cells, glial and oligodendroctyes. In this study, a thioketal-containing and ROS-scavenging hydrogel was prepared for encapsulation of the bone marrow derived mesenchymal stem cells (BMSCs), which promoted the neurogenesis and axon regeneration by scavenging the overproduced ROS and re-building a regenerative microenvironment. The hydrogel could effectively encapsulate BMSCs, and played a remarkable neuroprotective role in vivo by reducing the production of endogenous ROS, attenuating ROS-mediated oxidative damage and downregulating the inflammatory cytokines such as interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), resulting in a reduced cell apoptosis in the spinal cord tissue. The BMSCs-encapsulated ROS-scavenging hydrogel also reduced the scar formation, and improved the neurogenesis of the spinal cord tissue, and thus distinctly enhanced the motor functional recovery of SCI rats. Our work provides a combinational strategy against ROS-mediated oxidative stress, with potential applications not only in SCI, but also in other central nervous system diseases with similar pathological conditions.

2.
Food Chem ; 398: 133930, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35988410

RESUMO

Enzymatic hydrolysis could reduce the allergenicity of pea protein. Box-Behnken model was used to extract vicilin with the lowest and highest allergenicity, and enzymatic hydrolysis, electrophoresis, spectroscopy, bioinformatics, and peptidomics of Nano-LC-MS/MS were utilized to explore the relationship between reduced allergenicity and structural changes. After enzymatic hydrolysis, the allergenicity of L-vicilin hydrolysates (L-VHs) and H-vicilin hydrolysates (H-VHs) decreased significantly (P < 0.05). Furthermore, large-molecular-weight subunits in L-vicilin and H-vicilin were decomposed into <11 kDa peptides, and their surface hydrophobicity were increased. The OH, NH, and CO groups underwent stretching vibrations, and α-helix and ß-sheet were transformed into ß-turn and random coils. Additionally, linear epitopes of P13918, D3VND7, D3VNE2, and P02856 in L-VHs and H-VHs were cut into different fragments. Among them, distinct linear epitope fragments of them might be responsible for the difference in their allergenicity. Therefore, enzymatic hydrolysis with Alclase could effectively reduce the allergenicity of vicilin by regulating sensitization sites.


Assuntos
Alérgenos , Proteínas de Ervilha , Hidrólise , Subtilisinas/metabolismo , Espectrometria de Massas em Tandem
3.
BMC Urol ; 22(1): 147, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36096829

RESUMO

BACKGROUND: To investigate the value of computed tomography (CT)-based radiomics model analysis in differentiating renal oncocytoma (RO) from renal cell carcinoma subtypes (chromophobe renal cell carcinoma, clear cell carcinoma) and predicting the expression of Cytokeratin 7 (CK7). METHODS: In this retrospective study, radiomics was applied for patients with RO, chRCC and ccRCC who underwent surgery between January 2013 and December 2019 comprised the training cohort, and the testing cohort was collected between January and October 2020. The corticomedullary (CMP) and nephrographic phases (NP) were manually segmented, and radiomics texture parameters were extracted. Support vector machine was generated from CMP and NP after feature selection. Shapley additive explanations were applied to interpret the radiomics features. A radiomics signature was built using the selected features from the two phases, and the radiomics nomogram was constructed by incorporating the radiomics features and clinical factors. Receiver operating characteristic curve was calculated to evaluate the above models in the two sets. Furthermore, Rad-score was used for correlation analysis with CK7. RESULTS: A total of 123 patients with RO, chRCC and ccRCC were analyzed in the training cohort and 57 patients in the testing cohort. Subsequently, 396 radiomics features were selected from each phase. The radiomics features combining two phases yielded the highest area under the curve values of 0.941 and 0.935 in the training and testing sets, respectively. The Pearson's correlation coefficient was statistically significant between Rad-score and CK7. CONCLUSION: We proposed a non-invasive and individualized CT-based radiomics nomogram to differentiation among RO, chRCC and ccRCC preoperatively and predict the immunohistochemical protein expression for accurate clinical diagnosis and treatment decision.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Adenoma Oxífilo , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Citidina Monofosfato , Humanos , Queratina-7 , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Estudos Retrospectivos
4.
Ecotoxicol Environ Saf ; 244: 114041, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36063618

RESUMO

The abuse of antibiotics in animal husbandry has brought many public health problems, among which the passive use of antibiotics caused by eating food containing residual antibiotics has attracted the most attention. However, few studies have examined the possible adverse effects of prenatal antibiotics exposure on fetal growth and development. In this study, we investigated the associations between prenatal antibiotics exposure and measures of fetal growth. A total of 429 mother-newborn pairs from a birth cohort were enrolled and spot urine samples (N = 1287) were collected during each trimester of pregnancy. Sixteen antibiotics from 7 categories, were selected for the determination of the targeted antibiotics in maternal urines by UHPLC-MS/MS. Fetal growth indicators including newborn birth weight, birth length and gestational age (GA), were obtained from medical record. Sixteen antibiotics were found in 92.3% of the urine samples with detection frequencies ranging from 0.3% to 41.3%. Among the 16 antibiotics detected, we found that the exposure level of ciprofloxacin in the first trimester of pregnancy was negatively correlated with GA (ß = -0.17 day, 95% CI, -0.32 to -0.02 day), which would increase the risk of preterm birth (OR=1.05, 95% CI, 1.00, 1.09). The exposure level of norfloxacin in the second trimester of pregnancy was negatively correlated with fetal birth weight (ß = -17.56 g, 95% CI, -31.13 to -3.99 g) and birth length (ß = -0.05 cm, 95% CI, -0.08 to -0.02 cm), and the exposure level of sulfamethoxazole in the third trimester of pregnancy was negatively correlated with fetal birth length (ß = -0.15 cm, 95% CI, -0.29 to -0.02 cm). Our findings suggest that prenatal exposure to norfloxacin and sulfamethoxazole may adversely affect fetal growth and development.

5.
Physiol Int ; 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36057104

RESUMO

Background: Myocardial infarction is the primary cause of high disability and mortality in patients with cardiovascular disease worldwide. The pathological process of myocardial ischemia/reperfusion (I/R) may trigger harmful inflammatory response and ultimately lead to serious cardiac dysfunction. The mechanism of myocardial repair post myocardial infarction has not been fully elucidated. The present study speculated that VSIG4 is related to the regulation of heart injury. Methods: The myocardial I/R injury model was established in Sprague-Dawley (SD) rats. Before I/R operation, the viral solution containing AAV-NC or AAV-VSIG4 was intravenously injected into rats. Cardiac function indicators, mRNA expression, the apoptosis ratio of cardiomyocytes, myocardial infarct area, phenotype polarization of macrophage, and the protein expression of apoptosis or macrophage phenotype were measured. Results: Myocardial I/R injury decreased the expression of VSIG4 and subsequently triggered myocardial apoptosis. The induction of AAV-VSIG4 produced a protective effect on general cardiac function and attenuated the I/R-induced cellular apoptosis in rats. Moreover, VSIG4 signaling might potentially modulate macrophage M1/M2-related inflammatory disorders via activation of PI3K/AKT and inhibition of TLR4/NF-κB expression. Conclusion: In summary, the present study provided evidence that VSIG4 had cardiac protective role in myocardial I/R injury. More importantly, enhanced VSIG4 expression inhibited M1 polarization of macrophages by blocking TLR4/NF-κB activation, subsequently suppressing cardiomyocyte apoptosis. This finding provides vital insights into the role of VSIG4 in I/R injury and may provide a new target for I/R therapy.

6.
Carbohydr Polym ; 296: 119923, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36087977

RESUMO

A reliable electrophysiological electrode interface (EEI) between bioelectronic devices and biological tissues is indispensable to achieve the high fidelity recording of bioelectricity. However, there is an inherent tradeoff among EEI's electrochemical characteristics, mechanical properties and biocompatibility when considering the desired nanostructure and optimum composition. Here, we proposed a mechanically matched, highly conductive and biocompatible EEI, a tissue-like metal-doped hydrogel which could enable excellent electro-biosensing, by bringing disulfide modified silver nanowires into difunctional hyaluronan/carboxymethyl chitosan composite. The intensity of cortical signals at specific frequency domain recorded by the hydrogel-based EEI is doubled, which is significant for the diagnosis of epilepsy. Furthermore, the natural gel matrix could lead to seamless bio-integration between EEI and the tissue site of interest, minimizing signal dissipation without causing obvious inflammatory response. Overall, the EEI we designed contributes to improving tissue-device integration as well as bioelectronic device's performance and further leads to more effective human-computer interfaces.


Assuntos
Hidrogéis , Nanofios , Eletrodos , Humanos , Hidrogéis/química , Polissacarídeos , Prata
7.
Am J Prev Cardiol ; 12: 100379, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36090536

RESUMO

Machine learning (ML) refers to computational algorithms that iteratively improve their ability to recognize patterns in data. The digitization of our healthcare infrastructure is generating an abundance of data from electronic health records, imaging, wearables, and sensors that can be analyzed by ML algorithms to generate personalized risk assessments and promote guideline-directed medical management. ML's strength in generating insights from complex medical data to guide clinical decisions must be balanced with the potential to adversely affect patient privacy, safety, health equity, and clinical interpretability. This review provides a primer on key advances in ML for cardiovascular disease prevention and how they may impact clinical practice.

8.
Acta Biomater ; 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36100175

RESUMO

Naturally derived protein-based biopolymers are considered potential biomaterials in biomedical applications and eco-friendly materials for replacing current petroleum-based polymers due to their good biocompatibility, low environmental impact, and tunable degradability. However, current strategies for fabricating protein-based materials with superior properties and tailored functionality in a scalable manner are still lacking. Here, we demonstrate an aqueous-based scalable approach for fabricating silk protein-based films through controlled molecular self-assembly (CMS) of silk proteins with plasticizers and salt ions. The films fabricated using this method can achieve a toughness of up to 64±5 MJ/m3 with a stretchability of up to 574±31%. We also demonstrate the tunable enzymatic degradability, low in vitro cytotoxicity, and good in vivo biocompatibility of the films. Furthermore, the films can be patterned with predesigned complex structures through laser cutting and functionalized with bioactive components. The functional silk protein-based films show great potential in various applications, including flexible electronics, bioelectronics, tissue engineering, and bioplastic packaging. STATEMENT OF SIGNIFICANCE: Inspired by the naturally optimized multi-scale self-assembly of silk proteins in natural silks, we develop an aqueous-based approach for scalable production of superior protein-based films through controlled molecular self-assembly (CMS) of silk proteins with glycerol and calcium ions. The prepared silk films present outstanding mechanical properties, controlled enzymatic biodegradability, low in vitro cytotoxicity, and good in vivo biocompatibility. Notably, the films fabricated using this method can achieve a high toughness of 64±5 MJ/m3 with a stretchability of 594±31%. The approach introduced in this work provides a facile route toward making silk-based materials with superior properties. It also paves new avenues for developing functional protein-based materials with precisely controlled structures and properties for various applications.

9.
Front Immunol ; 13: 901176, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059480

RESUMO

Objective: To identify less invasive and easily applicable serum cytokine-derived biomarkers which contribute to the diagnostic utility and risk assessment ability of the prostate health index (PHI) based multivariable model in grey zone aggressive prostate cancer (AG PCa) early detection. Methods: Serum 45 cytokines screening was performed in a small training cohort consisting of 10 sera by Luminex liquid array-based multiplexed immunoassays and identified TRAIL and IL-10 as new biomarkers for PHI diagnostic utility adjustment for further validation with a multivariable predictive model in a cohort including 79 aggressive prostate cancer patients and 209 benign prostatic hyperplasia or indolent PCa patients within the PSA grey zone. Results: TRAIL and IL-10 were identified as potential serum biomarkers for AG PCa detection by the result of multi-cytokines screening in the univariate analysis, while multivariable logistic regression confirmed the AUC of the full risk predictive model (0.915) including tPSA, fPSA, PHI, TRAIL, and IL-10 was higher than various diagnostic strategies. DCA suggested a superior net benefit and indicated a good discriminative ability of the full risk model consistently with the result of the nomogram. Conclusion: We suggest a significant advantage for the PHI-based multivariate combinations of serum TRAIL and IL-10 comparing to PHI or other serum-derived biomarkers alone in the detection and risk stratification of grey zone AG PCa.


Assuntos
Interleucina-10 , Próstata , Neoplasias da Próstata , Ligante Indutor de Apoptose Relacionado a TNF , Biomarcadores Tumorais/sangue , Citocinas/sangue , Detecção Precoce de Câncer , Humanos , Interleucina-10/sangue , Interleucina-10/genética , Interleucina-10/metabolismo , Masculino , Próstata/metabolismo , Próstata/patologia , Antígeno Prostático Específico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Ligante Indutor de Apoptose Relacionado a TNF/sangue , Ligante Indutor de Apoptose Relacionado a TNF/genética , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo
10.
Front Pharmacol ; 13: 954684, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36071850

RESUMO

The gut microbiota (GM) has received extensive attention in recent years, and its key role in the establishment and maintenance of health and in the development of diseases has been confirmed. A strong correlation between the GM and the progression of endometriosis (EMS) has been observed in emerging research. Alterations in the composition and function of the GM have been described in many studies on EMS. In contrast, the GM in the environment of EMS, especially the GM metabolites, such as bile acids and short-chain fatty acids that are related to the pathogenesis of EMS, can promote disease progression. Chenodeoxycholic acid (CDCA), as one of the primary bile acids produced in the liver, is metabolized by various enzymes derived from the GM and is critically important in maintaining intestinal homeostasis and regulating lipid and carbohydrate metabolism and innate immunity. Given that the complexity of CDCA as a signalling molecule and the interaction between the GM and EMS have not been clarified, the role of the CDCA and GM in EMS should be understood from a novel perspective. However, few articles on the relationship between CDCA and EMS have been reviewed. Therefore, we review the available and possible potential links between CDCA, the GM and EMS and put forward the hypothesis that CDCA and its derivative obeticholic acid can improve the symptoms of EMS through the GM.

11.
Artigo em Inglês | MEDLINE | ID: mdl-36082180

RESUMO

Endometriosis (EM) is a common chronic inflammatory disease in women. Sampson's retrograde menstruation theory is the most widely accepted theory of EM pathogenesis. The periodic bleeding of ectopic lesions is an important pathological feature of this disease, and the occurrence and progression of EM are closely associated with the iron overload caused by ectopic lesions. However, animal models that simulate menstrual-blood reflux and hemorrhage from EM lesions are lacking. In this study, we performed intraperitoneal injection of endometrial fragments and periodic intraperitoneal blood injection to simulate the real cause and disease state of EM and successfully constructed a mouse model of EM iron overload. Our research found that the number, size, and degree of adhesion of EM lesions in the iron-overload model mouse were significantly higher than those in the model mouse. Moreover, the iron concentration in the abdominal fluid and ovary significantly increased, and the level of malondialdehyde (MDA) in the ovary increased. Conversely, GPX4, GSH, and other anti-ferroptosis-related proteins were downregulated, proving the occurrence of ferroptosis. Huayu Jiedu Fang (HYJDF) is an empirical prescription for EM treatment. This study combined animal experiments, UHPLC-QE-MS analysis, and network pharmacology to analyze whether HYJDF can inhibit ferroptosis to slow down the progression of EM and protect ovarian function. Based on the constructed iron-overload model, HYJDF can reduce the volume of EM lesions and the degree of adhesion, downregulate the total iron concentration in the peritoneal fluid and ovary, upregulate GPX4 expression and GSSG in the ovary, downregulate the level of MDA in the ovary, and promote the development of follicles. We further confirmed that HYJDF can inhibit the progression of EM disease and improve the ovarian function of the model mouse by inhibiting ferroptosis. Finally, through UHPLC-QE-MS and network pharmacology analysis, the natural compounds in HYJDF were identified and verified and the regulatory effect of HYJDF on the EM ferroptosis pathway through the IL-6/hepcidin pathway was preliminarily elucidated.

12.
Eur Radiol ; 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36070092

RESUMO

OBJECTIVES: We analyzed the diagnostic efficiency of 68Ga-pentixafor PET/CT for functional nodules in primary aldosteronism (PA). Furthermore, we compared the correlation of CXCR4 expression with aldosterone synthase (CYP11B2) expression and PET/CT uptake in these patients. METHODS: We prospectively assessed 50 patients diagnosed with PA and 10 patients with non-functional adrenal adenoma (NFA). All patients underwent 68Ga-pentixafor PET/CT before adrenalectomy. Immunohistochemistry (IHC) was performed to detect the protein expression of CYP11B2 and the G-protein-coupled receptor CXCR4. RESULTS: CYP11B2 IHC revealed the presence of 43 functional nodules. Subsequently, 40/43 functional nodules could be detected on 68Ga-pentixafor PET/CT, while negative imaging findings were noted for 11/13 non-functional nodules (sensitivity, 93.0%; specificity, 84.6%). The optimum SUVmax cut-off for the identification of functional nodules was 8.95 (AUC 0.914 [0.828-1.000], p < 0.001). Regarding the size of functional nodules, diagnostic efficiency appeared to be much higher for nodules greater than 1 cm in size (sensitivity, up to 97.3%). Moreover, we examined the relationship between CXCR4 and CYP11B2 expression in 56 lesions. All 43 CYP11B2-positive nodules were CXCR4-positive, but one of the 13 CYP11B2-negative nodules (7.7%) showed false-positive staining for CXCR4. Moreover, the consistency between PET/CT uptake and CXCR4 staining results was 92.9% (52/56). CONCLUSIONS: At least 90% of functional nodules show positive uptake on 68Ga-pentixafor PET/CT, and the detection ability is much better for nodules with a diameter ≥ 1 cm. With its high sensitivity and specificity, 68Ga-pentixafor PET/CT can be considered a promising surgical decision-making tool for patients with PA. KEY POINTS: • 68Ga-pentixafor PET/CT could be a useful tool for the identification of functional adrenal nodules in APAs and even IHAs. • The diagnostic efficiency appears to be much higher for nodules ≥ 1 cm in size. • There is high consistency between the results of 68Ga-pentixafor PET/CT imaging and CXCR4 immunohistochemistry.

13.
J Transl Med ; 20(1): 399, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064568

RESUMO

BACKGROUND: Peripheral biomarkers are increasingly vital non-invasive methods for monitoring coronary artery disease (CAD) progression. Their superiority in early detection, prognosis evaluation and classified diagnosis is becoming irreplaceable. Nevertheless, they are still less explored. This study aimed to determine and validate the diagnostic and therapeutic values of differentially expressed immune-related genes (DE-IRGs) in CAD. METHODS: We downloaded clinical information and RNA sequence data from the GEO database. We used R software, GO, KEGG and Cytoscape to analyze and visualize the data. A LASSO method was conducted to identify key genes for diagnostic model construction. The ssGSEA analysis was used to investigate the differential immune cell infiltration. Besides, we constructed CAD mouse model (low-density lipoprotein receptor deficient mice with high fat diet) to discover the correlation between the screened genes and severe CAD progress. We further uncovered the role of IL13RA1 might play in atherosclerosis. RESULTS: A total of 762 differential genes were identified between the peripheral blood of 218 controls and 199 CAD patients, which were significantly associated with infection, immune response and neural activity. 58 DE-IRGs were obtained by overlapping the differentially expressed genes(DEGs) and immune-related genes downloaded from ImmpDb database. Through LASSO regression, CCR9, CER1, CSF2, IL13RA1, INSL5, MBL2, MMP9, MSR1, NTS, TNFRSF19, CXCL2, HTR3C, IL1A, and NR4A2 were distinguished as peripheral biomarkers of CAD with eligible diagnostic capabilities in the training set (AUC = 0.968) and test set (AUC = 0.859). The ssGSEA analysis showed that the peripheral immune cells had characteristic distribution in CAD and also close relationship with specific DE-IRGs. RT-qPCR test showed that CCR9, CSF2, IL13RA1, and NTS had a significant correlation with LDLR-/- mice. IL13RA1 knocked down in RAW264.7 cell lines decreased SCARB1 and ox-LDL-stimulated CD36 mRNA expression, TGF-ß, VEGF-C and α-SMA protein levels and increased the production of IL-6, with downregulation of JAK1/STAT3 signal pathway. CONCLUSIONS: We constructed a diagnostic model of advanced-stage CAD based on the screened 14 DE-IRGs. We verified 4 genes of them to have a strong correlation with CAD, and IL13RA1 might participate in the inflammation, fibrosis, and cholesterol efflux process of atherosclerosis by regulating JAK1/STAT3 pathway.


Assuntos
Aterosclerose , Doença da Artéria Coronariana , Animais , Aterosclerose/genética , Biomarcadores/metabolismo , Doença da Artéria Coronariana/genética , Perfilação da Expressão Gênica , Camundongos , Transdução de Sinais/genética
14.
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 , Hemoglobina A Glicada , Humanos , Gordura Intra-Abdominal , Obesidade/diagnóstico , Obesidade/epidemiologia , Fenilpropionatos , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Estudos Retrospectivos , Fatores de Risco
15.
EJNMMI Phys ; 9(1): 62, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104468

RESUMO

BACKGROUND: The total-body positron emission tomography (PET) scanner provides an unprecedented opportunity to scan the whole body simultaneously, thanks to its long axial field of view and ultrahigh temporal resolution. To fully utilize this potential in clinical settings, a dynamic scan would be necessary to obtain the desired kinetic information from scan data. However, in a long dynamic acquisition, patient movement can degrade image quality and quantification accuracy. METHODS: In this work, we demonstrated a motion correction framework and its importance in dynamic total-body FDG PET imaging. Dynamic FDG scans from 12 subjects acquired on a uEXPLORER PET/CT were included. In these subjects, 7 are healthy subjects and 5 are those with tumors in the thorax and abdomen. All scans were contaminated by motion to some degree, and for each the list-mode data were reconstructed into 1-min frames. The dynamic frames were aligned to a reference position by sequentially registering each frame to its previous neighboring frame. We parametrized the motion fields in-between frames as diffeomorphism, which can map the shape change of the object smoothly and continuously in time and space. Diffeomorphic representations of motion fields were derived by registering neighboring frames using large deformation diffeomorphic metric matching. When all pairwise registrations were completed, the motion field at each frame was obtained by concatenating the successive motion fields and transforming that frame into the reference position. The proposed correction method was labeled SyN-seq. The method that was performed similarly, but aligned each frame to a designated middle frame, was labeled as SyN-mid. Instead of SyN, the method that performed the sequential affine registration was labeled as Aff-seq. The original uncorrected images were labeled as NMC. Qualitative and quantitative analyses were performed to compare the performance of the proposed method with that of other correction methods and uncorrected images. RESULTS: The results indicated that visual improvement was achieved after correction of the SUV images for the motion present period, especially in the brain and abdomen. For subjects with tumors, the average improvement in tumor SUVmean was 5.35 ± 4.92% (P = 0.047), with a maximum improvement of 12.89%. An overall quality improvement in quantitative Ki images was also observed after correction; however, such improvement was less obvious in K1 images. Sampled time-activity curves in the cerebral and kidney cortex were less affected by the motion after applying the proposed correction. Mutual information and dice coefficient relative to the reference also demonstrated that SyN-seq improved the alignment between frames over non-corrected images (P = 0.003 and P = 0.011). Moreover, the proposed correction successfully reduced the inter-subject variability in Ki quantifications (11.8% lower in sampled organs). Subjective assessment by experienced radiologists demonstrated consistent results for both SUV images and Ki images. CONCLUSION: To conclude, motion correction is important for image quality in dynamic total-body PET imaging. We demonstrated a correction framework that can effectively reduce the effect of random body movements on dynamic images and their associated quantification. The proposed correction framework can potentially benefit applications that require total-body assessment, such as imaging the brain-gut axis and systemic diseases.

16.
EJNMMI Phys ; 9(1): 63, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104580

RESUMO

PURPOSE: Efforts have been made both to avoid invasive blood sampling and to shorten the scan duration for dynamic positron emission tomography (PET) imaging. A total-body scanner, such as the uEXPLORER PET/CT, can relieve these challenges through the following features: First, the whole-body coverage allows for noninvasive input function from the aortic arteries; second, with a dramatic increase in sensitivity, image quality can still be maintained at a high level even with a shorter scan duration than usual. We implemented a dual-time-window (DTW) protocol for a dynamic total-body 18F-FDG PET scan to obtain multiple kinetic parameters. The DTW protocol was then compared to several other simplified quantification methods for total-body FDG imaging that were proposed for conventional setup. METHODS: The research included 28 patient scans performed on an uEXPLORER PET/CT. By discarding the corresponding data in the middle of the existing full 60-min dynamic scan, the DTW protocol was simulated. Nonlinear fitting was used to estimate the missing data in the interval. The full input function was obtained from 15 subjects using a hybrid approach with a population-based image-derived input function. Quantification was carried out in three areas: the cerebral cortex, muscle, and tumor lesion. Micro- and macro-kinetic parameters for different scan durations were estimated by assuming an irreversible two-tissue compartment model. The visual performance of parametric images and region of interest-based quantification in several parameters were evaluated. Furthermore, simplified quantification methods (DTW, Patlak, fractional uptake ratio [FUR], and standardized uptake value [SUV]) were compared for similarity to the reference net influx rate Ki. RESULTS: Ki and K1 derived from the DTW protocol showed overall good consistency (P < 0.01) with the reference from the 60-min dynamic scan with 10-min early scan and 5-min late scan (Ki correlation: 0.971, 0.990, and 0.990; K1 correlation: 0.820, 0.940, and 0.975 in the cerebral cortex, muscle, and tumor lesion, respectively). Similar correlationss were found for other micro-parameters. The DTW protocol had the lowest bias relative to standard Ki than any of the quantification methods, followed by FUR and Patlak. SUV had the weakest correlation with Ki. The whole-body Ki and K1 images generated by the DTW protocol were consistent with the reference parametric images. CONCLUSIONS: Using the DTW protocol, the dynamic total-body FDG scan time can be reduced to 15 min while obtaining accurate Ki and K1 quantification and acceptable visual performance in parametric images. However, the trade-off between quantification accuracy and protocol implementation feasibility must be considered in practice. We recommend that the DTW protocol be used when the clinical task requires reliable visual assessment or quantifying multiple micro-parameters; FUR with a hybrid input function may be a more feasible approach to quantifying regional metabolic rate with a known lesion position or organs of interest.

17.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(9): 996-1000, 2022 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-36082573

RESUMO

OBJECTIVE: To analyze the clinical features and genetic basis for a child with pyruvate carboxylase deficiency type A (PCD-A). METHODS: Clinical data of the child was retrospectively analyzed. The child and his parents were subjected to trio-whole exome sequencing, and candidate variants were verified by bioinformatics analysis. RESULTS: The child was admitted due to fever with vomiting and disturbance of consciousness. His clinical manifestations included severe decompensated acidosis, hypotension and intractable shock. Cranial MRI showed abnormal signal in the brain, and chest X-ray revealed acute pulmonary edema. DNA sequencing revealed that he has harbored compound heterozygous variants of the PC gene, namely c.182T>C (p.I61T) and c.2581G>A (p.V861M), which were respectively inherited from his father and mother. Neither variant was retrievable in the ClinVar and HGMD databases. Through prediction of protein structure, both variants may affect the functional stability of the protein product. CONCLUSION: The compound heterozygous variants of the PC gene probably underlay the PCD-A in this child. Combined with the clinical features, the child was ultimately diagnosed as PCD-A. Above finding has enriched the spectrum of PC gene variation underlying PCD-A.


Assuntos
Doença da Deficiência de Piruvato Carboxilase , Criança , Família , Humanos , Masculino , Mutação , Estudos Retrospectivos , Sequenciamento Completo do Exoma
18.
J Am Heart Assoc ; 11(17): e024885, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36056720

RESUMO

Background Mobile health (mHealth) has an emerging role in the prevention of cardiovascular disease. This study evaluated possible inequities in mHealth access in older adults. Methods and Results mHealth access was assessed from 2019 to 2020 in MESA (Multi-Ethnic Study of Atherosclerosis) telephone surveys of 2796 participants aged 62 to 102 years. A multivariable logistic regression model adjusted for general health status assessed associations of mHealth access measures with relevant demographic, socioeconomic, and cognitive characteristics. There were lower odds of all access measures with older age (odds ratios [ORs], 0.37-0.59 per 10 years) and annual income <$50 000 (versus ≥$50 000 ORs, 0.55-0.62), and higher odds with higher Cognitive Abilities Screening Instrument Score (ORs, 1.22-1.29 per 5 points). Men (versus women) had higher odds of internet access (OR, 1.32 [95% CI,1.05-1.66]) and computing device ownership (OR, 1.31 [95% CI, 1.05-1.63]) but lower fitness tracker ownership odds (OR, 0.70 [95% CI, 0.49-0.89]). For internet access and computing device ownership, we saw lower odds for Hispanic participants (versus White participants OR, 0.61 [95% CI, 0.44-0.85]; OR, 0.69 [95% CI, 0.50-0.95]) and less than a high school education (versus bachelor's degree or higher OR, 0.27 [95% CI, 0.18-0.40]; OR, 0.32 [95% CI, 0.28-0.62]). For internet access, lower odds were seen for Black participants (versus White participants OR, 0.64 [95% CI, 0.47-0.86]) and other health insurance (versus health maintenance organization/private OR, 0.59 [95% CI, 0.47-0.74]). Chinese participants (versus White participants) had lower internet access odds (OR, 0.63 [95% CI, 0.44-0.91]) but higher computing device ownership odds (OR, 1.87 [95% CI, 1.28-2.77]). Conclusions Among older-age adults, mHealth access varied by major demographic, socioeconomic, and cognitive characteristics, suggesting a digital divide. Novel mHealth interventions should consider individual access barriers. Registration URL: https://www.clinicaltrials.gov/; Unique identifier: NCT00005487.


Assuntos
Aterosclerose , Telemedicina , Idoso , Idoso de 80 Anos ou mais , Cognição , Etnicidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos , Telemedicina/métodos
19.
Drugs R D ; 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36136273

RESUMO

BACKGROUND AND OBJECTIVES: Aspirin is a common drug for the treatment of pre-eclampsia. We aimed to explore whether quercetin as a supplement to aspirin could enhance the therapeutic outcome in pre-eclampsia rat models. We further aimed to evaluate the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome as a potential pre-eclampsia-related molecular mechanism, which can be affected by quercetin treatment. METHODS: Rat pre-eclampsia models were established using an intravenous lipopolysaccharide injection after gestation. Rats were treated with aspirin and quercetin at 6-18 days after pregnancy. On day 20, blood, fetus, and placenta were harvested. Blood pressure and the level of proteinuria were measured every 4 days. Fetal outcomes were analyzed by pup body weight. Serum soluble Fms-like tyrosine kinase-1, PIGF, interleukin-6, and interleukin-10 levels were measured using the enzyme-linked immunosorbent assay. Caspase-1, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain, and p-caspase-1 levels in the placenta were assessed using western blot or quantitative real-time polymerase chain reaction analyses. RESULTS: Pre-eclampsia rat models showed a pronounced increase in systolic blood pressure and proteinuria after 4 days of pregnancy, while aspirin, quercetin, and aspirin/quercetin combinatory treatment significantly attenuated the blood pressure and proteinuria abnormalities. Notably, the aspirin/quercetin combinatory treatment showed the highest efficacy in attenuating pre-eclampsia-like symptoms. Placental caspase-1 and NLRP3 levels also showed the greatest attenuation in pre-eclampsia rats after aspirin/quercetin treatment. CONCLUSIONS: Our data suggested that quercetin supplementation to aspirin is more effective in attenuating symptoms of pre-eclampsia and improving pregnancy outcomes compared with quercetin or aspirin alone. Quercetin can ameliorate placental NLRP3 inflammasome activation, which might serve as an underlying mechanism for its therapeutic efficacies in pre-eclampsia.

20.
Am J Cancer Res ; 12(8): 3693-3712, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119820

RESUMO

Lysine-specific demethylase 1 (LSD1) is widely involved in the proliferation, invasion, and metastasis of cancers. However, it is uncertain whether LSD1 plays a role in facilitating colon cancer progression. Here, we have clarified the molecular mechanism by which LSD1 interacts with X-ray repair cross complementing protein 5 (Ku80) to promote colon cancer progression by directly targeting forehead protein transcription factor 2 (FOXF2). First, the interacting proteins of LSD1 were identified by immunoprecipitation and mass spectrometry. The expression of Ku80 and FOXF2 in colon cancer was detected using immunohistochemistry, real-time quantitative transcription polymerase chain reaction, and western blot. Next, the proliferation, invasion, and metastasis of colon cancer in vitro and in vivo were detected by methyl thiazolyl tetrazolium, 5-ethynyl-20-deoxyuridine, colony formation, wound healing, and nude mice xenograft model assays, respectively. Chromatin immunoprecipitation (ChIP) and ChIP-PCR were performed to investigate the molecular mechanism of LSD1 and Ku80 in colon cancer. Our results indicated that Ku80 expression was positively correlated with the invasion and migration of colon cancer cells, and negatively correlated with FOXF2 expression. More importantly, the high expression of Ku80 and the low expression of FOXF2 were particularly associated with driving the progression of colon cancer. Ku80 knockdown and LSD1 silencing inhibited the proliferation, migration, and invasion of colon cancer in vitro and in vivo. Mechanically, LSD1 interacts with Ku80 and also binds directly to the 687-887-bp portion of the FOXF2 promoter region. The upregulated methylation level of H3K4me2 in the FOXF2 promoter region facilitated the transcriptional activation of FOXF2, and downregulated protein expression associated with the Wnt/ß-catenin signaling pathway. In conclusion, our study suggests that LSD1 regulates the FOXF2-mediated Wnt/ß-catenin signaling pathway by interacting with Ku80, promoting the malignant biological properties of colon cancer, highlighting the binding of LSD1 and Ku80 as a useful anti-cancer target for colon cancer.

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