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1.
Hematology ; 27(1): 1196-1203, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36326455

RESUMO

AIM: This study aims to explore the expression and role of CD72 in B lymphocytes in immune thrombocytopenic purpura (ITP). METHODS: The expression level of CD72 in B lymphocytes was detected by flow cytometry in 18 ITP patients and 19 controls of healthy donor or iron-deficiency anemia patients. B cell proliferation was determined by 5-bromo-2'-deoxyuridine incorporation (BrdU) in the culture of 17 ITP patients' and 11 controls' peripheral mononuclear cells (PMNCs). The secretion levels of antibodies against human platelet antigens (HPA), as well as B cell proliferation-related cytokine interleukin 1(IL-1) and macrophage migration inhibitory factor (MIF) in culture supernatants were measured by ELISA. RESULTS: CD72 was significantly increased in B cells of newly diagnosed or persistent ITP compared with ITP in remission. B cell proliferation in culture with CD72 antibody addition was significantly decreased both in ITP patients and in controls compared with isotype antibody addition. CD72 antibody did not significantly alter HPA antibody level in ITP patients. CD72 antibody increased IL-1 and MIF levels in ITP patients' cell culture supernatant but not in controls. CONCLUSION: CD72 expression elevation accompanies the active status of ITP. In vitro addition of CD72 antibody has a negative impact on B cell proliferation. The function of CD72 in B cell proliferation in ITP may be related to IL-1 and MIF secretion.


Assuntos
Fatores Inibidores da Migração de Macrófagos , Púrpura Trombocitopênica Idiopática , Humanos , Antígenos CD , Antígenos de Diferenciação de Linfócitos B , Proliferação de Células , Interleucina-1 , Ativação Linfocitária
2.
Front Bioeng Biotechnol ; 10: 996723, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338129

RESUMO

Objectives: We developed a 3D U-Net-based deep convolutional neural network for the automatic segmentation of the vertebral cortex. The purpose of this study was to evaluate the accuracy of the 3D U-Net deep learning model. Methods: In this study, a fully automated vertebral cortical segmentation method with 3D U-Net was developed, and ten-fold cross-validation was employed. Through data augmentation, we obtained 1,672 3D images of chest CT scans. Segmentation was performed using a conventional image processing method and manually corrected by a senior radiologist to create the gold standard. To compare the segmentation performance, 3D U-Net, Res U-Net, Ki U-Net, and Seg Net were used to segment the vertebral cortex in CT images. The segmentation performance of 3D U-Net and the other three deep learning algorithms was evaluated using DSC, mIoU, MPA, and FPS. Results: The DSC, mIoU, and MPA of 3D U-Net are better than the other three strategies, reaching 0.71 ± 0.03, 0.74 ± 0.08, and 0.83 ± 0.02, respectively, indicating promising automated segmentation results. The FPS is slightly lower than that of Seg Net (23.09 ± 1.26 vs. 30.42 ± 3.57). Conclusion: Cortical bone can be effectively segmented based on 3D U-net.

3.
Nutrients ; 14(19)2022 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-36235838

RESUMO

Liver oxygen stress is one of the main extraintestinal manifestations of colitis and 5% of cases develop into a further liver injury and metabolic disease. 2'-fucosyllactose (2'-FL), a main member of human milk oligosaccharides (HMOs), has been found to exert efficient impacts on remitting colitis. However, whether 2'-FL exerts the function to alleviate colitis-induced liver injury and how 2'-FL influences the metabolism via regulating gut microbiota remain unknown. Herein, in our study, liver oxygen stress was measured by measuring liver weight and oxygen-stress-related indicators. Then, 16S full-length sequencing analysis and non-target metabolome in feces were performed to evaluate the overall responses of metabolites and intestinal bacteria after being treated with 2'-FL (400 mg/kg b.w.) in colitis mice. The results showed that, compared with the control group, the liver weight of colitis mice was significantly decreased by 18.30% (p < 0.05). After 2'-FL treatment, the liver weight was significantly increased by 12.65% compared with colitis mice (p < 0.05). Meanwhile, they exhibited higher levels of oxidation in liver tissue with decreasing total antioxidant capacity (T-AOC) (decreased by 17.15%) and glutathione (GSH) levels (dropped by 22.68%) and an increasing malondialdehyde (MDA) level (increased by 36.24%), and 2'-FL treatment could reverse those tendencies. Full-length 16S rRNA sequencing revealed that there were 39 species/genera differentially enriched in the control, dextran sulphate sodium (DSS), and DSS + 2'-FL groups. After treatment with 2'-FL, the intestinal metabolic patterns, especially glycometabolism and the lipid-metabolism-related process, in DSS mice were strikingly altered with 33 metabolites significantly down-regulated and 26 metabolites up-regulated. Further analysis found DSS induced a 40.01%, 41.12%, 43.81%, and 39.86% decline in acetic acid, propionic acid, butyric acid, and total short chain fatty acids (SCFAs) in colitis mice (all p < 0.05), respectively, while these were up-regulated to different degrees in the DSS + 2'-FL group. By co-analyzing the data of gut microbiota and metabolites, glycometabolism and lipid-metabolism-associated metabolites exhibited strong positive/negative relationships with Akkermansia_muciniphila (all p < 0.01) and Paraprevotella spp. (all p < 0.01), suggesting that the two species might play crucial roles in the process of 2'-FL alleviating colitis-induced liver oxygen stress. In conclusion, in the gut-liver-microbiotas axis, 2'-FL mediated in glucose and lipid-related metabolism and alleviated liver oxygen stress via regulating gut microbiota in the DSS-induced colitis model. The above results provide a new perspective to understand the probiotic function of 2'-FL.


Assuntos
Colite , Propionatos , Animais , Antioxidantes/metabolismo , Butiratos/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colo/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Ácidos Graxos Voláteis/metabolismo , Glucose/metabolismo , Glutationa/metabolismo , Humanos , Fígado/metabolismo , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Oxigênio/metabolismo , Propionatos/metabolismo , RNA Ribossômico 16S/genética , Trissacarídeos
4.
Artigo em Inglês | MEDLINE | ID: mdl-36239295

RESUMO

OBJECTIVE: To estimate the association between smoking and Schneiderian membrane perforation in sinus floor augmentation. MATERIALS AND METHODS: Searches were conducted in PubMed, Web of Science, Embase, and Cochrane Library. Data were extracted by two authors independently. The inclusion criteria were the (1) age of patients >18, (2) the number of participants >10, and (3) smoking and the patients of Schneiderian membrane perforation were accurately recorded. The risk of bias was assessed by the Newcastle-Ottawa scale (NOS). Statistics analyses were conducted using Reman5.4.1 and Stata (15.0). The association of Schneiderian membrane perforation with smoking habits during maxillary sinus floor elevation was expressed as odds ratios (ORs) with a 95% confidence interval (95% CIs). And the I2 statistic was used to estimate statistical heterogeneity. The funnel plot and Egger's tests were used to evaluate the reliability and stability of the results. RESULTS: Of 1463 articles screened, nine studies were included in our systematic review, and eight were synthesized for meta-analysis. Eight were retrospective observational studies and one was a clinical trial, with a total of 1424 patients included. The nine studies were proved as high quality according to the NOS. There was no significant publication bias in the studies (p = 0.827). A random-effects model was used because of differences in the adopted methodologies (p = 0.39, I2  = 5%). During maxillary sinus augmentation, smoking and Schneiderian membrane perforation were associated (odds ratios, 1.58 [95% CI, 1.10-2.25]). CONCLUSION: Smoking increased the risk of membrane perforation in maxillary sinus floor augmentation. Our evaluation was limited by the poor reporting of the number of cigarettes smoked per day (PROSPERO number was CRD42022306570).

5.
Front Endocrinol (Lausanne) ; 13: 963246, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36313781

RESUMO

Objective: To investigate the value of CT imaging features of paravertebral muscles in predicting abnormal bone mass in patients with type 2 diabetes mellitus. Methods: The clinical and QCT data of 149 patients with type 2 diabetes mellitus were collected retrospectively. Patients were randomly divided into the training group (n = 90) and the validation group (n = 49). The radiologic model and Nomogram model were established by multivariate Logistic regression analysis. Predictive performance was evaluated using receiver operating characteristic (ROC) curves. Results: A total of 829 features were extracted from CT images of paravertebral muscles, and 12 optimal predictive features were obtained by the mRMR and Lasso feature selection methods. The radiomics model can better predict bone abnormality in type 2 diabetes mellitus, and the (Area Under Curve) AUC values of the training group and the validation group were 0.94(95% CI, 0.90-0.99) and 0.90(95% CI, 0.82-0.98). The combined Nomogram model, based on radiomics and clinical characteristics (vertebral CT values), showed better predictive efficacy with an AUC values of 0.97(95% CI, 0.94-1.00) in the training group and 0.95(95% CI, 0.90-1.00) in the validation group, compared with the clinical model. Conclusion: The combination of Nomogram model and radiomics-clinical features of paravertebral muscles has a good predictive value for abnormal bone mass in patients with type 2 diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 2 , Tomografia Computadorizada por Raios X , Humanos , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Nomogramas , Músculos
6.
Polymers (Basel) ; 14(16)2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-36015648

RESUMO

Keloid is a poorly understood fibrotic skin disease that commonly occurs during wound-healing. As a polymer composed of nucleic acid and proteins, the structure of chromatin could be dynamically regulated in the nucleus. In this study, we explored the dynamics of chromatin accessibility and the transcriptome in dermal fibroblasts (DFs) in keloid formation. Compared to normal samples, chromatin accessibility and transcriptome were extensively altered in keloid DFs. In addition, changes in chromatin accessibility were closely associated with changes in gene expression in DFs. Breast cancer type 1 (BRCA1) was significantly downregulated in keloid DFs, and its knockdown promoted the proliferation and attenuated the migration ability of normal DF cells. Mechanistically, BRCA1 suppression significantly reduced the expression of neuronal pentraxin 2 (NPTX2), a cell viability-related gene. BRCA1 binding affinity at the NPTX2 enhancer and the chromatin accessibility in the same region were significantly lower in keloid DFs than in normal DFs, which might contribute to NPTX2 inhibition. In conclusion, this study identified BRCA1 inhibition in DFs as a novel pathological factor in keloids and preliminarily explored its potential mechanisms, which will help us understand the formation of keloids.

7.
Cancer Sci ; 113(8): 2849-2861, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35661486

RESUMO

Although resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) has gradually become a major challenge in the maintenance therapy for high-grade serous ovarian carcinoma (HGSOC), there are no universal indicators for resistance monitoring in patients. A key resistance mechanism to PARPi is the restoration of homologous recombination repair (HRR), including BRCA reversion mutations and changes in DNA damage repair proteins. To explore mutation profiles associated with PARPi resistance, we undertook targeted 42-gene deep sequencing of circulating cell-free DNA (cfDNA) extracted from HGSOC patients pre- and post-treatment with olaparib maintenance therapy. We found that pathogenic germline mutations in the HRR pathway, including BRCA1/2, were strongly associated with improved clinical outcomes, and newly acquired MRE11A mutations significantly shortened the progression-free survival (PFS) of patients. Furthermore, dynamic fluctuations of somatic mutation sites in CHEK2:p.K373E and CHEK2:p.R406H can be used for evaluating the therapeutic efficacy of patients. MRE11A:p.K464R might be a vital driving factor of olaparib resistance, as patients with newly acquired MRE11A:p.K464R in post-treatment cfDNA had significantly shorter PFS than those without it. These findings provide potential noninvasive biomarkers for efficacy evaluation and resistance monitoring of olaparib treatment, and lay the foundation for developing combination treatment after olaparib resistance.


Assuntos
Ácidos Nucleicos Livres , Neoplasias Ovarianas , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Mutação , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Ftalazinas/farmacologia , Ftalazinas/uso terapêutico , Piperazinas , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico
8.
Front Aging Neurosci ; 14: 851929, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35601621

RESUMO

Background: The pathophysiological mechanism of cognitive impairment by osteoporosis in type 2 diabetes mellitus (T2DM) remains unclear. This study aims to further investigate the regional spontaneous brain activity changes of patients with diabetic osteoporosis (DOP), and the correlation between abnormal brain regions and bone metabolites. Methods: A total of 29 subjects with T2DM were recruited, including fourteen patients with DOP and thirteen patients without osteoporosis (Control group). Based on the resting-state functional magnetic resonance imaging (rs-fMRI) datasets acquired from all the subjects, a two-sample t-test was performed on individual normalized regional homogeneity (ReHo) maps. Spearman correlation analysis was performed between the abnormal ReHo regions with the clinical parameters and Montreal Cognitive Assessment (MOCA) scores. Results: In the DOP group, we demonstrated the significantly increased ReHo values in the left middle temporal gyrus (MTG), right superior occipital gyrus (SOG), aright superior parietal lobule (SPL), right angular gyrus (AG), and left precuneus (PE). Additionally, we also found a significant positive correlation between increased ReHo values in the left MTG and the average bone mineral density (BMD AVG), and average T scores (T AVG). The ReHo values of the right SOG and right SPL showed a negative correlation with MOCA scores, as well as a negative correlation between increased ReHo values in the right SPL and osteocalcin (OC) level. Conclusion: Patients with DOP showed increased spontaneous activity in multiple brain regions. The results indicated that osteoporosis exacerbated cognitive impairment and brain damage. Also, the OC might be considered as a bone marker to track the progression of cognitive impairment.

9.
ACS Appl Mater Interfaces ; 14(19): 22582-22592, 2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35533358

RESUMO

Organic-inorganic hybrid perovskite (OIHP) polycrystalline films are the key light-absorbing layers of laminated-structure OIHP-based devices that have attracted increasing attention in photoelectronics and flexible electronics. Internal stresses induced by the mismatched responses of laminated layers to long-term and cyclic multiphysical fields generate time-dependent mechanical deformation in OIHP polycrystalline films, which makes the mechanical constitution relation of great significance. However, few studies focus on either the mechanical properties and behaviors of OIHP polycrystalline films or the underlying mechanism coupled with the grain structure and ion diffusion. Here, we uncovered the heterogeneous viscoelasticity of MAPbBr3 films strongly correlated with the grain structure. Combining experiments and modeling, we revealed that the organic cation diffusion from grain interiors to grain boundaries leads to heterogeneity in the chemical distribution and viscoelastic modulus. Our work provides the nanomechanical understanding of the OIHP polycrystalline films that are crucial for safety design and performance optimization in OIHP-based electronics.

10.
BMC Musculoskelet Disord ; 23(1): 424, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524240

RESUMO

BACKGROUND: Osteoporosis is associated with a decrease of bone mineralized component as well as a increase of bone marrow fat. At present, there are few studies using radiomics nomogram based fat-water material decomposition (MD) images of dual-energy spectral CT as an evaluation method of abnormally low Bone Mineral Density (BMD). This study aims to establish and validate a radiomics nomogram based the fat-water imaging of dual-energy spectral CT in diagnosing low BMD. METHODS: Ninety-five patients who underwent dual-energy spectral CT included T11-L2 and dual x-ray absorptiometry (DXA) were collected. The patients were divided into two groups according to T-score, normal BMD(T ≥ -1) and abnormally low BMD (T < -1). Radiomic features were selected from fat-water imaging of the dual-energy spectral CT. Radscore was calculated by summing the selected features weighted by their coefficients. A nomogram combining the radiomics signature and significant clinical variables was built. The ROC curve was performed to evaluate the performance of the model. Finally, we used decision curve analysis (DCA) to evaluate the clinical usefulness of the model. RESULTS: Five radiomic features based on fat-water imaging of dual-energy spectral CT were constructed to distinguish abnormally low BMD from normal BMD, and its differential performance was high with an area under the curve (AUC) of 0.95 (95% CI, 0.89-1.00) in the training cohort and 0.97 (95% CI, 0.91-1.00) in the test cohort. The radiomics nomogram showed excellent differential ability with AUC of 0.96 (95%CI, 0.91-1.00) in the training cohort and 0.98 (95%CI, 0.93-1.00) in the test cohort, which performed better than the radiomics model and clinics model only. The DCA showed that the radiomics nomogram had a higher benefit in differentiating abnormally low BMD from normal BMD than the clinical model alone. CONCLUSION: The radiomics nomogram incorporated radiomics features and clinical factor based the fat-water imaging of dual-energy spectral CT may serve as an efficient tool to identify abnormally low BMD from normal BMD well.


Assuntos
Nomogramas , Osteoporose , Humanos , Osteoporose/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Água
11.
BMC Musculoskelet Disord ; 23(1): 316, 2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35366843

RESUMO

BACKGROUND: Fragility fracture is one of the most serious consequences of female aging, which can increase the risk of death. Therefore, paying attention to the pathogenesis of postmenopausal osteoporosis (PMOP) is very important for elderly women. METHODS AND MATERIALS: Forty 12-week-old female rats were divided into two groups including the ovariectomy (OVX) group and the control group. Four rats in each group were selected at 1, 4, 8, 12 and 16 weeks after operation. Vertebral bones and femurs were dissected completely for micro-Computed Tomography (micro-CT) scanning, biological modulus detection and histomorphological observation. RESULTS: In OVX group, bone volume/total volume (BV/TV), bone trabecular connection density (Conn.D) and trabecular bone number (Tb.N) decreased significantly with time (P < 0.05). The elastic modulus of femur in OVX group was lower than that in control group, but there was no significant difference between them (P > 0.05). Over time, the tartrate resistant acid phosphatase (TRAP), osteocalcin (BGP), type I procollagen amino terminal propeptide (PINP) and type I collagen carboxy terminal peptide (CTX-I) in OVX group increased significantly (P < 0.05). The micrographs of the OVX group showed sparse loss of the trabecular interconnectivity and widening intertrabecular spaces with time. CONCLUSION: The bone loss patterns of vertebral body and femur were different in the early stage of estrogen deficiency. The bone turnover rate of OVX rats increased, however the changes of biomechanical properties weren't obvious.


Assuntos
Osteoporose , Idoso , Animais , Remodelação Óssea , Feminino , Humanos , Osteoporose/etiologia , Ovariectomia/efeitos adversos , Ratos , Ratos Sprague-Dawley , Microtomografia por Raio-X
12.
J Xray Sci Technol ; 30(3): 631-640, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35253725

RESUMO

BACKGROUND: In vertebrae, the amount of cortical bone has been estimated at 30-60%, but 45-75% of axial load on a vertebral body is borne by cortical bone. OBJECTIVE: To compare the role of L1 CT-attenuation and cortical thickness in predicting osteoporosis by opportunistic CT and explore cortical thickness value in osteoporosis. METHODS: We collected data of 94 patients who underwent DXA and thoracic and/or abdominal CT to demonstrate an entire L1 for other indications in routine practice. Patients were divided into three groups according to T-score: osteoporosis, osteopenia, or normal. CT-attenuation value and cortical thickness of L1 were measured. ANOVA analysis was utilized to analyze CT-attenuation and cortical thickness among the three groups. Sensitivity, specificity, and area under the curve (AUC) predicting low BMD were determined using ROC. Pearson correlations were employed to describe relationship between L1 BMD and CT-attenuation value, BMD, as well as cortical thickness. RESULTS: The mean cortical thickness was 0.83±0.11, 0.72±0.10, and 0.64±0.09 mm for normal, osteopenia, and osteoporotic subgroups, respectively. A statistically significant difference was observed in cortical thickness and CT-attenuation value among these three subgroups. A mean CT-attenuation value threshold of > 148.7 yielded 73.0% sensitivity and 86.0% specificity for distinguishing low BMD from normal with an AUC = 0.83. Pearson correlation analysis indicated that BMD was positively correlated with CT-attenuation (r = 0.666, P < 0.001) and cortical thickness (r = 0.604, P < 0.001). CONCLUSIONS: L1 CT-attenuation and cortical thickness measured on opportunistic CT can help predict osteoporosis. Compared with cortical thickness, CT-attenuation is a more sensitive and accurate index for distinguishing low BMD from normal.


Assuntos
Doenças Ósseas Metabólicas , Osteoporose , Absorciometria de Fóton , Densidade Óssea , Humanos , Vértebras Lombares , Osteoporose/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
13.
Front Nutr ; 9: 814095, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35284454

RESUMO

In nutrition science, malnutrition is a state of imbalance between intake and the needs of the organism, leading to metabolic changes, impaired physiological functions, and weight loss. Regardless of the countless efforts being taken and researched for years, the burden of malnutrition is still alarming and considered a significant agent of mortality across the globe. Around 45% of 12 million children deaths (0-5 years old) annually are due to malnutrition, mostly from developing countries. Malnutrition develops associations with other infections and leads to substantial clinical outcomes, such as mortality, more visits to hospitals, poor quality of life and physical frailty, and socioeconomic issues. Here, in this review, we intend to provide an overview of the current burden, underlying risk factors, and co-existence of malnutrition and other infections, such as cancer. Following the rising concern of the vicious interplay of malnutrition and other medical illnesses, we believed that this narrative review would highlight the need to re-make and re-define the future strategies by giving comprehensive and sustainable programs to alleviate poverty and combat the rampant infectious diseases and those nutrition-related health problems. Furthermore, the study also raises the concern for hospitalized malnourished cancer patients as it is crucially important to knowledge the caregiver healthcare staff for early interventions of providing nutritional support to delay or prevent the onset of malnutrition.

14.
Front Nutr ; 9: 822020, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35252301

RESUMO

Gut microbiota dysbiosis, together with goblet cells dysfunction has been observed in ulcerative colitis cases. This study aims to evaluate the potential of 2'-fucosyllactose (2'-FL) supplementation in inhibiting intestinal inflammation through regulating gut microbiota, protecting goblet cells, and stimulating mucin secretion. 2'-FL was orally administered to C57BL/6J mice daily (400 mg/kg bw) for 21 days and 5% dextran sulfate sodium (DSS) was used to induce the colitis in the last 7 days. Meanwhile, fecal microbiota transplantation (FMT) was conducted to test the roles of gut microbiota in the remission of colitis by 2'-FL. Gut microbiota alteration was analyzed through 16S ribosomal RNA (16S rRNA) sequencing. Periodic acid-Schiff (PAS), immunofluorescence staining, as well as mucin 2 (MUC2) and NOD-like receptor family pyrin domain containing 6 (NLRP6) messenger RNA (mRNA) expression in colon fragments was performed and detected. The results showed that the DSS + 2'-FL mice were found to have a slower rate of weight loss, lower disease activity index (DAI) scores, and longer colon lengths than the DSS group (p < 0.05), so in the FMT recipient mice which received fecal microbiota from the DSS + 2'-FL group. In addition, the data revealed that 2'-FL relieved the disorder of DSS-induced gut microbiota, including decreasing the high abundance of mucin-utilizing bacteria in the DSS group, such as Bacteroides, Lachnospiraceae NK4A136, Lachnospiraceae, and Bacteroides vulgatus. PAS and immunofluorescence staining showed that 2'-FL treatment promoted the recovery of goblet cells and enhanced MUC2 and NLRP6 expression, which was also observed in the FM (DSS + 2'-FL) group. Moreover, NLRP6, which has been proved to be a negative regulator for Toll-like receptor 4/myeloid differential protein-8/nuclear factor-kappa B (TLR4/MyD88/NF-κB) pathway, was upregulated by 2'-FL in colon tissue. In conclusion, this study suggests that 2'-FL ameliorates colitis in a gut microbiota-dependent manner. The underlying protective mechanism associates with the recovery of goblet cells number and improves MUC2 secretion through TLR4-related pathway.

15.
Eur J Radiol ; 149: 110197, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35149339

RESUMO

PURPOSE: This paper aims to use radiomics-clinical analysis based on CT imaging to distinguish between acute and chronic osteoporotic vertebral fractures. METHOD: A total of 147 patients who underwent both dual-energy X-ray absorptiometry (DEXA), CT and MRI of the spine were analyzed retrospectively. The patients were assigned to either a training cohort (n = 103) or a validation cohort (n = 44). The radiomics model and combined nomogram model were established by multivariate logistic regression analysis. The predictive performance was assessed with receiver operating characteristic (ROC) curve. RESULTS: Fourteen radiomic features based on spine CT images were constructed to distinguish acute versus chronic osteoporotic vertebral fractures, and its differentialperformance was good with an area under the curve (AUC) of 0.90 (95% CI, 0.84-0.95) in the training cohort and 0.82 (95% CI, 0.69-0.94) in the validation cohort. Based on the radiomic signature and clinical fracture line feature, a combined nomogram was developed and showed excellent differential ability with highest AUC of 0.93 (95 %CI,0.88-0.98) in the training cohort and 0.86 (95 %CI,0.73-0.98) in the validation cohort, which performed better than the clinical model significantly only. CONCLUSIONS: A quantitative nomogram based on clinical fracture line feature and radiomic features of CT images can be used to distinguish acute and chronic osteoporotic vertebral fractures with excellent predictive ability, which can be served as a potential decision support tool to assist clinicians in evaluating the phase of vertebral fractures timely, especially in situation where spine MRI was not available for patient.


Assuntos
Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Humanos , Fraturas por Osteoporose/diagnóstico por imagem , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos
16.
Phytomedicine ; 94: 153823, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34763315

RESUMO

BACKGROUND: Epidemiological and clinical evidence suggests that diabetes increases the risk of liver cancer. Although the co-occurrence of type 2 diabetes (T2D) and liver cancer is becoming more frequent, the underlying mechanisms remain unclear. Even though baicalin, extensively used in traditional Chinese medicine (TCM), can control T2D and inhibit liver cancer separately, minimal research is available regarding its possible effect on T2D-induced liver cancer. Thus, in the present study, we aimed to investigate the role of baicalin in T2D-induced hepatocellular cancer, and for the first time, we particularly emphasized the regulation of baicalin in genes RNA m6A in hepatocellular cancer. METHODS: Here, we constructed a cell culture model under a high concentration of glucose and a T2D-induced liver tumor model to evaluate the in vitro and in vivo role of baicalin in T2D-induced liver cancer progression. After confirming the suppressive effect of baicalin and the HKDC1 antibody on T2D-induced liver tumors, the epigenetic alterations (DNA 5mC and RNA m6A) of the baicalin-regulated HKDC1 gene were detected using MS and q-PCR. Next, the METTL3 gene-regulated m6A (2854 site) was investigated using SELECT PCR. Finally, the impact of the other three baicalin analogs (baicalein, wogonoside, and wogonin) on tumor inhibition was tested in vivo while verifying the related RNA m6A mechanism. RESULTS: The results showed that baicalin and the HKDC1 antibody suppressed T2D-induced liver tumor progression in vitro and in vivo. Furthermore, baicalin significantly inhibited the epigenetic modification (DNA 5mC and RNA m6A) of HKDC1 in HepG2 tumors, mainly targeting the RNA m6A site (2854). The m6A-related gene, METTL3, regulated the RNA m6A site (2854) of HKDC1, which was also restricted by baicalin. Moreover, the study verified that baicalin regulated the METTL3/HKDC1/JAK2/STAT1/caspase-3 pathway in liver cancer cells when exposed to a high glucose concentration. In addition, the three baicalin analogs were proven to regulate the m6A (2854 site) of HKDC1 and suppress T2D-induced liver tumors. CONCLUSIONS: The findings of this study revealed that baicalin suppressed T2D-induced liver tumor progression by regulating the METTL3/m6A/HKDC1 axis, which might support its potential application for preventing and treating T2D-induced liver cancer.


Assuntos
Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Flavonoides/farmacologia , Humanos , Janus Quinase 2 , Neoplasias Hepáticas/tratamento farmacológico , Metiltransferases/metabolismo , Fator de Transcrição STAT1
17.
Int Immunopharmacol ; 101(Pt A): 108149, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34634739

RESUMO

Lipopolysaccharide (LPS) can remain in dairy products after the sterilization of milk powder and may pose a threat to the health of infants and young children. There is a large amount of alkaline phosphatase (ALP) in raw milk, which can remove the phosphate bond of LPS, thus, detoxifying it. ALP is regarded as an indicator of the success of milk sterilization due to its strong heat resistance. ALP can alleviate the toxicity of LPS in enteritis and nephritis models, but the mechanism by which oral-intake of ALP protects liver tissue from LPS stimulation is unclear. In this study, an in vivo acute mouse liver injury model was induced by C. sakazakii LPS (200 µg/kg) and used to verify the protective mechanism of ALP (200 U/kg) on mice livers. The related pathways were also verified by in vitro cell culture. Enzyme linked immunosorbent assays (ELISAs), quantitative reverse transcription PCR (RT-qPCR) and western blotting were used to detect the levels of inflammatory factors at the protein level and RNA level, and to confirm the inflammation of liver tissue caused by LPS. ALP was found to alleviate acute liver injury in vitro by activating miR-146a. We found that ALP could up-regulate the level of miR146a and subsequently alleviates the expression of TLR4, TNF-α, matured IL-1ß, and NF-κB in mouse liver tissue and hepatocytes; thus, reducing liver inflammation. Herein, we demonstrated for the first time that oral-intake of ALP protected liver tissue by up-regulating the expression of miR-146a and alleviating inflammatory reactions; thus, providing a research basis for the proper processing of milk. This study also suggests that producers should improve the awareness of the protective effects of bioactive proteins in raw milk.


Assuntos
Fosfatase Alcalina/administração & dosagem , Cronobacter sakazakii/imunologia , Doenças Transmitidas por Alimentos/prevenção & controle , Hepatite/prevenção & controle , Leite/efeitos adversos , Administração Oral , Fosfatase Alcalina/metabolismo , Animais , Modelos Animais de Doenças , Doenças Transmitidas por Alimentos/imunologia , Doenças Transmitidas por Alimentos/patologia , Hepatite/imunologia , Hepatite/patologia , Humanos , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/imunologia , Lipopolissacarídeos/metabolismo , Fígado/imunologia , Fígado/patologia , Masculino , Camundongos , Leite/enzimologia , Leite/imunologia
18.
Small ; 17(40): e2102733, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34477301

RESUMO

Oxygen detection by organic-inorganic halide perovskites (OIHPs) has demonstrated advantages in operating temperature, response time, and reversibility over traditional materials. However, OIHPs can only sense O2 in light and the unavoidable O2 exposure during detection easily induces the degradation of OIHPs. The trade-off between sensitivity and stability makes the OIHP-based oxygen sensors impractical. By replacing organic groups with Cs, the compact films of all-inorganic halide perovskites (AIHPs) that can adsorb O2 at grain boundaries in dark are developed. AIHPs show conductance increase of 1875.5% from 1 × 10-5 to 700 Torr of O2 pressure, associated with full reversibility and long-term stability. Combining experiments and modeling, this work reveals the donor-acceptor competition via halide vacancy filling leading to the modulation of carrier concentration and mobility. This work offers understandings on oxygen sensing by perovskite materials and paves the way for further optimization of AIHPs as promising oxygen sensors with high sensitivity and stability.

19.
Magn Reson Imaging ; 84: 84-91, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34560231

RESUMO

PURPOSE: To explore the application of intravoxel incoherent motion diffusion-weighted imaging(IVIM-DWI) on account of field-of-view optimized and constrained undistorted single shot (FOCUS) and iteraterative decomposition of water and fat with echo asymmetry and least-squares estimation quantitation(IDEAL-IQ) sequences in evaluating the vertebral microenvironment changes of type 2 diabetes mellitus(T2DM) patients and the correlation with bone mineral density(BMD). METHOD: 128 T2DM patients (mean age 63.4 ± 5.28 years) underwent both dual-energy X-ray absorptiometry (DEXA) and spine MRI. The FOCUS IVIM-DWI and IDEAL-IQ derived parameters of the vertebral body(L1, L2, L3, L4)were measured on corresponding maps of the lumbar spine. The subjects were divided into 3 groups according to T-scores as follows: normal (n = 37), osteopenia (n = 43), and osteoporosis(n = 48) group.One-way analysis of variance (ANOVA) were used to compare the vertebral parameters(ADCslow, ADCfast, f, FF, R2*) among three BMD cohorts.Receiver operating characteristic (ROC) analyses and Spearman's rank correlation were performed to test the diagnostic performance and the correlation between them respectively. RESULTS: There were significant differences in vertebral ADCslow, ADCfast, FF and R2* between the three groups (P < 0.05).Statistically, BMD was moderately negatively correlated with FF (r = -0.584, P < 0.001) and weakly positively with ADCslow (r = 0.334, P < 0.001), meanwhile moderately positively correlated with R2*(r = 0.509, P < 0.001) and ADCfast(0.545, P < 0.001).ADCfast was moderately negatively correlated with FF (r = -0.417, P < 0.001), weakly positively correlated with R2*(0.359, P < 0.001).Compared with the area under the curve (AUC) of ADCslow, ADCfast, FF and R2*, the AUC of ADCfast was higher in identifying between normal and abnormal(osteopenia and osteoporosis), normal from osteopenia, while the AUC of FF was higher in identifying osteopenia from osteoporosis. CONCLUSIONS: FOCUS IVIM-DWI and IDEAL-IQ of lumbar spine might be useful to evaluate the vertebral microenvironment changes of T2DM patients.


Assuntos
Diabetes Mellitus Tipo 2 , Osteoporose , Idoso , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Humanos , Vértebras Lombares/diagnóstico por imagem , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Osteoporose/diagnóstico por imagem
20.
Food Sci Nutr ; 9(7): 3449-3459, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34262705

RESUMO

As classical MRPs, the toxic effects of furosine, pyralline, and 5-hydroxymethylfurfural (5-HMF) in liver tissue are evaluated and the related mechanism is investigated here, and the protective effects of lactoferrin on liver injury caused by Maillard reaction products (MRPs) with furan ring are proved in vitro and in vivo. First, we detect the concentrations of furosine, pyralline, and 5-HMF in several foods using ultrahigh-performance liquid chromatography (UHPLC). Then, the effects of the three MRPs on liver cells (HL-7702) viability, as well as liver tissue, are performed and evaluated. Furthermore, the regulations of three MRPs on necroptosis-related pathway in liver cells are investigated. Additionally, the effects of lactoferrin in alleviating liver injury, as well as regulating necroptosis pathway, were evaluated. Results elucidate that lactoferrin protects liver injury caused by MRPs with furan ring structure through activating RIPK1/RIPK3/p-MLKL necroptosis pathway and downstream inflammatory reaction.

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