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1.
Food Chem ; 404(Pt A): 134481, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36240562

RESUMO

The inhibition of α-glucosidase activity has been recognized as an effective approach for treating type 2 diabetes mellitus (T2DM). In recent years, much emphasis has been placed on identifying peptides with α-glucosidase inhibitory activity and elucidating the mechanisms underlying their inhibitory effect in treating T2DM. This study aims to identify peptides with good α-glucosidase inhibitory activity from the hydrolysate of ginkgo biloba seed cake protein isolate (GCPI) using in silico screening. It was found that the hydrolysate from Alcalase exhibited the strongest inhibitory effect on α-glucosidase (IC50 12.94 ± 0.37 mg/mL). Three novel peptides with α-glucosidase inhibitory activity, i.e., Leu-Ser-Met-Ser-Phe-Pro-Pro-Phe (LSMSFPPF), Val-Pro-Lys-Ile-Pro-Pro-Pro (VPKIPPP) and Met-Pro-Gly-Pro-Pro-Ser-Asp (MPGPPSD), were further identified from the hydrolysate of Alcalase by in silico screening. LSMSFPPF exhibited the strongest inhibitory activity (IC50 454.33 ± 32.45 µM), followed by MPGPPSD (IC50 943.82 ± 73.10 µM) and VPKIPPP (IC50 1446.81 ± 66.98 µM). The pharmacophore model revealed that hydrogen bonds played a critical role in α-glucosidase inhibition.

2.
Neural Regen Res ; 18(2): 258-266, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35900400

RESUMO

Central nervous system (CNS) trauma, including traumatic brain injury and spinal cord injury, has a high rate of disability and mortality, and effective treatment is currently lacking. Previous studies have revealed that neural inflammation plays a vital role in CNS trauma. As the initial enzyme in neuroinflammation, cytosolic phospholipase A2 (cPLA2) can hydrolyze membranous phosphatides at the sn-2 position in a preferential way to release lysophospholipids and ω3-polyunsaturated fatty acid dominated by arachidonic acid, thereby inducing secondary injuries. Although there is substantial fresh knowledge pertaining to cPLA2, in-depth comprehension of how cPLA2 participates in CNS trauma and the potential methods to ameliorate the clinical results after CNS trauma are still insufficient. The present review summarizes the latest understanding of how cPLA2 participates in CNS trauma, highlighting novel findings pertaining to how cPLA2 activation initiates the potential mechanisms specifically, neuroinflammation, lysosome membrane functions, and autophagy activity, that damage the CNS after trauma. Moreover, we focused on testing a variety of drugs capable of inhibiting cPLA2 or the upstream pathway, and we explored how those agents might be utilized as treatments to improve the results following CNS trauma. This review aimed to effectively understand the mechanism of cPLA2 activation and its role in the pathophysiological processes of CNS trauma and provide clarification and a new referential framework for future research.

3.
Front Cardiovasc Med ; 9: 813710, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35369304

RESUMO

Purpose: This study is to assess the diagnostic value of noninvasive regional myocardial work (MW) by echocardiography for detecting the functional status of coronary stenosis using fractional flow reserve (FFR) as a standard criterion. Methods: A total of 84 consecutive patients were included in this study, among which 92 vessels were identified with ≥50% stenosis confirmed by invasive coronary angiography. Patients were investigated by invasive FFR and transthoracic echocardiography. Regional MW indices including myocardial work index (MWI), myocardial constructive work (MCW), myocardial wasted work, and myocardial work efficiency were calculated. Results: MWI and MCW were significantly impaired in the FFR ≤ 0.75 group compared with the FFR > 0.75 group (both p < 0.01). There were significant positive associations between MWI and MCW with FFR. In total group, MWI <1,623.7 mmHg% [sensitivity, 78.4%; specificity, 72.2%; area under the curve value, 0.768 (0.653-0.883)] and MCW <1,962.4 mmHg% [77.0%; 72.2%; 0.767 (0.661-0.872)], and in single-vessel subgroup, MWI <1,412.1 mmHg% [93.5%; 63.6%; 0.808 (0.652-0.965)] and MCW <1,943.3 mmHg% [(84.8%; 72.7%; 0.800 (0.657-0.943)] were optimal to detect left ventricular segments with an FFR ≤ 0.75. MWI and MCW significantly increased after percutaneous coronary intervention in 13 cases. Conclusion: In patients with coronary artery disease, especially those with single-vessel stenosis, the regional MW measured by echocardiography exhibited a good diagnostic value in detecting significant myocardial ischemia compared to the standard FFR approach.

4.
Sci Total Environ ; 858(Pt 3): 159919, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36336033

RESUMO

AIMS: Increases in nitrogen (N) deposition may significantly affect the organic carbon (OC) cycle in soil. The inconsistent findings of the influence of added N on soil OC pools highlight the need of quantifying responses of the OC pool distribution to N addition. Moreover, the influence of N addition with a mixture of organic and inorganic N on OC pool distribution and stabilization in grassland soil remains unclear. METHODS: We carried out a five-year field experiment with adding N to examine the effects of different types of N addition on soil OC pool distribution and transformation in a meadow steppe in Inner Mongolia. We applied N in the ratios of inorganic N (IN) and organic N (ON) at 10:0 (N1), 7:3 (N2), 5:5 (N3), 3:7 (N4), 0:10 (N5), and 0:0 (CK), respectively. We measured OC content in bulk soil, particulate organic matter (POM), and mineral-associated organic matter (MAOM) fractions. Additionally, a short-term soil incubation was conducted to assess potential OC mineralization. RESULTS: Our study showed no significant effect on soil organic carbon content of different ratios of IN/ON addition. N addition reduced microbial biomass C/N ratio, the fraction of mineral-associated organic matter, cumulative CO2 emission, and microbial metabolic quotient. Compared with ON addition alone, IN addition alone showed a stronger effect on the C in different soil fractions and soil OC mineralization. The particulate organic matter (POM) fraction was more sensitive to N addition than the mineral-associated organic matter (MAOM) fraction. CONCLUSIONS: Our results suggest that the contribution of N in organic and inorganic forms affecting OC pool distribution with different turnover rates should be considered when assessing the effects of N addition types on soil OC processes in grassland.

5.
Front Bioeng Biotechnol ; 10: 1031833, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338126

RESUMO

In recent years, a huge number of individuals all over the world, elderly people, in particular, have been suffering from Alzheimer's disease (AD), which has had a significant negative impact on their quality of life. To intervene early in the progression of the disease, accurate, convenient, and low-cost detection technologies are gaining increased attention. As a result of their multiple merits in the detection and assessment of AD, biosensors are being frequently utilized in this field. Behavioral detection is a prospective way to diagnose AD at an early stage, which is a more objective and quantitative approach than conventional neuropsychological scales. Furthermore, it provides a safer and more comfortable environment than those invasive methods (such as blood and cerebrospinal fluid tests) and is more economical than neuroimaging tests. Behavior detection is gaining increasing attention in AD diagnosis. In this review, cutting-edge biosensor-based devices for AD diagnosis together with their measurement parameters and diagnostic effectiveness have been discussed in four application subtopics: body movement behavior detection, eye movement behavior detection, speech behavior detection, and multi-behavior detection. Finally, the characteristics of behavior detection sensors in various application scenarios are summarized and the prospects of their application in AD diagnostics are presented as well.

6.
Front Chem ; 10: 1005843, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339047

RESUMO

Animal bile is an important component of natural medicine and is widely used in clinical treatment. However, it is easy to cause mixed applications during processing, resulting in uneven quality, which seriously affects and harms the interests and health of consumers. Bile acids are the major bioactive constituents of bile and contain a variety of isomeric constituents. Although the components are structurally similar, they exhibit different pharmacological activities. Identifying the characteristics of each animal bile is particularly important for processing and reuse. It is necessary to establish an accurate analysis method to distinguish different types of animal bile. We evaluated the biological activity of key feature markers from various animal bile samples. In this study, a strategy combining metabolomics and machine learning was used to compare the bile of three different animals, and four key markers were screened. Quantitative analysis of the key markers showed that the levels of Glycochenodeoxycholic acid (GCDCA) and Taurodeoxycholic acid (TDCA) were highest in pig bile; Glycocholic acid (GCA) and Cholic acid (CA) were the most abundant in bovine and sheep bile, respectively. In addition, four key feature markers significantly inhibited the production of NO in LPS-stimulated RAW264.7 macrophage cells. These findings will contribute to the targeted development of bile in various animals and provide a basis for its rational application.

7.
Front Mol Biosci ; 9: 1034928, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339715

RESUMO

Background: Increasing evidence illustrated that m6A regulator-mediated modification plays a crucial role in regulating tumor immune and angiogenesis microenvironment. And the combination of immune checkpoint inhibitor and anti-angiogenic therapy has been approved as new first-line therapy for advanced HCC. This study constructed a novel prognosis signature base on m6A-mediated modification and explored the related mechanism in predicting immune and anti-angiogenic responses. Methods: Gene expression profiles and clinical information were collected from TCGA and GEO. The ssGSEA, MCPCOUNT, and TIMER 2.0 algorithm was used to Estimation of immune cell infiltration. The IC50 of anti-angiogenic drugs in GDSC was calculated by the "pRRophetic" package. IMvigor210 cohort and Liu et al. cohort were used to validate the capability of immunotherapy response. Hepatocellular carcinoma single immune cells sequencing datasets GSE140228 were collected to present the expression landscapes of 5 hub genes in different sites and immune cell subpopulations of HCC patients. Results: Three m6A clusters with distinct immune and angiogenesis microenvironments were identified by consistent cluster analysis based on the expression of m6A regulators. We further constructed a 5-gene prognosis signature (termed as m6Asig-Score) which could predict both immune and anti-angiogenic responses. We illustrated that high m6Asig-Score is associated with poor prognosis, advanced TNM stage, and high TP53 mutation frequency. Besides, the m6Asig-Score was negatively associated with immune checkpoint inhibitors and anti-angiogenic drug response. We further found that two of the five m6Asig-Score inner genes, B2M and SMOX, were associated with immune cell infiltration, immune response, and the sensitivity to sorafenib, which were validated in two independent immunotherapy cohorts and the Genomics of Drug Sensitivity in Cancer (GDSC) database. Conclusion: We constructed a novel prognosis signature and identified B2M and SMOX for predicting immune and anti-angiogenic efficacy in HCC, which may guide the combined treatment strategies of immunotherapy and anti-angiogenic therapy in HCC.

8.
Polymers (Basel) ; 14(21)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36365634

RESUMO

Fast-growing wood has become a major source of materials for the wood industry in recent years, but defects have limited its use. Therefore, modification is urgently needed for the more efficient application of wood products. In this study, a 30 to 50% solution of furfuryl alcohol (FA) was impregnated into Douglas fir sapwood. The microstructure and thermal properties of the specimens before and after furfurylation were evaluated by different techniques. The weight percentage gain (WPG) of modified wood increased up to 22.97%, with the polymerized FA distributed in cell lumens and cell walls, as well as chemically bound to wood components. The polyfurfuryl alcohol (PFA) was mainly located in the tracheids, ray parenchyma cells, and resin canals. In addition, the furfurylated cell walls were greatly thickened. Raman spectra showed that modified wood had significant background fluorescence that covered other peaks. Differential Scanning Calorimetry analysis revealed that the cross-linking reaction between FA and wood changed the shape of curves, with no endothermic or exothermic peaks within the programmed temperature. Moreover, Thermogravimetry and Dynamic Mechanical Analysis results both confirmed that the furfurylation increased the thermal stability of Douglas fir. The percentage of the final mass loss of untreated specimen was 80.11%, while the highest one of furfurylated specimen was 78.15%, and it gradually decreased with increasing FA concentration. The storage modulus (E') and loss modulus (E″) of the furfurylated wood were both lower, and the damping factor (tan δ) was higher than the untreated one. When the temperature reaches about 75 °C, the untreated specimen began to soften and deform. At 90 °C, it fractured completely while the furfurylatedone remained stable. This study demonstrated that furfurylation can improve wood properties and elongate its service life.

9.
Orphanet J Rare Dis ; 17(1): 413, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36371238

RESUMO

BACKGROUND: Renal hypodysplasia/aplasia-3 (RHDA3), as the most severe end of the spectrum of congenital anomalies of the kidney and urinary tract, is mainly caused by mutations in GREB1L. However, the mutations in GREB1L identified to date only explain a limited proportion of RHDA3 cases, and the mechanism of GREB1L mutations causing RHDA3 is unclear. RESULTS: According to whole-exome sequencing, a three-generation family suffering from RHDA3 was investigated with a novel missense mutation in GREB1L, c.4507C>T. All three-generation patients suffered from unilateral absent kidney. This missense mutation resulted in sharp downregulation of mRNA and protein expression, which might lead to RHDA3. Mechanistically, through RNA-sequencing, it was found that the mRNA levels of PAX2 and PTH1R, which are key molecules involved in the development of the kidney, were significantly downregulated by knocking out GREB1L in vitro. CONCLUSIONS: This novel missense mutation in GREB1L can be helpful in the genetic diagnosis of RHDA3, and the discovery of the potential mechanism that GREB1L mutations involved in RHDA3 pathogenesis can promote the adoption of optimal treatment measures and the development of personalized medicine directly targeting these effects.


Assuntos
Rim , Mutação de Sentido Incorreto , Humanos , Mutação de Sentido Incorreto/genética , Rim/patologia , Sequenciamento Completo do Exoma/métodos , Mutação , RNA Mensageiro , Linhagem
10.
Artigo em Inglês | MEDLINE | ID: mdl-36376466

RESUMO

Impaired working memory (WM) is a core neuropsychological dysfunction of schizophrenia, however complex interactions among the information storage, information processing and attentional aspects of WM tasks make it difficult to uncover the psychophysiological mechanisms of this deficit. Thirty-six first-episode and drug-naïve schizophrenia and 29 healthy controls (HCs) were enrolled in this study. Here, we modified a WM task to isolate components of WM storage and WM processing, while also varying the difficulty level (load) of the task to study regional differences in load-specific activation using mixed effects models, and its relationship to distributed gene expression. Comparing patients with HCs, we found both attentional deficits and WM deficits, with WM processing being more impaired than WM storage in patients. In patients, but not controls, a linear modulation of brain activation was observed mainly in the frontoparietal and dorsal attention networks. In controls, an inverted U-shaped response pattern was identified in the left anterior cingulate cortex. The vertex of this inverted U-shape was lower in patients than controls, and a left-shifting axis of symmetry was associated with better WM performance in patients. Both the above linear and U-shaped modulation effects were associated with the expressions of the genes enriched in the dopamine neurotransmitter system across all cortical brain regions. These findings indicate that a WM processing deficit is evident in schizophrenia from an early stage before antipsychotic treatment, and associated with a dopamine pathway related aberration in nonlinear response pattern at the cingulate cortex when processing WM load.

11.
Artigo em Inglês | MEDLINE | ID: mdl-36394639

RESUMO

Membrane capacitive deionization (MCDI) has emerged as a promising electric-field-driven technology for brackish water desalination and specific salt or charged ion separation. The use of carbon-based or pseudocapacitive materials alone for MCDI usually suffers from the drawbacks of low desalination capacity and poor cycling stability due to their limited accessible adsorption sites and obstructed charge-carrier diffusion pathways. Therefore, developing a hybrid electrode material with multiple charge storage mechanisms and continuous electron/ion transport pathways that can synergistically improve its specific capacitance and cycling durability has currently become one of the most critical technical demands. Herein, we developed a novel hierarchically architectured hybrid electrode by first spinning MXene into polyacrylonitrile (PAN)-based carbon nanofibers (MCNFs) to obtain a highly conductive carbon nanocomposite framework. The excellent spatial support structure can effectively prevent the dense packing of Cl-- and DBS--doped polypyrrole (PPy) molecular chains during the following electrodeposition process, which not only ensures the efficient transport of electrons in the continuous hybrid carbon nanofibrous skeleton but also provides abundant accessible sites for ion adsorption and insertion. The obtained self-supporting membrane electrodes (MCNF@PPy+Cl- and MCNF@PPy+DBS-) have the advantages of outstanding specific capacitance (318.4 and 153.9 F/g, respectively), low charge transfer resistance (10.0 and 5.3 Ω, respectively), and excellent cycling performance (78% and 90% capacitance retention ratios, respectively, after 250 electrochemical cycles). Furthermore, the asymmetrical membrane electrodes showed a superior desalination capacity of 91.2 mg g-1 in 500 mg/L NaCl aqueous solution and obvious divalent ion (Ca2+, Mg2+) selective adsorption properties in high-salt water from the cooling towers of thermal power plants.

13.
PeerJ ; 10: e14330, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36353608

RESUMO

Cigarette smoking is one of the major risk factors for the occurrence and progression of oral squamous cell carcinoma (OSCC). Receptor-interacting protein 2 (RIP2) has been involved in mucosal immunity and homeostasis via a positive regulation of nuclear factor κB (NF-κB) transcription factor activity. Caspase-12 can bind to RIP2 and dampen mucosal immunity. However, the roles of RIP2/NF-κB and caspase-12 in OSCC induced by cigarette smoking remain unknown. Herein, we investigated the effects of cigarette smoking on the RIP2/NF-κB and caspase-12 in human OSCC tissues and OSCC cell lines (HSC-3). We first observed that RIP2 mediated NF-κB activation and caspase-12 upregulation in OSCC patients with cigarette smoking and cigarette smoke extract (CSE)-treated HSC-3 cells, respectively. Moreover, we confirmed that the downregulation of RIP2 by siRNA resulted in the reduction of caspase-12 expression and NF-κB activity in the presence of CSE treatment in vitro. In summary, our results indicated that cigarette smoking induced the activation of the RIP2/caspase-12/NF-κB axis and it played an important role in the development of OSCC. The RIP2/caspase-12/NF-κB axis could be a target for OSCC prevention and treatment in the future.

14.
Front Pharmacol ; 13: 976473, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386207

RESUMO

Exposure to ultraviolet (UV) light triggers the rapid generation and accumulation of reactive oxygen species (ROS) in skin cells, which increases oxidative stress damage and leads to photoaging. Nuclear factor E2-related factor 2 (Nrf2) modulates the antioxidant defense of skin cells against environmental factors, especially ultraviolet radiation. Natural products that target Nrf2-regulated antioxidant reactions are promising candidates for anti-photoaging. The aim of this study was to investigate the protective effect of Modified Qing'e Formula (MQEF) on UV-induced skin oxidative damage and its molecular mechanisms. In this study, the photoaging models of human keratinocytes (HaCaT) and ICR mice were established by UV irradiation. In vitro models showed that MQEF displayed potent antioxidant activity, significantly increased cell viability and reduced apoptosis and excess ROS levels. Meanwhile, the knockdown of Nrf2 reversed the antioxidant and anti-apoptotic effects of MQEF. In vivo experiments indicated that MQEF could protect the skin against UV-exposed injury which manifested by water loss, sensitivity, tanning, wrinkling, and breakage of collagen and elastic fibers. The application of MQEF effectively increased the activity of antioxidant enzymes and reduced the content of malondialdehyde (MDA) in mice. In addition, MQEF was able to activate Nrf2 nuclear translocation in mouse skin tissue. In summary, MQEF may attenuate UV-induced photoaging by upregulating Nrf2 expression and enhancing antioxidant damage capacity. MQEF may be a potential candidate to prevent UV-induced photoaging by restoring redox homeostasis.

15.
Front Oncol ; 12: 971871, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387085

RESUMO

Objectives: To propose a deep learning-based classification framework, which can carry out patient-level benign and malignant tumors classification according to the patient's multi-plane images and clinical information. Methods: A total of 430 cases of spinal tumor, including axial and sagittal plane images by MRI, of which 297 cases for training (14072 images), and 133 cases for testing (6161 images) were included. Based on the bipartite graph and attention learning, this study proposed a multi-plane attention learning framework, BgNet, for benign and malignant tumor diagnosis. In a bipartite graph structure, the tumor area in each plane is used as the vertex of the graph, and the matching between different planes is used as the edge of the graph. The tumor areas from different plane images are spliced at the input layer. And based on the convolutional neural network ResNet and visual attention learning model Swin-Transformer, this study proposed a feature fusion model named ResNetST for combining both global and local information to extract the correlation features of multiple planes. The proposed BgNet consists of five modules including a multi-plane fusion module based on the bipartite graph, input layer fusion module, feature layer fusion module, decision layer fusion module, and output module. These modules are respectively used for multi-level fusion of patient multi-plane image data to realize the comprehensive diagnosis of benign and malignant tumors at the patient level. Results: The accuracy (ACC: 79.7%) of the proposed BgNet with multi-plane was higher than that with a single plane, and higher than or equal to the four doctors' ACC (D1: 70.7%, p=0.219; D2: 54.1%, p<0.005; D3: 79.7%, p=0.006; D4: 72.9%, p=0.178). Moreover, the diagnostic accuracy and speed of doctors can be further improved with the aid of BgNet, the ACC of D1, D2, D3, and D4 improved by 4.5%, 21.8%, 0.8%, and 3.8%, respectively. Conclusions: The proposed deep learning framework BgNet can classify benign and malignant tumors effectively, and can help doctors improve their diagnostic efficiency and accuracy. The code is available at https://github.com/research-med/BgNet.

16.
Front Plant Sci ; 13: 1013331, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388515

RESUMO

Exploring the diversity and formation mechanism of under-ground bud banks is essential for understanding the renewal of plant populations and community succession. However, there are few studies on the response of bud bank size and composition to different degradation gradients in alpine meadows. In view of this, we investigated the size and composition of bud bank under four degradation gradients (non-degraded:ND, lightly degraded:LD, moderately degraded:MD, and heavily degraded:HD) caused by overgrazing in a typical alpine meadow in Tibet, China, using a unit area excavation sampling method, and analyzed the correlation between above-ground plant community composition and bud bank density. Our results showed that: (i) in the ND alpine meadow, rhizome buds were dominant, in the LD, tiller buds were dominant, and in the MD, root-sprouting buds were dominant; (ii) total bud bank and cyperaceae bud density decreased with increasing degradation gradient, the density of leguminosae was insignificant in each degradation gradient, and the density of gramineae and forb were dominant in LD and MD meadows, respectively; (iii) total bud bank density was significantly and positively correlated with total above-ground biomass in the LD gradient, tiller bud density was significantly positively correlated with the species diversity index of above-ground vegetation under the ND gradient, rhizome bud density was significantly and positively correlated with total above-ground biomass in the LD gradient, and root-sprouting density was significantly negatively correlated with total above-ground biomass in ND meadows, but was significantly positively correlated with the species diversity index of the LD gradient. Therefore, our research shows that rhizome buds are more important in ND meadow habitats, tiller buds are more important in LD meadow habitats, and root-sprouting buds are more important in MD meadows. The response of bud banks to degradation gradient varies with different types of bud banks and different functional groups of plants, and the survival strategy of bud banks is of great value for community restoration and regeneration, which should be paid more attention to in subsequent alpine meadow research.

17.
Front Immunol ; 13: 1018567, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36341405

RESUMO

Recurrent aphthous ulcer (RAU), one of the most common diseases in humans, has an unknown etiology and is difficult to treat. Thalidomide is an important immunomodulatory and antitumor drug and its effects on the gut microbiota still remain unclear. We conducted a metagenomic sequencing study of fecal samples from a cohort of individuals with RAU, performed biochemical assays of cytokines, immunoglobulins and antimicrobial peptides in serum and saliva, and investigated the regulation effects of thalidomide administration and withdrawal. Meanwhile we constructed the corresponding prediction models. Our metagenome-wide association results indicated that gut dysbacteriosis, microbial dysfunction and immune imbalance occurred in RAU patients. Thalidomide regulated gut dysbacteriosis in a species-specific manner and had different sustainable effects on various probiotics and pathogens. A previously unknown association between gut microbiota alterations and RAU was found, and the specific roles of thalidomide in modulating the gut microbiota and immunity were determined, suggesting that RAU may be affected by targeting gut dysbacteriosis and modifying immune imbalance. In-depth insights into sophisticated networks consisting of the gut microbiota and host cells may lead to the development of emerging treatments, including prebiotics, probiotics, synbiotics, and postbiotics.


Assuntos
Microbioma Gastrointestinal , Estomatite Aftosa , Humanos , Talidomida/uso terapêutico , Disbiose/complicações , Metagenoma
18.
Biomark Res ; 10(1): 84, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36384586

RESUMO

BACKGROUND: Children with birth defects (BD) are more likely to develop cancer and the increased risk of cancer persists into adulthood. Prior population-based assessments have demonstrated that even non-chromosomal BDs are associated with at least two-fold increase of cancer risk. Identification of variants that are associated with malignant tumor in BD patients without chromosomal anomalies may improve our understanding of the underlying molecular mechanisms and provide clues for early cancer detection in children with BD. METHODS: In this study, whole genome sequencing (WGS) data of blood-derived DNA for 1653 individuals without chromosomal anomalies were acquired from the Kids First Data Resource Center (DRC), including 541 BD probands with at least one type of malignant tumors, 767 BD probands without malignant tumor, and 345 healthy family members who are the parents or siblings of the probands. Recurrent variants exclusively seen in cancer patients were selected and mapped to their corresponding genomic regions. The targeted genes/non-coding RNAs were further reduced using random forest and forward feature selection (ffs) models. RESULTS: The filtered genes/non-coding RNAs, including variants in non-coding areas, showed enrichment in cancer-related pathways. To further support the validity of these variants, blood WGS data of additional 40 independent BD probands, including 25 patients with at least one type of cancers from unrelated projects, were acquired. The counts of variants of interest identified in the Kid First data showed clear deviation in the validation dataset between BD patients with cancer and without cancer. Furthermore, a deep learning model was built to assess the predictive abilities in the 40 patients using variants of interest identified in the Kids First cohort as feature vectors. The accuracies are ~ 75%, with the noteworthy observation that variants mapped to non-coding regions provided the highest accuracy (31 out of 40 patients were labeled correctly). CONCLUSION: We present for the first time a panorama of genetic variants that are associated with cancers in non-chromosomal BD patients, implying that our approach may potentially serve for the early detection of malignant tumors in patients with BD.

19.
Cancer Cell Int ; 22(1): 357, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36376836

RESUMO

BACKGROUND: Due to the rarity of PBL and the lack of large-scale studies, the prognostic value of IPI in PBL was controversial. Especially in the rituximab era, the ability of IPI to stratify prognosis in patients receiving immunochemotherapy was severely reduced. Then revised IPI (R-IPI) and National Comprehensive Cancer Network IPI (NCCN-IPI) were introduced. The present study aimed to evaluate the prognostic value of IPI and the other IPIs in patients with PBL in a Chinese population. METHODS: We performed a multicenter retrospective study of 71 patients with PBL from 3 institutions in China. The Kaplan-Meier method and log-rank tests were used for the survival analysis. Cox regression analysis was performed to evaluate the prognostic factors. Subgroup analysis was performed to assess the prognostic significance of IPI scores, R-IPI scores, and NCCN-IPI scores. RESULTS: The median follow-up was 4.7 years (0.7-21.8 years). The 5-year progression-free survival (PFS) and overall survival (OS) rates were 90.2% and 96.3%. In the multivariate analysis, only IPI scores and radiotherapy were significantly associated with OS and PFS (P < 0.05). Applying the R-IPI in our patient cohort indicates a significant difference in PFS between the two groups of R-IPI (P = 0.034) but not for OS (P = 0.072). And the NCCN-IPI was prognostic for OS (P = 0.025) but not for PFS (P = 0.066). Subgroup analyses of IPI showed that survival analysis of IPI scores for the PFS and OS of patients using rituximab were not significantly different (P > 0.05). CONCLUSIONS: Our study confirms the prognostic value of IPI in patients with PBL, but the predictive value of IPI proved to be relatively low with the addition of the rituximab. The R-IPI and NCCN-IPI can accurately assess the high and low-risk groups of PBL patients but were insufficient to evaluate the intermediate risk group.

20.
Dig Dis ; 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36366818

RESUMO

OBJECTIVE: To elusive the underlying mechanism and functions of miR-3682-3p in hepatocellular carcinoma (HCC). METHODS: Thirty pairs of tumor tissues and adjacent tissues were obtained from HCC patients. mRNA and protein expressions were detected by quantitative real-time PCR and western blot, respectively. The migration and invasion were measured using transwell or wound healing assays. Dual luciferase and ChIP assays were utilized to detect gene interactions. RESULTS: miR-3682-3p was highly expressed in HCC tissues and cell lines. Silencing of miR-3682-3p inhibited cell migration and invasion, increased E-cadherin expression, and decreased N-cadherin, Vimentin and Snail expressions, as well as the of SOX2, OCT4 and Bmi1 expression, thereby restraining EMT and stemness of HCC in vitro. miR-3682-3p was positively activated by c-Myc, and could directly target PTEN to activate PI3K/AKT/ß-catenin pathway. In addition, inhibition of PTEN weakened the anti-migration and anti-stemnesic effects of miR-3682-3p downregulation in HCC cells. CONCLUSION: miR-3682-3p promoted HCC migration and stemness through PTEN/PI3K/AKT/ß-catenin signaling, implying that miR-3682-3p might be a promising target for HCC clinical treatment.

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