Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 402
Filtrar
1.
Chem Eng J ; 429: 132332, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34539223

RESUMO

The ongoing outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted that new diagnosis technologies are crucial for controlling the spread of the disease. Especially in the resources-limit region, conveniently operated detection methods such as "naked-eye" detection are urgently required that no instrument is needed. Herein, we have designed a novel and facile strategy to fabricate covalent organic framework (COF) capsules, which can be utilized to establish a new colorimetric assay for naked-eye detection of SARS-CoV-2 RNA. Specifically, we employ the digestible ZIF-90 as the sacrificial template to prepare the hollow COF capsules for horseradish peroxidase (HRP) encapsulation. The fabricated COF capsules can provide an appropriate microenvironment for the enzyme molecules, which may improve the conformational freedom of enzymes, enhance the mass transfer, and endow the enzyme with high environmental resistance. With such design, the proposed assay exhibits outstanding analytical performance for the detection of SARS-CoV-2 RNA in the linear range from 5 pM to 50 nM with a detection limit of 0.28 pM which can go parallel to qTR-PCR analysis. Our method also possesses excellent selectivity and reproducibility. Moreover, this method can also be served to analyze the clinical samples, and can successfully differentiate COVID-19 patients from healthy people, suggesting the promising potential in clinical diagnosis.

2.
Cell Rep ; 37(5): 109913, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34731618

RESUMO

Opiates produce a strong rewarding effect, but abstinence from opiate use emerges with severe negative emotions. Depression is one of the most frequent emotion disorders associated with opiate abstinence, which is thought to be a main cause for relapse. However, neurobiological bases of such an aversive emotion processing are poorly understood. Here, we find that morphine abstinence activates κ-opioid receptors (KORs) by increasing endogenous KOR ligand dynorphin expression in the amygdala, which in turn facilitates glutamate transporter 1 (GLT1) expression by activation of p38 mitogen-activated protein kinase (MAPK). Upregulation of GLT1 expression contributes to opiate-abstinence-elicited depressive-like behaviors through modulating amygdalar glutamatergic inputs to the nucleus accumbens (NAc). Intra-amygdala injection of GLT1 inhibitor DHK or knockdown of GLT1 expression in the amygdala significantly suppresses morphine-abstinence-induced depressive-like behaviors. Pharmacological and pharmacogenetic activation of amygdala-NAc projections prevents morphine-abstinence-induced behaviors. Overall, our study provides key molecular and circuit insights into the mechanisms of depression associated with opiate abstinence.

3.
Bioengineered ; 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34787068

RESUMO

Thromboangiitis obliterans (TAO) is a non-atherosclerotic, segmental, chronic vascular inflammatory disease. Our aim was to explore the underlying mechanisms of long non-coding RNA (lncRNA)-related competing endogenous RNAs (ceRNAs) in TAO. Six blood samples were collected from patients with TAO and healthy individuals (three for each category). Total RNA was extracted from the blood of each participant and sequenced. Differentially expressed lncRNAs (DE-lncRNAs) and miRNAs (DE-miRNAs) were screened, and ceRNA networks associated with TAO were constructed. Thereafter, the genes in the ceRNA network were subjected to functional analyses. Finally, a ceRNA relationship (lncRNA NEAT1-hsa-miR-1-3p-mRNA GNA12) was selected for further validation. Analysis revealed that 347 DE-lncRNAs (150 downregulated and 197 upregulated) and 16 DE-miRNAs (3 downregulated and 13 upregulated) were identified in TAO. Further, TAO-associated ceRNA networks, which included 219 lncRNAs, 6 miRNAs, and 53 mRNAs, were proposed and subjected to gene annotation and pathway analysis. Additionally, NEAT1 and GNA12 levels were significantly upregulated, while miR-1-3p levels were evidently downregulated in TAO patients, as compared with those in healthy controls. Dual luciferase reporter assays showed that NEAT1, miR-1-3p, and GNA12 interacted with each other. We report potential TAO-associated ceRNA regulatory networks and suggest activation of NEAT1/miR-1-3p/GNA12 signaling as a novel mechanism for TAO progression.

4.
Front Pharmacol ; 12: 742954, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803688

RESUMO

Thrombosis is a general pathological phenomenon during severe disturbances to homeostasis, which plays an essential role in cardiovascular and cerebrovascular diseases. Leonurine (LEO), isolated from Leonurus japonicus Houtt, showes a crucial role in anticoagulation and vasodilatation. However, the properties and therapeutic mechanisms of this effect have not yet been systematically elucidated. Therefore, the antithrombotic effect of LEO was investigated in this study. Hematoxylin-Eosin staining was used to detect the thrombosis of zebrafish tail. Fluorescence probe was used to detect the reactive oxygen species. The biochemical indexes related to oxidative stress (lactate dehydrogenase, malondialdehyde, superoxide dismutase and glutathione) and vasodilator factor (endothelin-1 and nitric oxide) were analyzed by specific commercial assay kits. Besides, we detected the expression of related genes (fga, fgb, fgg, pkcα, pkcß, vwf, f2) and proteins (PI3K, phospho-PI3K, Akt, phospho-Akt, ERK, phospho-ERK FIB) related to the anticoagulation and fibrinolytic system by quantitative reverse transcription and western blot. Beyond that, metabolomic analyses were carried out to identify the expressions of metabolites associated with the anti-thrombosis mechanism of LEO. Our in vivo experimental results showed that LEO could improve the oxidative stress injury, abnormal platelet aggregation and coagulation dysfunction induced by adrenalin hydrochloride. Moreover, LEO restored the modulation of amino acids and inositol metabolites which are reported to alleviate the thrombus formation. Collectively, LEO attenuates adrenalin hydrochloride-induced thrombosis partly via modulating oxidative stress, coagulation cascade and platelet activation and amino acid and inositol metabolites.

5.
J Vis Exp ; (176)2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34747411

RESUMO

Type 1 diabetes mellitus (T1DM) is caused by autoimmune destruction of pancreatic ß cells, which results in little or no insulin production. Islet transplantation plays an important role in the treatment of T1DM, with the improved glycometabolic control, the reduced progression of complications, the reduction of hypoglycemic episodes when compared with traditional insulin therapy. The results of phase III clinical trial also demonstrated the safety and efficacy of islet allotransplantation in T1DM. However, the shortage of pancreas donors limits its widespread use. Animals as a source of islets such as the pig offer an alternative choice. Because the architecture of the pig pancreas is different from the islets of mice or humans, the pig islet isolation procedure is still challenging. Since the translation of alternative porcine islet sources (xenogeneic) to the clinical setting for treating T1DM through cellular transplantation is of great importance, a cost-effective, standardized, and reproducible protocol for isolating porcine islets is urgently needed. This manuscript describes a simplified and cost-effective method to isolate and purify adult porcine islets based on the previous protocols that have successfully transplanted porcine islets to non-human primates. This will be a beginners guide without the use of specialized equipment such as a COBE 2991 Cell Processor.

6.
Front Public Health ; 9: 741637, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722448

RESUMO

Background: The adverse health effects of air pollutants are widely reported, and the elderly are susceptible to toxic environments. This study aimed to evaluate the association between use of solid fuels for cooking and mortality among the elderly. Methods: A total of 5,732 and 3,869 participants from the Chinese Longitudinal Healthy Longevity Survey were enrolled in two (2014 and 2018) and three surveys (2011, 2014, and 2018) of survey. Cooking fuel was divided into clean and solid fuel. Cox proportional hazards models were used to estimate the mortality hazard ratio (HR). Subgroup analyses were performed to assess the potential interaction effect. Results: Among the participants in the 2011-2018 survey, 53% reported using solid fuel. Such group was associated with a 9% increase in mortality risk relative to clean fuel users (HR = 1.09, 95% CI = 1.01-1.18). Among participants in the 2014-2018 survey, 339 reported a switch from solid to clean fuels and they were not at increased mortality risk relative to the 488 people that reported a stable use of clean fuels (HR = 1.14, 95% CI = 0.99-1.31) although the estimated HR was similar to the one for stable solid fuel users (HR = 1.19, 95%CI = 1.04-1.36 n = 509). Interaction and stratified analyses showed that solid fuel use had an impact on mortality in participants who were non-current smokers, had low dietary diversity scores, and were living in areas with high PM2.5 concentrations (>50 µg/m3) and city population below 8 million (P for interaction < 0.05). The association was robust in the three sensitivity analyses. Conclusion: The finding showed a clear association between solid fuel use and mortality among older Chinese, and an even stronger association between risk of mortality and solid fuel use among individuals exposed to high levels of PM2.5.


Assuntos
Poluição do Ar em Ambientes Fechados , Idoso , China/epidemiologia , Humanos , Estudos Longitudinais , Estudos Prospectivos , Estudos Retrospectivos
7.
Front Public Health ; 9: 733314, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34796159

RESUMO

Objective: This study aims to estimate the prevalence of dementia and Alzheimer's disease (AD) and associated risk factors among the general Chinese population. Methods: We carried out a nationwide study including 24,117 participants aged 60 years and older in China using a multistage clustered sampling. Dementia and AD were diagnosed according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders and the criteria issued by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association. Face-to-face interviews were administered by the trained interviewers to obtain information on demographics, lifestyle factors, and previous diseases. Results: The overall weighted prevalence of dementia was 4.22% (95%CI 2.27-6.17%) for people aged 60 years and older, was higher in women than in men and increased with age. Daily tea drinking and daily exercises were the protective factors for both dementia and AD. Engaging in social and intellectual activities was significantly associated with a lower risk of dementia and AD. Conclusions: A large number of population with dementia posed a significant challenge to China where the population is rapidly aging. The increase of public awareness, building more care facilities, and training dementia specialists and professional caregivers are all urgently needed and should be the future priorities of dementia care in China.

8.
BMC Plant Biol ; 21(1): 512, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732145

RESUMO

BACKGROUND: Senescence represents the last stage of flower development. Phosphorylation is the key posttranslational modification that regulates protein functions, and kinases may be more required than phosphatases during plant growth and development. However, little is known about global phosphorylation changes during flower senescence. RESULTS: In this work, we quantitatively investigated the petunia phosphoproteome following ethylene or air treatment. In total, 2170 phosphosites in 1184 protein groups were identified, among which 2059 sites in 1124 proteins were quantified. To our surprise, treatment with ethylene resulted in 697 downregulated and only 117 upregulated phosphosites using a 1.5-fold threshold (FDR < 0.05), which showed that ethylene negatively regulates global phosphorylation levels and that phosphorylation of many proteins was not necessary during flower senescence. Phosphoproteome analysis showed that ethylene regulates ethylene and ABA signalling transduction pathways via phosphorylation levels. One of the major targets of ethylene-induced dephosphorylation is the plant mRNA splicing machinery, and ethylene treatment increases the number of alternative splicing events of precursor RNAs in petunia corollas. CONCLUSIONS: Protein dephosphorylation could play an important role in ethylene-induced senescence, and ethylene treatment increased the number of AS precursor RNAs in petunia corollas.

9.
Sci Rep ; 11(1): 20269, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34642418

RESUMO

Acute kidney injury (AKI) is commonly present in critically ill patients with sepsis. Early prediction of short-term reversibility of AKI is beneficial to risk stratification and clinical treatment decision. The study sought to use machine learning methods to discriminate between transient and persistent sepsis-associated AKI. Septic patients who developed AKI within the first 48 h after ICU admission were identified from the Medical Information Mart for Intensive Care III database. AKI was classified as transient or persistent according to the Acute Disease Quality Initiative workgroup consensus. Five prediction models using logistic regression, random forest, support vector machine, artificial neural network and extreme gradient boosting were constructed, and their performance was evaluated by out-of-sample testing. A simplified risk prediction model was also derived based on logistic regression and features selected by machine learning algorithms. A total of 5984 septic patients with AKI were included, 3805 (63.6%) of whom developed persistent AKI. The artificial neural network and logistic regression models achieved the highest area under the receiver operating characteristic curve (AUC) among the five machine learning models (0.76, 95% confidence interval [CI] 0.74-0.78). The simplified 14-variable model showed adequate discrimination, with the AUC being 0.76 (95% CI 0.73-0.78). At the optimal cutoff of 0.63, the sensitivity and specificity of the simplified model were 63% and 76% respectively. In conclusion, a machine learning-based simplified prediction model including routine clinical variables could be used to differentiate between transient and persistent AKI in critically ill septic patients. An easy-to-use risk calculator can promote its widespread application in daily clinical practice.

10.
Front Oncol ; 11: 752725, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34707994

RESUMO

Targeted therapies such as oral tyrosine kinase inhibitors (TKIs) are the main therapeutic strategy effective for advanced hepatocellular carcinoma (HCC). Currently six tyrosine kinase inhibitors for HCC therapy have been approved. The newly approved first-line drug donafenib represent the major milestones in HCC therapeutics in recent years. However, drug resistance in HCC remains challenging due to random mutations in target receptors as well as downstream pathways. TKIs-based combinatorial therapies with immune checkpoint inhibitors such as PD-1/PD-L1 antibodies afford a promising strategy to further clinical application. Recent developments of nanoparticle-based TKI delivery techniques improve drug absorption and bioavailability, enhance efficient targeting delivery, prolonged circulation time, and reduce harmful side effects on normal tissues, which may improve the therapeutic efficacy of the TKIs. In this review, we summarize the milestones and recent progress in clinical trials of TKIs for HCC therapy. We also provide an overview of the novel nanoparticle-based TKI delivery techniques that enable efficient therapy.

11.
BMJ Open ; 11(10): e051761, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663665

RESUMO

INTRODUCTION: Diabetic retinopathy (DR) is one of the most prevalent microvascular complications of diabetes mellitus. Guidelines for DR screening in different countries vary greatly, including fundus photography, slit-lamp biomicroscopy, indirect ophthalmoscopy, Optical Coherence Tomography (OCT), OCT-A and Fundus Fluorescein Angiography (FFA). Two-field non-mydriatic fundus photography (NMFP) is an effective screening method due to its low cost and less time-consuming process. However, it is controversial due to the sensitivity and specificity of two-field NMFP. This review intends to evaluate the performance of the two-field NMFP in diagnosing DR and helps clinicians determine the most optimal screening method. METHODS AND ANALYSIS: Two reviewers will independently search on the Medline, Embase, Cochrane databases, ProQuest, Opengrey, Chinese National Knowledge Infrastructure, Wanfang Data, VIP China Science and Technology Journal Database, Chinese BioMedical Literature Database, ISRCTN, ClinicalTrials.gov and the WHO ICTRP to identify relevant studies. There is no restriction posed on the language of the study. Included studies focus on the performance of two-field NMFP in detecting DR in diabetes patients. Analysis and evaluation of the studies will be examined by two reviewers independently using the Quality Assessment for Diagnostic Accuracy Studies-2 tool and later evaluated using the Population, Intervention, Comparison, Outcome, Study design criteria. A random-effect model will calculate the diagnostic indicators, including the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic OR, area under the curve and 95% CIs. We will also develop a summary receiver operating characteristic curve. We anticipate analysing subgroups according to the factors, which may lead to heterogeneity, including DR levels of patients, the reference standards, camera models, the interpretation criteria. The data will be analysed by STATA software. This study was registered with PROSPERO. ETHICS AND DISSEMINATION: This review will analyse the published data. Patients/the public were not involved in this research. The results of this study will be published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42020203608.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Retinopatia Diabética/diagnóstico , Técnicas de Diagnóstico Oftalmológico , Humanos , Metanálise como Assunto , Fotografação , Literatura de Revisão como Assunto , Revisões Sistemáticas como Assunto
12.
Abdom Radiol (NY) ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635941

RESUMO

PURPOSE: To demonstrate the feasibility and diagnostic value of high-frequency magnetic resonance elastography (MRE) for evaluation of prostatic disease in patients with lower urinary tract symptoms (LUTS). METHODS: 41 patients who underwent preoperative prostate MRI and MRE with a modified driver were enrolled retrospectively from May 2016 to September 2021. All were included in the assessment of MRE image quality, using a qualitative visual inspection and a quantitative confidence map. 35 patients (prostate cancer (PCa), n = 13; non-PCa, n = 22) undergoing prostatectomy or biopsy were evaluated for the diagnostic performance of stiffness values. The confidence values and the stiffness values were analyzed by one-way analysis of variance (ANOVA) and independent samples T test, respectively. Area under the receiver operating characteristic (AUROC) analysis was performed. RESULTS: Through the qualitative analysis, all MRE acquisitions were successful at 60, 90, 120 and 150 Hz. The quantitative confidence values were significantly lower at 60 Hz (0.683 ± 0.055) and 90 Hz (0.762 ± 0.048) than that at 120 Hz (0.814 ± 0.049) and 150 Hz (0.840 ± 0.049), all P < 0.001. The stiffness of PCa was higher than non-PCa at 90 Hz (P = 0.008), 120 Hz (P < 0.001) and 150 Hz (P < 0.001). The AUCs were 0.773, 0.881 and 0.944, respectively. CONCLUSION: Prostate MRE using the modified driver is feasible at 60-150 Hz and image quality is better at higher frequencies. Prostate MRE may be useful and helpful to evaluate prostate diseases in patients with LUTS at higher frequencies; however, further study may be warranted with larger population in future.

13.
Front Cardiovasc Med ; 8: 700497, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616779

RESUMO

Purpose: We aimed to evaluate the safety and effectiveness of applying an excimer laser in debulking human carotid atherosclerotic plaques by investigating the distal debris, plaque luminal gain, and micromorphology of the plaque surface. Methods: Eighteen plaque samples obtained from carotid endarterectomy (CEA) were randomly allocated to the excimer laser ablation (45 mJ/mm2, 25 Hz) alone group (group 1), balloon angioplasty (8 atm) alone group (group 2), and excimer laser ablation combined with balloon angioplasty group (group 3). Hematoxylin-eosin staining and Movat's pentachrome staining were performed on the collected particles to quantify the size and composition of the debris. The superficial micromorphological structure of the plaque lumen surface after device treatments was observed using a scanning electron microscope. Micro-CT, tissue sections, and pathological stainings were applied to the treated plaques. The plaque lumen and artery lumen were three-dimensionally reconstructed using clinical computed tomography angiography and the micro-CT images. Lumen enlargement was set as the main measurement of effectiveness. Results: Group 3 produced the highest luminal gain (5.40 ± 4.51 mm2), while the other two groups had gains of 4.05 ± 3.20 and 3.77 ± 2.55 mm2. Both devices caused disruptions to the plaque lumen surface. Laser ablation exposed the fibers under the endothelium and balloon angioplasty cracked the surface. The mean amounts were 3,611 ± 1,475.4 for group 1, 2,828 ± 1,266.7 for group 2, and 4,400 ± 2,567.9 for group 3. More than 90% of the distal debris was smaller than 10 µm. Group 2 produced the most debris with Feret (maximum caliper diameter) ≥ 40 µm; group 1 had the least. There was little difference in the contents of collagen and reticular fiber in the debris in each group, but a big difference was observed in the contents of fibrin and mucin. Conclusion: Excimer laser ablation could significantly increase the luminal gain of carotid plaque with high stenosis. Excimer laser combined with balloon angioplasty achieved the highest lumen enlargement. Our result also suggests that the embolic protection strategy needs to be renewed for the application of a plaque debulking device in the future.

14.
Elife ; 102021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34698634

RESUMO

Sequential mannose trimming of N-glycan, from M9 to M8B and then to oligosaccharides exposing the α1,6-linked mannosyl residue (M7A, M6, and M5), facilitates endoplasmic reticulum-associated degradation of misfolded glycoproteins (gpERAD). We previously showed that EDEM2 stably disulfide-bonded to the thioredoxin domain-containing protein TXNDC11 is responsible for the first step (George et al., 2020). Here, we show that EDEM3 and EDEM1 are responsible for the second step. Incubation of pyridylamine-labeled M8B with purified EDEM3 alone produced M7 (M7A and M7C), M6, and M5. EDEM1 showed a similar tendency, although much lower amounts of M6 and M5 were produced. Thus, EDEM3 is a major α1,2-mannosidase for the second step from M8B. Both EDEM3 and EDEM1 trimmed M8B from a glycoprotein efficiently. Our confirmation of the Golgi localization of MAN1B indicates that no other α1,2-mannosidase is required for gpERAD. Accordingly, we have established the entire route of oligosaccharide processing and the enzymes responsible.

15.
Int Immunopharmacol ; 101(Pt B): 108240, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34666304

RESUMO

Endothelial-to-mesenchymal transition (EndMT) is a process of transdifferentiation in which endothelial cells gradually adopt the phenotypic characteristics of mesenchymal cells. Emerging studies demonstrate the importance of EndMT in endothelial dysfunction during inflammation. Sirtuin 6 (SIRT6), a member of the mammalian NAD+-dependent deacetylase sirtuin family, plays a critical role in cardiovascular diseases by regulating the inflammatory response. However, little is known about the effect of SIRT6 on EndMT during vascular inflammation. Therefore, we aimed to investigate the effect of SIRT6 on EndMT in endothelium-specific SIRT6 knockout (ecSIRT6-/-) mice and human umbilical vein endothelial cells (HUVECs) stimulated with inflammatory cytokines. First, we found that TNF-α and IL-1ß co-treatment induced EndMT and down-regulated SIRT6 expression in HUVECs. Adenovirus-mediated SIRT6 overexpression suppressed inflammation-induced EndMT in HUVECs. In contrast, SIRT6 knockdown further promoted EndMT. Our findings also revealed that SIRT6 attenuated the inflammatory response of HUVECs. Additionally, vascular inflammation was induced by carotid artery ligation in ecSIRT6-/- mice. Results showed that the intima of ligated carotid arteries in ecSIRT6-/- mice was significantly thickened compared to that in ecSIRT6+/+ ligated mice. Moreover, endothelium-specific SIRT6 knockout promoted EndMT and increased the expression of proinflammatory cytokines in the carotid arteries of mice. These results suggest that SIRT6 inhibits EndMT through attenuating the vascular endothelial inflammatory response. These findings may have significance for reducing the occurrence of EndMT and ameliorating certain aspects of vascular inflammation.

16.
Bioengineered ; 12(1): 5892-5903, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34482807

RESUMO

Bladder cancer is one of the most severe genitourinary cancers, causing high morbidity worldwide. However, the underlying molecular mechanism is not clear, and it is urgent to find target genes for treatment. G-protein-coupled receptors are currently a target of high interest for drug design. Thus, we aimed to identify a target gene-related to G-protein-coupled receptors for therapy. We used The Cancer Genome Atlas (TCGA) and DepMap databases to obtain the expression and clinical data of RGS19. The results showed that RGS19 was overexpressed in a wide range of tumor, especially bladder cancer. We also explored its effect on various types of cancer. High expression of RGS19 was also shown to be significantly associated with poor prognosis. Cell models were constructed for cell cycle detection. shRGS19 can halt the cell cycle at a polyploid point. RGS19 is a G-protein-coupled receptor signaling pathway-related gene with a significant effect on survival. We chose RGS19 as a therapeutic target gene in bladder cancer. The drug GSK1070916 was found to inhibit the effect of RGS19 via cell rescue experiments in vitro.

17.
Front Med ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34570311

RESUMO

Cancer imposes a severe threat to people's health and lives, thus pressing a huge medical and economic burden on individuals and communities. Therefore, early diagnosis of cancer is indispensable in the timely prevention and effective treatment for patients. Exosome has recently become an attractive cancer biomarker in noninvasive early diagnosis because of the unique physiology and pathology functions, which reflects remarkable information regarding the cancer microenvironment, and plays an important role in the occurrence and evolution of cancer. Meanwhile, biosensors have gained great attention for the detection of exosomes due to their superior properties, such as convenient operation, real-time readout, high sensitivity, and remarkable specificity, suggesting promising biomedical applications in the early diagnosis of cancer. In this review, the latest advances of biosensors regarding the assay of exosomes were summarized, and the superiorities of exosomes as markers for the early diagnosis of cancer were evaluated. Moreover, the recent challenges and further opportunities of developing effective biosensors for the early diagnosis of cancer were discussed.

18.
Reprod Toxicol ; 106: 1-8, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34555461

RESUMO

This study aimed to analyze the potential association between trichloroethylene (TCE) exposure and congenital heart disease (CHD) and to explore the effect of metabolic enzyme gene polymorphisms on heart development. A multicenter case-control study was conducted. The trichloroethylene concentrations were measured by UPLC-MSMS in urine. Fourteen SNPs in the GSTA1, GSTP1, MPO, NAT1, NAT2, CYP1A1, CYP1A2, CYP2E1 and EPHX1 genes were genotyped using an improved multiplex ligation detection reaction (iMLDR) technique. A total of 283 cases and 331 controls with maternal urine and/or venous blood were included in the present study. The median NAcDCVC was 7.65 ng/mL in the case group and 7.43 ng/mL in the control group. There was no significant difference in the NAcDCVC concentration between the CHD subtypes and controls (P > 0.05). The GA/AA of GSTA1 rs3957357 could increase the risk of CHDs under the dominant model (aOR = 2.26, 95 % CI: 1.31, 3.90), but other SNPs were not associated with CHDs (P > 0.05). GA or AA genotypes of GSTA1 rs3957357 with lower levels of TCE exposure were 3.53 times at risk relative to mothers carrying the wild type genotype. In conclusion, maternal exposure to trichloroethylene alone is not associated with the occurrence of fetal CHD and CHD subtypes. Maternal GSTA1 rs3957357 may increase the risk of CHD in offspring. TCE exposure and metabolic gene polymorphisms probably interact with each other to induce fetal cardiovascular malformation, but larger sample size studies are needed to confirm this hypothesis.

19.
Curr Pharm Des ; 27(40): 4160-4170, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34477512

RESUMO

BACKGROUND: Vascular endothelial growth factor (VEGF) is a supergene family derived from a platelet growth factor. It plays a pivotal role in regulating angiogenesis and lymphangiogenesis. sFlt-1 is a soluble antagonist of VEGF with an essential effect of maintaining the balance of vascular growth. Recently, sFlt-1 has emerged as a new marker for early diagnosis and disease surveillance of angiogenesis-related diseases. However, few comprehensive reviews focus on the relationship between sFlt-1 and related diseases despite that many results have yielded. METHODS: In this review, we analyzed the relationship between sFlt-1 and angiogenesis-related diseases by searching PubMed, Web of Science, and other databases, and summarized our current understanding of the role of sFlt-1 in angiogenesis-related diseases. RESULTS: sFlt-1 is associated with pre-eclampsia, perinatal cardiomyopathy, diabetic nephropathy, hypertension, tumor, atherosclerosis, and other diseases. The mechanisms of sFlt-1 that regulate those diseases are mainly associated with the bioavailability of VEGF and vascular endothelial cell integrity. CONCLUSION: From the summary article, sFlt-1 is a double regulator in angiogenesis-related diseases; too much or too little may cause different diseases. Therefore, maintaining the stability of sFlt-1 content in the body is essential to control the development of related diseases.

20.
Phytomedicine ; 91: 153694, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34403879

RESUMO

BACKGROUND: Atherosclerosis is a chronic vascular inflammatory disease with complex pathogenesis. Its serious consequence is insufficient blood supply to heart and brain, which eventually leads to myocardial ischemia, infarction and stroke. Hydroxysafflor yellow A (HSYA), a single chalcone glycoside compound with a variety of pharmacological effects, which has shown a potential biological activity for prevention and treatment of atherosclerosis. PURPOSE: The main purpose of this review is to comprehensively elucidate the mechanism of HSYA on atherosclerosis and its risk factors (hyperlipidemia, hypertension and diabetes mellitus). METHOD: The literatures on HSYA in the treatment of atherosclerosis and its risk factors were searched in PubMed, Google Scholar, China National Knowledge Infrastructure, including in vitro (cell), in vivo (animal) and clinical (human) studies, and summarized reasonably. RESULTS: HSYA is a promising natural product for treating atherosclerosis. It can suppress foam cell formation, vascular endothelial cell dysfunction, vascular smooth muscle cell proliferation and migration, and platelet activation. The mechanisms are achieved by regulating the reverse cholesterol transport process, fatty acid synthesis, oxidative stress, PI3K/Akt/mTOR, NLRP3 inflammasome, TNFR1/NF-κB, NO-cGMP, Bax/Bcl-2, MAPKs, CDK/CyclinD and TLR4/Rac1/Akt signaling pathways. Besides, HSYA is devoted to lowering blood lipids, regulating ion channels, reducing vascular inflammation, and protecting pancreatic beta cells, which is conducive to reducing the harm of independent risk factors of atherosclerosis. CONCLUSIONS: HSYA exhibits the preventive and therapeutic effects on atherosclerosis and its risk factors in vivo and in vitro, which is relevant to multiple mechanisms. The clinical trials of HSYA need to be further investigated to provide a solid foundation for its clinical application.


Assuntos
Aterosclerose , Carthamus tinctorius , Chalcona , Quinonas , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Carthamus tinctorius/química , Chalcona/análogos & derivados , Chalcona/farmacologia , Humanos , Compostos Fitoquímicos/farmacologia , Quinonas/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...