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1.
J Affect Disord ; 296: 434-442, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34606808

RESUMO

BACKGROUND: Preventive intervention can significantly reduce the human and economic costs of postpartum depression (PPD) compared with treatment post-diagnosis. However, identifying women with a high PPD risk and making a judgement as to the benefits of preventive intervention is a major challenge. METHODS: This is a retrospective study of parturients that underwent a cesarean delivery. Control group was used as development cohort and validation cohort to construct the risk prediction model of PPD and determine a risk threshold. Ketamine group and development cohort were used to verify the risk classification of parturients by evaluating whether the incidence of PPD decreased significantly after ketamine treatment in high-risk for PPD population. RESULTS: The AUC for the development cohort and validation cohort of the PPD prediction model were 0.751 (95%CI:0.700-0.802) and 0.748 (95%CI:0.680-0.816), respectively. A threshold of 19% PPD risk probability was determined, with a specificity and sensitivity in the validation cohort are 0.766 and 0.604, respectively. After matching the high-risk group and the low-risk group by propensity score, the results demonstrated that PPD incidence significantly reduced in the high-risk group following ketamine, versus non-ketamine, intervention (p < 0.01). In contrast, intervention in the low-risk group showed no significant difference in PPD outcomes (p > 0.01). LIMITATION: Randomized trials are needed to further verify the feasibility of the model and the thresholds proposed. CONCLUSION: This prediction model developed in this study shows utility in predicting PPD risk. Ketamine intervention significantly lowers PPD incidence in parturients with a risk classification threshold greater than 19%.

2.
Cartilage ; : 19476035211053824, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34719950

RESUMO

OBJECTIVE: Synovial inflammation influences the progression of osteoarthritis (OA). Herein, we aimed to identify potential biomarkers and analyze transcriptional regulatory-immune mechanism of synovitis in OA using weighted gene coexpression network analysis (WGCNA). DESIGN: A data set of OA synovium samples (GSE55235) was analyzed based on WGCNA. The most significant module with OA was identified and function annotation of the module was performed, following which the hub genes of the module were identified using Pearson correlation and a protein-protein interaction network was constructed. A transcriptional regulatory network of hub genes was constructed using the TRRUST database. The immune cell infiltration of OA samples was evaluated using the single-sample Gene Set Enrichment Analysis (ssGSEA) method. The hub genes coexpressed in multiple tissues were then screened out using data sets of synovium, cartilage, chondrocyte, subchondral bone, and synovial fluid samples. Finally, transcriptional factors and coexpressed hub genes were validated via experiments. RESULTS: The turquoise module of GSE55235 was identified via WGCNA. Functional annotation analysis showed that "mineral absorption" and "FoxO signaling pathway" were mostly enriched in the module. JUN, EGR1, FOSB, and KLF4 acted as central nodes in protein-protein interaction network and transcription factors to connect several target genes. "Activated B cell," "activated CD4T cell," "eosinophil," "neutrophil," and "type 17 T helper cell" showed high immune infiltration, while FOSB, KLF6, and MYBL2 showed significant negative correlation with type 17 T helper cell. CONCLUSIONS: Our results suggest that the expression level of apolipoprotein D (APOD) was correlated with OA. Furthermore, transcriptional regulatory-immune network was constructed, which may contribute to OA therapy.

3.
J Cell Mol Med ; 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34734681

RESUMO

Antibody-mediated rejection (AMR) is one of the most dominant mechanisms responsible for the loss of kidney grafts. Previous researches have shown that donor-specific antibodies (DSAs) are the major mediators of AMR. In order to prolong the survival time of grafts, it is vital to reduce the incidence of AMR and inhibit the generation of DSAs. We established an animal model of AMR by performing kidney transplantation in pre-sensitized rats. Then, we investigated the effect of bortezomib (BTZ) on AMR. We found that BTZ could reduce the serum level of DSAs and alleviate post-transplantation inflammation in peritubular capillaries (PTCs) and glomeruli, which was demonstrated by the reduction of C4d and IgG deposition in PTCs, and the reduced number of B cell and plasma cell in peripheral blood and the transplanted kidney (p < 0.05). Our results also suggested that BTZ increased the number of regulatory T cell (Treg) and significantly reduced the proportion of T helper (Th17) cell (p < 0.05). Besides, BTZ induced the significant upregulation of anti-inflammatory cytokines but downregulated pro-inflammatory cytokines (p < 0.05). After dealing with Atg5 siRNA-lentivirus, the effect of BTZ alleviating AMR was reversed and Th17/Treg proportions were also significantly modulated. Collectively, these findings show that BTZ slows down the process of AMR and Atg5 may be the key mechanism. Furthermore, Atg5 silencing results may be demonstrated that Atg5 alleviated AMR by modulating the ratio of Th17/Treg.

4.
Chem Sci ; 12(40): 13398-13403, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34777758

RESUMO

We report herein catalytic asymmetric transformations of racemic α-borylmethyl-(E)-crotylboronate. The Brønsted acid-catalyzed kinetic resolution-allylboration reaction sequence of the racemic reagent gave (Z)-δ-hydroxymethyl-anti-homoallylic alcohols with high Z-selectivities and enantioselectivities upon oxidative workup. In parallel, enantioconvergent pathways were utilized to synthesize chiral nonracemic 1,5-diols and α,ß-unsaturated aldehydes with excellent optical purity.

5.
Front Cardiovasc Med ; 8: 678467, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778385

RESUMO

Background: Epicardial adipose tissue (EAT) has been linked with the pathogenesis of heart failure (HF). Limited data have been reported about the clinical value of EAT for cardiac resynchronization therapy (CRT) in non-ischemic systolic HF. We aimed to explore the values of EAT measured from CT to predict the response to CRT in patients with non-ischemic systolic HF. Methods: Forty-one patients with CRT were consecutively recruited for our study. All patients received both gated resting Single Photon Emission CT (SPECT) myocardial perfusion imaging (MPI) and dual-source multi-detector row CT scans. EAT thickness was assessed on both the parasternal short and horizontal long-axis views. The area of EAT was calculated at the left main coronary artery level. Left ventricular systolic mechanical dyssynchrony (LVMD) was measured by phase standard deviation (PSD) and phase histogram bandwidth (PBW). The definition of CRT response was an improvement of 5% in left ventricular ejection fraction (LVEF) at 6 months after CRT implantation. Results: After 6 months of follow-up, 58.5% (24 of 41) of patients responded to CRT. A greater total perfusion deficit (TPD) was observed in the left ventricle, and a narrower QRS complex was observed in the nonresponse group than in the response group (p < 0.05). Meanwhile, the systolic PSD and systolic PBW were statistically greater in the CRT group with no response than in the response group (p < 0.05). Meanwhile, the baseline QRS duration, TPD, systolic PSD, systolic PBW, EAT thicknesses of the left ventricular (LV) apex, right atrioventricular (AV) groove, and left AV groove were all significantly related to the CRT response in the univariate logistic regression analysis. Furthermore, the QRS duration and EAT thicknesses of the right AV groove and left AV groove were independent predictors of CRT response in the multivariate logistic regression analysis. Conclusions: The EAT thickness of the left AV groove in patients with non-ischemic systolic HF is associated with the TPD of LV and LV systolic dyssynchrony. The EAT thickness of the AV groove has a good predictive value for the CRT response in patients with non-ischemic systolic HF.

6.
J Mech Behav Biomed Mater ; 125: 104944, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34740013

RESUMO

Sintering is a comprehensive process that involves the complex evolution of material microstructures and properties, being recognized as a critical factor to improve the machinability of ceramics. The present work aims to address the evolution of the material removal mechanisms of the 3 mol% yttria-stabilized tetragonal zirconia polycrystal (3Y-TZP) during the sintering process based on the micro scratching tests. The impacts of sintering temperatures on the material removal behaviors, including scratching forces, scratch morphologies, specific scratching energies, and critical transition depths, were rigorously studied. The acquired results indicate that the intergranular bonding strength is a critical factor that determinines the material removal mechanisms of 3Y-TZP, and 1100 °C signifies the transition threshold for the material removal mode. After 1100 °C, the material removal mechanism has gradually converted into the typical ductile-brittle removal regime. Moreover, the critical depth in ductile regime at 1200 °C is about 1.89 times that at 1500 °C, and the critical depth of ductile-brittle transition at 1200 °C is approximately 2.08 times that at 1500 °C.

7.
Pestic Biochem Physiol ; 179: 104966, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34802516

RESUMO

Pesticide resistance in spider mites drives the development of acaricides with novel mode of action, which could benefit from RNAi as a screening tool in search of new molecular targets. RNAi via oral delivery of dsRNA has been frequently reported in spider mites, but injection of dsRNA is rarely reported. We compare here the efficiency of oral delivery versus injection of dsRNA in female adult mites. When comparing silencing efficiency, oral delivery of dsRNAs silenced 40.6 ± 8.9% of CPR, 63.8 ± 6.9% of CHMP2A, and 37.7 ± 5.7% of CHMP3 genes. Similar silencing efficiencies were found for injection (48.6 ± 3.7% of CPR, 70.2 ± 4.1% of CHMP2A, 59.8 ± 2.2% of CHMP3), but with much lower quantities of dsRNAs. Oral delivery of dsRNA failed to silence the expression of the CHMP4B gene, but this could be accomplished by injection of dsRNA (23.1 ± 1.0%). When scoring the phenotypic effects of silencing, both oral delivery and injection of CHMP2A- and CHMP3-dsRNA influenced the locomotion speed of mites significantly. For CPR, silencing could only be accomplished by dsRNA injection, not by feeding. CPR silencing significantly impacted the toxicity of a typical acaricide, pyridaben, as the susceptibility of mites raised 2.75-fold. Last, injection of Eya-dsRNA in adults produced transgenerational phenotypic effects on 3.59% of offspring, as quantified by an observed deviation in eye development, while oral delivery of Eya-dsRNA did not. In conclusion, injection of dsRNA is superior to oral delivery in silencing the expression of the selected genes in this study and could be considered the method of choice to study gene function in reverse genetic approaches.


Assuntos
Acaricidas , Ácaros , Tetranychidae , Animais , Ácaros/genética , Interferência de RNA , RNA de Cadeia Dupla/genética
8.
Pestic Biochem Physiol ; 179: 104970, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34802520

RESUMO

The widespread use of herbicides has raised considerable concern with regard to their harmful consequences on plant growth, crop yield and the soil ecological environment. It has been well documented that colonization of rhizobacteria in the plant root system has a positive effect on activation of plant defenses to protect the plant from damage. Using the platform of high-throughput analysis with tandem mass spectrometry and Illumina sequencing, we identified the specific activated rhizobacteria, the key growth stimulating substances and the metabolic pathways involved in seedling stage tolerance to mefenacet stress in rice. The relative abundance of beneficial rhizospheremicrobes such as Acidobacteria and Firmicutes increased with mefenacet treatment, indicating that the rhizosphere recruited some beneficial microbes to resist mefenacet stress. Mefenacet treatment induced alterations in several interlinked metabolic pathways, many of which were related to activation of defense response signaling, especially the indole-3-pyruvate pathway. Indole-3-acetaldehyde and indole-3-ethanol from this pathway may act as flexible storage pools for indole-3-acetic acid (IAA). Our findings also suggest that a significant increase of IAA produced by the enrichment of beneficial rhizospheremicrobes, for example genus Bacillus, alleviated the dwarfing phenomenon observed in hydroponic medium following mefenacet exposure, which may be a key signaling molecule primarily for phytostimulation and phytotolerance in microbe-plant interactions.


Assuntos
Oryza , Rizosfera , Acetanilidas , Benzotiazóis , Raízes de Plantas , Microbiologia do Solo
9.
Theranostics ; 11(20): 9953-9966, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34815797

RESUMO

Background: Serum-derived exosomes are correlated with disease severity of human systemic lupus erythematosus (SLE). The proteins in the T-cell-derived exosomes from SLE patients could contribute to inflammation. Methods: We characterized proteins of T cell-derived exosomes from SLE patients and healthy controls by proteomics. To study the potential pathogenic role of the identified exosomal protein, we generated and characterized T-cell-specific transgenic mice that overexpressed the identified protein in T cells using immunohistochemistry, immunoblotting, and single-cell RNA sequencing. Results: We identified an overexpressed protein, bactericidal/permeability-increasing protein (BPI), in SLE T cells and T-cell-derived exosomes. T-cell-specific BPI transgenic (Lck-BPI Tg) mice showed multi-tissue inflammation with early induction of serum IL-1ß levels, as well as serum triglyceride and creatinine levels. Interestingly, exosomes of Lck-BPI Tg T cells stimulated IL-1ß expression of wild-type recipient macrophages. Remarkably, adoptive transfer of BPI-containing exosomes increased serum IL-1ß and autoantibody levels in recipient mice. The transferred exosomes infiltrated into multiple tissues of recipient mice, resulting in hepatitis, nephritis, and arthritis. ScRNA-seq showed that Lck-BPI Tg T cells displayed a decrease of Treg population, which was concomitant with ZFP36L2 upregulation and Helios downregulation. Furthermore, in vitro Treg differentiation was reduced by BPI transgene and enhanced by BPI knockout. Conclusions: BPI is a negative regulator of Treg differentiation. BPI overexpression in T-cell-derived exosomes or peripheral blood T cells may be a biomarker and pathogenic factor for human SLE nephritis, hepatitis, and arthritis.

10.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(5): 543-547, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34816670

RESUMO

Objective: To investigate the effects of moxibustion on the behavioral performance, brain morphological structure of mice with hypoxia-ischemia brain injury and to explore its mechanisms. Methods: One hundred and six ICR mice were randomly divided into three groups, sham group (n=23), model group (n=46) and moxibustion-treated group (n=37). Neonatal hypoxic-ischemia brain injury was induced by ligation of common carotid artery followed by hypoxia (8% oxygen, 100 min), and pups in the moxibustion-treated group were administered suspended moxibustion on the Dazhui points (GV14) at a height of approximately 2 cm over a hairless area of the skin once a day for 4 days (i.e. at 2, 24, 48 and 72 hours after hypoxia-ischemia procedure). Behavioral tests were used to evaluate behavioral performance. HE staining was used to observe brain morphological structure. Western blot was used to detect the expression of SOD2 protein, and spectrophotometry was used to determine the content of MDA in the ipsilateral brain. Results: Mouse pups in sham group showed that the behavioral performance was normal, the brain tissue cells were densely and neatly arranged, the expression of SOD2 and the level of MDA in the brain tissues were normal. Compared with sham group, mouse pups in the HI model group exhibited a significant longer latency to complete the righting reflex, geotaxis reflex, cliff avoidance (P<0.05) and a marked shorter latency to complete the grip test (P<0.05); and the HI model group had dramatic brain morphological changes showing missing regions, decreased expression of SOD2 protein (P<0.05) and increased level of MDA in the brain. Compared with HI model group, mouse pups in the moxibustion-treated group exhibited a significant shorter latency to complete the righting reflex, geotaxis reflex, cliff avoidance test (P<0.05) and a marked longer latency to complete the grip test (P<0.05); and the moxibustion-treated group had less brain morphological changes, increased expression of SOD2 protein (P<0.05) and decreased level of MDA in the brain (P<0.05) . Conclusion: Moxibustion could improve behavioral performance and attenuate hypoxia-ischemia brain injury, which might be related to increasing the expression of SOD2 protein and decreasing the content of MDA, thus enhancing the anti-oxidative ability.

11.
Front Oncol ; 11: 770565, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804972

RESUMO

Background: It is undeniable that the tumor microenvironment (TME) plays an indispensable role in the progression of kidney renal clear cell carcinoma (KIRC). However, the precise mechanism of activities in TME is still unclear. Methods and Results: Using the CIBERSORT and ESTIMATE calculation methods, the scores of the two main fractions of tumor-infiltrating immune cells (TICs) from The Cancer Genome Atlas (TCGA) database of 537 KIRC patients were calculated. Subsequently, differentially expressed genes (DEGs) were drawn out by performing an overlap between Cox regression analysis and protein-protein interaction (PPI) network. Aquaporin 9 (AQP9) was identified as a latent predictor through the process. Following research revealed that AQP9 expression was positively correlated with the pathological characteristics (TNM stage) and negatively connected with survival time. Then, by performing gene set enrichment analysis (GSEA), it can be inferred that genes with high expression level of AQP9 were mainly enriched in immune-related activities, while low AQP9 group was associated with functions of cellular metabolism. Further studies have shown that regulatory T cells (Tregs), macrophages M2, macrophages M0, CD4+ T cells, and neutrophils were positively correlated with AQP9 expression. While the levels of mast cells, natural killer (NK) cells, and CD8+ T cells are negatively correlated with AQP9. The result of multiple immunohistochemistry (mIHC) suggests a negative relevance between AQP9 and CD8+ T cells and reveals a trend of consistent change on AQP9 and M2 macrophages. Conclusion: The expression level of AQP9 may be helpful in predicting the prognosis of patients with KIRC, especially to the TME state transition, the mechanism of which is possibly through lipid metabolism and P53, Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways that affect M2 polarization. AQP9 was associated with the expression levels of M2, tumor-associated macrophages (TAMs), and the recruitment of CD8+ T cells in tumor environment. The research result indicates that AQP9 may be an obstacle to maintain the immune activity of TME.

12.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21266241

RESUMO

There is clinical need for a quantifiable point-of-care (PoC) SARS-CoV-2 neutralizing antibody (nAb) test that is adaptable with the pandemics changing landscape. Here, we present a rapid and semi-quantitative nAb test that uses finger stick or venous blood to assess the nAb response of vaccinated population against wild-type, alpha, beta, gamma, and delta variant receptor binding domains. It captures a clinically relevant range of nAb levels, and effectively differentiates pre-vaccination, post 1st dose and post 2nd dose vaccination samples within 10 minutes. The data observed against alpha, beta, gamma, and delta variants agrees with published results evaluated in established serology tests. Finally, our test revealed a substantial reduction in nAb level for beta, gamma, and delta variants between early BNT162b2 vaccination group (within 3 months) and later vaccination group (post 3 months). This test is highly suited for PoC settings and provides an insightful nAb response in a post-vaccinated population.

13.
Food Funct ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34746942

RESUMO

The oligopeptides derived from Auxis thazard protein (ATO) are a class of small peptides with molecular weight <1 kDa and good bioactivity. This paper aimed to explore the hypouricemic, hepatoprotective, and nephroprotective effects of ATO and its potential mechanisms in hyperuricemia in mice induced by potassium oxonate. The results showed that ATO significantly reduced serum UA, serum creatinine levels, inhibited XOD and ADA activities in the liver (p < 0.05), and accelerated UA excretion by downregulating the gene expression of renal mURAT1 and mGLUT9 and upregulating the gene expression of mABCG2 and mOAT1. ATO could also reduce the levels of liver MDA, increase the activities of SOD and CAT, and reduce the levels of IL-1ß, MCP-1 and TNF-α. Histological analysis also showed that ATO possessed hepatoprotective and nephroprotective activities in hyperuricemic mice. Thus, ATO could reduce the serum UA level in hyperuricemic mice by decreasing UA production and promoting UA excretion from the kidney, suggesting that ATO could be developed as a dietary supplement for hyperuricemia treatment.

14.
J Nucl Med Technol ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34750234

RESUMO

To investigate minimal required sub milli-Sievert (mSv) ultra-low dose CT and corresponding tube current and voltage for reliable attenuation correction and semi- quantitation in 18F-FDG PET-CT in an effort for radiation dose reduction. Methods: We performed a PET-CT investigational study using a NEMA torso phantom containing six spheres (diameter: 10, 13, 17, 22, 28, 37 mm) filled with a fixed concentration of 60 kBq/ml and a background of 15 kBq/ml of 18F-FDG. Two sets of PET images, separated by 2 hours, were acquired for 3 minutes in a single bed position using 3-D mode with and without time-of-flight in a GE D-690 scanner. Several sets of CT images were acquired for attenuation correction with different combinations of tube voltage (80, 100, 120 kVp) and effective mAs (tube current-time product divided by pitch), using the maximum beam collimation (64 x 0.625 mm). The lowest CT acquisition technique available on this scanner is 10 mA, 0.4 s and 1.375 for the tube current, tube rotation time and pitch, respectively. The CT radiation dose was estimated based on the computed tomography dose index volume (CTDIvol) measurements performed following the standard methodology and the Imaging Performance Assessment of CT Scanners (ImPACT) calculator. Each of the CT techniques was used for attenuation correction to the same PET acquisition, using ordered-subset expectation maximum (OSEM) algorithm with 24 subsets and 2 iterations. The maximal and average radioactivity (kBq/ml) and standardized uptake values (SUV) of the spheres were measured. The minimal ultra-low dose CT for attenuation correction was determined by reproducible SUV measurements (±10%) compared to our reference CT protocol of 100 kVp and 80 mA for 0.5 s rotation. Results: The minimal ultra-low dose of CT for reproducible quantification in all spheres (<10% relative difference) was determined to be 0.3 mSv for a combination of 100 kVp and 10 mA at 0.5 s rotation, 0.984 helical pitch (0.26 mGy measured CTDIvol) . Based on these results we could confidently determine the CT parameters for reliable attenuation correction of PET images while significantly reducing the associated radiation dose. Conclusion: Our phantom study provided guidance in using ultra-low dose CT for precise attenuation correction and semi-quantification of 18F-FDG PET imaging, which can further reduce CT dose and radiation exposure to patients in clinical PET-CT studies. Clinical application: Based on the data, we can further reduce the radiation dose to sub-mSv using an ultra-low dose CT protocol for reliable attenuation correction in clinical 18F-FDG PET-CT studies.

15.
Biomed J ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34801764

RESUMO

BACKGROUND: To determine a reliable method to predict prevalent vertebral fractures (VF) by assessing the association between dysmobility syndrome (DS) and VF in a community-dwelling population. MATERIAL AND METHODS: This cross-sectional study enrolled 518 participants from fracture-prevention educational activities held in multiple communities in Taiwan. Assessments included questionnaires, fracture risk assessment tool (FRAX), bone mineral density (BMD) and body composition using dual-energy x-ray absorptiometry (DXA), lateral thoracolumbar spine x-rays (specifically T8-S1), grip strength (GS), walking speed, and fall history. RESULTS: DS was noted in 257 participants (49.6%) and VF was identified in 196 participants (37.8%). A higher prevalence of VF was noted in those with DS. The prevalence of VF was significantly associated with age, gender, FRAX both with and without BMD, osteoporosis, low GS, and DS. In multivariate models accounting for age and sex, the c-index was greater in those with low GS plus osteoporosis as compared to DS alone. Low GS, osteoporosis, and pre-BMD FRAX all had similar c-indexes. Pre-BMD FRAX plus low GS and osteoporosis was superior in predicting VF compared to pre-BMD FRAX plus low GS or osteoporosis alone. Besides the inclusion of age and gender, the nomogram with pre-BMD FRAX major osteoporosis fracture probability (MOF) plus low GS had improved correlation between the estimated and actual VF probability than those with pre-BMD FRAX MOF plus osteoporosis. CONCLUSIONS: The constructed nomogram containing pre-BMD FRAX MOF plus low GS may be considered as a first-line prevalent VF screening method. Those with high-risk scores should subsequently undergo vertebral radiography and/or BMD.

16.
Artigo em Inglês | MEDLINE | ID: mdl-34769592

RESUMO

Tuberculosis (TB) can cause chronic inflammation. The occurrence of aortic aneurysm (AA) and aortic dissection (AD) may be associated with chronic inflammatory disease, but whether TB increases the risk of AA and AD remains to be determined. This study aimed to investigate the association between TB and the development of AA and AD. We conducted a population-based cohort study using data obtained from the Taiwan National Health Insurance Database. We selected 31,220 individuals with TB and 62,440 individuals without TB by matching the cohorts according to age, sex, and index year at a ratio of 1:2. Cox regression analysis revealed that the TB cohort had a 1.711-fold higher risk of AA and AD than the non-TB cohort after adjustment for sex, age, socioeconomic status, and comorbidities (adjusted hazard ratio = 1.711; 95% confidence interval = 1.098-2.666). Patients with pulmonary, extrapulmonary, and miliary TB had a 1.561-, 1.892-, and 8.334-fold higher risk of AA and AD, respectively. Furthermore, patients with TB at <6 months, 6-12 months, and 1-5 years of follow-up had a 6.896-, 2.671-, and 2.371-fold risk of AA and AD, respectively. Physicians should consider the subsequent development of AA and AD while treating patients with TB.


Assuntos
Aneurisma Aórtico , Tuberculose , Aneurisma Aórtico/epidemiologia , Estudos de Coortes , Dissecação , Humanos , Incidência , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Tuberculose/epidemiologia
17.
Front Oncol ; 11: 768879, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34796115

RESUMO

Dihydroartemisinin (DHA), a well-known antimalarial drug, has been widely investigated for its antitumor effects in multiple malignancies. However, its effects and regulatory mechanisms in colorectal cancer (CRC) are still unproved. In this study, in vitro experiments including CCK8, EdU, Transwell, and flow cytometry analyses and an in vivo tumorigenesis model were conducted to assess the effects of DHA on the bio-behaviors of CRC cells. Additionally, RNA-seq combined with gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses was used to obtain the targets of DHA, and these were verified by molecular docking, qRT-PCR, and Western blotting. As a result, we found that DHA significantly suppressed the proliferation, DNA synthesis, and invasive capabilities and induced cell apoptosis and cell cycle arrest in HCT116, DLD1, and RKO cells in vitro and in vivo. Further analyses indicated that the targets of DHA were predominantly enriched in cell cycle-associated pathways, including CDK1, CCNB1, and PLK1; and DHA could bind with the CDK1/CCNB1 complex and inhibit the activation of CDK1/CCNB1/PLK1 signaling. Moreover, cucurbitacin E, a specific inhibitor of the CDK1/CCNB1 axis, enhanced the inhibitory effects of DHA on DNA synthesis and colony formation in HCT116 and DLD1 cells. In short, DHA could suppress the tumorigenesis and cycle progression of CRC cells by targeting CDK1/CCNB1/PLK1 signaling.

18.
Front Oncol ; 11: 736640, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34760698

RESUMO

Purpose: This study aimed i) to identify the best cutoff points of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) that predict sarcopenia and ii) to illustrate the association between sarcopenia risk and NLR or PLR in renal cell carcinoma (RCC) patients undergoing laparoscopic partial or radical nephrectomy. Methods: A total of 343 RCC patients who underwent laparoscopic partial or radical nephrectomy between 2014 and 2019 were enrolled in our study. Sarcopenia was assessed by lumbar skeletal muscle index (SMI). Receiver operating characteristic (ROC) curve was used to identify the best cutoff point of NLR or PLR to predict sarcopenia risk. Univariate and multivariate logistic regression and dose-response analysis curves of restricted cubic spline function were conducted to assess the relationship between sarcopenia and NLR or PLR. Results: The best cutoff points of NLR >2.88 or PLR >135.63 were confirmed by the ROC curve to predict sarcopenia risk. Dose-response curves showed that the risk of sarcopenia increased with raising NLR and PLR. Patients with NLR >2.88 or PLR >135.63 had a higher sarcopenia risk than those in the NLR ≤2.8 or PLR ≤135.63 group, respectively. By adjusting for all variables, we found that patients with NLR >2.88 and PLR >135.63 had 149% and 85% higher risk to develop sarcopenia, respectively, than those with NLR ≤2.8 (aOR = 2.49; 95% CI = 1.56-3.98; p < 0.001) or PLR ≤135.63 (aOR = 1.85; 95% CI = 1.16-2.95; p = 0.010). Conclusion: In RCC patients receiving laparoscopic partial or radical nephrectomy, NLR and PLR, which were biomarkers of systemic inflammation, were associated with sarcopenia risk.

19.
Mol Cancer ; 20(1): 142, 2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-34740354

RESUMO

Circular RNAs are a new class of non-coding RNAs that have been shown to play critical roles in the development and progression of renal cell carcinoma (RCC). However, little is known about the functional mechanisms and therapeutic role of ciRS-7 in RCC. A series of in vitro and in vivo experiments were performed to investigate the functional mechanism and therapeutic role of ciRS-7, such as real-time quantitative PCR, CCK-8, wound healing, transwell, colony formation, Edu, tumor xenograft and lung metastasis in NSG mice. RNA pull-down, dual luciferase reporter, fluorescence in situ hybridization (FISH) and rescue assays were used to determine the relationship between ciRS-7, miR-139-3p and TAGLN. In addition, we constructed PBAE/si-ciRS-7 nanocomplexes with PBAE material to evaluate the therapeutic effect of the nanocomplexes on tumor in vivo. ciRS-7 was highly expressed in RCC tumor tissues and cell lines, and high ciRS-7 expression correlated with tumor size, high Fuhrman grade and poor survival. Depletion of ciRS-7 significantly inhibited RCC cell proliferation, invasion, tumor growth and metastasis in vivo, while overexpression of ciRS-7 had the opposite effect. Mechanistically, ciRS-7 acts as a "ceRNA" for miR-139-3p to prevent TAGLN degradation and promoting RCC progression and metastasis via the PI3K/AKT signaling pathway. In addition, miR-139-3p mimics or inhibitor could reverse the altered malignant tumor behavior caused by ciRS-7 overexpression or silencing. Furthermore, the PBAE/siciRS-7 nanocomplexes could significantly inhibit RCC tumor progression and metastasis in vivo. ciRS-7 acts as a tumor promoter by regulating the miR-139-3p/TAGLN axis and activating the PI3K/AKT signaling pathway to promote RCC progression and metastasis. Drug development of PBAE/si-ciRS-7 nanocomplexes targeting ciRS-7 may represent a promising gene therapeutic strategy for RCC.

20.
Cancer Lett ; 525: 84-96, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34740608

RESUMO

Wnt/ß-catenin signaling is a highly conserved pathway that regulates cell proliferation, differentiation, apoptosis, stem cell self-renewal, tissue homeostasis, and wound healing. Dysregulation of the Wnt pathway is intricately involved in almost all stages of tumorigenesis in various cancers. Through direct and/or indirect effects on effector T cells, T-regulatory cells, T-helper cells, dendritic cells, and other cytokine-expressing immune cells, abnormal activation of Wnt/ß-catenin signaling benefits immune exclusion and hinders T-cell-mediated antitumor immune responses. Activation of Wnt signaling results in increased resistance to immunotherapies. In this review, we summarize the process by which Wnt signaling affects cancer and immune surveillance, and the potential for targeting the Wnt-signaling pathway via cancer immunotherapy.

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