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1.
Bioact Mater ; 8: 140-152, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34541392

RESUMO

Magnesium (Mg) alloys that have both antibacterial and osteogenic properties are suitable candidates for orthopedic implants. However, the fabrication of ideal Mg implants suitable for bone repair remains challenging because it requires implants with interconnected pore structures and personalized geometric shapes. In this study, we fabricated a porous 3D-printed Mg-Nd-Zn-Zr (denoted as JDBM) implant with suitable mechanical properties using selective laser melting technology. The 3D-printed JDBM implant exhibited cytocompatibility in MC3T3-E1 and RAW267.4 cells and excellent osteoinductivity in vitro. Furthermore, the implant demonstrated excellent antibacterial ratios of 90.0% and 92.1% for methicillin-resistant S. aureus (MRSA) and Escherichia coli, respectively. The 3D-printed JDBM implant prevented MRSA-induced implant-related infection in a rabbit model and showed good in vivo biocompatibility based on the results of histological evaluation, blood tests, and Mg2+ deposition detection. In addition, enhanced inflammatory response and TNF-α secretion were observed at the bone-implant interface of the 3D-printed JDBM implants during the early implantation stage. The high Mg2+ environment produced by the degradation of 3D-printed JDBM implants could promote M1 phenotype of macrophages (Tnf, iNOS, Ccl3, Ccl4, Ccl5, Cxcl10, and Cxcl2), and enhance the phagocytic ability of macrophages. The enhanced immunoregulatory effect generated by relatively fast Mg2+ release and implant degradation during the early implantation stage is a potential antibacterial mechanism of Mg-based implant. Our findings indicate that 3D-printed porous JDBM implants, having both antibacterial property and osteoinductivity, hold potential for future orthopedic applications.

2.
Environ Pollut ; 292(Pt B): 118464, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34763019

RESUMO

The use of biomass for cooking and heating is considered an important factor associated with chronic obstructive pulmonary disease (COPD), but few studies have previously addressed its underlying mechanisms. Therefore, this research aimed to evaluate the effects of biomass-related PM2.5 (BRPM2.5) exposure on 16HBE human airway epithelial cells and in mice with regard to mitochondrial dysfunction. Our study indicated that BRPM2.5 exposure of 16HBE cells resulted in mitochondrial dysfunction, including decreased mitochondrial membrane potential, increased expression of fission proteins-phospho-DRP1, increased mitochondrial ROS (mtROS), and decreased levels of ATP. BRPM2.5 altered the mitochondrial metabolism of 16HBE cells by decreasing mitochondrial oxygen consumption and glycolysis. However, Mitochondria targeted peptide SS-31 eliminated mitochondrial ROS and alleviated the ATP deficiency and proinflammatory cytokines release. BRPM2.5 exposure resulted in abnormal mitochondrial morphological alterations both in 16HBE and in lung tissue. Taken together, these results suggest that BRPM2.5 has detrimental effects on human airway epithelial cells, leading to mitochondrial dysfunction, abnormal mitochondrial metabolism and altered mitochondrial dynamics. The present study provides the first evidence that disruption of mitochondrial structure and mitochondrial metabolism may be one of the mechanisms of BRPM2.5-induced respiratory dysfunction.


Assuntos
Células Epiteliais , Pulmão , Animais , Biomassa , Humanos , Pulmão/química , Camundongos , Material Particulado/análise , Material Particulado/toxicidade , Espécies Reativas de Oxigênio
3.
Glia ; 70(1): 106-122, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34498776

RESUMO

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized primarily by impaired social communication and rigid, repetitive, and stereotyped behaviors. Many studies implicate abnormal synapse development and the resultant abnormalities in synaptic excitatory-inhibitory (E/I) balance may underlie many features of the disease, suggesting aberrant neuronal connections and networks are prone to occur in the developing autistic brain. Astrocytes are crucial for synaptic formation and function, and defects in astrocytic activation and function during a critical developmental period may also contribute to the pathogenesis of ASD. Here, we report that increasing hippocampal astrogenesis during development induces autistic-like behavior in mice and a concurrent decreased E/I ratio in the hippocampus that results from enhanced GABAergic transmission in CA1 pyramidal neurons. Suppressing the aberrantly elevated GABAergic synaptic transmission in hippocampal CA1 area rescues autistic-like behavior and restores the E/I balance. Thus, we provide direct evidence for a developmental role of astrocytes in driving the behavioral phenotypes of ASD, and our results support that targeting the altered GABAergic neurotransmission may represent a promising therapeutic strategy for ASD.

4.
J Vis Exp ; (176)2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34723944

RESUMO

Phase-change droplets are a class of ultrasound contrast agents that can convert into echogenic microbubbles in situ with the application of sufficient acoustic energy. Droplets are smaller and more stable than their microbubble counterparts. However, traditional ultrasound contrast agents are not trackable beyond acoustic feedback measurements, which makes quantifying contrast agent bio-distribution or accumulation ex vivo difficult. Researchers may have to rely on fluorescent or optically absorbent companion diagnostic particles to infer bio-distribution. The purpose of this protocol is to detail steps for creating multi-modal phase-change porphyrin droplets using a condensation method. Porphyrins are fluorescent molecules with distinct absorbance bands that can be conjugated onto lipids and incorporated into droplets to extend droplet versatility, enabling more robust bio-distribution while retaining acoustic properties. Seven formulations with varying porphyrin-lipid and base lipid contents were made to investigate microbubble and droplet size distributions. Characterizations suited to porphyrin-containing structures are also described in the protocol to demonstrate their analytic versatility in-solution. Sizing showed that the post-condensed mean diameters were 1.72 to 2.38 times smaller than precursor populations. Absorbance characterization showed intact assemblies had a Q-band peak of 700 nm while disrupted samples had an absorbance peak at 671 nm. Fluorescence characterization showed intact 30% porphyrin-lipid assemblies were fluorescently quenched (>97%), with fluorescence recovery achieved upon disruption. Acoustic vaporization showed that porphyrin droplets were non-echogenic at lower pressures and could be converted into echogenic microbubbles with sufficient pressures. These characterizations show the potential for porphyrin droplets to eliminate the need for absorbance or fluorescence-based companion diagnostic strategies to quantify ultrasound contrast agent bio-distribution for delivery or therapeutic applications in vivo or ex vivo.

5.
BMC Med Inform Decis Mak ; 21(1): 325, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809614

RESUMO

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) experience deficits in exercise capacity and physical activity as their disease progresses. Pulmonary rehabilitation (PR) can enhance exercise capacity of patients and it is crucial for patients to maintain a lifestyle which is long-term physically active. This study aimed to develop a home-based rehabilitation mHealth system incorporating behavior change techniques (BCTs) for COPD patients, and evaluate its technology acceptance and feasibility. METHODS: Guided by the medical research council (MRC) framework the process of this study was divided into four steps. In the first step, the prescription was constructed. The second step was to formulate specific intervention functions based on the behavior change wheel theory. Subsequently, in the third step we conducted iterative system development. And in the last step two pilot studies were performed, the first was for the improvement of system functions and the second was to explore potential clinical benefits and validate the acceptance and usability of the system. RESULTS: A total of 17 participants were enrolled, among them 12 COPD participants completed the 12-week study. For the clinical outcomes, Six-Minute Walk Test (6MWT) showed significant difference (P = .023) over time with an improvement exceeded the minimal clinically important difference (MCID). Change in respiratory symptom (CAT score) was statistically different (P = .031) with a greater decrease of - 3. The mMRC levels reduced overall and showed significant difference. The overall compliance of this study reached 82.20% (± 1.68%). The results of questionnaire and interviews indicated good technology acceptance and functional usability. The participants were satisfied with the mHealth-based intervention. CONCLUSIONS: This study developed a home-based PR mHealth system for COPD patients. We showed that the home-based PR mHealth system incorporating BCTs is a feasible and acceptable intervention for COPD patients, and COPD patients can benefit from the intervention delivered by the system. The proposed system played an important auxiliary role in offering exercise prescription according to the characteristics of patients. It provided means and tools for further individuation of exercise prescription in the future.

6.
J Cell Sci ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34817059

RESUMO

The disruption of endosomal actin architecture negatively affects endocytic recycling. However, the underlying homeostatic mechanisms that regulate actin organization during recycling remain unclear. In this study, we identified a synergistic endosomal actin assembly restricting mechanism in C. elegans involving WTS-1/LATS kinase, which is a core component of the Hippo pathway. WTS-1 resides on the sorting endosomes and colocalizes with the actin polymerization regulator PTRN-1/CAMSAPs. We observed an increase in PTRN-1-labeled structures in WTS-1-deficient cells, indicating that WTS-1 can limit the endosomal localization of PTRN-1. Accordingly, the actin overaccumulation phenotype in WTS-1-depleted cells was mitigated by the associated PTRN-1 loss. We further demonstrated that recycling defects and actin overaccumulation in WTS-1-deficient cells were reduced by the overexpression of constitutively active UNC-60A/cofilin(S3A), which aligns with the role of LATS as a positive regulator of cofilin activity. Altogether, our data confirmed previous findings, and we proposed an additional model: WTS-1 acts alongside the UNC-60A/cofilin-mediated actin disassembly to restrict the assembly of endosomal F-actin by curbing PTRN-1 dwelling on endosomes, preserving recycling transport.

7.
Medicine (Baltimore) ; 100(46): e27622, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34797285

RESUMO

ABSTRACT: Patients with chronic obstructive pulmonary disease (COPD) have a reduced cross-sectional area (CSA) of small pulmonary vessels and decreased pulmonary function test (PFT) indexes. This study investigated the value of small pulmonary vessel CSA in diagnosing and evaluating the severity of COPD and its correlation with PFT.This retrospective case-control study included patients with COPD who underwent multi-slice spiral computed tomography (CT) between March 2015 and December 2018. COPD severity was graded. Patients with normal CT results were included as controls. The CSA of small pulmonary vessels at the sub-segmental (5-10 mm2) and sub-sub-segmental (<5 mm2) levels was measured. Receiver operating characteristic (ROC) curves were used to evaluate the effect of CSA for COPD risk prediction. The correlation between CSA% and PFT indexes was evaluated.There were 124 and 106 patients in the COPD and control groups, respectively. The %CSA <5 and %CSA5-10 were smaller in the COPD group than in controls (P  < .05). The %CSA <5 in each subgroup stratified by COPD severity was smaller than in controls (P  < .05). The % CSA5-10 was significantly smaller in the moderate and severe groups than in controls (P  < .05). At 0.655%CSA <5 cut-off, the ROC area under the curve (AUC) was 0.765. For %CSA5-10, a 0.565 cut-off led to an AUC of 0.752. Both %CSA <5 and %CSA5-10 were positively correlated with all PFT indexes (r = 0.180-0.462, all P  < .05).CSA was positively correlated with PFT. Analysis of small pulmonary vessel CSA based on CT images contributes to diagnosing and assessing the severity of COPD.

8.
Dalton Trans ; 50(45): 16620-16630, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34748622

RESUMO

Surface acid site regulation of photocatalysts is a promising strategy to improve their performance. Herein, surface acid sites of cadmium sulfide were rationally regulated by cerium doping, which resulted in significantly increased photocatalytic activity for tetracycline hydrochloride (TC-HCl) degradation. The generated Brønsted acid sites were verified to favor the adsorption of organic molecules because of their strong affinity. Meanwhile, Lewis acid sites acted as the active sites for C-C bond cleavage via a nucleophilic substitution process, which was testified by the Fukui function and electrostatic potential. Besides, Ce3+ doping suppressed the recombination of electron-hole pairs, which also boosted the performance of TC-HCl degradation. Moreover, the degradation pathway of TC-HCl was deduced based on theoretical calculations and HPLC-MS results. The toxicity of pollutants and intermediates was also evaluated. This work provided new insight into the rational design and preparation of highly efficient photocatalysts for environmental purification.

9.
Int J Ophthalmol ; 14(11): 1666-1673, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804855

RESUMO

AIM: To evaluate the potential efficacy and mechanisms of nintedanib in corneal neovascularization (NV) in rabbit models. METHODS: Corneal NV was induced using 1 mol/L NaOH. Rabbits (n=21) were randomized to 3 groups: Group 1 were treated with 0.9% NaCl, Group 2 with Avastin (5 mg/mL), and Group 3 with nintedanib (1 mg/mL). All treatments started 1d after alkaline burns and were topically performed 3 times a day for 2wk. Photographs were taken on a slit lamp microscope on day 7 and 14. The NV area, the length of the vascularization and angiogenesis index (AI) were used to evaluate the corneal NV. On day 14, the immunohistochemical (IHC) studies of the cornea were examined. Western blot was performed to test the expression levels of vascular endothelial growth factor (VEGF), Akt, p-Akt, P38, p-P38, MMP-2 and MMP-9. RESULTS: The corneal NV area, vessel length and AI in Group 3 were significantly lower than Group 2, with both being lower than Group 1. IHC staining showed that VEGF was significantly overexpressed in the epithelium and stroma of cornea following alkaline burns. In contrast, the level of VEGF was significantly suppressed in both Group 2 and Group 3. Western blot results further confirmed that, compared with Group 1, Group 3 had significantly reduced expressions of VEGF, Akt, p-Akt, p-P38, MMP-2, and MMP-9 in corneal tissues. Trends of lower levels of MMP-2, AKT, and p-AKT in Group 3 than Group 2 were identified. CONCLUSION: Nintedanib and Avastin can effectively inhibit corneal NV, with P38 MAPK and AKT signaling pathways being possibly involved. Nintedanib seems more effective than Avastin and has the potential to be a novel therapy for preventing corneal NV.

10.
J Cardiothorac Surg ; 16(1): 327, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34749774

RESUMO

BACKGROUND: CircMMP11 is a characterized circRNA with oncogenic function in breast cancer. In this study, we explored the involvement of circMMP11 in non-small cell lung cancer (NSCLC). METHODS: Paired cancer and non-cancer tissues were collected from 66 NSCLC patients, and the expression of circMMP11 and miR-143 in these tissues were detected using RT-qPCRs. Overexpression levels of circMMP11 and miR-143 were performed by transfection, and their crosstalk was analyzed by RT-qPCRs. The effect of circMMP11 overexpression on miR-143 methylation was analyzed by methylation-specific PCR. CCK-8 assay was performed to analyze the roles of miR-143 and circMMP11 in regulating NSCLC cell proliferation. RESULTS: We found that circMMP11 was overexpressed in NSCLC and predicted patients' poor survival. Moreover, a close correlation between circMMP11 and miR143 was observed. In NSCLC cells, circMMP11 overexpression reduced miR-143 expression and increased miR-143 methylation. CCK-8 assay analysis showed that miR-143 reversed the enhancing effects of circMMP11 overexpression on cell proliferation. CONCLUSIONS: CircMMP11 is overexpressed in NSCLC and predicts poor survival. In addition, circMMP11 may downregulate miR-143 through methylation to suppress cell proliferation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , RNA Complementar/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Proliferação de Células , Humanos , Neoplasias Pulmonares/genética , Metilação , MicroRNAs/genética , MicroRNAs/metabolismo
11.
Risk Manag Healthc Policy ; 14: 4393-4399, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34729027

RESUMO

Background and Aim: Relevant studies show that population migration has a great impact on the early spread of infectious diseases. Therefore, it is important to explore whether there is an explicit relationship between population migration and the number of confirmed cases for the control of the COVID-19 epidemic. This paper mainly explores the impact of population migration on early COVID-19 transmission, and establishes a predictive nonlinear mathematical model to predict the number of early cases. Methods: Data of confirmed cases were sourced from the official website of the Municipal Health Committee, and the proportions of migration from Wuhan to other cities were sourced from the Baidu data platform. The data of confirmed cases and the migration proportions of 14 cities in Hubei Province were collected, the COVID-19 cases study period was determined as 10 days based on the third quartile of the interval of the incubation period, and a non-linear mathematical model was constructed to clarify the relationship between the migration proportion and the number of confirmed COVID-19 cases. Finally, eight typical regions were selected to verify the accuracy of the model. Results: The daily population migration rates and the growth curves of the number of confirmed cases in the 14 cities were basically consistent, and Pearson's correlation coefficient was 0.91. The specific mathematical expression of 14 regions is . In each of the fourteen cities, The nonlinear exponential model structure is as follows:. It was found that the R 2 values of the fitted mathematical model were greater than 0.8 in all studied regions, excluding Suizhou (p < 0.05). The established mathematical model was used to fit eight regions in China, and the correlations between the predicted and actual numbers of confirmed cases were greater than 0.9, excluding that of Hebei Province (0.82). Conclusion: The study found that population migration has a positive and significant impact on the spread of COVID-19. Modeling COVID-19 risk may be a useful strategy for directing public health surveillance and interventions. Restricting the migration of the population is of great significance to the joint prevention and control of the pandemic worldwide.

12.
Exp Biol Med (Maywood) ; : 15353702211049149, 2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34743578

RESUMO

In our studies, cyclin B1 (CCNB1) mRNA and protein were overexpressed in hepatocellular carcinoma (HCC) tissues compared with non-HCC tissues. Moreover, CCNB1 was overexpressed in the serum of HCC patients. The expression of CCNB1 was associated with several crucial clinicopathologic characteristics, and the HCC patients with overexpressed CCNB1 had worse overall survival outcomes. In the screening of interactional genes, a total of 266 upregulated co-expression genes, which were positively associated with CCNB1, were selected from the datasets, and 67 downregulated co-expression genes, which were negatively associated with CCNB1, were identified. The key genes might be functionally enriched in DNA replication and the cell cycle pathways. CDC20, CCNA2, PLK1, and FTCD were selected for further research because they were highly connected in the protein-protein interaction networks. Upregulated CDC20, CCNA2, and PLK1 and downregulated FTCD might result in undesirable overall survival outcomes for HCC patients. The univariate Cox analysis results showed that CDC20 and PLK1 might be two independent risk factors, while FTCD might be protective in HCC. Therefore, CCNB1 may participate in the cell cycle of HCC by regulating DNA replication, and CCNB1 may provide a direction for the diagnosis of early-stage HCC and targeted HCC therapy.

13.
Mol Ther Nucleic Acids ; 26: 879-891, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34760335

RESUMO

RNA editing is widely involved in stem cell differentiation and development; however, RNA editing events during human cardiomyocyte differentiation have not yet been characterized and elucidated. Here, we identified genome-wide RNA editing sites and systemically characterized their genomic distribution during four stages of human cardiomyocyte differentiation. It was found that the expression level of ADAR1 affected the global number of adenosine to inosine (A-to-I) editing sites but not the editing degree. Next, we identified 43, 163, 544, and 141 RNA editing sites that contribute to changes in amino acid sequences, variation in alternative splicing, alterations in miRNA-target binding, and changes in gene expression, respectively. Generally, RNA editing showed a stage-specific pattern with 211 stage-shared editing sites. Interestingly, cardiac muscle contraction and heart-disease-related pathways were enriched by cardio-specific editing genes, emphasizing the connection between cardiomyocyte differentiation and heart diseases from the perspective of RNA editing. Finally, it was found that these RNA editing sites are also related to several congenital and noncongenital heart diseases. Together, our study provides a new perspective on cardiomyocyte differentiation and offers more opportunities to understand the mechanisms underlying cell fate determination, which can promote the development of cardiac regenerative medicine and therapies for human heart diseases.

14.
Front Pharmacol ; 12: 709528, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603024

RESUMO

Purpose: Lung cancer is the largest cause of cancer deaths in the world. Platinum-based chemotherapy is a foundation of first-line chemotherapy. However, the prognosis of lung cancer treated with platinum-based chemotherapy is still a challenge. Single nucleotide polymorphism of non-coding RNA has the potential to be a biomarker, but its effectiveness has yet to be comprehensively assessed. In this study, we explored the association between polymorphisms of non-coding RNA and prognosis of lung cancer patients receiving platinum-based chemotherapy. Materials and Methods: For 446 lung cancer patients receiving platinum-based chemotherapy, 22 single nucleotide polymorphisms of microRNA and long noncoding RNA were genotyped by MALDI-TOF mass spectrometry. Cox regression analysis, Kaplan-Meier method, and long-rank test have been performed to assess the association of overall and progression-free survival with polymorphisms. Results: In the additive and dominant models, genetic polymorphism of ANRIL rs1333049 (G > C) was significantly associated with progression-free survival. Additive model: CC vs GC vs GG [HR = 0.84, p = 0.021, 95% CI (0.73-0.97)]; Recessive model: CC vs GG + GC [HR = 0.77, p = 0.026, 95% CI (0.61-0.97)]. In the dominant model, compared with the CC genotype patients, lower risk of death [HR = 0.81, p = 0.036, 95% CI (0.66-0.99)] and lower risk of progression [HR = 0.81, p = 0.040, 95% CI (0.67-0.99)] have been observed on the patients with CG or GG genotype in miR-146A rs2910164. Conclusion: Our research demonstrated the potential of using ANRIL rs1333049 (G > C) and miR-146A rs2910164 (C > G) as biomarkers to support the prediction of a better prognosis for lung cancer patients receiving platinum-based chemotherapy.

15.
Opt Express ; 29(17): 27542-27553, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34615168

RESUMO

This paper presents an optically transparent active bandstop frequency selective surface (FSS) with wideband tunability of two resonance frequencies using the concept of miniaturized element FSS (MEFSS). The proposed design consists of metallic square loop arrays on a new optically transparent substrate as the top layer, a glass interlayer, and periodic patterns of cross dipoles on the substrate as the bottom layer. Two kinds of resonant elements loaded with varactors and the designed bias networks achieve two independent tunable stopbands. The proposed FSS has two large tuning ranges, one is from 1.20 GHz to 2.63 GHz and another is from 2.0 GHz to 5.9 GHz (75% and 99% with respect to the center frequency, respectively). The wideband dual-tuning mechanism is theoretically analyzed and demonstrated by deriving its equivalent circuit (EC) model. The experiment results exhibit reasonable agreement with the numerical simulation responses. This proposed design, with low profile, angular stability, polarization insensitivity, optical transparency, and wideband dual-tunability can play an important role in manipulating electromagnetic wave propagation for manifold applications.

16.
Endocrine ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34608552

RESUMO

PURPOSE: The differential diagnosis of adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome remains a challenge in clinical practice. The present study was aimed at assessing the diagnostic performance of pituitary dynamic contrast-enhanced magnetic resonance imaging (dMRI), high-dose dexamethasone suppression test (HDDST), and a combination of both tests for patients with ACTH-dependent Cushing's syndrome. METHODS: A total of 119 consecutive patients with ACTH-dependent Cushing's syndrome confirmed surgically were enrolled: 101 with proven Cushing's disease and 18 with proven ectopic ACTH syndrome. All patients underwent pituitary dMRI and HDDST. The sensitivity and specificity of pituitary dMRI, HDDST, and a combination of both tests were determined. RESULTS: The sensitivity and specificity of pituitary dMRI for diagnosing Cushing's disease were 80.2 and 83.3%, respectively, with a positive predictive value of 96.4%. The sensitivity and specificity of HDDST were 70.3 and 77.8%, respectively, with positive predictive value of 94.7%. A combination of both tests showed that the combined criteria of more than 50% suppression of serum cortisol on HDDST and a positive pituitary dMRI finding yielded a high specificity of 94.4 and sensitivity of 59.4%. The combined criteria of more than 68% suppression on HDDST and/or a positive pituitary dMRI finding yielded a sensitivity of 86.1% and specificity of 83.3%. CONCLUSIONS: Pituitary dMRI was superior to HDDST in the differential diagnosis of ACTH-dependent Cushing's syndrome. HDDST is recommended in combination with pituitary dMRI to establish a diagnosis process because of the significantly increased specificity with the combination.

17.
J Agric Food Chem ; 69(40): 11982-11991, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34606256

RESUMO

Advanced glycation end-products (AGEs) have been identified as the etiological factors associated with the fatty kidney. Thioredoxin-interacting protein (TXNIP) might be a mediator involved in AGE-induced fatty kidney. This study focused on investigating how TXNIP affected the AGE-mediated renal lipid deposition. In an in vivo experiment, the db/db mice injected with the lentiviral vector encoding shRNA targeting TXNIP were given the AIN-76 basal or the high-AGE diet. TXNIP-targeting siRNA-transfected human renal proximal tubular epithelial (HK-2) cells were exposed to AGE-BSA in a study in vitro. The results showed that the silencing of TXNIP reduced tubular lipid droplets and intracellular cholesterol content, as well as upregulated Insig-1 and downregulated HMGCoAR, LDLr, nSREBP-2, and SCAP in the kidneys of the db/db mice, the high-AGE-diet-fed db/db mice, and AGE-BSA-treated HK-2 cells. Furthermore, AGE-BSA enhanced SCAP-SREBP-2 complex formation while promoting their transportation to the Golgi apparatus. However, these could be inhibited by TXNIP silencing in the HK-2 cells. The above findings indicated that TXNIP knockdown mitigated the accumulation of renal tubular lipids in diabetes through the regulation of SCAP, thereby inhibiting the SCAP-SREBP-2 signaling pathway, resulting in reduced cholesterol uptake and synthesis. Therefore, TXNIP might be a potential therapeutic target to treat a diabetic fatty kidney.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Animais , Rim , Túbulos Renais , Camundongos , Transdução de Sinais , Tiorredoxinas/genética
18.
Nat Commun ; 12(1): 5827, 2021 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625553

RESUMO

During meiosis, chromosomes exhibit dramatic changes in morphology and intranuclear positioning. How these changes influence homolog pairing, alignment, and recombination remain elusive. Using Hi-C, we systematically mapped 3D genome architecture throughout all meiotic prophase substages during mouse spermatogenesis. Our data uncover two major chromosome organizational features varying along the chromosome axis during early meiotic prophase, when homolog alignment occurs. First, transcriptionally active and inactive genomic regions form alternating domains consisting of shorter and longer chromatin loops, respectively. Second, the force-transmitting LINC complex promotes the alignment of ends of different chromosomes over a range of up to 20% of chromosome length. Both features correlate with the pattern of homolog interactions and the distribution of recombination events. Collectively, our data reveal the influences of transcription and force on meiotic chromosome structure and suggest chromosome organization may provide an infrastructure for the modulation of meiotic recombination in higher eukaryotes.


Assuntos
Meiose/fisiologia , Animais , Pareamento Cromossômico/genética , Pareamento Cromossômico/fisiologia , Citometria de Fluxo , Recombinação Homóloga/genética , Recombinação Homóloga/fisiologia , Humanos , Hibridização in Situ Fluorescente , Masculino , Meiose/genética , Camundongos , Camundongos Endogâmicos C57BL , RNA-Seq , Espermatócitos/metabolismo
19.
Oncol Lett ; 22(6): 816, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34671430

RESUMO

MicroRNAs (miRNAs/miRs) are highly conserved single-stranded small non-coding RNAs, which are involved in the physiological and pathological processes of breast cancer, and affect the prognosis of patients with breast cancer. The present study used the Gene Expression Omnibus (GEO)2R tool to detect miR-100 expression in breast cancer tissues obtained from GEO breast cancer-related datasets. Bioinformatics analysis revealed that miR-100 expression was downregulated in different stages, grades and lymph node metastasis stages of breast cancer, and patients with high miR-100 expression had a more favorable prognosis. Based on these analyses, Cell Counting Kit-8, wound healing and Transwell assays were performed, and the results demonstrated that overexpression of miR-100 inhibited the proliferation, migration and invasion of breast cancer cells. To verify the tumor-suppressive effect of miR-100 in breast cancer, the LinkedOmics and PITA databases were used to assess the association between miR-100 and forkhead box A1 (FOXA1). The results demonstrated that miR-100 had binding sites within the FOXA1 gene, and FOXA1 expression was negatively associated with miR-100 expression in breast cancer tissues. Similarly, a negative association was observed between miR-100 and FOXA1 expression, using the StarBase V3.0 database. The association between miR-100 and FOXA1 was further verified via reverse transcription-quantitative PCR and western blot analyses, and the dual-luciferase reporter assay. The results demonstrated that miR-100 targeted the 3'-untranslated region of FOXA1 in breast cancer cells. Furthermore, rescue experiments were performed to confirm whether miR-100 exerts its antitumor effects by regulating FOXA1. The results demonstrated that overexpression of FOXA1 promoted the proliferation, migration and invasion of breast cancer cells; thus, the antitumor effects of miR-100 in breast cancer were reversed following overexpression of FOXA1. Taken together, the results of the present study suggest that miR-100 inhibits the proliferation, migration and invasion of breast cancer cells by targeting FOXA1 expression. These results may provide a novel insight and an experimental basis for identifying effective therapeutic targets of high specificity for breast cancer.

20.
Hepatology ; 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34626132

RESUMO

BACKGROUND & AIMS: The mechanism underlying hepatocellular carcinoma (HCC) metastasis remains unclear, many oncogenes are known to regulate this process. However, the role of alternative splicing (AS) in pro-metastatic HCC is poorly understood. APPROACH & RESULTS: By performing RNA-seq of 9 pairs of primary HCC tissues with extrahepatic metastasis (EHMH) and 9 pairs of metastasis-free HCC tissues (MFH), we depicted the AS landscape in HCC and found that a higher frequency of AS events in EHMH compared with MFH. Moreover, 28 differentially expressed splicing regulators were identified in EHMH compared with MFH. Among these, DEAD-box RNA helicase 17 (DDX17) was significantly upregulated in EHMH and was also strongly associated with patient outcome. Functional studies indicated that DDX17 knockout inhibited the degradation of the extracellular matrix, and diminished the invasive ability of HCC cells. A significant reduction in lung metastasis induced by DDX17 deficiency was also demonstrated in a diethylnitrosamine (DEN)-induced DDX17HKO mouse model. Mechanistically, high DDX17 induced intron 3 retention of PXN-AS1 and produced a novel transcript (termed PXN-AS1-IR3). The novel transcript PXN-AS1-IR3 acted as an important promoter of HCC metastasis by inducing MYC transcription activation via recruitment the complex of Tex10 and p300 to MYC enhancer region, which leading to transcriptional activation of several metastasis-associated downstream genes. Finally, the PXN-AS1-IR3 level was significantly higher in serum and HCC tissues with extrahepatic metastasis. CONCLUSIONS: DDX17 and PXN-AS1-IR3 act as important metastatic promoters by modulating MYC signaling, suggesting that DDX17 and PXN-AS1-IR3 may be potential prognostic markers for metastatic HCC.

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