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1.
Hypertension ; : HYPERTENSIONAHA12117177, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34333987

RESUMO

Hemodynamic overload induces pathological cardiac hypertrophy, which is an independent risk factor for intractable heart failure in long run. Beyond neurohumoral regulation, mechanotransduction has been recently recognized as a major regulator of cardiac hypertrophy under a myriad of conditions. However, the identification and molecular features of mechanotransducer on cardiomyocytes are largely sparse. For the first time, we identified Piezo1 (Piezo type mechanosensitive ion channel component 1), a novel mechanosensitive ion channel with preference to Ca2+ was remarkably upregulated under pressure overload and enriched near T-tubule and intercalated disc of cardiomyocyte. By applying cardiac conditional Piezo1 knockout mice (Piezo1fl/flMyh6Cre+, Piezo1Cko) undergoing transverse aortic constriction, we demonstrated that Piezo1 was required for the development of cardiac hypertrophy and subsequent adverse remodeling. Activation of Piezo1 by external mechanical stretch or agonist Yoda1 lead to the enlargement of cardiomyocytes in vitro, which was blocked by Piezo1 silencing or Yoda1 analog Dooku1 or Piezo1 inhibitor GsMTx4. Mechanistically, Piezo1 perturbed calcium homeostasis, mediating extracellular Ca2+ influx and intracellular Ca2+ overload, thereby increased the activation of Ca2+-dependent signaling, calcineurin, and calpain. Inhibition of calcineurin or calpain could abolished Yoda1 induced upregulation of hypertrophy markers and the hypertrophic growth of cardiomyocytes in vitro. From a comprehensive view of the cardiac transcriptome, most of Piezo1 affected genes were highly enriched in muscle cell physiology, tight junction, and corresponding signaling. This study characterizes an undefined role of Piezo1 in pressure overload induced cardiac hypertrophy. It may partially decipher the differential role of calcium under pathophysiological condition, implying a promising therapeutic target for cardiac dysfunction.

2.
Bioengineered ; 12(1): 4719-4735, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34338146

RESUMO

To probe into the efffects of miR-101-3p via regulating CUL4B within PI3K/AKT/mTOR signaling pathway on progression of prostate cancer (PCA). Western blot and qRT-PCR were adopted to detect CUL4B and miR-101-3p expressions in 75 cases with PCA . The cellular strains of PCA (LNCaP and PC3) were chose as the objects to check the targeting correlation between CUL4B and miR-101-3p through dual-luciferase reporter experiments. LNCaP cells and PC3 cells were randomly divided into the blank group, miR-101-3p mimic group, siRNA negative control (NC) group, CUL4B siRNA group and CUL4B siRNA plus the miR-101-3p inhibitor group. Cellular bioactivity measurement was done via Cell-Light EDU, MTT, Annexin-V-FITC/PI, scratch-heal experiments and invasion tests of Transwell. MiR-101-3p expression was decreased more signally in tumor tissues than in normal tissues adjacent to the cancer. MiR-101-3p inhibited cellular proliferating, migrating and invasion. Nevertheless, it promoted cellular apoptosis, up-regulated apoptotic proteins as well as down-regulated anti-apoptotic proteins. CUL4B siRNA and miR-101-3p simulation were similar in terms of their outcomes. Nonetheless, these results could be reversed through the miR-101-3p inhibitor. Besides, CUL4B siRNA and the simulation halted a serious of PI3K signal in PCA cells. MiR-101-3p expression was down-regulated in PCA patients. CUL4B was upregulated in PCA patients. Moreover, miR-101-3p suppressed cellular invasion, migration, proliferation and led to cellular apoptosis, which might be related to the PI3K/AKT/mTOR signaling pathway suppression. Finally, we found, MiR-101-3P suppressed PCA progression via aiming for CUL4B, which may offer the new molecular target for PCA clinical treatment.

3.
EMBO Rep ; : e51978, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34232545

RESUMO

Zika virus (ZIKV) infection during pregnancy is linked to various developmental brain disorders. Infants who are asymptomatic at birth might have postnatal neurocognitive complications. However, animal models recapitulating these neurocognitive phenotypes are lacking, and the circuit mechanism underlying behavioral abnormalities is unknown. Here, we show that ZIKV infection during mouse pregnancy induces maternal immune activation (MIA) and leads to autistic-like behaviors including repetitive self-grooming and impaired social memory in offspring. In the medial prefrontal cortex (mPFC), ZIKV-affected offspring mice exhibit excitation and inhibition imbalance and increased cortical activity. This could be explained by dysregulation of inhibitory neurons and synapses, and elevated neural activity input from mPFC-projecting ventral hippocampus (vHIP) neurons. We find structure alterations in the synaptic connections and pattern of vHIP innervation of mPFC neurons, leading to hyperconnectivity of the vHIP-mPFC pathway. Decreasing the activity of mPFC-projecting vHIP neurons with a chemogenetic strategy rescues social memory deficits in ZIKV offspring mice. Our studies reveal a hyperconnectivity of vHIP to mPFC projection driving social memory deficits in mice exposed to maternal inflammation by ZIKV.

4.
BMC Complement Med Ther ; 21(1): 195, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34229670

RESUMO

BACKGROUND: Metastatic castration-resistant prostate cancer (CRPC) is the leading cause of death among men diagnosed with prostate cancer. Piperlongumine (PL) is a novel potential anticancer agent that has been demonstrated to exhibit anticancer efficacy against prostate cancer cells. However, the effects of PL on DNA damage and repair against CRPC have remained unclear. The aim of this study was to further explore the anticancer activity and mechanisms of action of PL against CRPC in terms of DNA damage and repair processes. METHODS: The effect of PL on CRPC was evaluated by MTT assay, long-term cell proliferation, reactive oxygen species assay, western blot assay, flow cytometry assay (annexin V/PI staining), ß-gal staining assay and DAPI staining assay. The capacity of PL to inhibit the invasion and migration of CRPC cells was assessed by scratch-wound assay, cell adhesion assay, transwell assay and immunofluorescence (IF) assay. The effect of PL on DNA damage and repair was determined via IF assay and comet assay. RESULTS: The results showed that PL exhibited stronger anticancer activity against CRPC compared to that of taxol, cisplatin (DDP), doxorubicin (Dox), or 5-Fluorouracil (5-FU), with fewer side effects in normal cells. Importantly, PL treatment significantly decreased cell adhesion to the extracellular matrix and inhibited the migration of CRPC cells through affecting the expression and distribution of focal adhesion kinase (FAK), leading to concentration-dependent inhibition of CRPC cell proliferation and concomitantly increased cell death. Moreover, PL treatment triggered persistent DNA damage and provoked strong DNA damage responses in CRPC cells. CONCLUSION: Collectively, our findings demonstrate that PL potently inhibited proliferation, migration, and invasion of CRPC cells and that these potent anticancer effects were potentially achieved via triggering persistent DNA damage in CRPC cells.

5.
BMC Genomics ; 22(1): 498, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34217203

RESUMO

BACKGROUND: Virescent mutation broadly exists in plants and is an ideal experimental material to investigate regulatory mechanisms underlying chlorophyll synthesis, photosynthesis and plant growth. Up to date, the molecular mechanisms in two virescent mutations have been clarified in cottons (Gossypiuma hirsutum). A virescent mutation has been found in the cotton strain Sumian 22, and the underlying molecular mechanisms have been studied. METHODS: The virescent mutant and wild type (WT) of Sumian 22 were cross-bred, and the F1 population were self-pollinated to calculate the segregation ratio. Green and yellow leaves from F2 populations were subjected to genome sequencing and bulked-segregant analysis was performed to screen mutations. Real-time quantitative PCR (RT-qPCR) were performed to identify genes in relations to chlorophyll synthesis. Intermediate products for chlorophyll synthesis were determined to validate the RT-qPCR results. RESULTS: The segregation ratio of green and virescent plants in F2 population complied with 3:1. Compared with WT, a 0.34 Mb highly mutated interval was identified on the chromosome D10 in mutant, which contained 31 genes. Among them, only ABCI1 displayed significantly lower levels in mutant than in WT. Meanwhile, the contents of Mg-protoporphyrin IX, protochlorophyllide, chlorophyll a and b were all significantly lower in mutant than in WT, which were consistent with the inhibited levels of ABCI1. In addition, a mutation from A to T at the -317 bp position from the start codon of ABCI1 was observed in the genome sequence of mutant. CONCLUSIONS: Inhibited transcription of ABCI1 might be the mechanism causing virescent mutation in Sumian 22 cotton, which reduced the transportation of protoporphyrin IX to plastid, and then inhibited Mg-protoporphyrin IX, Protochlorophyllide and finally chlorophyll synthesis. These results provided novel insights into the molecular mechanisms underlying virescent mutation in cotton.


Assuntos
Melhoramento Vegetal , Folhas de Planta , Clorofila , Clorofila A , Mapeamento Cromossômico , Mutação , Fenótipo
6.
J Endourol ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34235970

RESUMO

Background This study compares surgical performance during analogous vesico-urethral anastomosis (VUA) tasks in two robotic training environments, virtual reality (VR) and dry-lab (DL), in order to investigate transferability of skills assessment across the two platforms. Utilizing computer-generated performance metrics and pupillary data we evaluated the two environments' ability to distinguish surgical expertise and ultimately whether performance in the VR simulation correlates to performance on the live robot in the dry-lab. Materials and Methods Experts (≥ 300 cases) and trainees (<300) performed analogous VUAs during VR and dry-lab sessions on a da Vinci robotic console. 22 metrics were generated in each environment (kinematic metrics, tissue metrics, biometrics). The dry-lab included 18 previously validated automated performance metrics (APMs) (kinematics, events metrics) and were captured by an Intuitive systems data recorder. In both settings, Tobii Pro Glasses 2 recorded task-evoked pupillary response (reported as Index of Cognitive Activity [ICA]) to indicate cognitive workload, analyzed by EyeTracking Cognitive Workload Software. Pearson Correlation, Mann-Whitney and Independent t-tests were used for the comparative analyses. Results Our study included 6 experts (median caseload 1300 [interquartile range 400-3000]) and 11 trainees (25 [0-250]). 8/9 metrics directly comparable between VR and DL showed significant positive correlation (r≥0.554, p≤0.032). 5/22 VR metrics distinguished expertise including: task time (p=0.031), clutch usage (p=0.040), unnecessary needle piercings (p=0.026) and suspected injury to endopelvic fascia (p=0.040). This contrasts with 14/22 APMs in dry-lab (p≤0.038) including: linear velocities of all three instruments (p≤0.038) and dominant-hand instrument wrist articulation (p=0.013). Trainees experienced higher cognitive workload (ICA) in both environments when compared to experts (p<0.036). Conclusions A majority of performance metrics between VR and dry-lab exhibited moderate to strong correlations, showing transferability of skills across the platforms. Comparing training environments, APMs during dry-lab tasks are better able to distinguish expertise than VR-generated metrics.

7.
Opt Lett ; 46(15): 3637-3640, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34329244

RESUMO

We propose a parabolic W-type thulium-doped fiber for the 1.7 µm high-energy femtosecond pulsed laser. Despite its attractive normal dispersion, the fiber offers high gain in 1.7 µm region thanks to its distributed short-pass filtering effect. With a proper dispersion management in an all-fiber chirped pulse amplification (CPA) scheme, we demonstrate so far the highest pulse energy of 128.0 nJ in a stable pulse of 174 fs in the 1.7-1.8 µm region, which marks above an order of magnitude improvement in pulse energy while exhibiting the shortest pulse duration among fiber-based CPA works at 1.7 µm. Hence, we provide a pathway to an energy scalable and efficient femtosecond laser at 1.7 µm via a compact and elegant all-fiber solution.

8.
Front Immunol ; 12: 697203, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248998

RESUMO

Neural stem cell (NSC) therapy is a promising therapeutic strategy for stroke. Researchers have frequently carried out genetic modification or gene editing of stem cells to improve survival or therapeutic function. However, NSC transplantation carries the risk of immune rejection, and genetic modification or gene-editing might further increase this risk. For instance, recent studies have reported on manipulating the stem cell genome and transplantation via the insertion of an exogenous gene derived from magnetotactic bacteria. However, whether transgene-modified stem cells are capable of inducing immunological reactions has not been explored. Although NSCs rarely express the major histocompatibility complex (MHC), they can still cause some immunological issues. To investigate whether transgene-modified NSCs aggravate immunological responses, we detected the changes in peripheral immune organs and intracerebral astrocytes, glial cells, and MHC-I and MHC-II molecules after the injection of GFP-labeled or mms6-GFP-labeled NSCs in a rat model. Xenogeneic human embryonic kidney (HEK-293T) cells were grafted as a positive control group. Our results indicated that xenogeneic cell transplantation resulted in a strong peripheral splenic response, increased astrocytes, enhanced microglial responses, and upregulation of MHC-I and MHC-II expression on the third day of transplantation. But they decreased obviously except Iba-1 positive cells and MHC-II expression. When injection of both mms6-GFP-labeled NSCs and GFP-labeled NSCs also induced similar responses as HEK-293T cells on the third days, but MHC-I and MHC-II expression decreased 3 weeks after transplantation. In addition, mms6 transgene-modified NSCs did not produce peripheral splenic response responses as well as astrocytes, microglial cells, MHC-I and MHC-II positive cells responses when compared with non-modified NSCs. The present study provides preliminary evidence that transgenic modification does not aggravate immunological responses in NSC transplantation.

9.
Biochem Biophys Res Commun ; 568: 174-179, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34246051

RESUMO

The aim of the study was to develop a model of coronary microembolization (CME) in rats at a lower cost. We developed a novel rat model without thoracotomy and ventilation under the guidance of echocardiography. Rats were sacrificed at 3 h, 24 h and 1 month postoperatively in both the Echo-CME and Open-chest CME groups for the comparison of the modeling accuracy, mortality, cardiopulmonary circulation, pleural adhesion and ventilation-induced lung injury (VILI). Results showed that the coronary microthrombus formed at 3 h and reached its peak at 24 h postoperatively, which included platelet aggregation and fibrin web. The Echo-group increases success rates, decreased mortality, postoperative complications including pleural adhesion, cardiopulmonary dysfunction and VILI postoperatively than the Open-chest group at 1month postoperatively. The ejection fraction of the CME group decreased to 50% and obvious cardiac fibrosis formed at 3 months postoperatively. Our unique surgical method provided a platform to study molecular mechanisms and potential new pathways for CME treatment.

10.
J Nat Prod ; 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34197108

RESUMO

A bioactivity-guided study on the leaves of Picrasma javanica led to the isolation of 19 quassinoids, including 13 new compounds. The structures of the new compounds were elucidated by a combination of spectroscopic data analysis, X-ray crystallography studies, and electronic circular dichroism (ECD) data interpretation. Compounds 1-7 are rare examples of quassinoids with a keto carbonyl group at C-12. The biological activities of 11 of the more abundant isolates were evaluated against five phytopathogenic fungi in vitro, and several of them including 6 and 15 showed moderate inhibitory effects that were comparative to those of the positive control, carbendazim. In addition, the preliminary structure-activity relationships (SARs) of these quassinoids were also investigated.

11.
Nat Plants ; 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34294906

RESUMO

Stem rust caused by the fungus Puccinia graminis f. sp. tritici (Pgt) is a devastating disease of the global staple crop wheat. Although this disease was largely controlled in the latter half of the twentieth century, new virulent strains of Pgt, such as Ug99, have recently evolved1,2. These strains have caused notable losses worldwide and their continued spread threatens global wheat production. Breeding for disease resistance provides the most cost-effective control of wheat rust diseases3. A number of rust resistance genes have been characterized in wheat and most encode immune receptors of the nucleotide-binding leucine-rich repeat (NLR) class4, which recognize pathogen effector proteins known as avirulence (Avr) proteins5. However, only two Avr genes have been identified in Pgt so far, AvrSr35 and AvrSr50 (refs. 6,7), and none in other cereal rusts8,9. The Sr27 resistance gene was first identified in a wheat line carrying an introgression of the 3R chromosome from Imperial rye10. Although not deployed widely in wheat, Sr27 is widespread in the artificial crop species Triticosecale (triticale), which is a wheat-rye hybrid and is a host for Pgt11,12. Sr27 is effective against Ug99 (ref. 13) and other recent Pgt strains14,15. Here, we identify both the Sr27 gene in wheat and the corresponding AvrSr27 gene in Pgt and show that virulence to Sr27 can arise experimentally and in the field through deletion mutations, copy number variation and expression level polymorphisms at the AvrSr27 locus.

12.
Materials (Basel) ; 14(14)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34300767

RESUMO

In an all-vanadium redox flow battery (VRFB), redox reaction occurs on the fiber surface of the graphite felts. Therefore, the VRFB performance highly depends on the characteristics of the graphite felts. Although atmospheric pressure plasma jets (APPJs) have been applied for surface modification of graphite felt electrode in VRFBs for the enhancement of electrochemical reactivity, the influence of APPJ plasma reactivity and working temperature (by changing the flow rate) on the VRFB performance is still unknown. In this work, the performance of the graphite felts with different APPJ plasma reactivity and working temperatures, changed by varying the flow rates (the conditions are denoted as APPJ temperatures hereafter), was analyzed and compared with those treated with sulfuric acid. X-ray photoelectron spectroscopy (XPS) indicated that the APPJ treatment led to an increase in O-/N-containing functional groups on the GF surface to ~21.0% as compared to ~15.0% for untreated GF and 18.0% for H2SO4-treated GF. Scanning electron microscopy (SEM) indicated that the surface morphology of graphite felt electrodes was still smooth, and no visible changes were detected after oxidation in the sulfuric acid or after APPJ treatment. The polarization measurements indicated that the APPJ treatment increased the limiting current densities from 0.56 A·cm-2 for the GFs treated by H2SO4 to 0.64, 0.68, and 0.64 A·cm-2, respectively, for the GFs APPJ-treated at 450, 550, and 650 °C, as well as reduced the activation overpotential when compared with the H2SO4-treated electrode. The electrochemical charge/discharge measurements showed that the APPJ treatment temperature of 550 °C gave the highest energy efficiency of 83.5% as compared to 72.0% with the H2SO4 treatment.

13.
Nanoscale ; 13(27): 11712-11733, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34227639

RESUMO

Trends in the development of modern medicine necessitate the efficient delivery of therapeutics to achieve the desired treatment outcomes through precise spatiotemporal accumulation of therapeutics at the disease site. Bioresponsive nanomedicine is a promising platform for this purpose. Dynamic covalent bonds (DCBs) have attracted much attention in studies of the fabrication of bioresponsive nanomedicines with an abundance of combinations of therapeutic modules and carrier function units. DCB-based nanomedicines could be designed to maintain biological friendly synthesis and site-specific release for optimal therapeutic effects, allowing the complex to retain an integrated structure before accumulating at the disease site, but disassembling into individual active components without compromising function in the targeted organs or tissues. In this review, we focus on responsive nanomedicines containing dynamic chemical bonds that can be cleaved by various specific stimuli, enabling achievement of targeted drug release for optimal therapy in various diseases.


Assuntos
Nanopartículas , Neoplasias , Sistemas de Liberação de Medicamentos , Humanos , Nanomedicina , Neoplasias/tratamento farmacológico
14.
Ann Palliat Med ; 10(6): 6909-6918, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34237988

RESUMO

BACKGROUND: Knee osteoarthritis (KOA) is a common joint disease worldwide, and the main cause of pain and disability in the elderly. Due to increased aging and rates of obesity of the global population, the number of patients with KOA is expected to increase. To reduce the burden of KOA, effective and safe interventions should be developed to reduce pain and improve range of motion, functionality, and quality of life. The aim of the proposed randomized controlled study was to evaluate the efficacy and safety of a traditional Chinese medicine (TCM) rehabilitation therapy in the treatment of KOA. METHODS: This multicenter, randomized, double-blind, parallel group, placebo-controlled trial will include a total of 200 patients with KOA. The enrolled patients will be randomly divided into the experimental group (n=100) and control group (n=100). The experimental group will receive basic treatment plus TCM rehabilitation therapy, while the control group will receive basic treatment plus physiotherapy regimen. Primary endpoints will include clinical efficacy outcomes, visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index score, and Knee Outcome Survey Activities of Daily Living Scale score. The data will help determine whether TCM rehabilitation therapy is beneficial for the treatment of KOA. DISCUSSION: The results will provide high-quality guidance for the current clinical treatment of KOA, and provide patients with more options for symptom relief. The findings from this study may provide updated evidence concerning the efficacy and safety of TCM for patients with KOA.


Assuntos
Osteoartrite do Joelho , Atividades Cotidianas , Idoso , Humanos , Medicina Tradicional Chinesa , Estudos Multicêntricos como Assunto , Medição da Dor , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
15.
Anal Chem ; 93(29): 10167-10174, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34278781

RESUMO

Surface-enhanced Raman scattering (SERS) has been recognized as a powerful tool for biosensors due to the ultrahigh sensitivity and unique fingerprint information. However, there are some limitations in trace target nucleic acid detection for the restricted signal-transducing and amplification strategies. Inspired by CRISPR/Cas12a with specific target DNA-activated collateral single-strand DNA (ssDNA) cleavage activity and liposome with signal molecule-loading properties, we first proposed a sensitive SERS-based on-site nucleic acid detection strategy mediated by CRISPR/Cas12a with trans-cleavage activity on ssDNA linkers utilized to capture liposomes. Liposomes loading two kinds of signal molecules, 4-nitrothiophenol (4-NTP) and cysteine, could achieve the dual-mode detection of target DNA with SERS and naked eye, respectively. The promptly amplified signals were initiated by the triggered breakdown of signal molecule-loaded liposomes. Emancipated 4-NTP, a biological-silent Raman reporter, would achieve highly selective and sensitive SERS measurement. Released cysteine induced the aggregation of plasmonic gold nanoparticles, leading to an obvious red to blue colorimetric shift to realize portable naked-eye detection. With this strategy, target nucleic acid concentration was dexterously converted into SERS and visualization signals and could be detected as low as 100 aM and 10 pM, respectively. The approach was also successfully applied to determine meat adulteration, achieving the detection of a low adulteration ratio in the complicated food matrix. We anticipate that this strategy will not only be regarded as a universal platform for the on-site detection of food authenticity but also broaden SERS application for the accurate determination of diverse biomarkers.

16.
Viruses ; 13(7)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202551

RESUMO

Porcine Epidemic Diarrhea Virus (PEDV) is the causative agent of swine epidemic diarrhea. In order to study the pathogenic mechanism of PEDV, PEDV was inoculated into Vero cells cultured in vitro, and the total RNA of Vero cells was extracted to construct a library for Illumina high-throughput sequencing and screening of differentially expressed genes (p < 0.05). Five differentially expressed genes for qRT-PCR verification analysis were randomly selected, and the verification results were consistent with the transcriptome sequencing results. The Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment analysis was performed on the differentially expressed genes screened above. The results showed that the target gene annotations of differentially expressed genes in the African green monkey genome were mainly enriched in the TNF signaling pathway, the P53 signaling pathway, the Jak-STAT signaling pathway, the MAPK signaling pathway, and immune inflammation. In addition, it has been reported that Puma can promote apoptosis and is a key mediator of P53-dependent and non-dependent apoptosis pathways. However, there is no report that PEDV infection can activate Puma and induce apoptosis in a P53-dependent pathway. It was found by flow cytometry that PEDV infection induced apoptosis, and by Western Blotting detection, PEDV infection significantly increased the expression of p53, BAX, and Puma apoptosis-related proteins. Treatment Vero cells with the p53 inhibitor, PFT-α, could significantly inhibit PEDV-induced apoptosis. Studies have shown that PEDV infection can activate Puma and induce apoptosis in a P53-dependent pathway. These findings provide data support for further elucidating the pathogenic mechanism of PEDV and developing an effective vaccine against PEDV.

17.
Mol Cell Endocrinol ; 535: 111396, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34271069

RESUMO

Although tumor stem-like cells (TSLCs) have been studied in a range of malignant tumors, evidence for the presence of these cells in pituitary adenomas needs further exploration. Here, we identified a small subset of sphere-forming cells possess tumor stem-like cell properties in rat prolactinoma MMQ cells, which resist to dopamine agonist treatment. Comparing to MMQ cells, sphere-forming cells showed higher cell viability after dopamine agonist (DA) treatment. Furthermore, the cells showed lower expression of prolactin (PRL) and dopamine 2 receptor (D2R). On the contrary, the daughter tumor cells differentiated from these cells restored the sensitivity to DA and showed high expression of PRL and D2R. The lower D2R expression and DA resistance might be due to DNA hypermethylation of D2R promoter. Our study demonstrates that the sphere-forming cells isolated from MMQ cells possess the trait of TSLCs and resist to DA treatment, which offers the opportunity to further investigate the mechanisms underlying tumor recurrence based on TSLCs.

18.
Neurochem Int ; 149: 105122, 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34284076

RESUMO

As a double-stranded DNA (dsDNA) sensor, the PYHIN family member absent in melanoma 2 (AIM2) is an essential component of the inflammasome families. Activation of AIM2 by dsDNA leads to the assembly of cytosolic multimolecular complexes termed the AIM2 inflammasome, resulting in activation of caspase-1, the maturation and secretion of pro-inflammatory cytokines interleukin (IL)-1ß and IL-18, and pyroptosis. Multiple central nervous system (CNS) diseases are accompanied by immune responses and inflammatory cascade. As the resident macrophage cells, microglia cells act as the first and main form of active immune defense in the CNS. AIM2 is highly expressed in microglia as well as astrocytes and neurons and is essential in neurodevelopment. In this review, we highlight the recent progress on the role of AIM2 inflammasome in CNS disorders, including cerebral stroke, brain injury, neuropsychiatric disease, neurodegenerative diseases, and glioblastoma.

19.
Molecules ; 26(14)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34299529

RESUMO

Aroma deterioration is one of the biggest problems in processing tea beverages. The aroma of tea infusion deteriorates fast during heat sterilization and the presence of ferrous ion (Fe2+) aggravates it. The underlying mechanism remains unveiled. In this study, Fe2+ was verified to deteriorate the aroma quality of green tea infusion with heat treatment. Catechins were necessary for Fe2+-mediated aroma deterioration. By enhancing the degradation of catechins, Fe2+ dramatically increased the production of hydrogen peroxide (H2O2). Fe2+ and H2O2 together exacerbated the aroma of green tea infusion with heat treatment. GC-MS analysis revealed that the presence of Fe2+ enhanced the loss of green/grassy volatiles and promoted the formation of new volatiles with diversified aroma characteristics, resulting in a dull scent of green tea infusion. Our results revealed how Fe2+ induced aroma deterioration of green tea infusion with heat treatment and could help guide tea producers in attenuating the aroma deterioration of tea infusion during processing.

20.
BMC Med Imaging ; 21(1): 115, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301205

RESUMO

BACKGROUND: The aim of this study was to investigate the potential use of renal ultrasonography radiomics features in the histologic classification of glomerulopathy. METHODS: A total of 623 renal ultrasound images from 46 membranous nephropathy (MN) and 22 IgA nephropathy patients were collected. The cases and images were divided into a training group (51 cases with 470 images) and a test group (17 cases with 153 images). A total of 180 dimensional features were designed and extracted from the renal parenchyma in the ultrasound images. Least absolute shrinkage and selection operator (LASSO) logistic regression was then applied to these normalized radiomics features to select the features with the highest correlations. Four machine learning classifiers, including logistic regression, a support vector machine (SVM), a random forest, and a K-nearest neighbour classifier, were deployed for the classification of MN and IgA nephropathy. Subsequently, the results were assessed according to accuracy and receiver operating characteristic (ROC) curves. RESULTS: Patients with MN were older than patients with IgA nephropathy. MN primarily manifested in patients as nephrotic syndrome, whereas IgA nephropathy presented mainly as nephritic syndrome. Analysis of the classification performance of the four classifiers for IgA nephropathy and MN revealed that the random forest achieved the highest area under the ROC curve (AUC) (0.7639) and the highest specificity (0.8750). However, logistic regression attained the highest accuracy (0.7647) and the highest sensitivity (0.8889). CONCLUSIONS: Quantitative radiomics imaging features extracted from digital renal ultrasound are fully capable of distinguishing IgA nephropathy from MN. Radiomics analysis, a non-invasive method, is helpful for histological classification of glomerulopathy.

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