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1.
FEMS Microbiol Lett ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33606020

RESUMO

In recent years, the relationship between type 2 diabetes (T2D) and gut microbiota has attracted much interest. Dendrobium officinale is a valuable traditional Chinese medicine (TCM) with anti-T2D potential, while its action mechanism remains to be further studied. This study was designed to investigate the modulation effects of Dendrobium officinale on gut microbiota of T2D model mice to provide clues to its pharmacology by high-throughput sequencing techniques. It was found that Dendrobium officinale supplement could significantly reduce the fasting blood glucose levels of T2D mice. Dendrobium officinale supplement could modulate the composition of gut microbiota and increase the relative abundances of key bacterial taxa associated with T2D development, including Akkermansia and Parabacteroides. Compared with placebo group mice, several Kyoto Encyclopedia of Gene and Genomes pathways associated with T2D altered in the Dendrobium officinale treated group. These findings indicated the modulation of Dendrobium officinale on gut microbiota of T2D mice, which provide potential pharmacological implications.

2.
Neurosci Lett ; : 135750, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33610670

RESUMO

Rodent animals exposed to early maternal separation (EMS) show abnormal behaviors. Our previous study reported that autophagy is inhibited in the hippocampus of EMS rats, and hyperforin (HYP) alleviates depressive-like and anxious-like behaviors induced by EMS. However, the underlying mechanism of HYP is still unclear. In this study, we tested whether HYP alleviates the psychiatric disorders of EMS rats via activating autophagy. Pups were randomly divided into the control (CON) group, the EMS group, the EMS +3 mg/kg/day HYP (EMS + HYP) group and the EMS + treatment with 3 mg/kg/day fluoxetine (EMS + FT) group. Pups were separated from their mothers for 6 h every day from postnatal day 1 (PD1) to PD21 except pups of the CON group. Besides, HYP and FT were administered from PD22 to PD35 in the EMS + HYP group and the EMS + FT group respectively. Data showed that HYP not only reduced the level of glutamate, decreased the expression of N-methyl-D-aspartate receptor subunit 2B and postsynaptic density-95, but also increased the expression of synaptophysin of EMS rats. Interestingly, the expression of beclin-1 and the ratio of LC3II/LC3I were up-regulated in the EMS + HYP group. Moreover, HYP reduced the expression of the Notch1 receptor and the acetylation of H3K9 of EMS rats. In conclusion, our findings demonstrated that HYP ameliorates the depressive-like and anxious-like behaviors via activating autophagy in the hippocampus of EMS rats.

3.
Exp Neurol ; 339: 113645, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33600815

RESUMO

Microglia are rapidly activated after acute ischemic stroke, and the polarization of microglial is associated with the prognosis of acute ischemic stroke. Lipoxin A4 (LXA4), an anti-inflammatory agent, has a protective effect against ischemic stroke. However, the role of LXA4 on the polarization of microglial after acute ischemic stroke remains undetermined. We hypothesized that LXA4 may exert the neuroprotective effect though regulating the polarization of microglial. In this study, clinical features of acute ischemic stroke were simulated using a rat model of model of middle cerebral artery occlusion (MCAO) in vivo and the BV2 microglia oxygen-glucose deprivation/reoxygenation model (OGD/R) in vitro. The protective effects of LXA4 on cerebral ischemia-reperfusion injury were determined using TTC staining, HE staining, and TUNEL staining. The expression of targeted genes was assayed using quantitative real-time PCR (qRT-PCR), immunofluorescence, and western blot to investigated the regulation of LXA4 on microglia polarization after acute ischemic stroke. We found that LXA4 exerted protective effects on focal cerebral ischemia-reperfusion injury and reduced the expression of the pro-inflammatory cytokines IL-1ß and TNF-α. Furthermore, LXA4 inhibited the expression of Notch-1, Hes1, iNOS and CD32 all of which are associated with the differentiation into M1 microglia. By contrast, LXA4 upregulated the expression of Hes5, Arg-1 and CD206 all of which are associated with M2 phenotype in microglia. In addition, blocking the Notch signaling pathway with the inhibitor DAPT significantly mitigated the effect of LXA4 on microglia differentiation. These data suggest that LXA4 may regulate the polarization of microglia after cerebral ischemia-reperfusion injury through the Notch signaling pathway.

4.
Addict Biol ; : e13025, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33609013

RESUMO

Oxycodone is one of the most commonly used analgesics in the clinic. However, long-term use can contribute to drug dependence. Accumulating evidence of changes in DNA methylation after opioid relapse has provided insight into mechanisms underlying drug-associated memory. The neuropeptide oxytocin is reported to be a potential treatment for addiction. The present study sought to identify changes in global and synaptic gene methylation after cue-induced reinstatement of oxycodone conditioned place preference (CPP) and the effect of oxytocin. We analyzed hippocampal mRNA of synaptic genes and also synaptic density in response to oxycodone CPP. We determined the mRNA levels of DNA methyltransferases (Dnmts) and ten-eleven translocations (Tets), observed global 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) levels, and measured DNA methylation status of four synaptic genes implicated in learning and memory (Arc, Dlg1, Dlg4, and Syn1). Both synaptic density and the transcription of 15 hippocampal synaptic genes significantly increased following cue-induced reinstatement of oxycodone CPP. Oxycodone relapse was also related to markedly decreased 5-mC levels and decreased transcription of Dnmt1, Dnmt3a, and Dnmt3b; in contrast, 5-hmC levels and the transcription of Tet1 and Tet3 were increased. Oxycodone exposure induced DNA hypomethylation at the exons of the Arc, Dlg1, Dlg4, and Syn1 genes. Intracerebroventricular (ICV) administration of oxytocin (2.5 µg/µl) specifically blocked oxycodone relapse, possibly by inhibition of Arc, Dlg1, Dlg4, and Syn1 hypomethylation in oxycodone-treated rats. Together, these data indicate the occurrence of epigenetic changes in the hippocampus following oxycodone relapse and the potential role of oxytocin in oxycodone addiction.

5.
J Colloid Interface Sci ; 590: 50-59, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33524720

RESUMO

Poor room-temperature ionic conductivity and lithium dendrite formation are the main issues of solid electrolytes. In this work, rod-shaped alumina incorporation and graphite coating were simultaneously applied to poly (propylene carbonate) (PPC)-based polymer solid electrolytes (Wang et al., 2018). The obtained alumina modified solid electrolyte membrane (Al-SE) achieves a high ionic conductivity of 3.48 × 10-4 S/cm at room temperature with a wide electrochemical window of 4.6 V. The assembled NCM622/Al-SE/Li solid-state battery exhibits initial discharge capacities of 198.2 mAh/g and 177.5 mAh/g at the current density of 0.1 C and 0.5 C, with the remaining capacities of 165.8 mAh/g and 161.3 mAh/g after 100 cycles respectively. The rod-shaped structure of Al2O3 provides fast transport channels for lithium ions and its Lewis acidity promotes the dissociation of lithium salts and release of free lithium ions. The lithiophilic Al2O3 and Graphite form intimate contact with metallic Li and create fast Li+ conductive layers of Li-Al-O layer and LiC6 layer, thus facilitating the uniform deposition of Li and inhibiting Li dendrite formation during long-term cycling. This kind of composite Al-SE is expected to provide a promising alternative for practical application in solid electrolytes.

6.
Mol Psychiatry ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542468

RESUMO

Pandemics have become more frequent and more complex during the twenty-first century. Posttraumatic stress disorder (PTSD) following pandemics is a significant public health concern. We sought to provide a reliable estimate of the worldwide prevalence of PTSD after large-scale pandemics as well as associated risk factors, by a systematic review and meta-analysis. We systematically searched the MedLine, Embase, PsycINFO, Web of Science, CNKI, WanFang, medRxiv, and bioRxiv databases to identify studies that were published from the inception up to August 23, 2020, and reported the prevalence of PTSD after pandemics including sudden acute respiratory syndrome (SARS), H1N1, Poliomyelitis, Ebola, Zika, Nipah, Middle Eastern respiratory syndrome coronavirus (MERS-CoV), H5N1, and coronavirus disease 2019 (COVID-19). A total of 88 studies were included in the analysis, with 77 having prevalence information and 70 having risk factors information. The overall pooled prevalence of post-pandemic PTSD across all populations was 22.6% (95% confidence interval (CI): 19.9-25.4%, I2: 99.7%). Healthcare workers had the highest prevalence of PTSD (26.9%; 95% CI: 20.3-33.6%), followed by infected cases (23.8%: 16.6-31.0%), and the general public (19.3%: 15.3-23.2%). However, the heterogeneity of study findings indicates that results should be interpreted cautiously. Risk factors including individual, family, and societal factors, pandemic-related factors, and specific factors in healthcare workers and patients for post-pandemic PTSD were summarized and discussed in this systematic review. Long-term monitoring and early interventions should be implemented to improve post-pandemic mental health and long-term recovery.

7.
Drug Discov Today ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33549529

RESUMO

Gold nanoparticles (AuNPs) have been shown to be useful as carriers of various anticancer drugs as well as diagnosis platforms. In this review, we discuss the synthesis and physiochemical properties of AuNPs. We also highlight the photothermal and photodynamic properties of AuNPs and relevant applications in therapeutic studies. Furthermore, we review the applications of AuNPs in cancer treatment as well as their underlying anticancer mechanisms in multiple types of cancer.

8.
Nanotechnology ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33535194

RESUMO

An asymmetric dual-gate (DG) MoS2 field effective transistor (FET) with ultrahigh electrical performance and optical responsivity using atomic-layer-deposited HfO2 as top-gate (TG) dielectric was fabricated and investigated. The effective DG modulation of MoS2 FET exhibited an outstanding electrical performance with a high on/off current ratio of 6×108. Furthermore, a large threshold voltage modulation could be obtained from -20.5 to -39.3 V as a function of the TG voltage in a DG MoS2 phototransistor. Meanwhile, the optical properties were systematically explored under a series of gate biases and illuminated optical power under the 550 nm laser illumination. And the ultrahigh photoresponsivity of 2.04×105 AW-1 has been demonstrated with the structure of DG MoS2 phototransistor because the electric field formed by DG can separate photogenerated electrons and holes efficiently. So, the DG design for the 2D materials with ultrahigh photoresponsivity gives promising opportunity for the application of optoelectronic devices.

9.
Neurol Sci ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33538915

RESUMO

BACKGROUND: Rigidity is one of the major manifestations of Parkinson's disease (PD), but no quantitative and objective imaging method has been developed to measure rigidity. Ultrasound shear wave elastography (SWE) can reflect the stiffness of tissue by providing a quantitative index. Thus, we conducted this study to evaluate the potential clinical value of SWE in assessing rigidity in PD. METHODS: A total of 63 subjects (44 patients with rigidity-dominant PD and 19 right-dominant-hand normal controls with matched age) were enrolled, and each underwent ultrasound SWE testing. The tests were conducted on the brachioradialis (BR) and biceps brachii (BB) on the more affected side in patients with PD and on the right side in normal controls. Differences in quantitative shear wave velocity (SWV) between patients with PD and normal controls were determined. The relationship of muscle SWV with joint rigidity, UPDRSIII, disease duration, sex, and age in patients with PD was analyzed. The intraclass correlation coefficient (ICC) was used to evaluate the reliability of SWE in assessing muscle stiffness in patients with PD. RESULTS: The mean SWVs of the BB and BR were higher in the PD group (3.65±0.46 and 4.62±0.89 m/s, respectively) than in normal controls (2.79±0.37 and 3.26±0.40 m/s, respectively). Stiffness in BR and BB was correlated with the upper-limb joint rigidity, UPDRSIII, and disease duration but not with sex or age in the PD group. The intraobserver correlation coefficients (ICCs) for interobserver and intraobserver variations in measuring SWV were 0.85 (95% confidence interval 0.56-0.95) and 0.85 (95% confidence interval 0.58-0.95), respectively, for BR and 0.90 (95% confidence interval 0.73-0.97) and 0.86 (95% confidence interval 0.61-0.95), respectively, for BB. CONCLUSIONS: SWV is associated with joint rigidity and disease duration, indicating that SWE can be potentially used as an objective and quantitative tool for evaluating rigidity.

10.
IEEE Trans Cybern ; PP2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33531332

RESUMO

Recent progress on salient object detection mainly aims at exploiting how to effectively integrate multiscale convolutional features in convolutional neural networks (CNNs). Many popular methods impose deep supervision to perform side-output predictions that are linearly aggregated for final saliency prediction. In this article, we theoretically and experimentally demonstrate that linear aggregation of side-output predictions is suboptimal, and it only makes limited use of the side-output information obtained by deep supervision. To solve this problem, we propose deeply supervised nonlinear aggregation (DNA) for better leveraging the complementary information of various side-outputs. Compared with existing methods, it: 1) aggregates side-output features rather than predictions and 2) adopts nonlinear instead of linear transformations. Experiments demonstrate that DNA can successfully break through the bottleneck of the current linear approaches. Specifically, the proposed saliency detector, a modified U-Net architecture with DNA, performs favorably against state-of-the-art methods on various datasets and evaluation metrics without bells and whistles.

11.
Asian J Androl ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33533741

RESUMO

Azoospermia patients who carry a monogenetic mutation that causes meiotic arrest may have their biological child through genetic correction in spermatogonial stem cells (SSCs). However, such therapy for infertility has not been experimentally investigated yet. In this study, a mouse model with an X-linked testis-expressed 11 (TEX11) mutation (Tex11PM/Y) identified in azoospermia patients exhibited meiotic arrest due to aberrant chromosome segregation. Tex11PM/Y SSCs could be isolated and expanded in vitro normally, and the mutation was corrected by clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated endonuclease 9 (Cas9), leading to the generation of repaired SSC lines. Whole-genome sequencing demonstrated that the mutation rate in repaired SSCs is comparable with that of autonomous mutation in untreated Tex11PM/Y SSCs, and no predicted off-target sites are modified. Repaired SSCs could restore spermatogenesis in infertile males and give rise to fertile offspring at a high efficiency. In summary, our study establishes a paradigm for the treatment of male azoospermia by combining in vitro expansion of SSCs and gene therapy.

12.
Oncogene ; 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33564073

RESUMO

Soft tissue sarcoma (STS) is a heterogeneous disease that arises from connective tissues. Clinical outcome of patients with advanced tumors especially de-differentiated liposarcoma and uterine leiomyosarcoma remains unsatisfactory, despite intensive treatment regimens including maximal surgical resection, radiation, and chemotherapy. MAP kinase-interacting serine/threonine-protein kinase 1 and 2 (MNK1/2) have been shown to contribute to oncogenic translation via phosphorylation of eukaryotic translation initiation factor 4E (eIF4E). However, little is known about the role of MNK1/2 and their downstream targets in STS. In this study, we show that depletion of either MNK1 or MNK2 suppresses cell viability, anchorage-independent growth, and tumorigenicity of STS cells. We also identify a compelling antiproliferative efficacy of a novel, selective MNK inhibitor ETC-168. Cellular responsiveness of STS cells to ETC-168 correlates positively with that of phosphorylated ribosomal protein S6 (RPS6). Mirroring MNK1/2 silencing, ETC-168 treatment strongly blocks eIF4E phosphorylation and represses expression of sarcoma-driving onco-proteins including E2F1, FOXM1, and WEE1. Moreover, combination of ETC-168 and MCL1 inhibitor S63845 exerts a synergistic antiproliferative activity against STS cells. In summary, our study reveals crucial roles of MNK1/2 and their downstream targets in STS tumorigenesis. Our data encourage further clinical translation of MNK inhibitors for STS treatment.

13.
J Food Sci ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33565634

RESUMO

Various bond disrupting agents including NaCl, GuHCl, urea, and SDS were introduced to investigate the intermolecular interactions between scallop (Patinopecten yessoensis) male gonad hydrolysates (SMGHs) and κ-carrageenan (κ-C), which were monitored by changes in rheological property, water distribution, conformation characterization and microstructure by using rheometer, low field-NMR relaxometry, Fourier transform infrared (FTIR) spectroscopy, cryo-scanning electron microscopy (cryo-SEM), and confocal laser scanning microscopy. The results showed that the bond disrupting agents deteriorated the rheological property of SMGHs/κ-C in a dose-dependent manner. Indeed, at the same concentration of 2 M, NaCl deteriorated the SMGHs/κ-C more obviously than GuHCl and urea. In addition, SMGHs/κ-C with bond disrupting agents possessed higher relaxation times including T21 and T23 , indicating the migration to free water direction of bound and free water. Moreover, the FITR results showed the red-shift in water regions (amide A and B bands), amide I and II bands, and indicated the breakdown of hydrogen bonds and electrostatic interactions, indicating a disordered structure in SMGHs/κ-C by various bond disrupting agents. Furthermore, cryo-SEM results showed the change of SMGHs/κ-C from a homogeneous network to a looser and ruptured one with larger void spaces, and indicated the disrupted and tattered microstructure of SMGHs/κ-C by various bond disrupting agents. Additionally, SMGHs/κ-C as well showed less aggregates stained by RITC by bond disrupting agents. These results suggest that electrostatic interactions would be mainly involved in the maintenance of SMGHs/κ-C gel network. This study could provide theoretical and methodological basis for hydrogel products with modified gel strength and microstructure by understanding the intermolecular interactions in gel system. PRACTICAL APPLICATION: Scallop (Patinopecten yessoensis) male gonads as a high-protein part of scallop, is usually discarded during processing despite its edibility. In recent years, scallop male gonads are regarded as good sources to develop protein matrices due to their high protein content and numerous nutrients. In this study, scallop male gonad hydrolysates (SMGHs) were obtained by trypsin-treated process. The considerable gelation behavior of SMGHs indicated that the SMGHs could be potentially utilized as a novel thickener and additive in production of kamaboko gels, can, sausage and spread with marine flavor.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33565868

RESUMO

Photodynamic therapy (PDT) is a new therapeutic strategy for hypertrophic scars (HSs), and nanoethosomes (ES) have attracted considerable attention as an efficient transdermal delivery system for PDT of HSs (HS-PDT). However, the delivery of photosensitizers and the hypoxic microenvironment of HSs limit HS-PDT efficacy. Consequently, functional transdermal ES (A/A-ES) that are loaded with the photosensitizer, 5-aminolevulinic acid (ALA), and immobilized nanoenzyme Au nanoclusters (ANCs) within the ES surface have been developed that exhibit superior co-delivery characteristics and produce catalase that enhances HS-PDT efficacy. The unique structure of A/A-ES enables them to co-deliver ALA and ANCs into the HS tissue and to efficiently decompose the endogenous hydrogen peroxide in the HS to generate oxygen. The findings from in vitro and in vivo experiments demonstrated that A/A-ES efficiently co-delivered ALA and ANCs into the HS tissue and that they improved the hypoxic microenvironment of the HS. Systematic assessments reveal that A/A-ES enhance HS-PDT efficacy and that they are highly effective at improving the morphology and promoting HS fibroblast apoptosis and the rearrangement of collagen. These works give rise to an effective treatment option for HSs that integrates the transdermal co-delivery of ALA and nanoenzymes, thereby enabling them to exert their respective beneficial effects, and they highlight the enhancement of HS-PDT efficacy via self-generating oxygen.

15.
Adv Skin Wound Care ; 34(3): 150-156, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33587476

RESUMO

OBJECTIVE: To describe the 10-year prevalence of pressure injury (PI) in a tertiary hospital in China and determine the clinical characteristics of inpatients with PI. METHODS: The authors performed a retrospective analysis of PI cases extracted from the electronic health record of a tertiary hospital. The trend of PI prevalence over 10 years was described by estimating the average percent change (EAPC). Comorbidities were described with the Charlson Comorbidity Index (CCI). The clinical characteristics of PI were described using the number of cases and composition ratio. RESULTS: The overall prevalence of PI was 0.59% (5,838/986,404). From 2009 to 2018, the rate increased from 0.19% to 1.00% (EAPC = 22.46%). When stage I PIs were excluded, the prevalence of PI ranged from 0.15% to 0.79% (EAPC = 21.90%). The prevalence of hospital-acquired PI was 0.13%. Prevalence increased with age (Ptrend < .001) and was significantly higher in men than women (P < .001). Patients with PI were more widely distributed in the ICU (20.58%), vasculocardiology department (11.73%), gastroenterology department (10.18%), and OR (8.29%). Of patients with PI, 71.3% had a CCI score 4 or higher. CONCLUSIONS: The PI prevalence in the study facility increased rapidly over the study period. Pressure injuries among patients in the gastroenterology department and in the community deserve more attention. The CCI may be a good indicator for PI risk assessment.

16.
Nutrients ; 13(2)2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33525398

RESUMO

(1) Background: Breastfeeding has been shown to support glucose homeostasis in women after a pregnancy complicated by gestational diabetes mellitus (GDM) and is potentially effective at reducing long-term diabetes risk. (2) Methods: Data from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study were analyzed to understand the influence of breastfeeding duration on long-term dysglycemia (prediabetes and diabetes) risk in women who had GDM in the index pregnancy. GDM and dysglycemia four to seven years postpartum were determined by the oral glucose tolerance test (OGTT). A Poisson regression model with a robust error variance was used to estimate incidence rate ratios (IRRs) for dysglycemia four to seven years post-delivery according to groupings of the duration of any breastfeeding (<1, ≥1 to <6, and ≥6 months). (3) Results: Women who had GDM during the index pregnancy and complete breastfeeding information and OGTT four to seven years postpartum were included in this study (n = 116). Fifty-one women (44%) had postpartum dysglycemia. Unadjusted IRRs showed an inverse association between dysglycemia risk and ≥1 month to <6 months (IRR 0.91; 95% confidence interval [CI] 0.57, 1.43; p = 0.68) and ≥6 months (IRR 0.50; 95% CI 0.27, 0.91; p = 0.02) breastfeeding compared to <1 month of any breastfeeding. After adjusting for key confounders, the IRR for the ≥6 months group remained significant (IRR 0.42; 95% CI 0.22, 0.80; p = 0.008). (4) Conclusions: Our results suggest that any breastfeeding of six months or longer may reduce long-term dysglycemia risk in women with a history of GDM in an Asian setting. Breastfeeding has benefits for mothers beyond weight loss, particularly for those with GDM.

17.
Mol Med Rep ; 23(3): 1, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33398366

RESUMO

Myocardial ischemia/reperfusion (MIR) injury, which occurs following acute myocardial infarction, can cause secondary damage to the heart. Tripartite interaction motif (TRIM) proteins, a class of E3 ubiquitin ligases, have been recognized as critical regulators in MIR injury. Zenglv Fumai Granule (ZFG) is a clinical prescription for the treatment of sick sinus syndrome, a disease that is associated with MIR injury. The present study aimed to investigate the effect of ZFG on MIR injury and to determine whether ZFG exerts its effects via regulation of TRIM proteins. In order to establish an in vitro MIR model, human cardiomyocyte cell line AC16 was cultured under hypoxia for 5 h and then under normal conditions for 1 h. Following hypoxia/reoxygenation (H/R) treatment, these cells were cultured with different ZFG concentrations. ZFG notably inhibited H/R-induced cardiomyocyte apoptosis. The expression levels of four TRIM proteins, TRIM7, TRIM14, TRIM22 and TRIM28, were also detected. These four proteins were significantly upregulated in H/R-injured cardiomyocytes, whereas their expression was inhibited following ZFG treatment. Moreover, TRIM28 knockdown inhibited H/R-induced cardiomyocyte apoptosis, whereas TRIM28 overexpression promoted apoptosis and generation of reactive oxygen species (ROS) in cardiomyocytes. However, the effects of TRIM28 overexpression were limited by the action of ROS inhibitor N-acetyl-L-cysteine. In addition, the mRNA and protein levels of antioxidant enzyme glutathione peroxidase (GPX)1 were significantly downregulated in H/R-injured cardiomyocytes. TRIM28 knockdown restored GPX1 protein levels but had no effect on mRNA expression levels. Co-immunoprecipitation and ubiquitination assays demonstrated that TRIM28 negatively regulated GPX1 via ubiquitination. In sum, the present study revealed that ZFG attenuated H/R-induced cardiomyocyte apoptosis by regulating the TRIM28/GPX1/ROS pathway. ZFG and TRIM28 offer potential therapeutic options for the treatment of MIR injury.

18.
Biomed Pharmacother ; 135: 111169, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33433359

RESUMO

The long noncoding RNAs (lncRNAs) are non-coding RNAs that are more than 200 nucleotides in length, and one of several types of non-coding RNAs (ncRNAs). The lncRNAs function in diverse biological processes in normal cells, such as cellular differentiation and cell cycle regulation. There is also evidence that some aberrantly regulated lncRNAs function as oncogenes or tumor suppressor genes in various cancers. For example, TTN-AS1 is a lncRNA that binds to titin mRNA (TTN) and has pro-oncogenic effects in many cancers. Overexpression of TTN-AS1 correlates with poor prognosis in breast cancer, lung cancer, digestive system neoplasms, reproductive system cancers, and other cancers. Furthermore, increased TTN-AS1 expression correlates with more advanced pathology and tumor malignancy. In this review, we comprehensively summarize recent studies on the molecular mechanisms of TTN-AS1 regulation and the role of TTN-AS1 in the carcinogenesis and progression of numerous tumors.

19.
Oxid Med Cell Longev ; 2021: 3010548, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33505580

RESUMO

Ischemia-reperfusion (I/R) injury caused by acute myocardial infarction (AMI) can initiate a strong inflammatory response. Polymorphonuclear cells (PMNs) are the most important inflammatory cells. Our previous studies found that the calcium-sensing receptor (CaSR) regulates the proinflammatory effects of PMNs. However, the role and mechanism of CaSR-regulated PMNs in I/R injury remain uncertain. A rat AMI model was developed in this study and showed that the expression of CaSR on PMNs increased in AMI; however, the levels of Bcl-xl and SOD in myocardial tissue decreased, while Bax and MDA levels increased. Then, after coculture with CaSR-stimulated PMNs, the expression of Bcl-xl in cardiomyocytes significantly increased, Bax expression and the apoptotic rate decreased, and ROS production was significantly inhibited. At the same time, the cardiomyocyte damage caused by hypoxia-reoxygenation was reduced. Furthermore, we found that exosomes derived from PMNs could be taken up by cardiomyocytes. Additionally, the exosomes secreted by CaSR-stimulated PMNs had the same effect on cardiomyocytes as CaSR-stimulated PMNs, while the increased phosphorylation level of AKT in cardiomyocytes could be revered by AKT transduction pathway inhibitors. Subsequently, we identified the exosomes derived from CaSR-stimulated PMNs by second-generation sequencing technology, and increased expression of lncRNA ENSRNOT00000039868 was noted. The data show that this lncRNA can prevent the hypoxia-reoxygenation injury by upregulating the expression of PDGFD in cardiomyocytes. In vivo, exosomes from CaSR-stimulated PMNs played a significant role against AMI and reperfusion injury in myocardial tissue. Thus, we propose that exosomes derived from CaSR-stimulated PMNs can reduce I/R injury in AMI, and this effect may be related to the AKT signaling pathway.

20.
Mol Plant Microbe Interact ; : MPMI03200071R, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33507814

RESUMO

Verticillium wilt is a vascular disease causing tremendous damage to cotton production worldwide. However, our knowledge of the mechanisms of cotton resistance or susceptibility to this disease is very limited. In this study, we compared the defense transcriptomes of cotton (Gossypium hirsutum) cultivars Shidalukang 1 (Verticillium dahliae resistant, HR) and Junmian 1 (V. dahliae susceptible, HS) before and after V. dahliae infection, identified hub genes of the network associated with responses to V. dahliae infection, and functionally characterized one of the hub genes involved in biosynthesis of lignin and phenolics. We identified 6,831 differentially expressed genes (DEGs) between the basal transcriptomes of HR and HS; 3,685 and 3,239 of these DEGs were induced in HR and HS, respectively, at different time points after V. dahliae infection. KEGG pathway analysis indicated that DEGs were enriched for genes involved in lignin biosynthesis. In all, 23 hub genes were identified based on a weighted gene coexpression network analysis of the 6,831 DEGs and their expression profiles at different time points after V. dahliae infection. Knockdown of Gh4CL30, one of the hub genes related to the lignin biosynthesis pathway, by virus-induced gene silencing, led to a decreased content of flavonoids, lignin, and S monomer but an increased content of G monomer, G/S lignin monomer, caffeic acid, and ferulic acid, and enhanced cotton resistance to V. dahliae. These results suggest that Gh4CL30 is a key gene modulating the outputs of different branches of the lignin biosynthesis pathway, and provide new insights into cotton resistance to V. dahliae.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

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