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1.
Oxid Med Cell Longev ; 2021: 7182914, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512869

RESUMO

Background: Pyruvate kinase L/R (PKLR) has been suggested to affect the proliferation of hepatocytes via regulation of the cell cycle and lipid metabolism. However, its impact on the global metabolome and its clinical implications remain unclear. Aims: We aimed to clarify the genetic impact of PKLR on the metabolomic profiles of hepatoma cells and its potential effects on grafts for liver transplantation (LT). Methods: Nontargeted and targeted metabolomic assays were performed in human hepatoma cells transfected with lentiviral vectors causing PKLR overexpression and silencing, respectively. We then constructed a molecular network based on integrative analysis of transcriptomic and metabolomic data. We also assessed the biological functions of PKLR in the global metabolome in LT grafts in patients via a weighted correlation network model. Results: Multiomic analysis revealed that PKLR perturbations significantly affected the pyruvate, citrate, and glycerophospholipid metabolism pathways, as crucial steps in de novo lipogenesis (DNL). We also confirmed the importance of phosphatidylcholines (PC) and its derivative lyso-PC supply on improved survival of LT grafts in patients. Coexpression analysis revealed beneficial effects of PKLR overexpression on posttransplant prognosis by alleviating arachidonic acid metabolism of the grafts, independent of operational risk factors. Conclusion: This systems-level analysis indicated that PKLR affected hepatoma cell viability via impacts on the whole process of DNL, from glycolysis to final PC synthesis. PKLR also improved prognosis after LT, possibly via its impact on the increased genesis of beneficial glycerophospholipids.

2.
Ann N Y Acad Sci ; 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34533853

RESUMO

The maximum diameter of the balloon used for balloon dilatation(BD) of esophagogastric anastomotic stricture (EAS) is generally 20 millimeters. This study aimed to evaluate the safety and efficacy of BD under fluoroscopy, using balloons with a diameter of 25-30 millimeters. We retrospectively analyzed the data of patients with benign EAS treated by large BD (balloon diameter, 25-30 mm) under fluoroscopy. The Cox proportional hazards model (PHM) was used to identify the factors associated with stricture-free survival. The results show that a total of 127 patients were included in this study, and 204 BDs were performed. The technical success rate was 96.6%, and the clinical success rate was 99.2%. The incidence of serious adverse events was 3.4% (7/204). One patient died of massive hemorrhage during BD, and nine patients were lost to follow-up. For the remaining 117 patients, the median stricture-free survival period was 14.9 months. In multivariable analysis using the Cox PHM, only balloon diameter was significantly associated with stricture-free survival. The stricture-free survival period tended to increase as balloon diameter increased. Large BD under fluoroscopy appears to be safe and effective for the treatment of benign EAS after esophagectomy.

3.
J Psychiatry Neurosci ; 46(5): E506-E515, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34467747

RESUMO

Background: Schizophrenia, bipolar disorder and major depressive disorder are increasingly being conceptualized as a transdiagnostic continuum. Disruption of white matter is a common alteration in these psychiatric disorders, but the molecular mechanisms underlying the disruption remain unclear. Neuregulin 1 (NRG1) is genetically linked with susceptibility to schizophrenia, bipolar disorder and major depressive disorder, and it is also related to white matter. Methods: Using a transdiagnostic approach, we aimed to identify white matter differences associated with NRG1 and their relationship to transdiagnostic symptoms and cognitive function. We examined the white matter of 1051 participants (318 healthy controls and 733 patients with major psychiatric disorders: 254 with schizophrenia, 212 with bipolar disorder and 267 with major depressive disorder) who underwent diffusion tensor imaging. We measured the plasma NRG1-ß1 levels of 331 participants. We also evaluated clinical symptoms and cognitive function. Results: In the patient group, abnormal white matter was negatively associated with NRG1-ß1 levels in the genu of the corpus callosum, right uncinate fasciculus, bilateral inferior fronto-occipital fasciculus, right external capsule, fornix, right optic tract, left straight gyrus white matter and left olfactory radiation. These NRG1-associated white matter abnormalities were also associated with depression and anxiety symptoms and executive function in patients with a major psychiatric disorder. Furthermore, across the 3 disorders we observed analogous alterations in white matter, NRG1-ß1 levels and clinical manifestations. Limitations: Medication status, the wide age range and our cross-sectional findings were limitations of this study. Conclusion: This study is the first to provide evidence for an association between NRG1, white matter abnormalities, clinical symptoms and cognition in a transdiagnostic psychiatric cohort. These findings provide further support for an understanding of the molecular mechanisms that underlie the neuroimaging substrates of major psychiatric disorders and their clinical implications.

4.
Anat Rec (Hoboken) ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34469051

RESUMO

Alzheimer's disease (AD) is a fatal neurodegenerative disease for which currently no cure is available. Electroacupuncture (EA) has been widely used in China as an alternative therapeutic approach for neurological diseases. The cognitive decline in patients with AD has been reported to be closely related to the deposition of amyloid-ß (Aß) in the hippocampus of the brain, and the Morris water maze (MWM) test is a widely used method for assessing the behavior of animal models. In this study, the MWM test was performed to evaluate the effects of EA treatment on cognitive function and memory, and the micro-positron emission tomography scan was used to assess the hippocampal Aß deposition. The results showed that the cognitive function of APP/PS1 mice was significantly improved and the rate of [18F]AV-45 uptake was reduced in the EA group, compared with the AD group. Our study suggested that EA can exert a therapeutic effect in AD by improving spatial learning and memory and inhibiting the hippocampal Aß deposition.

5.
Int J Biol Macromol ; 188: 272-282, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34364943

RESUMO

Choline kinase (CK) gene plays an important role in plants growth, development and resistance to stress. It mainly regulates the biosynthesis of phosphatidylcholine. This study aims to explore the structure-function relationship, and to provide a framework for functional validation and biochemical characterization of various CK genes. Our analysis showed that 87 CK genes were identified in cotton and 7 diploid plants, of which 43 genes encode CK proteins in 4 cotton species, and 13 genes were identified in Gossypium hirsutum. Most of GhCK genes are affected by the abiotic stress conditions, indicating the importance of CK proteins for plant development and response to abiotic stress. RT-qPCR analysis showed the tissue specificity of GhCK genes in response to Cd2+ and other abiotic stresses. Under Cd2+ stress, the expression level of GhCK gene family members has undergone different changes. The expression level of GhCK5 was enhanced, indicating that Cd2+ stress caused the increase of phosphatidylcholine content, which in turn reacted on the plant cell membrane, finally reached the absorption of Cd2+ into plant cells to repair Cd2+ the purpose of contaminated soil. This study will further broaden our understanding of the association between evolution and function of the GhCK gene family.

6.
Med Image Anal ; 74: 102205, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34425317

RESUMO

With the global outbreak of COVID-19 in early 2020, rapid diagnosis of COVID-19 has become the urgent need to control the spread of the epidemic. In clinical settings, lung infection segmentation from computed tomography (CT) images can provide vital information for the quantification and diagnosis of COVID-19. However, accurate infection segmentation is a challenging task due to (i) the low boundary contrast between infections and the surroundings, (ii) large variations of infection regions, and, most importantly, (iii) the shortage of large-scale annotated data. To address these issues, we propose a novel two-stage cross-domain transfer learning framework for the accurate segmentation of COVID-19 lung infections from CT images. Our framework consists of two major technical innovations, including an effective infection segmentation deep learning model, called nCoVSegNet, and a novel two-stage transfer learning strategy. Specifically, our nCoVSegNet conducts effective infection segmentation by taking advantage of attention-aware feature fusion and large receptive fields, aiming to resolve the issues related to low boundary contrast and large infection variations. To alleviate the shortage of the data, the nCoVSegNet is pre-trained using a two-stage cross-domain transfer learning strategy, which makes full use of the knowledge from natural images (i.e., ImageNet) and medical images (i.e., LIDC-IDRI) to boost the final training on CT images with COVID-19 infections. Extensive experiments demonstrate that our framework achieves superior segmentation accuracy and outperforms the cutting-edge models, both quantitatively and qualitatively.

7.
J Immunother Cancer ; 9(8)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34452929

RESUMO

BACKGROUND: Cancer vaccines are a promising strategy for cancer immunotherapy. Cancer vaccines elicits a specific cytotoxic immune response to tumor antigens. However, the efficacy of traditional peptide-based cancer vaccines is limited due to the inefficient delivery of antigens and adjuvants to dendritic cells (DCs). Therefore, it is necessary to develop a novel rationally designed cancer vaccine to maximize its desired effects. METHODS: A Self-assembling Vehicle-free Multi-component Antitumor nanoVaccine (SVMAV) was constructed by using an unsaturated fatty acid docosahexaenoic acid (DHA)-conjugated antigen and R848 (a Toll-like receptor 7/8 agonist) to encapsulate stattic (a signal transducer and activator of transcription 3 inhibitor). The characteristics of SVMAV were investigated. The ability of SVMAV to promote DC functions was examined by in vitro analysis. The antitumor effects of SVMAV and its combination with antiprogrammed cell death protein 1 antibody (aPD-1) were also investigated in vivo. The potential application of SVMAV for neoantigen-targeted, personalized cancer vaccines was examined in an orthotopic hepatocellular carcinoma model. RESULTS: The obtained SVMAV efficiently migrated into lymph nodes and primed CD8+ T cells for exert neoantigen-specific killing by promoting the antigen uptake by DCs, stimulating DC maturation, and enhancing antigen cross-presentation, due to the simultaneous delivery of the antigen, R848 and stattic. SVMAV could not only yield a robust antitumor effect for primary melanoma allografts, but also exert a protective effect for lung metastases. Moreover, combination treatment of SVMAV and aPD-1 exerted synergistic antitumor activity and extended the survival duration of melanoma-bearing mice. Notably, a cell line-specific neoantigen-based SVMAV was designed according to predicted neoantigens for Hepa1-6 cells to examine the potential application of SVMAV for personalized cancer vaccine. Encouragingly, neoantigen-specific SVMAV achieved stronger antitumor activity than aPD-1 in an orthotopic hepatocellular cancer model established with Hepa1-6 cells. CONCLUSIONS: In summary, this study offers an efficient codelivery platform for neoantigens and immunoregulatory compounds to enhance immune responses during cancer immune therapy.

8.
Curr Microbiol ; 78(10): 3741-3750, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34459935

RESUMO

Sulfitobacter pseudonitzschiae H46, a marine bacterium associated with microalgae, exhibits algicidal activity against harmful algal bloom microalgae Chattonella marina and Alexandrium tamarense. The complete genome of S. pseudonitzschiae H46 was sequenced to investigate its algicidal mechanism further. One chromosome, eight circular plasmids and add one not circularized plasmid (Plas II) were identified, which are 4.93 Mb in length with 4871 open reading frames. The genome contains 43 transfer RNA (tRNA) genes; six ribosome RNA (rRNA) genes that can be classified into two 5S rRNA, two 16S rRNA, two 23S rRNA, and two small RNA (sRNA) genes. Genomic annotation revealed that S. pseudonitzschiae H46 has two pairs of LuxI/R-type Quorum-sensing (QS) systems. The QS systems can regulate the functions involved in host colonization and biofilm formation. Moreover, the existence of 49 Type-IV and Dddl genes in the chromosome indicated that Dimethylsulfoniopropionate (DMSP) catabolism of S. pseudonitzschiae H46 is the main interaction with marine microalgae. S. pseudonitzschiae H46 utilizes DMSP produced by microalgae as the carbon source, and this may induce algicidal activity. The complete genome sequence of S. pseudonitzschiae H46 can provide useful information on the underlying molecular mechanism between QS and algicidal activity.


Assuntos
Microalgas , Rhodobacteraceae , Proliferação Nociva de Algas , Microalgas/genética , Percepção de Quorum , RNA Ribossômico 16S/genética , Rhodobacteraceae/genética
9.
Isotopes Environ Health Stud ; 57(5): 516-534, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34347540

RESUMO

Shallow groundwater and lake water are the dominant water resources in the Badain Jaran Desert. There are still controversial hypotheses related to the origin of groundwater in this desert. Few studies have been conducted to explore the Sr provenance of these waters and assess the water-rock interactions using a Sr isotope approach until now. In this text, the Sr isotope data of waters in the hinterland of the Badain Jaran Desert and neighbouring areas are reported. The waters in the Badain Jaran Desert have few links to its surrounding rivers, but could be influenced by the precipitation in the Yabulai Mountains. The 87Sr/86Sr ratio changes constantly, while the Sr2+ concentration of shallow groundwater gradually decreases from Yabulai to the desert hinterland to Gurinai-Guaizihu. Combined with hydrochemical data and hydrodynamic conditions, these results show that the dissolved Sr of waters in the desert hinterland is controlled by the Yabulai precipitation and catchment weathering. They further show that the desert shallow groundwater Sr originates mainly from the Yabulai precipitation (> 94 %), while whole-rock weathering contributes little (< 6 %), as calculated using isotope mass balance equations. Relative Sr contributions to lakes from shallow groundwater and catchment weathering are calculated to be 92.5 and 7.5 %, respectively.

10.
Int J Mol Sci ; 22(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34445597

RESUMO

Spermatogenesis is a complicated process involving mitotically proliferating spermatogonial cells, meiotically dividing spermatocytes, and spermatid going through maturation into spermatozoa. The post-translational modifications of proteins play important roles in this biological process. S-palmitoylation is one type of protein modifications catalyzed by zinc finger Asp-His-His-Cys (ZDHHC)-family palmitoyl S-acyltransferases. There are 23 mammalian ZDHHCs that have been identified in mouse. Among them, Zdhhc19 is highly expressed in adult testis. However, the in vivo function of Zdhhc19 in mouse spermatogenesis and fertility remains unknown. In this study, we knocked out the Zdhhc19 gene by generating a 2609 bp deletion from exon 3 to exon 6 in mice. No differences were found in testis morphology and testis/body weight ratios upon Zdhhc19 deletion. Spermatogenesis was not disrupted in Zdhhc19 knockout mice, in which properly developed TRA98+ germ cells, SYCP3+ spermatocytes, and TNP1+ spermatids/spermatozoa were detected in seminiferous tubules. Nevertheless, Zdhhc19 knockout mice were male infertile. Zdhhc19 deficient spermatozoa exhibited multiple defects including abnormal morphology of sperm tails and heads, decreased motility, and disturbed acrosome reaction. All of these led to the inability of Zdhhc19 mutant sperm to fertilize oocytes in IVF assays. Taken together, our results support the fact that Zdhhc19 is a testis enriched gene dispensable for spermatogenesis, but is essential for sperm functions in mice.

11.
Mol Biochem Parasitol ; 245: 111408, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34343548

RESUMO

Thioredoxin peroxidase (TPx) plays an important role in protecting parasites against oxidative damage. However, studies on the role of TPxs in Echinococcus multilocularis are limited. In this study, one tpx gene of E. multilocularis, named as emtpx-1, was identified. EmTPx-1 shares two positionally conserved cysteine residues (Cys48 and Cys169) with orthologs from other platyhelminths. EmTPx-1 is highly expressed in the germinal layer and present in exosome-like vesicles secreted by E. multilocularis metacestodes. EmTPx-1 displays peroxidase activity, which removes hydrogen peroxide in the presence of dithiothreitol. Furthermore, EmTPx-1 could protect DNA from oxidative damages, and EmTPx-1-expressing E. coli cells had an enhanced resistance to oxidative stress. In addition, EmTPx-1 enhanced the expression of arg1, ym1, and il-10, but suppressed inos, tnf-α, and il-1ß expression in LPS-stimulated macrophages. Our data suggest a critical role for EmTPx-1 in oxidative stresses and M2 macrophage polarization.

12.
J Arthroplasty ; 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34419317

RESUMO

BACKGROUND: Alcohol withdrawal (AW) syndrome is an independent risk factor for postoperative complications. This study aims to evaluate the influence of AW on perioperative outcomes in patients who underwent primary total knee (TKA) or total hip arthroplasty (THA). METHODS: We used the National Inpatient Sample database to identify patients undergoing TKA/THA from 2003 to 2014. The primary exposure of interest was AW. Multivariable adjusted models were used to evaluate the association of AW with in-hospital medical complications, surgical complications, mortality, cost, and length of stay (LOS) in patients undergoing TKA/THA. RESULTS: There were 2,971,539 adult hospitalizations for THAs and 6,367,713 hospitalizations for TKAs included in the present study, among which 0.14% of AW for THA patients and 0.10% of AW for TKA patients. Multivariable adjustment analysis suggested that AW was associated with an increased risk of medical complications (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.79-2.42, P < .0001), surgical complications (OR 1.75, 95% CI 1.51-2.03, P < .0001), and had 4.79 times increase of in-hospital mortality, 26% increase of total cost, and 53% increase of LOS in THA procedures. For TKA procedures, AW was also associated with increased risk of medical complications (OR 3.14, 95% CI 2.78-3.56, P < .0001), surgical complications (OR 2.07, 95% CI 1.82-2.34, P < .0001) and 4.24 times increase of in-hospital mortality, 29% increase of total cost, and 58% increase of LOS after multivariable adjustment. CONCLUSION: AW is associated with increased risk of in-hospital mortality, medical and surgical complications. Proactive surveillance and management of AW may be important in improving outcomes in patients who underwent THA and TKA procedure.

13.
Endocr Res ; : 1-7, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34409914

RESUMO

PURPOSE: The purpose of this study is to review observational studies on the effect of insulin use and mortality in patients with COVID-19 and diabetes. METHODS: A systematic literature search was performed using the PubMed, Medline, EMBASE, and Cochrane Library databases. The meta-analysis was performed using a random effects model, and I2 was applied to evaluate heterogeneity. Sensitivity and subgroup analyses were also performed. RESULTS: Overall, 1,338 patients over six studies were ultimately included. Insulin use was related to a higher risk of death in diabetic patients with COVID-19 compared to those who did not use insulin (odds ratio: 2.59, 95% confidence interval: 1.66-4.05; P < .0001; I2: 57%). CONCLUSIONS: This meta-analysis revealed a correlation between insulin usage and increased mortality in diabetic patients with COVID-19. These results showed that insulin requirement in patients with COVID-19 and diabetes might indicate a poor prognosis.

14.
Xenobiotica ; : 1-9, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34382487

RESUMO

miR-199a-5p is an important regulator of many biological processes. However, whether and how CYP enzymes are regulated by miR-199a-5p are unknown. Here, we aimed to investigate the potential role of mmu-miR-199a-5p in regulating CYP2 enzymes.Regulatory effects of mmu-miR-199a-5p on CYP expression were assessed in mouse AML-12 hepatocytes. The metabolic activity of CYP2B10 was probed using cyclophosphamide (CPA) as a specific substrate. The regulatory mechanism was investigated using combined luciferase reporter assays and chromatin immunoprecipitation.Of several important drug-metabolizing CYPs, mmu-miR-199a-5p significantly increased the mRNA levels of Cyp2a10, Cyp2c29, and Cyp2j5 in AML-12 cells with Cyp2a10 altered the most. Consistently, mmu-miR-199a-5p enhanced the expression of CYP2B10 protein and cellular metabolism of CPA. Based on database analysis, Cyp2b10 was not a direct target gene of mmu-miR-199a-5p. Thus, a mediator is necessary for the miRNA regulation of CYP2B10. We found that E4BP4 repressed Cyp2b10 transcription and expression through specific binding to a D-box element in the gene promoter. Moreover, mmu-miR-199a-5p inhibited the expression of E4bp4 at the posttranscriptional level by directly targeting the 59-65 nt segment in its 3'-UTR.In conclusion, mmu-miR-199a-5p positively regulates CYP2B10 expression through inhibiting its repressor E4BP4. Our findings may provide an increased understanding of the complex regulatory pathways for CYP2B10.

15.
J Phys Chem B ; 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34424697

RESUMO

In the operation of proton exchange membrane fuel cells, its ionomeric-polymer membrane is easily attacked by free radicals, resulting in the degradation of performance. In this work, the chemical degradation effect of hydrated Nafion membranes on gas adsorption, diffusion, and permeation behaviors is evaluated by molecular dynamics and Monte Carlo simulation. The correlation of pore ratio, free volume, hydrophilic/hydrophobic interface as well as the connectivity of the hydrophilic domain of Nafion membranes with gas transport characteristics are revealed. The results demonstrate that large free volume, high large pore ratio, smooth hydrophilic/hydrophobic interface, and good connectivity of the hydrophilic domain are favorable for adsorption, diffusion, and permeability processes. The C-S bond and C-O-C bond attack of membranes can increase the gas adsorption amount, which becomes weak after the tertiary carbon is attacked.

16.
J Am Chem Soc ; 143(33): 13124-13134, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34382392

RESUMO

Enantioenriched 1,1-silylboryl alkanes possess silyl and boryl groups that are both connected to the same stereogenic carbon center at well-defined orientations. As these chiral multifunctionalized compounds potentially offer two synthetic handles, they are highly valued building blocks in asymmetric synthesis as well as medicinal chemistry. Despite the potential usefulness, efficient synthetic approaches for their preparation are scarce. Seeking to address this deficiency, an enantioselective cobalt-catalyzed hydrosilylation/hydroboration cascade of terminal alkynes has been realized. This protocol constitutes an impressive case of chemo-, regio-, and stereoselectivity wherein the two different hydrofunctionalization events are exquisitely controlled by a single set of metal catalyst and ligand, an operation which would usually require two separate catalytic systems. Downstream transformations of enantioenriched 1,1-silyboryl alkanes led to various valuable chiral compounds. Mechanistic studies suggest that the present reaction undergoes highly regioselective and stereocontrolled sequential hydrosilylation and hydroboration processes.

17.
J Clin Neurosci ; 91: 62-68, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34373060

RESUMO

AIM: Construct a clinical predictive model based on easily accessible clinical features and imaging data to identify patients 65 years of age and younger with mild cognitive impairment(MCI) who may progress to Alzheimer's disease(AD). METHODS: From the ADNI database, patients with MCI who were less than or equal to 65 years of age and who had been followed for 6-60 months were selected.We collected demographic data, neuropsychological test scale scores, and structural magnetic images of these patients. Clinical characteristics were then screened, and VBM and SBM analyses were performed using structural nuclear magnetic images to obtain imaging histology characteristics. Finally, predictive models were constructed combining the clinical and imaging histology characteristics. RESULTS: The constructed nomogram has a cross-validated AUC of 0.872 in the training set and 0.867 in the verification set, and the calibration curve fits well.We also provide an online model-based forecasting tool. CONCLUSION: The model has good performance and uses convenience,it should be able to provide assistance in clinical work to screen relatively young MCI patients who may progress to AD.

18.
Dig Dis Sci ; 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34373985

RESUMO

BACKGROUND: Poorly differentiated colorectal cancers are more aggressive. Metabolism reprogramming is a significant hallmark in cancer, and aerobic glycolysis is common. However, how cancer cells reprogramming glucose metabolism contributes to cell differentiation was largely unknown. Previous studies have reported that tumor suppressor NDRG2 could promote colorectal cancers differentiation. AIMS: This study aims to demonstrate that NDRG2 promotes the differentiation of colorectal cancers, potentially through the inhibition of aerobic glycolysis via TXNIP induction. METHODS: Western blotting, qRT-PCR and immunohistochemical staining were used to detect the expression of related molecules. MTT assay was used to reflect cell viability and proliferation. Immunofluorescent assay was performed to identify the expression and distribution of molecules. Luciferase analysis and CHIP assays were used to investigate the mechanism. Bioinformatic analysis was performed to predict the relevance. RESULTS: In colorectal cancers, NDRG2 could inhibit cell proliferation, reduce glucose uptake and decrease expression of key glycolysis enzymes. Upregulated NDRG2 is associated with differentiated cancer. However, deletion of TXNIP, a classic glucose metabolism inhibitor, could obviously alter the function of NDRG2 in differentiation, glucose uptake, expression of key glycolysis enzymes and proliferation. Mechanistically, high glucose flux promotes the activity of TXNIP promoter. And NDRG2 promotes the occupancy of transcription factor Mondo A on TXNIP promoter, predominantly through the suppression of c-myc, which could complete with Mondo A binding to TXNIP promoter. In clinical samples, high expression of TXNIP indicates good prognosis and outcome. CONCLUSIONS: NDRG2-dependent induction of TXNIP is critical for the aerobic glycolysis during colorectal cancers differentiation.

19.
Virol J ; 18(1): 165, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384430

RESUMO

BACKGROUND: Canine distemper caused by canine distemper virus that belongs to the Morbillivirus genus of the Paramyxoviridae family is still a global epidemic significant infectious disease, especially in pet dogs in China and serious harm to the development of the dog industry. It has been known that apoptosis caused by the canine distemper virus can show in culture cells, lymphoid tissues, and the cerebellum. However, its occurrence in brain tissue cells remains unclear. To investigate the relationship among canine distemper infecting brain tissues, apoptosis in brain tissue cells, and demyelinating pathogenesis was investigated. METHODS: 16 naturally infected dogs that exhibited clinical signs of CD and tested positive for the anti-CDV monoclonal antibody and six healthy dogs that served as the control, were used in the research. Brain specimens were divided into the cerebrum, brain stem, and cerebellum embedded in paraffin and made the sections respectively. Approximately 5 µm-thick sections were stained by hematoxylin-eosin, methyl green pyronin, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling technique, and immunohistochemistry. CDV nucleocapsid protein was detected by immune streptavidin-biotinylated peroxidase complex. RESULTS: Alterations in the brain tissues of CDV-infected dogs involved both various cells and nerve fibers. CDV had varying degrees of cytotropism to all brain tissue cells; apoptosis also occurred in all brain cells, especially in the endothelia of cerebral vessels, astrocytes, oligodendrocytes, and ependymal cells, the more serious infection, the more obvious apoptosis. Serious infections also involved the pyramidal and Purkinje cells. The nervous fibers exhibited demyelinating lesions (showed small multifocal vacuole), and some axonal neuron atrophy gradually disappeared (formed large vacuole). CONCLUSIONS: Apoptosis in brain tissue cells was mainly related to the propagation path and cytotropism of CDV. The apoptosis of astrocytes, oligodendrocytes, and some neurons may play a significant role in the demyelinating pathogenesis in dogs with acute canine distemper. A lot of diverse nervous signs shown in the clinic may be related to different neuron apoptosis.

20.
BMC Plant Biol ; 21(1): 386, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34416873

RESUMO

BACKGROUND: The abiotic stress such as soil salinization and heavy metal toxicity has posed a major threat to sustainable crop production worldwide. Previous studies revealed that halophytes were supposed to tolerate other stress including heavy metal toxicity. Though HMAD (heavy-metal-associated domain) was reported to play various important functions in Arabidopsis, little is known in Gossypium. RESULTS: A total of 169 G. hirsutum genes were identified belonging to the HMAD gene family with the number of amino acids ranged from 56 to 1011. Additionally, 84, 76 and 159 HMAD genes were identified in each G. arboreum, G. raimondii and G. barbadense, respectively. The phylogenetic tree analysis showed that the HMAD gene family were divided into five classes, and 87 orthologs of HMAD genes were identified in four Gossypium species, such as genes Gh_D08G1950 and Gh_A08G2387 of G. hirsutum are orthologs of the Gorai.004G210800.1 and Cotton_A_25987 gene in G. raimondii and G. arboreum, respectively. In addition, 15 genes were lost during evolution. Furthermore, conserved sequence analysis found the conserved catalytic center containing an anion binding (CXXC) box. The HMAD gene family showed a differential expression levels among different tissues and developmental stages in G. hirsutum with the different cis-elements for abiotic stress. CONCLUSIONS: Current study provided important information about HMAD family genes under salt-stress in Gossypium genome, which would be useful to understand its putative functions in different species of cotton.


Assuntos
Adaptação Fisiológica/genética , Estudo de Associação Genômica Ampla , Genótipo , Gossypium/genética , Gossypium/fisiologia , Metais Pesados/toxicidade , Filogenia , Produtos Agrícolas/genética , Produtos Agrícolas/fisiologia , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Variação Genética , Família Multigênica
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