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1.
Neural Regen Res ; 18(4): 913-921, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36204863

RESUMO

Successful establishment of reconnection between retinal ganglion cells and retinorecipient regions in the brain is critical to optic nerve regeneration. However, morphological assessments of retinorecipient regions are limited by the opacity of brain tissue. In this study, we used an innovative tissue cleaning technique combined with retrograde trans-synaptic viral tracing to observe changes in retinorecipient regions connected to retinal ganglion cells in mice after optic nerve injury. Specifically, we performed light-sheet imaging of whole brain tissue after a clearing process. We found that pseudorabies virus 724 (PRV724) mostly infected retinal ganglion cells, and that we could use it to retrogradely trace the retinorecipient regions in whole tissue-cleared brains. Unexpectedly, PRV724-traced neurons were more widely distributed compared with data from previous studies. We found that optic nerve injury could selectively modify projections from retinal ganglion cells in the hypothalamic paraventricular nucleus, intergeniculate leaflet, ventral lateral geniculate nucleus, central amygdala, basolateral amygdala, Edinger-Westphal nucleus, and oculomotor nucleus, but not the superior vestibular nucleus, red nucleus, locus coeruleus, gigantocellular reticular nucleus, or facial nerve nucleus. Our findings demonstrate that the tissue clearing technique, combined with retrograde trans-synaptic viral tracing, can be used to objectively and comprehensively evaluate changes in mouse retinorecipient regions that receive projections from retinal ganglion cells after optic nerve injury. Thus, our approach may be useful for future estimations of optic nerve injury and regeneration.

2.
J Environ Manage ; 325(Pt B): 116576, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36308965

RESUMO

Ecological engineering is an important measure to promote ecosystem adaptation and restoration to deal with environmental change and human disturbance. To assess the effectiveness of ecological construction and analyze the influencing factors of ecosystem changes in the Qinghai-Tibet Plateau (QTP), this study detected the spatial changes and dynamic hotspots of vegetation ecosystems in the ecological construction regions of the QTP (QTPE) and regions without ecological construction (QTPWE) using hot spot analysis and comprehensive dynamic degree model. Then the random forest (RF) model and geographical weighted regression model were used to study the degree and spatial heterogeneity of impacts of climate and human activities on normalized difference vegetation index (NDVI). Results showed that the vegetation restoration of the QTPE was obvious during 2001-2018 as the area of the increasing NDVI accounted for 74.15%. In addition, the effects of climate and human activities on NDVI of vegetation ecosystem showed significant spatial heterogeneity. The RF model showed that population density was the most significant factor affecting ecosystem vegetation in the QTPE, and its relative importance was between 26.1-32.6%, followed by downward shortwave radiation (7.9-16.8%). However, climate factors still had the greatest impact in the QTPWE, with the relative importance of precipitation and temperature being 45% and 15%, respectively. These findings provide a scientific basis for the restoration and management of vegetation on the QTP, and are of great significance for the deployment of future ecological engineering projects.


Assuntos
Mudança Climática , Ecossistema , Humanos , Tibet , Monitoramento Ambiental , Clima , Temperatura , China
3.
J Org Chem ; 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36383065

RESUMO

Present here is a density functional theory (DFT) study of the mechanism and origin of enantioselectivity of Ni-catalyzed desymmetric cyclization of alkyne-tethered malononitriles and aryl boronic acids. The reaction starts from transmetalation and arylnickel addition, followed by trans to cis isomerization to give cis-alkenyl nickel species. The stereodetermining step is the CN insertion, which prefers a transition state with the bystander CN group staying away from the ligand to reduce steric repulsion, and gives the final (R)-product.

4.
Zool Stud ; 61: e20, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330024

RESUMO

This study presents a new species of free-living marine nematode, Ptycholaimellus luoyang sp. nov., from mangrove wetlands in China. The identification was confirmed by analyzing morphological characteristics and three genes: COI, 18S rDNA, and 28S rDNA. This species is distinguished from allied species by its short cephalic setae, cylindrical pharynx with anterior swelling, sclerotized transverse ridges occurring near the dorsal tooth, rod-like gubernaculum and proximal, arch-like, slightly waved, middle curved, and distally pointed spicules. The Bayesian topology was regarded as morphological evidence of P. luoyang sp. nov. being a distinct species. Interspecific and intrageneric thresholds of the K2P distance divergence have been presented here for the first time.

5.
Front Pharmacol ; 13: 1025540, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339536

RESUMO

Objective: Network pharmacology provides new methods and references for the research of traditional Chinese medicine, but some problems remain, such as single evaluation components and index methods, imperfect relevant databases, unscientific prediction results, and lack of verification of results. Herein, we used a modified network pharmacology research method to explore the potential network analysis mechanism of Huoxue Qingre decoction in the treatment of coronary heart disease and utilized clinical trials for assessment. Methods: Based on literature research, the targets corresponding to the drug were obtained with the assistance of the TCMSP database and Swiss Target Prediction, and the target proteins were corrected using the UniProt database. The targets related to coronary heart disease was obtained through the GeneCards database. A protein-protein interaction network diagram was constructed, and a "component-intersection target" network diagram was drawn based on Cytoscape 3.6.2 software. The mapped targets were imported into the DAVID bioinformatics platform, which underwent Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and the network pharmacology prediction results were evaluated through clinical trials. Results: We obtained 151 compounds related to Huoxue Qingre decoction, 286 genes after evaluation and deduplication, and 426 genes related to coronary heart disease. Finally, 81 common target genes were obtained with 32 pathways according to the KEGG pathway enrichment analysis. The validation results of the clinical trials showed that a total of 98 differential metabolites were found in the treatment of coronary heart disease with Huoxue Qingre decoction, involving a total of 16 metabolic pathways. Compared with the network pharmacology prediction results, it was found that only the pathways in cancer (hsa05200) were the common pathways in the top 32 signaling pathways predicted by network pharmacology. The expanded network pharmacology prediction results revealed that the sphingolipid signaling pathway (hsa04071) and prostate cancer pathway (hsa05215) matched the predicted metabolic pathways, with differential metabolites of N-oleoyl-D-sphingomyelin and 1-methyl-6-phenyl-1h-imidazole[4,5-b]pyridine-2-amine. Conclusion: Through the network analysis and metabolomic evaluation, there may be three signaling pathways that involve the Huoxue Qingre decoction in the treatment of coronary heart disease: pathways in cancer (hsa05200), sphingolipid signaling pathway (hsa04071), and prostate cancer pathway (hsa05215).

6.
Int J Biol Macromol ; 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36427618

RESUMO

Sterile homogeneous egg white (EW) is obtained through a three-step process, high-speed homogenization, centrifugation, and ultraviolet radiation. After incorporating 1.056 × 1010 CFU/g of Escherichia coli, the EW mixture was dehydrated by slow drying to form a brittle, water-soluble, and transparent bacteria-embedded egg white glass (BE-EWG). The BE-EWG stored at -20 °C for 4 months maintains almost all the cell growth functions and proliferation activities of the labeled E. coli, and most of the cell functions and 60 % of the proliferation activities are maintained for up to one year. The BE-EWG exhibits a porous hydrogel membrane structure after heat treatment, and many E. coli cells are accommodated in a grid with a pore size of 2-10 mm. The loss of bacteria-carrying viability after storage at room temperature may be related to the Maillard reaction between protein and glucose in EW, which results in the structural changes caused by protein cross-linking, darkened color and water insolubility of the BE-EWG. Therefore, the method of embedding E. coli cells in EWG as solid form at room temperature to avoid ice crystal formation during cryopreservation is more beneficial for storage, packaging and shipping at -20 °C.

7.
Immunology ; 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36353754

RESUMO

SjÓ§gren's syndrome (SS) is an autoimmune inflammatory disease characterized by chronic inflammation and dysfunction of exocrine glands and causes dry mouth, dry eyes and various systemic health problems. The objective of this study is to define the in vivo actions of the endogenous NLRP3 inflammasome, a key initiator and mediator of various immune and inflammatory conditions, in newly established SS disease. MCC950, a highly specific small-molecule inhibitor of NLRP3 inflammasome formation and activation, was intraperitoneally administered to the female non-obese diabetic (NOD) mice aged 11 weeks, which have newly established SS-like hyposalivation and pathologies. The injection was conducted three times weekly for three consecutive weeks and mice were analysed for characteristic SS pathologies at the end of the treatments. MCC950 treatment resulted in a marked reduction in salivary secretion and an exacerbation of leukocyte infiltration of submandibular glands. The disease-worsening effect of MCC950 treatment was accompanied by increased T and B cell numbers, enhanced T helper 1 response and reduced aquaporin 5 expression in submandibular glands. Hence, ablation of endogenous NLRP3 inflammasome activity by MCC950 with established autoimmune exocrinopathy exacerbates salivary gland dysfunction and inflammation, indicating a disease-alleviating and inflammation-dampening action of the endogenous NLRP3 inflammasome activity during established SS disease in the non-obese diabetic mouse model.

8.
Int J Mol Sci ; 23(21)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36361787

RESUMO

Interleukin-22 (IL-22) affects epithelial tissue function and integrity in a context-dependent manner. IL-22 levels are elevated in salivary glands of Sjögren's syndrome (SS) patients, but its role in the pathogenesis of this disease remains unclear. The objective of this study is to elucidate the impact of IL-22 on salivary gland tissue integrity and function in murine models. We showed that IL-22 levels in sera and salivary glands increased progressively in female non-obese diabetic (NOD) mice, accompanying the development of SS. Administration of IL-22 to the submandibular glands of NOD mice prior to the disease onset reduced salivary secretion and induced caspase-3 activation in salivary gland tissues, which were accompanied by alterations in multiple genes controlling tissue integrity and inflammation. Similarly, IL-22 administration to submandibular glands of C57BL/6 mice also induced hyposalivation and caspase-3 activation, whereas blockade of endogenous IL-22 in C57BL/6 mice treated with anti-CD3 antibody mitigated hyposalivation and caspase-3 activation. Finally, IL-22 treatment reduced the number of viable C57BL/6 mouse submandibular gland epithelial cells cultured in vitro, indicating a direct impact of this cytokine on these cells. We conclude that IL-22 exerts a detrimental impact on salivary gland tissues.


Assuntos
Síndrome de Sjogren , Xerostomia , Camundongos , Feminino , Animais , Camundongos Endogâmicos NOD , Caspase 3 , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Glândulas Salivares , Xerostomia/patologia
9.
Chin J Integr Med ; 28(12): 1105-1110, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36417139

RESUMO

OBJECTIVE: To observe the pressure pain threshold (PPT), skin conductance (SC) and blood perfusion (BP) of the sensitized acupoints in patients with knee osteoarthritis (KOA), and explore the mechanism of acupuncture at the sensitized acupoints for treating diseases. METHODS: Eleven healthy subjects and 11 unilateral KOA patients were recruited from July 2020 to March 2021 in this study. The PPT, SC and BP of control acupoints in healthy controls, and non-sensitized and sensitized acupoints in KOA patients were measured and compared between baseline and after manual acupuncture (MA) treatment. RESULTS: Before MA treatment, lower PPT was observed at the sensitized acupoints compared with non-sensitized and control acupoints (P<0.05). After MA treatment, PPT at the sensitized acupoints increased significantly in KOA patients (P<0.05). Before MA treatment, there was no statistical difference in SC and BP among control, non-sensitized and sensitized acupoints (P>0.05). Compared with the control and non-sensitized acupoints, there were significant increases of SC and BP in sensitized acupoints of KOA patients after MA treatment (P<0.05 or P<0.01). CONCLUSION: MA at sensitized acupoints could elevate PPT of KOA patients, which may be associated with the increment of SC and BP.


Assuntos
Terapia por Acupuntura , Acupuntura , Osteoartrite do Joelho , Humanos , Pontos de Acupuntura , Limiar da Dor , Osteoartrite do Joelho/terapia , Dor
10.
Cell Rep ; 41(8): 111694, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36417861

RESUMO

The establishment of a functional vasculature requires endothelial cells to enter quiescence during the completion of development, otherwise pathological overgrowth occurs. How such a transition is regulated remains unclear. Here, we uncover a role of Zeb1 in defining vascular quiescence entry. During quiescence acquisition, Zeb1 increases along with the progressive decline of endothelial progenitors' activities, with Zeb1 loss resulting in endothelial overgrowth and vascular deformities. RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin sequencing (ATAC-seq) analyses reveal that Zeb1 represses Wif1, thereby activating Wnt/ß-catenin signaling. Knockdown of Wif1 rescues the overgrowth induced by Zeb1 deletion. Importantly, local administration of surrogate Wnt molecules in the retina ameliorates the overgrowth defects of Zeb1 mutants. These findings show a mechanism by which Zeb1 induces quiescence of endothelial progenitors during the establishing of vascular homeostasis, providing molecular insight into the inherited neovascular pathologies associated with human ZEB1 mutations, suggesting pharmacological activation of Wnt/ß-catenin signaling as a potential therapeutical approach.


Assuntos
Células Endoteliais , beta Catenina , Humanos , beta Catenina/metabolismo , Células Endoteliais/metabolismo , Via de Sinalização Wnt/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética
11.
Front Nutr ; 9: 962212, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36438768

RESUMO

The influence of B vitamins on human fertility and infertility treatments remains elusive. Therefore, this study investigated the association of most B vitamins with IVF-ET outcomes. A total of 216 subjects aged <35 year in their first oocyte retrieval cycle were recruited. Blood samples from the participants were collected before the oocyte pick-up procedure, and serum levels of riboflavin, niacin, pantothenic acid, vitamin B6 (including PA and PLP), folate, and methylmalonic acid (MMA) were detected using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Endpoints were classified into three groups according to tertiles (lower, middle, and upper) of each vitamin index, and the association of the serum vitamin status with intermediate and clinical outcomes was analyzed using a generalized estimating equation model. Higher riboflavin levels were associated with elevated probabilities of high-quality embryos, as well as clinical pregnancy after embryo transfer. A greater likelihood of transferable embryos was found in the middle tertile of serum folate. Similarly, a negative correlation of serum MMA, a marker of vitamin B12 deficiency, with high-quality embryos was identified. No significance was observed for other vitamins in terms of all endpoints. Therefore, sufficient levels of pre-conception riboflavin, folate, and vitamin B12 are recommended for successful infertility treatment and pregnancy planning; further evidence is needed to confirm our conclusion.

12.
Chemosphere ; 312(Pt 1): 137254, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36395892

RESUMO

Nanoparticles and antibiotics are toxic to humans and ecosystems, and they inevitably coexist in the wastewater treatment plants. Hence, the co-existence effects and stress mechanism of copper (II) oxide nanoparticles (CuO NPs) and ciprofloxacin (CIP) on simultaneous nitrification, endogenous denitrification and phosphorus removal (SNEDPR) by aerobic granular sludge (AGS) were investigated here. The co-existence stress of 5 mg/L CuO NPs and 5 mg/L CIP resulted in the synergistic inhibitory effect on nutrient removal. Transformation inhibition mechanisms of carbon (C), nitrogen (N) and phosphorus (P) with CuO NPs and CIP addition were time-dependent. Furthermore, the long-term stress mainly inhibited PO43--P removal by inhibiting phosphorus release process, while short-term stress mainly inhibited phosphorus uptake process. The synergistic inhibitory effect of CuO NPs and CIP may be due to the changes of physicochemical characteristics under the co-existence of CuO NPs and CIP. This further altered the sludge characteristics, microbial community structure and functional metabolic pathways under the long-term stress. Resistance genes analysis exhibited that the co-existence stress of CuO NPs and CIP induced the amplification of qnrA (2.38 folds), qnrB (4.70 folds) and intI1 (3.41 folds) compared with the control group.

13.
Theriogenology ; 196: 79-87, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36401935

RESUMO

Alternative polyadenylation (APA) affects the composition of cis-elements in 3'-untranslated region (3'-UTR), to regulate gene expression and localization, and subsequently the downstream biological processes. Acute heat stress could change rapidly the cellular transcriptome, however the underlying molecular changes are less explored. Here, we systematically catalogued the global 3'-UTRome dynamics, by analyzing our previously reported transcriptome sequencing data of porcine immature Sertoli (iST) cells before (Control group), acute heat stress treatment at 43 °C for 0.5h (HS0.5 group), and 36h recovery culture (HS0.5-R36h group) after acute heat stress treatment. After three group comparisons (HS0.5 vs. Control, HS0.5-R36 vs. HS0.5, and HS0.5-R36 vs. Control), DaPars (dynamic analysis of alternative polyadenylation) identified 639, 464 and 290 mRNAs, and APAtrap (a tool to identify APA sites and detect changes of APA site usage) identified 713, 518 and 321 mRNAs, with significantly different 3'-UTRs (Padj.≤0.05), respectively. These genes with different 3'-UTR patterns were mainly enriched in P53, glycolysis/gluconeogenesis, HIF-1, apoptosis, PI3K-Akt and AMPK signaling pathways. Further analysis identified that average 3'-UTR lengths of Acss2, Inpp1 and Nr1h4 were more than 140 nt longer (HS0.5-R36 vs. HS0.5), and contained different cis-elements (PAS, CPE and microRNA binding sites). Moreover, Hsp70.2, Inhbb and Dhrs were identified to have extremely different 3'-UTR abundances. Further 3'RACE assays validated several 3'-UTRs of Nr1h4, and RT-qPCR confirmed the abundance changes of different 3'-UTR isoforms for Nr1h4 and Hsp70.2. Our findings provide useful information and resources to further uncover the molecular role of 3'-UTR, in regulating the response of porcine iST cells to acute heat stress.

14.
Cell Tissue Res ; 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36422735

RESUMO

Bepridil is a commonly used medication for arrhythmia and heart failure. It primarily exerts hemodynamic effects by inhibiting Na+/K+ movement and regulating the Na+/Ca2+ exchange. In comparison to other Ca2+ inhibitors, bepridil has a long half-life and a complex pharmacology. Additionally, it is widely used in antiviral research and the treatment of various diseases. However, the toxicity of this compound and its other possible effects on embryonic development are unknown. In this study, we investigated the toxicity of bepridil on rat myocardial H9c2 cells. After treatment with bepridil, the cells became overloaded with Ca2+ and entered a state of cytoplasmic vacuolization and nuclear abnormality. Bepridil treatment resulted in several morphological abnormalities in zebrafish embryo models, including pericardium enlargement, yolk sac swelling, and growth stunting. The hemodynamic effects on fetal development resulted in abnormal cardiovascular circulation and myocardial weakness. After inhibiting the Ca2+ transmembrane, the liver of zebrafish larvae also displayed an ectopic and deficient spatial location. Additionally, the results of the RNA-seq analysis revealed the detailed gene expression profiles and metabolic responses to bepridil treatment in zebrafish embryonic development. Taken together, our study provides an important evaluation of antiarrhythmic agents for clinical use in prenatal heart patients.

15.
Plants (Basel) ; 11(21)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36365318

RESUMO

Seed germination and stand establishment are the first steps of crop growth and development. However, low seed vigor, improper seedbed preparation, unfavorable climate, and the occurrence of pests and diseases reduces the germination rate and seedling quality, resulting in insufficient crop populations and undesirable plant growth. Seed coating is an effective method that is being developed and applied in modern agriculture. It has many functions, such as improving seed vigor, promoting seedling growth, and reducing the occurrence of pests and diseases. Yet, during seed coating procedures, several factors, such as difficulty in biodegradation of coating materials and hindrance in the application of chemical ingredients to seeds, force us to explore reliable and efficient coating formulations. Biochar, as a novel material, may be expected to enhance seed germination and seedling establishment, simultaneously ensuring agricultural sustainability, environment, and food safety. Recently, biochar-based seed coating has gained much interest due to biochar possessing high porosity and water holding capacity, as well as wealthy nutrients, and has been proven to be a beneficial agent in seed coating formulations. This review presents an extensive overview on the history, methods, and coating agents of seed coating. Additionally, biochar, as a promising seed coating agent, is also synthesized on its physico-chemical properties. Combining seed coating with biochar, we discussed in detail the agricultural applications of biochar-based seed coating, such as the promotion of seed germination and stand establishment, the improvement of plant growth and nutrition, suitable carriers for microbial inoculants, and increase in herbicide selectivity. Therefore, this paper could be a good source of information on the current advance and future perspectives of biochar-based seed coating for modern agriculture.

16.
Diagn Cytopathol ; 50(12): 565-571, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36317759

RESUMO

OBJECTIVE: To explore the diagnostic value of DNA aneuploidy analysis combined with radial endobronchial ultrasound (R-EBUS)-guided transbronchial biopsy in peripheral lung lesions. METHOD: We performed a retrospective analysis of patients who underwent R-EBUS examination. DNA aneuploidy analysis of bronchial washing from the target bronchial segment were performed. The clinical information, R-EBUS data, pathological results and DNA image cytometry (DNA-ICM) results were collected. For patients who did not have a clear diagnosis after bronchoscopy, follow-up data was recorded. RESULTS: A total of 42 cases were included. Thirty patients had confirmed malignant tumor of the lung, 19 of which were confirmed by pathology after bronchoscopy, and 11 cases were confirmed later by surgery or percutaneous lung puncture. Twelve patients were finally considered to have benign lesions. The sensitivity of R-EBUS is 63.3% and the specificity is 100%. DNA-ICM has a sensitivity of 76.7% and a specificity of 91.7%. When combined, they have a sensitivity of 90%, and specificity 91.7%. As for malignant lesions, we further analyzed smoking, the size and location of lesions on chest CT, the number of aneuploid cells and the maximum value of DNA content. The results indicated that increased number of aneuploid cells or increased max value of DNA content may predict higher probability of malignancy. CONCLUSION: DNA-ICM combined with R-EBUS can improve the diagnostic sensitivity of malignant peripheral lung lesions. Increased number of aneuploid cells or increased max value of DNA content may indicate that the lesions are more likely to be malignant.


Assuntos
Neoplasias Pulmonares , Humanos , Estudos Retrospectivos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Endossonografia/métodos , Broncoscopia/métodos , Pulmão/patologia , Aneuploidia , DNA
17.
Virol J ; 19(1): 176, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329446

RESUMO

BACKGROUND: Avian influenza A H7N9 emerged in 2013, threatening public health and causing acute respiratory distress syndrome, and even death, in the human population. However, the underlying mechanism by which H7N9 virus causes human infection remains elusive. METHODS: Herein, we infected A549 cells with H7N9 virus for different times and assessed tripartite motif-containing protein 46 (TRIM46) expression. To determine the role of TRIM46 in H7N9 infection, we applied lentivirus-based TRIM46 short hairpin RNA sequences and overexpression plasmids to explore virus replication, and changes in type I interferons and interferon regulatory factor 3 (IRF3) phosphorylation levels in response to silencing and overexpression of TRIM46. Finally, we used Co-immunoprecipitation and ubiquitination assays to examine the mechanism by which TRIM46 mediated the activity of TANK-binding kinase 1 (TBK1). RESULTS: Type I interferons play an important role in defending virus infection. Here, we found that TRIM46 levels were significantly increased during H7N9 virus infection. Furthermore, TRIM46 knockdown inhibited H7N9 virus replication compared to that in the control group, while the production of type I interferons increased. Meanwhile, overexpression of TRIM46 promoted H7N9 virus replication and decrease the production of type I interferons. In addition, the level of phosphorylated IRF3, an important interferon regulatory factor, was increased in TRIM46-silenced cells, but decreased in TRIM46 overexpressing cells. Mechanistically, we observed that TRIM46 could interact with TBK1 to induce its K48-linked ubiquitination, which promoted H7N9 virus infection. CONCLUSION: Our results suggest that TRIM46 negatively regulates the human innate immune response against H7N9 virus infection.


Assuntos
Subtipo H7N9 do Vírus da Influenza A , Influenza Aviária , Influenza Humana , Interferon Tipo I , Animais , Humanos , Subtipo H7N9 do Vírus da Influenza A/genética , Ubiquitinação , Proteínas Serina-Treonina Quinases/genética
18.
Stem Cells Int ; 2022: 2361376, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338026

RESUMO

Transforming growth factor-ß1 (TGF-ß1) is an important multifunctional cytokine with dual effects on stem cell differentiation. However, the role of TGF-ß1 on odontogenic differentiation of dental pulp stem cells (DPSCs) remains to be entirely elucidated. In the present study, we initially investigated the effect of TGF-ß1 at a range of concentrations (0.1-5 ng/mL) on the proliferation, cell cycle, and apoptosis of DPSCs. Subsequently, to determine the effect of TGF-ß1 on odontogenic differentiation, alkaline phosphatase (ALP) activity and Alizarin Red S (ARS) staining assays at different concentrations and time points were performed. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis were used to determine the levels of odonto-/osteo-genic differentiation-related gene and protein expression, respectively. For in vivo studies, newly formed tissue was assessed by Masson's trichrome and von Kossa staining. Data indicated that TGF-ß1 inhibited DPSCs proliferation in a concentration-and time-dependent manner (p < 0.05) and induced cell cycle arrest but did not affect apoptosis. ALP activity was enhanced, while ARS reduced gradually with increasing TGF-ß1 concentrations, accompanied by increased expression of early marker genes of odonto-/osteo-genic differentiation and decreased expression of late-stage mineralization marker genes (p < 0.05). ALP expression was elevated in the TGF-ß1-treatment group until 14 days, and the intensity of ARS staining was attenuated at days 14 and 21 (p < 0.05). Compared with the control group, abundant collagen but no mineralized tissues were observed in the TGF-ß1-treatment group in vivo. Overall, these findings indicate that TGF-ß1 promotes odontogenic differentiation of DPSCs at early-stage while inhibiting later-stage mineralization processes.

19.
Cancer Gene Ther ; 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36369341

RESUMO

The enhancer of zeste homolog 2 (EZH2) and its highly related homolog EZH1 are considered to be epigenetic silencing factors, and they play key roles in the growth and differentiation of cells as the core components of polycomb repressive complex 2 (PRC2). EZH1 and EZH2 are known to have a role in human malignancies, and alterations in these two genes have been implicated in transformation of human malignancies. Inhibition of EZH1/2 has been shown to result in tumor regression in humans and has been studied and evaluated in the preclinical setting and in multiple clinical trials at various levels. Our work thus contributes to the understanding of the relationship between regulatory molecules associated with EZH1/2 proteins and tumor progression, and may provide new insights for mechanism-based EZH1/2-targeted therapy in tumors.

20.
Artigo em Inglês | MEDLINE | ID: mdl-36377924

RESUMO

Ring-opening transformations of donor-acceptor (D-A) cyclopropanes enable the rapid assembly of complex molecules. However, the enantioselective formation of chiral quaternary stereocenters using substrates bearing two different acceptors remains a challenge. Herein, we describe the first palladium-catalyzed highly diastereo- and enantioselective (3+2) cycloaddition of vinyl cyclopropanes bearing two different electron-withdrawing groups, a subset of D-A cyclopropanes. The key to the success of this reaction is the remote stereoinduction through hydrogen bond from chiral ligands, which thereby addressed the aforementioned challenge. A variety of chiral five-membered heterocycles were produced in good yields and with high stereoselectivity (up to 99% yields, 99:1 er and >19:1 dr). In-depth mechanistic investigations, including control experiments and theoretical calculations, revealed the origin of the stereoselectivity and the importance of H-bonding in stereocontrol.

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