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1.
J Clin Lab Anal ; : e24719, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36181286

RESUMO

BACKGROUND: Pancreatic cancer (PC) is a fatal malignancy that frequently involves perineural invasion (PNI). This study aims to investigate the function and underlying mechanisms of matrix metalloproteinase-1 (MMP1) in PNI of PC. METHODS: Human pancreatic cancer PANC-1 cells were co-cultured with dorsal root ganglion in vitro. The expression of MMP1, epithelial-mesenchymal transition (EMT) markers, Schwann cell markers, neurotrophic factors, NT-3, and TrkC was measured by qRT-PCR or Western blot. Transwell assay was performed to evaluate cell migration and invasion. In vivo model of PNI was established via inoculating PANC-1 cells into mice. PANC-1 cells and mice were also treated with LM22B-10 (an activator of TrkC) to confirm the mechanisms involving NT-3/TrkC in PNI of PC both in vivo and in vitro. RESULTS: The expression of MMP1 was significantly higher in PDAC tissues than non-cancerous tissues, which was positively associated with PNI. MMP1 knockdown repressed the migration and invasion of PANC-1 cells. Except for E-cadherin, the expression of EMT markers, Schwann cell markers, neurotrophic factors, NT-3, and TrkC was inhibited by MMP1 silencing. The same effects of MMP1 knockdown on the above factors were also observed in the PNI model. Moreover, MMP1 knockdown elevated the sciatic nerve function and reduced PNI in the model mice. LM22B-10 partially abolished the effects of MMP1 knockdown both in vivo and in vitro. CONCLUSIONS: Silencing of MMP1 prevents PC cells from EMT and Schwann-like cell differentiation via inhibiting the activation of the NT-3/TrkC signaling pathway, thus alleviating the PNI of PC.

2.
Pest Manag Sci ; 2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-36054691

RESUMO

BACKGROUND: Harmonia axyridis (Coleoptera: Coccinellidae) is a beneficial predatory arthropod in the agricultural ecosystem. For the success and development of integrated pest management strategies, it is essential to assess the toxicity risks of commonly used pesticides to nontarget arthropods. RESULTS: The glass tube residue method was used to determine the risk of nine pesticides to H. axyridis after second-instar exposure. To assess the potential risk of the selected pesticides, the pre-adult LR50 values were calculated by the hazard quotient (HQ) method. The LR50 (application rate causing 50% mortality) values of imidacloprid, dinotefuran, thiamethoxam, acetamiprid, bifenthrin, and dimethoate were 0.44, 0.82, 0.10, 0.05, 0.04, and 0.21 g a.i. ha-1 , respectively, showing unacceptable risk to H. axyridis after exposure to in and off field. However, emamectin benzoate and two fungicides, tebuconazole and myclobutanil, posed a low risk to H. axyridis and their HQ values were less than the trigger value of 5. CONCLUSIONS: The four neonicotinoid insecticides (imidacloprid, dinotefuran, thiamethoxam, and acetamiprid), pyrethroid bifenthrin, and organophosphorus dimethoate showed a high risk to H. axyridis. Emamectin benzoate, tebuconazole, and myclobutanil showed a low risk to H. axyridis under both exposure scenarios. The results provide critical scientific evidence to guide future regulation of pesticide management practices and protection of nontarget arthropods like H. axyridis. © 2022 Society of Chemical Industry.

3.
J Clin Ultrasound ; 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36069389

RESUMO

Early identification and treatment of high-risk coronary artery disease (CAD) is the main goal of current cardiovascular disease treatments. Speckle-tracking ultrasound technology can quantify myocardial work using pressure-strain loops. Because myocardial work takes into account the effect of the left ventricular systolic function afterload, it can more objectively reflect left ventricular myocardial mechanical function than the overall left ventricular longitudinal strain. Therefore, this technique is more widely used in diseases caused by CAD. This article reviews the evaluation and prediction of different CAD types using a variety of myocardial work parameters and provides a new method for clinical research to assess myocardial function, which is expected to become a new prediction method for CAD.

4.
J Oncol ; 2022: 3588117, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072975

RESUMO

Objective: Accumulating evidence suggests that DNA damage is associated with numerous gynecological illnesses, particularly advanced uterine corpus endometrial carcinoma (UCEC), illustrating the involvement of the DNA damage pathway in the advancement of UCEC. This research aimed to discover a robust subtype with the potential to contribute to the scientific treatment of UCEC. Methods: In this work, the expression patterns of prognostic DNA damage-related genes were curated, and consensus clustering analyses were undertaken to determine DNA damage subtypes in patients with UCEC in the TCGA cohort. Two DNA damage-related subtypes were identified for further investigation. Differentially expressed genes (DEGs) analysis, gene ontology analysis, mutation analysis, and immune cell infraction analysis were performed to find the molecular mechanism behind it. Finally, the polymerase chain reaction (PCR) was conducted to verify the correlation of the hub genes. Results: In total, 545 patients with UCEC were tested for two distinct DNA damage subtypes. The clinical prognosis was poorer among patients with DNA damage subtype 2 than those in subtype 1. The DEGs analysis and PPI analysis showed that ASMP, BUB1, CENPF, MAD2L1, NCAPG, SGO2, and TOP2A were expressed higher in UCEC tissues than in the normal tissues. Immune cell infraction analysis showed that hub genes were associated with the tumor microenvironment (TME). Conclusion: Altogether, our research identified two distinct DNA damage subtypes that are complicated and heterogeneous. A better knowledge of the characteristics of the TME may be gained by quantitative measurement of DNA damage subtypes in individual patients, which can also lead to the development of more successful treatment regimens.

5.
Front Mol Biosci ; 9: 962435, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090054

RESUMO

Background: Fatty acid metabolism (FAM)-related genes play a key role in the development of stomach adenocarcinoma (STAD). Although immunotherapy has led to a paradigm shift in STAD treatment, the overall response rate of immunotherapy for STAD is low due to heterogeneity of the tumor immune microenvironment (TIME). How FAM-related genes affect TIME in STAD remains unclear. Methods: The univariate Cox regression analysis was performed to screen prognostic FAM-related genes using transcriptomic profiles of the Cancer Genome Atlas (TCGA)-STAD cohort. Next, the consensus clustering analysis was performed to divide the STAD cohort into two groups based on the 13 identified prognostic genes. Then, gene set enrichment analysis (GSEA) was carried out to identify enriched pathways in the two groups. Furthermore, we developed a prognostic signature model based on 7 selected prognostic genes, which was validated to be capable in predicting the overall survival (OS) of STAD patients using the univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression analyses. Finally, the "Estimation of STromal and Immune cells in MAlignant Tumours using Expression data" (ESTIMATE) algorithm was used to evaluate the stromal, immune, and ESTIMATE scores, and tumor purity of each STAD sample. Results: A total of 13 FAM-related genes were identified to be significantly associated with OS in STAD patients. Two molecular subtypes, which we named Group 1 and Group 2, were identified based on these FAM-related prognostic genes using the consensus clustering analysis. We showed that Group 2 was significantly correlated with poor prognosis and displayed higher programmed cell death ligand 1 (PD-L1) expressions and distinct immune cell infiltration patterns. Furthermore, using GSEA, we showed that apoptosis and HCM signaling pathways were significantly enriched in Group 2. We constructed a prognostic signature model using 7 selected FAM-related prognostic genes, which was proven to be effective for prediction of STAD (HR = 1.717, 95% CI = 1.105-1.240, p < 0.001). After classifying the patients into the high- and low-risk groups based on our model, we found that patients in the high-risk group tend to have more advanced T stages and higher tumor grades, as well as higher immune scores. We also found that the risk scores were positively correlated with the infiltration of certain immune cells, including resting dendritic cells (DCs), and M2 macrophages. We also demonstrated that elevated expression of gamma-glutamyltransferase 5 (GGT5) is significantly associated with worse OS and disease-free survival (DFS), more advanced T stage and higher tumor grade, and increased immune cell infiltration, suggesting that STAD patients with high GGT5 expression in the tumor tissues might have a better response to immunotherapy. Conclusion: FAM-related genes play critical roles in STAD prognosis by shaping the TIME. These genes can regulate the infiltration of various immune cells and thus are potential therapeutic targets worthy of further investigation. Furthermore, GGT5 was a promising marker for predicting immunotherapeutic response in STAD patients.

6.
Nat Commun ; 13(1): 5462, 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36115848

RESUMO

Generalization is a fundamental cognitive ability of organisms to deal with the uncertainty in real-world situations. Excessive fear generalization and impaired reward generalization are closely related to many psychiatric disorders. However, the neural circuit mechanism for reward generalization and its role in anxiety-like behaviours remain elusive. Here, we found a robust activation of calbindin 1-neurons (Calb 1) in the posterior basolateral amygdala (pBLA), simultaneous with reward generalization to an ambiguous cue after reward conditioning in mice. We identify the infralimbic medial prefrontal cortex (IL) to the pBLACalb1 (Calb 1 neurons in the pBLA) pathway as being involved in reward generalization for the ambiguity. Activating IL-pBLA inputs strengthens reward generalization and reduces chronic unpredictable mild stress-induced anxiety- and depression-like behaviours in a manner dependent on pBLACalb1 neuron activation. These findings suggest that the IL-pBLACalb1 circuit could be a target to promote stress resilience via reward generalization and consequently ameliorate anxiety- and depression-like behaviours.


Assuntos
Complexo Nuclear Basolateral da Amígdala , Animais , Ansiedade , Calbindina 1 , Depressão , Humanos , Camundongos , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia
7.
Front Plant Sci ; 13: 978468, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119584

RESUMO

Wheat seedlings are becoming popular for its high nutritional value. Effects of White (W), White + Red (WR), and White + Blue (WB) light-emitting diodes (LEDs) treatments on growth, nutritional characteristics and antioxidant properties of wheat seedlings were studied in a plant factory. The results showed that height, leaf area, shoot fresh, and shoot dry weight per wheat seedling were the highest under WR at 13 and 22 days after planting. Soluble sugar content in leaves and stems were 22.3 and 65% respectively higher under WB than those under W. Soluble protein content in leaves and stems were 36.8 and 15.2% respectively lower under WR than those under W. Contents of total flavonoids, glutathione (GSH) and ascorbic acid (ASA) in leaves were the highest under WB, whereas malondialdehyde (MDA) content in leaves was the lowest under WB. The activities of antioxidant enzymes [superoxide dismutase (SOD), peroxidase (POD), and ascorbate peroxidase (APX)] in leaves and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability were also the highest under WB. In conclusion, WR promoted the growth of wheat seedlings, and WB promoted antioxidant level and nutritional accumulation. This study provides guidance for wheat seedlings to carry out preferential production (biomass or quality).

8.
G3 (Bethesda) ; 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36124949

RESUMO

Norovirus is the most common cause of acute gastroenteritis worldwide. During 2016-2017, a novel recombinant G II.P16-G II.2 genotype of norovirus suddenly appeared and over the next several years became the predominant strain in both China and worldwide. To better understand the origin and diffusion of the G II.P16-G II.2 genotype in China, we conducted molecular evolutionary analyses, including phylodynamics and phylogeography. Moreover, to trace person-to-person transmission of G II.P16-G II.2 norovirus, we applied the novel method, TransPhylo, to a historical phylogeny using sequences obtained from a publicly available database. A time-scaled phylogenetic tree indicated that the most recent common ancestor (tMRCA) of the G II.P16-G II.2 major capsid protein (VP1) gene diverged from the G II.P2-G II.2 VP1 gene at 2001.03 with an evolutionary rate of 3.32 × 10-3 substitutions/site/yr. The tMRCA of the G II.P16-G II.2 RNA-dependent RNA polymerase (RdRp) region diverged from the G II.P16-G II.4 RdRp region at 2013.28 with an evolutionary rate of 9.44 × 10-3 substitutions/site/yr. Of these two genomic regions, VP1 gene sequence variations were the most influenced by selective pressure. A phylogeographic analysis showed that G II.P16-G II.2 strains in China communicated most frequently with those in the United States, Australia, Thailand and Russia, suggesting import from Australia to Taiwan and from the United States to Guangdong. TransPhylo analyses indicated that the basic reproductive number (R0) and sampling proportion (pi) of G II.P16-G II.2 norovirus were 1.99 (95% CI: 1.58-2.44) and 0.76 (95% CI: 0.63-0.88), respectively. Strains from the United States and Australia were responsible for large spread during the evolution and transmission of the virus. Coastal cities and places with high population densities should be closely monitored for norovirus.

9.
Molecules ; 27(18)2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36144560

RESUMO

Gastric cancer is a common type of cancer that poses a serious threat to human health. Polysaccharides are important functional phytochemicals, and research shows that polysaccharides have good anti-gastric cancer effects. We collated all relevant literature published from 2000 to 2020 and found that more than 60 natural polysaccharides demonstrate anti-gastric cancer activity. At the present, the sources of these polysaccharides include fungi, algae, tea, Astragalus membranaceus, Caulis Dendrobii, and other foods and Chinese herbal medicines. By regulating various signaling pathways, including the PI3K/AKT, MAPK, Fas/FasL, Wnt/ß-catenin, IGF-IR, and TGF-ß signaling pathways, polysaccharides induce gastric cancer cell apoptosis, cause cell cycle arrest, and inhibit migration and invasion. In addition, polysaccharides can enhance the immune system and killing activity of immune cells in gastric cancer patients and rats. This comprehensive review covers the extraction, purification, structural characterization, and mechanism of plant and fungal polysaccharides against gastric cancer. We hope this review is helpful for researchers to design, research, and develop plant and fungal polysaccharides.


Assuntos
Polissacarídeos Fúngicos , Neoplasias Gástricas , Animais , Humanos , Fosfatidilinositol 3-Quinases , Polissacarídeos/química , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Proteínas Proto-Oncogênicas c-akt , Ratos , Neoplasias Gástricas/tratamento farmacológico , Chá , Fator de Crescimento Transformador beta , beta Catenina/metabolismo
10.
Genes (Basel) ; 13(9)2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36140689

RESUMO

Endothelial cell senescence has a vital implication for vascular dysfunction, leading to age-related cardiovascular disease, especially hypertension and atherosclerosis. E2F transcription factor 2 (E2F2) plays a critical role in cell proliferation, differentiation, and DNA damage response. Up to date, no study has ever connected E2F2 to vascular endothelial cell senescence. Here, we demonstrate that E2F2 is involved in endothelial cellular senescence. We found that E2F2 expression is decreased during the replicative senescence of human umbilical vein endothelial cells (HUVECs) and the aortas of aged mice. The knockdown of E2F2 in young HUVECs induces premature senescence characterized by an increase in senescence-associated ß-galactosidase (SA-ß-gal) activity, a reduction in phosphorylated endothelial nitric oxide synthase (p-eNOS) and sirtuin 1 (SIRT1), and the upregulation of senescence-associated secretory phenotype (SASP) IL-6 and IL-8. The lack of E2F2 promoted cell cycle arrest, DNA damage, and cell proliferation inhibition. Conversely, E2F2 overexpression reversed the senescence phenotype and enhanced the cellular function in the senescent cells. Furthermore, E2F2 deficiency downregulated downstream target genes including CNNA2, CDK1, and FOXM1, and overexpression restored the expression of these genes. Our findings demonstrate that E2F2 plays an indispensable role in endothelial cell senescence.


Assuntos
Óxido Nítrico Sintase Tipo III , Sirtuína 1 , Animais , Células Cultivadas , Senescência Celular/genética , Fatores de Transcrição E2F/metabolismo , Fator de Transcrição E2F2/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Interleucina-6 , Interleucina-8 , Camundongos , Óxido Nítrico Sintase Tipo III/metabolismo , Sirtuína 1/genética , beta-Galactosidase
11.
J Pharm Biomed Anal ; 220: 115020, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36049377

RESUMO

Artemether, an artemisinin derivative, is a component of the commonly used artemisinin-based combination therapy, artemether-lumefantrine. In this study, we cloned the VH and VL genes of a cell line (mAb 2G12E1) producing a monoclonal antibody specific to artemether, and used to construct a recombinant DNA of single-chain variable fragment (scFv). The scFv was constructed into prokaryotic expression vectors pET32a (+), pET22b (+), pGEX-2T, and pMAL-p5x, respectively. However, only the pMAL-p5x/scFv could be induced to express soluble scFv with comparable sensitivity and specificity to that of mAb 2G12E1. Based on the anti-artemether scFv, an indirect competitive enzyme-linked immunosorbent assay (icELISA) was developed. The 50% of inhibition concentration (IC50) value and the working range based on IC20 to IC80 were 4.33 ng mL-1 and 1.05-22.65 ng mL-1, respectively. The artemether content in different drugs were determined by the developed icELISA, and the results were consistent to those determined by ultra performance liquid chromatography (UPLC). The anti-artemether scFv prepared in the current study could be a valuable genetically engineered antibody applied for artemether monitoring and specific binding mechanism studying.


Assuntos
Antimaláricos , Artemisininas , Anticorpos de Cadeia Única , Anticorpos Monoclonais , Artemeter , Combinação Arteméter e Lumefantrina , Artemisininas/análise , DNA Recombinante , Ensaio de Imunoadsorção Enzimática/métodos , Anticorpos de Cadeia Única/química , Anticorpos de Cadeia Única/genética
12.
Front Mol Biosci ; 9: 907092, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36032674

RESUMO

Background : Altered basophil identification markers have been discovered to associate with allergic asthma (AA) in recent years. However, little is known about the expression of basophil markers in blood granulocytes. Aim: To parallel test blood basophils in peripheral blood mononuclear cell (PBMC) and granulocyte populations of patients with AA and AA combined with allergic rhinitis (ARA) Methods: The expressions of surface molecules were determined via flow cytometry. CD123 expressing cells in blood were isolated using a cell sorting technique, and mouse AA models were employed for in vivo study. Results: The numbers of CD123+HLA-DR- cells in the granulocytes of AA and ARA patients markedly increased. However, only 49.7% of CD123+HLA-DR- cells in granulocytes and 99.0% of CD123+HLA-DR- cells in PBMCs were basophils. Almost all CD123+HLA-DR- cells expressed CD63 regardless in granulocytes or PBMC. The numbers of CD63, Fc epsilon receptor I (FcεRI), and CD203c expressing cells markedly enhanced in CD123+HLA-DR- granulocytes of AA and ARA patients. Mean fluorescence intensity (MFI) of CD63 and CD203c expressions on CD123+HLA-DR- PBMC and granulocytes of AA and ARA patients dramatically elevated. House dust mite extract (HDME) and Artemisia sieversiana wild allergen extract (ASWE) enhanced the numbers of CD63+CD123+HLA-DR- granulocytes and PBMC and the MFI of CD203c expression on CD123+HLA-DR- granulocyte of AA and ARA patients. Histamine, tryptase, and PGD2 enhanced proportions of CD123+ KU812 cells. ASWE- and HDME-induced AA mice showed upregulated CD63 expression on basophils. In conclusion, upregulated expressions of CD123, CD203c, CD63, and FcεRIα in PBMC and granulocytes of patients with AA and ARA suggest that CD123+HLA-DR- cells may contribute to the development of AA and ARA.

13.
Front Neurosci ; 16: 910574, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35968361

RESUMO

Background: Electroacupuncture (EA) has been commonly used for the management of neck pain caused by cervical spondylosis (NPCS); however, current electrical instruments have limitations on intelligence, digitalization, and visualization. The intelligent electronic stimulator (CX-DZ-II) is a digital device with an evidence-based diagnosis and treatment system. This study aimed to investigate the efficacy and safety of the CX-DZ-II intelligent EA instrument for NPCS. Materials and Methods: A total of 164 patients with NPCS [mean age (SD), 49.48 (13.47) years] were randomly assigned to receive 8 sessions (over 2 weeks) EA of the intelligent electronic stimulator (CX-DZ-II) or the regular electronic stimulator (SDZ-II). The primary outcome was the change of the visual analog scale (VAS) from baseline to 2 weeks of treatment. Secondary outcomes included mean scores of the VAS after each treatment in 1 week, responder rate, drug-usage rate of non-steroidal antipyretic analgesics (NSAAs), the occurrence rate of adverse events (AEs), proportions of apparatus with defect during treatment, and excellent rate of apparatus. Results: The intelligent electronic stimulator (CX-DZ-II) was non-inferior to the regular electronic stimulator (SDZ-II) for changes from baseline in the VAS [3.36 vs. 3.23, with a difference of 0.17 (95% CI, -0.36 to 0.69), P < 0.025 for non-inferiority]. No between-group differences were found in outcomes of VAS in 1 week, overall responders, and drug-usage rate of NSAAs. The defect rate and excellent rate of the instrument were similar in the CX-DZ-II and SDZ-II groups. Adverse events occurred in 9 (10.84%) patients in the CX-DZ-II group and 4 (5.00%) patients in the SDZ-II group. Conclusion: The intelligent electronic stimulator (CX-DZ-II) was non-inferior to the regular electronic stimulator (SDZ-II) in relieving neck pain. The intelligent electronic stimulator (CX-DZ-II) is a promising non-inferior alternative instrument for NPCS. Clinical Trial Registration: [https://clinicaltrials.gov/], identifier [NCT030 05301].

14.
Sci Adv ; 8(35): eabo4884, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36044579

RESUMO

Although the prelimbic (PrL) area is associated with social behaviors, the neural ensembles that regulate social preference toward novelty or familiarity remain unknown. Using miniature two-photon microscopy (mTPM) to visualize social behavior-associated neuronal activity within the PrL in freely behaving mice, we found that the Ca2+ transients of GABAergic neurons were more highly correlated with social behaviors than those of glutamatergic neurons. Chemogenetic suppression of social behavior-activated GABAergic neurons in the PrL disrupts social novelty behaviors. Restoring the MeCP2 level in PrL GABAergic neurons in MECP2 transgenic (MECP2-TG) mice rescues the social novelty deficits. Moreover, we identified and characterized sparsely distributed NewPNs and OldPNs of GABAergic interneurons in the PrL preferentially responsible for new and old mouse exploration, respectively. Together, we propose that social novelty information may be encoded by the responses of NewPNs and OldPNs in the PrL area, possibly via synergistic actions on both sides of the seesaw.

15.
Proc Natl Acad Sci U S A ; 119(34): e2202821119, 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-35969743

RESUMO

Sonic hedgehog (Shh) signaling plays a critical role in regulating cerebellum development by maintaining the physiological proliferation of granule neuron precursors (GNPs), and its dysregulation leads to the oncogenesis of medulloblastoma. O-GlcNAcylation (O-GlcNAc) of proteins is an emerging regulator of brain function that maintains normal development and neuronal circuitry. Here, we demonstrate that O-GlcNAc transferase (OGT) in GNPs mediate the cerebellum development, and the progression of the Shh subgroup of medulloblastoma. Specifically, OGT regulates the neurogenesis of GNPs by activating the Shh signaling pathway via O-GlcNAcylation at S355 of GLI family zinc finger 2 (Gli2), which in turn promotes its deacetylation and transcriptional activity via dissociation from p300, a histone acetyltransferases. Inhibition of OGT via genetic ablation or chemical inhibition improves survival in a medulloblastoma mouse model. These data uncover a critical role for O-GlcNAc signaling in cerebellar development, and pinpoint a potential therapeutic target for Shh-associated medulloblastoma.


Assuntos
Neoplasias Cerebelares , Meduloblastoma , Animais , Carcinogênese/genética , Carcinogênese/metabolismo , Proliferação de Células , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/metabolismo , Cerebelo/metabolismo , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Meduloblastoma/genética , Meduloblastoma/metabolismo , Camundongos , Neurogênese/fisiologia
16.
Clin Exp Immunol ; 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36001730

RESUMO

Increased expression of substance P (SP) and neurokinin-1 receptor (NK1R) has been noticed in patients with allergic rhinitis (AR) and allergic asthma (AA). However, little is known of the expression of SP and NK1R in monocytes and B cells of AR and AA. In the present study, the expression levels of SP and NK1R were determined by flow cytometry and mouse AR and AA models. The results showed that both percentages of SP + monocytes and SP + B cells, and mean fluorescence intensity (MFI) of SP in monocytes were elevated in the blood of AA and AR combined with AA (ARA) patients. Similarly, the percentages of NK1R + monocytes were elevated in the blood of AR, AA and ARA patients. Allergens artemisia sieversiana wild allergen extract (ASWE), house dust mite extract (HDME) and platanus pollen allergen extract (PPE) increased the expression density of SP molecules (determined by MFI) in an individual monocyte of AR patients. HDME and PPE appeared to enhance SP and NK1R expression in the B cells of ARA and AR patients. In the mouse AR and AA models, the percentages of NK1R + monocytes and B cells were elevated in blood following OVA sensitization and challenge. Knocking out the FcεRI molecule completely abolished the OVA-induced upregulation of expression of NK1R in monocytes and B cells of AA mice. In conclusion, upregulated expressions of SP and NK1R may contribute to the pathogenesis of airway allergy.

17.
Front Plant Sci ; 13: 897746, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36003825

RESUMO

Plant phenotyping is essential in plant breeding and management. High-throughput data acquisition and automatic phenotypes extraction are common concerns in plant phenotyping. Despite the development of phenotyping platforms and the realization of high-throughput three-dimensional (3D) data acquisition in tall plants, such as maize, handling small-size plants with complex structural features remains a challenge. This study developed a miniaturized shoot phenotyping platform MVS-Pheno V2 focusing on low plant shoots. The platform is an improvement of MVS-Pheno V1 and was developed based on multi-view stereo 3D reconstruction. It has the following four components: Hardware, wireless communication and control, data acquisition system, and data processing system. The hardware sets the rotation on top of the platform, separating plants to be static while rotating. A novel local network was established to realize wireless communication and control; thus, preventing cable twining. The data processing system was developed to calibrate point clouds and extract phenotypes, including plant height, leaf area, projected area, shoot volume, and compactness. This study used three cultivars of wheat shoots at four growth stages to test the performance of the platform. The mean absolute percentage error of point cloud calibration was 0.585%. The squared correlation coefficient R 2 was 0.9991, 0.9949, and 0.9693 for plant height, leaf length, and leaf width, respectively. The root mean squared error (RMSE) was 0.6996, 0.4531, and 0.1174 cm for plant height, leaf length, and leaf width. The MVS-Pheno V2 platform provides an alternative solution for high-throughput phenotyping of low individual plants and is especially suitable for shoot architecture-related plant breeding and management studies.

18.
J Enzyme Inhib Med Chem ; 37(1): 2357-2369, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36039017

RESUMO

Curcumin is a natural medicine with a wide range of anti-tumour activities. However, due to ß-diketone moiety, curcumin exhibits poor stability and pharmacokinetics which significantly limits its clinical applications. In this article, two types of dicarbonyl curcumin analogues with improved stability were designed through the calculation of molecular stability by density functional theory. Twenty compounds were synthesised, and their anti-tumour activity was screened. A plurality of analogues had significantly stronger activity than curcumin. In particular, compound B2 ((2E,2'E)-3,3'-(1,4-phenylene)bis(1-(2-chlorophenyl)prop-2-en-1-one)) exhibited excellent anti-lung cancer activity in vivo and in vitro. In addition, B2 could upregulate the level of reactive oxygen species in lung cancer cells, which in turn activated the endoplasmic reticulum stress and led to cell apoptosis and pyroptosis. Taken together, curcumin analogue B2 is expected to be a novel candidate for lung cancer treatment with improved chemical and biological characteristics.


Assuntos
Antineoplásicos , Curcumina , Neoplasias Pulmonares , Antineoplásicos/química , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Diarileptanoides/farmacologia , Humanos , Neoplasias Pulmonares/patologia , Piroptose , Espécies Reativas de Oxigênio/metabolismo
19.
World J Pediatr ; 2022 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-35951258

RESUMO

BACKGROUND: Home oxygen therapy (HOT) is indicated upon discharge in some preterm infants with severe bronchopulmonary dysplasia (BPD). There is a lack of evidence-based consensus on the indication for HOT among these infants. Because wide variation in the institutional use of HOT exists, little is known about the role of regional social-economic level in the wide variation of HOT. METHODS: This was a secondary analysis of Chinese Neonatal Network (CHNN) data from January 1, 2019 to December 31, 2019. Infants at gestational ages < 32 weeks, with a birth weight < 1500 g, and with moderate or severe BPD who survived to discharge from tertiary hospitals located in 25 provinces were included in this study. Infants with major congenital anomalies and those who were discharged against medical advice were excluded. RESULTS: Of 1768 preterm infants with BPD, 474 infants (26.8%) were discharged to home with oxygen. The proportion of HOT use in participating member hospitals varied from 0 to 89%, with five of 52 hospitals' observing proportions of HOT use that were significantly greater than expected, with 14 hospitals with observing proportions significantly less than expected, and with 33 hospitals with appropriate proportions. We noted a negative correlation between different performance groups of HOT and median GDP per capita (P = 0.04). CONCLUSIONS: The use of HOT varied across China and was negatively correlated with the levels of provincial economic levels. A local HOT guideline is needed to address the wide variation in HOT use with respect to different regional economic levels in countries like China.

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