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1.
Signal Transduct Target Ther ; 6(1): 71, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33602894

RESUMO

Mitochondrial fusion/fission dynamics plays a fundamental role in neuroprotection; however, there is still a severe lack of therapeutic targets for this biological process. Here, we found that the naturally derived small molecule echinacoside (ECH) significantly promotes mitochondrial fusion progression. ECH selectively binds to the previously uncharacterized casein kinase 2 (CK2) α' subunit (CK2α') as a direct cellular target, and genetic knockdown of CK2α' abolishes ECH-mediated mitochondrial fusion. Mechanistically, ECH allosterically regulates CK2α' conformation to recruit basic transcription factor 3 (BTF3) to form a binary protein complex. Then, the CK2α'/BTF3 complex facilitates ß-catenin nuclear translocation to activate TCF/LEF transcription factors and stimulate transcription of the mitochondrial fusion gene Mfn2. Strikingly, in a mouse middle cerebral artery occlusion (MCAO) model, ECH administration was found to significantly improve cerebral injuries and behavioral deficits by enhancing Mfn2 expression in wild-type but not CK2α'+/- mice. Taken together, our findings reveal, for the first time, that CK2 is essential for promoting mitochondrial fusion in a Wnt/ß-catenin-dependent manner and suggest that pharmacologically targeting CK2 is a promising therapeutic strategy for ischemic stroke.

2.
Acta Pharmacol Sin ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33633363

RESUMO

Immune checkpoint inhibition is an important strategy in cancer therapy. Blockade of CTLA-4 and PD-1/PD-L1 is well developed in clinical practice. In the last few years, LAG-3 has received much interest as an emerging novel target in immunotherapy. It was recently reported that FGL1 is a major ligand of LAG-3, which is normally secreted by the liver but is upregulated in several human cancers. FGL1 is a crucial biomarker and target for cancer immunotherapy. As the efficacy of immunotherapy is limited to specific types of patients, the subset of patients needs to be selected appropriately to receive precise treatment according to different biomarkers. To date, there is no test to accurately assess FGL1 expression levels. Nanobodies have some outstanding features, such as high stability, solubility and affinity for diagnostic and therapeutic applications. Here, we report the development and validation of a rapid, sensitive, and cost-effective nanobody-based immunoassay for the detection of FGL1 in human serum. In this study, human FGL1 recombinant protein was expressed and purified for the first time as an immunized antigen. Then, we constructed a nanobody phage display library and screened several nanobodies that bind FGL1 with high affinity. We selected two nanobodies targeting different epitopes of FGL1, one as a capture and the other conjugated with HRP as a probe. The double nanobody-based sandwich ELISA to detect the concentration of FGL1 showed a good response relationship in the range of 15.625-2000 ng/mL, and the recoveries from the spiked sample were in the range of 78% and 100%. This assay could be used as a potential approach for evaluating FGL1 expression for patient stratification and for predicting the therapeutic efficacy of targeting the LAG3/FGL1 axis.

3.
Mol Neurobiol ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33411247

RESUMO

Somatostatin (SST) and its analogues like octreotide (OCT) have analgesic effect on a variety of pain through peripheral SST receptors (SSTRs). However, the precise molecular mechanisms have not yet been fully elucidated. This research aimed to identify possible antinociceptive mechanisms, showing functional links of the SSTR2 and acid-sensing ion channels (ASICs). Herein, we reported that OCT inhibited the electrophysiological activity of ASICs in rat dorsal root ganglia (DRG) neurons. OCT concentration-dependently decreased the peak amplitude of acid-evoked inward currents, which were mediated by ASICs. OCT shifted concentration-response curve to protons downwards, with a decrease of 36.53 ± 5.28% in the maximal current response to pH 4.5 in the presence of OCT. OCT inhibited ASIC-mediated currents through SSTR2, since the inhibition was blocked by Cyn 154806, a specific SSTR2 antagonist. The OCT inhibition of ASIC-mediated currents was mimicked by H-89, a membrane-permeable inhibitor of PKA, and reversed by internal treatment of an adenylyl cyclase activator forskolin or 8-Br-cAMP. OCT also decreased the number of action potentials induced by acid stimuli through SSTR2. Finally, peripheral administration of 20 µM OCT, but not 2 µM OCT, significantly relieved nociceptive responses to intraplantar injection of acetic acid in rats. This occurred through local activation of SSTR2 in the injected hindpaw and was reversed following co-application of Cyn 154806. Our results indicate that activation SSTR2 by OCT can inhibit the activity of ASICs via an intracellular cAMP and PKA signaling pathway in rat DRG neurons. These observations demonstrate a cross-talk between ASICs and SSTR2 in peripheral sensory neurons, which was a novel peripheral analgesic mechanism of SST and its analogues.

4.
Int J Med Sci ; 18(3): 646-651, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33437199

RESUMO

Objectives: A significant proportion of discharged COVID-19 patients still have some symptoms. Traditional Chinese medicine (TCM) has played an important role in the treatment of COVID-19, but whether it is helpful for discharged patients is still unknown. The aim of this study was to retrospectively analyze the impacts of TCM treatment on the convalescents of COVID-19. Methods: A total of 372 COVID-19 convalescents from February 21 to May 3 in Shenzhen, China were retrospectively analyzed, 291 of them accepted clinically examined at least once and 191 convalescents accepted TCM. Results: After retrospective analysis of the clinical data of convalescents accepted TCM treatment or not, we found that the white blood cell count, as well as serum interleukin-6 and procalcitonin decreased in TCM group. Serum γ-glutamyl transpeptidase was significantly decreased, while prealbumin and albumin increased in TCM group. Red blood cell, hemoglobin, and platelet count increased in TCM group. The mechanisms of TCM treatment might be the overall regulations, including balanced immune response, improved hematopoiesis and coagulation systems, enhanced functions of liver and heart, increased nutrient intake and lipid metabolism. Conclusions: This study suggested that TCM treatment would be beneficial for discharged COVID-19 patients. However, long-term medical observation and further study with randomized trial should be done to confirm this result. Besides, the potential molecular mechanisms of TCM treatment should be further revealed.


Assuntos
/reabilitação , Convalescença , Medicamentos de Ervas Chinesas/administração & dosagem , /sangue , Hospitais de Isolamento/estatística & dados numéricos , Humanos , Estudos Retrospectivos , Resultado do Tratamento
5.
Food Chem ; 348: 129091, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-33508603

RESUMO

Phospholipids are critical for milk digestion and infant development. But the profile of phospholipid molecular species in human milk and its dynamic changes during the lactation period have never been reported. The present study elucidated precise qualitative and quantitative analysis of 258 phospholipid molecular species in 486 human milk samples. Phosphatidylcholine is the most abundant class, followed by phosphatidylserine, phosphatidylethanolamine and sphingomyelin as the second abundant class in different lactation period. The plasmalogens declined along the lactation period, and the polyunsaturated-phospholipids decreased after 10-15 days. The decrease of phosphatidylcholines and phosphatidylglycerols, and the increase of lysophosphatidylethanolamines and lysophosphatidylcholines are critical changes from 0 to 5 days to 10-15 days; increase of phosphatidylinositols, phosphatidylserines, lysophosphatidylethanolamines and lysophosphatidylcholines is the key changes from 10-15 days to 40-45 days; the decrease of most phospholipid molecular species is the characteristic change from 40-45 days to 200-240 days; and the phospholipid profile achieved stability after 200 days.

6.
Int J Med Sci ; 18(2): 419-431, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390811

RESUMO

Background: In recent years, LncRNA acts as a member of competing endogenous RNA (ceRNA), playing an important role in drug resistance of lung cancer. The aim of this study was to identify potential biomarkers about cisplatin resistant lung cancer cells using a comprehensive ceRNA network. Methods: GSE6410 (GPL-201) analyzed gene expression changes about cisplatin resistance in A549 NSCLC cells. GSE43249 (GPL-14613) included noncoding RNA expression profiling derived from the cisplatin resistant A549 lung cells. GEO2R, an online analysis tool, analyzed the differentially expressed mRNAs and miRNAs (DEmRNAs and DEmiRNAs). To explore the functional enrichment implication of differentially expressed mRNAs, we used the GO (Gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis. Through miRDB, Targetscan, Starbase and miRWalk, we found targeted miRNAs. The Kaplan-Meier curve method was used to show clinical survival analysis of targeted RNAs (P<0.05). The Starbase database predicted potential lncRNAs mediated targeted miRNAs. Eventually, the novel ceRNA network of lncRNAs, miRNAs, mRNA was constructed by cytoscape3.7.2. Results: 118 differentially expressed mRNAs were the basis of the mediated ceRNA network. DAVID and Kaplan-Meier picked out BAX, an apoptosis regulator. Venn diagram demonstrated 8 miRNAs commonly regulating BAX. Starbase predicted lncRNA XIST mediated miRNAs. Finally, lncRNA XIST may be a useful biomarker regulating cisplatin resistance in lung cancer cells and further, we explored the BAX may effect tumor-infiltrating immune cells. Conclusions: LncRNA XIST competitively bound to miRNA 520 in the regulation of cisplatin resistance by BAX, participating apoptosis in the p53 signaling pathway.

7.
Mol Med Rep ; 23(1): 1, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33179078

RESUMO

Curcumin has a therapeutic effect on ulcerative colitis, but the underlying mechanism has yet to be elucidated. The aim of the present study was to clarify the possible mechanisms. Dextran sulfate sodium­induced colitis mice were treated with curcumin via gavage for 7 days. The effects of curcumin on disease activity index (DAI) and pathological changes of colonic tissue in mice were determined. Interleukin (IL)­6, IL­10, IL­17 and IL­23 expression levels were measured by ELISA. Flow cytometry was used to detect the ratio of mouse spleen regulatory T cells (Treg)/Th17 cells, and western blotting was used to measure the nuclear protein hypoxia inducible factor (HIF)­1α level. The results demonstrated that curcumin can significantly reduce DAI and spleen index scores and improve mucosal inflammation. Curcumin could also regulate the re­equilibration of Treg/Th17. IL­10 level in the colon was significantly increased, while inflammatory cytokines IL­6, IL­17 and IL­23 were significantly reduced following curcumin treatment. No significant difference in HIF­1α was observed between the colitis and the curcumin group. It was concluded that oral administration of curcumin can effectively treat experimental colitis by regulating the re­equilibration of Treg/Th17 and that the regulatory mechanism may be closely related to the IL­23/Th17 pathway. The results of the present study provided molecular insight into the mechanism by which curcumin treats ulcerative colitis.

9.
Turk J Gastroenterol ; 31(11): 819-824, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33361046

RESUMO

BACKGROUND/AIMS: This study aimed to analyze the data of 24 cases of multiple perforation or obstruction of the digestive tract caused by accidental ingestion of magnetic beads, to improve the understanding of its harmfulness to children and explore the best treatment. MATERIALS AND METHODS: In total, 24 cases were collected and retrospectively analyzed. These patients were divided into two groups: perforation group and non-perforation group. The medical history, number of magnetic beads, white blood cell (WBC) count, and C-reactive protein (CRP) were analyzed. RESULTS: There was no significant difference in age, gender, medical history, number of magnetic beads, and WBC count between the perforation group and non-perforation group, but there was a significant difference in CRP. After the diagnosis, 70% of the cases underwent laparotomy and perforation repair. All cases recovered smoothly after the operation, and no complications occurred during the follow-up. CONCLUSION: This study offers diagnosis and treatment methods for the perforation or obstruction of the digestive tract caused by accidental ingestion of magnetic beads and raises the awareness regarding the harmfulness of the presence of foreign bodies in the digestive tract.

10.
Technol Cancer Res Treat ; 19: 1533033820984177, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33357130

RESUMO

OBJECTIVE: The incidence of colorectal cancer is increasing every year, and autophagy may be related closely to the pathogenesis of colorectal cancer. Autophagy is a natural catabolic mechanism that allows the degradation of cellular components in eukaryotic cells. However, autophagy plays a dual role in tumorigenesis. It not only promotes normal cell survival and tumor growth but also induces cell death and suppresses tumors survival. In addition, the pathogenesis of various conditions, including inflammation, neurodegenerative diseases, or tumors, is associated with abnormal autophagy. The present work aimed to examine the significance of autophagy-related genes (ARGs) in prognosis prediction, to construct an autophagy prognostic model, and to identify independent prognostic factors for colorectal cancer (CRC). METHODS: This study discovered a total of 36 ARGs in CRC cases using The Cancer Genome Atlas (TCGA) and Human Autophagy-dedicated (HADd) databases along with functional enrichment analysis. Then, an autophagy prognostic model was constructed using univariate Cox regression analysis, and the key prognostic genes were screened. Finally, independent prognostic markers were determined through independent prognostic analysis and clinical correlation analysis of key genes. RESULTS: Of the 36 differentially expressed ARGs, 13 were related to prognosis, as determined by univariate Cox regression analysis. A total of 6 key genes were obtained by a multivariate Cox regression analysis. Independent prognostic values were shown by 3 genes, namely, microtubule-associated protein 1 light chain 3 (MAP1LC3C), small GTPase superfamily and Rab family (RAB7A), and WD-repeat domain phosphoinositide-interacting protein 2 (WIPI2) by independent prognostic analysis and clinical correlation. CONCLUSIONS: In this study, molecular bioinformatics technology was employed to determine and construct a prognostic model of autophagy for colon cancer patients, which revealed 3 autophagy-related features, namely, MAP1LC3C, WIPI2, and RAB7A.

11.
Front Oncol ; 10: 560779, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33163400

RESUMO

Background: Recent research has shown that immune-related lncRNA plays a crucial part in the tumor immune microenvironment. This study tried to identify immune-related lncRNAs and construct a robust prediction model to increase the predicted value of lung adenocarcinoma (LUAD). Methods: RNA expression data of LUAD were download from the Cancer Genome Atlas (TCGA) database. Immune genes were acquired from the Molecular Signatures Database (MSigDB). The immune gene related lncRNAs were acquired by the "limma R" package and Cytoscape3.7.1. Cox regression analysis was applied to construct this forecast model. The prognostic model was validated by the testing cohort which was acquired by the bootstrap method. Results: A total of 551 lncRNA expression profiles including 497 LUAD tissues and 54 non-LUAD tissues were obtained. A total of 331 immune genes were acquired. The result of the Cox regression analysis showed that seven lncRNAs (AC022784-1, NKILA, AC026355-1, AC068338-3, LINC01843, SYNPR-AS1, and AC123595-1) can be performed to construct the prediction model to forecast the prognosis of LUAD. Kaplan-Meier curves indicated that our prediction model can distribute LUAD patients into two different risk groups (high and low) with significant statistical significance (P = 1.484e-07). Cox analysis and independent analysis illustrated that the seven-lncRNAs prediction model was an isolated factor by comparing it with other clinical variables. We validated the accuracy of our model in the testing dataset. Furthermore, the prognostic model also showed higher predictive efficiency than three other published prognostic models. The two different survival groups represented diverse immune features according to principal components analysis. GSEA analysis (gene set enrichment analysis) indicated that seven-lncRNAs signatures may be involved in the progression of tumorigenesis. Conclusions: We have established a seven immune-related lncRNAs prediction model. This prognostic model had significant clinical significance that increased the predicted value and guided the personalized treatment for LUAD patients.

12.
J Agric Food Chem ; 68(43): 11939-11945, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33059450

RESUMO

Three novel dimeric bithiophenes, echinbithiophenedimers A-C (1-3), along with two known thiophenes, 4 and 5, were obtained from Echinops latifolius, and their structures were identified through extensive spectroscopic analysis and electronic circular dichroism calculations. Compounds 1-3 possessed new carbon skeletons; they are dimeric bithiophenes with 1 and 2 featuring an unprecedented 1,3-dioxolane ring system and 3 featuring an unusual 1,4-dioxane ring. These compounds are the first examples of bithiophene dimers furnished by different cyclic diethers. Dimeric bithiophenes 1-3 had good antifungal activities against five phytopathogenic fungi, and compound 3 showed excellent activity against Alternaria alternate and Pyricularia oryzae, with a minimal inhibitory concentration value of 8 µg/mL, which was close to or higher than that of carbendazim. Moreover, its effect on the mycelial morphology was observed by scanning electron microscopy. Compounds 1-3, which were demonstrated to be nonphototoxic thiophenes, exhibited better nematicidal activity than the commercial nematicide ethoprophos against Meloidogyne incognita. This study revealed that dimeric bithiophenes containing 1,3-dioxolane or 1,4-dioxane rings could be used as novel antifungal and nematicidal agents for controlling plant fungal and nematode pathogens.

13.
Int J Med Sci ; 17(16): 2427-2439, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029085

RESUMO

Background and aim: Competing endogenous RNA (ceRNA) is believed to play vital roles in tumorigenesis. The goal of this study was to screen prognostic biomarkers in lung adenocarcinoma (LUAD). Methods: Common differentially expressed genes (DEGs) were collected from Gene Expression Omnibus (GEO) databases and The Cancer Genome Atlas databases (TCGA) using GEO2R and "limma" package in R, respectively. Overlapping DEGs were conducted using enrichment of functions and protein-protein interaction (PPI) network to discover significant candidate genes. By using a comprehensive analysis, we constructed an mRNA mediated ceRNA network. Survival rates were used Kaplan-Meier analysis. Statistical analysis was used to further identify the prognosis of studied genes. Results: Integrated analysis of GSE32863 and TCGA databases, a total of 886 overlapping DEGs, including 279 up-regulated and 607 down-regulated genes were identified. Considering the highest term of candidate genes in PPI, we identified TPX2, which was enriched in cell division signaling pathway. Besides, 35 differentially expressed miRNAs (DEmiRNAs) were predicted to target TPX2 and only 7 DEmiRNAs were identified to be prognostic biomarkers in LUAD. Then, 30 differentially expressed lncRNAs (DElncRNAs) were predicted to bind these 7 DEmiRNAs. Finally, we found that 7 DElncRNAs were correlated with the overall survival (all p <0.05). Furthermore, we identified elevated TPX2 was strongly correlated with the worse survival rate among 458 samples. Univariate and multivariate cox analysis showed TPX2 may act as an independent factor for prognosis in LUAD (p <0.05). Then pathway enrichment results suggested that TPX2 may facilitate tumorigenesis by participating in several cancer-related signaling pathways in LUAD, especially in Notch signal pathway. Conclusions: TPX2-related lncRNAs and miRNAs are related to the survival of LUAD. 7 lncRNAs, 7 miRNAs and TPX2 may serve as prognostic biomarkers in LUAD.

14.
JCI Insight ; 5(19)2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33004687

RESUMO

Depression and anxiety are frequently observed in patients suffering from neuropathic pain. The underlying mechanisms remained unclear. The ventrolateral orbital cortex (VLO) has attracted considerable interest in its role in antidepressive effect in rodents. In the present study, we further investigated the role of the VLO in the anxiodepressive consequences of neuropathic pain in a chronic constriction injury of infraorbital nerve-induced trigeminal neuralgia (TN) mouse model. Elevated plus maze, open field, forced swimming, tail suspension, and sucrose preference tests were used to evaluate anxiodepressive-like behaviors. The results show that chemogenetic activation of bilateral VLO neurons, especially CaMK2A+ pyramidal neurons, blocked the TN-induced anxiodepressive-like behaviors. Chemogenetic and optogenetic activation of VGLUT2+ or inhibition of VGAT+ VLO neurons was sufficient to produce an antianxiodepressive effect in TN mice. Pharmacological activation of D1-like receptors (D1Rs) but not D2Rs in the VLO significantly alleviated TN-induced depressive-like behaviors. Electrophysiological recordings revealed a decreased excitability of VLO excitatory neurons following neuropathic pain. Furthermore, activation of submedius thalamic nucleus-VLO (Sm-VLO) projection mimicked the antianxiodepressive effect of VLO excitation. Conversely, activation of VLO-periaqueductal gray matter (PAG) projection had no effect on TN-induced anxiodepressive behaviors. This study provides a potentially novel mechanism-based therapeutic strategy for the anxiodepressive consequences of neuropathic pain.

15.
Neuropharmacology ; 181: 108356, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33069757

RESUMO

Endothelin-1 (ET-1), an endogenous vasoconstrictor, has been known as a pro-nociceptive agent involved in multitude of pain. ET-1 acts on endothelin receptors on vascular endothelial cells, sensitizes release of ATP, which then acts on P2X3 receptors on nociceptors and results in mechanical hyperalgesia. Both endothelin receptors and P2X3 receptors are present in primary sensory neuron, where it remains unclear whether there is an interaction between them. Herein, we reported that ET-1 potentiated the electrophysiological activity of P2X3 receptors in rat dorsal root ganglia (DRG) neurons. ET-1 concentration-dependently increased α,ß-methylene-ATP (α,ß-meATP)-evoked inward currents, which were mediated by P2X3 receptors. ET-1 shifted the α,ß-meATP concentration-response curve upwards, with an increase of 34.38 ± 4.72% in the maximal current response to α,ß-meATP in the presence of ET-1. ET-1 potentiation of α,ß-meATP-evoked currents was voltage-independent. ET-1 potentiated P2X3 receptor-mediated currents through endothelin-A receptors (ETAR), but not endothelin-B receptors (ETBR). ET-1 potentiation was supressed by blockade of intracellular G-protein or protein kinase C (PKC) signaling. Moreover, there is a synergistic effect on mechanical allodynia induced by intraplantar injection of ET-1 and α,ß-meATP in rats. Pharmacological blockade of P2X3 receptors also alleviated ET-1-induced mechanical allodynia. These results suggested that ET-1 sensitized P2X3 receptors in primary sensory neurons via an ETAR and PKC signaling pathway. Our data provide evidence that cutaneous ET-1 induced mechanical allodynia not only by increasing the release of ATP from vascular endothelial cells, but also by sensitizing P2X3 receptors on nociceptive DRG neurons.

16.
J Int Med Res ; 48(8): 300060520939672, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32865090

RESUMO

OBJECTIVE: We investigated physical deviation and precocious puberty among school-aged children in Leshan City, to provide a theoretical basis for the management of precocious puberty in children. METHODS: We selected 12 primary schools of Leshan City using a cluster random sampling method and conducted physical examinations among healthy students aged 4 12 years. A total of 11,000 students were recruited (5502 boys and 5498 girls). We measured body mass index (BMI), and participants were tested for precocious puberty according to the Tanner stages and standard maps. Nutritional status was also evaluated. RESULTS: Obese and overweight children accounted for a high proportion of participants; the prevalence of underweight was the lowest. The prevalence of obesity among boys was higher than that in girls. Precocious puberty was mainly observed in girls, particularly those age 7 years old. The prevalence of precocious puberty among overweight and obese children was higher than that in children with normal weight. CONCLUSION: We identified a significant sex difference in precocious puberty among children in Leshan City. Overweight and obesity may be associated with precocious puberty.

17.
Onco Targets Ther ; 13: 8069-8077, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32884292

RESUMO

Background: NY-ESO-1 is an ideal target for multiple myeloma immunotherapy. Alum, CpG ODN and HH2 complex is a safe and effective adjuvant for cancer vaccine. Methods: We constructed NY-ESO-1 protein vaccine combined with alum, CpG ODN, and HH2 complex adjuvant to immunize the BALB/c mice inoculated with NS-1 murine multiple myeloma cells. Then, we determined the immunogenicity and anti-tumor effects in prophylactic and therapeutic models by analyzing the NY-ESO-1 antibody titer, evaluating IL4/INF-γ expression, and assessing cytotoxic T lymphocytes activities. The side-effects of vaccines were also evaluated. Results: The group of NY-ESO-1 protein vaccine combining alum, CpG ODN, and HH2 complex adjuvant is more capable of stimulating both humoral and cellular tumor-specific immune responses to prolong the survival of the mice and inhibit tumor growth in prophylactic and therapeutic immunotherapy. The marked side-effects were not detected in immunized mice. Discussion: The results suggest that alum, CpG ODN, and HH2 complex as a novel immune adjuvant combined cancer vaccine could improve the immunity efficiency in a murine multiple myeloma model.

18.
Neuron ; 108(1): 180-192.e5, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-32827455

RESUMO

During development, endothelial tip cells (ETCs) located at the leading edge of growing vascular plexus guide angiogenic sprouts to target vessels, and thus, ETC pathfinding is fundamental for vascular pattern formation in organs, including the brain. However, mechanisms of ETC pathfinding remain largely unknown. Here, we report that Piezo1-mediated Ca2+ activities at primary branches of ETCs regulate branch dynamics to accomplish ETC pathfinding during zebrafish brain vascular development. ETC branches display spontaneous local Ca2+ transients, and high- and low-frequency Ca2+ transients cause branch retraction through calpain and branch extension through nitric oxide synthase, respectively. These Ca2+ transients are mainly mediated by Ca2+-permeable Piezo1 channels, which can be activated by mechanical force, and mutating piezo1 largely impairs ETC pathfinding and brain vascular patterning. These findings reveal that Piezo1 and downstream Ca2+ signaling act as molecular bases for ETC pathfinding and highlight a novel function of Piezo1 and Ca2+ in vascular development.


Assuntos
Vasos Sanguíneos/crescimento & desenvolvimento , Encéfalo/irrigação sanguínea , Cálcio/metabolismo , Células Endoteliais/metabolismo , Canais Iônicos/genética , Neovascularização Fisiológica/genética , Proteínas de Peixe-Zebra/genética , Animais , Encéfalo/crescimento & desenvolvimento , Sinalização do Cálcio , Calpaína/metabolismo , Canais Iônicos/metabolismo , Mecanotransdução Celular , Mutação , Óxido Nítrico Sintase/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismo
19.
J Agric Food Chem ; 68(34): 9061-9069, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32786848

RESUMO

Germinating seeds can release diverse phytochemicals that repel, inhibit, or kill pathogens such as root-knot nematodes and seed-borne fungi. However, little is known about the composition of these phytochemicals and their effects on pathogens. In this study, we demonstrated that tomato seed exudates can attract the nematode Meloidogyne incognita using a dual-choice assay. Eighteen compounds were then isolated and identified from the exudates. Of these, esters (1-3), fatty acids (4-6), and phenolic acids (10-12) were proven to be the signaling molecules that facilitated the host-seeking process of second-stage juveniles (J2s) of nematodes, while alkaloids (17 and 18) disrupted J2s in locating their host. Furthermore, some phenolic acids and alkaloids showed antifungal effects against seed-borne fungi. In particular, ferulic acid (12) showed obvious activity against Aspergillus flavus (minimum inhibitory concentration (MIC), 32 µg/mL), while dihydrocapsaicin (17) showed noticeable activity against Fusarium oxysporum (MIC, 16 µg/mL). Overall, this study presents the first evidence that M. incognita can be attracted to or deterred by various compounds in seed exudates through identification of the structures of the compounds in the exudates and analysis of their effects on nematodes. Furthermore, some antifungal compounds were also found. The findings of this work suggest that seed exudates are new source for finding insights into the development of plant protective substances with nematocidal and antifungal effects.

20.
J Orthop Surg Res ; 15(1): 214, 2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32517761

RESUMO

BACKGROUND: While the cities in China in which spinal cord injury (SCI) studies have been conducted previously are at the forefront of medical care, northwest China is relatively underdeveloped economically, and the epidemiological characteristics of SCI have rarely been reported in this region. METHODS: The SCI epidemiological survey software developed was used to analyze the data of patients treated with SCI from 2014 to 2018. The sociodemographic characteristics of patients, including name, age, sex, and occupation, were recorded. The following medical record data, obtained from physical and radiographic examinations, were included in the study: data on the cause of injury, fracture location, associated injuries, and level of injury. Neurological function was evaluated using the American Spinal Injury Association (ASIA) impairment scale. In addition, the treatment and complications during hospitalization were documented. RESULTS: A total of 3487 patients with SCI with a mean age of 39.5 ± 11.2 years were identified in this study, and the male to female ratio was 2.57:1. The primary cause of SCI was falls (low falls 47.75%, high falls 37.31%), followed by traffic accidents (8.98%), and impact with falling objects (4.39%). Of all patients, 1786 patients (51.22%) had complications and other injuries. According to the ASIA impairment scale, the numbers of grade A, B, C, and D injuries were 747 (21.42%), 688 (19.73%), 618 (17.72%), and 1434 (41.12%), respectively. During the hospitalization period, a total of 1341 patients experienced complications, with a percentage of 38.46%. Among all complications, pulmonary infection was the most common (437, 32.59%), followed by hyponatremia (326, 24.31%), bedsores (219, 16.33%), urinary tract infection (168, 12.53%), deep venous thrombosis (157, 11.71%), and others (34, 2.53%). Notably, among 3487 patients with SCI, only 528 patients (15.14%) received long-term rehabilitation treatment. CONCLUSION: The incidence of SCI in northwest China was on the rise with higher proportion in males; fall and the MCVs were the primary causes of SCI. The occupations most threatened by SCI are farmers and workers. The investigation and analysis of the epidemiological characteristics of SCI in respiratory complications are important factors leading to death after SCI, especially when the SCI occurs in the cervical spinal cord. Finally, the significance of SCI rehabilitation should be addressed.

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