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1.
J Ethnopharmacol ; 284: 114794, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34732357

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Danhong injection (DHI),which is extracted from Salviae miltiorrhizae and Flos carthami,has been widely prescribed to patients with unstable angina pectoris (UAP) in China. However, a high quality clinical trial is needed. AIM OF THE STUDY: To determine whether DHI can relieve symptoms of transient myocardial ischemia in patients with unstable angina pectoris. MATERIALS AND METHODS: A double-blind, placebo-controlled, randomized clinical trial was conducted in nine hospitals in China. Inpatients with UAP with blood stasis syndrome (BSS) were randomized 1:1 to receive DHI or placebo. The primary outcome was improvement rate in the quantification score of angina pectoris. Secondary outcomes included blood stasis syndrome scale, nitrates use, electrocardiogram recordings, PCI procedures, Seattle Angina Questionnaire (SAQ) and biochemical indexes. RESULTS: 160 participants were enrolled and 159 were analyzed. There was no significant difference in primary outcome as compared with control group at the end of 7-day treatment, but significant difference at 28-day follow up (70.53% [95% CI, 59.97-81.09%] and 54.34% [95% CI, 42.68-65.99%]; P = 0.0423). The BSS score was significantly lower in the DHI group than that in the control group at day 28 (6.49 [6.96] vs 10.53 [9.07], P = 0.0034). In addition, DHI was significantly superior to placebo in the angina stability score of SAQ (91.10 [17.37] versus 78.21 [22.08], P < 0.001). There were no significant differences in other secondary outcome measures. CONCLUSIONS: A small decrease in the total effective rate and an increase in the angina stability score were observed 28 days after implementation of DHI in UAP with a total blood stasis syndrome score decrease, but the efficacy was not observed at day 7. The findings support that DHI may potentially relieve clinical symptoms and can benefit angina stability. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02007187.

2.
Nat Genet ; 53(10): 1493-1503, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34594040

RESUMO

How two subgenomes in allo-tetraploids adapt to coexistence and coordinate through structure and expression evolution requires extensive studies. In the present study, we report an improved genome assembly of allo-tetraploid common carp, an updated genome annotation of allo-tetraploid goldfish and the chromosome-scale assemblies of a progenitor-like diploid Puntius tetrazona and an outgroup diploid Paracanthobrama guichenoti. Parallel subgenome structure evolution in the allo-tetraploids was featured with equivalent chromosome components, higher protein identities, similar transposon divergence and contents, homoeologous exchanges, better synteny level, strong sequence compensation and symmetric purifying selection. Furthermore, we observed subgenome expression divergence processes in the allo-tetraploids, including inter-/intrasubgenome trans-splicing events, expression dominance, decreased expression levels, dosage compensation, stronger expression correlation, dynamic functionalization and balancing of differential expression. The potential disorders introduced by different progenitors in the allo-tetraploids were hypothesized to be alleviated by increasing structural homogeneity and performing versatile expression processes. Resequencing three common carp strains revealed two major ecotypes and uncovered candidate genes relevant to growth and survival rate.


Assuntos
Carpas/genética , Evolução Molecular , Regulação da Expressão Gênica , Genoma , Carpa Dourada/genética , Tetraploidia , Processamento Alternativo/genética , Animais , Sequência de Bases , Variação Genética , Cariótipo , Funções Verossimilhança , Anotação de Sequência Molecular , Filogenia , Seleção Genética , Especificidade da Espécie , Sintenia/genética
3.
J Exp Clin Cancer Res ; 40(1): 290, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526098

RESUMO

BACKGROUND: Accumulating evidence indicates that circRNAs may serve as essential regulators in the progression of several human cancers, but the function and mechanism of circRNAs in intrahepatic cholangiocarcinoma (ICC) are largely unknown. METHODS: RNA-seq was used to assess differentially expressed circRNAs between 4 ICC and peritumor tissues. Quantitative RT-PCR and in situ hybridization were used to determine the circHMGCS1-016 expression in ICC tissues. The function and mechanism of circHMGCS1-016 were further identified via in vivo experiments. The clinical characteristics and prognostic significance of circHMGCS1-016 were analyzed by a retrospective study. The functions of circHMGCS1-016 were assessed via modifying circRNA expression in ICC cells. Moreover, the molecular mechanisms of circHMGCS1-016 in ICC cells were explored by circRNA precipitation, miRNA immunoprecipitation, SILAC and luciferase reporter assays. RESULTS: We identified that compared with peritumor tissues, ICC tissues expressed hsa_circ_0008621 (circHMGCS1-016) high by RNA-seq, which was further identified by qRT-PCR and in situ hybridization. Moreover, the expression of circHMGCS1-016 was revealed to be associated with survival and recurrence of ICC patients. By regulating circHMGCS1-016 expression, we found that elevated circHMGCS1-016 promoted ICC development both in vitro and in vivo. By SILAC and circRNA-pull down, we demonstrated that circHMGCS1-016 induced ICC cell invasion and reshaped the tumor immune microenvironment via the miR-1236-3p/CD73 and GAL-8 axis. In ICC tissues, we uncovered that a high level of circHMGCS1-016 was positively associated with CD73 and GAL-8 expression and negatively related to the CD8+ T cells infiltration, which was further validated by establishing a humanized mouse tumor model. Importantly, we displayed that ICC patients with high levels of circHMGCS1-016 in tumor tissues benefited less from anti-PD1 treatment compared to those with low levels of circHMGCS1-016. CONCLUSIONS: CircHMGCS1-016 is a forceful contributor in ICC development and immune tolerance via miR-1236-3p/CD73 and GAL-8 axis. CircHMGCS1-016 can be explored as a new potential biomarker and therapeutic target for PD1-resistant ICC.

4.
J Cancer ; 12(15): 4655-4660, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149929

RESUMO

Background: Despite recent improvements in the diagnosis and therapy of intrahepatic cholangiocarcinoma (ICC), the prognosis for ICC patients remains poor. Therefore, it is needed to identify new biological indicators for ICC progression. Methods: Immunohistochemistry was engaged to inspect the ecto-5'-nucleotidase (CD73) and CD8 expressions in tissue microarrays including tissues from 140 ICC patients. Then, the association between the level of CD73/CD8 and clinicopathologic characteristics of ICC was analysed. Finally, the prognostic value of CD73 and CD8 levels in ICC patients was assessed by Kaplan-Meier and multivariate and univariate analyses. Results: The CD73 expression was evidently upregulated in ICC tissues compared to the corresponding peritumoral tissues. The elevated CD73 expression was positively related to the lymphatic metastasis (p=0.049). While the level of tumour-infiltrating CD8 T+ cells in tumour tissues was negatively associated with serum AFP (p=0.019), tumor size (p=0.028), and lymphatic metastasis (p=0.039). Additionally, patients with elevated CD73 expression or low tumour-infiltrating CD8+ T cells exhibited shorter overall survival (OS) and higher disease-free survival (DFS) rates than patients with low CD73 expression and/or high tumour-infiltrating CD8+ T cells. Notably, the overexpression of CD73 or low tumour-infiltrating CD8+ T cells was an independent indicator for predicting the OS and DFS of ICC patients. Conclusions: We revealed that CD73 expression and low tumour-infiltrating CD8+T cells are valuable predictors of survival and recurrence in patients with ICC.

5.
Mol Biol Rep ; 48(3): 2399-2410, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33742327

RESUMO

BACKGROUND: Teleost scale not only provides a protective layer resisting penetration and pathogens but also participate in coloration. It is interesting to study the mechanism of teleost scale formation. Furthermore, whether there existed consensus genes between scale coloration and skin coloration has not been examined yet. METHODS AND RESULTS: We analyzed the transcriptome profiles of red scale, white scale, red skin, and white skin of common carp (Cyprinus carpio). Pair-wise comparison identified 3391 differentially expressed genes (DEGs) between scale and skin, respectively. The 1765 up-regulated genes (UEGs) in scale, as the down-regulated genes in skin, preferred mineralization and other scale development-related processes. The 1626 skin UEGs were enriched in the morphogenesis of skin and appendages. We also identified 195 UEGs in white scale and 223 UEGs in red scale. The white scale UEGs primarily participated in regulation of growth and cell migration. The UEGs in red scale preferred pigment cell differentiation and retinoid metabolic process. A total of 22 DEGs had consensus expression patterns in skin and scale of the same coloration. The expression levels of these DEGs clearly grouped skin and scale of the same coloration together with principle component analysis and correlation analysis. Eleven consensus DEGs were homologous to the orthologs of Poropuntius huangchuchieni, 82% of which were under strong purifying selection. Eight processes including lipid storage and lipid catabolism were shared in both scale pigmentation and skin pigmentation. CONCLUSIONS: We identified consensus DEGs and biological processes in scale and skin pigmentation. Our transcriptome analysis will contribute to further elucidation of mechanisms of teleost scale formation and coloration.


Assuntos
Carpas/genética , Análise de Sequência de RNA , Pigmentação da Pele/genética , Transcriptoma/genética , Escamas de Animais/metabolismo , Animais , Sequência Conservada/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Genoma , Especificidade de Órgãos/genética , Pele/metabolismo
6.
Dig Dis Sci ; 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33576946

RESUMO

BACKGROUND: Elevated expression of eukaryotic initiation factor 3c (eIF3C) was recently uncovered to promote several types of cancer progression by inducing cell proliferation. Here, we aimed to assess the expression and prognostic value of eIF3C in intrahepatic cholangiocarcinoma (ICC) patients. METHODS: Expression of eIF3C was analyzed by immunohistochemistry in tissue microarrays (TMAs) containing 138 ICC and paired peritumoral tissues from ICC patients. Then, the roles of eIF3C in ICC cells were investigated by RNA interference, and the relationship between the eIF3C and KI67 expression was explored in ICC cells and tissues. Finally, the relation between the eIF3C level and clinicopathologic features of ICC was probed, and Kaplan-Meier and Cox's analyses were performed to assess the prognostic merit of eIF3C and KI67 in ICC patients. RESULTS: The expression of eIF3C was elevated in ICC tissues compared to paired peritumoral tissues, which was consistent with the result from the GEPIA database. The downregulation of eIF3C in ICC cells impaired the cellular invasion, metastasis, colony formation, and proliferation. Moreover, we further found a positive relationship between the eIF3C and KI67 expression in ICC cells and tissues. The expression of eIF3C in ICC tissues was positively correlated with lymphatic metastasis (p = 0.049), and the high level of KI67 was frequently found in ICC patients with the large tumor (p = 0.028), high serum AFP (p = 0.019), or lymphatic metastasis (p = 0.039). Notably, patients with the eIF3C or KI67 overexpression had shorter overall survival and higher disease-free survival rates than those with low expression of eIF3C or KI67, and the combination of eIF3C or KI67 expression was an independent parameter for predicting the prognosis and recurrence of ICC patients. CONCLUSIONS: Elevated eIF3C expression promotes ICC development, and combination of eIF3C and KI67 is a valuable predictor of the survival and recurrence of ICC patient.

7.
Genomics ; 113(1 Pt 2): 601-612, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33002624

RESUMO

Lepidoptera (moths and butterflies) and Trichoptera (caddisflies), belonging to the superorder Amphiesmenoptera, are the most diverse insect orders as representatives of the terrestrial and aquatic insects, respectively. The insects of the two orders possess different biological and behavioral characteristics, especially their larvae, presumably resulting in the differences of the ionotropic receptor (IR) genes in numbers, sequence characteristics or gene structure. Here, we employed genomics, transcriptomics, bioinformatics, phylogenetics and molecular biology strategies to characterize the IR gene repertoire in Lepidoptera and Trichoptera. Genome and transcriptome analyses with exhaustive homology-based searches and manual efforts, in 32 lepidopterans and five trichopterans, led to the identification of 1449 genes encoding IRs with 1170 full-length sequences, representing the most comprehensive set of chemoreceptor superfamilies across the Amphiesmenoptera. Analysis of gene gains and losses in orthologous groups implied that some IRs were lost in related species, and multiple gene copies occurred mainly in divergent IRs (D-IRs) by gene duplications. Phylogenetic analysis of 2442 IR proteins from 67 species revealed that Lepidoptera and Trichoptera IRs could be classified into three subfamilies, i.e., 14 antennal IRs (A-IRs), five Lepidoptera-specific IRs (LS-IRs) and four D-IRs. Of the three subfamilies, A-IRs and LS-IRs members within orthologous groups exhibited high conservation of gene structure, but D-IRs shared extremely low amino acid identities (below 30%). Expression profiles revealed functional diversities of IRs from Bombyx mori and Papilio xuthus involving smell, taste or reproduction, in which some genes displayed sex-biased expression in antennae associated with specific chemosensory behaviors of female or male adults. Our current study has provided insights into the evolution, conservation and divergence of IRs between/within Lepidoptera and Trichoptera, and allows for further experiments to investigate IR functions.

8.
Dig Dis Sci ; 66(2): 474-482, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32193860

RESUMO

BACKGROUND: Liver metastasis is an indicator of unfavorable responses to immunotherapy in colorectal cancer patients. However, the difference of immune microenvironment between primary tumors and liver metastases has not been well understood. PATIENTS AND METHODS: Fifty-four colon cancer with liver metastasis patients who received resection of both primary and metastasis lesions have been analyzed. The immune score is based on the density of infiltrating immune cells (CD3+ cell, CD8+ cell, CD11b+ cell, CD11c+ cell, and CD33+ cell) in the center and margin of the tumor. The expression of immune markers between the primary tumor and hepatic metastases was analyzed using Wilcoxon's signed rank test. RESULTS: All the five markers had higher expression in tumor margins than center tumor in both primary tumor and hepatic metastases lesions. The expression of CD11c and CD11b had no difference between metastatic lesions and primary tumor. In tumor margins, except CD11b, all the other 4 markers expressed significantly higher in hepatic metastases than in primary tumor. Intra-tumor, CD3 had higher expression in primary tumor than in hepatic metastases, while CD33 had higher expression in hepatic metastases than in primary tumor. CD8+ CD3+ cells of the total CD8+ cell population in primary tumor was significantly higher than in hepatic metastases (36.42% vs. 24.88%, p = 0.0069). CONCLUSIONS: The immune microenvironment between primary tumor and hepatic metastasis is different. More immunosuppressing cells in liver may partially explain why immunotherapy in colon cancer is less effective with liver metastatic disease.


Assuntos
Biomarcadores , Neoplasias do Colo/imunologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/secundário , Microambiente Tumoral/fisiologia , Neoplasias do Colo/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Estudos Retrospectivos , Linfócitos T/imunologia , Linfócitos T/patologia
9.
Genet Mol Biol ; 43(4): e20190266, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33063817

RESUMO

Herein, we aimed to investigate the functions of ADAMTS6 in colon cancer and its potential mechanism. Based on the data acquired from TCGA database, we revealed that ADAMTS6 was highly expressed in colon cancer tissues, and high expression of ADAMTS6 predicted worse prognosis in patients with colon cancer. Moreover, qRT-PCR demonstrated that the levels of ADAMTS6 were higher in colon cancer cell lines (NCI-H508, Caco-2, CW-2 and HCT 116) than that in normal control cell line CCD-18Co. Functional experiments displayed that depletion of ADAMTS6 repressed NCI-H508 cell growth, invasion and migration whilst overexpression of ADAMTS6 facilitated Caco-2 cell growth, invasion and migration. Moreover, ADAMTS6 silencing enhanced the protein expression of E-cadherin and reduced the levels of N-cadherin, Vimentin and Snail in NCI-H508 cells, whereas ADAMTS6 overexpression showed the counter effects in Caco-2 cells. The protein levels of p-AKT and p-p65 were decreased by depletion of ADAMTS6 in NCI-H508 cells, while their levels were enhanced by overexpression of ADAMTS6 in Caco-2 cells. These consequences indicated that the accelerating effect of ADAMTS6 on colon cancer cell growth, migration and invasion might be achieved by modulating EMT and AKT/NF-κB signaling pathway, offering important foundations for colon cancer treatment.

10.
Oxid Med Cell Longev ; 2020: 8291413, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32774686

RESUMO

Aging is an important risk factor in the occurrence of many chronic diseases. Senescence and exhaustion of adult stem cells are considered as a hallmark of aging in organisms. In this study, a senescent human amniotic mesenchymal stem cell (hAMSC) model subjected to oxidative stress was established in vitro using hydrogen peroxide. We investigated the effects of ganoderic acid D (GA-D), a natural triterpenoid compound produced from Ganoderma lucidum, on hAMSC senescence. GA-D significantly inhibited ß-galactosidase (a senescence-associated marker) formation, in a dose-dependent manner, with doses ranging from 0.1 µM to 10 µM, without inducing cytotoxic side-effects. Furthermore, GA-D markedly inhibited the generation of reactive oxygen species (ROS) and the expression of p21 and p16 proteins, relieved the cell cycle arrest, and enhanced telomerase activity in senescent hAMSCs. Furthermore, GA-D upregulated the expression of phosphorylated protein kinase R- (PKR-) like endoplasmic reticulum kinase (PERK), peroxidase III (PRDX3), and nuclear factor-erythroid 2-related factor (NRF2) and promoted intranuclear transfer of NRF2 in senescent cells. The PERK inhibitor GSK2656157 and/or the NRF2 inhibitor ML385 suppressed the PERK/NRF2 signaling, which was activated by GA-D. They induced a rebound for the generation of ROS and ß-galactosidase-positive cells and attenuated the differentiation capacity. These findings suggest that GA-D retards hAMSC senescence through activation of the PERK/NRF2 signaling pathway and may be a promising candidate for the discovery of antiaging agents.


Assuntos
Células-Tronco Mesenquimais/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Triterpenos/uso terapêutico , Envelhecimento , Senescência Celular , Humanos , Estresse Oxidativo , Fatores de Risco , Transdução de Sinais , Triterpenos/farmacologia
11.
Mol Med Rep ; 21(6): 2357-2366, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32236637

RESUMO

CD44 antigen (CD44) is a transmembrane protein found in cell adhesion molecules and is involved in the regulation of various physiological processes in cells. It was hypothesized that CD44 directly affected the chondrogenic differentiation of human amniotic mesenchymal stem cells (hAMSCs). In the present study, the expression of chondrocyte­associated factors was detected in the absence and presence of the antibody blocker anti­CD44 antibody during the chondrogenic differentiation of hAMSCs. Following inhibition of CD44 expression, the transcriptional levels of chondrocyte­associated genes SRY­box transcription factor 9, aggrecan and collagen type II α 1 chain, as well as the production of chondrocyte markers type II collagen and aggrecan were significantly decreased in hAMSCs. Further investigation indicated that there was no significant change in total ERK1/2 expression following inhibition of CD44 expression; however, phosphorylated (p)­ERK1/2 expression was decreased. The expression of p­Smad2/3 was also upregulated following CD44 inhibition. These data indicated that CD44 may affect the differentiation of hAMSCs into chondrocytes by regulating the Smad2/3 and ERK1/2 signaling pathway.


Assuntos
Âmnio/metabolismo , Diferenciação Celular/efeitos dos fármacos , Condrócitos/metabolismo , Receptores de Hialuronatos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Transdução de Sinais/efeitos dos fármacos , Agrecanas/metabolismo , Condrogênese/efeitos dos fármacos , Colágeno Tipo II/metabolismo , Humanos , Receptores de Hialuronatos/genética , Sistema de Sinalização das MAP Quinases , Fosforilação , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo
12.
Comp Biochem Physiol B Biochem Mol Biol ; 243-244: 110431, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32142896

RESUMO

The longhorned beetles, Rhaphuma horsfieldi and Xylotrechus quadripes, are two polyphagous insects with larvae feeding on different host plants. In this study, we identified and characterized three gene superfamilies of cytochrome P450s (CYPs), carboxylesterases (COEs) and glutathione-S-transferases (GSTs) involved in the detoxification of endobiotics (e.g., hormones and steroids) and xenobiotics (e.g., insecticides, sex pheromones and plant allelochemicals) through a combination approach of bioinformatics, phylogenetics, expression profiles and genomics. Transcriptome analyses led to the identification of 281 transcripts encoding 135 P450s, 108 COEs and 38 GSTs from the two beetles, coupled with comparative studies of detoxification genes among coleopteran species, suggesting a correlation between host range and the sizes of P450 or COE gene repertoires. The P450s of two beetles were phylogenetically classified into four clades, representing the majority of genes in the CYP3 clan. The COEs from R. horsfieldi and X. quadripes were separately grouped into 11 and 10 clades, and the GST superfamily was assigned into six clades. Expression profiles revealed that the detoxification genes were broadly expressed in various tissues as an implication of functional diversities. Ultimately and more importantly, five alternative splicing events in the Epsilon GSTs, including RhorGSTe7.1/GSTe7.2 and XquaGSTe3.1/GST3.2, were acquired in Coleoptera, in which these genes and their orthologs shared highly conserved gene structure. Our current study has complemented the resources for the detoxification genes in the family Cerambycidae, and allows for functional experiments to identify candidate molecular targets involved in pest resistance to insecticides like organophosphates, organochlorines and pyrethroids.


Assuntos
Hidrolases de Éster Carboxílico/genética , Besouros/genética , Sistema Enzimático do Citocromo P-450/genética , Glutationa Transferase/genética , Inseticidas/metabolismo , Processamento Alternativo , Animais , Hidrolases de Éster Carboxílico/metabolismo , Clonagem Molecular , Besouros/enzimologia , Sistema Enzimático do Citocromo P-450/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Hidrocarbonetos Clorados/metabolismo , Hidrocarbonetos Clorados/toxicidade , Inativação Metabólica , Filogenia , Piretrinas/metabolismo , Piretrinas/toxicidade
13.
Genomics ; 112(4): 2713-2728, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32145380

RESUMO

Through an exhaustive homology-based approach, coupled with manual efforts, we annotated and characterized 128 sensory neuron membrane proteins (SNMPs) from genomes and transcriptomes of 22 coleopteran species, with 107 novel candidates. Remarkably, we discovered, for the first time, a novel SNMP group, defined as Group 4 based on the phylogeny, sequence characteristics, gene structure and organization. The lineage-specific expansions in SNMPs occurred mainly in the family Scarabaeidae, harboring 12 representatives in Onthophagus taurus as a typical gene duplication and the most massive set of SNMPs in insects to date. Transcriptome sequencing of Rhaphuma horsfieldi resulted in the yields of approximately 611.9 million clean reads that were further assembled into 543,841 transcripts and 327,550 unigenes, respectively. From the transcriptome, 177 transcripts encoding 84 odorant (ORs), 62 gustatory (GRs), 20 ionotropic (IRs), and 11 ionotropic glutamate (iGluRs) receptors were identified. Phylogenetic analysis classified RhorORs into six groups, RhorGRs into four subfamilies, and RhorIRs into 10 conserved antennal IRs and one divergent IRs. Expression profiles revealed that over 80% of chemosensory genes were specifically or highly transcribed in antennae or tarsi, suggestive of their olfactory and/or gustatory roles. This study has greatly complemented the resources for chemosensory genes in the cerambycid beetles, and most importantly, identifies a novel group of SNMPs in Coleoptera.


Assuntos
Besouros/genética , Proteínas de Insetos/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Receptores de Superfície Celular/genética , Animais , Feminino , Genes de Insetos , Genoma de Inseto , Proteínas de Insetos/classificação , Masculino , Proteínas de Membrana/classificação , Família Multigênica , Proteínas do Tecido Nervoso/classificação , Filogenia , Receptores Odorantes/classificação , Receptores Odorantes/genética , Transcriptoma
14.
Artigo em Inglês | MEDLINE | ID: mdl-32211385

RESUMO

Osteoarthritis (OA) is one of the most common refractory degenerative articular cartilage diseases. Human amniotic mesenchymal cells (hAMSCs) have emerged as a promising stem cell source for cartilage repair, and hyaluronic acid (HA) has proven to be a versatile regulator for stem cell transplantation. Herein, an effective and straightforward intra-articular injection therapy using a cocktail of hAMSCs and HA was developed to treat knee OA in a rat model. The injured cartilage was remarkably regenerated, yielding results comparable to normal cartilage levels after 56 days of treatment. Both hAMSCs and HA were indispensable organic components in this therapy, in which HA could synergistically enhance the effects of hAMSCs on cartilage repair. The regenerative mechanism was attributed to the fact that the addition of HA comprehensively enhances the activities of hAMSCs, including chondrogenic differentiation, proliferation, colonization, and regenerative modulation. This cocktail paves a new avenue for injection therapy to treat OA, holding the potential to realize rapid clinical translation.

15.
Exp Cell Res ; 384(2): 111642, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31562862

RESUMO

Our hypothesis is that hyaluronic acid may regulate the differentiation of human amniotic epithelial cells (hAECs) into insulin-producing cells and help the treatment of type 1 diabetes. Herein, a protocol for the stepwise in vitro differentiation of hAECs into functional insulin-producing cells was developed by mimicking the process of pancreas development. Treatment of hAECs with hyaluronic acid enhanced their differentiation of definitive endoderm and pancreatic progenitors. Endodermal markers Sox17 and Foxa2 and pancreatic progenitor markers Pax6, Nkx6.1, and Ngn3 were upregulated an enhanced gene expression in hAECs, but hAECs did not express the ß cell-specific transcription factor Pdx1. Interestingly, hyaluronic acid promoted the expression of major pancreatic development-related genes and proteins after combining with commonly used inducers of stem cells differentiation into insulin-producing cells. This indicated the potent synergistic effects of the combination on hAECs differentiation in vitro. By establishing a multiple injection transplantation strategy via tail vein injections, hAECs transplantation significantly reduced hyperglycemia symptoms, increased the plasma insulin content, and partially repaired the islet structure in type 1 diabetic mice. In particular, the combination of hAECs with hyaluronic acid exhibited a remarkable therapeutic effect compared to both the insulin group and the hAECs alone group. The hAECs' paracrine action and hyaluronic acid co-regulated the local immune response, improved the inflammatory microenvironment in the damaged pancreas of type 1 diabetic mice, and promoted the trans-differentiation of pancreatic α cells into ß cells. These findings suggest that hyaluronic acid is an efficient co-inducer of the differentiation of hAECs into functional insulin-producing cells, and hAECs treatment with hyaluronic acid may be a promising cell-replacement therapeutic approach for the treatment of type 1 diabetes.


Assuntos
Âmnio/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/terapia , Células Epiteliais/efeitos dos fármacos , Ácido Hialurônico/farmacologia , Ativinas/metabolismo , Âmnio/metabolismo , Animais , Técnicas de Cultura de Células/métodos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Células Cultivadas , Modelos Animais de Doenças , Células-Tronco Embrionárias/efeitos dos fármacos , Células-Tronco Embrionárias/metabolismo , Endoderma/efeitos dos fármacos , Endoderma/metabolismo , Células Epiteliais/metabolismo , Humanos , Inflamação/metabolismo , Insulina/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Masculino , Camundongos , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo
16.
Life Sci ; 232: 116669, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31326566

RESUMO

AIMS: This study investigated the effects of hyaluronic acid (HA), a commonly used osteogenic medium referred to as DAG, and the combined administration of HA and DAG (CG) on the osteogenic differentiation of human amniotic mesenchymal stem cells (hAMSCs), and the underlying mechanism. MAIN METHODS: The phenotype of hAMSCs was detected by flow cytometry and immunocytochemical staining. Alkaline phosphatase (ALP) and calcium deposition assays were employed for evaluating the osteogenic differentiation of hAMSCs. The expression of osteogenesis-related genes and proteins was determined by quantitative reverse transcription PCR (qRT-PCR) and Western blotting, respectively. Meanwhile, the molecular mechanism of osteogenic differentiation of hAMSCs was detected by PCR array and qRT-PCR. KEY FINDINGS: The results showed that treatment with CG could significantly stimulate hAMSC ALP activity and calcium deposition compared to treatment with DAG, while HA had little effect. The expression of osteogenesis-related molecules and stemness-related molecules was up-regulated at the mRNA and protein levels in all three groups, and this up-regulation was most significant in the CG group. In addition, treatment with CG significantly increased the gene expressions involved in regulation of the TGF-ß/Smad signalling pathway compared to treatment with DAG. Furthermore, the pro-osteogenic differentiation effects as well as the up-regulated expression of genes observed in the CG treatment group were significantly inhibited when the cells were pre-treated with SB431542, an inhibitor of the TGF-ß/Smad pathway. SIGNIFICANCE: These results suggest that HA in combination with DAG could significantly enhance the osteogenic differentiation of hAMSCs, potentially via the TGF-ß/Smad signalling pathway.


Assuntos
Âmnio/citologia , Diferenciação Celular/efeitos dos fármacos , Ácido Hialurônico/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Transdução de Sinais , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Células Cultivadas , Humanos , Ácido Hialurônico/química , Células-Tronco Mesenquimais/citologia , Peso Molecular
17.
J Nanosci Nanotechnol ; 19(12): 7532-7538, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31196257

RESUMO

Nanostructured Fe3O4/C composites are very attractive for high-performance magnetic targeted drug carriers. Herein, Fe3O4/C composite nanospheres with good dispersity are prepared by a simple one-step hydrothermal synthesis and subsequent heat treatment in Ar. The composite nanospheres consist of clustered primary nanoparticles, and exhibit a hierarchical architecture with a high specific surface area of 119.3 m² g-1. The Fe3O4/C composite nanospheres show a high saturation magnetization value of 101 emu g-1 and good biocompatibility. In particular, the composite nanospheres deliver a large loading content (85.8%) of epirubicin hydrochloride (EPI), resulting from their unique composition and microstructure. More importantly, the release of EPI from the EPI-loaded magnetic carrier (Fe3O4/C-EPI) may be enhanced by both a slightly acidic environment and a rotating magnetic field induced by a simple motor-driven magnet system. The above favorable properties make the hierarchical Fe3O4/C composite sample a promising candidate for magnetic targeting nanocarriers of EPI.


Assuntos
Hipertermia Induzida , Nanopartículas , Preparações Farmacêuticas , Epirubicina , Fenômenos Magnéticos
18.
Ecotoxicol Environ Saf ; 166: 446-452, 2018 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-30292111

RESUMO

A new theoretical method was established for the combinatorial calculation of the dissociation rate constant (K-1) of the metal-organic complexes (MLs), the concentration of free ionic soil metals (CM), the labile concentration of soil metal-organic complexes (CML) based on diffusive gradients in thin-films (DGT) technique with a range of diffusive layer thicknesses (0.053-0.173 mm) in soils. The fitting results agreed well with the determined values. The values of K-1, CML and CM were calculated without other morphological analysis software and the fitting results agreed well with the determined values with some advantages such as the use of fewer hypothetical parameters, ease of calculation, the full embodiment of the contribution of MLs to the labile content. According to the results of model fitting, cation exchange capacity and soil organic matter were found to be the key environmental factors for K-1 values of Cd and Ni, respectively. The labile contents of Cd and Ni in soil were closely related with pH, soil organic matter and the total contents of heavy metals.


Assuntos
Cádmio/análise , Monitoramento Ambiental/métodos , Níquel/análise , Poluentes do Solo/análise , Solo/química , Difusão , Cinética
19.
Oncol Lett ; 16(4): 4480-4488, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30214583

RESUMO

Recent studies have demonstrated that the overexpression of H19 may contribute towards development of tumorigenesis in various types of cancer. To investigate the role of H19 in the development of non-small cell lung cancer (NSCLC), 76 NSCLC tissues samples and their adjacent normal tissue samples were collected. Expression level of H19, and its association with clinicopathological features and overall survival was analyzed. It was found that compared with normal adjacent tissues, H19 expression was elevated in NSCLC tissues along with a decreased miR-203 expression level. It was also found that patients who were in advanced clinical stages had a higher H19 and a lower miR-203 expression compared to normal tissues. The overall survival time of patients with higher H19 expression was shorter compared with the lower H19 expression group. Upregulation of A549 enhanced cell proliferation and promoted invasion. Overexpression of H19 stimulated the epithelial-mesenchymal transition (EMT) process in lung cancer cells and demonstrated typical morphological characteristics of EMT. The level of mesenchymal marker protein, such as Vimentin and SNAI1 increased; while CDH1 protein level decreased. Also, H19 negatively regulated miR-203. Inhibition of H19 attenuated miR-203 induced EMT process. Upregulation of H19 contributes to poor clinical features in patients with NSCLC, induces occurrence of EMT, promotes proliferation and stimulates cell invasion in NSCLC cell line through regulating miRNA-203 mediated EMT.

20.
Gastroenterol Rep (Oxf) ; 6(3): 195-201, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30151204

RESUMO

Background: The necessity for adjuvant chemotherapy (ACT) in locally advanced rectal cancer (LARC) patients who achieve pathological complete response (pCR) after pre-operative chemoradiotherapy (CRT) is still not identified. We aimed to investigate the therapeutic value of ACT in these patients. Methods: Clinical data were retrospectively collected from 105 consecutive LARC patients who achieved pCR after pre-operative CRT and underwent radical tumor resection between December 2008 and April 2014 in a comprehensive cancer center. Perioperative chemotherapy (CT) was administered by combining oxaliplatin with capecitabine (XELOX regimen). Disease-free survival (DFS) and overall survival (OS) rates of patients with or without ACT were compared. Results: Eighty-three (79.0%) patients received ACT and 22 (21.0%) did not. With a median follow-up of 49 months, the ACT group had a significantly higher 3-year DFS rate (92.8 vs 86.4%, p = 0.029) and 3-year OS rate (95.1 vs 86.1%, p = 0.026) than the non-ACT group. In multivariable analyses, the presence of ACT was an independent prognostic factor for DFS (hazard ratio [HR]: 0.271; 95% confidence interval (CI): 0.080-0.916; p = 0.036) but not for OS. This benefit was more obvious in patients younger than 60 years via subgroup analysis (adjusted HR: 0.106; 95% CI: 0.019-0.606; p = 0.012). Conclusions: Oxaliplatin-containing ACT may confer survival benefits to patients with pCR, particularly younger patients. However, the routine use of ACT in patients with pCR needs further validation.

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