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1.
Cell Death Dis ; 15(6): 436, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902268

RESUMO

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide, necessitating the identification of novel therapeutic targets. Lysosome Associated Protein Transmembrane 4B (LAPTM4B) is involved in biological processes critical to cancer progression, such as regulation of solute carrier transporter proteins and metabolic pathways, including mTORC1. However, the metabolic processes governed by LAPTM4B and its role in oncogenesis remain unknown. In this study, we conducted unbiased metabolomic screens to uncover the metabolic landscape regulated by LAPTM4B. We observed common metabolic changes in several knockout cell models suggesting of a role for LAPTM4B in suppressing ferroptosis. Through a series of cell-based assays and animal experiments, we demonstrate that LAPTM4B protects tumor cells from erastin-induced ferroptosis both in vitro and in vivo. Mechanistically, LAPTM4B suppresses ferroptosis by inhibiting NEDD4L/ZRANB1 mediated ubiquitination and subsequent proteasomal degradation of the cystine-glutamate antiporter SLC7A11. Furthermore, metabolomic profiling of cancer cells revealed that LAPTM4B knockout leads to a significant enrichment of ferroptosis and associated metabolic alterations. By integrating results from cellular assays, patient tissue samples, an animal model, and cancer databases, this study highlights the clinical relevance of the LAPTM4B-SLC7A11-ferroptosis signaling axis in NSCLC progression and identifies it as a potential target for the development of cancer therapeutics.


Assuntos
Sistema y+ de Transporte de Aminoácidos , Carcinoma Pulmonar de Células não Pequenas , Ferroptose , Neoplasias Pulmonares , Complexo de Endopeptidases do Proteassoma , Ubiquitina , Ferroptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Animais , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitina/metabolismo , Camundongos , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Proteínas Oncogênicas/metabolismo , Proteínas Oncogênicas/genética , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Linhagem Celular Tumoral , Ubiquitinação , Camundongos Nus , Proteólise/efeitos dos fármacos
2.
Biol Trace Elem Res ; 202(1): 221-232, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37059921

RESUMO

In the process of tooth development, the interaction between genetic information, epigenetic inheritance, and environment jointly affects the teeth formation. At present, the mechanism of dental fluorosis is rarely studied from transcriptomics, and there is no report on epigenetic perspective. In the study, SD rats were randomly divided into dental fluorosis group and control group fed with NaF (150 mg/L) or distilled water for 8 weeks. After 3.5 days of birth, the RNAs or DNA of rat mandibular molars were detected by RNA-seq or MethylTarget, respectively. The results demonstrated that a total of 1723 differentially expressed genes (DEGs) and 2511 differential expression lncRNAs (DE-lncRNAs) were mainly involved in the ion channels, calcium ion transport, and immunomodulatory signaling pathways. ATP2C1 and Nr1d1, which were related to Ca2+ transport, cellular calcium homeostasis, endoplasmic reticulum stress and immunity, may be the key genes in the formation of dental fluorosis. Notably, we also found that the immune response plays an important role in the formation of dental fluorosis, and a large amount of DEGs was enriched in immune regulation and NF-κB signaling pathways. Furthermore, the methylation levels of 13 sites were increased in Ago4, Atf3, Atp2c1, Dusp1, Habp4, and Mycl, while methylation levels of 5 CpG sites decreased in Ago4, Atp2c1, Habp4, and Traf6, and conformably, the expression of these genes have been significantly changed. This study comprehensively analyzed the occurrence mechanism of dental fluorosis from transcriptomics and epigenetics, so as to provide theoretical reference for further research.


Assuntos
Fluorose Dentária , RNA Longo não Codificante , Ratos , Animais , Fluoretos/metabolismo , Fluorose Dentária/epidemiologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Metilação de DNA/genética , Ratos Sprague-Dawley , Expressão Gênica
3.
Eur J Med Res ; 28(1): 462, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37885044

RESUMO

BACKGROUND: Cisplatin (CDDP) is a common anticancer drug whose side effects limit its clinical applications. Tannins (TA) are plant-derived polyphenols that inhibit tumor growth in different types of cancer. Here, we evaluated the anticancer effect of TA combined with CDDP on lung cancer cell lines (GLC-82 and H1299) and investigated the underlying molecular mechanism of endoplasmic reticulum (ER) stress-induced apoptosis. METHODS: Cell lines were treated with CDDP, TA, and CDDP + TA, and the effect of the combination was assessed using MTT assay and observed under light and fluorescence microscopes. Cell apoptosis was detected by flow cytometry, and the levels of ERS apoptosis pathway related genes were valuated by qRT-PCR and western blotting. The effects of the drug combination on the tumors of nude mice injected with H1299 cells were investigated, and the expression of key factors in the ER stress apoptotic pathway was investigated. RESULTS: The combination of CDDP and TA significantly inhibited lung cancer cell viability indicating a synergistic antitumoral effect. The mRNA and protein expression levels of key ER stress factors in the CDDP + TA group were considerably higher than those in the CDDP and TA groups, the tumor volume in tumor-bearing mice was the smallest, and the number of apoptotic cells and the protein expression levels of the key ER stress in the combination group were considerably higher. CONCLUSIONS: The combination of TA and CDDP may produce synergistic antitumoral effects mediated by the PERK-ATF4-CHOP apoptotic axis, suggesting a novel adjuvant treatment for lung cancer.


Assuntos
Neoplasias Pulmonares , Animais , Camundongos , Apoptose , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Camundongos Nus , Taninos/farmacologia , Taninos/uso terapêutico , Humanos
4.
Sci Rep ; 13(1): 18454, 2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891201

RESUMO

Clear cell renal cell carcinoma (ccRCC) is regulated by methylation modifications and long noncoding RNAs (lncRNAs). However, knowledge of N7-methylguanosine (m7G)-related lncRNAs that predict ccRCC prognosis remains insufficient. A prognostic multi-lncRNA signature was created using LASSO regression to examine the differential expression of m7G-related lncRNAs in ccRCC. Furthermore, we performed Kaplan-Meier analysis and area under the curve (AUC) analysis for diagnosis. In all, a model based on five lncRNAs was developed. Principal component analysis (PCA) indicated that the risk model precisely separated the patients into different groups. The IC50 value for drug sensitivity divided patients into two risk groups. High-risk group of patients was more susceptible to A.443654, A.770041, ABT.888, AMG.706, and AZ628. Moreover, a lower tumor mutation burden combined with low-risk scores was associated with a better prognosis of ccRCC. Quantitative real-time polymerase chain reaction (qRT-PCR) exhibited that the expression levels of LINC01507, AC093278.2 were very high in all five ccRCC cell lines, AC084876.1 was upregulated in all ccRCC cell lines except 786-O, and the levels of AL118508.1 and DUXAP8 were upregulated in the Caki-1 cell line. This risk model may be promising for the clinical prediction of prognosis and immunotherapeutic responses in patients with ccRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , RNA Longo não Codificante , Humanos , Carcinoma de Células Renais/patologia , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Renais/patologia , Estadiamento de Neoplasias , Linhagem Celular Tumoral
5.
Sci Transl Med ; 15(716): eadf7547, 2023 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-37792956

RESUMO

Bioprinting is a promising alternative method to generate skin substitutes because it can replicate the structural organization of the skin into biomimetic layers in vitro. In this study, six primary human skin cell types were used to bioprint a trilayer skin construct consisting of epidermis, dermis, and hypodermis. Transplantation of the bioprinted skin with human cells onto full-thickness wounds of nu/nu mice promoted rapid vascularization and formation of epidermal rete ridges analogous to the native human epidermis, with a normal-looking extracellular matrix. Cell-specific staining confirmed the integration of the implanted cells into the regenerated skin. Using a similar approach, a 5 centimeter-by-5 centimeter bioprinted autologous porcine skin graft was transplanted onto full-thickness wounds in a porcine excisional wound model. The bioprinted skin graft improved epithelialization, reduced skin contraction, and supported normal collagen organization with reduced fibrosis. Differential gene expression demonstrated pro-remodeling protease activity in wounds transplanted with bioprinted autologous skin grafts. These results demonstrate that bioprinted skin can support skin regeneration to allow for nonfibrotic wound healing and suggest that the skin bioprinting technology may be applicable for human clinical use.


Assuntos
Pele , Cicatrização , Camundongos , Humanos , Suínos , Animais , Epiderme , Regeneração , Reepitelização , Transplante de Pele
6.
BMC Plant Biol ; 23(1): 444, 2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37730528

RESUMO

BACKGROUND: The genus Sanicula comprises ca. 45 taxa, widely distributed from East Asia to North America, which is a taxonomically difficult genus with high medicinal value in Apiaceae. The systematic classification of the genus has been controversial for a long time due to varied characters in key morphological traits. China is one of the most important distributed centers, with ca. 18 species and two varieties. At present, chloroplast genomes are generally considered to be conservative and play an important role in evolutionary relationship study. To investigate the plastome evolution and phylogenetic relationships of Chinese Sanicula, we comprehensively analyzed the structural characteristics of 13 Chinese Sanicula chloroplasts and reconstructed their phylogenetic relationships. RESULTS: In present study, four newly complete chloroplast genome of Sanicula taxa by using Illumina sequencing were reported, with the typical quadripartite structure and 155,396-155,757 bp in size. They encoded 126 genes, including 86 protein-coding genes, 32 tRNA genes and 8 rRNA genes. Genome structure, distributions of SDRs and SSRs, gene content, among Sanicula taxa, were similar. The nineteen intergenic spacers regions, including atpH-atpI, ndhC-trnM, petB-petD, petD-rpoA, petN-psbM, psaJ-rpl33, rbcL-accD, rpoB-trnC, rps16-trnQ, trnE-psbD, trnF-ndhJ, trnH-psbA, trnN-ndhF, trnS-psbZ, trnS-trnR, trnT-trnF, trnV-rps12, ycf3-trnS and ycf4-cemA, and one coding region (ycf1 gene) were the most variable. Results of maximum likelihood analysis based on 79 unique coding genes of 13 Chinese Sanicula samples and two Eryngium (Apiaceae-Saniculoideae) species as outgroup taxa revealed that they divided into four subclades belonged to two clades, and one subclade was consistent with previously traditional Sanicula section of its system. The current classification based on morphology at sect. Sanicla and Sect. Tuberculatae in Chinese Sanicula was not supported by analysis of cp genome phylogeny. CONCLUSIONS: The chloroplast genome structure of Sanicula was similar to other angiosperms and possessed the typical quadripartite structure with the conserved genome arrangement and gene features. However, their size varied owing to expansion/contraction of IR/SC boundaries. The variation of non-coding regions was larger than coding regions of the chloroplast genome. Phylogenetic analysis within these Chinese Sanicula were determined using the 79 unique coding genes. These results could provide important data for systematic, phylogenomic and evolutionary research in the genus for the future studies.


Assuntos
Apiaceae , Sanicula , Filogenia , China , Cloroplastos/genética , DNA Intergênico
7.
BMC Genomics ; 24(1): 571, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37752438

RESUMO

BACKGROUND: Malvaceae is an economically important plant family of 4,225 species in nine subfamilies. Phylogenetic relationships among the nine subfamilies have always been controversial, especially for Brownlowioideae, whose phylogenetic position remains largely unknown due to the lack of samples in previous analysis datasets. To greatly clarify the phylogenetic relationship of Malvaceae, we newly sequenced and assembled the plastome of Diplodiscus trichospermus taxonomically located in Brownlowioideae, and downloaded the allied genomes from public database to build a dataset covering all subfamily members of Malvaceae. RESULTS: The annotation results showed that the plastome of Diplodiscus trichospermus has a typical quadripartite structure, comprising 112 unique genes, namely 78 protein-coding genes, 30 tRNA genes and 4 rRNA genes. The total length was 158,570 bp with 37.2% GC content. Based on the maximum likelihood method and Bayesian inference, a robust phylogenetic backbone of Malvaceae was reconstructed. The topology showed that Malvaceae was divided distinctly into two major branches which were previously recognized as Byttneriina and Malvadendrina. In the Malvadendrina clade, Malvoideae and Bombacoideae formed, as always, a close sister clade named as Malvatheca. Subfamily Helicteroideae occupied the most basal position and was followed by Sterculioideae which was sister to the alliance of Malvatheca, Brownlowioideae, Dombeyoideae, and Tilioideae. Brownlowioideae together with the clade comprising Dombeyoideae and Tilioideae formed a sister clade to Malvatheca. In addition, one specific conservation SSR and three specific palindrome sequences were observed in Brownlowioideae. CONCLUSIONS: In this study, the phylogenetic framework of subfamilies in Malvaceae has been resolved clearly based on plastomes, which may contribute to a better understanding of the classification and plastome evolution for Malvaceae.


Assuntos
Genoma de Cloroplastos , Malvaceae , Filogenia , Malvaceae/genética , Teorema de Bayes , Sequência de Bases
8.
Cell Adh Migr ; 17(1): 1-14, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37749865

RESUMO

The LMNA gene encoding lamin A/C is amplified in some clear cell renal cell carcinoma (ccRCC) samples. Our data showed that depletion of the tumor suppressor PBRM1 can upregulate lamin A/C levels, and lamin A/C could interact with PBRM1. However, the role of lamin A/C in ccRCC is not yet fully understood. Our functional assays showed that although the proliferation ability was slightly impaired after LMNA depletion, the migration and invasion of ccRCC cells were significantly inhibited. This suppression was accompanied by a reduction in MMP2, MMP9, AKT/p-AKT, and Wnt/ß-catenin protein levels. Our data therefore suggest that lamin A/C, as an interaction partner of the tumor suppressor PBRM1, plays a crucial role in tumor invasion and metastasis in ccRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , beta Catenina/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Lamina Tipo A/genética , Lamina Tipo A/metabolismo , Proliferação de Células/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
9.
Environ Pollut ; 336: 122448, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37640222

RESUMO

Microplastics (MPs) have been found to be widely distributed in aquatic environments, where they will interact with toxic heavy metals and result in more serious adverse effects on the aquatic environments and organisms. However, after entering the aquatic environments, MPs are quickly covered by biofilms, which significantly modify MPs properties and relevant heavy metals adsorption-desorption characteristics In order to better understand the adsorption behavior of heavy metals on biofilm developed MPs (BMPs), we comprehensively reviewed representative studies in this area. First, we summarized the formation process of biofilms on MPs. Subsequently, we reviewed the current understanding on the influence of biofilm formation on the properties of MPs and discussed the metal adsorption-desorption characteristics of MPs affected by these changes. Finally, based on the systematic literature review, some future research needs and strategies were proposed to further understand the interactions between MPs and heavy metals.

10.
Biomed Res Int ; 2023: 4038278, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36820224

RESUMO

Hard tissues make up the vast majority of teeth and are mineralized from the surrounding matrix. If the development of tooth germ is affected during mineralization, hypoplasia of the tooth tissue can occur. To better understand the mechanisms mediating hypoplasia, we need to first study normal development. Using a rodent model, we highlight the transcriptomic changes that occur from the differentiation to secretion stages of mandibular molar germs. The tooth germ was dissected from rats at postnatal day 1.5 or 3.5 for high-throughput sequencing. Combining transcriptome analysis and DNA methylation, we identified 590 differentially expressed genes (436 upregulated and 154 downregulated) and 551 differentially expressed lncRNAs (long noncoding RNA; 369 upregulated and 182 downregulated) which were linked to the biological processes of odontogenesis, amelogenesis, tooth mineralization, and the alteration of extracellular matrix (ECM), especially matrix metalloproteinases (MMPs) and elastin. We found DNA methylation changes in 32 selected fragments involved in 5 chromosomes, 26 targets, and 2 haplotypes. Finally, three novel genes were identified: MMP20, Tgfb3, and Dusp1. Further analysis revealed that MMP20 has a role in odontogenesis and amelogenesis by influencing Slc24a4 and DSPP; Tgfb3 is involved in epithelial cell proliferation, cellular component disassembly process, ECM cellular component, and decomposition of cell components. But lncRNA expression could affect DNA methylation and mRNA expression. Moreover, the degree of DNA methylation could also affect the transcriptome level. Thus, Tgfb3 had no difference in DNA methylation, and Dusp1 conferred no difference at the transcriptome level. These three genes were all enriched in the MAPK pathway and played an important role in ECM remodeling. These data suggest that during the period of the bell differentiation stage to the secretory stage, along with enamel/dentin matrix secretion and hard tissue occurrence, the ECM is remodeled via MAPK signaling.


Assuntos
Transcriptoma , Fator de Crescimento Transformador beta3 , Ratos , Animais , Metaloproteinase 20 da Matriz , Germe de Dente , Odontogênese , Diferenciação Celular , Matriz Extracelular , Perfilação da Expressão Gênica , Transdução de Sinais
11.
Proc Natl Acad Sci U S A ; 120(2): e2214492120, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36595698

RESUMO

Reproductive systems of flowering plants are evolutionarily fluid, with mating patterns changing in response to shifts in abiotic conditions, pollination systems, and population characteristics. Changes in mating should be particularly evident in species with sexual polymorphisms that become ecologically destabilized, promoting transitions to alternative reproductive systems. Here, we decompose female mating portfolios (incidence of selfing, outcross mate number, and intermorph mating) in eight populations of Primula oreodoxa, a self-compatible insect-pollinated herb. This species is ancestrally distylous, with populations subdivided into two floral morphs that usually mate with each other (disassortative mating). Stages in the breakdown of polymorphism also occur, including "mixed" populations of distylous and homostylous (self-pollinating) morphs and purely homostylous populations. Population morph ratios vary with elevation in association with differences in pollinator availability, providing an unusual opportunity to investigate changes in mating patterns accompanying transitions in reproductive systems. Unexpectedly, individuals mostly outcrossed randomly, with substantial disassortative mating in at most two distylous populations. As predicted, mixed populations had higher selfing rates than distylous populations, within mixed populations, homostyles selfed almost twice as much as the distylous morphs, and homostylous populations exhibited the highest selfing rates. Populations with homostyles outcrossed with fewer mates and mate number varied negatively with population selfing rates. These differences indicate maintenance of distyly at low elevation, transition to monomorphic selfing at high elevation, and uncertain, possibly variable fates at intermediate elevation. By quantifying the earliest changes in mating that initiate reproductive transitions, our study highlights the key role of mating in promoting evolutionary divergence.


Assuntos
Flores , Reprodução , Humanos , Flores/genética , Reprodução/genética , Polinização/genética , Polimorfismo Genético , Evolução Biológica
12.
Biomolecules ; 12(12)2022 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-36551318

RESUMO

(1) Objective: We aimed to mine cuproptosis-related LncRNAs with prognostic value and construct a corresponding prognostic model using machine learning. External validation of the model was performed in the ICGC database and in multiple renal cancer cell lines via qPCR. (2) Methods: TCGA and ICGC cohorts related to renal clear cell carcinoma were included. GO and KEGG analyses were conducted to determine the biological significance of differentially expressed cuproptosis-related LncRNAs (CRLRs). Machine learning (LASSO), Kaplan-Meier, and Cox analyses were conducted to determine the prognostic genes. The tumor microenvironment and tumor mutation load were further studied. TIDE and IC50 were used to evaluate the response to immunotherapy, a risk model of LncRNAs related to the cuproptosis genes was established, and the ability of this model was verified in an external independent ICGC cohort. LncRNAs were identified in normal HK-2 cells and verified in four renal cell lines via qPCR. (3) Results: We obtained 280 CRLRs and identified 66 LncRNAs included in the TCGA-KIRC cohort. Then, three hub LncRNAs (AC026401.3, FOXD2-AS1, and LASTR), which were over-expressed in the four ccRCC cell lines compared with the human renal cortex proximal tubule epithelial cell line HK-2, were identified. In the ICGC database, the expression of FOXD2-AS1 and LASTR was consistent with the qPCR and TCGA-KIRC. The results also indicated that patients with low-risk ccRCC-stratified by tumor-node metastasis stage, sex, and tumor grade-had significantly better overall survival than those with high-risk ccRCC. The predictive algorithm showed that, according to the three CRLR models, the low-risk group was more sensitive to nine target drugs (A.443654, A.770041, ABT.888, AG.014699, AMG.706, ATRA, AP.24534, axitinib, and AZ628), based on the estimated half-maximal inhibitory concentrations. In contrast, the high-risk group was more sensitive to ABT.263 and AKT inhibitors VIII and AS601245. Using the CRLR models, the correlation between the tumor immune microenvironment and cancer immunotherapy response revealed that high-risk patients are more likely to respond to immunotherapy than low-risk patients. In terms of immune marker levels, there were significant differences between the high- and low-risk groups. A high TMB score in the high-risk CRLR group was associated with worse survival, which could be a prognostic factor for KIRC. (4) Conclusions: This study elucidates the core cuproptosis-related LncRNAs, FOXD2-AS1, AC026401.3, and LASTR, in terms of potential predictive value, immunotherapeutic strategy, and outcome of ccRCC.


Assuntos
Apoptose , Carcinoma de Células Renais , Neoplasias Renais , RNA Longo não Codificante , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/terapia , Imunoterapia , Neoplasias Renais/genética , Neoplasias Renais/terapia , Aprendizado de Máquina , RNA Longo não Codificante/genética , Microambiente Tumoral/genética , Cobre
13.
PhytoKeys ; 195: 1-13, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35800211

RESUMO

The genus Paracladopus was established based on the type species P.chiangmaiensis in 2006. The two Paracladopus species are distributed in Thailand and Laos; however, neither of them has been documented in China to date. During our field work in 2020, we collected a river-weed in Wuzhi Mountain, Hainan Province of China. After checking the morphological characters, it was identified as P.chiangmaiensis. Then, we assembled and annotated its chloroplast genome based on the genome skimming data. The results showed that the complete chloroplast genome was 133,748 bp with 35% GC content, consisting of 76 protein-coding genes, 30 tRNA genes, and 4 rRNA genes. A maximum-likelihood tree constructed based on the matk genes showed that WuMS109 was clustered with P.chiangmaiensis (AB537420, AB698348) without base difference and together with the remains of Paracladopus formed a sister clade to Cladopus. This is the first report of P.chiangmaiensis that represents a new generic record for China. The discovery of this river-weed could lay the foundation for investigating their biogeographical patterns and species evolution in further studies.

14.
PeerJ ; 10: e13369, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35602902

RESUMO

Objective: The expression of ERGIC3 is increased in a variety of tumors and promotes the growth and metastasis of liver cancer, but the molecular mechanism needs to be further studied.In this study, we aimed to analyze the molecular mechanism of ERGIC3 regulating the proliferation of human hepatocellular carcinoma (HCC) SMMC-7721 cells using transcriptomics. Methods: ERGIC3 was knocked down in SMMC-7721 cells by RNAi technique, and the expression of ERGIC3 was detected by Q-RT-PCR and Western Blot. RNA sequencing was performed in the Illumina HiSeq platform in the control group and the ERGIC3i group and bioinformatics methods were selected to analyze the data. Results: The expression of ERGIC3 was reduced to 10% in SMMC-7721 cells by RNAi technique, and 176 genes were up-regulated and 34 genes were down-regulated in ERGIC3i group compared with the control group. Analysis of the pathways and biological processes that enrich the function of differentially expressed genes showed thatthese differentially expressed genes were mainly involved in vesicular transport, growth factors, PI3K-Akt, NOD-like, Jak-STAT, NF-kappa B and other protein kinase-coupled receptors mediated signal transduction pathways, tumor immune response, collagen-integrin receptor-actin axis, and miRNA pathways. More importantly, most of the significantly altered pathways were related to immunity. ERGIC3 may be a key immune-related gene. Conclusion: Based on the transcriptomic analysis, the mechanism of ERGIC3 promoting the growth of HCC is link with the transport of growth factor receptor, cytokine receptor and collagen. Then it is involved in signal transduction pathways mediated by protein kinase-coupled receptors, PI3K-Akt, NOD-like, Jak-STAT and NF-kappa B. In particular, the mechanism is also involved in the ERGIC3-dependent immune pathways. ERGIC3 is a potential target for prevention and treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Transcriptoma/genética , Proteínas Proto-Oncogênicas c-akt/genética , NF-kappa B/genética , Fosfatidilinositol 3-Quinases/genética , Linhagem Celular Tumoral , Imunidade , Proteínas de Membrana/genética
15.
Tissue Eng Regen Med ; 19(3): 451-461, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35320505

RESUMO

The oral and maxillofacial region contains oral organs and facial soft tissues. Due to the complexity of the structures and functions of this region, the repair of related defects is complicated. Different degrees of defects require different repair methods, which involve a great combination of medicine and art, and the material requirements are extremely high. Hence, clinicians are plagued by contemporary oral repair materials due to the limitations of bone harvesting, immune rejection, low osteogenic activity and other problems. Decellularized extracellular matrix has attracted much attention as a bioactive scaffold material because of its nonimmunogenic properties, good osteogenic properties, slow release of growth factors, promotion of seed cell adhesion and maintenance of stem cell characteristics. This article reviews the sources, preparation methods, application and research progress of extracellular matrix materials in the repair of oral and maxillofacial defects to provide an overview for fundamental research and clinical development.


Assuntos
Medicina Bucal , Alicerces Teciduais , Osso e Ossos , Matriz Extracelular/metabolismo , Osteogênese , Alicerces Teciduais/química
16.
J Clin Transl Res ; 8(1): 71-79, 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35224238

RESUMO

BACKGROUND AND AIM: This study retrospectively explored the potential association between CK19 expression and efficacy of adjuvant conventional transarterial chemoembolization (TACE) after hepatic resection in patients with hepatocellular carcinoma (HCC) at high risk of recurrence. METHODS: Patients (n = 508) who underwent hepatic resection between January 2012 and December 2017 were enrolled. Overall survival (OS) and recurrence-free survival (RFS) were compared between groups. Survival analysis was performed using the Kaplan-Meier method, and groups were compared using the log-rank test. RESULTS: OS and RFS were worse for CK19-positive patients than for CK19-negative patients, regardless of whether patients were matched on the basis of propensity scores. Among CK19-positive patients in the absence of propensity score matching, TACE was associated with better RFS. Among CK19-negative patients in the absence of propensity matching, TACE was associated with better OS and RFS. Among patients treated with TACE, CK19-positive patients showed worse OS but similar RFS as CK19-negative patients. Multivariate analysis identified the following independent predictors of worse OS: CK19 positivity, no adjuvant TACE, macrovascular invasion, microvascular invasion, tumor size >5 cm, alanine transaminase >80 U/L, and aspartate transaminase >80 U/L. Multivariate analysis identified the following predictors of worse RFS: CK19 positivity, no adjuvant TACE, age ≥60 years, alpha-fetoprotein ≥400 ng/ml, and Barcelona Clinic Liver Cancer stage B/C. CONCLUSION: This study suggests that among HCC patients at high risk of recurrence, adjuvant TACE can significantly prolong OS and RFS of CK19-negative patients, while it may prolong only RFS of CK19-positive patients. RELEVANCE FOR PATIENTS: Not all patients will benefit from adjuvant TACE, therefore, it is necessary to select the best benefit subsets before TACE. By studying the relationship between CK19 expression and TACE benefit, it will be possible to help guide decision-making about adjuvant TACE in HCC patients at high risk of recurrence.

17.
Regen Med ; 16(8): 709-718, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34334016

RESUMO

Background: This study aimed to investigate the expression of regeneration-related genes in canine urine during bladder repair. Materials & methods: Canine urine samples were collected after partial cystectomy. Regenerative mRNA of hypoxia-inducible factor (HIF), vascular endothelial growth factor (VEGF), key stem cell transcription factors and cholinergic signals were detected. Results: HIF-1α, VEGF, CD44, IL-6 and prominin-1 expression in canine urine after partial cystectomy exhibited two similar peaks at ∼2 weeks. HIF-1α and VEGF expression were higher in the afternoon than the morning. The expression of key stem cell transcription factors and cholinergic signals also exhibited a rhythm along with bladder healing. Conclusions: The expression of HIF-1α, VEGF, key stem cell transcription factors and cholinergic signals exhibited a time curve distribution during canine bladder healing. The expression trend of some regenerative genes was similar during bladder healing, and a cooperative effect may exist.


Assuntos
Bexiga Urinária , Fator A de Crescimento do Endotélio Vascular , Animais , Biomarcadores , Cães , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , RNA Mensageiro , Fator A de Crescimento do Endotélio Vascular/genética , Cicatrização/genética
18.
J Oral Pathol Med ; 50(2): 236-243, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33187014

RESUMO

BACKGROUND: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease that gradually affects the articular cartilage, synovium, and bone structure. To date, the molecular mechanism of TMJOA pathogenesis remains unclear. The aim of this study was to explore the biological function of the micro-ribonucleic acid 101a-3p (miR-101a-3p) and its role in TMJOA. METHODS: We detected the effect of interleukin-1ß (IL-1ß) on chondrocyte proliferation using Cell Counting Kit-8 (CCK-8) technology. Using quantitative polymerase chain reaction (qPCR), we detected transcription levels of miR-101a-3p in a rat model with TMJOA and inflamed chondrocytes, as well as in a group of normal rats. The effect of miR-101a-3p on apoptosis was examined in vitro using flow cytometry (FCM). We then analyzed the target of miR-101a-3p via bioinformatics and confirmed it using a luciferase reporter assay (LRA). RESULTS: We showed that IL-1ß could inhibit proliferation of chondrocytes. We found that miR-101a-3p levels were significantly lower in the rat inflammation model with TMJOA and inflamed chondrocytes than in the normal group. Additionally, miR-101a-3p substantially promoted apoptosis of chondrocytes, and both bioinformatic analyses and LRA found that this miRNA targeted the genes ubiquitin-conjugating enzyme 2D1 (UBE2D1) and Frizzled class receptor 4 (FZD4). CONCLUSION: Our results suggested that miR-101a-3p was involved in the pathogenesis of TMJOA and that its mechanism was probably interaction with its target genes UBE2D1 and FZD4.


Assuntos
Cartilagem Articular , MicroRNAs , Osteoartrite , Animais , Apoptose/genética , Condrócitos , Receptores Frizzled , MicroRNAs/genética , Osteoartrite/genética , Ratos , Articulação Temporomandibular
19.
Mitochondrial DNA B Resour ; 5(1): 929-931, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33366814

RESUMO

We sequenced, assembled, and annotated the complete mitochondrial genome of the seed beetle Caryopemon giganteus, which represents the first report in the tribe Caryopemini from the subfamily Bruchinae of Chrysomelidae. The circular mitochondrial genome of the species contains 15,727 bases, 13 protein-coding genes (PCGs), 22 tRNA genes, 2 rRNA genes, and a non-coding region. The GC content of the genome is 25.3%, which is higher than any other reported mitochondrial genomes within Bruchinae. The 16S ribosomal RNA gene and the 12S ribosomal RNA gene are 1284 and 835 bp in length, respectively. 12 PCGs started with the typical ATN codon, except for ND1 initiated with TTG. Five PCGs have the typical stop codon of TAA or TGA, while the remainder PCGs are terminated with incomplete stop codons (TA or T). The phylogenetic analysis based on a combination of 13 genes of the mitochondrial genomes of six species of Bruchinae and 23 species from other 10 subfamilies of Chrysomelidae recovered a generally well resolved and strongly supported tree topology, which shows that C. giganteus has the basalmost position in Bruchinae.

20.
PhytoKeys ; 146: 109-115, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32440255

RESUMO

Jasminum parceflorum (Oleaceae), a new species from tropical limestone habitats in Yunnan, China, is described and illustrated here. The new species is similar to J. pierreanum and J. rarum, but can be distinguished by its linear calyx lobes, dry calyces without ridges, terminal 1 (or 3)-flowered cymes and axillary solitary flowers.

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