Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 114
Filtrar
1.
Tzu Chi Med J ; 36(2): 136-141, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38645790

RESUMEN

Cerebrovascular accidents, also known as strokes, represent a major global public health challenge and contribute to substantial mortality, disability, and socioeconomic burden. Multidisciplinary approaches for poststroke therapies are crucial for recovering lost functions and adapting to new limitations. This review discusses the potential of neuromodulation techniques, repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, spinal cord stimulation (SCS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS), as innovative strategies for facilitating poststroke recovery. Neuromodulation is an emerging adjunct to conventional therapies that target neural plasticity to restore lost function and compensate for damaged brain areas. The techniques discussed in this review have different efficacies in enhancing neural plasticity, optimizing motor recovery, and mitigating poststroke impairments. Specifically, rTMS has shown significant promise in enhancing motor function, whereas SCS has shown potential in improving limb movement and reducing disability. Similarly, VNS, typically used to treat epilepsy, has shown promise in enhancing poststroke motor recovery, while DBS may be used to improve poststroke motor recovery and symptom mitigation. Further studies with standardized protocols are warranted to elucidate the efficacy of these methods and integrate them into mainstream clinical practice to optimize poststroke care.

2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(5): 1537-1542, 2023.
Artículo en Chino | MEDLINE | ID: mdl-37846713

RESUMEN

OBJECTIVE: The characteristics of the full-length mRNA sequences of MNS blood group-related genes GYPA, GYPB and GYPE were analyzed to understand the polymorphism of MNS blood group genes. METHODS: Anticoagulated blood within 24 h from 500 unpaid blood donors (8 ml each) were randomly selected, and MN, Ss and Mia blood types were identified by serological methods. 5 samples with different combinations of MNS and Mia blood types were randomly selected from 500 samples, and peripheral blood mononuclear cells (PBMC) were isolated by density gradient centrifugation, then total mRNA was extracted. cDNA was prepared by using the reverse transcription kit. The target fragments were amplified by nested PCR, and the full-length mRNA sequences of GYPA, GYPB and GYPE were sequenced after gel cutting and recycling, and the base sequences were analyzed by Oligo 6.0 software. RESULTS: The MN, Ss and Mia phenotypes were detected by serological methods, and there were differences in agglutination intensity of red blood cells (RBC) and anti-Mia serum between different individuals. The full-length mRNA sequences of GYPA, GYPB and GYPE genes in 5 samples of different phenotype combinations were detected. The exon-6 was completely deleted from the GYPA mRNA in 1 sample, and the full-length of GYPA mRNA in the other 4 samples were complete. The exon-2 was completely deleted from the GYPB mRNA in 2 samples, with Mia blood type negative. 2 samples showed complete full-length of GYPB mRNA, with Mia blood type positive. There was base substitution in exon-5 of GYPB mRNA in 1 sample. The full-length of GYPE mRNA was intact in 5 samples. CONCLUSION: MNS blood group related-genes have obvious polymorphism, and the detection of full-length mRNA sequence lays a foundation for the analysis of GYPA, GYPB and GYPE gene structure and in-depth study of MNS blood group antigen expression.

3.
Front Bioeng Biotechnol ; 11: 1261288, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37691909

RESUMEN

The effective regeneration and functional restoration of damaged spinal cord tissue have been a long-standing concern in regenerative medicine. Treatment of spinal cord injury (SCI) is challenging due to the obstruction of the blood-spinal cord barrier (BSCB), the lack of targeting of drugs, and the complex pathophysiology of injury sites. Lipid nanovesicles, including cell-derived nanovesicles and synthetic lipid nanovesicles, are highly biocompatible and can penetrate BSCB, and are therefore effective delivery systems for targeted treatment of SCI. We summarize the progress of lipid nanovesicles for the targeted treatment of SCI, discuss their advantages and challenges, and provide a perspective on the application of lipid nanovesicles for SCI treatment. Although most of the lipid nanovesicle-based therapy of SCI is still in preclinical studies, this low immunogenicity, low toxicity, and highly engineerable nanovesicles will hold great promise for future spinal cord injury treatments.

4.
Clin Anat ; 2023 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-37681447

RESUMEN

This study aimed to validate and compare the anatomical variations of the superior intercostal veins, focusing on their origin, course, anastomoses, and destination. In addition, the results were compared with findings from other relevant studies. Fifty Korean and 16 Chinese adult cadavers were dissected for this study. The superior intercostal veins were dissected and measured. In our study of 66 specimens, the right superior intercostal vein was observed in 92.3% of cases, while the left superior intercostal vein was observed in 50%. The right superior intercostal vein was subdivided into six types based on its composition, which mainly drained the second and third right posterior intercostal veins. Similarly, the left superior intercostal vein was subdivided into eight types, primarily involving the second to fourth left posterior intercostal veins. This detailed anatomical study successfully identified and classified the various morphologic types of the superior intercostal vein and reviewed the clinical significance of this vein. The findings of this study can offer valuable anatomical evidence to physicians, aiding in their understanding and utilization of the superior intercostal vein.

5.
Iran J Immunol ; 20(1): 129-134, 2023 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-36934323

RESUMEN

Several cases of the hemolytic disease of the fetus and newborn (HDFN) caused by immunoglobulin G (IgG) anti-M antibodies have been reported, in which almost all the HDFN-associated anti-M were warmly reacting. Here we report two cases of severe HDFN associated with cold-reacting IgG anti-M. In both cases, pregnancy was terminated, in weeks 33 and 23 respectively, due to a diagnosis of fetal growth retardation (FGR). To our knowledge, these are the most severe HDFN cases caused by cold-reacting IgG anti-M.


Asunto(s)
Antígenos de Grupos Sanguíneos , Eritroblastosis Fetal , Embarazo , Femenino , Recién Nacido , Humanos , Inmunoglobulina G , Eritroblastosis Fetal/diagnóstico , Eritroblastosis Fetal/etiología , Feto
6.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-975164

RESUMEN

ObjectiveTo obtain high-quality chloroplast genome information on Stemona tuberosa and clarify its structure, sequence features, and phylogenetic status. MethodThe Illumina NovaSeq 6000 and PacBio RS Ⅱ platforms were used for library construction and sequencing of S. tuberosa, respectively. The data from both sequencing platforms were combined and subjected to bioinformatics analysis for genome assembly and base correction, resulting in a high-quality chloroplast genome. Subsequently, sequence features, repetitive sequences, gene diversity, and phylogeny were analyzed. ResultThe chloroplast genome size of S. tuberosa was determined to be 154 379 bp. The structure of the chloroplast genome followed the typical quadripartite circular form, consisting of a pair of inverted repeat regions (IRs) with a length of 27 074 bp, a small single-copy region (SSC) of 17 924 bp, and a large single-copy region (LSC) of 82 307 bp. The average GC content was 37.86%. A total of 121 genes were annotated, including 30 tRNA genes, four rRNA genes, and 87 protein-coding genes. Among them, six tRNA genes and 12 protein-coding genes contained introns. In the chloroplast genome of S. tuberosa, 49 long repetitive sequences and 59 single-nucleotide simple sequence repeats (SSRs) were identified. Comparative analysis of chloroplast genomes among four Stemona species revealed high diversity in the ycf1 and ndhF genes. The phylogenetic tree constructed based on the chloroplast genome showed consistent classification with the current taxonomic status of S. tuberosa. ConclusionThe high-quality chloroplast genome of S. tuberosa was successfully assembled, providing valuable information on the structure and sequence features of chloroplast genomes in four Stemona species, including S. tuberosa. These findings lay a foundation for the identification, evolution, and phylogenetic studies of medicinal plants in the genus Stemona.

7.
Transfusion ; 62(11): 2184-2187, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36264119

RESUMEN

BACKGROUND: The null phenotype in P1PK blood group, known as "p," is extremely rare in the whole world. Individuals of p phenotype spontaneously form anti-PP1PK isoantibody. Here, we report a case of p phenotype with naturally occurring anti-PP1PK isoantibodies in a Chinese individual. STUDY DESIGN AND METHODS: Serology tests, containing alloantibodies screening and identification, were conducted to demonstrate the phenotype in P1PK blood group. The genotype of A4GALT gene was identified by haplotypes separation and sequencing. RESULTS: The serological assay demonstrated the p phenotype of the proband, presenting with 1:64 titer of anti-PP1PK . The sequencing data revealed a compound heterozygote consisting of A4GALT*P1.01 with c.343A>T and a novel allele based on A4GALT*01N.05 with an addition polymorphism c.100G>A. The sequence of the novel allele has been submitted to GenBank and the accession number OM912503 was assigned. CONCLUSION: Our study demonstrates a case of naturally occurring anti-PP1Pk in a Chinese individual with p phenotype, which is based on compound heterozygosity including one novel allele. As the proband is a young lady, monitoring the titer of anti-PP1PK and early initiation of medical intervention are essential after her pregnancy.


Asunto(s)
Antígenos de Grupos Sanguíneos , Galactosiltransferasas , Humanos , Embarazo , Femenino , Alelos , Galactosiltransferasas/genética , Antígenos de Grupos Sanguíneos/genética , Fenotipo , Genotipo , Isoanticuerpos/genética , China
9.
Adv Clin Exp Med ; 31(7): 723-730, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35302299

RESUMEN

BACKGROUND: The miR-21 has been implicated in the process of neuroinflammation as well as neuropathic pain. OBJECTIVES: To explore the relationship between the plasma and local expression of miR-21 with disease severity of lumbar disc herniation (LDH) patients with sciatic pain. MATERIAL AND METHODS: Ninety-two LDH patients with sciatic pain and 25 scoliosis patients as painless controls were enrolled in the current study. Samples from nucleus pulposus (NP), annulus fibrosus (AF) and soft tissues around nerve root (STANR) were obtained. The plasma and local expressions of miR-21 were detected with quantitative reverse transcription polymerase chain reaction (qRT-PCR). The visual analogue scale (VAS) for lumbar pain and leg pain, and Japanese Orthopedic Association (JOA) score were selected to evaluate the clinical severity. The degree of disc compression on nerve was evaluated using the Pfirrmann grade based on the magnetic resonance imaging (MRI) findings. For the convenience of analysis, LDH patients with sciatic pain were classified into a severe pain (SP) group (VAS ≥ 6) and a mild-moderate pain (MP) group (VAS < 6). Receiver operating characteristic (ROC) curve analysis was performed to detect the potential diagnostic power of miR-21 with regard to the Pfirrmann grade. RESULTS: There were no significant differences in serum miR-21 expressions among SP LDH patients, MP LDH patients and scoliosis painless controls. Local expressions of miR-21 in STANR, AF and NP were all drastically upregulated in the SP group in comparison with the MP group and scoliosis painless group. Local NP and STANR miR-21 expressions were positively associated with the Pfirrmann grade. Local miR-21 expressions in STANR and AF were positively associated with VAS score and negatively related to JOA score. The ROC curve analysis indicated that both STANR and AF miR-21 expressions may serve as significant diagnostic factors for the Pfirrmann grade. CONCLUSIONS: Increased local miR-21 expressions are linked with clinical severity of LDH in patients with sciatic pain.


Asunto(s)
Desplazamiento del Disco Intervertebral , Dolor de la Región Lumbar , MicroARNs , Escoliosis , Humanos , Desplazamiento del Disco Intervertebral/genética , Desplazamiento del Disco Intervertebral/fisiopatología , Vértebras Lumbares , MicroARNs/genética
10.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-939655

RESUMEN

OBJECTIVES@#To investigate the serum level of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific RBD IgG antibody (SARS-CoV-2 IgG antibody for short) in children with SARS-CoV-2 Omicron variant infection during the recovery stage, as well as the protective effect of SARS-CoV-2 vaccination against Omicron infection.@*METHODS@#A retrospective analysis was performed on 110 children who were diagnosed with coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 Omicron variant infection in Tianjin of China from January 8 to February 7, 2022. According to the status of vaccination before diagnosis, they were divided into a booster vaccination (3 doses) group with 2 children, a complete vaccination (2 doses) group with 90 children, an incomplete vaccination (1 dose) group with 5 children, and a non-vaccination group with 13 children. The clinical data and IgG level were compared among the 4 groups.@*RESULTS@#The complete vaccination group had a significantly higher age than the non-vaccination group at diagnosis (P<0.05), and there was a significant difference in the route of transmission between the two groups (P<0.05). There were no significant differences among the four groups in sex, clinical classification, and re-positive rate of SARS-CoV-2 nucleic acid detection (P>0.05). All 97 children were vaccinated with inactivated vaccine, among whom 85 children (88%) were vaccinated with BBIBP-CorV Sinopharm vaccine (Beijing Institute of Biological Products, Beijing, China). At 1 month after diagnosis, the booster vaccination group and the complete vaccination group had a significantly higher level of SARS-CoV-2 IgG antibody than the non-vaccination group (P<0.05), and at 2 months after diagnosis, the complete vaccination group had a significantly higher level of SARS-CoV-2 IgG antibody than the non-vaccination group (P<0.05). For the complete vaccination group, the level of SARS-CoV-2 IgG antibody at 2 months after diagnosis was significantly lower than that at 1 month after diagnosis (P<0.05).@*CONCLUSIONS@#Vaccination with inactivated SARS-CoV-2 vaccine has a protective effect against Omicron infection in children. For children vaccinated with 2 doses of the vaccine who experience Omicron infection, there may be a slight reduction in the level of SARS-CoV-2 IgG antibody at 2 months after diagnosis. Citation:Chinese Journal of Contemporary Pediatrics, 2022, 24(7): 736-741.


Asunto(s)
Niño , Humanos , Anticuerpos Antivirales , COVID-19 , Vacunas contra la COVID-19 , Inmunoglobulina G , Estudios Retrospectivos , SARS-CoV-2 , Vacunas Virales
11.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-928167

RESUMEN

Through literature research and standard retrieval, Corydalis-derived medicinal materials, the origins, and related standards were summarized. Finally, 27 medicinal materials were screened out, involving 71 species(varieties). Among them, only 11 are recorded in Chinese Pharmacopoeia(2020), National Standard for Chinese Patent Drugs·Tibetan Medicine, Tibetan Medicine Standards, and other local standards, including Corydalis Bungeanae Herba and Corydalis Herba. The names and original plants of the medicinal materials are different in different standards, and the phenomena of "same medicinal material with different names" and "same name for different medicinal materials" are prominent. Most standards only include the traits, microscopic identification, and physico-chemical property identification, with unsound quality criteria. Thus, efforts should be made to strengthen the sorting of Corydalis medicinal plants, herbal textual research, and investigation of the resources and utilization. Moreover, via modern techniques, the chemical components and medicinal material basis of different original plants should be explored and sound quality standards should be established to improve the safety and quality of Corydalis-derived medicinal materials. Summarizing Corydalis medicinal plants, Corydalis-derived medicinal materials, and related standards, this study is expected to provide a reference for the standard formulation, quality evaluation, expansion of drug sources, and rational development and utilization of Corydalis resources.


Asunto(s)
Corydalis , Medicamentos Herbarios Chinos/química , Medicina Tradicional China , Medicina Tradicional Tibetana , Plantas Medicinales/química , Estándares de Referencia
12.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-940674

RESUMEN

ObjectiveTo identify the molecular biology of various species of Tibetan Codonopsis plants based on internal transcribed spacer(ITS)2 and psbA-trnH sequence barcode technology. MethodThe genomic DNA of 28 Tibetan Codonopsis plant samples from four species (Codonopsis canescens,C. foetens subsp. nervosa,C. pilosula, and C. thalictrifolia var. mollis) were extracted,and the ITS2 and psbA-trnH sequences were amplified and sequenced. The related sequences of 81 Tibetan Codonopsis plant samples belonging to 15 species were downloaded from GenBank, and MEGA 6.0 was used for sequence comparison and mutation site analysis. The GC content and genetic distance within and between species were calculated. Additionally, phylogenetic trees were constructed by maximum likelihood (ML) method, neighbor-joining (NJ) method,and unweighted pair-group method with arithmetic means (UPGMA) . ResultAccording to the mutation site,C. canescens, C. pilosula,C. pilosula subsp. tangshen, C. pilosula var. modesta,C. bhutanica,C. clematidea,C. lanceolata,C. subglobosa and C. foetens were distinguished. In the phylogenetic trees,the optimal clustering effects for ITS2 and psbA-trnH sequences were obtained using the ML method and the UPGMA method, respectively, and 12 species were effectively clustered. ConclusionITS2 and psbA-trnH sequences have a high identification rate for species of single origin,but there are still some limitations in identifying variants and original variants. This study provides basis for the identification of affinity relationship and clinical safety of Tibetan Codonopsis plants.

13.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-927388

RESUMEN

To analyze the research status of acupuncture and moxibustion for cancer at home and abroad in the past 45 years by using bibliometric and scientific knowledge map methods,and explore the development trends in future. The literature of acupuncture and moxibustion for cancer was retrieved from CNKI and Web of Science (WOS) till December 31, 2020 since the database establishment, and CiteSpace and VOSviewer software were used to perform visual map analysis through cooperation network, keyword co-occurrence, keyword timeline, keyword emergence and other methods. Totally, 1 585 literature in CNKI and 1 564 literature in WOS were included, and the annual publication amount showed a fluctuating upward trend. Cooperation between countries was centered on China and the United States, and there was relatively little cooperation among different institutions. The analysis of keyword and cited literature showed that researches focused on the control of acupuncture and moxibustion therapy on cancer complications and adverse reactions of western medicine. The main research types in WOS were systematic review and randomized controlled trial (RCT), while in CNKI was review, depth studies on mechanism of acupuncture and moxibustion for cancer were rare. The concern about the quality of life of cancer patients may become research emphasis in the field of acupuncture and moxibustion for cancer in future, and the research scope tends to integrative and holistic oncology.


Asunto(s)
Humanos , Acupuntura , Terapia por Acupuntura , Bibliometría , Moxibustión , Neoplasias/terapia
14.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-995036

RESUMEN

Sepsis and septic shock are obstetric emergencies, which bring clinical issues for obstetricians to pay attention to, such as early identification and emergency intervention before transferring the patients to intensive care. Physiological changes during pregnancy and puerperium result in difficulty in identifying the clinical features of sepsis. Simple bedside screening tools can be used for early identification and screening for possible sepsis. If initial sepsis screening is positive with suspected or evidence of infection, regardless of the presence of fever, further evaluation of organ damage is required for the diagnosis of sepsis. Bundle therapy should be initiated within 1 h after the identification of sepsis: For pregnant women or puerpera with suspected or confirmed sepsis, bacterial culture (blood, urine, respiratory tract, and other body fluids) and serum lactate level detection should be conducted promptly, moreover, empirical broad-spectrum antibiotics given within 1 h are recommended; For patients with sepsis complicated by hypotension or organ hypoperfusion, it is recommended to administer 1-2 L crystal solution as soon as possible for liquid resuscitation; For those with persistent hypotension and/or organ hypoperfusion despite fluid resuscitation, vasopressors are recommended to maintain mean arterial pressure ≥65 mmHg (1 mmHg=0.133 kPa), with norepinephrine as the first-line vasopressor. When sepsis is suspected or confirmed, the focus of infection should be actively sought to effectively control the source. Termination of pregnancy should be considered individually and comprehensively on the basis of obstetric indications, gestational age, and maternal and fetal conditions, but not depend on sepsis alone. If intrauterine infection is confirmed, pregnancy should be terminated immediately. Cesarean delivery usually requires general anesthesia for pregnant women with sepsis and intraspinal anesthesia is relatively contraindicated. The diagnosis and treatment of sepsis in pregnancy and puerperium should be individualized in accordance with the corresponding guidelines.

15.
Front Genet ; 12: 790426, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34956331

RESUMEN

Atrial septal defects (ASDs) are the most common types of cardiac septal defects in congenital heart defects. In addition to traditional therapy, interventional closure has become the main treatment method. However, the molecular events and mechanisms underlying the repair progress by occlusion device remain unknown. In this study, we aimed to characterize differentially expressed genes (DEGs) in the blood of patients treated with occlusion devices (metal or poly-L-lactic acid devices) using RNA-sequencing, and further validated them by qRT-PCR analysis to finally determine the expression of key mediating genes after closure of ASD treatment. The result showed that total 1,045 genes and 1,523 genes were expressed differently with significance in metal and poly-L-lactic acid devices treatment, respectively. The 115 overlap genes from the different sub-analyses are illustrated. The similarities and differences in gene expression reflect that the body response process involved after interventional therapy for ASDs has both different parts that do not overlap and the same part that crosses. The same portion of body response regulatory genes are key regulatory genes expressed in the blood of patients with ASDs treated with closure devices. The gene ontology enrichment analysis showed that biological processes affected in metal device therapy are immune response with CXCR4 genes and poly-L-lactic acid device treatment, and the key pathways are nuclear-transcribed mRNA catabolic process and proteins targeting endoplasmic reticulum process with ribosomal proteins (such as RPS26). We confirmed that CXCR4, TOB1, and DDIT4 gene expression are significantly downregulated toward the pre-therapy level after the post-treatment in both therapy groups by qRT-PCR. Our study suggests that the potential role of CXCR4, DDIT4, and TOB1 may be key regulatory genes in the process of endothelialization in the repair progress of ASDs, providing molecular insights into this progress for future studies.

16.
Bioorg Med Chem Lett ; 53: 128420, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34728369

RESUMEN

In this paper, a new class of novel sulfonamides incorporating aminosaccharide tails were designed and synthesized based on the sugar-tail approach. Then, all the novel compounds were evaluated for their inhibitory activities against three carbonic anhydrase (CA, EC 4.2.1.1) isoenzymes (hCA I, hCA II and hCA IX). Interestingly, effective inhibition of these three CA isoforms were observed, especially the glaucoma associated isoform hCA II. It is worth noting that these glycoconjugated sulfonamide derivatives also showed better CA inhibitory effects compared to the initial segment carzenide. Among them, compound 8d was the most effective inhibitor with IC50 of 60 nM against hCA II. Subsequent physicochemical properties studies showed that all compounds have good water solubility and neutral pH values in solutions. And these important physicochemical properties make target compounds acquire obvious advantages in the preparation of topical and nonirritating antiglaucoma drugs. Moreover, the target compounds showed lower corneal cytotoxicity than acetazolamide (AAZ) and good metabolic stability in vitro. In addition, molecular docking studies confirmed the interactions between aminosaccharide fragment and hydrophilic subpocket of hCA II active site were crucial for the enhanced CA inhibitory activity. Taken together, these results suggested 8d would be a promising lead compound for the development of topical antiglaucoma CAIs.


Asunto(s)
Aminas/farmacología , Carbohidratos/farmacología , Anhidrasa Carbónica II/antagonistas & inhibidores , Inhibidores de Anhidrasa Carbónica/farmacología , Descubrimiento de Drogas , Sulfonamidas/farmacología , Aminas/química , Animales , Carbohidratos/química , Anhidrasa Carbónica II/metabolismo , Inhibidores de Anhidrasa Carbónica/síntesis química , Inhibidores de Anhidrasa Carbónica/química , Línea Celular , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Isoenzimas/antagonistas & inhibidores , Isoenzimas/metabolismo , Ratones , Microsomas Hepáticos/química , Microsomas Hepáticos/metabolismo , Estructura Molecular , Relación Estructura-Actividad , Sulfonamidas/síntesis química , Sulfonamidas/química
19.
Int J Biol Sci ; 17(10): 2461-2475, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34326687

RESUMEN

Background: We investigated the roles of breast cancer anti-estrogen resistance 1 (BCAR1/p130Cas) in the formation and immunoevasion of invasive circulating tumor cells (CTCs) in lung adenocarcinoma (LUAD). Methods: Biomarkers of CTCs including BCAR1 and CD274, were evaluated by the CanPatrol method. Proteomics analysis of LUAD cells and exosomes after BCAR1 overexpression (BCAR1-OE) was performed by mass spectrometry. Cell functions and relevant signaling pathways were investigated after BCAR1 knockdown (BCAR1-KO) or BCAR1-OE in LUAD cells. Lastly, in vitro and in vivo experiments were performed to confirm the roles of BCAR1 in the formation and immunoevasion of CTCs. Results: High expression of BCAR1 by CTCs correlated with CD274 expression and epithelial-to-mesenchymal transition (EMT). RAC1, together with BCAR1, was found to play an important role in the carcinogenesis of LUAD. RAC1 functioned with BCAR1 to induce EMT and to enhance cell proliferation, colony formation, cell invasion and migration, and anoikis resistance in LUAD cells. BCAR1 up-regulated CD274 expression probably by shuttling the short isoform of BRD4 (BRD4-S) into the nucleus. CTCs, as well as tumor formation, were prohibited in nude mice xenografted with BCAR1-KO cells. The co-expression of BCAR1/RAC1 and BCAR1/CD274 was confirmed in LUAD. BCAR1 expression in LUAD is an indicator of poor prognosis, and it associates with immunoevasion. Conclusion: BCAR1, as a new target for the treatment of LUAD, plays roles in the formation and immunoevasion of invasive CTCs. The mechanism includes triggering EMT via RAC1 signaling and up-regulating CD274 expression by shuttling BRD4-S into the nucleus.


Asunto(s)
Adenocarcinoma del Pulmón/genética , Proteína Sustrato Asociada a CrK/genética , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Células Neoplásicas Circulantes/patología , Adenocarcinoma del Pulmón/mortalidad , Adenocarcinoma del Pulmón/patología , Animales , Antígeno B7-H1/metabolismo , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Proteína Sustrato Asociada a CrK/metabolismo , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Transducción de Señal , Factores de Transcripción/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...