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1.
Cancer Cell Int ; 24(1): 96, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38439072

RESUMO

BACKGROUND: N6-methyladenosine (m6A) is dysregulated in various cancers, including colorectal cancer (CRC). Herein, we assess the diagnostic potential of peripheral blood (PB) m6A levels in CRC. METHODS: We collected PB from healthy controls (HCs) and patients with CRC, analyzed PB RNA m6A levels and the expression of m6A-related demethylase genes FTO and ALKBH5, cocultured CRC cells with PB mononuclear cells (PBMCs), and constructed an MC38 cancer model. RESULTS: PB RNA m6A levels were higher in the CRC than that in HCs. The area under the curve (AUC) of m6A levels (0.886) in the CRC was significantly larger compared with carbohydrate antigen 199 (CA199; 0.666) and carcinoembryonic antigen (CEA; 0.834). The combination of CEA and CA199 with PB RNA m6A led to an increase in the AUC (0.935). Compared with HCs, the expression of FTO and ALKBH5 was decreased in the CRC. After coculturing with CRC cells, the PBMCs RNA m6A were significantly increased, whereas the expression of FTO and ALKBH5 decreased. Furthermore, m6A RNA levels in the PB of MC38 cancer models were upregulated, whereas the expression of FTO and ALKBH5 decreased. CONCLUSIONS: PB RNA m6A levels are a potential diagnostic biomarker for patients with CRC.

2.
Biochem Biophys Res Commun ; 622: 149-156, 2022 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-35863089

RESUMO

Bone marrow mesenchymal stem cells (BMSCs) are an integral part of the acute myeloid leukemia (AML) bone marrow microenvironment and contribute to AML progression. In this study, we explored the communication between BMSCs and AML cells via exosomes. The AML cells co-cultured with BMSCs-Exos were found to have lower chemosensitivity exposed to cytarabine, suggesting that BMSCs-Exos could protect AML cells from cytarabine. Interestingly, miR-10a was elevated in BMSCs-Exos derived from AML (AML-BMSCs-Exos) compared with that from healthy donor. The expression levels of miR-10a in AML cells was significantly up-regulated after co-culture with BMSCs-Exos. Furthermore, the up-regulated miR-10a was an crucial factor contributing to the chemoresistance of leukemia cells. Down-regulation of miR-10a substantially increase chemosensitivity of AML cells treated with BMSCs-Exos. Chemosensitivity of AML cells was also decreased through down-regulating RPRD1A by miR-10a that ultimately lead to the stimulation of the Wnt/ß-catenin signaling pathway. Collectively, our findings demonstrated that AML-BMSCs could deliver miR-10a to AML cells via exosomes, which could target RPRD1A and activate Wnt/ß-catenin signaling pathway that subsequently decreased chemosensitivity of AML cells.


Assuntos
Exossomos , Leucemia Mieloide Aguda , Células-Tronco Mesenquimais , MicroRNAs , Células da Medula Óssea/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células , Citarabina/farmacologia , Exossomos/metabolismo , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Repressoras/metabolismo , Microambiente Tumoral
3.
Exp Cell Res ; 392(2): 112003, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32278689

RESUMO

Dendritic cells (DCs) play a central role in autoimmunity, immune homeostasis, and presentation of tumor antigens to T cells in order to prime antitumor responses. The number of tumor-infiltrating DCs is associated with survival and prognosis in cancer. Twist1 is a well-known regulator of tumor initiation and promotion, but whether and how DC-derived Twist1 regulates antitumor responses remains poorly understood. Here, we generated a mouse line with Twist1 conditionally depleted in DCs and found that Twist1-deficiency in DCs did not affect the DCs and T cell homeostasis under steady-state conditions; however, in melanoma models, the proportion of conventional DCs (cDCs) in draining lymph nodes (DLNs) was significantly decreased. Accordingly, a decreased ratio and number of tumor-infiltrating cDCs were observed, which reduced the recruitment of tumor-infiltrating T cells. Furthermore, production of IFN-γ, a crucial antitumor factor, by T cells, was dramatically decreased, which can further dampen the T cell antitumor functions. Collectively, our data indicate that Twist1 in DCs regulates antitumor functions by maintain the number of tumor-infiltrating DCs and T cells, and their antitumor activity.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Imunidade Celular/imunologia , Linfócitos do Interstício Tumoral/imunologia , Melanoma Experimental/imunologia , Proteína 1 Relacionada a Twist/fisiologia , Animais , Antígenos de Neoplasias/imunologia , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Camundongos Knockout
4.
Biochem Biophys Res Commun ; 521(2): 434-440, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31672271

RESUMO

In this study, we aimed to explore the role of liver kinase b1 (Lkb1) in the biological characteristics and immune regulation of amniotic mesenchymal stem cells (AMSCs). AMSCs were identified via the cell surface markers using flow cytometry. We knocked down the expression of Lkb1 in AMSCs using lentivirus-mediated Lkb1-specific shRNA. The efficiency of the knockdown was detected by flow cytometry, RT-qPCR, and western blot. The AMSC-related phenotype was determined by flow cytometric analysis via staining surface markers. Fibroblast colony-forming cells (CFU-F) assay and Ki-67 intracellular staining assay were used to determine the proliferative capacity. The differentiated and immunosuppressive capabilities were determined by conditional induction of differentiation and co-culture experiments. We observed that AMSCs along with Lkb1 knockdown (AMSCs-Lkb1) displayed similar cellular morphology and surface antigen expression patterns as those observed in AMSCs. However, AMSCs-Lkb1 exhibited an enhanced differentiation capacity towards osteogenesis and chondrogenesis while it showed defective proliferation and increased apoptosis. Furthermore, AMSCs-Lkb1 showed an enhanced immunosuppressive capacity by directly inhibiting conventional T cells and indirectly inducing production of regulatory T cells (Treg). Interestingly, Treg produced by AMSCs-Lkb1 displayed stronger proliferative capacity as compared to those produced by AMSCs. Our results indicate that Lkb1 plays a vital role in maintaining self-renewal of AMSCs and regulating immune equivalence, and may hold potential for the clinical management of diseases such as GVHD.


Assuntos
Diferenciação Celular , Proliferação de Células , Células-Tronco Mesenquimais/citologia , Proteínas Serina-Treonina Quinases/fisiologia , Linfócitos T Reguladores/citologia , Quinases Proteína-Quinases Ativadas por AMP , Âmnio/citologia , Animais , Apoptose , Autorrenovação Celular , Células Cultivadas , Condrogênese , Técnicas de Silenciamento de Genes , Humanos , Tolerância Imunológica , Osteogênese , Proteínas Serina-Treonina Quinases/genética
5.
Exp Cell Res ; 384(2): 111650, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31563695

RESUMO

Liver kinase B1 (Lkb1) in dendritic cells (DCs) plays a key role in maintaining immunity homeostasis and adaptive immunity by controlling the CD4+Foxp3+T regulatory cell (CD4+Tregs) pool and T cells activation. However, the function of Lkb1 in DCs for the regulation of CD8+Foxp3+T regulatory cells (CD8+Tregs) has not been addressed. Herein, we found that Lkb1-deficient DCs could lead to excessive CD8+Tregs expansion in multiple organs. We found that OX40 expression was significantly higher in Lkb1-deficient DCs compared with that in wild-type (WT) mice, suggesting a potential pathway of CD8+Treg expansion. Moreover, we found that CD8+Tregs from mice with conditional deletion Lkb1 in DCs (KO) displayed an activated phenotype and expressed higher levels of specific markers, including ICOS and CD103. Interestingly, compared with the WT mice without lipopolysaccharide(LPS) treatment, we found that CD8+Tregs population increased in the WT mice with LPS treatment which can selectively delete Lkb1 protein in DCs. However, there was no significant difference in CD8+Tregs population in the KO mice between LPS treatment group and non-LPS treatment. Collectively, our findings identified Lkb1 in DCs as a crucial regulator of CD8+Treg expansion.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Fatores de Transcrição Forkhead/imunologia , Proteínas Serina-Treonina Quinases/imunologia , Linfócitos T Reguladores/imunologia , Proteínas Quinases Ativadas por AMP , Animais , Antígenos CD/imunologia , Proliferação de Células/fisiologia , Proteína Coestimuladora de Linfócitos T Induzíveis/imunologia , Cadeias alfa de Integrinas/imunologia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(12): 1336-1339, 2020 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-33306816

RESUMO

OBJECTIVE: To explore the genetic and clinical characteristics of near-tetraploidy/tetraploidy karyotype (NT/T) in patients with myelodysplastic syndrome (MDS). METHODS: Cytogenetic findings of 1576 inpatients with primary MDS were retrospective analyzed, among which 9 were diagnosed with NT/T. Clinical data including gender, age, morphology, genetic feature and prognosis were analyzed. RESULTS: The prevalence of MDS patients with NT/T (NT/T-MDS) among all cases was 0.57%. Karyotyping analysis suggested that eight MDS patients had sole NT/T, while the remainder one had a complex karyotype. In addition to the typical morphology of MDS, NT/T-MDS had unique morphology including huge blast, double-nuclear cell and irregular nuclear membrane. One NT/T-MDS patient gave up therapy, and the remaining eight underwent the first course of treatment, albeit with poor prognosis. Only one patient had complete remission, one had partial remission, three had no remission; and three had converted to acute myeloid leukemia. CONCLUSION: NT/T-MDS is rare and has unique morphology. Generally, NT/T-MDS patients have poor prognosis. However, NT/T cannot be simply classified as high-risk group, but with consideration whether they have affected particular chromosomal structures as well as other clinical data.


Assuntos
Síndromes Mielodisplásicas , Tetraploidia , Humanos , Cariótipo , Leucemia Mieloide Aguda/complicações , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Prognóstico , Estudos Retrospectivos
8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 35(5): 733-736, 2018 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-30298507

RESUMO

OBJECTIVE: To explore the genetic and clinical features of patients with acute myeloid leukemia (AML) and near-tetraploidy/tetraploidy (NT/T) karyotype. METHODS: Cytogenetic findings of 1836 cases of primary AML were retrospectively analyzed. Karyotypes of the identified cases were confirmed by fluorescence in situ hybridization (FISH). Clinical data including gender, age, morphology, immunophenotype, genetics, and prognosis were reviewed. RESULTS: Nine male and two female patients with NT/T were identified with a median age of 63 years. Microscopically, the patients were characterized by large blasts and irregular nuclear contours. All patients expressed CD34, and nine of them expressed HLA-DR. Ten patients had complete remission during the first course of treatment. One patient showed primary drug resistance. CONCLUSION: NT/T AML primarily occurs in elder males and has a characteristic morphology and genetics. The prognosis is better than AML patients with complex karyotypes.


Assuntos
Leucemia Mieloide Aguda/genética , Tetraploidia , Idoso , Feminino , Humanos , Cariótipo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
9.
Br J Biomed Sci ; 73(3): 110-114, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27327088

RESUMO

PURPOSE: To assess whether immunostimulatory cytosine-phosphate-guanine oligodeoxynucleotides (CpG-ODN) combined with interleukin-2 (IL-2) improves the number of mitotic metaphases and the detection rate of chromosomal abnormalities in chronic lymphocytic leukaemia (CLL). MATERIALS AND METHODS: Bone marrow specimens were collected from 36 patients with CLL. CLL cells were cultured with CpG-ODN type DSP30 plus IL-2 for 72 h, following which R-banding analysis was conducted. Conventional culture without the immunostimulant served as the control group. The incidence of genetic abnormalities was measured by fluorescence in situ hybridisation (FISH) using a panel of five specific probes: D13S25 (13q14.3), RB1 (13q14), P53 (17p13), ATM (11q22.3) and CSP12 (trisomy 12, +12). RESULTS: In the control group, chromosome analysis achieved a success rate of only 22.2, and 11.1% of abnormal karyotypes were detected. After immunostimulation with DSP30 plus IL-2, chromosome analysis achieved a success rate of up to 91.6, and 41.6% of abnormal karyotypes were detected. FISH analysis detected 77.7% of abnormalities. FISH combined with CpG-ODN DSP30 plus IL-2 improved the detection rate of chromosomal abnormalities in CLL to 83.3%. CONCLUSION: CpG-ODN DSP30 combined with IL-2 is effective in improving the detection rate of chromosomal abnormalities in CLL cells. This combination with FISH analysis is conducive to increasing the detection rate of genetic abnormalities in CLL.


Assuntos
Interleucina-2/imunologia , Cariotipagem/métodos , Leucemia Linfocítica Crônica de Células B/genética , Oligonucleotídeos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade
10.
Artigo em Chinês | MEDLINE | ID: mdl-26829723

RESUMO

OBJECTIVE: To investigate the clinical application of fluorescent in situ hybridization (FISH) for the differential diagnosis of myelodysplastic syndromes (MDS) and aplastic anemia (AA). METHODS: A FISH kit capable of detecting the chromosomal abnormalities related to MDS was used to analyze 94 patients who were suspected to have AA by bone marrow morphology. RESULTS: Cytogenetic abnormalities were detected in 11 of the 94 patients, which included trisomy 8 (5 cases), 20q- (1 case) and -Y (1 case). There were 4 cases related to MDS, which included 3 cases of 5q-, in which 1 case carry 20q- at the same time, and 7q- (1 case). No significant difference was found between the MDS and AA groups in terms of age, sex or routine blood examination including absolute neutrophil count, hemoglobin content and platelet count. CONCLUSION: FISH can detect certain cytogenetic abnormalities related to MDS in patients morphologically diagnosed as AA.


Assuntos
Anemia Aplástica/diagnóstico , Anemia Aplástica/genética , Células da Medula Óssea/citologia , Hibridização in Situ Fluorescente/métodos , Adolescente , Adulto , Idoso , Criança , Aberrações Cromossômicas , Cromossomos Humanos Par 7/genética , Cromossomos Humanos Par 8/genética , Feminino , Humanos , Cariotipagem , Masculino , Pessoa de Meia-Idade , Trissomia/genética
11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 33(3): 344-8, 2016 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-27264818

RESUMO

OBJECTIVE: To explore the pathogenetic mechanism for a female patient affected with hemophilia A (HA). METHODS: Potential genetic defect was detected with inverse shifting-polymerase chain reaction (IS-PCR). The pattern of X chromosome inactivation was determined with a human androgen receptor assay (HUMARA assay). G-banded karyotyping was carried out to exclude potential chromosome aberrations. RESULTS: IS-PCR showed that the defect of FVIII gene was the distal type of intron 22 inversion. The HUMARA assay showed that the X chromosome inactivation was non-random, and that the mother's X chromosome activity was lower than that of the father's X chromosome which has carried the inverted FVIII gene. No abnormalities were found with G-banded chromosomes. CONCLUSION: The prevalence of female HA patient may be caused by non-random inactivation of X chromosomes.


Assuntos
Hemofilia A/genética , Inativação do Cromossomo X , Adolescente , Feminino , Hemofilia A/etiologia , Humanos , Cariotipagem , Reação em Cadeia da Polimerase , Receptores Androgênicos/análise
12.
Immunobiology ; 229(6): 152856, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39369651

RESUMO

BACKGROUND: Our previous research has shown that LKB1 in amniotic mesenchymal stem cells (MSCs) serves as a vital regulator of regulatory T cell differentiation and T cell proliferation, which may have a similar role in bone marrow MSCs (BMMSCs). Therefore, we investigated the role of LKB1 in BMMSCs for regulating CD4+ T cell proliferation in the bone micro-environment of AML. METHODS: RT-PCR was used to assessed LKB1 expression in BMMSCs derived from AML patients and healthy controls. Subsequently, LKB1 was knocked down in the BMMSCs line HS-5 (HS-5-LKB1KD). Co-cultures in vitro were established to analyze the effect of HS-5-LKB1KD on CD4+ T cell. Flow cytometry was employed to measure PD-L1 and CD4+ T cell proliferation levels. Western blot was utilized to detect related proteins. RESULTS: The expression of LKB1 in BMMSCs derived from AML patients was decreased. Knockdown of LKB1 in HS-5 resulted in upregulation of PD-L1 expression. Co-culture of peripheral blood CD4+ T cell with HS-5-LKB1KD exhibited reduced CD4+ T cell proliferation compared to co-culture with HS-5-LKB1con. Furthermore, blocking PD-L1 in the co-culture conditions could restore the reduced CD4+ T cell proliferation. Additionally, it was found that upregulation of the Wnt signaling pathway-related proteins following LKB1 knockdown in HS-5, indicating that downregulating LKB1 could promote PD-L1 expression through activation of the Wnt signaling pathway. CONCLUSIONS: The decreased expression of LKB1 in BMMSCs may activate the Wnt signaling pathway, leading to increased PD-L1 expression. This inhibited CD4+ T cell proliferation, which might lead to impaired anti-tumor immunity in AML patients and promote AML progression.

13.
Adv Mater ; : e2408686, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39240027

RESUMO

Simultaneously controlling defects and film morphology at the buried interface is a promising approach to improve the power conversion efficiency (PCE) of inverted perovskite solar cells (PSCs). Here, two new donor‒acceptor type semiconductive covalent organic frameworks (COFs) are developed, COFTPA and COFICZ. The carefully designed COFs structure not only effectively regulates the morphology and defects of the buried interface film, but also realizes the alignment with the energy level of the perovskite film and enhances the extraction and transmission of the interface charge. Among them, COFICZ-treated inverted PSCs achieved a maxmum PCE of 25.68% (certified 25.14%), the inverted PCE reached a minimum PCE of 22.92% for 1 cm2 device. The efficiency of inverted PSCs with a 1.68 eV wide bandgap reached 22.92%, which is the highest datum of the reported 1.68 eV wide bandgap PSC. This lays the groundwork for the commercialization of perovskite/silicon tandem solar cells. Additionally, the unencapsulated devices demonstrated a high degree of stability during operational use and when subjected to conditions of high humidity and temperature.

14.
J Extracell Vesicles ; 13(8): e12491, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39175282

RESUMO

In the quest for efficient tumor diagnosis via liquid biopsy, extracellular vesicles (EVs) have shown promise as a source of potential biomarkers. This study addresses the gap in biomarker efficacy for predicting clinically significant prostate cancer (csPCa) between the Western and Chinese populations. We developed a urinary extracellular vesicles-based prostate score (EPS) model, utilizing the EXODUS technique for EV isolation from 598 patients and incorporating gene expressions of FOXA1, PCA3, and KLK3. Our findings reveal that the EPS model surpasses prostate-specific antigen (PSA) testing in diagnostic accuracy within a training cohort of 234 patients, achieving an area under the curve (AUC) of 0.730 compared to 0.659 for PSA (p = 0.018). Similarly, in a validation cohort of 101 men, the EPS model achieved an AUC of 0.749, which was significantly better than PSA's 0.577 (p < 0.001). Our model has demonstrated a potential reduction in unnecessary prostate biopsies by 26%, with only a 3% miss rate for csPCa cases, indicating its effectiveness in the Chinese population.


Assuntos
Biomarcadores Tumorais , Vesículas Extracelulares , Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/urina , Neoplasias da Próstata/diagnóstico , Vesículas Extracelulares/metabolismo , Pessoa de Meia-Idade , Idoso , Biomarcadores Tumorais/urina , Medição de Risco/métodos , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Fator 3-alfa Nuclear de Hepatócito/genética , Calicreínas/urina , Antígenos de Neoplasias/urina , Biópsia Líquida/métodos
15.
FEBS Open Bio ; 13(2): 270-278, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36515008

RESUMO

The tumor suppressor Lkb1 is known to regulate the expression of forkhead box P3 (Foxp3), thereby maintaining the levels of Foxp3+ regulatory T cells (Treg) that play a crucial role in self-tolerance. However, the effect of Lkb1 in Treg on hematopoietic stem cells (HSCs) in the bone marrow (BM) remains obscure. Here, we demonstrated that conditional deletion of Lkb1 in Treg causes loss of Treg in the BM, which leads to failure of HSC homeostasis and the abnormal expansion. Moreover, the loss of BM Treg results in dysregulation of other developing progenitors/stem cell populations, leading to the defective differentiation of T cells and B cells. In addition, HSC from the BM with Treg loss exhibited poor engraftment efficiency, indicating that loss of Treg leads to irreversible impairment of HSC. Collectively, these results demonstrated the essential role of Lkb1 in Treg for maintaining HSC homeostasis and differentiation in mice. These findings provide insight into the mechanisms of HSC regulation and guidance for a strategy to improve the outcomes and reduce complications of HSC transplantation.


Assuntos
Medula Óssea , Células-Tronco Hematopoéticas , Linfócitos T Reguladores , Animais , Camundongos , Medula Óssea/metabolismo , Diferenciação Celular , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/farmacologia , Células-Tronco Hematopoéticas/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Linfócitos T Reguladores/metabolismo
16.
Anticancer Res ; 43(10): 4491-4509, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37772558

RESUMO

BACKGROUND/AIM: Kremen2 has been shown to play an important role in multiple cancers formation as a negative regulatory factor in the Wnt signaling pathway. Our study aimed to explore the potential value of KREMEN2 in pan-cancer and investigate the molecular mechanisms associated with tumor development, providing a basis for prognostic factors and new therapeutic targets for cancer. MATERIALS AND METHODS: Raw RNA-seq data for 32 types of cancers were obtained from The Cancer Genome Atlas (TCGA), while Xena database provided overall survival (OS) and progression-free survival (PFI) data for TCGA patients. R language was used to identify the association between KREMEN2 and immune response, tumor mutational burden (TMB), and microsatellite instability (MSI). Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA) were conducted in pan-cancer. A Nomogram prediction model and weighted gene co-expression network analysis (WGCNA) were constructed in colorectal cancer (CRC). RESULTS: KREMEN2 was found highly expressed in 17 types of tumor tissues compared to normal tissues. KREMEN2 was only correlated with some tumor pathological stages. KREMEN2 with high expression had poor prognosis in pan-cancer. KREMEN2 expression was significantly associated with immune infiltration, immune checkpoints, immune-related genes, commonly regulated tumor-related genes, TMB, and MSI. Moreover, GSVA and GSEA analyses suggested that KREMEN2 played a role in cell cycle in pan-cancer. KREMEN2 expression had a significant impact on the performance of Nomogram prediction model in CRC, and WGCNA analysis indicated that KREMEN2 performed special functions in CRC. CONCLUSION: The comprehensive pan-cancer analysis revealed that KREMEN2 is a promising tumor prognostic biomarker and a potential anti-tumor immunotherapeutic target in human tumors.


Assuntos
Neoplasias , Humanos , Prognóstico , Neoplasias/genética , Neoplasias/terapia , Biomarcadores Tumorais/genética , Ciclo Celular , Instabilidade de Microssatélites , Imunoterapia
17.
Adv Mater ; 35(11): e2210772, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36519670

RESUMO

Organic electronics has made great progress in the past decades, which is inseparable from the innovative development of organic electronic devices and the diversity of organic semiconductor materials. It is worth mentioning that both of these great advances are inextricably linked to the development of organic high-performance semiconductor materials, especially the representative n-type organic small-molecule semiconductor materials with high electron mobilities. The n-type organic small molecules have the advantages of simple synthesis process, strong intermolecular stacking, tunable molecular structure, and easy to functionalize structures. Furthermore, the n-type semiconductor is a remarkable and important component for constructing complementary logic circuits and p-n heterojunction structures. Therefore, n-type organic semiconductors play an extremely important role in the field of organic electronic materials and are the basis for the industrialization of organic electronic functional devices. This review focuses on the modification strategies of organic small molecules with high electron mobility at molecular level, and discusses in detail the applications of n-type small-molecule semiconductor materials with high mobility in organic field-effect transistors, organic light-emitting transistors, organic photodetectors, and gas sensors.

18.
Immun Inflamm Dis ; 11(10): e1034, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37904703

RESUMO

Heat stroke is a life-threatening disease with high mortality and complications. Endothelial glycocalyx (EGCX) is essential for maintaining endothelial cell structure and function as well as preventing the adhesion of inflammatory cells. Potential relationship that underlies the imbalance in inflammation and coagulation remains elusive. Moreover, the role of EGCX in heat stroke-induced organ injury remained unclear. Therefore, the current study aimed to illustrate if EGCX aggravates apoptosis, inflammation, and oxidative damage in human pulmonary microvascular endothelial cells (HPMEC). Heat stress and lipopolysaccharide (LPS) were employed to construct in vitro models to study the changes of glycocalyx structure and function, as well as levels of heparansulfate proteoglycan (HSPG), syndecan-1 (SDC-1), heparansulfate (HS), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, Von Willebrand factor (vWF), endothelin-1 (ET-1), occludin, E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and reactive oxygen species (ROS). Here, we showed that heat stress and LPS devastated EGCX structure, activated EGCX degradation, and triggered oxidative damage and apoptosis in HPMEC. Stimulation of heat stress and LPS decreased expression of HSPG, increased levels of SDC-1 and HS in culture supernatant, promoted the production and release of proinflammation cytokines (TNF-α and IL-6,) and coagulative factors (vWF and ET-1) in HPMEC. Furthermore, Expressions of E-selection, VCAM-1, and ROS were upregulated, while that of occludin was downregulated. These changes could be deteriorated by heparanase, whereas they meliorated by unfractionated heparin. This study indicated that EGCX may contribute to apoptosis and heat stroke-induced coagulopathy, and these effects may have been due to the decrease in the shedding of EGCX.


Assuntos
Células Endoteliais , Golpe de Calor , Humanos , Células Endoteliais/metabolismo , Glicocálix/metabolismo , Lipopolissacarídeos/toxicidade , Fator de Necrose Tumoral alfa/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Heparina/metabolismo , Heparina/farmacologia , Fator de von Willebrand/metabolismo , Fator de von Willebrand/farmacologia , Proteoglicanas de Heparan Sulfato/metabolismo , Proteoglicanas de Heparan Sulfato/farmacologia , Ocludina/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo , Molécula 1 de Adesão de Célula Vascular/farmacologia , Inflamação/metabolismo , Interleucina-6/farmacologia , Golpe de Calor/metabolismo , Resposta ao Choque Térmico
19.
Talanta ; 251: 123793, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35952501

RESUMO

Circulating tumor cells (CTCs), as a type of tumor, have attracted wide attention because of their characteristics of shedding from the primary tumor and spreading to other tissues and organs through peripheral blood. The circulating tumor DNA (ctDNA), the DNA released by CTCs and other tumor cells into the peripheral blood, was considered as a promising detection substance for clinical application. By utilizing the biocompatibility of red blood cells to realize the attachment of tetrahedral DNA (TDN), as well as the specific target recognition ability of TDN to enable efficient recognition of targets, a biocompatible electrochemical biosensor for effective and rapid detection of ctDNA was developed using methylene blue (MB) as the signal probe. The current signal and the logarithm of ctDNA concentration were linearly correlated in the range from 1 fM to 100 pM with the detection limit of 0.66 fM. With high specificity, the TDN-based biosensor can detect ctDNA efficiently in the real biological environment such as serum, which provided a potential opportunity for the early clinical diagnosis.


Assuntos
Técnicas Biossensoriais , DNA Tumoral Circulante , Nanoestruturas , Células Neoplásicas Circulantes , DNA/química , Técnicas Eletroquímicas , Eritrócitos , Humanos , Limite de Detecção , Azul de Metileno , Nanoestruturas/química
20.
Front Endocrinol (Lausanne) ; 14: 1287463, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38260160

RESUMO

Introduction: Previous observational studies have reported a positive correlation between obesity and susceptibility to hypothyroidism; however, there is limited evidence from alternative methodologies to establish a causal link. Methods: We investigated the causal relationship between obesity and hypothyroidism using a two-sample bidirectional Mendelian randomization (MR) analysis. Single-nucleotide polymorphisms (SNPs) associated with obesity-related traits were extracted from a published genome-wide association study (GWAS) of European individuals. Summarized diagnostic data of hypothyroidism were obtained from the UK Biobank. Primary analyses were conducted using the inverse variance-weighted (IVW) method with a random-effects model as well as three complementary approaches. Sensitivity analyses were performed to ascertain the correlation between obesity and hypothyroidism. Results: MR analyses of the IVW method and the analyses of hypothyroidism/myxedema indicated that body mass index (BMI) and waist circumference (WC) were significantly associated with higher odds and risk of hypothyroidism. Reverse MR analysis demonstrated that a genetic predisposition to hypothyroidism was associated with an increased risk of elevated BMI and WC, which was not observed between WC adjusted for BMI (WCadjBMI) and hypothyroidism. Discussion: Our current study indicates that obesity is a risk factor for hypothyroidism, suggesting that individuals with higher BMI/WC have an increased risk of developing hypothyroidism and indicating the importance of weight loss in reducing the risk of hypothyroidism.


Assuntos
Estudo de Associação Genômica Ampla , Hipotireoidismo , Humanos , Análise da Randomização Mendeliana , Hipotireoidismo/complicações , Hipotireoidismo/genética , Causalidade , Obesidade/complicações , Obesidade/genética
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