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2.
J Mol Histol ; 55(4): 391-401, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38869753

RESUMEN

BACKGROUND: Sorting nexin 14 (SNX14) is a member of the sorting junction protein family. Its specific roles in cancer development remain unclear. Therefore, in this study, we aimed to determine the effects and underlying mechanisms of SNX14 on autophagy of breast cancer cells to aid in the therapeutic treatment of breast cancer. METHODS: In this study, we performed in vitro experiments to determine the effect of SNX14 on breast cancer cell growth. Moreover, we used an MCF7 breast cancer tumor-bearing mouse model to confirm the effect of SNX14 on tumor cell growth in vivo. We also performed western blotting and quantitative polymerase chain reaction to identify the mechanism by which SNX14 affects breast cancer MCF7 cells. RESULTS: We found that SNX14 regulated the onset and progression of breast cancer by promoting the proliferation and inhibiting the autophagy of MCF7 breast cancer cells. In vivo experiments further confirmed that SNX14 knockdown inhibited the tumorigenicity and inhibited the growth of tumor cells in tumor tissues of nude mice. In addition, western blotting analysis revealed that SNX14 modulate the autophagy of MCF7 breast cancer cells via the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin kinase signaling pathway. CONCLUSION: Our findings indicate that SNX14 is an essential tumor-promoting factor in the development of breast cancer.


Asunto(s)
Autofagia , Neoplasias de la Mama , Proliferación Celular , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Nexinas de Clasificación , Serina-Treonina Quinasas TOR , Animales , Femenino , Humanos , Ratones , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Células MCF-7 , Ratones Desnudos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Nexinas de Clasificación/metabolismo , Nexinas de Clasificación/genética , Serina-Treonina Quinasas TOR/metabolismo
3.
Sci Rep ; 14(1): 7654, 2024 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561419

RESUMEN

Epidermal growth factor receptor (EGFR) exon 19 deletion is a major driver for the drug resistance of non-small cell lung cancer (NSCLC). Identification small inhibitor capable of selectively inhibiting EGFR-19del NSCLC is a desirable strategy to overcome drug resistance in NSCLC. This study aims to screen an inhibitor for EGFR exon 19 deletion cells and explore its underlying mechanism. High through-put screen was conducted to identify an inhibitor for EGFR-19del NSCLC cells. And tenovin-3 was identified as a selective inhibitor of PC9 cells, an EGFR-19del NSCLC cells. Tenovin-3 showed particular inhibition effect on PC9 cells proliferation through inducing apoptosis and ferroptosis. Mechanistically, tenovin-3 might induce the apoptosis and ferroptosis of PC9 cells through mitochondrial pathway, as indicated by the change of VDAC1 and cytochrome c (cyt c). And bioinformatics analyses showed that the expression levels of SLC7A11 and CPX4 were correlated with NSCLC patient's survival. Our findings provide evidences for tenovin-3 to be developed into a novel candidate agent for NSCLC with EGFR exon 19 deletion. Our study also suggests that inducing ferroptosis may be a therapeutic strategy for NSCLC with EGFR exon 19 deletion.


Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Ferroptosis , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Receptores ErbB/metabolismo , Apoptosis , Línea Celular Tumoral , Resistencia a Antineoplásicos , Inhibidores de Proteínas Quinasas/farmacología , Mutación
4.
Curr Eye Res ; 49(9): 972-979, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38679893

RESUMEN

PURPOSE: To investigate the effects of resveratrol (Res) on human fetal scleral fibroblasts (HFSFs) and its potential mechanism. METHODS: HFSFs were randomly divided into the Res-treated group and the control group. Following, HFSFs were treated with or without a concentration of 10 µM Res for 48 h. To detect the expression of related genes, reverse transcription quantitative PCR (RT-qPCR) and western blotting were used. The apoptosis rate of different groups was determined using flow cytometry. RESULTS: The mRNA expression of matrix metalloproteinase 2 (MMP-2), Collagen, Type I, Alpha 1 (COL1A1), Janus Kinase 2 (JAK2), and Signal Transducer and Activator of Transcription 3 (STAT3)" was downregulated in the Res-treatment group compared to the control group, according to RT-qPCR. Western blotting revealed that Res therapy reduced the expression of MMP-2, JAK2, P-JAK2, STAT3, P-STAT3, and Bcl-2 associated protein X (Bax) while increasing the expression of COL1A1 and B-cell lymphoma-2 (Bcl-2). Flow cytometry showed that the cell apoptosis rate was significantly lower in HFSFs treated with Res. CONCLUSIONS: In conclusion, these findings suggest that Res increases COL1A1 expression while inhibiting MMP-2 and cell apoptosis in HFSFs, possibly through modulation of the JAK2/STAT3 signaling pathway.


Asunto(s)
Apoptosis , Western Blotting , Fibroblastos , Citometría de Flujo , Janus Quinasa 2 , Metaloproteinasa 2 de la Matriz , Resveratrol , Factor de Transcripción STAT3 , Esclerótica , Resveratrol/farmacología , Humanos , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/genética , Células Cultivadas , Apoptosis/efectos de los fármacos , Janus Quinasa 2/metabolismo , Janus Quinasa 2/genética , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Esclerótica/metabolismo , Esclerótica/citología , Cadena alfa 1 del Colágeno Tipo I , ARN Mensajero/genética , Colágeno Tipo I/metabolismo , Colágeno Tipo I/genética , Colágeno Tipo I/biosíntesis , Estilbenos/farmacología , Reacción en Cadena en Tiempo Real de la Polimerasa , Regulación de la Expresión Génica , Transducción de Señal , Antioxidantes/farmacología
5.
Clin Cosmet Investig Dermatol ; 17: 547-552, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38476341

RESUMEN

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic inflammatory disease mainly manifested as skin and osteoarticular lesions. Herein, we describe a female patient with SAPHO syndrome exhibited paradoxical psoriasis and primary palmoplantar pustulosis (PPP) worsened during treatment with adalimumab. We then switched to secukinumab and obtained significant improvement in both skin lesions and osteoarticular pain. These findings suggest that secukinumab might be an appropriate option for patients with SAPHO syndrome who present with TNF-α-inhibitor-induced paradoxical psoriasis.

6.
J Exp Clin Cancer Res ; 43(1): 83, 2024 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-38493151

RESUMEN

BACKGROUND: Tumor angiogenesis inhibitors have been applied for non-small cell lung cancer (NSCLC) therapy. However, the drug resistance hinders their further development. Intercellular crosstalk between lung cancer cells and vascular cells was crucial for anti-angiogenenic resistance (AAD). However, the understanding of this crosstalk is still rudimentary. Our previous study showed that Glioma-associated oncogene 1 (Gli1) is a driver of NSCLC metastasis, but its role in lung cancer cell-vascular cell crosstalk remains unclear. METHODS: Conditioned medium (CM) from Gli1-overexpressing or Gli1-knockdown NSCLC cells was used to educate endothelia cells and pericytes, and the effects of these media on angiogenesis and the maturation of new blood vessels were evaluated via wound healing assays, Transwell migration and invasion assays, tube formation assays and 3D coculture assays. The xenograft model was conducted to establish the effect of Gli1 on tumor angiogenesis and growth. Angiogenic antibody microarray analysis, ELISA, luciferase reporte, chromatin immunoprecipitation (ChIP), bFGF protein stability and ubiquitination assay were performed to explore how Gli1 regulate bFGF expression. RESULTS: Gli1 overexpression in NSCLC cells enhanced the endothelial cell and pericyte motility required for angiogenesis required for angiogenesis. However, Gli1 knockout in NSCLC cells had opposite effect on this process. bFGF was critical for the enhancement effect on tumor angiogenesis. bFGF treatment reversed the Gli1 knockdown-mediated inhibition of angiogenesis. Mechanistically, Gli1 increased the bFGF protein level by promoting bFGF transcriptional activity and protein stability. Importantly, suppressing Gli1 with GANT-61 obviously inhibited angiogenesis. CONCLUSION: The Gli1-bFGF axis is crucial for the crosstalk between lung cancer cells and vascular cells. Targeting Gli1 is a potential therapeutic approach for NSCLC angiogenesis.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Pericitos/metabolismo , Pericitos/patología , Proteína con Dedos de Zinc GLI1/genética , Proteína con Dedos de Zinc GLI1/metabolismo , Angiogénesis , Neovascularización Patológica/genética , Neovascularización Patológica/patología , Movimiento Celular , Línea Celular Tumoral , Proliferación Celular
7.
Exp Cell Res ; 437(1): 113998, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38513962

RESUMEN

Plasma saturated free fatty acid (FFA)-induced endothelial dysfunction (ED) contributes to the pathogenesis of atherosclerosis and cardiovascular diseases. However, the mechanism underlying saturated FFA-induced ED remains unclear. This study demonstrated that palmitic acid (PA) induced ED by activating the NADPH oxidase (NOX)/ROS signaling pathway to activate protein phosphatase 4 (PP4) and protein phosphatase 2A (PP2A), thereby reducing endothelial nitric oxide synthase (eNOS) phosphorylation at Ser633 and Ser1177, respectively. Okadaic acid (OA) and fostriecin (FST), which are inhibitors of PP2A, inhibited the PA-induced decreases in eNOS phosphorylation at Ser633 and Ser1177. The antioxidants N-acetylcysteine (NAC) and apocynin (APO) or knockdown of gp91phox or p67phox (NOX subunits) restored PA-mediated downregulation of PP4R2 protein expression and eNOS Ser633 phosphorylation. Knockdown of the PP4 catalytic subunit (PP4c) specifically increased eNOS Ser633 phosphorylation, while silencing the PP2A catalytic subunit (PP2Ac) restored only eNOS Ser1177 phosphorylation. Furthermore, PA dramatically decreased the protein expression of the PP4 regulatory subunit R2 (PP4R2) but not the other regulatory subunits. PP4R2 overexpression increased eNOS Ser633 phosphorylation, nitric oxide (NO) production, cell migration and tube formation but did not change eNOS Ser1177 phosphorylation levels. Coimmunoprecipitation (Co-IP) suggested that PP4R2 and PP4c interacted with the PP4R3α and eNOS proteins. In summary, PA decreases PP4R2 protein expression through the Nox/ROS pathway to activate PP4, which contributes to ED by dephosphorylating eNOS at Ser633. The results of this study suggest that PP4 is a novel therapeutic target for ED and ED-associated vascular diseases.


Asunto(s)
Óxido Nítrico Sintasa de Tipo III , Fosfoproteínas Fosfatasas , Enfermedades Vasculares , Humanos , Fosforilación , Óxido Nítrico Sintasa de Tipo III/metabolismo , Ácido Palmítico/farmacología , Serina/metabolismo , Especies Reactivas de Oxígeno , Células Cultivadas , Proteína Fosfatasa 2/metabolismo , Óxido Nítrico/metabolismo
8.
Zookeys ; 1188: 251-264, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38239384

RESUMEN

Three new species of the genus Oecleopsis Emeljanov, 1971 from China, O.acerbus Lv & Chen, sp. nov. and O.panxianensis Lv & Chen, sp. nov. from Guizhou Province, and O.digitatus Lv & Chen, sp. nov. from Sichuan Province, are described and illustrated. With these additions, the number of species in the genus is increased to 18. An updated identification key and checklist of all known species of Oecleopsis are provided as well as a map of their geographic distributions.

9.
Sci Rep ; 14(1): 359, 2024 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-38172590

RESUMEN

This study aimed to investigate the molecular mechanism of sporotrichosis and identify possible novel therapeutic targets. Total RNA was extracted from skin lesion samples from sporotrichosis patients and used to construct a long-chain RNA transcriptome library and miRNA transcriptome library for whole transcriptome sequencing. The differentially expressed genes (DEGs) between the groups were identified, and then Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis enrichment analyses were performed based on the DEGs. An lncRNA-miRNA-mRNA ceRNA network was constructed. The expressions of JAK/STAT pathway-related proteins were detected in the patient and control tissues using RT-qPCR and Western blot analysis. Enrichment analysis showed that the DEGs were mainly enriched in various infectious diseases and immune response-related signaling pathways. Competing endogenous RNA network analysis was performed and identified the hub lncRNAs, miRNAs, and mRNAs. Compared with the control group, the mRNA expressions of SOCS3, IL-6, and JAK3 were significantly upregulated, while the expression of STAT3 did not change significantly. Also, the protein expressions of SOCS3, IL-6, JAK3, and STAT3, as well as phosphorylated JAK3 and STAT3, were significantly upregulated. We identified 671 lncRNA DEGs, 3281 mRNA DEGs, and 214 miRNA DEGs to be involved in Sporothrix globosa infection. The study findings suggest that the JAK/STAT pathway may be a therapeutic target for sporotrichosis.


Asunto(s)
MicroARNs , ARN Largo no Codificante , Esporotricosis , Humanos , ARN Largo no Codificante/genética , Esporotricosis/genética , Secuenciación del Exoma , Interleucina-6/genética , Quinasas Janus/genética , Redes Reguladoras de Genes , Transducción de Señal/genética , Factores de Transcripción STAT/genética , MicroARNs/genética , Transcriptoma , ARN Mensajero/genética
10.
Sci Rep ; 13(1): 17803, 2023 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-37853132

RESUMEN

Increasing evidences demonstrate that chlorogenic acid (CGA), a polyphenol with multiple effects such as anti-inflammatory and anti-oxidation, protects against myocardial ischemia-reperfusion injury (MIRI) in vitro and in vivo. But its detailed cardiac protection mechanism is still unclear. The MIRI mice model was established by ligating the left anterior descending branch (LAD) of the left coronary artery in C57BL/6 mice. Sixty C57BL/6 mice were randomly divided into four groups. CGA group and CGA + I/R group (each group n = 15) were gavaged with 30 mg/kg/day CGA for 4 weeks. Sham group and I/R group mice (each group n = 15) were administered equal volumes of saline. In vitro MIRI model was constructed by hypoxia and reoxygenation of HL-1 cardiomyocytes. The results showed that CGA pretreatment reduced myocardial infarction size and cTnT contents in serum, simultaneously reduced the levels of Lnc Neat1 expression and attenuated NLRP3 inflammasome-mediated pyroptosis in myocardial tissue. Consistent with in vivo results, the pretreatment of 0.2 µM and 2 µM CGA for 12 h in HL-1 cardiomyocytes depressed hypoxia/reoxygenation-induced Lnc Neat1 expression, NLRP3 inflammasome activation and pyroptosis. Lnc Neat1 shRNA transfection mediated by lentivirus in HL-1 cardiomyocytes significantly reduced activation of NLRP3 inflammasome and pyroptosis. Our findings suggest that CGA protects against MIRI by depressing Lnc Neat1 expression and NLRP3 inflammasome-mediated pyrotosis. Inhibiting the levels of Lnc Neat1 expression may be a therapeutic strategy for MIRI.


Asunto(s)
Inflamasomas , Daño por Reperfusión Miocárdica , Ratones , Animales , Inflamasomas/metabolismo , Piroptosis , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/prevención & control , Daño por Reperfusión Miocárdica/metabolismo , Ácido Clorogénico/farmacología , Ácido Clorogénico/uso terapéutico , Ratones Endogámicos C57BL , Hipoxia
11.
Mycopathologia ; 188(5): 515-522, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37022619

RESUMEN

OBJECTIVES: To investigate the current etiological, diagnostic, and therapeutic characteristics of tinea capitis in children in Jilin Province. METHODS: Sixty pediatric patients with tinea capitis were enrolled between August 2020 and December 2021. Data on calcofluor white (CFW) fluorescence microscopy, fungal culture, Wood's lamp examination, dermoscopy, treatment, and follow-up were collected and analyzed. RESULTS: 1. Of all the enrolled patients, 48 had a history of animal contact, mostly with cats and dogs. Fifty-one strains were isolated, of which 46 were Microsporum canis (M. canis). 2. All enrolled patients were examined using fluorescence microscopy, and 59 were positive. Forty-one cases of tinea alba were examined using Wood's lamp, and 38 were positive. Forty-two cases of tinea alba were examined using dermoscopy, and 39 demonstrated specific signs. Effective treatment manifested as a fading bright green fluorescence, decreased mycelial/spore load, reduced specific dermoscopic signs, and hair regrowth. 3. Treatment was terminated in 23 and 37 cases based on mycological and clinical cures, respectively. No recurrence occurred during follow-up. CONCLUSION: 1. M. canis is the predominant pathogen causing tinea capitis in children in Jilin Province. Animal contact is considered the main risk factor. 2. CFW fluorescence microscopy, Wood's lamp, and dermoscopy can be used to diagnose ringworms and follow-up patients. 3. Both mycological and clinical cures can be the endpoint of adequate treatment for tinea capitis.


Asunto(s)
Tiña del Cuero Cabelludo , Tiña , Humanos , Niño , Animales , Gatos , Perros , Tiña del Cuero Cabelludo/diagnóstico , Tiña del Cuero Cabelludo/epidemiología , Tiña del Cuero Cabelludo/tratamiento farmacológico , Microsporum , Cabello/microbiología
12.
Curr Med Sci ; 43(1): 173-183, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36867361

RESUMEN

OBJECTIVE: To investigate the etiology, clinical characteristics, diagnosis, and treatment strategies and efficacy of pulsatile tinnitus (PT) caused by vascular anatomy abnormality. METHODS: The clinical data of 45 patients with PT in our hospital from 2012 to 2019 were collected and retrospectively analyzed. RESULTS: All 45 patients had vascular anatomical abnormalities. The patients were divided into 10 categories according to the different locations of vascular abnormalities: sigmoid sinus diverticulum (SSD), sigmoid sinus wall dehiscence (SSWD), SSWD with high jugular bulb, pure dilated mastoid emissary vein, aberrant internal carotid artery (ICA) in the middle ear, transverse-sigmoid sinus (TSS) transition stenosis, TSS transition stenosis with SSD, persistent occipital sinus stenosis, petrous segment stenosis of ICA, and dural arteriovenous fistula. All patients complained of PT synchronous with heartbeat rhythm. Endovascular interventional therapy and extravascular open surgery were used according to the location of the vascular lesions. Tinnitus disappeared in 41 patients, was significantly relieved in 3 patients, and was unchanged in 1 patient postoperatively. Except for one patient with transient headache postoperatively, no obvious complications occurred. CONCLUSION: PT caused by vascular anatomy abnormalities can be identified by detailed medical history and physical and imaging examination. PT can be relieved or even completely alleviated after appropriate surgical treatments.


Asunto(s)
Procedimientos Endovasculares , Acúfeno , Humanos , Constricción Patológica , Estudios Retrospectivos , Frecuencia Cardíaca
13.
J Nat Prod ; 86(2): 368-379, 2023 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-36692021

RESUMEN

Angiogenesis and vasculogenic mimicry (VM) are crucial for the growth and metastasis of non-small-cell lung cancer (NSCLC). Most tumor angiogenesis inhibitors mainly target endothelial cell-mediated angiogenesis, ignoring tumor-cell-mediated VM and frequently leading to tumor recurrence and metastasis. Thus, development of bioactive molecules interfering with both tumor angiogenesis and VM is necessary. Identifying novel angiogenesis inhibitors from natural products is a promising strategy. Scoparasin B, a pimarane diterpene extracted from a marine-derived fungus, Eutypella sp. F0219, has an antibacterial effect. However, its effect on angiogenesis and VM remains unexplored. In this study, we first certified that scoparasin B showed a strong inhibition effect on angiogenesis and the VM process in vitro and ex vivo. Moreover, scoparasin B prominently impeded tumor growth, angiogenesis, and VM in an NCI-H1299 xenograft model. Further study revealed that scoparasin B restrained tumor angiogenesis and VM by reducing the VEGF-A level and suppressing the VEGF-A/VEGFR2 signaling pathway. This study first demonstrated scoparasin B inhibited tumor angiogenesis, VM, and tumor growth of NSCLC and revealed its underlying mechanism. These new findings further support the potential of scoparasin B as a novel angiogenesis inhibitor and give a hint for further exploring potential angiogenesis inhibitors from natural products.


Asunto(s)
Productos Biológicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Inhibidores de la Angiogénesis/farmacología , Productos Biológicos/uso terapéutico , Línea Celular Tumoral , Neoplasias Pulmonares/patología , Recurrencia Local de Neoplasia , Neovascularización Patológica , Factor A de Crecimiento Endotelial Vascular
14.
Biomed Mater Eng ; 34(1): 1-11, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35180101

RESUMEN

BACKGROUND: Acute liver failure is one of the most intractable clinical problems. The use of bioartificial livers may solve donor shortage problems. Human umbilical cord mesenchymal stem cells (hUCMSCs) are an excellent seed cell choice for artificial livers because they change their characteristics to resemble hepatocyte-like cells (HLCs) following artificial liver transplantation. OBJECTIVE: This study aimed to determine whether the immunological characteristics of hUCMSCs are changed after being transformed into hepatocyte-like cells. METHODS: HUCMSCs were isolated by the adherent method. The following hUCMSC surface markers were detected using flow cytometry: CD45, CD90, CD105, CD34, and octamer-binding transcription factor 4 (OCT-4). Functional detection of adipogenic differentiation was performed. The hUCMSCs were cultured in complete medium (control group) or induction medium (induction group), and flow cytometry was used to detect cell surface markers. Peritoneal lavage fluid was collected after intraperitoneal injection of 1 × 106 cells/mouse over 40 minutes. The leukocyte count, labeled CD45, CD3, CD4 and CD8 antibodies, and flow detection of T lymphocyte subsets were determined using the peritoneal lavage fluid. RESULTS: Using phenotypic and functional identification, hUCMSCs were successfully isolated using a two-step induction method. The surface markers of the hUCMSCs cells changed after HLC induction. In vivo immune results showed that hUCMSCs and HLsC induced leukocyte production. CONCLUSION: Hepatic induction of hUCMSCs changes their cell surface markers. Both HLCs and hUCMSCs cause leukocytosis in vivo, but the immune response induced by HLCs is slightly stronger.


Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Humanos , Animales , Ratones , Diferenciación Celular , Hígado , Hepatocitos , Cordón Umbilical , Trasplante de Células Madre Mesenquimatosas/métodos
15.
Acta Pharm Sin B ; 12(10): 3877-3890, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36213531

RESUMEN

Metastasis is crucial for the mortality of non-small cell lung carcinoma (NSCLC) patients. The epithelial-mesenchymal transition (EMT) plays a critical role in regulating tumor metastasis. Glioma-associated oncogene 1 (Gli1) is aberrantly active in a series of tumor tissues. However, the molecular regulatory relationships between Gli1 and NSCLC metastasis have not yet been identified. Herein, we reported Gli1 promoted NSCLC metastasis. High Gli1 expression was associated with poor survival of NSCLC patients. Ectopic expression of Gli1 in low metastatic A549 and NCI-H460 cells enhanced their migration, invasion abilities and facilitated EMT process, whereas knock-down of Gli1 in high metastatic NCI-H1299 and NCI-H1703 cells showed an opposite effect. Notably, Gli1 overexpression accelerated the lung and liver metastasis of NSCLC in the intravenously injected metastasis model. Further research showed that Gli1 positively regulated Snail expression by binding to its promoter and enhancing its protein stability, thereby facilitating the migration, invasion and EMT of NSCLC. In addition, administration of GANT-61, a Gli1 inhibitor, obviously suppressed the metastasis of NSCLC. Collectively, our study reveals that Gli1 is a critical regulator for NSCLC metastasis and suggests that targeting Gli1 is a prospective therapy strategy for metastatic NSCLC.

16.
Pharmgenomics Pers Med ; 15: 583-588, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35698621

RESUMEN

We aimed to detect the pathogenic gene mutations in a patient with lamellar ichthyosis (LI). The genomic DNA of the patient was examined using high-throughput whole-exome sequencing to identify the causative mutations. Compound heterozygous mutations of c.1187G>T (p.Arg396Leu) and c.607C>T (p.Gln203*) were found in the transglutaminase-1 gene (TGM1) on chromosome 14 of the proband. The mutations stated above have been reported to impair the function of TGM1 protein and to be pathogenic. Our data suggest that the proband carried compound heterozygous mutations of c.1187G>T(p.Arg396Leu) and c.607C>T(p.Gln203*) in TGM1, which were in the trans position and the cause of his disease. We also found some dermoscopic in this patient which may be specific in LI.

17.
Ophthalmic Res ; 65(5): 566-574, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35605595

RESUMEN

INTRODUCTION: The purpose of this study was to determine whether miR-29a regulates cell survival and apoptosis and the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), MMP-2, and collagen I in scleral fibroblasts. METHODS: We transfected scleral fibroblasts with the miR-29a mimic and inhibitor. The effects of miR-29a on cell proliferation and apoptosis were determined using the CCK-8 assay and flow cytometry, respectively. Quantitative polymerase chain reaction (qPCR) was used to determine whether miR-29a regulates the mRNA levels of PTEN, MMP-2, and collagen I. The protein expression of PTEN, MMP-2, and collagen I was also assessed by western blot analysis. RESULTS: The results of CCK-8 showed that, at 0, 24, 48, and 72 h after transfection, the relative optical density values in the mimic group were 0.233 ± 0.005, 0.380 ± 0.008, 0.650 ± 0.040, and 0.906 ± 0.032, and in the inhibitor group were 0.272 ± 0.011, 0.393 ± 0.029, 0.597 ± 0.059, and 0.950 ± 0.101, respectively. The flow cytometry results showed that the apoptosis rates of each group were as follows: the mimic group (0.043 ± 0.007), the NC group (0.040 ± 0.006), the inhibitor group (0.032 ± 0.003), the inhibitor NC group (0.027 ± 0.010), the lipofectamine group (0.027 ± 0.005), and the blank group (0.031 ± 0.009). The qPCR results indicated that in the mimic group, PTEN (0.795 ± 0.182, p = 0.2783), MMP-2 (0.621 ± 0.105, p = 0.0033), and COL1A1 (0.271 ± 0.100, p = 0.0002) expression decreased, whereas in the inhibitor group, PTEN (1.211 ± 0.100, p = 0.2614), MMP-2 (1.161 ± 0.053, p = 0.1190), and COL1A1 (1.7040 ± 0.093, p = 0.0003) increased. Western blot analysis showed that in the mimic group, the expression of PTEN (0.392 ± 0.039, p < 0.0001), MMP-2 (0.577 ± 0.017, p < 0.0001), and COL1A1 (0.072 ± 0.006, p < 0.0001) protein decreased, whereas in the inhibitor group, PTEN (1.043 ± 0.042, p = 0.9413), MMP-2 (1.397 ± 0.075, p = 0.0002), and COL1A1 (1.935 ± 0.081, p < 0.0001) expression increased. CONCLUSION: MiR-29a inhibits the expression of PTEN, MMP-2, and collagen I on scleral fibroblasts, which may provide a basis studies in sclera.


Asunto(s)
Metaloproteinasa 2 de la Matriz , MicroARNs , Apoptosis/genética , Proliferación Celular , Colágeno/farmacología , Fibroblastos , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Esclerótica , Tensinas/metabolismo
18.
Quant Imaging Med Surg ; 12(5): 2792-2804, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35502366

RESUMEN

Background: To investigate the prognostic value of clinical features and metabolic parameters in pretreatment 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/X-ray computed tomography (PET/CT) scans of patients with angiosarcoma, a rare neoplasm that has not been well characterized. Methods: In this retrospective study, 19 patients with a histopathologically confirmed diagnosis of angiosarcoma who had undergone pretreatment 18F-FDG PET/CT scans were enrolled. We recorded the age at presentation, sex, underlying diseases, sites of primary tumors, Karnofsky Performance Status (KPS) score, Eastern Cooperative Oncology Group (ECOG) score, time from onset to diagnosis, laboratory examinations, sites and sizes of primary tumors, treatment modalities, histologic features and American Joint Committee on Cancer (AJCC) stage, maximum standardized uptake value (SUVmax), average SUV (SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of primary tumors and the whole body. Univariate and multivariate survival analyses for overall survival were performed according to the metabolic parameters and other clinical variables. Results: Patients ranged in age from 27 to 79 years (median: 59 years) with different angiosarcoma types covering all tumor grades and subtypes. Seven (7/19) patients had anemia of varying degrees of severity. Lymph node metastases (n=10) and/or distant metastases (n=11) of angiosarcoma were common. Bone or bone marrow (10/19) and lung (8/19) were the most common distant metastatic organs. Patients with bone metastases, low hemoglobin levels and high ferritin levels had significantly poorer overall survival than those with non-bone metastases, normal hemoglobin levels and normal ferritin levels by the log-rank test, with P values of 0.027, 0.030 and 0.015, respectively. Patients with multiple organ metastases had significantly poorer overall survival than those with single organ metastasis (log-rank P=0.008). In multivariate survival analysis, only whole-body metabolic tumor volume using SUVmax cut-off value of 2.5 (wMTV2.5) was a significant independent prognostic factor. For wMTV2.5, 870.3 cm3 was the best cut-off point to discriminate between a good and poor prognosis (log-rank P=0.01). Conclusions: The systemic 18F-FDG PET/CT with high sensitivity and specificity has significant advantages in the evaluation of angiosarcoma, particularly in detecting occult metastases. Bone metastases on 18F-FDG PET/CT, low hemoglobin levels and high ferritin levels were all associated with a poorer prognosis. MTV2.5 of the whole body is a significant independent metabolic prognostic factor for overall survival in patients with angiosarcoma.

19.
Chem Biol Interact ; 361: 109966, 2022 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-35513012

RESUMEN

Tumor angiogenesis inhibitors such as Bevacizumab, Ramucirumab and Endostar have been applied to the therapy of non-small cell lung carcinoma (NSCLC) patients, especially for lung adenocarcinoma (LUAD). However, several safe concerns such as neutropenia, febrile neutropenia and hypertension pulmonary hemorrhage limit their further development. And they often showed poor efficacy and serious side effect for lung squamous cell carcinoma (LUSC) patient. Thus, identification of effective and safe tumor angiogenesis inhibitor for NSCLC therapy is warranted. Apigenin is a bioflavonoid with potential anti-tumor effect and perfect safety, but its effect on tumor angiogenesis and underlying mechanism are still unclear. Herein, we found that apigenin not merely suppressed endothelial cells related motilities but also reduced pericyte coverage. Further research showed that apigenin had strong suppressive activity against HIF-1α expression and its downstream VEGF-A/VEGFR2 and PDGF-BB/PDGFßR signaling pathway. Apigenin also reduced microvessel density and pericyte coverage on the xengraft model of NCI-H1299 cells, leading to suppression of tumor growth. Moreover, apigenein showed perfect anti-angiogenic effect in xengraft model of LUSC cell NCI-H1703 cells, indicating it may be developed into a potential angiogenesis inhibitor for LUSC patient. Collectively, our study provides new insights into the anti-tumor mechanism of apigenin and suggests that apigenin is a safe and effective angiogenesis inhibitor for NSCLC therapy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Apigenina/farmacología , Apigenina/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Células Endoteliales/metabolismo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Pulmonares/patología , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo
20.
Infect Drug Resist ; 15: 1753-1765, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35431560

RESUMEN

Introduction: This study was aimed to examine the clinical and epidemiological characteristics of sporotrichosis in China and specifically Jilin Province, which is one of the areas with the highest incidence worldwide, and to provide data support for the global prevalence of sporotrichosis. Methods: A total of 4969 cases of sporotrichosis diagnosed at the Second Hospital of Jilin University from January 1, 1990 to December 31, 2019 were collected. Results: In Jilin Province, the male-to-female ratio was 1:2, the average age at onset was 48 ± 1 years, and the average disease duration was 4.8 ± 2.7 months. The most susceptible individuals were farmers. Cases occurred more commonly in the winter and spring (71.5%) than in the summer and autumn (28.5%). The fixed type infection was more prevalent. Among the cases, 64.8% showed typical mycological changes, and 77.6% showed atypical pathological changes. Regarding the epidemiological characteristics of sporotrichosis in China, 6565 cases were retrieved from the literature from January 1, 2010 to December 31, 2019. Among them, the most affected area was Jilin Province, followed by Heilongjiang Province, and Liaoning Province. The male-to-female ratio was 1:1.46. The fixed type infection was the most common. A total of 241 strains were identified by molecular biotechnology; among these, 217 were identified as Sporothrix globosa and 24 were identified as S. schenckii sensu stricto. Discussion: The results add clarity to the clinical epidemiology of sporotrichosis in China and specifically Jilin Province. We believe these data will help improve the epidemiology knowledge of sporotrichosis worldwide.

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