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1.
Proc Natl Acad Sci U S A ; 120(13): e2215132120, 2023 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-36961927

RESUMEN

Distant metastasis is a major contributor to cancer-related mortality. However, the role of circRNAs in this process remains unclear. Herein, we profiled the circRNA expression in a cohort of 68 colorectal carcinoma (CRC) primary tumors and their paired liver metastatic lesions. By overlapping with the TGFß-responsive circRNAs, circNEIL3 (hsa_circ_0001460) was identified as a TGFß-repressive and metastasis-related circRNA. Functionally, circNEIL3 effectively inhibited tumor metastasis in both and in vivo and in vivo models of various cancer types. Mechanistically, circNEIL3 exerts its metastasis-repressive function through its direct interaction with oncogenic protein, Y-box-binding protein 1 (YBX1), which consequently promotes the Nedd4L-mediated proteasomal degradation of YBX1. Importantly, circNEIL3 expression was negatively correlated to YBX1 protein level and metastatic tendency in CRC patient samples. Collectively, our findings indicate the YBX1-dependent antimetastatic function of circNEIL3 and highlight the potential of circNEIL3 as a biomarker and therapeutic option in cancer treatment.


Asunto(s)
Neoplasias Colorrectales , Ubiquitina-Proteína Ligasas , Humanos , Ubiquitina-Proteína Ligasas/genética , ARN Circular/genética , ARN Circular/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Proteína 1 de Unión a la Caja Y/genética , Proteína 1 de Unión a la Caja Y/metabolismo
2.
J Chem Phys ; 161(6)2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39140446

RESUMEN

It has been supposed that the interplay of elasticity and activity plays a key role in triggering the non-equilibrium behaviors in biological systems. However, the experimental model system is missing to investigate the spatiotemporally dynamical phenomena. Here, a model system of an active chain, where active eccentric-disks are linked by a spring, is designed to study the interplay of activity, elasticity, and friction. Individual active chain exhibits longitudinal and transverse motions; however, it starts to self-rotate when pinning one end and self-beat when clamping one end. In addition, our eccentric-disk model can qualitatively reproduce such behaviors and explain the unusual self-rotation of the first disk around its geometric center. Furthermore, the structure and dynamics of long chains were studied via simulations without steric interactions. It was found that a hairpin conformation emerges in free motion, while in the constrained motions, the rotational and beating frequencies scale with the flexure number (the ratio of self-propelling force to bending rigidity), χ, as ∼(χ)4/3. Scaling analysis suggests that it results from the balance between activity and energy dissipation. Our findings show that topological constraints play a vital role in non-equilibrium synergy behaviors.

3.
Cell Mol Life Sci ; 80(4): 115, 2023 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-37014433

RESUMEN

CircRNAs are a class of single-stranded molecules with tissue/development-specific expression patterns. Increasing evidence demonstrates that circRNAs play important roles in physiological or pathological conditions. Here, we provide a brief discussion of circRNA in renal fibrosis.


Asunto(s)
Enfermedades Renales , MicroARNs , Humanos , ARN Circular/genética , Fibrosis , Enfermedades Renales/genética , MicroARNs/genética , ARN/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ARN
4.
J Sci Food Agric ; 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961686

RESUMEN

Hyacinth bean [Lablab purpureus (L.) Sweet], a plant belonging to the leguminous family and traditionally used for medicinal purposes in China, is a valuable resource with a wide range of health benefits. This review examines the bioactive compounds, health-promoting properties and functional food potential of hyacinth bean, highlighting its role in protecting against metabolic diseases and the underlying molecular mechanisms. According to existing research, hyacinth bean contains a diverse array of bioactive compounds, Consumption of hyacinth beans and hyacinth bean-related processed food products, as well as their use in medicines, is associated with a variety of health benefits that are increasingly favoured by the scientific community. In light of these findings, we posit that hyacinth bean holds great promise for further research and food application. © 2024 Society of Chemical Industry.

5.
J Sci Food Agric ; 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39276015

RESUMEN

BACKGROUND: Understanding the effects of different additions of adzuki bean flour (ABF) on structural and functional characteristics of extruded buckwheat noodles is important in developing high-quality starchy foods with desirable glycemic indexes. This study explored how varying amounts of ABF in extruded buckwheat noodles influenced their structural and functional characteristics. RESULTS: The findings indicated that adding ABF substantially boosted the levels of protein and flavonoids, while decreasing the content of fat and starch. Adding ABF to the noodles extended the optimum cooking time and led to a reduction in both the stickiness of the cooked noodles and the pore size of the starch gel structure, compared with pure buckwheat noodles. Fourier transform infrared spectroscopy indicated that R1047/1022 increased with the content of ABF increased, while R1022/995 decreased. X-ray diffraction showed that the relative crystallinity of buckwheat noodles was enhanced with increasing ABF amount. Adding ABF notably significantly decreased the estimated glycemic index. The buckwheat noodles extruded with 20% ABF addition demonstrated notably stronger α-glucosidase inhibitory effects than those extruded with no ABF addition. CONCLUSION: The present study demonstrates that the additions of ABF improved the structure and hypoglycemic activity of extruded buckwheat noodles while decreasing starch digestibility, and the optimal value was reached at an ABF addition of 20%. The study might fill gaps in starch noodle research and provide a new strategy for the development of functional food in the food industry. © 2024 Society of Chemical Industry.

6.
Mol Cancer ; 21(1): 63, 2022 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-35236349

RESUMEN

BACKGROUND: Circular RNAs (circRNAs) are differentially expressed between normal and cancerous tissues, contributing to tumor initiation and progression. However, comprehensive landscape of dysregulated circRNAs across cancer types remains unclear. METHODS: In this study, we conducted Ribo-Zero transcriptome sequencing on tumor tissues and their adjacent normal samples including glioblastoma, esophageal squamous cell carcinoma, lung adenocarcinoma, thyroid cancer, colorectal cancer, gastric cancer and hepatocellular carcinoma. CIRCexplorer2 was employed to identify circRNAs and dysregulated circRNAs and genes were determined by DESeq2 package. The expression of hsa_circ_0072309 (circLIFR) was measured by reverse transcription and quantitative real-time PCR, and its effect on cell migration was examined by Transwell and wound healing assays. The role of circLIFR in tumor metastasis was evaluated via mouse models of tail-vein injection and spleen injection for lung and liver metastasis, respectively. RESULTS: Distinct circRNA expression signatures were identified among seven types of solid tumors, and the dysregulated circRNAs exhibited cancer-specific expression or shared common expression signatures across cancers. Bioinformatics analyses indicated that aberrant expression of host genes and/or RNA-binding proteins contributed to circRNA dysregulation in cancer. Finally, circLIFR was experimentally validated to be downregulated in six solid tumors and to significantly inhibit cell migration in vitro and tumor metastasis in vivo. CONCLUSIONS: Our results provide a comprehensive landscape of differentially expressed circRNAs in solid tumors and highlight that circRNAs are extensively involved in cancer pathogenesis.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Animales , Movimiento Celular/genética , Biología Computacional/métodos , Humanos , Ratones , ARN/genética , ARN/metabolismo , ARN Circular/genética
7.
Hepatology ; 71(5): 1643-1659, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31509262

RESUMEN

BACKGROUND AND AIMS: Tumor metastasis is a major factor of high recurrence and mortality in hepatocellular carcinoma (HCC), but its underlying mechanism remains elusive. We report that PDZ and LIM domain protein 1 (PDLIM1) is significantly down-regulated in metastatic human HCC tissues, which predicts unfavorable prognosis, suggesting that PDLIM1 may play an important inhibitory role during HCC metastasis. APPROACH AND RESULTS: Functional studies indicate that PDLIM1 knockdown induces epithelial-to-mesenchymal transition (EMT) of HCC cells, elevates their invasive capacity, and promotes metastasis in vitro and in vivo, whereas overexpression of PDLIM1 exhibits opposite phenotypes. Mechanistically, PDLIM1 competitively binds to the cytoskeleton cross-linking protein alpha-actinin 4 (ACTN4), leading to the disassociation of ACTN4 from F-actin, thus preventing F-actin overgrowth. In contrast, loss of PDLIM1 induces excessive F-actin formation, resulting in dephosphorylation of large tumor suppressor kinase 1 and activation of Yes-associated protein, thereby promoting HCC metastasis. Moreover, Asn145 (N145) of PDLIM1 is critical for its interaction with ACTN4, and N145A mutation abolishes its regulatory function in Hippo signaling and HCC metastasis. CONCLUSIONS: Our findings indicate that PDLIM1 suppresses HCC metastasis by modulating Hippo signaling, suggesting that PDLIM1 may be a potential prognostic marker for metastatic HCC.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/secundario , Proteínas con Dominio LIM/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Factores de Transcripción/metabolismo , Actinina/metabolismo , Actinas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Transición Epitelial-Mesenquimal , Vía de Señalización Hippo , Humanos , Proteínas con Dominio LIM/genética , Neoplasias Hepáticas/genética , Metástasis de la Neoplasia , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal , Factores de Transcripción/genética , Proteínas Señalizadoras YAP
8.
Mol Cancer ; 19(1): 77, 2020 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-32295598

RESUMEN

Hepatocellular carcinoma (HCC) is the most frequent subtype of primary liver cancer and one of the leading causes of cancer-related death worldwide. However, the molecular mechanisms underlying HCC pathogenesis have not been fully understood. Emerging evidences have recently suggested the crucial role of long noncoding RNAs (lncRNAs) in the tumorigenesis and progression of HCC. Various HCC-related lncRNAs have been shown to possess aberrant expression and participate in cancerous phenotypes (e.g. persistent proliferation, evading apoptosis, accelerated vessel formation and gain of invasive capability) through their binding with DNA, RNA or proteins, or encoding small peptides. Thus, a deeper understanding of lncRNA dysregulation would provide new insights into HCC pathogenesis and novel tools for the early diagnosis and treatment of HCC. In this review, we summarize the dysregulation of lncRNAs expression in HCC and their tumor suppressive or oncogenic roles during HCC tumorigenesis. Moreover, we discuss the diagnostic and therapeutic potentials of lncRNAs in HCC.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/patología , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/patología , ARN Largo no Codificante/genética , Animales , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/genética
9.
J Cell Physiol ; 234(12): 22400-22410, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31120582

RESUMEN

Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with low survival rate, so new therapies are urgently needed. Histone deacetylases (HDACs) play a critical role in tumorigenesis, and HDACs inhibition is a potential therapeutic target in ESSC. In our study, we evaluated the effect and molecular mechanism of MS-275 (an inhibitor of HDACs) on ESCC cells. We found that HDAC1 and HDAC2 were overexpressed in ESCC tissues and related with clinical pathological features of patients with ESCC. MS-275 markedly reduced HDAC1 and HDAC2 expression, whereas increased the level of AcH3 and AcH2B. MS-275 suppressed proliferation and clonogenicity of ESCC cells in a concentration-dependent manner. In addition, MS-275 induced apoptosis, arrested cell cycle, and inhibited migration, epithelial-mesenchymal transition, and sphere-forming ability of ESCC cells in vitro. Moreover, p-Akt1 and p-mTOR were downregulated by MS-275. Finally, MS-275 significantly inhibited tumor growth in vivo. Taken together, HDAC1 and HDAC2 are associated with the progression of ESCC, and MS-275 hinders the progression and stemness of ESCC cells by suppressing the PI3K/Akt/mTOR pathway. Our findings show that MS-275 inhibits ESCC cells growth in vitro and in vivo, which is a potential drug for the ESCC therapy.


Asunto(s)
Benzamidas/farmacología , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Piridinas/farmacología , Serina-Treonina Quinasas TOR/metabolismo , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular , Línea Celular , Movimiento Celular , Supervivencia Celular/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Histona Desacetilasa 1/antagonistas & inhibidores , Histona Desacetilasa 1/genética , Histona Desacetilasa 1/metabolismo , Histona Desacetilasa 2/antagonistas & inhibidores , Histona Desacetilasa 2/genética , Histona Desacetilasa 2/metabolismo , Humanos , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Neoplasias Experimentales , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética
10.
Mol Cancer ; 18(1): 98, 2019 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-31118036

RESUMEN

Cancer-associated chromosomal translocations are reported to generate oncogenic circular RNA (circRNA), contributing to tumorigenesis. The fusion gene SLC34A2-ROS1 (solute carrier family 34 member 2 and ROS proto-oncogene 1) plays an important role in non-small cell lung cancer (NSCLC) progression. However, whether SLC34A2-ROS1 gene can produce circRNA remains unknown. Here, we identified two novel circRNAs (F-circSR1 and F-circSR2) generated from SLC34A2-ROS1 fusion gene, while F-circSR1 has higher expression than F-circSR2. Functional studies through gain- and loss-of-function strategies showed that both F-circSRs promote cell migration in lung cancer cells, whereas they have little effect on cell proliferation. Using the minigene GFP reporter assay, we verified that the flanking complementary sequences with canonical splicing sites are essential for F-circSR biogenesis. Therefore, our findings demonstrate the oncogenic role of F-circSR in NSCLC and highlight its therapeutic potential.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Proteínas de Fusión Oncogénica/genética , ARN Circular/genética , Células A549 , Línea Celular Tumoral , Movimiento Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas Tirosina Quinasas/genética , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas/genética , Proteínas Cotransportadoras de Sodio-Fosfato de Tipo IIb/genética , Translocación Genética , Regulación hacia Arriba
11.
Hepatology ; 68(2): 547-560, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29381806

RESUMEN

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, but there are few effective treatments. Aberrant microRNA (miRNA) biogenesis is correlated with HCC development. We previously demonstrated that peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) participates in miRNA biogenesis and is a potential HCC treatment target. However, how Pin1 modulates miRNA biogenesis remains obscure. Here, we present in vivo evidence that Pin1 overexpression is directly linked to the development of HCC. Administration with the Pin1 inhibitor (API-1), a specific small molecule targeting Pin1 peptidyl-prolyl isomerase domain and inhibiting Pin1 cis-trans isomerizing activity, suppresses in vitro cell proliferation and migration of HCC cells. But API-1-induced Pin1 inhibition is insensitive to HCC cells with low Pin1 expression and/or low exportin-5 (XPO5) phosphorylation. Mechanistically, Pin1 recognizes and isomerizes the phosphorylated serine-proline motif of phosphorylated XPO5 and passivates phosphorylated XPO5. Pin1 inhibition by API-1 maintains the active conformation of phosphorylated XPO5 and restores XPO5-driven precursor miRNA nuclear-to-cytoplasm export, activating anticancer miRNA biogenesis and leading to both in vitro HCC suppression and HCC suppression in xenograft mice. CONCLUSION: Experimental evidence suggests that Pin1 inhibition by API-1 up-regulates miRNA biogenesis by retaining active XPO5 conformation and suppresses HCC development, revealing the mechanism of Pin1-mediated miRNA biogenesis and unequivocally supporting API-1 as a drug candidate for HCC therapy, especially for Pin1-overexpressing, extracellular signal-regulated kinase-activated HCC. (Hepatology 2018).


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , MicroARNs/biosíntesis , Peptidilprolil Isomerasa de Interacción con NIMA/metabolismo , Nucleósidos/farmacología , Animales , Carcinoma Hepatocelular/patología , Proliferación Celular/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Xenoinjertos , Carioferinas/metabolismo , Neoplasias Hepáticas/patología , Ratones , Ratones Endogámicos BALB C , Transducción de Señal
12.
Bioorg Med Chem ; 27(11): 2235-2244, 2019 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-31027708

RESUMEN

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) participates in diverse cancer-associated signaling pathways, playing an oncogenic role in multiple human cancers, including hepatocellular carcinoma (HCC). Our recent works clarify that Pin1 modulates miRNAs biogenesis by interacting with ERK-phosphorylated exportin-5 (XPO5) and changing XPO5 conformation, giving a potential target for HCC treatment. Herein, we discover 4,6-bis(benzyloxy)-3-phenylbenzofuran (TAB29) as a novel Pin1 inhibitor that targets Pin1 PPIase domain. TAB29 potently inhibits Pin1 activity with the IC50 value of 874 nM and displays an excellent selectivity toward Pin1 in vitro. Cell-based biological evaluation reveals that TAB29 significantly suppresses cell proliferation of HCC cells through restoring the nucleus-to-cytoplasm export of XPO5 and upregulating mature miRNAs expression. Collectively, this work provides a promising small molecule lead compound for Pin1 inhibition, highlighting the therapeutic potential of miRNA-based treatment for human cancers.


Asunto(s)
Antineoplásicos/farmacología , Benzofuranos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Inhibidores Enzimáticos/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Peptidilprolil Isomerasa de Interacción con NIMA/antagonistas & inhibidores , Antineoplásicos/síntesis química , Antineoplásicos/metabolismo , Benzofuranos/síntesis química , Benzofuranos/metabolismo , Sitios de Unión , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Carioferinas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Simulación del Acoplamiento Molecular , Peptidilprolil Isomerasa de Interacción con NIMA/química , Peptidilprolil Isomerasa de Interacción con NIMA/metabolismo , Unión Proteica , Regulación hacia Arriba/efectos de los fármacos
13.
Cell Mol Life Sci ; 75(24): 4667-4681, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30293090

RESUMEN

Long non-coding RNA (lncRNA) plays an important role in tumor progression and metastasis. Emerging evidence indicates that lncRNA actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1) is dysregulated in certain tumors. However, the function of AFAP1-AS1 in non-small cell lung cancer (NSCLC) remains elusive. In this study, we conducted global lncRNA profiling and identified that AFAP1-AS1 is significantly upregulated in NSCLC, suggesting that AFAP1-AS1 may be important for lung cancer development. For the first time, the transcription initiation and termination sites of AFAP1-AS1 were identified by rapid amplification of cDNA ends technology, and the sequencing data indicated that AFAP1-AS1 in lung cancer cells is a novel transcript variant. Through gain- and loss-of-function studies, AFAP1-AS1 was demonstrated to promote cell migration and invasion. Mechanistically, AFAP1-AS1 functions through positively regulating the expression of AFAP1 protein. On the other hand, the expression of lncRNA AFAP1-AS1 negatively correlates with CpG methylation status of its gene promoter, identified in both lung cancer cells and patient tissues, and treatment with DNA methyltransferase inhibitor decitabine significantly activates AFAP1-AS1 expression, strongly supporting that AFAP1-AS1 expression is tightly regulated by DNA methylation. Taken together, this study demonstrates that AFAP1-AS1 acts as an oncogene in NSCLC to promote cell migration partly by upregulating AFAP1 expression, while its own expression is controlled by DNA methylation, and highlights its diagnostic and therapeutic values for NSCLC patients.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Movimiento Celular , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Invasividad Neoplásica/genética , ARN Largo no Codificante/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Metilación de ADN , Humanos , Neoplasias Pulmonares/patología , Proteínas de Microfilamentos/genética , Invasividad Neoplásica/patología , Regulación hacia Arriba
14.
Appl Opt ; 58(27): 7298-7304, 2019 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-31674373

RESUMEN

The conical diffraction Offner hyperspectral imaging spectrometer (CDO-HIS) is a hyperspectral calibrator for monitoring the radiation stability of an ocean color sensor. The spectrometer adopts the structure of the conical diffraction Offner configuration (CDO-CF), containing a convex blazed grating to produce a nearly nondistortion and high spectral fidelity image. The theory analysis of the conical diffraction Offner is discussed and introduced to the instrument design. The optimization procedure and design results of CDO-HIS and the conical diffraction grating are provided based on the design ideas, which show benefits of the employment of CDO-CF. The results of laboratory characterization are presented, including the grating diffraction efficiency and the instrument performance.

15.
Cell Tissue Res ; 373(2): 379-393, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29500491

RESUMEN

Mesenchymal stem cells (MSCs) are unique precursor cells characterized by active self-renewal and differentiation potential. These cells offer the advantages of ease of isolation and limited ethical issues as a resource and represent a promising cell therapy for neurodegenerative diseases. However, replicative senescence during cell culture as well as low efficiency of cell migration and differentiation after transplantation are major obstacles. In our previous study, we found that FOXQ1 binds directly to the SIRT1 promoter to regulate cellular senescence and also promotes cell proliferation and migration in many tumor cell lines. Currently, little is known about the effects of FOXQ1 on normal somatic cells. Therefore, we examine the effects of FOXQ1 on senescence and migration of MSCs. Lentiviral vector-mediated overexpression of FOXQ1 in human umbilical cord mesenchymal stem cells (hUC-MSCs) resulted in enhanced cell proliferation and viability. Furthermore, the expression of proteins and markers positively associated with senescence (p16, p21, p53) was reduced, whereas expression of proteins negatively associated with senescence (SIRT1, PCNA) was promoted. Following transplantation of hUC-MSCs overexpressing FOXQ1 in an animal model of Alzheimer's disease (APPV717I transgenic mice) resulted in amelioration of the effects of Alzheimer's disease (AD) on cognitive function and pathological senescence accompanied the increased numbers of hUC-MSCs in the AD brain. In conclusion, FOXQ1 overexpression promotes anti-senescence and migration of hUC-MSCs in vitro and in vivo. These findings also suggest that this strategy may contribute to optimization of the efficiency of stem cell therapy.


Asunto(s)
Movimiento Celular/genética , Senescencia Celular/genética , Factores de Transcripción Forkhead/metabolismo , Células Madre Mesenquimatosas/metabolismo , Cordón Umbilical/citología , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Animales , Diferenciación Celular/genética , Proliferación Celular/genética , Modelos Animales de Enfermedad , Factores de Transcripción Forkhead/genética , Células HEK293 , Humanos , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Ratones Transgénicos
16.
Cell Physiol Biochem ; 40(1-2): 370-378, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27866195

RESUMEN

BACKGROUND: To compare the impact of telbivudine (LDT) and entecavir (ETV) administration on nephritic function. METHOD: One hundred thirty patients diagnosed with hepatitis B virus (HBV)-related compensated cirrhosis were randomly divided into LDT (600 mg/d) or ETV (0.5 mg/d) groups. RESULTS: The drug resistance rate was higher following LDT treatment compared to ETV treatment (16.9% vs. 1.5%, P=0.0006). The mean creatinine level decreased compared to baseline in the LDT group (0.81 vs. 0.94 mg/dl, P=0.000). The change in median glomerular filtration rate (eGFR) compared to baseline in the LTD and ETV groups was 22.3 and -3.3, respectively, at 2 years (P=0.000). In patients with mild nephritic injury (eGFR< 90 ml/min/1.73m2), the median eGFR increased by 28.0 ml/min/1.73m2 in the LDT group and decreased by 4.3 ml/min/1.73m2 in the ETV group (p=0.000). The eGFR in 88.5% of patients (23/26) from the LDT group increased > 90 ml/min/1.73m2. The percentage of patients with an eGFR > 90 ml/min/1.73m2 increased from 60.0% to 92.3% in the LDT group and from 64.6% to 69.2% in the ETV group. CONCLUSION: In patients with HBV-related compensated cirrhosis, LDT treatment was more effective in protecting nephritic function and was associated with a higher drug resistance rate, but did not contribute to a better outcome compared with ETV treatment.


Asunto(s)
Farmacorresistencia Viral , Guanina/análogos & derivados , Virus de la Hepatitis B/fisiología , Riñón/fisiopatología , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/virología , Timidina/análogos & derivados , Creatinina/sangre , ADN Viral/genética , Farmacorresistencia Viral/efectos de los fármacos , Femenino , Tasa de Filtración Glomerular , Guanina/efectos adversos , Guanina/farmacología , Guanina/uso terapéutico , Humanos , Riñón/efectos de los fármacos , Pruebas de Función Renal , Cirrosis Hepática/sangre , Cirrosis Hepática/fisiopatología , Masculino , Persona de Mediana Edad , Telbivudina , Timidina/efectos adversos , Timidina/farmacología , Timidina/uso terapéutico
17.
Opt Express ; 24(18): 21070-80, 2016 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-27607710

RESUMEN

Wavefront coding system can realize defocus invariance of PSF/OTF with a phase mask inserting in the pupil plane. Ideally, the derivative of the PSF/OTF with respect to defocus error should be close to zero as much as possible over the extended depth of field/focus for the wavefront coding system. In this paper, we propose an analytical expression for the computation of the derivative of PSF. With this expression, the derivative of PSF based merit function can be used in the optimization of the wavefront coding system with any type of phase mask and aberrations. Computation of the derivative of PSF using the proposed expression and FFT respectively are compared and discussed. We also demonstrate the optimization of a generic polynomial phase mask in wavefront coding system as an example.

18.
Nanoscale ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39319561

RESUMEN

Cellular forces play a crucial role in numerous biological processes, including tissue development, morphogenesis, and disease progression. However, existing methods for detecting cellular forces, such as traction force microscopy and atomic force microscopy, often face limitations in terms of high throughput, real-time monitoring, and applicability to complex biological systems. In this study, we utilized a novel Photonic Crystal Cellular Force Microscopy (PCCFM) system to visualize and quantify dynamic cellular forces. This system consists of a conventional optical microscope and a photonic crystal substrate formed by the periodic arrangement of silica nanoparticles within polyacrylamide hydrogels. Taking MDCK cells and BMSCs as examples, we found that PCCFM can capture dynamic cellular forces with high spatial and temporal resolution during the cell adhesion, spread, proliferation, and osteogenic differentiation. The application of this technique revealed distinct force patterns in different cellular stages, offering insights into the interplay between cellular forces and morphological changes. By investigating the migration of cells from MDCK cyst fragments, we could gain significant insights into tumour cell migration behaviours. The real-time, high-throughput analysis of cellular biomechanics from the PCCFM system offers valuable information on the mechanisms of tumour metastasis, potentially guiding therapeutic development and improving disease treatment strategies.

19.
Shock ; 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39193891

RESUMEN

BACKGROUND: Multiple cell death modalities are implicated in sepsis pathobiology. However, the clinical relevance of NINJ1, a key mediator of plasma membrane rupture during lytic cell death, in sepsis progression and outcomes has remained poorly explored. METHODS: Circulating NINJ1 levels were measured in 116 septic ICU patients, 16 non-septic ICU controls, and 16 healthy controls. Comparative analysis of serum NINJ1 across these groups was performed. Correlations between NINJ1 and clinical disease severity scores (SOFA, APACHE II) as well as laboratory parameters were examined in the sepsis cohort. Furthermore, we assessed the prognostic performance of NINJ1 for predicting 28-day mortality in septic patients using receiver operating characteristic (ROC) analyses. RESULTS: Circulating NINJ1 levels were elevated in septic patients and positively correlated with sepsis severity scores. NINJ1 also showed positive correlations with liver injury markers (AST/ALT) and coagulation parameters (D-dimer, APTT, PT, TT) in sepsis. Further analysis using the ISTH overt DIC scoring system revealed an association between NINJ1 and sepsis-induced coagulopathy.ROC analysis demonstrated NINJ1 outperformed traditional inflammatory biomarkers PCT and CRP in predicting 28-day sepsis mortality, although its prognostic accuracy was lower than SOFA and APACHE II scores. Combining NINJ1 with SOFA improved mortality prediction from an AUC of 0.6843 to 0.773. CONCLUSIONS: Circulating NINJ1 serves as a novel sepsis biomarker indicative of disease severity, coagulopathy and mortality risk, and its integration with SOFA and APACHE II scores substantially enhances prognostic risk stratification. These findings highlight the prospective clinical utility of NINJ1 for sepsis prognostication and monitoring, warranting further validation studies to facilitate implementation.

20.
Food Res Int ; 180: 114065, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38395582

RESUMEN

Tartary buckwheat is rich in nutrients and its protein supports numerous biological functions. However, the digestibility of Tartary buckwheat protein (TBP) poses a significant limitation owing to its inherent structure. This study aimed to assess the impact of high moisture extrusion (HME, 60 % moisture content) on the structural and physicochemical attributes, as well as the in vitro digestibility of TBP. Our results indicated that TBP exhibited unfolded and amorphous microstructures after HME. The protein molecular weight of TBP decreased after HME, and a greater degradation was observed at 70 °C than 100 °C. In particular, HME at 70 °C caused an almost complete disappearance of bands near 35 kDa compared with HME at 100 °C. In addition, compared with native TBP (NTBP, 44.53 µmol/g protein), TBP subjected to HME at 70 °C showed a lower disulfide bond (SS) content (42.67 µmol/g protein), whereas TBP subjected to HME at 100 °C demonstrated a higher SS content (45.70 µmol/g protein). These changes endowed TBP with good solubility (from 55.96 % to 83.31 % at pH 7), foaming ability (20.00 %-28.57 %), and surface hydrophobicity (8.34-23.07). Furthermore, the emulsifying activity (EA) and in vitro digestibility are closely related to SS content. Notably, extruded TBP (ETBP) obtained at 70 °C exhibited higher EA and digestibility than NTBP, whereas ETBP obtained at 100 °C showed the opposite trend. Consequently, HME (especially at 70 °C) demonstrated significant potential as a processing technique for improving the functional and digestive properties of TBP.


Asunto(s)
Fagopyrum , Fagopyrum/química , Solubilidad , Digestión , Proteínas de Unión al GTP/metabolismo
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