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231.
Liangjun Li Lin Lin Ming Li Weiling Li 《Journal of cellular and molecular medicine》2020,24(3):2308-2318
As a highly potent and highly selective oral inhibitor of FLT3/AXL, gilteritinib showed activity against FLT3D835 and FLT3‐ITD mutations in pre‐clinical testing, although its role on colorectal cancer (CRC) cells is not yet fully elucidated. We examined the activity of gilteritinib in suppressing growth of CRC and its enhancing effect on other drugs used in chemotherapy. In this study, we observed that, regardless of p53 status, treatment using gilteritinib induces PUMA in CRC cells via the NF‐κB pathway after inhibition of AKT and activation of glycogen synthase kinase 3β (GSK‐3β). PUMA was observed to be vital for apoptosis in CRC cells through treatment of gilteritinib. Moreover, enhancing induction of PUMA through different pathways could mediate chemosensitization by using gilteritinib. Furthermore, PUMA deficiency revoked the antitumour role of gilteritinib in vivo. Thus, our results indicate that PUMA mediates the antitumour activity of gilteritinib in CRC cells. These observations are critical for the therapeutic role of gilteritinib in CRC. 相似文献
232.
Yao Wu Peng Chen Li Sun Shengtao Yuan Zujue Cheng Ligong Lu Hongzhi Du Meixiao Zhan 《Journal of cellular and molecular medicine》2020,24(17):9495-9506
Sepiapterin reductase, a homodimer composed of two subunits, plays an important role in the biosynthesis of tetrahydrobiopterin. Furthermore, sepiapterin reductase exhibits a wide distribution in different tissues and is associated with many diseases, including brain dysfunction, chronic pain, cardiovascular disease and cancer. With regard to drugs targeting sepiapterin reductase, many compounds have been identified and provide potential methods to treat various diseases. However, the underlying mechanism of sepiapterin reductase in many biological processes is unclear. Therefore, this article summarized the structure, distribution and function of sepiapterin reductase, as well as the relationship between sepiapterin reductase and different diseases, with the aim of finding evidence to guide further studies on the molecular mechanisms and the potential clinical value of sepiapterin reductase. In particular, the different effects induced by the depletion of sepiapterin reductase or the inhibition of the enzyme suggest that the non‐enzymatic activity of sepiapterin reductase could function in certain biological processes, which also provides a possible direction for sepiapterin reductase research. 相似文献
233.
234.
Jacopo Burrello Sara Bolis Carolina Balbi Alessio Burrello Elena Provasi Elena Caporali Lorenzo Grazioli Gauthier Andrea Peirone Fabrizio D'Ascenzo Silvia Monticone Lucio Barile Giuseppe Vassalli 《Journal of cellular and molecular medicine》2020,24(17):9945-9957
The current standard biomarker for myocardial infarction (MI) is high‐sensitive troponin. Although powerful in clinical setting, search for new markers is warranted as early diagnosis of MI is associated with improved outcomes. Extracellular vesicles (EVs) attracted considerable interest as new blood biomarkers. A training cohort used for diagnostic modelling included 30 patients with STEMI, 38 with stable angina (SA) and 30 matched‐controls. Extracellular vesicle concentration was assessed by nanoparticle tracking analysis. Extracellular vesicle surface‐epitopes were measured by flow cytometry. Diagnostic models were developed using machine learning algorithms and validated on an independent cohort of 80 patients. Serum EV concentration from STEMI patients was increased as compared to controls and SA. EV levels of CD62P, CD42a, CD41b, CD31 and CD40 increased in STEMI, and to a lesser extent in SA patients. An aggregate marker including EV concentration and CD62P/CD42a levels achieved non‐inferiority to troponin, discriminating STEMI from controls (AUC = 0.969). A random forest model based on EV biomarkers discriminated the two groups with 100% accuracy. EV markers and RF model confirmed high diagnostic performance at validation. In conclusion, patients with acute MI or SA exhibit characteristic EV biomarker profiles. EV biomarkers hold great potential as early markers for the management of patients with MI. 相似文献
235.
Xu Wang Yujia Chen Wei Liu Tao Liu Di Sun 《Journal of cellular and molecular medicine》2020,24(17):9908-9924
Hsa_circ_0128846 was found to be the most significantly up‐regulated circRNA in our bioinformatics analysis. However, the role of hsa_circ_0128846 in colorectal cancer has not been explored. We thus aim to explore the influence and mechanism of hsa_circ_0128846 in colorectal cancer by sponging its downstream miRNA target miR‐1184. We collected 40 colorectal cancer patients’ tumour tissues to analyse the expression of hsa_circ_0128846, miR‐1184 and AJUBA using qRT‐PCR and Western blot where needed. Then, we constructed stably transfected SW480 and HCT116 cells to study the influence of hsa_circ_0128846, miR‐1184 and AJUBA on colorectal cancer cell phenotypes. To obtain reliable results, a plethora of experiments including RNA immunoprecipitation assay, flow cytometry, EdU incorporation assay, wound healing migration assay, transwell invasion assay and live imaging of nude mice xenograft assay were performed. The binding relationship between hsa_circ_0128846, miR‐1184 and AJUBA mRNA in colorectal cancer was validated by reported gene assay. In colorectal cancer tissues, circ_0128846 and AJUBA were both significantly up‐regulated, while miR‐1184 was significantly down‐regulated compared with healthy tissues. Meanwhile, hsa_circ_0128846 can absorb miR‐1184 to promote the progression of CRC in vivo and SW480 and HCT116 cell phenotypes in vitro. The knockdown of AJUBA, a downstream target of miR‐1184, reversed the effect of miR‐1184 in CRC cells via enhancing the phosphorylation of the Hippo/YAP signalling pathway proteins MST1, LATS1 and YAP. This study revealed that hsa_circ_0128846 contributed to the development of CRC by decreasing the expression of miR‐1184, thereby increasing AJUBA expression and inactivating Hippo/YAP signalling. 相似文献
236.
Miaoda Shen Zhuoyang Li Duo Lv Ge Yang Ronghuan Wu Jun Pan Shuo Wang Yifan Li Sanzhong Xu 《Journal of cellular and molecular medicine》2020,24(13):7370-7377
This study aimed to describe the 25‐hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) status of Southeast Chinese individuals influenced by season. The secondary aim was to determine the cutoff for sufficient 25(OH)D in a four‐season region. From January 2011 to June 2014, a total of 17 646 individuals were evaluated in our study. The serum levels of PTH were detected simultaneously in 5579 cases. A total of 25(OH)D and intact PTH were measured by the electrochemiluminescent immunoassay. The distribution of the concentration, prevalence and seasonal variability of 25(OH)D and PTH were studied. The mean 25(OH)D concentration in our study was 43.00(30.40) nmol/L. The prevalence of insufficiency (25(OH)D < 50 nmol/L) was 62.87% and that of deficiency (<30 nmol/L) was 28.54%. Mean serum 25(OH)D levels revealed a limited sinusoidal profile throughout the year and were significantly higher in Autumn. On the other hand, PTH levels showed an opposite response to seasonal effects relative to 25(OH)D. Age, BMI and daylight were not significantly correlated with 25(OH)D and serum PTH reached a plateau at higher values of serum 25(OH)D of 42.86 nmol/L. This study demonstrated that Vitamin D insufficiency is highly prevalent in Southeast China. The concentration of 25(OH)D in the male group was generally higher than that in the female group. Seasonal variation was an important aspect of 25(OH)D and PTH concentration. This study revealed that the optimal serum threshold of 25(OH)D for bone health should be between 40 and 50 nmol/L for Southeast Chinese individuals. 相似文献
237.
Neekun Sharma Anthony M. Belenchia Ryan Toedebusch Lakshmi Pulakat Chetan P. Hans 《Journal of cellular and molecular medicine》2020,24(13):7393-7404
Clinical and experimental studies show that angiotensin II (AngII) promotes vascular pathology via activation of AngII type 1 receptors (AT1Rs). We recently reported that NP‐6A4, a selective peptide agonist for AngII type 2 receptor (AT2R), exerts protective effects on human vascular cells subjected to serum starvation or doxorubicin exposure. In this study, we investigated whether NP‐6A4–induced AT2R activation could mitigate AngII‐induced abdominal aortic aneurism (AAA) using AngII‐treated Apoe?/? mice. Male Apoe?/? mice were infused with AngII (1 µg/kg/min) by implanting osmotic pumps subcutaneously for 28 days. A subset of mice was pre‐treated subcutaneously with NP‐6A4 (2.5 mg/kg/day) or vehicle for 14 days prior to AngII, and treatments were continued for 28 days. NP‐6A4 significantly reduced aortic stiffness of the abdominal aorta induced by AngII as determined by ultrasound functional analyses and histochemical analyses. NP‐6A4 also increased nitric oxide bioavailability in aortic tissues and suppressed AngII‐induced increases in monocyte chemotactic protein‐1, osteopontin and proteolytic activity of the aorta. However, NP‐6A4 did not affect maximal intraluminal aortic diameter or AAA incidences significantly. These data suggest that the effects of AT2R agonist on vascular pathologies are selective, affecting the aortic stiffness and proteolytic activity without affecting the size of AAA. 相似文献
238.
Giovanna Carr Paolo Nicoli Marcello Francesco Lingua Beatrice Maffeo Antonio Cartell Paola Circosta Mara Brancaccio Guido Parvis Valentina Gaidano Angelo Guerrasio Giuseppe Saglio Riccardo Taulli Alessandro Morotti 《Journal of cellular and molecular medicine》2020,24(2):1650-1657
The development of drugs able to target BTK, PI3k‐delta and BCL2 has dramatically improved chronic lymphocytic leukaemia (CLL) therapies. However, drug resistance to these therapies has already been reported due to non‐recurrent changes in oncogenic pathways and genes expression signatures. In this study, we investigated the cooperative role of the BCL2 inhibitor venetoclax and the BRD4 inhibitor JQ1. In particular, we found that JQ1 shows additional activity with venetoclax, in CLL cell lines and in ex vivo isolated primary CD19+ lymphocytes, arguing in favour of combination strategies. Lastly, JQ1 is also effective in venetoclax‐resistant CLL cell lines. Together, our findings indicated that the BET inhibitor JQ1 could be a promising therapy in CLL, both as first‐line therapy in combination with venetoclax and as second‐line therapy, after the emergence of venetoclax‐resistant clones. 相似文献
239.
Xiaojiao Zeng Guohong Liu Yunbao Pan Yirong Li 《Journal of cellular and molecular medicine》2020,24(15):8326-8349
Inflammation indicators, such as systemic inflammation response index (SIRI), systemic immune‐inflammation index (SII), neutrophil‐to‐lymphocyte ratio (NLR) and platelet‐lymphocyte ratio (PLR), are associated with poor prognosis in various solid cancers. In this study, we investigated the predictive value of these inflammation indicators in nasopharyngeal carcinoma (NPC). This retrospective study involved 559 patients with NPC and 500 patients with chronic rhinitis, and 255 NPC patients were followed up successfully. Continuous variables and qualitative variables were measured by t test and chi‐square test, respectively. The optimal cut‐off values of various inflammation indicators were determined by receiver operating characteristic (ROC) curve. Moreover, the diagnostic value for NPC was decided by the area under the curves (AUCs). The Kaplan‐Meier methods and the log‐rank test were used to analyse overall survival (OS) and disease‐free survival (DFS). The independent prognostic risk factors for survival and influencing factors of side effects after treatment were analysed by Cox and logistic regression analysis, respectively. Most haematological indexes of NPC and rhinitis were significantly different between the two groups, and PLR was optimal predictive indicators of diagnosis. In the multivariable Cox regression analysis, PLR, WBC, RDW, M stage and age were independent prognostic risk factors. Many inflammation indicators that affected various side effects were evaluated by logistic regression analysis. In conclusion, the combined inflammation indicators were superior to single haematological indicator in the diagnosis and prognosis of NPC. These inflammation indicators can be used to supply the current evaluation system of the TNM staging system to help predict the prognosis in NPC patients. 相似文献
240.
Yun Ge Man Huang Yao Wu Ning Dong Yong‐Ming Yao 《Journal of cellular and molecular medicine》2020,24(2):2027-2039
Naturally occurring CD4+CD25+ regulatory T cells (Tregs) are required to limit immune‐induced pathology and to maintain homeostasis during the early‐phase of sepsis. This study aimed to investigate the role of interleukin (IL)‐38, a newly described member of the IL‐1 cytokine family, in mediated immune response of CD4+CD25+ Tregs in sepsis. Here, we provide evidence that expressions of IL‐38 and its receptor were detected in murine CD4+CD25+ Tregs. Stimulation of CD4+CD25+ Tregs with LPS markedly up‐regulated the expression of IL‐38. Treatment with rmIL‐38 dramatically enhanced the immunosuppressive activity of CD4+CD25+ Tregs after LPS stimulation and in septic mice induced by CLP, resulting in amplification of helper T cell (Th) 2 response and reduction in the proliferation of effector T cells. These effects were robustly abrogated when anti–IL‐38 antibody was administered. Administration of rmIL‐38 improved the survival rate of CLP mice. In addition, CD4+CD25+ Tregs depletion before the onset of sepsis obviously abolished IL‐38–mediated protective response. These findings suggest that IL‐38 enhances the immunosuppressive activity of CD4+CD25+ Tregs, which might contribute to the improvement of host immune function and prognosis in the setting of sepsis. 相似文献