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Δευτέρα 8 Μαρτίου 2021

ASPP2 expression predicts the prognosis of patients with hepatocellular carcinoma after transcatheter arterial chemoembolization

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Exp Ther Med. 2021 Apr;21(4):397. doi: 10.3892/etm.2021.9828. Epub 2021 Feb 24.

ABSTRACT

Transcatheter arterial chemoembolization (TACE) induces ischemia-hypoxia and local chemotherapy-induced cytotoxicity which destroys cancerous cells. However, some patients do not respond to TACE. The causes for such a lack of response remain unclear. Recent studies have revealed that self-regulation of apoptosis-stimulating p53 protein 2 (ASPP2) may play an important role in promoting cell survival under hypoxic conditions as well as chemotherapy resistance via autophagy in various types of cancer. We measured the expression of ASPP2, autophagy-related proteins and apoptotic proteins by western blot assays. Multivariate logistic regression analysis was used to identify the independent risk factor. The present study found that ASPP2 expression was negatively correlated with that of BECN-1 (Beclin-1) in hepatocellular carcinoma (HCC) tissues. The expression of ASPP-1 was lower while that of Beclin-1 was higher in patients who underwent recurrence of HCC following TACE, than in those who do not undergo such a relapse. ASPP2 expression was also lower in cancerous tissues subjected to TACE, compared with that of directly resected cancerous tissue. The expression of LC3-II was also higher in patients with post-operative recurrence of HCC than in those without relapse. In vitro experiments showed that administration of an autophagy inhibitor, together with hypoxia activation and 5-FU treatment, promoted apoptosis in HepG2 liver cancer cells and primary HCC cells. Multivariate logistic regression analysis revealed that ASPP2 expression in cancer tissue following TACE is an independent risk factor for HCC recurrence as well as overall survival. Higher levels of ASPP2 expression were notably associated with higher objective responses evaluated via mRECIST. Thus, patients with resectable HCC showing high levels of ASPP2 ex pression may benefit from neoadjuvant TACE prior to resection. Our study provided a novel biomarker for HCC prognosis following TACE, based on cell survival mechanisms related to autophagy.

PMID:33680119 | PMC:PMC7918402 | DOI:10.3892/etm.2021.9828

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Schisantherin A improves learning and memory abilities partly through regulating the Nrf2/Keap1/ARE signaling pathway in chronic fatigue mice

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Exp Ther Med. 2021 Apr;21(4):385. doi: 10.3892/etm.2021.9816. Epub 2021 Feb 23.

ABSTRACT

Chronic fatigue is frequently accompanied by decreased learning and memory capabilities. Schizantherin A (SCA) is one of the main active monomer components in Schisandra chinensis lignans. In the present study, a chronic fatigue mouse model was established using the exhausted swimming approach to investigate the effects of SCA on learning and memory and its associated mechanism of action. Learning and memory abilities were tested by step through tests and water maze methods. Levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA) in hippocampal tissue were measured by corresponding assays. The effect of SCA on the expression of kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Bcl2, Bax and cleaved caspase-3 were determined by we stern blot. The present results showed that SCA can improve the learning and memory capabilities of chronic fatigue mice. SCA was found to increase the activities of SOD and CAT in addition to increasing the levels of GSH but reduced the levels of MDA in hippocampus tissues. Furthermore, SCA treatment downregulated the protein expression levels of Keap1, Bax and cleaved caspase-3 and upregulated the protein expression levels of Nrf2, HO1 and Bcl2 in the hippocampus. These results suggested that modulations in the Nrf2-Keap1-antioxidant response element pathway, anti-oxidative and anti-apoptosis effects are the causes underlying the improvements from SCA treatment on the learning and memory abilities of chronic fatigue mice.

PMID:33680107 | PMC:PMC7918174 | DOI:10.3892/etm.2021.9816

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Long non-coding RNA SNHG7 facilitates pancreatic cancer progression by regulating the miR-146b-5p/Robo1 axis

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Exp Ther Med. 2021 Apr;21(4):398. doi: 10.3892/etm.2021.9829. Epub 2021 Feb 24.

ABSTRACT

Long non-coding RNA (lncRNA) small nucleolar RNA host gene 7 (SNHG7) plays a crucial role in the progression of pancreatic cancer (PC). SNHG7 is upregulated in PC; therefore, the purpose of the present study was to investigate the role and underlying mechanism of SNHG7 on PC progression. In the present study, the mRNA expression levels of SNHG7, microRNA(miR)-146b-5p and roundabout homolog 1 (Robo1) were measured via reverse transcription-quantitative PCR. Moreover, cell viability and apoptosis were assessed by MTT and flow cytometry assays, respectively. The ability of cells to migrate and invade was evaluated by Transwell assays. In addition, dual-luciferase reporter, RNA immunoprecipitation and RNA pull-down assays were conducted to assess the interaction between miR-146b-5p and SNHG7 or Robo1. The protein expression of Robo1 was measured via we stern blotting. Furthermore, mouse xenograft models were established to further investigate the effect of SNHG7 on PC progression in vivo. The results indicated that SNHG7 was highly expressed in PC tissues and cells. It was also found that SNHG7 was sponged by miR-146b-5p and that Robo1 was a target of miR-146b-5p. Moreover, it was demonstrated that SNHG7 knockdown inhibited cell proliferation, migration and invasion, as well as tumorigenesis and apoptosis of PC cells in vitro and in vivo by regulating miR-146b-5p. The results also suggested that miR-146b-5p overexpression inhibited the progression of PC cells by modulating Robo1. Furthermore, silencing of SNHG7 downregulated Robo1 expression by sponging miR-146b-5p. Collectively, the present results indicate that SNHG7 promotes PC progression by sponging miR-146b-5p and upregulating Robo1.

PMID:33680120 | PMC:PMC7918173 | DOI:10.3892/etm.2021.9829

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Visfatin promotes angiogenesis of RF/6A cells through upregulation of VEGF/VEGFR-2 under high-glucose conditions

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Exp Ther Med. 2021 Apr;21(4):389. doi: 10.3892/etm.2021.9820. Epub 2021 Feb 24.

ABSTRACT

Visfatin is a type of adipocytokine that is highly expressed in the serum and vitreous of patients with diabetic retinopathy. The purpose of the present study was to investigate the effect and mechanism of visfatin on angiogenesis in RF/6A monkey chorioretinal retinal endothelial cells under high glucose (HG) conditions in vitro. RF/6A cells were randomly divided into four groups: Control group, under high glucose (HG) group (25 mM D-glucose), visfatin group 1 (10 nM visfatin + 25 mM D-glucose), visfatin group 2 (20 nM visfatin + 25 mM D-glucose) and visfatin group 3 (30 nM visfatin + 25 mM D-glucose). After 24 and 48 h, a Cell Counting Kit-8, wound-healing assay and Matrigel tube formation assay were used to detect cell proliferation, migration and cell tube formation, respectively. Subsequently, the expression levels of VEGF and VEGF recep tor 2 (VEGFR-2) in cells of visfatin group 3 were observed by western blot and reverse transcription-quantitative PCR analyses. At 24 and 48 h, the cell proliferation and migration distance in the HG group were reduced compared with those in the control group (P<0.05). Compared with those in the HG group, the cell proliferation and migration distance in all visfatin groups were significantly increased (P<0.05), with the highest significance in visfatin group 3. Visfatin significantly promoted tube-like structure formation by RF/6A cells, particularly at the concentration of 30 nM. The protein and mRNA expression levels of VEGF and VEGFR-2 were significantly increased in the HG group as compared with those in the control group (P<0.05). Furthermore, compared with those in the HG group, VEGF and VEGFR-2 protein and mRNA expression levels were significantly increased in visfatin group 3 (P<0.05). Overall, visfatin promoted the proliferation, migration and tube formation of RF/6A cells under HG conditions, suggesting that visfatin has a potent effect on retinal neovascularization and its mechanism may be associated with the promotion of VEGF and VEGFR-2 expression under HG conditions.

PMID:33680111 | PMC:PMC7918108 | DOI:10.3892/etm.2021.9820

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Good's syndrome with a relapsed bloodstream infection induced by Alcaligenes sp. after thymectomy: A case report

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Exp Ther Med. 2021 Apr;21(4):399. doi: 10.3892/etm.2021.9830. Epub 2021 Feb 24.

ABSTRACT

Good's syndrome (GS) or thymoma-associated immunodeficiency is a rare clinical syndrome with poor prognosis. The varied and unspecified clinical manifestations of GS commonly lead to a missed or delayed diagnosis. Thus, misdiagnosis and missed diagnosis are common. The present case study reports on a patient who suffered from a relapsed bloodstream infection caused by Alcaligenes sp. 6 months after thymectomy. The patient was finally diagnosed with GS after analyzing the clinical features and detecting T-lymphocyte subsets in the peripheral blood and humoral immune function. The patient's condition improved after anti-infection treatment and supplementation with intravenous immunoglobulin. Furthermore, no infection was observed during the 1-year follow-up.

PMID:33680121 | PMC:PMC7918125 | DOI:10.3892/etm.2021.9830

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Insulin-like growth factor 2-enhanced osteogenic differentiation of stem cell spheroids by regulation of Runx2 and Col1 expression

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Exp Ther Med. 2021 Apr;21(4):383. doi: 10.3892/etm.2021.9814. Epub 2021 Feb 22.

ABSTRACT

Insulin-like growth factor 2 (IGF-2) is a growth factor that is involved in various functions of cells, including stem cells. The effects of IGF-2 on the cellular viability and osteogenic differentiation of stem cell spheroids were investigated in the present study. Stem cell spheroids were formed using concave microwells in the presence of IGF-2 at final concentrations of 0, 10 and 100 ng/ml. Cellular viability was measured qualitatively using a microscope and quantitatively using an assay kit based on water-soluble tetrazolium salt. The level of alkaline phosphatase activity, and an anthraquinone dye assay for calcium deposit evaluation, were used to assess osteogenic differentiation. A quantitative PCR analysis was conducted to evaluate the expression of Runx2 and Col1. Spheroid formation was noticed on day 1 in the microwells, and the spheroida l shape was maintained up to day 7. The cell viability assay values for IGF-2 at 0, 10 and 100 ng/ml at day 1 were 0.193±0.002, 0.191±0.002 and 0.201±0.006, respectively (P>0.05). The absorbance values at 405 nm for the alkaline phosphatase activity assays on day 21 were 0.221±0.006, 0.375±0.010 and 0.280±0.015 for IGF-2 at 0, 10 and 100 ng/ml, respectively. There were significantly higher values for IGF-2 in the 10 and 100 ng/ml groups when compared with the control (P<0.05). Significantly higher Alizarin red staining was noted for IGF-2 in the 10 ng/ml group when compared with the unloaded control at day 21 (P<0.05). Quantitative PCR revealed that mRNA levels of Runx2 and Col1 were significantly higher at 100 ng/ml on day 7. Conclusively, the present study demonstrated that the application of IGF-2 increased alkaline phosphatase activity, Alizarin red staining, and Runx2 and Col1 expression of stem cell spheroids.

PMID:33680105 | PMC:PMC7918416 | DOI:10.3892/etm.2021.9814

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Programmed cell death-1/programmed cell death-ligand 1 inhibitors exert antiapoptosis and antiinflammatory activity in lipopolysaccharide stimulated murine alveolar macrophages

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Exp Ther Med. 2021 Apr;21(4):400. doi: 10.3892/etm.2021.9831. Epub 2021 Feb 24.

ABSTRACT

Acute lung injury caused by sepsis remains one of the most difficult challenges faced by patients in intensive care units and is associated with a high mortality rate. The aim of the present study was to investigate whether programmed cell death (PD)-1/programmed cell death-ligand 1 (PD-L1) inhibitors reduce alveolar macrophage apoptosis, reduce inflammatory factor release and relieve inflammation. For this purpose, murine alveolar macrophages, MH-S, were cultured and divided into control, lipopolysaccharide (LPS) and LPS+BMS-1 (PD-1/PD-L1 inhibitors) groups. LPS (10 ng/ml) was added to the LPS and LPS+BMS-1 groups for 24 h and PD-1/PD-L1 inhibitor BMS-1 (1 µmol/l) was added to the LPS+BMS-1 group for 72 h. PD-1 mRNA expression was detected using reverse transcription-quantitative PCR and PD-1 protein expression was detected using western blotting in the control, LPS and LPS+BMS-1 groups of macrophages. MH-S apoptosis was detected using flow cytometry with Annexin V/PI staining. The levels of the inflammatory factors interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and IL-10 were detected by ELISA. Murine alveolar macrophages expressed PD-1 at both the molecular and protein levels and PD-1 expression was increased in MH-S cells stimulated with LPS. Compared with the LPS group, the expression of PD-1 in the LPS+BMS-1 group was significantly decreased. Flow cytometry demonstrated that there was increased apoptosis of alveolar macrophages in the LPS group compared with the control group, whereas, alveolar macrophages notably decreased apoptosis in the LPS+BMS-1 group compared with the LPS group. There was no statistical difference between the control group and the LPS+BMS-1 group. IL-1β, IL-6, TNF-α and IL-10 were increased in the LPS group compared with the control group. The levels of IL-1β, IL-6 and TNF-α in th e LPS+BMS-1 group were lower compared with those in the LPS group whereas IL-10 was further increased. In vitro, the PD-1/PD-L1 inhibitor, BMS-1, decreases alveolar macrophage apoptosis compared with the LPS group to maintain effective immune clearance and reduce inflammatory factor release. This decreased the inflammatory response and reduced acute lung injury caused by sepsis. Therefore, PD-1/PD-L1 inhibitors may be a potential therapeutic target for acute lung injury in patients with sepsis.

PMID:33680122 | PMC:PMC7918472 | DOI:10.3892/etm.2021.9831

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MicroRNA-1 affects the development of the neural crest and craniofacial skeleton via the mitochondrial apoptosis pathway

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Exp Ther Med. 2021 Apr;21(4):379. doi: 10.3892/etm.2021.9810. Epub 2021 Feb 19.

ABSTRACT

The neural crest is one of the key features of craniofacial development. MicroRNA-1 (miR-1) is a single-stranded noncoding RNA that serves an important role in embryonic development. However, the function of miR-1 in neural crest cells (NCCs) is unknown. Therefore, to evaluate the role of miR-1 in NCC development, a miR-1 mutant zebrafish was generated in the current study. Mouse NCCs were isolated from the first branchial arch of embryos at gestational day E9.5, and miR-1 was silenced using a miR-1 inhibitor. To the best of our knowledge, the present study was the first to report that homozygous zebrafish lacking miR-1 exhibited developmental defects in NCC-derived craniofacial bones, heart, melanocytes and iridophores. These defects may be caused by an increase in apoptosis of NCCs during their migration and differentiation in embryonic developme nt. Moreover, the apoptosis analysis and western blotting results demonstrated that this effect was modulated via the mitochondrial apoptosis pathway, and miR-1 inhibited NCC apoptosis by modulating this pathway. These results collectively suggested that miR-1 in NCCs may be essential for craniofacial development.

PMID:33680101 | PMC:PMC7918114 | DOI:10.3892/etm.2021.9810

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Low fluid intake volume during the first 24 h and persistent negative fluid balance from the second day are associated with favorable prognosis for patients with sepsis

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Exp Ther Med. 2021 Apr;21(4):387. doi: 10.3892/etm.2021.9818. Epub 2021 Feb 23.

ABSTRACT

For patients with sepsis and septic shock, it remains controversial when to restrict fluid intake and achieve a negative fluid balance. The present study aimed to evaluate the effects of the fluid intake volume during the first 24 h as well as fluid balance for 7 days on the prognosis of sepsis or septic shock. A total of 337 patients diagnosed with sepsis or septic shock at Ruijin Hospital (Shanghai, China) were enrolled in the present retrospective study. Patients with a low fluid intake volume during the first 24 h (fluid intake, 28.1±10.6 ml/kg) had lower in-hospital mortality rates (18.0 vs. 27.3%, P=0.043) and a shorter duration of mechanical ventilation [0 (0-6) vs. 3 (0-11), P=0.025] than the high-fluid volume intake group (62.6±17.6 ml/kg). Furthermore, survivors exhibited a daily negative net fluid balance from the second day (48 h), wh ereas non-survivors had a daily positive net fluid balance for 7 days, where fluid balance volumes were significantly lower in survivors compared with those in non-survivors. Finally, binary logistic regression analysis was used to determine whether the mean daily fluid balance (P<0.001) and the Acute Physiologic and Chronic Health Evaluation II score (P=0.048) were independent prognostic factors for patients with sepsis or septic shock. It was indicated that a low fluid intake volume during the first 24 h and a persistent negative fluid balance from the second day were associated with favorable outcomes. The mean daily fluid balance was an independent prognostic factor or patients with sepsis or septic shock.

PMID:33680109 | PMC:PMC7918047 | DOI:10.3892/etm.2021.9818

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Bilateral Subdural Hygromas After Deep Brain Stimulation Implantation in the Setting of Unrecognized Intracranial Hypotension

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Cureus. 2021 Jan 30;13(1):e13018. doi: 10.7759/cureus.13018.

ABSTRACT

Cerebrospinal fluid (CSF)-venous fistulas are a recently recognized cause of spontaneous spinal CSF leak and present most commonly with Valsalva ("cough")-exacerbated or orthostatic headaches. By inducing CSF hypotension, they cause diffuse pachymeningeal enhancement and brain sag on MRI. This unusual case demonstrates the potential for bilateral subdural hygroma development in a patient with an undiagnosed CSF-venous fistula after ventral intermediate nucleus (VIM) deep brain stimulation (DBS) implantation. A 68-year-old gentleman with medically-refractory essential tremor underwent extensive preoperative evaluation by the Mayo Clinic-Rochester DBS Committee. Initial MRI during preoperative evaluation had no evidence of CSF hypotension, but MRI performed the day before surgery demonstrated diffuse pachymeningeal enhancement. He underwent bilateral VIM DBS implantation and presented in the subacute postoperative period with bilateral subdural hygromas. Further testing identified a prominent hyperdense paraspinal vein arising from the T10/T11 nerve root, consistent with CSF-venous fistula. Even when patients undergo rigorous preoperative evaluations for surgical procedures, insidious pathologies can develop and cause unexpected postoperative complications.

PMID:33680583 | PMC:PMC7924968 | DOI:10.7759/cureus.13018

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