[Corrigendum] The effect of NFATc1 on vascular generation and the possible underlying mechanism in epithelial ovarian carcinoma.

Subsequently to the publication of the above article [and an already published Corrigendum that has indicated a corrected version of Fig. 6 (DOI: 10.3892/ijo.2020.5131; published online on October 12, 2020)], the authors have realized that some incorrect data were also included in Fig. 3 in their paper; essentially, Fig. 3A, which was intending to show the siRNA knockdown data for NFATc1 expression in xenograft tumor tissue via immunohistochemical staining, was inadvertently derived from the same data as that shown for Fig. 4F. The corrected version of Fig. 3, featuring the correct data for Fig. 3A, is shown below. The authors confirm that this error did not significantly influence either the results or the conclusions in their paper. The authors are grateful to the Editor of International Journal of Oncology for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in International Journal of Oncology 48: 1457­1466, 2016; DOI: 10.3892/ijo.2016.3355].

[Corrigendum] The effect of NFATc1 on vascular generation and the possible underlying mechanism in epithelial ovarian carcinoma.

Following the publication of the above article, the authors have realized that some incorrect data were included in Fig. 6 in their paper; essentially, the CXCR2 protein bands that were included in the figure were irrelevant, and data for interleukin­8 (IL­8) should have been selected and included in the figure instead. The corrected version of Fig. 6 is shown opposite, now featuring the IL­8 data. The authors confirm that these errors did not significantly influence either the results or the conclusions in their paper. The authors are grateful to the Editor of International Journal of Oncology for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in International Journal of Oncology 48: 1457­1466, 2016; DOI: 10.3892/ijo.2016.3355].

Chinese guidelines for the assessment and provision of nutrition support therapy in critically ill children.

BACKGROUND: This document represents the first evidence-based guidelines to describe best practices in nutrition therapy in critically ill children (> 1 month and < 18 years), who are expected to require a length of stay more than 2 or 3 days in a Pediatric Intensive Care Unit admitting medical patients domain. METHODS: A total of 25,673 articles were scanned for relevance. After careful review, 88 studies appeared to answer the pre-identified questions for the guidelines. We used the grading of recommendations, assessment, development and evaluation criteria to adjust the evidence grade based on the quality of design and execution of each study. RESULTS: The guidelines emphasise the importance of nutritional assessment, particularly the detection of malnourished patients. Indirect calorimetry (IC) is recommended to estimate energy expenditure and there is a creative value in energy expenditure, 50 kcal/kg/day for children aged 1-8 years during acute phase if IC is unfeasible. Enteral nutrition (EN) and early enteral nutrition remain the preferred routes for nutrient delivery. A minimum protein intake of 1.5 g/kg/day is suggested for this patient population. The role of supplemental parenteral nutrition (PN) has been highlighted in patients with low nutritional risk, and a delayed approach appears to be beneficial in this group of patients. Immune-enhancing cannot be currently recommended neither in EN nor PN. CONCLUSION: Overall, the pediatric critically ill population is heterogeneous, and an individualized nutrition support with the aim of improving clinical outcomes is necessary and important.

CGRP attenuates hyperoxia-induced oxidative stress-related injury to alveolar epithelial type II cells via the activation of the Sonic hedgehog pathway.

The aim of this study was to examine the effect of calcitonin gene-related peptide (CGRP) on primary alveolar epithelial type II (AECII) cells and expression of Sonic hedgehog (SHH) signaling pathway components following exposure to hyperoxia. The AECII cells were isolated and purified from premature rats and exposed to air (21% oxygen), air + CGRP, hyperoxia (95% oxygen) or hyperoxia + CGRP. The production of intracellular reactive oxygen species (ROS) was determined using the 2',7'-dichlorofluorescin diacetate molecular probe. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in the culture supernatant were detected by spectrophotometry. The apoptosis of AECII cells was assayed by flow cytometry, and the mRNA and protein expression levels of Shh and Ptc1 in the AECII cells were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot analysis and immunofluorescence, respectively. The cellular pathological changes partly improved and apoptosis was markedly decreased upon treatment with CGRP under hyperoxic conditions. The levels of ROS in the hyperoxia + CGRP group were significantly lower than thoe in the hyperoxia group. In addition, the hyperoxia-induced increase in MDA levels and the decrease in SOD activity in the culture supernatant of the AECII cells were attenuated by CGRP. Compared with the cells exposed to air, hyperoxia markedly inhibited the mRNA and protein expression levels of Shh and Ptc1 in the AECII cells; however, this inhibition was partly attenuated by treatment with CGRP. On the whole, our data suggest that CGRP can partly protect AECII cells from hyperoxia-induced injury, and the upregulation of CGRP may be a potential therapeutic approach with which to combat hyperoxia-induced lung injury, which may be associated with the activation of the SHH signaling pathway.

Clinical Significance and Prognostic Effect of Serum 25-hydroxyvitamin D Concentrations in Critical and Severe Hand, Foot and Mouth Disease.

OBJECTIVE: To examine the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with critical and severe hand, foot and mouth disease (HFMD) and assess the clinical significance and prognostic effect of 25(OH)D concentrations in children with HFMD. METHODS: This is a prospective observational study. The 138 children with HFMD were divided into common (49 cases), severe (52 cases), and critical (37 cases) HFMD groups. Another 59 healthy children undergoing outpatient medical examinations during the same period were chosen as the control group. Serum 25(OH)D concentrations were measured in all the subjects, and each group was subdivided by serum 25(OH)D concentration into 25(OH)D normal (≥30 ng/mL); insufficiency (20-29.9 ng/mL), and deficiency (<20 ng/mL) groups. The pediatric critical illness score (PCIS) was recorded for the critical and severe HFMD group upon admission to the pediatric intensive care unit (PICU). Children with critical and severe HFMD were also monitored for blood lactate (LAC), serum calcium ions (Ca++), D-dimer (DD), lactate dehydrogenase (LDH), and creatine kinase-MB (CK-MB) levels; the incidences of brainstem encephalitis, neurogenic pulmonary edema, and circulatory failure; and the 14-day mortality rate. RESULTS: Serum 25(OH)D concentrations were generally low in all groups. The critical HFMD group showed a significantly lower serum 25(OH)D mean concentration (20.0 ± 8.4 ng/mL) and a higher proportion of deficiency (18%) compared with the control group (28.1 ± 6.6 ng/mL, 8%), common (29.5 ± 8.1 ng/mL, 10%) and severe (31.9 ± 9.7 ng/mL, 8%) HFMD groups (p < 0.05). In the critical and severe HFMD groups, the 25(OH)D deficiency group had lower PCISs than the 25(OH)D normal and insufficiency groups (p < 0.05); and had higher values than the latter two groups for LAC, LDH, CK-MB and DD; and the incidences of brainstem encephalitis, neurogenic pulmonary edema, circulatory failure, and mortality (p < 0.05). The death group showed significantly lower serum 25(OH)D concentrations and PCISs than the survival group (p < 0.05) and had higher LAC, LDH, CK-MB and DD levels and higher incidences of brainstem encephalitis, neurogenic pulmonary edema, and circulatory failure (p < 0.05). Logistic regression analysis revealed that the serum 25(OH)D concentration was an independent factor that influenced mortality in children with critical and severe HFMD. CONCLUSIONS: In this study, we find the serum 25(OH)D concentrations are substantially reduced in children with critical and severe HFMD and are associated with the severity of HFMD. The serum 25(OH)D concentrations may have clinical value for determining the progression of critical HFMD and predicting the risk of death. Further evidence is needed before it can be stated that 25(OH)D concentrations have clinical value in HMFD diagnosis.

NFATc1 regulates cell proliferation, migration, and invasion of ovarian cancer SKOV3 cells in vitro and in vivo.

NFATc1 (nuclear factor of activated T­cells c1) is associated with malignancy in several cancer models. However, the expression and function of NFATc1 in ovarian cancer remain elusive. In the present study, we investigated the role of NFATc1 in human epithelial ovarian cancer (EOC) using human ovarian adenocarcinoma SKOV3 cells and patient characteristics. NFATc1 expression was silenced by siRNA in the SKOV3 ovarian cancer cell line and in human ovarian cancer nude mouse xenografts. Real­time PCR, western blotting, immunohistochemical staining, MTT, flow cytometry, transwell, erasion trace and mouse assays were used to detect NFATc1 expression, cell proliferation, apoptosis, cell invasion and migration, tumor growth and angiogenesis. Survival analysis was performed to assess the correlation between NFATc1 expression and survival. NFATc1 was overexpressed in the SKOV3 ovarian cancer cell line and in human serous/mucinous ovarian cancer tissues. The silencing of NFATc1 expression by siRNA reduced cell proliferation and migration and promoted apoptosis in vitro and decreased the ovarian cancer cell tumorigenesis in vivo in nude mice. NFATc1 overexpression in high­grade serous ovarian carcinomas was an independent prognostic factor of poor overall survival and of early relapse (P<0.01) in a univariate analysis. Our present data provide evidence that NFATc1 is overexpressed in human serous/mucinous ovarian cancer and is associated with a poor prognosis. NFATc1 silencing regulates the cell cycle, apoptosis, invasion and migration. NFATc1 thus has the potential to be a therapeutic target and to be used in EOC diagnosis and prognosis.

The effect of NFATc1 on vascular generation and the possible underlying mechanism in epithelial ovarian carcinoma.

We investigated the effect of nuclear factor of activated T cells c1 (NFATc1) on the growth and vascular generation of human ovarian carcinoma SKOV3 cell-transplanted tumors in nude mice and explored the possible underlying mechanism. NFATc1 siRNA was transfected into the SKOV3 cells, which were then subjected to immunofluorescence tests and real-time reverse transcription polymerase chain reaction (RT-PCR) to determine the transfection-induced inhibition rate. The tumor volumes in the nude mice in all groups were measured to determine the in vivo antitumor effect of NFATc1 siRNA. Immunohistochemical (IHC) methods were employed to detect NFATc1 expression in tumor tissue, combined with cytokeratin (CK) staining to label the epithelial origin of the tumor tissue. CD34 and podoplanin were used as markers for labeling microvessels and microlymphatic vessels, respectively. The densities of microvessels and microlymphatic vessels in each group were calculated and statistically analyzed. RT-PCR and western blotting were performed to detect the protein and mRNA expression levels of NFATc1, the ELR+ CXC chemokine interleukin (IL)-8, fibroblast growth factor-2 (FGF-2), and platelet-derived growth factor BB (PDGF BB) in xenografted tumor tissue in all groups. NFATc1 was highly expressed in tumor tissue in the control groups. The intervention group exhibited a tumor growth inhibition rate of 57.08% and presented a lower tumor weight and volume compared with the two control groups. In the control groups, the microvessel densities were 12.00 ± 1.65 and 11.47 ± 0.32, respectively, and the microlymphatic vessel densities were 10.03 ± 0.96 and 9.95 ± 1.12; these values were significantly higher than in the intervention group. RT-PCR and western blot shows that NFATc1 siRNA could markedly suppress the expression of IL-8, FGF-2 and PDGF BB at the mRNA and the protein level. In conclusion, it was shown that NFATc1 siRNA significantly suppresses the growth and vascular generation of SKOV3 human ovarian carcinoma cell-transplanted tumors subcutaneously xenografted into nude mice. The downregulation of the expression of IL-8, FGF-2 and PDGF BB may be one of the mechanisms underlying the above inhibitory effects.

Fasudil, an inhibitor of Rho-associated coiled-coil kinase, attenuates hyperoxia-induced pulmonary fibrosis in neonatal rats.

BACKGROUND: Oxygen therapy is important during the management of high-risk neonatal infants, such as those with preterm birth, low birth weight, and asphyxia. However, prolonged exposure to high oxygen concentrations can readily lead to diffuse nonspecific inflammation, which promotes airway remodeling and pulmonary fibrosis. The Rho/Rho-associated coiled-coil kinase (Rho/ROCK) signaling pathway plays an important role in numerous developmental and proliferative diseases. This study was performed to determine the efficacy of ROCK inhibitor fasudil in blocking the development of hyperoxia-induced lung injury and fibrosis in neonatal rats. METHODS: Neonatal rats were randomly divided into four groups: air + saline group, air + fasudil group, hyperoxia + saline group, and hyperoxia + fasudil group. The hyperoxia + saline and Hyp + fasudil groups were exposed to 95% oxygen for 21 days and administered intraperitoneal saline or fasudil once daily. The air + saline and air + fasudil group were exposed to 21% oxygen (room air) and administered the same volume of intraperitoneal saline or fasudil. RESULTS: Fasudil-treated rats exhibited improved histopathological changes and decreased lung hydroxyproline content. Fasudil attenuated the protein level of alpha-smooth muscle actin, transforming growth factor-ß1, and connective tissue growth factor. Additionally, fasudil reduced the activation of ROCK1 and myosin phosphatase targeting subunit 1 protein in the Rho/ROCK signaling pathway. CONCLUSIONS: Fasudil may be a potentially effective therapeutic drug for hyperoxia-induced pulmonary fibrosis.