Salubrinal Enhances Cancer Cell Death during Glucose Deprivation through the Upregulation of xCT and Mitochondrial Oxidative Stress.

Cancer cells have the metabolic flexibility to adapt to heterogeneous tumor microenvironments. The integrated stress response (ISR) regulates the cellular adaptation response during nutrient stress. However, the issue of how the ISR regulates metabolic flexibility is still poorly understood. In this study, we activated the ISR using salubrinal in cancer cells and found that salubrinal repressed cell growth, colony formation, and migration but did not induce cell death in a glucose-containing condition. Under a glucose-deprivation condition, salubrinal induced cell death and increased the levels of mitochondrial reactive oxygen species (ROS). We found that these effects of salubrinal and glucose deprivation were associated with the upregulation of xCT (SLC7A11), which functions as an antiporter of cystine and glutamate and maintains the level of glutathione to maintain redox homeostasis. The upregulation of xCT did not protect cells from oxidative stress-mediated cell death but promoted it during glucose deprivation. In addition, the supplementation of ROS scavenger N-acetylcysteine and the maintenance of intracellular levels of amino acids via sulfasalazine (xCT inhibitor) or dimethyl-α-ketoglutarate decreased the levels of mitochondrial ROS and protected cells from death. Our results suggested that salubrinal enhances cancer cell death during glucose deprivation through the upregulation of xCT and mitochondrial oxidative stress.

Ampelopsins A and C Induce Apoptosis and Metastasis through Downregulating AxL, TYRO3, and FYN Expressions in MDA-MB-231 Breast Cancer Cells.

Ampelopsins A and C are resveratrol oligostilbenes whose role in cancer development remains unknown. This study evaluated the antimetastatic and apoptosis-inducing properties of ampelopsins A and C in MDA-MB-231 cells. The IC50 values of ampelopsins A and C against MDA-MB-231 cells at 72 h were 38.75 ± 4.61 and 2.71 ± 0.21 µM, respectively. However, at 24 h, ampelopsins A and C decreased cell metastasis significantly. Among the 71 proteins present on the human phosphoreceptor tyrosin kinase array, ampelopsin C decreased the phosphorylated protein level of AXL, Dtk (TYRO3), EphA2, EphA6, Fyn, Hck, and SRMS. Additionally, antiproliferation effects of ampelopsin C were enhanced when combined with luteolin and chrysin compared to either two or a single agent in MDA-MB-231 cells. Overall, ampelopsins A and C extracted from Vitis thunbergii are both novel antimetastatic agents and potential therapeutic targets in patients with breast cancer.

ICF-CY code set for infants with early delay and disabilities (EDD Code Set) for interdisciplinary assessment: a global experts survey.

PURPOSE: Comprehensive description of functioning is important in providing early intervention services for infants with developmental delay/disabilities (DD). A code set of the International Classification of Functioning, Disability and Health: Children and Youth Version (ICF-CY) could facilitate the practical use of the ICF-CY in team evaluation. The purpose of this study was to derive an ICF-CY code set for infants under three years of age with early delay and disabilities (EDD Code Set) for initial team evaluation. METHODS: The EDD Code Set based on the ICF-CY was developed on the basis of a Delphi survey of international professionals experienced in implementing the ICF-CY and professionals in early intervention service system in Taiwan. RESULTS: Twenty-five professionals completed the Delphi survey. A total of 82 ICF-CY second-level categories were identified for the EDD Code Set, including 28 categories from the domain Activities and Participation, 29 from body functions, 10 from body structures and 15 from environmental factors. CONCLUSIONS: The EDD Code Set of 82 ICF-CY categories could be useful in multidisciplinary team evaluations to describe functioning of infants younger than three years of age with DD, in a holistic manner. Future validation of the EDD Code Set and examination of its clinical utility are needed. IMPLICATIONS FOR REHABILITATION: The EDD Code Set with 82 essential ICF-CY categories could be useful in the initial team evaluation as a common language to describe functioning of infants less than three years of age with developmental delay/disabilities, with a more holistic view. The EDD Code Set including essential categories in activities and participation, body functions, body structures and environmental factors could be used to create a functional profile for each infant with special needs and to clarify the interaction of child and environment accounting for the child's functioning.

Linkage of ICF-CY codes with environmental factors in studies of developmental outcomes of infants and toddlers with or at risk for motor delays.

PURPOSE: Environmental variables have been explored in studies of the development of young children with motor delays. Linking environmental variables to the International Classification of Functioning, Disability and Health - Children and Youth (ICF-CY), environmental factors (EFs) categories can provide a common language for documenting their contribution to developmental outcomes. This review of studies aimed to (1) link EFs for developmental outcomes in infants with or at risk for motor delays to ICF-CY categories and (2) synthesize the influences of EFs (with ICF-CY linkage) on developmental outcomes. METHOD: A systematic literature search was performed of multiple databases. After applying selection criteria, environmental variables in 28 articles were linked to ICF-CY categories and underwent qualitative synthesis. RESULTS: Results indicated that physical environmental variables could be linked successfully to ICF-CY EFs categories, but not social environmental variables. Multiple environmental variables were associated with motor and other developmental outcomes. CONCLUSION: Difficulties in linking social factors to ICF-CY categories indicate that additional EFs codes may need to be considered in the ICF-CY revision processes. The review provides empirical data on relationships between EFs and developmental outcomes in children with or at risk for motor delay.

[Wood smoke condensate had weak proliferation and strong necrotic effects on human airway smooth muscle cells].

OBJECTIVE: To investigate the effect of wood smoke condensate (WSC) on proliferation and necrosis of human airway smooth muscle cells (HASMCs). METHODS: Primary cultured HASMCs between passage 2 and 8 were divided into 3 groups: a control group, a WSC group and a cigarette smoke condensate (CSC) group. The viability of cells was examined by the CCK8 assays. The ratio of cellular proliferative stage (S phase) and cell cycle index were examined by fluorescent-labeled thymidine analogue uptake assays and flow cytometry. The expression of cyclin D1 was detected by quantitative reverse transcriptase polymerase chain reaction (Q-PCR) and Western blot. Cell apoptosis and necrosis were observed by the annexin-V and PI staining. Statistical analysis was performed by using the One-way ANOVA and LSD-t test. RESULTS: Cell viability reached peak at WSC 1 mg/L[(126 ± 12)%] and at CSC 10 mg/L exposure level [(142 ± 11) %] respectively. While at WSC 10 mg/L and CSC 60 mg/L exposure levels, cell viability decreased significantly to 86% and 76%, respectively, as compared with that of the blank control group[(100 ± 0)%] (q = 3.63- 9.33, P < 0.05). In the WSC 1 mg/L group, the cell proliferation ratio and the expression of cyclin D1 protein were (124 ± 20)% and 1.31 ± 0.64, respectively, the differences being significant as compared with the blank control group [(100 ± 0)%, 1.0 ± 0.0] (q = 5.85, 5.91, P < 0.05), while the expression of cyclin D1 mRNA and the percentage of S+G2M phase were 1.18 ± 0.21 and (103 ± 4)%, respectively, not significantly different as compared to the control group [(100 ± 0)%, 1.0 ± 0.0], (q = 1.16, 2.05, P > 0.05). In the CSC 10 mg/L group, the above-mentioned values were (204 ± 45)%, 1.80 ± 0.25, (140 ± 6)%, 1.48 ± 0.2, respectively, which were significantly higher than those in the blank control group (q = 5.38-16.51, P < 0.05) and in the WSC group (q = 3.33-15.35, P < 0.05). However, when HASMCs were exposed to WSC 10 mg/L, the cell death ratio was (13.39 ± 0.15)%, higher than that of the blank control group [(1.57 ± 0.41)%] and the CSC group [(6.61 ± 1.91)%] (q = 18.03, 10.34, P < 0.05). Apoptosis ratio in the CSC 40 mg/L group was [(61.8 ± 10.6)%], higher than that of the blank control group [(0.0 ± 0.0)%] and the WSC group [(1.7 ± 0.4)%] (q = 17.44, 16.95, P < 0.05). CONCLUSIONS: Exposure to WSC caused a weak proliferation of HASMCs, but resulted in cell necrosis instead of apoptosis at high doses. There was a slight difference in cell effects between the WSC group and the CSC group.

Test-retest and inter-rater reliability for the Comprehensive Developmental Inventory for Infants and Toddlers diagnostic and screening tests.

BACKGROUND: Reliability information for the Comprehensive Developmental Inventory for Infants and Toddlers diagnostic (CDIITDT) and screening tests (CDIITST) is inadequate. AIM: To assess the test-retest and inter-rater reliability of the CDIITDT and CDIITST. STUDY DESIGN: A repeated measures design was selected. SUBJECTS: Non-disabled term (n=15; mean age 8.4+/-1.6 months) and preterm infants (n=16; mean age 9.3+/-2.9 months), and children with developmental disabilities (n=15; mean age 24.7+/-11.8 months) were recruited. A single rater assessed the children twice in 3 days to examine the test-retest reliability; and a second rater observed and scored performance while the same rater conducted the first assessment for the inter-rater reliability analysis. OUTCOME MEASURES: The raw score, developmental age (DA) and developmental quotient (DQ)/Z score for the six subtests, two motor subdomains and the whole test were used as outcome measures for the CDIITDT and CDIITST. RESULTS: The test-retest reliabilities for the CDIITDT were rated good for the three pediatric groups (ICC 0.76-1.00), with the exception of moderate ratings for the self-help subtest for the term infants and for the social, self-help and fine-motor DQs for the preterm group. The CDIITDT inter-rater reliabilities were good for the three groups (ICC 0.76-1.00), with the exception of only moderate reliability for the cognitive DQs for the preterm infants. The reliabilities for the whole CDIITST for the three groups were high (ICC 0.93-1.00). CONCLUSION: The reliabilities for the whole CDIITDT and its various subtests and the whole CDIITST are acceptable for clinical use.