Adaptor protein Shc acts as an immune-regulator for the LPS-stimulated maturation of bone marrow-derived dendritic cells

<p>Abstract</p> <p>Background</p> <p>The Shc isoforms is known to mediate immune responses and has been indicated as a negative regulator of autoimmunity and lymphocyte activation. We aimed to evaluate the immune-regulatory role of Shc in rat bone marrow-derived DCs in the maturation process triggered by LPS.</p> <p>Results</p> <p>We found that, in response to LPS, expression of Shc proteins was induced and that neutralization of Shc inhibited the LPS-induced transient phosphorylation of p52Shc on pTyr239/240 in DCs of Lewis (LEW; RT1^l) rats. Moreover, the significantly enhanced expression of IL-10 and the surface level of costimulatory molecule CD80, as well as suppressed expression of IL-6 and IL-12 in the Shc-silenced DCs were also observed. Similar IκB phosphorylation occurred in Shc-silenced DCs primed by LPS, indicating Shc is not associated with NF-κB pathway. We further demonstrate that Shc blockade on LPS-treated DCs results in significant increase of the overall STAT3 phosphorylation and the relative levels of phospho-STAT3 in the nuclear fraction. STAT3 activation by LPS with or without Shc blockade was totally abolished by SU6656, a selective Src family kinases inhibitor, underscoring the critical role of Src-mediated activation.</p> <p>Conclusions</p> <p>We conclude that Shc blockade in LPS-primed DC leads to the development of tolerogenic DC via Src-dependent STAT3 activation and that adaptor protein Shc might play a pivotal role in mediating immunogenic and tolerogenic properties of DCs.</p

Frontal Function, Disability and Caregiver Burden in Elderly Patients With Major Depressive Disorder

Caregivers of patients with late-life major depressive disorder experience a significant level of general caregiver burden. Disability in patients is possibly one of the origins of caregiver burden. Frontal lobe dysfunction might be the source of disability. This study investigated if frontal lobe dysfunction (body level) of patients with late-life major depressive disorder was associated with their disability (individual level), and if it led to a high level of caregiver burden (societal level). Thirty-four unselected pairs of caregivers and their family members with late-life major depressive disorder were recruited. Frontal Assessment Battery and Timed Instrumental Activities of Daily Living (TIADL) were used to assess patients' frontal function and disability, and Caregiver Burden Inventory was used to measure caregiver burden. Frontal Assessment Battery correlated with TIADL (r= −0.47; p<0.006). TIADL score was also associated with two subscales of the Caregiver Burden Inventory: social (r = 0.38, p=0.026) and time-dependent (r= 0.37, p= 0.033). This study supported the hypothesis that frontal lobe dysfunction in elderly patients with depression is associated with their disability in instrumental activities of daily living. Disability is related to social and time-dependent aspects of caregiver burden. Further studies to examine proposed cognitive interventions are suggested to reduce patient disability and caregiver burden

Prophylactic Treatment with Adlay Bran Extract Reduces the Risk of Severe Acute Radiation Dermatitis: A Prospective, Randomized, Double-Blind Study

Acute radiation dermatitis is a frequent adverse effect in patients with breast cancer undergoing radiotherapy, but there are only a small number of studies providing evidence-based interventions for this clinical condition. Adlay is a cereal crop that has been previously shown to have anti-inflammatory and antioxidant properties. In this study, we seek to evaluate the effectiveness of oral prophylactic treatment with adlay bran extract in reducing the risk of severe acute radiation dermatitis. A total of 110 patients with breast cancer undergoing radiotherapy were analyzed. Using a prospective, randomized, double-blind design, 73 patients received oral treatment with adlay bran extract and 37 patients received olive oil (placebo). Treatment was started at the beginning of radiation therapy and continued until the termination of radiation treatment. Our results showed that the occurrence of severe acute radiation dermatitis (RTOG grade 2 or higher) was significantly lower in patients treated with oral adlay bran extract compared to placebo (45.2% versus 75.7%, adjusted odds ratio 0.24). No serious adverse effects from adlay bran treatment were noted. In conclusion, prophylactic oral treatment with adlay bran extract reduces the risk of severe acute radiation dermatitis and may have potential use in patients with breast cancer undergoing radiotherapy

Correction: Huang, H.W.; et al. Sinularin Selectively Kills Breast Cancer Cells Showing G2/M Arrest, Apoptosis, and Oxidative DNA Damage. Molecules 2018, 23, 849

The authors wish to make the following correction to their paper [1].[...

Sinularin Selectively Kills Breast Cancer Cells Showing G2/M Arrest, Apoptosis, and Oxidative DNA Damage

The natural compound sinularin, isolated from marine soft corals, is antiproliferative against several cancers, but its possible selective killing effect has rarely been investigated. This study investigates the selective killing potential and mechanisms of sinularin-treated breast cancer cells. In 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H- tetrazolium, inner salt (MTS) assay, sinularin dose-responsively decreased the cell viability of two breast cancer (SKBR3 and MDA-MB-231) cells, but showed less effect on breast normal (M10) cells after a 24 h treatment. According to 7-aminoactinomycin D (7AAD) flow cytometry, sinularin dose-responsively induced the G2/M cycle arrest of SKBR3 cells. Sinularin dose-responsively induced apoptosis on SKBR3 cells in terms of a flow cytometry-based annexin V/7AAD assay and pancaspase activity, as well as Western blotting for cleaved forms of poly(ADP-ribose) polymerase (PARP), caspases 3, 8, and 9. These caspases and PARP activations were suppressed by N-acetylcysteine (NAC) pretreatment. Moreover, sinularin dose-responsively induced oxidative stress and DNA damage according to flow cytometry analyses of reactive oxygen species (ROS), mitochondrial membrane potential (MitoMP), mitochondrial superoxide, and 8-oxo-2′-deoxyguanosine (8-oxodG)). In conclusion, sinularin induces selective killing, G2/M arrest, apoptosis, and oxidative DNA damage of breast cancer cells

Risk of Mortality in Association with Pregnancy in Women Following Motor Vehicle Crashes: A Systematic Review and Meta-Analysis

The aim of the study was to provide a systematic review and meta-analysis of studies examining the association between mortality risk and motor vehicle crashes (MVCs) in pregnant women compared with nonpregnant women. We used relevant MeSH terms to identify epidemiological studies of mortality risk in relation to MVCs from PubMed, Embase, and MEDLINE databases. The Newcastle&ndash;Ottawa Scale (NOS) was used for quality assessment. For comparison of mortality from MVCs between pregnant and nonpregnant women, the pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random effects model. The eight studies selected met all inclusion criteria. These studies included 14,120 injured victims who were pregnant at the time of the incident and 207,935 victims who were not pregnant. Compared with nonpregnant women, pregnant women had a moderate but insignificant decrease in mortality risk (pooled OR = 0.68, 95% CI = 0.38&ndash;1.22, I2 = 88.71%). Subgroup analysis revealed that the pooled OR significantly increased at 1.64 (95% CI = 1.16&ndash;2.33, I2 &lt; 0.01%) for two studies with a similar difference in the mean injury severity score (ISS) between pregnant and nonpregnant women. Future studies should further explore the risk factors associated with MVCs in pregnant women to reduce maternal mortality