BAY 11-7082 Is a Broad-Spectrum Inhibitor with Anti-Inflammatory Activity against Multiple Targets

BAY 11-7082 (BAY) is an inhibitor of κB kinase (IKK) that has pharmacological activities that include anticancer, neuroprotective, and anti-inflammatory effects. In this study, BAY-pharmacological target pathways were further characterized to determine how this compound simultaneously suppresses various responses. Primary and cancerous (RAW264.7 cells) macrophages were activated by lipopolysaccharide, a ligand of toll-like receptor 4. As reported previously, BAY strongly suppressed the production of nitric oxide, prostaglandin E2, and tumor necrosis factor-α and reduced the translocation of p65, major subunit of nuclear factor-κB, and its upstream signaling events such as phosphorylation of IκBα, IKK, and Akt. In addition, BAY also suppressed the translocation and activation of activator protein-1, interferon regulatory factor-3, and signal transducer and activator of transcription-1 by inhibiting the phosphorylation or activation of extracellular signal-related kinase, p38, TANK-binding protein, and Janus kinase-2. These data strongly suggest that BAY is an inhibitor with multiple targets and could serve as a lead compound in developing strong anti-inflammatory drugs with multiple targets in inflammatory responses

Predictors of the Change in the Expression of Emotional Support within an Online Breast Cancer Support Group: A Longitudinal Study

OBJECTIVES: To explore how the expression of emotional support in an online breast cancer support group changes over time, and what factors predict this pattern of change. METHODS: We conducted growth curve modeling with data collected from 192 participants in an online breast cancer support group within the Comprehensive Health Enhancement Support System (CHESS) during a 24-week intervention period. RESULTS: Individual expression of emotional support tends to increase over time for the first 12 weeks of the intervention, but then decrease slightly with time after that. In addition, we found that age, living situation, comfort level with computer and the Internet, coping strategies were important factors in predicting the changing pattern of expressing emotional support. CONCLUSIONS: Expressing emotional support changed in a quadratic trajectory, with a range of factors predicting the changing pattern of expression. PRACTICAL IMPLICATIONS: These results can provide important information for e-health researchers and physicians in determining the benefits individuals can gain from participation in should CMSS groups as the purpose of cancer treatment

Engineered biosynthesis of milbemycins in the avermectin high-producing strain Streptomyces avermitilis

Additional file 3 : Figure S2. HPLC analysis of milbemycins produced from S. avermitilis mutant strains and authentic standard milbemycins

Impairment of Release Site Clearance within the Active Zone by Reduced SCAMP5 Expression Causes Short-Term Depression of Synaptic Release

Summary: Despite being a highly enriched synaptic vesicle (SV) protein and a candidate gene for autism, the physiological function of SCAMP5 remains mostly enigmatic. Here, using optical imaging and electrophysiological experiments, we demonstrate that SCAMP5 plays a critical role in release site clearance at the active zone. Truncation analysis revealed that the 2/3 loop domain of SCAMP5 directly interacts with adaptor protein 2, and this interaction is critical for its role in release site clearance. Knockdown (KD) of SCAMP5 exhibited pronounced synaptic depression accompanied by a slower recovery of the SV pool. Moreover, it induced a strong frequency-dependent short-term depression of synaptic release, even under the condition of sufficient release-ready SVs. Super-resolution microscopy further proved the defects in SV protein clearance induced by KD. Thus, reduced expression of SCAMP5 may impair the efficiency of SV clearance at the active zone, and this might relate to the synaptic dysfunction observed in autism. : Park et al. show that SCAMP5 plays an important role in release site clearance during intense neuronal activity. Loss of SCAMP5 results in a traffic jam at release sites, causing aberrant short-term synaptic depression that might be associated with the synaptic dysfunction observed in autism. Keywords: secretory carrier membrane protein, SCAMP5, autism spectrum disorder, adaptor protein 2, release site clearance, presynaptic active zone, short-term depression, endocytosis, super-resolution microscop

Socioeconomic inequalities in obesity among Korean women aged 19-79 years: the 2016 Korean Study of Women’s Health-Related Issues

OBJECTIVES While the prevalence of obesity in Asian women has remained stagnant, studies of socioeconomic inequalities in obesity among Asian women are scarce. This study aimed to examine the recent prevalence of obesity in Korean women aged between 19 years and 79 years and to analyze socioeconomic inequalities in obesity. METHODS Data were derived from the 2016 Korean Study of Women’s Health-Related Issues. The chi-square test and logistic regression analysis were used to analyze the associations between socioeconomic factors and obesity using Asian standard body mass index (BMI) categories: low (<18.5 kg/m2 ), normal (18.5-22.9 kg/m2 ), overweight (23.0-24.9 kg/m2 ), and obese (≥25.0 kg/ m2 ). As inequality-specific indicators, the slope index of inequality (SII) and relative index of inequality (RII) were calculated, with adjustment for age and self-reported health status. RESULTS Korean women were classified into the following BMI categories: underweight (5.3%), normal weight (59.1%), overweight (21.2%), and obese (14.4%). The SII and RII revealed substantial inequalities in obesity in favor of more urbanized women (SII, 4.5; RII, 1.4) and against of women who were highly educated (SII, -16.7; RII, 0.3). Subgroup analysis revealed inequalities in obesity according to household income among younger women and according to urbanization among women aged 65-79 years. CONCLUSIONS Clear educational inequalities in obesity existed in Korean women. Reverse inequalities in urbanization were also apparent in older women. Developing strategies to address the multiple observed inequalities in obesity among Korean women may prove essential for effectively reducing the burden of this disease

A Case of Placenta Increta Presenting as Delayed Postabortal Intraperitoneal Bleeding in the First Trimester

Placenta increta is an uncommon and life-threatening complication of pregnancy characterized by complete or partial absence of the decidua basalis. Placenta increta usually presents with vaginal bleeding during difficult placental removal in the third-trimester. Although placenta increta may complicate first and early second-trimester pregnancy loss, the diagnosis can be very difficult during early pregnancy and thus the lesion is difficult to identify. We encountered with a woman who was diagnosed with placenta increta after receiving emergency hysterectomy due to intraperitoneal bleeding 2 months after an uncomplicated dilatation and curettage in the first trimester. Therefore, we report this case with a brief review of the literature

In vivo genome editing with a small Cas9 orthologue derived from Campylobacter jejuni

Several CRISPR-Cas9 orthologues have been used for genome editing. Here, we present the smallest Cas9 orthologue characterized to date, derived from Campylobacter jejuni (CjCas9), for efficient genome editing in vivo. After determining protospacer-adjacent motif (PAM) sequences and optimizing single-guide RNA (sgRNA) length, we package the CjCas9 gene, its sgRNA sequence, and a marker gene in an all-in-one adeno-associated virus (AAV) vector and produce the resulting virus at a high titer. CjCas9 is highly specific, cleaving only a limited number of sites in the human or mouse genome. CjCas9, delivered via AAV, induces targeted mutations at high frequencies in mouse muscle cells or retinal pigment epithelium (RPE) cells. Furthermore, CjCas9 targeted to the Vegfa or Hif1a gene in RPE cells reduces the size of laser-induced choroidal neovascularization, suggesting that in vivo genome editing with CjCas9 is a new option for the treatment of age-related macular degeneration.