Enhancement of exercise endurance capacity by fermented deer antler in BALB/c mice

To investigate the activity of fermented deer antler on exercise endurance capacity, we evaluated endurance capacity in five-week-old male BALB/c mice by administering the fermented deer antler extract (FA) or the non-fermented deer antler extract (NFA) and then subjected the mice to exercise in the form of swimming. The mice administered 500?mg/kg/day of FA showed a significant increase in swimming time compared with mice administered placebo (16.55?min vs. 21.64?min, P?<?0.05). Serum lactate dehydrogenase (LDH), the marker of the liver and muscle damage, was significantly lower in FA groups. However, NFA groups did not show significantly different swimming time or serum LDH from that of the control group. Moreover, the FA-500 group had significantly higher hepatic superoxide dismutase (SOD) activity after forced swimming than the control and NFA groups (P?<?0.05). These findings suggest that fermentation may increase the exercise endurance capacity of the deer antler.     

Prognostic Value of Lactate and Central Venous Oxygen Saturation after Early Resuscitation in Sepsis Patients

The objective of this study was to evaluate the prognostic value of static and dynamic variables of central venous oxygen saturation (ScvO₂) and lactate in patients with severe sepsis or septic shock who underwent early quantitative resuscitation. We also investigated whether ScvO₂ measured after initial resuscitation could provide additive prognostic value to that of lactate. We analyzed the sepsis registry for patients presenting to the emergency department and included patients with simultaneous measurements of lactate and ScvO₂ at the time of presentation (H0) and 6 hours (H6) after resuscitation. The primary outcome was 28-day mortality and multivariable logistic analysis was used to adjust for confounders. A total of 363 patients were included, and the overall 28-day mortality was 18%. The area under the receiver operator characteristic curve for predicting 28-day mortality was as follows: lactate (H6), 0.81; lactate (H0), 0.73; relative lactate change, 0.67; ScvO₂ (H6), 0.65; relative ScvO₂ change 0.59; ScvO₂ (H0), 0.58. Patients with lactate normalization showed significantly lower 28-day mortality compared to patients without lactate normalization (3% vs. 28%, P<0.01). However, in those who achieved ScvO₂ (H6) ≥70%, there was a significant difference in 28-mortality only in patients without lactate normalization (21% vs. 39%, P<0.01) but no difference in those with lactate normalization (4% vs. 3%, P = 0.71). In multivariable analysis, lactate normalization was significantly associated with 28-day mortality (adjusted odds ratio [OR] for 28-day mortality, 0.20; 95% confidence interval [CI], 0.07–0.54; P <0.01), but ScvO₂ (H6) ≥70% showed only a marginal association (the adjusted OR for 28-day mortality, 0.51; 95% CI, 0.26–1.01; P = 0.05). ScvO₂ (H6) ≥70% was associated with 28-day mortality only in cases without lactate normalization in subgroup analysis (adjusted OR 0.37, 95% CI, 0.18–0.79; P = 0.01). Six-hour lactate was the strongest predictor of 28-day mortality in patients with severe sepsis or septic shock. Six-hour ScvO₂ provided additional prognostic value only in cases where lactate values were not normalized after resuscitation.     

Fluctuations in fruit fly abundance and infestation in sweet gourd fields in relation to varied meteorological factors

The study was conducted with the aim of furthering our understanding of seasonality in the population dynamics and infestation rates of the fruit fly Bactrocera spp. in sweet gourd (Cucurbita moschata) during winter and summer in 2017. We also investigated the effects of using methyl eugenol traps on fly abundance and infestation. Two fruit fly species, namely, B. cucurbitae and B. dorsalis, were present in the sweet gourd field, and we observed fluctuations in their abundance. Compared to B. dorsalis, B. cucurbitae was significantly more abundant in both winter and summer. Infestation level was found to be the highest in fields lacking methyl eugenol traps in both seasons. Fruit fly larval population per infested fruit was higher in summer than in winter. Fly abundance was significantly and positively correlated with mean temperature and rainfall but significantly and negatively correlated with light intensity. Relative humidity was insignificantly but positively correlated with fly abundance. The temperature, light intensity, relative humidity, and rainfall individually explained 48.9, 24.1, 0.8, and 1.6% of variation in fruit fly abundance, respectively. The combined effect of the weather parameters on fruit fly abundance was 75.4% and was significant predictor of fruit fly abundance.     

Investigation of B,C-ring truncated deguelin derivatives as heat shock protein 90 (HSP90) inhibitors for use as anti-breast cancer agents

On the basis of deguelin, a series of the B,C-ring truncated surrogates with N-substituted amide linkers were investigated as HSP90 inhibitors. The structure activity relationship of the template was studied by incorporating various substitutions on the nitrogen of the amide linker and examining their HIF-1α inhibition. Among them, compound 57 showed potent HIF-1α inhibition and cytotoxicity in triple-negative breast cancer lines in a dose-dependent manner. Compound 57 downregulated expression and phosphorylation of major client proteins of HSP90 including AKT, ERK and STAT3, indicating that its antitumor activity was derived from the inhibition of HSP90 function. The molecular modeling of 57 demonstrated that 57 bound well to the C-terminal ATP-binding pocket in the open conformation of the hHSP90 homodimer with hydrogen bonding and pi-cation interactions. Overall, compound 57 is a potential antitumor agent for triple-negative breast cancer as a HSP90 C-terminal inhibitor.     

Improved insulin sensitivity and adiponectin level after exercise training in obese Korean youth

Objective: The objective of this study was to investigate the association among adiposity, insulin resistance, and inflammatory markers [high‐sensitivity C‐reactive protein (hs‐CRP), interleukin (IL)‐6, and tumor necrosis factor (TNF)‐α] and adiponectin and to study the effects of exercise training on adiposity, insulin resistance, and inflammatory markers among obese male Korean adolescents. Research Methods and Procedures: Twenty‐six obese and 14 lean age‐matched male adolescents were studied. We divided the obese subjects into two groups: obese exercise group (N = 14) and obese control group (N = 12). The obese exercise group underwent 6 weeks of jump rope exercise training (40 min/d, 5 d/wk). Adiposity, insulin resistance, lipid profile, hs‐CRP, IL‐6, TNF‐α, and adiponectin were measured before and after the completion of exercise training. Results: The current study demonstrated higher insulin resistance, total cholesterol, LDL‐C levels, triglyceride, and inflammatory markers and lower adiponectin and HDL‐C in obese Korean male adolescents. Six weeks of increased physical activity improved body composition, insulin sensitivity, and adiponectin levels in obese Korean male adolescents without changes in TNF‐α, IL‐6, and hs‐CRP. Discussion: Obese Korean male adolescents showed reduced adiponectin levels and increased inflammatory cytokines. Six weeks of jump rope exercise improved triglyceride and insulin sensitivity and increased adiponectin levels.     

The AMPA Receptor Subunit GluA1 is Required for CA1 Hippocampal Long-Term Potentiation but is not Essential for Synaptic Transmission

AMPA receptors mediate the majority of excitatory glutamatergic transmission in the mammalian brain and are heterotetramers composed of GluA1-4 subunits. Despite genetic studies, the roles of the subunits in synaptic transmission and plasticity remain controversial. To address this issue, we investigated the effects of cell-specific removal of GluA1 in hippocampal CA1 pyramidal neurons using virally-expressed GluA1 shRNA in organotypic slice culture. We show that this shRNA approach produces a rapid, efficient and selective loss of GluA1, and removed?>?80% of surface GluA1 from synapses. This loss of GluA1 caused a modest reduction (up to 57%) in synaptic transmission and when applied in neurons from GluA3 knock-out mice, a similar small reduction in transmission occurred. Further, we found that loss of GluA1 caused a redistribution of GluA2 to synapses that may compensate functionally for the absence of GluA1. We found that LTP was absent in neurons lacking GluA1, induced either by pairing or by a theta-burst pairing protocol previously shown to induce LTP in GluA1 knock-out mice. Our findings demonstrate a critical role of GluA1 in CA1 LTP, but no absolute requirement for GluA1 in maintaining synaptic transmission. Further, our results indicate that GluA2 homomers can mediate synaptic transmission and can compensate for loss of GluA1.

     

The structure of AcrIE4-F7 reveals a common strategy for dual CRISPR inhibition by targeting PAM recognition sites

Bacteria and archaea use the CRISPR-Cas system to fend off invasions of bacteriophages and foreign plasmids. In response, bacteriophages encode anti-CRISPR (Acr) proteins that potently inhibit host Cas proteins to suppress CRISPR-mediated immunity. AcrIE4-F7, which was isolated from Pseudomonas citronellolis, is a fused form of AcrIE4 and AcrIF7 that inhibits both type I-E and type I-F CRISPR-Cas systems. Here, we determined the structure of AcrIE4-F7 and identified its Cas target proteins. The N-terminal AcrIE4 domain adopts a novel α-helical fold that targets the PAM interaction site of the type I-E Cas8e subunit. The C-terminal AcrIF7 domain exhibits an αβ fold like native AcrIF7, which disables target DNA recognition by the PAM interaction site in the type I-F Cas8f subunit. The two Acr domains are connected by a flexible linker that allows prompt docking onto their cognate Cas8 targets. Conserved negative charges in each Acr domain are required for interaction with their Cas8 targets. Our results illustrate a common mechanism by which AcrIE4-F7 inhibits divergent CRISPR-Cas types.     

Altered corticotropin-releasing factor (CRF) receptor immunoreactivity in the gerbil hippocampal complex following spontaneous seizure

Considerable attention has been focused on the role of corticotropin-releasing factor (CRF) in neuropsychiatric disorders and neurodegenerative diseases including epilepsy. Therefore, in the present study, we investigated the temporal and spatial alteration of CRF receptor in the gerbil hippocampal complex in order to characterize the possible changes and associations with different sequelae of spontaneous seizure in these animals. Thirty minutes postictal, a decline in CRF receptor immunoreactivity was observed in the granule cells and hilar neurons. In the subiculum, CRF receptor immunoreactivity was also significantly decreased at this time point. Twenty-four hours after seizure onset, the immunoreactivity in these regions recovered to the pre-seizure level. Moreover, 30 min after seizure in the entorhinal cortex, the density of CRF receptor immunoreactivity began to decrease, particularly in the layers II and III, compared to pre-seizure group. Nevertheless, 24h after seizure onset, CRF receptor immunodensity had recovered to its seizure-sensitive (SS) level. These results suggest that altered CRF receptor expression in the hippocampal complex may affect tissue excitability and seizure activity in SS gerbils.